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BACKGROUND: Primary vesicoureteral reflux (PVUR) is the most common malformation of the kidney and urinary tract, and reflux nephropathy is a major cause of chronic kidney disease in children. Recently, we reported mutations in the tenascin XB gene (TNXB) as a cause of PVUR with joint hypermobility. METHODS: To define the role of rare variants in tenascin genes in the etiology of PVUR, we screened a cohort of patients with familial PVUR (FPVUR) and non-familial PVUR (NFPVUR) for rare missense variants inTNXB and the tenascin C gene (TNC) after excluding mutations in ROBO2 and SOX17. RESULTS: The screening procedure identified 134 individuals from 112 families with PVUR; two families with mutations in ROBO2 were excluded from further analysis. Rare missense variants in TNXB were found in the remaining 110 families, of which 5/55 (9%) families had FPVUR and 2/55 (4%) had NFPVUR. There were no differences in high-grade reflux or renal parenchymal scarring between patients with and without TNXB variants. All patients with TNXB rare variants who were tested exhibited joint hypermobility. Overall we were able to identify causes of FPVUR in 7/57 (12%) families (9% in TNXB and 3% in ROBO2). CONCLUSIONS: In conclusion, the identification of a rare missense variant in TNXB in combination with a positive family history of VUR and joint hypermobility may represent a non-invasive method to diagnose PVUR and warrants further evaluation in other cohorts.
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Mutación Missense , Tenascina/genética , Reflujo Vesicoureteral/genética , Niño , Preescolar , Femenino , Humanos , Lactante , Inestabilidad de la Articulación/diagnóstico , Masculino , Mutación , LinajeRESUMEN
In insects, the chemical senses influence most vital behaviors, including mate seeking and egg laying; these sensory modalities are predominantly governed by odorant receptors (ORs), ionotropic receptors (IRs), and gustatory receptors (GRs). The codling moth, Cydia pomonella, is a global pest of apple, pear, and walnut, and semiochemically based management strategies limit the economic impacts of this species. The previous report of expression of a candidate pheromone-responsive OR in female codling moth ovipositor and pheromone glands raises further questions about the chemosensory capacity of these organs. With an RNA-sequencing approach, we examined chemoreceptors' expression in the female codling moth abdomen tip, sampling tissues from mated and unmated females and pupae. We report 37 ORs, 22 GRs, and 18 IRs expressed in our transcriptome showing overlap with receptors expressed in adult antennae as well as non-antennal candidate receptors. A quantitative PCR approach was also taken to assess the effect of mating on OR expression in adult female moths, revealing a few genes to be upregulated or downregulating after mating. These results provide a better understanding of the chemosensory role of codling moth female abdomen tip organs in female-specific behaviors. Future research will determine the function of specific receptors to augment current semiochemical-based strategies for codling moth management.
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PURPOSE: This study aimed to analyze organ system-based causes and non-organ system-based mechanisms of death (COD, MOD) in people with myelomeningocele (MMC), comparing urological to other COD. METHODS: A retrospective review was performed of 16 institutions in Canada/United States of non-random convenience sample of people with MMC (born > = 1972) using non-parametric statistics. RESULTS: Of 293 deaths (89% shunted hydrocephalus), 12% occurred in infancy, 35% in childhood, and 53% in adulthood (documented COD: 74%). For 261 shunted individuals, leading COD were neurological (21%) and pulmonary (17%), and leading MOD were infections (34%, including shunt infections: 4%) and non-infectious shunt malfunctions (14%). For 32 unshunted individuals, leading COD were pulmonary (34%) and cardiovascular (13%), and leading MOD were infections (38%) and non-infectious pulmonary (16%). COD and MOD varied by shunt status and age (p < = 0.04), not ambulation or birthyear (p > = 0.16). Urology-related deaths (urosepsis, renal failure, hematuria, bladder perforation/cancer: 10%) were more likely in females (p = 0.01), independent of age, shunt, or ambulatory status (p > = 0.40). COD/MOD were independent of bladder augmentation (p = >0.11). Unexplained deaths while asleep (4%) were independent of age, shunt status, and epilepsy (p >= 0.47). CONCLUSION: COD varied by shunt status. Leading MOD were infectious. Urology-related deaths (10%) were independent of shunt status; 26% of COD were unknown. Life-long multidisciplinary care and accurate mortality documentation are needed.
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Hidrocefalia , Meningomielocele , Femenino , Humanos , Meningomielocele/complicaciones , Meningomielocele/cirugía , Estudios Retrospectivos , Causas de Muerte , Derivación Ventriculoperitoneal/efectos adversos , Hidrocefalia/cirugíaRESUMEN
PURPOSE: Neurogenic bowel dysfunction (NBD) affects 80% of individuals with spina bifida. Performing and disseminating research on NBD to reach the appropriate audience is difficult given the variability among medical specialties managing NBD. This study aimed to identify which medical specialties and types of providers are currently managing NBD in the United States. METHODS: A survey was developed and sent to 75 spina bifida clinics. Surveys queried which specialty was primarily responsible for medical and surgical management of NBD and any others that assist in NBD care. The license and certification level of the providers were collected. Descriptive statistics were performed to describe the results. RESULTS: Response rate was 68%. Urology was the leading specialty primarily responsible for NBD management (39%) followed by rehabilitation medicine and developmental pediatrics (22% and 20%, respectively). Physicians were the primary providers of care followed by nurse practitioners (54% vs 31%). Urology performs 65% of NBD surgeries. CONCLUSION: Multiple specialties and providers are involved in NBD management with variation among clinics. Development of improved NBD care should include a spectrum of specialties and providers. Dissemination of research should be aimed at multiple specialty groups.
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Intestino Neurogénico , Médicos , Disrafia Espinal , Niño , Humanos , Pautas de la Práctica en Medicina , Disrafia Espinal/complicaciones , Disrafia Espinal/terapia , Encuestas y Cuestionarios , Estados UnidosRESUMEN
PURPOSE: The objective of this study was to test a low-carbohydrate diet (LCD) plus walking to reduce androgen deprivation therapy (ADT)-induced metabolic disturbances. MATERIALS AND METHODS: This randomized multi-center trial of prostate cancer (PCa) patients initiating ADT was designed to compare an LCD (≤20g carbohydrate/day) plus walking (≥30 min for ≥5 days/week) intervention vs. control advised to maintain usual diet and exercise patterns. Primary outcome was change in insulin resistance by homeostatic model assessment at 6 months. To detect 20% reduction in insulin resistance, 100 men were required. The study was stopped early after randomizing 42 men due to slow accrual. Secondary outcomes included weight, body composition, lipids, and prostate-specific antigen (PSA). Changes from baseline were compared between arms using rank-sum tests. RESULTS: At 6 months, LCD/walking reduced insulin resistance by 4% vs. 36% increase in control (p = 0.13). At 3 months, vs. control, LCD/walking arm significantly lost weight (7.8kg; p<0.001), improved insulin resistance (↑36%; p = 0.015), hemoglobin A1c (↓3.3%; p = 0.01), high-density lipoprotein (HDL) (↑13%; p = 0.004), and triglyceride (↓37%; p = 0.036). At 6 months, weight loss (10.6kg; p<0.001) and HDL (↑27%; p = 0.003) remained significant. LCD/walking preserved total body bone mineral count (p = 0.025), reduced fat mass (p = 0.002), lean mass (p = 0.036), and percent body fat (p = 0.004). There were no differences in PSA. Limitations include the effect of LCD, weight loss vs. walking instruction are indistinguishable, and small sample size. CONCLUSIONS: In an underpowered study, LCD/walking did not improve insulin sensitivity at 6 months. Given most secondary outcomes were improved at 3 months with some remaining improved at 6 months and a secondary analysis showed that LCD/walking reduced insulin resistance over the study, supporting future larger studies of LCD/walking intervention to reduce ADT-induced disturbances.
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Antagonistas de Andrógenos/efectos adversos , Dieta Baja en Carbohidratos , Síndrome Metabólico/terapia , Neoplasias de la Próstata/tratamiento farmacológico , Caminata/fisiología , Anciano , Composición Corporal/fisiología , Peso Corporal/fisiología , Estilo de Vida Saludable , Humanos , Masculino , Síndrome Metabólico/inducido químicamente , Síndrome Metabólico/metabolismo , Persona de Mediana Edad , Resultado del Tratamiento , Pérdida de Peso/fisiologíaRESUMEN
BACKGROUND: Pbx genes encode TALE class homeodomain transcription factors that pattern the developing neural tube, pancreas, and blood. Within the hindbrain, Pbx cooperates with Hox proteins to regulate rhombomere segment identity. Pbx cooperates with Eng to regulate midbrain-hindbrain boundary maintenance, and with MyoD to control fast muscle cell differentiation. Although previous results have demonstrated that Pbx is required for proper eye size, functions in regulating retinal cell identity and patterning have not yet been examined. RESULTS: Analysis of retinal ganglion cell axon pathfinding and outgrowth in pbx2/4 null embryos demonstrated a key role for pbx genes in regulating neural cell behavior. To identify Pbx-dependent genes involved in regulating retino-tectal pathfinding, we conducted a microarray screen for Pbx-dependent transcripts in zebrafish, and detected genes that are specifically expressed in the eye and tectum. A subset of Pbx-dependent retinal transcripts delineate specific domains in the dorso-temporal lobe of the developing retina. Furthermore, we determined that some Pbx-dependent transcripts also require Meis1 and Gdf6a function. Since gdf6a expression is also dependent on Pbx, we propose a model in which Pbx proteins regulate expression of the growth factor gdf6a, which in turn regulates patterning of the dorso-temporal lobe of the retina. This, in concert with aberrant tectal patterning in pbx2/4 null embryos, may lead to the observed defects in RGC outgrowth. CONCLUSION: These data define a novel role for Pbx in patterning the vertebrate retina and tectum in a manner required for proper retinal ganglion cell axon outgrowth.