Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake.

Leptin is an adipose tissue hormone that maintains homeostatic control of adipose tissue mass by regulating the activity of specific neural populations controlling appetite and metabolism. Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons. However, whereas AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect.

A subcortical feeding circuit linking an interoceptive node to jaw movement.

The brain processes an array of stimuli, enabling the selection of appropriate behavioural responses, but the neural pathways linking interoceptive inputs to outputs for feeding are poorly understood. Here we delineate a subcortical circuit in which brain-derived neurotrophic factor (BDNF)-expressing neurons in the ventromedial hypothalamus (VMH) directly connect interoceptive inputs to motor centres, controlling food consumption and jaw movements. VMH neuron inhibition increases food intake by gating motor sequences of feeding through projections to premotor areas of the jaw.

In Silico Insights: QSAR Modeling of TBK1 Kinase Inhibitors for Enhanced Drug Discovery.

TBK1, or TANK-binding kinase 1, is an enzyme that functions as a serine/threonine protein kinase. It plays a crucial role in various cellular processes, including the innate immune response to viruses, cell proliferation, apoptosis, autophagy, and antitumor immunity. Dysregulation of TBK1 activity can lead to autoimmune diseases, neurodegenerative disorders, and cancer.

Mice Condition Cephalic-Phase Insulin Release to Flavors Associated with Postoral Actions of Concentrated Glucose.

Rats can condition cephalic-phase insulin responses (CPIRs) to specific sounds or times of the day that predict food availability. The present study asked whether mice can condition a CPIR to the flavor of sapid solutions that produce postoral glucose stimulation. To this end, we subjected C57BL/6 mice to one of six experimental protocols.

Emerging Targets and Therapeutics in Immuno-Oncology: Insights from Landscape Analysis.

In the ever-evolving landscape of cancer research, immuno-oncology stands as a beacon of hope, offering novel avenues for treatment. This study capitalizes on the vast repository of immuno-oncology-related scientific documents within the CAS Content Collection, totaling over 350,000, encompassing journals and patents. Through a pioneering approach melding natural language processing with the CAS indexing system, we unveil over 300 emerging concepts, depicted in a comprehensive "Trend Landscape Map".

Genetic mapping of , a pupal lethal mutation in .

An EMS mutagenesis screen was conducted in to identify growth control mutants. The multi-institution Fly-CURE consortium phenotypically characterized the mutant using the system which displayed a mutant lethal phenotype with reduced head development, and darkened ocular tissue. Complementation mapping was conducted to identify the affected gene.

Quantitative Structure-Activity Relationship Machine Learning Models and their Applications for Identifying Viral 3CLpro- and RdRp-Targeting Compounds as Potential Therapeutics for COVID-19 and Related Viral Infections.

In response to the ongoing COVID-19 pandemic, there is a worldwide effort being made to identify potential anti-SARS-CoV-2 therapeutics. Here, we contribute to these efforts by building machine-learning predictive models to identify novel drug candidates for the viral targets 3 chymotrypsin-like protease (3CLpro) and RNA-dependent RNA polymerase (RdRp). Chemist-curated training sets of substances were assembled from CAS data collections and integrated with curated bioassay data.

Progress on the BL2 beam measurement of the neutron lifetime.

A precise value of the neutron lifetime is important in several areas of physics, including determinations of the quark-mixing matrix element │ │, related tests of the Standard Model, and predictions of light element abundances in Big Bang Nucleosynthesis models. We report the progress on a new measurement of the neutron lifetime utilizing the cold neutron beam technique. Several experimental improvements in both neutron and proton counting that have been developed over the last decade are presented.

Low vaccination rates among patients with rheumatoid arthritis in a German outpatient clinic.

Patients with rheumatoid arthritis (RA) are at an increased risk of acquiring infections due to two reasons: the disease itself and the immunosuppressive therapy. Vaccinations against preventable diseases are therefore of utmost importance for these group of patients. To estimate vaccination frequencies among patients with rheumatoid arthritis, we studied patients in a survey and calculated vaccination rates based on their vaccination documents.

Adjunctive Bare-Metal Stenting Associated With Improved Outcomes in Patients With Multivessel Disease Treated With Drug-Eluting Stents.

Background: The use of both bare-metal stents (BMSs) and drug-eluting stents (DESs) in the setting of multivessel percutaneous coronary intervention (PCI) continues because of cost considerations.

Methods: A retrospective analysis of patients with ≥ 2 coronary arteries with angiographic stenoses of ≥ 70% severity who were treated with multivessel PCI and ≥ 2 stents between April 2007 and March 2011 was performed using a prospective single-centre PCI registry. Follow-up data were obtained from the Discharge Abstract Database of the Canadian Institute for Health Information and the Registered Persons Database.

Clinical outcomes of treatment by percutaneous coronary intervention versus coronary artery bypass graft surgery in patients with chronic kidney disease undergoing index revascularization in Ontario.

Background: There is a paucity of data on the comparative effectiveness of percutaneous coronary intervention using contemporary drug-eluting stent (DES) compared with coronary artery bypass graft (CABG) surgery in patients with chronic kidney disease.

Methods And Results: A population-based study was performed using the Cardiac Care Network, a provincial registry of all patients undergoing cardiac catheterization in Ontario, to evaluate patients treated with either percutaneous coronary intervention using DES or CABG between October 1, 2008, and September 30, 2011. Chronic kidney disease was defined as creatinine clearance <60 mL/min.

Rotational atherectomy through the radial artery is associated with similar procedural success when compared with the transfemoral route.

Objectives: Rotational atherectomy (RA) has traditionally been carried out using 7 or 8 Fr guides through a transfemoral approach to allow for passage of 2.0 mm burrs or larger. With transradial percutaneous coronary intervention becoming more common, our aim was to investigate whether transradial RA would offer equivalent rates of procedural success when compared with transfemoral RA.

Long-term outcome of unprotected left main stenting: a Canadian tertiary care experience.

Background: Coronary stenting is increasingly used to treat unprotected left main disease in selected patients. However, there is a paucity of data on the long-term outcome of these patients in a Canadian context outside of clinical trials.

Methods: We retrospectively reviewed all provincially-insured patients undergoing left main coronary stenting at a large tertiary referral centre from 2000-2011.

Association between drug-eluting stent type and clinical outcomes in patients with chronic kidney disease undergoing percutaneous coronary intervention.

Background: The comparative efficacy of first- vs second-generation drug-eluting stents (DESs) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) is unknown.

Methods: A retrospective analysis of consecutive patients undergoing PCI at a tertiary PCI center from 2007-2011 was performed, with linkage to administrative databases for long-term outcomes. CKD was defined as creatinine clearance (CrCl) < 60 mL/min.

Dysphagia and associated risk factors following extubation in cardiovascular surgical patients.

Following cardiovascular (CV) surgery, prolonged mechanical ventilation of >48 h increases dysphagia frequency over tenfold: 51 % compared to 3-4 % across all durations. Our primary objective was to identify dysphagia frequency following CV surgery with respect to intubation duration. Our secondary objective was to explore characteristics associated with dysphagia across the entire sample.

Increasing mortality burden among adults with complex congenital heart disease.

Background: Progress in management of congenital heart disease has shifted mortality largely to adulthood. However, adult survivors with complex congenital heart disease are not cured and remain at risk of premature death as young adults. Thus, our aim was to describe the evolution and mortality risk of adult patient cohorts with complex congenital heart disease.

Radiological presentation of neurosarcoidosis.

Introduction: In diagnostics of neurosarcoidosis, radiological diagnostic procedures are available, non-invasive and they contribute significantly to the diagnosis of this disease. The aim of this paper is to present a brief overview of the radiological diagnostic methods, their application, and their importance in daily clinical work with these patients. RADIOLOGICAL PRESENTATION OF NEUROSARCOIDOSIS: Magnetic resonance is the method of choice in diagnostics of this disease.

Predictors of radial artery size in patients undergoing cardiac catheterization: insights from the Good Radial Artery Size Prediction (GRASP) study.

Background: Radial artery occlusion occurs after transradial cardiac catheterization or percutaneous coronary intervention. Although use of a sheath larger than the artery is a risk factor for radial artery occlusion, radial artery size is not routinely measured. We aimed to identify bedside predictors of radial artery diameter.

[Effects of vestibuloprotectors mexidol and melatonin on animal cerebellum].

In experiments with cats, air-assisted microinjections of mexidol and melatonin had a direct effect on 71-81% Purkinje cells inducing the inhibitory response 4.2-6.3 times more often than exiting.

Sex differences in the management and outcomes of Ontario patients with cardiogenic shock complicating acute myocardial infarction.

Background: Sex differences in the management of acute myocardial infarction (AMI) patients with cardiogenic shock (CS) have not been well studied.

Methods: We examined mortality and revascularization rates of 9750 patients with CS between 1992 and 2008 in the Ontario Myocardial Infarction Database. Men and women were compared in the entire cohort and in subgroups divided by age (aged < 75 years vs aged ≥ 75 years) and revascularization availability at presenting hospital.

Toronto hypertrophic cardiomyopathy genotype score for prediction of a positive genotype in hypertrophic cardiomyopathy.

Background: Genotyping in hypertrophic cardiomyopathy has gained increasing attention in the past decade. Its major role is for family screening and rarely influences decision-making processes in any individual patient. It is associated with substantial costs, and cost-effectiveness can only be achieved in the presence of high-detection rates for disease-causing sarcomere protein gene mutations.

Long-term outcomes using a two-stent technique for the treatment of coronary bifurcations.

Background: The crush and culotte are probably the most common two-stent techniques utilized for percutaneous coronary intervention (PCI) of complex bifurcation lesions. Long-term outcome associated with the utilization of these techniques is unknown. Our objective was to evaluate the long-term outcomes after bifurcation PCI utilizing these 2 techniques with a prospective PCI registry.

Antithrombotic therapy after coronary stenting in patients with nonvalvular atrial fibrillation.

Background: The safety and efficacy of triple therapy (TT; warfarin with dual antiplatelet therapy [DAPT]) in post-percutaneous coronary intervention (PCI) patients with atrial fibrillation (AF) are unclear. We aimed to determine whether TT is associated with a decreased stroke rate and an acceptable bleeding rate in this population.

Methods: This was a single-centre, retrospective study.

Relationship of bipolar and unipolar electrogram voltage to scar transmurality and composition derived by magnetic resonance imaging in patients with nonischemic cardiomyopathy undergoing VT ablation.

Background: Bipolar voltage mapping has a role in defining endocardial-based scar in postinfarct patients undergoing ventricular tachycardia catheter ablation. The utility of bipolar and unipolar voltages in characterizing scar has not been evaluated in patients with nonischemic cardiomyopathy.

Objective: To relate left ventricular (LV) endocardial bipolar and unipolar voltages in these patients to scar transmurality (endocardial vs nonendocardial) and composition (homogeneous core vs heterogeneous gray).