Obesity is a risk factor for type 2 diabetes (T2D), however not all obese individuals develop the disease. In this study, we aimed to investigate the cause of differential insulin secretion capacity of pancreatic islets from T2D and non-T2D (ND) especially obese donors (BMI ≥30 kg/m²). Islets from obese T2D donors had reduced insulin secretion, decreased β-cell exocytosis and higher expression of fatty acid translocase CD36. We tested the hypothesis that CD36 is a key molecule in the reduced insulin secretion capacity. Indeed, CD36 overexpression led to decreased insulin secretion, impaired exocytosis and reduced granule docking. This was accompanied with reduced expression of the exocytotic proteins, SNAP25, STXBP1 and VAMP2, likely because CD36 induced down-regulation of the IRS proteins, suppressed insulin signaling PI3K-AKT pathway and increased nuclear localization of the transcription factor FoxO1. CD36 antibody treatment of the human β-cell line, EndoC-βH1, increased IRS1 and exocytotic protein levels, improved granule docking and enhanced insulin secretion. Our results demonstrate that β-cells from obese T2D donors have dysfunctional exocytosis likely due to an abnormal lipid handling represented by differential CD36 expression. Hence, CD36 could be a key molecule to limit β-cell function in T2D associated with obesity.

Hepatic steatosis, the excess storage of intrahepatic lipids, is a rampant clinical problem associated with the obesity epidemic. Hepatic steatosis is linked to increased risk for insulin resistance, type 2 diabetes, and cardiovascular and advanced liver disease. Accumulating evidence shows that physical activity, exercise, and aerobic capacity have profound effects on regulating intrahepatic lipids and mediating susceptibility for hepatic steatosis. Moreover, exercise can effectively reduce hepatic steatosis independent of changes in body mass. In this perspective, we highlight 1) the relationship between obesity and metabolic pathways putatively driving hepatic steatosis compared with changes induced by exercise; 2) the impact of physical activity, exercise, and aerobic capacity compared with caloric restriction on regulating intrahepatic lipids and steatosis risk; 3) the effects of exercise training (modalities, volume, intensity) for treatment of hepatic steatosis, and 4) evidence for a sustained protection against steatosis induced by exercise. Overall, evidence clearly indicates that exercise powerfully regulates intrahepatic storage of fat and risk for steatosis.

6 November 2015 , Volume 91, Number 6

As the Mets, Nationals and Phillies have made multiple upgrades, Braves GM Alex Anthopoulos has thus far limited his offseason activity to giving Josh Donaldson a record one-year deal and bringing to fruition the desires of Brian McCann and Nick Markakis to play for the Braves.

Invitation Only Research Event

Event participants

Dr Ashwini Swain, Fellow, CUTS Institute for Regulation and Competition
Glada Lahn, Senior Research Fellow, Energy, Environment and Resources, Chatham House
Dr Gareth Price, Senior Research Fellow, Asia Programme, Chatham House

Members Event

Event participants

Penny Mordaunt MP, Member of Parliament for Portsmouth North; Secretary of State for Defence (2019); Secretary of State for International Development (2017-2019)

Chair: Thomas Raines, Director, Europe Programme, Chatham House

Large outflows of educated young people escaping high levels of unemployment, in tandem with inflows of unauthorized migrants, pose a fresh set of challenges for Greek policymakers. This Transatlantic Council on Migration report examines Greek emigration, and its economic implications, before exploring policy directions to minimize the costs and maximize the benefits of this mobility.

Robert R. Henry
Mar 1, 2015; 38:412-419
Evolving Tactics With Inhibition of Sodium-Glucose Cotransporters

Ogden, Utah — The Office for Civil Rights announced March 3 that it had reached a settlement with Dr. Steven A. Porter’s medical practice to settle a potential violation of the Health Insurance Portability and Accountability Act security rule.

The Association is asking member dentists and their dental teams to increase their vigilance over phishing emails as a result of the coronavirus, known as COVID-19.
Attackers often use emergencies as an opportunity to send fake emails tailored to that situation, the association said.

On this webinar, MPI researchers and Utah and Colorado refugee coordinators explore promising practices to better serve refugee families, including education services for refugee youth, innovative efforts to secure better jobs for adult refugees, and other services designed to aid integration over time. They also discuss the potential for implementing and supporting two-generation approaches to refugee integration at a time when the system’s funding and capacity are in peril.  

OBJECTIVE

In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34⁺ cells predicted cardiovascular mortality at 18 months after revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker.

With the Trump administration having announced the end of the DACA program, Congress is facing growing calls to protect unauthorized immigrants who came to the U.S. as children. This fact sheet examines DREAM Act bills introduced in Congress as of mid-2017, offering estimates of who might earn conditional legal status—and ultimately legal permanent residence—based on educational, professional, and other requirements in the legislation.

Across Europe, grassroots efforts have emerged in the wake of crisis that draw members of the public into the process of receiving refugees and supporting their integration. This policy brief examines the many forms community-based or private sponsorship can take, what benefits such approaches may hold for European communities, and the tradeoffs policymakers face in their implementation.

One of the major challenges Canada faced during its extraordinary push to resettle 25,000 Syrian refugees during a four-month period was to find housing for these newcomers. This report explores how the government, resettlement case workers, and private citizens tackled this challenge—balancing cost and location, access to services, and more—and how lessons learned can improve refugee housing practices for other countries going forward.

At a time when the U.S. refugee resettlement system is facing unprecedented challenges, innovative and cost-effective tools for supporting refugee integration are in demand. This report explores how a two-generation approach to service provision could help all members of refugee families—from young children to working-age adults and the elderly—find their footing.

As the U.S. workforce ages and the economy becomes ever more knowledge-based, policymakers face a key question: Do workers have the skills to meet tomorrow's demands? This report examines how immigrants and their children—the primary source of future labor-market growth—fit into the discussion. The report offers a first-ever profile of the 30 million immigrant-origin adults without a postsecondary credential.

BRUSSELS — While the European Union has called on Member States to expand channels for foreign workers as a way to meet labour market needs and potentially tackle spontaneous migration, they have struggled to deliver on this pledge. To date, policies have focused more on attracting high-skilled workers, but less attention has been paid to admission of low- or middle-skilled nationals. Policymakers would do well not to overestimate the potential of legal channels to reduce irregular migration.

Home visiting programs for young families are growing in popularity across the United States, and have demonstrated their effectiveness in supporting maternal health and child well-being. At the same time, more infants and toddlers are growing up in immigrant families and households where a language other than English is spoken. Why then are these children under-represented in these programs? This brief explores common barriers, ways to address them, and why it is important to do so.

Huy A. Tran
Jul 1, 2004; 22:141-143
Case Studies

Andrew M. Davis
Apr 1, 2008; 26:58-62
Feature Articles

The NCAA is expected to formally approve rules changes that will allow athletes to get endorsement income in 2021.

In 2017 the Department of the Prime Minister and Cabinet and Australian Defence Force (Australian Army) undertook a joint review of the Army Aboriginal Community Assistance Programme (AACAP) to assess its efficiency and effectiveness. The review found AACAP is a highly regarded and effective means of achieving positive environmental and primary health outcomes for Aboriginal and Torres Strait Islander communities while providing valuable training outcomes for Army. AACAP's objectives align with the Council of Australian Governments (COAG) 'Closing the Gap' targets in Indigenous disadvantage and with the Australian Government's Indigenous Advancement Strategy (IAS). The report identified areas for potential improvement, recommending greater support for the sustainability of infrastructure and project investment, enhanced employment and training opportunities and strengthening of project governance.

Heredity -- Genetics.

195?

Ben Jones, Andreas Artemiou, Bing Li.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 1--23.

Abstract:
We give a probabilistic analysis of a phenomenon in statistics which, until recently, has not received a convincing explanation. This phenomenon is that the leading principal components tend to possess more predictive power for a response variable than lower-ranking ones despite the procedure being unsupervised. Our result, in its most general form, shows that the phenomenon goes far beyond the context of linear regression and classical principal components — if an arbitrary distribution for the predictor $X$ and an arbitrary conditional distribution for $Yvert X$ are chosen then any measureable function $g(Y)$, subject to a mild condition, tends to be more correlated with the higher-ranking kernel principal components than with the lower-ranking ones. The “arbitrariness” is formulated in terms of unitary invariance then the tendency is explicitly quantified by exploring how unitary invariance relates to the Cauchy distribution. The most general results, for technical reasons, are shown for the case where the kernel space is finite dimensional. The occurency of this tendency in real world databases is also investigated to show that our results are consistent with observation.

Karim Fifel
Jan 24, 2018; 38:784-786
Journal Club

Jeremy R. Manning
Oct 28, 2009; 29:13613-13620
BehavioralSystemsCognitive

Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39. However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Hgf. Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness.

SIGNIFICANCE STATEMENT Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 bp deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic.

The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ.

SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies.

Today’s fisheries sector hosts a multibillion dollar industry that is a vital source of food and nutrition, employment, trade, economic wellbeing and recreation. What is blue growth? The concept of a "blue economy" came out of the 2012 Rio+20 Conference and emphasizes conservation and sustainable management, based on the premise that healthy ocean ecosystems are more productive and a must for sustainable [...]

The Bank of Canada, the Bank of England, the Bank of Japan, the European Central Bank, the Sveriges Riksbank and the Swiss National Bank, together with the Bank for International Settlements (BIS), have created a group to share experiences as they assess the potential case for central bank digital currency (CBDC) in their home jurisdictions. (Press release, 21 January 2020)

Apple is shifting a substantial portion of its current AirPods production from China to Vietnam, and appears to be considering a release schedule later than previously predicted for an AirPods refresh.

An adolescent girl with a history of frequent electronic cigarette use of nicotine was hospitalized with severe necrotizing pneumonia. Blood cultures obtained before the administration of empirical broad-spectrum intravenous antibiotics had positive results for the growth of Fusobacterium necrophorum. The pathogen is an uncommon but well-known cause of anaerobic pneumonia with unique features that are collectively referred to as Lemierre syndrome or postanginal sepsis. The syndrome begins as a pharyngeal infection. Untreated, the infection progresses to involve the ipsilateral internal jugular vein, resulting in septic thrombophlebitis with direct spread from the neck to the lungs causing multifocal necrotizing pneumonia. The teenager we present in this report had neither a preceding pharyngeal infection nor Doppler ultrasonographic evidence for the presence of deep neck vein thrombi, leading us to explore alternative mechanisms for her pneumonia. We propose the possibility that her behavior of frequent vaping led to sufficient pharyngeal irritation such that F necrophorum colonizing her oropharynx was inhaled directly into her lungs during electronic cigarette use. Preexisting, but not yet recognized, vaping-related lung injury may have also contributed to her risk of developing the infection. The patient was hospitalized for 10 days. At follow-up one month later, she still became short of breath with minimal exertion.

A BIOTECH veteran has hailed a Glasgow firm that claims to have discovered two separate potential treatments for Covid-19 patients for use before they are put on ventilators.

A textbook is no longer enough in many classrooms, writes Dan McDowell, but finding the right OER materials can be tricky.

Critics argue that pediatric research without the potential for clinical benefit treats children as mere means to benefit others. Yet, there are no data to assess whether adolescents who participate in research, or their parents, agree with this view.

Respondents felt that by participating in research the adolescents were making important contributions to help others, and the adolescents felt proud to be doing so. These findings support the view that nonbeneficial pediatric research involves a type of charitable activity. (Read the full article)

Bisphenol A (BPA) is an environmental endocrine disruptor that can leach from polycarbonate plastics and epoxy resins, leading to widespread exposure. Fetal and early postnatal periods are particularly vulnerable to exposure to BPA.

This study identified medical devices as a potential source of exposure to BPA among premature infants in the NICU, even when efforts to reduce polycarbonate plastics were taken. (Read the full article)

Impaired visual development has been reported in infants born to mothers prescribed methadone in pregnancy. Immature visual evoked potentials have been reported in this population, but data were confounded by gestation, growth restriction, and illicit drug use.

Visual evoked potentials are small and immature in infants exposed to methadone and other drugs of misuse in utero. These changes are independently associated with methadone exposure and persist after controlling for gestation, socioeconomic deprivation, alcohol consumption, and cigarette smoking. (Read the full article)

Studies have highlighted a lack of patient awareness of potential increased cancer risks associated with computed tomography (CT) scans in adult patients and in nonurgent settings. However, little is known about parental awareness of these risks in an emergency setting.

Approximately half of parents were aware of the potential cancer risks from CT scans in an emergency setting. Although risk disclosure moderately reduced willingness to proceed with recommended testing, almost all parents preferred an informed discussion before CT imaging. (Read the full article)

Certain characteristics of the sleep environment increase the risk for sleep-related, sudden, and unexplained infant death. These characteristics have the potential to generate asphyxia. The relationship between the deaths occurring in these environments and neurochemical abnormalities in the brainstem that may impair protective responses to asphyxia is unknown.

We report neurochemical brainstem abnormalities underlying cases of sudden infant death that are associated with and without potential asphyxial situations in the sleep environment at death. The means to detect and treat these abnormalities in infants at risk are needed. (Read the full article)

The demand for donor kidneys for transplantation exceeds supply. En bloc kidney transplantation and donation after determination of circulatory death from pediatric donors increases the potential donor pool.

Newborn infants undergoing elective withdrawal of life support in the NICU are a previously unrecognized source of potential kidney donors. (Read the full article)

Hospitalized pediatric patients are often exposed to many medications during an inpatient admission. Drug–drug interactions may increase the risk of developing medication-related adverse drug events, leading to serious clinical morbidity and mortality.

Exposure to "major" potential drug–drug interactions occurs in 41% of pediatric hospitalizations in children’s hospitals. One-half of all these exposures were due to less common specific drug pairs (≤3% of patients exposed per hospital day) and thus may be less clinically familiar. (Read the full article)