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1.
Public Health ; 226: 80-83, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38016199

RESUMEN

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.


Asunto(s)
COVID-19 , Obesidad Infantil , Adolescente , Humanos , Niño , Obesidad Infantil/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Longitudinales , Estudios Retrospectivos , Hong Kong/epidemiología , Pandemias , Sobrepeso/epidemiología
2.
Biomaterials ; 285: 121539, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35500393

RESUMEN

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.


Asunto(s)
Neoplasias Pulmonares , Nanopartículas , Aerosoles , Animales , Línea Celular Tumoral , Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Ratones , Nanopartículas/química , Polímeros/química , ARN Interferente Pequeño/genética , Tubulina (Proteína) , Microambiente Tumoral
3.
AJNR Am J Neuroradiol ; 42(9): 1702-1708, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34266866

RESUMEN

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.


Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Tumor Rabdoide , Humanos , Imagen por Resonancia Magnética , Meduloblastoma/diagnóstico por imagen , Fenotipo , Estudios Retrospectivos , Tumor Rabdoide/diagnóstico por imagen
4.
J Frailty Aging ; 10(2): 156-159, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33575705

RESUMEN

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.


Asunto(s)
Trastornos de Deglución , Hogares para Ancianos , Casas de Salud , Anciano , Anciano de 80 o más Años , Trastornos de Deglución/terapia , Humanos , Evaluación de Programas y Proyectos de Salud , Resultado del Tratamiento
5.
J Dent Res ; 100(4): 415-422, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33164649

RESUMEN

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.


Asunto(s)
Anodoncia , Displasia Ectodermal Anhidrótica Tipo 1 , Animales , Anodoncia/genética , Humanos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , Ratones , Mutación/genética , Fenotipo , Secuenciación del Exoma , Vía de Señalización Wnt/genética
6.
J Dent Res ; 99(3): 311-319, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31914354

RESUMEN

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.


Asunto(s)
Odontogénesis , Diente , Animales , Ratones , Diente Molar , Proteínas del Tejido Nervioso , Odontogénesis/genética , Raíz del Diente , Proteínas Wnt
7.
Med J Malaysia ; 74(4): 281-287, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31424034

RESUMEN

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.


Asunto(s)
Calidad de Vida/psicología , Disrafia Espinal/psicología , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Indicadores de Salud , Humanos , Modelos Lineales , Malasia , Masculino , Intestino Neurogénico/etiología , Intestino Neurogénico/psicología , Hijo Único/psicología , Estudios Prospectivos , Disrafia Espinal/complicaciones , Disrafia Espinal/fisiopatología , Disrafia Espinal/terapia , Adulto Joven
8.
J Dent Res ; 97(2): 155-162, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28910570

RESUMEN

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.


Asunto(s)
Anodoncia/genética , Análisis Mutacional de ADN , Factor de Transcripción PAX9/genética , Adolescente , Adulto , Niño , China , Ensayo de Cambio de Movilidad Electroforética , Femenino , Técnica del Anticuerpo Fluorescente , Estudios de Asociación Genética , Humanos , Factor de Transcripción MSX1/genética , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , Reacción en Cadena de la Polimerasa , Trastornos del Gusto/genética
9.
Med J Malaysia ; 73(6): 382-387, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30647208

RESUMEN

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.


Asunto(s)
Departamentos de Hospitales/estadística & datos numéricos , Pediatría/estadística & datos numéricos , Transición a la Atención de Adultos/estadística & datos numéricos , Adolescente , Adulto , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Humanos , Pacientes Internos/psicología , Pacientes Internos/estadística & datos numéricos , Automanejo/psicología , Automanejo/estadística & datos numéricos , Factores Socioeconómicos , Encuestas y Cuestionarios , Centros de Atención Terciaria/estadística & datos numéricos , Adulto Joven
11.
Gene Ther ; 23(10): 727-733, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27383253

RESUMEN

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.


Asunto(s)
Cadenas Ligeras de Inmunoglobulina/genética , Cadenas kappa de Inmunoglobulina/genética , Paraproteinemias/terapia , Tratamiento con ARN de Interferencia/métodos , Animales , Células de la Médula Ósea/metabolismo , Línea Celular , Línea Celular Tumoral , Células Cultivadas , Femenino , Humanos , Cadenas Ligeras de Inmunoglobulina/metabolismo , Cadenas kappa de Inmunoglobulina/metabolismo , Ratones
12.
Am J Infect Control ; 44(5): 587-92, 2016 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-26874406

RESUMEN

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.


Asunto(s)
Infecciones Relacionadas con Catéteres/mortalidad , Cateterismo Venoso Central/efectos adversos , Unidades de Cuidados Intensivos , Sepsis/mortalidad , Adulto , Anciano , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo
13.
Nat Genet ; 44(7): 751-9, 2012 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-22683710

RESUMEN

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.


Asunto(s)
Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Proteínas Supresoras de Tumor/deficiencia , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/deficiencia , Ubiquitina Tiolesterasa/genética , Anciano , Carcinoma de Células Renales/metabolismo , Procesos de Crecimiento Celular/fisiología , Células Cultivadas , Proteínas de Unión al ADN , Exoma , Femenino , Expresión Génica/genética , Factor C1 de la Célula Huésped/genética , Factor C1 de la Célula Huésped/metabolismo , Humanos , Neoplasias Renales/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Dominios y Motivos de Interacción de Proteínas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/metabolismo
14.
Exp Physiol ; 97(12): 1249-62, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22613740

RESUMEN

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.


Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Barorreflejo , Reposo en Cama , Encéfalo/fisiopatología , Descondicionamiento Cardiovascular , Inclinación de Cabeza , Hipovolemia/fisiopatología , Adulto , Análisis de Varianza , Presión Arterial , Sistema Nervioso Autónomo/metabolismo , Biomarcadores/sangre , Mapeo Encefálico/métodos , Diuréticos , Epinefrina/sangre , Femenino , Frecuencia Cardíaca , Humanos , Hipovolemia/sangre , Hipovolemia/inducido químicamente , Presión Negativa de la Región Corporal Inferior , Imagen por Resonancia Magnética , Masculino , Actividad Motora , Norepinefrina/sangre , Ontario , Volumen Plasmático , Renina/sangre , Espironolactona , Factores de Tiempo , Adulto Joven
15.
Colorectal Dis ; 14(9): 1132-7, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22107130

RESUMEN

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.


Asunto(s)
Colectomía/métodos , Ergonomía/métodos , Laparoscopía/métodos , Cavidad Abdominal/cirugía , Colon Ascendente/cirugía , Humanos
16.
Seizure ; 20(7): 546-53, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21530324

RESUMEN

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.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Epilepsia/genética , Sitios Genéticos , Haplotipos , Subfamilia B de Transportador de Casetes de Unión a ATP , Alelos , Anticonvulsivantes/uso terapéutico , Carbamazepina/uso terapéutico , Epilepsia/tratamiento farmacológico , Femenino , Frecuencia de los Genes , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Ácido Valproico/uso terapéutico
17.
Seizure ; 20(5): 387-94, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21316268

RESUMEN

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.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Pueblo Asiatico/genética , Epilepsia/genética , Polimorfismo Genético/genética , Receptores de Esteroides/genética , Población Blanca/genética , Subfamilia B de Transportador de Casetes de Unión a ATP , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Pueblo Asiatico/etnología , Carbamazepina/uso terapéutico , Niño , Epilepsia/tratamiento farmacológico , Epilepsia/etnología , Femenino , Estudios de Asociación Genética/métodos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Receptor X de Pregnano , Resultado del Tratamiento , Ácido Valproico/uso terapéutico , Población Blanca/etnología , Adulto Joven
18.
Malays J Nutr ; 17(3): 277-86, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22655450

RESUMEN

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.


Asunto(s)
Ejercicio Físico , Diálisis Renal , Adulto , Anciano , Creatinina/sangre , Dieta , Escolaridad , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Renta , Malasia , Masculino , Persona de Mediana Edad , Potasio , Insuficiencia Renal/etiología , Insuficiencia Renal/terapia , Encuestas y Cuestionarios
19.
J Med Primatol ; 38 Suppl 1: 2-7, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19863672

RESUMEN

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.


Asunto(s)
Infecciones por Herpesviridae/metabolismo , Interleucina-6/metabolismo , Trastornos Linfoproliferativos/metabolismo , Rhadinovirus/metabolismo , Infecciones Tumorales por Virus/metabolismo , Animales , Técnica del Anticuerpo Fluorescente , Infecciones por Herpesviridae/complicaciones , Interacciones Huésped-Patógeno , Trastornos Linfoproliferativos/virología , Macaca mulatta , Virus de la Inmunodeficiencia de los Simios/fisiología , Infecciones Tumorales por Virus/complicaciones
20.
Neurology ; 73(7): 518-25, 2009 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-19687453

RESUMEN

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.


Asunto(s)
Epilepsia del Lóbulo Temporal/complicaciones , Epilepsia del Lóbulo Temporal/cirugía , Trastornos del Lenguaje/etiología , Red Nerviosa/cirugía , Plasticidad Neuronal/fisiología , Lóbulo Temporal/cirugía , Adulto , Mapeo Encefálico , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Lóbulo Frontal/anatomía & histología , Lóbulo Frontal/fisiopatología , Lateralidad Funcional/fisiología , Giro del Cíngulo/anatomía & histología , Giro del Cíngulo/fisiología , Humanos , Trastornos del Lenguaje/patología , Trastornos del Lenguaje/fisiopatología , Pruebas del Lenguaje , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/fisiopatología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiopatología , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/métodos , Recuperación de la Función/fisiología , Habla/fisiología , Percepción del Habla/fisiología , Lóbulo Temporal/anatomía & histología , Lóbulo Temporal/patología , Lóbulo Temporal/fisiopatología , Resultado del Tratamiento
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