Genotype characterization and phylogenetic analysis of hepatitis B virus isolates from Iranian patients

Hepatitis B virus (HBV) is one of the major causative agents of acute and chronic liver disease worldwide and is believed to be responsible for a million deaths annually. Eight genotypes of HBV, A to H, have been described on the basis of similarity of the complete genomes sequence. Although, it is reported that the predominant HBV genotype in the Mediterranean area and the middle east is genotype D, there are no reports on HBV genotypes prevalent in Iran. In this study, the C and S regions of HBV from 26 chronic hepatitis B Iranian patients were amplified and sequenced. Phylogenetic analysis revealed that all Iranian HBV isolates sequences were classified into genotype D with bootstrap values of 100%, 73%, and 100% (1,000 replicates each) for S, C, and preS2 regions, respectively. The mean percent intra-distance of S and C regions were 0.8% and 2.3%, respectively. The mean percent inter-distance of S and C regions between Iranians and genotype D isolates were 1.7% and 3.0%, respectively, and the range of mean percent nucleotide distance of S and C regions between Iranians and the other reference isolates were 7.9%-17.5% and 4.8%-14.7%, respectively. Thirteen out of 23 HBV C region sequences showed nucleotide "A" at position 1896 (precore mutant) in C region. Nucleotide 1858 showed presence of "T" in all isolates. No insertion or deletion was found in both regions. SimPlot and BootScanning analyses did not show any recombination between Iranian isolates and other genotypes in both regions.     

Novel sequence variants in the TMC1 gene in Pakistani families with autosomal recessive hearing impairment

Though many hearing impairment genes have been identified, only a few of these genes have been screened in population studies. For this study, 168 Pakistani families with autosomal recessive hearing impairment not due to mutations in the GJB2 (Cx26) gene underwent a genome scan. Two-point and multipoint parametric linkage analyses were carried out. Twelve families had two-point or multipoint LOD scores of 1.4 or greater within the transmembrane cochlear expressed gene 1 (TMC1) region and were subjected to further screening with direct DNA sequencing. Five novel putatively functional non-synonymous sequence variants, c.830A>G (p.Y277C), c.1114G>A (p.V372M), c.1334G>A (p.R445H), c.2004T>G (p.S668R), and c.2035G>A (p.E679K), were found to segregate within seven families, but were not observed in 234 Pakistani control chromosomes. The variants c.830A>G (p.Y277C), c.1114G>A (p.V372M), and c.1334G>A (p.R445H) occurred at highly conserved regions and were predicted to lie within hydrophobic transmembrane domains, while non-synonymous variants c.2004T>G (p.S668R) and c.2035G>A (p.E679K) occurred in extracellular regions that were not highly conserved. There is evidence that the c.2004T>G (p.S668R) variant may have occurred at a phosphorylation site. One family has the known splice site mutation c.536 -8T>A. The prevalence of non-syndromic hearing impairment due to TMC1 in this Pakistani population is 4.4% (95%CI: 1.9, 8.6%). The TMC1 protein might have an important function in K(+) channels of inner hair cells, which would be consistent with the hypothetical structure of protein domains in which sequence variants were identified.     

Influence of age on iminodipropionitrile-induced vestibular and neurobehavioral toxicities in rats

A direct association between aging and drug-induced dyskinesia has been reported by several investigators. Iminiodipropionitrile (IDPN), a prototype nitrile compound produces a motor syndrome in rodents, which resembles neuroleptic drug induced dyskinesia. In this investigation attempt has been made to study the effect of age on IDPN induced vestibular hair cell degeneration and resulting dyskinetic syndrome. Male Wistar rats aged 3, 6 and 12 weeks received IDPN in the doses of 0, 200 and 400 mg/kg, intraperitoneally for 3 consecutive days. IDPN-induced dyskinesia was assessed using a behavioral testing battery on days 3, 4, 5, 6, 7, 14, 21 and 28. The rats were sacrificed on day 28; temporal bones were excised for vestibular histopathology and sera were collected for measuring the indices of oxidative stress (glutathione and conjugated dienes). IDPN in the dose of 200 mg/kg produced dyskinesia in 12 weeks old rats, but failed to do so in 3 and 6 weeks old rats. The high dose of IDPN (400 mg/kg) caused dyskinesia in all age groups, however, its onset and severity were age-dependent. Older rats showed an early onset and significantly high incidence of dyskinesia as compared to younger rats. The susceptibility of rats to IDPN-induced behavioral deficits was proportional to oxidative stress and degeneration of sensory hair cells in the crista ampullaris.     

Correlation between the number of apoptotic cells and expression of the apoptosis-related antigens Fas, Ley and bcl-2 protein in non-Hodgkin's lymphomas

The relationship between the number of apoptotic cells and the expression of apoptosis-related antigens was examined In 56 cases of non-Hodgkin's lymphomas and in 10 cases of reactive hyperplastic lymph nodes (RHL). Apoptosis was visually quantified by the in situ end-labeling (ISEL) method, and the expression of Fas, Le^y antigens and bcl-2 protein was examined by Immunohistochemistry. The expression of Le^y antigen was observed in germinal centers of RHL and 45% of non-Hodgkin's lymphomas. The apoptotic cell count (AC) in follicular lymphomas was significantly less than that in diffuse lymphomas. The distribution pattern of apoptotic cells In follicular lymphomas was inverse to that in RHL. In follicular lymphomas, AC was lower in follicles than in inter-follicular areas. In contrast, AC was higher in follicles than in Interfollicular areas in RHL. Le^y antigen-positive lymphomas showed a significantly higher AC than the negative cases. The Fas antigen-positive lymphomas showed a higher AC than the negative cases. However, AC in bcl-2 protein-positive and negative cases was not significantly different. These results suggest that Le^y and Fas antigens appear to be involved in the apoptotic tendency of tumor cells in non-Hodgkin's lymphomas, whereas bcl-2 does not necessarily.     

A novel frame shift mutation in the HMG box of the SRY gene in a patient with complete 46,XY pure gonadal dysgenesis.

Pure gonadal dysgenesis or Swyer syndrome is a sex-reversal disorder resulting from embryonic testicular regression sequences especially during the first few weeks of fetal life and is induced by mutations in the SRY gene. In the present report, we describe a nonmosaic XY sex-reversed female with pure gonadal dysgenesis. Molecular analysis using sequential PCR to detect Y chromosomal microdeletions showed the presence of SRY, ZFY and AZFa, b and c regions. Automated sequencing of the SRY region revealed a new mutation (deletion of A (adenine) in codon 82 at position +244), leading to a frame shift mutation within the helix I of the HMG-box domain. This mutation generates a truncated protein and is very likely to produce an impairment of SRY DNA binding activity. The present findings further support the functional importance of the putative DNA binding activity of the SRY HMG-box domain.     

Dietary patterns and health-related quality of life among Iranian adolescents

Quality of Life Research - Examining the associations of a-posteriori-defined dietary patterns and health-related quality of life (HRQOL) among Iranian adolescents. This cross-sectional study was...     

Association of obesity with illness severity in hospitalized patients with COVID-19: A retrospective cohort study

BackgroundAlthough recent studies have shown an association between obesity and adverse coronavirus disease 2019 (COVID-19) patient outcomes, there is a paucity in large studies focusing on hospitalized patients. We aimed to analyze outcomes associated with obesity in a large cohort of hospitalized COVID-19 patients.MethodsWe performed a retrospective study at a tertiary care health system of adult patients with COVID-19 who were admitted between March 1 and April 30, 2020. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m 2) and non-obese (BMI < 30 kg/m 2) cohorts. Primary outcomes were mortality, intensive care unit (ICU) admission, intubation, and 30-day readmission.ResultsA total of 1983 patients were included of whom 1031 (51.9%) had obesity and 952 (48.9%) did not have obesity. Patients with obesity were younger (P < 0.001), more likely to be female (P < 0.001) and African American (P < 0.001) compared to patients without obesity. Multivariable logistic models adjusting for differences in age, sex, race, medical comorbidities, and treatment modalities revealed no difference in 60-day mortality and 30-day readmission between obese and non-obese groups. In these models, patients with obesity had increased odds of ICU admission (adjusted OR, 1.37; 95% CI, 1.07?1.76; P = 0.012) and intubation (adjusted OR, 1.37; 95% CI, 1.04?1.80; P = 0.026).ConclusionsObesity in patients with COVID-19 is independently associated with increased risk for ICU admission and intubation. Recognizing that obesity impacts morbidity in this manner is crucial for appropriate management of COVID-19 patients.     

Does there exist an obesity paradox in COVID-19? Insights of the international HOPE-COVID-19-registry

BackgroundObesity has been described as a protective factor in cardiovascular and other diseases being expressed as ‘obesity paradox’. However, the impact of obesity on clinical outcomes including mortality in COVID-19 has been poorly systematically investigated until now. We aimed to compare clinical outcomes among COVID-19 patients divided into three groups according to the body mass index (BMI).MethodsWe retrospectively collected data up to May 31^st, 2020. 3635 patients were divided into three groups of BMI (<25 kg/m²; n = 1110, 25?30 kg/m²; n = 1464, and >30 kg/m²; n = 1061). Demographic, in-hospital complications, and predictors for mortality, respiratory insufficiency, and sepsis were analyzed.ResultsThe rate of respiratory insufficiency was more recorded in BMI 25?30 kg/m² as compared to BMI < 25 kg/m² (22.8% vs. 41.8%; p < 0.001), and in BMI > 30 kg/m² than BMI < 25 kg/m², respectively (22.8% vs. 35.4%; p < 0.001). Sepsis was more observed in BMI 25?30 kg/m² and BMI > 30 kg/m² as compared to BMI < 25 kg/m², respectively (25.1% vs. 42.5%; p = 0.02) and (25.1% vs. 32.5%; p = 0.006). The mortality rate was higher in BMI 25?30 kg/m² and BMI > 30 kg/m² as compared to BMI < 25 kg/m², respectively (27.2% vs. 39.2%; p = 0.31) (27.2% vs. 33.5%; p = 0.004). In the Cox multivariate analysis for mortality, BMI < 25 kg/m² and BMI > 30 kg/m² did not impact the mortality rate (HR 1.15, 95% CI: 0.889?1.508; p = 0.27) (HR 1.15, 95% CI: 0.893?1.479; p = 0.27). In multivariate logistic regression analyses for respiratory insufficiency and sepsis, BMI < 25 kg/m² is determined as an independent predictor for reduction of respiratory insufficiency (OR 0.73, 95% CI: 0.538?1.004; p = 0.05).ConclusionsHOPE COVID-19-Registry revealed no evidence of obesity paradox in patients with COVID-19. However, Obesity was associated with a higher rate of respiratory insufficiency and sepsis but was not determined as an independent predictor for a high mortality.