In vitro proliferation and differentiation of mouse spermatogonial stem cells in decellularized human placenta matrix.

Utilizing natural scaffold production derived from extracellular matrix components presents a promising strategy for advancing in vitro spermatogenesis. In this study, we employed decellularized human placental tissue as a scaffold, upon which neonatal mouse spermatogonial cells (SCs) were cultured three-dimensional (3D) configuration. To assess cellular proliferation, we examined the expression of key markers (Id4 and Gfrα1) at both 1 and 14 days into the culture. Our quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed a notable increase in Gfrα1 gene expression, with the 3D culture group exhibiting the highest levels. Furthermore, the relative frequency of Gfrα1-positive cells significantly rose from 38.1% in isolated SCs to 46.13% and 76.93% in the two-dimensional (2D) and 3D culture systems, respectively. Moving forward to days 14 and 35 of the culture period, we evaluated the expression of differentiating markers (Sycp3, acrosin, and Protamine 1). Sycp3 and Prm1 gene expression levels were upregulated in both 2D and 3D cultures, with the 3D group displaying the highest expression. Additionally, acrosin gene expression increased notably within the 3D culture. Notably, at the 35-day mark, the percentage of Prm1-positive cells in the 3D group (36.4%) significantly surpassed that in the 2D group (10.96%). This study suggests that the utilization of placental scaffolds holds significant promise as a bio-scaffold for enhancing mouse in vitro spermatogenesis.

Predicting outcomes in patients with low ejection fraction undergoing coronary artery bypass graft.

Introduction: Reduced left ventricular ejection fraction (LVEF) is a well-known predictor of adverse events after cardiac surgery. We aimed to assess the outcomes in patients with low LVEF undergoing coronary artery bypass graft. Methods: In this retrospective cohort, we included all patients with left ventricular ejection fraction ≤ 40 who underwent coronary artery bypass grafting between March 2007 and March 2016 (with a median follow-up of nine years) at Tehran Heart Center. Demographics and clinical characteristics were extracted from the data registry. Akaike information criterion (AIC) was used. The univariate Cox regression was performed. We investigated the predictors of mortality and major adverse cardiac and cerebrovascular events (MACCE) using Cox multivariable regression. Results: In total, 5,532 cases (79 % male) with a mean age of 65.58 were included in the study. The nine-year overall survival was calculated at 68 %, and more than half of the patients had MACCE (55 %). In adjusted multivariable Cox regression analysis, moderate to severe mitral valve regurgitation, glomerular filtration rate ≤ 60, mild right ventricular dysfunction, and valvular heart disease independently predicted higher mortality. The abovementioned predictors and peripheral vascular disease significantly increased MACCE. Conclusion: Our study indicates the clinical significance of mitral regurgitation, valvular heart disease, and renal function in patients with low ejection fraction treated by coronary artery bypass grafting surgery. Identifying predictors of adverse events can help with clinical decision-making and risk stratification, ultimately improving patient outcomes.

Predictors of major adverse cardiac and cerebrovascular events after percutaneous coronary intervention in older adults: a systematic review and meta-analysis.

AIM: We systematically reviewed and meta-analyzed the predictors of major adverse cardiac and cerebrovascular events (MACE/MACCE) in older adults who underwent PCI. METHODS: Three databases, PubMed, Embase, and Scopus, were searched for observational studies considering the out-of-hospital MACE/MACCE in adults ≥ 60 years old with coronary artery disease (acute or chronic) who underwent PCI. Studies were eligible if they had determined at least two statistically significant predictors of MACE/MACCE by multivariable analysis. We used the QUIPS tool to evaluate the risk of bias in the studies. Random-effects meta-analysis was utilized to pool the hazard ratios (HRs) of the most reported predictors. RESULTS: A total of 34 studies were included in the review. Older age (HR = 1.04, 95% Confidence Interval (CI): 1.03-1.06, P-value < 0.001), diabetes (HR = 1.36, 95% CI: 1.22-1.53, P < 0.001), history of myocardial infarction (MI) (HR = 1.88, 95% CI: 1.37-2.57, P < 0.001), ST-elevation MI (STEMI) at presentation (HR = 1.72, 95% CI: 1.37-2.18, P < 0.001), reduced left ventricular ejection fraction (LVEF) (HR = 2.01, 95% CI: 1.52-2.65, P < 0.001), successful PCI (HR = 0.35, 95% CI: 0.27-0.47, P < 0.001), eGFR (HR = 0.99, 95% CI: 0.97-1.00; P-value = 0.04) and left main coronary artery (LMCA) disease (HR = 2.07, 95% CI: 1.52-2.84, P < 0.001) were identified as predictors of MACE. CONCLUSION: We identified older age, diabetes, history of MI, STEMI presentation, lower LVEF, and LMCA disease increased the risk of MACE/MACCE after PCI in older adults. Meanwhile, higher eGFR and successful PCI predicted lower adverse events risk. Future studies should focus on a more robust methodology and a precise definition of MACE. REGISTRATION: PROSPERO (CRD42023480332).

Study on synergistic effects of curcumin and bixin against foodborne pathogens.

Various studies have shown that natural colorants, in addition to their coloring attributes, have valuable biological effects such as antioxidant, anti-inflammation, and anticarcinogenic properties. Moreover, their use as a food colorant can restrict the potential disadvantages of synthetic additives and turn foods into functional products. In this study, in vitro antimicrobial activities of two natural colorants of bixin and curcumin against some important foodborne pathogens: Staphylococcus aureus (S. aureus), Listeria innocua (L. innocua), and Escherichia coli (E. coli) were investigated by disk diffusion method. Minimum inhibitory concentration and minimum bactericidal concentration values were determined by agar dilution and broth microdilution methods. The synergistic activity of the colorants against selected microorganisms was assayed by the checkerboard microdilution method. The results showed that the inhibitory effects of bixin against S. aureus were more pronounced than E. coli and L. innocua. The lowest concentration of curcumin (0.6 mg/mL) in the disk diffusion method was not inhibited by any tested bacteria. However, it was effective at the higher concentrations against three microorganisms, but its diameter of inhibition zones was lower than gentamicin in all concentrations. Synergetic effects were observed by curcumin and bixin combination against S. aureus (FICI ≤ 0.5), but they act as an antagonist against E. coli and L. innocua. The results of the synergy test were confirmed by the isobologram curves.

The principal component analysis of key and significant features of the safety and nutritional value of Mahyaveh sauce.

The objective of present research is to evaluate the changes in the chemical, microbial, and biogenic amines in Persian fish sauce (Mahyaveh) during 40 days of fermentation. In the current survey, the parameters of salt percentage, pH, total nitrogen concentration, amino nitrogen concentration, Brix, color features, cadaverine, and histamine concentration were measured in the fish sauce. The amino nitrogen content, total protein, Brix, and salt were increased along with the progression of fermentation process. The microbial population of Mahyaveh sauce demonstrated that lactic acid bacteria (LAB), total bacterial count, and Enterobacteriaceae decreased during fermentation. The population of lactic acid bacteria and the total count of bacteria were around one logarithmic cycle lower in the presence of 10% salt than under low salt conditions. Histamine and cadaverine concentrations increased to 43.49 and 42.76 mg/kg during the fermentation period, respectively. As a result, the population density of histamine-producing bacteria rose from 3.00 log CFU/mL at the beginning to 4.58 log CFU/mL at the end of process. The population density of cadaverine-producing bacteria was 3.43 and 5.24 log CFU/mL on the 20th and 40th days of fermentation, respectively. Sensory evaluation results indicated that our sample of fish sauce had an overall acceptability score of 5.1 (good). On the other hand, Principal Component Analysis (PCA) demonstrated a positive correlation between the most of chemical parameters and the fermentation period. The concentration of cadaverine and histamine has a positive association with the pH and type of bacteria producing the biogenic amines.

Long-Term Effects of Opium Consumption Following Percutaneous Coronary Intervention: A 10-year Follow-Up Study.

Background: Opium consumption has been an overlooked health issue in the Iranian population, and the prognostic role of opium consumption in patients undergoing coronary revascularization is unknown. Hypothesis: We aimed to assess the association between opium consumption and long-term cardiovascular outcomes after percutaneous coronary intervention (PCI). Methods: We screened 2203 consecutive patients who underwent elective PCI between April 2009 and April 2010 at Tehran Heart Center. Exclusion criteria were unsuccessful PCI, non-elective PCI, and missing opium use data. Opium consumption was defined as self-reported ever use of any traditional opium substances. Outcomes of interest were all-cause mortality and a composite of major adverse cardiac and cerebrovascular events (MACCE). The association between opium use and study outcomes was evaluated using the inverse probability of treatment weighting (IPTW) method. Cumulative hazard curves were demonstrated to further assess the association visually. Furthermore, the effect of opium consumption on individual components of MACCE was evaluated in a competing risk setting. Results: A total of 2025 elective PCI patients were included (age: 58.7 ± 10.67, 29.1% women), among whom 297 (14.6%) patients were opium users. After a median follow-up of 10.7 years, opium consumption was associated with a higher risk of all-cause mortality (IPTW-hazard ratio [HR] = 1.705, 95% CI: 1.125-2.585; P = 0.012) and MACCE (IPTW-HR = 1.578, 95% CI: 1.156-2.153; P = 0.004). The assessment of MACCE components suggested a non-significant borderline trend for higher non-fatal myocardial infarction (IPTW-sub-distribution HR [SHR] = 1.731, 95% CI: 0.928-3.231; P = 0.084) and mortality (IPTW-SHR = 1.441, 95% CI: 0.884-2.351; P = 0.143) among opium users. Conclusions: Opium consumption is associated with a more than 50% increase in long-term risk of mortality and MACCE in patients undergoing PCI. These findings accentuate the importance of preventive strategies to quit opium addiction in this population.

NF-kB affects migration of vascular smooth muscle cells after treatment with heparin and ibrutinib.

The migration of vascular smooth muscle cells (VSMCs) is one of the most important events in the remodeling of atherosclerosis plaque. The aim of study was to investigate the role of Heparin in the VSMC migration and its association with the NF-kB, collagen 1 and collagen 3 expression levels. Moreover, the incorporation of Heparin was studied in the VSMC cultures including Betulinic acid and Ibrutinib. Twelve cell groups were cultured and treated with the Heparin, Betulinic acid and Ibrutinib based on the viability and toxicity in 24-h and 48-h periods. The gene and protein expression levels were measured by RT-qPCR and western blotting techniques. The VSMC migration was determined by scratch test. In contrast with Ibrutinib (2 µM), Heparin (30 IU) increased significantly (P < 0.05) the NF-kB gene and protein expression levels and the VSMC migration during the exposure periods. Heparin (15 IU and 30 IU) also increased the collagen 1 gene expression level in the 48-h period while Heparin (5 IU and 15 IU) increased the collagen 3 gene expression levels in both periods. Incorporating Heparin into the cultures including Betulinic acid and Ibrutinib affected the collagen 1 and collagen 3 expression levels. The data suggested that the cell migration relates to NF-kB in the VSMCs treated with Heparin and Ibrutinib. Furthermore, the Heparin doses (5 IU and 15 IU) were safe for VSMCs based on the NF-kB, and collagen 3 expression levels.

Comparison of Omicron and Delta Variants of SARS-CoV-2: A Systematic Review of Current Evidence.

INTRODUCTION: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) caused the outbreak of coronavirus disease 2019 (COVID-19) in late 2019 in Wuhan, China. In early 2020, the disease spread rapidly around the world. Since the pandemic, SARS-CoV-2 has evolved dramatically into a wide variety of variants endowed with devastating properties. As of March 6, 2022, five SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, Delta, and Omicron strains have been identified. Due to the crucial importance of understanding the differences between the Omicron and Delta variants, this systematic review was conducted. METHODS: This systematic review investigated new variants of Omicron SARS-CoV-2 based on cur-rent studies. Online databases were searched for English articles as of January 03, 2023. Selection of publications was a two-step process of title/abstract and full-text assessment against eligibility crite-ria. The relevant data from the included articles were systematically collected and organized in a designed table for analysis. To ensure the quality of the review, the PRISMA checklist and Newcas-tle-Ottawa Scale (NOS) of quality assessment were utilized. RESULTS: The data extracted from 58 articles were analyzed, including 10003 pieces of evidence. Lower risk of hospitalization, ICU admission, and mortality after vaccination were reported in the Omicron variant compared to the Delta variant. Additionally, the Delta variant led to more severe clinical symptoms in comparison to the Omicron variant. CONCLUSION: The Omicron variant of SARS-CoV-2 results in less severe disease outcomes as com-pared to Delta. Nevertheless, it remains crucial to maintain ongoing monitoring, implement contain-ment measures, and adapt vaccination protocols to effectively address the evolving variants.

Differential gene expression patterns in ST-elevation Myocardial Infarction and Non-ST-elevation Myocardial Infarction.

The ST-elevation Myocardial Infarction (STEMI) and Non-ST-elevation Myocardial Infarction (NSTEMI) might occur because of coronary artery stenosis. The gene biomarkers apply to the clinical diagnosis and therapeutic decisions in Myocardial Infarction. The aim of this study was to introduce, enrich and estimate timely the blood gene profiles based on the high-throughput data for the molecular distinction of STEMI and NSTEMI. The text mining data (50 genes) annotated with DisGeNET data (144 genes) were merged with the GEO gene expression data (5 datasets) using R software. Then, the STEMI and NSTEMI networks were primarily created using the STRING server, and improved using the Cytoscape software. The high-score genes were enriched using the KEGG signaling pathways and Gene Ontology (GO). Furthermore, the genes were categorized to determine the NSTEMI and STEMI gene profiles. The time cut-off points were identified statistically by monitoring the gene profiles up to 30 days after Myocardial Infarction (MI). The gene heatmaps were clearly created for the STEMI (high-fold genes 69, low-fold genes 45) and NSTEMI (high-fold genes 68, low-fold genes 36). The STEMI and NSTEMI networks suggested the high-score gene profiles. Furthermore, the gene enrichment suggested the different biological conditions for STEMI and NSTEMI. The time cut-off points for the NSTEMI (4 genes) and STEMI (13 genes) gene profiles were established up to three days after Myocardial Infarction. The study showed the different pathophysiologic conditions for STEMI and NSTEMI. Furthermore, the high-score gene profiles are suggested to measure up to 3 days after MI to distinguish the STEMI and NSTEMI.

Testosterone, ß-estradiol, and hepatocellular carcinoma: stimulation or inhibition? A comparative effect analysis on cell cycle, apoptosis, and Wnt signaling of HepG2 cells.

Unlike breast and prostate cancers, which are specifically affected by estrogens or androgens, hepatocellular carcinoma has been reported to be influenced by both sex hormones. Given the coincidental differences of hepatocellular carcinoma in men and women, we investigated the effects of ß-estradiol and testosterone on the cell cycle, apoptosis, and Wnt signaling in a model of hepatocellular carcinoma to understand the sex hormone-related etiology. To determine the effective concentration of both hormones, an MTT assay was performed. The effects of ß-estradiol and testosterone on cell proliferation and death were evaluated by specific staining and flow cytometry. In addition, gene expression levels of estimated factors involved in GPC3-Wnt survival signaling were analyzed using quantitative real-time polymerase chain reaction. Both hormones inhibited hepatic cell proliferation through arresting the cell cycle at S/G2 and increased the apoptosis rate in HepG2 cells. Both hormones dose-dependently decreased GPC3, Wnt, and DVL expression levels as activators of the Wnt-signaling pathway. In the case of Wnt-signaling inhibitors, the effects of both hormones on WIF were negligible, but they increased DKK1 levels in a dose-dependent manner. In each of the effects mentioned above, ß-estradiol was notably more potent than testosterone. In contrast to the primary hypothesis of the project, in which testosterone was considered a stimulating carcinogenic factor in HCC pathogenesis, testosterone inhibited the occurrence of HCC similarly to ß-estradiol. However, this inhibitory effect was weaker than that of ß-estradiol and requires further study.

Systems biology approach to identify biomarkers and therapeutic targets for colorectal cancer.

Background: Colorectal cancer (CRC), is the third most prevalent cancer across the globe, and is often detected at advanced stage. Late diagnosis of CRC, leave the chemotherapy and radiotherapy as the main options for the possible treatment of the disease which are associated with severe side effects. In the present study, we seek to explore CRC gene expression data using a systems biology framework to identify potential biomarkers and therapeutic targets for earlier diagnosis and treatment of the disease. Methods: The expression data was retrieved from the gene expression omnibus (GEO). Differential gene expression analysis was conducted using R/Bioconductor package. The PPI network was reconstructed by the STRING. Cystoscope and Gephi software packages were used for visualization and centrality analysis of the PPI network. Clustering analysis of the PPI network was carried out using k-mean algorithm. Gene-set enrichment based on Gene Ontology (GO) and KEGG pathway databases was carried out to identify the biological functions and pathways associated with gene groups. Prognostic value of the selected identified hub genes was examined by survival analysis, using GEPIA. Results: A total of 848 differentially expressed genes were identified. Centrality analysis of the PPI network resulted in identification of 99 hubs genes. Clustering analysis dissected the PPI network into seven interactive modules. While several DEGs and the central genes in each module have already reported to contribute to CRC progression, survival analysis confirmed high expression of central genes, CCNA2, CD44, and ACAN contribute to poor prognosis of CRC patients. In addition, high expression of TUBA8, AMPD3, TRPC1, ARHGAP6, JPH3, DYRK1A and ACTA1 was found to associate with decreased survival rate. Conclusion: Our results identified several genes with high centrality in PPI network that contribute to progression of CRC. The fact that several of the identified genes have already been reported to be relevant to diagnosis and treatment of CRC, other highlighted genes with limited literature information may hold potential to be explored in the context of CRC biomarker and drug target discovery.

Differentially expressed genes of RNA-seq data are suggested on the intersections of normalization techniques.

Data normalization is the critical step for the RNA-seq data analysis. Several techniques are suggested for the normalization of transcript reads in the samples. In this study, the differentially expressed genes (DEGs) are generated from the TCGA normalized laryngeal cancer data obtained using the TPM, FPKM, and DESeq2 techniques. The results showed that the reports of DEGs were different based on the normalization techniques. We suggested that the DEG intersections obtain the top transcripts from the normalized data in support of the pathway enrichment process.

Short and mid-term outcomes of valve-sparing, aortic root reimplantation (David's procedure).

BACKGROUND: In the current study, we aimed to report the short- and mid-term outcomes of patients undergoing valve-sparing aortic root reimplantation (VSARR) and our center's experience with the procedure. METHODS: Forty patients with aortic root aneurysms underwent VSARR at our center from 2010 until 2022. We retrospectively reviewed the medical records of these patients and extracted the relevant data. After carefully examining the aortic valve, the surgeon decided to perform Bentall or David's procedure during the operation. RESULTS: The study population comprised 31 (77.5%) men and nine (22.5%) women, with a mean age of 55.35 ± 15.40. One patient developed hemodynamic instability post-surgery in the hospital and died from multi-organ failure. Another patient had severe AI in the intraoperative echocardiography, and aortic valve replacement with a prosthetic graft was performed during the same operation. In pre-operation echocardiography, 25 (62.5%) patients had severe, nine (22.5%) had moderate, and six (15%) had mild AI. In the in-hospital post-operation follow-up echo, AI was improved, and no patients had severe AI (P < 0.001). Only eight patients had moderate AI in post-one-year follow-up echo exams, while the rest had mild AI. CONCLUSION: David's procedure showed excellent mid-term results in our center, with only one in-hospital mortality.

An exact and vigorous kinetic Monte Carlo simulation to determine the properties of bimodal HDPE synthesized with a dual-site metallocene catalyst.

A vigorous and progressed Monte Carlo strategy was developed to precisely simulate the ethylene and 1-butene copolymerization within the presence of hydrogen by dual-site metallocene catalyst. The results showed up that the ethylene and 1-butene consumption rates at the second catalyst site were approximately 5 times higher than at the first site, and hydrogen transfer rates at the first catalyst site were over 3 times more rapid than at the second site. It was found that the most elevated molar percentage of 1-butene inside the copolymers synthesized from the second site was around 12% and within the copolymers gotten from the first site was around 2%. At a steady hydrogen concentration, with 8 times increase in the 1-butene concentration within the initial feed, the overall weight average molecular weight (M‾w) and an overall number average molecular weight (M‾n) extended by approximately 50% and 40%, respectively. Besides, at a consistent 1-butene concentration, with 8 times increase in the concentration of hydrogen, M‾w and M‾n diminished by approximately 18% and 22%, separately. Due to the synthesis of two groups of chains with distinct molecular weights, the overall dispersity (D) was slightly higher than the dispersity resulting from each catalyst site (1.5-2.1). With increasing 1-butene concentrations, the overall bimodal molecular weight distribution (MWD) widened, and the peak sizes grew smaller and moved towards higher molecular weights. As hydrogen concentration increased, peaks became taller and move toward shorter chain lengths. It was observed that the first site created chain lengths between 102 and 103 while the second site generated chain lengths between 102 and 106. As the concentration of 1-butene was increased in the initial feed, the number of short chain branching per 1000 carbon atoms (SCB/1000C) increased from 10 to 50. Compared to the first site, there were 5 times as many SCBs at the chains produced from the second site. By diminishing the ratio of ethylene to 1-butene, the melt index (MI) tended towards smaller numbers (0.2≤MI≤2). With an increase in the ratio of ethylene to 1-butene and ethylene to hydrogen, the weight fraction of crystals raised from 67.4 to 69.5% and diminished from 71 to 69.5%, respectively. At last, increasing the temperature led to a diminish in molecular weight, a narrowing of the bimodal MWD, an increment within the thickness and weight fraction of crystals, and an increment within the density of HDPE.

Beta arrestin-related signalling axes are influenced by dexamethasone and metformin in vascular smooth muscle cells cultured in high glucose condition.

BACKGROUND: Metformin (Met) and dexamethasone (Dexa) are known to reduce blood sugar levels and anti-inflammatory effects, respectively. Based on the acceleration of atherosclerosis process in diabetes, the ß-arrestin 2 (BARR2) gene and protein expression levels were evaluated in vascular smooth muscle cells (VSMCs) treated with Met and Dexa in high glucose conditions in this study. METHODS AND MATERIALS: Human VSMCs were cultured in Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM-F12) medium and, were treated with different values of Met (1 mM, 5 mM and 7 mM) and Dexa (10-7 M, 10-6 M and 10-5 M) in 24- and 48-h periods. The BARR2 gene and protein expression levels were identified with RT-qPCR and western blotting techniques, respectively. The signalling axes were predicted from gene network made using Cytoscape software and, were annotated with Gene Ontology. RESULTS: The BARR2 gene and protein expression levels reduced in VSMCs treated with Dexa and Met after 24- and 48-h periods. These results were more changed after 48 h. Furthermore, many BARR2-related signalling axes were found from the network genes. CONCLUSION: Met and Dexa suppressed the BARR2 protein and gene expression levels in the VSMCs. Moreover, the gene network suggested some the cellular signalling axes related to BARR2 that may be affected by Met and Dexa.

The Comparison Between 3.5- and 4.5-mm T-plates for Management of the Patients with Schatzker Type II Tibial Plateau Fractures that Referred to our Emergency Department: A Clinical Trial.

Background: Tibial plateau fractures have become more frequent in recent years. The most prevalent Schatzker classification is type II, which is a lateral tibial plateau fracture with depression. Our null hypothesis was that the 3.5 T-plate and the 4.5 T-plate have no difference in the management of patients with Schatzker type II tibial plateau fractures. Materials and Methods: The current study is a clinical trial that was conducted on patients with tibial plateau fractures. The Knee Society Score (KSS) was this study's main outcome. Tourniquet time (TT) and patient quality of life using the 36-item Short Form Survey Instrument (SF-36) were secondary goals of the outcomes measurement study. VAS measured pain. Among 176 patients, 89 and 87 of cases underwent surgical treatment with 3.5-mm (group A) and 4.5-mm (group B) T-plate, respectively. The data were entered into SPSS software (version 25, IBM Corporation, Armonk, NY) and analyzed. Results: In our study, we evaluated 176 patients with a mean age of 34.8 ± 15.2 years. Functional and clinical KSS scores were similar between the two groups throughout follow-up (P > 0.05). Regarding the other variables of VAS, TT, SF-36 physical function, and SF-36 mental health, no significant difference was observed between the two groups, and the two groups had similar averages in terms of these indicators (P > 0.05). Conclusion: According to the results, both plates had the appropriate functional outcomes in patients with split depression tibial plateau fracture.

Watershed infarction in COVID-19: The necessity of neuroimaging in patients with subtle neurological symptoms.

Background: Cerebrovascular diseases comprise a significant portion of neurological disorders related to coronavirus disease 2019 (COVID-19). We evaluated the clinical and imaging characteristics of a cohort of COVID-19 patients with stroke and also identified patients with watershed infarcts. Methods: In this cross-sectional study, seventy-three COVID-19 patients with ischemic stroke were included between October 2020 and January 2021. Patients were evaluated based on the following clinical and imaging features: severity of COVID-19 (critical/ non-critical), stroke type, presence/absence of clinical suspicion of stroke, medical risk factors, Fazekas scale, atherothrombosis, small vessel disease, cardiac pathology, other causes, and dissection (ASCOD) criteria classification, and presence or absence of watershed infarction. Clinical outcomes were assessed based on Modified Rankin Scale (MRS) and mortality. Results: Most cases of ischemic stroke were due to undetermined etiology (52.1%) and cardioembolism (32.9%). In terms of imaging pattern, 17 (23.0%) patients had watershed infarction. Watershed infarction was associated with the clinically non-suspicious category [odds ratio (OR) = 4.67, P = 0.007] and death after discharge (OR = 7.1, P = 0.003). Patients with watershed infarction had a higher odds of having high Fazekas score (OR = 5.17, P = 0.007) which was also shown by the logistic regression model (adjusted OR = 6.87, P = 0.030). Thirty-one (42%) patients were clinically non-suspected for ischemic stroke. Critical COVID-19 was more common among patients with watershed infarct and clinically non-suspicious patients (P = 0.020 and P = 0.005, respectively). Patients with chronic kidney disease (CKD) were more prone to having stroke with watershed pattern (P = 0.020). Conclusion: Watershed infarct is one of the most common patterns of ischemic stroke in patients with COVID-19, for which clinicians should maintain a high index of suspicion in patients with critical COVID-19 without obvious clinical symptoms of stroke.

Epstein-Barr virus infection leading to multiorgan involvement in an immunocompetent man.

Epstein-Barr virus (EBV) is a commonly asymptomatic widespread human herpes virus affecting over 90% of the population. It mostly originates complications like simple sore throat and infectious mononucleosis but severe manifestations are rare. Herein we report a 30-year-old immunocompetent man who presented with fever, sore throat, general weakness, and drowsiness. The diagnosis was formulated based on the positive RT-PCR test for EBV DNA and serological detection of IgM antibody against viral capsid antigen. The patient developed severe meningoencephalitis, myocarditis, and bowel perforation and passed away after 72 days of hospitalization.

GABBR2 as a Downstream Effector of the Androgen Receptor Induces Cisplatin Resistance in Bladder Cancer.

The precise molecular mechanisms responsible for resistance to cisplatin-based chemotherapy in patients with bladder cancer remain elusive, while we have indicated that androgen receptor (AR) activity in urothelial cancer is associated with its sensitivity. Our DNA microarray analysis in control vs. AR-knockdown bladder cancer sublines suggested that the expression of a GABA B receptor GABBR2 and AR was correlated. The present study aimed to determine the functional role of GABBR2 in modulating cisplatin sensitivity in bladder cancer. AR knockdown and dihydrotestosterone treatment considerably reduced and induced, respectively, GABBR2 expression, and the effect of dihydrotestosterone was at least partially restored by an antiandrogen hydroxyflutamide. A chromatin immunoprecipitation assay further revealed the binding of AR to the promoter region of GABBR2 in bladder cancer cells. Meanwhile, GABBR2 expression was significantly elevated in a cisplatin-resistant bladder cancer subline, compared with control cells. In AR-positive bladder cancer cells, knockdown of GABBR2 or treatment with a selective GABA B receptor antagonist, CGP46381, considerably enhanced the cytotoxic activity of cisplatin. However, no additional effect of CGP46381 on cisplatin-induced growth suppression was seen in GABBR2-knockdown cells. Moreover, in the absence of cisplatin, CGP46381 treatment and GABBR2 knockdown showed no significant changes in cell proliferation or migration. These findings suggest that GABBR2 represents a key downstream effector of AR signaling in inducing resistance to cisplatin treatment. Accordingly, inhibition of GABBR2 has the potential of being a means of chemosensitization, especially in patients with AR/GABBR2-positive bladder cancer.

Assessment of human gait after total knee arthroplasty by dynamic time warping algorithm.

Today, the elderly population is increasing, and there are many drawbacks for them, especially defects in their knee joints which lead to improper gait. To solve this problem, their knee joint can be replaced with knee arthroplasty. In this letter, level of improvement in the human gait before and after total knee arthroplasty (TKA) surgery is investigated using the dynamic time warping (DTW) algorithm. For this purpose, several volunteers who have problems with their knees are incorporated in a test before and after TKA surgery. Then, the data of gait analysis is collected and the data is compared with a reference using the DTW algorithm. The outcome results illustrate an improvement of 89%-97% by the proposed algorithm after TKA surgery. Therefore, patients can see improvement with high accuracy and very fast that result in more use this technique in TKR surgery.