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1.
Public Health ; 226: 80-83, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38016199

RESUMO

OBJECTIVE: This study is to evaluate if there is any difference in the balance between incidence of and remission from overweight/obesity in Hong Kong school-age children before and during the COVID-19 pandemic over three years. METHODS: This is a retrospective longitudinal study that involved children aged 6-16 years from a database of the School Physical Fitness Award Scheme. RESULTS: 2765 students were longitudinally followed up for two years. The prevalence of childhood overweight/obesity was increased between the 2019 and 2021 academic years (P < 0.001). During the COVID-19 pandemic, the rate of obesity remission significantly reduced by 7.9 % (P = 0.003), at a background of a plateau of obesity among children and adolescents. CONCLUSIONS: Our study provides evidence on the impact of school closure and home confinement as a standard infection control measure for the prevention of COVID-19, which are likely to break the balance between incidence of and remission from childhood obesity.


Assuntos
COVID-19 , Obesidade Infantil , Adolescente , Humanos , Criança , Obesidade Infantil/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Estudos Longitudinais , Estudos Retrospectivos , Hong Kong/epidemiologia , Pandemias , Sobrepeso/epidemiologia
2.
Biomaterials ; 285: 121539, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35500393

RESUMO

Lung cancer is a major contributor to cancer-related death worldwide. siRNA nanomedicines are powerful tools for cancer therapeutics. However, there are challenges to overcome to increase siRNA delivery to solid tumors, including penetration of nanoparticles into a complex microenvironment following systemic delivery while avoiding rapid clearance by the reticuloendothelial system, and limited siRNA release from endosomes once inside the cell. Here we characterized cell uptake, intracellular trafficking, and gene silencing activity of miktoarm star polymer (PDMAEMA-POEGMA) nanoparticles (star nanoparticles) complexed to siRNA in lung cancer cells. We investigated the potential of nebulized star-siRNA nanoparticles to accumulate into orthotopic mouse lung tumors to inhibit expression of two genes [ßIII-tubulin, Polo-Like Kinase 1 (PLK1)] which: 1) are upregulated in lung cancer cells; 2) promote tumor growth; and 3) are difficult to inhibit using chemical drugs. Star-siRNA nanoparticles internalized into lung cancer cells and escaped the endo-lysosomal pathway to inhibit target gene expression in lung cancer cells in vitro. Nebulized star-siRNA nanoparticles accumulated into lungs and silenced the expression of ßIII-tubulin and PLK1 in mouse lung tumors, delaying aggressive tumor growth. These results demonstrate a proof-of-concept for aerosol delivery of star-siRNA nanoparticles as a novel therapeutic strategy to inhibit lung tumor growth.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Aerossóis , Animais , Linhagem Celular Tumoral , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Camundongos , Nanopartículas/química , Polímeros/química , RNA Interferente Pequeno/genética , Tubulina (Proteína) , Microambiente Tumoral
3.
AJNR Am J Neuroradiol ; 42(9): 1702-1708, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34266866

RESUMO

BACKGROUND AND PURPOSE: Atypical teratoid/rhabdoid tumors and medulloblastomas have similar imaging and histologic features but distinctly different outcomes. We hypothesized that they could be distinguished by MR imaging-based radiomic phenotypes. MATERIALS AND METHODS: We retrospectively assembled T2-weighted and gadolinium-enhanced T1-weighted images of 48 posterior fossa atypical teratoid/rhabdoid tumors and 96 match-paired medulloblastomas from 7 institutions. Using a holdout test set, we measured the performance of 6 candidate classifier models using 6 imaging features derived by sparse regression of 900 T2WI and 900 T1WI Imaging Biomarker Standardization Initiative-based radiomics features. RESULTS: From the originally extracted 1800 total Imaging Biomarker Standardization Initiative-based features, sparse regression consistently reduced the feature set to 1 from T1WI and 5 from T2WI. Among classifier models, logistic regression performed with the highest AUC of 0.86, with sensitivity, specificity, accuracy, and F1 scores of 0.80, 0.82, 0.81, and 0.85, respectively. The top 3 important Imaging Biomarker Standardization Initiative features, by decreasing order of relative contribution, included voxel intensity at the 90th percentile, inverse difference moment normalized, and kurtosis-all from T2WI. CONCLUSIONS: Six quantitative signatures of image intensity, texture, and morphology distinguish atypical teratoid/rhabdoid tumors from medulloblastomas with high prediction performance across different machine learning strategies. Use of this technique for preoperative diagnosis of atypical teratoid/rhabdoid tumors could significantly inform therapeutic strategies and patient care discussions.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Tumor Rabdoide , Humanos , Imageamento por Ressonância Magnética , Meduloblastoma/diagnóstico por imagem , Fenótipo , Estudos Retrospectivos , Tumor Rabdoide/diagnóstico por imagem
4.
J Frailty Aging ; 10(2): 156-159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575705

RESUMO

Oropharyngeal dysphagia is a widespread condition in older people and thus poses a serious health threat to the residents of nursing homes. The management of dysphagia relies mainly on compensatory strategies, such as diet and environmental modification. This study investigated the efficacy of an intervention program using a single-arm interventional study design. Twenty-two participants from nursing homes were included and had an average of 26 hours of intervention, including oromotor exercises, orosensory stimulation and exercises to target dysphagia and caregiver training. Four of the 22 participants exhibited improvement in functional oral intake scale (FOIS) but was not statistically significant as a group. All oromotor function parameters, including the range, strength, and coordination of movements, significantly improved. These results indicate that this intervention program could potentially improve the oromotor function, which were translated into functional improvements in some participants' recommended diets. The validity of this study could be improved further by using standardized swallowing and feeding assessment methods or an instrumental swallowing assessment.


Assuntos
Transtornos de Deglutição , Instituição de Longa Permanência para Idosos , Casas de Saúde , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/terapia , Humanos , Avaliação de Programas e Projetos de Saúde , Resultado do Tratamento
5.
J Dent Res ; 100(4): 415-422, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33164649

RESUMO

Genes associated with the WNT pathway play an important role in the etiology of tooth agenesis. Low-density lipoprotein receptor-related protein 6 encoding gene (LRP6) is a recently defined gene that is associated with autosomal dominant inherited tooth agenesis. Here, we aimed to identify novel LRP6 mutations in patients with tooth agenesis and investigate the significance of Lrp6 during tooth development. Using whole-exome sequencing, we identified 4 novel LRP6 heterozygous mutations (c.2292G>A, c.195dup, c.1095dup, and c.1681C>T) in 4 of 77 oligodontia patients. Notably, a patient who carried a nonsense LRP6 mutation (c.2292G>A; p.W764*) presented a hypohidrotic ectodermal dysplasia phenotype. Preliminary functional studies, including bioinformatics analysis and TOP-/FOP-flash reporter assays, demonstrated that the activation of WNT/ß-catenin signaling was compromised as a consequence of LRP6 mutations. RNAscope in situ hybridization revealed dynamic and special changes of Lrp6 expression during murine tooth development from E11.5 to E16.5. It was noteworthy that Lrp6 was specifically expressed in the epithelium at E11.5 to E13.5 but was expressed in both dental epithelium and dental papilla from E14.5 and persisted in both tissues at later stages. Our study broadens the mutation spectrum of human tooth agenesis and is the first to identify a LRP6 mutation in patients with hypohidrotic ectodermal dysplasia and reveal the dynamic expression pattern of Lrp6 during tooth development. Information from this study is conducive to understanding the functional significance of Lrp6 on the biological process of tooth development.


Assuntos
Anodontia , Displasia Ectodérmica Anidrótica Tipo 1 , Animais , Anodontia/genética , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Camundongos , Mutação/genética , Fenótipo , Sequenciamento do Exoma , Via de Sinalização Wnt/genética
6.
J Dent Res ; 99(3): 311-319, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31914354

RESUMO

WNT10A (Wingless-type MMTV integration site family, member 10A) plays a crucial role in tooth development, and patients with biallelic WNT10A mutation and mice lacking Wnt10a show taurodontism. However, whether epithelial or mesenchymal WNT10A controls the initiation of the root furcation formation remains unclear, and the functional significance of WNT10A in regulating root morphogenesis has not been clarified. Here, we investigated how Wnt10a affects tooth root development by generating different tissue-specific Wnt10a conditional knockout mice. Wnt10a knockout in the whole tissue (EIIa-Cre;Wnt10aflox/flox) and in dental epithelium (K14-Cre;Wnt10aflox/flox) led to an absence of or apically located root furcation in molars of mice, a phenotype that resembled taurodontism. An RNAscope analysis showed that the dynamic epithelial and mesenchymal Wnt10a expression pattern occurred during root development. Immunofluorescent staining of E-cadherin and EdU revealed decreased epithelial cell proliferation at the cervical region of the molar in K14-Cre;Wnt10aflox/flox mice at postnatal day 0 (PN0), just before the initiation of root morphogenesis. Interestingly, we found increased pulpal mesenchymal cell proliferation in the presumptive root furcating region of the molar in K14-Cre;Wnt10aflox/flox mice at PN4 and PN7. RNA-seq indicated that among the Wnt ligands with high endogenous expression levels in molars, Wnt4 was increased after epithelial knockout of Wnt10a. The RNAscope assay confirmed that the expression of Wnt4 and Axin2 in the dental papilla of the presumptive root furcating region, where dental pulp overgrowth occurred, was increased in K14-Cre;Wnt10aflox/flox molars. Furthermore, after suppression of the elevated Wnt4 level in K14-Cre;Wnt10aflox/flox molars by Wnt4 shRNA adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study provides the first in vivo evidence that epithelial Wnt10a guides root furcation formation and plays a crucial role in controlling the organized proliferation of adjacent mesenchymal cells by regulating proper Wnt4 expression during root furcation morphogenesis.


Assuntos
Odontogênese , Dente , Animais , Camundongos , Dente Molar , Proteínas do Tecido Nervoso , Odontogênese/genética , Raiz Dentária , Proteínas Wnt
7.
Med J Malaysia ; 74(4): 281-287, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31424034

RESUMO

INTRODUCTION: The average incidence of spina bifida (SB) in Malaysia is 0.43 among 1,000 live births. The burden of the disease and its impact on the overall development and health though tremendously improved, remains significant. Therefore, current patient management strategies must include quality of life (QOL) measures. METHODS: This was a prospective, cross-sectional study on spina bifida children aged 5-20 years, attending the paediatric spina bifida clinics of Universiti Kebangsaan Malaysia Medical Centre Kuala Lumpur and Hospital Tuanku Jaanku Seremban. Scores were obtained using the validated disease specific Parkin QOL questionnaire. Univariate and multivariate analysis were used to investigate factors that were determinants for these outcomes. Results were expressed as beta coefficient and 95% confidence intervals (95%CI). RESULTS: A total of 54 children and adolescents aged between 5-20 years completed the questionnaires. Presence of neurogenic bowel (p=0.003), neurogenic bladder (p=0.041), shunt (p=0.044), non-ambulators (p=0.007) and being the only child in the family (p=0.037) were associated with lower QOL scores. Multivariate analysis showed presence of neurogenic bowel (ß=0.375, 95%CI: 0.00, 0.15) and being the only child in the family (ß=0.250, 95%CI: 0.04, 0.17) explained 22.1% of the variance in the QOL mean percentage scores. CONCLUSION: Being a single child in the family was the only socio-demographic variable associated with lower QOL scores. Although several clinical factors appeared to contribute significantly to QOL in spina bifida children, the presence of neurogenic bowel had the greatest impact.


Assuntos
Qualidade de Vida/psicologia , Disrafismo Espinal/psicologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Indicadores Básicos de Saúde , Humanos , Modelos Lineares , Malásia , Masculino , Intestino Neurogênico/etiologia , Intestino Neurogênico/psicologia , Filho Único/psicologia , Estudos Prospectivos , Disrafismo Espinal/complicações , Disrafismo Espinal/fisiopatologia , Disrafismo Espinal/terapia , Adulto Jovem
8.
Med J Malaysia ; 73(6): 382-387, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30647208

RESUMO

INTRODUCTION: A smooth transition of healthcare for young people with chronic illnesses from paediatric to adult healthcare services is important to ensure optimal outcome. At the moment, there are no standard guidelines to assess a patient's readiness to transfer care. METHODS: A cross-sectional study using a self-administered questionnaire, adapted from UNC (University of North Carolina) TRxANSITION self-assessment tool was conducted to evaluate patients' transition care readiness in paediatric haematology and paediatric diabetes clinic. RESULTS: A total of 80 patients (37 thalassaemia and 43 diabetes) with the mean age of 21.2 (SD±4.3) years, were recruited during the 3-month study period. Majority of the patients have basic knowledge regarding their medications, and were able to comply with their follow-up. The mean total score obtained by the respondents on this questionnaire was 15.3 (SD±3.59). Self-management skills and knowledge on disease were the two poorly scored section; with mean score of 3.78 (SD±1.38) and 4.28 (SD±1.20) respectively. Overall, only 21 (26.2%) respondents obtained high score (score above 75th percentile). Seventy-five percent of the respondents admitted that they were not ready for transfer to an adult healthcare service yet at the time of the study. CONCLUSION: We suggest that patients with high score should be prepared for transition to adult facility whereas those with a low score need to be identified to ensure provision of continuous education.


Assuntos
Departamentos Hospitalares/estatística & dados numéricos , Pediatria/estatística & dados numéricos , Transição para Assistência do Adulto/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pacientes Internados/psicologia , Pacientes Internados/estatística & dados numéricos , Autogestão/psicologia , Autogestão/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
9.
J Dent Res ; 97(2): 155-162, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28910570

RESUMO

Tooth agenesis is one of the most common developmental anomalies affecting function and esthetics. The paired-domain transcription factor, Pax9, is critical for patterning and morphogenesis of tooth and taste buds. Mutations of PAX9 have been identified in patients with tooth agenesis. Despite significant progress in the genetics of tooth agenesis, many gaps in knowledge exist in refining the genotype-phenotype correlation between PAX9 and tooth agenesis. In the present study, we complete genetic and phenotypic characterization of multiplex Chinese families with nonsyndromic (NS) tooth agenesis. Direct sequencing of polymerase chain reaction products revealed 9 novel (c.140G>C, c.167T>A, c.332G>C, c.194C>A, c.271A>T, c.146delC, c.185_189dup, c.256_262dup, and c.592delG) and 2 known heterozygous mutations in the PAX9 gene among 120 probands. Subsequently, pedigrees were extended, and we confirmed that the mutations co-segregated with the tooth agenesis phenotype (with exception of families in which DNA analysis was not available). In 1 family ( n = 6), 2 individuals harbored both the PAX9 c.592delG mutation and a heterozygous missense mutation (c.739C>T) in the MSX1 gene. Clinical characterization of families segregating a PAX9 mutation reveal that all affected individuals were missing the mandibular second molar and their maxillary central incisors are most susceptible to microdontia. A significant reduction of bitter taste perception was documented in individuals harboring PAX9 mutations ( n = 3). Functional studies revealed that PAX9 haploinsufficiency or a loss of function of the PAX9 protein underlies tooth agenesis.


Assuntos
Anodontia/genética , Análise Mutacional de DNA , Fator de Transcrição PAX9/genética , Adolescente , Adulto , Criança , China , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Imunofluorescência , Estudos de Associação Genética , Humanos , Fator de Transcrição MSX1/genética , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Reação em Cadeia da Polimerase , Distúrbios do Paladar/genética
11.
Gene Ther ; 23(10): 727-733, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27383253

RESUMO

Treatment of light chain (LC) deposition diseases both nonfibrillar and fibrillar is aimed at eliminating LC production but success is limited. We report on the testing of an small interfering RNA pool targeting the κ LC constant region mRNA (si[IGKC]) designed for use against all κ plasma cell clones. To test for changes in κ LC message and protein production we used real-time PCR, immunoblot, intracellular mean fluorescence intensity and κ LC secretion by enzyme-linked immunosorbent assay. In vitro we employed 4 human cell lines that make κ LCs and 20 specimens of CD138-selected marrow plasma cells from patients with κ plasma cell diseases. In vivo, we used a murine flank plasmacytoma xenograft model. In vitro and in vivo, there were significant reductions in message and protein production by all modalities in all cell types despite diversity in variable region sequence. In addition, in clones producing intact immunoglobulin, caspase 3/7 activity with si[IGKC] was significantly increased compared with clones producing κ LC only, consistent with the triggering of a terminal unfolded protein response by excess unpaired heavy chains. In conclusion, si[IGKC] can significantly reduce κ LC production by κ plasma cells. Further preclinical development is needed to optimize delivery.


Assuntos
Cadeias Leves de Imunoglobulina/genética , Cadeias kappa de Imunoglobulina/genética , Paraproteinemias/terapia , Terapêutica com RNAi/métodos , Animais , Células da Medula Óssea/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Humanos , Cadeias Leves de Imunoglobulina/metabolismo , Cadeias kappa de Imunoglobulina/metabolismo , Camundongos
12.
Am J Infect Control ; 44(5): 587-92, 2016 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-26874406

RESUMO

OBJECTIVE: To explore the risk-adjusted association between intensive care unit (ICU)-acquired central line-associated bloodstream infection (CLABSI) and in-hospital mortality. DESIGN: Retrospective observational study. SETTING: Forty-five-bed adult ICU. PATIENTS: All non-extracorporeal membrane oxygenation ICU admissions between July 1, 2008, and April 30, 2014, requiring a central venous catheter (CVC), with a length of stay > 48 hours, were included. METHODS: Data were extracted from our infection prevention and ICU databases. A multivariable logistic regression model was constructed to identify independent risk factors for ICU-acquired CLABSI. The propensity toward developing CLABSI was then included in a logistic regression of in-hospital mortality. RESULTS: Six thousand three hundred fifty-three admissions were included. Forty-six cases of ICU-acquired CLABSI were identified. The overall CLABSI rate was 1.12 per 1,000 ICU CVC-days. Significant independent risk factors for ICU-acquired CLABSI included: double lumen catheter insertion (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.16-5.77), CVC exposure > 7 days (OR, 2.07; 95% CI, 1.06-4.04), and CVC insertion before 2011 (OR, 2.20; 95% CI, 1.22-3.97). ICU-acquired CLABSI was crudely associated with greater in-hospital mortality, although this was attenuated once the propensity to develop CLABSI was adjusted for (OR, 1.20; 95% CI, 0.54-2.68). CONCLUSIONS: A greater propensity toward ICU-acquired CLABSI was independently associated with higher in-hospital mortality, although line infection itself was not. The requirement for prolonged specialized central venous access appears to be a key risk factor for ICU-acquired CLABSI, and likely informs mortality as a marker of persistent organ dysfunction.


Assuntos
Infecções Relacionadas a Cateter/mortalidade , Cateterismo Venoso Central/efeitos adversos , Unidades de Terapia Intensiva , Sepse/mortalidade , Adulto , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco
13.
Nat Genet ; 44(7): 751-9, 2012 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-22683710

RESUMO

The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitinase, is inactivated in 15% of clear cell RCCs. BAP1 cofractionates with and binds to HCF-1 in tumorgrafts. Mutations disrupting the HCF-1 binding motif impair BAP1-mediated suppression of cell proliferation but not deubiquitination of monoubiquitinated histone 2A lysine 119 (H2AK119ub1). BAP1 loss sensitizes RCC cells in vitro to genotoxic stress. Notably, mutations in BAP1 and PBRM1 anticorrelate in tumors (P = 3 × 10(-5)), [corrected] and combined loss of BAP1 and PBRM1 in a few RCCs was associated with rhabdoid features (q = 0.0007). BAP1 and PBRM1 regulate seemingly different gene expression programs, and BAP1 loss was associated with high tumor grade (q = 0.0005). Our results establish the foundation for an integrated pathological and molecular genetic classification of RCC, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Proteínas Supressoras de Tumor/deficiência , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/deficiência , Ubiquitina Tiolesterase/genética , Idoso , Carcinoma de Células Renais/metabolismo , Processos de Crescimento Celular/fisiologia , Células Cultivadas , Proteínas de Ligação a DNA , Exoma , Feminino , Expressão Gênica/genética , Fator C1 de Célula Hospedeira/genética , Fator C1 de Célula Hospedeira/metabolismo , Humanos , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Domínios e Motivos de Interação entre Proteínas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo
14.
Exp Physiol ; 97(12): 1249-62, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22613740

RESUMO

Cardiovascular arousal is associated with patterned cortical activity changes. Head-down-tilt bed rest (HDBR) dimishes the baroreflex-mediated cardiac control. The present study tested the hypothesis that HDBR deconditioning would modify the forebrain organization for heart rate (HR) control during baroreflex unloading. Heart rate variability (HRV), blood pressure and plasma hormones were analysed at rest, whereas HR and cortical autonomic activation patterns (functional magnetic resonance imaging) were measured during graded and randomly assigned lower body negative pressure treatments (LBNP, -15 and -35 mmHg) both before (Pre) and after (Post) a 24 h HDBR protocol (study 1; n = 8). An additional group was tested before and following diuretic-induced hypovolaemia (study 2; n = 9; spironolactone, 100 mg day(-1) for 3 days) that mimicked the plasma volume lost during HDBR (-15% in both studies; P < 0.05). Head-down bed rest with hypovolaemia did not affect baseline HR, mean arterial pressure, HRV or plasma catecholamines. Head-down bed rest augmented the LBNP-induced HR response (P < 0.05), and this was associated with bed-rest-induced development of the following changes: (i) enhanced activation within the genual anterior cingulate cortex and the right anterior insular cortex; and (ii) deactivation patterns within the subgenual regions of the anterior cingulate cortex. Diuretic treatment (without HDBR) did not affect baseline HR and mean arterial pressure, but did reduce resting HRV and elevated circulating noradrenaline and plasma renin activity (P < 0.05). The greater HR response to LBNP following diuretic (P < 0.05) was associated with diminished activation of the right anterior insula. Our findings indicate that 24 h of HDBR minimized the impact of diuretic treatment on baseline autonomic and cardiovascular variables. The findings also indicate that despite the similar augmentation of HR responses to LBNP and despite similar pre-intervention cortical activation patterns, HDBR and diuretic treatment produced different effects on the cortical responses, with HDBR affecting anterior cingulate cortex and right insula regions, whereas diuretic treatment affected primarily the right insula alone, but in a direction that was opposite to HDBR. The data indicate that physical deconditioning can induce rapid functional changes within the cortical circuitry associated with baroreflex unloading, changes that are distinct from diuretic-induced hypovolaemia. The results suggest that physical activity patterns exert a rapid and notable impact on the cortical circuitry associated with cardiovascular control.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Barorreflexo , Repouso em Cama , Encéfalo/fisiopatologia , Descondicionamento Cardiovascular , Decúbito Inclinado com Rebaixamento da Cabeça , Hipovolemia/fisiopatologia , Adulto , Análise de Variância , Pressão Arterial , Sistema Nervoso Autônomo/metabolismo , Biomarcadores/sangue , Mapeamento Encefálico/métodos , Diuréticos , Epinefrina/sangue , Feminino , Frequência Cardíaca , Humanos , Hipovolemia/sangue , Hipovolemia/induzido quimicamente , Pressão Negativa da Região Corporal Inferior , Imageamento por Ressonância Magnética , Masculino , Atividade Motora , Norepinefrina/sangue , Ontário , Volume Plasmático , Renina/sangue , Espironolactona , Fatores de Tempo , Adulto Jovem
15.
Colorectal Dis ; 14(9): 1132-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22107130

RESUMO

AIM: Port placement in laparoscopic surgery has important ergonomic implications. A manipulation angle (MA) of 60° has been shown to maximize task efficiency. We calculated the MA used during various stages of both right hemicolectomy (RH) and high anterior resection (AR). METHOD: We compared two methods of port placement for each operation. RH-PP1 included ports in the left iliac fossa and left upper quadrant. RH-PP2 included ports suprapubically and in the left iliac fossa. We calculated the MA of each of these methods in mobilizing both the caecum and hepatic flexure. AR-PP1 included ports in the right iliac fossa and right upper quadrant. AR-PP2 included ports suprapubically and in the right iliac fossa. We calculated the MA of each of these methods in mobilizing the splenic flexure, descending-sigmoid junction and the recto-sigmoid junction. RESULTS: For RH-PP1, the mean MA for mobilizing the caecum and hepatic flexure was 38° and 52°, respectively. For RH-PP2, the mean MA for mobilising the caecum and hepatic flexure was 58° and 44°, respectively. For AR-PP1, the mean MA for mobilizing the splenic flexure, the descending-sigmoid junction and the recto-sigmoid junction was 77°, 41° and 18°, respectively. For AR-PP2, the mean MA for mobilizing the splenic flexure, the descending-sigmoid junction and the recto-sigmoid junction was 40°, 56° and 34°, respectively. CONCLUSION: There are no two port placements that will allow for an ideal MA at every stage of mobilization for either right- or left-sided resection.


Assuntos
Colectomia/métodos , Ergonomia/métodos , Laparoscopia/métodos , Cavidade Abdominal/cirurgia , Colo Ascendente/cirurgia , Humanos
16.
Seizure ; 20(7): 546-53, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21530324

RESUMO

Approximately one third of newly treated epilepsy patients do not respond to antiepileptic drugs (AEDs). Overexpression of P-glycoprotein (P-gp) efflux transporter has been proposed to have a critical role in causing resistance to AEDs. P-gp is a product of the ATP-binding cassette subfamily B member 1 (ABCB1) gene. The purpose of this study was to investigate a possible link between ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes with response to carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in Malaysian epilepsy patients. No ABCB1 haplotype association was found with response to either CBZ or VPA monotherapy in the Chinese, Indian, and Malay patients. C3435 allele carriers of the Indian males with cryptogenic epilepsy were more prone to resistance to either CBZ or VPA than carriers of T allele. Moreover, rs3789243T allele carriers of Malay females with symptomatic epilepsy were more resistant to either CBZ or VPA than C allele carriers. Our findings suggest that the ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes do not contribute to response to AED treatment in epilepsy.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Epilepsia/genética , Loci Gênicos , Haplótipos , Subfamília B de Transportador de Cassetes de Ligação de ATP , Alelos , Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia/tratamento farmacológico , Feminino , Frequência do Gene , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Ácido Valproico/uso terapêutico
17.
Seizure ; 20(5): 387-94, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21316268

RESUMO

It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Povo Asiático/genética , Epilepsia/genética , Polimorfismo Genético/genética , Receptores de Esteroides/genética , População Branca/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Povo Asiático/etnologia , Carbamazepina/uso terapêutico , Criança , Epilepsia/tratamento farmacológico , Epilepsia/etnologia , Feminino , Estudos de Associação Genética/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Receptor de Pregnano X , Resultado do Tratamento , Ácido Valproico/uso terapêutico , População Branca/etnologia , Adulto Jovem
18.
Malays J Nutr ; 17(3): 277-86, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22655450

RESUMO

INTRODUCTION: There is mounting evidence demonstrating the importance of adequate physical activity to promote better well-being among hemodialysis patients. Available data pertaining to the levels of physical activity and its determinants among hemodialysis patients is, however, scarce in Malaysia. The objectives of this study are hence to determine the levels of physical activity and it associated factors among hemodialysis patients. METHODOLOGY: A total of 70 subjects were recruited from three dialysis centres in Selangor. A face-to-face interview was conducted to obtain socio-demographic data and subjects' knowledge on dietary sources. Medical history, biochemical parameters and weight status were obtained from medical records. Physical activity level (PAL) was assessed using the Global Physical Activity Questionnaire (GPAQ). RESULTS: A total of 81.4% and 18.6% of the respondents had low and moderate PALs, respectively. Thus, none of the respondents had high PAL. Serum creatinine, education level, personal income and knowledge score on potassium-related medical complications were factors found to correlate significantly with PAL. Multiple linear regression analysis showed that higher PAL was predicted by a lower knowledge score on dietary sodium source, higher education and higher serum creatinine. CONCLUSION: Despite consistent documentation of the potential positive impact of physical exercise on hemodialysis outcomes, the level of physical activity remains low among these patients. It is hoped that these findings can add to the existing body of knowledge and serve as a supporting document for the formulation of appropriate interventions to improve the status of physical activity among hemodialysis patients in Malaysia.


Assuntos
Exercício Físico , Diálise Renal , Adulto , Idoso , Creatinina/sangue , Dieta , Escolaridade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Renda , Malásia , Masculino , Pessoa de Meia-Idade , Potássio , Insuficiência Renal/etiologia , Insuficiência Renal/terapia , Inquéritos e Questionários
19.
J Med Primatol ; 38 Suppl 1: 2-7, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19863672

RESUMO

BACKGROUND: Rhesus macaques (RM) co-infected with simian immunodeficiency virus (SIV) and rhesus macaque rhadinovirus (RRV) develop abnormal cellular proliferations characterized as extra-nodal lymphoma and retroperitoneal fibromatosis (RF). RRV encodes a viral interleukin-6 (vIL-6), much like Kaposi's sarcoma-associated herpesvirus, and involvement of the viral cytokine was examined in proliferative lesions. METHODS: Formalin fixed tissue from RM co-infected with SIV and RRV were analyzed for RRV genomes by in situ hybridization and RRV vIL-6 expression by immunofluorescence analysis. RESULTS: In situ hybridization analysis indicated that RRV is present in both types of lesions. Immunofluorescence analysis of different lymphomas and RF revealed positive staining for vIL-6. Similarly to KS, RF lesion is positive for vimentin, CD117 (c-kit), and smooth muscle actin (SMA) and contains T cell, B cell and monocytes/macrophage infiltrates. CONCLUSIONS: Our data support the idea that vIL-6 may be critical to the development and progression of lymphoproliferative disorder in RRV/SIV-infected RM.


Assuntos
Infecções por Herpesviridae/metabolismo , Interleucina-6/metabolismo , Transtornos Linfoproliferativos/metabolismo , Rhadinovirus/metabolismo , Infecções Tumorais por Vírus/metabolismo , Animais , Imunofluorescência , Infecções por Herpesviridae/complicações , Interações Hospedeiro-Patógeno , Transtornos Linfoproliferativos/virologia , Macaca mulatta , Vírus da Imunodeficiência Símia/fisiologia , Infecções Tumorais por Vírus/complicações
20.
Neurology ; 73(7): 518-25, 2009 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-19687453

RESUMO

BACKGROUND: Functional MRI was used to study the impact of temporal lobe epilepsy (TLE) and anterior temporal lobectomy (ATL) on the cortical language network in patients with medically refractory TLE. METHODS: Nineteen patients with medically refractory TLE and 11 healthy control subjects were enrolled in this study. Ten patients underwent left ATL (mean age 35.2 +/- 3.8 years), and 9 underwent right ATL (mean age 35.9 +/- 2.6 years). The subjects silently generated verbs in response to a series of visually presented nouns inside the scanner. Correlation analysis was performed between the subjects' performance on the clinical language tests and their neural response in the a priori cortical regions. RESULTS: Preoperative data revealed that the patients with TLE showed increased neural activity in the right inferior frontal gyri (IFG) and middle frontal gyri (MFG). The right TLE patients demonstrated strong correlation between their language performance and the level of cortical activation within the typical language areas. However, such a correlation was absent in the left TLE patients. After the ATL surgery, the left TLE patients showed reduced activation in the left MFG and right IFG, whereas no difference was observed in the right TLE patients. In the right TLE patients, the correlation between language performance and neural response shifted from the typical language areas to the anterior cingulate cortex. CONCLUSION: This study demonstrates that the cortical language network is affected differently by the left and right temporal lobe epilepsy and is reorganized after anterior temporal lobectomy.


Assuntos
Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/cirurgia , Transtornos da Linguagem/etiologia , Rede Nervosa/cirurgia , Plasticidade Neuronal/fisiologia , Lobo Temporal/cirurgia , Adulto , Mapeamento Encefálico , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Lobo Frontal/anatomia & histologia , Lobo Frontal/fisiopatologia , Lateralidade Funcional/fisiologia , Giro do Cíngulo/anatomia & histologia , Giro do Cíngulo/fisiologia , Humanos , Transtornos da Linguagem/patologia , Transtornos da Linguagem/fisiopatologia , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/fisiopatologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiopatologia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Recuperação de Função Fisiológica/fisiologia , Fala/fisiologia , Percepção da Fala/fisiologia , Lobo Temporal/anatomia & histologia , Lobo Temporal/patologia , Lobo Temporal/fisiopatologia , Resultado do Tratamento
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