The Effectiveness of Laboratory Parameters in Predicting the in-Hospital Mortality of Iranian Patients with Coronavirus Disease 2019 (COVID-19).

Background: The novel coronavirus 2019-nCoV (now SARS-CoV-2) has spread globally and affected healthcare systems worldwide. Due to lack of long-term immunization and effective specific treatments for the COVID-19 disease, there is a need of identifying the patients who are at the risk of a fatal outcome, according to the available epidemiological data and laboratory parameters. Objective: Thus, we aimed to evaluate the prognostic value of epidemiological data and laboratory para-meters for in-hospital case fatality in patients with COVID-19. Materials and Methods: A retrospective cohort of patients with COVID-19 admitted to the Shahid Mostafa Khomeini Hospital of Ilam University of Medical Sciences from February 29 until March 29, 2020 was performed. Epidemiologic data and laboratory results were collected. Univariate and multivariate logistic regression models were performed to evaluate the prognostic value of the laboratory parameters for in-hospital death. Results: A total of 256 Iranian COVID-19 patients were included in the evaluation; 38 of them died, resulting in a in-hospital case-fatality rate of 14.8%. The univariate analysis showed that advanced age [OR=1.04, 95% CI: 1.02, 1.06, P=0.001], smoking [OR=4.041, 95% CI: 1.546-10.563, P=0.004], white blood cells [OR=0.941, 95% CI: 0.904-0.980, P =0.003] and hematocrit [OR=1.060, 95% CI: 1.009-1.113, P=0.020] were positively associated with the risk of a fatal outcome. Multivariate logistic regression analysis revealed that COVID-19 patients with an elevated white blood cell count and elevated hemoglobin level had 1% and 9% greater risk of an in-hospital death for each elevated unit [OR=1.07; 95 %CI: 1.024-1.088, P =0.002 and OR=1.379; 95% CI 0.064-1.788, P =0.015, respectively]. Conclusions: An increase in white blood cell count and an increase in hemoglobin level might be indepen-dent risk factors for in-hospital death in Iranian patients with COVID-19. Further studies are necessary in order to conferm the prognostic value of the variables discussed.

Effects of synaptic and myelin plasticity on learning in a network of Kuramoto phase oscillators.

Models of learning typically focus on synaptic plasticity. However, learning is the result of both synaptic and myelin plasticity. Specifically, synaptic changes often co-occur and interact with myelin changes, leading to complex dynamic interactions between these processes. Here, we investigate the implications of these interactions for the coupling behavior of a system of Kuramoto oscillators. To that end, we construct a fully connected, one-dimensional ring network of phase oscillators whose coupling strength (reflecting synaptic strength) as well as conduction velocity (reflecting myelination) are each regulated by a Hebbian learning rule. We evaluate the behavior of the system in terms of structural (pairwise connection strength and conduction velocity) and functional connectivity (local and global synchronization behavior). We find that adaptive myelination is able to both functionally decouple structurally connected oscillators as well as to functionally couple structurally disconnected oscillators. With regard to the latter, we find that for conditions in which a system limited to synaptic plasticity develops two distinct clusters both structurally and functionally, additional adaptive myelination allows for functional communication across these structural clusters. These results confirm that network states following learning may be different when myelin plasticity is considered in addition to synaptic plasticity, pointing toward the relevance of integrating both factors in computational models of learning.

Association of the c.-9C>T and c.368A>G transitions in H2BFWT gene with male infertility in an Iranian population.

The H2BFWT (H2B family, member W, testis specific) gene is a testis-specific histone which is involved in the spermatogenesis process. This study aimed to investigate the association of H2BFWT gene c.-9C>T and c.368A>G polymorphisms with male infertility in an Iranian population. The 232 independent individuals, including 109 infertile men and 123 healthy controls, were recruited from IVF centre (Kashan, Iran). The allele types of c.-9C>T and c.368A>G polymorphisms were detected by using PCR-RFLP method. In overall analysis, we found that the c.-9T (OR: 1.75, 95% CI: 1.04-2.95, p = .035) and c.368G (OR: 1.71, 95% CI: 1.02-2.89, p = .042) alleles are associated with male infertility. The c.-9T allele was also associated with nonobstructive azoospermia (OR: 2.08, 95% CI: 1.01-4.25, p = .046), while c.368G allele was associated with oligozoospermia (OR: 2.10, 95% CI: 1.15-3.85, p = .016). It is concluded that H2BFWT gene c.-9C>T and c.368A>G polymorphisms might be genetic risk factors for idiopathic male infertility.

Effect of prepartal and postpartal dietary fat level on performance and plasma concentration of metabolites in transition dairy cows.

The objective of this study was to determine the effects of 2 levels of dietary fat (low and high) offered during the prepartal and postpartal periods on dry matter intake (DMI), plasma concentration of metabolites, and milk yield and composition. Twenty-four Holstein dry cows were assigned on d 21 relative to expected parturition date to 1 of 4 treatments in a 2×2 factorial arrangement of 2 levels of fat fed during the prepartal period and 2 levels of fat fed during the postpartal period: prepartal low fat and postpartal low fat (LF-LF), prepartal low fat and postpartal high fat (LF-HF), prepartal high fat and postpartal low fat (HF-LF), or prepartal high fat and postpartal high fat (HF-HF). Prepartal and postpartal LF diets contained no fat supplement. Prepartal HF diets contained 1.60% calcium salts of soybean oil. The proportion of calcium salts of soybean oil was increased to 1.70% of DM for the first 21 d of lactation and to 2.27% of DM from d 21 to 56 of lactation in the HF diet. Diets were fed for ad libitum intake from d 21 before calving until d 56 of gestation. Prepartal DMI was lower for cows fed the HF diet compared with those fed the LF diet (12.6 vs. 16.2kg/d). Postpartum, cows fed the HF-HF and HF-LF diets had, respectively, the lowest and highest DMI, although no significant differences existed between HF-LF and LF-LF. Net energy intake was higher for cows fed the postpartal HF diets compared with those fed the LF diets. Prepartal fat level had no effect on net energy intake. Cows offered the prepartal HF diet had higher milk yield when offered the postpartal LF diet compared with those offered the postpartal HF diet and no effect of the postpartal fat level was detected when cows were fed the prepartal LF diet. Milk composition was similar among treatments. Plasma cholesterol concentration postpartum was higher for cows fed the prepartal LF diet than for those fed the prepartal HF diet (5.16 vs. 3.74mmol/L) and postpartal fat level had no effect. Prepartal diet had no significant effect on postpartal plasma triglyceride concentration but the postpartal HF diet increased triglyceride and low-density lipoprotein concentrations compared with the postpartal LF diet. In conclusion, switching from a high to a low fat proportion in the postpartal diet may alleviate the negative effects of a high proportion of fat in the prepartal diet as shown by increased feed intake and milk production during the first 56 d of lactation.

Improved antioxidant defense in the ventral tegmental area increases pain tolerance in male rats.

The ventral tegmental area (VTA) is a brain region recently shown to interfere with pain perception. According to previous studies, improvement of antioxidant defense mechanisms reduces pain. The aim of this study was to show that lack of social interaction influences oxidative stress in the VTA and that this results in increased pain tolerance. In this study, 21 male Sprague-Dawley rats were randomly divided into 2 groups: paired and socially isolated (SI). After one week of acclimatization, the SI rats were isolated for 14 days and the other rats were paired for the same period. On day 15, pain tolerance was assessed through the tail flick test, and two days later the rats were investigated for anxiety in an elevated plus maze (EPM). Indices of oxidative stress (levels of malondialdehyde, glutathione, nitrite/nitrate and catalase activity in the VTA) were then studied in the animals. Malondialdehyde in the VTA was found to be reduced in the SI rats compared with the paired rats. Furthermore, catalase activity, glutathione and nitrite/nitrate levels in the VTA were increased in SI compared with paired rats. Pain tolerance on the tail flick test was increased in SI rats compared with paired rats, while anxiety, as assessed by EPM, was reduced in the SI rats compared with the paired rats. Improvement of antioxidant defense and reduction of oxidative stress in the VTA increases pain tolerance and reduces anxiety. In this sense, environmental conditions play an important role in pain control.

Association analysis of rs1049255 and rs4673 transitions in p22phox gene with coronary artery disease: A case-control study and a computational analysis.

BACKGROUND: The p22phox gene encodes the main subunit of NADH/NADPH-oxidase. This enzyme is expressed in smooth muscle cells of arteries, and it produces the reactive oxygen species. On the other hand, oxidative stress plays a main role in the pathogenesis of coronary artery disease (CAD). AIM: The aim of this study is to evaluate the association between rs4673 and rs1049255 polymorphisms of p22phox gene with CAD in an Iranian population which was followed with a computational analysis approach. METHODS: In a cross-sectional study, we collected blood samples of 302 Iranian Caucasian including 143 patients and 159 healthy controls. Genotype of the polymorphisms was detected through PCR-RFLP method. A computational analysis was also performed using SNAP, Polyphen-2, Chou-Fasman, RNAsnp, and miRNA SNP databases. RESULTS: Data of case control study demonstrated that CT genotype (R = 1.84, 95% CI = 1.13-3.00, p = 0.014) and T allele (OR = 1.53, 95% CI = 1.09-2.15, p = 0.013) of rs4673 polymorphism, have a significant association with enhanced risk of CAD. But rs1049255 analysis demonstrated the absence of such an association with CAD. Indeed, in silico data analysis demonstrated that rs4673 transition could impact on function of p22phox protein (SNAP score 56, expected accuracy 75%; Polyphen-2 score 0.99, sensitivity 0.09, specificity 0.99). Data derived from miRNA SNP database demonstrated that rs1049255 polymorphism increases the affinity of attachment between has-miR-3689a-3b with 3'-UTR of p22phox gene. CONCLUSION: Our data demonstrated that rs4673 transition may be involved in susceptibility to CAD and could be applied as a potential biomarker for this disease.

Serum high-sensitivity C-reactive protein as a biomarker in patients with metabolic syndrome: evidence-based study with 7284 subjects.

BACKGROUND/OBJECTIVES: Metabolic syndrome (MetS) is characterized by abdominal obesity, dyslipidemia, hypertension and glucose intolerance, and is associated with an increased risk of developing cardiovascular disease (CVD), diabetes mellitus and related diseases. Circulating levels of inflammatory markers such as C-reactive-protein (CRP) have reported to be associated with CVD. Against this background, the prevalence of MetS is increasing globally, and thus predictive biomarkers are required for identification of MetS patients at an increased risk. Here we explored the value of CRP as a biomarker in 7284 subjects and also investigated which features of MetS have the greatest association with the hs-CRP level. SUBJECTS/METHODS: The subjects were recruited from the Mashhad stroke and heart atherosclerotic disorder study. Anthropometric factors and biochemical parameters (for example, high-sensitivity CRP (hs-CRP), high-density lipoprotein/low-density lipoprotein, triglycerides (TGs) and fasting blood glucose (FBG)) were determined. Univariate and multivariate analyses were conducted to evaluate the association of hs-CRP and MetS. RESULTS: Our results illustrated that the concentration of serum hs-CRP increased progressively with the number of MetS components, and subjects who fulfilled the criteria of MetS for waist circumference, TGs, blood pressure and FBG were found to have hs-CRP of 0.53, 0.38, 0.34 and 0.71 mg/l, respectively, higher than matched-subjects. Importantly, FBG had the greatest association with hs-CRP concentration. CONCLUSIONS: Our data demonstrate the significant association between MetS components with hs-CRP, indicating that this association was cumulative by increasing the number of the defining features of MetS, supporting further studies to explore the value of emerging marker as a novel method for detecting individuals at high risk of developing MetS.

Plasma protein extravasation into the rat knee joint induced by calcitonin gene-related peptide.

In previous experiments, intra-articular administration of calcitonin gene-related peptide (CGRP) failed to elicit plasma protein extravasation into synovial fluid. In the present study, using a sensitive technique to assay protein in synovial fluid, intra-articular perfusion of CGRP (10(-6) M) was found to produce protein extravasation which was sustained throughout the period of infusion. Both lower (10(-7) M) and higher (10(-5) M) concentrations of CGRP failed to produce extravasation. This failure at the highest concentration of CGRP was the likely consequence of a significant fall in arterial blood pressure which occurred with administration of CGRP at this concentration. In the presence of arterial hypotension induced by an alpha-adrenoceptor antagonist, 10(-6) M CGRP failed to produce extravasation. Plasma extravasation induced by CGRP was a specific effect and not merely a consequence of its potent vasodilator properties as similar vasodilator responses induced by a beta-adrenoceptor agonist failed to induce protein leakage. These findings indicate that CGRP can alter blood vessel permeability and therefore could additionally contribute to neurally mediated inflammatory responses.

Participation of the beta-ketoadipate transport system in chemotaxis.

beta-Ketoadipate serves as a chemoattractant for Pseudomonas putida. The chemotactic response is inducible, and a regulatory mutant strain that forms the beta-ketoadipate transport system at high levels exhibits a heightened chemotactic response to beta-ketoadipate. Adipate and succinate, compounds that interact with the transport system, inhibit chemotaxis toward beta-ketoadipate. Some, but not all, mutants that fail to respond chemotactically to beta-ketoadipate lack the beta-ketoadipate transport system. It thus appears that the transport of beta-ketoadipate is associated with its function as a chemoattractant. It is likely that the metabolite attracts fluorescent Pseudomonas species to environments in which complex aromatic polymers undergo microbial dissimilation.