BioMed doi: 10.3390/biomed6020012

Authors: Neha Seth Phyu Thin Naing Pratik Q. Deb

Nodal T-follicular helper cell lymphomas comprise a biologically similar but morphologically diverse family of T-cell neoplasms, including angioimmunoblastic T-cell lymphoma, nodal T-follicular helper cell lymphoma, follicular-type, and nodal TFH lymphoma, not otherwise specified. Despite recurrent molecular alterations involving RHOA, IDH2, TET2, and DNMT3A, the diagnosis of TFH lymphomas remains challenging because of their mimicry of other lymphoid neoplasms and reactive lymphadenopathy. A key pitfall is confusion with classical Hodgkin lymphoma, as admixed Epstein–Barr virus-positive large B-cells with Reed–Sternberg cell-like morphology and immunophenotype can be found in TFH lymphomas. Similarly, follicular-type TFH lymphoma is often misclassified as follicular B-cell lymphoma unless T-cell lineage is investigated by immunophenotyping and the absence of BCL2 or BCL6 rearrangement is established. The ‘not otherwise specified’ category should be reserved for cases with proven T-follicular helper immunophenotype but lacks definitive angioimmunoblastic or follicular architecture. Comparing current frameworks, 5th edition of the World Health Organization classification permits rare CD4/CD8 double negative cases, while International Consensus Classification requires CD4 positivity. Some of these distinctions may appear taxonomic as all T-follicular helper T-cell lymphoma subtypes share molecular alterations, prognosis, and treatment approach. However, these classifications are meaningful from the perspective of a histopathologic diagnosis as a wrong diagnosis may lead to ineffective treatment approach. Accurate recognition of these lymphomas prevents misclassification, avoids inappropriate regimens, and ensures eligibility for proper clinical trials. A structured approach integrating morphology, multiparameter immunohistochemistry, flow cytometry, and molecular testing provides the best safeguard against diagnostic pitfalls and refines classification across subtypes.

BioMed doi: 10.3390/biomed6020011

Authors: Joshua Louis Davies Yimeng Zhang Inuri Patabendi Sudarshan Ramachandran Jyoti Baharani

Background/Objectives: Cardiovasc{Citation}ular disease accounts for 50% of chronic kidney disease (CKD) mortality, yet fewer than 40% of patients achieve guideline LDL-cholesterol (LDL-C) targets on statins. Injectable lipid-lowering therapies (ILLTs)—PCSK9 inhibitors and inclisiran—offer 50–70% LDL-C reductions but lack comprehensive CKD-specific evidence synthesis. This systematic review evaluated ILLT efficacy, safety, and implementation across kidney function stages including dialysis. Methods: Following PROSPERO registration (CRD42024612594), we searched MEDLINE, Embase, Cochrane Library, CINAHL, and Google Scholar (1995–August 2025). Two reviewers independently screened studies using PICOS criteria: adults with CKD stages G3-G5, dialysis, or transplant recipients receiving injectable lipid therapies. Primary outcomes were LDL-C percentage change and major adverse cardiovascular events. Quality was assessed using NIH tools. Given heterogeneity, we performed narrative synthesis following SWiM guidance. Results: Eight studies (n = 28,013) met the criteria. The FOURIER trial demonstrated that evolocumab achieved 58–59% LDL-C reductions across kidney function strata (interaction p = 0.77) with preserved cardiovascular benefit (HR 0.82–0.89). Absolute risk reduction was greater in advanced CKD (2.5% vs. 1.7%), reflecting higher baseline rates. Pharmacokinetic studies showed no eGFR-exposure correlation requiring dose adjustment; evolocumab was not removed by haemodialysis. Inclisiran achieved a 67–80% PCSK9 reduction and a 35–58% LDL-C reduction across renal groups, with twice-yearly maintenance dosing. Both classes reduced non-HDL-C (45–50%), apoB (40–45%), and lipoprotein(a) (20–25%). Safety was favourable, with mild injection-site reactions (< 5%); no renal decline signals emerged. Conclusions: Evidence for injectable lipid-lowering therapies in CKD are driven largely by a single large post hoc subgroup analysis (FOURIER) and small phase 1–2 PK/PD studies, with minimal dialysis representation and no transplant data. These agents appear to provide substantial LDL-C reductions across CKD stages G3–G5 without dose adjustment, but cardiovascular and renal outcome data in advanced CKD and dialysis remain limited and should be interpreted cautiously.

BioMed doi: 10.3390/biomed6020010

Authors: Rezak Drali Lionel Chollet Emilie Deroubaix Cecile Poggi Amira Doudou Laurent Deblir Chalom Sayada Sofiane Mohamed

Background/Objectives: Influenza, RSV, and SARS-CoV-2 co-circulate and evolve under immune and therapeutic pressures, complicating decision-making for both vaccine formulation and antiviral use. Fragmented, pathogen-specific sequencing approaches limit cross-virus comparability. Methods: We applied a standardized, multiplexed, amplicon-based next-generation sequencing (NGS) workflow to 34 diagnostic specimens (Ct < 35) positive for influenza A/B, RSV-A/B, or SARS-CoV-2. Sequencing libraries were generated and run on an Illumina MiSeq platform (2 × 250 bp). Although the wet-lab workflow is standardized across pathogens, consensus generation and annotation utilized two different analysis environments: Geneious Prime for influenza and MicrobioChek for RSV and SARS-CoV-2. Quality metrics included genome breadth and depth of coverage. Results: Near-complete genomes (mean coverage ≥98%) were recovered for all samples. Influenza A(H1N1)pdm09 sequences clustered in clade 6B.1A; A(H3N2) clustered in subclade 3C.2a1b.2a.2; and influenza B belonged to the Victoria lineage V1A.3a.2. RSV sequences were assigned to Nextclade clades A.D.5.1, A.D.1.10, A.D.2.1, and A.D.3 (RSV-A) and to B.D.4.1.3 and B.D.E.1 (RSV-B), consistent with the ON1 (RSV-A) and BA (RSV-B) genotypes prevalent in recent seasons. Clinically relevant mutations included changes in the influenza HA site and neuraminidase substitutions, RSV F-protein polymorphisms, and spike protein substitutions associated with recent Omicron sublineages (L455F/S, F456L) in SARS-CoV-2. Conclusions: A unified amplicon–NGS approach yields harmonized genomic data across respiratory viruses, enabling timely detection of antigenic drift and resistance markers while supporting integrated, cross-pathogen surveillance.

BioMed doi: 10.3390/biomed6010009

Authors: Marine Schott Estelle Leroux Chloé Libaud Audrey Lafragette Mallorie Depond Ophélie Dauphouy Benoît Decouture Aurélia Leroux Stéphanie Boutroy-Perrin Patricia Forest-Villegas Olivier Gauthier Gwenola Touzot-Jourde

During hemorrhagic procedures, autotransfusion is one of the main strategies for patient blood management. While conventional cell savers only concentrate red blood cells due to the centrifugation method, the innovative same™ autotransfusion medical device (i-SEP, Nantes, France), based on a hollow-fiber filtration technology, has the ability to preserve red blood cells along with the majority of platelets. Background/Objectives: The present study aimed at comparing the functionality of preserved platelets in the clot formation by using Quantra® and/or ROTEM® Point-Of-Care coagulation tests, after blood treatment for autotransfusion with either a standard centrifugation-based system (Xtra® device, LivaNova, London, UK), or the filtration-based same™ device. Methods: First, coagulation was assessed in an in vitro experiment, where human blood samples were used to obtain ten treated blood products by each autotransfusion device that were evaluated with or without supplementation of plasma poor or rich in platelets. Then, to confirm the potential clinical benefit of the platelet preservation in a surgical context, coagulation was studied in vivo using a massive surgical hemorrhagic model on eight minipigs per device. Samples were collected after reinfusion steps and during a 6 h post-operative follow-up. Results: Both in vitro and in vivo, the same™ device consistently retained more platelets compared to the Xtra® device. This enhanced preservation resulted in significantly stronger clot formation, likely due to higher platelet concentration and superior functional integrity. Conclusions: These findings highlight the potential clinical benefit of same™-recovered platelets for improving hemostasis during hemorrhagic surgery.

BioMed doi: 10.3390/biomed6010008

Authors: Stiliani Andreadou Angeliki Tanti Foteini Gkiliri Kriton Chatzikonstantinou Eleni Vatista Anna Christakou

Background: Pulmonary rehabilitation (PR) is increasingly used across the lung-cancer care pathway, but the scope, effectiveness, and optimal delivery of programmes remain variably reported. Objective: To examine the effectiveness of PR in adults undergoing lung cancer surgery across preoperative perioperative, and post operating settings. Methods: We conducted a narrative synthesis of studies evaluating PR interventions in patients undergoing lung cancer resection. Eligible designs included randomised, non-randomised trials and observational studies published between 2021 and 2025. Interventions were classified by timing (preoperative, perioperative, postoperative) and by completeness of PR content. Full PR was defined as programmes including structured exercise training, at least one respiratory-specific component, and structured education and/or supportive interventions. Outcomes of interest included postoperative pulmonary complications (PPCs), length of stay (LOS), functional capacity, ventilatory function, symptoms and health-related quality of life (HRQoL). Results: Across perioperative phases, PR was feasible and safe, with consistent improvements in functional capacity and patient-reported outcomes. Preoperative PR reliably improved presurgical fitness with reductions in PPCs and LOS most evident in supervised and physiologically targeted programmes. Perioperative PR integrated within enhanced recovery pathways supported early mobilisation and respiratory recovery. Postoperative PR accelerated recovery of exercise capacity, respiratory symptoms, and HRQoL beyond expected natural recovery. Programmes classified as Full PR demonstrated more consistent and broader benefits across outcome domains compared with Partial PR. Substantial heterogeneity in intervention design and outcome measurement was observed. Conclusions: Pulmonary rehabilitation is an effective, multidimensional intervention across the surgical lung cancer continuum. Comprehensive, multimodal programmes appear to confer the greatest clinical benefit. Standardisation of PR content and outcome measurement is needed to strengthen evidence synthesis and guide implementation in perioperative lung cancer care.

BioMed doi: 10.3390/biomed6010007

Authors: Giovannino Silvestri

Glutamine metabolism has emerged as one of the most critical bioenergetic and biosynthetic programs sustaining leukemic cell growth, survival, stemness and therapeutic resistance. In both acute and chronic leukemias, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), malignant cells display a strong dependency on extracellular glutamine to support mitochondrial respiration, anabolic biosynthesis and redox homeostasis. This dependency is reinforced by oncogenic signaling networks, post-transcriptional metabolic regulation and microenvironmental adaptation within the bone marrow niche. Therapeutic strategies targeting glutamine utilization, including glutaminase inhibition, transporter blockade and enzymatic glutamine depletion, have demonstrated robust antileukemic activity in preclinical models, and early clinical efforts have begun to explore glutamine-directed interventions in myeloid neoplasms. However, metabolic plasticity, microenvironment-derived nutrient buffering and systemic toxicity remain significant limitations to clinical translation. This review provides a detailed synthesis of the biochemical framework of glutamine metabolism in leukemia, the molecular mechanisms enforcing glutamine addiction, the downstream functional consequences on proliferation, redox balance and leukemic stem cell biology, the current landscape of therapeutic strategies and emerging directions aimed at overcoming resistance and improving clinical efficacy.

BioMed doi: 10.3390/biomed6010006

Authors: Areej Safdar Behnaz Sohani Faiz Iqbal Roohollah Barzamini Amir Rahmani Aliyu Aliyu

Breast cancer remains the most frequently diagnosed cancer in women worldwide, with outcomes strongly dependent on stage at detection. Conventional imaging modalities such as mammography, ultrasound and MRI are limited by reduced sensitivity in dense breasts, radiation exposure, high cost and restricted availability in low-resource settings. This review critically examines microwave imaging (MWI) as a non-invasive, radiation-free and an emerging resource-efficient breast imaging modality that exploits dielectric contrast between healthy and malignant breast tissues. We first summarise experimental and clinical evidence on breast dielectric properties and their implications for numerical phantoms and device design. We then review passive, active (tomographic and radar-based) and hybrid MWI systems, including key clinical prototypes such as SAFE, MammoWave, MARIA and Wavelia, and analyse associated image-reconstruction algorithms from classical inverse scattering to advanced beamforming, Huygens-based methods and AI based reconstruction. Finally, we discuss outstanding challenges—tissue heterogeneity, calibration, hardware constraints and computational complexity—and identify future directions including AI-assisted reconstruction, multimodal hybrid imaging and large-scale clinical validation needed to translate MWI into routine breast cancer screening and diagnosis.

BioMed doi: 10.3390/biomed6010005

Authors: Upamanyu Nath Iulia Valeria Rusu Anand Pillai

Background/Objectives: Diabetic Foot Ulceration (DFU) is one of the most debilitating and costly complications of diabetes mellitus, representing a significant cause of morbidity, disability, and healthcare burden worldwide. Refractory non-healing ulcers that fail to respond to conventional therapies require novel adjuvant treatment modalities. This clinical audit aimed to evaluate the long-term clinical outcomes of an autologous, bioactive platelet-rich fibrin (PRF) matrix combined with topical gentamicin in patients with chronic, non-healing DFUs. Methods: A retrospective observational audit was conducted, involving eleven patients with refractory DFUs who underwent adjunctive treatment with a PRF matrix (Arthrozheal®) and co-applied gentamicin. Patients were followed at three-week intervals using standardised wound imaging (Silhouette® 3D) to assess healing parameters. Long-term follow-up data, evaluating healing durability and complications, is presented. Results: All patients completed the treatment protocol, with significant reductions in mean wound area (87.9%), perimeter, depth, and volume (all p < 0.05). Epithelialised tissue increased from 24.7% to 82.8%. At 12 months, 81.8% of patients maintained complete ulcer healing. Two patients experienced complications: one ulcer recurrence requiring surgical debridement and one unrelated amputation due to osteomyelitis. Conclusions: The combination of autologous PRF matrix and gentamicin demonstrated promising results in promoting sustained healing of refractory DFUs with minimal complications. These findings support further investigation in larger, controlled studies to validate this biologic-antimicrobial approach as a safe, effective, and durable therapy for complex diabetic wounds.

BioMed doi: 10.3390/biomed6010004

Authors: Ali Fouad Yasser ElSherbini Elsayed Abdelhady Mohamed Abdraboh

Background/Objectives: Mesenchymal stem cells (MSCs) are deemed to be a highly safe model for autologous and allogeneic cellular therapy, owing to their inherent lack of HLA-DR expression, immunomodulatory properties, homing ability, and plasticity allowing differentiation into different cell types. The interest in activating autophagic signaling in MSCs has recently grown due to its significant potential in maintaining stemness, enhancing paracrine signaling, and providing therapeutic benefits for cancer and neurodegenerative diseases. This study aimed to explore the impact of autophagy induction on enhancing the therapeutic potential of MSCs by maintaining their plasticity and to assess different induction agents. Methods: In this study, MSCs were first extracted from the fat tissue of Sprague–Dawley (SD) rats and characterized phenotypically and molecularly by their positive expression of stemness markers CD29, CD106, and CD44, and their negative expression of hematopoietic surface markers CD14, CD34, and CD45, using a flow cytometry approach. Isolated MSCs were then treated separately with two FDA-approved autophagy inducers: Lithium Chloride and Trehalose, following assessment of autophagy activity. Results: Treated MSCs showed significant increases in autophagic activity at both the transcriptional and translational levels. The successful induction of autophagy in MSCs was confirmed through the elevated expression of autophagy-related genes such as ATG3, ATG13, ATG14, P62, and ULK1. These data were confirmed by the significant upregulation in LC3 protein expression and the formation of autophagosomes, which was detected using a transmission electron microscope. Furthermore, the expression of Oct4, Sox2, and Nanog genes was significantly enhanced after treatment with Trehalose and Lithium Chloride compared with untreated control MSCs which may indicate an upregulation of pluripotency. Meanwhile, Lithium Chloride and Trehalose did not significantly induce cellular apoptosis, indicated by the Bax/Bcl-2 expression ratio, and significantly decreased the expression of the antioxidant markers SOD and GPx. Conclusions: Treatment of MSCs with Trehalose and, in particular, Lithium Chloride significantly activated autophagic signaling, which showed a profound effect in enhancing cells’ pluripotency, reinforcing the usage of treated MSCs for autologous and/or allogenic cellular therapy. However, further in vivo studies for activating autophagy in cellular grafts should be conducted before their use in clinical trials.

BioMed doi: 10.3390/biomed6010003

Authors: Boon Chong Kwok Justin Xuan Li Lim John Kok Hong Wong

Background/Objectives: Pilates is a form of exercise that benefits people with bodily pain and movement limitations. The Clinical Pilates method assesses a patient through history taking and exercise testing to identify the patient’s problem side and directional preference. This study is a technical report of two case studies to evaluate the feasibility of the Clinical Pilates conceptual framework for the management of neck and shoulder musculoskeletal conditions. Methods: A conceptual framework on the use of the diagnostic bullseye for neck and shoulder movements are presented. To illustrate the application of the framework, two independent case studies with neck and shoulder pain were interpreted. These cases were assessed for upper and lower quadrant movement preferences using the Clinical Pilates method. Patient self-reported outcome measures included the pain numeric rating scale (/10), patient-specific functional scale (/10), and shoulder pain and disability index (%). Results: In both case studies, the clinical outcomes improved by more than 50% from the baseline. These improvements showed that the conceptualized framework is feasible for use among individuals with neck and musculoskeletal conditions. Conclusions: The neck and shoulder diagnostic bullseyes developed provide an extension from existing lower quadrant diagnostic bullseye. The feasibility of the Clinical Pilates method for neck and shoulder conditions was illustrated in the two case studies.

BioMed doi: 10.3390/biomed6010002

Authors: Di-Sheng Huang Tse-Hao Chen

A 57-year-old man presented with fever and progressive odynophagia three days after a suspected fish bone impaction. Laboratory tests revealed leukocytosis (17,400/µL) and an elevated C-reactive protein level (8.93 mg/dL). Initial chest radiography was unremarkable, ruling out pneumomediastinum. Contrast-enhanced computed tomography (CT) of the neck revealed focal thickening of the cervical esophageal wall, along with a low-attenuation collection and mild fat stranding surrounding the esophagus. Also, extraluminal air was absent. These findings supported the diagnosis of intramural abscess rather than free perforation. Upper endoscopy revealed a submucosal bulging lesion with a pinpoint mucosal defect that was actively draining pus, consistent with a contained intramural collection. Water-soluble contrast esophagogram confirmed smooth passage without extravasation, obstruction, or the double-lumen sign. The patient received bowel rest, intravenous piperacillin/tazobactam, and close observation. Symptoms and inflammatory markers improved, and follow-up CT confirmed the resolution of the intramural collection. Esophageal intramural abscesses develop when an infection spreads within the submucosa after a mucosal breach. In East Asia, this often occurs due to fish bone impaction. Early CT enables the differentiation of esophageal intramural abscess from perforation or dissection and guides the selection of conservative, rather than interventional, management.

BioMed doi: 10.3390/biomed6010001

Authors: John E. Madias

Takotsubo syndrome (TTS), popularly known as “broken heart syndrome”, is a type of reversible but not benign acute heart failure condition of unknown etiology, usually triggered by physical or emotional stress, affecting primarily elderly women. Recently a subtype of TTS, triggered by positive/pleasant emotions, has been identified (“happy heart syndrome”) with affected patients showing the same complications, including in-hospital and long-term mortality, as the patients afflicted with the “broken heart syndrome”. There is a need to increase the awareness of physicians, other medical providers, our patients, and the general public about the existence of “happy heart syndrome”.

BioMed doi: 10.3390/biomed5040029

Authors: Ana Rodriguez-Ventura Nayeli Zuñiga-Puente Luis F. Figueroa-Sanchez Jessica Guerrero Esveidy Sánchez Tanya Perez Fernanda Calzad Diana Peña

Background/Objectives: Bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) are the gold standard to measure fat mass, but they are unavailable in regular consultations. Relative Fat Mass (RFM) and Pediatric Relative Fat Mass (pRFM) equations are calculated using DXA images in adults and children, but they have not been correlated with BIA. Methods: A longitudinal prospective study was conducted with 531 children from a public school followed over one year; sex, age, weight, height, waist circumference and fat mass percentage were recorded. We calculated body mass index Z-score (Z-BMI), body mass index percentile (Pc BMI), waist-to-height ratio (WHtR), and RFM-pRFM to diagnose Overweight (Ow)/Obesity (Ob). We used descriptive statistics, Pearson’s correlation, sensitivity and specificity, 95% CI, and ROC curves; SPSS version 22 was used. Results: Adiposity was found in 34.5%, 33.2%, 21.5% and 43.5% of children using Z-BMI, Pc BMI, WHtR, and BIA, respectively; excluding children younger than 8 years old, the frequency of adiposity was 51.5% by RFM-pRFM. The highest correlation was between RFM-pRFM and BIA (0.84, p < 0.000). Of the total measurements of each visit considered as normal weight using Z-BMI, 21.5% had adiposity using BIA, and the proportion of girls underdiagnosed was twice that of boys. Conclusions: RFM-pRFM had the highest correlation with BIA but Z-BMI, Pc BMI, and WHtR are also helpful. It is important to consider that 21.5% of children with apparent normal weight present adiposity.

BioMed doi: 10.3390/biomed5040028

Authors: Manuel Andrada Alonso Nerea Mateo Guarch Matías Alfonso Olmos-García Conrado Saiz Modol Julio Doménech Fernández Rafael Llombart-Blanco

Central sensitization of pain (CSP) is defined as the “increased responsiveness of nociceptive neurons in the central nervous system (CNS) to normal or subthreshold afferent input” The primary objective of this study is to compare the prevalence of CSP between patients presenting with foot and ankle conditions and those presenting with low back pain. Materials and Methods: A cross-sectional study was conducted comparing a cohort of patients with a first consultation for foot and ankle disorders to another cohort with a first consultation for lumbar spine pain at the same institution. Demographic variables, pain duration, main diagnosis, and a series of questionnaires assessing pain and disability were collected. The Central Sensitization Inventory (CSI) was administered to determine the presence of CSP within the groups. Statistical analyses were performed using STATA. Results: A total of 195 patients presenting with foot/ankle conditions and 252 patients with low back pain were included. Among the foot/ankle cohort, 16.4% (95% CI, 10.92–21.9%) were classified as having CSP, compared to 22.2% (95% CI, 16.85–27.6%) in the lumbar pain cohort. The difference in CSP prevalence between groups was not statistically significant (difference 5.79%, Chi2 = 2.357, p = 0.125). However, the difference in mean scores on Part A of the CSI was statistically significant (31.82 ± 13.88 vs. 25.20 ± 14.31, z = 4.237, p < 0.001). Among foot/ankle pathologies, plantar fasciitis showed the highest prevalence of CSP (21.9%), followed by hallux valgus (18.8%). A significant association was observed between CSP and higher levels of pain and disability. Female patients demonstrated a higher prevalence of CSP. Conclusions: Patients with low back pain exhibited higher CSI scores and a greater prevalence of central sensitization compared with those with foot and ankle disorders. Recognizing these mechanisms may help clinicians tailor more effective, multidisciplinary treatment strategies.

BioMed doi: 10.3390/biomed5040027

Authors: Ashley Horne Amelia Payne Harry Crawford Clare Dempsey Hitesh Mistry Gareth Price Corinne Faivre-Finn

Introduction: Current treatments for patients with stage III non-small-cell lung cancer (NSCLC) are not sufficiently personalized, resulting in suboptimal outcomes and high mortality rates. The Developing Circulating and Imaging Biomarkers Towards Personalized Radiotherapy in Lung Cancer (VIGILANCE) study employs innovative health technologies to collect a range of clinical data and features. This includes longitudinal analyses of cell-free and circulating tumor DNA from blood samples and radiomic features extracted from standard-of-care imaging. Additionally, patient-reported outcome measures will be collected to capture patients’ symptoms and quality of life. This will provide invaluable insight into the patient experience during and after radiotherapy. We aim to evaluate whether the data, including patient-reported outcomes, can serve as biomarkers to refine treatment strategies, improve post-treatment follow-up and provide patients with realistic outcome predictions. Key endpoints include the following: (1) assessing whether baseline ctDNA status and its early on-treatment dynamics can identify patients with radioresistant disease who could benefit from treatment intensification; (2) determining whether post-radiotherapy ctDNA clearance can predict benefit from consolidation durvalumab, potentially sparing ctDNA-negative patients from unnecessary immunotherapy; and (3) developing integrated models combining novel ctDNA and radiomic biomarkers to distinguish between radiation fibrosis and tumor recurrence and to predict survival. We adopt a pragmatic approach by recruiting patients receiving standard-of-care treatments in a real-world setting. In addition, most of the clinical data is already routinely collected in our center, except for the blood tests for cell-free and circulating tumor DNA analysis. Methods and analysis: This is a single-center, prospective, exploratory, longitudinal, follow-up study, recruiting patients with stage III NSCLC undergoing standard-of-care curative-intent radiotherapy (with or without systemic therapy). Data collection spans from baseline to during radiotherapy and is extended up to 1 year following radiotherapy. The longitudinal analysis aims to describe and characterize dynamic changes in the collected features and assess their utility as prognostic and response biomarkers. Trial registration number: NCT06086574.

BioMed doi: 10.3390/biomed5040026

Authors: Robyn Okereke Anthony Linfante

Background and Clinical Significance: Primary Cutaneous Cribriform Apocrine Carcinoma (PCCAC) is a rare, inert low-grade cutaneous malignancy that is diagnosed on histopathologic assessment. PCCAC usually presents in middle-aged adults as a solitary, subcutaneous nodule on the extremities. Characterized by anastomosing tubules and solid/cribriform nests of atypical epithelial cells generating a sieve-like display, the tumor is a histopathological variant of apocrine metaplasia of the skin. PCCAC also follows characteristic staining patterns. It is important to distinguish PCCAC from other similar histological variants, which may hold more grievous indications. Case Presentation: A 47-year-old female presented with an enlarging, itchy growth of several months on her back. On physical exam, an indurated pink, nontender papule of 8 mm on the left lateral side wall was noted. Histopathology demonstrated a well-circumscribed, pandermal tumor composed of anastomosing solid and cribriform nests, tubules, and cords of mildly atypical, eosinophilic epithelial cells forming a glandular lumina. An immunohistochemical study revealed the tumoral epithelium to express CK7, CK5/6, BER-EP4, CD117 (C-kit), and S100. Positive EMA and CEA staining highlighted intratumoral glandular ductal differentiation and apocrine secretion. Immunohistochemical stains for CK20, GATA-3, and p63 were negative. Conclusions: We present this case to distinguish the histological attributes of PCCAC and help differentiate it from more concerning visceral metastatic malignancies. We follow with a narrative review of the histopathologic differential for PCCAC and feature reconciliation of corresponding staining patterns reported in the literature.

BioMed doi: 10.3390/biomed5040025

Authors: Nikhil Sathe Eugene Athan Arnab Kapat Cenk Suphioglu

Background/Objectives: Bacteriophages are considered promising alternatives for the treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa infections. Methods: Five bacteriophages with lytic activity against MDR P. aeruginosa were isolated from lake and sewage samples and characterized for their biological properties, host range, and efficacy in biofilm and in vitro infection models. Results: The phages displayed broad host ranges, producing zones of lysis in 40–53% of MDR isolates. The average burst size was 112 ± 70 PFU per cell. All phages, either individually or in combination, inhibited biofilm formation and were capable of disrupting preformed biofilms. While treatment with single phages led to bacterial regrowth, the cocktail of all five phages achieved complete bacterial lysis with no regrowth observed. In an in vitro wound and burn infection model, the phage cocktail significantly enhanced cell proliferation and promoted healing. Transmission electron microscopy (TEM) analysis identified phage PA2 as a Myovirus based on its morphology. Conclusions: The phage isolates demonstrated strong activity in multiple in vitro models, effectively targeting both planktonic and biofilm-associated P. aeruginosa. Notably, the five-phage combination prevented the emergence of bacterial resistance, supporting its potential as a biocontrol strategy against MDR P. aeruginosa.

BioMed doi: 10.3390/biomed5040024

Authors: Michelle Silva Szekut Tatiana Jung Ágatha Kniphoff da Cruz Laura Marina Ohlweiler Luiza Pedralli Rafaela Wickert Witz Fernanda Majolo Guilherme Liberato da Silva

Background and objectives: Clinical laboratory analyses are essential for diagnosing and treating allergic diseases mediated by immunoglobulin E (IgE). Identifying the sources of sensitivity, subject to regional variations, enables the implementation of effective management strategies, such as prevention and immunotherapy. Through a cross-sectional study, this study aimed to determine the sensitivity profile to aeroallergens (latent class) and their correlation with age, sex, and season in the population sampled. Methods: The purpose was to map the concentrations of specific IgE serum levels linked to the most prevalent allergens, considering variations related to age, specific IgE levels, and seasons of the year through a cross-sectional study. Results: The 995 reports of specific IgE tests analyzed were clustered into six aeroallergen categories and were predominantly composed of female individuals (57.1%). The most prevalent age group was younger than 18 (56.5%), and most exams were performed in the spring (27.7%). The aeroallergen category ‘grass’ significantly correlated with sex and age, indicating that men have a 65% greater probability of having high levels of specific IgE as a response to this allergen, and age is related to higher IgE levels. Latent class analysis identified an optimal three-class solution for specific IgE sensitization patterns: Class 1: Moderate Sensitization; Class 2: Low Sensitization; and Class 3: High Sensitization. Conclusion: The present study highlights the importance of knowing the local aeroallergen profile for early diagnosis and prevention of allergic diseases, emphasizing the relevance of the allergen category related to the age and sex of the individuals.

BioMed doi: 10.3390/biomed5040023

Authors: Yuen Keong Chua Jonas Rui Cheng Ang John Kok Hong Wong Boon Chong Kwok

Background/Objectives: Chronic ankle instability is a common issue after lateral ankle sprain. The DMA Clinical Pilates method hypothesizes impairments in tibialis anterior and fibularis longus muscles. Methods: A total of 14 adults with chronic ankle instability, and 15 recovered and 16 healthy individuals were prospectively recruited and assessed for lower back, hip, knee, and ankle muscle activities during dominant and non-dominant sides single-leg stand on stable and unstable surfaces using wireless surface electromyography. Results: The study found consistent dysfunction in tibialis anterior muscle activity in adults with chronic ankle instability when compared with healthy adults during single-leg stand on stable and unstable surfaces, and against recovered individuals on unstable surface. As compared to healthy controls, chronic ankle instability group showed higher vastus lateralis activation during dominant side single-leg stand across surface conditions and during dominant side single-leg stand, while the higher dominant side longissimus dorsi activity on stable surface changed to higher dominant side medial gastrocnemius activity on unstable surface. As compared to recovered controls, chronic ankle instability group also showed higher gluteus medius and fibularis longus muscle activities on unstable surface. Conclusions: Tibialis anterior muscle is the main dysfunction among individuals with chronic ankle instability side.

BioMed doi: 10.3390/biomed5040022

Authors: Constantinos Tsioutis Panagiotis Symvoulidis Marilena Solonos Haralambous Sakis Lambrianides Periklis Zavridis Paris Papakostas Aris P. Agouridis

Background/Objectives: Black hairy tongue syndrome (BHT) is characterized by structural epithelial changes and a dark discoloration on the surface of the tongue, causing a variety of symptoms such as xerostomia, altered taste, and nausea. Methods: Herein, we report a 70-year-old female patient with a history of Sjogren’s syndrome, rheumatoid arthritis, and occasional use of intranasal and inhaled corticosteroids, who presented with BHT exacerbated by consumption of colored beverages and carbohydrates. We also provide a review of the literature on published articles reporting cases of BHT syndrome. Results: Our patient’s condition improved after implementing dietary restrictions in combination with local care. A literature review revealed that the most common reported exposures and underlying conditions in patients with BHT were the recent administration of antibiotics, solid organ or hematologic malignancy, immunosuppressants, smoking, corticosteroids, autoimmune conditions, receipt of antidepressants, local radiation therapy, proton pump inhibitors, and alcohol. The majority of cases were successfully managed with the elimination of implicated factors when possible and local hygiene. Conclusions: Different factors may contribute to the development of BHT. Discontinuation of implicated medications together with measures for topical care constitute the most effective ways to achieve resolution.

BioMed doi: 10.3390/biomed5030021

Authors: Aganze Gloire-Aimé Mushebenge David Ditaba Mphuthi

Monkeypox (Mpox), a re-emerging zoonotic disease, has garnered global attention due to its evolving epidemiology, diverse clinical manifestations, and significant public health impact. The rapid international spread of the Mpox prompted the World Health Organization to designate the outbreak as a Public Health Emergency of International Concern. Accurate and timely diagnosis is hindered by its critical resemblance to other orthopoxviruses and viral exanthems, underscoring the need for improved diagnostic tools. Point-of-care diagnostic innovations, including CRISPR-based and smartphone-integrated technologies, have revolutionized outbreak management, offering rapid and accurate detection critical for containment and treatment. The effective control of Mpox outbreak underscores the necessity of strengthened global surveillance, equitable healthcare access, rapid diagnostics, the prompt isolation of infected individuals, and the implantation of ring vaccination strategies. The integration of a “One Health” framework that links human, animal, and environmental health is vital for sustained preparedness. Advances in vaccine development, including novel bionic self-adjuvating vaccines and platforms utilizing DNA, mRNA, and viral vectors, highlight promising prevention efforts. However, issues such as vaccine hesitancy, limited immunization coverage and accessibility in resource-constrained regions remain significant barriers. Therapeutic interventions like tecovirimat and the JYNNEOS vaccine demonstrate efficacy but face challenges in scalability and deployment. To address these multifaceted challenges, this review delves into the molecular insights, clinical features, epidemiological trends, and diagnostic challenges posed by Mpox. This review further highlights the critical need for robust scientific evidence and sustained research to inform effective, evidence-based responses, and long-term management strategies for Mpox outbreaks.

BioMed doi: 10.3390/biomed5030020

Authors: Mario Jerčić Maja Rogić Vidaković Anita Markotić Nikolina Režić Mužinić

Background: multiple sclerosis (MS) presentation varies depending on the location and severity of the lesions affecting different areas of the spinal cord and brain. Extensive research has focused on specific systems to detect the disease in its various stages. The objective of this study was to investigate the concentration of the soluble scavenger receptor for haptoglobin–haemoglobin complex (Hb-Hp), sCD163, which is mostly expressed by monocytes and protects tissues from oxidative damage, in patients with MS. Methods: enzyme-Linked Immunosorbent Assay (ELISA) analysis was conducted in plasma samples collected from twenty-three relapsing–remitting MS (RRMS) subjects treated with teriflunomide and ten healthy control subjects (HCs). Results: the study results showed no differences between RRMS subjects and HCs in the concentration of CD163. A significantly higher concentration of sCD163 in RRMS was found in men in comparison to women (p = 0.038, Cohen d = 0.97). Conclusions: a significant correlation between disease activity, estimated using plasma-soluble CD163 (sCD163) and clinical assessment of the Expanded Disability Status Scale (EDSS) (p = 0.021), was detected in female patients with RRMS.

BioMed doi: 10.3390/biomed5030019

Authors: Jeremy Seymour

Background/Objectives—The personalisation agenda—matching the correct psychological therapy to diverse and comorbid mental disorders—is an unanswered dilemma in the worldwide literature which has far reaching consequences for public health. This hypothesis article addresses the question: can a biomedical approach resolve the personalisation agenda? Methods—Narrative review drawing on clinical psychology, translational psychiatry, and biomedical science literature. Results—Diverse attempts to resolve the personalisation agenda have not yet succeeded. Randomised controlled trials are uniquely biased due to unwanted placebo effects; network meta-analysis cannot address adequately which psychological therapy to use; new methodologies have not yet produced data; and neuroscientific analysis cannot yet explain how trauma-based therapies work. However, a biomedical model which divides psychological therapy into low, medium and high intensity interventions can resolve the personalisation agenda. Conclusions—Combining low intensity (placebo), with medium intensity (cognitive behavioural techniques) and high intensity interventions (trauma-based therapies) are theoretically synergistic if combined with psychosocial treatments/exercise, and used in sequence in the correct order. A biomedical model based on recent advances in placebo studies and neuroplasticity can resolve the personalisation agenda, and improve outcomes for mental disorder.

BioMed doi: 10.3390/biomed5030018

Authors: Lily S. Ardiani Sharita R. Siregar Iwan Soebijantoro

Background: The incidence of chemical ocular trauma after accidentally instilling the “wrong” eyedrops is still frequent, but cases resulting from stamper ink refills are rare. Case Presentation: A 73-year-old man presented to our emergency department with a history of inadvertently instilling stamper ink refill into both eyes (BEs) instead of artificial tears. Immediate irrigation and evaluation were performed. The initial visual acuity (VA) was 0.4 in the right eye (RE) and 0.8 in the left eye (LE). Slit lamp examination showed edema palpebra with periocular blue staining in BEs, chemotic conjunctiva with a much darker color in the RE than the LE, and epithelial defects with a positive fluorescein test in BEs. A diagnosis of bilateral corneal abrasion and chemotic conjunctiva was established. Ten hours after the emergency visit, RE VA decreased to 0.2, and corneal edema was found during the follow-up examination. Medications including levofloxacin antibiotic, sodium hyaluronate, sodium chloride, combined polymyxin sulfate–neomycin sulfate and dexamethasone eyedrops, mefenamic acid, and ascorbic acid tablets were prescribed. The RE corneal edema still occurred, and the endothelial cell count was 1952 and 987 cells/mm2 in the RE and LE at the one-week follow-up. After three weeks, corneal edema had fully resolved, and the VA was 0.4 and 0.8 in the RE and LE, respectively. Conclusions: This case report adds to the spectrum of the continuing problem of chemical ocular trauma after mistakenly instilling the eyedrops. Promoting and changing to different packages for non-ophthalmic products in plastic bottles mimicking eyedroppers is essential to minimize these injuries.

BioMed doi: 10.3390/biomed5030017

Authors: Sariah Watchalotone Nicholas J. Smith Mehar A. Singh Imtiaz Ahmed

Diverticulosis is characterized by sac-like bulges of the mucosa through weakened portions of the intestinal wall, and is a common pathology observed in adult patient populations. The majority of diverticular disease and associated complications, such as inflammation of diverticula, form within the colon, with less frequent cases of diverticular disease observed in the small bowel. We present the case of a 48-year-old female who presented to the emergency department with a two-day history of abdominal pain, fever, and nausea. Upon admission, vital signs indicated fever and laboratory analysis demonstrated elevated white blood cell count. The patient’s workup included a computed tomography (CT) scan of the abdomen which revealed diffuse small bowel diverticulitis with surrounding inflammation, lymph node enlargement, and bowel wall thickening. CT scan of the abdomen with evidence of diverticula in the bowel wall is diagnostic of diverticulosis. Treatment could include bowel rest, clear liquid diet, broad-spectrum antibiotics, or surgical intervention. This case emphasizes the importance of CT imaging and consideration of broad differential diagnosis in patients presenting with abdominal pain due to the rare presentation of small bowel diverticulitis and aims to contribute to the current understanding and treatment of clinically significant diverticular pathologies.

BioMed doi: 10.3390/biomed5030016

Authors: Shanti M. Pinto Nahir A. Habet Tamar C. Roomian Kathryn M. Williams Marc Duemmler Kelly A. Werts Stephen H. Sims Mark A. Newman

Objective: The primary objective was to identify whether there were differences in performance for the individual subcomponents of the instrumented timed “Up and Go” (iTUG) between adults with traumatic brain injury (TBI) and healthy controls. Methods: Fifteen adults with moderate-to-severe TBI and fifteen age- and sex-matched controls completed two separate trials of the iTUG. Paired t-tests or Wilcoxon signed rank tests were used to determine the differences between groups. Results: Adults with moderate-to-severe TBI took more time to complete the iTUG (14.50 ± 2.36 s vs. 9.85 ± 1.71 s; p-value = 0.0002), had slower chest flexion angular velocities (63.52 ± 23.25 s vs. 88.19 ± 29.20 s; p-value = 0.0486) and vertical acceleration (2.22 [1.23–2.74] s vs. 3.89 [3.36–5.02] s; p-value = 0.0005) during the sit-to-stand movements, and had slower angular velocities during the turns (p-value < 0.05 for both mean and peak turn angular velocities) compared with the controls. Conclusions: Adults with moderate-to-severe TBI completed the iTUG more slowly than healthy controls. Significant differences were noted in the sit-to-stand and turn subcomponents for adults with moderate-to-severe TBI compared with healthy controls, which would not be apparent from evaluating the total time taken alone.

BioMed doi: 10.3390/biomed5030015

Authors: Joseph A. Aweeya Lord J. J. Gowans Engelbert A. Nonterah Victor Asoala Patrick Ansah Michele Ramsay Godfred Agongo

Background/Objectives: Cardiovascular diseases are a global health issue with an increasing burden and are exacerbated by hypertension. High blood pressure is partly attributed to genetic variants that are generally not well understood or extensively studied in sub-Saharan African populations. Variants linked to blood pressure have been found through genome-wide association studies (GWASs), which were mostly conducted among European ancestry populations; however, limited research has been undertaken in Africa. The current study evaluated single-nucleotide polymorphisms (SNPs) of PCSK9, ABCA1, LPL, and PON1 in relation to blood pressure measurements of 1839 Ghanaian adults. Methods: Genotypes were extracted from data generated by the H3Africa SNP array. After adjusting for sex, age, smoking, and body mass index (BMI), inferential statistics were used to investigate the relationships between SNPs and blood pressure (BP) indices. Additionally, Bonferroni correction was used to adjust for multiple testing. Results: Diastolic blood pressure (DBP) and the minor allele T of the PCSK9 variant (rs17111557) were positively associated at p = 0.006 after covariate adjustments. Although this novel DBP-associated variant is located in the 3′ untranslated region (3′ UTR) of the PCSK9 gene, in silico functional prediction suggests it is an expression quantitative trait locus (eQTL) that may change the binding site of transcription factors, potentially altering the rate of transcription and impacting DBP in this Ghanaian population. Conclusions: Our findings highlight the role of genetics in hypertension risk and the potential of discovering new therapies targeting isolated diastolic blood pressure in this rural African population.

BioMed doi: 10.3390/biomed5020014

Authors: Emily Lundstrum Haylee Hudson Parth Patel Caitlyn Busch Channelle Gordon Anastasia Kerr-German

Background/Objectives: This study investigates sex differences in the neural profiles of children with and without ADHD using functional near-infrared spectroscopy (fNIRS). Specifically, it explores the functional connectivity patterns in female and male children, considering both group membership and symptom severity scores. Methods: Participants aged 6–8 (N = 52) years performed a Passive Viewing Paradigm resting-state task while fNIRS was used to measure resting-state functional connectivity. ADHD diagnoses and subtypes were determined using the K-SADS interview, from which a continuous symptom severity score was calculated across both group and subtype. Results: The results revealed that female children with combined-type ADHD exhibited distinct neural profiles compared to male children, both overall and according to symptom severity. Male children with ADHD, across all subtypes, demonstrated less refined functional connectivity, with male children in the combined-type group showing particularly weak connectivity. Additionally, connectivity patterns varied with symptom severity: in male children, connectivity increased as symptom severity increased, while in female children, the opposite trend was observed, with connectivity decreasing as symptom severity rose. These patterns contrasted with those observed in typically developing peers. Conclusions: This study highlights significant sex differences in neural connectivity profiles in children with ADHD. Male children tend to show less refined connectivity, particularly in the combined-type subtype, whereas female children exhibit an inverse relationship between connectivity and symptom severity. These findings provide important insights into the neural mechanisms underlying ADHD and suggest that sex may play a crucial role in the neural presentation of the disorder.

BioMed doi: 10.3390/biomed5020013

Authors: Kory S. London Philip Durney TaReva Warrick-Stone Karen Alexander Jennifer L. Kahoud

Background/Objectives: Philadelphia has experienced a surge in illicit fentanyl adulterated with alpha-2 agonist sedatives. Initially, xylazine (“tranq”) was the predominant adulterant, and a novel multimodal withdrawal protocol was effective at mitigating symptoms. However, since mid-2024, medetomidine—a more potent sedative—has largely supplanted xylazine. Clinicians have reported more severe, treatment-resistant opioid withdrawal during this transition. To assess whether a previously effective withdrawal management protocol retained efficacy after the emergence of medetomidine as the primary fentanyl adulterant in a community. Methods: We conducted a retrospective cohort study of patients receiving protocol-based opioid withdrawal treatment at two emergency departments in Philadelphia between September 2022 and April 2025. Patients were divided into the xylazine era (September 2022–July 2024) and medetomidine era (August 2024–April 2025). The primary outcome was a change in Clinical Opioid Withdrawal Scale (COWS) score from pre- to post-treatment. Secondary outcomes included rates of discharge against medical advice (AMA) and ICU admission, as well as the impact of a revised treatment protocol. Results: Among 1269 encounters with full data, 616 occurred during the xylazine era and 770 during the medetomidine era. Median COWS reduction was greater in the xylazine group (−9.0 vs. −4.0 points, p < 0.001), with more patients achieving symptom relief (COWS ≤ 4: 65.6% vs. 14.2%, p < 0.001). ICU admission occurred in 8.5% of xylazine era patients and 16.8% of medetomidine era patients (p < 0.001). Rates of AMA were higher during the medetomidine era as well (6.5% vs. 3.6%) (p = 0.038). Revision of treatment protocols showed promise. Conclusions: The protocol was significantly less effective during the medetomidine era, though a protocol change may be helping. Findings highlight the need to adapt withdrawal treatment protocols in response to changes in the illicit drug supply.

BioMed doi: 10.3390/biomed5020012

Authors: Miguel B. Royo-Salvador Marco V. Fiallos-Rivera Horia C. Salca

Background: Patients with Ehlers–Danlos Syndrome (EDS) and craniocervical instability are treated with extensive craniocervical fixation. A new argument and treatment are proposed related to filum terminale collagen dysfunction: the Neuro-Cranio-vertebral syndrome theory (NCVS). Objectives: To analyse clinical manifestation and imaging features of NCVS patients associated with EDS compared with 373 NCVS-affected controls, to propose an aetiopathogenic mechanism for NCVS in EDS patients, and to analyse and assess postoperative changes in NCVS patients with EDS after sectioning of the filum terminale. Methods: We conducted a retrospective study and selected ten patients diagnosed with EDS and NCVS. We present the images, signs, and symptoms in these cases, compared to those of 373 patients with NCVS alone. In addition, we report postsurgical findings in four EDS–NCVS patients after sectioning of the filum terminale. Results: Patients with EDS and NCVS had more cranial and vertebral symptoms. There were also significant differences in the neurological signs present in EDS–NCVS compared to those in NCVS alone. Patients who underwent sectioning of the filum terminale showed a significant improvement in signs and symptoms. Conclusions: The concept of craniocervical instability due to EDS does not explain a large number of neurological signs and symptoms, which seem to fit better in our new NCVS theory. Surgical treatment would only involve sectioning the filum terminale, while cervical fusion would never be justified in such patients.

BioMed doi: 10.3390/biomed5020011

Authors: Ken Meng Tai Justin Mooteeram Sara Metaoy Anand Pillai

Background: Diabetic foot osteomyelitis is a complex condition to manage, with substantial risk of treatment failure, which could necessitate major amputations. Surgical debridement and prolonged systemic antibiotic therapy have been the mainstay of treatment, but recurrence rates remain high. The use of adjuvant local antibiotic therapy has been proposed as a potential adjunct to improve outcomes. Methods: This retrospective study involved 113 patients with diabetic foot osteomyelitis, who underwent debridement and application of antibiotic-loaded hydroxyapatite ceramic from the year 2018 to 2023. Clinical outcomes of interest were eradication of infection, ulcer healing, recurrence of infection, prevention of major amputation and mortality rate. Patient-associated factors were identified and analysed. Results: Eradication of infection was achieved in 96%, healing of ulcer in 93% and limb salvage in 95% of patients. The mortality rate at 1 year was 5.4%. Peripheral arterial disease, HbA1c and CRP levels were statistically significant in affecting treatment outcomes. Other factors had no impact on the treatment success. Conclusions: This is the largest single-centre study involving Cerament G and V in the management of diabetic foot osteomyelitis and the first investigating the specific factors associated with outcome goals. The use of these antibiotic-loaded carriers demonstrated excellent eradication of infection, healing of ulcer and limb salvage and prevention of recurrence of infection.

BioMed doi: 10.3390/biomed5020010

Authors: Duc My Vo Anees Abrol Zening Fu Vince D. Calhoun

Background: In functional magnetic resonance imaging (fMRI), functional network connectivity (FNC) captures temporal coupling among intrinsic connectivity networks (ICNs). Traditional FNC analyses often rely on linear models, which may overlook complex nonlinear interactions. We propose a multi-layered neural network that generates nonlinear heatmaps from FNC matrices, which we visualize at multiple layers, enabling us to better characterize multi-level interactions and improve interpretability. Methods: Our approach consists of two training stages. In the first, a deep convolutional neural network (DCNN) is trained to produce heatmaps from multiple convolution layers. In the second, a t-test-based feature selection identifies relevant heatmaps that help distinguish different groups. In addition, we introduce ‘source-based features’ which summarize the multi-layer model output using an independent component analysis-based procedure that provides valuable, interpretable insights into the specific layer outputs. We tested this approach on a large dataset of schizophrenia patients and healthy controls, split into training and validation sets. Furthermore, this method clarifies how underlying neural mechanisms differ between schizophrenia patients and healthy controls, revealing crucial patterns in the default mode and visual networks. Results: The results indicate increased default mode network connectivity with itself and cognitive control regions in patients, while controls showed stronger visual and sensorimotor connectivity. Our DCNN approach achieved 92.8% cross-validated classification accuracy, outperforming competing methods. We also separated individuals into three cognitive performance groups based on cognitive scores and showed that the model can accurately predict the cognitive level using the FNC data. Conclusion: Our novel approach demonstrates the advantage of employing more sophisticated models in characterizing complex brain connectivity patterns while enhancing the interpretability of results. These findings underscore the significance of modeling nonlinear dynamics in fMRI analysis, shedding new light on the intricate interplays underlying cognitive and psychiatric phenomena.

BioMed doi: 10.3390/biomed5020009

Authors: Edoardo Ugolini Giorgio La Civita Moad Al Aidroos Samuele Salti Giuseppe Lisanti Emanuele Ghedini Gianluca Faggioli Mauro Gargiulo Giovanni Rossi

Background: Accurate prognoses are challenging in high-risk vascular conditions, such as abdominal aortic aneurysms, and limited diagnostic standards, decision-making criteria, and data semantics often hinder clinical reliability and impede diagnostics’ digital transition. This study aims to evaluate the performance, robustness, and usability of an automatic, replicable pipeline for aortic lumen surface reconstruction for pathological vessels. The goal is to provide a solid tool for geometric reconstruction to a more complex enhanced diagnostic framework. Methods: A U-Net convolutional neural network is trained using preoperative CTA scans, with 101 for model training and 14 for model testing, covering a wide anatomical and aortoiliac pathology spectrum. Validation included segmentation metric, robustness, reliability, and usability assessments. Performances are investigated by means of the test set’s prediction metrics for several instances of the model’s input. Clinical reliability is evaluated based on manual measurements performed by a vascular surgeon on the obtained 3D aortic lumen surfaces. Results: The test set is selected to cover a wide portion of aortoiliac pathologies. The algorithm demonstrated robustness with an average F1-score of 0.850 ± 0.120 and an intersection over union score of 0.760 ± 0.150 in the test set. Clinical reliability is assessed using the mean absolute errors for diameter and length measurements, respectively, of 1.73 mm and 2.27 mm. The 3D surface reconstruction demonstrated reliability, low processing times, and clinically valid reconstructions. Conclusions: The proposed algorithm can correctly reconstruct pathological vessels. Secondary aortoiliac pathologies are detected properly for challenging anatomies. To conclude, the proposed 3D reconstruction application to a digital, patient-specific diagnostic tool is, therefore, possible. Automatic replicable pipelines ensured the usability of the model’s outputs.

BioMed doi: 10.3390/biomed5010008

Authors: Julia Inglot Joanna Katarzyna Strzelczyk Dorota Bartusik-Aebisher David Aebisher

Background/Objectives: Thyroid cancer is the most common cancer of the endocrine system worldwide. Despite many available therapeutic options, the mortality rate of some subtypes, including anaplastic thyroid cancer, is still significant. Photodynamic therapy brings hope, which, through local activation of cell death pathways, as well as its effect on the immune system and vessels feeding the tumor, brings effects incomparable to classical methods. Photosensitizers particularly used in the case of thyroid cancer are hypericin, porphyrin, photophrin, radachlorin, or 5-aminolevulinic acid. Even better effects are achieved by administering sulforaphene, carboplatin, or genistein before therapy. Methods: For this research, we review articles in regard to provide a critical summary of the existing literature on thyroid cancer to explain the current state of scientific evidence on this topic. Conclusions: Photodynamic therapy is undoubtedly a technique of the future; the main advantages of which are low invasiveness, the possibility of combining with other treatment methods, or the possibility of outpatient use.

BioMed doi: 10.3390/biomed5010007

Authors: Philipp Dörschmann Justine Wilke Nina Tietze Johann Roider Alexa Klettner

Background: Age-related macular degeneration (AMD) is the leading cause of severe vision loss in industrialized nations. AMD models based on standardized optimized cell culture models are warranted. The aim of this study is to implement a standard operation protocol for the preparation of porcine retinal pigment epithelium (RPE) from pig eyes with cells from one eye designated for one culture, generating a genetic homology within one culture and genetic heterogeneity between cultures, thereby implementing a relevant in vitro model for AMD investigations. In addition, the use of pigs’ eyes from slaughterhouse waste material is an active measure to reduce animal experimentation in ophthalmological research. Methods: Primary porcine RPE cells were prepared, and cells from one eye were seeded into one well of a twelve-well polystyrene plate. They were cultured for 7, 14, and 28 days. Different post-mortem times (2, 4, and 6 h), coatings (collagen I, IV, Poly-d-Lysine, fibronectin, and laminin), and serum content of media (1%, 5%, and 10%) were tested. The success rate for confluence and survival was determined. At the different time points, cell number (trypan blue exclusion assay), confluence and morphology (microscope imaging), VEGF content of supernatants, and gene and protein expression, as well as tight junctions (fluorescence imaging), were examined. In addition, a baseline for RPE morphometry using CellProfiler software was established. Results: A post-mortem time of 4 to 5 h is most suitable. A coating with Poly-d-Lysine is recommended due to high success rates, the fastest confluence, the highest expression of RPE65, and suitable morphologic properties. The results for confluence, protein expression, and morphology showed that a reduction of 10% to 5% FBS is acceptable. Conclusion: A basic best practice protocol for the preparation of porcine single-eye cultures with optimized parameters was established and is provided.

BioMed doi: 10.3390/biomed5010006

Authors: Chris Mohrmann Kai M. Fiedler Axel Heep Christiane E. Beck Matthias Lange

Background: Although “found down” trauma patients are not subject to any general definition in Germany, the term describes a recurrent clinical picture in the care of adult patients, especially in pre-hospital emergency settings. It is characterized by immobilization-related morbidity due to rhabdomyolysis and electrolyte disturbance-related severe arrhythmias. The aim of this work is to identify cases of pediatric “found down” patients treated at our institution and to define diagnostic and therapeutic measures. Methods: In a retrospective, monocentric observational study, the hospital information system was searched for “found down”-associated diagnoses on admission to the pediatric intensive care unit (PICU) of the University of Oldenburg for the period 1 January 2011 to 31 December 2022. After viewing 17 patient records, an interdisciplinary consensus concerning the clinical picture of “found down” was identified in five patients, and these patients were analyzed. Results: The mean age of patients was 8.73 (0.17–17.35) years, and patients were at the PICU for an average of 18.2 (14–24) days. Prolonged immobilization (n = 1), acute trauma (n = 2), and acute (n = 1) and chronic (n = 1) neurometabolic disorders were identified as triggers. The survival rate was 100%. Numerous associated disease symptoms, such as central nervous deficits, were detected. Conclusions: There are various causes for the pediatric clinical picture of “found down” trauma patients. However, pediatric “found down” trauma describes a complex, life-threatening disease affecting multiple organ systems. The diversity of the underlying causes of the diseases represents a challenge for adequate management. The acronym “STAND UP 4C” aims to provide guidance for the diagnosis and therapy.

BioMed doi: 10.3390/biomed5010005

Authors: Sheila Galbreath Tarun Goswami

Introduction: Women wear exterior breast support for most of the day. A female’s breast tissue and skin affect the comfort of the ADLs, exercise, health, and work environments. Understanding the breast tissue’s normal anatomy and mechanical and material properties is related to a woman’s daily health and quality of life outcomes. Considering the importance and impact of female breasts throughout one’s lifespan, additional research is needed to address the research gaps to provide solutions to improve daily lives and clinical interventions. Breast stability and behavior are dependent on its internal mechanical properties and applied external forces. Objective: To evaluate the current knowledge and research gaps on the adult female breast tissue’s anatomy, the factors that impact its growth and development, variations among racial populations, the internal and external mechanical properties of the tissue, and the factors employed to evaluate the pathology risk. Review sections: The review sections are as follows: 3. Anatomy of Breast, 4. Effects of Age and Stages of Breast Development, 5. Breast Skin, and 6. Breast Tissue Mechanics. Conclusions: Numerous research gaps have been identified within the field of female breasts.

BioMed doi: 10.3390/biomed5010004

Authors: Leah Mitra Bourgan Lindsay Michelle Wong Prithvi Setty Adan Junaid Shahnawaz Karim Forshing Lui

Background: Cocaine has been shown to cause cytotoxic neuronal damage, which has been implicated in cases of leukoencephalopathy. We present a case of cocaine-induced toxic encephalopathy resulting in predominant lesions to the gray matter on magnetic resonance imaging (MRI). Case Presentation: A 70-year-old female presented acutely with confusion, agitation, and disorientation. She was markedly hypertensive with other vital signs within normal range. On presentation to the emergency department, she was uncooperative and had an unsteady gait but showed no focal neurological deficits. Her lab work was positive for elevated cardiac troponins, elevated D-dimer, and a urine drug screen positive only for cocaine. Head computed tomography (CT) showed no hemorrhage and head CT angiogram showed no abnormalities and no significant vascular stenosis. Chest X-ray and CT showed diffuse ground glass opacities compatible with atypical pneumonia. Antibiotics were initiated to treat the pneumonia and antihypertensives were administered to manage her blood pressure. She was also given IV thiamine. Brain MRI showed restricted diffusion involving bilateral hippocampi, thalami, putamen, caudate, and right occipital lobe, findings suspicious for cytotoxic edema. After acute stabilization, the patient demonstrated profound anterograde and retrograde amnesia, which improved gradually over days to weeks. She was eventually discharged to a skilled nursing facility. Conclusion: To our knowledge, this is the first reported case of profound amnesia secondary to cocaine-induced toxic encephalopathy with bilateral hippocampal involvement. These symptoms correlate with the implicated neuroanatomical structures. This case demonstrates that cocaine may be implicated in toxic encephalopathy affecting the brain’s gray matter and highlights a unique presentation of these findings.

BioMed doi: 10.3390/biomed5010003

Authors: Karla Aketzalli Hernández-Contreras Fausto Rojas-Durán María Elena Hernández-Aguilar Deissy Herrera-Covarrubias Marycarmen Godinez-Victoria Jorge Manzo-Denes César Antonio Pérez-Estudillo Fernando Rafael Ramos-Morales Rebeca Toledo-Cárdenas Gonzalo Emiliano Aranda-Abreu

Background: Alzheimer’s disease (AD), the leading cause of dementia worldwide, poses an increasing global health burden, yet its pathogenesis remains poorly understood. Diabetes mellitus (DM), characterized by chronic hyperglycemia, has been identified as a significant risk factor for AD development, suggesting a potential metabolic and molecular link between these diseases. Methods: This study examines the impact of sustained high glucose levels on astrocyte-like C6 glial cells, focusing on key cellular processes associated with AD. We evaluated mitochondrial function, oxidative stress, glucose uptake, and the expression of hallmark AD proteins, including β-amyloid and hyperphosphorylated tau. Results: Our findings demonstrate that high glucose exposure triggers mitochondrial hyperactivity, oxidative stress, and increased Tau phosphorylation, though β-amyloid levels were unaffected within the experimental timeframe. Conclusions: These results shed light on the early cellular dysfunctions contributing to the DM-AD connection, providing valuable insights into the metabolic pathways involved and identifying potential therapeutic targets to mitigate AD progression in individuals with DM.

BioMed doi: 10.3390/biomed5010002

Authors: Chen-Hao Liao Tse-Hao Chen

Spinal infections involving gas-forming pathogens are exceedingly rare, particularly in the cervical spine. We report the case of a 63-year-old male with a history of hypopharyngeal cancer who presented with neck pain and right upper limb weakness. Imaging studies revealed cervical epidural air bubbles and spinal cord edema at C1–C3. Laboratory findings were indicative of infection, and Streptococcus was identified through blood cultures. Urgent surgical decompression via laminectomy was performed, followed by antibiotic treatment. This case highlights the critical role of multimodal imaging, including computed tomography (CT) and magnetic resonance imaging (MRI), in diagnosing spinal infections, especially when conventional radiographs are inconclusive. CT scans identified gas inclusions and soft tissue changes, while MRI provided superior visualization of spinal edema and complications such as medullary compression. Management requires a multidisciplinary approach combining timely surgical intervention with prolonged antibiotic regimens.

BioMed doi: 10.3390/biomed5010001

Authors: Jude Eteneneng Enoh Roland Tiagha Akah Benedicta Nkeh-Chungag

Background: Cardiometabolic risk factors such as hypertension, overweight, and obesity have become increasingly common among African students who tend to become more sedentary in urban environments. This systematic review aimed to determine and identify major risk factors of cardiometabolic disease prevalence reported among African university students. Methods: The protocol was registered with PROSPERO (registration no.CRD42024553280). A comprehensive literature search was performed using scientific databases from Google Scholar, PubMed, Web of Science, Scopus, ProQuest, and African Journals Online (AJOL). The search was limited to articles published between 2000 and 2024, which reported cardiometabolic diseases/risk factors among African university students. Data were extracted using a standardised form, capturing details on study characteristics (author, year, location, study design), participant demographics (age, sex), prevalence of cardiometabolic diseases, and associated risk factors. Results: A total of thirty-seven studies that met the inclusion criteria, thirty-six cross-sectional and one longitudinal, were included in the study. The prevalence range of the various risk factors identified was 0.6–21.7% (obesity) and 0.28–26.4% (hypertension), 1.7–18.8% (diabetes), 0.5–18.2% (pre-diabetes), 1.9–48.6% (metabolic syndrome), and 1.1% to 57.3% (dyslipidemia). Some common sedentary lifestyles and unhealthy behaviours identified among the students were fast foods (21.3–85.73%), alcohol (3.7–63%), and smoking (1.02–13%). Conclusions: The review’s findings suggest that rapid urbanisation and changes in lifestyle and behaviours are responsible for an increased prevalence of cardiometabolic risk factors in African university students. Targeted health promotion programmes, regular screening, and policy interventions might all go a long way in preventing the predicted increase in the prevalence of cardiovascular and metabolic diseases among this group of young adults in Africa.

BioMed doi: 10.3390/biomed4040041

Authors: Sayantan Ghosh Domokos Máthé Purushothaman Bhuvana Harishita Pramod Sankarapillai Anand Mohan Raghavan Bhuvanakantham Balázs Gulyás Parasuraman Padmanabhan

There have been multiple technological advancements that promise to gradually enable devices to measure and record signals with high resolution and accuracy in the domain of brain–computer interfaces (BCIs). Multimodal BCIs have been able to gain significant traction given their potential to enhance signal processing by integrating different recording modalities. In this review, we explore the integration of multiple neuroimaging and neurophysiological modalities, including electroencephalography (EEG), magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), electrocorticography (ECoG), and single-unit activity (SUA). This multimodal approach leverages the high temporal resolution of EEG and MEG with the spatial precision of fMRI, the invasive yet precise nature of ECoG, and the single-neuron specificity provided by SUA. The paper highlights the advantages of integrating multiple modalities, such as increased accuracy and reliability, and discusses the challenges and limitations of multimodal integration. Furthermore, we explain the data acquisition approaches for each of these modalities. We also demonstrate various software programs that help in extracting, cleaning, and refining the data. We conclude this paper with a discussion on the available literature, highlighting recent advances, challenges, and future directions for each of these modalities.

BioMed doi: 10.3390/biomed4040040

Authors: Neev Shah Rif S. El-Mallakh Philip May

Background: Obesity is a common problem in adults with intellectual disability, but to our knowledge, there are no reports which address the problem of “sarcopenic obesity” in younger adults with intellectual disability. Methods: We performed an analysis of the body composition of 93 men and women with intellectual disability, and 70 matched men and women without intellectual disability, aged between 20 and 50 years. Results: Truncal Fat Index (TFI) was significantly higher in these younger adults with intellectual disability when compared to same-age individuals without intellectual disability, for both men and women. Additionally, using Skeletal Muscle Index (SMI), we found significant negative effects of truncal fat on skeletal muscle mass. These effects were much greater for those with intellectual disability, and especially for women with intellectual disability. Conclusions: This report underscores the importance of evaluation of skeletal muscle mass in all individuals with obesity, but this need appears to be greater for those with intellectual disability, especially women.

BioMed doi: 10.3390/biomed4040039

Authors: Jose Castillo Michael Le Christopher Pivetti Jordan Jackson Edwin Kulubya Zachary Paxton Camille Reed Khadija Soufi Arash Ghaffari-Rafi Allan Martin Richard Price Kee Kim Diana Farmer Aijun Wang Rachel Russo

Background: Cervical spinal cord injuries (SCIs) are the most common type of human SCI. Although various animal SCI contusion models have been developed to mirror human pathology, few have described cervical-level injuries. This study aims to validate and establish optimal impact parameters to produce consistent incomplete cervical SCIs for testing novel therapies. Methods: Using a precise impactor, 3 cervical spinal cord hemi-contusions of varying severities were induced by modifying penetration depths and controlling dwell times. Penetration depths of 2.11 mm (n = 4), 2.24 mm (n = 4), and 2.36 mm (n = 3) were used with a dwell time of 0.05 s to create mild, moderate, and severe injuries. Behavioral assessments in weeks 1, 2, 5, and 8 included grooming test, forelimb asymmetry test, and the Irvine, Beatties, and Bresnahan forelimb scale (IBB). After 8 weeks, rats were euthanized, and spinal cord histology was performed. Results: Within each group, animals exhibited consistent motor deficits and functional recovery. Mean IBB scores varied significantly between each group at week 8 (p < 0.0001). Ipsilateral forelimb usage significantly improved throughout the study period in the mild (2.11 mm) and moderate (2.24 mm) groups, while the severely (2.36 mm) injured group continued to exhibit 100% asymmetrical forelimb usage. Conclusions: This study demonstrates that a precise impactor can create reproducible models of incomplete cervical SCIs. A penetration depth of 2.24 mm resulted in moderate injury with significant motor deficits that slowly improved over time, permitting future therapeutic studies in functional recovery.

BioMed doi: 10.3390/biomed4040038

Authors: Nazanin Tataei Sarshar Soroush Sadeghi Mohammadreza Kamsari Mahrokh Avazpour Saeid Jafarzadeh Ghoushchi Ramin Ranjbarzadeh

Background/Objectives: The accurate categorization of brain MRI images into tumor and non-tumor categories is essential for a prompt and effective diagnosis. This paper presents a novel methodology utilizing advanced Convolutional Neural Network (CNN) designs to tackle the complexity and unpredictability present in brain MRI data. Methods: The methodology commences with an extensive preparation phase that includes image resizing, grayscale conversion, Gaussian blurring, and the delineation of the brain region for preparing the MRI images for analysis. The Multi-verse Optimizer (MVO) is utilized to optimize data augmentation parameters and refine the configuration of trainable layers in VGG16 and ResNet50. The model’s generalization capabilities are significantly improved by the MVO’s ability to effectively balance computational cost and performance. Results: The amalgamation of VGG16 and ResNet50, further refined by the MVO, exhibits substantial enhancements in classification metrics. The MVO-optimized hybrid model demonstrates enhanced performance, exhibiting a well-calibrated balance between precision and recall, rendering it exceptionally trustworthy for medical diagnostic applications. Conclusions: The results highlight the effectiveness of MVO-optimized CNN models for classifying brain tumors in MRI data. Future investigations may examine the model’s applicability to multiclass issues and its validation in practical clinical environments.

BioMed doi: 10.3390/biomed4040037

Authors: Vanessa Nadia Dargenio Vincenzo Rutigliano Baldassarre Martire Bénédicte Pigneur Costantino Dargenio Ruggiero Francavilla Fernanda Cristofori

Background/Objectives: Monogenic primary immunodeficiencies represent a group of disorders with varying levels of severity, many of which remain poorly understood. Activated phosphoinositide-3 kinase delta syndrome (APDS) is a rare genetic condition resulting from dominant point mutations in the phosphoinositide-3 kinase delta (PI3Kδ) gene, which leads to hyperactivation of the PI3Kδ enzyme, primarily expressed in T and B lymphocytes. Children with this mutation often have recurrent sinopulmonary infections and immunodeficiency. Additional complications may include increased susceptibility to herpes virus infections, lymphoid hyperplasia, and autoimmune conditions. In this case, report, we describe the clinical course of a young boy diagnosed with APDS who developed unclassified inflammatory bowel disease (U-IBD) and explore a personalized treatment approach. Methods: We detail the clinical course of a 12-year-old boy with APDS who presented with fever, diarrhea, anemia, and significant weight loss. Diagnostic evaluations, including endoscopy and histological analysis, led to a diagnosis of U-IBD. Genetic testing confirmed a heterozygous PIK3CD mutation (c.G3061A, p.E1021K). Results: Although APDS is characterized by a broad spectrum of immune dysregulation, the occurrence of IBD in this context is rare. We managed the patient’s IBD with exclusively enteral nutrition to induce remission, followed by a maintenance regimen combining the Crohn’s Disease Exclusion Diet (CDED) and mesalamine, achieving sustained long-term clinical remission. Conclusions: This case underscores the importance of personalized treatment approaches in managing the complex manifestations of APDS.

BioMed doi: 10.3390/biomed4040036

Authors: Ebenezer C. Nnadozie Kennedy I. Ogunwa Vitalis I. Chukwuike Onyinyechukwu O. Nnadozie Charles Ehikhase

Carbonaceous materials have gained significant attention in recent years for their various applications in the field of medicine and biotechnology. This comprehensive review explores the synthesis and characterization of carbon-based materials and their potentials in various medical applications. The paper delves into the methods of fabrication of carbon-based nanoparticles, such as carbon nanotubes, biochar, and graphene, while highlighting their unique properties. Characterization techniques, such as microscopy, spectroscopy, and surface analysis, are discussed to provide insights into the chemical and structural properties of these materials. Furthermore, the review examined their wide-ranging medical applications, encompassing tissue engineering, drug delivery, biosensing, and imaging, showcasing the versatility and promising contributions of carbonaceous materials in the healthcare industry. The review outlines the current challenges and prospects in the field, emphasizing the growing significance of carbon-based materials as valuable tools in advancing medical science and technology, as well as public health.

BioMed doi: 10.3390/biomed4040035

Authors: Karishma Gangwani Nandika Row Shashi Anand Srijan Acharya

Smokeless tobacco (ST) is an alternative to smoking, which involves not the burning of tobacco. Although ST has been used for thousands of years, its health effects are not well characterized, and it is the subject of misconceptions throughout society. Therefore, it is crucial to identify the risks associated with ST use. We conducted a comprehensive search of the scientific literature to identify studies reporting associations between tobacco chewing and the risk of oral cancer and premalignant lesions. Our review discusses the molecular mechanisms associated with ST components, along with the role of ST use in speech impairment and cancer progression. We also examine the effectiveness of tobacco cessation strategies and review the existing perceptions held by ST consumers. Our findings indicate significant health risks associated with ST use, including increased cancer risk and speech impairments. As societal perceptions and misconceptions about ST are important factors that influence its use, there is a need for comprehensive public awareness campaigns to correct these misconceptions and to promote healthier lifestyle choices. We call for further research to improve cessation interventions and to increase public awareness of relevant research discoveries. By providing a thorough discussion of the health impacts of ST, we aim to inform policy decisions and public health strategies to reduce the prevalence of ST use.

BioMed doi: 10.3390/biomed4040034

Authors: Nonyelum Aniebo Tarun Goswami

Background/Objectives: Alzheimer’s disease (AD) is a leading cause of death worldwide, affecting millions of older Americans and resulting in a substantial economic burden. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) aims to investigate and develop treatments for AD. Methods: This study included 60 participants, divided equally into AD and control cohorts, and utilized magnetic resonance imaging (MRI) scans to detect gray matter volumetric alterations, a key biomarker of AD. The participants’ cortical volume and surface area were quantified using an automated pipeline in MIMICS (Materialise Interactive Medical Imaging Control System). Results: A multivariate regression analysis was conducted to explore the relationship between cortical measurements and potential factors influencing AD susceptibility. The study found that both cortical volume and surface area were statistically significant predictors of AD (p = 0.0004 and p = 0.011, respectively). Age was also a significant factor, with the 65–70 age group showing the strongest association (p < 0.001). The model achieved an accuracy of 0.68 in predicting AD. Conclusions: While voxel-based morphometry (VBM) using MIMICS showed promise, further development of the automated pipeline could enhance accuracy and correlation indices. These findings contribute to our understanding of brain atrophy in AD pathophysiology and highlight the potential of MRI morphometry as a tool for AD biomarker development.

BioMed doi: 10.3390/biomed4040033

Authors: Riki Tanaka Yutaka Shigemori Tetsushi Moriguchi

Background: Muscle biopsy, the gold standard for assessing muscle aerobic capacity, is an invasive procedure. Noninvasive alternatives, such as 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and near-infrared spectroscopy (NIRS), provide valuable insights, with NIRS providing superior time resolution and ease of use compared with 31P-MRS. Objectives: This study aimed to evaluate muscle metabolism using a 6 s muscle contraction phase with electrical muscle stimulation (EMS) and to assess the impact of EMS on exercise performance under hyperbaric conditions with elevated oxygen pressure. Methods: This study included nine male participants (21 ± 2 years) who underwent 5 min of EMS on the forearm flexor muscle group, with muscle oxygen dynamics assessed using NIRS. For statistical analysis, the mean values between groups were assessed using paired t-tests, and associations were evaluated using Pearson’s correlation coefficient. Results: Spontaneous blood flow interruption during EMS-induced muscle activity indicated the potential for assessing muscle metabolism without disrupting external blood flow. A significant negative correlation was observed between oxygen consumption and changes in oxygenated hemoglobin levels during muscle activity under hyperbaric conditions. Conclusions: This study demonstrates that skeletal muscle metabolism can be measured using a brief 6 s quantitative EMS. Furthermore, hyperbaric exercise appears to enhance aerobic capacity by increasing the rate and availability of oxygen consumption during exercise.

BioMed doi: 10.3390/biomed4040032

Authors: Roshan Kumar Mahat Prasanna Kumar Rathor Vedika Rathore Manisha Arora Suchismita Panda Gujaram Marndi

Background: Vitamin D deficiency is thought to increase the likelihood of insulin resistance (IR) and diabetes onset. The objective of this study was to examine the association between the triglyceride glucose (TyG) index and vitamin D levels in individuals with prediabetes and type 2 diabetes mellitus (T2DM) in the tribal community of India. Methods: This study included 270 participants, consisting of 90 individuals with prediabetes, 90 individuals with T2DM, and 90 control patients. Anthropometric and biochemical characteristics were evaluated in all participants. 25-hydroxyvitamin D [25(OH)D] levels were measured using a chemiluminescent immunoassay. The TyG index was computed as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Spearman correlation analysis and linear regression analysis were performed to assess the relationship between the TyG index and 25(OH)D levels in people diagnosed with prediabetes and T2DM. The optimum cut-off value of the TyG index for detecting vitamin D deficiency was determined by receiver operating characteristic (ROC) curve analysis. Results: We observed a significant reduction in vitamin D levels in individuals with prediabetes and T2DM compared to those in the control group. However, the TyG index was significantly greater in individuals with prediabetes and T2DM than in controls. Statistical analysis revealed a significant negative correlation between the TyG index and 25(OH)D in both prediabetes and T2DM. Conclusions: The TyG index demonstrated a negative association with vitamin D levels and was identified as an independent predictor of vitamin D deficiency in individuals with prediabetes and T2DM.

BioMed doi: 10.3390/biomed4040031

Authors: Khalid M. Aloufi

Aim: This study aims to estimate equivalent doses (EqDs) and life attributable risks (LARs) for pediatric patients who underwent chest–abdominal–pelvic (CAP) CT examinations in Madinah, Saudi Arabia. Methodology: This retrospective study collected data from 120 pediatric patients who underwent CAP CT examinations. The data were categorized by the age and gender of the pediatric patients. Then, the EqDs were computed using the NCICT (National Cancer Institute dosimetry system for computed tomography) program, and LARs were estimated from the equivalent dose (EqD) results using age- and gender-specific cancer risk models found in the Committee on the Biological Effects of Ionizing Radiation (BEIR) VII Phase 2 (2006). Results: The EqD range was 0.9 to 7.55 mSv for the prostate and colon (males and females), respectively. LARs for female breast and lung cancers were considered to have the highest values among the age groups. Nevertheless, LARs of the colon, liver, and leukemia cancers were higher for males than females. The LAR range of cancer incidence was 0.6 to 63.1 per 100,000 cases for prostate (aged 10–≤15 years) and breast (females aged 1≤–<5 years), respectively. The LAR range of cancer mortality was 0.1 to 41.9 per 100,000 cases for prostate (aged 10–≤15 years) and lung (females aged 1≤–<5 years). Conclusions: LARs of all cancer incidence and mortality from CAP CT examination were higher for pediatric females than males (with an average of 54%). This highlights the importance of considering pediatric patient gender and implementing optimization and protective measures in CAP CT examinations. LARs of breast and lung (for females) and colon (for males) cancers were found to have the highest values among the age groups. However, LARs of cancer incidence and mortality for colon, liver, and leukemia for males were higher than those for females.

BioMed doi: 10.3390/biomed4040030

Authors: Ayesha Iqbal Yuhashinee Kumaradev Gizem Gülpinar Claire Brandish Maxencia Nabiryo Frances Garraghan Helena Rosado Victoria Rutter

Background: The hub-and-spoke model (HSM) offers a framework for efficient healthcare service delivery. This scoping review seeks to explore the implementation and effectiveness of the HSM in antimicrobial stewardship (AMS) programmes. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) reporting guideline was followed. A systematic search was conducted in four electronic databases (PubMed, Medline, Cochrane Library, and Google Scholar) from inception until January 2024. Studies where the HSM was used for delivering any AMS activity, intervention, or action, were included. No study-specific filters were applied and all populations, study designs, and health settings were included. Data screening and selection were achieved using Rayyan. Three authors independently screened studies, with conflicts resolved by a fourth author. Data were narratively synthesised. Standard appraisal tools were impractical; however, critical evaluation of data collection and outcome reporting was ensured. Results: Out of 1438 articles, three were included in the scoping review. The primary interventions utilising the HSM in AMS involved reducing antibiotic misuse, training healthcare professionals, case-based learning, establishing AMS programmes, developing antibiograms, and formulating policies or guidelines pertinent to AMS. The studies demonstrated significant clinical improvements in AMS. Clinical outcomes from the studies include a significant reduction in antimicrobial usage and improved antibiotic management, with a notable decrease in days on antimicrobial therapy and increased antibiotic de-escalation. Key facilitators for AMS programme success were tailored education, collaborative learning, strong leadership, strategic practices, and data-driven decisions. Key barriers were leadership challenges, change resistance, knowledge gaps, inadequate data systems, resource limitations, and technological constraints. Conclusions: The review identified a literature gap in HSM use in AMS programmes. Further studies are needed to assess HSM’s effectiveness, feasibility, and cost-effectiveness in AMS contexts.

BioMed doi: 10.3390/biomed4040029

Authors: Laura Clara Grandi Stefania Bruni

Background. The COVID-19 pandemic introduced unprecedented social distancing measures, resulting in significant deprivation of physical contact. Objective. This opinion article explores the implications of this tactile deprivation on psychological well-being, emphasizing its impact on emotional and cognitive development. Physical contact, particularly social touch mediated by C-tactile fibers, is essential for emotional stability and social bonding. Methods. Drawing on evidence from studies on orphaned children and primates, this opinion article argues for the critical importance of reintroducing physical contact to support mental health. Results. The pandemic’s reduction in physical touch has been associated with increased anxiety, depression, and stress, with notable declines in mood and heightened loneliness. Conclusions. While alternative methods such as virtual reality offer temporary solutions, the article stresses the need for safe, physical interactions as restrictions ease. Future discourse should focus on the long-term effects of touch deprivation and explore effective strategies for mitigating its impacts in similar scenarios.

BioMed doi: 10.3390/biomed4030028

Authors: Muhammad Hassaan Ahmed Jacques-Ezechiel N’Guessan Ranjan Das Matthew Leineweber Sachin Goyal

Background/Objectives: This study explores an optimization-based strategy for muscle force estimation by employing simplified cost functions integrated with physiologically relevant muscle models. Methods: Considering elbow flexion as a case study, we employ an inverse-dynamics approach to estimate muscle forces for the biceps brachii, brachialis, and brachioradialis, utilizing different combinations of cost functions and muscle constitutive models. Muscle force generation is modeled by accounting for active and passive contractile behavior to varying degrees using Hill-type models. In total, three separate cost functions (minimization of total muscle force, mechanical work, and muscle stress) are evaluated with each muscle force model to represent potential neuromuscular control strategies without relying on electromyography (EMG) data, thereby characterizing the interplay between muscle models and cost functions. Results: Among the evaluated models, the Hill-type muscle model that incorporates both active and passive properties, combined with the stress minimization cost function, provided the most accurate predictions of muscle activation and force production for all three arm flexor muscles. Our results, validated against existing biomechanical data, demonstrate that even simplified cost functions, when paired with detailed muscle models, can achieve high accuracy in predicting muscle forces. Conclusions: This approach offers a versatile, EMG-free alternative for estimating muscle recruitment and force production, providing a more accessible and adaptable tool for muscle force analysis. It has profound implications for enhancing rehabilitation protocols and athletic training, not only broadening the applicability of muscle force estimation in clinical and sports settings but also paving the way for future innovations in biomechanical research.

BioMed doi: 10.3390/biomed4030027

Authors: Michel Luhembwe Richard Ingwe Aimée Lulebo Dalau Nkamba John Ditekemena

Antiretroviral treatment (ART) has revolutionized the management of the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), enabling long-term viral load (VL) suppression in patients. Despite the proven effectiveness of ART, a significant proportion of patients with HIV receiving ART fail to achieve viral load suppression (VLS). This study aimed to identify factors associated with low VLS in the Tanganyika province. An unmatched case–control study was conducted from January 2022 to June 2023, including 22 care facilities with viral load data. Data were collected from patient records. For each reviewed record, the patient was invited for an interview upon providing informed consent. Data were analyzed using SPSS version 27. In a multivariable binary logistic regression model, variables with a p-value < 0.05 and a 95% confidence interval for the adjusted odds ratio were considered significantly associated with unsuppressed VL. A total of 462 individuals, including 156 cases and 306 controls, were included in the study. The mean age (standard deviation) of participants was 42.12 (±11.6) years. The following covariates were significantly associated with unsuppressed VL: poor HIV status disclosure to a confidant [adjusted OR = 2.10, 95% CI (1.33–3.31), p = 0.001], poor ART adherence [adjusted OR = 2.01, 95% CI (1.25–3.23), p = 0.004], ART interruption [adjusted OR = 3.43, 95% CI (2.00–5.88), p < 0.001], no participation in support groups [adjusted OR = 2.16, 95% CI (1.25–3.71), p = 0.005], baseline WHO clinical stage 3 and 4 [adjusted OR = 2.24, 95% CI (1.32–3.79), p = 0.003], opportunistic infections (OIs) [adjusted OR = 2.30, 95% CI (1.27–4.16), p = 0.006], and non-communicable chronic diseases (NCDs) [adjusted OR = 2.30, 95% CI (1.10–4.79), p = 0.026]. Given the clear association between several factors and unsuppressed VL, prevention should involve the implementation of innovative strategies targeting at-risk patient groups. Strengthening the monitoring of these factors among active patients at each appointment is recommended to achieve this goal.

BioMed doi: 10.3390/biomed4030026

Authors: Muhammad Jawad Zai Matthew James Cheesman Ian Edwin Cock

Overuse or misuse of broad-spectrum antibiotics increases the risk of the emergence of antibiotic-resistant bacteria, which increases the possibility of antimicrobial-resistant (AMR) bacterial infections, and subsequently raises healthcare costs. The excessive use of broad-spectrum antibiotics has also been linked to increased death rates, whilst the benefits that they offer against antibiotic-resistant bacterial pathogens are minimal. Patients infected with antibiotic-resistant bacterial pathogens frequently receive inadequate antimicrobial therapies due to a lack of effective options than those with non-resistant infections, resulting in poor health outcomes and longer recovery times, especially among patients who are critically ill. Broad-spectrum antibiotics also disturb the gut microbiome, which is increasingly recognized as a regulator of immune health. This study offers insights into the use of targeted antimicrobial therapies for bacterial infections, focusing on strategies that mitigate the risk of antibiotic resistance and unwanted side effects associated with the use of broad-spectrum antibiotics. We focus on identifying the genotype and phenotype of bacterial pathogens and then using either nanoparticle-based, vaccine-based, bacteriophage-based, monoclonal antibody-based, and CRISPR-based targeted therapies to directly kill those pathogens and reduce collateral damage. Furthermore, the mechanisms of action of these targeted therapies and their advantages and disadvantages are discussed.

BioMed doi: 10.3390/biomed4030025

Authors: Daniel Amsterdam

Although advances in contemporary medical care have broadened access to healthcare and extended the human life span, deaths resulting from antimicrobial-resistant pathogens continue to increase. This minireview summarizes the evidence that AI and machine learning, coupled with precision medicine and alternative therapies, such as repurposing non-antibiotic drugs and the use of bacteriophages, has promise to halt this advance.

BioMed doi: 10.3390/biomed4030024

Authors: Mikołaj Hurła Damian Pikor Klaudia Kościelecka Alicja Drelichowska Natalia Banaszek Małgorzata Paul

Neurocysticercosis (NCC), a parasitic infection of the central nervous system caused by the larval stage of Taenia solium, presents a diagnostic conundrum due to its rare and often nonspecific clinical manifestations. This paper aims to unravel the diagnostic mystery surrounding NCC, shedding light on its epidemiology, pathophysiology, clinical presentation, and the challenges encountered in its diagnosis. Despite being considered a rare disease, NCC is the leading cause of acquired epilepsy worldwide, underscoring its clinical significance. The complexity of NCC diagnosis lies in its diverse clinical presentations, which can range from headaches, dizziness, and seizures to more severe neurological cognitive deficits. This diversity often leads to misdiagnosis. Furthermore, the limitations of current diagnostic methods, including serological tests and neuroimaging, contribute to the diagnostic dilemma. This paper emphasises the need for improved diagnostic criteria and novel diagnostic tools to enable early and accurate detection of NCC. By enhancing our understanding of NCC, we can pave the way for better management strategies, ultimately improving patient outcomes in this under-recognised disease.

BioMed doi: 10.3390/biomed4030023

Authors: Thomas Neumann Nadette Peters Laila Schneidewind William Krüger

Background: Our aim is to investigate cardiovascular risk factors, chronic graft-versus-host disease (CGvHD), and vitamin D metabolism in very long-term survivors of adult allogeneic stem cell transplantation (alloSCT). Methods: This study is a prospective unicentric, non-interventional trial. The detailed study protocol is available via the WHO Clinical Trial Registry. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 12; 36.4%). The median survival time was 9.0 years (IQR 8.5–13.0). Relevant cardiovascular risk factors in the study population are the body mass index, cholesterol, LDL cholesterol, and lipoprotein(a). Cardiovascular risk factors have no significant impact on HRQoL. CGvHD of the skin as a limited disease was present in six patients (18.2%), and it has no impact on HRQoL. CGvHD was significantly associated with eosinophilia in peripheral blood (p = 0.003). Three patients (9.1%) had a shortage of calcitriol, and one patient (3.0%) took calcium substitution. The shortage is significantly associated with increased infection rates (p = 0.038). Conclusions: Cardiovascular risk factors and CGvHD need to be closely monitored. Eosinophilia might be a good and convenient monitoring parameter for CGvHD.

BioMed doi: 10.3390/biomed4030022

Authors: Adam Mustapha Ahmed AlSharksi Ukpai Eze Rahma Samaila Boniface Ukwah Arinze Anyiam Shivanthi Samarasinghe Musa Ibrahim

Klebsiella pneumoniae is an opportunistic Gram-negative bacterium in the Enterobacteriaceae family associated with a wide range of diseases, such as pneumonia, bloodstream infections, meningitis and urinary tract infections. Infections caused by drug-resistant strains of Klebsiella pneumoniae pose a significant threat to the effectiveness of conventional antibiotics. Hence, this has led to the need to explore alternative antimicrobial therapies, especially natural products derived from plant sources. This study assessed the phytochemical composition and antibacterial properties and performed a molecular docking analysis of Henna leaves (Lawsonia inermis L.) extracts on strains of Klebsiella pneumoniae. Crude ethanol and methanol extracts of L. inermis L. were prepared at different concentrations (25, 50, 75 and 100 mg/mL) and tested on extended spectrum beta-lactamases (ESBLs)-producing strains of Klebsiella pneumoniae. Phytocompounds were identified using gas chromatography–mass spectrometry (GC-MS) and further subjected to virtual ligands screening with DataWarrior (v05.02.01) and a molecular docking analysis using AutoDock4.2 (v4.2.6). The active compounds of L. inermis L. were determined by the docking analysis, including phytochemical, physicochemical, pharmacokinetics and docking score. The GC-MS analysis identified 27 phytoconstituents, including ethyl acetate, sclareol, 2-[1,2-dihydroxyethyl]-9-[β-d-ribofuranosyl] hypoxanthine, α-bisabolol and 2-Isopropyl-5-methylcyclohexyl 3-(1-(4-chlorophenyl)-3-oxobutyl)-coumarin-4-yl carbonate. The 27 compounds were then screened for their physicochemical and pharmacokinetic properties. The results revealed that the methanol extracts at 100 mg/mL showed significantly higher (p < 0.05) zones of inhibition (13.7 ± 1.2 mm), while the ethanol extracts at 50 mg/mL were significantly lower (6.3 ± 0.6 mm) compared to all the other treatments. The docking analysis revealed that out of the 27 compounds identified, only twelve (12) compounds have a drug-likeness activity. The 12 compounds were further subjected to docking analysis to determine the binding energies with the CTX-M protein of Klebsiella pneumoniae. Only one compound [CID_440869; (2-[1,2-dihydroxyethyl]-9-[β-d-ribofuranosyl] hypoxanthine)] had the best binding energy of −9.76 kcal/mol; hence, it can be considered a potentially suitable treatment for infections caused by ESBLs-producing strains of Klebsiella pneumoniae. This study has demonstrated that L. inermis L. extracts have antibacterial effects. Further research could explore the potential antimicrobial applications of L. inermis L. extracts to many bacterial strains.

BioMed doi: 10.3390/biomed4030021

Authors: E. Maruthi Prasad Ramesh Kinha Rajesh Bendre

Neonatal deaths, which usually occur in the first week after delivery, account for nearly 75 percent of all deaths of children under 5 years of age. Prematurity, birth difficulties, infections, and birth defects are responsible for about 40 percent of these deaths. Although mortality rates have declined since 2000, access to quality healthcare remains a major problem for mothers and infants worldwide. In perspective, the present study aimed to establish clear biological reference intervals for 17α-hydroxyprogesterone (17-OHP), immunoreactive trypsinogen (IRT), and biotinidase in Indian neonates. The statistical analysis of data from up to 3200 dried blood spot (DBS) samples of Indian newborns provided valuable information for the new cut-off values in newborn screening (NBS) programs. We applied correlation analysis to fix the relationship for NBS parameters such as 17-OHP, IRT, and biotinidase. This study provided important information about the distribution and comparison of key cut-offs for biomarkers considering body weights and gestational age in the Indian newborn population for the first time, which can help healthcare experts make easier treatment decisions.

BioMed doi: 10.3390/biomed4030020

Authors: Wen Hon Darren Wee Zhi Wei Nicholas Matthias Tan Clara X. Quek Jing Hui Yik Sean Wei Loong Ho

Rotator cuff repair is a common orthopaedic procedure. Despite advancements in the mechanics of rotator cuff repair, the re-tear rate post repair remains significant. This review assesses the available literature on usage of collagen bio-inductive scaffolds for rotator cuff repairs. Augmentation of biology is a key strategy to improving success of rotator cuff repair. Current evidence suggests that augmentation of rotator cuff repairs with a collagen bio-inductive scaffold improves the thickness of the rotator cuff. There is a favourable safety profile, and its usage may improve re-tear rates. However, there is currently no consensus on whether clinical outcomes are improved by the usage of collagen bio-inductive scaffolds. Further research is necessary to increase our understanding of the clinical effects of using collagen bio-inductive scaffolds and to determine which patient profiles will best benefit from its usage.

BioMed doi: 10.3390/biomed4030019

Authors: Shilpi Goenka

The increasing use of e-cigarettes (ECs) has raised public health concerns due to the observed cytotoxic effects in both in vitro and in vivo studies. Infants and young children, being particularly vulnerable groups, exhibit heightened susceptibility to potential hazards arising from maternal use of ECs, as well as exposure to second-hand and third-hand aerosols emitted by ECs. Melanocytes are neural-crest-derived cells that regulate multiple biological functions. Melanocyte death, triggered by chemical exposure, is a known etiological cause of pigmentation abnormalities and neurodevelopmental disorders. Prior reports have demonstrated nicotine-induced differential cytotoxicity to neonatal human melanocytes derived from lightly pigmented (LP) and darkly pigmented (DP) donors. We recently reported that the vehicle base propylene glycol (PG) in e-liquid can alter the functions of LP melanocytes. However, to date, the effects of e-liquid flavors on LP and DP cells remain unexplored. Hence, in this preliminary study, a panel of twenty EC refill liquids comprising ten popular flavors (strawberry, grape, banana, vanilla, butterscotch, cinnamon, menthol, chocolate, cola, and tobacco), where each flavored e-liquid contained either 0 or 18 mg/mL nicotine, was examined for in vitro cytotoxicity to neonatal human melanocytes derived from LP and DP donors. Our results reveal that of the ten flavors, five (menthol, cinnamon, vanilla, tobacco, and banana) were highly cytotoxic, with their half-maximal inhibitory concentration (IC50) values within the tested concentration ranges. Moreover, the cytotoxicity of the specific flavors menthol, cinnamon, and vanilla was enhanced in the presence of nicotine, indicative of interactive effects, with nicotine and flavor contributing to greater melanocyte injury. The cytotoxicity of menthol (both with and without nicotine) and cinnamon (without nicotine) e-liquids was found to be higher in LP cells as compared to DP cells. In contrast, nicotine-containing vanilla e-liquid induced higher cytotoxicity in DP cells than LP cells. Only three flavors, cola (without nicotine), strawberry (without nicotine), and chocolate (without nicotine), were non-cytotoxic to both LP and DP cells. The findings that popular flavors in e-liquids induced moderate to high degree of melanocytotoxicity even in the absence of nicotine suggests that ECs are not harmless. This information may assist EC users identify particular flavors in refill liquids that may be detrimental to melanocytes. A first-screen identification of flavors in e-liquids that show a racial/ethnicity dependence can provide a baseline to identify cytotoxicity concentration ranges for popular flavors and help inform the regulatory guidelines for EC toxicity to young children and youth.

BioMed doi: 10.3390/biomed4030018

Authors: Maximilien Fil Sandrine Alibert

Amid the global health crisis instigated by COVID-19, the resurgence of tuberculosis (TB) has underscored the urgent need for innovative solutions. With TB claiming 1.6 million lives in 2021, it remains a formidable challenge, particularly in underdeveloped regions. Central to Mycobacterium tuberculosis (Mtb) pathogenesis is the decaprenylphosphoryl-β-D-ribose oxidase (DprE1)/decaprenylphosphoryl-2-keto-β-D-erythropentose reductase (DprE2) complex, pivotal for synthesizing decaprenylphosphoryl-arabinofuranose (DPA), a critical component of mycobacterial cell walls. DprE1 has emerged as a prime therapeutic target, with several inhibitors in clinical trials. This review elucidates the indispensability of DprE1, examines existing ligands, and delineates key considerations for the development of next-generation anti-TB therapeutics. Our analysis highlights the potential of DprE1 inhibitors to revolutionize TB treatment, emphasizing the need for continued research and development in this area to address the evolving landscape of TB and drug resistance.

BioMed doi: 10.3390/biomed4030017

Authors: William A. Barragán Flores Carlos Carrillo George José María Sandoval Claudia Cívico Sánchez Cristina Flores Victoria Muñoz Tomás Fernández Aparicio

Background: Lymph node involvement (N+) in bladder cancer indicates a poor prognosis. Current preoperative evaluations of N+ are often inaccurate. We aimed to develop a predictive model for N+ using basic clinical variables and assess the diagnostic accuracy of Computed Tomography (CT). Methods: A retrospective cohort study was conducted. We include 62 MIBC patients who underwent radical cystectomy (RC) from 2010 to 2019 in our center. We evaluated diagnostic concordance between CT and histopathology for extravesical extension (T3a≥) and N+. Univariate and multivariate logistic regressions were used to create a predictive model, with an ROC curve and nomogram developed. Results: We found 59% sensitivity and 69% specificity for CT for staging cT3≥ and a sensitivity of 22% and a specificity of 21% for N+. NLR > 2.60 (OR 6.03, p = 0.02) and lymphovascular invasion (LVInv) in the TURB sample (OR 9.26, p = 0.04) were correlated with N+. Both fundus lesions (OR 0.21, p = 0.04) and creatinine > 0.94 mg/dL (OR 0.17, p = 0.025) were associated with reduced risk. The ROC curve of the model showed 80.4% AUC. Conclusions: A predictive model with good diagnostic performance for N+ can be developed from basic clinical data. CT sensitivity and specificity for the detection of N+ patients are limited.

BioMed doi: 10.3390/biomed4030016

Authors: Li Yi Tan Ryan Han Rong Teh Boon Chong Kwok

Background: Pilates is among the best conservative management strategies for chronic low back pain. However, several variations of Pilates exist. This study aimed to investigate physical measures that would detect immediate changes after a brief session of Clinical Pilates exercises. Changes in self-reported clinical outcomes, pain and function were also evaluated. Methods: A prospective cohort study was conducted. Eighteen young adults with chronic low back pain participated in this study. Participants were assessed for pain and function subjectively, and hip/knee strength and trunk/hip flexibility objectively, followed by a session of Clinical Pilates assessment and exercises. After the exercises, the participants were immediately reassessed for pain, function, strength, and flexibility. Results: Trunk/hip flexibility showed statistically significant changes after exercise, which were measured with the sit-and-reach test (−3.44 cm, 95% CI [−5.10, −1.79], p < 0.001) and the finger-to-floor test (−6.29 cm [−9.51, −3.06], p = 0.001). Statistical significance was not found in detecting strength changes in hip extension, hip abduction, and knee extension. Changes in pain (1.56 points [0.83, 2.28], p < 0.001) and patient-specific functional scale (−1.52 points [−1.93, −1.10], p < 0.001) were also found after exercise. Conclusions: Trunk/hip flexibility measures detected physical changes after Clinical Pilates exercise, as well as self-reported pain and function outcomes, without reducing strength performance.

BioMed doi: 10.3390/biomed4020015

Authors: Tânia Lourenço Lara Marques Eduarda Ribeiro Nuno Vale

Prostate and bladder cancer treatments have several challenges, including intense side effects and mechanisms of resistance. Thus, it is urgent to find drugs that can fill these gaps. For this purpose, Entecavir (ETV) was tested alone and in combination with 5-Fluorouracil (5-FU). Prior to this, a preliminary computational analysis was conducted to evaluate the combination of these two drugs. After exposing PC-3 and UM-UC-5 cells to the drugs, cell morphology was assessed using a microscope, while cell viability, proliferation, and cytotoxicity were evaluated using the MTT assay, and finally, the statistical analysis was performed. It was concluded that ETV showed significant cytotoxic effects in the PC-3 cells, and 5-FU, although not as effective as in other tumor types, it managed to inhibit the viability of the PC-3 cells. The combination of 5-FU with ETV after 72 h of exposure is an advantageous association, surpassing the results of each drug alone. In the UM-UC-5 cells, ETV alone did not produce the expected effect, neither did the combination. Nevertheless, repurposing ETV has proven to be an effective strategy in PC, especially through its combination with 5-FU.

BioMed doi: 10.3390/biomed4020014

Authors: Ahmed Sherif El-Gizawy Xuewei Ma Joshua C. Arnone Ammar A. Melaibari

Existing implants used with Total Knee Arthroplasty (TKA), Total Hip Arthroplasty (THA), and other joint reconstruction treatments, have displayed premature failures and frequent needs for revision surgery in recent years, particularly with young active patients who represent more than 55% of all joint reconstruction patients. Bone cement and stress shielding have been identified as the major reasons for premature joint failures. A breakdown of the cement may happen, and revision surgery may be needed because of the aseptic loosening. The significant mismatch of stiffness properties of patient trabecular bones and metallic implant materials in joint reconstruction surgery results in the stress shielding phenomenon. This could lead to significant bone resorption and increased risk of bone fracture and the aseptic loosening of implants. The present project introduces an approach for development of customized cellular structures to match the mechanical properties and architecture of human trabecular bone. The present work aims at fulfilling the objectives of the introduced approach by exploring new designs of customized lattice structures and texture tailored to mimic closely patients’ bone anisotropic properties and that can incorporate an engineered biological press-fit fixation technique. The effects of various lattice design variables on the mechanical performance of the structure are examined through a systematic experimental plan using the statistical design of experiments technique and analysis of variance method. All tested lattice designs were explored under realistic geometrical, biological, and manufacturing constraints. Of the four design factors examined in this study, strut thickness was found to have the highest percent contribution (41%) regarding the structure stiffness, followed by unit cell type, and cell size. Strut shape was found to have the lowest effect with only 11% contribution. The introduced solution offers lattice structure designs that can be adjusted to match bone stiffness distribution and promote bone ingrowth and hence eliminating the phenomenon of stress shielding while incorporating biological press-fit fixation technique.

BioMed doi: 10.3390/biomed4020013

Authors: Raphael O. Betschart Georgios Koliopanos Paras Garg Linlin Guo Massimiliano Rossi Sebastian Schönherr Stefan Blankenberg Raphael Twerenbold Tanja Zeller Andreas Ziegler

Lipoprotein (a) (Lp(a)) is a risk factor for cardiovascular diseases and mainly regulated by the complex LPA gene. We investigated the types of variation in the LPA gene and their predictive performance on Lp(a) concentration. We determined the Kringle IV-type 2 (KIV-2) copy number (CN) using the DRAGEN LPA Caller (DLC) and a read depth-based CN estimator in 8351 short-read whole genome sequencing samples from the GENESIS-HD study. The pentanucleotide repeat in the promoter region was genotyped with GangSTR and ExpansionHunter. Lp(a) concentration was available in 4861 population-based subjects. Predictive performance on Lp(a) concentration was investigated using random forests. The agreement of the KIV-2 CN between the two specialized callers was high (r = 0.9966; 95% confidence interval [CI] 0.9965–0.9968). Allele-specific KIV-2 CN could be determined in 47.0% of the subjects using the DLC. Lp(a) concentration can be better predicted from allele-specific KIV-2 CN than total KIV-2 CN. Two single nucleotide variants, 4925G>A and rs41272114C>T, further improved prediction. The genetically complex LPA gene can be analyzed with excellent agreement between different callers. The allele-specific KIV-2 CN is more important for predicting Lp(a) concentration than the total KIV-2 CN.

BioMed doi: 10.3390/biomed4020012

Authors: Justin Lee Jessica Lee Mouath Abu-Daoud Yazan A. Al-Ajlouni

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily affecting females, characterized by developmental regression and significant communication impairments. Despite the critical role of communication in maintaining quality of life, the long-term efficacy and optimal utilization of augmentative and assistive communication (AAC) devices in RTT remain underexplored. This study evaluates the impact of AAC devices on communication outcomes and quality of life in individuals with RTT through a case report and narrative review. We conducted a comprehensive literature review and thematic analysis categorizing technologies into communication aids, mobility aids, educational tools, and daily living aids, assessing their effectiveness and challenges. The results show that AAC technologies, including eye-tracking devices, speech-generating devices, and adapted computers, enhance communication, cognitive development, and quality of life for individuals with RTT. The case report of Patient E, utilizing the Tobii Dynavox device, highlights the transformative impact of AAC devices despite challenges in device complexity and therapist training. AAC devices are indispensable for supporting individuals with RTT, though challenges persist related to accessibility, device complexity, and therapist training. Future research should focus on longitudinal studies to assess the sustained impact of AAC technologies and explore family-centered approaches to AAC integration.

BioMed doi: 10.3390/biomed4020011

Authors: Kung-Chia Li Ching-Hsiang Hsieh Ting-Hua Liao Chih-Hung Chen

The objective of this study was to retrospectively assess the impact of manual reduction (MR) on patients with subacute osteoporotic thoracolumbar burst fractures and severe compression fractures (OTLBFSCFs). From January 2016 to May 2020, 101 cases of OTLBFSCFs were reviewed, comprising 73 women and 28 men, with an average age of 77.4 ± 8.5 years. Preoperative radiographs, CT or MRI scans, intraoperative C-arm fluoroscopic images, and postoperative X-ray films were utilized to evaluate spinal radiographic parameters. Initially, all patients underwent 3 min of prone positioning as posture reduction (PR), followed by 1–3 sessions of six-member MR to approximate anatomical reduction of the fracture. The average preoperative anterior body height ratio (ABH%) and lateral Cobb angle (LCA) were 38.8% ± 6.2% and 22.6° ± 4.2°, respectively. Post-PR, the average ABH% and LCA were 50.5% ± 8.0% and 14.7° ± 2.7°, respectively. Following MR, the average ABH% and LCA were 99.6% ± 2.4% and 0.4° ± 2.4°, respectively. PR achieved an ABH% correction of 11.7%, while MR achieved 49.1%. LCA restoration was 7.9° with PR and 14.3° with MR. It was deduced that MR proved to be safe and efficacious for subacute OTLBFSCFs and could potentially alter the approach to subsequent surgeries.

BioMed doi: 10.3390/biomed4020010

Authors: Antonia F. Oladipo Maansi Jayade

The purpose of this review is to elucidate the different laboratory and biomarker testing methods available for screening and diagnosis of preeclampsia. These include routine testing, such as blood pressure readings, qualitative and quantitative urine testing, complete blood count with platelets, serum creatinine levels, liver chemistries, and serum bilirubin levels. This review also details the use of non-routine testing, such as screening for angiogenic and anti-angiogenic markers, such as placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Blood pressure measurements and proteinuria are the most routinely used screening tools used for preeclampsia and there are limited data on the utility of other screening techniques because of a greater focus on the etiology and treatment of preeclampsia. Similarly, serum angiogenic biomarkers are not routinely collected, so there is limited evidence regarding using them as screening tools for preeclampsia and more data are needed to determine their significance in the screening and diagnosis of preeclampsia.

BioMed doi: 10.3390/biomed4020009

Authors: Kodai Kitagawa Ryo Takashima Tadateru Kurosawa Chikamune Wada

Caregivers experience lower back pain due to patient transfer. Foot position is an important and adjustable posture for reducing lumbar loads during patient transfer. Specifically, a suitable foot position provides the use of the lower limbs instead of the lumbar region in patient handling. Thus, we have developed a monitoring and feedback system for foot positioning using wearable sensors to instruct suitable foot positions. However, existing measurement methods require multiple specific wearable sensors. In addition, the existing method has not been evaluated in patient transfer, including twisting and lowering. Thus, the objective of this study was to develop and evaluate a measurement method using only a smartphone-installed inertial sensor for foot position during patient transfer, including twisting and lowering. The smartphone attached to the trunk measures the acceleration, angular velocity, and geomagnetic field. The proposed method recognizes anteroposterior and mediolateral foot positions by machine learning using inertial data. The proposed method was tested using simulated patient transfer motions, including horizontal rotation. The results showed that the proposed method could recognize the two foot positions with more than 90% accuracy. These results indicate that the proposed method can be applied to wearable monitoring and feedback systems to prevent lower back pain caused by patient transfer.

BioMed doi: 10.3390/biomed4020008

Authors: Nickolai J. P. Martonick Russell T. Baker Craig P. McGowan

Instrument-assisted soft tissue mobilization (IASTM) techniques use specialized hand-held instruments for applying controlled mechanical forces to the body with the goal of facilitating healing, improving range of motion, and reducing pain. Nevertheless, an optimal range of forces for achieving clinical outcomes has yet to be established. A barrier to advancing research on IASTM force optimization is the lack of commercially available instruments that quantify treatment forces. The aim of the current study was to assess the feasibility of attaching a flexible force sensor to a commercially available IASTM instrument to obtain valid force measurements. The validity of this novel approach was assessed by comparing data between the flexible force sensor and a force plate during a simulated treatment. Intraclass correlation coefficients, linear regression models, and Bland Altman plots all indicated excellent agreement between the force plate and flexible sensor when the instrument was used at 45°, 65°, and 90° treatment angles. Agreement between measures decreased when the instrument was held at 30°. Thus, commercially available instruments with attached sensors could make force measurement more accessible and feasible for a wider range of research settings, facilitating the advancement of IASTM research and ultimately informing clinical decision-making to improve patient care.

BioMed doi: 10.3390/biomed4020007

Authors: Brady Green Molly Coventry Tania Pizzari Ebonie K. Rio Myles C. Murphy

Practitioners routinely use the single leg heel raise (SLHR) to quantify calf function in healthy and injured populations. Despite this, approaches vary and the impact of cueing on SLHR performance and results interpretation in athletesis unknown. The primary aim of this study was to quantify the level of agreement of the cued versus non-cued SLHR tests. The secondary aim was to explore test outcomes and the potential impact of intrinsic factors. Cued and non-cued SLHR tests were conducted in fifty-one Australian football players (23 women, 28 men). Metronome pacing (60 bpm) and five key cues were included in the cued condition. The level of agreement (Bland–Altman) between tests was measured for capacity (repetitions to failure) and asymmetry. Data from 100 legs were included. The non-cued and cued SLHR tests demonstrated poor agreement in both capacity and asymmetry. More repetitions to failure were performed in the non-cued SLHR [Mean (SD) = 33.9 (10.3) vs. 21.9 (5.3), p < 0.001)], and men had greater capacity (36.8 (10.4) vs. 30.3 (9.2), p < 0.001). During the cued SLHR, older players (age ≥ 30 years: −5.1 repetitions, p = 0.01) and Indigenous players (−3.4 repetitions, p = 0.002) and had reduced calf muscle function. Cueing the SLHR test significantly changes the result—outcomes are not comparable or interchangeable with the commonly used non-cued SLHR. These findings can guide practitioners quantifying calf capacity.

BioMed doi: 10.3390/biomed4020006

Authors: Liraz Cohen-Biton Dan Buskila Rachel Nissanholtz-Gannot

Objective: This study sought to examine whether the sense of coherence (SoC) and resilience among female fibromyalgia (FM) patients increased after participation in a fibrotherapy intervention program (FTI) and whether SoC and resilience increased among female FM patients (FFMPs) exposed to security threats who changed their coping strategies to problem-oriented coping. Methods: Ninety-six FFMPs aged 19–75 enrolled in the FTI program led by Rabbi Firer in Sderot, Israel. The intervention program is divided into three stages, each comprising a distinct weekly treatment plan. The treatment plans encompass the following modalities: physiotherapy adapted to FM conditions, group therapy, hydrotherapy, horticultural therapy/cooking therapy, Pilates, pottery therapy, and kundalini yoga. Each stage spans a duration of 10 weeks, culminating in a total program duration of 30 weeks. Results: The findings show that after participating in FTI, the problem-orientation level of coping and health indicators, including functional ability and physiological scores (pre- and post-exertion), increased while psychological distress levels decreased. Overall, all the physiological scales measured before and after the FTI showed a significant improvement among the entire sample. FFMPs with problem-oriented strategies reported higher levels of SoC and resilience after participating in the FTI program. Conclusions: The FTI provided FFMPs with tools to understand the meaning of their disease and its management, whereas before they were preoccupied with the presence of the disease and its negative impact on their lives. The participation of FFMPs in the FTI leads to a perceptual change, the adoption of problem-oriented coping strategies, and the increased utilization of coping resources, namely, SoC and resilience. Problem-oriented coping combined with high SoC and resilience led FFMPs to adopt health strategies such as physical activity and other empowering activities that raised their physical and mental health indicators.

BioMed doi: 10.3390/biomed4010005

Authors: Zuriatou Yajeh Tanka Naphtali Odogu Ankoro Vincent Ngouana Franklin Loïc Tchinda Taghu Abongta Lum Mforbesi Branly-Natalien Nguena-Dongue Julius Nsami Ndi Boniface Pone Kamdem Paul Keilah Lunga Fabrice Fekam Boyom

Caused by pathogenic microorganisms, infectious diseases are known to cause high mortality rates, severe burdens of disability, and serious worldwide aftermaths. Drug-resistant pathogens have reduced the efficacy of available therapies against these diseases, thus accentuating the need to search for effective antimicrobials. Medicinal plants have served as starting material for the preparation of a number of antimicrobial agents. To this end, the present study highlights the green synthesis of Cocos nucifera-based nanomaterials and evaluation of the mechanistic basis of their antimicrobial action. Accordingly, Cocos nucifera extract was used for the reduction of silver nitrate solution to afford silver nanoparticles. These entities were further incorporated onto sulfuric-acid-based activated carbons to generate the nanocomposites. The antimicrobial activity of the as-prepared nanomaterials was evaluated using the broth microdilution method, while the antioxidant activity was assessed through standard methods. The cytotoxicity of potent nanomaterials was assessed on Vero cells by the spectrophotometric method. As a result, nanoparticles were successfully synthesized, as evidenced by the ultraviolet–visible spectroscopy analysis that revealed an intense absorption spectrum at 433 nm. Fourier Transform Infrared Spectroscopy presented the functional group moieties involved as a capping and reducing agent in the synthesis of the nanomaterials. The incubation of nanomaterials with selected bacterial and fungal strains has led to significant inhibitory effects of these pathogens with minimum inhibitory concentrations ranging from 7.813 to 250 μg/mL. In antioxidant assays, the nanocomposites presented scavenging activities comparable to those of ascorbic acid. Cytotoxicity experiment revealed no toxic effects on Vero cells (range of selectivity indices: from >4 to >128). These results provide evidence of the implication of Cocos nucifera-based nanomaterials in targeting bacterial or fungal systems that mediate free-radical damage or by inhibiting the oxidative damage caused by selected bacteria and fungi, the most susceptible being Escherichia coli and Candida albicans, respectively.

BioMed doi: 10.3390/biomed4010004

Authors: Assaf Albagli Assaf Kadar Ron Gurel Elchanan Luger Yaniv Warschawski Shai Factor

Objective: Arthrodesis of the first metatarsophalangeal joint (MTPJ) is a reliable procedure for treating various pathologies related to this joint. However, non-union is a common and debilitating complication of the procedure. The purpose of this study was to assess whether the use of a mechanical reamer to prepare the joint surface increases the risk of non-union compared to traditional manual osteotomy. Methods: A retrospective study of all patients who underwent their first MTPJ arthrodesis surgery in our medical center between 2010 and 2015. The articular surface preparation of the MTPJ was either manually performed (Group 1) or mechanically conducted with reamers (Group 2). Data regarding demographic characteristics, indications for surgery, osteosynthesis methods, and post-operative complications, including non-union, infection, and revision rates, were collected for all patients. Results: A total of 83 patients with 92 primary first MTPJ arthrodesis (44 cases in Group 1 and 48 cases in Group 2) were included with a mean follow-up time of 45.3 months (SD 16.8). The two groups were comparable in terms of age, gender, comorbidities, indication for surgery, and follow-up time. The non-union rate was 15.9% in Group 1 and 25% in Group 2 (p = 0.28). Group 2 showed a significantly higher rate of revision surgery compared to Group 1 (43.7% vs. 22.7%, p = 0.03). Conclusions: The mechanical reamer group had a higher non-union rate and a significantly higher rate of revision surgery compared to low-energy manual joint preparation. In light of these findings, the use of mechanical reamers for joint preparation in the first MTPJ arthrodesis was discontinued at our medical center.

BioMed doi: 10.3390/biomed4010003

Authors: Ryota Kobayashi Hideyuki Negoro

Hardening of arterial walls associated with elevated postprandial blood glucose levels increases the risk of cardiovascular disease; however, the impact of intermittent aerobic training on reducing arterial stiffness is unknown. The aim of this study was to examine the chronic effects of intermittent aerobic exercise on arterial stiffness during hyperglycemia in middle-aged adults: 30 healthy middle-aged adults were randomly assigned to an 8-week intermittent aerobic training group (n = 15, jogging or running, 30 min/run, 3 times/week, 65% reserve heart rate) and a control group (n = 15, no training). Pulse wave velocity (PWV) of carotid-femoral (cf) and brachial-ankle (ba), heart rate, blood pressure, and blood glucose was measured before a 75 g oral glucose tolerance test (OGTT) and 30, 60, and 90 min after the test, before the exercise intervention, and 4 and 8 weeks after intervention. The baPWV and blood glucose levels before the intervention were elevated at 30, 60, and 90 min in both groups compared to levels before the 75 g OGTT (p < 0.01). The baPWV and blood glucose levels after 4 and 8 weeks of intervention were unchanged in the training group compared to that before the 75 g OGTT, but increased at 30, 60, and 90 min in the control group compared to that before the 75 g OGTT (p < 0.01). The baPWV and blood glucose levels at 30 and 60 min after the 75 g OGTT after 4 and 8 weeks of intervention were lower in the training group than in the control group (p < 0.01). These results indicate that intermittent aerobic exercise training may reduce the acute increase in arterial stiffness after hyperglycemia.

BioMed doi: 10.3390/biomed4010002

Authors: Rachel L. Washburn

The organs of the male reproductive tract, including the testis, epididymis, prostate, seminal vesicles, and semen, must provide an immunoregulatory environment conducive to germ cell viability and successful fertilization. Many immune components, such as immune cells, have been investigated regarding reproductive immunology and function; however, the investigation of the role of complement in this system has only more recently been gaining traction in research. This review focuses on complement in the male reproductive tract, with the goal of compiling information currently known about complement components detected in male reproductive organs and identifying areas in need of further research. Considering the recent and upcoming research about the noncanonical functions of complement, this information is relevant and applicable in the fields of reproductive immunology, fertility, and immune regulation.

BioMed doi: 10.3390/biomed4010001

Authors: Ezekiel Taiwo Adebayo Olunike Rebecca Abodunrin Ifeoluwa E. Adewole Abideen Olurotimi Salako Joanne Lusher Folahanmi Tomiwa Akinsolu Maha El Tantawi Omolola Titilayo Alade George Uchenna Eleje Oliver Chukwujekwu Ezechi Moréniké Oluwátóyìn Foláyan

This scoping review mapped and critically reviewed the extant literature exploring associations between oral disease status and adverse pregnancy outcomes among women residing in sub-Saharan Africa. A literature search was conducted in July 2023 using PubMed, Cochrane Library and Google Scholar. The articles selected were those published in the English language between 1990 and 2022. After screening 833 potential studies, 15 articles met the inclusion criteria. Among these, 12 (80.0%) adopted a descriptive research design, while 3 (20.0%) used experimental methodologies. Eight (53.3%) studies were conducted in East Africa, fourteen (93.3%) studies were hospital-based, and one (6.7%) study was community-based. Periodontitis was linked with low birth weight, preterm birth, preterm birth and low birthweight, stunting, wasting, and underweight in most studies. Periodontitis was, however, not linked with adverse pregnancy outcomes in four studies. Caries was not linked with adverse pregnancy outcomes, but its sequalae was linked with low birth weight, preterm birth, neonatal stunting, and small head circumference. Two studies showed that periodontal diseases were linked with preeclampsia and chorioamnionitis. Maternal poor oral hygiene was linked with stunting. Two other studies showed no links between maternal periodontal disease and preterm premature rupture of membranes, eclampsia, spontaneous abortion, and vaginal bleeding. Furthermore, two intervention studies found that the treatment of periodontal diseases during pregnancy reduced the risk of adverse pregnancy outcomes. Further studies are needed to fully elucidate the effect size of the links observed between oral diseases and adverse pregnancy outcomes in sub-Saharan Africa.

BioMed doi: 10.3390/biomed3040040

Authors: Opeyemi Adeola Olawunmi Fatusi Azuka Njokanma Adewale Adejobi

Mandibular third molars are the most commonly impacted teeth. The prevalence and pattern of impacted mandibular third molars in patients presenting to the Obafemi Awolowo University Teaching Hospitals Complex, a tertiary hospital in south-western Nigeria, are largely unknown. This retrospective study examined 469 patient records, extracting socio-demographic and clinical information for analysis. It also determined the prevalence and pattern of impacted mandibular third molars from January 2015 to December 2019. The positioning of impacted teeth was assessed via periapical radiographs utilizing Winter’s classification. Data were subjected to analysis with IBM SPSS version 20, utilizing frequencies, percentages, and likelihood ratios, with statistical significance set at p < 0.05. The prevalence of impacted mandibular third molars within the study cohort was 2.51%, with a higher incidence observed in the 21–29 age group (p < 0.001). Mesioangular impaction was the most prevalent, with pericoronitis being the primary reason for extraction, and periodontal pockets being the most common associated pathology.

BioMed doi: 10.3390/biomed3040039

Authors: Adonis Sfera Jonathan J. Anton Hassan Imran Zisis Kozlakidis Carolina Klein Carolina Osorio

Psychosocial trauma has accompanied mankind since time immemorial and has been sufficiently portrayed in art and literature to suggest that posttraumatic stress disorder may be as old as combat itself. Since war is more frequent in human history than peace, public health measures are confined to mitigating the detrimental impact of battlefield experiences on combat participants. At present, PTSD outcome studies show mixed results, marked by high nonresponse rates, therapy dropout, and completed suicide, suggesting that novel strategies are urgently needed. Those of us who work routinely with combat veterans have noted an increasing trend of patients preferring mindfulness-based therapies as opposed to trauma-centered treatments, such as prolonged exposure or trauma-focused cognitive behavioral therapy. Preference for mindfulness over trauma-based therapies appears to coincide with the shift in research focus from the amygdala and fear to the insular cortex and interoceptive awareness. Therefore, rethinking PTSD as insular pathology is driven by the recent findings that neurons in this cortical area not only regulate cardiac rhythm but also record past intestinal inflammations. These discoveries likely explain the high comorbidity of stress-related disorders with premature endothelial senescence and a dysfunctional intestinal barrier. Moreover, the identification of the cholinergic anti-inflammatory pathway and the revelation that endothelial cells express alpha-7 nicotinic receptors has brought PTSD prevention and early detection within reach. In this narrative review, we discuss the relationship between early vascular aging, gut barrier disruption, and PTSD. We also examine the link between this pathology and faulty interoceptive awareness, surmising that hypertension and decreased heart rate variability are PTSD risk factors, while lipopolysaccharide, lipopolysaccharide binding protein, soluble CD14, microbial cell-free DNA, acyloxyacyl hydrolase, and IL22 comprise early detection markers of this disorder.

BioMed doi: 10.3390/biomed3040038

Authors: Marco Fabian Wittwer Soung-Yung Kim Alexander Leichtle Sabina Berezowska Sabina A. Guler Thomas Geiser Johannes Heverhagen Britta Maurer Alexander Poellinger

Idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and systemic sclerosis (SSc) are among the most common entities that cause pulmonary fibrosis. Alveolar collapse with subsequent collapse induration of lung tissue is thought to contribute to the fibrotic transformation. The purpose of this study was to examine lung tissue in computed tomography (CT) of non-diseased appearance during expiration for signs of increased density suggesting collapsibility in fibrosing lung diseases. We further analyzed the diaphragmatic movements during the respiratory cycle to determine relationships between density differences and the apex–diaphragm diameter. Significant differences in attenuation changes between inspiration and expiration of unaffected lung parenchyma were detected between IPF and controls and between HP and controls for all lung lobes (p < 0.001). Only minor differences were found between SSc and controls. There was no clinically relevant difference between patients with IPF and those with HP. The measured absolute apex–diaphragm diameter in inspiration and expiration demonstrated a statistically significant difference between patients with IPF versus normal controls. However, the diaphragmatic excursions were not different between these groups. Compared to controls, CT lung density increases significantly more during expiration in the fibrotic lungs of IPF and HP patients. The observed increase in density might indicate the collapse of alveoli during expiration and may represent a common pathophysiologic feature of fibrosing lung diseases. The density changes and lung extensions do not have the same ratios across different diseases and controls.

BioMed doi: 10.3390/biomed3040037

Authors: Olunike Rebecca Abodunrin Mobolaji Timothy Olagunju Omolola Titilayo Alade Morẹ́nikẹ́ Oluwátóyìn Foláyan

The aim of this scoping review was to map the research that links oral health and sustainable development goals (SDGs). The question that guided this review was what is the published evidence specifically linking oral health and SDGs? The search of articles published between 2015 and June 2023 in English was conducted in June 2023 in PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and Scopus. The extracted data from the 12 of the 520 publications that met the inclusion criteria were synthesized. These were publications from the African (n = 2) and European (n = 1) regions. Ten of the studies were not country specific. There were three observational studies. The referenced SDGs were SDG 1 (n = 1), SDG 3 (n = 11), SDG 4 (n = 3), SDG 5 (n = 2), and SDG 13 (n = 1). The studies linking oral health to SDG3 discussed a range of issues related to integrated oral health care, dental education on the SDGs, improved health equalities, access to universal health care, and sustainable health approaches. The small number of studies identified suggests the need to take proactive steps to generate research-based evidence that explores the interplay between oral diseases, oral health, and SDGs to address the dearth in the literature. By so doing, resources allocated to the SDGs can also be effectively uses to control oral diseases.

BioMed doi: 10.3390/biomed3040036

Authors: Yuval Arbel Yifat Arbel Amichai Kerner Miryam Kerner

This study investigates the impact of more densely populated urban environments proxied by the number of skyscrapers on the obesity prevalence among young vs. old populations at a US statewide level. Obesity is a global pandemic, as well as a major risk factor for a long series of health problems and increased mortality rates. We employ a quadratic model, which relaxes the a priori assumption of the monotonic rise or drop in obesity prevalence with the number of skyscrapers. The outcomes demonstrated a U-shaped curve and a sharper decrease (increase) in the projected obesity prevalence with the number of skyscrapers in the range of 0–147 (147–270) skyscrapers for the old population age cohorts above 65 years old. One possible explanation is the different motivation for physical activity among dissimilar age cohorts. While younger people are focused on maintaining a slim body shape, older people identify with the importance of sports. The public policy outcome of our study is the need to implement different recommendations in dissimilar urban environments based on age cohort stratification. Given that skyscrapers are the manifestation of wealth economics and present the typical characteristics of modern cities, which, in turn, are the future of economic development and productivity, these recommendations might prove to be important.

BioMed doi: 10.3390/biomed3040035

Authors: Morẹ́nikẹ́ Oluwátóyìn Foláyan Omowumi Moromoke Femi-Akinlosotu Bolu Adeoti Oluwatosin Eunice Olorunmoteni

Untreated early childhood caries (ECC) is a global public health concern. In the short term, untreated ECC can lead to pain, infection, and disrupted sleep, among other issues. In the long term, it is associated with poor oral health in later life, increased risk of caries in permanent teeth, and adverse effects on physical and psychological development. There may be a link between untreated ECC and adverse cognitive and neurodevelopmental outcomes in young children, although the exact pathways are not fully understood. One possible pathway is through the relationship between mastication and brain stimulation. Impaired masticatory function due to ECC can affect the hippocampus, a key region responsible for memory and learning. Furthermore, untreated ECC can cause chronic inflammation, leading to the release of pro-inflammatory cytokines that may damage the brain. Sleep disturbances resulting from ECC-related pain and discomfort can also impact brain development and cognitive functioning. Additionally, frequent use of antibiotics and analgesics to address ECC-related infections can disrupt the gut microbiome, potentially affecting the brain through the gut–brain axis. Untreated ECC can cause nutritional deficiencies and elevated nutritional risk, and can further hinder brain development. Addressing ECC comprehensively with early childhood health initiatives can help mitigate potential long-term consequences and promote optimal brain development in young children.

BioMed doi: 10.3390/biomed3030034

Authors: Mikhail A. Nikolskiy Dmitriy A. Lioznov Evgeniy U. Gorelik Tatyana V. Vishnevskaya

Background: Human herpes virus-6 (HHV-6) is a ubiquitous virus known as an etiological agent of exanthem subitum. HHV-6-encephalitis in immunocompetent children is a rare complication of the primary infection. There are a lack of data on the prevalence of HHV-6-encephalitis in Russia. The aim of our study was to analyze the prevalence of HHV-6 DNA in the cerebrospinal fluid (CSF) of immunocompetent children with suspected acute meningoencephalitis. Materials and Methods: A total of 712 CSF samples were tested using qualitative PCR over 12 years at N.F. Filatov Children’s City Clinical Hospital No.5, Saint-Petersburg, Russia. Results: HHV-6 DNA was detected in 20 (2.8%) of the samples. Retrospectively, we analyzed the medical records of 15 cases. There were seven boys and eight girls from 1 month to 7 years old; the mean age was 22.3 ± 5.6 months. Most HHV-6 DNA-positive cases were due to the primary form of HHV-6 infection. There were, in total, four cases of HHV-6-meningoencephalitis. All the children had a complete recovery, without neurological deficits or death. Conclusions: HHV-6 encephalitis is a very rare disease in immunocompetent children (four cases among 712 samples over 12 years). Additional studies are needed to develop accurate diagnostic criteria and therapeutic approaches.

BioMed doi: 10.3390/biomed3030033

Authors: Adebola Oluyemisi Ehizele Adebukunola Olajumoke Afolabi Ukachi Chiwendu Nnawuihe Omolola Titilayo Alade Joanne Lusher George Uchenna Eleje Olunike Rebecca Abodunrin Folahanmi Tomiwa Akinsolu Ucheoma Nwaozuru Maha El Tantawi Morẹ́nikẹ́ Oluwátóyìn Foláyan Francisca Obiageri Nwaokorie

This scoping review provides an overview of the tools used to assess for early childhood caries (ECC) in Nigeria. A search of the literature in African Journals Online, Google Scholar, Medline, and Cochrane database was conducted in June 2023 using the PRISMA-ScR guidelines. A combination of keywords related to caries risk assessment, preschool children, and evaluation tools was used for the search. Studies reported in English and assessing ECC were extracted. Descriptive statistics were used to summarise the information on study characteristics, types of caries assessment tools, and study outcome. Caries assessment tools were divided into behavioural, social, and biological. After screening 964 potential studies, 16 were included in the review. ECC assessment tools were categorised into behavioural (snacking, frequency of consumption of refined carbohydrate in-between-meals, dental service utilisation, frequency of tooth brushing, use of fluoridated toothpaste, breast and bottle feeding patterns and duration), biological (birth rank, age, sex, anthropometric measures, molecular characterisation of isolated organisms, presence of plaque), and social (socioeconomic status of the child’s household, mother’s level of education, maternal income, occupation of the father, maternal decision-making ability). Twelve studies used behavioural assessment tools, 11 used biological, and 11 used social tools. Furthermore, 11 (70.1%) used a combination of tools, four (25.0%) used only biological tools, and one (6.2%) used only behavioural tools to assess ECC experience. No study screened for the risk of caries. In conclusion, we identified the need for comprehensive studies to identify the risk indicators of ECC in Nigeria. This will support the development of a caries risk assessment tool appropriate for the country context.

BioMed doi: 10.3390/biomed3030032

Authors: Morenike Folayan Maha El Tantawi

The decarbonization of transport is a global initiative aimed at reducing greenhouse gas emissions and addressing the risks of global warming. This article explores the potential connections between the decarbonization of transport and oral health, highlighting the need for further research in this area. Emissions from vehicle exhausts, such as carbon dioxide, methane, and nitrous oxide, may have a modest impact on the risk of early childhood caries and other oral health diseases like periodontal diseases, oral cancer, and dental caries. Active transportation, which promotes regular exercise, has beneficial effects on overall health, including stimulating salivary protein production and reducing the risk of diabetes and cardiovascular diseases, both of which are linked to poor oral health. Transitioning to electric vehicles can also reduce noise pollution, positively impacting mental well-being, which is associated with improved oral hygiene practices. Furthermore, the development of sustainable infrastructure, including efficient public transportation systems, can enhance access to dental services. Further research is needed to establish stronger evidence for these connections and to explore how the global decarbonization of transport agenda can incorporate oral health considerations.

BioMed doi: 10.3390/biomed3030031

Authors: Fuminori Takayama

Background: The effects of the use of continuous glucose monitoring (CGM) in elite endurance athletes are unclear. This case study reported the blood glucose (BG) levels of a female national-level marathon runner during a real-world marathon race. Methods: Heart rate and BG levels were monitored throughout the race. Results: The runner completed the race in 2:46 h:min, which was an improvement from her previous personal record by just under one min. Her BG levels were stable from approximately 5–40 km of the race at a mean concentration of 7.13 mmol/L, with a standard deviation of 0.20 mmol/L and a coefficient of variation of 2.8%. Increases in BG levels and heart rate were observed 6 min after the race and during the 40–42.195 km section, respectively. Conclusions: The runner broke her own record and exhibited stable BG levels throughout the race, with the highest BG value detected immediately after the race. Considering that quantity, content, and timing of pre-race meals and supplementation during the race can affect BG levels, future studies should assess additional detailed parameters in more detail and monitor multiple races with the same elite endurance athletes to acquire more definitive evidence on CGM usefulness among elite endurance athletes.

BioMed doi: 10.3390/biomed3030030

Authors: Ruth D. Neill Paula McFadden Jill Manthorpe John Mallett Denise Currie Heike Schroder Jermaine Ravalier Patricia Nicholl John Moriarty Susan McGrory Rachel Naylor Hannah Davies Justin MacLochlainn

Aim: to explore the psychological wellbeing and work-related quality of life amongst United Kingdom (UK) health and social care workers during the COVID-19 pandemic. Subject and methods: Health and social care professionals within nursing, midwifery, allied health professions, social care and social work occupations working in the UK during the pandemic were recruited. Repeated cross-sectional online surveys were conducted during six time periods of the pandemic (May–July 2020, November–February 2021, May–July 2021, November 2021–February 2022, May–July 2022 and November 2022–February 2023). Results: Over 14,000 participants completed the surveys during the data collection periods. The findings revealed that over the pandemic, psychological wellbeing and work-related quality of life scores significantly decreased. Conclusions: The overall psychological wellbeing and work-related quality of life of health and social care workers during the COVID-19 pandemic significantly declined. Further research is warranted on the lasting impact of the pandemic on this workforce. The health and social care workforce needs support to prevent further deterioration and to rebuild its wellbeing and resilience.

BioMed doi: 10.3390/biomed3030029

Authors: Anna Tsiakiri Pinelopi Vlotinou Aikaterini Paschalidou Christos Konstantinidis Foteini Christidi Dimitrios Tsiptsios Georgia Detsaridou Alexandra Petridou Aimilios Gkantzios Stella Karatzetzou Konstantinos Tsamakis Erasmia Giannakou Maria Emmanouilidou Konstantinos Vadikolias Nikolaos Aggelousis

The purpose of the present study was to review all available work published within the last decade focusing on coping strategies in stroke caregivers and their impact on quality of Life (QoL) and psycho-emotional status. A literature search of two databases (MEDLINE, Scopus) was conducted to identify all relevant full-text English studies published between 2013–2023. Sixteen articles were traced and were finally included. Cognitive and behavioral coping strategies were beneficial for stroke caregivers’ and survivors’ QoL. The level of mutuality in the caregiver-survivor relationship was associated with the impact of depressive symptoms on caregivers’ QoL and the protective effect of mutuality on survivors’ QoL over time. The level and quality of social support were positively associated with QoL for stroke caregivers and survivors. Caregivers’ preparedness was a moderator for the impact of depression on both caregivers’ and survivors’ QoL. High levels of spirituality had a significant role in ameliorating the negative impact of depressive symptoms on the psychological and physical QoL of stroke caregivers and survivors. In conclusion, the study of coping strategies can be used as a psychological reserve in the process of stroke rehabilitation and actively contribute to improving the QoL of both caregivers and stroke survivors.

BioMed doi: 10.3390/biomed3030028

Authors: Michael Wiblishauser Tori Chapa K’Ondria Ellis

There exist a plethora of studies examining the psychological and physical impacts of COVID-19 on infected victims. Fewer studies have been published assessing the different types of impacts that an individual’s COVID-19 infection has on close friends and family members. This is the first scoping review to gauge the reported psychosocial issues and daily hassles that impact the relatives and friends of infected individuals. This study was conducted by inputting key terms/MeSH terms into selected internet databases to locate prospective studies. The frameworks of scoping reviews by Arksey et al. and the preferred reporting items for systematic review and meta-analyses (PRISMA) were utilized in the methodology for identifying and selecting the studies. After data extraction, 37 studies were deemed suitable for analysis. The findings generated from each study were placed into combined categories. A total of 16 combined categories were generated from the amalgamation of the findings. The results show that psychosocial feelings (e.g., anxiety, stress, and depression) were the category with the highest prevalence of grouped findings. The results from this study may serve as the impetus for future interventions targeting the alleviation of psychosocial feelings or day-to-day hassles associated with having a loved one inflicted with a severe illness.

BioMed doi: 10.3390/biomed3030027

Authors: Ronald B. Brown

Polypharmacy, the use of multiple and potentially inappropriate medications, is an increasing problem among older adults. The global polypharmacy prevalence is 34.6% in patients with COVID-19, and polypharmacy in COVID-19 increases with age. The present paper proposes that polypharmacy in older adults with COVID-19 and other comorbid conditions is linked to the medication outcome reporting bias of randomized controlled trials. Outcome reporting bias can occur when treatment efficacy is reported as relative risk reductions, which overestimates medication benefits and exaggerates disease/illness risk reductions compared to unreported absolute risk reductions. The comorbidities common in patients with COVID-19 include high blood pressure, cardiovascular disease, dementia or cerebrovascular disease, and diabetes. Accordingly, the present paper reassesses the relative and absolute risk reductions in clinical trials from a small convenience sample of antihypertension, statin, anticoagulant, and antihyperglycemic medications. Examples demonstrate a wide gap between reported relative risk reductions and unreported absolute risk reductions in medication clinical trials. This paper concludes that medication clinical trial outcome reporting bias is an important upstream factor that contributes to biased medication benefits and poor clinical decision making, leading to polypharmacy in older adults with COVID-19 and other comorbid conditions. Public health campaigns are urgently needed to educate the public about the link between polypharmacy and medication outcome reporting bias.

BioMed doi: 10.3390/biomed3030026

Authors: Dimitrios Spaggoulakis Antonios Kontaxakis Andreas Asimakos Stavroula Spetsioti Archontoula Antonoglou Pantelis Gounopoulos Martha Katsarou Helen Iasonidou Stergios-Stylianos Gatzonis Paraskevi Katsaounou

Dysautonomia in the post-COVID-19 condition appears to affect a significant number of patients, with reports raising the incidence up to 61%, having an overlap with myalgic encephalomyelitis/chronic fatigue syndrome. Quality of life and daily function are significantly impacted and conservative management interventions, despite the lack of high-quality evidence to date, are needed to ameliorate disability. A total of 50 adults with a dysautonomia post-COVID-19 diagnosis based on the Ewing battery and a NASA lean test will be enrolled in a randomized single blinded controlled trial with a crossover design. Feasibility and lack of definite dysautonomia diagnosis will be the primary outcomes, while secondary outcomes will be health-related, clinical and cardiopulmonary exercise test indicators. Safety and acceptance will also be checked, primarily excluding participants with post-exertional malaise. The Long-COVID patients Causal Diagnosis and Rehabilitation study in patients with Dysautonomia (LoCoDiRE-Dys) intervention will consist of an educational module, breathing retraining and an individualized exercise intervention of biweekly sessions for two months with regular assessment of both groups. LoCoDiRe-Dys aims to be the first post-COVID-19 randomized study in people with dysautonomia offering a multimodal intervention both in diagnosis and management. The need for evidence in effectively supporting patients is eminent.

BioMed doi: 10.3390/biomed3020025

Authors: Alexandra Moura Lara Lopes Luís Carlos Matos Jorge Machado Maria Begoña Criado

The rapid spread of the new coronavirus disease (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Although specific vaccines are available and natural drugs are being researched, supportive care and specific treatments to alleviate symptoms and improve patient quality of life remain critical. Chinese medicine (CM) has been employed in China due to the similarities between the epidemiology, genomics, and pathogenesis of SARS-CoV-2 and SARS-CoV. Moreover, the integration of other traditional oriental medical systems into the broader framework of integrative medicine can offer a powerful approach to managing the disease. Additionally, it has been reported that integrated medicine has better effects and does not increase adverse drug reactions in the context of COVID-19. This article examines preventive measures, potential infection mechanisms, and immune responses in Western medicine (WM), as well as the pathophysiology based on principles of complementary medicine (CM). The convergence between WM and CM approaches, such as the importance of maintaining a strong immune system and promoting preventive care measures, is also addressed. Current treatment options, traditional therapies, and classical prescriptions based on empirical knowledge are also explored, with individual patient circumstances taken into account. An analysis of the potential benefits and challenges associated with the integration of complementary and Western medicine (WM) in the treatment of COVID-19 can provide valuable guidance, enrichment, and empowerment for future research endeavors.

BioMed doi: 10.3390/biomed3020024

Authors: Mariacristina Poliseno Edoardo Paolo Drago Melita Anna Poli Maurantonio Altamura Serena Rita Bruno Angela Calamo Anna Giannelli Giovanni Infante Michele Mazzola Damiana Moschetta Sergio Lo Caputo Teresa Antonia Santantonio Sergio Carbonara

Despite the availability of vaccines and antivirals and the biological evolution of SARS-CoV-2, the rate of hospitalizations and deaths from COVID-19 remains high in Italy. It is crucial to understand whether and how the clinical characteristics of patients hospitalized for COVID-19 have changed over 2021–2022 and which risk factors are currently associated with adverse outcomes to develop targeted interventions. In this study, we present and compare the characteristics and outcomes of 310 patients with COVID-19 who were hospitalized between 1 August and 9 December 2021, when the Delta SARS-CoV-2 variant was prevalent (Group A), and between 3 January and 30 June 2022, when the Omicron variant was predominant (Group B). Using Survival Analysis, we estimated the cumulative 28-day hazard ratio (H.R.) of Intensive Care Unit (ICU) admission/death of patients in Group B vs. A. We built uni- and multivariate Cox regression models for the overall population and each group to identify risk factors for ICU admission/death among patient features. We found that Group B had a comparable risk of ICU admission/death (HR 1.60, 95% Confidence Interval, C.I. 1.00–2.58, p = 0.05) but a higher prevalence of elderly and co-morbid subjects than Group A. Non-invasive ventilation requirement was associated with adverse outcomes in both Group A (HR 21.03, 95% C.I. 5.34–82.80, p < 0.001) and Group B (HR 4.53, 95% C.I. 2.39–8.59, p < 0.001), as well as in the overall population (HR 3.88, 95% C.I. 2.49–6.06, p < 0.001). During the Omicron wave, elderly and co-morbid subjects had the highest risk of hospitalization and poor outcomes.

BioMed doi: 10.3390/biomed3020023

Authors: Matthew T. J. Halma Joshua Guetzkow

The COVID crisis of the past three years has greatly impacted stakeholder relationships between scientists, health providers, policy makers, pharmaceutical industry employees, and the public. Lockdowns and restrictions of civil liberties strained an already fraught relationship between the public and policy makers, with scientists also seen as complicit in providing the justification for the abrogation of civil liberties. This was compounded by the suppression of open debate over contentious topics of public interest and a violation of core bioethical principles embodied in the Nuremberg Code. Overall, the policies chosen during the pandemic have had a corrosive impact on public trust, which is observable in surveys and consumer behaviour. While a loss of trust is difficult to remedy, the antidotes are accountability and transparency. This narrative review presents an overview of key issues that have motivated public distrust during the pandemic and ends with suggested remedies. Scientific norms and accountability must be restored in order to rebuild the vital relationship between scientists and the public they serve.