Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder.

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target.

Trisomía 18: nuevo signo ecográfico de tamizaje (dedo puntero) / Trisomy 18: a new screening ultrasonographic sign (finger pointer)

Se reporta un nuevo signo ecográfico observado en un feto de 22 semanas portador de trisomía 18 o síndrome de Edwards, que consiste en hiperextensión permanente de ambos dedos índices (signo que le denominamos ‘dedo puntero’) asociado a artrogriposis de las muñecas. La relevancia del hallazgo está en que podría reconocerse como un marcador más en el tamizaje de esta patología.

A new ultrasound sign observed in a 22-week fetus with trisomy 18 or Edwards syndrome, consisting of permanent hyperextension of both index fingers (sign named "pointer finger"), and associated with arthrogryposis of wrists is reported. The relevance of this finding is that it could be recognized as another marker in the screening for this disease.

Higroma quístico y translucencia nucal aumentada como marcadores de anomalías cromosómicas

Objetivos: Determinar la importancia del espacio retronucal en fetos entre las 11 y 13+6 semanas, identificando sus características, la asociación con anomalías cromosómicas y las posibles diferencias entre higroma quístico y translucencia nucal aumentada. Diseño: Estudio transversal prospectivo. Institución: Instituto Latinoamericano de salud Reproductiva, Lima, Perú. Participantes: Gestantes y sus fetos con diagnóstico citogenético prenatal. Intervenciones: Entre el año 2007 y junio 2012, se revisó 266 casos con diagnóstico citogenético prenatal, que correspondieron a 230 amniocentesis realizadas después de las 14 semanas y 36 biopsias de vellosidades coriales (BVC), entre las 11 a 13 semanas. Principales medidas de resultados: Marcadores ecográficos prenatales. Resultados: Se detectó 106 casos de anomalías cromosómicas (39,9%). El higroma quístico (HQ) fue el marcador que con más frecuencia, en relación al aumento de la translucencia de la nuca (TN) (30,8% versus 11,3%), se asoció a anomalías cromosómicas (68,3% versus 31%), correspondiendo al HQ una sensibilidad (S) de 45%, valor predictivo positivo (VPP) de 62%, ratio de probabilidad+ (LR+) de 2,4, y para la TN aumentada S 11%, VPP 40%, LR+ 1. El HQ se asoció en 35,7% a monosomía X, la TN aumentada a trisomías. Conclusiones: El HQ fue el marcador de anomalías cromosómicas más frecuente encontrado entre las 11 y 13+6 semanas y tuvo mayor valor predictivo que la TN aumentada. Ambas serían dos entidades distintas, siendo necesaria su diferenciación.

Objectives: To determine the importance of nuchal translucence in fetuses 11 to 13 +6 weeks, identifying characteristics, association with chromosomal anomalies and differences between cystic hygroma and increased nuchal translucency. Design: Prospective cross-sectional study. Setting: Instituto Latinoamericano de Salud Reproductiva, Lima, Peru. Participants: Pregnant women and their fetuses with prenatal cytogenetic diagnosis. Interventions: Between 2007 and June 2012, 266 cases with prenatal cytogenetic diagnosis had 230 amniocentesis after 14 gestational weeks and 36 chorionic villi biopsy (CVS) between 11-13 gestational weeks. Main outcome measures: Prenatal ultrasound markers. Results: One hundred and six cases of chromosomal abnormalities (39.9%) were found. Cystic hygroma (CH) was more often found than nuchal translucency (NT) (30.8% versus 11.3%) associated with chromosomal abnormalities (68.3% versus 31%), corresponding to HQ sensitivity (S) 45%, positive predictive value (PPV) 62%, likehood ratio+ (LR+) 2.4, and for increased TN S 11%, PPV 40%, LR+ 1. CH was associated in 35.7% to monosomy X, and NT to trisomy. Conclusions: CH was the most common chromosomal abnormalities marker found between 11 and 13 +6 weeks and had greater predictive value than increased NT. Each would represent separate entities requiring differentiation.

Multiple dose toxicity study of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 intravenously administered to Cercopithecus aethiops sabaeus monkeys.

The h-R3 is a humanized growth factor receptor monoclonal antibody (mAb) in development for the treatment of head and neck tumours in which malignant cells overexpress the Epidermal Growth Factor receptor. The present study was designed to evaluate the toxicity of repeated intravenous doses of the h-R3 mAb in a relevant species demonstrated by the avidin-biotin-peroxidase immunohistochemical (IHC) technique in skin biopsy samples from three Cercopithecus aethiops sabaeus monkeys (green monkeys). Additionally, 18 green monkeys were daily intravenously treated during 14 consecutive days. Monkeys were distributed into three experimental groups with three animals of each sex in each group. Group I received saline solution and served as control group; group II received 2.85 mg/kg of h-R3 mAb; and group III received 11.4 mg/kg of the h-R3 mAb. During the study there were no deaths, neither pathological clinical signs, or variations in the corporal weight curve. The electroneurophysiological and sanguine chemistry results did not evidence alterations related to the assay substance. Areas of haematomas, haemorrhages and inflammation, probably related with the administration procedure, were observed at the administration zones of all animals; this fact could also explain the increase in the neutrophil count of all animals at the end of the study. The electrocardiography study showed that in the 14 days of the study one female monkey, from the higher dose group, shifted its cardiac axis from +60 degrees to + 120 degrees; this finding could be interpreted as a right ventricular elongation due to the relative high daily administered volume. It is concluded that doses up to 11.4 mg/kg of h-R3, intravenously administered during 14 consecutive days to Cercopithecus aethiops sabaeus monkeys do not produce considerable toxic effects in the studied system.

[Perinatal conditions of newborns of adolescent mothers in the state of Sinaloa, Mexico]. / Condiciones perinatales en recién nacidos de madres adolescentes del estado de Sinaloa, México.

UNLABELLED: The objective was to compare perinatal conditions of newborns and obstetric complications between a group of adolescent mothers and one of adult mothers. It is a retrolective comparative survey, at the General Hospital "Bernardo J. Gastelum" SSA and General Hospital IMSS, Sinaloa, Mexico. PATIENTS: 10634 clinical records of patients in labour at obstetric unit from 1990 to 1994. A randomized sample of 215 adolescent pregnant patients and 215 adult pregnant patients were selected and the following data were analysed regarding to the mother: age, pregnancy outcome and obstetric complications; in regard to the newborn: gender, weight, height, cefalic circumference and Apgar score. The mean adolescent mother's age was 16 years, and 25 in adult mothers; mean adolescent mother newborn birthweight was 3.297 SD 0.414 kg. and in adult mothers was 3.393 SD 0.591 kg. (p = 0.09), adolescent mothers newborns with Apgar score less than 7 at first minute was 20% and 5% for adult mothers newborns. Statistically significant difference was observed (p = 0.02). There were not statistically significant differences between the groups in obstetric outcome and complications, birthweight. It was concluded that pregnancy in adolescence it's not a risk factor for the mother and the newborn.

[Cervical labor induction with prostaglandin E2 in patients with fetal death]. / Maduración cervical con prostaglandina E2 en pacientes con feto muerto.

The objective was to compare the effectiveness and efficacy of prostaglandin E2 (prepidil gel) plus oxitocin with that of intravenous oxitocin in the treatment of delivery induction in patients complicated with fetal death. Fifteen patients received prepidil gel plus oxitocin and 15 patients oxitocin. In the treatment group only one dosage of 0.5 ng in 2 ml of prepidil gel was administered intracervically and simultaneously oxitocin by intravenous infusion, dosage was increased 2 mUI/min every 30 minutes. In the control group only intravenous oxitocin was administered at the same dosage. The mean duration in hours of delivery in the treatment group was 13.1 +/- h and in the control group was 30.9 +/- 9.1 h. There were statistically significant differences between the groups in reduction of delivery duration (p = 0.0007). It is concluded that prostaglandin E2 plus oxitocin provide better short-term outcomes than oxitocine treatment and gave more short periods of labor in patients with fetal death.

Western blot of Entamoeba histolytica antigenic fractions: reactivity analysis with sera from intestinal amoebiasis patients.

The reactivity of sera from acute-phase intestinal amoebiasis patients (two weeks evolution) was studied to determine which of the Entamoeba histolytica antigens are most frequently immunogenic. Sera were examined by means of immunoelectrotransferase assay using crude extract of HM1:IMSS E. histolytica trophozoites. Three populations of clinically healthy adults from Mexico, Canada and Germany, with no evidence of parasites in faeces, were used as controls. The frequency of antigen recognition was analysed. In ailing individuals, the bands of 23, 24, 26 and 51 kDa were recognized most frequently (65 and 60%) followed by the 62 kDa band (56%). The combination of some of these bands, namely 3.4, 4.1 and 6.7, with molecular weights of 62, 51 and 24 kDa, increased the recognition frequency of patients to 91.4%. These results constitute a first but important step towards the design of more accurate methods for the successful immunodiagnosis and epidemiology of acute intestinal amoebiasis.