Elevated serum vitamin B12 concentrations in a patient with pancreatic exocrine insufficiency.

This case describes a patient with pancreatic exocrine insufficiency and persistently elevated serum vitamin B12 concentrations that were not due to supplementation or associated with hepatic or hematological pathology. Laboratory investigations suggested the presence of macro-B12 as the cause of this patient's raised serum vitamin B12. Macro-B12 is often formed when vitamin B12-vitamin binding proteins (transcobalamin and haptocorrin) complex with immunoglobulins.

Caution when using network partners for target identification in drug discovery.

Identifying novel, high-yield drug targets is challenging and often results in a high failure rate. However, recent data indicates that leveraging human genetic evidence to identify and validate these targets significantly increases the likelihood of success in drug development. Two recent papers from Open Targets claimed that around half of FDA-approved drugs had targets with direct human genetic evidence.

Interdisciplinary Oral Nutrition Support and Supplementation After Hip Fracture Surgery in Older Adult Inpatients: A Global Cross-Sectional Survey (ONS-STUDY).

Background: Malnutrition predicts poor outcomes following hip fracture, affecting patient recovery, healthcare performance, and costs. Evidence-based guidelines recommend multicomponent, interdisciplinary nutrition care to improve intake, reduce complications, and enhance outcomes. This study examines global variation in oral nutrition support for older (65+ years) hip fracture inpatients.

TMJ Replacement in Degenerative Disease: A Systematic Review.

: This study aims to describe and analyze the indications and clinical results of total TMJ replacement in participants with degenerative and/or inflammatory joint diseases, defining patient and intervention conditions. : A systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Intervention and reported according to the PRISMA Items update. The search strategy was from 1997 to July 2024 in Pubmed, Embase, Scopus, and Web of Science.

Exosomal Liquid Biopsy in Prostate Cancer: A Systematic Review of Biomarkers for Diagnosis, Prognosis, and Treatment Response.

Prostate cancer, a leading cause of cancer-related mortality among men, often presents challenges in accurate diagnosis and effective monitoring. This systematic review explores the potential of exosomal biomolecules as noninvasive biomarkers for the diagnosis, prognosis, and treatment response of prostate cancer. A thorough systematic literature search through online public databases (Medline via PubMed, Scopus, and Web of science) using structured search terms and screening using predefined eligibility criteria resulted in 137 studies that we analyzed in this systematic review.

Soluble Herpes Virus Entry Mediator and Type II/III Interferons Are Upregulated in Primary Biliary Cholangitis.

Bacterial translocation-induced inflammation and immune dysfunction are recognised factors contributing to the pathogenesis of primary biliary cholangitis (PBC). However, the specific involvement of interferons (IFNs) and soluble checkpoints (sol-CRs) in shaping the immune landscape in PBC patients remains unexplored. Furthermore, the influence of ursodeoxycholic acid (UDC) on these immune mediators is unknown.

Updates in Biliary Atresia: Aetiology, Diagnosis and Surgery.

Biliary atresia (BA) is an obliterative disease of the bile ducts affecting between 1 in 10,000-20,000 infants with a predominance in Asian countries. It is clinically heterogeneous with a number of distinct variants (e.g.

Normothermic Crystalloid Polarizing Cardioplegia Improves Systolic and Diastolic Function in a Porcine Model of Cardiopulmonary Bypass.

Previously, we showed that blood-based polarizing cardioplegia exerted beneficial cardioprotection during hypothermic ischemia; however, these positive effects of blood-based polarizing cardioplegia were reduced during normothermic ischemia compared to blood-based hyperkalemic (depolarizing) cardioplegia. This study compares crystalloid polarizing cardioplegia to crystalloid depolarizing cardioplegia in a normothermic porcine model of cardiopulmonary bypass; Methods: Twelve pigs were randomized to receive either normothermic polarizing ( = 7) or depolarizing ( = 5) crystalloid cardioplegia. After the initiation of cardiopulmonary bypass, normothermic arrest (34 °C, 60 min) was followed by 60 min of on-pump and 90 min of off-pump reperfusion.

Bariatric Surgery as a Molecular Modulator: The Role of FSHR Polymorphisms in Enhancing eNOS Expression and Reproductive Hormone Dynamics in Women with Severe Obesity.

Background/objectives: Severe obesity (BMI > 40 kg/m) has a severe influence on vascular health and reproduction. This study looks at how bariatric surgery affects endothelial nitric oxide synthase (eNOS) expression and reproductive hormone regulation across different follicle-stimulating hormone receptor (FSHR) polymorphism groups in women with extreme obesity.

Methods: Twenty-nine women with extreme obesity had bariatric surgery.

Performance analysis of Leica Biosystems p16 monoclonal antibody in oropharyngeal squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer death globally, with newly diagnosed oropharyngeal squamous cell carcinoma (OPSCC) cases rising to 54,000 in the US alone in the year 2022. Recently, human papilloma virus (HPV) infection was more prevalent in OPSCC patients than the traditionally known carcinogens such as tobacco or alcohol. HPV 16 is the most common causative HPV strain, which is found in 5-10% of HNSCC patients.

Access to child-appropriate medicines: an exploratory survey of the use of paediatric use marketing authorisation products in the UK.

The Paediatric Use Marketing Authorisation (PUMA) was introduced in the European Union to incentivise the development of off-patent medicines in children. However, there is limited data on the accessibility of PUMA products at the healthcare provider level. This study aimed to identify factors affecting real-world accessibility to PUMA products in the United Kingdom (UK).

Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease.

Obesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity strongly influences circulating protein levels, we investigated proteins mediating the effects of obesity on coronary artery disease, stroke and type 2 diabetes. By integrating two-step proteome-wide Mendelian randomization, colocalization, epigenomics and single-cell RNA sequencing, we identified five mediators and prioritized collagen type VI α3 (COL6A3).

Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

Molecular allergy diagnosis enabling personalized medicine.

Allergic patients are characterized by complex and patient-specific IgE sensitization profiles to various allergens, which are accompanied by different phenotypes of allergic disease. Molecular allergy (MA) diagnosis establishes the patient's IgE reactivity profile at a molecular allergen level and has moved allergology into the "Precision Medicine" era. Molecular allergology started in the late 1980s with the isolation of the first allergen-encoding DNA sequences.

Raman Spectroscopic Probe Provides Optical Biomarkers of Cartilage Composition Predictive of Tissue Function.

Objective: The diagnosis of early osteoarthritis when therapeutic interventions may be most effective at reversing cartilage degeneration presents a clinical challenge. We describe a Raman arthroscopic probe and spectral analysis that measures biomarkers reflective of the content of predominant cartilage ECM constituents-glycosaminoglycans (GAG), collagen, water-essential to cartilage function. We compare the capability of Raman-probe-derived biomarkers to predict functional properties of cartilage to quantitative MRI and histopathology assessments.

Predicting a strongly positive fluid balance in critically ill patients with acute kidney injury: A multicentre, international study.

Background: In critically ill patients with acute kidney injury (AKI), a fluid balance (FB) > 2 L at 72 h after AKI diagnosis is associated with adverse outcomes. Identification of patients at high-risk for such fluid accumulation may help prevent it.

Methods: We used Australian electronic medical record (EMR)-based clinical data to develop the "AKI-FB risk score", validated it in a British cohort and used it to predict a positive FB >2 L at 72 h after AKI diagnosis.

Exploring specific alterations at the explicit and perceptual levels in sense of ownership, agency, and body schema in Functional Motor Disorder: A pilot comparative study with Irritable Bowel Syndrome.

Functional Motor Disorders (FMD) consists in symptoms of altered motor function not attributable to typical neurological and medical conditions. This study aimed to explore explicit and perceptual measures of Sense of Ownership, Agency, and Body Schema in FMD patients, and assess whether these alterations are specific to FMD or shared with other functional disturbances. Twelve FMD patients, ten with Irritable Bowel Syndrome (IBS, a functional gastrointestinal disorder) and fifteen healthy controls (HC) underwent: (i) the Mirror Box Illusion (MBI), requiring participants to perform tapping movements with their dominant hand concealed from sight, while visual feedback was provided by an alien hand under visuo-motor congruency or incongruency conditions; (ii) a Forearm Bisection Task before and after exposure to the MBI, and the Embodiment Questionnaire after the MBI, as perceptual and explicit indices of the embodiment illusion, respectively.

At mid gestation, markers of placental function rather than maternal cardiac function are stronger determinants of birthweight.

Background: The role of maternal cardiac and hemodynamic assessment during normal and complicated pregnancies has gained attention during the last few years. Some researchers suggested that the manifestation of complications in pregnancy suffering from impaired placentation is mainly driven by pre-existing cardiac changes, identifiable at an early stage by echocardiographic and hemodynamic assessment. It is therefore of great importance to determine the link between placental perfusion and maternal cardiac function and hemodynamics.

Surgical Site Infection after Craniotomy in Neuro-Oncology (SINO): A protocol for an international prospective multicentre service evaluation across the United Kingdom and Ireland.

Introduction: Given its proximity to the central nervous system, surgical site infections (SSIs) after craniotomy (SSI-CRAN) represent a serious adverse event. SSI-CRAN are associated with substantial patient morbidity and mortality. Despite the recognition of SSI in other surgical fields, there is a paucity of evidence in the neurosurgical literature devoted to skin closure, specifically in patients with brain tumors.

A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms.

Background: Healthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a 'pro-nociceptive profile' cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti-nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation.