"You Don't Look Anorexic": Atypical anorexia patient experiences of weight stigma in medical care.

Eating disorders (ED) and weight stigma pose significant healthcare challenges. Patients at higher weights, like some with atypical anorexia (AAN), may face increased challenges due to weight stigma. This study analyzed patients' lived experiences with weight stigma in healthcare.

Optimal LentiCRISPR-Based System for Sequential CRISPR/Cas9 Screens.

The advent of genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening has advanced the understanding of molecular systems within cells. Here, we demonstrate the utility of sequentially performed CRISPR knockout screens that use an existing library to explore a biological question across the human genome, and then the remaining cells are used to examine each gene candidate against one common gene of interest. We call this approach "Many vs One" CRISPR screening, made possible by a modified 7SK promoter in place of the U6 promoter to drive expression of a single guide RNA.

Blockade of 20-hydroxyeicosatetraenoic acid receptor lowers blood pressure and alters vascular function in mice with smooth muscle-specific overexpression of CYP4A12-20-HETE synthase.

Objective: 20-Hydroxyeicosatetraenoic acid (20-HETE) is a vasoactive eicosanoid exhibiting effects on vascular smooth muscle cell (VSMC) via G-protein coupled receptor 75 (GPR75) and include stimulation of contractility, migration, and growth. We examined whether VSMC-targeted overexpression of CYP4A12, the primary 20-HETE-producing enzyme in mice, is sufficient to promote hypertension.

Methods: Mice with VSM-specific Cyp4a12 overexpression (Myh11-4a12) and their littermate controls (WT) were generated by crossbreeding Cyp4a12-floxed with Myh11-Cre mice.

Attraction of the Mosquitoes Aedes aegypti and Aedes albopictus (Diptera: Culicidae) to a 3-Part Phytochemical Blend in a Mesocosm.

Aedes aegypti (L.) and Aedes albopictus (Skuse) mosquitoes of both sexes were attracted to a 3-part volatile synthetic phytochemical blend but differed according to their component ratios, 7:3:2 or 1:1:1, and their initial concentrations. These arbovirus vectors were presented with the blends as baits in paired baited and blank CFG traps in a large greenhouse mesocosm.

Social and economic cost of eating disorders in the United States: Evidence to inform policy action.

Objective: To estimate one-year costs of eating disorders in the United States (U.S.) from a societal perspective, including the costs to the U.

Burkitt Lymphomas Evolve to Escape Dependencies on Epstein-Barr Virus.

Epstein-Barr Virus (EBV) can transform B cells and contributes to the development of Burkitt lymphoma and other cancers. Through decades of study, we now recognize that many of the viral genes required to transform cells are not expressed in EBV-positive Burkitt lymphoma (BL) tumors, likely due to the immune pressure exerted on infected cells. This recognition has led to the hypothesis that the loss of expression of these viral genes must be compensated through some mechanisms.

Practice patterns and incidence of adenovirus infection in allogeneic hematopoietic cell transplant recipients: Multicenter survey of transplant centers in the United States.

Background: Adenovirus (AdV) is increasingly recognized as a threat to successful outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Guidelines have been developed to inform AdV screening and treatment practices, but the extent to which they are followed in clinical practice in the United States is still unknown. The incidence of AdV in the United States is also not well documented.

Perfluoroalkyl substances and likelihood of stroke in persons with and without diabetes.

Objective: The main objective of this study is to evaluate the relationship of perfluoroalkyl substances with stroke and any modifying influence of diabetes.

Methods: Data on 3921 adults aged ⩾20 years with and 44,285 without diabetes were drawn from the C8 Health Project. Four perfluoroalkyl substances were investigated: perfluorohexane sulphate, C8 - perfluorooctanoic acid, perfluoroctane sulfonate and perfluorononaoic acid.

The Second Wave of Public Policy Advocacy for Eating Disorders: Charting the Course to Maximize Population Impact.

Over the past decade, a first wave of US public policy advocacy for eating disorders made substantial progress, with passage of the federal 21st Century Cures Act in 2016 as its crowning achievement. However, the US response to eating disorders continues to fall short in several ways. On the cusp of a second wave of policy advocacy, efforts must be broadened to target structural determinants of illness and inequities to maximize clinical impact and diminish suffering.

Perfluoroalkyl substances are inversely associated with coronary heart disease in adults with diabetes.

Aims: Perfluoroalkyl substances (PFAS) are environmentally and biologically persistent synthetic environmental contaminants linked to adverse health outcomes. Though null to modest inverse relationships between PFAS and coronary heart disease (CHD) have been reported, studies regarding relationships in high risk populations such as those with diabetes are sparse. We investigated the relationship of PFAS with CHD in persons with diabetes.

Elevated 20-HETE in metabolic syndrome regulates arterial stiffness and systolic hypertension via MMP12 activation.

Arterial stiffness plays a causal role in development of systolic hypertension. 20-hydroxyeicosatetraeonic acid (20-HETE), a cytochrome P450 (CYP450)-derived arachidonic acid metabolite, is known to be elevated in resistance arteries in hypertensive animal models and loosely associated with obesity in humans. However, the role of 20-HETE in the regulation of large artery remodeling in metabolic syndrome has not been investigated.

Evaluating the Impact of the Affordable Care Act on HIV Care, Outcomes, Prevention, and Disparities: A Critical Research Agenda.

In the United States (U.S.), health care policy plays a critical role in ensuring adequate care for people living with HIV (PLWH), eliminating new HIV infections, and reducing health disparities.

Monovalent Cation Activation of the Radical SAM Enzyme Pyruvate Formate-Lyase Activating Enzyme.

Pyruvate formate-lyase activating enzyme (PFL-AE) is a radical S-adenosyl-l-methionine (SAM) enzyme that installs a catalytically essential glycyl radical on pyruvate formate-lyase. We show that PFL-AE binds a catalytically essential monovalent cation at its active site, yet another parallel with B enzymes, and we characterize this cation site by a combination of structural, biochemical, and spectroscopic approaches. Refinement of the PFL-AE crystal structure reveals Na as the most likely ion present in the solved structures, and pulsed electron nuclear double resonance (ENDOR) demonstrates that the same cation site is occupied by Na in the solution state of the as-isolated enzyme.

Computational fluid dynamics evaluation of posterior septectomy as a viable treatment option for large septal perforations.

Background: Numerous surgical techniques exist to treat nasal septal perforation (NSP). The surgical closure of large NSPs (>2 cm) is still challenging. Posterior septectomy has been reported as a simple alternative to treat large NSP, yet its mechanisms for symptom relief are not clear, and if failed, its consequence cannot be easily reversed.

Elevated 20-HETE impairs coronary collateral growth in metabolic syndrome via endothelial dysfunction.

Coronary collateral growth (CCG) is impaired in metabolic syndrome (MetS). microRNA-145 (miR-145-Adv) delivery to our rat model of MetS (JCR) completely restored and neutrophil depletion significantly improved CCG. We determined whether low endogenous levels of miR-145 in MetS allowed for elevated production of 20-hydroxyeicosatetraenoic acid (20-HETE), which, in turn, resulted in excessive neutrophil accumulation and endothelial dysfunction leading to impaired CCG.

Mechanisms of Comorbidities Associated With the Metabolic Syndrome: Insights from the Corpulent Rat Strain.

Obesity and its metabolic complications have emerged as the epidemic of the new millennia. The use of obese rodent models continues to be a productive component of efforts to understand the concomitant metabolic complications of this disease. In 1978, the rat model was developed with an autosomal recessive corpulent () trait resulting from a premature stop codon in the extracellular domain of the leptin receptor.

Radical SAM catalysis via an organometallic intermediate with an Fe-[5'-C]-deoxyadenosyl bond.

Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to cleave SAM to initiate diverse radical reactions. These reactions are thought to involve the 5'-deoxyadenosyl radical intermediate, which has not yet been detected. We used rapid freeze-quenching to trap a catalytically competent intermediate in the reaction catalyzed by the radical SAM enzyme pyruvate formate-lyase activating enzyme.

miR-21-mediated decreased neutrophil apoptosis is a determinant of impaired coronary collateral growth in metabolic syndrome.

Coronary collateral growth (CCG) is impaired in metabolic syndrome. microRNA-21 (miR-21) is a proproliferative and antiapoptotic miR, which we showed to be elevated in metabolic syndrome. Here we investigate whether impaired CCG in metabolic syndrome involved miR-21-mediated aberrant apoptosis.

miR-21 normalizes vascular smooth muscle proliferation and improves coronary collateral growth in metabolic syndrome.

Inadequate cell proliferation is considered a major causative factor for impaired coronary collateral growth (CCG). Proangiogenic growth factors (GFs) stimulate cell proliferation, but their administration does not promote CCG in patients. These GFs are increased in patients with metabolic syndrome and in animal models, where CCG is impaired.

Personal and contextual factors related to delayed HIV diagnosis among men who have sex with men.

Delayed HIV diagnosis among men who have sex with men (MSM) in the United States continues to be a significant personal and public health issue. Using qualitative and quantitative data from 75 recently tested, HIV-sero-positive MSM (38 delayed and 37 nondelayed testers), the authors sought to further elucidate potential personal and contextual factors that may contribute to delayed HIV diagnosis among MSM. Findings indicate that MSM who experience multiple life stressors, whether personal or contextual, have an increased likelihood of delaying HIV diagnosis.

Impaired coronary collateral growth in the metabolic syndrome is in part mediated by matrix metalloproteinase 12-dependent production of endostatin and angiostatin.

Objective: We have previously shown that transient coronary artery occlusion stimulated coronary collateral growth (CCG) in healthy (Sprague Dawley) but not in metabolic syndrome (JCR:LA-cp [JCR] ) rats. Here, we sought to determine whether matrix metalloproteinases (MMPs) negatively regulate CCG in the metabolic syndrome via release of endostatin and angiostatin.

Approach And Results: Rats underwent transient, repetitive left anterior descending occlusion and resultant myocardial ischemia (RI) for 0 to 10 days.

MicroRNA-145 restores contractile vascular smooth muscle phenotype and coronary collateral growth in the metabolic syndrome.

Objective: Transient, repetitive occlusion stimulates coronary collateral growth (CCG) in normal animals. Vascular smooth muscle cells (VSMCs) switch to synthetic phenotype early in CCG, then return to contractile phenotype. CCG is impaired in the metabolic syndrome.

Radical SAM enzymes in methylation and methylthiolation.

Radical S-adenosyl-l-methionine (SAM) enzymes are a large and diverse superfamily with functions ranging from enzyme activation through a single H atom abstraction to complex organic and metal cofactor synthesis involving a series of steps. Though these enzymes carry out a variety of functions, they share common structural and mechanistic characteristics. All of them contain a site-differentiated [4Fe-4S] cluster, ligated by a CX(3)CX(2)C or similar motif, which binds SAM at the unique iron.