Identification of a GABAergic neural circuit governing leptin signaling deficiency-induced obesity.

The hormone leptin is known to robustly suppress food intake by acting upon the leptin receptor (LepR) signaling system residing within the agouti-related protein (AgRP) neurons of the hypothalamus. However, clinical studies indicate that leptin is undesirable as a therapeutic regiment for obesity, which is at least partly attributed to the poorly understood complex secondary structure and key signaling mechanism of the leptin-responsive neural circuit. Here, we show that the LepR-expressing portal neurons send GABAergic projections to a cohort of α3-GABA receptor expressing neurons within the dorsomedial hypothalamic nucleus (DMH) for the control of leptin-mediated obesity phenotype.

Levonorgestrel 52-mg Intrauterine Device Efficacy and Safety After More Than 8 Years of Use.

Funding Source: Medicines360. The Sponsor, Medicines360, designed the study and oversaw its conduct, including funding the trial and providing all study product free of charge to participants.

Clinical Trial Registration: ClinicalTrials.

Barriers and facilitators to recruitment and retention of underrepresented racial and ethnic minoritized students to PhD programs in nursing: A qualitative descriptive study.

Background: There is a global shortage of Doctor of Philosophy (PhD)-trained nurses, which is amplified among underrepresented racial and ethnic groups who are minoritized.

Purpose: This study explores barriers and facilitators to recruiting under-represented racial-ethnic group who are minoritized (UREM) PhD nursing students, defined as African American, Black, American Indian, Alaskan Native, or Hispanic/Latinx.

Methods: Using a qualitative descriptive design, interviews of 23 UREM PhD nursing students were analyzed with conventional content analysis.

Interpretation Threshold Values for the Oxford Hip Score in Patients Undergoing Total Hip Arthroplasty: Advancing Their Clinical Use.

Background: Patient-reported outcome measures such as the Oxford Hip Score (OHS) can capture patient-centered perspectives on outcomes after total hip arthroplasty (THA). The OHS assesses hip pain and functional limitations, but defining interpretation threshold values for the OHS is warranted so that numerical OHS values can be translated into whether patients have experienced clinically meaningful changes. Therefore, we determined the minimal important change (MIC), patient acceptable symptom state (PASS), and treatment failure (TF) threshold values for the OHS at 12 and 24-month follow-up in patients undergoing THA.

Mapping definitions, measures and methodologies of assessing police violence in the health literature: a scoping review protocol.

Introduction: Police violence is a growing public health issue in the USA. Emerging evidence suggests that negative police encounters are associated with adverse physical and mental health outcomes. There is a critical need to examine the relationship between police violence and health disparities.

Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of -Overexpressing Metastatic Breast Cancer.

Purpose: To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with -overexpressing metastatic breast cancer.

Patients And Methods: One hundred fourteen women with -overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly.

Results: The objective response rate was 26% (95% confidence interval [CI], 18.

Enhancement of visual cues to self-motion during a visual/vestibular conflict.

Perceiving our orientation and motion requires sensory information provided by vision, our body and acceleration. Normally, these cues are redundant however in some situations they can conflict. Here, we created a visual-vestibular conflict by simulating a body-upright virtual world while participants were either standing (no conflict), supine or prone (conflict) and assessed the perception of "forward" distance travelled induced by visual motion.

Fate of foodborne pathogens during soaking and drying of walnuts.

Walnuts are among the most popular tree nuts that are soaked at home. Recipes for preparing soaked walnut kernels from online blogs (n = 71) and YouTube videos (n = 29) were reviewed to identify typical consumer handling practices that were then used to determine the fate of foodborne pathogens during soaking and subsequent drying of walnut kernels. Individual five-strain cocktails of rifampin-resistant Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella, grown on agar plates and diluted in water, were inoculated onto walnuts and then dried.

Involvement of Epithelial-Mesenchymal Transition Genes in Small Cell Lung Cancer Phenotypic Plasticity.

Small cell lung cancer (SCLC) is an aggressive cancer recalcitrant to treatment, arising predominantly from epithelial pulmonary neuroendocrine (NE) cells. Intratumor heterogeneity plays critical roles in SCLC disease progression, metastasis, and treatment resistance. At least five transcriptional SCLC NE and non-NE cell subtypes were recently defined by gene expression signatures.

Experiential Learning for Prelicensure Nursing Students: A Pediatric Special Needs Respite Program.

Background: A respite program at a southeastern university was developed to provide respite services to local families of children with special needs and to integrate a hands-on clinical experience for nursing students.

Method: To assess the nursing students' perceptions of participating in the respite program experience, a survey was administered to prelicensure nursing students.

Results: Analysis of survey data revealed all participants were satisfied with the respite experience, perceived they will be able to apply knowledge obtained, and acknowledged opportunities to enhance soft skills.

Reduced fire severity offers near-term buffer to climate-driven declines in conifer resilience across the western United States.

Increasing fire severity and warmer, drier postfire conditions are making forests in the western United States (West) vulnerable to ecological transformation. Yet, the relative importance of and interactions between these drivers of forest change remain unresolved, particularly over upcoming decades. Here, we assess how the interactive impacts of changing climate and wildfire activity influenced conifer regeneration after 334 wildfires, using a dataset of postfire conifer regeneration from 10,230 field plots.

Phase II Study of Palbociclib (PD-0332991) in CCND1, 2, or 3 Amplification: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1B.

Purpose: Cyclin D/CDK4/6 is critical in controlling the G1 to S checkpoint. CCND, the gene encoding cyclin D, is known to be amplified in a variety of solid tumors. Palbociclib is an oral CDK4/6 inhibitor, approved in advanced breast cancer in combination with endocrine therapy.

The effectiveness of naive optimization of the egress path for an active-shooter scenario.

There have been 130 mass shootings in the United States from 1982 to June, 2022 according to the Mother Jones database of active shooter events. In these critical scenarios, making the right decisions while evacuating can be the difference between life and death. However, emergency evacuation is intensely stressful, which along with lack of verifiable real-time information may lead to costly incorrect decisions.

Implementation of Virtual Fontan Heart Camps During a Pandemic.

Background: Children with a Fontan operation represent a unique form of congenital heart disease (CHD) that requires multiple cardiac surgeries and procedures with an uncertain long-term outcome. Given the rarity of the types of CHD that require this procedure, many children with a Fontan do not know any others like them.

Methods: With the cancelation of medically supervised heart camps due to the COVID-19 pandemic, we have organized several physician-led virtual day camps for children with a Fontan operation to connect with others in their province and across Canada.

The discovery of 12β-methyl-17-epi-18-nor-bile acids as potent and selective TGR5 agonists.

Recent discoveries have demonstrated that the physiological function of bile acids extends to the regulation of diverse signaling processes through interactions with nuclear and G protein-coupled receptors, most notably the Farnesoid-X nuclear receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5). Targeting such signaling pathways pharmacologically, i.e.

Larval Therapy and Larval Excretions/Secretions: A Potential Treatment for Biofilm in Chronic Wounds? A Systematic Review.

Chronic wounds present a global healthcare challenge and are increasing in prevalence, with bacterial biofilms being the primary roadblock to healing in most cases. A systematic review of the to-date knowledge on larval therapy's interaction with chronic-wound biofilm is presented here. The findings detail how larval therapy-the controlled application of necrophagous blowfly larvae-acts on biofilms produced by chronic-wound-relevant bacteria through their principle pharmacological mode of action: the secretion and excretion of biologically active substances into the wound bed.

What is the Link Between Different Components of Empathy and Burnout in Healthcare Professionals? A Systematic Review and Meta-Analysis.

Research on healthcare shows that the relationship between empathy and burnout is complex. The aim of this systematic review and meta-analysis is to clarify the link between different empathic components and burnout components in healthcare professionals. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance.

Positive Nipple Margins and Oncologic Outcomes of Nipple-Sparing Mastectomy in a Large Community-Based Hospital System.

The American Society of Breast Surgeons recommends sending separate nipple margins (NMs) when performing nipple-sparing mastectomies (NSMs). However, the definition of a positive NM is vague. We evaluated NM management and outcomes in breast cancer patients undergoing NSM from 2010 to 2021 at our community-based hospital system through a retrospective review and descriptive analysis.

Minority Health Social Vulnerability Index and COVID-19 vaccination coverage - The United States, December 14, 2020-January 31, 2022.

Introduction: In 2021, HHS Office of Minority Health and CDC developed a composite measure of social vulnerability called the Minority Health Social Vulnerability Index (MHSVI) to assess the needs of communities most vulnerable to COVID-19. The MHSVI extends the CDC Social Vulnerability Index with two new themes on healthcare access and medical vulnerability. This analysis examines COVID-19 vaccination coverage by social vulnerability using the MHSVI.

COVID-19 Vaccination Coverage and Demographic Characteristics of Infants and Children Aged 6 Months-4 Years - United States, June 20-December 31, 2022.

Although severe COVID-19 illness and hospitalization are more common among older adults, children can also be affected (1). More than 3 million cases of COVID-19 had been reported among infants and children aged <5 years (children) as of December 2, 2022 (2). One in four children hospitalized with COVID-19 required intensive care; 21.

Describing epilepsy-related anxiety to inform the design of a virtual reality exposure therapy: Results from Phase 1 of the AnxEpiVR clinical trial.

People with epilepsy (PwE) are at a greater risk of comorbid anxiety, which is often related to the fear of having another seizure for safety or social reasons. While virtual reality (VR) exposure therapy (ET) has been successfully used to treat several anxiety disorders, no studies to date have investigated its use in this population. This paper discusses Phase 1 of the three-phase AnxEpiVR pilot study.

Novel GluN2B-Selective NMDA Receptor Negative Allosteric Modulator Possesses Intrinsic Analgesic Properties and Enhances Analgesia of Morphine in a Rodent Tail Flick Pain Model.

Many cases of accidental death associated with drug overdose are due to chronic opioid use, tolerance, and addiction. Analgesic tolerance is characterized by a decreased response to the analgesic effects of opioids, requiring increasingly higher doses to maintain the desired level of pain relief. Overactivation of GluN2B-containing -methyl-d-Aspartate receptors is thought to play a key role in mechanisms underlying cellular adaptation that takes place in the development of analgesic tolerance.

The Ontology of Biological Attributes (OBA) - Computational Traits for the Life Sciences.

Existing phenotype ontologies were originally developed to represent phenotypes that manifest as a character state in relation to a wild-type or other reference. However, these do not include the phenotypic trait or attribute categories required for the annotation of genome-wide association studies (GWAS), Quantitative Trait Loci (QTL) mappings or any population-focused measurable trait data. Moreover, variations in gene expression in response to environmental disturbances even without any genetic alterations can also be associated with particular biological attributes.