Lessons Learned from a Quality Improvement Initiative to Increase COVID-19 Vaccination in Hospitalized Children.

Introduction: Pediatric coronavirus disease 2019 (COVID-19) vaccination rates in the United States remain lower compared with adults. We aimed to (1) implement a quality improvement initiative to increase COVID-19 vaccination 2-fold in hospitalized patients 12-21 years of age from 4.7% during the baseline period (August 10, 2021-November 1, 2021) to 9.

An examination of sugar-sweetened beverage tax regulations in six jurisdictions: Applying a social justice perspective to beverage taxation and exemptions.

Taxes, legislation and politics are social determinants of health, which can impact health through multiple pathways. The purpose of this study was to review regulations regarding sugar-sweetened beverage (SSB) taxation and describe taxation/exemption of various beverage categories. We reviewed SSB taxation regulations from Mexico, the United Kingdom, Berkeley, Philadelphia, San Francisco and South Africa.

Increasing access to mental health supports for 12-17-year-old Indigenous youth with the JoyPop mobile mental health app: study protocol for a randomized controlled trial.

Background: Indigenous youth in Northwestern Ontario who need mental health supports experience longer waits than non-Indigenous youth within the region and when compared to youth in urban areas. Limited access and extended waits can exacerbate symptoms, prolong distress, and increase risk for adverse outcomes. Innovative approaches are urgently needed to provide support for Indigenous youth in Northwestern Ontario.

ANGPTL3 Deficiency and Risk of Hepatic Steatosis.

Background: ANGPTL3 (angiopoietin-like 3) is a therapeutic target for reducing plasma levels of triglycerides and low-density lipoprotein cholesterol. A recent trial with vupanorsen, an antisense oligonucleotide targeting hepatic production of ANGPTL3, reported a dose-dependent increase in hepatic fat. It is unclear whether this adverse effect is due to an on-target effect of inhibiting hepatic ANGPTL3.

Autophagy impairment and lifespan reduction caused by Atg1 RNAi or Atg18 RNAi expression in adult fruit flies (Drosophila melanogaster).

Autophagy, an autophagosome and lysosome-based eukaryotic cellular degradation system, has previously been implicated in lifespan regulation in different animal models. In this report, we show that expression of the RNAi transgenes targeting the transcripts of the key autophagy genes Atg1 or Atg18 in adult fly muscle or glia does not affect the overall levels of autophagosomes in those tissues and does not change the lifespan of the tested flies but the lifespan reduction phenotype has become apparent when Atg1 RNAi or Atg18 RNAi is expressed ubiquitously in adult flies or after autophagy is eradicated through the knockdown of Atg1 or Atg18 in adult fly adipocytes. Lifespan reduction was also observed when Atg1 or Atg18 was knocked down in adult fly enteroblasts and midgut stem cells.

A Novel Mouse Model to Analyze Non-Genomic ERα Physiological Actions.

Nongenomic effects of estrogen receptor α (ERα) signaling have been described for decades. Several distinct animal models have been generated previously to analyze the nongenomic ERα signaling (eg, membrane-only ER, and ERαC451A). However, the mechanisms and physiological processes resulting solely from nongenomic signaling are still poorly understood.

Systemic lipolysis promotes physiological fitness in .

Since interventions such as caloric restriction or fasting robustly promote lipid catabolism and improve aging-related phenotypical markers, we investigated the direct effect of increased lipid catabolism via overexpression of (, FBgn0036449), the major triglyceride hydrolase in on lifespan and physiological fitness. Comprehensive characterization was carried out using RNA-seq, lipidomics and metabolomics analysis. Global overexpression of strongly promoted numerous markers of physiological fitness, including increased female fecundity, fertility maintenance, preserved locomotion activity, increased mitochondrial biogenesis and oxidative metabolism.

Health Disparities in the Treatment of Supraventricular Tachycardia in Pediatric Patients.

Supraventricular tachycardia (SVT) is a common pediatric arrhythmia. The objective of this investigation was to investigate the existence and degree of the health disparities in the treatment of pediatric patients with supraventricular tachycardia based on sociodemographic factors. This was retrospective cohort study at a large academic medical center including children ages 5-18 years old diagnosed with SVT.

Cannabis use of patients with inflammatory bowel disease in Germany: a cross-sectional survey.

Background And Aims:  Progressive legalization and increasing utilization of medical cannabis open up potential new applications, including for inflammatory bowel disease (IBD). This study aimed to collect current figures on the use of and experience with cannabis among IBD patients in Germany.

Methods:  A 71-item questionnaire was mailed to a randomly selected representative sample of 1000 IBD patients.

Fine-tuning autophagy maximises lifespan and is associated with changes in mitochondrial gene expression in Drosophila.

Increased cellular degradation by autophagy is a feature of many interventions that delay ageing. We report here that increased autophagy is necessary for reduced insulin-like signalling (IIS) to extend lifespan in Drosophila and is sufficient on its own to increase lifespan. We first established that the well-characterised lifespan extension associated with deletion of the insulin receptor substrate chico was completely abrogated by downregulation of the essential autophagy gene Atg5.

Hippo Signaling: Autophagy Waits in the Wings.

Crosstalk between signaling networks can help coordinate diverse cellular functions. In this issue of Developmental Cell, Tyra et al. identify connections between the cell-growth-promoting transcription factor YAP/Yorkie and the autophagy-regulating kinase Ulk1/Atg1.

Kinesiology training in patients with Parkinson's disease: results of a pilot study.

Complementary therapies are an essential component of the treatment of patients with Parkinson's disease. They aim to ameliorate disease symptoms in conjunction with dopamine substitution. Kinesiology trains about the effective use of physical, mental and emotional skills.

A Tissue- and Temporal-Specific Autophagic Switch Controls Drosophila Pre-metamorphic Nutritional Checkpoints.

Properly timed production of steroid hormones by endocrine tissues regulates juvenile-to-adult transitions in both mammals (puberty) and holometabolous insects (metamorphosis). Nutritional conditions influence the temporal control of the transition, but the mechanisms responsible are ill defined. Here we demonstrate that autophagy acts as an endocrine organ-specific, nutritionally regulated gating mechanism to help ensure productive metamorphosis in Drosophila.

Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells is enhanced by an aragonite scaffold.

Bone graft substitutes and bone void fillers are predominantly used to treat bone defects and bone fusion in orthopaedic surgery. Some aragonite-based scaffolds of coralline exoskeleton origin exhibit osteoconductive properties and are described as useful bone repair scaffolds. The purpose of this study was to evaluate the in vitro osteogenic potential of the bone phase of a novel aragonite-based bi-phasic osteochondral scaffold (Agili-C™, CartiHeal Ltd.

Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy induction and activity in .

The self-degradative process of autophagy is important for energy homeostasis and cytoplasmic renewal. This lysosome-mediated pathway is negatively regulated by the target of rapamycin kinase (TOR) under basal conditions, and requires the vesicle trafficking machinery regulated by Rab GTPases. However, the interactions between autophagy, TOR and Rab proteins remain incompletely understood Here, we identify Rab6 as a critical regulator of the balance between TOR signaling and autolysosome function.

Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply.

Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO Here we show that islet surface density can be substantially increased safely by increasing gas chamber pO to a supraphysiological level that maintains all islets viable and functional.

Mechanical stress regulates insulin sensitivity through integrin-dependent control of insulin receptor localization.

Insulin resistance, the failure to activate insulin signaling in the presence of ligand, leads to metabolic diseases, including type 2 diabetes. Physical activity and mechanical stress have been shown to protect against insulin resistance, but the molecular mechanisms remain unclear. Here, we address this relationship in the larval fat body, an insulin-sensitive organ analogous to vertebrate adipose tissue and livers.

Membrane Trafficking in Autophagy.

Macroautophagy is an intracellular pathway used for targeting of cellular components to the lysosome for their degradation and involves sequestration of cytoplasmic material into autophagosomes formed from a double membrane structure called the phagophore. The nucleation and elongation of the phagophore is tightly regulated by several autophagy-related (ATG) proteins, but also involves vesicular trafficking from different subcellular compartments to the forming autophagosome. Such trafficking must be tightly regulated by various intra- and extracellular signals to respond to different cellular stressors and metabolic states, as well as the nature of the cargo to become degraded.

A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation.

Autophagy plays an essential role in the cellular homeostasis of neurons, facilitating the clearance of cellular debris. This clearance process is orchestrated through the assembly, transport, and fusion of autophagosomes with lysosomes for degradation. The motor protein dynein drives autophagosome motility from distal sites of assembly to sites of lysosomal fusion.

Atg1-independent induction of autophagy by the Drosophila Ulk3 homolog, ADUK.

Although canonical autophagy regulation requires a multi-protein complex centered on the Ser/Thr-kinase Atg1 (mammalian Ulk1/2), alternative signals can induce autophagy independent of Atg1 through unknown mechanisms. Here we identify the Drosophila Ulk3 ortholog, another Drosophila Unc-51-like kinase (ADUK), as an Atg1-independent autophagy inducer. ADUK interacts with Atg1 complex members Atg13 and 200 kDa FAK family kinase-interacting protein, and requires Atg13 but not Atg1 for autophagy induction.

Differential Activation of a Mouse Estrogen Receptor β Isoform (mERβ2) with Endocrine-Disrupting Chemicals (EDCs).

Background: Endocrine-disrupting chemicals (EDCs) are suspected of altering estrogenic signaling through estrogen receptor (ER) α or β (mERβ1 in mice). Several EDC effects have been reported in animal studies and extrapolated to human studies. Unlike humans, rodents express a novel isoform of ERβ (mERβ2) with a modified ligand-binding domain sequence.

Autophagosomes take the Klp98-A train.

The intracellular movement of membrane-bound vesicles is closely tied to their formation, maturation and ultimate function within the cell. Motor proteins and their associated cytoskeletal networks are critical for vesicle transport, but whether these factors play a more direct role in vesicle biogenesis is unclear. In recent work, we found that the Drosophila kinesin proteins Khc and Klp98A are both required for the normal anterograde movement of autophagosomes and autolysosomes during starvation-induced autophagy.

Coordination of autophagosome-lysosome fusion and transport by a Klp98A-Rab14 complex in Drosophila.

Degradation of cellular material by autophagy is essential for cell survival and homeostasis, and requires intracellular transport of autophagosomes to encounter acidic lysosomes through unknown mechanisms. Here, we identify the PX-domain-containing kinesin Klp98A as a new regulator of autophagosome formation, transport and maturation in Drosophila. Depletion of Klp98A caused abnormal clustering of autophagosomes and lysosomes at the cell center and reduced the formation of starvation-induced autophagic vesicles.

Kibra and aPKC regulate starvation-induced autophagy in Drosophila.

Autophagy is a bulk degradation system that functions in response to cellular stresses such as metabolic stress, endoplasmic reticulum stress, oxidative stress, and developmental processes. During autophagy, cytoplasmic components are captured in double-membrane vesicles called autophagosomes. The autophagosome fuses with the lysosome, producing a vacuole known as an autolysosome.