Abstract Our aim was to develop and apply a comprehensive noninvasive prenatal test (NIPT) by using high-coverage targeted next-generation sequencing to estimate fetal fraction, determine fetal sex, and detect trisomy and monogenic disease without parental genotype information. We analyzed 45 pregnancies, 40 mock samples, and eight mother-child pairs to generate 35 simulated datasets. Fetal fraction (FF) was estimated based on analysis of the single nucleotide polymorphism (SNP) allele fraction distribution. A Z-score was calculated for trisomy of chromosome 21 (T21), and fetal sex detection. Monogenic disease detection was performed through variant analysis. Model validation was performed using the simulated datasets. The novel model to estimate FF was robust and accurate (r2= 0.994, p-value < 2.2e-16). For samples with FF > 0.04, T21 detection had 100% sensitivity (95% CI: 63.06 to 100%) and 98.53% specificity (95% CI: 92.08 to 99.96%). Fetal sex was determined with 100% accuracy. We later performed a proof of concept for monogenic disease diagnosis of 5/7 skeletal dysplasia cases. In conclusion, it is feasible to perform a comprehensive NIPT by using only data from high coverage targeted sequencing, which, in addition to detecting trisomies, also make it possible to identify pathogenic variants of the candidate genes for monogenic diseases.

Resumo Contexto A cirurgia bariátrica é considerada a melhor opção para o tratamento da obesidade, cujos pacientes são considerados de alto risco para fenômenos tromboembólicos. Objetivos Comparar o uso de doses diferentes de heparina de baixo peso molecular (HBPM) na profilaxia da trombose venosa profunda (TVP) em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, alteração na dosagem do fator anti-Xa e sangramento pré ou pós-operatório. Métodos Estudo comparativo transversal em pacientes submetidos à cirurgia bariátrica distribuídos em dois grupos, que receberam doses de HBPM de 40 mg (grupo controle, GC) e 80 mg (grupo de estudo, GE). Foram avaliados por ultrassonografia vascular e dosagem de KPTT, TAP, plaquetas e fator anti-Xa. Resultados Foram avaliados 60 pacientes, sendo 34 no GC e 26 no GE. Foi observada diferença significativa somente no peso (p = 0,003) e índice de massa corporal (p = 0,018) no GE em relação ao GC. Não houve diferença na dosagem de KPTT, TAP, plaquetas e fator anti-Xa entre os grupos. Não foram detectados TVP ou sangramentos significativos em ambos os grupos. Conclusões Não houve diferença estatisticamente significativa na utilização de doses maiores de HBPM na profilaxia da TVP em pacientes candidatos à cirurgia bariátrica em relação ao risco de TVP, dosagem do fator anti-Xa e sangramento pré ou pós-operatório.

Abstract Background Bariatric surgery is considered the best treatment option for patients with obesity who are classed as high risk for thromboembolic events. Objectives To compare two different doses of low weight molecular heparin (LWMH) for prevention of deep venous thrombosis (DVT) in candidates for bariatric surgery, in terms of DVT risk, abnormal anti-Xa levels, and preoperative and/or postoperative bleeding. Methods A cross-sectional comparative study of bariatric surgery patients divided into two groups given different doses of LWMH; 40 mg of LWMH (control group, CG) and 80 mg of LWMH (study group, SG), both evaluated by vascular ultrasonography (VU) and according to the results of PTT, PT, platelets, and anti-Xa factor assays. Results Sixty patients were evaluated, 34 in the CG and 26 in the SG. The only significant differences between the patients in the SG and the CG were weight (p = 0.003) and body mass index (p = 0.018). There were no differences between the groups in PTT, PT, platelets, or anti-Xa factor levels. There was no DVT or significant bleeding in either group. Conclusions There were no statistical differences when higher doses of LWMH were used for prevention of DVT in bariatric surgery patients, in terms of DVT risk, anti-Xa factor levels, or preoperative and postoperative bleeding.

OBJECTIVES: To analyze the influence of lying in prone position on a specially designed stretcher on the maternal-fetal hemodynamic parameters and comfort of pregnant women. METHODS: A randomized, controlled trial with 33 pregnant women divided into 2 groups: pregnant group sequence 1 and pregnant group sequence 2. The order of positions used in sequence 1 was Fowler’s position, prone position, supine position, left lateral, Fowler’s position 2, supine position 2, prone position 2 and left lateral 2. The order of positions used in sequence 2 was Fowler’s position, prone position, left lateral, supine position, Fowler’s position 2, left lateral 2, prone position 2 and supine position 2. Each woman remained in each position for 6 minutes. For the statistical analyses, we used Wilcoxon’s test for 2 paired samples when comparing the prone position with the other positions. The variables are presented in graphs showing the means and 95% confidence intervals. Trial Registration: Clinical Trial No. ISRCTN41359519 RESULTS: All the parameters were within the standards of normality. There were no differences between positions in terms of maternal heart rate, diastolic blood pressure, oxygen saturation and fetal heart rate. However, there were significant decreases in respiratory rate and systolic blood pressure in prone position 2 compared with left lateral 2. There was an increase in oxygen saturation in prone position compared with Fowler’s position and supine position 2 in both sequences. All the women reported feeling comfortable in the prone position. CONCLUSIONS: The prone position was considered safe and comfortable and could be advantageous for improving oxygen saturation and reducing the systolic blood pressure and respiratory rate.

OBJETIVO: descrever as alterações estruturais e/ou funcionais fetais à ultra-sonografia e à ecocardiografia fetais e os resultados perinatais em gestantes soropositivas para o vírus da imunodeficiência humana (HIV) em relação a um grupo controle de pacientes atendidas pelo pré-natal de baixo risco. MÉTODOS: foram avaliadas, prospectivamente, 109 gestantes soropositivas para o HIV em uso de anti-retrovirais (Grupo de Estudo, GE) e 200 gestantes controles (GC), sendo realizado acompanhamento ultra-sonográfico obstétrico mensal e ecocardiografia fetal e pós-natal com a avaliação do volume de líquido amniótico, da adequação do peso fetal, da presença de alterações estruturais fetais e dos resultados perinatais. RESULTADOS: foram observados oito casos de alterações estruturais fetais (7,3%) contra dois (1%) no GC (p=0,61). Observamos quatro casos de cardiopatia congênita e quatro de hidronefrose no GE, com diferença estatística para as cardiopatias (p=0,015). Foram diagnosticados, no GE, oito (7,3%) casos de oligoidrâmnio e 11 (10%) casos de polidrâmnio contra dois casos (1%) de oligoidrâminio e nenhum de polidrâmnio (p de 0,004 e p<0,001, respectivamente). Onze recém-nascidos (10%) foram pequenos para a idade gestacional no GE contra três (2,7%) no GC (p=0,002). A incidência de prematuridade foi de 8,7 e 2,5% nos grupos de estudo e controle, respectivamente (p=0,041). A taxa de óbito fetal foi de 5,5% (seis casos) no GE, contra nenhum no GC (p=0,002). CONCLUSÕES: observamos maior prevalência de cardiopatia fetal e de alterações da quantidade de líquido amniótico no grupo estudado em relação ao GC. A taxa de óbito fetal no GE provavelmente está vinculada à presença de malformações fetais; já a incidência de neonatos pequenos para a idade gestacional e de prematuridade, está associada à terapia anti-retroviral e ao uso do tabaco e de drogas ilícitas.

PURPOSE: to evaluate fetal structural and/or functional abnormalities by ultrasound examination and fetal echocardiography, in pregnant women positive for human immunodeficiency virus (HIV). METHODS: we analyzed prospectively 109 HIV positive pregnant women under antiretroviral therapy (Study Group) and 200 low risk pregnant patients (Control Group). All of them were submitted to ultrasound scan and fetal and neonatal echocardiography once a month. The amniotic fluid volume, fetal growth, fetal structural and functional alteration and the perinatal outcome were evaluated. RESULTS: there were eight (7.3%) cases of fetal structural abnormality in the Study Group and two (1%) in the Control Group (p=0.616). There were four cases of congenital heart disease and four cases of hydronephrosis in the Study Group, with statistic significance (p=0.015) for the cardiac abnormalities. There were eight cases (7.3%) of oligohydramnios and 11 cases (10%) of polyhydramnios in the Study Group against two cases (1%) of oligohydramnios and none of polyhydramnios in the Control Group (p=0.004 and p<0.001). Eleven (10%) newborn babies were too small for their gestation age in the Study Group, against three (2.7%) in the Control Group (p=0,002). The incidence of preterm delivery was 8.7 and 2.5% in the Study and Control Groups respectively (p=0.041). It was observed six cases (5.5%) of fetal death in the Study Group and none in the Control Group (p=0.002). CONCLUSIONS: in the present study, we have observed higher prevalence of amniotic fluid volume and congenital heart abnormalities in the Study Group as compared to the Control Group. Statistical significance was found in both situations. The high fetal death rate found in the Study Group was probably due to fetal malformation, whereas the high prematurity rate and the prevalence of small size for the gestational age of the newborn babies were probably related to antiretroviral therapy, smoking and drug abuse.

INTRODUÇÃO: A gravidez traz importantes modificações hormonais e anatômicas que têm efeito sobre a musculatura do assoalho pélvico. A cinesioterapia aplicada à musculatura do assoalho pélvico na gestação pode ser grande aliada no controle das alterações músculo-esqueléticas. OBJETIVOS: Avaliar efeitos da cinesioterapia no assoalho pélvico durante a gravidez, por meio da perineometria com e sem "biofeedback" e da avaliação funcional do assoalho pélvico, e correlacionar os valores da avaliação funcional com as perineometrias. MÉTODOS: Estudamos 46 gestantes nulíparas em seguimento pré-natal no Departamento de Obstetrícia do Hospital das Clínicas da Universidade de São Paulo, entre novembro de 2003 e dezembro de 2004, com até 20 semanas de gestação, atendidas no Setor de Baixo-Risco, divididas em dois grupos: Grupo exercício (23 casos): pacientes submetidas à cinesioterapia para a musculatura do assoalho pélvico; e grupo controle (23 casos): sem a prática da cinesioterapia. Por 12 semanas, até a 36ª semana, seguiu-se um protocolo, com treinamento de 60 minutos semanais, executando-se quatro séries de 10 contrações destes músculos com seis segundos de manutenção e 12 segundos de relaxamento, em decúbitos distintos. Realizaram-se 2 avaliações: 1ª (até 20 semanas) e 2ª (36 semanas gestacionais), por meio da avaliação funcional do assoalho pélvico e da perineometria. RESULTADOS: Na avaliação funcional do assoalho pélvico, tanto o grupo exercício como o grupo controle apresentaram aumento significativo da 1ª avaliação para a 2ª avaliação. Para a perineometria sem "biofeedback", na 2ª avaliação, somente o grupo exercício obteve aumento significativo, com p < 0,001. Quanto à perineometria com "biofeedback", tanto o grupo exercício como o controle tiveram aumento significativo nos valores, porém o delta porcentual foi maior no grupo exercício. Houve correlação significativa e positiva entre a avaliação funcional do assoalho pélvico e as perineometrias sem e com "biofeedback" nas duas primeiras avaliações. CONCLUSÕES: Os efeitos da cinesioterapia nos músculos do assoalho pélvico revelaram aumento significativo na pressão e na força durante a gestação. Durante o período gestacional houve correlação positiva e significativa entre a avaliação funcional do assoalho pélvico e as perineometrias.

OJETIVE: The objective of the present study was to evaluate the effect of pelvic floor muscle training in 46 nulliparous pregnant women. METHODS: The women were divided into 2 groups: an exercise group and a control group. Functional evaluation of the pelvic floor muscle was performed by digital vaginal palpation using the strength scale described by Ortiz and by a perineometer (with and without biofeedback). RESULTS: The functional evaluation of the pelvic floor muscles showed a significant increase in pelvic floor muscle strength during pregnancy in both groups (P < .001). However, the magnitude of the change was greater in the exercise group than in the control group (47.4% vs. 17.3%, P < .001). The study also showed a significant positive correlation (Spearman's test, r = 0.643; P < .001) between perineometry and digital assessment in the strength of pelvic floor muscles. CONCLUSIONS: Pelvic floor muscle training resulted in a significant increase in pelvic floor muscle pressure and strength during pregnancy. A significant positive correlation between functional evaluation of the pelvic floor muscle and perineometry was observed during pregnancy.

Dentre 1708 necrópsias de chagásicos crônicos, de um total de 4690, diagnosticamos 273 megas. Destes o mais freqüente foi o megacólon, seguido pelo megaesôfago, ocupando a associação megacólon e megaesôfago o terceiro lugar. Discutem-se e comparam-se os achados com outros de ordem clinico-epidemiológica e anatomopatológica. Confirmando dados da literatura, nossos achados atuais mostram, que a exemplo do que sucede na cardiopatia chagásica, o megacólon e o megaesôfago predominam no sexo masculino, discutindo-se os fatores que poderiam explicar a razão desse fato.

One thousand seven hundred and eight chronic chagasic post-mortem examinations studied from a total of4690 autopsies perfomed at our Institution. Two hundred and seventy-three chagasic had megas. Megacolon was the most frequent, followed by megaesophagus. Megacolon associated with megaesophagus was, the third mostcommom finding. Our data are discussed and compared with the literature. Megacolon and megaesophagus were more prevalent in man, as shown by other workers. Higher parasitemia perhaps could explain this finding.