SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Antibacterial and Cytotoxic Potential of Biosynthesized Silver Nanoparticles by Some Plant Extracts

The provision of nanoparticles using biogenic material as a part of green chemistry is an attractive nanotechnology. The current research aimed to test the antimicrobial and cytotoxic efficacy of silver nanoparticles synthesized by extracts of Phoenix dactylifera, Ferula asafetida, and Acacia nilotica as reductant and stabilizing agents in silver nanoparticle formation. Synthesized nanoparticles were evaluated for their antimicrobial activity against Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa and Escherichia coli (Gram-negative) using an agar well diffusion assay. Furthermore, cytotoxic ability was investigated against LoVo cells. The potential phyto-constituents of plant extracts were identified by Fourier-transform infrared spectroscopy (FT-IR) techniques. Field emission scanning electron microscopy (FE-SEM), transmission electron microscope (TEM), and zeta potential analyzed the size and morphology of the biogenic nanoparticles. The current study revealed the ability of the tested plant extract to convert silver ions to silver nanoparticles with an average size that ranged between 67.8 ± 0.3 and 155.7 ± 1.5 nm in diameter. Biogenic AgNPs showed significant antibacterial ability (10 to 32 mm diameter) and anticancer ability against a LoVo cell with IC50 ranged between 35.15–56.73 μg/mL. The innovation of the present study is that the green synthesis of NPs, which is simple and cost effective, provides stable nano-materials and can be an alternative for the large-scale synthesis of silver nanoparticles

Bayesian and non-Bayesian estimations of truncated inverse power Lindley distribution under progressively type-II censored data with applications

In this article, we introduce and study the truncated inverse power Lindley distribution. The aim is to transpose the remarkable flexibility of the two-parameter inverse power Lindley distribution to the interval [0,1]. The corresponding probability density function has the potential to be unimodal, decreasing, right-skewed, and heavy-tailed. On the other hand, the hazard rate function can be increasing, N-shaped, or U-shaped. These shapes’ versatility enables accurate representation and analysis of proportional or percentage data across a wide range of applications, such as survival analysis, reliability, and uncertainty modeling. Several statistical features, such as the mode, quantiles, Bowley’s skewness, Moor’s kurtosis, MacGillivray’s skewness, moments, inverse moments, incomplete moments, and probability-weighted moments, are computed. In practice, for the estimation of the model parameters from truncated data under the progressively type-II censoring scheme, the maximum likelihood, maximum product spacing, and Bayesian approaches are used. The Tierney–Kadane approximation and Markov chain Monte Carlo techniques are employed to produce the Bayesian estimates under the squared error loss function. We present some simulation results to evaluate these approaches. Four applications based on real-world datasets—one of them is on times of infection, the second is on failure times, and the other two are on the rate of inflation in Asia and Africa—explain the significance of the new truncated model in comparison to some reputed comparable models, such as the inverse power Lindley, Kumaraswamy, truncated power Lomax, beta, truncated Weibull, unit-Weibull, Kumaraswamy Kumaraswamy, and exponentiated Kumaraswamy models

Factors influencing knowledge and practice of self-medication among college students of health and non-health professions

Background and objectives: Self-medication is commonly practiced throughout the world. The aim of this study was to ascertain the use prevalence and knowledge of harmful effects of self-medication among college students of health professions and non-health professions. Methods: A cross-sectional study was performed among 1,167 students from 12 faculties of a public university and two private universities in Kuwait. Data were collected using a self-administered pretested questionnaire containing 32 questions. Results: Among the participants, 70.4% (822/1,167) used self-medication. The prevalence of self-medication was significantly higher among students of non-health professions compared with those of health professions (35.9% vs. 25.9%, p = 0.004, 95% CI, 6.28% to 13.73%, respectively). Pain killer medicines (52.9%), vitamins/minerals (13.1%), and antihistamines (9.0%) were the most commonly used non-prescription medications. Antibiotics and sleeping pills were used without a prescription in 2.9% and 2.1%, respectively. Older age, non-Kuwaiti national, and students of 5th to 7th year of study were significant predictors of self-medication. Knowledge scores of harmful effects of self-medication were about two-fold higher among females than their male counterparts. Similarly, students of higher years of study (5th to 7th year) had higher knowledge score compared with others. Conclusions: The prevalence of self-medication was alarmingly high among young adults in Kuwait. People should be informed about adverse effects of self-medication through mass and social media campaign. IMC J Med Sci 2018; 12(2): 57-68. EPub date: 19 June 2018 Address for Correspondence: Prof. Amal K. Mitra, Professor of Epidemiology, Department of Epidemiology and Biostatistics, Jackson State University, 350 W. Woodrow Wilson Dr., PO Box 17038, Jackson, MS 39213, E-mail: [email protected]

Inverse power Ramos–Louzada distribution with various classical estimation methods and modeling to engineering data

This work uses the inverse-power transformation to create the inverse power Ramos–Louzada distribution (IPRLD), a novel two-parameter version of the Ramos–Louzada distribution. The failure rate of the new distribution can be represented by a reverse bathtub shape, a rising shape, or a decreasing shape, making it appropriate for a range of real data. Asymmetrical and unimodal densities can be produced via the IPRLD. Its mathematical characteristics are computed in some cases. The novel proposed model’s structural characteristics are derived. To estimate the model parameters, several estimating strategies are explored, including ten classical methods. Simulation results with their partial and total ranks are used to evaluate the ranking and behavior of various approaches. Finally, two real-world datasets are used to experimentally show the suggested distribution’s adaptability. The analysis of the data reveals that the introduced distribution offers a better fit than some significant rival distributions, including the inverse Ramos–Louzada, inverse power Burr Hatke, inverse Nakagami-M, inverse log-logistic, inverse weighted Lindley, inverse Lindley, and Ramos–Louzada

Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia

Objectives: To report the experience with Middle East respiratory syndrome coronavirus (MERS-CoV) infection at a single center in Saudi Arabia. Methods: Cases of laboratory-confirmed MERS-CoV occurring from October 1, 2012 to May 31, 2014 were reviewed retrospectively. Information sources included medical files, infection control outbreak investigations, and the preventive medicine database of MERS-CoV-infected patients. Data were collected on clinical and epidemiological aspects and outcomes. Results: Seventy consecutive patients were included. Patients were mostly of older age (median 62 years), male (46, 65.7%), and had healthcare acquisition of infection (39, 55.7%). Fever (43, 61.4%), dyspnea (42, 60%), and cough (38, 54.3%) were the most common symptoms. The majority developed pneumonia (63, 90%) and required intensive care (49, 70%). Infection commonly occurred in clusters. Independent risk factors for severe infection requiring intensive care included concomitant infections (odds ratio (OR) 14.13, 95% confidence interval (CI) 1.58–126.09; p = 0.018) and low albumin (OR 6.31, 95% CI 1.24–31.90; p = 0.026). Mortality was high (42, 60%), and age ≥65 years was associated with increased mortality (OR 4.39, 95% CI 2.13–9.05; p < 0.001). Conclusions: MERS-CoV can cause severe infection requiring intensive care and has a high mortality. Concomitant infections and low albumin were found to be predictors of severe infection, while age ≥65 years was the only predictor of increased mortality

Biallelic ZNFX1 variants are associated with a spectrum of immuno-hematological abnormalities

Biallelic changes in the ZNFX1 gene have been recently reported to cause severe familial immunodeficiency. Through a search of our bio/databank with information from genetic testing of >55 000 individuals, we identified nine additional patients from seven families with six novel homozygous ZNFX1 variants. Consistent with the previously described phenotype, our patients suffered from monocytosis, thrombocytopenia, hepatosplenomegaly, recurrent infections, and lymphadenopathy. The two most severely affected probands also had renal involvement and clinical presentations compatible with hemophagocytic lymphohistiocytosis. The disease was less lethal among our patients than previously reported. We identified two missense changes, two variants predicted to result in complete protein loss through nonsense-mediated decay, and two frameshift changes that likely introduce a truncation. Our findings (i) independently confirm the role of ZNFX1 in primary genetic immunodeficiency, (ii) expand the genetic and clinical spectrum of ZNFX1-related disease, and (iii) illustrate the utility of large, well-curated, and continually updated genotype–phenotype databases in resolving molecular diagnoses of patients with initially negative genetic testing findings

Accelerating Novel Candidate Gene Discovery in Neurogenetic Disorders via Whole-Exome Sequencing of Prescreened Multiplex Consanguineous Families

Our knowledge of disease genes in neurological disorders is incomplete. With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known disease genes had been excluded by autozygosity mapping and candidate gene analysis. This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described (SPDL1, TUBA3E, INO80, NID1, TSEN15, DMBX1, CLHC1, C12orf4, WDR93, ST7, MATN4, SEC24D, PCDHB4, PTPN23, TAF6, TBCK, FAM177A1, KIAA1109, MTSS1L, XIRP1, KCTD3, CHAF1B, ARV1, ISCA2, PTRH2, GEMIN4, MYOCD, PDPR, DPH1, NUP107, TMEM92, EPB41L4A, and FAM120AOS). We also encountered instances in which the phenotype departed significantly from the established clinical presentation of a known disease gene. Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function

List of participating sites and ethics committee approvals.

(PDF)</p