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Objective: To evaluate the influence of prune belly syndrome (PBS) on the development of penises in human fetuses.Methods: We studied 39 human fetuses (including 4 with PBS) aged 11-22 weeks post conception. We measured the length and width of the free portion and penis root and the penis total length (PTL). In 21 fetuses of the control group and in 3 with PBS we analyze the penile with histochemical and immunohistochemical methods. The total penile area, area of corpora cavernosa, area of corpus spongiosum, and thickness of tunica albuginea were measured by stereological method. Means were compared using the Kolmogorov-Smirnov and ANOVA test (P <.05).Results: We did not observe difference in PTL (P = .999) when we compared the control group (4.69-29.77 mm, mean = 16.2 mm; SD = 6.34 mm) with the PBS (12.23-23 mm, mean = 16.16; SD = 4.99). The total penile area (P = .002), the area of corpora cavernosa (P = .023) and the area of corpus spongiosum (P = .004) had a significant increase when comparing the PBS with the control group.Conclusion: In fetuses with PBS there is no change in the length of the penis but we observed a low rate of growth in all the other histologic parameters analyzed, suggesting that PBS impacts the penile development. [ABSTRACT FROM AUTHOR]

Analyze the biometric parameters and the size (area) of abdominal wall defect (AWD) in fetuses with gastroschisis and omphaloceles and correlate them with the herniated internal organs. We studied 22 fetuses (11 with AWDs and 11 without anomalies). In all fetuses we evaluated the xiphopubic distance (XPD) and iliac crest distance (ICD). In fetuses with AWDs we dissected the abdominal wall and measured the width and length of the defect for calculating its area and studying the correlation between the size of the defect with the organs that were herniated. For statistical analysis, the Anova and Tukey post-test were used (p < 0.05). The XPD in the control group had mean of 4.2 mm (2.3–5.9; SD ± 1.11), while in the AWDs it was 4.2 mm (2.9–5.5; SD ± 0.98) (p = 0.4366). The ICD had mean values of 2.5 mm (1.6–3.4; SD ± 0.58) in the control group, and 2.3 mm (1.2–3.0; SD ± 0.56) in AWDs fetuses (p = 0.6963). The number of herniate organs do not have significant correlation with the area of the defect (r2 = 0.2504, p = 0.5068). There is no correlation between the size (area) of abdominal wall defects and the number of the internal organs that herniated. Therefore, the hole size is not a predictor of the severity of the gastroschisis or omphalocele. [ABSTRACT FROM AUTHOR]

Objective: To characterize the bulbospongiosus muscle (BSM) in patients with bulbar urethral strictures.Materials and Methods: We studied 21 patients divided into 2 groups: Stricture Group (n = 14; mean age = 62.00 years) with bulbar stricture submitted to open urethroplasty; and Control Group (n = 7; mean age = 60.14 years) with penile strictures (hypospadias cripples, penile cancer and/or penile infection) who were submitted to perineal urethrostomy. Samples of the BSM were dissected and histologic sections were stained by histochemical and immunohistochemical techniques. Histomorphometric analyzes were performed on photomicrographs. Means were statistically compared using the unpaired Student t test and the Mann-Whitney test (P <.05).Results: The etiology of bulbar urethral stricture was idiopathic in 2 cases (14.29%), post-TURP in 6 (42.86%), post open radical prostatectomy in 5 (35.71%) and post open prostatectomy in 1 case (7.14%). The average length of the stricture was 2.08 cm. The only parameter analyzed with significant difference between the groups was the vessels (significant difference between the control group: 5.11 ± 1.98% and stricture group: 3.57 ± 1.32%, P = .0460). The quantitative analysis of collagen (Control Group: 10.63 ± 5.37% and Stricture Group: 10.83 ± 4.55%, P = .9296); diameter of BSM muscle fibers (Control Group: 41.71 ± 14.63 µm and Stricture Group: 40.11 ± 8.59 µm, P = .76 and elastic system fibers (Control Group; 3.83 ± 1.54% and Stricture Group: 5.43 ± 2.90%, P = .2601) showed no significant difference.Conclusions: Histologic analysis showed a significant decrease of the BSM vessels in urethral stricture, without changes in elastic fibers, collagen, nerves, and muscle fiber diameter. These findings show that the bulbar urethral stricture causes minimal alterations in the structure of the BSM. [ABSTRACT FROM AUTHOR]

Objective: To evaluate, by using scanning electron microscopy (SEM), the possible alterations of the foreskin connective tissue in patients with true phimosis submitted to topical treatment with betamethasone and hyaluronidase ointment.Materials and Methods: We studied 15 patients (mean 5.3 years old) submitted or not to topical application of betamethasone 0.2% and hyaluronidase cream. For qualitative analysis of the connective tissue, we studied 5 samples from each foreskin, with 2 mm length. The samples were submitted to fixation for SEM by immersing tissue fragments in a modified Karnovsky solution for 48 hours at 4°C. The obtained acellular preparations were then processed for high-vacuum SEM, and observations were performed on a LEO 435 (Zeiss, Oberkochen, Germany) scanning electron microscope with an acceleration voltage of 15 to 20 kV.Results: Parents of 7 children did not agree with the clinical treatment and opted for circumcision directly. These patients served as the control group (nontreated). Eight patients submitted to topical treatment could not expose the glans and were referred for circumcision. In SEM, with a magnification of 5000×, we observed important differences in the organization of the collagen and elastic system fibers when comparing treated and nontreated patients with betamethasone and hyaluronidase. Treated patients presented a different organization of collagen with a clear decrease in the elastic system fibers.Conclusion: The treatment of phimosis with betamethasone + hyaluronidase showed changes in the structure of the foreskin with a decrease of elastic system fibers, which is characteristic of the healing processes. [ABSTRACT FROM AUTHOR]

Background: The penile erectile tissue has a complex microscopic anatomy with important functions in the mechanism of penile erection. The knowledge of such structures is necessary for understanding the normal physiology of the adult penis. Therefore, it is important to know the changes of these penile structures during fetal development. This study aims to analyze the development of the main components of the erectile tissue, such as collagen, smooth muscle fibers and elastic system fibers, in human fetuses. Methodology/Principal Findings: We studied the penises of 56 human fetuses aged 13 to 36 weeks post-conception (WPC). We used histochemical and immunohistochemical staining, as well as morphometric techniques to analyze the collagen, smooth muscle fibers and elastic system fibers in the corpus cavernosum and in the corpus spongiosum. These elements were identified and quantified as percentage by using the Image J software (NIH, Bethesda, USA). From 13 to 36 WPC, in the corpus cavernosum, the amount of collagen, smooth muscle fibers and elastic system fibers varied from 19.88% to 36.60%, from 4.39% to 29.76% and from 1.91% to 8.92%, respectively. In the corpus spongiosum, the amount of collagen, smooth muscle fibers and elastic system fibers varied from 34.65% to 45.89%, from 0.60% to 11.90% and from 3.22% to 11.93%, respectively. Conclusions: We found strong correlation between the elements analyzed with fetal age, both in corpus cavernosum and corpus spongiosum. The growth rate of these elements was more intense during the second trimester (13 to 24 WPC) of gestation, both in corpus cavernosum and in corpus spongiosum. There is greater proportional amount of collagen in the corpus spongiosum than in corpus cavernosum during all fetal period. In the corpus spongiosum, there is about four times more collagen than smooth muscle fibers and elastic system fibers, during all fetal period studied. [ABSTRACT FROM AUTHOR]

Working towards mentally healthy societies is fundamental for Latin American countries, in order to keep the pace of development. Although awareness about the importance of mental health research is increasing in Latin America, the mismatch between needs and investment (the 10/90 gap) is still present. During recent years, many initiatives have been fostered to promote mental health research in the region. This paper summarizes the information collected through those efforts, in addition to presenting the current state of research in the field of psychiatry and mental health in Latin American countries. Future perspectives for the field in the region are discussed in terms of funding, research priorities and research resources, as well as the potential of Latin American countries to insert themselves within global psychiatry/mental health research efforts. [ABSTRACT FROM AUTHOR]

Background: Research evidence is essential to inform policies, interventions and programs, and yet research activities in mental and neurological (MN) health have been largely neglected, particularly in low- and middle-income countries. Many challenges have been identified in the production and utilization of research evidence in Latin American countries, and more work is needed to overcome this disadvantageous situation. This study aims to address the situation by identifying initiatives that could improve MN health research activities and implementation of their results in the Latin American region. Methods: Thirty-four MN health actors from 13 Latin American countries were interviewed as part of an initiative by the Global Forum for Health Research and the World Health Organization to explore the status of MN health research in low- and middle-income countries in Africa, Asia and Latin-America. Results: A variety of recommendations to increase MN health research activities and implementation of their results emerged in the interviews. These included increasing skilled human resources in MN health interventions and research, fostering greater participation of stakeholders in the generation of research topics and projects, and engendering the interest of national and international institutions in important MN health issues and research methodologies. In the view of most participants, government agencies should strive to have research results inform the decision-making process in which they are involved. Thus these agencies would play a key role in facilitating and funding research. Participants also pointed to the importance of academic recognition and financial rewards in attracting professionals to primary and translational research in MN health. In addition, they suggested that institutions should create intramural resources to provide researchers with technical support in designing, carrying out and disseminating research, including resources to improve scientific writing skills. Conclusion: Fulfillment of these recommendations would increase research production in MN health in Latin American countries. This, in turn, will raise the profile of these health problems, and consequently will underscore the need of continued high-quality and relevant research, thus fostering a virtuous cycle in the decision-making process to improve MN health care. [ABSTRACT FROM AUTHOR]

Objective: The World Health Organization Atlas Project identified important deficiencies in world mental and neurological health resources. These deficiencies, especially evident in low and middle-income countries, can be overcome by improving research capacity. The objective of this study is to assess the status of mental and neurological research in Latin American countries and identify the main difficulties encountered in conducting research, publishing results, and shaping health policies, interventions, and programs. Method; Semi-structured interviews were conducted with 34 key informants from 13 Latin American countries. Results: Participants reported that production of mental and neurological research in Latin American countries is love Lack of financial and human resources, including lack of support from government agencies, were identified as the main factors contributing to the dearth of local research. The few research projects that do take place in Latin American countries are often funded at researchers' personal expense. Few policies, interventions, or programs are generated from research results. To address these deficiencies, participants called for training in research methodology, mechanisms for identifying funding opportunities, and greater recognition of their research products. Conclusions: Researchers and stakeholders recognize the need to mobilize local and international efforts aimed at strengthening research capacity and results implementation. This will lead to an overall optimization of mental and neurological research in the region. [ABSTRACT FROM AUTHOR]

Human ear morphology, a complex anatomical structure represented by a multidimensional set of correlated and heritable phenotypes, has a poorly understood genetic architecture. In this study, we quantitatively assessed 136 ear morphology traits using deep learning analysis of digital face images in 14,921 individuals from five different cohorts in Europe, Asia, and Latin America. Through GWAS meta-analysis and C-GWASs, a recently introduced method to effectively combine GWASs of many traits, we identified 16 genetic loci involved in various ear phenotypes, eight of which have not been previously associated with human ear features. Our findings suggest that ear morphology shares genetic determinants with other surface ectoderm-derived traits such as facial variation, mono eyebrow, and male pattern baldness. Our results enhance the genetic understanding of human ear morphology and shed light on the shared genetic contributors of different surface ectoderm-derived phenotypes. Additionally, gene editing experiments in mice have demonstrated that knocking out the newly ear-associated gene (Intu) and a previously ear-associated gene (Tbx15) causes deviating mouse ear morphology. Author summary: Human ear morphology varies widely, with largely inherited differences. However, the genetic basis for these differences is not well understood. To better understand the genetics of human ear morphology, we analyzed 136 ear traits from digital facial images of 14,921 individuals from three continents using GWAS meta-analysis and the recently developed C-GWAS method. We identified 16 genetic loci associated with ear morphology, eight of which had not been previously associated with ear features. These genetic loci can serve as candidates for future research to understand the function of these genes. Additionally, we have demonstrated the impact of two ear-associated loci on ear morphology in gene-edited mice. This study provides new insights into the complex genetics of the human ear. [ABSTRACT FROM AUTHOR]

Dental size variation in modern humans has been assessed from regional to worldwide scales, especially under microevolutionary and forensic contexts. Despite this, populations of mixed continental ancestry such as contemporary Latin Americans remain unexplored. In the present study we investigated a large Latin American sample from Colombia (N = 804) and obtained buccolingual and mesiodistal diameters and three indices for maxillary and mandibular teeth (except third molars). We evaluated the correlation between 28 dental measurements (and three indices) with age, sex and genomic ancestry (estimated using genome-wide SNP data). In addition, we explored correlation patterns between dental measurements and the biological affinities, based on these measurements, between two Latin American samples (Colombians and Mexicans) and three putative parental populations: Central and South Native Americans, western Europeans and western Africans through PCA and DFA. Our results indicate that Latin Americans have high dental size diversity, overlapping the variation exhibited by the parental populations. Several dental dimensions and indices have significant correlations with sex and age. Western Europeans presented closer biological affinities with Colombians, and the European genomic ancestry exhibited the highest correlations with tooth size. Correlations between tooth measurements reveal distinct dental modules, as well as a higher integration of postcanine dentition. The effects on dental size of age, sex and genomic ancestry is of relevance for forensic, biohistorical and microevolutionary studies in Latin Americans. [ABSTRACT FROM AUTHOR]

Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions. One region includes EDAR , a gene known to impact dental features in East Asians. Furthermore, we find that EDAR variants increase the mesiodistal diameter of all teeth, following an anterior-posterior gradient of decreasing strength. Among the 17 novel-associated regions, we replicate 7/13 in an independent human cohort and find that 4/12 orthologous regions affect molar size in mice. Two association signals point to compelling candidate genes. One is ∼61 kb from PITX2 , a major determinant of tooth development. Another overlaps HS3ST3A1 , a paralogous neighbor of HS3ST3B1 , a tooth enamel knot factor. We document the expression of Pitx2 and Hs3st3a1 in enamel knot and dental epithelial cells of developing mouse incisors. Furthermore, associated SNPs in PITX2 and HS3ST3A1 overlap enhancers active in these cells, suggesting a role for these SNPs in gene regulation during dental development. In addition, we document that Pitx2 and Hs3st3a1/Hs3st3b1 knockout mice show alterations in dental morphology. Finally, we find that associated SNPs in HS3ST3A1 are in a DNA tract introgressed from Neanderthals, consistent with an involvement of HS3ST3A1 in tooth size variation during human evolution. • Genome-wide association identifies variants impacting dental crown dimensions • EDAR variants affect tooth dimensions following an anterior-posterior gradient • Variants in PITX2 and HS3ST3A1 regulate gene expression during tooth development • Associated variants in HS3ST3A1 were introgressed from Neanderthals Tooth morphology varies through evolution and in modern human populations, but little is known about the genetics of this variation. Li et al. identify genes associated with tooth crown dimensions and expressed during dental development. Variants in one gene stem from Neanderthal, suggesting their role in human dental evolution. [ABSTRACT FROM AUTHOR]

Purpose: One of the most common malformations of the central nervous system is related to embryonic neural tube alterations. We hypothesized that anencephaly affects the development of the vagina during the human second trimester of pregnancy. Our study compared the biometric parameters of the vagina in human female fetuses with neural tube defects. Methods: In our study, 34 female fetuses were analyzed, 22 normal and 12 anencephalic, aged between 12 and 22 weeks post conception (WPC). After dissection of the pelvis and individualization of the genital tract, we evaluated the length and width of the vagina using the Image J software. We compared the means statistically using the Wilcoxon–Mann–Whitney test and performed linear regression. Results: We do not identify statistical significance between the groups for the measurements of vaginal length (Control 3.12–18.33 mm/mean = 9.08 mm/SD + − 3.77 vs. Anencephalic 2.91–13.10 mm/mean = 7.24 mm/SD + − 2.28, p = 0.3469) and vaginal width (Control 1.04–4.86 mm/mean = 2.71 mm/SD + − 0.94 vs. Anencephalic 1.35–3.17 mm/mean = 2.13 mm/SD + − 0.65; p = 0.2503). The linear regression analysis indicated that 78.57% significance was found in the correlations in normocephalic fetuses and 57.14% significance in anencephalic fetuses (12.3–18.6 WPC). Conclusions: We do not find differences in the length and width of the vagina in anencephalic fetuses but the vaginal length and width shows a lesser tendency of growth in the anencephalic fetuses during the second trimester suggesting that anencephaly can impact the development of the vagina. [ABSTRACT FROM AUTHOR]

One of the most common malformations of the central nervous system is related to embryonic neural tube alterations. We hypothesized that anencephaly affects the development of the uterus during the human second trimester of pregnancy. The objective of this study was to study the biometric parameters of the uterus in fetuses with anencephaly and compare them with normocephalic fetuses at that important. In our study, 34 female fetuses were analyzed, 22 normal and 12 anencephalic, aged between 12 and 22 weeks post-conception (WPC). After dissection of the pelvis and individualization of the genital tract, we evaluated the length and width of the uterus using the Image J software. We compared the means statistically using the Wilcoxon-Mann–Whitney test and performed linear regression. We identify significant differences between the uterus length (mm)/weight (g) × 100 (p = 0.0046) and uterus width (mm)/weight (g) × 100 (p = 0.0013) when we compared the control with the anencephalic group. The linear regression analysis indicated that 80% significance was found in the correlations in normocephalic fetuses (12.9 to 22.6 WPC) and 40% significance in anencephalic fetuses (12.3 to 18.6 WPC). The measurements of the uterus were greater in anencephalic group but there are no difference in the uterine width and length growth curves during the period studied. Further studies are required to support the hypothesis suggesting that anencephaly may affect uterine development during the human fetal period. [ABSTRACT FROM AUTHOR]

Objectives. To assess the predictive effect of key individual-level characteristics to identify cases of alcohol use problems among patients visiting an emergency room. Materials and methods. The study sample was composed of 371 people attending an emergency room in a public hospital in Lima, Peru, during a period of seven complete days in January, 2005. for data gathering, we used a questionnaire for demographic information, the SIDUC/CICAD for recent use (i.e., in the last 6 hours) of psychoactive substances before arriving to the emergency room, and the AUDIT, to identify alcohol use problems in the last year. Univariate and multivariate logistic regression models were used to estimate the predictive effect of age, sex, area of attention in the emergency room, presence of physical injuries and recent use of alcohol. Results. The odds of being a case of alcohol use problem for males is 26 times the odds of having that problem for females (p-value<0,001). Stratified analysis by sex and adjusted by age and area of attention in the emergency room, showed that males who had recent use of alcohol were more likely of having alcohol use problems as compared to those who did not have recent alcohol use (OR=5.2; 95% CI: 2.4 - 11.5; p<0,001), while for females such an association did not exist. Conclusions. These results support screening initiatives for those males who have recent alcohol use before arriving to an emergency room in order to identify cases of alcohol-related problems and refer them for an appropriate counseling or medical treatment. [ABSTRACT FROM AUTHOR]

The Human Leukocyte Antigen (HLA) loci are extremely well documented targets of balancing selection, yet few studies have explored how selection affects population differentiation at these loci. In the present study we investigate genetic differentiation at HLA genes by comparing differentiation at microsatellites distributed genomewide to those in the MHC region. Our study uses a sample of 494 individuals from 30 human populations, 28 of which are Native Americans, all of whom were typed for genomewide and MHC region microsatellites. We find greater differentiation in the MHC than in the remainder of the genome (F ST-MHC = 0.130 and F ST-Genomic = 0.087), and use a permutation approach to show that this difference is statistically significant, and not accounted for by confounding factors. This finding lies in the opposite direction to the expectation that balancing selection reduces population differentiation. We interpret our findings as evidence that selection favors different sets of alleles in distinct localities, leading to increased differentiation. Thus, balancing selection at HLA genes simultaneously increases intra-population polymorphism and inter-population differentiation in Native Americans. [ABSTRACT FROM AUTHOR]

Self-perception of ethnicity is a complex social trait shaped by both, biological and non-biological factors. We developed a comprehensive analysis of ethnic self-perception (ESP) on a large sample of Latin American mestizos from five countries, differing in age, socio-economic and education context, external phenotypic attributes and genetic background. We measured the correlation of ESP against genomic ancestry, and the influence of physical appearance, socio-economic context, and education on the distortion observed between both. Here we show that genomic ancestry is correlated to aspects of physical appearance, which in turn affect the individual ethnic self-perceived ancestry. Also, we observe that, besides the significant correlation among genomic ancestry and ESP, specific physical or socio-economic attributes have a strong impact on self-perception. In addition, the distortion among ESP and genomic ancestry differs across age ranks/countries, probably suggesting the underlying effect of past public policies regarding identity. Our results indicate that individuals' own ideas about its origins should be taken with caution, especially in aspects of modern life, including access to work, social policies, and public health key decisions such as drug administration, therapy design, and clinical trials, among others. [ABSTRACT FROM AUTHOR]

The American continent was the last to be occupied by modern humans, and native populations bear the marks of recent expansions, bottlenecks, natural selection, and population substructure. Here we investigate how this demographic history has shaped genetic variation at the strongly selected HLA loci. In order to disentangle the relative contributions of selection and demography process, we assembled a dataset with genome-wide microsatellites and HLA-A, -B, -C, and -DRB1 typing data for a set of 424 Native American individuals. We find that demographic history explains a sizeable fraction of HLA variation, both within and among populations. A striking feature of HLA variation in the Americas is the existence of alleles which are present in the continent but either absent or very rare elsewhere in the world. We show that this feature is consistent with demographic history (i.e., the combination of changes in population size associated with bottlenecks and subsequent population expansions). However, signatures of selection at HLA loci are still visible, with significant evidence selection at deeper timescales for most loci and populations, as well as population differentiation at HLA loci exceeding that seen at neutral markers. [ABSTRACT FROM AUTHOR]

Recently, there has been a major shift in the field of psychiatry towards the exploration of complex relationships between blood-based biomarkers and the pathophysiology of psychiatric and neuropsychiatric disorders. However, issues with study reproducibility, validity and reliability have hindered progress towards the identification of clinically relevant biomarkers for psychiatry. The achievement of laboratory validity is a crucial first step for the posterior development of clinical validity. There is evidence that the variability observed in blood-based research studies may be minimised with the implementation of standardised pre-analytical methods and uniform clinical protocols (i.e., pre-venipuncture). It has been documented that errors made in the pre-analytical phase account for 46–68.2% of laboratory testing errors. Thus, standardising clinical assessment, ethical procedures and pre-analytical phase of clinical research is essential for the reproducibility, validity and reliability of blood marker assessment, and reducing the risk of invalid test results. Various other areas of research have already moved towards guidelines for the standardised collection of blood-based biomarkers. Here we aim to provide a set of guidelines that we believe would improve biomarker research: (1) pre-venipuncture information and documentation, (2) ethics of participant consent and (3) pre-analytical methods. Ultimately, we hope this will assist study planning and will improve data comparison across studies allowing for the discovery of biomarkers in psychiatry with both laboratorial and clinical validity. [ABSTRACT FROM AUTHOR]

Abstract Background Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. Methods We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. Results Only two loci were associated with SUA levels: SLC2A9 (β = −0.47 mg/dl, P = 1.57 × 10−42 for lead SNP rs7678287) and ABCG2 (β = 0.23 mg/dl, P = 2.42 × 10−10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (P = 0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. Conclusions SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD. Highlights • High uric acid levels have been associated with coronary artery disease. • The causality of this association is a matter of debate. • A GWAS identified SLC2A9 and ABCG2 associated with SUA levels in Mexicans. • Mendelian randomization did not support a causal role for premature CAD. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the variation in dental nonmetric traits and to evaluate the utility of this variation for inferring genetic ancestry proportions in a sample of admixed Latin Americans. Materials and Methods: We characterized a sample from Colombia (N = 477) for 34 dental traits and obtained estimates of individual Native American, European, and African ancestry using genome‐wide SNP data. We tested for correlation between dental traits, genetic ancestry, age, and sex. We carried out a biodistance analysis between the Colombian sample and reference continental population samples using the mean measure of divergence statistic calculated from dental trait frequencies. We evaluated the inference of genetic ancestry from dental traits using a regression approach (with 10‐fold cross‐validation) as well as by testing the correlation between estimates of ancestry obtained from genetic and dental data. Results: Latin Americans show intermediate dental trait frequencies when compared to Native Americans, Europeans, and Africans. Significant correlations were observed for several dental traits, genetic ancestry, age, and sex. The biodistance analysis displayed a closer relationship of Colombians to Europeans than to Native Americans and Africans. Mean ancestry estimates obtained from the dental data are similar to the genetic estimates (Native American: 32% vs. 28%, European: 59% vs. 63%, and African: 9% vs. 9%, respectively). However, dental features provided low predictive power for genetic ancestry of individuals in both approaches tested (R2 < 5% for all genetic ancestries across methods). Discussion: The frequency of dental traits in Latin Americans reflects their admixed Native American, European and African ancestry and can provide reasonable average estimates of genetic ancestry. However, the accuracy of individual genetic ancestry estimates is relatively low, probably influenced by the continental differentiation of dental traits, their genetic architecture, and the distribution of genetic ancestry in the individuals examined. [ABSTRACT FROM AUTHOR]

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10−10) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10−8). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10−11) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is common in pregnant women and infants. The present study aimed to investigate the effects of vitamin D restricted diet on the Wistar rats offspring penis morphology. Mother rats received either standard diet (SC) or vitamin D restricted (VitD) diet. At birth, offspring were divided into SC/SC (from SC mothers, fed with SC diet) and VitD/VitD (from VitD mothers, fed with VitD diet). After euthanasia the penises were processed for histomorphometric analysis. The VitD/VitD offspring displayed metabolic changes and reduction in the cross-sectional area of the penis, corpus cavernosum, tunica albuginea, and increased area of the corpus spongiosum. The connective tissue, smooth muscle, and cell proliferation percentages were greater in the corpus cavernosum and corpus spongiosum in the VitD/VitD offspring. The percentages of sinusoidal spaces and elastic fibers in the corpus cavernosum decreased. The elastic fibers in the tunica albuginea of the corpus spongiosum in the VitD/VitD offspring were reduced. Vitamin D restriction during perinatal and postnatal periods induced metabolic and structural changes and represented important risk factors for erectile dysfunction in the penis of the adult offspring. These findings suggest that vitamin D is an important micronutrient in maintaining the cytoarchitecture of the penis. [ABSTRACT FROM AUTHOR]

The genetic basis of earlobe attachment has been a matter of debate since the early 20 th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). Meta-analysis of the three expert-rater-scored cohorts revealed six associated loci harboring numerous candidate genes, including EDAR , SP5 , MRPS22 , ADGRG6 ( GPR126 ), KIAA1217 , and PAX9 . The large self-reported 23andMe cohort recapitulated each of these six loci. Moreover, meta-analysis across all four cohorts revealed a total of 49 significant (p < 5 × 10 −8 ) loci. Annotation and enrichment analyses of these 49 loci showed strong evidence of genes involved in ear development and syndromes with auricular phenotypes. RNA sequencing data from both human fetal ear and mouse second branchial arch tissue confirmed that genes located among associated loci showed evidence of expression. These results provide strong evidence for the polygenic nature of earlobe attachment and offer insights into the biological basis of normal and abnormal ear development. [ABSTRACT FROM AUTHOR]

Objectives:Schizophrenia is a severe psychiatric disease affecting about 1% of the general population. The relative contribution of genetic factors has been estimated to be up to 80%. The mode of inheritance is complex, non-Mendelian, and in most cases involving the combined action of large numbers of genes. Methods:This review summarises recent efforts to identify genetic variants associated with schizophrenia detected, e.g., through genome-wide association studies, studies on copy-number variants or next-generation sequencing. Results:A large, new body of evidence on genetics of schizophrenia has accumulated over recent years. Many new robustly associated genetic loci have been detected. Furthermore, there is consensus that at least a dozen microdeletions and microduplications contribute to the disease. Genetic overlap between schizophrenia, other psychiatric disorders, and neurodevelopmental syndromes raised new questions regarding the current classification of psychiatric and neurodevelopmental diseases. Conclusions:Future studies will address especially the functional characterisation of genetic variants. This will hopefully open the doors to our understanding of the pathophysiology of schizophrenia and other related diseases. Complementary, integrated systems biology approaches to genomics, transcriptomics, proteomics and metabolomics may also play crucial roles in enabling a precision medicine approach to the treatment of individual patients. [ABSTRACT FROM PUBLISHER]

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10−27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data. [ABSTRACT FROM AUTHOR]

Accurate gathering of phenotypic information is a key aspect in several subject matters, including biometrics, biomedical analysis, forensics, and many other. Automatic identification of anatomical structures of biometric interest, such as fingerprints, iris patterns, or facial traits, are extensively used in applications like access control and anthropological research, all having in common the drawback of requiring intrusive means for acquiring the required information. In this regard, the ear structure has multiple advantages. Not only the ear's biometric markers can be easily captured from the distance with non intrusive methods, but also they experiment almost no changes over time, and are not influenced by facial expressions. Here we present a new method based on Geometric Morphometrics and Deep Learning for automatic ear detection and feature extraction in the form of landmarks. A convolutional neural network was trained with a set of manually landmarked examples. The network is able to provide morphometric landmarks on ears' images automatically, with a performance that matches human landmarking. The feasibility of using ear landmarks as feature vectors opens a novel spectrum of biometrics applications. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under- or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in antidepressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4andHTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (includingBDNF, cortisol and soluble TNF-α receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions. [ABSTRACT FROM PUBLISHER]

The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries. [ABSTRACT FROM AUTHOR]

ABSTRACT Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genome's heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant, the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estimators, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise. Am J Phys Anthropol 157:58-70, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives. Describe the availability of psychotropic medications for the treatment of mental disorders in the health care facilities of the Ministry of Health of Peru. Materials and methods. Monthly inventory reports of the availability and consumption of medications in facilities of the Ministry of Health during 2011 were analyzed. Using a cross sectional design, the availability of seven classes of psychotropic medications was determined. Also, the level of care of the establishments and the level of decisional autonomy to purchase medications were determined. Results. Anti-anxiety medications were available in health facilities of all levels of care. Antidepressants and antipsychotics were available in about two thirds of hospitals and in less than 20% of health centers and small health clinics. The other four classes of psychotropic medications (lithium, hypnotics and sedatives, psychostimulants/ADHD, and anti-dementia drugs) were only available in hospitals and not in health centers and small health clinics. 5% of hospitals had a sufficient supply to meet the demand for the year. Conclusions. There is a significant gap in the availability of psychotropic medications in the health care facilities of the Ministry of Health of Peru. This was observed both in hospitals and in primary care facilities. Actions are needed in health policy and management, including more funding and greater mental health training for staff in primary care, among other initiatives. [ABSTRACT FROM AUTHOR]

The understanding of the complex genotype-phenotype architecture of human pigmentation has clear implications for the evolutionary history of humans, as well as for medical and forensic practices. Although dozens of genes have previously been associated with human skin color, knowledge about this trait remains incomplete. In particular, studies focusing on populations outside the European-North American axis are rare, and, until now, admixed populations have seldom been considered. The present study was designed to help fill this gap. Our objective was to evaluate possible associations of 18 single nucleotide polymorphisms (SNPs), located within nine genes, and one pseudogene with the Melanin Index (MI) in two admixed Brazilian populations (Gaucho, N = 352; Baiano, N = 148) with different histories of geographic and ethnic colonization. Of the total sample, four markers were found to be significantly associated with skin color, but only two (SLC24A5 rs1426654, and SLC45A2 rs16891982) were consistently associated with MI in both samples (Gaucho and Baiano). Therefore, only these 2 SNPs should be preliminarily considered to have forensic significance because they consistently showed the association independently of the admixture level of the populations studied. We do not discard that the other two markers (HERC2 rs1129038 and TYR rs1126809) might be also relevant to admixed samples, but additional studies are necessary to confirm the real importance of these markers for skin pigmentation. Finally, our study shows associations of some SNPs with MI in a modern Brazilian admixed sample, with possible applications in forensic genetics. Some classical genetic markers in Euro-North American populations are not associated with MI in our sample. Our results point out the relevance of considering population differences in selecting an appropriate set of SNPs as phenotype predictors in forensic practice. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether l-arginine has protective effects against radiation-induced alterations in the morphology and regulatory factors of vesical blood vessels in rats. Methods: Male rats aged 3-4 months were divided into groups of 10 animals each: (a) controls, consisting of non-treated animals; (b) radiated-only rats; and (c) radiated rats receiving l-arginine supplementation. Radiation was in one session of 10 Gy and was aimed at the pelvic-abdominal region. l-arginine was administered once a day (0.65 g/kg body weight), starting 7 days before radiation and continuing until killing on the 16th day after radiation. The density, relative area, and wall thickness of blood vessels were measured in the vesical lamina propria using histological methods, and the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGF) in the bladder wall was assessed by RT-PCR. Results: Compared with controls, radiation alone decreased the density and relative area of blood vessels by 32 % ( p < 0.01) and 25 % ( p < 0.05), respectively, and reduced the arterial wall thickness by 42 % ( p < 0.004). VEGF and FGF mRNA levels after radiation were diminished by 67 % ( p < 0.002) and 56 % ( p < 0.04), respectively. The radiated animals supplemented with l-arginine were not significantly different from controls. Conclusions: Pelvic radiation leads to significant vesical modifications, as in the morphology of blood vessels and in VEGF and FGF expression. All these changes, however, were prevented by l-arginine treatment. These results emphasize, therefore, the potential use of this amino acid as a radioprotective drug. [ABSTRACT FROM AUTHOR]

We report an integrated analysis of nuclear (autosomal, X- and Y-chromosome) short tandem repeat (STR) data and mtDNA D-loop sequences obtained in the same set of 22 Native populations from across the Americas. A north to south gradient of decreasing population diversity was observed, in agreement with a settlement of the Americas from the extreme northwest of the continent. This correlation is stronger with 'least cost distances,' which consider the coasts as facilitators of migration. Continent-wide estimates of population structure are highest for the Y-chromosome and lowest for the autosomes, consistent with the effective size of the different marker systems examined. Population differentiation is highest in East South America and lowest in Meso America and the Andean region. Regional analyses suggest a deviation from mutation-drift equilibrium consistent with population expansion in Meso America and the Andes and population contraction in Northwest and East South America. These data hint at an early divergence of Andean and non-Andean South Americans and at a contrasting demographic history for populations from these regions. [ABSTRACT FROM AUTHOR]

The large and diverse population of Latin America is potentially a powerful resource for elucidating the genetic basis of complex traits through admixture mapping. However, no genome-wide characterization of admixture across Latin America has yet been attempted. Here, we report an analysis of admixture in thirteen Mestizo populations (i.e. in regions of mainly European and Native settlement) from seven countries in Latin America based on data for 678 autosomal and 29 Xchromosome microsatellites. We found extensive variation in Native American and European ancestry (and generally low levels of African ancestry) among populations and individuals, and evidence that admixture across Latin America has often involved predominantly European men and both Native and African women. An admixture analysis allowing for Native American population subdivision revealed a differentiation of the Native American ancestry amongst Mestizos. This observation is consistent with the genetic structure of pre-Columbian populations and with admixture having involved Natives from the area where the Mestizo examined are located. Our findings agree with available information on the demographic history of Latin America and have a number of implications for the design of association studies in population from the region. [ABSTRACT FROM AUTHOR]

We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians--signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas. [ABSTRACT FROM AUTHOR]

Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America. [ABSTRACT FROM AUTHOR]

Objectives: This article aims to assess the contribution of genomic ancestry and socioeconomic status to obesity in a sample of admixed Latin Americans. Methods: The study comprised 6776 adult volunteers from Brazil, Chile, Colombia, Mexico, and Peru. Each volunteer completed a questionnaire about socioeconomic variables. Anthropometric variables such as weight, height, waist, and hip circumference were measured to calculate body indices: body mass index, waist‐to‐hip ratio and waist‐to‐height ratio (WHtR). Genetic data were extracted from blood samples, and ancestry was estimated using chip genotypes. Multiple linear regression was used to evaluate the relationship between the indices and ancestry, educational level, and economic well‐being. The body indices were dichotomized to obesity indices by using appropriate thresholds. Odds ratios were calculated for each obesity index. Results: The sample showed high percentages of obesity by all measurements. However, indices did not overlap consistently when classifying obesity. WHtR resulted in the highest prevalence of obesity. Overall, women with low education level and men with high economic wellness were more likely to be obese. American ancestry was statistically associated with obesity indices, although to a lesser extent than socioeconomic variables. Conclusions: The proportion of obesity was heavily dependent on the index and the population. Genomic ancestry has a significant influence on the anthropometric measurements, especially on central adiposity. As a whole, we detected a large interpopulation variation that suggests that better approaches to overweight and obesity phenotypes are needed in order to obtain more precise reference values. [ABSTRACT FROM AUTHOR]