Analysis of Nucleotide Variations in Human G-Quadruplex Forming Regions Associated with Disease States.

While the role of G quadruplex (G4) structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify sequence level changes and their effect on the alteration of the G4 secondary structure. A total of 37,515 G4 SNVs in the COSMIC database and 2378 in CLINVAR were identified. Of those, 7236 COSMIC (19.3%) and 457 (19%) of the CLINVAR variants result in G4 loss, while 2728 (COSMIC) and 129 (CLINVAR) SNVs gain a G4 structure. The remaining variants potentially affect the folding energy without affecting the presence of a G4. Analysis of mutational patterns in the G4 structure shows a higher selective pressure (3-fold) in the coding region on the template strand compared to the reverse strand. At the same time, an equal proportion of SNVs were observed among intronic, promoter, and enhancer regions across strands.

Structural and Functional Classification of G-Quadruplex Families within the Human Genome.

G-quadruplexes (G4s) are short secondary DNA structures located throughout genomic DNA and transcribed RNA. Although G4 structures have been shown to form in vivo, no current search tools that examine these structures based on previously identified G-quadruplexes and filter them based on similar sequence, structure, and thermodynamic properties are known to exist. We present a framework for clustering G-quadruplex sequences into families using the CD-HIT, MeShClust, and DNACLUST methods along with a combination of Starcode and BLAST. Utilizing this framework to filter and annotate clusters, 95 families of G-quadruplex sequences were identified within the human genome. Profiles for each family were created using hidden Markov models to allow for the identification of additional family members and generate homology probability scores. The thermodynamic folding energy properties, functional annotation of genes associated with the sequences, scores from different prediction algorithms, and transcription factor binding motifs within a family were used to annotate and compare the diversity within and across clusters. The resulting set of G-quadruplex families can be used to further understand how different regions of the genome are regulated by factors targeting specific structures common to members of a specific cluster.

Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states.

While the role of G4 G quadruplex structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify sequence level changes and their effect on alteration of G4 secondary structure. 37,515 G4 SNVs in the COSMIC database and 2,115 in CLINVAR were identified. Of those, 7,236 COSMIC (19.3%) and 416 (18%) of the CLINVAR variants result in G4 loss, while 2,728 (COSMIC) and 112 (CLINVAR) SNVs gain a G4 structure. The gene ontology term "GnRH (Gonadotropin-releasing hormone) secretion" is enriched in 21 genes in this pathway that have a G4 destabilizing SNV. Analysis of mutational patterns in the G4 structure show a higher selective pressure (3-fold) in the coding region on the template strand compared to the non-template strand. At the same time, an equal proportion of SNVs were observed among intronic, promoter and enhancer regions across strands. Using GO and pathway enrichment, genes with SNVs for G4 forming propensity in the coding region are enriched for Regulation of Ras protein signal transduction and Src homology 3 (SH3) domain binding.

Prevalence of Elevated D-dimer Levels in Confirmed COVID-19 Cases in Intensive Care Unit of a Tertiary Care Centre of Western Nepal.

INTRODUCTION: D-dimer is currently the best available marker for COVID-19 associated hemostatic abnormalities. This study aims to find out the prevelance of elevated D-dimer levels in confirmed COVID-19 cases in intensive care unit of a tertiary care hospital of western Nepal. METHODS: This descriptive cross-sectional study was conducted among 95 patients admitted to COVID Intensive Care Unit of a teriary care centre from August 2020 to January 2021 after taking ethical clearence from Institutional Review Committee in order to determine the D-dimer levels in confirmed COVID-19 cases. D-dimer value was measured at the admission and the highest D-dimer value was recorded during the course of hospital stay with the risk of mortality in confirmed COVID-19 cases. The normal range of D-dimer was taken as <0.35 mg/dl as per our hospital laboratory standards. Convenience sampling method was used. Data entry and descriptive analysis were done in Statistical Package for the Social Sciences version 25.0, point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Out of total 95 cases of COVID-19 included in this study, 25 (89.3%) patients with age ≥ 65 years and 42 (62.69%) patients aged <65 years had elevated D-dimer on admission. Data showed that 29 (67.4%) patients having elevated D-dimer at admission had mortality. CONCLUSIONS: Elevated D-dimer levels was frequently seen in patients admitted in Intensive Care Unit with COVID-19. Our study suggested that measurement of D-dimer may guide in clinical decision making.

Lipid Profile Abnormalities in Newly Diagnosed Primary Hypothyroidism in a Tertiary Care Centre of Western Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: Thyroid hormones have a major influence on synthesis, mobilization and metabolism of lipids. Hypothyroidism accounts for a notable cause of secondary dyslipidemia. This can increase the risk for cardiovascular morbidity and mortality. This study was performed to find out the prevalence of lipid profile abnormalities in newly diagnosed primary hypothyroid states. METHODS: This descriptive cross-sectional study was conducted among 71 patients in the context of newly diagnosed primary hypothyroidism patients visiting outpatient department of internal medicine from 9th December 2018 to 30th June 2020 after taking ethical clearance from Institutional Review Committee. Case screening for lipid profile changes was performed at the time of diagnosis of primary hypothyroidism. A convenience sampling method was used. Data entry and descriptive analysis were done in Statistical Package for the Social Sciences version 16.0. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: In this study including 71 cases of newly diagnosed primary hypothyroidism, 49 (69.0%) (95% Confidence Interval= 58.24-79.76) had abnormal lipid profiles. Among them, 5 (38.5%) out of 13 (18.3%) cases of subclinical hypothyroidism and 44 (75.9%) out of 58 (81.7%) cases of overt hypothyroidism had abnormal lipid profiles. CONCLUSIONS: The prevalence of abnormal lipid profile parameters was similar to the study done in various studies in similar settings except for high-density lipid which showed both similarity and dissimilarity with other studies. Our study suggested that all newly diagnosed cases of primary hypothyroidism are to be investigated for dyslipidemia thus ensuring early treatment and prevention of complications.

Strenuous Exercise-Induced Tremendously Elevated Transaminases Levels in a Healthy Adult: A Diagnostic Dilemma.

The liver function test (LFT) is a commonly performed test in clinical practice in order to assess well-being of the liver; however, derangement in liver enzymes, however, may not necessarily imply an underlying liver pathology. The standard liver function test measures alanine aminotransferase (ALT), aspartate aminotransferase (AST), alanine phosphatase (ALP), bilirubin levels (total, direct, and indirect), proteins (total protein and albumin), and PT-INR (prothrombin time and international normalized ratio). In addition to common causes, liver enzyme levels can also be elevated due to extrahepatic causes, such as muscular injury can elevate transaminases levels. Here in, we present a case of an asymptomatic healthy male who was doing vigorous exercise and presented with reports of elevated transaminase levels. During evaluation of the case, most of his reports came to be within normal range. Additionally, when reevaluated after discontinuation of vigorous exercise, 3 weeks later and then a month later, his liver enzyme levels were observed to be within normal range. Hence, we suspect that muscle damage-induced transaminitis might not have been considered in the differential diagnosis during the evaluation of a patient with raised transaminases levels and also suggest that it should be kept as a differential in the given scenario.

Fever among COVID-19 Patients in a Tertiary Care Hospital of Western Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: COVID-19 has a wide spectrum of clinical presentation ranging from asymptomatic infection to acute respiratory distress syndrome and multi organ dysfunction. Data regarding this is scarce in our setting. This study aims to study the prevalence of fever in confirmed COVID-19 cases in a tertiary care hospital of western Nepal. METHODS: We conducted a descriptive cross-sectional study among patients admitted to COVID-19 wards and intensive care units of a tertiary care hospital. We enrolled patients from August 2020 to January 2021 and the study proposal was approved by the Institutional Review Committee (reference number: 069/20). Convenience sampling method was used. Data entry and descriptive analysis were done in Statistical Package for the Social Sciences version 16.0. Point estimate at 95% Confidence Interval was calculated along with frequency and descriptive statistics. RESULTS: Among 206 cases of COVID-19, the most common symptom was fever 136 (66.1%) (95% Confidence Interval= 58.14.63-74.05). Sixty-seven (49.3%) of those with fever required intensive care units admission whereas 27 (19.9%) of patients with fever had mortality. Most common comorbidities in the patient having fever is Diabetes mellitus 41 (66.1%) followed by hypertension 20 (62.5%). CONCLUSIONS: Fever was the most common presenting complaint with high prevalence as compared to similar studies done in similar settings. We stress the importance of considering the presence of COVID-19 even in the absence of fever as many patients presented without fever.