An IL-2 mutein increases regulatory T cell suppression of dendritic cells via IL-10 and CTLA-4 to promote T cell anergy.

Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3 regulatory T (T) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.

Climate, climate change and the global diversity of human houses.

Globally, human house types are diverse, varying in shape, size, roof type, building materials, arrangement, decoration and many other features. Here we offer the first rigorous, global evaluation of the factors that influence the construction of traditional (vernacular) houses. We apply macroecological approaches to analyse data describing house features from 1900 to 1950 across 1000 societies.

Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism.

Objective: Glucagon-like peptide 1 (GLP-1) receptor agonists reduce food intake, producing remarkable weight loss in overweight and obese individuals. While much of this weight loss is fat mass, there is also a loss of lean mass, similar to other approaches that induce calorie deficit. Targeting signaling pathways that regulate skeletal muscle hypertrophy is a promising avenue to preserve lean mass and modulate body composition.

An IL-2 mutein increases IL-10 and CTLA-4-dependent suppression of dendritic cells by regulatory T cells.

Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3 regulatory T (T) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.

-associated spinocerebellar ataxia with craniofacial features-additional evidence for germline mosaicism.

Inositol 1,4,5-triphosphate receptor type 1 () is an endoplasmic reticulum-bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.

IV Diuresis in Alternative Treatment Settings for the Management of Heart Failure: Implications for Mortality, Hospitalizations and Cost.

Background: Recent advances in heart failure (HF) care have sought to shift management from inpatient to outpatient and observation settings. We evaluated the association among HF treatment in the (1) inpatient; (2) observation; (3) emergency department (ED); and (4) outpatient settings with 30-day mortality, hospitalizations and cost.

Methods: Using 100% Medicare inpatient, outpatient and Part B files from 2011-2018, 1,534,708 unique patient encounters in which intravenous (IV) diuretics were received for a primary diagnosis of HF were identified.

Populism and De Facto Central Bank Independence.

Although central bank independence is a core tenet of monetary policy-making, it remains politically contested: In many emerging markets, populist governments are in frequent public conflict with the central bank. At other times, the same governments profess to respect the monetary authority's independence. We model this conflict drawing on the crisis bargaining literature.

A Focus on the Right Atrium: Right Atrial Diverticulum and Atrial Flutter.

We report a case of a 70-year-old woman who presented for a cavotricuspid isthmus atrial flutter ablation that was aborted prematurely. On subsequent imaging, she was discovered to have a right atrial diverticulum, which was present on prior imaging but not reported, likely due to unfamiliarity with the entity. ().

Phenotypic variability and gastrointestinal manifestations/interventions for growth in NAA10-related neurodevelopmental syndrome.

Our study of 61 children with NAA10-related neurodevelopmental syndrome, an X-linked disorder due to NAA10 gene variants, demonstrated a high prevalence of growth failure, with weight and height percentiles often in the failure-to-thrive diagnostic range; however, dramatic weight fluctuations and phenotypic variability is evidenced in the growth parameters of this population. Although never previously explored in depth, the gastrointestinal pathology associated with NAA10-related neurodevelopmental syndrome includes feeding difficulties in infancy, dysphagia, GERD/silent reflux, vomiting, constipation, diarrhea, bowel incontinence, and presence of eosinophils on esophageal endoscopy, in order from most to least prevalent. Additionally, the gastrointestinal symptom profile for children with this syndrome has been expanded to include eosinophilic esophagitis, cyclic vomiting syndrome, Mallory Weiss tears, abdominal migraine, esophageal dilation, and subglottic stenosis.

Identifying socioeconomic and biophysical factors driving forest loss in protected areas.

Protected areas (PAs) are a commonly used strategy to confront forest conversion and biodiversity loss. Although determining drivers of forest loss is central to conservation success, understanding of them is limited by conventional modeling assumptions. We used random forest regression to evaluate potential drivers of deforestation in PAs in Mexico, while accounting for nonlinear relationships and higher order interactions underlying deforestation processes.

What needs to happen for school autonomy to be mobilised to create more equitable public schools and systems of education?

The series of responses in this article were gathered as part of an online mini conference held in September 2021 that sought to explore different ideas and articulations of school autonomy reform across the world (Australia, Canada, England, Ireland, the USA, Norway, Sweden and New Zealand). It centred upon an important question: what needs to happen for school autonomy to be mobilised to create more equitable public schools and systems of education? There was consensus across the group that school autonomy reform creates further inequities at school and system levels when driven by the logics of marketisation, competition, economic efficiency and public accountability. Against the backdrop of these themes, the conference generated discussion and debate where provocations and points of agreement and disagreement about issues of social justice and the mobilisation of school autonomy reform were raised.

Global-run on sequencing identifies as an Akt-dependent long noncoding RNA involved in insulin sensitivity.

The insulin responsive Akt and FoxO1 signaling axis is a key regulator of the hepatic transcriptional response to nutrient intake. Here, we used global run-on sequencing (GRO-seq) to measure the nascent transcriptional response to fasting and refeeding as well as define the specific role of hepatic Akt and FoxO1 signaling in mediating this response. We identified 599 feeding-regulated transcripts, as well as over 6,000 eRNAs, and mapped their dependency on Akt and FoxO1 signaling.

Zoonotic Transmission of Diphtheria from Domestic Animal Reservoir, Spain.

Toxigenic Corynebacterium ulcerans is as an emerging zoonotic agent of diphtheria. We describe the zoonotic transmission of diphtheria caused by toxigenic C. ulcerans from domestic animals in Spain, confirmed by core-genome multilocus sequence typing.

COVID-19: Rapid prototyping and production of face shields flat, laser-cut, and 3D-printed models.

The use of personal protective equipment (PPE) has become essential to reduce the transmission of coronavirus disease 2019 (COVID-19) as it prevents the direct contact of body fluid aerosols expelled from carriers. However, many countries have reported critical supply shortages due to the spike in demand during the outbreak in 2020. One potential solution to ease pressure on conventional supply chains is the local fabrication of PPE, particularly face shields, due to their simplistic design.

An interprofessional approach to reducing hospital-onset Clostridioides difficile infections.

Background: Clostridioides difficile is the most prevalent hospital-onset (HO) infection. There are significant financial and safety impacts associated with HO-C. difficile infections (HO-CDIs) for both patients and health care organizations.

Acute Deletion of the FOXO1-dependent Hepatokine FGF21 Does not Alter Basal Glucose Homeostasis or Lipolysis in Mice.

The hepatic transcription factor forkhead box O1 (FOXO1) is a critical regulator of hepatic and systemic insulin sensitivity. Previous work by our group and others demonstrated that genetic inhibition of FOXO1 improves insulin sensitivity both in genetic and dietary mouse models of metabolic disease. Mechanistically, this is due in part to cell nonautonomous control of adipose tissue insulin sensitivity.

Activation of Liver mTORC1 Protects Against NASH via Dual Regulation of VLDL-TAG Secretion and De Novo Lipogenesis.

Background & Aims: Dysregulation of liver lipid metabolism is associated with the development and progression of nonalcoholic fatty liver disease, a spectrum of liver diseases including nonalcoholic steatohepatitis (NASH). In the liver, insulin controls lipid homeostasis by increasing triglyceride (TAG) synthesis, suppressing fatty acid oxidation, and enhancing TAG export via very low-density lipoproteins. Downstream of insulin signaling, the mechanistic target of rapamycin complex 1 (mTORC1), is a key regulator of lipid metabolism.

Introduction of a standardized protocol for cardiac risk assessment in candidates for liver transplant - A retrospective cohort analysis.

Introduction: Recommendations on non-invasive imaging to assess pre-operative cardiac risk among liver transplant candidates vary amongst societal guidelines and individual institutional practices. In 2018, a standardized pre-transplant coronary evaluation protocol was established at Beth Israel Deaconess Medical Center, Boston MA, to ensure appropriate and consistent pre-operative testing was performed.

Methods: All patients who underwent liver transplant evaluation between January 1st, 2016 and December 31st, 2019, were retrospectively analyzed and divided into three cohorts; before the introduction of the protocol (prior to 2018), initial protocol favoring invasive coronary angiography (ICA) (2018), and amended protocol favoring coronary computed tomography angiography (CCTA) (post-2018).

AKT controls protein synthesis and oxidative metabolism via combined mTORC1 and FOXO1 signalling to govern muscle physiology.

Background: Skeletomuscular diseases result in significant muscle loss and decreased performance, paralleled by a loss in mitochondrial and oxidative capacity. Insulin and insulin-like growth factor-1 (IGF-1) are two potent anabolic hormones that activate a host of signalling intermediates including the serine/threonine kinase AKT to influence skeletal muscle physiology. Defective AKT signalling is associated with muscle pathology, including cachexia, sarcopenia, and disuse; however, the mechanistic underpinnings remain unresolved.

Autosomal recessive variants in a proband with a cerebrorenal syndrome and no parental consanguinity.

An associated cerebrorenal syndrome was first reported in consanguineous Bedouin kindred by Perez et al. in 2017. Although the function of the gene has not yet been fully elucidated, it may be implicated in Wnt signaling and nuclear regulation, as well as in cell and mitochondrial zinc regulation.