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INTRODUCTION: Although nerves and vessels of the penis play important role in erection, there are few studies on their development in human fetus. Therefore, the objective of the present study is to analyze, quantitatively, in the corpora cavernosa and corpus spongiosum, the development of the nerves and vessels in the fetal penis at different gestational ages. MATERIAL AND METHODS: Fifty-six fresh, macroscopically normal human fetuses aged from 13 to 36 weeks post-conception (WPC) were used. Gestational age was determined by the foot length criterion. Penises were immediately fixed in 10% formalin, and routinely processed for paraffin embedding, after which tissue sections from the mid-shaft were obtained. We used immunohistochemical staining to analyze the nerves and vessels in the corpus cavernous and in the corpus spongiosum. These elements were identified and quantified as percentage by using the Image-J software. RESULTS: The quantitative analysis showed that the percentage of nerves varied from 3.03% to 20.35% in the corpora cavernosa and from 1.89% to 23.88% in the corpus spongiosum. The linear regression analysis indicated that nerves growth (incidence) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.9421, p<0.0001) and (r2=0.9312, p<0.0001), respectively, during the whole fetal period studied. Also, the quantitative analysis showed that the percentage of vessels varies from 2.96% to 12.86% in the corpora cavernosa and from 3.62% to 14.85% in the corpus spongiosum. The linear regression analysis indicated that vessels growth (appearance) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.8722, p<0.0001) and (r2=0.8218, p<0.0001), respectively, during the whole fetal period studied. In addition, the linear regression analysis demonstrated a more intense growth rate of nerves in the corpus spongiosum during the 2nd trimester of gestation, when compared with nerves in the corpora cavernosa. In addition, the linear regression analysis demonstrated a more intense growth rate of vessels in the corpus spongiosum when compared with the corpora cavernosa, during the whole fetal period studied. CONCLUSIONS: In the fetal period, the human penis undergoes major developmental changes, notably in the content and distribution of nerves and vessels. We found strong correlation between nerves and vessels growth (amount) with fetal age, both in the corpora cavernosa and corpus spongiosum. There is significant greater proportional number of nerves than vessels during the whole fetal period studied. Also, nerves and vessels grow in a more intense rate than that of the corpora cavernosa and corpus spongiosum areas.

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ABSTRACT Purpose: To analyze the histology and distribution of abdominal testicular vessels in human fetuses Patients and Methods: We studied 19 fetuses (34 testes) ranging in age from 12 to 19 weeks post-conception. The fetuses were evaluated regarding crown-rump length (CRL), total length (TL) and body weight immediately before dissection. Each testis was dissected and embedded in paraffin, from which 5 µm thick sections were obtained and stained with Masson's trichrome and Anti-CD31 antibody to quantify the vessels. The stereological analysis was carried out with the Image Pro and Image J programs, using a grid to determine volumetric densities (Vv). Means were statistically compared using the unpaired T-test (p<0.05). Results: The fetuses presented mean weight of 222.5g, mean CRL of 15.3 cm and mean TL of 23.2 cm. All testes were in the abdominal position. The mean percentage of vessels (Vv) in the upper portion of the testis was 7.6% (4.6 to 15%) and in the lower portion the mean was 5.11% (2.3 to 9.8%), with a significant difference (p=0.0001). In the analysis between the upper portion of the right and left testes (p=0.99) and in the analysis of the lower portion of the right and left testes (p=0.83), we did not observe significant differences. Conclusion: The upper portion of the abdominal testis in human fetuses had a higher concentration of vessels than the lower portion. These results suggest that manipulation of the lower end of the testis during Fowler-Stephens surgery should be avoided in order to preserve the collateral circulation.

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PURPOSE: To analyze the histology and distribution of abdominal testicular vessels in human fetuses Patients and Methods: We studied 19 fetuses (34 testes) ranging in age from 12 to 19 weeks post-conception. The fetuses were evaluated regarding crown-rump length (CRL), total length (TL) and body weight immediately before dissection. Each testis was dissected and embedded in paraffin, from which 5 µm thick sections were obtained and stained with Masson's trichrome and Anti-CD31 antibody to quantify the vessels. The stereological analysis was carried out with the Image Pro and Image J programs, using a grid to determine volumetric densities (Vv). Means were statistically compared using the unpaired T-test (p<0.05). RESULTS: The fetuses presented mean weight of 222.5g, mean CRL of 15.3 cm and mean TL of 23.2 cm. All testes were in the abdominal position. The mean percentage of vessels (Vv) in the upper portion of the testis was 7.6% (4.6 to 15%) and in the lower portion the mean was 5.11% (2.3 to 9.8%), with a significant difference (p=0.0001). In the analysis between the upper portion of the right and left testes (p=0.99) and in the analysis of the lower portion of the right and left testes (p=0.83), we did not observe significant differences. CONCLUSION: The upper portion of the abdominal testis in human fetuses had a higher concentration of vessels than the lower portion. These results suggest that manipulation of the lower end of the testis during Fowler-Stephens surgery should be avoided in order to preserve the collateral circulation.

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ABSTRACT Objective The objective of the present study is to evaluate the anatomy of the inferior hypogastric plexus, correlating it with urological pathologies, imaging exams and surgeries of the female pelvis, especially for treatment of endometriosis. Material and Methods We carried out a review about the anatomy of the inferior hypogastric plexus in the female pelvis. We analyzed papers published in the past 20 years in the databases of Pubmed, Embase and Scielo, and we included only papers in English and excluded case reports, editorials, and opinions of specialists. We also studied two human fixed female corpses and microsurgical dissection material with a stereoscopic magnifying glass with 2.5x magnification. Results Classical anatomical studies provide few details of the morphology of the inferior hypogastric plexus (IHP) or the location and nature of the associated nerves. The fusion of pelvic splanchnic nerves, sacral splanchnic nerves, and superior hypogastric plexus together with visceral afferent fibers form the IHP. The surgeon's precise knowledge of the anatomical relationship between the hypogastric nerve and the uterosacral ligament is essential to reduce the risk of complications and postoperative morbidity of patients surgically treated for deep infiltrative endometriosis involving the uterosacral ligament. Conclusion Accurate knowledge of the innervation of the female pelvis is of fundamental importance for prevention of possible injuries and voiding dysfunctions as well as the evacuation mechanism in the postoperative period. Imaging exams such as nuclear magnetic resonance are interesting tools for more accurate visualization of the distribution of the hypogastric plexus in the female pelvis.

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INTRODUCTION: in videolaparoscopic surgery, movements are conducted from a twenty times magnified image of an indirect operative field. The video interface used assumes the need for depth perception using two dimensions instead of three. OBJECTIVE: to evaluate the effectiveness of training to perform the laparoscopic knot in a silicone model, in 8-hour courses, and to analyze the correlation of learning outcomes with factors such as: sex, age, laterality, previous knowledge in endosuture and medical specialty. MATERIAL AND METHODS: in this prospective and randomized study, 56 students were evaluated, who took 8-hour courses, with groups of up to ten students. We used: a white box with camera, LCD screen and silicone piece. Four exercises were performed on the silicone mold: right hand, left hand, needle at 45° and back hand. RESULTS: 56 students (mean age = 33.28 years). The female group, n=18, mean age 29.61 years, 17 right-handed and 1 left-handed. The male group, n=38, mean age 34.57 years, 35 right-handers, 1 left-handed and 2 ambidextrous. In both groups, no correlation was observed between the analyzes of well performed knots when correlated with the age or sex of the participants. CONCLUSION: laparoscopic knot training, in silicone molds, in 8 h courses, proved to be effective. Factors such as gender, age, laterality, previous knowledge in endosuture and medical specialty do not interfere with the learning results.

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OBJECTIVE: The objective of the present study is to evaluate the anatomy of the inferior hypogastric plexus, correlating it with urological pathologies, imaging exams and surgeries of the female pelvis, especially for treatment of endometriosis. MATERIAL AND METHODS: We carried out a review about the anatomy of the inferior hypogastric plexus in the female pelvis. We analyzed papers published in the past 20 years in the databases of Pubmed, Embase and Scielo, and we included only papers in English and excluded case reports, editorials, and opinions of specialists. We also studied two human fixed female corpses and microsurgical dissection material with a stereoscopic magnifying glass with 2.5x magnification. RESULTS: Classical anatomical studies provide few details of the morphology of the inferior hypogastric plexus (IHP) or the location and nature of the associated nerves. The fusion of pelvic splanchnic nerves, sacral splanchnic nerves, and superior hypogastric plexus together with visceral afferent fibers form the IHP. The surgeon's precise knowledge of the anatomical relationship between the hypogastric nerve and the uterosacral ligament is essential to reduce the risk of complications and postoperative morbidity of patients surgically treated for deep infiltrative endometriosis involving the uterosacral ligament. CONCLUSION: Accurate knowledge of the innervation of the female pelvis is of fundamental importance for prevention of possible injuries and voiding dysfunctions as well as the evacuation mechanism in the postoperative period. Imaging exams such as nuclear magnetic resonance are interesting tools for more accurate visualization of the distribution of the hypogastric plexus in the female pelvis.

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ABSTRACT Introduction: in videolaparoscopic surgery, movements are conducted from a twenty times magnified image of an indirect operative field. The video interface used assumes the need for depth perception using two dimensions instead of three. Objective: to evaluate the effectiveness of training to perform the laparoscopic knot in a silicone model, in 8-hour courses, and to analyze the correlation of learning outcomes with factors such as: sex, age, laterality, previous knowledge in endosuture and medical specialty. Material and Methods: in this prospective and randomized study, 56 students were evaluated, who took 8-hour courses, with groups of up to ten students. We used: a white box with camera, LCD screen and silicone piece. Four exercises were performed on the silicone mold: right hand, left hand, needle at 45° and back hand. Results: 56 students (mean age = 33.28 years). The female group, n=18, mean age 29.61 years, 17 right-handed and 1 left-handed. The male group, n=38, mean age 34.57 years, 35 right-handers, 1 left-handed and 2 ambidextrous. In both groups, no correlation was observed between the analyzes of well performed knots when correlated with the age or sex of the participants. Conclusion: laparoscopic knot training, in silicone molds, in 8 h courses, proved to be effective. Factors such as gender, age, laterality, previous knowledge in endosuture and medical specialty do not interfere with the learning results.

RESUMO Introdução: na cirurgia videolaparoscópica os movimentos são conduzidos a partir de uma imagem magnificada de vinte vezes de um campo operatório indireto. A interface de vídeo utilizada pressupõe a necessidade de percepção de profundidade utilizando duas dimensões ao invés de três. Objetivo: avaliar a eficácia do treinamento de execução do nó laparoscópico em modelo de silicone, em cursos de 8h, e analisar a correlação dos resultados de aprendizagem com fatores como: sexo, idade, lateralidade, conhecimentos prévios em endosutura e especialidade médica. Material e Métodos: Neste estudo, prospectivo e randomizado, foram avaliados 56 alunos, que realizaram cursos de 8h de duração, com turmas de até dez alunos. Foram utilizados: uma caixa branca com câmera, tela de LCD e peça de silicone. No molde de silicone foram executados quatro exercícios: mão direita, mão esquerda, agulha a 45° e back hand. Resultados: 56 alunos (média de idade = 33,28 anos). O grupo feminino, n=18, média de idade 29,61 anos, 17 destras e 1 canhota. O grupo masculino, n=38, média de idade 34,57 anos, 35 destros, 1 canhoto e 2 ambidestros. Em ambos grupos não foram observados nenhuma correlação entre as análises de nós bem executados quando correlacionados com a idade ou sexo dos participantes. Conclusão: o treinamento de nó laparoscópico, em moldes de silicone, em cursos de 8h de duração, mostrou-se eficaz. Fatores como sexo, idade, lateralidade, conhecimentos prévios em endosutura e especialidade médica, não interferem nos resultados do aprendizado.

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ABSTRACT Objective: To evaluate the anatomical aspects of the kidney surface in human fetuses during the second gestational trimester. Material and Methods: We studied 108 kidneys obtained from 54 human fetuses (29 males and 25 females). The kidney was dissected and the number of clefts was counted. The renal volume was also assessed. To compare the quantitative data in both sexes, the Students-t-test was used (p < 0.05). Simple linear correlations were calculated for all kidney measurements, according to fetal age. Statistical analysis was performed with the R program (Version 3.5.1). Results: The fetuses ranged in age between 11.4 to 23 weeks post-conception. The renal volume of the right kidney ranged from 0.09 to 2.397 cm (mean=0.8479) and the renal volume of the left kidney ranged from 0.07 to 2.416 cm (mean=0.8036). The mean number of renal clefts in fetuses studied was 15.25 (7 to 28). There was no statistical significant difference in renal clefts between the sides either in males (p = 0.646) or in females (p = 0.698). Also, there was no significant difference in the mean number of renal clefts between male and female fetuses in right kidney (p = 0.948) and in left kidney (p = 0.939). Conclusions: The number of renal clefts has a great variation, weak correlation and no tendency to decrease during the 2nd gestational trimester. The number of clefts in right kidney of total sample and female fetuses has a significant development with age.

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OBJECTIVE: To evaluate the anatomical aspects of the kidney surface in human fetuses during the second gestational trimester. MATERIAL AND METHODS: We studied 108 kidneys obtained from 54 human fetuses (29 males and 25 females). The kidney was dissected and the number of clefts was counted. The renal volume was also assessed. To compare the quantitative data in both sexes, the Students-t-test was used (p < 0.05). Simple linear correlations were calculated for all kidney measurements, according to fetal age. Statistical analysis was performed with the R program (Version 3.5.1). RESULTS: The fetuses ranged in age between 11.4 to 23 weeks post-conception. The renal volume of the right kidney ranged from 0.09 to 2.397 cm (mean=0.8479) and the renal volume of the left kidney ranged from 0.07 to 2.416 cm (mean=0.8036). The mean number of renal clefts in fetuses studied was 15.25 (7 to 28). There was no statistical significant difference in renal clefts between the sides either in males (p = 0.646) or in females (p = 0.698). Also, there was no significant difference in the mean number of renal clefts between male and female fetuses in right kidney (p = 0.948) and in left kidney (p = 0.939). CONCLUSIONS: The number of renal clefts has a great variation, weak correlation and no tendency to decrease during the 2nd gestational trimester. The number of clefts in right kidney of total sample and female fetuses has a significant development with age.

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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.

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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.

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Preeclampsia is a multi-organ complication of pregnancy characterized by sudden hypertension and proteinuria that is among the leading causes of preterm delivery and maternal morbidity and mortality worldwide. The heterogeneity of preeclampsia poses a challenge for understanding its etiology and molecular basis. Intriguingly, risk for the condition increases in high-altitude regions such as the Peruvian Andes. To investigate the genetic basis of preeclampsia in a population living at high altitude, we characterized genome-wide variation in a cohort of preeclamptic and healthy Andean families (n = 883) from Puno, Peru, a city located above 3,800 meters of altitude. Our study collected genomic DNA and medical records from case-control trios and duos in local hospital settings. We generated genotype data for 439,314 SNPs, determined global ancestry patterns, and mapped associations between genetic variants and preeclampsia phenotypes. A transmission disequilibrium test (TDT) revealed variants near genes of biological importance for placental and blood vessel function. The top candidate region was found on chromosome 13 of the fetal genome and contains clotting factor genes PROZ, F7, and F10. These findings provide supporting evidence that common genetic variants within coagulation genes play an important role in preeclampsia. A selection scan revealed a potential adaptive signal around the ADAM12 locus on chromosome 10, implicated in pregnancy disorders. Our discovery of an association in a functional pathway relevant to pregnancy physiology in an understudied population of Native American origin demonstrates the increased power of family-based study design and underscores the importance of conducting genetic research in diverse populations.

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ABSTRACT Background: To analyze the incidence of epididymal anomalies (EAs) associated to spermatic obstruction in patients with undescended testis (UT) according to testicular position and age. Materials and Methods: We studied 87 patients (110 testis) with cryptorchidism and analyzed the presence of EAs correlated with the testicular position, age and patency of the processus vaginalis (PV). To analyze the relations between the testis and epididymis we considered three situations: (a) Normal pattern: the epididymis was attached to the testis at the head and tail and epididymis totally attached to the testis; (b) EAs: when the epididymis was attached to the testis only at the head (Figure-1A) and (c) EAs associated to spermatic obstruction: epididymis was attached to the testis only at the tail (Figure-1B) and when there are no visible connection between testis and epididymis (Figure-1C). We used the Wilcoxon-Mann-Whitney test and the Chi-square test for contingency analysis (p <0.05). Results: The mean age of the patients was 5.18 years (SD=2.867). Of 110 testes analyzed, 14 were abdominal (12.72%); 83 inguinal (75.45%) and 13 suprascrotal (11.81%). Normal relationships between testis and epididymis were observed in 54 patients (62.1%) with no significant differences in relation to the patient's age (p=0.666). Epididymal tail disjunction was observed in 23 patients (26.44%), with no significant differences in relation to age (p=0.59). EAs associated to spermatic obstruction were observed in 16 patients (18.4%), also with no significant differences in relation to age (p=0.684). We did not observe significant correlation between the testis position and the incidence of EAs (p=0.119). We did not observe significant correlations between patency of the PV (64.7%) and incidence of EAs (p=0.742). Conclusions: Epididymal anomalies associated with spermatic obstruction are present in almost 20% of undescended testes, without significant correlation with age, testicular position and patency of the PV. This information needs to be correlated to the infertility risk of this congenital anomaly.

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BACKGROUND: To analyze the incidence of epididymal anomalies (EAs) associated to spermatic obstruction in patients with undescended testis (UT) according to testicular position and age. MATERIALS AND METHODS: We studied 87 patients (110 testis) with cryptorchidism and analyzed the presence of EAs correlated with the testicular position, age and patency of the processus vaginalis (PV). To analyze the relations between the testis and epididymis we considered three situations: (a) Normal pattern: the epididymis was attached to the testis at the head and tail and epididymis totally attached to the testis; (b) EAs: when the epididymis was attached to the testis only at the head (Figure-1A) and (c) EAs associated to spermatic obstruction: epididymis was attached to the testis only at the tail (Figure-1B) and when there are no visible connection between testis and epididymis (Figure-1C). We used the Wilcoxon-Mann-Whitney test and the Chi-square test for contingency analysis (p <0.05). RESULTS: The mean age of the patients was 5.18 years (SD=2.867). Of 110 testes analyzed, 14 were abdominal (12.72%); 83 inguinal (75.45%) and 13 suprascrotal (11.81%). Normal relationships between testis and epididymis were observed in 54 patients (62.1%) with no significant differences in relation to the patient's age (p=0.666). Epididymal tail disjunction was observed in 23 patients (26.44%), with no significant differences in relation to age (p=0.59). EAs associated to spermatic obstruction were observed in 16 patients (18.4%), also with no significant differences in relation to age (p=0.684). We did not observe significant correlation between the testis position and the incidence of EAs (p=0.119). We did not observe significant correlations between patency of the PV (64.7%) and incidence of EAs (p=0.742). CONCLUSIONS: Epididymal anomalies associated with spermatic obstruction are present in almost 20% of undescended testes, without significant correlation with age, testicular position and patency of the PV. This information needs to be correlated to the infertility risk of this congenital anomaly.

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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.

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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.

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BACKGROUND: The second gestational trimester is a very important period for male genital development. We analyzed the testicular and prostatic volume growth and compared them to the biometric parameters in human fetuses. METHODS: We studied 64 testes and 32 prostates from 32 fetuses, aged 10-22 weeks postconception. Fetuses were evaluated regarding total length, crown-rump length, and bodyweight. The same observer performed all the measurements. After testicular and prostatic dissection, the prostate and testicular length, width and thickness were recorded with the aid of computer programs (Image Pro and ImageJ software, version 1.46r). Testicular volume (TV) and prostatic volume (PV) were calculated using the ellipsoid formula. Statistical analysis was performed with the GraphPad Prism program (version 6.01). RESULTS: The fetuses presented PV between 6.1 and 297.18 mm2  (mean = 77.98 mm3 ). Linear regression analysis indicated that the PV in these fetuses increased significantly and positively with fetal age (r2 = .3120; p < .0001). We did not observe significant differences between the TV (right testis: 0.39-63.94 mm3 ; mean = 19.84 mm3 ; left testis: ​​​​​​0.52-55.37 mm3 , mean = 17.25 mm3 ). Linear regression analysis also indicated that the right and left TV (right: r2 = .6649; p < .0001 and left: r2 = .6792; p < .001) increased significantly and positively with fetal age. CONCLUSION: The prostatic growth was slower during the second gestational trimester, with significant correlations with fetal biometric parameters. The testicular growth was moderate and showed a significant correlation with fetal parameters during the studied period in human fetuses.

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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.

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BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10-5 ) and Europeans (P = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.

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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.

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