RESUMO
We investigated whether likely pathogenic variants co-segregating with gastroschisis through a family-based approach using bioinformatic analyses were implicated in body wall closure. Gene Ontology (GO)/Panther functional enrichment and protein-protein interaction analysis by String identified several biological networks of highly connected genes in UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, AOX1, NOTCH1, HIST1H2BB, RPS3, THBS1, ADCY9, and FGFR4. SVS-PhoRank identified a dominant model in OR10G4 (also as heterozygous de novo), ITIH3, PLEKHG4B, SLC9A3, ITGA2, AOX1, and ALPP, including a recessive model in UGT1A7, UGT1A6, PER2, PTPRD, and UGT1A3. A heterozygous compound model was observed in CDYL, KDM5A, RASGRP1, MYBPC2, PDE4DIP, F5, OBSCN, and UGT1A. These genes were implicated in pathogenetic pathways involving the following GO related categories: xenobiotic, regulation of metabolic process, regulation of cell adhesion, regulation of gene expression, inflammatory response, regulation of vascular development, keratinization, left-right symmetry, epigenetic, ubiquitination, and regulation of protein synthesis. Multiple background modifiers interacting with disease-relevant pathways may regulate gastroschisis susceptibility. Based in our findings and considering the plausibility of the biological pattern of mechanisms and gene network modeling, we suggest that the gastroschisis developmental process may be the consequence of several well-orchestrated biological and molecular mechanisms which could be interacting with gastroschisis predispositions within the first ten weeks of development.
Assuntos
Parede Abdominal/patologia , Biologia Computacional/métodos , Gastrosquise/genética , Variação Genética , Ontologia Genética , Humanos , Padrões de Herança/genética , Mapas de Interação de Proteínas/genética , RecidivaRESUMO
BACKGROUND: Genes involved in gastroschisis have shown a strong interaction with environmental factors. However, less is known about its influence. We aimed to systematically review the genetic associations of gastroschisis, to summarize whether its genetic susceptibility has been restricted to the interaction with the environment, and to identify significant gaps that remain for consideration in future studies. METHODS: Genetic association studies of gastroschisis published 1980-2017 (PubMed/MEDLINE) were independently searched by two reviewers. Significant SNP-gastroschisis associations were grouped into crude and stratified risks, whereas SNPs were assessed from two or more independent studies. Frequencies, odds ratios, and 95% confidence intervals were pooled using descriptive analysis and Chi-square test accounting for heterogeneity. RESULTS: Seven eligible articles capturing associations of 14 SNPs from 10 genes for crude risk (including 10 and 4 SNPs with increased and decreased risk, respectively) and 30 SNPs from 14 genes for stratified risk in gastroschisis (including 37 and 14 SNPs with increased and decreased risk, respectively) were identified (Fisher's exact test, P = 0.438). The rs4961 (ADD1), rs5443 (GNB3), rs1042713, and rs1042714 (ADRB2) were significantly associated with gastroschisis. CONCLUSIONS: Genetic susceptibility in gastroschisis is not restricted to the interaction with the environment and should not be too narrowly focused on environmental factors. We found significant associations with four SNPs from three genes related to blood pressure regulation, which supports a significant role of vascular disruption in the pathogenesis of gastroschisis. Future studies considering gene-gene or gene-environmental interactions are warranted for better understanding the etiology of gastroschisis.
Assuntos
Meio Ambiente , Gastrosquise/genética , Predisposição Genética para Doença , Variação Genética , HumanosRESUMO
STUDY OBJECTIVE: To explore the prevalence, mortality, and spatial distribution of gastroschisis using a large population-based sample with cases identified according to birth and death certificates (ICD-10 diagnosis code Q79.3, gastroschisis) through the General Directorate of Health Information of the Secretary Health of Mexico, over the course of a 15-year period. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A descriptive study examining 10,287 cases of gastroschisis was performed from 2000-2014 using public natality data for denominators (more than 25 million live births). Gastroschisis prevalence and mortality was calculated for each of year, state, maternal, and newborn characteristics. Spatial distribution was analyzed according to gastroschisis prevalence in the 32 states of Mexico. RESULTS: Gastroschisis prevalence was 4.01 per 10,000 live births (annual trend 2.09-6.85). Mortality associated with gastroschisis was 1.28 per 10,000 live births. Women younger than 20 years old, primiparae, and preterm infants had the highest gastroschisis-related prevalence (13.12, 5.83, and 7.51 per 10,000 live births, respectively). Gastroschisis prevalence and mortality did not differ according to newborn sex. A negative binomial distribution, variance (82,391.87) greater than the mean (321.47) was identified. CONCLUSION: Our findings show an increasing temporal trend for gastroschisis since 2000 in Mexico. Additionally, gastroschisis might follow in future instances a positive binomial or Poisson distribution. Therefore, improving surveillance of risk factors and supporting research for gastroschisis is warranted among maternal age younger than 25, particularly, younger than 20 years of age.
Assuntos
Gastrosquise/epidemiologia , Adulto , Bases de Dados Factuais , Demografia , Feminino , Gastrosquise/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Gravidez , Prevalência , Fatores de RiscoRESUMO
PURPOSE: There is uncertainty over whether familial recurrences in gastroschisis might be higher. Moreover, scant information is available regarding its sociodemographic features. We aim to explore the recurrence risk, sex-dependent influence, and geographical distribution of familial gastroschisis. METHODS: A systematic review of the literature and data extraction from population-based studies published 1970-2017 (PubMed/MEDLINE) was independently performed by two reviewers. Familial ocurrence of gastroschisis, whereas sociodemographic features from 11 studies were pooled including 862 probands as a base. A descriptive analysis and Chi-square test were performed. RESULTS: Twenty-four probands had a positive family history of gastroschisis including 49 affected family members, for a recurrence risk of 5.7 and 3% adjusted for proband. Siblings' recurrence was 4.3%. Sex-dependent influence analysis (n = 879, from three studies) evidenced an increased susceptibility to gastroschisis in males (2.5%) compared to females (1.3%) adjusted for proband. Heterogeneity was identified by Fisher's exact test (P = 0.023). CONCLUSION: Our findings support a greater liability attributable to familial factors on gastroschisis along with significant information for family and prenatal counseling. We suggest that future studies should include for a more accurate account for both familial and environmental confounding factors to uncover relatives and environmental exposures that more limited family histories may have missed.
Assuntos
Gastrosquise/genética , Predisposição Genética para Doença , Gastrosquise/epidemiologia , Humanos , Recidiva , Risco , Fatores Sexuais , IrmãosRESUMO
PURPOSE: To evaluate the occurrence of gastroschisis attributable to familial factors in a Mexican population-based setting. METHODS: A descriptive study was performed among gastroschisis cases born from 2010 through 2016 at Tijuana General Hospital (Baja California, Mexico) to generate multigenerational pedigrees. RESULTS: There were 87 gastroschisis cases from 57,217 live births. Six probands (6.9%) had another affected family member. Two half-siblings, a set of monozygotic twins, a mother-and-daughter occurrence, a distant paternal cousin and a distant maternal uncle were identified. Sibling recurrence was 5.5%. From 174 males and 153 females studied (n=327, involving 180 nuclear families), sex-dependent influence analysis evidenced an increased susceptibility to gastroschisis in males (3.2%) compared to females (1.8%) with an overall of 2.5% adjusted for proband. CONCLUSIONS: Our results provide a greater liability attributable to familial factors on gastroschisis. In spite of the predominant sporadic occurrence, underlying genetic susceptibility and environmental influences point to a complex interplay between genes and environmental factors in gastroschisis. LEVEL OF EVIDENCE: Level IV.
Assuntos
Gastrosquise/epidemiologia , Gastrosquise/genética , Predisposição Genética para Doença , Família , Feminino , Humanos , Masculino , México/epidemiologia , Linhagem , Gravidez , Fatores de Risco , Gêmeos MonozigóticosRESUMO
OBJECTIVE: The aim of the present study was to describe the clinical course, laboratory tests, and the cardiac involvement in rheumatic carditis patients in functional class III and IV, submitted to pulse therapy combined with oral prednisone. METHODS: A total of 120 patients with severe carditis due to acute rheumatic fever were treatment with three cycles of pulse therapy combined with oral corticosteroids. The patients were followed up from the hospital admission until the end of the treatment and returned after 30, 60, and 90 days to control. The patients were evaluated by clinical, laboratory, and transthoracic echocardiogram. RESULTS: In total, 23 (19.2%) patients at first attack of rheumatic fever and 97 (80.8%) with recurrent carditis were evaluated. Cardiac surgery was performed in 8 (6.6%) patients. The patients showed improved laboratory and radiological parameters (p<0.001) and were discharged, 74 (61.7%) in functional class I and 46 (38.3%) in functional class II. Hospitalisation time ranged from 21 to 176 days, with a mean of 69.1 days. Reduction of left atrium and ventricle diameters was observed, measured by means of transthoracic echocardiography, at hospital admission and discharge (p<0.001). None of the patients experienced rebound. CONCLUSIONS: The pulse therapy was effective in controlling severe rheumatic carditis and the oral corticosteroid prevented rebound episodes. Prolonged hospital stay was required for the clinical stabilisation of patients and to avoid the interruption of medication.
Assuntos
Corticosteroides/administração & dosagem , Miocardite/tratamento farmacológico , Febre Reumática/complicações , Cardiopatia Reumática/complicações , Cardiopatia Reumática/tratamento farmacológico , Administração Oral , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Ecocardiografia , Feminino , Seguimentos , Frequência Cardíaca , Humanos , Injeções Intravenosas , Masculino , Miocardite/diagnóstico , Miocardite/etiologia , Estudos Retrospectivos , Febre Reumática/tratamento farmacológicoRESUMO
Abstract Objective: The aim of the present study was to describe the clinical course, laboratory tests, and thecardiac involvement in rheumatic carditis patients in functional class III and IV, submitted to pulse therapycombined with oral prednisone. Methods: A total of 120 patients with severe carditis due to acute rheumatic feverwere treatment with three cycles of pulse therapy combined with oral corticosteroids. The patients were followedup from the hospital admission until the end of the treatment and returned after 30, 60, and 90 days to control.The patients were evaluated by clinical, laboratory, and transthoracic echocardiogram. Results: In total, 23(19.2%) patients at first attack of rheumatic fever and 97 (80.8%) with recurrent carditis were evaluated. Cardiacsurgery was performed in 8 (6.6%) patients. The patients showed improved laboratory and radiologicalparameters (p<0.001) and were discharged, 74 (61.7%) in functional class I and 46 (38.3%) in functional classII. Hospitalisation time ranged from 21 to 176 days, with a mean of 69.1 days. Reduction of left atrium andventricle diameters was observed, measured by means of transthoracic echocardiography, at hospital admissionand discharge (p <0.001). None of the patients experienced rebound. Conclusions: The pulse therapy was effectivein controlling severe rheumatic carditis and the oral corticosteroid prevented rebound episodes. Prolongedhospital stay was required for the clinical stabilisation of patients and to avoid the interruption of medication...
Assuntos
Doença das Coronárias , Efeito Rebote , Febre Reumática , Insuficiência Cardíaca , MetilprednisolonaRESUMO
Se describe el caso clínico de un paciente de 43 años de edad, presumiblemente saludable, quien acudió al cuerpo de guardia del Hospital Clinicoquirúrgico Docente Dr Joaquín Castillo Duany de Santiago de Cuba por presentar dolor torácico opresivo, desgarrante, súbito e intenso, que se irradiaba hacia la parte superior del abdomen cuando realizaba esfuerzo físico de moderada intensidad. Los exámenes complementarios efectuados confirmaron el diagnóstico de disección aórtica aguda toracoabdominal, por lo cual fue operado en el Cardiocentro de esta ciudad, donde evolucionó satisfactoriamente y egresó sin complicaciones(AU)
The case report of an apparently healthy 43 year-old patient is described, who went to the emergency department of Dr Joaquín Castillo Duany Teaching Clinical Surgical Hospital due to sudden, severe and ripping oppressive thoracic pain irradiating toward the upper abdominal region while he was making a physical effort of moderate intensity. Complementary tests confirmed the diagnosis of thoracoabdominal acute aortic dissection, reason why he underwent surgery at the Cardiology Center of this city, where he made good progress and was discharged without complications(AU)
Assuntos
Humanos , Masculino , Adulto , Aorta Abdominal , Aorta Abdominal/cirurgia , Dor no Peito , DissecaçãoRESUMO
Se describe el caso clínico de un paciente de 43 años de edad, presumiblemente saludable, quien acudió al cuerpo de guardia del Hospital Clinicoquirúrgico Docente "Dr. Joaquín Castillo Duany" de Santiago de Cuba por presentar dolor torácico opresivo, desgarrante, súbito e intenso, que se irradiaba hacia la parte superior del abdomen cuando realizaba esfuerzo físico de moderada intensidad. Los exámenes complementarios efectuados confirmaron el diagnóstico de disección aórtica aguda toracoabdominal, por lo cual fue operado en el Cardiocentro de esta ciudad, donde evolucionó satisfactoriamente y egresó sin complicaciones.
The case report of an apparently healthy 43 year-old patient is described, who went to the emergency department of "Dr. Joaquín Castillo Duany" Teaching Clinical Surgical Hospital due to sudden, severe and ripping oppressive thoracic pain irradiating toward the upper abdominal region while he was making a physical effort of moderate intensity. Complementary tests confirmed the diagnosis of thoracoabdominal acute aortic dissection, reason why he underwent surgery at the Cardiology Center of this city, where he made good progress and was discharged without complications.
RESUMO
1. El manejo protocolizado de los trastornos de los carbohidratos durante el embarazo nos conduce a resultados perinatales similares a los de la población embarazada general, tal y como lo demuestran en nuestro estudio: La incidencia de muertes fetales y neonatales. Los marcadores de asfixia neonatal. La hiperbilirrubinemia. El síndrome de insuficiencia respiratoria. 2. La incidencia de macrosomía lo hemos logrado reducir a cifras muy aceptables. 3. El momento de interrupción del embarazo nos garantiza obtener neonatos maduros, contrario a lo que ocurría en tiempos pasados
Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Carboidratos , Carbono , Diabetes Gestacional , Diabetes Mellitus , Gravidez em Diabéticas , Asfixia Neonatal/prevenção & controle , Insuficiência Respiratória/prevenção & controle , Costa Rica , Morte Fetal/prevenção & controle , Hiperbilirrubinemia/prevenção & controleRESUMO
A total of 118 nursing home admissions were studied to determine the prevalence of M. tuberculosis infection and the prevalence of risk factors for the development of active tuberculosis. The overall prevalence of positive tests was 22.5 per cent. The most prevalent risk factors for development of active tuberculosis were diabetes mellitus (42.4 per cent), being more than 10 per cent below ideal body weight (41.5 per cent), and alcohol abuse (12.7 per cent). Thirty-four percent of admissions had albumin levels below 3.5 g/dl. No associations were found when logistic regression was used to determine the impact of age and poor nutritional status on the prevalence of positive PPD tests on admission. These results show a substantial difference between the prevalence of positive PPD tests found upon nursing home admissions (22.5 per cent) and the prevalence found previously among residents in the same in nursing home (42.9 per cent).