BioMed

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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