Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

Background Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. Methods Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. Results 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). Conclusions CD4/CD8 > 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1)

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Somatização em migrantes de baixa renda no Brasil Somatization in Brazil's low-income migrants

Este artigo tem por objetivo compreender o entrelaçamento da cultura com reações psicológicas de indivíduos expostos ao processo de migração e estabelecer relações entre o fenômeno da migração e adoecimento psicossomático. O enfoque metodológico é essencialmente qualitativo, baseado em representações sociais de pacientes migrantes e da equipe de funcionários e profissionais de um centro de saúde do município próximo de Campinas. A análise demonstrou que a migração era percebida negativamente, como uma causadora de doenças quando havia perda do emprego/renda e fragmentação de laços familiares e comunitários. Se tais elementos estavam estabilizados, fatores estressantes do cotidiano permaneciam mascarados (mantidos fora da consciência) e a piora da saúde não era atribuída à migração ou à qualidade de vida. O problema da migração e doença, pela perspectiva do centro de saúde, incluía abordagem terapêutica exclusivamente biológica sem outra perspectiva que contribuísse para os sujeitos assimilarem as novas condições de vida num novo ambiente sócio-cultural.<br>This paper aims to debate relations between culture and psychological reactions of individuals exposed to the process of migration and to establish relations between migration and psychosomatic sickening. The methodological approach is essentially qualitative and based on social representations of migrant patients, staff and professionals of a public health unit near Campinas. The analysis demonstrated that migration was negatively experienced as producing ailments when loss of job/income, break of family/community ties was involved. When these elements were stabilized, stressful factors of daily life remained covered (out of conscience) and worsening in health condition was attributed neither to migration nor to life quality. The problem of migration and ailments, from the health center perspective, involved merely biological procedures and did not include additional perspectives to help patients to assimilate their new life conditions in a new social environment

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022, The Author(s)