Clinical actionability

Lysine specific demethylase-1 (LSD1) serves as a regulator of transcription and represents a promising epigenetic target for anticancer treatment. LSD1 inhibitors are in clinical trials for the treatment of Ewing's sarcoma (EWS), acute myeloid leukemia, and small cell lung cancer, and the development of robust inhibitors requires accurate methods for probing demethylation, potency, and selectivity. Here, the inhibition kinetics on the H3K4me2 peptide and nucleosome substrates was examined, comparing the rates of demethylation in the presence of reversible [CC-90011 (PD) and SP-2577 (SD)] and irreversible [ORY-1001 (ID) and tranylcypromine (TCP)] inhibitors...

OBJECTIVES: For over 30 years, quality improvement (QI) methods have been used as a means of increasing the quality and safety of healthcare services, but with mixed success. One explanation highlighted in the literature for this outcome is the overemphasis on technical elements of change, and a failure to fully appreciate the human side of change. Behavioral insights (BI) is an approach that utilizes knowledge and tools from a broad range of scientific disciplines, such as neuroscience and behavioral psychology, to support behavior change...

Plants provide a wide array of compounds that can be explored for potential anticancer properties. Siphonochilone, a furanoterpene that represents one of the main components of the African plant Siphonochilus aethiopicus, shows numerous health benefits. However, to date, its antiproliferative properties have not been tested. The aim of this study was to analyze the cytotoxic effects of siphonochilone on a panel of cancer cell lines and its underlying mechanism of action. Our results demonstrated that siphonochilone exhibited significant cytotoxic effects on pancreatic, breast, lung, colon, and liver cancer cell lines showing a IC50 ranging from 22 to 124 μM at 72 h of treatment and highlighting its cytotoxic effect against MCF7 and PANC1 breast and pancreas cancer cell lines (22...

Variants of the oxygen free radical scavenging enzyme superoxide dismutase-1 (SOD1) are associated with the neurodegenerative disease amyotrophic lateral sclerosis (ALS). These variants occur in roughly 20% of familial ALS cases, and 1% of sporadic ALS cases. Here, we identified a novel SOD1 variant in a patient in their 50s who presented with movement deficiencies and neuropsychiatric features. The variant was heterozygous and resulted in the isoleucine at position 149 being substituted with a serine (I149S)...

INTRODUCTION: Unilateral gamma knife thalamotomy (GKT) is a treatment option for pharmacoresistant tremor of various aetiologies. There have been to date no randomised controlled trials performed to assess its safety and efficacy. Our aim was to summarise a two-year multimodal observation of patients with tremor caused by Parkinson's Disease (PD) or essential tremor (ET). MATERIAL AND METHODS: 23 patients with PD (n = 12) or ET (n = 11) were included. They underwent assessments before, V0 (n = 23), and 12 months, V12 (n = 23), and 24 months, V24 (n = 15), after unilateral GKT...

The development of engineered nanomaterials has been considered a promising strategy to control oral infections. In this study, silver-embedded carbon nitrides (Ag@g-CN) were synthesized and tested against Candida albicans , investigating their antifungal action and biocompatibility in animal cells. Ag@g-CN was synthesized by a simple one-pot thermal polymerization technique and characterized by various analytical techniques. X-ray diffraction (XRD) analysis revealed slight alterations in the crystal structure of g-CN upon the incorporation of Ag...

Universal depression screening in adolescent primary care often encompasses questions about suicide risk. We conducted a retrospective chart review of well-child visits where adolescents (ages 13-17.9) had endorsed self-injurious thoughts and behaviors or suicidal ideation. The goal was to investigate primary care providers' follow-up actions, including documentation, further assessment, and referrals. Over 3-quarters of the progress notes showed evidence of further assessment, and two-thirds documented same-day actions, including mental health referrals, emergency department referrals, safety plans, medication changes, primary-care follow-up, and talking to parents...

Obesity, a chronic global health problem, is associated with an increase in various comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, hypertension, and certain types of cancer. The increasing global prevalence of obesity requires research into new therapeutic strategies. Glucagon-like peptide-1 receptor agonists, specifically semaglutide and liraglutide, designed for type 2 diabetes mellitus treatment, have been explored as drugs for the treatment of obesity. This minireview describes the molecular mechanisms of semaglutide and liraglutide in different metabolic pathways, and its mechanism of action in processes such as appetite regulation, insulin secretion, glucose homeostasis, energy expenditure, and lipid metabolism...

BACKGROUND: Primary central nervous system (CNS) lymphoma is a very rare extranodal non-Hodgkin lymphoma. The bilateral pattern, as we call it "mirror type", has been identified in other CNS lesions such as gliomas, metastases, and demyelinating lesions, so the differential diagnosis includes imaging studies such as magnetic resonance imaging contrasted with spectroscopy, ruling out immunodeficiency or metastatic disease. CASE DESCRIPTION: A 65-year-old female presented progressing headache, loss of memory and language alterations, as well as sensory alterations...

In this study, a molecularly imprinted polymer film (MIP) was prepared on the surface of a disposable carbon screen-printed electrode (C-SPE) using (3-acrylamidopropyl)trimethylammonium chloride (AMPTMA) as a functional monomer and the cancer biomarker carbohydrate antigen 15-3 (CA 15-3) as a template. The MIP was synthesized by in situ electropolymerization (ELP) of the AMPTMA monomer in the presence of the CA 15-3 protein on the C-SPE surface. The target was subsequently removed from the polymer matrix by the action of proteinase K, resulting in imprinted cavities with a high affinity for CA 15-3...

The sources of antimicrobial peptides (AMPs), also known as peptide-based antibiotics, are diverse, such as plants, animals, microorganisms including human leukocytes, saliva, human defense peptides, and human sweat. These natural sources provide a rich variety of AMPs with unique characteristics and potential therapeutic applications, including wound-healing and antimicrobial properties. AMPs derived from these sources have shown promise in combating a wide range of pathogens, making them valuable targets for further research and potential clinical applications...

BACKGROUND: Abuse of healthcare workers (HCWs) and lack of public trust threaten the foundation of the physician-patient relationship. This growing global problem creates an even more difficult professional environment and hinders the delivery of high-quality clinical care. OBJECTIVE: The primary aim was to determine the prevalence of violence against Trinbagonian HCWs in the public sector. Secondary objectives included determining risk factors for violence and mistrust between the public and providers...

BACKGROUND:  Sequential combined spinal epidural anesthesia (CSEA) is probably the greatest advancement in the central neuraxial block in this decade for geriatric patients due to the potential advantages of both spinal and epidural anesthesia. This study was designed to compare the clinical effects of sequential CSEA versus spinal and epidural anesthesia in geriatric patients undergoing transurethral resection of the prostate (TURP). METHODS:  Ninety patients aged 65 to 80 years were randomly allocated into three groups of 30 each...

Phycotoxins are responsible for foodborne intoxications. Symptoms depend on the ingested toxins but mostly imply gastro-intestinal and neurological disorders. Importantly, humans are exposed to combinations of several phycotoxins, resulting in possible mixture effects. Most previous studies, however, have been focused on single toxin effects. Thus, the aim of this study was to examine the effects of binary mixtures of three main phycotoxins, okadaic acid (OA), azaspiracid-1 (AZA1) and yessotoxin (YTX), on human intestinal Caco-2 cells...

OBJECTIVES: This study assessed the transparency and replicability of exercise-based interventions following bariatric surgery by evaluating the content reporting of exercise-based clinical trials. DESIGN: The study design of the present article is a systematic review. DATA SOURCES: PubMed, Scopus, Web of Sciences, PsycINFO, and Cochrane were searched from their inception to May 2023. ELIGIBILITY CRITERIA: Eligible studies were clinical trials including exercise interventions in participants following bariatric surgery...

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BACKGROUND AND PURPOSE: Nicorandil, a selective opener of potassium channels, used to treat angina, has drawn attention for its potential in mitigating lung injury, positioning it as a promising therapeutic approach to treat drug-induced lung toxicity. This study aimed to explore the protective role of nicorandil in arsenic trioxide (ATO)-induced lung injury and to elucidate the underlying mechanistic pathways. EXPERIMENTAL APPROACH: We assessed the effects of nicorandil (15 mg·kg-1 , p...

The emergence of personalized medicine, facilitated by the progress in -omics technologies, has initiated a new era in medical diagnostics and treatment. This review examines the potential of -omics approaches in heart failure, a condition that has not yet fully capitalized on personalized strategies compared to other medical fields like cancer therapy. Here, we argue that integrating multi-omics technology with systems medicine approaches could fundamentally transform heart failure management, moving away from the traditional paradigm of 'one size fits all'...

BACKGROUND: The Global Patient Safety Action Plan, an initiative of the World Health Organization (WHO), draws attention to patient safety as being an issue of utmost importance in healthcare. In response, the World Federation of Chiropractic (WFC) has established a Global Patient Safety Task Force to advance a patient safety culture across all facets of the chiropractic profession. This commentary aims to introduce principles and call upon the chiropractic profession to actively engage with the Global Patient Safety Action Plan beginning immediately and over the coming decade...

BACKGROUND: Estetrol (E4) is a natural estrogen produced by the fetal liver during pregnancy. Due to its favorable safety profile, E4 was recently approved as estrogenic component of a new combined oral contraceptive. E4 is a selective ligand of estrogen receptor (ER)α and ERβ, but its binding to the G Protein-Coupled Estrogen Receptor (GPER) has not been described to date. Therefore, we aimed to explore E4 action in GPER-positive Triple-Negative Breast Cancer (TNBC) cells...