Involvement of heparanase in the pathogenesis of acute kidney injury: Nephroprotective effect of PG545

Despite the high prevalence of acute kidney injury (AKI) and its association with increased morbidity and mortality, therapeutic approaches for AKI are disappointing. This is largely attributed to poor understanding of the pathogenesis of AKI. Heparanase, an endoglycosidase that cleaves heparan sulfate, is involved in extracellular matrix turnover, inflammation, kidney dysfunction, diabetes, fibrosis, angiogenesis and cancer progression. The current study examined the involvement of heparanase in the pathogenesis of ischemic reperfusion (I/R) AKI in a mouse model and the protective effect of PG545, a potent heparanase inhibitor. I/R induced tubular damage and elevation in serum creatinine and blood urea nitrogen to a higher extent in heparanase over-expressing transgenic mice vs. wild type mice. Moreover, TGF-\u3b2, vimentin, fibronectin and \u3b1-smooth muscle actin, biomarkers of fibrosis, and TNF\u3b1, IL6 and endothelin-1, biomarkers of inflammation, were upregulated in I/R induced AKI, primarily in heparanase transgenic mice, suggesting an adverse role of heparanase in the pathogenesis of AKI. Remarkably, pretreatment of mice with PG545 abolished kidney dysfunction and the up-regulation of heparanase, pro-inflammatory (i.e., IL-6) and pro-fibrotic (i.e., TGF-\u3b2) genes induced by I/R. The present study provides new insights into the involvement of heparanase in the pathogenesis of ischemic AKI.Our results demonstrate that heparanase plays a deleterious role in the development of renal injury and kidney dysfunction,attesting heparanase inhibition as a promising therapeutic approach for AKI

IDIOMS AND CULTURE: EXPLORING THE INTER-INFLUENCE BETWEEN ENGLISH AND OTHER LANGUAGES

Purpose of the study: The aim of this paper is to study the interplay of multilingual idioms through source and time with a caveat that it is an endless pursuit. Methodology: In this research, logical analysis and modeling are used. Results: For the very reason that idioms are formed in a context, such learners and users must be very careful while using them. It is important for them to be well versed with the nuances and fine points of the foreign language before they venture into the use of idioms. Also, straightaway translating idioms from one’s native language into a foreign language can truly lead to disastrous communication glitches. Applications of this study: This research can be used for the universities, teachers, and students. Novelty/Originality of this study: In this research, the model of the Idioms and culture is presented in a comprehensive and complete manner

Numerical Study of Optimum Configuration of Unconventional Airfoil with Steps and Rotating Cylinder for Best Aerodynamics Performance

Numerical study of separation control on symmetrical airfoil, four digits (NACA 0012) by using rotating cylinder with double steps on its upper surface based on the computation of Reynolds-average Navier- Stokes equations was carried out to find the optimum configuration of unconventional airfoil for best aerodynamics performance. A model based on collocated Finite Volume Method was developed to solve the governing equations on a body-fitted coordinate system. A revised (k-w) model was proposed as a known turbulence model. This model was adapted to simulate the control effects of rotating cylinder. Numerical solutions were performed for flow around unconventional airfoil with cylinder to main stream velocities ratio in the range of 1 to 4 and for various positions of the steps on the airfoil from the leading edge, 0.1c, 0.2c, 0.3c, 0.4c, 0.5c for the first step and 0.5c, 0.6c, 0.7c, 0.8c for the second step with constant step depth and length of 0.03c and 0.125c respectively. Reynolds number of 700,000 which was based on the cord length (c), with angle of attacks 0, 5, 8, 10, 12, 15 degrees was considered for the assessment of the unconventional airfoil performance. The numerical investigation showed that the optimum configuration for the unconventional airfoil was found to be at velocities ratio (U/U∞=4) with the steps positions at 0.5c and 0.8c for best airfoil performance

Reduced microvascular density in omental biopsies of children with chronic kidney disease

Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of "uremic microangiopathy", we have measured microvascular density in biopsies of the omentum of children with CKD.Omental tissue was collected from 32 healthy children (0-18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2.Microvascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, p<0.0021 and by automated quantification (total microvascular surface area 0.89% vs. 1.17% p = 0.01). Density measured by manual imaging was significantly associated with age, height, weight and body surface area in CKD patients and healthy controls. In multivariate analysis, age and serum creatinine level were the only independent, significant predictors of microvascular density (r2 = 0.73). There was no immunohistochemical evidence for apoptosis or autophagy. Quantitative staining showed similar expression levels of the angiogenesis regulators VEGF-A, VEGF-receptor 2 and Angpt1 (p = 0.11), but Angpt2 was significantly lower in CKD children (p = 0.01).Microvascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished Angpt2 signaling. Microvascular rarefaction could be an early systemic manifestation of CKD-induced cardiovascular disease

Type 1 and Type 2 Diabetes among Youths in Jordan: Incidence and Trends for the period (2011-2016)

This study aimed at analyzing the incidence of Type 1 and Type 2 diabetes among youths in Jordan for the period (2011-2016), the researchers adopted the survey methodology for the period of five years from the records of the medical centers (public and private) in Jordan. Also investigated the differences between Type 1 and Type 2 diabetes in diagnosis and treatments. Results showed significant upward trend in the incidence of type 1 diabetes was observed overall with considerable variation across demographic subgroups of age, sex. And also showed among youths who were 10 to 19 years of age, unadjusted models revealed significant increases in the incidence of type 2 diabetes with increases observed across all age and sex

Collaborative metabolic curation of an emerging model marine bacterium, Alteromonas macleodii ATCC 27126

Inferring the metabolic capabilities of an organism from its genome is a challenging process, relying on computationally-derived or manually curated metabolic networks. Manual curation can correct mistakes in the draft network and add missing reactions based on the literature, but requires significant expertise and is often the bottleneck for high-quality metabolic reconstructions. Here, we present a synopsis of a community curation workshop for the model marine bacterium Alteromonas macleodii ATCC 27126 and its genome database in BioCyc, focusing on pathways for utilizing organic carbon and nitrogen sources. Due to the scarcity of biochemical information or gene knock-outs, the curation process relied primarily on published growth phenotypes and bioinformatic analyses, including comparisons with related Alteromonas strains. We report full pathways for the utilization of the algal polysaccharides alginate and pectin in contrast to inconclusive evidence for one-carbon metabolism and mixed acid fermentation, in accordance with the lack of growth on methanol and formate. Pathways for amino acid degradation are ubiquitous across Alteromonas macleodii strains, yet enzymes in the pathways for the degradation of threonine, tryptophan and tyrosine were not identified. Nucleotide degradation pathways are also partial in ATCC 27126. We postulate that demonstrated growth on nitrate as sole nitrogen source proceeds via a nitrate reductase pathway that is a hybrid of known pathways. Our evidence highlights the value of joint and interactive curation efforts, but also shows major knowledge gaps regarding Alteromonas metabolism. The manually-curated metabolic reconstruction is available as a "Tier-2" database on BioCyc

Studies of Anomalous Microwave Emission (AME) with the SKA

In this chapter, we will outline the scientific motivation for studying Anomalous Microwave Emission (AME) with the SKA. AME is thought to be due to electric dipole radiation from small spinning dust grains, although thermal fluctuations of magnetic dust grains may also contribute. Studies of this mysterious component would shed light on the emission mechanism, which then opens up a new window onto the interstellar medium (ISM). AME is emitted mostly in the frequency range $\sim 10$--100\,GHz, and thus the SKA has the potential of measuring the low frequency side of the AME spectrum, particularly in band 5. Science targets include dense molecular clouds in the Milky Way, as well as extragalactic sources. We also discuss the possibility of detecting rotational line emission from Poly-cyclic Aromatic Hydrocarbons (PAHs), which could be the main carriers of AME. Detecting PAH lines of a given spacing would allow for a definitive identification of specific PAH species

P73 Preliminary results of the Study of Acute Liver Transplant (SALT): NSAID exposure and risk of acute liver failure leading to transplantation in 7 European countries

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Anxiety among adolescents and young adults during COVID-19 pandemic: A multi-country survey

(1) Background: Adolescents-and-young-adults (AYA) are prone to anxiety. This study assessed AYA's level of anxiety during the COVID-19 pandemic; and determined if anxiety levels were associated with country-income and region, socio-demographic profile and medical history of individuals. (2) Methods: A survey collected data from participants in 25 countries. Dependent-variables included general-anxiety level, and independent-variables included medical problems, COVID-19 infection, age, sex, education, and country-income-level and region. A multilevel-multinomial-logistic regression analysis was conducted to determine the association between dependent, and independent-variables. (3) Results: Of the 6989 respondents, 2964 (42.4%) had normal-anxiety, and 2621 (37.5%), 900 (12.9%) and 504 (7.2%) had mild, moderate and severe-anxiety, respectively. Participants from the African region (AFR) had lower odds of mild, moderate and severe than normal-anxiety compared to those from the Eastern-Mediterranean-region (EMR). Also, participants from lower-middle-income-countries (LMICs) had higher odds of mild and moderate than normal-anxiety compared to those from low-income-countries (LICs). Females, older-adolescents, with medical-problems, suspected-but-not-tested-for-COVID-19, and those with friends/family-infected with COVID-19 had significantly greater odds of different anxiety-levels. (4) Conclusions: One-in-five AYA had moderate to severe-anxiety during the COVID-19-pandemic. There were differences in anxiety-levels among AYAs by region and income-level, emphasizing the need for targeted public health interventions based on nationally-identified priorities

Cigarettes' use and capabilities-opportunities-motivation-for-behavior model:a multi-country survey of adolescents and young adults

The use of cigarettes among adolescents and young adults (AYA) is an important issue. This study assessed the association between regular and electronic-cigarettes use among AYA and factors of the Capability-Motivation-Opportunity-for-Behavior-change (COM-B) model. A multi-country survey was conducted between August-2020 and January-2021, Data was collected using the Global-Youth-Tobacco-Survey and Generalized-Anxiety-Disorder-7-item-scale. Multi-level logistic-regression-models were used. Use of regular and electronic-cigarettes were dependent variables. The explanatory variables were capability-factors (COVID-19 status, general anxiety), motivation-factors (attitude score) and opportunity-factors (country-level affordability scores, tobacco promotion-bans, and smoke free-zones) controlling for age and sex. Responses of 6,989-participants from 25-countries were used. Those who reported that they were infected with COVID-19 had significantly higher odds of electronic-cigarettes use (AOR = 1.81, P = 0.02). Normal or mild levels of general anxiety and negative attitudes toward smoking were associated with significantly lower odds of using regular-cigarettes (AOR = 0.34, 0.52, and 0.75, P < 0.001) and electronic-cigarettes (AOR = 0.28, 0.45, and 0.78, P < 0.001). Higher affordability-score was associated with lower odds of using electronic-cigarettes (AOR = 0.90, P = 0.004). Country-level-smoking-control policies and regulations need to focus on reducing cigarette affordability. Capability, motivation and opportunity factors of the COM-B model were associated with using regular or electronic cigarettes