Cyclisation of Cell Penetrating PDZ-Binding Peptides Directed to PSD95

Excitatory glutamatergic neurotransmission via N-methyl-D-aspartate receptor (NMDAR) is critical for synaptic plasticity and survival of neurons. Excessive NMDAR activity, however can cause excitotoxicity and promote cell death, underlying a potential mechanism of neurodegeneration occurring in Alzheimer’s disease (AD). The regulation of calcium levels at synapses is important for pre- and post-synaptic activation in the hippocampus, where glutamate is the primary neurotransmitter, acting via metabotropic and ionotropic receptors

New Benzotriozole Phthalocyanine Nickel(II) Photostabilizer for Low Density Polyethylene

Benzotiozole Phthalocyanine Nickel(II) has been prepared and characterized by elemental analysis and FT-IR techniques. This new compound imposes three bathways to stablize low density polyethylene (LDPE) due to nature of its complex structure.The prepared complex contains four benzotrizoles which absorb U.V. light while Nickel(II) derivative destroye hydrogen peroxides and scavenge free radicals. The experimental investigation carried out on Benzotriozole phthalocyanine Nickel(II) shows that this complex has excellent photostabilizer for LDPE compared with commercial antioxidants. Keywords: Photostabilizer, Phthalocyanine Nickel(II) derivatives, LDP

Polycyclic aromatic hydrocarbons in citrus fruit irrigated with fresh water under arid conditions: Concentrations, sources, and risk assessment

In Jordan, as well as in all the world countries, consumption of citrus fruits is an essential part of the daily diet, so it is important to assess the potential risk of the persistent organic pollutants such as polyaromatic hydrocarbons (PAHs) in these fruits to the human health and identify their sources in order to eliminate or reduce them. This study reports 16 priority PAHs content in four types of peeled citrus fruits grown in Jordan valley. PAHs were detected in all the studied samples in variable quantities depending on the type of citrus fruits. The results showed that the highest PAH level corresponded to acenaphthene (35.018 µg/kg) in grapefruit. Among the carcinogenic PAHs, benzo[a]anthracene (BaA) and benzo(a)pyrene (BaP) were the most representative and found in all the analyzed fruit, soil, and water samples, whereas anthracene (ANT) was not detected at all. The mean ∑16 PAHs for the different fruits were found to be 62.593 µg kg−1 in grapefruit, 24.840 µg kg−1 in lemon, 22.901 µg kg−1 in mandarin, and 5.082 µg kg−1 in orange. The dominance of naphthalene (NAP) and acenaphthene (ACE) in soil under hot climatic conditions indicates the recent and continuous input of these types in the investigated area. The bioconcentration factor (BCF) for ∑16 PAHs was observed in the order of grapefruit > lemon > mandarin > orange. Based on the results of the principal component analysis (PCA), the primary sources of PAHs in agricultural soils mainly originated from biomass burning and vehicular emissions. The incremental lifetime cancer risk (ILCR) indicated that consumption of these four citrus fruits may expose human health to potential cancer risk. The findings of this study call the policymakers and public administrations to the formulation of stringent policies and actions to control biomass burning and vehicular emissions

A systematic review of internet-based worksite wellness approaches for cardiovascular disease risk management: outcomes, challenges & opportunities.

ContextThe internet is gaining popularity as a means of delivering employee-based cardiovascular (CV) wellness interventions though little is known about the cardiovascular health outcomes of these programs. In this review, we examined the effectiveness of internet-based employee cardiovascular wellness and prevention programs.Evidence acquisitionWe conducted a systematic review by searching PubMed, Web of Science and Cochrane library for all published studies on internet-based programs aimed at improving CV health among employees up to November 2012. We grouped the outcomes according to the American Heart Association (AHA) indicators of cardiovascular wellbeing--weight, BP, lipids, smoking, physical activity, diet, and blood glucose.Evidence synthesisA total of 18 randomized trials and 11 follow-up studies met our inclusion/exclusion criteria. Follow-up duration ranged from 6-24 months. There were significant differences in intervention types and number of components in each intervention. Modest improvements were observed in more than half of the studies with weight related outcomes while no improvement was seen in virtually all the studies with physical activity outcome. In general, internet-based programs were more successful if the interventions also included some physical contact and environmental modification, and if they were targeted at specific disease entities such as hypertension. Only a few of the studies were conducted in persons at-risk for CVD, none in blue-collar workers or low-income earners.ConclusionInternet based programs hold promise for improving the cardiovascular wellness among employees however much work is required to fully understand its utility and long term impact especially in special/at-risk populations

Accumulation, Source Identification, and Cancer Risk Assessment of Polycyclic Aromatic Hydrocarbons (PAHs) in Different Jordanian Vegetables

The accumulation of polyaromatic hydrocarbons in plants is considered one of the most serious threats faced by mankind because of their persistence in the environment and their carcinogenic and teratogenic effect on human health. The concentrations of sixteen priority polycyclic aromatic hydrocarbons (16 PAHs) were determined in four types of edible vegetables (tomatoes, zucchini, eggplants, and cucumbers), irrigation water, and agriculture soil, where samples were collected from the Jordan Valley, Jordan. The mean total concentration of 16 PAHs (∑16PAHs) ranged from 10.649 to 21.774 µg kg−1 in vegetables, 28.72 µg kg−1 in soil, and 0.218 µg L−1 in the water samples. The tomato samples posed the highest ∑16PAH concentration level in the vegetables, whereas the zucchini samples had the lowest. Generally, the PAHs with a high molecular weight and four or more benzene rings prevailed among the studied samples. The diagnostic ratios and the principal component analysis (PCA) revealed that the PAH contamination sources in soil and vegetables mainly originated from a pyrogenic origin, traffic emission sources, and biomass combustion. The bioconcentration factors (BCF) for ∑16PAHs have been observed in the order of tomatoes > cucumbers and eggplants > zucchini. A potential cancer risk related to lifetime consumption was revealed based on calculating the incremental lifetime cancer risk of PAHs (ILCR). Therefore, sustainable agricultural practices and avoiding biomass combusting would greatly help in minimizing the potential health risk from dietary exposure to PAHs

The association of clinical indication for exercise stress testing with all-cause mortality: the FIT Project

INTRODUCTION: We hypothesized that the indication for stress testing provided by the referring physician would be an independent predictor of all-cause mortality. MATERIAL AND METHODS: We studied 48,914 patients from The Henry Ford Exercise Testing Project (The FIT Project) without known congestive heart failure who were referred for a clinical treadmill stress test and followed for 11 ±4.7 years. The reason for stress test referral was abstracted from the clinical test order, and should be considered the primary concerning symptom or indication as stated by the ordering clinician. Hierarchical multivariable Cox proportional hazards regression was performed, after controlling for potential confounders including demographics, risk factors, and medication use as well as additional adjustment for exercise capacity in the final model. RESULTS: A total of 67% of the patients were referred for chest pain, 12% for shortness of breath (SOB), 4% for palpitations, 3% for pre-operative evaluation, 6% for abnormal prior testing, and 7% for risk factors only. There were 6,211 total deaths during follow-up. Compared to chest pain, those referred for palpitations (HR = 0.72, 95% CI: 0.60-0.86) and risk factors only (HR = 0.72, 95% CI: 0.63-0.82) had a lower risk of all-cause mortality, whereas those referred for SOB (HR = 1.15, 95% CI: 1.07-1.23) and pre-operative evaluation (HR = 2.11, 95% CI: 1.94-2.30) had an increased risk. In subgroup analysis, referral for palpitations was protective only in those without coronary artery disease (CAD) (HR = 0.75, 95% CI: 0.62-0.90), while SOB increased mortality risk only in those with established CAD (HR = 1.25, 95% CI: 1.10-1.44). CONCLUSIONS: The indication for stress testing is an independent predictor of mortality, showing an interaction with CAD status. Importantly, SOB may be associated with higher mortality risk than chest pain, particularly in patients with CAD

Birth prevalence of non-syndromic orofacial clefts in Saudi Arabia and the effects of parental consanguinity

Objectives: To describe the characteristics and prevalence of non-syndromic orofacial clefting (NSOFC) and assess the effects of parental consanguinity on NSOFC phenotypes in the 3 main cities of Saudi Arabia. Methods: All infants (114,035) born at 3 referral centers in Riyadh, and 6 hospitals in Jeddah and Madinah between January 2010 and December 2011 were screened. The NSOFC cases (n=133) were identified and data was collected through clinical examination and records, and information on consanguinity through parent interviews. The diagnosis was confirmed by reviewing medical records and contacting the infants’ pediatricians. Control infants (n=233) matched for gender and born in the same hospitals during the same period, were selected. Results: The prevalence of NSOFC was 1.07/1000 births in Riyadh, and 1.17/1000 births overall; cleft lip (CL) was 0.47/1000 births, cleft lip and palate (CLP) was 0.42/1000 births, and cleft palate (CP) was 0.28/1000 births. Cleft palate was significantly associated with consanguinity (p=0.047, odds ratio: 2.5, 95% confidence interval: 1 to 6.46), particularly for first cousin marriages. Conclusion: The birth prevalence of NSOFC in Riyadh alone, and in the 3 main cities of Saudi Arabia were marginally lower than the mean global prevalence. While birth prevalence for CLP was comparable to global figures, the CL:CLP ratio was high, and only CP was significantly associated with consanguinity

Using imputed whole-genome sequence data to improve the accuracy of genomic prediction for parasite resistance in Australian sheep

International audienceAbstractBackgroundThis study aimed at (1) comparing the accuracies of genomic prediction for parasite resistance in sheep based on whole-genome sequence (WGS) data to those based on 50k and high-density (HD) single nucleotide polymorphism (SNP) panels; (2) investigating whether the use of variants within quantitative trait loci (QTL) regions that were selected from regional heritability mapping (RHM) in an independent dataset improved the accuracy more than variants selected from genome-wide association studies (GWAS); and (3) comparing the prediction accuracies between variants selected from WGS data to variants selected from the HD SNP panel.ResultsThe accuracy of genomic prediction improved marginally from 0.16 ± 0.02 and 0.18 ± 0.01 when using all the variants from 50k and HD genotypes, respectively, to 0.19 ± 0.01 when using all the variants from WGS data. Fitting a GRM from the selected variants alongside a GRM from the 50k SNP genotypes improved the prediction accuracy substantially compared to fitting the 50k SNP genotypes alone. The gain in prediction accuracy was slightly more pronounced when variants were selected from WGS data compared to when variants were selected from the HD panel. When sequence variants that passed the GWAS -log10(pvalue)\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$- log_{10} (p\,value)$$\end{document} threshold of 3 across the entire genome were selected, the prediction accuracy improved by 5% (up to 0.21 ± 0.01), whereas when selection was limited to sequence variants that passed the same GWAS -log10(pvalue)\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$- log_{10} (p\,value)$$\end{document} threshold of 3 in regions identified by RHM, the accuracy improved by 9% (up to 0.25 ± 0.01).ConclusionsOur results show that through careful selection of sequence variants from the QTL regions, the accuracy of genomic prediction for parasite resistance in sheep can be improved. These findings have important implications for genomic prediction in sheep

Evaluation of aspirin and statin therapy use and adherence in patients with premature atherosclerotic cardiovascular disease

Importance: Studies on the use of and adherence to secondary prevention therapies in patients with premature and extremely premature atherosclerotic cardiovascular disease (ASCVD) are lacking.Objective: To evaluate and compare aspirin use, any statin use, high-intensity statin use, and statin adherence among patients with premature or extremely premature ASCVD compared with patients with nonpremature ASCVD.Design, setting, and participants: This multicenter cross-sectional study used the clinical and administrative data sets of the US Department of Veterans Affairs (VA) to identify adult patients with at least 1 primary care visit in the VA health care system between October 1, 2014, and September 30, 2015. The study cohort comprised patients with ASCVD (ischemic heart disease, peripheral arterial disease, or ischemic cerebrovascular disease) who were enrolled in the Veterans With Premature Atherosclerosis (VITAL) registry. Patients with missing data for date of birth or sex and those with limited life expectancy were excluded. Data were analyzed from November 1, 2019, to January 1, 2020.Exposures: Premature (the first ASCVD event occurred at age women) vs nonpremature (the first ASCVD event occurred at age ≥55 years for men or age ≥65 years for women) ASCVD and extremely premature (the first ASCVD event occurred at age \u3c40 \u3eyears) vs nonpremature ASCVD.Main outcomes and measures: The primary outcomes were aspirin use, any statin use, high-intensity statin use, and statin adherence (measured by proportion of days covered [PDC] ≥0.8).Results: Of the 1 248 158 patients identified, 135 703 (10.9%) had premature ASCVD (mean [SD] age, 49.6 [5.8] years; 116 739 men [86.0%]), 1 112 455 (89.1%) had nonpremature ASCVD (mean [SD] age, 69.6 [8.9] years; 1 104 318 men [99.3%]), and 7716 (0.6%) had extremely premature ASCVD (mean [SD] age, 34.2 [4.3] years; 6576 men [85.2%]). Patients with premature ASCVD vs those with nonpremature ASCVD had lower rates of aspirin use (96 468 [71.1%] vs 860 726 [77.4%]; P \u3c .001) and any statin use (98 908 [72.9%] vs 894 931 [80.5%]; P \u3c .001); had a statin PDC of 0.8 or higher (57 306 [57.9%] vs 644 357 [72.0%]; P \u3c .001); and a higher rate of high-intensity statin use (49 354 [36.4%] vs 332 820 [29.9%]; P \u3c .001). Similarly, patients with extremely premature ASCVD were less likely to use aspirin (odds ratio [OR], 0.27; 95% CI, 0.26-0.29), any statin (OR, 0.25; 95% CI, 0.24-0.27), or high-intensity statin (OR, 0.78; 95% CI, 0.74-0.82) and to be statin adherent (OR, 0.44; 95% CI, 0.41-0.47).Conclusions and relevance: In this study, patients with premature or extremely premature ASCVD appeared to be less likely to use aspirin or statins and to adhere to statin therapy. This finding warrants further investigation into premature ASCVD and initiatives, including clinician and patient education, to better understand and mitigate the disparities in medication use and adherence