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OBJECTIVES: Abnormal motility of the residual colon has been reported in post-pull-through Hirschsprung disease (PT-HSCR) patients with persistent defecation problems. We reviewed the role of colonic manometry (CM) in the management of defecation disorders in these patients. METHODS: We retrospectively reviewed the medical record of PT-HSCR children who underwent CM for persistent symptoms of abnormal defecation. We reviewed their clinical course and its relation to CM findings. RESULTS: Thirty PT-HSCR patients underwent CM, of which five were diagnosed with transition zone pull-through and were excluded. Of the remaining 25 patients, 16 had colonic dysmotility, 8 had normal CM, and one had colonic hypermotility. In patients with dysmotility, five responded to ongoing medical management, three required surgical intervention (ileostomy), three remained symptomatic with medical management but not yet received surgical intervention, and five were lost to follow-up. In patients with normal CM, four responded to ongoing medical therapy, two required additional surgery (antegrade enema procedure), and two were lost to follow-up. The patient with hypermotility improved with adding loperamide. CONCLUSIONS: Colonic dysmotility can occur in PT-HSCR patients with persistent defecation problems. CM was helpful in delineating the degree of colonic neuromuscular dysfunction. CM results were used in conjunction with other clinical data to determine optimal management. Our findings support that medical management should first be optimized before consideration of colonic manometry and surgical interventions.
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Colon , Motilidad Gastrointestinal , Enfermedad de Hirschsprung , Manometría , Humanos , Enfermedad de Hirschsprung/cirugía , Enfermedad de Hirschsprung/fisiopatología , Manometría/métodos , Estudios Retrospectivos , Colon/fisiopatología , Colon/cirugía , Femenino , Masculino , Lactante , Preescolar , Niño , Defecación , Estreñimiento/fisiopatología , Estreñimiento/etiologíaRESUMEN
To study the differences in VASH2 expression in pediatric medulloblastoma (MB) tumor tissues of different molecular subtypes, to analyze the correlation between VASH2 and the molecular subtypes of medulloblastoma, clinicopathological data, and prognosis, and to explore the specific mechanism of VASH2's role in SHH medulloblastoma cell lines DAOY. We analyzed 47 pediatric medulloblastoma cases admitted to the Department of Pediatric Neurosurgery of the First Affiliated Hospital of Xinjiang Medical University from January 2011 to December 2019, and the expression levels of YAP1 and GAB1 in these tumor tissues were detected by immunohistochemistry (IHC) and molecularly typed (WNT-type, SHH-type, and non-WNT/SHH-type). The correlation between VASH2 and molecular typing of medulloblastoma was analyzed. We also analyzed the medulloblastoma dataset in the GEO database (GSE30074 and GSE202043) to explore the correlation between VASH2 and the prognosis of medulloblastoma patients, as well as performed a comprehensive GO enrichment analysis specifically for the VASH2 gene to reveal the underlying biological pathways of its complex molecular profile. We used vasopressin 2 (VASH2) as a research target and overexpressed and knocked down VASH2 in SHH medulloblastoma cell lines DAOY by lentiviral vectors in vitro, respectively, to investigate its role in SHH medulloblastoma cell lines DAOY cell proliferation, apoptosis, migration, invasion and biological roles in the cell cycle. (1) Among 47 pediatric medulloblastoma cases, 8 were WNT type, 29 were SHH type, and 10 were non-WNT/SHH type. the positive rate of VASH2 was highest in the SHH type with a 68.97% positive rate, followed by non-WNT/SHH and lowest in the WNT type. The results of the multifactorial analysis showed that positive expression of VASH2 was associated with medulloblastoma molecular subtype (SHH type), site of tumor development (four ventricles), and gender (male), P < 0.05. (2) The results of cellular experiments showed that overexpression of VASH2 increased the invasion and migration ability of medulloblast Daoy, while knockdown of VASH2 inhibited the invasion and Overexpression of VASH2 upregulated the expression of Smad2 + 3, Smad4, Mmp2 and the apoptotic indicators Bcl-2 and Caspase3, while knockdown of VASH2 suppressed the expression of Smad2 + 3 and Mmp2, and silenced the expression of Smad4 and the apoptotic indicators Bcl2, Caspase3 expression. Flow cytometric cycle analysis showed that VASH2 overexpression increased the S phase in the Daoy cell cycle, while VASH2 knockdown decreased the S phase in the SHH medulloblastoma cell lines DAOY cell cycle. Bioinformatics analysis showed that there was no statistically significant difference between the expression of VASH2 genes in the GSE30074 and GSE202043 datasets and the prognosis of the patients, but the results of this dataset analysis suggested that we need to continue to expand the sample size of the study in the future. The results of the GO enrichment analysis showed that the angiogenic pathway was the most significantly enriched, and the PPI interactions network of VASH2 was obtained from the STRING database. Using the STRING database, we obtained the PPI interaction network of VASH2, and the KEGG enrichment analysis of VASH2-related genes showed that VASH2-related genes were related to the apoptosis pathway, and therefore it was inferred that VASH2 also affects the development of tumors through apoptosis. We found for the first time that the positive expression rate of VASH2 was closely associated with SHH-type pediatric medulloblastoma and that VASH2 was involved in the invasion, migration, cell cycle, and apoptotic capacity of SHH medulloblastoma cell lines DAOY by affecting downstream indicators of the TGF-ß pathway. This suggests that it is involved in the progression of pediatric medulloblastoma, and VASH2 is expected to be a diagnostic and therapeutic target for SHH-type pediatric medulloblastoma.
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Neoplasias Cerebelosas , Meduloblastoma , Humanos , Masculino , Niño , Meduloblastoma/patología , Metaloproteinasa 2 de la Matriz , Neoplasias Cerebelosas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Vasopresinas/uso terapéutico , Proteínas Angiogénicas/genéticaRESUMEN
Introduction: Helicobacter pylori (HP) infection is associated with gastritis, peptic ulcer disease (PUD) in the stomach and duodenum, and an increased risk of gastric cancer. The risk of infection, secondary symptoms, and negative outcomes is known to be increased in low- and middle-income countries and vastly less substantial in the United States and Europe. Current North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines recommend endoscopic diagnosis and susceptibility-guided therapy, which is not reflected by current adult guidelines for therapy. In this study, we complete a single-center retrospective review of HP risk by nativity status, as well as the results of the use of standard empiric therapy in HP and PUD patients. Methods: We retrospectively reviewed all endoscopies with patients aged 1-21 years with a known nativity status and identified all HP diagnoses. We also completed the classification of Kyoto scores and classified patients as gastritis versus PUD. Treatment records were obtained, as well as downstream documentation of the impact of empiric therapy. HP prevalence and severity were compared between non-native and native US populations. Results: In total 332 patients were identified, with 59 HP diagnoses. However, 64 patients were immigrants, and 268 were US natives. Totally 39.1% of all immigrant patients had an endoscopically identified HP infection, compared to only 12.7% of US native patients (P < 0.01, relative risk 3.07). HP severity was worse in immigrant patients (Kyoto score 1.5 versus 0.89; P = 0.008). Empiric high-dose amoxicillin triple therapy was equally effective in reducing symptoms in gastritis versus PUD patients. Conclusions: Immigrant patients have a substantially higher risk and severity of HP infection than US natives. Empiric therapy remains highly effective at relieving symptoms. These findings in aggregate suggest that North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines may not adequately serve non-native pediatric patients, with an additional prospective multicenter study needed to confirm. In addition, a prospective study of treatment based on stool antigen tests, as well as a larger prospective study of empiric therapy, may suggest alterations to our approach in line with recent changes to adult Gastroenterology practice.
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Purpose: To summarize the relevant evidence for nondrug nursing programs in neonatal operational pain management. Methods: Computer search for the literature on neonatal procedural pain from 2015 to 2020 in Up To Date, JBI, NICE, SIGN, RNAO, NGC, PubMed, Cochrane Library, CNKI, and Wanfang database was conducted. All literature works that may meet the inclusion criteria were independently evaluated by two researchers to determine the quality grade of the articles. Results: Finally, 9 literature works were extracted, including 4 guidelines, 3 systematic reviews, and 2 evidence summaries. The relevant contents of the literature were extracted and summarized, and 20 pieces of the best evidence were obtained. Conclusion: Breast feeding, sweetener, Kangaroo mother care, sensory stimulation, nonnutritive sucking, and other nondrug nursing programs can reduce the neonatal operational pain, which has guiding significance in neonatal operational pain management.
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Color design for 3D indoor scenes is a challenging problem due to many factors that need to be balanced. Although learning from images is a commonly adopted strategy, this strategy may be more suitable for natural scenes in which objects tend to have relatively fixed colors. For interior scenes consisting mostly of man-made objects, creative yet reasonable color assignments are expected. We propose C3 Assignment, a system providing diverse suggestions for interior color design while satisfying general global and local rules including color compatibility, color mood, contrast, and user preference. We extend these constraints from the image domain to [Formula: see text], and formulate 3D interior color design as an optimization problem. The design is accomplished in an omnidirectional manner to ensure a comfortable experience when the inhabitant observes the interior scene from possible positions and directions. We design a surrogate-assisted evolutionary algorithm to efficiently solve the highly nonlinear optimization problem for interactive applications, and investigate the system performance concerning problem complexity, solver convergence, and suggestion diversity. Preliminary user studies have been conducted to validate the rule extension from 2D to 3D and to verify system usability.
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ABSTRACT: The influence of family history on children with irritable bowel syndrome (IBS) is unknown. We conducted a retrospective study to compare the clinical profile and management differences between children with a family history of IBS (FH-IBS) versus without. A total of 251 children were included in the study, 75 (30%) had FH-IBS and 176 (70%) did not. No significant differences were observed between the 2 groups in sex composition, age at initial visit, age of IBS diagnosis, dietary modifications, supplements, laxatives, antispasmodics, antidiarrheals, and cyproheptadine use. Children with FH-IBS were, however, more like to have psychological comorbidities (41% vs 23%, Pâ=â0.003), and were more likely to receive psychological counseling (49% vs 23%, Pâ<â0.001) and antidepressant treatment (36% vs 15%, Pâ<â0.001) versus children without. We concluded that children with FH-IBS are more likely to have underlying psychological disorders and receive psychological interventions.
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Síndrome del Colon Irritable , Antidiarreicos/uso terapéutico , Niño , Humanos , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/tratamiento farmacológico , Laxativos/uso terapéutico , Parasimpatolíticos/uso terapéutico , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate the associations between BADL/IADL disability and depressive symptoms from the perspective of gender among older adults in China. METHODS: This cross-sectional study used the data from the second wave of the China Health and Retirement Longitudinal Study (CHARLS). The sample included 3463 older adults aged 60â¯years and older across China. Multivariable logistic regression models were conducted. RESULTS: Among 3463 older adults, 1240 (35.8%) were classified as depressed, the prevalence of BADL and IADL disabilities were 756 (21.8%) and 1194 (34.5%), respectively. After controlling for covariates, BADL/IADL disability was significantly associated with an increased risk of depression prevalence both in men and women among older adults. Compared with IADL independent, IADL disability was about two times more likely to develop depressive symptoms in men (ORâ¯=â¯2.165, 95% CIâ¯=â¯1.661-2.822), which was much higher than that in women (ORâ¯=â¯1.748, 95% CIâ¯=â¯1.415-2.160). In contrast, the odds of being depressed for women with BADL disability (ORâ¯=â¯1.824, 95% CIâ¯=â¯1.447-2.299) were much higher than the odds for men with BADL disability (ORâ¯=â¯1.791, 95% CIâ¯=â¯1.348-2.379). CONCLUSIONS: Older adults with BADL/IADL disability were more likely to have depressive symptoms both for men and women. However, the associations between depressive symptoms and BADL/IADL disability were different in gender. Our results suggest that differential institutional care service and appropriate strategies for improvement in mental health are required.
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Actividades Cotidianas , Depresión/epidemiología , Anciano , Anciano de 80 o más Años , China/epidemiología , Estudios Transversales , Depresión/etiología , Personas con Discapacidad/psicología , Personas con Discapacidad/estadística & datos numéricos , Femenino , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Factores Sexuales , Encuestas y CuestionariosRESUMEN
UVR8 is a novel UV-B photoreceptor that regulates a range of plant responses and is already used as a versatile optogenetic tool. Instead of an exogenous chromophore, UVR8 uniquely employs tryptophan side chains to accomplish UV-B photoreception. UV-B absorption by homodimeric UVR8 induces monomerization and hence signaling, but the underlying photodynamic mechanisms are not known. Here, by using a combination of time-resolved fluorescence and absorption spectroscopy from femto- to microseconds, we provide the first experimental evidence for the UVR8 molecular signaling mechanism. The results indicate that tryptophan residues at the dimer interface engage in photoinduced proton coupled electron transfer reactions that induce monomerization.
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Proteínas de Arabidopsis/química , Arabidopsis/química , Proteínas Cromosómicas no Histona/química , Transporte de Electrón , Electrones , Luz , Modelos Moleculares , Procesos Fotoquímicos , Multimerización de Proteína , Protones , Espectrometría de FluorescenciaRESUMEN
Aromatic amino acid side chains have a rich role within proteins and are often central to their structure and function. Suitable isotopic-labelling strategies enable studies of sub-nanosecond aromatic-ring dynamics using solution NMR relaxation methods. Surprisingly, it was found that the three aromatic side chains in human ubiquitin show a sharp thermal dynamical transition at approximately 312â K. Hydrostatic pressure has little effect on the low-temperature behavior, but somewhat decreases the amplitude of motion in the high-temperature regime. Therefore, below the transition temperature, ring motion is largely librational. Above this temperature, a complete ring-rotation process that is fully consistent with a continuous diffusion not requiring the transient creation of a large activated free volume occurs. Molecular dynamics simulations qualitatively corroborate this view and reinforce the notion that the dynamical character of the protein interior has much more liquid-alkane-like properties than previously appreciated.
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Ubiquitina/química , Humanos , Simulación de Dinámica Molecular , Resonancia Magnética Nuclear Biomolecular , Conformación Proteica , TemperaturaRESUMEN
High-pressure NMR spectroscopy has emerged as a complementary approach for investigating various structural and thermodynamic properties of macromolecules. Noticeably absent from the array of experimental restraints that have been employed to characterize protein structures at high hydrostatic pressure is the residual dipolar coupling, which requires the partial alignment of the macromolecule of interest. Here we examine five alignment media that are commonly used at ambient pressure for this purpose. We find that the spontaneous alignment of Pf1 phage, d(GpG) and a C12E5/n-hexnanol mixture in a magnetic field is preserved under high hydrostatic pressure. However, DMPC/DHPC bicelles and collagen gel are found to be unsuitable. Evidence is presented to demonstrate that pressure-induced structural changes can be identified using the residual dipolar coupling.
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Resonancia Magnética Nuclear Biomolecular , Proteínas/química , Bacteriófago Pf1/química , Dimiristoilfosfatidilcolina/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Humanos , Presión Hidrostática , Micelas , Proteínas de Unión Periplasmáticas/química , Éteres Fosfolípidos/química , Estructura Secundaria de Proteína , Ubiquitina/químicaRESUMEN
The cooperative nature of protein substructure and internal motion is a critical aspect of their functional competence about which little is known experimentally. NMR relaxation is used here to monitor the effects of high pressure on fast internal motion in the protein ubiquitin. In contrast to the main chain, the motions of the methyl-bearing side chains have a large and variable pressure dependence. Within the core, this pressure sensitivity correlates with the magnitude of motion at ambient pressure. Spatial clustering of the dynamic response to applied hydrostatic pressure is also seen, indicating localized cooperativity of motion on the sub-nanosecond time scale and suggesting regions of variable compressibility. These and other features indicate that the native ensemble contains a significant fraction of members with characteristics ascribed to the recently postulated "dry molten globule". The accompanying variable side-chain conformational entropy helps complete our view of the thermodynamic architecture underlying protein stability, folding, and function.