Proposal to inform European institutions regarding the regulation of conscientious objection to abortion.

The aim of this paper is to define a set of proposals to inform European institutions in the regulation of Conscientious Objection to abortion. The board of the European Society of Contraception and Reproductive Health Care (ESC) was informed on the elements that should in the opinion of the authors be included in a future regulation of Conscientious Objection to abortion in Europe. These elements are outlined in this paper and the debate about them could form the basis for recommendations to the international scientific community and the European institutions. As current measures governing the principle of conscientious objection result in negative consequences regarding women's access to sexual and reproductive health services, they should be changed. Healthcare services should adopt measures to guarantee that a woman's right to voluntary abortion is not limited by the practitioner's stance on the principle of conscientious objection. In the countries where conscientious objection is allowed, the regulation must clearly delineate the extent of the duties and the exemptions of professionals based on the principles of established social consensus. The recommendations included in this document specify measures on the rights of women, the rights and duties of the practitioner, the role of institutions and the role of professional associations

Changes in Social and Clinical Determinants of COVID-19 Outcomes Achieved by the Vaccination Program: A Nationwide Cohort Study

Background: The objective of this study was to assess changes in social and clinical determinants of COVID-19 outcomes associated with the first year of COVID-19 vaccination rollout in the Basque population. Methods: A retrospective study was performed using the complete database of the Basque Health Service (n = 2,343,858). We analyzed data on age, sex, socioeconomic status, the Charlson comorbidity index (CCI), hospitalization and intensive care unit (ICU) admission, and COVID-19 infection by Cox regression models and Kaplan–Meier curves. Results: Women had a higher hazard ratio (HR) of infection (1.1) and a much lower rate of hospitalization (0.7). With older age, the risk of infection fell, but the risks of hospitalization and ICU admission increased. The higher the CCI, the higher the risks of infection and hospitalization. The risk of infection was higher in high-income individuals in all periods (HR = 1.2–1.4) while their risk of hospitalization was lower in the post-vaccination period (HR = 0.451). Conclusion: Despite the lifting of many control measures during the second half of 2021, restoring human mobility patterns, the situation could not be defined as syndemic, clinical determinants seeming to have more influence than social ones on COVID-19 outcomes, both before and after vaccination program implementation

The effect of mixed vaccination rollout strategy: A modelling study

Vaccines have measurable efficacy obtained first from vaccine trials. However, vaccine efficacy (VE) is not a static measure and long-term population studies are needed to evaluate its performance and impact. COVID-19 vaccines have been developed in record time and the currently licensed vaccines are extremely effective against severe disease with higher VE after the full immunization schedule. To assess the impact of the initial phase of the COVID-19 vaccination rollout programmes, we used an extended Susceptible - Hospitalized - Asymptomatic/mild - Recovered ($SHAR$) model. Vaccination models were proposed to evaluate different vaccine types: vaccine type 1 which protects against severe disease only but fails to block disease transmission, and vaccine type 2 which protects against both severe disease and infection. VE was assumed as reported by the vaccine trials incorporating the difference in efficacy between one and two doses of vaccine administration. We described the performance of the vaccine in reducing hospitalizations during a momentary scenario in the Basque Country, Spain. With a population in a mixed vaccination setting, our results have shown that reductions in hospitalized COVID-19 cases were observed five months after the vaccination rollout started, from May to June 2021. Specifically in June, a good agreement between modelling simulation and empirical data was well pronounced.BERC 2022-2025 Marie Curie No~792494 Severo Ochoa CEX2021-001142-S/ MICIN / AEI / 10.13039/501100011033 EITB Marathon 2021 call BIO21/COV/00

Definition of the viral targets of protective HIV-1-specific T cell responses

<p>Abstract</p> <p>Background</p> <p>The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity.</p> <p>Methods</p> <p>Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders.</p> <p>Results</p> <p>For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes.</p> <p>Conclusions</p> <p>The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.</p

HIV Infection and Gut Mucosal Immune Function: Updates on Pathogenesis with Implications for Management and Intervention

HIV is primarily a sexually transmitted infection. However, given that the gastrointestinal tract (GIT) houses most of the body’s lymphocytes, including activated memory CD4+ T cells that are preferential targets for HIV, recent research has focused on the role of the GIT in transmission and pathogenesis. In health, the GIT maintains a balance between immune tolerance and rapid responsiveness. A complex network of innate and adaptive responses maintains this balance, which is severely perturbed in HIV infection. Recent studies have focused on mechanisms of GIT CD4+ T-cell depletion and epithelial disruption in HIV infection, the role of inflammation in accelerating viral dissemination, the kinetics of the adaptive response following transmission, and the extent of T-cell reconstitution following antiretroviral therapy. This review summarizes the results of recent investigations that may have important implications for the development of vaccines, microbicides, and therapeutic interventions for HIV and other mucosal pathogens

The HIV Envelope but Not VSV Glycoprotein Is Capable of Mediating HIV Latent Infection of Resting CD4 T Cells

HIV fusion and entry into CD4 T cells are mediated by two receptors, CD4 and CXCR4. This receptor requirement can be abrogated by pseudotyping the virion with the vesicular stomatitis virus glycoprotein (VSV-G) that mediates viral entry through endocytosis. The VSV-G-pseudotyped HIV is highly infectious for transformed cells, although the virus circumvents the viral receptors and the actin cortex. In HIV infection, gp120 binding to the receptors also transduces signals. Recently, we demonstrated a unique requirement for CXCR4 signaling in HIV latent infection of blood resting CD4 T cells. Thus, we performed parallel studies in which the VSV-G-pseudotyped HIV was used to infect both transformed and resting T cells in the absence of coreceptor signaling. Our results indicate that in transformed T cells, the VSV-G-pseudotyping results in lower viral DNA synthesis but a higher rate of nuclear migration. However, in resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration. The viral particles entering through the endocytotic pathway were destroyed within 1–2 days. These results indicate that the VSV-G-mediated endocytotic pathway, although active in transformed cells, is defective and is not a pathway that can establish HIV latent infection of primary resting T cells. Our results highlight the importance of the genuine HIV envelope and its signaling capacity in the latent infection of blood resting T cells. These results also call for caution on the endocytotic entry model of HIV-1, and on data interpretation where the VSV-G-pseudotyped HIV was used for identifying HIV restriction factors in resting T cells