Dysregulated Leukotriene Metabolism in Patients with COVID-19.

This study aimed to examine the leukotriene metabolism during COVID-19. In total, 180 participants were included in this study, of which 60 were healthy controls, 60 required intensive care units (ICU), and 60 did not require intensive care (non-ICU). The serum levels of 5-lipoxygenase (5-LO), 5-LO activating protein (ALOX5AP), and cysteinyl leukotriene (CYSLT) were measured, and the mRNA expression levels of 5-LO, ALOX5AP, and cysteinyl leukotriene receptor 1 (CYSLTR1) were investigated. Compared with the control group, both the non-ICU and ICU groups had lower levels of 5-LO and mRNA expression. ICU patients had lower levels of 5-LO and mRNA expression than non-ICU patients. CYSLTR1 mRNA expression was highest in the ICU group, followed by the non-ICU group, and healthy controls had the lowest mRNA expression levels. CYSLT levels were higher in the control group than in the non-ICU and ICU groups. CYSLTR1 expression was higher in patients than in controls; therefore, selective leukotriene receptor blockers can be used as treatment options. CYSLTR1 expression was higher in the ICU group than in the non-ICU group. Furthermore, CYSLTR1 mRNA expression may be a promising biomarker of COVID-19 severity.

Protective effect of ursodeoxycholic acid and resveratrol against tacrolimus induced hepatotoxicity.

Tacrolimus (TAC) is a potent and well-tolerated immunosuppressive drug, but serious side effects including nephrotoxicity and hepatotoxicity have been reported. Ursodeoxycholic acid (UDCA) and resveratrol (RSV) exhibit hepatoprotective effects in liver diseases. We investigated the hepatoprotective effect of UDCA and RSV against TAC induced hepatotoxicity. We divided 40 male rats into five equal groups: A) control group, B) TAC group, C) TAC + UDCA group, D) TAC + RSV group, E) TAC + UDCA + RSV group. We administered 0.5 mg/kg TAC once daily, 25 mg/kg UDCA twice daily and 10 mg/kg RSV once daily. The drugs in the experimental groups were given by gavage from the first day of the study and continued for 21 days. Histopathologic and biochemical analyses were performed on day 22. In group B, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), total oxidative status (TOS) and malondialdehyde (MDA) levels were higher compared to group A, and catalase (CAT), superoxide dismutase (SOD) levels and total antioxidant status (TAS) were lower compared to group A. Severe cellular swelling, degeneration and focal necrosis were more evident in group B than in groups C-E. Histopathological improvement was observed in groups C-E, where UDCA and RSV were combined, compared to group B. We found that UDCA and RSV, together or separately, protected the liver against oxidative stress damage caused by TAC.

Comprehensive analysis of circulating viral DNA in maternal plasma at population-scale using low-pass whole-genome sequencing.

As the most readily adopted molecular screening test, low-pass WGS of maternal plasma cell-free DNA for aneuploidy detection generates a vast amount of genomic data. This large-scale method also allows for high-throughput virome screening. NIPT sequencing data, yielding 6.57 terabases of data from 187.8 billion reads, from 12,951 pregnant Turkish women was used to investigate the prevalence and abundance of viral DNA in plasma. Among the 22 virus sequences identified in 12% of participants were human papillomavirus, herpesvirus, betaherpesvirus and anellovirus. We observed a unique pattern of circulating viral DNA with a high prevalence of papillomaviruses. The prevalence of herpesviruses/anellovirus was similar among Turkish, European and Dutch populations. Hepatitis B prevalence was remarkably low in Dutch, European and Turkish populations, but higher in China. WGS data revealed that herpesvirus/anelloviruses are naturally found in European populations. This represents the first comprehensive research on the plasma virome of pregnant Turkish women.

Examination of the correlation between hand grip strength and muscle mass, balance, mobility, and daily life activities in elderly individuals living in nursing homes.

BACKGROUND: Aging is a process that includes progressive physiological changes. Grip strength is an important indicator of current health in the elderly. OBJECTIVE: The aim of the study was to examine the correlation between dominant-hand grip strength (HGS) and cognitive function, mid-upper arm circumference, muscle-bone mass, balance, mobility, and daily life activities in elderly individuals living in nursing homes and determine the effect rates of these factors on HGS. METHODS: Seventy-two elderly individuals aged over 65 who lived in a nursing home were included in the study. Dominant HGS and mid-upper forearm circumference were measured. Muscle and bone masses were measured with bioelectrical impedance analysis. Mid-upper arm circumference was measured using a non-elastic tape. HGS was measured using a hand dynamometer. Cognitive function was evaluated with the Standardized Mini-Mental Test (SMMT); mobility and balance were evaluated with the Timed Up and Go Test (TUGT) and Berg Balance Scale (BBS); the Katz Activities of Daily Living Scale (KATZ ADL) was used to evaluate daily life activities. RESULTS: There was a significant correlation between HGS and muscle and bone masses (p < 0.001). A significant correlation was found between HGS and TUGT, ADL (p = 0.001, p = 0.016). There was no significant correlation between HGS and BBS (p = 0.2). There was a correlation between HGS and SMMT at the statistical significance limit (p = 0.055). On HGS, the Body Mass Index had a 64.9% effect; the muscle mass had a 30.9% effect; the TUGT had a 27.7% effect. These parameters were found to explain 59.9% of the variance. CONCLUSION: As a global indicator of muscle strength, HGS can be used to predict age-related functional changes. Approaches to increase physical activity levels in elderly can be effective in reducing age-related negativities.

Validation of the five-item version of the Geriatric Depression Scale (GDS-5) in a Turkish elderly population.

BACKGROUND: Late-life depression is a geriatric syndrome which should be taken seriously. Many clinical scales have been developed for the screening of geriatric depression. Most of these have been validated at different times and in diverse populations. A five-question version of the Geriatric Depression Scale (GDS-5) was developed in 1997. This test has been validated and used in different populations. In the present study, we plan to validate the GDS-5 for the Turkish elderly population. METHODS: Patients aged 60 years and older who applied to the Geriatrics Clinic of our hospital between November 2018 and November 2019 were included in the study. We compared the effectiveness of Yesavage Geriatric Depression Scale-30 (YGDS-30) and GDS-5 in screening depression, based on Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) depression criteria. RESULTS: Four hundred participants were included in the study. A significant positive correlation was found between the DSM-5 scale and the GDS-5 scale (rho = 0.726, P <0.001). According to DSM-5, YGDS-30 and GDS-5, 112 participants (28%), 154 patients (%38.5) and 199 patients (%49.8) were diagnosed with depression respectively. When the cut-off value was taken as ≥2, the sensitivity, specificity, positive predictive and negative predictive values for the GDS-5 scale were determined as 96%, 68%, 54%, and 98%, respectively. We obtained these diagnostic measures with 95% confidence intervals. CONCLUSION: This study demonstrated the validity and reliability of the GDS-5 for Turkish elderly populations. This five-question scale will be significant in daily use to screen for depression in elderly individuals with multiple problems.

Frailty in Patients with Parkinson's Disease: Associations with Disability and Timed Up and Go.

INTRODUCTION: Aim of this study was identify the prevalence of frailty in patients with idiopathic Parkinson's disease (PD), to describe the relationship between severity of the disease and frailty, and to evaluate if timed up and go (TUG) is an eligible test for determination of frailty in idiopathic PD patients. METHODS: We conducted a cross-sectional study which included 66 patients, aged 60 and over in a tertiary hospital. Frailty was assessed by the Fried Frailty Index (FFI). Severity of the idiopathic PD was detected by the Hoehn and Yahr (H&Y) scale. Mobility was measured by the TUG test. Demographic characteristics and comprehensive geriatric assessments were evaluated. Descriptive statistics and logistic regression were used in analyses. Receiver operating characteristic (ROC) curves were used to identify the discriminative effect of TUG test on frailty. RESULTS: The numbers of frail, prefrail, and robust subjects were 34 (51.5%), 24 (36.4%), and 8 (12.1%), respectively. Dependency in instrumental activities of daily living (IADL) was significantly associated with frailty (Odds ratio (OR): 36.00, Confidence interval (CI): 8.43-153.80). Multivariate logistic regression analysis results yielded, depression (OR: 10.37, CI: 2.82-38.12) and higher levodopa doses (OR: 6.28, CI: 1.77-22.24) were independently associated with frailty. TUG test performance was strongly associated with frailty with high sensitivity (0.806) and specificity (0.826) (Area under the curve (AUC): 0.831). CONCLUSIONS: Frailty is highly prevalent in idiopathic PD and is strongly associated with disabilities as well as specific risk factors of the disease. The TUG may be a reliable test for prediction of frailty in patients with idiopathic PD.

Soluble vascular endothelial growth factor receptor-1 as a novel marker of arteriovenous fistula stenosis in hemodialysis patients.

INTRODUCTION: Arteriovenous fistula (AVF) stenosis is one of the most important clinical problems in hemodialysis patients. The histopathological findings of neointimal hyperplasia and impaired angiogenesis have been well established in stenotic AVFs. Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) has been implicated in pathological angiogenesis. Thus, we aimed to investigate the association between sVEGFR-1 and AVF stenosis in hemodialysis patients. METHODS: This prospective cohort study included 70 patients with end-stage renal disease. Forty-five patients were included in the final analysis, and the median follow-up period was 36 months. Venous stenosis was detected by physical examination and documented by fistulography. Blood samples were analyzed a day before the fistula operation, and serum levels of sVEGFR-1 were measured. FINDINGS: The median sVEGFR-1 level was higher in the stenosis group than in the nonstenosis group (17 pg/mL [89.5%] vs. 5 pg/mL [19.2%], respectively; P < 0.001]. According to body mass index (BMI) categories, obese patients (BMI > 30 kg/m2 ) had the shortest stenosis-free survival (20 months [9.35-30.65]). Multivariate Cox analysis showed that sVEGFR-1, serum creatinine, and parathyroid hormone levels were associated with AVF stenosis risk. Kaplan-Meier survival curves showed that patients with less than the median value of sVEGFR-1 (<6093.07 pg/mL) had longer cumulative stenosis-free survival than patients with sVEGFR-1 levels above the median value (P < 0.001). DISCUSSION: Increased levels of sVEGFR-1 and obesity were found to be associated with AVF stenosis in hemodialysis patients.

How does body mass index affect semen parameters and reproductive hormones in infertile males?

OBJECTIVE: The aim of this study was to invastigate the effect of body mass index (BMI) on semen parameters and reproductive hormone levels in infertile males. MATERIAL AND METHODS: Overall, 858 infertile male patients, aged between 18 and 55 years, referred to our infertility clinic were included in the study. Patients without risk factors, besides obesity, that could affect semen parameters or reproductive hormones were evaluated. Patients were separated into the following three groups: non-obese (<25 kg/m2), overweight (25-29.9 kg/m2), and obese (≥30 kg/m2). Age, semen parameters, and reproductive hormones were evaluated and compared among the groups. In addition, subgroups based on sperm concentration were compared. RESULTS: Total testosterone and testosterone-estradiol ratio negatively correlated with BMI (p<0.001). A positive correlation was observed between BMI and age (p<0.001). Even when adjusted for age, the decrease in total testosterone was significant in all groups parallel to the increase in BMI. Although age, prolactin level, and total testosterone had a significant relationship in univariate analysis, the only significant parameters were prolactin and total testosterone according to multivariate analysis. There were no significant differences between BMI and semen parameters. No significant difference related to BMI was observed among the infertile groups [severe oligospermia (34.3%), oligospermia (18.2%), and normospermia (47.6%)]. CONCLUSION: A significant negative correlation was observed between increasing BMI and total testosterone. No relationship was observed between BMI and semen parameters except progressive motility. Nevertheless, prospective longitudinal clinical trials with larger sample sizes involving weight loss are needed to understand the precise relationship of BMI with reproductive hormones and semen parameters in the same individual.

Sarcopenia, dynapenia, and body composition in Parkinson's disease: are they good predictors of disability?: a case-control study.

BACKGROUND/AIM: To assess sarcopenia and dynapenia and their relationship with disease severity and disabilities in PD and to state body composition in PD. METHODS: We conducted a case-control, cross-sectional study that included 70 patients with idiopathic PD and 85 controls. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Dynapenia was detected by a handheld dynamometer. Bioimpedance analysis (BIA) was performed, and the SARC-F questionnaire was applied. Disabilities were appointed according to the Katz and Lawton indexes. RESULTS: Sarcopenia and dynapenia were more prevalent in PD than in controls (50 vs 30.6% and 31.4 vs 17.6%, respectively). Dynapenia was significantly associated with the severity of the disease and disabilities (p = 0.047, p = 0.001); however, sarcopenia was not. The skeletal muscle mass index (SMMI), fat mass index (FMI), and fat-free mass index (FFMI) did not differ between the PD and controls. FMI was lower in the advanced stages of the disease. Higher scores in the SARC-F questionnaire were significantly associated with disabilities and the severity of the disease (p < 0.001, p < 0.001). CONCLUSION: Muscle strength was closely associated with the severity of the disease and disabilities in PD, but muscle mass was not. Sarcopenia, defined by the SARC-F questionnaire, was a good predictor of disabilities in PD, while the EWGSOP criteria were not. PD patients have a favorable body composition even in advanced stages of the disease with lower FMI and protected lean mass.

MLSeq: Machine learning interface for RNA-sequencing data.

BACKGROUND AND OBJECTIVE: In the last decade, RNA-sequencing technology has become method-of-choice and prefered to microarray technology for gene expression based classification and differential expression analysis since it produces less noisy data. Although there are many algorithms proposed for microarray data, the number of available algorithms and programs are limited for classification of RNA-sequencing data. For this reason, we developed MLSeq, to bring not only frequently used classification algorithms but also novel approaches together and make them available to be used for classification of RNA sequencing data. This package is developed using R language environment and distributed through BIOCONDUCTOR network. METHODS: Classification of RNA-sequencing data is not straightforward since raw data should be preprocessed before downstream analysis. With MLSeq package, researchers can easily preprocess (normalization, filtering, transformation etc.) and classify raw RNA-sequencing data using two strategies: (i) to perform algorithms which are directly proposed for RNA-sequencing data structure or (ii) to transform RNA-sequencing data in order to bring it distributionally closer to microarray data structure, and perform algorithms which are developed for microarray data. Moreover, we proposed novel algorithms such as voom (an acronym for variance modelling at observational level) based nearest shrunken centroids (voomNSC), diagonal linear discriminant analysis (voomDLDA), etc. through MLSeq. MATERIALS: Three real RNA-sequencing datasets (i.e cervical cancer, lung cancer and aging datasets) were used to evalute model performances. Poisson linear discriminant analysis (PLDA) and negative binomial linear discriminant analysis (NBLDA) were selected as algorithms based on dicrete distributions, and voomNSC, nearest shrunken centroids (NSC) and support vector machines (SVM) were selected as algorithms based on continuous distributions for model comparisons. Each algorithm is compared using classification accuracies and sparsities on an independent test set. RESULTS: The algorithms which are based on discrete distributions performed better in cervical cancer and aging data with accuracies above 0.92. In lung cancer data, the most of algorithms performed similar with accuracies of 0.88 except that SVM achieved 0.94 of accuracy. Our voomNSC algorithm was the most sparse algorithm, and able to select 2.2% and 6.6% of all features for cervical cancer and lung cancer datasets respectively. However, in aging data, sparse classifiers were not able to select an optimal subset of all features. CONCLUSION: MLSeq is comprehensive and easy-to-use interface for classification of gene expression data. It allows researchers perform both preprocessing and classification tasks through single platform. With this property, MLSeq can be considered as a pipeline for the classification of RNA-sequencing data.

Using a high-flow nasal cannula provides superior results to OxyMask delivery in moderate to severe bronchiolitis: a randomized controlled study.

The effectiveness of using a face mask with a small diffuser for oxygen delivery (OxyMask) was compared to use of a high-flow nasal cannula (HFNC) in patients with moderate or severe bronchiolitis.The study population in this open, phase 4, randomized controlled trial consisted of 60 patients aged 1-24 months diagnosed with moderate or severe bronchiolitis and admitted to an intensive care unit (ICU) for oxygen therapy. The patients were randomized into two groups according to the method of oxygen delivery: a diffuser mask group and an HFNC group.There were seven failures in the mask group and none in the HFNC group. The survival probability differed significantly between the two treatment methods (p = 0.009).Time to weaning off oxygen therapy was 56 h in the HFNC group and 96 h in the mask group (p < 0.001).Conclusion: HFNC use decreased the treatment failure rate and the duration of both oxygen therapy and ICU treatment compared to the diffuser mask, which implies that an HFNC should be the first choice for treating patients admitted to the ICU with severe bronchiolitis. What is known: • A high-flow nasal cannula (HFNC) does not significantly reduce the time on oxygen compared to standard therapy in children with moderate to severe bronchiolitis. Observational studies show that, since the introduction of HFNC, fewer children with bronchiolitis need intubation. For children with moderate to severe bronchiolitis there is no proof of its benefit. What Is New: • In children with moderate to severe bronchiolitis, HFNC provides faster and more effective improvement than can be achieved with a diffuser mask.

High Doses of Boron Have No Protective Effect Against Nephrolithiasis or Oxidative Stress in a Rat Model.

Boron plays roles in the metabolism of calcium, vitamin D, steroid hormones, healthy bone development, and maintenance of cell membranes. The biological effects of boron are dose-dependent but follow a U-shaped pattern, rendering it important to define the active range. The studies of Bahadoran et al. on rats and Naghii et al. on humans showed that low doses of boron (3 and 10 mg/day) prevented kidney stone formation. The aim of this study was to determine whether high doses of boron have an anti-urolithiatic or antioxidant effect on nephrolithiasis in an experimental rat model. The study was conducted on 50 adult male Wistar rats randomized to five groups. Nephrolithiasis was induced with water containing 0.75% ethylene glycol (EG) and 2% ammonium chloride (AC). This treatment was given to animals in all groups for 10 days, except the positive and negative controls. Simultaneously, groups 2, 3, and 4 were given boric acid via gavage at doses of 25, 50, and 100 mg/kg/day (equivalent to 4/8/16 mg boron respectively) as the source of boron. Animals in the negative and positive control groups were given 6 µL/g distilled water without boric acid. At day 10, intra-cardiac blood samples were drawn from all animals. The right and left kidneys were removed for biochemical and histopathological examinations, respectively. The groups were compared with respect to serum urea, creatinine, calcium, phosphorous, total antioxidant status (TAS), total oxidant status (TOS), serum paraoxonase (PON1) activity, tissue calcium and oxalate levels, and stone burden as determined by histopathological examination. Serum urea and creatinine levels were significantly higher (p < 0.001 and p < 0.05, respectively), while serum calcium and phosphorous levels were significantly lower (p < 0.001 and p < 0.001, respectively), in animals given EG/AC compared to negative controls. No significant differences were detected in serum calcium, phosphorous, urea, or creatinine levels between animals treated with boron and positive controls (p > 0.05). Serum PON1 activity was significantly lower in animals given EG/AC than in negative controls (p < 0.001), while no significant difference in serum PON1 level was detected between rats treated with boron and positive controls. No significant differences were detected in vitamin D, TAS, TOS, tissue calcium, or tissue oxalate levels among groups. No stone formation was detected on histopathological examination in negative controls. No significant differences were found in stone formation between rats treated with boron and positive controls. Based on this study, high doses of boron had no protective effect against nephrolithiasis and oxidative stress.

A comprehensive simulation study on classification of RNA-Seq data.

RNA sequencing (RNA-Seq) is a powerful technique for the gene-expression profiling of organisms that uses the capabilities of next-generation sequencing technologies. Developing gene-expression-based classification algorithms is an emerging powerful method for diagnosis, disease classification and monitoring at molecular level, as well as providing potential markers of diseases. Most of the statistical methods proposed for the classification of gene-expression data are either based on a continuous scale (eg. microarray data) or require a normal distribution assumption. Hence, these methods cannot be directly applied to RNA-Seq data since they violate both data structure and distributional assumptions. However, it is possible to apply these algorithms with appropriate modifications to RNA-Seq data. One way is to develop count-based classifiers, such as Poisson linear discriminant analysis and negative binomial linear discriminant analysis. Another way is to bring the data closer to microarrays and apply microarray-based classifiers. In this study, we compared several classifiers including PLDA with and without power transformation, NBLDA, single SVM, bagging SVM (bagSVM), classification and regression trees (CART), and random forests (RF). We also examined the effect of several parameters such as overdispersion, sample size, number of genes, number of classes, differential-expression rate, and the transformation method on model performances. A comprehensive simulation study is conducted and the results are compared with the results of two miRNA and two mRNA experimental datasets. The results revealed that increasing the sample size, differential-expression rate and decreasing the dispersion parameter and number of groups lead to an increase in classification accuracy. Similar with differential-expression studies, the classification of RNA-Seq data requires careful attention when handling data overdispersion. We conclude that, as a count-based classifier, the power transformed PLDA and, as a microarray-based classifier, vst or rlog transformed RF and SVM classifiers may be a good choice for classification. An R/BIOCONDUCTOR package, MLSeq, is freely available at https://www.bioconductor.org/packages/release/bioc/html/MLSeq.html.