Genetic Warfarin-Resistance Resulting in Surgery to Change a Prosthetic Valve

Warfarin is a readily available anticoagulant used worldwide in a variety of clinical scenarios. Patients who need more than 15 mg/day are considered to be warfarin resistant. Numerous genes have been implicated in warfarin pharmacogenetics, with genes encoding CYP2C9 and VKORC1 shown to be the most important determinants of drug dosage requirements. A 27-year-old woman was admitted as she had a sub-therapeutic international normalized ratio (INR) after prosthetic mitral valve replacement. Even after a warfarin dose of 50 mg/day, her INR was not in the therapeutic range, so the heart team decided to replace her metallic valve with a bioprosthetic valve, thus alleviating the need for anticoagulation

Thyroid function analysis in COVID-19: A retrospective study from a single center.

Background and objectiveCoronavirus disease 2019 (COVID-19) is an on-going epidemic with a multitude of long-ranging effects on the physiological balance of the human body. It can cause several effects on thyroid functions as well. We aimed to assess the lasting sequelae of COVID-19 on thyroid hormone and the clinical course of the disease as a result.MethodsOut of 76 patients, 48 patients of COVID-19 positive and 28 patients of COVID-19 negative polymerase chain reaction (PCR) were assessed for thyroid functions, IL-6, and Procalcitonin between moderate, severe, and critical pneumonia on HRCT.ResultsSeventy-five percent of patients with COVID-19 had thyroid abnormalities and higher IL-6 levels (76.10 ± 82.35 vs. 6.99 ± 3.99, 95% CI 52.18-100.01, P-value ConclusionThis pilot study from Pakistan demonstrates that changes in serum TSH and TT3 levels may be important manifestations of the courses of COVID-19 pneumonia

Reasons for Lack of Research In Dentistry; A Cross Sectional Survey on Dentists and Students in Teaching Hospitals of Pakistan: Lack of research in dentistry

OBJECTIVES: The purpose of this study was to determine the barriers or factors preventing dentists from engaging in research in teaching institutes of Pakistan. METHODOLOGY: The descriptive, cross sectional online survey was conducted at the department of Prosthodontics, Rehman College of Dentistry, Peshawar over a period of six months. Sample size of 780 was taken in the descriptive study and questionnaires were communicated through emails and the response was noted. The data was analyzed using the IBM SPSS statistic version 20. Statistical analysis was done using counts and percentages and the results were further analyzed statistically by the Chi square test. RESULTS: Completed surveys were collected from 280 participants. Completed surveys were collected from 780 dentists, 40.7% were male and 59.3% were female. Participants’ age ranged between 20-50 years; about half of them (55%) were younger than 30 years of age. Other demographic characteristics of the participants such as designation, work experience, and qualification given in Table 1 were also recorded. Majority of the participants were dentists (35%), followed by senior registrar (10%) and assistant (10.7%), associate (and professors (4.3%). Details are depicted in Table 1. Overall, 47.9% participants were found to be involved in research and having publications. Simple graduates were more in number as compared to postgraduates. When inquired about publication published in an indexed journal or not 22.1% responded with yes and 46.4% responded with No. 65% participants had received workshops for writing papers and only 34.3% institute conducted continuous training programs. The main reason reported for lack of research was lack of motivation and don’t know how to do it. Other less common factors were lack of funds and no professional benefits as depicted in Table 2. CONCLUSION: Identifying and minimizing all the barriers in the way of research may help dental authorities to intervene for enhancing research friendly environments

Evaluation of antimicrobial efficacy of 1% phytic acid incorporated with 0.2% chitosan nanoparticles against Enterococcus faecalis: An in vitro study

Aim: The aim of the study was to evaluate the antimicrobial activity of 1% phytic acid and ethylenediaminetetraacetic acid (EDTA) incorporated with 0.2% of chitosan nanoparticles (Csnps) against Enterococcus faecalis (E. faecalis) by agar diffusion and biofilm model. Materials and Methods: Antimicrobial efficacy was evaluated in two stages: (i) agar well-diffusion method and (ii) biofilm model. E faecalis (American Type Culture Collection 29212) strain was subcultured and grown on the blood agar plates, followed by placement of test solutions in punched holes (5 mm diameter) and incubated for 24 h at 37°C as follows (n = 10): Group 1: normal saline (control), Group 2: EDTA, Group 3: EDTA +0.2% Csnps, Group 4: 1% phytic acid, and Group 5: 1% phytic acid + 0.2% Csnps followed by measurement of inhibition zone. For biofilm model, standardized dentin blocks were prepared from fifty human-extracted single-rooted premolars and sterilized and contaminated for 2 weeks by transferring 50 μl of bacterial inoculum to sterilized test tubes containing 1 mL of Mueller–Hinton agar broth (MHA) with alternate day replenishment of the broth. The specimens were cleaned and subjected to test solutions as mentioned above. Serial decimal dilutions were prepared, followed by inoculation on MHA plates and incubation for 24 h, accompanied by counting of the colonies per milliliter (colony-forming unit per milliliter). Results were statistically analyzed using one-way analysis of variance and Post hoc Tukey's tests (P < 0.05). Results: Phytic acid incorporated with Csnps exhibited a greater zone of inhibition and least colony count against E. faecalis biofilm compared to all groups. Conclusion: Combination of Csnps and phytic acid exhibits effective antimicrobial activity against E. faecalis

A comprehensive review of security threats and solutions for the online social networks industry

The term “cyber threats” refers to the new category of hazards that have emerged with the rapid development and widespread use of computing technologies, as well as our growing reliance on them. This article presents an in-depth study of a variety of security and privacy threats directed at different types of users of social media sites. Furthermore, it focuses on different risks while sharing multimedia content across social networking platforms, and discusses relevant prevention measures and techniques. It also shares methods, tools, and mechanisms for safer usage of online social media platforms, which have been categorized based on their providers including commercial, open source, and academic solutions

Computational modeling and functional characterization of a GgChi: A class III chitinase from corms of Gladiolus grandiflorus

The present study describes the predicted model and functional characterization of an endochitinase (30 kDa) from corms of Gladiolus grandiflorus. ESI-QTOF-MS generated peptide showed 96% sequence homology with family 18, Class III acidic endochitinase of Gladiolus gandavensis. Purified G. grandiflorus chitinase (GgChi) hydrolyzed 4-methylumbelliferyl b-DN, N0,N00-triacetylchitotriose substrate showing specific endochitinase activity. Since no structural details of GgChi were available in the Protein Data Bank (PDB), a homology model was predicted using the coordinate information of Crocus vernus chitinase (PDB ID: 3SIM). Ramachandran plot indicated 84.5% in most favored region, 14.8% in additional and 0.6% in generously allowed region while no residue in disallowed region. The predicted structure indicated a highly conserved (b/a)8 (TIM barrel) structure similar to the family 18, class III chitinases. The GgChi also showed sequence and structural homologies with other active chitinases. The GgChi (50 mg/disc) showed no antibacterial activity, but did provide mild growth inhibition of phytopathogenic fungus Fusarium oxysporum at a concentration of 500 mg/well Similarly, insect toxicity bioassays of GgChi (50 mg) against nymphs of Bemisia tabaci showed 14% reduction in adult emergence and 14% increase in mortality rate in comparison to control values. The GgChi (1.5 mg) protein showed significant reduction in a population of flour beetle (Tribolium castaneum) after 35 days, but lower reactivity against rice weevil (Sitophilus oryzae). The results of this study provide detai.led insight on functional characterization of a family 18 class III acidic plant endochitinase

Association of ABO blood group with COVID-19 severity, acute phase reactants and mortality.

IntroductionCoronavirus disease 2019 (COVID-19) is the ongoing pandemic with multitude of manifestations and association of ABO blood group in South-East Asian population needs to be explored.MethodsIt was a retrospective study of patients with COVID-19. Blood group A, B, O, and AB were identified in every participant, irrespective of their RH type and allotted groups 1, 2,3, and 4, respectively. Correlation between blood group and lab parameters was presented as histogram distributed among the four groups. Multivariate regression and logistic regression were used for inferential statistics.ResultsThe cohort included 1067 patients: 521 (48.8%) participants had blood group O as the prevalent blood type. Overall, 10.6% COVID-19-related mortality was observed at our center. Mortality was 13.9% in blood group A, 9.5% in group B, 10% in group C, and 10.2% in AB blood group (p = 0.412). IL-6 was elevated in blood group A (median [IQR]: 23.6 [17.5,43.8]), Procalcitonin in blood group B (median [IQR]: 0.54 [0.3,0.7]), D-dimers and CRP in group AB (median [IQR]: 21.5 [9,34]; 24 [9,49], respectively). Regarding severity of COVID-19 disease, no statistical difference was seen between the blood groups. Alteration of the acute phase reactants was not positively associated with any specific blood type.ConclusionIn conclusion, this investigation did not show significant association of blood groups with severity and of COVID-19 disease and COVID-19-associated mortality

Biallelic loss-of-function variants of ZFTRAF1 cause neurodevelopmental disorder with microcephaly and hypotonia

Purpose: Neurodevelopmental disorders exhibit clinical and genetic heterogeneity, ergo manifest dysfunction in components of diverse cellular pathways; the precise pathomechanism for the majority remains elusive.Methods: We studied five affected individuals from three unrelated families manifesting global developmental delay, postnatal microcephaly, and hypotonia. We employed exome sequencing and prioritized variants that were subsequently characterized using immunofluorescence, immunoblotting, pulldown assays, and RNA sequencing.Results: We identified biallelic variants in ZFTRAF1, encoding a protein of yet unknown function. Four affected individuals from two unrelated families segregated two homozygous frameshift variants in ZFTRAF1, whereas, in the third family, an intronic splice site variant was detected. We investigated ZFTRAF1 at the cellular level and signified it as a nucleocytoplasmic protein in different human cell lines. ZFTRAF1 was completely absent in the fibroblasts of two affected individuals. We also identified 110 interacting proteins enriched in mRNA processing and autophagy-related pathways. Based on profiling of autophagy markers, patient-derived fibroblasts show irregularities in the protein degradation process.Conclusion: Thus, our findings suggest that biallelic variants of ZFTRAF1 cause a severe neurodevelopmental disorder

Whole exome sequencing identifies variable expressivity of CLN6 variants in Progressive myoclonic epilepsy affected families

Progressive myoclonic epilepsies (PMEs) are a group of neurodegenerative disorders, predominantly affecting adolescents and, characterized by generalized worsening myoclonus epilepsies, ataxia, cognitive deficits, and dementia. To date, several genes, having implications in diverse phenotypic expressions associated with PMEs, have been identified. Genetic diagnosis is available for most of the adolescence-onset myoclonic epilepsies. This study aimed to elucidate the genetic basis of PMEs in three multiplex Pakistani families exhibiting clinically variable phenotypes. Causative variant(s) in the studied families, and mode of segregation were identified by Whole Exome Sequencing (WES) of the probands, followed by bi-directional Sanger sequencing for final validation. We identified homozygous recessive CLN6 missense variant c.768 C>G (p.Asp256Glu) in Family 1, and c.889 C>A (p.Pro297Thr) variant in Family 2. While in Family 3, we found a homozygous variant (c.316dup) that caused a frameshift mutation, leading to a premature stop codon in the CLN6 protein, resulting in a truncated protein (p.Arg106ProfsTer26). Though CLN6 is previously identified to underlie late infantile and adolescent onset neuronal ceroid lipofuscinosis, this study supports and expands the phenotypic spectrum of CLN6 mutations and signifies diagnositc potential CLN6 variants for PMEs. Diverse pathological effects of variant c .768 C>G were observed in Family 1, with same genotypes, suggesting clinical heterogeneity and/or variable expressivity that might be the implication of pleiotropic effects of the gene in these cases

Multi-element uptake and growth responses of Rice (Oryza sativa L.) to TiO2 nanoparticles applied in different textured soils

The aim of present work was to evaluate the effects of titanium dioxide nanoparticles (TiO2 NPs) on rice’s growth (Oryza sativa L.) and nutrient availability under different soil textures. Greenhouse experiment was carried out with three soil textures (sandy loam, silt loam and silty clay loam) and two concentrations of TiO2 NPs (500, 750 mg kg−1). Control (without TiO2 NPs) was also maintained for the comparison. Growth parameters including chlorophyll content, root/shoot length, fresh/dry biomass and nutrients’ uptake including calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), phosphorous (P), potassium (K) and zinc (Zn) were determined. The results revealed that application of 500 mg kg−1 TiO2 NPs in silty clay loam soil increased the chlorophyll content (3.3-folds), root length (49%), shoot length (31%), root and shoot biomass (41% &amp; 39%, respectively) as compared to other soil textures. The maximum plant growth was observed in silty clay loam > silt loam > sandy loam. Concentration of Cu, Fe, P and Zn in shoot was increased by 8 − , 2.3 − , 0.4 − , 0.05 −folds in silty clay loam upon 500 mg kg−1 TiO2 NPs application as compared to the control. Backward selection method to model the parameters (nutrients in soil) for the response variables (root/shoot length and biomass) showed that Ca, Fe, P are the main nutrients responsible for the increase in plant length and biomass. Overall, the growth of rice was better in silty clay loam at 500 mg kg−1 of TiO2 NPs