General health status of youth with autism with and without intellectual disabilities transitioning from special education, and its relationship to personal and family circumstances:Longitudinal cohort study

Objective: Transition from school to early adulthood incurs many changes and may be associated with deterioration in general health in youth with autism. We aimed to investigate this. Method: The National Longitudinal Transitions Study-2 is a USA nationally representative sample of youth receiving special education services, aged 13–17 at wave 1, followed-up over 10 years in five data collection waves. We conducted random-effects ordered logistic regressions to determine the odds ratios (OR) with 95% confidence intervals of wave, age, sex, ethnicity/race, additional intellectual disabilities, parental/guardian relationship status, and household income being associated with general health status in youth with autism. Results: Across waves, only between 74.3%–69.6% had excellent/very good health (71.7%–58.8% in those with co-occurring intellectual disabilities), but wave was not associated with health status. Associations were with age OR = 1.18 (1.04, 1.33), co-occurring intellectual disabilities OR = 1.56 (1.00, 2.44), and household income OR = 0.61 (0.40, 0.94) at $30,001–$50,000, OR = 0.44 (0.27, 0.72) at $50,001–$70,000, and OR = 0.34 (0.20, 0.56) at $70,001+. Sex, ethnicity/race, and parental/guardian relationship status were not associated with health status. Conclusion: There was little change in general health status longitudinally across the transitional period, but the proportion with excellent/very good health was low at each wave. Transitional planning should consider co-occurring intellectual disabilities, and the wider socioeconomic context in which children/youth with autism are raised. Lack of other longitudinal studies indicates a need for replication

Effect of a reduction in glomerular filtration rate after nephrectomy on arterial stiffness and central hemodynamics: rationale and design of the EARNEST study

Background: There is strong evidence of an association between chronic kidney disease (CKD) and cardiovascular disease. To date, however, proof that a reduction in glomerular filtration rate (GFR) is a causative factor in cardiovascular disease is lacking. Kidney donors comprise a highly screened population without risk factors such as diabetes and inflammation, which invariably confound the association between CKD and cardiovascular disease. There is strong evidence that increased arterial stiffness and left ventricular hypertrophy and fibrosis, rather than atherosclerotic disease, mediate the adverse cardiovascular effects of CKD. The expanding practice of live kidney donation provides a unique opportunity to study the cardiovascular effects of an isolated reduction in GFR in a prospective fashion. At the same time, the proposed study will address ongoing safety concerns that persist because most longitudinal outcome studies have been undertaken at single centers and compared donor cohorts with an inappropriately selected control group.<p></p> Hypotheses: The reduction in GFR accompanying uninephrectomy causes (1) a pressure-independent increase in aortic stiffness (aortic pulse wave velocity) and (2) an increase in peripheral and central blood pressure.<p></p> Methods: This is a prospective, multicenter, longitudinal, parallel group study of 440 living kidney donors and 440 healthy controls. All controls will be eligible for living kidney donation using current UK transplant criteria. Investigations will be performed at baseline and repeated at 12 months in the first instance. These include measurement of arterial stiffness using applanation tonometry to determine pulse wave velocity and pulse wave analysis, office blood pressure, 24-hour ambulatory blood pressure monitoring, and a series of biomarkers for cardiovascular and bone mineral disease.<p></p> Conclusions: These data will prove valuable by characterizing the direction of causality between cardiovascular and renal disease. This should help inform whether targeting reduced GFR alongside more traditional cardiovascular risk factors is warranted. In addition, this study will contribute important safety data on living kidney donors by providing a longitudinal assessment of well-validated surrogate markers of cardiovascular disease, namely, blood pressure and arterial stiffness. If any adverse effects are detected, these may be potentially reversed with the early introduction of targeted therapy. This should ensure that kidney donors do not come to long-term harm and thereby preserve the ongoing expansion of the living donor transplant program.<p></p&gt

General health status in young people with intellectual disabilities with and without Down syndrome in, and transitioning from, special education: findings from the National Longitudinal Transitions Study‐2

Background: There has been little prior investigation of the general health of young people with intellectual disabilities across transition, nor separately for youth with intellectual disabilities with or without Down syndrome, despite general health being a strong predictor of subsequent health service use, hospital admissions and mortality in the general population. We aimed to investigate general health status in youth with intellectual disabilities with and without Down syndrome over the transitional period and quantify the extent to which personal characteristics, parental relationship and household income are associated with general health status. Methods: The National Longitudinal Transitions Study‐2 includes a nationally representative sample of youth receiving special education services aged 13–17 years at wave 1, followed up over 10 years in five waves of data collection. Data on general health status of youth with intellectual disabilities with and without Down syndrome were obtained from parent reports. We summarised overall demographics and general health status and plotted general health status for those who had health data available for all five waves. We then used random‐effects ordered logistic regression to investigate whether wave of data collection, age, sex, Down syndrome, ethnicity, parental relationship status and household income are associated with general health status. Results: At wave 1, data on intellectual disabilities were available on 9008/9576 (94.1%) young people, and 871/9008 (9.7%) of them had intellectual disabilities, of whom 125/871 (14.4%) had Down syndrome. Youth with intellectual disabilities with or without Down syndrome had low rates of excellent or very good health. Across waves 1–5, there was a shallow gradient in the proportion of youth with intellectual disabilities reporting excellent/very good health, from 57.7% at 13–17 years to 52.6% at 21–25 years, being more marked for those without Down syndrome (57.8% at 13–17 years to 51.8% at 21–25 years). However, contrary to our expectations, an ordinal measure of general health status did not decline over this transitional period and did not differ between youth with and without Down syndrome. There was a gradient with higher income associated with better health, significantly so over $50 001 (odds ratio = 0.559, 95% confidence interval 0.366–0.854). Poorer health was experienced by youth with Hispanic, Latino or Spanish ethnicity (odds ratio = 1.790, 95% confidence interval 1.051–3.048). Female sex and parental relationship status were not associated with health status. Conclusions: Young people with intellectual disabilities have bad health, and require support across all ages, including transition. Schools, teachers and staff in transitional services should consider health, and health care and support during transitional planning due to change in service provision and be aware of ethnicity and the stressful effects of low household income. This is important as interventions based on provision of greater support can prevent adverse consequences

Enhanced Activity of Meprin-α, a Pro-Migratory and Pro-Angiogenic Protease, in Colorectal Cancer

Meprin-α is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-α levels on tumor progression is not known. We investigated the effect of this protease on cell migration and angiogenesis in vitro and studied the expression of meprin-α mRNA, protein and proteolytic activity in primary tumors at progressive stages and in liver metastases of patients with colorectal cancer, as well as inhibitory activity towards meprin-α in sera of cancer patient as compared to healthy controls. We found that the hepatocyte growth factor (HGF)- induced migratory response of meprin-transfected epithelial cells was increased compared to wild-type cells in the presence of plasminogen, and that the angiogenic response in organ-cultured rat aortic explants was enhanced in the presence of exogenous human meprin-α. In patients, meprin-α mRNA was expressed in colonic adenomas, primary tumors UICC (International Union Against Cancer) stage I, II, III and IV, as well as in liver metastases. In contrast, the corresponding protein accumulated only in primary tumors and liver metastases, but not in adenomas. However, liver metastases lacked meprin-α activity despite increased expression of the corresponding protein, which correlated with inefficient zymogen activation. Sera from cancer patients exhibited reduced meprin-α inhibition compared to healthy controls. In conclusion, meprin-α activity is regulated differently in primary tumors and metastases, leading to high proteolytic activity in primary tumors and low activity in liver metastases. By virtue of its pro-migratory and pro-angiogenic activity, meprin-α may promote tumor progression in colorectal cancer

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Effect of adenosine on LEC viability and proliferation.

<p>Cell viability (a) and proliferation (b–c) were evaluated in HMVEC-dLy ( = LEC) cultured for 48 h (left panel) or 72 h (right panel) in medium containing 2% FBS (CTRL). Cells were treated with EHNA alone (EHNA 10 μM), EHNA with different concentrations of adenosine (AE), the A2a agonist CGS21680 or the A2b agonist NECA. For cell viability (a), results are expressed as percentage of dead cells (black) and living cells (white). Cell proliferation (b–c) was measured with a CyQANT assay. * p<0.05 vs control (CTRL), *** p<0.001 vs CTRL. Data are expressed as mean ± SEM (n = 3).</p

Quantitative PCR primers.

<p>Quantitative PCR primers.</p

Effect of adenosine on LEC migration in scratch test.

<p>HMVEC-dLy were treated during 24 h in medium containing 2% FBS, in the presence of EHNA alone (EHNA, 10 μM) or EHNA with different concentrations of adenosine (AE). Pictures were taken at 0 h, 8 h, 16 h and 24 h after insert removing. Results are expressed as percentage of wound closure (percentage closure) (mean ± SEM). * p<0.05 vs CTRL, ***p<0.001 vs CTRL. Each experiment was performed three times and a representative picture of each condition is shown.</p