Analysis of KRT5 and KRT14 gene mutations and mode of inheritance in Iranian patients with clinical suspicion of Epidermolysis bullosa simplex

Background: Epidermolysis bullosa simplex is a hereditary skin disorder caused by mutations in several genes such as KRT5 and KRT14. Skin fragility in basal keratinocytes presence regions led to the cytolysis of epidermis and blistering. Aim of this study was to detect the molecular defects in KRT5 and KRT14 genes hot spots in patients with clinical suspicion of EBS and investigation of their probable genotype-phenotype correlations. Methods: Exons 1 and 6-7 of KRT5 and exons 1 and 4-7 of KRT14 amplification and mutation detection were performed by polymerase chain reaction and Sanger sequencing, respectively. Novel variants pathogenicity evaluated by bioinformatics tools. Results: Nine important variants detected in seven different patients within 6 Iranian families affected by Epidermolysis bullosa simplex, of which four variants were novel. Three patients had a mottled pigmentation phenotype G96D (p. Gly96Asp) and F97I (p. Phe97Ile) in KRT5. One of them showed a Dowling-Meara phenotype A417P (p. Ala417Pro) and E477D (p. Glu477Asp) in KRT5 and another had a Koebner type phenotype R397I (p. Arg397Ile) and Q444* (p. Gln444Ter) in KRT5. A novel variant G92E (p. Gly92Glu) in KRT5 in a double heterozygous state with a challenging variant A413T (p. Ala413Thr) in KRT14 identified in one patient with Koebner type phenotype. Also, a previously reported mutation I377T (p. Ile377Thr) in KRT14 gene identified in this study. Conclusion: The results of molecular data analysis showed that the most severe phenotypes were associated with mutations in highly conserved regions. In some cases, different inheritance modes were observed. © Iran University of Medical Sciences

An Experience of Using Cinemascience Format for 3D Scientific Visualization

To visualize any new entity, a visualization algorithm should be designed and programmed. Investigating approaches for programming new scientific visualizations, we come with the following technique: utilize CinemaScience format to describe 3D scenes. CinemaScience is developed for storing and visualizing supercomputer and physical modelling results, and differs with simplicity both for human and machine. It has a set of interesting features, for example it allows to specify dynamics in views dependent on parameters. However, the technique currently known applications are 2D graphics, and in this paper we extend it for 3D case. The main feature of the approach is treating of Cinema artifacts as visual objects of explicit type. We successfully used the suggested approach in various visualization tasks, examples are presented in the paper. We developed the open-source web application that implements the suggested approach. It is open-source and its main features are also described in the paper. © 2021 National Research Nuclear University. All rights reserved

Ligation of the Jugular Veins Does Not Result in Brain Inflammation or Demyelination in Mice

An alternative hypothesis has been proposed implicating chronic cerebrospinal venous insufficiency (CCSVI) as a potential cause of multiple sclerosis (MS). We aimed to evaluate the validity of this hypothesis in a controlled animal model. Animal experiments were approved by the institutional animal care committee. The jugular veins in SJL mice were ligated bilaterally (n = 20), and the mice were observed for up to six months after ligation. Sham-operated mice (n = 15) and mice induced with experimental autoimmune encephalomyelitis (n = 8) were used as negative and positive controls, respectively. The animals were evaluated using CT venography and 99mTc-exametazime to assess for structural and hemodynamic changes. Imaging was performed to evaluate for signs of blood-brain barrier (BBB) breakdown and neuroinflammation. Flow cytometry and histopathology were performed to assess inflammatory cell populations and demyelination. There were both structural changes (stenosis, collaterals) in the jugular venous drainage and hemodynamic disturbances in the brain on Tc99m-exametazime scintigraphy (p = 0.024). In the JVL mice, gadolinium MRI and immunofluorescence imaging for barrier molecules did not reveal evidence of BBB breakdown (p = 0.58). Myeloperoxidase, matrix metalloproteinase, and protease molecular imaging did not reveal signs of increased neuroinflammation (all p>0.05). Flow cytometry and histopathology also did not reveal increase in inflammatory cell infiltration or population shifts. No evidence of demyelination was found, and the mice remained without clinical signs. Despite the structural and hemodynamic changes, we did not identify changes in the BBB permeability, neuroinflammation, demyelination, or clinical signs in the JVL group compared to the sham group. Therefore, our murine model does not support CCSVI as a cause of demyelinating diseases such as multiple sclerosis

Asymptomatic bacteriuria in type 2 Iranian diabetic women: a cross sectional study

BACKGROUND: The risk of developing infection in diabetic patients is higher and urinary tract is the most common site for infection. Serious complications of urinary infection occur more commonly in diabetic patients. To study the prevalence and associates of asymptomatic bacteriuria (ASB) in women with type 2 diabetes mellitus in the Iranian population, this study was conducted. METHODS: Between February 10, 2004 and October 15, 2004; 202 nonpregnant diabetic (type 2) women (range: 31 to 78 years old) with no abnormalities of the urinary tract system were included in this clinic based study. We defined ASB as the presence of at least 10(5 )colony-forming units/ml of 1 or 2 bacterial species, in two separated cultures of clean-voided midstream urine. All the participants were free from any symptoms of urinary tract infection (UTI). Associates for developing bacteriuria was assessed and compared in participants with and without bacteriuria. RESULTS: In this study, the prevalence of ASB was 10.9% among diabetic women. E. coli was the most prevalent microorganism responsible for positive urine culture. Most of the isolated microorganisms were resistant to Co-trimoxazole, Nalidixic acid and Ciprofloxacin. Pyuria (P < 0.001) and glucosuria (P < 0.05) had a meaningful relationship with bacteriuria but no association was evident between age (P < 0.45), duration of diabetes (P < 0.09), macroalbuminuria (P < 0.10) and HbA(1c )level (P < 0.75), and the presence of ASB. CONCLUSION: The prevalence of ASB is higher in women with type 2 diabetes, for which pyuria and glucosuria can be considered as associates. Routine urine culture can be recommended for diabetic women even when there is no urinary symptom

Resilient cooling strategies – A critical review and qualitative assessment

The global effects of climate change will increase the frequency and intensity of extreme events such as heatwaves and power outages, which have consequences for buildings and their cooling systems. Buildings and their cooling systems should be designed and operated to be resilient under such events to protect occupants from potentially dangerous indoor thermal conditions. This study performed a critical review on the state-of-the-art of cooling strategies, with special attention to their performance under heatwaves and power outages. We proposed a definition of resilient cooling and described four criteria for resilience—absorptive capacity, adaptive capacity, restorative capacity, and recovery speed —and used them to qualitatively evaluate the resilience of each strategy. The literature review and qualitative analyses show that to attain resilient cooling, the four resilience criteria should be considered in the design phase of a building or during the planning of retrofits. The building and relevant cooling system characteristics should be considered simultaneously to withstand extreme events. A combination of strategies with different resilience capacities, such as a passive envelope strategy coupled with a low-energy space-cooling solution, may be needed to obtain resilient cooling. Finally, a further direction for a quantitative assessment approach has been pointed out

Potential toxic elements in stream sediments, soils and waters in an abandoned radium mine (central Portugal)

The Alto da Várzea radium mine (AV) exploited ore and U-bearing minerals, such as autunite and torbernite. The mine was exploited underground from 1911 to 1922, closed in 1946 without restoration, and actually a commercial area is deployed. Stream sediments, soils and water samples were collected between 2008 and 2009. Stream sediments are mainly contaminated in As, Th, U and W, which is related to the AV radium mine. The PTEs, As, Co, Cr, Sr, Th, U, W, Zn, and electrical conductivity reached the highest values in soils collected inside the mine influence. Soils are contaminated with As and U and must not be used for any purpose. Most waters have pH values ranging from 4.3 to 6.8 and are poorly mineralized (EC = 41-186 µS/cm; TDS = 33-172 mg/L). Groundwater contains the highest Cu, Cr and Pb contents. Arsenic occurs predominantly as H2(AsO4)- and H(AsO4)2-. Waters are saturated in goethite, haematite and some of them also in lepidocrocite and ferrihydrite, which adsorbs As (V). Lead is divalent in waters collected during the warm season, being mobile in these waters. Thorium occurs mainly as Th(OH)3(CO3)-, Th(OH)2(CO3) and Th(OH)2(CO3) 22- , which increase water Th contents. Uranium occurs predominantly as UO2CO3, but CaUO2(CO3) 32- and CaUO2(CO3)3 also occur, decreasing its mobility in water. The waters are contaminated in NO2-, Mn, Cu, As, Pb and U and must not be used for human consumption and in agricultural activities. The water contamination is mainly associated with the old radium mine and human activities. A restoration of the mining area with PTE monitoring is necessary to avoid a public hazard.Thanks are due to Prof. Joao Coutinho for the determination of organic matter and cation exchange capacity in samples of stream sediments and soils and A. Rodrigues for the water analyses, EDM for some information on the Alto da Varzea mine area. This study had the support of Portuguese Fundacao para a Ciencia e Tecnologia (FCT), through the strategic projects UID/GEO/04035/2013 and UID/MAR/04292/2013 (MARE).info:eu-repo/semantics/publishedVersio

Albumin and multiple sclerosis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Leakage of the blood–brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council