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OBJECTIVE: To assess the efficacy of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agent (AA) therapy in the management of paediatric monosymptomatic nocturnal enuresis (MNE) using a network meta-analysis. MATERIALS AND METHODS: We searched the electronic databases PubMed, Cochrane Library, EMBASE and Web of Science from inception to 1 March 2018. Randomized controlled trials (RCTs) that compared desmopressin, alarm, desmopressin plus alarm, and desmopressin plus AAs were identified. The network meta-analysis was conducted with software R 3.3.2 and STATA 14.0. RESULTS: Eighteen RCTs with a total of 1 649 participants were included. The meta-analysis results showed that complete response (CR) and success rates with desmopressin plus AAs were higher than with desmopressin or alarm monotherapy. Success rates for desmopressin plus alarm therapy were higher than for alarm monotherapy. No obvious difference was observed between desmopressin plus AAs and desmopressin plus alarm therapy with regard to CR rate and success rate. The relapse rate with alarm monotherapy was much lower than with desmopressin monotherapy. Adverse events seemed to be infrequently and tolerable for all treatments. The ranking probability results were as follows: desmopressin plus AA ranked first for the outcomes of CR and success, desmopressin plus alarm therapy ranked first for mean number of wet nights per week, and alarm therapy had the lowest relapse rate. CONCLUSIONS: The network meta-analysis showed that desmopressin had similar efficacy to alarm therapy but a higher relapse rate. Desmopressin plus AA therapy was associated with better efficacy than and a similar relapse rate to desmopressin monotherapy. Desmopressin plus alarm therapy was similar to both desmopressin and alarm monotherapy in efficacy. All treatments, including desmopressin plus AAwere associated with tolerable adverse events; however, additional high-quality studies are needed for further evaluation of these treatments.
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Fármacos Antidiuréticos/uso terapéutico , Antagonistas Colinérgicos/uso terapéutico , Alarmas Clínicas , Desamino Arginina Vasopresina/uso terapéutico , Enuresis Nocturna/tratamiento farmacológico , Niño , Humanos , Metaanálisis en Red , Enuresis Nocturna/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Resultado del TratamientoRESUMEN
Background: A significant number of women die from pregnancy and childbirth complications globally, particularly in low- and middle-income countries (LMICs). Receiving at least four antenatal care (ANC) visits may be important in reducing maternal and perinatal deaths. This study investigates factors associated with attending ≥ 4 ANC visits in Sarlahi district of southern Nepal. Methods: A secondary analysis was conducted on data from the Nepal Oil Massage Study (NOMS), a cluster-randomized, community-based longitudinal pregnancy cohort study encompassing 34 Village Development Committees. We quantified the association between receipt/attendance of ≥ 4 ANC visits and socioeconomic, demographic, morbidity, and pregnancy history factors using logistic regression; Generalized Estimating Equations were used to account for multiple pregnancies per woman. Results: All pregnancies resulting in a live birth (n=31,867) were included in the model and 31.4% of those pregnancies received 4+ ANC visits. Significant positive associations include socioeconomic factors such as participation in non-farming occupations for women (OR=1.52, 95% CI: 1.19, 1.93), higher education (OR=1.79, 95% CI: 1.66, 1.93) and wealth quintile OR=1.44, 95% CI: 1.31, 1.59), nutritional status such as non-short stature (OR=1.17, 95% CI: 1.07, 1.27), obstetric history such as adequate interpregnancy interval (OR=1.31, 95% CI: 1.19, 1.45) and prior pregnancy but no live birth (OR=2.14, 95% CI: 1.57, 2.92), symptoms such as vaginal bleeding (OR=1.35, 95% CI:1.11, 1.65) and awareness of the government's conditional cash transfer ANC program (OR=2.26, 95% CI: 2.01, 2.54). Conversely, belonging to the lower Shudra caste (OR=0.56, 95% CI: 0.47, 0.67), maternal age below 18 or above 35 (OR=0.81, 95% CI:0.74, 0.88; OR=0.77, 95% CI: 0.62, 0.96)), preterm birth (OR=0.41, 95% CI: 0.35, 0.49), parity ≥ 1 (OR=0.66, 95% CI: 0.61, 0.72), and the presence of hypertension during pregnancy (OR=0.79, 95% CI: 0.69, 0.90) were associated with decreased likelihood of attending ≥ 4 ANC visits. Conclusions: These findings underscore the importance of continuing and promoting the government's program and increasing awareness among women. Moreover, understanding these factors can guide interventions aimed at encouraging ANC uptake in the most vulnerable groups, subsequently reducing maternal-related adverse outcomes in LMICs. Trial registration: The clinicaltrial.gov trial registration number for NOMS was #NCT01177111. Registration date was August 6th, 2010.
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Little is known about links of circadian rhythm alterations with neuropsychiatric symptoms and cognition in memory impaired older adults. Associations of actigraphic rest/activity rhythms (RAR) with depressive symptoms and cognition are examined using function-on-scalar regression (FOSR). Forty-four older adults with memory impairment (mean: 76.84 ± 8.15 years; 40.9% female) completed 6.37 ± 0.93 days of actigraphy, the Beck depression inventory-II (BDI-II), mini-mental state examination (MMSE) and consortium to establish a registry for Alzheimer's disease (CERAD) delayed word recall. FOSR models with BDI-II, MMSE, or CERAD as individual predictors adjusted for demographics (Models A1-A3) and all three predictors and demographics (Model B). In Model B, higher BDI-II scores are associated with greater activity from 12:00-11:50 a.m., 2:10-5:50 p.m., 8:40-9:40 p.m., 11:20-12:00 a.m., higher CERAD scores with greater activity from 9:20-10:00 p.m., and higher MMSE scores with greater activity from 5:50-10:50 a.m. and 12:40-5:00 p.m. Greater depressive symptomatology is associated with greater activity in midafternoon, evening, and overnight into midday; better delayed recall with greater late evening activity; and higher global cognitive performance with greater morning and afternoon activity (Model B). Time-of-day specific RAR alterations may affect mood and cognitive performance in this population.
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Enfermedad de Alzheimer , Cognición , Humanos , Femenino , Masculino , Anciano , Pruebas Neuropsicológicas , Ritmo Circadiano , Trastornos de la Memoria/diagnósticoRESUMEN
OBJECTIVE: To assess the efficacy and safety of double J (DJ) stented, external stented and stent-less procedures in pediatric pyeloplasty by adopting a network meta-analysis (NMA). MATERIAL AND METHODS: Electronic databases including PubMed, Cochrane Library, Web of science and Embase database were retrieved. The trials that compared double J (DJ) stented, external stented or stent-less procedures in pediatric pyeloplasty were identified. A network meta-analysis was conducted with the software of STATA 14.0. Probability-based ranking results were performed to identify the best treatment, and publication bias was analyzed by funnel plots. RESULTS: 15 studies with 1731 participants were enrolled in the analysis, including 4 randomized controlled trials (RCT) and 11 retrospective studies. The NMA results revealed that no significant differences were detected in the outcomes of operative time, operative success, hospital stay, improvement of renal functions, overall complications and redo pyeloplasty. DJ stented and external stented procedures were associated with more postoperative pain than that of stent-less procedures [DJ stented: ORâ¯=â¯4.47, 95%CI(1.05,19.08); external stented: ORâ¯=â¯5.83, 95%CI(0.09,1.43)]. DJ stented procedure had a lower rate of urine leakage than those of external stented procedure [ORâ¯=â¯0.18, 95%CI (0.04, 0.76)] and stent-less procedure [ORâ¯=â¯0.07, 95%CI=(0.01, 0.34)]. No significant difference was observed in other types of complications such as urinary tract infection (UTI), stent migration, recurrent ureteropelvic junction obstruction (UPJO) and fever. The probabilities of ranking results indicated that the DJ stented procedure was the best treatment in the outcomes of hospital stay, operative success, improvement of renal functions, and the complication of urine leakage. Stent-less procedure showed its advantages in the outcomes of operative time, flank pain and UTI. External stented procedure had the lowest rate of overall complications and redo pyeloplasty. CONCLUSIONS: There were no obvious differences in operative time, operative success, hospital stay, improvement of renal functions, overall complications between external stented, DJ stented and stent-less procedures for pediatric pyeloplasty. When considering the ranking results, the DJ stented procedure seemed to be more beneficial for pediatric pyeloplasty than the other methods. However, with the limitation of our study, additional high-quality studies are needed for further evaluation.
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Pelvis Renal/cirugía , Metaanálisis en Red , Procedimientos de Cirugía Plástica/métodos , Stents , Obstrucción Ureteral/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Niño , Humanos , Tiempo de Internación , Estudios RetrospectivosRESUMEN
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant disorder that is caused by the abnormal amplification of cytosine-adenine-guanine (CAG) trinucleotide repeats in the ATXN3 gene. The main feature of SCA3 is progressive ataxia. Currently, no effective treatment exists for this condition. For this study, we obtained dermal fibroblasts from a patient. The fibroblasts were successfully transformed into induced pluripotent stem cells (iPSCs) by employing episomal plasmids expressing OCT3/4, SOX2, KLF4, LIN28, and L-MYC. Our approach offers a resource for further research into SCA3 mechanism in an attempt to facilitate the development and screening of pharmaceutical and gene therapy.
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Técnicas de Reprogramación Celular , Dermis , Fibroblastos , Células Madre Pluripotentes Inducidas , Enfermedad de Machado-Joseph , Ataxina-3/genética , Ataxina-3/metabolismo , Línea Celular , Dermis/metabolismo , Dermis/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Amplificación de Genes , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Factor 4 Similar a Kruppel , Enfermedad de Machado-Joseph/genética , Enfermedad de Machado-Joseph/metabolismo , Enfermedad de Machado-Joseph/patología , Proteínas Represoras/genética , Proteínas Represoras/metabolismoRESUMEN
Neuroglobin (Ngb) has been reported to be increased in early and moderately advanced Alzheimer's disease (AD) stages but declined in the severe stage. However, its regulatory mechanisms and pathophysiological roles in the disease remain to be defined. In this study, we found that Ngb expression was significantly upregulated by low dose Aß25-35, the neurotoxic fragment of Aß1 - 40 and Aß1 - 42, but was not further increased by a higher dose of Aß25-35. Mutation analysis and supershift assay demonstrated that transcription factor Nuclear Factor κB (NFκB), κB2 and κB3 sites located in mouse Ngb promoter region were involved in dynamic regulation of Ngb expression in response to different doses of Aß25-35 stimulation. In addition, we found that suppression of endogenous Ngb expression exacerbated Aß25-35-induced neuronal cell death and mitochondrial dysfunction. Our results indicate that endogenous Ngb expression may be upregulated by low dose Aß25-35, which is responsible for protecting against Aß25-35-mediated neurotoxicity. These experimental findings suggest that upregulation of endogenous Ngb expression might be an effective intervention approach for AD.
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Péptidos beta-Amiloides/farmacología , FN-kappa B/metabolismo , Neuroglobina/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fragmentos de Péptidos/farmacología , Regulación hacia Arriba/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Animales , Células Cultivadas , Corteza Cerebral/citología , Relación Dosis-Respuesta a Droga , Complejo III de Transporte de Electrones/genética , Complejo III de Transporte de Electrones/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Embrión de Mamíferos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/genética , Ratones , Ratones Endogámicos C57BL , Neuroblastoma/patología , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Estadísticas no Paramétricas , TransfecciónRESUMEN
Recently, mutations of DNAJC12 gene were reported to be associated with early-onset parkinsonism, progressive neurodevelopmental delay, and dystonia in several unrelated pedigrees. This study aimed to evaluate DNAJC12 coding mutations in sporadic Chinese Han patients with Parkinson's disease (PD) and test whether an age-of-onset effect exists. Seven hundred two Chinese Han sporadic PD patients, including 181 early-onset PD and 521 late-onset PD, and 728 healthy controls were recruited. No documented disease-causing mutation of DNAJC12 was identified, but we found 7 single-nucleotide polymorphisms. Allele frequencies did not differ between all the PD patients and controls or between any 2 subgroups for all these single-nucleotide polymorphisms. Our study suggests that DNAJC12 mutation is not a risk factor of PD in Chinese Han population, and no age-of-onset effect was verified.