Engineering a high-throughput clone for industrial-scale production of long-acting GLP-1 analogue with retained bio-efficacy.

Type 2 diabetes mellitus (T2DM) and obesity are critical global health issues with rising incidence rates. Glucagon-like peptide-1 (GLP-1) analogues have emerged as effective treatments due to their ability to regulate blood glucose levels and gastric emptying through central nervous signals involving hypothalamic receptors, such as leptin. To address the short plasma half-life of native GLP-1, a C-16 fatty acid was conjugated to lysine in the GLP-1 analogue sequence to enhance its longevity.

Disruptive multiple cell death pathways of bisphenol-A.

Endocrine-disrupting chemicals (EDCs) significantly contribute to health issues by interfering with hormonal functions. Bisphenol A (BPA), a prominent EDC, is extensively utilized as a monomer and plasticizer in producing polycarbonate plastic and epoxy resins, making it one of the highest-demanded chemicals in commercial use. This is the major component used in plastic products, including bottles, containers, storage items, and food serving ware.

Development and Beta Validation of an mHealth-Based Hearing Screener (SRESHT) for Young Children in Resource-Limited Countries: Pilot Validation Study.

Background: The prevalence of hearing loss in infants in India varies between 4 and 5 per 1000. Objective-based otoacoustic emissions and auditory brainstem response have been used in high-income countries for establishing early hearing screening and intervention programs. Nevertheless, the use of objective screening tests in low- and middle-income countries (LMICs) such as India is not feasible.

The interplay of heart rate variability and ventricular repolarization parameters in the obese state: a review.

The impact of obesity on heart rate variability (HRV) and ventricular repolarization, both vital indicators of cardiovascular health, is the focus of this review. Obesity, measured by BMI, waist circumference, and waist-to-hip ratio, significantly increases cardiovascular disease (CVD) risk due to structural and autonomic heart changes. Findings show that obese individuals exhibit prolonged QT and Tpeak-to-Tend (Tpe) intervals, suggesting delayed ventricular recovery and greater arrhythmia risk.

A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.

Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.

Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.

Malpractice Liability Exposure and the Sports Medicine Team Physician: Caring for Professional Athletes in the National Football League, Major League Baseball, and National Hockey League.

Background: Orthopaedic surgeons play a critical role in ensuring the health and safety of professional athletes. Despite the privilege of treating elite athletes, there exists great financial exposure to individual physicians in the event of a malpractice lawsuit.

Hypothesis/purpose: The purpose of this study was to evaluate and model malpractice liability exposure of the sports medicine surgeon caring for athletes in the National Football League (NFL), Major League Baseball (MLB), and National Hockey League (NHL) with respect to player position and additional supplemental malpractice insurance needs.

Hypertension and obesity independently drive hypertrophy and alter mitochondrial metabolism in a mouse model of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) has recently emerged as an insidiously and increasingly prevalent heart failure phenotype. HFpEF often occurs in the context of hypertension and obesity and presents with diastolic dysfunction, ventricular hypertrophy, and myocardial fibrosis. Despite growing study of HFpEF, the causal links between early metabolic changes, bioenergetic perturbations, and cardiac structural remodeling remain unclear.

Aging-dependent Change in Th17 and Cytokine Response in Multiple Sclerosis.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease damaging the central nervous system. Diminished inflammatory disease activity (DA) as people with MS (pwMS) age motivated randomized clinical trials assessing disease-modifying therapy (DMT) discontinuation in older pwMS given the concern for risks outweighing benefits. This study aims to examine whether peripheral production of Myelin Basic Protein (MBP)-driven cytokine responses mediate the aging-associated decline in MS inflammatory DA.

Role of miR-125b-5p in modulating placental SIRT7 expression and its implications for lipid metabolism in gestational diabetes.

Gestational diabetes is marked impaired glucose tolerance, poses various adverse outcomes including increased BMI and obesity. These outcomes results from excess lipid accumulation which is marked by elevated triglycerides. In GDM, placenta exhibits altered lipid metabolism, including reduced fatty acid oxidation and increased triglyceride accumulation.

Effectiveness of Inhalational Tranexamic Acid in Patients with Nonmassive Hemoptysis-A Systematic Review and Meta-Analysis.

Background: Hemoptysis, the expectoration of blood from the lower respiratory tract, varies in severity and necessitates effective management to mitigate morbidity. Traditional treatments include bronchial artery embolization and pharmacological approaches. Tranexamic acid (TXA), an antifibrinolytic agent known for its efficacy in reducing bleeding during surgery and trauma, is being explored for its efficacy in treating Hemoptysis via both intravenous and inhalational routes.

Challenges in the implementation of cardio-oncology trials: lessons learnt from investigating statins in the prevention of anthracycline cardiotoxicity.

Despite advanced in targeted cancer therapies, anthracyclines remain essential in treating various malignancies, albeit with risks of cancer therapy-related cardiac dysfunction (CTRCD). Out of the myriad of mitigation strategies for CTRCD, statins are an attractive preventive therapy for anthracycline associated CTRCD given their widespread availability, cheap costs and added benefit of atherosclerotic cardiovascular disease (ASCVD) risk reduction. Recent trials of PREVENT, SPARE-HF, and STOP-CA investigated atorvastatin's efficacy in preventing CTRCD, with mixed outcomes.

Large Language Models Applied to Health Care Tasks May Improve Clinical Efficiency, Value of Care Rendered, Research, and Medical Education.

Large language models (LLMs) are generative artificial intelligence models that create content on the basis of the data on which it was trained. Processing capabilities have evolved from text only to being multimodal including text, images, audio, and video features. In health care settings, LLMs are being applied to several clinically important areas, including patient care and workflow efficiency, communications, hospital operations and data management, medical education, practice management, and health care research.

Ethical Application of Generative Artificial Intelligence in Medicine.

Generative artificial intelligence (AI) may revolutionize health care, providing solutions that range from enhancing diagnostic accuracy to personalizing treatment plans. However, its rapid and largely unregulated integration into medicine raises ethical concerns related to data integrity, patient safety, and appropriate oversight. One of the primary ethical challenges lies in generative AI's potential to produce misleading or fabricated information, posing risks of misdiagnosis or inappropriate treatment recommendations, which underscore the necessity for robust physician oversight.

Editorial Commentary: Thoughtful Application of Artificial Intelligence Technique Improves Diagnostic Accuracy and Supportive Clinical Decision-Making.

Medical research within areas of deep learning, particularly in computer vision for medical imaging, has shown promise over the past decade with an increasing volume of technical papers published in orthopaedics related to imaging artificial intelligence (AI). However, as more tools and models are developed and deployed, it is easy for clinicians to get overwhelmed with the different types of models, leaving "artificial intelligence" as an empty buzzword where true value can be unclear. As with surgery, the techniques of deep learning require thoughtful application and cannot follow a one-size-fits-all approach as different problems require differential levels of technical complexity with model application.

Statin Consumption and Appealing Colors: Exploring Statin-Related Injuries for Children Under the Age of Three Years.

Introduction: Statins are frequently prescribed to lower the risk of atherosclerosis and cardiovascular-related diseases. While statins are considered safe, there are occasional accidental overdoses in children that warrant concern for how to protect children from unintended consumption. We aimed to determine which statins were more prone to injury, characterize the injury types commonly seen for each statin, assess the age at which statin-related injuries were most frequent, and compare statin-related injuries among genders.

Therapeutic potential of SMAD7 targeting miRNA in the pathogenesis of diabetic nephropathy.

Diabetic nephropathy (DN) is a common complication of diabetes and a leading cause of end-stage renal disease, characterized by progressive kidney fibrosis and inflammation. The transforming growth factor-beta (TGF-β) signaling pathway plays a crucial role in the pathogenesis of diabetes nephropathy, and SMAD7 is a key negative regulator of this pathway. Recent studies have highlighted the involvement of miRNA in the progression of DN.

Applications of Artificial Intelligence for Health Care Providers.

Recent research shows that physicians lack the knowledge and ability to use artificial intelligence (AI) effectively. We thus introduce a new series of articles, "Applications of Artificial Intelligence for Health Care Providers." Like the arthroscope, AI is a powerful tool, and we must adapt our skills to effectively incorporate and apply this tool in our practices.

Immunotherapy-mediated myocarditis and concurrent vasospastic angina in a patient with established ischaemic heart disease: a case report.

Background: Immunotherapy has become a pillar of modern oncological management but is associated with significant immunotherapy-related adverse events (IRAEs). While myocarditis is a prominent IRAE which clinicians are increasingly aware of, immunotherapy-related coronary vasospasm is far less appreciated and can be especially difficult to elucidate in pre-existing coronary artery disease. This case demonstrates the approach to diagnosis and management of multiple cardiovascular and non-cardiovascular IRAEs.

Pseudoaneurysms of lower limb of orthopaedic traumatological origin: a literature review and our experience of 18 cases.

Introduction And Aims: Arterial pseudoaneurysm is a rare yet potentially life-threatening complication that can arise as a late sequelae of penetrating injuries or orthopaedic procedures. We aim at sharing our institutional experience of managing 18 cases of lower limb arterial pseudoaneurysms in orthopaedic practice and to provide technical tips for emergency management of severe bleeding. A comprehensive literature review resulting from fractures and orthopaedic surgeries is also presented.

Enhancing human activity recognition for the elderly and individuals with disabilities through optimized Internet-of-Things and artificial intelligence integration with advanced neural networks.

Elderly and individuals with disabilities can greatly benefit from human activity recognition (HAR) systems, which have recently advanced significantly due to the integration of the Internet of Things (IoT) and artificial intelligence (AI). The blending of IoT and AI methodologies into HAR systems has the potential to enable these populations to lead more autonomous and comfortable lives. HAR systems are equipped with various sensors, including motion capture sensors, microcontrollers, and transceivers, which supply data to assorted AI and machine learning (ML) algorithms for subsequent analyses.

Lower Island Trapezius Flap for a Rare Scalp Tumor.

A 54-year-old male with a past history of acute pancreatitis and pulmonary embolism presented with a scalp tumor in the occipital region for a six-month duration. With a biopsy report of squamous cell carcinoma, wide local excision with the lower island trapezius myocutaneous flap with skin grafting was done. However, the final pathology report revealed a proliferating trichilemmal tumor with clear margins.

A Co-Culture System for Studying Cellular Interactions in Vascular Disease.

Cardiovascular diseases (CVDs) are leading causes of morbidity and mortality globally, characterized by complications such as heart failure, atherosclerosis, and coronary artery disease. The vascular endothelium, forming the inner lining of blood vessels, plays a pivotal role in maintaining vascular homeostasis. The dysfunction of endothelial cells contributes significantly to the progression of CVDs, particularly through impaired cellular communication and paracrine signaling with other cell types, such as smooth muscle cells and macrophages.

Enhancing Outcomes and Efficiency in Large Epidermal Cyst Management: Quality Improvement Approach in Primary Care.

Background: Epidermal cysts are common benign lesions encountered in primary care, especially in minor surgery clinics. The management of large epidermal cysts (>5 cm in diameter) poses significant challenges, including surgical intervention requirements, potential for complications, and impacts on patient care and clinic workflow. The prevalence of these cysts underlines the need for optimised management strategies that are essential for enhancing patient outcomes and clinic efficiency.