HLA-G 3'UTR haplotype frequencies in highland and lowland South Native American populations.

Human Leukocyte Antigen (HLA)-G participates in several biological processes, including reproduction, vascular remodeling, immune tolerance, and hypoxia response. HLA-G is a potential candidate gene for high altitude adaptation since its expression is modulated in both micro and macro environment under hypoxia and constant cellular stress. Besides the promoter region, the HLA-G 3'untranslated region (UTR) influences HLA-G expression patterns through several post-transcriptional mechanisms. Currently, the 3'UTR genetic diversity in terms of altitude adaptation of Native American populations is still unexplored, particularly at high altitude ecoregions. Here, we evaluated 288 Native Americans from 9 communities located in the Andes [highland (HL); ≥2,500 m (range = 2,838-4,433 m)] and 8 populations located in lowland (LL) regions [<2,500 m (range = 80-431 m); Amazonian tropical forest, Brazilian central plateau, and Chaco] of South America. In total, nine polymorphic sites and ten haplotypes were observed. The most frequent haplotypes (UTR-1, UTR-2, and UTR-3) accounted for âˆ¼ 77% of haplotypes found in LL, while in the HL, the same haplotypes reach âˆ¼ 93%. Also, a remarkable high frequency of putative ancestral UTR-5 haplotype was observed in LL (21.5%), while in HL UTR-2 reaches up to 47%. Further, UTR-2 frequency positively correlates with altitude-related variables, while a negative correlation for UTR-5 was observed. From an evolutionary perspective, we observed a tendency towards balancing selection in HL and LL populations thus suggesting that haplotypes of ancient and more derived alleles may have been co-opted for relatively recent adaptations such as those experienced by modern humans in the highland and lowland of South America. We also discuss how long-term balancing selection can be a reservoir of genetic variants that can be positively selected. Finally, our study provides some pieces of evidence that HLA-G 3'UTR haplotypes may have contributed to high altitude adaptation in the Andes.

Telemedicine in Pediatric Intensive Care Units: Perspectives From a Brazilian Experience.

Purpose of Review: To present the implementation of a telemedicine project (TeleICU) in pediatric intensive care units (ICU) throughout different Brazilian regions. Recent Findings: Although telemedicine in pediatric ICUs has shown evidence of benefit in numerous studies with potential to 18 mitigate existing disparities, in Brazil, its use is still under development. Brazil has several opportunities for implementing this resource since, according to the National Registry of Healthcare 20 Establishments (NRHE), there is a discrepancy in the density of pediatric intensive care physicians per patient and the availability 21 of pediatric ICU beds per number of inhabitants. Summary: Health technologies are being widely used to fill gaps in the healthcare system. Telemedicine has been an important tool to meet demands in intensive care units, especially the demand for specialized assistance. TeleICU is a Brazilian model of telemedicine that performs multidisciplinary telerounds in remote pediatric ICUs and develops continuing education activities for the healthcare teams. The project aims to systematize and to qualify care, as well as to reduce risks for patients admitted to pediatric ICUs engaged in the project. Preliminary results have demonstrated a positive impact regarding this approach, providing medical care to 6640 inpatients-day in two Brazilian pediatric ICUs, for 616 patients during 946 daily telerounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s40124-021-00242-z.

Genetic Variations in the TP53 Pathway in Native Americans Strongly Suggest Adaptation to the High Altitudes of the Andes.

The diversity of the five single nucleotide polymorphisms located in genes of the TP53 pathway (TP53, rs1042522; MDM2, rs2279744; MDM4, rs1563828; USP7, rs1529916; and LIF, rs929271) were studied in a total of 282 individuals belonging to Quechua, Aymara, Chivay, Cabanaconde, Yanke, Taquile, Amantani, Anapia, Uros, Guarani Ñandeva, and Guarani Kaiowá populations, characterized as Native American or as having a high level (> 90%) of Native American ancestry. In addition, published data pertaining to 100 persons from five other Native American populations (Surui, Karitiana, Maya, Pima, and Piapoco) were analyzed. The populations were classified as living in high altitude (≥ 2,500 m) or in lowlands (< 2,500 m). Our analyses revealed that alleles USP7-G, LIF-T, and MDM2-T showed significant evidence that they were selected for in relation to harsh environmental variables related to high altitudes. Our results show for the first time that alleles of classical TP53 network genes have been evolutionary co-opted for the successful human colonization of the Andes.