New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Caracterización del Banco de La Concepción

Se integra información hidrográfica, geomorfológica, sedimentológica, biológica, sobre hábitats marinos y pesquera, para establecer las bases ecológicas necesarias para la protección y conservación del Banco de La ConcepciónEl proyecto INDEMARES ha permitido utilizar amplios medios económicos y personales para estudiar en detalle y desde múltiples perspectivas la zona del Banco de La Concepción. Se han aplicado metodologías para el estudio de la hidrografía, caracterizando la región, describiendo sus principales masas de agua y la hidrodinámica de las corrientes. También se ha abordado la geología de la zona, incluyendo levantamientos batimétricos, perfiles sísmicos, muestreos de sedimento y petrológicos, obteniendo modelos digitales del terreno, mapas de tipos de fondo, geomorfológicos. Se han caracterizado las comunidades bentopelágicas, demersales, epibentónicas y endobentónicas, prestando especial atención a aquellas que conforman o estructuran los hábitats sensibles cuyo inventariado y cartografía era objeto principal del proyecto. Los trabajos de identificación de hábitats se han realizado con muestreadores directos, pero también con muestreadores visuales, que han permitido hacer un mayor esfuerzo de muestreo sin aumentar el impacto sobre los fondos de la zona. Por otro lado se ha estudiado la huella pesquera de la zona por medio del análisis de los datos VMS y los cuadernos de pesca proporcionados por la SGP, además de una ardua labor a pie de puerto de entrevistas y encuestas. Toda la información ha sido gestionada y analizada por diferentes grupos de investigación de diferentes centros (Universidad de La Laguna, Instituto Universitario de Ciencias Políticas y Sociales, Universidad de Las Palmas de Gran Canaria, Instituto de Ciencias del Mar de Barcelona, Universidad de Barcelona, Centro de Investigaciones Medioambientales del Atlántico, Centro Oceanográfico de Santander y Centro Oceanográfico de Málaga del Instituto Español de Oceanografía, …), aunque el grueso de esta labor, además de la coordinación, se ha llevado a cabo en el Centro Oceanográfico de Canarias del Instituto Español de Oceanografía. Los resultados permiten tener un conocimiento profundo y multidisciplinar de la zona de estudio comparable a pocos proyectos de investigación marina en la macaronesia. El estudio oceanográfico, el geológico, y el de las comunidades biológicas, ha permitido la caracterización de los hábitats de la zona, y su cartografiado mediante el intenso muestreo y la aplicación de análisis de idoneidad de hábitats.INDEMARES Project made possible to bring together economic and staff resources to study in detail, and from multiple perspectives, the area of Banco de La Concepción. Methodologies have been applied to study hydrography, making a regional characterization, depicting main water masses, and current hydrodynamics. Geology has been tackled including bathymetric uplifting, seismic profiles, sediment and petrological sampling, obtaining digital terrain models, type of bottom maps, geomorphological maps, as an output. Benthopelagic, demersal, epibenthic and endobenthic communities have been characterized, paying special attention to sensitive habitats which inventory and mapping was the project’s main aim. Habitat identification has been made with direct and visual samplers, the latter making a major sampling effort possible without an increase of bottom impact. Moreover, fisheries footprint has been identified by Vessel Monitoring System data, together with logbooks from Secretaría General de Pesca (Fisheries Ministry), as well as a hard interviewing and surveying task at landing points. Information has been managed and analysed by different research groups from different Centres (Universidad de La Laguna, Instituto Universitario de Ciencias Políticas y Sociales, Universidad de Las Palmas de Gran Canaria, Instituto de Ciencias del Mar de Barcelona, Universidad de Barcelona, Centro de Investigaciones Medioambientales del Atlántico, Centro Oceanográfico de Santander y Centro Oceanográfico de Málaga del Instituto Español de Oceanografía), although the main body of the work, plus coordination, has been made by the Canary Islands Oceanographic Centre, from the Spanish Institute of Oceanography. Results let us have a multidisciplinary profound knowledge of the study zone, comparable to few other marine research projects off Macaronesia. The study about oceanography, geology and biologic communities has allowed the habitats characterization and mapping by means of intensive sampling and habitat suitability analysis.Instituto Español de Oceanografía, Comisión Europea Programa LIFE+, Fundación Biodiversida

Caracterización del Sur de Fuerteventura

Se integra información hidrográfica, geomorfológica, sedimentológica, biológica, sobre hábitats marinos y pesquera, para establecer las bases ecológicas necesarias para la protección y conservación del Sur de Fuerteventura (Montes de Amanay y El Banquete)El proyecto INDEMARES ha permitido utilizar amplios medios económicos y personales para estudiar en detalle y desde múltiples perspectivas la zona del Sur de Fuerteventura (montes de Amanay y El Banquete). Se han aplicado metodologías para el estudio de la hidrografía, caracterizando la región, describiendo sus principales masas de agua y la hidrodinámica de las corrientes. También se ha abordado la geología de la zona, incluyendo levantamientos batimétricos, perfiles sísmicos, muestreos de sedimento y petrológicos, obteniendo modelos digitales del terreno, mapas de tipos de fondo, geomorfológicos. Se han caracterizado las comunidades bentopelágicas, demersales, epibentónicas y endobentónicas, prestando especial atención a aquellas que conforman o estructuran los hábitats sensibles cuyo inventariado y cartografía era objeto principal del proyecto. Los trabajos de identificación de hábitats se han realizado con muestreadores directos, pero también con muestreadores visuales, que han permitido hacer un mayor esfuerzo de muestreo sin aumentar el impacto sobre los fondos de la zona. Por otro lado se ha estudiado la huella pesquera de la zona por medio del análisis de los datos VMS y los cuadernos de pesca proporcionados por la SGP, además de una ardua labor a pie de puerto de entrevistas y encuestas. Toda la información ha sido gestionada y analizada por diferentes grupos de investigación de diferentes centros (Universidad de La Laguna, Instituto Universitario de Ciencias Políticas y Sociales, Universidad de Las Palmas de Gran Canaria, Instituto de Ciencias del Mar de Barcelona, Universidad de Barcelona, Centro de Investigaciones Medioambientales del Atlántico, Centro Oceanográfico de Santander y Centro Oceanográfico de Málaga del Instituto Español de Oceanografía, …), aunque el grueso de esta labor, además de la coordinación, se ha llevado a cabo en el Centro Oceanográfico de Canarias del Instituto Español de Oceanografía. Los resultados permiten tener un conocimiento profundo y multidisciplinar de la zona de estudio comparable a pocos proyectos de investigación marina en la Macaronesia. El estudio oceanográfico, el geológico, y el de las comunidades biológicas, ha permitido la caracterización de los hábitats de la zona, y su cartografiado mediante el intenso muestreo y la aplicación de análisis de idoneidad de hábitats.Abstract: INDEMARES Project made possible to bring together economic and staff resources to study in detail, and from multiple perspectives, the area of South of Fuerteventura (Amanay and El Banquete Semounts). Methodologies have been applied to study hydrography, making a regional characterization, depicting main water masses, and current hydrodynamics. Geology has been tackled including bathymetric uplifting, seismic profiles, sediment and petrological sampling, obtaining digital terrain models, type of bottom maps, geomorphological maps, as an output. Benthopelagic, demersal, epibenthic and endobenthic communities have been characterized, paying special attention to sensitive habitats which inventory and mapping was the project’s main aim. Habitat identification has been made with direct and visual samplers, the latter making a major sampling effort possible without an increase of bottom impact. Moreover, fisheries footprint has been identified by Vessel Monitoring System data, together with logbooks from Secretaría General de Pesca (Fisheries Ministry), as well as a hard interviewing and surveying task at landing points. Information has been managed and analysed by different research groups from different Centres (Universidad de La Laguna, Instituto Universitario de Ciencias Políticas y Sociales, Universidad de Las Palmas de Gran Canaria, Instituto de Ciencias del Mar de Barcelona, Universidad de Barcelona, Centro de Investigaciones Medioambientales del Atlántico, Centro Oceanográfico de Santander y Centro Oceanográfico de Málaga del Instituto Español de Oceanografía), although the main body of the work, plus coordination, has been made by the Canary Islands Oceanographic Centre, from the Spanish Institute of Oceanography. Results let us have a multidisciplinary profound knowledge of the study zone, comparable to few other marine research projects off Macaronesia. The study about oceanography, geology and biologic communities has allowed the habitats characterization and mapping by means of intensive sampling and habitat suitability analysis.Instituto Español de Oceanografía, Comisión Europea Programa LIFE+, Fundación Biodiversida

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity.Findings We identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27–47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91–0·99), sensitivity 0·84 (0·70–0·93), and specificity 0·95 (0·85–0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91–0·95).Interpretation Our findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529

Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination

Exploring the psychological morbidity of waiting for sinus surgery using a mixed methods approach

Abstract Background Patients with chronic rhinosinusitis (CRS) often have to endure significant wait times for endoscopic sinus surgery (ESS). The pyschiatric impact of placement on a waitlist for ESS has not been explored. Methods Questionnaires measuring CRS symptom severity and health-related anxiety and stress (SNOT-22, HADS, WPAI-GH) were sent to patients diagnosed with CRS and currently on a waitlist for ESS. Fifteen representative waitlisted patients participated in one-on-one semi-structured interviews discussing their experience with their wait for ESS. A deductive thematic analysis was used to interpret the interview data using a quantitative driven mixed methods analysis. Results Participants waiting for ESS reported worsening clinical symptomatology during their waiting period. Participants reported waitlist and CRS impact on both work and social aspects of their lives. The HADS scale showed no overall significant level of depression or anxiety in the HADS screening questionnaire. The qualitative data describe the effects of the symptom burden of CRS. Conclusions Patients waitlisted for ESS did not demonstrate any significant level of psychiatric distress, however variability exists. The qualitative arm of this study elucidates how patients cope with their wait

Viral hepatitis among drug users in methadone maintenance: associated factors, vaccination outcomes, and interventions.

Drug users are at high risk of viral Hepatitis A, B, and C. The prevalence of Hepatitis A, Hepatitis B, and Hepatitis C, associated factors, and vaccine seroconversion among drug treatment program participants in a randomized controlled trial of hepatitis care coordination were examined. Of 489 participants, 44 and 47% required Hepatitis A/Hepatitis B vaccinations, respectively; 59% were Hepatitis C positive requiring linkage to care. Factors associated with serologic statuses, and vaccine seroconversion are reported; implications for strategies in drug treatment settings are discussed. Results suggest generalizable strategies for drug treatment programs to expand viral hepatitis screening, prevention, vaccination, and linkage to care

Viral hepatitis among drug users in methadone maintenance: associated factors, vaccination outcomes, and interventions.

Drug users are at high risk of viral Hepatitis A, B, and C. The prevalence of Hepatitis A, Hepatitis B, and Hepatitis C, associated factors, and vaccine seroconversion among drug treatment program participants in a randomized controlled trial of hepatitis care coordination were examined. Of 489 participants, 44 and 47% required Hepatitis A/Hepatitis B vaccinations, respectively; 59% were Hepatitis C positive requiring linkage to care. Factors associated with serologic statuses, and vaccine seroconversion are reported; implications for strategies in drug treatment settings are discussed. Results suggest generalizable strategies for drug treatment programs to expand viral hepatitis screening, prevention, vaccination, and linkage to care