Male infertility is a multifactorial complex disease with highly heterogeneous phenotypic representation and in at least 15% of cases, this condition is related to known genetic disorders, including both chromosomal and single-gene alterations. In about 40% of primary testicular failure, the etiology remains unknown and a portion of them is likely to be caused by not yet identified genetic anomalies. During the last 10 years, the search for 'hidden' genetic factors was largely unsuccessful in identifying recurrent genetic factors with potential clinical application. The armamentarium of diagnostic tests has been implemented only by the screening for Y chromosome-linked gr/gr deletion in those populations for which consistent data with risk estimate are available. On the other hand, it is clearly demonstrated by both single nucleotide polymorphisms and comparative genomic hybridization arrays, that there is a rare variant burden (especially relevant concerning deletions) in men with impaired spermatogenesis. In the era of next generation sequencing (NGS), we expect to expand our diagnostic skills, since mutations in several hundred genes can potentially lead to infertility and each of them is likely responsible for only a small fraction of cases. In this regard, system biology, which allows revealing possible gene interactions and common biological pathways, will provide an informative tool for NGS data interpretation. Although these novel approaches will certainly help in discovering 'hidden' genetic factors, a more comprehensive picture of the etiopathogenesis of idiopathic male infertility will only be achieved by a parallel investigation of the complex world of gene environmental interaction and epigenetics.

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Genetics of male infertility: from research to clinic

Background Laboratory testing is commonly performed in patients with COVID-19. Each of the laboratory parameters has potential value for risk stratification and prediction of COVID-19 outcomes. This systematic review and meta-analysis aimed to evaluate the difference between these parameters in severe and nonsevere disease and to provide the optimal cutoff value for predicting severe disease. Method We performed a systematic literature search through electronic databases. The variables of interest were serum procalcitonin, albumin, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) levels in each group of severity outcomes from COVID-19. Results There were a total of 4848 patients from 23 studies. Our meta-analysis suggest that patients with severe COVID-19 infections have higher procalcitonin, (mean difference 0.07; 95% CI 0.05–0.10; p  Conclusion This meta-analysis suggests elevated procalcitonin, CRP, D-dimer, and LDH and decreased albumin can be used for predicting severe outcomes in COVID-19.

Inflammatory and hematologic markers as predictors of severe outcomes in COVID-19 infection: A systematic review and meta-analysis.

Type 2 diabetes mellitus (T2DM), by definition is a heterogeneous, multifactorial, polygenic syndrome which results from insulin receptor dysfunction. It is an outcome of oxidative stress caused by interactions of reactive metabolites (RMs) interactions with lipids, proteins and other mechanisms of human body. Production of RMs mainly superoxide (O2(-)) has been found in a variety of predominating cellular enzyme systems including NAD(P)H oxidase, xanthine oxidase (XO), cyclooxygenase (COX), uncoupled endothelial nitric oxide synthase (eNOS) and myeloperoxidase (MPO). The four main RM related molecular mechanisms are: increased polyol pathway flux; increased advanced glycation end-product (AGE) formation; activation of protein kinase C (PKC) isoforms and increased hexosamine pathway flux which have been implicated in glucose-mediated vascular damage. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), nitric oxide synthase (NOS) are antioxidant enzymes involved in scavenging RMs in normal individuals. Functional polymorphisms of these antioxidant enzymes have been reported to be involved in pathogenesis of T2DM individuals. The low levels of antioxidant enzymes or their non-functionality results in excessive RMs which initiate stress related pathways thereby leading to insulin resistance and T2DM. An attempt has been made to review the role of RMs and antioxidant enzymes in oxidative stress resulting in T2DM.

Reactive metabolites and antioxidant gene polymorphisms in Type 2 diabetes mellitus

Background Preliminary evidence from the COVID-19 pandemic shows the presence of health disparities, especially in terms of morbidity and mortality. This study aimed to systematically review the evidence on the association of racial/ethnic and socioeconomic status (SES) with health outcomes and access to healthcare services during the COVID-19 pandemic. Methods We retrieved published evidence from late December 2019 through March 1, 2021. The target population was the population of the countries during the COVID-19 pandemic. The exposures were defined as belonging to racial/ethnic minority groups and/or low SES. The primary outcomes of interest include (1) death from COVID-19, (2) COVID-19 incidence/infection, (3) COVID-19 hospitalization, (4) ICU admission, (5) need for mechanical ventilation, (6) confirmed diagnosis, and (7) access to testing. We systematically synthesized the findings from different studies and provided a narrative explanation of the results. Results After removing the duplicate results and screening for relevant titles and abstracts, 77 studies were selected for full-text review. Finally, 52 studies were included in the review. The majority of the studies were from the United States (37 studies). Despite the significant incongruity among the studies, most of them showed that racial/ethnic minority groups had higher risks of COVID-19 infection and hospitalization, confirmed diagnosis, and death. Additionally, most of the studies cited factors such as low level of education, poverty, poor housing conditions, low household income, speaking in a language other than the national language in a country, and living in overcrowded households as risk factors of COVID-19 incidence/infection, death, and confirmed diagnosis. However, findings in terms of the association of lack of health insurance coverage and unemployment with the outcome measures as well as the association of requiring mechanical ventilation, ICU admission, and access to testing for COVID-19 with race/ethnicity were limited and inconsistent. Conclusion It is evident that racial/ethnic minority groups and those from low SES are more vulnerable to COVID-19; therefore, public health policymakers, practitioners, and clinicians should be aware of these inequalities and strive to narrow the gap by focusing on vulnerable populations. This systematic review also revealed a major incongruity in the definition of the racial/ethnic minority groups and SES among the studies. Systematic review registration PROSPERO CRD42020190105.

A systematic review of racial/ethnic and socioeconomic disparities in COVID-19.

In biological systems there is a balance between the production and neutralization of reactive oxygen species (ROS). This balance is maintained by the presence of natural antioxidants and antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase. The enhancement of lipid peroxidation or the decrease of antioxidant protection present in metabolic diseases or bad lifestyle can induce endothelial dysfunction and atherosclerosis. Clinical studies have shown that oxidative stress can increase ROS reducing the formation of antioxidant defences, especially in subjects with coronary artery disease (CAD). Some observation indicated that in the early stages of the disease there is a homeostatic up-regulation of the antioxidant enzyme system in response to increased free radicals to prevent vascular damage. As soon as free radicals get to chronically elevated levels, this compensation ceases. Therefore, SOD and the other enzymes may represent a good therapeutic target against ROS, but they are not useful markers for the diagnosis of CAD. In conclusion antioxidant enzymes are reduced in presence of metabolic disease and CAD. However the existence of genes that promote their enzymatic activity could contribute to create new drugs for the treatment of damage caused by metabolic diseases or lifestyle that increases the plasma ROS levels.

Enzymatic antioxidant system in vascular inflammation and coronary artery disease.

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients.

This is a retrospective single-center study of 417 consecutive patients with coronavirus disease 2019 (COVID-19) admitted to Jaber Al-Ahmad Hospital in Kuwait between February 24, 2020 and May 24, 2020. In total, 39.3% of patients were asymptomatic, 41% were symptomatic with mild/moderate symptoms, 19.7% were admitted to the intensive care unit (ICU). Most common symptoms in cohort patients were fever (34.3%) and dry cough (32.6%) while shortness in breath was reported in (75.6%) of ICU admissions. Reported complications requiring ICU admission included Sepsis (68.3%), acute respiratory distress syndrome (95.1%) and heart failure (63.4%). ICU patients were more likely to have comorbidities, in comparison to non-ICU patients, including diabetes (35.4% vs 20.3%) and hypertension (40.2% vs 26.9%). Mortality rate of cohort was 14.4% and mean age of death was 54.20 years (± 11.09) and 90% of death cases were males. Chest high-resolution computed tomography for ICU cases reveled multifocal large patchy areas of ground glass opacification mixed with dense consolidation. Cases admitted to ICU showed abnormal levels of markers associated with infection, inflammation, abnormal blood clotting, heart problems and kidney problems. Mean hospital stay for asymptomatic cases was 20.69 days ±8.57 and for mild/moderate cases was 21.4 days ±8.28. Mean stay in ICU to outcome for survivors was 11.95 days ±8.96 and for death cases 13.15 days ±10.02. In this single-center case series of 417 hospitalized COVID-19 patients in Kuwait 39.3% were asymptomatic cases, 41% showed mild/moderate symptoms and 18.7% were admitted to ICU with a mortality rate of 14.4%.

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Clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Kuwait.

This is a retrospective single-center study of 417 consecutive patients with coronavirus disease 2019 (COVID-19) admitted to Jaber Al-Ahmad Hospital in Kuwait between February 24, 2020 and May 24, 2020. In total, 39.3% of patients were asymptomatic, 41% were symptomatic with mild/moderate symptoms, 5.3% were admitted to the intensive care unit (ICU) and recovered, and 14.4% died. The mean age of death cases was 54.20 years (± 11.09). Comorbidities were more prevalent in patients who died compared with others. Key findings include abnormal levels of markers assicated with infection, inflammation, abnormal blood clotting, heart problems and kidney problems in patients with severe form of the disease and poor putcome. We report a rapidly deteriorating estimated glomerular filtration rate (eGFR) in deaths during ICU stay with kidney injury complications reported in 65% of deaths (p

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Clinical characteristics of Coronavirus Disease 2019 (COVID-19) patients in Kuwait

Association of CYP1A1 gene variants rs4646903 (T>C) and rs1048943 (A>G) with cervical cancer in a North Indian population.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.27076

Mohammad Abbas

Papers

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients.

Clinical characteristics of coronavirus disease 2019 (COVID-19) patients in Kuwait.

Clinical characteristics of Coronavirus Disease 2019 (COVID-19) patients in Kuwait

Association of CYP1A1 gene variants rs4646903 (T>C) and rs1048943 (A>G) with cervical cancer in a North Indian population.

Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome.