Genetic Basis of Nonsyndromic Sensorineural Hearing Loss in the Sub-Saharan African Island Population of São Tomé and Príncipe: The Role of the DFNB1 Locus?

Hearing loss (HL) is a common condition with both genetic and environmental causes, and it greatly impacts global health. The prevalence of HL is reportedly higher in developing countries such as the Sub-Saharan African island of São Tomé and Príncipe, where the deaf community is estimated to be less than 1% of the population. We investigated the role of the DFNB1 locus (GJB2 and GJB6 genes) in the etiology of nonsyndromic sensorineural hearing loss (NSSHL) in São Tomé and Príncipe. A sample of 316 individuals, comprising 136 NSSHL patients (92 bilateral, 44 unilateral) and 180 controls, underwent a clinical and audiological examination. Sequencing of the GJB2 coding region and testing for the (GJB6-D13S1830) and del(GJB6-D13S1854) GJB6 deletions were performed. A total of 311 out of 316 individuals were successfully analyzed regarding the GJB2 and GJB6 genetic variations, respectively. The frequency of the GJB2 coding mutations in patients and controls was low. Some of those coding mutations are the most commonly found in Eurasian and Mediterranean populations and have also been identified in Portugal. None of the GJB6 deletions was present. The presence of certain coding variants in São Tomé and Príncipe suggests a non-Sub-Saharan genetic influx and supports the previously reported genetic influx from European (mainly Portuguese) ancestors. In summary, DFNB1 locus does not appear to be a major contributor to NSSHL in São Tomé and Príncipe. However, the presence of both pathogenic and likely pathogenic mutations in GJB2 suggests that GJB2-related NSSHL might still occur in this population, warranting further research on GJB2 testing in NSSHL cases

Global trends and correlates of covid-19 vaccination hesitancy: Findings from the icare study

The success of large-scale COVID-19 vaccination campaigns is contingent upon people being willing to receive the vaccine. Our study explored COVID-19 vaccine hesitancy and its correlates in eight different countries around the globe. We analyzed convenience sample data collected between March 2020 and January 2021 as part of the iCARE cross-sectional study. Univariate and multivariate statistical analyses were conducted to explore the correlates of vaccine hesitancy. We included 32,028 participants from eight countries, and observed that 27% of the participants exhibited vaccine hesitancy, with increases over time. France reported the highest level of hesitancy (47.3%) and Brazil reported the lowest (9.6%). Women, younger individuals (≤29 years), people living in rural areas, and those with a lower perceived income were more likely to be hesitant. People who previously received an influenza vaccine were 70% less likely to report COVID-19 vaccine hesitancy. We observed that people reporting greater COVID-19 health concerns were less likely to be hesitant, whereas people with higher personal financial concerns were more likely to be hesitant. Our findings indicate that there is substantial vaccine hesitancy in several countries, with cross-national differences in the magnitude and direction of the trend. Vaccination communication initiatives should target hesitant individuals (women, younger adults, people with lower incomes and those living in rural areas), and should highlight the immediate health, social and economic benefits of vaccination across these settings. Country-level analyses are warranted to understand the complex psychological, socio-environmental, and cultural factors associated with vaccine hesitancy

aeGEPUCI: a database of gene expression in the dengue vector mosquito, Aedes aegypti

<p>Abstract</p> <p>Background</p> <p><it>Aedes aegypti </it>is the principal vector of dengue and yellow fever viruses. The availability of the sequenced and annotated genome enables genome-wide analyses of gene expression in this mosquito. The large amount of data resulting from these analyses requires efficient cataloguing before it becomes useful as the basis for new insights into gene expression patterns and studies of the underlying molecular mechanisms for generating these patterns.</p> <p>Findings</p> <p>We provide a publicly-accessible database and data-mining tool, aeGEPUCI, that integrates 1) microarray analyses of sex- and stage-specific gene expression in <it>Ae. aegypti</it>, 2) functional gene annotation, 3) genomic sequence data, and 4) computational sequence analysis tools. The database can be used to identify genes expressed in particular stages and patterns of interest, and to analyze putative <it>cis</it>-regulatory elements (CREs) that may play a role in coordinating these patterns. The database is accessible from the address <url>http://www.aegep.bio.uci.edu</url>.</p> <p>Conclusions</p> <p>The combination of gene expression, function and sequence data coupled with integrated sequence analysis tools allows for identification of expression patterns and streamlines the development of CRE predictions and experiments to assess how patterns of expression are coordinated at the molecular level.</p

Binary orbits as the driver of γ-ray emission and mass ejection in classical novae

Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems. Novae typically expel �10,000 solar masses of material at velocities exceeding 1,000 km/s. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of the thermonuclear runaway, prolonged optically thick winds, or binary interaction with the nova envelope. Classical novae are now routinely detected in GeV gamma-rays, suggesting that relativistic particles are accelerated by strong shocks in nova ejecta. Here we present high-resolution imaging of the gamma-ray-emitting nova V959 Mon at radio wavelengths, showing that its ejecta were shaped by binary motion: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion. At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of gamma-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae, explaining why many novae are gamma-ray emitters

Outcomes of meningococcal serogroup B disease in children after implementation of routine infant 4CMenB vaccination in England: an active, prospective, national surveillance study.

BACKGROUND: In 2015, the UK included 4CMenB, a multi-component, recombinant protein-based vaccine against meningococcal serogroup B (MenB) disease, in the national infant immunisation programme. We aimed to assess the effect of 4CMenB vaccination on the severity of MenB disease presentation and outcomes. METHODS: In this active, prospective, national surveillance study, we used data from the UK Health Security Agency national surveillance of meningococcal disease. We included data from follow-up of children younger than 5 years with laboratory-confirmed MenB disease who were eligible for 4CMenB vaccination with general practice 3-6 months after disease onset. All invasive MenB isolates were tested using the Meningococcal Antigen Typing System to determine whether the isolate was potentially preventable by 4CMenB. Admission to intensive care, death, and, when possible, reported sequelae in survivors were reviewed alongside vaccine status. For the epidemiological analysis, we compared laboratory-confirmed MenB disease cases before 4CMenB implementation (Sept 1, 2010, to March 31, 2015) with those after implementation (Sept 1, 2015, to March 31, 2020). For clinical follow-up and outcomes, we included all children younger than 5 years with laboratory-confirmed MenB disease between Sept 1, 2015, and March 31, 2021. FINDINGS: Between Sept 1, 2015, and March 31, 2021, there were 371 cases of MenB disease in children younger than 5 years, including 256 (69%) in those younger than 1 year and 128 (35%) in those younger than 3 months. After the introduction of 4CMenB, the peak age of patients with MenB disease shifted from 5-6 months to 1-3 months. Overall, 108 (29%) of 371 children were too young for vaccination, unvaccinated, or developed MenB disease within 14 days of the first dose. Of 110 meningococcal strains characterised, 11 (92%) of 12 were potentially preventable by 4CMenB in unvaccinated children compared with 53 (66%) of 80 in partly vaccinated and 11 (69%) of 16 in fully vaccinated children. 78 (21%) of 371 children required intensive care, and the case fatality ratio was 5% (17 of 371), with 11 of 17 deaths occurring before 1 year of age, including seven in infants who were too young (<8 weeks) for vaccination. Of 354 survivors, 57 (16%) had 74 sequelae reported; 45 (61%) of 74 were neurological, 17 (23%) were physical, two (3%) were behavioural or psychological, and ten (14%) were other complications. Prevalence of sequelae was similar in unvaccinated (15 [15%] of 98) and vaccinated (42 [16%] 256) children, as were composite outcomes of death or sequelae, and intensive care or death or sequelae. INTERPRETATION: Cases of MenB disease in vaccine-eligible children declined after 4CMenB implementation, but morbidity in vaccinated and unvaccinated children remained unchanged, highlighting the importance of vaccination to prevent MenB disease. The lower peak age of infants with MenB disease after 4CMenB implementation, with a higher case fatality ratio in young infants, highlights the importance of timely vaccination. FUNDING: UK Health Security Agency

Epidemiological and strain characteristics of invasive meningococcal disease prior to, during and after COVID-19 pandemic restrictions in England

Objectives In 2020, COVID-19 pandemic restrictions led to a major suppression of meningococcal disease in England. Here we describe the epidemiology of invasive meningococcal disease in the three years prior to the COVID-19 pandemic, and the three years immediately after the introduction of restrictions. Methods The UK Health Security Agency conducts national meningococcal disease surveillance in England consisting of laboratory-based case confirmation with strain characterisation by culture and/or molecular detection, as well as clinical follow-up of all cases. Results In the pre-pandemic period, 554–742 IMD cases were laboratory-confirmed per year. MenB caused 57.2% of cases, followed by MenW (22.7%), MenY (10.6%) and MenC (7.7%). The introduction of restrictions in late March 2020 led to a 73% reduction in IMD. After the removal of restrictions in 2021, a resurgence in MenB was observed, primarily in teenagers and young adults. During the following winter period (2022/23), MenB disease increased to the highest level since 2012 with cases rising across multiple age groups, however, cases in young children eligible for MenB vaccination remained lower than prior to the pandemic. MenACWY cases remained very low throughout the pandemic period. Conclusions Once pandemic restrictions in England were removed, MenB quickly rebounded- initially driven by a resurgence in teenagers/young adults, but later among other age groups. MenACWY cases remain very low due to the protection afforded by the adolescent MenACWY conjugate vaccine programme

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Invasive serogroup B meningococci in England following three years of 4CMenB vaccination - First real-world data.

OBJECTIVES: In 2015 the UK became the first country to implement the meningococcal B (MenB) vaccine, 4CMenB, into the national infant program. 4CMenB is expected to cover meningococci expressing sufficient levels of cross-reactive proteins. This study presents clonal complex, 4CMenB antigen genotyping, and 4CMenB coverage data for all English invasive MenB isolates from 2014/15 (1 year pre-vaccine) through 2017/18 and compares data from vaccinated and unvaccinated ≤3 year olds. METHODS: Vaccine coverage of all invasive MenB isolates from 2014/15 to 2017/18 (n = 784) was analysed using the Meningococcal Antigen Typing System. Genotyping utilised the Meningococcus Genome Library. RESULTS: Among ≤3 year olds, proportionally fewer cases in vaccinees (1, 2 or 3 doses) were associated with well-covered strains e.g. cc41/44 (20.5% versus 36.4%; P<0.01) and antigens e.g. PorA P1.4 (7.2% versus 17.3%; P = 0.02) or fHbp variant 1 peptides (44.6% vs 69.1%; P<0.01). Conversely, proportionally more cases in vaccinees were associated with poorly-covered strains e.g. cc213 (22.9% versus 9.6%; P<0.01) and antigens e.g. variant 2 or 3 fHbp peptides (54.2% versus 30.9%; P<0.01). CONCLUSIONS: 4CMenB reduces disease due to strains with cross-reactive antigen variants. No increase in absolute numbers of cases due to poorly covered strains was observed in the study period