Exploring Adaptive Phenotypes for the Human Calcium-Sensing Receptor Polymorphism R990G.

Rainforest hunter-gatherers from Southeast Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S)-fat accumulation localized in the hips (DSWS phenotype). Based on previous evidence in the Andamanese population, we first characterized signatures of adaptive natural selection around the calcium-sensing receptor gene in Southeast Asian rainforest groups presenting the DSWS phenotype and identified the R990G substitution (rs1042636) as a putative adaptive variant for experimental follow-up. Although the calcium-sensing receptor has a critical role in calcium homeostasis by directly regulating the parathyroid hormone secretion, it is expressed in different tissues and has been described to be involved in many biological functions. Previous works have also characterized the R990G substitution as an activating polymorphism of the calcium-sensing receptor associated with hypocalcemia. Therefore, we generated a knock-in mouse for this substitution and investigated organismal phenotypes that could have become adaptive in rainforest hunter-gatherers from Southeast Asia. Interestingly, we found that mouse homozygous for the derived allele show not only lower serum calcium concentration but also greater body weight and fat accumulation, probably because of enhanced preadipocyte differentiation and lipolysis impairment resulting from the calcium-sensing receptor activation mediated by R990G. We speculate that such differential features in humans could have facilitated the survival of hunter-gatherer groups during periods of nutritional stress in the challenging conditions of the Southeast Asian tropical rainforests.

Human genetic adaptation related to cellular zinc homeostasis.

SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.

Telemonitoring System Oriented towards High-Risk Pregnant Women.

A high-risk pregnancy is one in which pathological problems or abnormal conditions are latent during pregnancy and childbirth, increasing dangers to the mother's or the infant's health. Based on international standards and studies, most of the harms and risks to both the mother and the infant can be detected, treated, and prevented through proper pregnancy monitoring, as well as through appropriate and timely diagnosis. In this paper, we present the analysis, design, development, and usability assessment of a telemonitoring system focused on the remote monitoring and control of pregnancy in women suffering from hypertension, diabetes, or high-risk pregnancy. Our system is composed of two mobile web applications. One of these is designed for the medical area, allowing remote monitoring of the patient's pregnancy, and the other one is directed towards the patient, who enters the alarm symptom data, hypertension data, diabetes data, and clinical analyses, allowing the detection of a risk situation on time. Furthermore, we performed a usability assessment of our system based on a laboratory study with seven doctors and seven patients to evaluate the users' satisfaction. Our telemonitoring system shows a satisfactory/favorable opinion from the users' perspectives based on the obtained results.

Influence of insole material density in the stability of patients with prosthetic unilateral transtibial amputation.

People with lower limb amputation present greater displacements of their centre of gravity in a static situation than able-bodied individuals, as they depend on visual information to a greater extent, which implies an altered stability pattern. The efficacy of different hardness of plantar support to help maintain stability has not yet been determined. The aim of the present study is to assess stability in people with unilateral transtibial amputation with prosthesis in a static situation with insoles of different degrees of hardness and visual conditions with respect to the able-bodied population. For this purpose, 25 patients with amputation and 25 able-bodied individuals were included in both groups, postural stability was assessed by stabilometry. This assessment was carried out under normal conditions (on the floor of the dynamometric platform with eyes open), and under altered conditions (with the interposition of different materials such as plantar support: rigid and soft insoles and, eyes shut). Three variables were considered to assess stability: length of movement of the barycenter (mm), lateral velocity (mm/sg) and anterior velocity (mm/sg). All of them were analysed with the patient in static on the dynamometric platform. The results showed statistically significant differences between the two groups, (amputees and controls) with less stability in the amputee group (p < 0.05) when analysing the variables of length of movement of the barycenter, lateral velocity and anterior velocity. Amputee patients with open eyes exhibited greater stability than those with closed eyes. The hard insoles improved the stability data in amputees (length of movement of the barycenter and anterior velocity) with respect to the barefoot condition, and the soft insoles showed less stability than the patients with hard insoles, or than the barefoot patients. From the results obtained in this study, we can conclude that the PP-DWST 4 mm rigid insoles improve static stability in people with amputation. However, soft insoles impair stability and are therefore discouraged.

[Incidence of endometriosis in infertile women: clinical and laparoscopic characteristics]. / Incidencia de la endometriosis en mujeres con infertilidad: características clínicas y laparoscópicas.

BACKGROUND: The incidence and symptomatology of endometriosis vary according to the different populations. OBJECTIVES: To determine the incidence of endometriosis as well as the clinical and laparoscopic characteristics in infertile women with endometriosis. PATIENTS AND METHODS: This study included 68 infertile patients with endometriosis diagnosed by laparoscopy; in all of them we analyzed the demographic and clinical characteristics. RESULTS: In 68 out of 197 medical files that were analyzed, endometriosis was reported (34.5%). The average age was 30.3 +/- 3.9 years. Forty patients had primary infertility (58.8%) and 28 (41.29%) secondary infertility. In 34 patients endometriosis (50%) was mild, moderate in 16 (23.5%) and severe in 18 (26.5%). Only one endometriosic foci was found in 25% of the patients and multiple foci in 75% of them. The most common sites in which it was found were the uterosacral ligaments, Douglas pouch and the ovaries. In patients with primary infertility it predominated the medium-high socioeconomic level and in those with secondary infertility the low one. In severe endometriosis the predominant symptom was the moderate or severe dysmenorrhea, while in mild and moderate endometriosis was mild dysmenorrhea (p < 0.007). Six out of 16 patients with severe endometriosis had endometrioma. CONCLUSIONS: The endometriosis incidence in infertile women was similar to that reported in literature, as well as age of presentation. It was also observed a direct relationship between endometriosis severity and dysmenorrhea intensity.