Impact of HIV Infection and Kaposi Sarcoma on Human Herpesvirus-8 Mucosal Replication and Dissemination in Uganda

Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.Participants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).78 participants collected a total of 2063 orals swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8 viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7-6.2, p<0.001), persons with KS (IRR = 3.9, 95% CI = 1.7-9.0, p = 0.001) and persons with HIV infection (IRR = 1.7, 95% CI = 1.0-2.7, p = 0.03). Importantly, oral HHV-8 detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly more common when HHV-8 DNA was detected from the oropharynx during the week prior than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8-5.9 p<0.001). Genital HHV-8 detection was rare (9 (3%) of 272 swabs).HHV-8 detection is frequent in the oropharynx and peripheral blood of Ugandans with endemic and epidemic KS. Replication at these sites is highly correlated, and viremia is increased in men and those with HIV. The high incidence of HHV-8 replication at multiple anatomic sites may be an important factor leading to and sustaining the high prevalence of KS in Uganda

SARS-CoV-2 surveillance in households with and without asthmatic/allergic children: The Human Epidemiology and Response to SARS-CoV-2 study (HEROS)

Rationale: Whether children and people with asthma and allergic diseases are at increased risk for SARS-CoV-2 infection is not known. Neither is their role in household transmission. Methods: Biweekly nasal sample collections and weekly surveys were conducted to identify incident SARS-CoV-2 infections among children (\u3c13 \u3eyears) and teenagers (13-21 years) enrolled in asthma/allergic disease focused cohorts, and their household members, from May 2020-February 2021. Probability of subject/household infections and household transmissions were calculated using time-to-event analyses, and factors associated with infection and transmission risk using regression analyses. Results: Household (N=1,394) and subject (N=4,142) SARS-CoV-2 infection probability was 25.8% and 14.0%, respectively, and was similar for children (14.0%,CI:8.0-19.6%), teenagers (12.1%,CI:8.2-15.9%), and adults (14.0%,CI:9.5-18.4%). Infections were symptomatic in 24.5% of children, 41.2% of teenagers, and 62.5% of adults. Exposure to both symptomatic (aHR=87.39,CI:58.02-131.63) and asymptomatic (aHR=27.80,CI:17.16–45.03) infected household members was a risk factor for infection. Food allergy was associated with decreased infection risk (aHR=0.50,CI:0.32-0.81), but asthma was not (aHR=1.04,CI:0.73-1.46). Household infection risk was associated with attending in-person school (aHR=1.67,CI:1.09-2.57). Household secondary attack rate was 57.7%. Decreased risk of household transmission was associated with teen age, lower BMI, and lower viral load. Conclusions: Asthma does not increase risk of SARS-CoV-2 infection, while food allergy is protective. SARS-CoV-2 infection risk in children is similar to that of teenagers and adults. SARS-CoV-2 transmission risk and secondary attack rate is much higher than previously estimated in households with children, likely driven by the high frequency of asymptomatic childhood infections

Mutationen im PTS-Gen und mögliche Auswirkungen auf Funktion und Struktur der 6-Pyruvoyl-Tetrahydropterin-Synthase

Background: Research on Juvenile Idiopathic Arthritis (JIA) should support patients, caregivers/parents (carers) and clinicians to make important decisions in the consulting room and eventually to improve the lives of patients with JIA. Thus far these end-users of JIA-research have rarely been involved in the prioritisation of future research. Main body: Dutch organisations of patients, carers and clinicians will collaboratively develop a research agenda for JIA, following the James Lind Alliance (JLA) methodology. In a 'Priority Setting Partnership' (PSP), they will gradually establish a top 10 list of the most important unanswered research questions for JIA. In this process the input from clinicians, patients and their carers will be equally valued. Additionally, focus groups will be organised to involve young people with JIA. The involvement of all contributors will be monitored and evaluated. In this manner, the project will contribute to the growing body of literature on how to involve young people in agenda setting in a meaningful way. Conclusion: A JIA research agenda established through the JLA method and thus co-created by patients, carers and clinicians will inform researchers and research funders about the most important research questions for JIA. This will lead to research that really matters.</p

Bone Marrow Transplantation Results in Human Donor Blood Cells Acquiring and Displaying Mouse Recipient Class I MHC and CD45 Antigens on Their Surface

Background: Mouse models of human disease are invaluable for determining the differentiation ability and functional capacity of stem cells. The best example is bone marrow transplants for studies of hematopoietic stem cells. For organ studies, the interpretation of the data can be difficult as transdifferentiation, cell fusion or surface antigen transfer (trogocytosis) can be misinterpreted as differentiation. These events have not been investigated in hematopoietic stem cell transplant models. Methodology/Principal Findings: In this study we investigated fusion and trogocytosis involving blood cells during bone marrow transplantation using a xenograft model. We report that using a standard SCID repopulating assay almost 100 % of the human donor cells appear as hybrid blood cells containing both mouse and human surface antigens. Conclusion/Significance: Hybrid cells are not the result of cell-cell fusion events but appear to be due to efficient surface antigen transfer, a process referred to as trogocytosis. Antigen transfer appears to be non-random and includes all donor cells regardless of sub-type. We also demonstrate that irradiation preconditioning enhances the frequency of hybrid cell

Dietary Intake of Advanced Glycation End Products (AGEs) and Mortality among Individuals with Colorectal Cancer

Funding [WCRF 2015/1391, PI: M. Jenab] was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant program. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de lEducation Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, the Catalan Institute of OncologyICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vaesterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). V. Fedirko is supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award (Grant ID RR200056). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were used to calculate hazard ratios and corresponding 95% confidence intervals for associations between dietary intake of AGEs with CRC-specific and all-cause mortality among 5801 participant cases diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition study between 1993 and 2013. Dietary intakes of AGEs were estimated using country-specific dietary questionnaires, linked to an AGE database, that accounted for food preparation and processing. During a median of 58 months of follow-up, 2421 cases died (1841 from CRC). Individually or combined, dietary intakes of AGEs were not associated with all-cause and CRC-specific mortality among cases. However, there was a suggestion for a positive association between AGEs and all-cause or CRC-specific mortality among CRC cases without type II diabetes (all-cause, P-interaction = 0.05) and CRC cases with the longest follow-up between recruitment and cancer diagnosis (CRC-specific, P-interaction = 0.003; all-cause, P-interaction = 0.01). Our study suggests that pre-diagnostic dietary intakes of AGEs were not associated with CRC-specific or all-cause mortality among CRC patients. Further investigations using biomarkers of AGEs and stratifying by sex, diabetes status, and timing of exposure to AGEs are warranted.Wereld Kanker Onderzoek Fonds (WKOF), World Cancer Research Fund International grant program WCRF 2015/1391World Health OrganizationDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDanish Cancer SocietyLigue Contre le Cancer (France) Institut Gustave Roussy (France) Mutuelle Generale de lEducation Nationale (France)Institut National de la Sante et de la Recherche Medicale (Inserm)Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany)Federal Ministry of Education & Research (BMBF)Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR)Netherlands GovernmentWorld Cancer Research Fund International (WCRF)Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII)Junta de Andalucia Regional Government of Asturias (Spain) Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain) Catalan Institute of OncologyICO (Spain)Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vaesterbotten (Sweden)Cancer Research UK 14136 C8221/A29017UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1 UK Research & Innovation (UKRI) Medical Research Council UK (MRC)European Commission MR/N003284/1 MC-UU_12015/1Cancer Research UK C864/A14136Cancer Prevention and Research Institute of Texas (CPRIT) Rising Stars Award RR20005

The Ups and Downs in Women's Employment: Shifting Composition or Behavior from 1970 to 2010?

This paper tracks factors contributing to the ups and downs in women’s employment from 1970 to 2010 using regression decompositions focusing on whether changes are due to shifts in the means (composition of women) or due to shifts in coefficients (inclinations of women to work for pay). Compositional shifts in education exerted a positive effect on women’s employment across all decades, while shifts in the composition of other family income, particularly at the highest deciles, depressed married women’s employment over the 1990s contributing to the slowdown in this decade. A positive coefficient effect of education was found in all decades, except the 1990s, when the effect was negative, depressing women’s employment. Further, positive coefficient results for other family income at the highest deciles bolstered married women’s employment over the 1990s. Models are run separately for married and single women demonstrating the varying results of other family income by marital status. This research was supported in part by an Upjohn Institute Early Career Research Award

Second intravenous immunoglobulin dose in patients with Guillain-Barre syndrome with poor prognosis (SID-GBS):a double-blind, randomised, placebo-controlled trial

Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome. Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of >= 6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1.4 (95% CI 0.6-3.3; p=0.45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation). Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved

A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity.

BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

Objective: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. Methods: HICs were identified in COHERE on the basis of \ue2\u89\ua55 consecutive viral loads (VL) \ue2\u89\ua4500 copies/mL over \ue2\u89\ua51 year whilst ART-naive, with the last VL \ue2\u89\ua4500 copies/mL measured \ue2\u89\ua55 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL &gt;2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models. Results: We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds. Discussion: Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs