Hypothesis: ‘Vasocrine’ signalling from perivascular fat - a mechanism linking insulin resistance and vascular disease

Adipose tissue expresses cytokines which inhibit insulin signalling pathways in liver and muscle. Obesity also results in impairment of endothelium-dependent vasodilatation to insulin. We propose a vasoregulatory role for local deposits of fat around the origin of arterioles supplying skeletal muscle. Isolated first order arterioles from rat cremaster muscle are under dual regulation by insulin, which activates both endothelin-1 mediated vasoconstriction and nitric oxide mediated vasodilatation. In obese rat arterioles, insulin-stimulated nitric oxide synthesis is impaired, resulting in unopposed vasoconstriction. We propose this to be the consequence of production of the adipocytokine tumour necrosis factor-α from the cuff of fat seen surrounding the origin of the arteriole in obese rats – a depot to which we ascribe a specialist vasoregulatory role. We suggest that this cytokine accesses the nutritive vascular tree to inhibit insulin-mediated capillary recruitment – a mechanism we term ‘vasocrine’ signalling. We also suggest a homology between this vasoactive periarteriolar fat and both periarterial and visceral fat, which may explain relationships between visceral fat, insulin resistance and vascular disease

Cyanobacteria blooms cannot be controlled by effective microorganisms (EM) from mud- or Bokashi-balls

In controlled experiments, the ability of ‘‘Effective Microorganisms (EM, in the form of mudballs or Bokashi-balls)’’ was tested for clearing waters from cyanobacteria. We found suspensions of EM-mudballs up to 1 g l-1 to be ineffective in reducing cyanobacterial growth. In all controls and EM-mudball treatments up to 1 g l-1 the cyanobacterial chlorophyll-a (Chl-a) concentrations increased within 4 weeks from&120 to 325–435 lg l-1. When pieces of EM-mudballs (42.5 g) were added to 25-l lake water with cyanobacteria, no decrease of cyanobacteria as compared to untreated controls was observed. In contrast, after 4 weeks cyanobacterial Chl-a concentrations were significantly higher in EM-mudball treatments (52 lg l-1) than in controls (20 lg l-1). Only when suspensions with extremely high EM-mudball concentrations were applied (i.e., 5 and 10 g l-1), exceeding the recommended concentrations by orders of magnitude, cyanobacterial growth was inhibited and a bloom forming concentration was reduced strongly. In these high dosing treatments, the oxygen concentration dropped initially to very low levels of 1.8 g l-1. This was most probably through forcing strong light limitation on the cyanobacteria caused by the high amount of clay and subsequent high turbidity of the water. Hence, this study yields no support for the hypothesis that EM is effective in preventing cyanobacterial proliferation or in terminating blooms. We consider EM products to be ineffective because they neither permanently bind nor remove phosphorus from eutroficated systems, they have no inhibiting effect on cyanobacteria, and they could even be an extra source of nutrients

Processing and Transmission of Information

Contains reports on four research projects.National Science Foundation (Grant G-16526)National Institutes of Health (Grant MH-04737-03)National Aeronautics and Space Administration (Grant NsG-496)Lincoln Laboratory (Purchase Order DDL BB-107)United States Air Force (Contract AF19(628)-500

The hypertension cascade of care in the midst of conflict: the case of the Gaza Strip

Although hypertension constitutes a substantial burden in conflict-affected areas, little is known about its prevalence, control, and management in Gaza. This study aims to estimate the prevalence and correlates of hypertension, its diagnosis and control among adults in Gaza. We conducted a representative, cross-sectional, anonymous, household survey of 4576 persons older than 40 years in Gaza in mid-2020. Data were collected through face-to-face interviews, anthropometric, and blood pressure measurements. Hypertension was defined in anyone with an average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg from two consecutive readings or a hypertension diagnosis. The mean age of participants was 56.9 ± 10.5 years, 54.0% were female and 68.5% were Palestinian refugees. The prevalence of hypertension was 56.5%, of whom 71.5% had been diagnosed. Hypertension was significantly higher among older participants, refugees, ex-smokers, those who were overweight or obese, and had other co-morbidities including mental illnesses. Two-thirds (68.3%) of those with hypertension were on treatment with one in three (35.6%) having their hypertension controlled. Having controlled hypertension was significantly higher in females, those receiving all medications for high blood pressure and those who never or rarely added salt to food. Investing in comprehensive but cost-effective initiatives that strengthen the prevention, early detection and timely treatment of hypertension in conflict settings is critical. It is essential to better understand the underlying barriers behind the lack of control and develop multi-sectoral programs to address these barriers

Associations of stunting in early childhood with cardiometabolic risk factors in adulthood

Abstract Early life stunting may have long-term effects on body composition, resulting in obesity-related comorbidities. We tested the hypothesis that individuals stunted in early childhood may be at higher cardiometabolic risk later in adulthood. 1753 men and 1781 women participating in the 1982 Pelotas (Brazil) birth cohort study had measurements of anthropometry, body composition, lipids, glucose, blood pressure, and other cardiometabolic traits at age 30 years. Early stunting was defined as height-for-age Z-score at age 2 years below -2 against the World Health Organization growth standards. Linear regression models were performed controlling for sex, maternal race/ethnicity, family income at birth, and birthweight. Analyses were stratified by sex when p-interaction<0.05. Stunted individuals were shorter (β=-0.71 s.d.; 95% CI: -0.78 to -0.64), had lower BMI (β=-0.14 s.d.; 95%CI: -0.25 to -0.03), fat mass (β=-0.28 s.d.; 95%CI: -0.38 to -0.17), SAFT (β=-0.16 s.d.; 95%CI: -0.26 to -0.06), systolic (β=-0.12 s.d.; 95%CI: -0.21 to -0.02) and diastolic blood pressure (β=-0.11 s.d.; 95%CI: -0.22 to -0.01), and higher VFT/SAFT ratio (β=0.15 s.d.; 95%CI: 0.06 to 0.24), in comparison with non-stunted individuals. In addition, early stunting was associated with lower fat free mass in both men (β=-0.39 s.d.; 95%CI: -0.47 to -0.31) and women (β=-0.37 s.d.; 95%CI: -0.46 to -0.29) after adjustment for potential confounders. Our results suggest that early stunting has implications on attained height, body composition and blood pressure. The apparent tendency of stunted individuals to accumulate less fat-free mass and subcutaneous fat might predispose them towards increased metabolic risks in later life.The last phase of the 1982 Pelotas (Brazil) birth cohort study was supported by the Wellcome Trust and the Fundação de Aparo à Pesquisa do Estado do Rio Grande do Sul; Brazil (Edital 04/2012 – PQG; Processo 12/2185-9). Earlier phases were funded by the International Development Research Centre (Canada), the WHO (Department of Child and Adolescent Health and Development and Human Reproduction Programme) to BLH, the Overseas Development Administration (currently the Department for International Development, United Kingdom), the European Union, the United Nations Development Fund for Women, the National Program for Centres of Excellence, the Pastorate of the Child (Brazil), the National Council for Scientific and Technological Development (CNPq; Brazil), and the Ministry of Health (Brazil). GVAF was supported by the Brazilian Coordination of Improvement of Higher Education Personnel (scholarship process BEX 5077/13-3). EDLR and KKO are supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel

Inflammation, insulin resistance, and diabetes-mendelian randomization using CRP haplotypes points upstream

Background Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables. Methods and Findings We genotyped three tagging SNPs (CRP + 2302G &gt; A; CRP + 1444T &gt; C; CRP + 4899T &gt; G) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study). Homeostasis model assessment-insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p=0.52-0.92). The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p=0.007-0.11). Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p=0.25-0.88). Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations. Conclusions Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP

Family-based pediatric weight management interventions in US primary care settings targeting children ages 6-12 years old: A systematic review guided by the RE-AIM framework.

Obesity is a pandemic that disproportionately affects children from vulnerable populations in the USA. Current treatment approaches in primary care settings in the USA have been reported to be insufficient at managing pediatric obesity, primarily due to implementation challenges for healthcare systems and barriers for families. While the literature has examined the efficacy of pediatric obesity interventions focused on internal validity, it lacks sufficient reporting and analysis of external validity necessary for successful translation to primary care settings. We conducted a systematic review of the primary-care-setting literature from January 2007 to March 2020 on family-based pediatric weight management interventions in both English and/or Spanish for children ages 6-12 years in the USA using the Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. A literature search, using PRISMA guidelines, was conducted in January 2022 using the following electronic databases: Medline Ovid, Embase, and Cochrane Library. 22 270 records were screened, and 376 articles were reviewed in full. 184 studies were included. The most commonly reported dimensions of the RE-AIM framework were Reach (65%), Efficacy/Effectiveness (64%), and Adoption (64%), while Implementation (47%) and Maintenance (42%) were less often reported. The prevalence of reporting RE-AIM construct indicators ranged greatly, from 1% to 100%. This systematic review underscores the need for more focus on external validity to guide the development, implementation, and dissemination of future pediatric obesity interventions based in primary care settings. It also suggests conducting additional research on sustainable financing for pediatric obesity interventions