HLA-G*14 bp indel variant in autism spectrum disorder in a population from southern Brazil.

Altered immune response during pregnancy has been associated with ASD susceptibility. HLA-G is expressed by the trophoblast at the maternal/fetal interface and induces allogenic tolerance toward the fetus. A 14-bp insertion in the HLA-G 3'UTR (rs371194629) was associated with reduced levels of HLA-G. We aimed to assess the influence of the HLA-G*14 bp indel variant in ASD susceptibility and symptomatology in a Brazilian admixed sample. The insertion genotype (14 bp+/14 bp+) was firstly associated with hetero aggression, but statistical significance was lost after correction (p = 0.035, pcorrected = 0.35). No association between the HLA-G variant and susceptibility to ASD or differential clinical manifestations were observed.

HIV Infection, Chromosome Instability, and Micronucleus Formation.

Genome integrity is critical for proper cell functioning, and chromosome instability can lead to age-related diseases, including cancer and neurodegenerative disorders. Chromosome instability is caused by multiple factors, including replication stress, chromosome missegregation, exposure to pollutants, and viral infections. Although many studies have investigated the effects of environmental or lifestyle genotoxins on chromosomal integrity, information on the effects of viral infections on micronucleus formation and other chromosomal aberrations is still limited. Currently, HIV infection is considered a chronic disease treatable by antiretroviral therapy (ART). However, HIV-infected individuals still face important health problems, such as chronic inflammation and age-related diseases. In this context, this article reviews studies that have evaluated genomic instability using micronucleus assays in the context of HIV infection. In brief, HIV can induce chromosome instability directly through the interaction of HIV proteins with host DNA and indirectly through chronic inflammation or as a result of ART use. Connections between HIV infection, immunosenescence and age-related disease are discussed in this article. The monitoring of HIV-infected individuals should consider the increased risk of chromosome instability, and lifestyle interventions, such as reduced exposure to genotoxins and an antioxidant-rich diet, should be considered. Therapies to reduce chronic inflammation in HIV infection are needed.

Iron deficiency and soil-transmitted helminth infection: classic and neglected connections.

Beyond participating in the oxygen transport by red blood cells, iron is an essential micronutrient and contributes to different physiological pathways and processes, such as cell proliferation, DNA repair, and other homeostatic functions. Iron deficiency affects millions of people, especially children and pregnant women. The consequences of iron deficiency are diverse, including inadequate child development, impaired cognition, and reduced productivity. Several factors contribute to iron deficiency, such as iron-poor diet, genetic factors, and infection with soil-transmitted helminths (STHs), especially roundworms (Ascaris lumbricoides), hookworms (Necator americanus and Ancylostoma duodenale), and whipworms (Trichuris trichiura). This review updates and summarizes the role of STHs as drivers of iron deficiency. Also, the poorly explored connections between STH infection, geophagia (a pica manifestation), immune response, and iron deficiency are discussed, highlighting how iron deficiency may act as a risk factor for infections by STHs, in addition to being a consequence of intestinal parasitic infections. Finally, strategies for control and management of iron deficiency and STH infection are described.

Synthesizing the connections between environmental disturbances and zoonotic spillover.

Zoonotic spillover is a phenomenon characterized by the transfer of pathogens between different animal species. Most human emerging infectious diseases originate from non-human animals, and human-related environmental disturbances are the driving forces of the emergence of new human pathogens. Synthesizing the sequence of basic events involved in the emergence of new human pathogens is important for guiding the understanding, identification, and description of key aspects of human activities that can be changed to prevent new outbreaks, epidemics, and pandemics. This review synthesizes the connections between environmental disturbances and increased risk of spillover events based on the One Health perspective. Anthropogenic disturbances in the environment (e.g., deforestation, habitat fragmentation, biodiversity loss, wildlife exploitation) lead to changes in ecological niches, reduction of the dilution effect, increased contact between humans and other animals, changes in the incidence and load of pathogens in animal populations, and alterations in the abiotic factors of landscapes. These phenomena can increase the risk of spillover events and, potentially, facilitate new infectious disease outbreaks. Using Brazil as a study model, this review brings a discussion concerning anthropogenic activities in the Amazon region and their potential impacts on spillover risk and spread of emerging diseases in this region.

Controlled hypobaric hypoxia increases immunological tolerance by modifying HLA-G expression, a potential therapy to inflammatory diseases.

One of the most striking characteristics of human beings is the incredible capacity to adapt to different environments. This capacity allowed humans to spread all over our planet, occupying habitats as diverse as deserts, tropical forests or tundra regions. Interactions with the environment, climate, food and water availability shaped our evolution and define our survival. Essential to human life, oxygen availability also controls human dispersion and adaptation. For example, low oxygen availability can lead to physiological adaptations in populations living in highlands. Moreover, the consequences of differential oxygen availability (or even exposure to hypoxia) are evident in process as fine-tuned controlled as gene regulation. Physiological responses to fluctuations in oxygen availability are crucial already from the early days of life, since the human fetal environment is characterized by hypoxia. Hypoxia-Inducible Factors (HIFs) act as major regulators of pathways involved in glycolysis, erythropoiesis, angiogenesis, cell proliferation and stem cells function. Here we explore the physiological consequences of hypoxia in the human organism. In this sense, and considering the existence of HIF sequences in promoter regions of genes important to immune regulation, we hypothesize that exposure to induced hypoxia through the use of hypobaric chambers can be used as a complementary therapy to control chronic inflammation in several diseases characterized by systemic inflammatory conditions. Among these inflammatory conditions we highlight autoimmune diseases and chronic inflammation in HIV infected individuals under antiretroviral treatment. Several experiments, including arthritis animal models, the evaluation of athletes that already use hypobaric chambers to induce erythropoiesis, and the potential consequences of hypoxia as an immunotolerogenic inducer in the HIV infection context are approached and discussed here.