BioMed

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article