Targeting Cytokine Storm to Manage Patients with COVID-19: A Mini-Review

Corona Virus Disease 2019 (COVID-19) pandemic is rapidly spreading all over the world. Excessive immune responses trigger life-threatening cytokine release syndrome (CRS) which can result in overproduction of pro-inflammatory cytokines including tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1β with different pro-inflammatory roles. Anecdotal evidence suggests that the modulation of systemic immune responses may have a potential role in the treatment of patients with COVID-19. Given the importance of the issue and the lack of therapeutic treatment or vaccine; anti-cytokine therapy such as IL-6, TNFα and IL-1 antagonists have been suggested for the alleviation of hyper-inflammation status in these patients. In this mini-review, we addressed the inflammatory pathways of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relationship with the host cytokine storm. Furthermore, the proposed therapeutic options to reverse hyper-inflammation in infected patients were mentioned. © 2020 IMS

Downregulation of miR-1266-5P, miR-185-5P and miR-30c-2 in prostatic cancer tissue and cell lines

Over the latest decade, the role of microRNAs (miRNAs/miRs) has received more attention. miRNAs are small non-coding RNAs that may serve a role as oncogenes or tumor suppressor genes. Certain miRNAs regulate the apoptosis pathway by influencing pro- or anti-apoptotic genes. We hypothesized that increases in the expression of B cell lymphoma 2 (BCL2) and BCL2-like 1 (BCL2L1) genes, which have been reported in various types of cancer tissues, may be due to the downregulation of certain miRNAs. The present study aimed to identify miRNAs that target BCL2 and BCL2L1 anti-apoptotic genes in prostate cancer (PCa) clinical tissue samples. Certain candidate miRNAs were selected bioinfor-matically and their expression in PCa samples was analyzed and compared with that in benign prostatic hyperplasia (BPH) tissue samples. The candidate miRNAs that targeted BCL2 and BCL2L1 genes were searched in online databases (miRWalk, microRNA.org, miRDB and TargetScan). A total of 12 miRNAs that target the 3'-untranslated region of the aforementioned genes and/or for which downregulation of their expression has previously been reported in cancer tissues. A total of 30 tumor tissue samples from patients with PCa and 30 samples tissues from patients with BPH were obtained and were subjected to reverse transcription-quantitative polymerase chain reaction for expression analysis of 12 candidate miRNAs, and the BCL2 and BCL2L1 genes. Additionally, expression of 3 finally selected miRNAs and genes was evaluated in prostate cancer PC3 and DU145 cell lines and human umbilical vein endothelial cells. Among 12 miRNA candidates, the expression of miR-1266, miR-185 and miR-30c-2 was markedly downregulated in PCa tumor tissues and cell lines. Furthermore, downregulation of these miRNAs was associated with upregulation of the BCL2 and BCL2L1 genes. An inverse association between three miRNAs (miR-1266, miR-185 and miR-30c-2) and two anti-apoptotic genes (BCL2 and BCL2L1) may be considered for interventional miRNA therapy of PCa. © 2018, Spandidos Publications. All rights reserved

Hepatitis b vertical transfer and its risk factors in pregnant women in the eastern part of iran

One of the main causes of chronic hepatitis is mother to child transfer which is also known as vertical transfer (VT). Although there are several studies regarding the VT mechanism and its risk factors, none of these studies succeeded in explaining this process, completely. We conducted this study aiming at investigating VT mechanism and risk factors in this region. The present study was a descriptive-analytic cross-sectional study on HBS Ag positive pregnant women, which was conducted from March 2018 to March 2020 in Amir-AlMomenin Hospital in Zabol, Sistan-and-Baluchestan province, Iran. In this study all samples were tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and HBV-DNA) and anti-HCV by enzyme-linked immunosorbent assay (ELISA). All statistical analyzes were performed using SPSS version 22 software. Totally 43 infants of HBS antigen positive mothers were investigated. HBe antibody and HBe antigen were found in 25 (62.5%) and 2 (5%) of mothers, respectively. There was no significant difference between the newborns with and without hepatitis B infection regarding maternal age (p=0.216), duration of the infection in mother (p=0.892), AST (0.779), AL (0.449) and ALP (0.065). Mothers with positive viral load during pregnancy delivered newborns with positive HBS antigen much more than mothers with negative HBS antigen. However, this difference was not statistically significant (p=0.642). Although positive viral load was more common in neonates delivered from positive viral load mothers, the observed difference was also remained non-significant (p=0.978). Our study provided evidences regarding that demographic, immunologic and clinical characteristics of mothers with hepatitis B infection did not play considerable role in the vertical transmission of the infection to the newborns as well as the severity of the following infection. We also suggested the possibility of placenta acting as a source of infection in VT. Further longitudinal studies with larger sample sizes are needed to show the exact predictors of transmission of the infection from infected mothers to their children, Amirian S., Afshari M., Parooie F., Keikhaie K.R., Shahramian I., Bazi A., Ostadrahimi P., Sheikh M., Mirzaie H., Aminisefat A. One of the main causes of chronic hepatitis is mother to child transfer which is also known as vertical transfer (VT). Although there are several studies regarding the VT mechanism and its risk factors, none of these studies succeeded in explaining this process, completely. We conducted this study aiming at investigating VT mechanism and risk factors in this region. The present study was a descriptive-analytic cross-sectional study on HBS Ag positive pregnant women, which was conducted from March 2018 to March 2020 in Amir-AlMomenin Hospital in Zabol, Sistan-and-Baluchestan province, Iran. In this study all samples were tested for HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and HBV-DNA) and anti-HCV by enzyme-linked immunosorbent assay (ELISA). All statistical analyzes were performed using SPSS version 22 software. Totally 43 infants of HBS antigen positive mothers were investigated. HBe antibody and HBe antigen were found in 25 (62.5%) and 2 (5%) of mothers, respectively. There was no significant difference between the newborns with and without hepatitis B infection regarding maternal age (p=0.216), duration of the infection in mother (p=0.892), AST (0.779), AL (0.449) and ALP (0.065). Mothers with positive viral load during pregnancy delivered newborns with positive HBS antigen much more than mothers with negative HBS antigen. However, this difference was not statistically significant (p=0.642). Although positive viral load was more common in neonates delivered from positive viral load mothers, the observed difference was also remained non-significant (p=0.978). Our study provided evidences regarding that demographic, immunologic and clinical characteristics of mothers with hepatitis B infection did not play considerable role in the vertical transmission of the infection to the newborns as well as the severity of the following infection. We also suggested the possibility of placenta acting as a source of infection in VT. Further longitudinal studies with larger sample sizes are needed to show the exact predictors of transmission of the infection from infected mothers to their childre

Downregulation of miR-1266-5P, miR-185-5P and miR-30c-2 in prostatic cancer tissue and cell lines

Over the latest decade, the role of microRNAs (miRNAs/miRs) has received more attention. miRNAs are small non-coding RNAs that may serve a role as oncogenes or tumor suppressor genes. Certain miRNAs regulate the apoptosis pathway by influencing pro- or anti-apoptotic genes. We hypothesized that increases in the expression of B cell lymphoma 2 (BCL2) and BCL2-like 1 (BCL2L1) genes, which have been reported in various types of cancer tissues, may be due to the downregulation of certain miRNAs. The present study aimed to identify miRNAs that target BCL2 and BCL2L1 anti-apoptotic genes in prostate cancer (PCa) clinical tissue samples. Certain candidate miRNAs were selected bioinfor-matically and their expression in PCa samples was analyzed and compared with that in benign prostatic hyperplasia (BPH) tissue samples. The candidate miRNAs that targeted BCL2 and BCL2L1 genes were searched in online databases (miRWalk, microRNA.org, miRDB and TargetScan). A total of 12 miRNAs that target the 3'-untranslated region of the aforementioned genes and/or for which downregulation of their expression has previously been reported in cancer tissues. A total of 30 tumor tissue samples from patients with PCa and 30 samples tissues from patients with BPH were obtained and were subjected to reverse transcription-quantitative polymerase chain reaction for expression analysis of 12 candidate miRNAs, and the BCL2 and BCL2L1 genes. Additionally, expression of 3 finally selected miRNAs and genes was evaluated in prostate cancer PC3 and DU145 cell lines and human umbilical vein endothelial cells. Among 12 miRNA candidates, the expression of miR-1266, miR-185 and miR-30c-2 was markedly downregulated in PCa tumor tissues and cell lines. Furthermore, downregulation of these miRNAs was associated with upregulation of the BCL2 and BCL2L1 genes. An inverse association between three miRNAs (miR-1266, miR-185 and miR-30c-2) and two anti-apoptotic genes (BCL2 and BCL2L1) may be considered for interventional miRNA therapy of PCa. © 2018, Spandidos Publications. All rights reserved

The effectiveness of ω-3 polyunsaturated fatty acid interventions during pregnancy on obesity measures in the offspring: an up-to-date systematic review and meta-analysis.

BACKGROUND: The potential role of ω-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on subsequent risk of obesity outcomes in the offspring is not clear and there is a need to synthesise this evidence. OBJECTIVE: A systematic review and meta-analysis of randomised controlled trials (RCTs), including the most recent studies, was conducted to assess the effectiveness of ω-3 LCPUFA interventions during pregnancy on obesity measures, e.g. BMI, body weight, fat mass in offspring. METHODS: Included RCTs had a minimum of 1-month follow-up post-partum. The search included CENTRAL, MEDLINE, SCOPUS, WHO's International Clinical Trials Reg., E-theses and Web of Science databases. Study quality was evaluated using the Cochrane Collaboration's risk of bias tool. RESULTS: Eleven RCTs, from ten unique trials, (3644 children) examined the effectiveness of ω-3 LCPUFA maternal supplementation during pregnancy on the development of obesity outcomes in offspring. There were heterogeneities between the trials in terms of their sample, type and duration of intervention and follow-up. Pooled estimates did not show an association between prenatal intake of fatty acids and obesity measures in offspring. CONCLUSION: These results indicate that maternal supplementation with ω-3 LCPUFA during pregnancy does not have a beneficial effect on obesity risk. Due to the high heterogeneity between studies along with small sample sizes and high rates of attrition, the effects of ω-3 LCPUFA supplementation during pregnancy for prevention of childhood obesity in the long-term remains unclear. Large high-quality RCTs are needed that are designed specifically to examine the effect of prenatal intake of fatty acids for prevention of childhood obesity. There is also a need to determine specific sub-groups in the population that might get a greater benefit and whether different ω-3 LCPUFA, i.e. eicosapentaenoic (EPA) vs. docosahexanoic (DHA) acids might potentially have different effects

Modulation of the peripheral blood transcriptome by the ingestion of probiotic yoghurt and acidified milk in healthy, young men

The metabolic health benefits of fermented milks have already been investigated using clinical biomarkers but the development of transcriptomic analytics in blood offers an alternative approach that may help to sensitively characterise such effects. We aimed to assess the effects of probiotic yoghurt intake, compared to non-fermented, acidified milk intake, on clinical biomarkers and gene expression in peripheral blood. To this end, a randomised, crossover study was conducted in fourteen healthy, young men to test the two dairy products. For a subset of seven subjects, RNA sequencing was used to measure gene expression in blood collected during postprandial tests and after two weeks daily intake. We found that the postprandial response in insulin was different for probiotic yoghurt as compared to that of acidified milk. Moreover changes in several clinical biomarkers were associated with changes in the expression of genes representing six metabolic genesets. Assessment of the postprandial effects of each dairy product on gene expression by geneset enrichment analysis revealed significant, similar modulation of inflammatory and glycolytic genes after both probiotic yoghurt and acidified milk intake, although distinct kinetic characteristics of the modulation differentiated the dairy products. The aryl hydrocarbon receptor was a major contributor to the down-regulation of the inflammatory genesets and was also positively associated with changes in circulating insulin at 2h after yoghurt intake (p = 0.05). Daily intake of the dairy products showed little effect on the fasting blood transcriptome. Probiotic yoghurt and acidified milk appear to affect similar gene pathways during the postprandial phase but differences in the timing and the extent of this modulation may lead to different physiological consequences. The functional relevance of these differences in gene expression is supported by their associations with circulating biomarkers

Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study

Background: There is an increased attention to stroke following SARS-CoV-2. The goal of this study was to better depict the short-term risk of stroke and its associated factors among SARS-CoV-2 hospitalized patients. Methods: This multicentre, multinational observational study includes hospitalized SARS-CoV-2 patients from North and South America (United States, Canada, and Brazil), Europe (Greece, Italy, Finland, and Turkey), Asia (Lebanon, Iran, and India), and Oceania (New Zealand). The outcome was the risk of subsequent stroke. Centres were included by non-probability sampling. The counts and clinical characteristics including laboratory findings and imaging of the patients with and without a subsequent stroke were recorded according to a predefined protocol. Quality, risk of bias, and heterogeneity assessments were conducted according to ROBINS-E and Cochrane Q-test. The risk of subsequent stroke was estimated through meta-analyses with random effect models. Bivariate logistic regression was used to determine the parameters with predictive outcome value. The study was reported according to the STROBE, MOOSE, and EQUATOR guidelines. Findings: We received data from 26,175 hospitalized SARS-CoV-2 patients from 99 tertiary centres in 65 regions of 11 countries until May 1st, 2020. A total of 17,799 patients were included in meta-analyses. Among them, 156(0.9) patients had a stroke�123(79) ischaemic stroke, 27(17) intracerebral/subarachnoid hemorrhage, and 6(4) cerebral sinus thrombosis. Subsequent stroke risks calculated with meta-analyses, under low to moderate heterogeneity, were 0.5 among all centres in all countries, and 0.7 among countries with higher health expenditures. The need for mechanical ventilation (OR: 1.9, 95 CI:1.1�3.5, p = 0.03) and the presence of ischaemic heart disease (OR: 2.5, 95 CI:1.4�4.7, p = 0.006) were predictive of stroke. Interpretation: The results of this multi-national study on hospitalized patients with SARS-CoV-2 infection indicated an overall stroke risk of 0.5(pooled risk: 0.9). The need for mechanical ventilation and the history of ischaemic heart disease are the independent predictors of stroke among SARS-CoV-2 patients. Funding: None. © 2020 The Author

A Simplified Multilevel Space Vector Pulsewidth Modulation (SVPWM) Based on Boundary Lines, Including Overmodulation Zone

Space vector pulsewidth modulation (SVPWM) is a superior switching technique offering several benefits for power electronic inverters. However, concerning multilevel inverters (MLIs), implementing SVPWM is a demanding and time-consuming task because it deals with the six sectors of the space vector modulation (SVM) plane and numerous regions and vectors. Several research works in the literature tried to simplify SVPWM implementation for MLIs. This article introduces an SVPWM strategy, aiming to simplify the designing process and reduce the computational burden of the multilevel SVPWM. In this method, the switching process is designed only for the first sector of the SVM plane. The duty cycles and the switching states of the other sectors are assigned by transferring and translating techniques. The proposed method only uses basic algebraic functions in order to save the limited hardware resources of the processor. The same basic functions are used to handle overmodulation operations. This method introduces the boundary lines concept, which is a useful tool to detect the region and assign the switching states. Simulation and hardware-in-the-loop results are provided to validate the functionality of the proposed SVPWM. The hardware resource used on the field-programmable gate array module is adopted as a criterion to compare the proposed method with one of the conventional SVPWMs. This article is accompanied by MATLAB simulation files, for a three-level and a five-level inverter, provided by the authors as supplementary material

Hardware-in-the-Loop Implementation of ROMAtrix, a Smart Transformer for Future Power Grids

The evolution of power generation brings about extensive changes in other parts of the grid, especially in the transmission and distribution components. Within the scope of the Internet of Energy (IoE), electric power flows more flexibly between different parts of the grid. DC power will play an essential role in IoE. Decentralized photovoltaic panels, energy storage, electric vehicle charging stations, and data centers are some of the significant components of future grids dealing with DC power. As a result, power transformers must be appropriately modified to manage power among the different parts of the grid. A power electronic transformer (PET), also known as a solid-state transformer (SST) or smart transformer (ST), is a solution enabling a power grid to deal with this growing complexity. ROMAtrix, as a matrix-converter-based ST, is a developing project targeting future power grids. ROMAtrix realizes the application of a medium voltage (MV) transformer using commercially available power electronic semiconductors. Due to the distinctive features of ROMAtrix and a high number of switches, the implementation of the control system using a single control board is highly demanding. This paper aims to illustrate the implementation, on a field-programmable gate array (FPGA), of pulse width modulation (SVMPWM) applied to the ROMAtrix, considering specific switching patterns. The proposed switching procedure was simulated with PLECS and validated with the hardware-in-the-loop using the OPAL-RT solver