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1.
Mol Syst Biol ; 18(2): e10629, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35156780

RESUMO

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel in secretory epithelia with a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. While remarkable treatment advances have been made recently in the form of modulator drugs directly rescuing CFTR dysfunction, there is still considerable scope for improvement of therapeutic effectiveness. Here, we report the application of a high-throughput screening variant of the Mammalian Membrane Two-Hybrid (MaMTH-HTS) to map the protein-protein interactions of wild-type (wt) and mutant CFTR (F508del), in an effort to better understand CF cellular effects and identify new drug targets for patient-specific treatments. Combined with functional validation in multiple disease models, we have uncovered candidate proteins with potential roles in CFTR function/CF pathophysiology, including Fibrinogen Like 2 (FGL2), which we demonstrate in patient-derived intestinal organoids has a significant effect on CFTR functional expression.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Animais , Membrana Celular/metabolismo , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrinogênio/genética , Fibrinogênio/metabolismo , Fibrinogênio/farmacologia , Ensaios de Triagem em Larga Escala , Humanos , Mamíferos , Mutação
2.
FASEB J ; 35(1): e21265, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33373067

RESUMO

Necrotizing enterocolitis (NEC) is one of the most severe gastrointestinal diseases affecting premature infants. It has been shown that NEC is associated with disrupted intestinal barrier and dysregulated endoplasmic reticulum (ER)-stress response. It has also been shown that stem cells derived from amniotic fluid (AFSC) rescued intestinal injury in experimental NEC. Herein, we hypothesized that the beneficial effects of AFSC in the injured intestine are due to the restoration of intestinal barrier function. We evaluated intestinal barrier function using an ex vivo intestinal organoid model of NEC. We found that AFSC restored the expression and localization of tight junction proteins in intestinal organoids, and subsequently decreased epithelial permeability. AFSC rescued tight junction expression by inducing a protective ER stress response that prevents epithelial cell apoptosis in injured intestinal organoids. Finally, we validated these results in our experimental mouse model of NEC and confirmed that AFSC induced sustained ER stress and prevented intestinal apoptosis. This response led to the restoration of tight junction expression and localization, which subsequently reduced intestinal permeability in NEC pups. These findings confirm that intestinal barrier function is disrupted during NEC intestinal injury, and further demonstrate the disruption can be reversed by the administration of AFSC through the activation of the ER stress pathway. This study provides insight into the pathogenesis of NEC and highlights potential therapeutic targets for the treatment of NEC.


Assuntos
Líquido Amniótico/metabolismo , Estresse do Retículo Endoplasmático , Enterocolite Necrosante/metabolismo , Mucosa Intestinal/metabolismo , Células-Tronco/metabolismo , Junções Íntimas/metabolismo , Animais , Apoptose , Enterocolite Necrosante/patologia , Mucosa Intestinal/patologia , Camundongos , Organoides/metabolismo , Organoides/patologia , Permeabilidade , Ratos , Células-Tronco/patologia , Junções Íntimas/patologia
3.
Am J Respir Cell Mol Biol ; 61(6): 755-764, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31189070

RESUMO

SLC6A14-mediated l-arginine transport has been shown to augment the residual anion channel activity of the major mutant, F508del-CFTR, in the murine gastrointestinal tract. It is not yet known if this transporter augments residual and pharmacological corrected F508del-CFTR in primary airway epithelia. We sought to determine the role of l-arginine uptake via SLC6A14 in modifying F508del-CFTR channel activity in airway cells from patients with cystic fibrosis (CF). Human bronchial epithelial (HBE) cells from lung explants of patients without CF (HBE) and those with CF (CF-HBE) were used for H3-flux, airway surface liquid, and Ussing chamber studies. We used α-methyltryptophan as a specific inhibitor for SLC6A14. CFBE41o-, a commonly used CF airway cell line, was employed for studying the mechanism of the functional interaction between SLC6A14 and F508del-CFTR. SLC6A14 is functionally expressed in CF-HBE cells. l-arginine uptake via SLC6A14 augmented F508del-CFTR function at baseline and after treatment with lumacaftor. SLC6A14-mediated l-arginine uptake also increased the airway surface liquid in CF-HBE cells. Using CFBE41o cells, we showed that the positive SLC6A14 effect was mainly dependent on the nitric oxide (NO) synthase activity, nitrogen oxides, including NO, and phosphorylation by protein kinase G. These finding were confirmed in CF-HBE, as inducible NO synthase inhibition abrogated the functional interaction between SLC6A14 and pharmacological corrected F508del-CFTR. In summary, SLC6A14-mediated l-arginine transport augments residual F508del-CFTR channel function via a noncanonical, NO pathway. This effect is enhanced with increasing pharmacological rescue of F508del-CFTR to the membrane. The current study demonstrates how endogenous pathways can be used for the development of companion therapy in CF.


Assuntos
Sistemas de Transporte de Aminoácidos/fisiologia , Arginina/metabolismo , Brônquios/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/fisiologia , Fibrose Cística/terapia , Sistemas de Transporte de Aminoácidos/antagonistas & inibidores , Sistemas de Transporte de Aminoácidos/genética , Transporte Biológico , Brônquios/citologia , Células Cultivadas , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/deficiência , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Genes Reporter , Humanos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Recombinantes/metabolismo , Propriedades de Superfície , Transdução Genética , Triptofano/análogos & derivados , Triptofano/farmacologia
4.
Mol Pharmacol ; 96(4): 515-525, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31427400

RESUMO

ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modest and variable, prompting the search for complementary interventions. As our previous work identified a positive effect of arginine-dependent nitric oxide signaling on residual F508del-Cftr function in murine intestinal epithelium, we were prompted to determine whether strategies aimed at increasing arginine would enhance F508del-cystic fibrosis transmembrane conductance regulator (CFTR) channel activity in patient-derived airway epithelia. Now, we show that the addition of arginine together with inhibition of intracellular arginase activity increased cytosolic nitric oxide and enhanced the rescue effect of ORKAMBI on F508del-CFTR-mediated chloride conductance at the cell surface of patient-derived bronchial and nasal epithelial cultures. Interestingly, arginine addition plus arginase inhibition also enhanced ORKAMBI-mediated increases in ciliary beat frequency and mucociliary movement, two in vitro CF phenotypes that are downstream of the channel defect. This work suggests that strategies to manipulate the arginine-nitric oxide pathway in combination with CFTR modulators may lead to improved clinical outcomes. SIGNIFICANCE STATEMENT: These proof-of-concept studies highlight the potential to boost the response to cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators, lumacaftor and ivacaftor, in patient-derived airway tissues expressing the major CF-causing mutant, F508del-CFTR, by enhancing other regulatory pathways. In this case, we observed enhancement of pharmacologically rescued F508del-CFTR by arginine-dependent, nitric oxide signaling through inhibition of endogenous arginase activity.


Assuntos
Aminofenóis/farmacologia , Aminopiridinas/farmacologia , Arginase/antagonistas & inibidores , Arginina/metabolismo , Benzodioxóis/farmacologia , Fibrose Cística/metabolismo , Óxido Nítrico/metabolismo , Quinolonas/farmacologia , Animais , Brônquios/citologia , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Células Cultivadas , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Citosol/metabolismo , Combinação de Medicamentos , Humanos , Mucosa Intestinal/metabolismo , Camundongos , Mutação , Nariz/citologia , Nariz/efeitos dos fármacos
5.
BMC Pregnancy Childbirth ; 19(1): 153, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060522

RESUMO

BACKGROUND: Birth ball is one of the non-pharmacologic pain relief methods to help mothers cope with the labouring process. A randomised controlled trial (RCT) is conducted to evaluate the effectiveness, safety and harm of birth ball use by pregnant women in labour compared to treatment as usual group. METHODS: A prospective multi-centre randomised controlled trial (RCT) will be conducted in Obstetrics and Gynaecological units of five public hospitals in Hong Kong, China. Data will be collected from March 2016 onward for 2 years. The target population is Chinese women with an uncomplicated singleton pregnancy at gestational age of 37 to 42 weeks. Participants are randomised based on parity (nulliparous and multiparous) and type of labour onset (spontaneous and induced). Women in the intervention group are actively offered and taught how to use a birth ball; those in the control group receive the usual midwifery care. The target sample size is 512. The primary outcome measures are maternal pain intensity, satisfaction with pain relief, sense of control in labour, assisted delivery and satisfaction with childbirth experience. Labour pain relief is measured by visual analogue scale (VAS). Other outcomes will be measured through four different validated questionnaires. To control for potential cluster effects, a linear mixed model will be used. An intention-to-treat analysis is adopted and performed by researchers unknown to subjects' group allocation. DISCUSSION: Results will provide rigorous scientific evidence for policy development and practice. We are using stratified randomisation according to potential confounders of parity and type of labour onset to give four possible combinations. If the results are favourable, it will facilitate systematic implementation to promote birth ball use for women in labour. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR), Registration number: ChiCTR-IIC-16008275 , Date of registration 12 April 2016 (retrospectively registered), Date of enrolment of the first participant to the trial 1 March 2016.


Assuntos
Parto Obstétrico/métodos , Dor do Parto/terapia , Modalidades de Fisioterapia/instrumentação , Adulto , Feminino , Idade Gestacional , Hong Kong , Humanos , Trabalho de Parto , Medição da Dor , Paridade , Satisfação do Paciente , Gravidez , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
Hum Mol Genet ; 25(20): 4590-4600, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-28171547

RESUMO

Cystic fibrosis is realizing the promise of personalized medicine. Recent advances in drug development that target the causal CFTR directly result in lung function improvement, but variability in response is demanding better prediction of outcomes to improve management decisions. The genetic modifier SLC26A9 contributes to disease severity in the CF pancreas and intestine at birth and here we assess its relationship with disease severity and therapeutic response in the airways. SLC26A9 association with lung disease was assessed in individuals from the Canadian and French CF Gene Modifier consortia with CFTR-gating mutations and in those homozygous for the common Phe508del mutation. Variability in response to a CFTR-directed therapy attributed to SLC26A9 genotype was assessed in Canadian patients with gating mutations. A primary airway model system determined if SLC26A9 shows modification of Phe508del CFTR function upon treatment with a CFTR corrector. In those with gating mutations that retain cell surface-localized CFTR we show that SLC26A9 modifies lung function while this is not the case in individuals homozygous for Phe508del where cell surface expression is lacking. Treatment response to ivacaftor, which aims to improve CFTR-channel opening probability in patients with gating mutations, shows substantial variability in response, 28% of which can be explained by rs7512462 in SLC26A9 (P = 0.0006). When homozygous Phe508del primary bronchial cells are treated to restore surface CFTR, SLC26A9 likewise modifies treatment response (P = 0.02). Our findings indicate that SLC26A9 airway modification requires CFTR at the cell surface, and that a common variant in SLC26A9 may predict response to CFTR-directed therapeutics.


Assuntos
Aminofenóis/metabolismo , Antiporters/genética , Fibrose Cística/metabolismo , Genes Modificadores , Pulmão/metabolismo , Variantes Farmacogenômicos , Quinolonas/metabolismo , Aminofenóis/farmacocinética , Aminofenóis/farmacologia , Aminofenóis/uso terapêutico , Antiporters/metabolismo , Canadá , Células Cultivadas , Agonistas dos Canais de Cloreto/metabolismo , Agonistas dos Canais de Cloreto/farmacocinética , Agonistas dos Canais de Cloreto/farmacologia , Agonistas dos Canais de Cloreto/uso terapêutico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Fibrose Cística/patologia , Regulador de Condutância Transmembrana em Fibrose Cística/agonistas , Feminino , França , Estudos de Associação Genética , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Modelos Genéticos , Gravidade do Paciente , Polimorfismo de Nucleotídeo Único , Medicina de Precisão , Quinolonas/farmacocinética , Quinolonas/farmacologia , Quinolonas/uso terapêutico , Transportadores de Sulfato
7.
Pain Manag Nurs ; 18(1): 50-57, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27964912

RESUMO

The purpose of the study was to investigate the effect of upper limb massage on relieving pain among infants undergoing venipuncture in Hong Kong. This study was a crossover, double-blind, randomized controlled trial. Eighty infants at the neonatal intensive care unit were randomly assigned to 2 groups in different order to receive interventions. The massage first group (N = 40) received 2-minute massage before venipuncture on the first occasion then received usual care (control) on the second occasion, and vice versa in the massage second group (N = 40). The infants' behavior and physiological responses were recorded on two occasions: (1) right after the intervention and (2) during the first 30 seconds of venipuncture procedure. The mean pain scores (Premature Infant Pain Profile) were significantly lower in infants who received massage (massage first: 6.0 [standard deviation = 3.3]; massage second: 7.30 [standard deviation = 4.4]) versus control (massage first: 12.0 [standard deviation = 4.3]; massage second: 12.7 [standard deviation = 3.1]). The crude and adjusted generalized estimating equations model showed that the infants had significantly lower pain score when receiving massage as compared to receiving the control treatment, and there were no significant time and carryover effects: -6.03 (95% confidence interval: -7.67 to -4.38), p < .001 and -5.96 (95% confidence interval: -7.56 to -4.36), p < .001, respectively. Upper limb massage may be effective in decreasing infants' venipuncture pain perception.


Assuntos
Massagem/normas , Dor/prevenção & controle , Flebotomia/efeitos adversos , Extremidade Superior/lesões , Feminino , Hong Kong , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/organização & administração , Masculino , Massagem/métodos , Dor/enfermagem
8.
Pain Manag Nurs ; 17(4): 262-71, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27292081

RESUMO

Little is known about how Chinese adolescent girls manage dysmenorrhea. This study aims to explore self-care strategies among Chinese adolescent girls with dysmenorrhea. The study uses a mixed methods design with two phases: a cross-sectional survey in phase I and semistructured interviews in phase II. This paper reports phase II. In line with the phase I findings, 28 adolescent girls with different characteristics (high or low levels of self-care behavior and pain intensity, who did or did not self-medicate, and who had or had not received menstrual education) were recruited for interviews. Content analysis was used for data analysis. Four categories emerged from the data: lifestyle changes, symptom management, communicating dysmenorrhea with others, and seeking medical advice. Girls selected their diets carefully and reduced physical activity during menstruation to avoid aggravating symptoms. Heat therapy commonly was employed for symptom management. A few girls self-medicated to obtain immediate relief from pain, but the majority expressed reservations about using medication because they worried about dependence and side effects. Some girls communicated dysmenorrhea with their family and friends, but the majority did not seek medical advice. The present study showed that girls employed various self-care strategies for dysmenorrhea, including some strategies stemming from traditional Chinese medicine. The findings revealed menstrual etiquette among Chinese adolescent girls with dysmenorrhea, and demonstrated that self-medication was not part of most girls' self-care. Understanding the self-care strategies of these girls is important, as it can help nurses develop a culturally-specific intervention to promote self-care among adolescent girls with dysmenorrhea.


Assuntos
Comportamento do Adolescente/psicologia , Dismenorreia/terapia , Autocuidado/psicologia , Automedicação/psicologia , Adolescente , Estudos Transversais , Dismenorreia/psicologia , Feminino , Humanos , Pesquisa Qualitativa
9.
J Nurs Scholarsh ; 47(3): 219-27, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25801754

RESUMO

PURPOSE: To test a hypothesized model that examines the relationship between selected basic conditioning factors, self-care agency, and self-care behaviors among adolescent girls with dysmenorrhea using Orem's self-care deficit nursing theory as a framework. DESIGN: This was a predictive correlational study conducted with a total of 531 secondary school girls. METHODS: Self-care agency, self-care behaviors, and 11 variables that have been theoretically or empirically justified in previous studies as relevant to basic conditioning factors were selected and collected by means of structured questionnaires. Path analyses were performed to test the hypothesized linkages among variables. FINDINGS: Path analysis revealed that age and received menstrual education had both direct and indirect effects through self-care agency on self-care behaviors. Mother's and father's educational level, pain intensity, and self-medication used when experiencing dysmenorrhea only affected the self-care behaviors directly. CONCLUSIONS: This is the first study that provided information about the relationship between basic conditioning factors, self-care agency, and self-care behaviors among adolescent girls with dysmenorrhea. Knowledge of the factors influencing self-care behaviors in these adolescent girls will assist healthcare professionals in developing effective interventions to promote self-care and ameliorate the adverse impact of this condition. CLINICAL RELEVANCE: Interventional strategies that aim at promoting self-care behaviors among adolescent girls with dysmenorrhea should strengthen girls' self-care agency and should target those with a younger age, higher pain intensity, mother with a higher educational level, father with a lower educational level, and those who do not take self-medication for dysmenorrhea.


Assuntos
Comportamento do Adolescente/psicologia , Dismenorreia/terapia , Teoria de Enfermagem , Autocuidado/psicologia , Adolescente , Dismenorreia/psicologia , Feminino , Promoção da Saúde , Humanos , Pesquisa em Enfermagem/métodos , Inquéritos e Questionários
10.
BMC Med Genet ; 15: 64, 2014 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-24898207

RESUMO

BACKGROUND: Shwachman-Diamond syndrome (SDS) is an autosomal recessive ribosomopathy caused mainly by compound heterozygous mutations in SBDS. Structural variation (SV) involving the SBDS locus has been rarely reported in association with the disease. We aimed to determine whether an SV contributed to the pathogenesis of a case lacking biallelic SBDS point mutations. CASE PRESENTATION: Whole exome sequencing was performed in a patient with SDS lacking biallelic SBDS point mutations. Array comparative genomic hybridization and Southern blotting were used to seek SVs across the SBDS locus. Locus-specific polymerase chain reaction (PCR) encompassing flanking intronic sequence was also performed to investigate mutation within the locus. RNA expression and Western blotting were performed to analyze allele and protein expression. We found the child harbored a single missense mutation in SBDS (c.98A > C; p.K33T), inherited from the mother, and an SV in the SBDS locus, inherited from the father. The missense allele and SV segregated in accordance with Mendelian expectations for autosomal recessive SDS. Complementary DNA and western blotting analysis and locus specific PCR support the contention that the SV perturbed SBDS protein expression in the father and child. CONCLUSION: Our findings implicate genomic rearrangements in the pathogenesis of some cases of SDS and support patients lacking biallelic SBDS point mutations be tested for SV within the SBDS locus.


Assuntos
Doenças da Medula Óssea/genética , Insuficiência Pancreática Exócrina/genética , Lipomatose/genética , Mutação de Sentido Incorreto , Proteínas/genética , Abdome/diagnóstico por imagem , Alelos , Doenças da Medula Óssea/diagnóstico , Linhagem Celular Transformada , Pré-Escolar , Hibridização Genômica Comparativa , Análise Mutacional de DNA , Insuficiência Pancreática Exócrina/diagnóstico , Feminino , Ordem dos Genes , Humanos , Lipomatose/diagnóstico , Mutagênese Insercional , Mutação , Linhagem , Radiografia Abdominal , Síndrome de Shwachman-Diamond , Ultrassonografia
11.
Pediatr Surg Int ; 30(12): 1217-22, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25358892

RESUMO

BACKGROUND: Early maternal separation could lead to significant intestinal barrier and epithelial dysfunction. However, the exact mechanism remains to be elucidated and need to be investigated. METHODS: Neonatal C57BL/6 mice were subjected to maternal separation: Maternal separation (MS) daily 3 h between postnatal day (PND) 5-9, single separation (SS) 3 h on PND 9 and no separation (NS). Colon and ileum permeability was measured by Ussing chamber. Severity of morphological changes in the colon was evaluated by blinded grading of histological stained sections. RESULTS: Trans-epithelial resistance of colon and ileum did not change indicating that the tissues remained intact during the course of the experiment. Permeability of trans-cellular tracer Horseradish peroxidase (HRP) was significantly increased in the colon of MS compared to SS and NS (p < 0.05 for SS and p < 0.001 for NS), but there was no difference in para-cellular permeability of fluorescein isothiocyanate-conjugated dextran (FD4). However, there was no change in permeability of both HRP and FD4 in the ileum. MS and SS groups had marked intestinal epithelium morphology changes in comparison to controls (p < 0.05). CONCLUSION: These preliminary observations indicate that neonatal maternal separation increases colonic trans-cellular permeability. This increase may be caused by the change of the transmural colonic morphology. The underlying mechanism is unknown and further investigation is necessary as it is of relevance to the development of early intestinal diseases such as necrotizing enterocolitis.


Assuntos
Permeabilidade da Membrana Celular/fisiologia , Colo/metabolismo , Mucosa Intestinal/metabolismo , Privação Materna , Prenhez , Animais , Animais Recém-Nascidos , Colo/citologia , Feminino , Mucosa Intestinal/citologia , Camundongos , Camundongos Endogâmicos C57BL , Gravidez
12.
Support Care Cancer ; 21(8): 2145-52, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23471538

RESUMO

PURPOSE: The purpose of this study is to determine the burden of the peak severity of oral mucositis and severity over time on selected clinical outcomes in paediatric and adolescent patients receiving chemotherapy. PATIENTS AND METHODS: A multicentre study enrolled 140 patients between the ages of 6 and 18 years, who had been treated with chemotherapy and completed the self-report Mouth and Throat Soreness-related questions of the Oral Mucositis Daily Questionnaire for 14 days. Clinical data were collected from patients' medical records during the first 14 days after starting chemotherapy. RESULTS: Forty-one percent developed oral mucositis. Multiple linear regression analysis revealed that oral mucositis was significantly associated with an increased loss of baseline body weight, after controlling for nausea/vomiting (ß = 0.34, p = 0.002). Multiple logistic regression analysis showed that severe mucositis was significantly associated with a higher probability of fluid replacement, after controlling for nausea/vomiting (adjusted OR = 12.8; 95 % CI = 2.7-61.0; p = 0.001). In addition, severe mucositis was significantly associated with a higher probability of fever, after controlling for neutropoenia (adjusted OR = 5.4; 95 % CI = 1.8-15.4; p = 0.002). No difference was observed for oral or systemic infections among the subgroups. About 5 % of the patients with oral mucositis had delays in chemotherapy (≤ 7 days). None of the patients had dose modification or unplanned hospitalization due to oral mucositis. The associations of peak severity and overall oral mucositis with adverse clinical outcomes in paediatric and adolescent patients were equivalent. CONCLUSION: Oral mucositis is associated with negative effects on clinical outcomes.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Estomatite/diagnóstico , Adolescente , Criança , Feminino , Humanos , Masculino , Neoplasias/complicações , Autorrelato , Índice de Gravidade de Doença , Estomatite/complicações , Resultado do Tratamento
13.
Am J Respir Crit Care Med ; 186(8): 732-9, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22859523

RESUMO

RATIONALE: ß-Adrenergically induced sweat secretion offers an expedient method to assess native cystic fibrosis transmembrane conductance regulator (CFTR) secretory function in vivo. OBJECTIVES: To evaluate the sensitivity, specificity, and reliability of a test based on the activity and secretory function of CFTR in the sweat gland. METHODS: Primary and validation trials with prospectively ascertained healthy control subjects, obligate heterozygotes, and patients with a CFTR-related disorder and CF (pancreatic sufficient and insufficient). MEASUREMENTS AND MAIN RESULTS: Diagnostic accuracy and reliability of ß-adrenergic sweat secretory rates using an evaporimeter was assessed and compared with sweat chloride concentrations. The cholinergically stimulated mean sweat rate did not differ among groups. The mean maximal ß-adrenergically stimulated sweat rate in heterozygotes was about half the rate of healthy control subjects, and completely absent in pancreatic-insufficient patients with CF and pancreatic-sufficient patients with CF (P < 0.0001). Subjects with a CFTR-related disorder showed reduced or absent ß-adrenergic sweat secretion. The ß-adrenergic secretory response demonstrated high diagnostic accuracy (area under a characteristic receiver-operator curve = 0.99; 95% confidence interval, 0.97-1.00) and reliability (intraclass correlation, 0.90; 95% confidence interval, 0.81-0.95). The diagnostic cutoff level for CF, derived from the primary trial, correctly identified all control subjects, heterozygotes, and patients with CF in the validation cohort, whereas concurrent sweat chloride measurements misclassified one heterozygote and five subjects with CF. The cholinergic and ß-adrenergic sweat secretion rates were lower in women compared with men (P < 0.001). CONCLUSIONS: ß-Adrenergic sweat secretion rate determined by evaporimetry is an accurate and reliable technique to assess different levels of CFTR function and to identify patients with CF.


Assuntos
Agonistas Adrenérgicos beta , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/diagnóstico , Suor/metabolismo , Adolescente , Adulto , Idoso , Biomarcadores/análise , Estudos de Casos e Controles , Cloretos/análise , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Triagem de Portadores Genéticos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suor/química , Perda Insensível de Água
14.
J Clin Nurs ; 22(11-12): 1510-20, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23228020

RESUMO

AIMS AND OBJECTIVES: To translate and evaluate the psychometric properties of the Chinese-Cantonese version of the Adolescent Dysmenorrhic Self-Care Scale. BACKGROUND: Adolescent girls prefer engaging in self-care activities for dysmenorrhoea. The Adolescent Dysmenorrhic Self-Care Scale is a reliable and valid scale for measuring the self-care behaviour of adolescent girls with dysmenorrhoea. However, it has not been validated in Hong Kong population. DESIGN: A cross-sectional design. METHODS: In phase one, the Adolescent Dysmenorrhic Self-Care Scale was translated into Chinese-Cantonese and was reviewed by an expert panel for the semantic equivalence and content validity. In phase two, the Chinese-Cantonese version of Adolescent Dysmenorrhic Self-Care Scale was administered to 396 girls with dysmenorrhoea. The construct validity was tested using confirmatory factor analysis and correlated with the Chinese version of the Generalized Self-Efficacy Scale. The reliability was assessed by Cronbach's alpha and test-retest reliability. RESULTS: Item 13 related to school nurses was deleted because of its poor relevance to the Hong Kong situation. Four items (items 26-29) related to the medical-orientated behaviours were considered by the expert panel as not relevant to the self-care construct in Hong Kong population. Therefore, confirmatory factor analyses were carried out to 39-item Chinese-Cantonese-Adolescent Dysmenorrhic Self-Care Scale (deletion of item 13) and the 35-item Chinese-Cantonese-Adolescent Dysmenorrhic Self-Care Scale (with further deletion of items 26-29). Confirmatory factor analysis did not confirm the 39-item Chinese-Cantonese-Adolescent Dysmenorrhic Self-Care Scale, but the results showed the goodness of fit in the 35-item of Chinese-Cantonese-Adolescent Dysmenorrhic Self-Care Scale (root-mean-square error of approximation = 0·075, standardised root-mean-square residual = 0·078, normed fit index = 0·95, non-normed fit index = 0·96, comparative fit index = 0·96). Significant correlations with Chinese version of the Generalized Self-Efficacy Scale (r = 0·46, p < 0·01) were identified. The Cronbach's alpha of 35-item Chinese-Cantonese-Adolescent Dysmenorrhic Self-Care Scale was 0·94. The intraclass correlation coefficient was 0·93. CONCLUSION: The 35-item Chinese-Cantonese-Adolescent Dysmenorrhic Self-Care Scale had satisfactory validity and reliability. RELEVANCE TO CLINICAL PRACTICE: Nurses may use the 35-item Chinese-Cantonese-Adolescent Dysmenorrhic Self-Care Scale in assessing the self-care behaviour of adolescent girls with dysmenorrhoea, so that girls with a low level of self-care behaviour can be identified and appropriate intervention can be provided.


Assuntos
Dismenorreia/fisiopatologia , Autocuidado , Tradução , Adolescente , Adulto , Dismenorreia/psicologia , Análise Fatorial , Feminino , Hong Kong , Humanos , Psicometria , Serviços de Enfermagem Escolar , Recursos Humanos , Adulto Jovem
15.
Life Sci Alliance ; 6(6)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024122

RESUMO

Highly effective drugs modulating the defective protein encoded by the CFTR gene have revolutionized cystic fibrosis (CF) therapy. Preclinical drug-testing on human nasal epithelial (HNE) cell cultures and 3-dimensional human intestinal organoids (3D HIO) are used to address patient-specific variation in drug response and to optimize individual treatment for people with CF. This study is the first to report comparable CFTR functional responses to CFTR modulator treatment among patients with different classes of CFTR gene variants using the three methods of 2D HIO, 3D HIO, and HNE. Furthermore, 2D HIO showed good correlation to clinical outcome markers. A larger measurable CFTR functional range and access to the apical membrane were identified as advantages of 2D HIO over HNE and 3D HIO, respectively. Our study thus expands the utility of 2D intestinal monolayers as a preclinical drug testing tool for CF.


Assuntos
Fibrose Cística , Humanos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Mutação , Intestinos , Organoides/metabolismo
16.
Pediatr Blood Cancer ; 59(5): 945-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22213587

RESUMO

Shwachman Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome (IBMFS) characterized by neutropenia, exocrine pancreatic dysfunction, and cancer predisposition. Patients are at risk for myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) but, unlike other IBMFS, there have been no reported cases of solid tumors. We report a novel case of a solid tumor in a patient with SDS and biallelic mutations in the Shwachman Bodian Diamond Syndrome gene (SBDS). Whether the development of breast cancer in this patient is due to SDS or an isolated case due to unknown factors requires further study.


Assuntos
Alelos , Doenças da Medula Óssea/genética , Neoplasias da Mama/genética , Insuficiência Pancreática Exócrina/genética , Lipomatose/genética , Mutação , Proteínas/genética , Adulto , Doenças da Medula Óssea/complicações , Insuficiência Pancreática Exócrina/complicações , Feminino , Humanos , Lipomatose/complicações , Síndrome de Shwachman-Diamond
17.
Res Nurs Health ; 35(5): 450-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22693037

RESUMO

Healthcare providers do not have a validated instrument to measure breastfeeding self-efficacy among Hong Kong Chinese. In this study, we sought to translate the breastfeeding self-efficacy scale-short form (BSES-SF) into Hong Kong Chinese and to examine the psychometric properties in a sample of 185 breastfeeding mothers. The construct validity of the translated scale was supported by confirmatory factor analysis and known group analysis. The receiver operating characteristics analysis indicated that the total score of the translated scale at 48-72 hours after delivery could be a useful diagnostic tool for identifying mothers likely to discontinue breastfeeding prematurely, before 6 months postpartum. Further research to cross-validate the suggested cut-off value of the scale is recommended.


Assuntos
Aleitamento Materno/psicologia , Autoeficácia , Adolescente , Adulto , Feminino , Hong Kong , Humanos , Paridade , Gravidez , Psicometria , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Inquéritos e Questionários , Tradução , Adulto Jovem
18.
Contemp Nurse ; 41(2): 253-62, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22800391

RESUMO

This study evaluated the effect of a structured education programme on improving the self-reflection skills of Chinese nursing undergraduates in managing clinical situations. Johns' Structured Reflection Model was used as a framework for the development of the education programme. Thirty-eight nursing undergraduates attended a 3-hour interactive workshop on reflective skills and were encouraged to practise the skills learned under the guidance of a nurse instructor during their 4-week clinical practicum. The findings indicated that the programme was helpful in improving the undergraduates' reflective skills though only a few of them reached the highest level as critical reflectors. Some undergraduates identified time constraints and the lack of a trusting relationship with their nurse instructor as barriers to their reflective learning. The findings may help nurse educators develop education programmes with structured learning strategies to promote nursing undergraduates' self-refection in clinical practice.


Assuntos
Estudantes de Enfermagem/psicologia , Adulto , Feminino , Hong Kong , Humanos , Masculino , Reprodutibilidade dos Testes
19.
Res Nurs Health ; 34(1): 49-59, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20872777

RESUMO

Self-efficacy increasingly has been reported as an important outcome measure in childbirth care. The purpose of this study was to evaluate the psychometrics of the short form of the Chinese Childbirth Self-Efficacy Inventory (CBSEI-C32) in mainland China. A convenience sample of 297 pregnant Chinese women who were attending the out-patient clinic of the study hospital in Guangzhou participated in the study. The participants were asked to complete the CBSEI-C32, the Chinese Self-Rating Anxiety Scale (CSAS), the Chinese Self-Efficacy Scale (CSE) and the socio-demographic questionnaire. A subgroup of 75 pregnant women was selected randomly from the total sample using a table of random numbers for test-retest reliability assessment. The findings demonstrate high internal consistency (Cronbach's α = .96) and test-retest reliability (intraclass correlation coefficient = .88) for the CBSEI-C32. Confirmatory factor analysis showed some support for a two-factor structure of the CBSEI-C32, and construct validity was further supported by a significant relationship with CSAS. The CBSEI-C32 has the potential to be used as a clinical and research instrument for measuring childbirth self-efficacy in women in mainland China.


Assuntos
Atitude Frente a Saúde/etnologia , Mães/psicologia , Parto/etnologia , Inventário de Personalidade/normas , Autoeficácia , Inquéritos e Questionários/normas , Adaptação Psicológica , Adulto , Ansiedade/diagnóstico , Ansiedade/etnologia , Ansiedade/prevenção & controle , Distribuição de Qui-Quadrado , China , Comparação Transcultural , Análise Fatorial , Feminino , Número de Gestações , Hong Kong/etnologia , Humanos , Mães/educação , Mães/estatística & dados numéricos , Pesquisa em Avaliação de Enfermagem , Variações Dependentes do Observador , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/etnologia , Complicações na Gravidez/prevenção & controle , Terceiro Trimestre da Gravidez , Psicometria , Autoavaliação (Psicologia)
20.
J Clin Nurs ; 20(11-12): 1685-95, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21255168

RESUMO

AIMS: The aims of this paper were to determine the level of knowledge and attitude of contraception and their relationships among Chinese migrant woman workers. BACKGROUND: Studies on psychosocial variables that lead to reproductive health behaviours among Chinese migrant woman workers in China remain limited. DESIGN: A cross-sectional, descriptive and correlational design. PARTICIPANTS: One hundred and ninety young woman workers of a factory in Guangdong, a representative city of factory base in mainland China, voluntarily participated in the study with a response rate of 63%. METHODS: Data were collected through self-administered questionnaires consisting of a socio-demographic sheet, the Contraceptive Knowledge Scale and the Contraceptive Attitude Scale. Pearson product moment correlation coefficient test was employed to examine the relationships between the contraceptive knowledge and attitude, with level of significance set at p<0·05. RESULTS: The Chinese migrant woman workers demonstrated lower contraceptive knowledge and less favourable contraceptive attitude compared with previous studies of adolescents in Taiwan and women seeking abortion in Hong Kong. Although it was a weak correlation, contraceptive knowledge was statistically associated with contraceptive attitudes among the respondents (r=0·276, p<0·001). Respondents' age, education level and working experience were significantly positively correlated with the contraceptive knowledge. CONCLUSIONS: Young Chinese migrant workers reported in the current study are found to be at higher sexual risk, when compared to the adolescents in Taiwan and Hong Kong women seeking abortion. Early educational intervention for reproductive health in particular contraception and its usage to these young women is indicated. RELEVANCE TO CLINICAL PRACTICE: Migrant woman workers in mainland demonstrated poor knowledge and unfavourable attitudes towards contraception, especially for the younger, single and less educated group. Greater effort is necessary to promote young migrant women's knowledge and attitude towards contraception and sexual health.


Assuntos
Comportamento Contraceptivo , Conhecimentos, Atitudes e Prática em Saúde , Migrantes , China , Estudos Transversais , Feminino , Humanos
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