Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents

OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8–17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3–10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1–18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/ no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients

Gene sequencing for pathogenic variants among adults with breast and ovarian cancer in the caribbean

Importance: Rates of breast and ovarian cancer are high in the Caribbean; however, to date, few published data quantify the prevalence of inherited cancer in the Caribbean population. Objective: To determine whether deleterious variants in genes that characterize the hereditary breast and ovarian cancer syndrome are associated with the development of breast and ovarian cancer in the English- and Creole-speaking Caribbean populations. Design, Setting, and Participants: This multisite genetic association study used data from germline genetic test results between June 2010 and June 2018 in the Bahamas, Cayman Islands, Barbados, Dominica, Jamaica, Haiti, and Trinidad and Tobago. Next-generation sequencing on a panel of 30 genes and multiplex ligation-dependent probe amplification (BRCA1 and BRCA2) were performed. Medical records were reviewed at time of study enrollment. Women and men diagnosed with breast and ovarian cancer with at least 1 grandparent born in the participating study sites were included; 1018 individuals were eligible and consented to participate in this study. Data were analyzed from November 4, 2019, to May 6, 2020. Exposures: Breast and/or ovarian cancer diagnosis Main Outcomes and Measures: Rate of inherited breast and ovarian cancer syndrome and spectrum and types of variants. Results: Of 1018 participants, 999 (98.1%) had breast cancer (mean [SD] age, 46.6 [10.8] years) and 21 (2.1%) had ovarian cancer (mean [SD] age, 47.6 [13.5] years). Three individuals declined to have their results reported. A total of 144 of 1015 (14.2%) had a pathogenic or likely pathogenic (P/LP) variant in a hereditary breast and ovarian cancer syndrome gene. A total of 64% of variant carriers had P/LP variant in BRCA1, 23% in BRCA2, 9% in PALB2 and 4% in RAD51C, CHEK2, ATM, STK11 and NBN. The mean (SD) age of variant carriers was 40.7 (9.2) compared with 47.5 (10.7) years in noncarriers. Individuals in the Bahamas had the highest proportion of hereditary breast and ovarian cancer (23%), followed by Barbados (17.9%), Trinidad (12%), Dominica (8.8%), Haiti (6.7%), Cayman Islands (6.3%), and Jamaica (4.9%). In Caribbean-born women and men with breast cancer, having a first- or second-degree family member with breast cancer was associated with having any BRCA1 or BRCA2 germline variant (odds ratio, 1.58; 95% CI, 1.24-2.01; P \u3c.001). A BRCA1 vs BRCA2 variant was more strongly associated with triple negative breast cancer (odds ratio, 6.33; 95% CI, 2.05-19.54; P =.001). Conclusions and Relevance: In this study, among Caribbean-born individuals with breast and ovarian cancer, 1 in 7 had hereditary breast and ovarian cancer. The proportion of hereditary breast and ovarian cancer varied by island and ranged from 23% in the Bahamas to 4.9% in Jamaica. Each island had a distinctive set of variants.

Effect of root canal preparation, type of endodontic post and mechanical cycling on root fracture strength

Objective: To evaluate the impact of the type of root canal preparation, intraradicular post and mechanical cycling on the fracture strength of roots. Material and Methods: Eighty human single rooted teeth were divided into 8 groups according to the instruments used for root canal preparation (manual or rotary instruments), the type of intraradicular post (fiber posts-FRC and cast post and core-CPC) and the use of mechanical cycling (MC) as follows: Manual and FRC; Manual, FRC and MC; Manual and CPC; Manual, CPC and MC; Rotary and FRC; Rotary, FRC and MC; Rotary and CPC; Rotary, CPC and MC. The filling was performed by lateral compactation. All root canals were prepared for a post with a 10 mm length, using the custom # 2 bur of the glass fiber post system. For mechanical cycling, the protocol was applied as follows: an angle of incidence of 45 degrees, 37 degrees C, 88 N, 4 Hz, 2 million pulses. All groups were submitted to fracture strength test in a 45 degrees device with 1 mm/min cross-head speed until failure occurred. Results: The 3-way ANOVA showed that the root canal preparation strategy (p<0.03) and post type (p<0.0001) affected the fracture strength results, while mechanical cycling (p=0.29) did not. Conclusion: The root canal preparation strategy only influenced the root fracture strength when restoring with a fiber post and mechanical cycling, so it does not seem to be an important factor in this scenario

Sob o prisma da equidade: financiamento federal do Sistema Único de Saúde no estado da Bahia

Resumo O objetivo deste artigo é analisar a distribuição dos recursos financeiros federais para os municípios do estado da Bahia, em 2010, na perspectiva da equidade. A metodologia utilizou o modelo "Contas Nacionais de Saúde" para identificação do fluxo de recursos; o Índice de Desenvolvimento Humano Municipal (IDHM) como proxy das necessidades de saúde; e indicadores de oferta de serviços de saúde por macrorregião. As transferências federais totalizaram R$2 bilhões, R$ 146,36 per capita, sendo 20% dos recursos destinados aos 219 municípios com menor IDHM. Os 37 municípios com melhor IDHM detiveram 60% dos recursos, ou seja, mais de R$1,23 bilhões. Evidenciou-se que 30$ 615,45 milhões) foram destinados a 40% da população do estado, espalhada por 348 municípios, e mais de R$ 1 bilhão foi transferido também para 40% da população, mas que se distribuía por apenas 17 municípios. A mais populosa das nove macrorregiões e de maior capacidade instalada recebeu, sozinha, 32,81% dos recursos. A macrorregião com mais equipes de saúde por habitante tinha o segundo melhor IDHM. Verificou-se grande concentração de recursos destinada a poucos municípios de grande porte populacional e com os mais altos IDHM, e fraco aporte para regiões com maiores necessidades de saúde

Desafíos políticos de los países de inmigración

13 págs.-- Publicado en "Confluencia XXI. Revista de Pensamiento Político" (México), nº 3 (Oct-Dic 2008) bajo el título monográfico "Migrantes: ¿Por qué se van? ¿Por qué se quedan?".Las migraciones, una práctica tan antigua como la propia condición humana, se han convertido en un factor estructural de primer orden, en uno de los macrofenómenos más definitorios de nuestra época y en un complejo reto para las sociedades contemporáneas. En prácticamente todos los países del mundo, todo lo que concierne a este complejo fenómeno ocupa un lugar destacado en la agenda política. La gestión, el control y la integración de los movimientos internacionales de personas se presentan como un policy field de creciente y prioritaria relevancia. No se trata, sin embargo, de una cuestión de mera moda: el número de países implicados de manera significativa en las migraciones internacionales ha aumentado considerablemente, hasta el punto de que resulta realmente difícil encontrar algún Estado que no sea bien un país de inmigración, bien un país de emigración o bien ambas cosas a la vez, cuando no al menos un país de tránsito. No ha de extrañar entonces que la mayoría de los gobiernos haya tomado conciencia de la necesidad de ofrecer una respuesta en términos legales e institucionales a un fenómeno de carácter permanente que puede llegar a alterar la estructura demográfica, social, cultural, económica y laboral de un país. Dada la complejidad de la cuestión, y por cuestiones de economía argumentativa, aquí se abordará de manera fundamental desde la perspectiva de los países receptores, que, por lo demás, es también la adoptada en forma habitual por los países europeos que registran mayor inmigración. Sin embargo, el fenómeno migratorio es fundamentalmente transnacional y tiene fehacientes repercusiones en los países de emigración.Peer reviewe

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

Background Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. Methods To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. Results We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). Conclusions To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769)