In silico evaluation of the impact of Omicron variant of concern sublineage BA.4 and BA.5 on the sensitivity of RT‐qPCR assays for SARS‐CoV‐2 detection using whole genome sequencing

alexandrossfakianakis shared this article with you from Inoreader In silico evaluation of the impact of Omicron variant of concern sublineage BA.4 and BA.5 on the sensitivity of RT‐qPCR assays for SARS‐CoV‐2 detection using whole genome sequencing via Journal of Medical Virology ABSTRACT Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VoC) Omicron (B.1.1.529) has rapidly spread around the world, presenting a new threat to global public human health. Due to the large number of mutations accumulated by SARS-CoV-2 Omicron, concerns have emerged over potentially reduced diagnostic accuracy of reverse transcription polymerase chain reaction (RT-qPCR), the gold standard diagnostic test for diagnosing coronavirus disease 2019 (COVID-19). Thus, we aimed to assess the impact of the currently endemic Omicron sublineages BA.4 and BA.5 on the integrity and sensitivity of RT-qPCR assays used for coronavirus disease 2019 (COVID-19) diagnosis via in silico analysis. We employed whole genome sequencing data and evaluated the potential for false negatives or test failure due to mismatches between primers/probes and Omicron VoC viral genome. Methods In silico sensitivity of 12 RT-qPCR tests (containing 30 primers and probe sets) developed for detection of SARS-CoV-2 reported by the World Health Organization (WHO) or available in the literature, was assessed for specifically detecting SARS-CoV-2 Omicron BA.4 and BA.5 sublineages, obtained after removing redundancy from publicly available genomes from National Center for Biotechnology Information (NCBI) and Global Initiative on Sharing Avian Influenza Data (GISAID) databases. Mismatches between amplicon regions of SARS-CoV-2 Omicron VoC and primers and probe sets were evaluated, and clustering analysis of corresponding amplicon sequences was carried out. Results From the 1164 representative SARS-CoV-2 Omicron VoC BA.4 sublineage genomes analyzed, a substitution in the first five nucleotides (C to T) of the amplicon's 3' end were observed in all samples resulting in 0% sensitivity for assays HKUnivRdRp/Hel (mismatch in reverse primer) and CoremCharite N (mismatch in both forward and reverse primers). Due to a mismatch in the forward primer's 5' end (3-nucleotide substitution, GGG to AAC), the sensitivity of ChinaCDC N assay was at 0.69%. The 10 nucleotide mismatches in the reverse primer resulted in 0.09% sensitivity for Omicron sublineage BA.4 for Thai N assay. Of the 1926 BA.5 sublineage genomes, HKUnivRdRp/Hel assay also had 0% sensitivity. A sensitivity of 3.06% was observed for ChinaCDC N assay because of a mismatch in the forward primer's 5' end (3-nucleotide substitution, GGG to AAC). Similarly, due to the 10 nucleotide mismatches in the reverse primer, Thai N assay's sensitivity was low at 0.21% for sublineage BA.5. Further, 8 assays for BA.4 sublineage retained high sensitivity (more than 97%) and 9 assays for BA.5 sublineage retained more than 99% sensitivity. Conclusion We observed four assays (HKUnivRdRp/Hel, ChinaCDC N, Thai N, CoremCharite N) that could potentially result in false negative results for SARS-CoV-2 Omicron VoCs BA.4 and BA.5 sublineages. Interestingl y, CoremCharite N had 0% sensitivity for Omicron Voc BA.4 but 99.53% sensitivity for BA.5. In addition, 66.67% of the assays for BA.4 sublineage and 75% of the assays for BA.5 sublineage retained high sensitivity. Further, amplicon clustering and additional substitutions analysis along with sensitivity analysis could be used for modification and development of RT-qPCR assays for detecting SARS-CoV-2 Omicron VoC sublineages. This article is protected by copyright. All rights reserved. View on Web

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The development of the Standardized Tool for the Assessment of Bruxism (STAB): An international road map

alexandrossfakianakis shared this article with you from Inoreader The development of the Standardized Tool for the Assessment of Bruxism (STAB): An international road map via Journal of Oral Rehabilitation Abstract This paper summarizes the background reasoning and work that led to the selection of the items included in the Standardized Tool for the Assessment of Bruxism (STAB), also introducing the list of items. The instrument is currently being tested for face validity and on-field comprehension. The underlying premise is that the different motor activities included in the bruxism spectrum (e.g., clenching versus grinding, with or without teeth contact) potentially need to be discriminated from each other, based on their purportedly different etiology, comorbidities, and potential consequences. Focus should be on a valid impression of the activities' frequency, intensity, and duration. The methods that can be used for the above purposes can be grouped into strategies that collect information from the patient's history (subject-based), from the clinical assessment performed by an examiner (clinically based), or from the use of instruments to measure certain outcomes (instrumentally based). The three strategies can apply to all aspects of bruxism (i.e., status, comorbid conditions, etiology, and consequences). The STAB will help gathering information on many aspects, factors, and conditions that are currently poorly investigated in the field of bruxism. To this purpose, it is divided into two axes. Axis A includes the self-reported information on bruxism status and potential consequences (subject-based report) together with the clinical (examiner report) and instrumental assessment (technology report). Axis B includes the self-reported information (subject-based report) on factors and conditions that may have an etiological or comorbid role for bruxism. This comprehensive multidimensional assessment system will allow building predictive model for clinical and research purposes. View on Web

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Gestational Hypertensive Disorders and Maternal Breast Cancer Risk

alexandrossfakianakis shared this article with you from Inoreader Gestational Hypertensive Disorders and Maternal Breast Cancer Risk in a Nationwide Cohort of 40,720 Parous Women via Epidemiology - Featured Articles - Featured Articles Background: Preeclampsia and gestational hypertension are hypothesized to be associated with reduced maternal breast cancer risk, but the epidemiologic evidence is inconclusive. Our objective was to examine associations between gestational hypertensive disorders and breast cancer in a nationwide cohort of women with a family history of breast cancer. Methods: Women ages 35–74 years who had a sister previously diagnosed with breast cancer, but had never had breast cancer themselves, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported diagnoses of eclampsia, preeclampsia, or gestational hypertension in each pregnancy. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between history of a gestational hypertensive disorder and incident invasive breast cancer or ductal carcinoma in situ among 40,720 parous women. We used age as the time scale and adjusted for birth cohort, race–ethnicity, and reproductive, socioeconomic, and behavioral factors. We examined effect measure modification by risk factors for gestational hypertensive disease and breast cancer and assessed possible etiologic heterogeneity across tumor characteristics. Results: The prevalence of gestational hypertensive disease was 12%. During follow-up (mean = 10.9 years), 3,198 eligible women self-reported a breast cancer diagnosis. History of a gestational hypertensive disorder was not associated with breast cancer risk (HR = 1.0; 95% CI = 0.90, 1.1). We did not observe clear evidence of effect measure modification or etiologic heterogeneity. Conclusions: History of a gestational hypertensive disorder was not associated with breast cancer risk in a cohort of women with a first-degree family history of breast cancer. View on Web

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Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function

alexandrossfakianakis shared this article with you from Inoreader Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com AbstractThe synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO4) to induce hair cell loss and retraction of nerve terminals, and then allowed animals to recover in dexamethasone for 48  h. Consistent with previous work, we observed significantly more regenerated hair cells in dexamethasone-treated larvae. Importantly, we found that th... View on Web

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