A novel sequencing-based vaginal health assay combining self-sampling, HPV detection and genotyping, STI detection, and vaginal microbiome analysis

The composition of the vaginal microbiome, including both the presence of pathogens involved in sexually transmitted infections (STI) as well as commensal microbiota, has been shown to have important associations for a woman´s reproductive and general health. Currently, healthcare providers cannot offer comprehensive vaginal microbiome screening, but are limited to the detection of individual pathogens, such as high-risk human papillomavirus (hrHPV), the predominant cause of cervical cancer. There is no single test on the market that combines HPV, STI, and microbiome screening. Here, we describe a novel inclusive vaginal health assay that combines self-sampling with sequencing-based HPV detection and genotyping, vaginal microbiome analysis, and STI-associated pathogen detection. The assay includes genotyping and detection of 14 hrHPV types, 5 low-risk HPV types (lrHPV), as well as the relative abundance of 31 bacterial taxa of clinical importance, including Lactobacillus, Sneathia, Gardnerella, and 3 pathogens involved in STI, with high sensitivity, specificity, and reproducibility. For each of these taxa, reference ranges were determined in a group of 50 self-reported healthy women. The HPV sequencing portion of the test was evaluated against the digene High-Risk HPV HC2 DNA test. For hrHPV genotyping, agreement was 95.3% with a kappa of 0.804 (601 samples); after removal of samples in which the digene hrHPV probe showed cross-reactivity with lrHPV types, the sensitivity and specificity of the hrHPV genotyping assay were 94.5% and 96.6%, respectively, with a kappa of 0.841. For lrHPV genotyping, agreement was 93.9% with a kappa of 0.788 (148 samples), while sensitivity and specificity were 100% and 92.9%, respectively. This novel assay could be used to complement conventional cervical cancer screening, because its self-sampling format can expand access among women who would otherwise not participate, and because of its additional information about the composition of the vaginal microbiome and the presence of pathogens.Fil: Bik, Elisabeth M.. Ubiome;Fil: Bird, Sara W.. Ubiome;Fil: Bustamante, Juan Pablo. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Leon, Luis E.. Ubiome

Impact of long-term viral suppression in CD4+ recovery of HIV-children on Highly Active Antiretroviral Therapy

BACKGROUND: The effects of HAART may differ between children and adults because children have a developing immune system, and the long-term immunological outcome in HIV-infected children on HAART is not well-known. A major aim of our study was to determine CD4+ evolution associated with long-term VL control during 4 years of observation on HAART. METHODS: We carried out a retrospective study on a cohort of 160 vertically HIV-infected children. It was carried out from 1996 to 2004 in six large Spanish pediatric referral hospitals. We compared 33 children who had long-term VL suppression (VL ≤400 copies/ml) in the first 12 months of follow-up and maintained that level throughout follow-up (Responders-group), and 127 children with persistently detectable VL in spite of ART switches (Non-Responders-group). RESULTS: We observed a quick initial and significant increase in CD4(+ )counts from the baseline to 12 months on HAART in both groups (p < 0.01). The Non-Responders group sustained CD4+ increases and most of these children maintained high CD4(+ )level counts (≥25%). The Non-Responders group reached a plateau between 26% and 27% CD4(+ )at the first 12 months of follow-up that remained stable during the following 3 years. However, the Responders group reached a plateau between 30% and 32% CD4(+ )at 24, 36 and 48 months of follow-up. We found that the Responders group had higher CD4(+ )count values and higher percentages of children with CD4(+ )≥25% than the Non-Responders group (p < 0.05) after month 12. CONCLUSION: Long-term VL suppression in turn induces large beneficial effects in immunological responses. However, it is not indispensable to recover CD4(+ )levels

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza

Abstract Introduction Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. Methods We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. Results Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. Conclusions While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness

Country-level gender inequality is associated with structural differences in the brains of women and men

男女間の不平等と脳の性差 --男女間の不平等は脳構造の性差と関連する--. 京都大学プレスリリース. 2023-05-10.Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7, 876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality

An ultrahot Neptune in the Neptune desert

About 1 out of 200 Sun-like stars has a planet with an orbital period shorter than one day: an ultrashort-period planet. All of the previously known ultrashort-period planets are either hot Jupiters, with sizes above 10 Earth radii (R⊕), or apparently rocky planets smaller than 2 R⊕. Such lack of planets of intermediate size (the ‘hot Neptune desert’) has been interpreted as the inability of low-mass planets to retain any hydrogen/helium (H/He) envelope in the face of strong stellar irradiation. Here we report the discovery of an ultrashort-period planet with a radius of 4.6 R⊕ and a mass of 29 M⊕, firmly in the hot Neptune desert. Data from the Transiting Exoplanet Survey Satellite revealed transits of the bright Sun-like star LTT 9779 every 0.79 days. The planet’s mean density is similar to that of Neptune, and according to thermal evolution models, it has a H/He-rich envelope constituting 9.0^(+2.7)_(−2.9)% of the total mass. With an equilibrium temperature around 2,000 K, it is unclear how this ‘ultrahot Neptune’ managed to retain such an envelope. Follow-up observations of the planet’s atmosphere to better understand its origin and physical nature will be facilitated by the star’s brightness (V_(mag) = 9.8)

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations

Red Nacional de reconocedores de suelos.

Los relevamientos sistemáticos de suelos en Argentina comenzaron en la década de 1960, en el marco del Plan Mapa de Suelos. Dicho plan, desarrollado y liderado por el INTA, dio impulso a la formación de especialistas y a la producción de cartografía de suelos a diferentes escalas. Sin embargo, a partir del año 2000 las actividades se redujeron notablemente y gran parte de los equipos provinciales formados hasta ese momento se desarticularon. Desde entonces los relevamientos continuaron de manera aislada sólo en aquellas provincias donde se mantuvieron los grupos de trabajo. Este hecho condujo a que actualmente diferentes regiones del país no cuenten con información acerca de las propiedades y distribución de suelos a una escala adecuada para la toma de decisiones. En este contexto, en el 2018 se crea la Red Nacional de Reconocedores de Suelos (RNRS) que organiza las capacidades técnicas y operativas a nivel nacional para dar pronta respuesta a la creciente demanda de cartografía. Se trata de un equipo interinstitucional e interdisciplinario de especialistas distribuidos por todo el país, que realiza tareas de relevamiento, produce y difunde cartografía básica y utilitaria de suelos, ofrece capacitación y genera espacios de discusión y actualización metodológica. A la fecha, la RNRS ha relevado aproximadamente 760.000 ha en el sur de Córdoba, estimando completar durante el presente año el relevamiento del departamento Río Cuarto. Esta estrategia organizacional permitirá avanzar en el mapeo semidetallado de suelos en nuestro país, estableciendo vinculaciones sinérgicas entre profesionales de diferentes instituciones a fin de fortalecer y potenciar los equipos de trabajo en cada región. El motivo de esta contribución es presentar la RNRS, sus objetivos, avances a la fecha y desafíos a futuro, haciendo una breve revisión del estado actual de los relevamientos a escala semidetallada en nuestro país.Fil: Moretti, Lucas M. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Cerro Azul; ArgentinaFil: Rodriguez, Darío M. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Schulz, Guillermo A. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Kurtz, Ditmar Bernardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Corrientes; ArgentinaFil: Altamirano D. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi; ArgentinaFil: Amin, S. Universidad Nacional de Río Cuarto; ArgentinaFil: Angelini, Marcos Esteban. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina. Wageningen University. Soil Geography and Landscape group; Holanda. International Soil Reference and Information Centre. World Soil Information; HolandaFil: Babelis, German Claudio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; ArgentinaFil: Becerra, Alejandra Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Bedendo, Dante Julian. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Paraná; ArgentinaFil: Boldrini, C. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez. Agencia de Extensión Rural Río Cuarto; AgentinaFil: Bongiovanni, C. Universidad Nacional de Río Cuarto; ArgentinaFil: Bozzer, S. Universidad Nacional de Río Cuarto; ArgentinaFil: Cabrera, A. Universidad Nacional de Río Cuarto; ArgentinaFil: Canale, A. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez. Agencia de Extensión Rural Río Cuarto; AgentinaFil: Chilano, Y. Universidad Nacional de Río Cuarto; ArgentinaFil: Cholaky, Carmen. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Cisneros; José Manuel. Universidad Nacional de Río Cuarto. Cátedra de Uso y Manejo de Suelos; ArgentinaFil: Colazo, Juan Cruz. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Luis; ArgentinaFil: Corigliano, J. Universidad Nacional de Río Cuarto; ArgentinaFil: Degioanni, Américo José. Universidad Nacional Río Cuarto. Facultad de Agronomía y Veterinaria. Departamento de Ecología Agraria; ArgentinaFil: de la Fuente, Juan Carlos Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Escobar, Dardo. Ministerio de Agricultura, Ganadería y Pesca; ArgentinaFil: Faule, L. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi. Córdoba. ArgentinaFil: Galarza, Carlos Martin. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: González, J. Universidad Nacional de Río Cuarto; ArgentinaFil: Holzmann, R. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Alto Valle; ArgentinaFil: Irigoin, Julieta. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina. Universidad Nacional de Luján. Departamento Tecnología; ArgentinaFil: Lanfranco, M. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi; ArgentinaFil: León Giacosa, C. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Matteio, J.P. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Márquez, C. Gobierno de Córdoba. Ministerio de Agricultura y Ganadería; ArgentinaFil: Marzari, R. Universidad Nacional de Río Cuarto; ArgentinaFil: Mattalia, M.L. Universidad Nacional de Río Cuarto; ArgentinaFil: Morales Poclava, P.C. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Muñoz, S. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Paladino, Ileana Ruth. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; Argentina. Universidad Nacional de Lomas de Zamora. Facultad de Ciencias Agrarias; ArgentinaFil: Parra, B. Universidad Nacional de Río Cuarto; ArgentinaFil: Pérez, M. Gobierno de Córdoba. Ministerio de Agricultura y Ganadería; ArgentinaFil: Pezzola, A. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Hilario Ascasubi; ArgentinaFil: Perucca, S. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez. Agencia de Extensión Rural Río Cuarto; ArgentinaFil: Porcel de Peralta, R. Gobierno de Córdoba. Ministerio de Agricultura y Ganadería; ArgentinaFil: Renaudeau, S. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Corrientes; ArgentinaFil: Salustio, M. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez. Agencia de Extensión Rural Río Cuarto; ArgentinaFil: Sapino, V. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Tenti Vuegen, L.M. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos. ArgentinaFil: Tosolini, R. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Vicondo, M.E. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi; Argentina. Universidad Nacional de Córdoba. ArgentinaFil: Vizgarra, L.A. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Quimili; ArgentinaFil: Ybarra, D.D. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Corrientes; ArgentinaFil: Winschel, C. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Hilario Ascasubi; ArgentinaFil: Zamora, E. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Corrientes; Argentin