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BACKGROUND: Since the publication in 2009 of the Guidelines on the Diagnosis and Treatment of Irritable Bowel Syndrome of the Asociación Mexicana de Gastroenterología (2009 Guidelines), there have been significant advances in our knowledge of the epidemiology, pathophysiology, diagnosis, and treatment of this disease. AIMS: To present a consensus review of the most current knowledge of IBS, updating the 2009 Guidelines by incorporating new internationally published scientific evidence, with a special interest in Mexican studies. METHODS: The PubMed literature from January 2009 to March 2015 was reviewed and complemented through a manual search. Articles in English and Spanish were included and preference was given to consensuses, guidelines, systematic reviews, and meta-analyses. Statements referring to the different aspects of the disease were formulated and voted upon by 24 gastroenterologists employing the Delphi method. Once a consensus on each statement was reached, the quality of evidence and strength of recommendation were determined through the GRADE system. RESULTS: Forty-eight statements were formulated, updating the information on IBS and adding the complementary data that did not appear in the 2009 Guidelines regarding the importance of exercise and diet, diagnostic strategies, and current therapy alternatives that were analyzed with more stringent scientific vigor or that emerged within the last 5 years. CONCLUSIONS: We present herein a consensus review of the most relevant advances in the study of IBS, updating and complementing the 2009 Guidelines. Several studies conducted in Mexico were included.
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Síndrome do Intestino Irritável/terapia , Consenso , Técnica Delphi , Medicina Baseada em Evidências , Guias como Assunto , Humanos , MéxicoRESUMO
BACKGROUND AND AIMS: Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD. METHODS: The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin. Breast milk proteomics was profiled using Olink inflammation panel. RESULTS: We analysed gut microbiota of 1034 faecal samples from 294 infants [80 born to mothers with and 214 to mothers without IBD]. Alpha diversity was driven by maternal IBD status and time point. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breast milk samples [91 from mothers with IBD], mothers with IBD displayed lower abundance of proteins involved in immune regulation, such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumour necrosis factor-beta, and C-C motif chemokine 20, as compared with control mothers [adjusted pâ =â 0.0016, 0.049, 0.049, and 0.049, respectively], with negative correlations with baby´s calprotectin, and microbiome at different time points. CONCLUSION: Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breast milk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby's gut microbiome and feacal calprotectin.
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Doenças Inflamatórias Intestinais , Microbiota , Lactente , Feminino , Humanos , Gravidez , Leite Humano/química , Estudos Prospectivos , RNA Ribossômico 16S/genética , Proteômica , Doenças Inflamatórias Intestinais/metabolismo , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , MãesRESUMO
BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipersensibilidade , Tuberculose , Humanos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Pessoal de SaúdeRESUMO
BACKGROUND: Acute pancreatitis (AP) etiology and frequency vary in relation to geographic region. AIMS: To determine the etiology, frequency, and mortality of AP in a Mexican population. PATIENTS AND METHODS: We carried out a prospective study of first episode AP patients over a period of 6 years. RESULTS: A total of 605 patients with a mean age of 40 years were included in the study. Sixty-four percent of them presented with overweight and/or obesity determined through BMI. Etiology was biliary in 66.60%, it was due to alcohol consumption in 15.90%, hypertriglyceridemia in 7.80%, it was post-endoscopic retrograde cholangiopancreatography (ERCP) in 2.10%, and was undetermined in 7.20%. Pancreatic infection was suspected in 70 patients and they underwent CT-guided fine needle aspiration. Thirty-two of those patients were diagnosed with pancreatic infection in which Staphylococcus spp was the most common microorganism. Overall mortality was 5.00% (2.60% < 30 years and 10.00% > 70 years). Necrosis, pancreatic infection, and mortality were more frequent in the cases in which etiology was due to alcohol ingestion. CONCLUSIONS: The most frequent AP etiology was biliary, but that caused by alcohol presented with more complications. Overall mortality was 5.00% and was higher in the elderly patients.
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Pancreatite/epidemiologia , Doença Aguda , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/complicações , Biópsia por Agulha Fina , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicações , Pancreatite/etiologia , Pancreatite/mortalidade , Estudos ProspectivosRESUMO
BACKGROUND: Due to the reported low incidence of gastrointestinal TB, there is a lack of data related to the prognosis, risk factors and frequency of resistant TB in this subgroup of patients.OBJECTIVE: To report the clinical presentation, diagnostic methods, treatment and outcomes in gastrointestinal TB.METHODS: We prospectively studied the demographic, clinical, and paraclinical data of all consecutive gastrointestinal TB inpatients over an 8-year period.RESULTS: We identified gastrointestinal TB in 28 (3.5%) out of 799 inpatients with TB infection. Seven patients (25%) were HIV-positive. Overall mortality was 35.7%, with the combined variable of haemoglobin <12 g/dL and albumin <2.8 g/dL being independently associated with mortality (OR 25.7, 95% CI 1.405-471.1, P = 0.029). No difference in the need for surgery (28.6% vs. 47.6%, P = 0.662), occurrence of septic shock (14.3 vs. 23.8%, P = 1.00) or mortality (14.3% vs. 42.9%, P = 0.364) was found between HIV and non-HIV patients.CONCLUSION: Gastrointestinal TB was rare among TB patients in Hospital Universitario "Dr José E. González" (3.5%), but had a high mortality rate (35.7%). Clinical evolution, drug susceptibility patterns and outcomes were similar in HIV and non-HIV patients. In both groups, the combined haemoglobin and albumin variable on admission was clearly associated with mortality.
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Infecções por HIV , Tuberculose , Humanos , Albuminas , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Incidência , Estudos Retrospectivos , Fatores de Risco , Tuberculose/mortalidadeRESUMO
BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.
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Tuberculose Latente , Tuberculose , Cuidadores , Criança , Humanos , Programas de Rastreamento , Padrões de Referência , Tuberculose/diagnóstico , Tuberculose/prevenção & controleRESUMO
During inertial confinement fusion experiments at the National Ignition Facility (NIF), a capsule filled with deuterium and tritium (DT) gas, surrounded by a DT ice layer and a high-density carbon ablator, is driven to the temperature and densities required to initiate fusion. In the indirect method, 2 MJ of NIF laser light heats the inside of a gold hohlraum to a radiation temperature of 300 eV; thermal x rays from the hohlraum interior couple to the capsule and create a central hotspot at tens of millions degrees Kelvin and a density of 100-200 g/cm3. During the laser interaction with the gold wall, m-band x rays are produced at â¼2.5 keV; these can penetrate into the capsule and preheat the ablator and DT fuel. Preheat can impact instability growth rates in the ablation front and at the fuel-ablator interface. Monitoring the hohlraum x-ray spectrum throughout the implosion is, therefore, critical; for this purpose, a Multilayer Mirror (MLM) with flat response in the 2-4 keV range has been installed in the NIF 37° Dante calorimeter. Precision engineering and x-ray calibration of components mean the channel will report 2-4 keV spectral power with an uncertainty of ±8.7%.
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The eighth edition of the Union for International Cancer Control (UICC) staging manual was recently introduced. The staging of oral cavity squamous cell carcinoma saw changes in relation to depth of invasion and extra-nodal extension. We aimed to evaluate this system and its prognostic ability in a UK cohort. A retrospective review was undertaken of patients diagnosed with squamous cell carcinoma (SCC) of the oral cavity between January 2009 and December 2013. Data were collected on demographics, histology, and recurrence-free (RFS) and five-year overall survival (OS). Patients were staged using both the seventh and eighth editions of the UICC staging manual. Stage-specific survival analysis was performed using the Kaplan-Meier method. A total of 191 records were reviewed and 87 were included in the analysis. The mean (range) age was 60 (37-88) years, and 53% were male. The tongue was the most common site (51%). Using the seventh edition patients were staged as stage I=30, II=14, III=7, IVa=35, and IVb=1. Applying the eighth edition, 26 patients (30%) were upstaged (I=24, II=15, III=14, IVa=17, IVb=17). Ten were upstaged based on pT and 16 on pN status. Both staging manuals showed statistically significant discrimination between stages for both OS and RFS. Patients upstaged from stage IVa in the seventh edition had significantly worse OS in the new system (p=0.043). Both staging systems discriminated accurately between stages. Patients upstaged in stage IVa showed significantly worse OS suggesting improved prognostication with the eighth edition and the changes introduced.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Reino UnidoRESUMO
The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.
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Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Nitroimidazóis/uso terapêutico , Oxazóis/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
The generalized mean spherical approximation of Stell and Sun [J. Chem. Phys. 63, 5333 (1975)] for the binary charge-symmetric restricted primitive model (electroneutral mixture of equally sized hard spheres) is extended to charge-asymmetric binary electrolytes and to the generally multicomponent, but still restricted (i.e., equally sized) primitive model.
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Proteins necessary for the normal regulation of the cell cycle include minichromosome maintenance protein 2 (Mcm2) and geminin. These are overexpressed in several premalignant and malignant tumours. The Mcm2/Ki67 ratio can be used to estimate the population of cells that are in early G(1) (licensed to proliferate), and the geminin/Ki67 ratio can determine the relative length of G(1). A high ratio indicates a short G(1) and a high rate of cell proliferation. Mcm2 and geminin have been scarcely explored in oral epithelial dysplasia (OED) and oral squamous-cell carcinoma (OSCC). The purpose of this study was to identify the expression pattern of Mcm2, Ki67 and geminin in normal oral mucosa (NOM), OED and their subsequent OSCC, to determine if expression could help predict the prognosis of OED. Paraffin sections of 41 OED cases that progressed to carcinoma, 40 OED without malignant progression, 38 OSCC and 15 NOM were immunostained with antibodies against Mcm2, geminin and Ki67. Labelling indices (LIs) increased progressively from NOM, OED and OSCC (Mcm2, P<0.001; geminin, P<0.001 and Ki67, P<0.001). In all the OED cases (n=81) the levels of expression of Mcm2 (LI, 73.6), geminin (LI, 24.4) and Ki67 (LI, 44.5) were elevated indicating a constant cell-cycle re-entry. When the OED groups were compared, Mcm2 protein expression was higher in the OED with malignant progression (P=0.04), likewise there was a significant increase in the Mcm2/Ki67 and geminin/Ki67 ratios (P=0.04 and 0.02 respectively). Mcm2 and geminin proteins seem to be novel biomarkers of growth and may be useful prognostic tools for OED.
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Carcinoma de Células Escamosas/química , Proteínas de Ciclo Celular/análise , Antígeno Ki-67/análise , Mucosa Bucal/química , Neoplasias Bucais/química , Proteínas Nucleares/análise , Lesões Pré-Cancerosas/química , Adulto , Idoso , Biomarcadores Tumorais/análise , Estudos de Casos e Controles , Feminino , Geminina , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo , Estudos RetrospectivosRESUMO
The self-consistent generalized Langevin equation (SCGLE) theory of colloid dynamics is employed to describe the ergodic-non-ergodic transition in model mono-disperse colloidal dispersions whose particles interact through hard-sphere plus short-ranged attractive forces. The ergodic-non-ergodic phase diagram in the temperature-concentration state space is determined for the hard-sphere plus attractive Yukawa model within the mean spherical approximation for the static structure factor by solving a remarkably simple equation for the localization length of the colloidal particles. Finite real values of this property signals non-ergodicity and determines the non-ergodic parameters f(k) and f(s)(k). The resulting phase diagram for this system, which involves the existence of reentrant (repulsive and attractive) glass states, is compared with the corresponding prediction of mode coupling theory. Although both theories coincide in the general features of this phase diagram, there are also clear qualitative differences. One of the most relevant is the SCGLE prediction that the ergodic-attractive glass transition does not preempt the gas-liquid phase transition, but always intersects the corresponding spinodal curve on its high-concentration side. We also calculate the ergodic-non-ergodic phase diagram for the sticky hard-sphere model to illustrate the dependence of the predicted SCGLE dynamic phase diagram on the choice of one important constituent element of the SCGLE theory.
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Tuberculosis (TB) in migrants represents an important clinical and public health threat, particularly in low TB incidence countries. The current review is aimed to assess issues related to screening and treatment of migrants with latent TB infection or TB disease.
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Migrantes , Tuberculose/prevenção & controle , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/prevenção & controle , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológicoRESUMO
La hemorragia del tracto digestivo superior (HTDS) es el sangrado originado por encima del ángulo de Treitz. A pesar del aumento en las estrategias de prevención, del incremento en los tratamientos con Inhibidor de bomba de protones (IBP) y de la intervención endoscópica temprana, esta patología sigue siendo una causa frecuente de consulta a urgencias, con una morbimortalidad no despreciable y alta carga para el sistema de salud. Esta revisión se enfoca en la HTDS de causa diferente a las varices. La principal causante de esta entidad es la enfermedad ácido-péptica, que es consecuencia del gran consumo de antiinflamatorios no esteroideos (AINES) y de la infección por Helicobacter Pylori. Otras causas son el síndrome de Mallory Weiss, la esofagitis erosiva, las malformaciones arteriovenosas y la malignidad.
Upper gastrointestinal bleeding (UGIB) refers to any bleeding originating above the angle of Treitz. Despite an increase in prevention strategies, proton pump inhibitor (PPI) therapy and early endoscopic intervention, this pathology continues to be an important cause of admission to the emergency department for gastrointestinal causes, having a pretty high morbidity and mortality in addition to a high burden on the health system. This review focuses on non-variceal UGIB. The main cause of this entity being peptic acid disease, due to great consumption of NSAIDs and Helicobacter Pylori infection. Other causes are Mallory Weiss syndrome, erosive esophagitis, arteriovenous malformations, and malignancy.
A hemorragia do trato digestivo superior (HTDS) é o sangrado originado acima do ângulo de Treitz. Apesar do aumento nas estratégias de prevenção, do incremento nos tratamentos com Inibidor da bomba de prótons (IBP) e da intervenção endoscópica precoce, esta patologia segue sendo uma causa frequente de consulta a urgências, com uma morbimortalidade não depreciável e alta carga para o sistema de saúde. Esta revisão se enfoca na HTDS de causa diferente às varizes. A principal causante desta entidade é a doença ácido-péptica, que é consequência do grande consumo de anti-inflamatórios não esteróideos (AINES) e da infecção por HelicobacterPylori. Outras causas são a síndrome de Mallory Weiss, a esofagites erosiva, as malformações arteriovenosas e a malignidade. Palavras-chave: hemorragia gastrointestinal; úlcera péptica; endoscopia gastrointestinal; inibidores da bomba de prótons; medicina geral.
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Humanos , Hemorragia Gastrointestinal , Úlcera Péptica , Anti-Inflamatórios não Esteroides , Endoscopia Gastrointestinal , Helicobacter pylori , Trato Gastrointestinal , Serviço Hospitalar de Emergência , Esofagite , Inibidores da Bomba de Prótons , Síndrome de Mallory-Weiss , NeoplasiasRESUMO
C3Hf (XVII) mice never develop spontaneous mammary tumors. However, the transplantation of an isologous pituitary gland under their kidney capsule is followed by a 10-fold increase in serum and pituitary prolactin content (180 ng/ml and 20 micrograms/mg of tissue, respectively), concomitant with an increase of prolactin receptors in mammary glands. Under these conditions, mammary tumors appear in 90% of the mice. If a racemic brominated triphenylethylene, i.e., broparestrol, is administered, serum and pituitary prolactin decrease rapidly (10 ng/ml and 4 micrograms/mg of tissue, respectively), and prolactin receptors in the mammary gland are markedly reduced. This compound also inhibits the development of normal mammary glands, prevents mammary carcinogenesis, and unexpectedly causes a significant atrophy of the ovaries. Our study confirms that prolactin is a key hormone involved in murine mammary carcinogenesis and that it can act directly on the mammary gland by stimulaing the level of its own receptor.
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Neoplasias Mamárias Experimentais/induzido quimicamente , Prolactina , Estilbenos/farmacologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos C3H , Hipófise/transplante , Prolactina/antagonistas & inibidores , Prolactina/sangue , Receptores de Superfície Celular/metabolismo , EstereoisomerismoRESUMO
BACKGROUND: High intake of sugar-sweetened beverages (SSB) has been suggested to contribute to the pediatric obesity epidemic, however, how the home food environment influence children's intake of SSB among Hispanic families is still poorly understood. OBJECTIVES: To evaluate the relationships between the home food environment and Hispanic children's diet in relation to weight status and insulin resistance (IR). METHODS: A food frequency questionnaire was administered to 187 Hispanic children (ages 10 to 14 years) and anthropometrics were measured. IR was estimated from fasting insulin and glucose levels using the homeostasis model assessment of insulin resistance (HOMAIR ). Parents reported on family demographics and the home food environment. A structural equation modelling approach was applied to examine the hypothesized relationships among variables. RESULTS: The prevalence of childhood overweight and obesity was 52.8% and it was positively associated with HOMAIR (ß = 0.687, P < .0001). Children's SSB consumption was positively associated with children's body mass index z-score (ß = 0.151, P < 0.05) and subsequently to HOMAIR . Children's SSB consumption was predicted by home availability (ß = 0.191) and parental intake of SSB (ß = 0.419) (P < 0.05). The model fit indices [χ(2) = 45.821 (d.f. = 30, P > 0.01 and < 0.05), χ(2) /d.f. = 1.53, root mean square error of approximation = 0.053 (90% confidence interval = 0.016, 0.082), comparative fit index = 0.904] suggested a satisfactory goodness-of-fit. CONCLUSIONS: The home food environment and parental diet seem to play an important role in the children's access to and intake of SSB, which in turn predicted children's weight status.
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Dieta , Comportamento Alimentar/psicologia , Hispânico ou Latino/psicologia , Pais/psicologia , Obesidade Infantil/prevenção & controle , Adolescente , Atitude Frente a Saúde , Bebidas , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Dieta/efeitos adversos , Ingestão de Alimentos , Feminino , Humanos , Resistência à Insulina , Masculino , Obesidade Infantil/psicologia , Valor Preditivo dos Testes , Inquéritos e Questionários , População UrbanaRESUMO
Mitoplasts isolated from rat liver mitochondria were treated with dimethyladipimidate, a bifunctional alkylating agent. This agent causes, concurrently with modification of amino groups, loss of osmotic response. It was found that after cross-linking, the movement effector, succinate, was unable to induce the aspartate aminotransferase release from mitoplasts. In contrast, dimethyladipimidate-treated mitoplasts were still able to internalize 125I-labeled aspartate aminotransferase upon removal of exogenous succinate. The possible involvement of membrane asymmetry in the mechanism of translocation of porteins through the inner mitochondrial membrane is discussed.
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Aspartato Aminotransferases/metabolismo , Membranas Intracelulares/metabolismo , Mitocôndrias Hepáticas/enzimologia , Animais , Reagentes de Ligações Cruzadas , Dimetil Adipimidato , Ratos , Succinatos/metabolismo , Sacarose/metabolismoRESUMO
Dystrophin, the protein defective in Duchenne muscular dystrophy (DMD), plays a critical role in the formation and maintenance of the neuromuscular junction. In addition to dystrophin, activation of internal promoters of the DMD gene leads to the production of several short products. Among these, Dp71, which consists of the C-terminal domain of dystrophin, is the most abundant product of the gene in non-muscle tissues and brain. In this report, we compare the temporal and regional expression patterns of dystrophin and Dp71 at different stages of embryonic development and during retinal differentiation in zebrafish. The Dp71 transcripts are the earliest to be expressed at 9-10 h post-fertilization (hpf) in the axial mesoderm. As development proceeds, intense Dp71 staining is observed in the notochord, the developing brain, the marginal regions of the somites and the eye primordium. At the completion of retinal differentiation, Dp71 is expressed in the ganglion and inner nuclear layers. Transcripts encoding dystrophin have a slightly later onset of expression, 13-14 hpf, and remain restricted to the transverse myosepta through all the developmental stages examined. The complementary patterns of expression of dystrophin and Dp71 suggest that these two proteins exert different functions during embryonic development in zebrafish.
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Distrofina/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Peixe-Zebra/embriologia , Animais , Encéfalo/metabolismo , Distrofina/análogos & derivados , Distrofina/química , Hibridização In Situ , Mesoderma/metabolismo , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Estrutura Terciária de Proteína , RNA Mensageiro/metabolismo , Retina/metabolismo , Fatores de TempoRESUMO
BACKGROUND: This study introduces a novel self-report instrument to measure children's time-use in physical and sedentary activities and examines the relationships between children's time-use and physical fitness and risks of obesity and diabetes. METHODS: The new instrument utilizes a series of timelines, each representing an activity type. 188 children (53% girls) aged 10 to 14 year-old participated in the study. Their time-use data for two weekdays and one weekend day were collected. Anthropometrics and cardiovascular fitness were measured and children's BMI z-score and PACER z-score were computed. One-time blood draw for fasting glucose and insulin were used to calculate insulin resistance using homeostasis model assessment for insulin resistance (HOMAIR). RESULTS: The reliability assessment of this instrument indicated a moderately reproducible procedure (ICC > 0.6) for six activity types. The validity correlation for motorized travel time was high (r = 0.226, P < 0.05) between self-report instrument and GPS tracks. PACER z-score was positively correlated with time-uses of play (r = 0.159, P < 0.05), and organized sports (r = 0.198, P < 0.05); and was highly inversely correlated with BMI z-score (r = -0.441, P < 0.0001) and HOMAIR (r = -0.472, P < 0.0001). Overall, only 14% of the children had physical activity for more than 60 minutes daily over three observation days. CONCLUSIONS: This instrument is particularly useful in assessing children's activity patterns, especially for specific physical activities. The new instrument provides a reproducible measure of children's perception of their activities. Our results emphasize the temporal context which is critical to formulating effective interventions targeting physical activity increase in children. Further efforts are needed to understand the differences between activity time obtained by the new self-report instrument and GPS tracks.
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In this study, the presence and cellular distribution of dystrophin family products (i.e. Dp71d, Dp71f-like protein and dystrobrevin) was examined by indirect immunofluorescence and Western blotting in guinea pig spermatozoa. Two dystrophin-associated proteins, beta-dystroglycan and alpha-syntrophin, and nNOS a protein frequently associated with alpha-syntrophin, were determined. In spermatozoa lacking plasma membrane and acrosome, Dp71f-like protein was found in the postacrosomal perinuclear theca and also in the middle piece of the flagellum. In the flagellum, Dp71f-like protein is localized together with alpha-syntrophin and nNOS. Dp71d was present in the plasma membrane of the middle piece with beta-dystroglycan, alpha-syntrophin and nNOS. Dp71d was also present in plasma membrane of the post acrosomal region, but only with nNOS. Finally, dystrobrevin was located all along skeletal flagellum structures and in the subacrosomal hemisphere of the perinuclear theca. This distinct and complementary distribution in various domains of spermatozoa may reveal a specific function for each short dystrophin family product, in the stabilization of the domains where they are located.