Objective To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the vagina of women diagnosed with coronavirus disease-19 (COVID-19) pneumonia. Study design ...The study was conducted prospectively in a university affiliated hospital. Forty-one women of reproductive age whose nasopharyngeal PCR test were positive for SARS-CoV-2 and clinically diagnosed with pneumonia were included in the study. Vaginal swabs were obtained for SARS-CoV-2 PCR tests when the patients were admitted to the inpatient service before pneumonia treatment was initiated. Results Vaginal swab samples of 38 patients were analysed with SARS-CoV-2 PCR tests. None of the vaginal swabs were positive for SARS-CoV-2. Conclusions SARS-CoV-2 does not infect the vagina of women diagnosed with SARS-CoV-2 pneumonia.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The 3MC syndrome is a rare autosomal recessive syndrome characterized by facial dysmorphism, multiple congenital abnormalities, and postnatal growth deficiency. Hypertelorism, blepharophimosis, ...blepharoptosis, high-arched eyebrows, and cleft lip/palate compose the facial gestalt, which is the key component for diagnosing the syndrome. Biallelic pathogenic variants in MASP1, COLEC11, and COLEC10 are responsible for 3MC syndrome in which both genotypic and phenotypic heterogeneity is described. To date, 16 homozygous/compound heterozygous pathogenic variations in 27 patients from 22 families have been reported in the MASP1 gene associated with 3MC syndrome. Here, we report a male patient with a novel homozygous pathogenic variant in MASP1 in whom macrocephaly, pyloric stenosis, and prenatal findings including polyhydramnios, aortic dilatation, and intracranial cysts beside the distinctive facial features were detected. Reporting detailed clinical and molecular findings in patients is pivotal in terms of enabling the phenotypic and genotypic spectrum of this rare syndrome to be delineated.
Next-generation sequencing (NGS) is used increasingly in hereditary cancer patients' (HCP) management. While enabling evaluation of multiple genes simultaneously, the technology brings to light the ...dilemma of variant interpretation. Here, we aimed to reveal the underlying reasons for the discrepancy in the evidence titles used during variant classification according to ACMG guidelines by two different bioinformatic specialists (BIs) and two different clinical geneticists (CGs). We evaluated final reports of 1920 cancer patients and 189 different variants from 285 HCP were enrolled to the study. A total of 173 of these variants were classified as pathogenic (n = 132) and likely pathogenic (n = 41) by the BI and an additional 16 variants, that were classified as VUS by at least one interpreter and their classification would change the clinical management, were compared for their evidence titles between different specialists. The attributed evidence titles and the final classification of the variants among BIs and CGs were compared. The discrepancy between P/LP final reports was 22.5%. The discordance between CGs was 30% whereas the discordance between two BIs was almost 75%. The use of PVS1, PS3, PP3, PP5, PM1, PM2, BP1, BP4 criteria markedly varied from one expert to another. This difference was particularly noticeable in PP3, PP5, and PM1 evidence and mostly in the variants affecting splice sites like BRCA1(NM_007294.4) c.4096 + 1 G > A and CHEK2(NM_007194.4) c.592 + 3 A > T. With recent advancements in precision medicine, the importance of variant interpretations is emerging. Our study shows that variant interpretation is subjective process that is in need of concrete definitions for accurate and standard interpretation.
Pathogenic variations in the BRCA2 gene have been detected with the development of next-generation sequencing (NGS)-based hereditary cancer panel testing technology. It also reveals an increasing ...number of variants of uncertain significance (VUSs). Well-established functional tests are crucial to accurately reclassifying VUSs for effective diagnosis and treatment. We retrospectively analyzed the multi-gene cancer panel results of 922 individuals and performed in silico analysis following ClinVar classification. Then, we selected five breast cancer-diagnosed patients’ missense BRCA2 VUSs (T1011R, T1104P/M1168K, R2027K, G2044A, and D2819) for reclassification. The effects of VUSs on BRCA2 function were analyzed using comet and H2AX phosphorylation (γH2AX) assays before and after the treatment of peripheral blood mononuclear cells (PBMCs) of subjects with the double-strand break (DSB) agent doxorubicin (Dox). Before and after Dox-induction, the amount of DNA in the comet tails was similar in VUS carriers; however, notable variations in γH2AX were observed, and according to combined computational and functional analyses, we reclassified T1001R as VUS-intermediate, T1104P/M1168K and D2819V as VUS (+), and R2027K and G2044A as likely benign. These findings highlight the importance of the variability of VUSs in response to DNA damage before and after Dox-induction and suggest that further investigation is needed to understand the underlying mechanisms.
Abstract Cardiovascular risk starts early in life, yet the patterns of changes in metabolic syndrome (MS) during puberty and normal development have not been completely defined. Sex hormones are ...shown to play a pivotal role in the modulation of insulin resistance and MS. Our aim is to clarify the relation between sex hormones and MS in normal children and adolescents. This is a cross-sectional study of 365 (8-12 and 14-18 years old) school students. We analyzed the associations of sex hormones (testosterone, free androgen index, estradiol, free estradiol index FEI, and sex hormone–binding globulin SHBG) with cardiovascular risk factors and MS. Prevalence of MS varied depending on the definition, and 33 (9%) students had MS based on at least 1 definition of MS. Frequency of MS doubled among 14- to 18-year–old adolescents compared with 8- to 12-year–old children (12.4% vs 5.6%, P = .02). Adolescent boys and girls with MS had significantly lower SHBG levels compared with controls. Adolescent boys with MS also had significantly higher FEI levels compared with controls. Logistic regression analysis was performed to find the predictors of MS. Among covariates of age, estradiol, testosterone, free androgen index, and FEI, SHBG was the only significant predictor of MS ( B = −0.3, odds ratio = 0.8, 95% confidence interval for odds ratio are 0.64 and 0.92, P = .005, Nagelkarke R2 = 0.48) in adolescent boys. In conclusion, sex hormone levels and androgen/estrogen balance may play an important role in determining MS and future cardiovascular risk among children and adolescents.
Cancer is a multifactorial disorder; however, 5–10% of all cancers show hereditary background. In recent years many targeted next generation sequencing panels comprising cancer predisposition genes ...have been developed and used for diagnostic purposes in patients with increased cancer risk. Screening multiple genes at a time allows multiple variants in different genes to be detected as well. This study aims to determine the cases with concurrent mutations in different hereditary cancer predisposition genes and how they are clinically affected. Here, we screened 1090 index cases by next generation sequencing based hereditary cancer panels and evaluated the reflection of multiple variations on the phenotype. We detected 11 (1%) cases with pathogenic variants in more than one gene. These concurrent variations occurred mostly in BRCA1/2 (7/11) accompanied with MUTYH, ATM, CHECK2, NBN, and RAD50. In addition, MUTYH&ATM, NBN&MSH6, MUTYH&CHEK2 double heterozygous cases were detected. Moreover, we identified a case with three heterozygous variations in CDH1, MUTYH, and CHEK2. These patients presented malignancies that were mostly related to pathogenic variations they carried. Although they are rare, defining double heterozygous cases is important for managing appropriate therapy and accurate genetic consulting for the patients and family members.
Background and AimThe impact of chronic hepatitis B virus (HBV) infection and nucleos(t)ide analogue (NUC) treatment on disease severity and clinical outcomes in patients with coronavirus 2019 ...(COVID-19) is unknown. The objective of this study was to determine whether HBV infection and the use of NUCs impacts mortality in patients with COVID-19. Materials and MethodsA total of 231 adult patients (77 with COVID-19 and HBV coinfection) with a laboratory-confirmed diagnosis of COVID-19 were enrolled in this retrospective study. Univariate and binary logistic regression analysis were performed to evaluate the risk factors for mortality from COVID-19. ResultsPatients with COVID-19 and HBV coinfection had a similar rate of mortality to those without HBV coinfection (7.8% vs 9.7%; p=0.627). Cardiovascular disease (odds ratio OR: 8.22, 95% confidence interval CI: 1.52-44.2; p=0.014) and a high basal aspartate transaminase level (OR: 7.94, 95% CI: 1.81-34.8; p=0.006) were independent predictors of mortality due to COVID-19. In the COVID-19 and HBV coinfection group, the patients who died had a significantly higher median level of HBV DNA than patients who survived (378 IU/mL vs 0 IU/mL; p=0.048). Thirty (39%) patients with HBV coinfection received NUC treatment, and none of these patients died. ConclusionHBV infection was not associated with mortality in patients with COVID-19, and it seems that NUC treatment for HBV infection might have an antiviral effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Cardiovascular risk starts early in life; therefore, it is of interest to clarify the relation between puberty, sex hormones, insulin resistance and lipid levels in children. This is a cross ...sectional study of 365 school students (8-18 years of age). We analyzed the associations of sex hormones (testosterone, free androgen index, estradiol, free estradiol index) and sex hormone-binding globulin (SHBG) with insulin resistance and lipid levels. Analyses were performed in prepubertal versus adolescent girls and boys. Among prepubertal boys, estradiol was significantly associated with increased log homeostasis model assessment-estimated insulin resistance (HOMA-IR; B = 0.9, model R(2) = 0.62, p < 0.001) and insulin levels (B = 0.8, model R(2) = 0.58, p < 0.001). Testosterone was associated with increased high-density lipoprotein cholesterol (HDL-C) levels among prepubertal boys (B = 10, model R(2) = 0.42, p = 0.04). Among adolescent girls, SHBG was significantly associated with decreased HOMA-IR (B = -0.8, model R(2) = 0.34, p = 0.01) and insulin levels (B = -0.7, model R(2) = 0.34, p = 0.01). SHBG was also related to increased HDL-C levels among prepubertal (B = 24, model R(2) = 0.42, p = 0.047) and adolescent girls (B = 21, model R(2) = 0.44, p = 0.002). In conclusion, sex hormone levels and SHBG have important effects on HDL-C and insulin resistance among children and adolescents.
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