BioMed

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article