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1.
Ultrasound Obstet Gynecol ; 60(2): 200-206, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35468236

RESUMO

OBJECTIVE: To assess whether pregnancy-associated plasma protein-A (PAPP-A) alters or provides equivalent screening performance as placental growth factor (PlGF) when screening for preterm pre-eclampsia (PE) at 11-13 weeks of gestation. METHODS: This was a secondary analysis of a non-intervention screening study of 6546 singleton pregnancies that were screened prospectively for preterm PE in the first trimester between December 2016 and June 2018. Patient-specific risks for preterm PE were estimated by maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), PlGF and PAPP-A. A competing-risks model with biomarkers expressed as multiples of the median was used. All women and clinicians were blinded to the risk for preterm PE. The performance of screening for preterm PE using PlGF vs PAPP-A vs both PAPP-A and PlGF was assessed by comparing areas under the receiver-operating-characteristics (AUC) curves. McNemar's test was used to compare detection rate at a fixed false-positive rate (FPR) of 10%. RESULTS: PlGF and PAPP-A were measured in 6546 women, of whom 37 developed preterm PE. The AUC and detection rate at 10% FPR using PlGF in combination with maternal history, MAP and UtA-PI were 0.854 and 59.46%, respectively. The respective values were 0.813 and 51.35% when replacing PlGF with PAPP-A and 0.855 and 59.46% when using both PAPP-A and PlGF. Statistically non-significant differences were noted in AUC when replacing PlGF with PAPP-A (ΔAUC, 0.04; P = 0.095) and when using both PAPP-A and PlGF (ΔAUC, 0.002; P = 0.423). However, on an individual case basis, screening using PlGF in conjunction with maternal history, MAP and UtA-PI identified three (8.1%) additional pregnancies that developed preterm PE and that were not identified when replacing PlGF with PAPP-A. Screening using PAPP-A in addition to maternal history and other biomarkers did not identify any additional pregnancies. CONCLUSION: On an individual case basis, adoption of a screening strategy that uses PAPP-A instead of PlGF results in reduced detection of preterm PE, consistent with previous literature. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Pré-Eclâmpsia , Proteína Plasmática A Associada à Gravidez , Biomarcadores , Feminino , Humanos , Recém-Nascido , Fator de Crescimento Placentário , Gravidez , Primeiro Trimestre da Gravidez , Fluxo Pulsátil , Artéria Uterina/diagnóstico por imagem
2.
Prenat Diagn ; 42(7): 862-872, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35441720

RESUMO

OBJECTIVE: The diagnostic yield for congenital heart defects (CHD) with routine genetic testing is around 10%-20% when considering pathogenic CNVs or aneuploidies as positive findings. This is a pilot study to investigate the utility of genome sequencing (GS) for prenatal diagnosis of CHD. METHODS: Genome sequencing (GS, 30X) was performed on 13 trios with CHD for which karyotyping and/or chromosomal microarray results were non-diagnostic. RESULTS: Trio GS provided a diagnosis for 4/13 (30.8%) fetuses with complex CHDs and other structural anomalies. Findings included pathogenic or likely pathogenic variants in DNAH5, COL4A1, PTPN11, and KRAS. Of the nine cases without a genetic etiology by GS, we had outcome follow-up data on eight. For five of them (60%), the parents chose to keep the pregnancy. A balanced translocation [46,XX,t(14; 22)(q32.33; q13.31)mat] was detected in a trio with biallelic DNAH5 mutations, which together explained the recurrent fetal situs inversus and dextrocardia that was presumably due to de novo Phelan-McDermid syndrome. A secondary finding of a BRCA2 variant and carrier status of HBB, USH2A, HBA1/HBA2 were detected in the cohort. CONCLUSIONS: GS expands the diagnostic scope of mutation types over conventional testing, revealing the genetic etiology for fetal heart anomalies. Patients without a known genetic abnormality indicated by GS likely opted to keep pregnancy especially if the heart defect could be surgically repaired. We provide evidence to support the application of GS for fetuses with CHD.


Assuntos
Doenças Fetais , Cardiopatias Congênitas , Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Feminino , Coração Fetal , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Humanos , Projetos Piloto , Gravidez , Diagnóstico Pré-Natal/métodos
4.
Hong Kong Med J ; 27(1): 177-183, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33602879

RESUMO

INTRODUCTION: To determine the carrier frequency and common mutations of Mendelian variants in Chinese couples using next-generation sequencing (NGS). METHODS: Preconception expanded carrier testing using NGS was offered to women who attended the subfertility clinic. The test was then offered to the partners of women who had positive screening results. Carrier frequency was calculated, and the results of the NGS panel were compared with those of a target panel. RESULTS: One hundred twenty-three women and 20 of their partners were screened. Overall, 84 (58.7%) individuals were identified to be carriers of at least one disease, and 68 (47.6%) were carriers after excluding thalassaemias. The most common diseases found were GJB2-related DFNB1 nonsyndromic hearing loss and deafness (1 in 4), alpha-thalassaemia (1 in 7), beta-thalassaemia (1 in 14), 21-hydroxylase deficient congenital adrenal hyperplasia (1 in 13), Pendred's syndrome (1 in 36), Krabbe's disease (1 in 48), and spinal muscular atrophy (1 in 48). Of the 43 identified variants, 29 (67.4%) were not included in the American College of Medical Genetics and Genomics or American College of Obstetrics and Gynecology guidelines. Excluding three couples with alpha-thalassaemia, six at-risk couples were identified. CONCLUSION: The carrier frequency of the investigated members of the Chinese population was 58.7% overall and 47.6% after excluding thalassaemias. This frequency is higher than previously reported. Expanded carrier screening using NGS should be provided to Chinese people to improve the detection rate of carrier status and allow optimal pregnancy planning.


Assuntos
Povo Asiático , Sequenciamento de Nucleotídeos em Larga Escala , Povo Asiático/genética , Feminino , Triagem de Portadores Genéticos , Hong Kong/epidemiologia , Humanos , Mutação , Projetos Piloto , Gravidez
5.
Ultrasound Obstet Gynecol ; 58(4): 603-608, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33219729

RESUMO

OBJECTIVE: To assess objectively the degree of fetal head elevation achieved by different maneuvers commonly used for managing umbilical cord prolapse. METHODS: This was a prospective observational study of pregnant women at term before elective Cesarean delivery. A baseline assessment of fetal head station was performed with the woman in the supine position, using transperineal ultrasound for measuring the parasagittal angle of progression (psAOP), head-symphysis distance (HSD) and head-perineum distance (HPD). The ultrasonographic measurements of fetal head station were repeated during different maneuvers, including elevation of the maternal buttocks using a wedge, knee-chest position, Trendelenburg position with a 15° tilt and filling the maternal urinary bladder with 100 mL, 300 mL and 500 mL of normal saline. The measurements obtained during the maneuvers were compared with the baseline measurements. RESULTS: Twenty pregnant women scheduled for elective Cesarean section at term were included in the study. When compared with baseline (median psAOP, 103.6°), the knee-chest position gave the strongest elevation effect, with the greatest reduction in psAOP (psAOP, 80.7°; P < 0.001), followed by filling the bladder with 500 mL (psAOP, 89.9°; P < 0.001) and 300 mL (psAOP, 94.4°; P < 0.001) of normal saline. Filling the maternal bladder with 100 mL of normal saline (psAOP, 96.1°; P = 0.001), the Trendelenburg position (psAOP, 96.8°; P = 0.014) and elevating the maternal buttocks (psAOP, 98.3°; P = 0.033) gave modest elevation effects. Similar findings were reported for HSD and HPD. The fetal head elevation effects of the knee-chest position, Trendelenburg position and elevation of the maternal buttocks were independent of the initial fetal head station, but that of bladder filling was greater when the initial head station was low. CONCLUSIONS: To elevate the fetal presenting part, the knee-chest position provides the best effect, followed by filling the maternal urinary bladder with 500 mL then 300 mL of fluid, respectively. Filling the bladder with 100 mL of fluid, the Trendelenburg position and elevation of the maternal buttocks have modest effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Feto/diagnóstico por imagem , Cabeça/embriologia , Apresentação no Trabalho de Parto , Posicionamento do Paciente/métodos , Ultrassonografia Pré-Natal/métodos , Adulto , Cesárea , Feminino , Feto/embriologia , Humanos , Períneo/diagnóstico por imagem , Gravidez , Período Pré-Operatório , Prolapso , Estudos Prospectivos , Nascimento a Termo/fisiologia , Cordão Umbilical
7.
Materials (Basel) ; 13(7)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32252396

RESUMO

A series of concrete mixes with metakaolin (MK) content ranging from 0 to 30% and water/cementitious materials (W/CM) ratio varying from 0.30 to 0.50 were produced for performance testing. The results showed that adding MK up to 20% as ordinary Portland cement (OPC) replacement best improved the 28-day and 70-day cube strengths, whereas adding MK up to 30% as OPC replacement always increased the cohesiveness and decreased the sorptivity, but impaired the workability. Moreover, the cement equivalent factor (CEF), i.e. the equivalent mass of OPC per mass of MK added, for each performance attribute, including workability and cohesiveness, was evaluated. Whilst the actual CEF of MK was generally higher at a higher W/CM ratio and lower at a higher MK content, overall, the average CEFs were found to be 1.98, 2.17, 3.83, 1.93, 2.12, and 4.70 for slump, flow, cohesiveness, 28-day cube strength, 70-day cube strength, and sorptivity coefficient, respectively. These CEF values indicated that the MK is a highly effective cementitious material for improving the cohesiveness, strength, and durability. Moreover, it has been demonstrated that the CEFs for workability and cohesiveness are useful parameters in aiding the mix design of MK concrete.

9.
Hong Kong Med J ; 23(6): 641-7, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29226832

RESUMO

OBJECTIVE: The estimated prevalence of irritable bowel syndrome in Hong Kong is 6.6%. With the increasing availability of pharmacological and non-pharmacological treatments, the Hong Kong Advisory Council on Irritable Bowel Syndrome has developed a set of consensus statements intended to serve as local recommendations for clinicians about diagnosis and management of irritable bowel syndrome. PARTICIPANTS: A multidisciplinary group of clinicians constituting the Hong Kong Advisory Council on Irritable Bowel Syndrome-seven gastroenterologists, one clinical psychologist, one psychiatrist, and one nutritionist-convened on 20 April 2017 in Hong Kong. EVIDENCE: Published primary research articles, meta-analyses, and guidelines and consensus statements issued by different regional and international societies on the diagnosis and management of irritable bowel syndrome were reviewed. CONSENSUS PROCESS: An outline of consensus statements was drafted prior to the meeting. All consensus statements were finalised by the participants during the meeting, with 100% consensus. CONCLUSIONS: Twenty-four consensus statements were generated at the meeting. The statements were divided into four parts covering: (1) patient assessment; (2) patient's psychological distress; (3) dietary and alternative approaches to managing irritable bowel syndrome; and (4) evidence to support pharmacological management of irritable bowel syndrome. It is recommended that primary care physicians assume the role of principal care provider for patients with irritable bowel syndrome. The current statements are intended to guide primary care physicians in diagnosing and managing patients with irritable bowel syndrome in Hong Kong.


Assuntos
Síndrome do Intestino Irritável/terapia , Adulto , Hong Kong/epidemiologia , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/prevenção & controle , Prevalência
10.
Neurochem Int ; 2016 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-27984169

RESUMO

Excitatory Amino Acid Transporter 5 (EAAT5) is abundantly expressed by retinal photoreceptors and bipolar cells, where it acts as a slow glutamate transporter and a glutamate-gated chloride channel. The chloride conductance is large enough for EAAT5 to serve as an "inhibitory" glutamate receptor. Our recent work in rodents has shown that EAAT5 is differentially spliced and exists in many variant forms. The chief aim of the present study was to examine whether EAAT5 is also alternately spliced in human retina and, if so, what significance this might have for retinal function in health and disease. Retinal tissues from human donor eyes were used in RT-PCR to amplify the entire coding region of EAAT5. Amplicons of differing sizes were sub-cloned and analysis of sequenced data revealed the identification of wild-type human EAAT5 (hEAAT5) and an abundant alternately spliced form, referred to as hEAAT5v, where the open reading frame is expanded by insertion of an additional exon. hEAAT5v encodes a protein of 619 amino acids and when expressed in COS7 cells, the protein functioned as a glutamate transporter. We raised antibodies that selectively recognized the hEAAT5v protein and have performed immunocytochemistry to demonstrate expression in photoreceptors in human retina. We noted that in retinas afflicted by dry aged-related macular degeneration (AMD), there was a loss of hEAAT5v from the lesioned area and from photoreceptors adjacent to the lesion. We conclude that hEAAT5v protein expression may be perturbed in peri-lesional areas of AMD-afflicted retinas that do not otherwise exhibit evidence of damage. The loss of hEAAT5v could, therefore, represent an early pathological change in the development of AMD and might be involved in its aetiology.

11.
Diabetes Obes Metab ; 18(6): 615-22, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26969812

RESUMO

AIM: To assess the relationship between weight change and glycated haemoglobin (HbA1c) change in dulaglutide-treated patients by analysing data from six head-to-head phase III AWARD clinical trials. METHODS: At 26 weeks, the relationship between weight and HbA1c was analysed in each trial rather than by pooling data because of differences in design and background therapy. The effect of baseline characteristics was also evaluated with regard to weight and HbA1c response. RESULTS: Across the studies, 87-97% and 83-95% of patients treated with dulaglutide 1.5 and 0.75 mg, respectively, had reductions in HbA1c levels, while 57-88% and 43-84% of patients treated with dulaglutide 1.5 and 0.75 mg, respectively, experienced weight loss. The majority (55-83%) of patients receiving dulaglutide 1.5 mg experienced weight loss and HbA1c reductions, while 41-79% of patients in the dulaglutide 0.75 mg arm lost weight and had reductions in HbA1c level. A weak and inconsistent correlation was observed between the changes in weight and HbA1c (range from -0.223 to 0.267) in patients treated with dulaglutide. The baseline characteristics of gender, age, duration of diabetes, HbA1c, body weight and BMI were not related to different combinations of weight and HbA1c responses. CONCLUSIONS: Dulaglutide is an effective treatment option across the type 2 diabetes treatment spectrum. Dulaglutide showed dose-dependent effects on both weight loss and HbA1c reduction. These effects had a weak correlation and appeared to be independent.


Assuntos
Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/administração & dosagem , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Feminino , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Proteínas Recombinantes de Fusão/efeitos adversos , Resultado do Tratamento , Redução de Peso/efeitos dos fármacos
12.
Spinal Cord ; 53(6): 432-5, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25644387

RESUMO

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate a modified compression model of spinal cord injury (SCI) in adult rats by using a room-air- inflated Fogarty balloon catheter. SETTING: Kaohsiung, Taiwan. METHODS: The rats were divided into injury, sham-operated and control groups. A 2-French Fogarty catheter was passed from the lumbar spine (L3-L4) epidurally, with a mini-laminectomy under the microscope, to the level of thoracic spine (T6-T7). The actual site of the catheter tip was confirmed with X-ray. The balloon of Fogarty catheter then was inflated with room air, 0.2 ml, for 10 min. Mini-laminectomy was performed without inserting the catheter in the sham-operated group. Quantitative neurological outcomes were evaluated with the Basso, Beattie and Bresnahan (BBB) locomotor rating scale daily. The gene expression of nitric oxide synthases (NOSs) of the spinal cord was investigated at the end of the functional assessment. RESULTS: The mean BBB locomotor scores were 10±1.85 and 10±1.85, respectively, on days 1 and 3 in the injury group, and 21 and 20.29±0.69, respectively, in the sham-operated group. There was a significantly increased gene expression of inducible NOS in the SCI group compared with the sham-operated group and control group. Endothelial NOS gene expression was not significantly different among the groups. CONCLUSION: The functional and molecular assessments show that this modified balloon-compression technique is a reproducible, simple and inexpensive model of SCI in rats.


Assuntos
Modelos Animais de Doenças , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Traumatismos da Medula Espinal/enzimologia , Medula Espinal/enzimologia , Animais , Catéteres , Expressão Gênica , Laminectomia , Locomoção/fisiologia , Vértebras Lombares , Masculino , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Índice de Gravidade de Doença
13.
J Mol Biol ; 425(7): 1101-10, 2013 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-23353824

RESUMO

LIM-only protein 4 (LMO4) is strongly linked to the progression of breast cancer. Although the mechanisms underlying this phenomenon are not well understood, a role is emerging for LMO4 in regulation of the cell cycle. We determined the solution structure of LMO4 in complex with CtIP (C-terminal binding protein interacting protein)/RBBP8, a tumour suppressor protein that is involved in cell cycle progression, DNA repair and transcriptional regulation. Our data reveal that CtIP and the essential LMO cofactor LDB1 (LIM-domain binding protein 1) bind to the same face on LMO4 and cannot simultaneously bind to LMO4. We hypothesise that overexpression of LMO4 may disrupt some of the normal tumour suppressor activities of CtIP, thereby contributing to breast cancer progression.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas de Transporte/química , Proteínas com Domínio LIM/química , Proteínas Nucleares/química , Estrutura Terciária de Proteína , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sequência de Aminoácidos , Sítios de Ligação/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Endodesoxirribonucleases , Feminino , Humanos , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ligação Proteica , Homologia de Sequência de Aminoácidos , Proteínas Supressoras de Tumor/química , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Técnicas do Sistema de Duplo-Híbrido
14.
Neurol Sci ; 34(3): 365-71, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22454035

RESUMO

The objective of the study was to evaluate the effect of silencing hypoxia-inducible factor 1α (HIF-1α) on proliferation, invasion, and migration of glioblastoma U87 cells. HIF-1α-shRNA lentiviral vector was designed for liposome-mediated transfection into U87 cells. The efficiency of interference was assessed by RT-PCR and Western blot. Cell proliferation was measured by MTT assay. Cell migration was observed by the migration test. The capabilities of invasion and migration were detected using the Transwell model. The research involved experiments in the interference group (shRNA transfected), the control interference group (empty vector transfected), and the untreated (non-transfected) group. Compared with the control interference group and the untreated group, the expressions of HIF-1α mRNA and protein were significantly down-regulated, and the proliferation and invasion of U87 cells were significantly inhibited in the interference group. HIF-1α mRNA and protein are effectively suppressed by HIF-1α-shRNA in U87 cells, which appears to inhibit proliferation, invasion, and migration of U87 cells.


Assuntos
Movimento Celular/fisiologia , Proliferação de Células , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , RNA Interferente Pequeno/metabolismo , Análise de Variância , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Vetores Genéticos/fisiologia , Glioblastoma/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Invasividade Neoplásica/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Transfecção
15.
J Neurooncol ; 108(3): 491-8, 2012 07.
Artigo em Inglês | MEDLINE | ID: mdl-22426926

RESUMO

We have tested the predictive value of apparent diffusion coefficient (ADC) histogram analysis in stratifying progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients with recurrent glioblastoma multiforme (GBM) from the multi-center BRAIN study. Available MRI's from patients enrolled in the BRAIN study (n = 97) were examined by generating ADC histograms from areas of enhancing tumor on T1 weighted post-contrast images fitted to a two normal distribution mixture curve. ADC classifiers including the mean ADC from the lower curve (ADC-L) and the mean lower curve proportion (LCP) were tested for their ability to stratify PFS and OS by using Cox proportional hazard ratios and the Kaplan-Meier method with log-rank test. Mean ADC-L was 1,209 × 10(-6)mm(2)/s ± 224 (SD), and mean LCP was 0.71 ± 0.23 (SD). Low ADC-L was associated with worse outcome. The hazard ratios for 6-month PFS, overall PFS, and OS in patients with less versus greater than mean ADC-L were 3.1 (95 % confidence interval: 1.6, 6.1; P = 0.001), 2.3 (95 % CI: 1.3, 4.0; P = 0.002), and 2.4 (95 % CI: 1.4, 4.2; P = 0.002), respectively. In patients with ADC-L <1,209 and LCP >0.71 versus ADC-L >1,209 and LCP <0.71, there was a 2.28-fold reduction in the median time to progression, and a 1.42-fold decrease in the median OS. The predictive value of ADC histogram analysis, in which low ADC-L was associated with poor outcome, was confirmed in bevacizumab-treated patients with recurrent GBM in a post hoc analysis from the multi-center (BRAIN) study.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Imagem de Difusão por Ressonância Magnética , Glioblastoma/diagnóstico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Algoritmos , Bevacizumab , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
16.
Obes Rev ; 13(5): 409-30, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22292480

RESUMO

Obesity is a major health hazard and despite lifestyle modification, many patients frequently regain any lost body weight. The use of western anti-obesity drugs has been limited by side effects including mood changes, suicidal thoughts, and gastrointestinal or cardiovascular complications. The effectiveness and safety of traditional Chinese medicine including Chinese herbal medicine (CHM) and acupuncture provide an alternative established therapy for this medical challenge. In this systematic review, we used standard methodologies to search, review, analyse and synthesize published data on the efficacy, safety and relapse of weight regain associated with use of CHM and acupuncture. We also examined the rationale, mechanisms and potential utility of these therapies. A total of 12 electronic databases, including Chinese, English, Korean and Japanese, were searched up to 28 February 2010. Randomized controlled trials (RCTs) for CHM and/or acupuncture with comparative controls were considered. We used the Jadad scale to assess methodological qualities, the random effect model in the pooled analysis of therapeutic efficacy to adjust for heterogeneity and funnel plots to explore publication bias. After screening 2,545 potential articles from the electronic databases, we identified 96 RCTs; comprising of 49 trials on CHM treatment, 44 trials on acupuncture treatment and 3 trials on combined therapy for appraisal. There were 4,861 subjects in the treatment groups and 3,821 in the control groups, with treatment duration ranging from 2 weeks to 4 months. Of the 77 publications written in Chinese, 75 had a Jadad score <3, while 16 of the 19 English publications had a Jadad score of >3. Efficacy was defined as body weight reduction ≥ 2 kg or body mass index (BMI) reduction ≥ 0.5 kg/m(2) . Compared with placebo or lifestyle modification, CHM and acupuncture exhibited respective 'risk ratio' (RR) of 1.84 (95% CI: 1.37-2.46) and 2.14 (95% CI: 1.58-2.90) in favour of body weight reduction, with a mean difference in body weight reduction of 4.03 kg (95% CI: 2.22-5.85) and 2.76 kg (95% CI: 1.61-3.83) and a mean difference in BMI reduction of 1.32 kg m(-2) (95% CI: 0.78-1.85) and 2.02 kg m(-2) (95% CI: 0.94-3.10), respectively. Compared with the pharmacological treatments of sibutramine, fenfluramine or orlistat, CHM and acupuncture exhibited an RR of 1.11 (95% CI: 0.96-1.28) and 1.14 (95% CI: 1.03-1.25) in body weight reduction, mean difference in body weight reduction of 0.08 kg (95% CI: -0.58 to 0.74) and 0.65 kg (95% CI: -0.61 to 1.91), and mean difference in BMI reduction of 0.18 kg m(-2) (95% CI: -0.39 to 0.75) and 0.83 kg m(-2) (95% CI: 0.29-1.37), respectively. There were fewer reports of adverse effects and relapses of weight regain in CHM intervention studies conducted in China than studies conducted outside China. CHM and acupuncture were more effective than placebo or lifestyle modification in reducing body weight. They had a similar efficacy as the Western anti-obesity drugs but with fewer reported adverse effects. However, these conclusions were limited by small sample size and low quality of methodologies.


Assuntos
Terapia por Acupuntura/métodos , Medicina Tradicional Chinesa/métodos , Obesidade/terapia , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Terapias Complementares , Humanos , Resultado do Tratamento
17.
Mol Psychiatry ; 17(7): 728-40, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21647149

RESUMO

Epigenetic studies of DNA and histone modifications represent a new and important activity in molecular investigations of human disease. Our previous epigenome-wide scan identified numerous DNA methylation differences in post-mortem brain samples from individuals affected with major psychosis. In this article, we present the results of fine mapping DNA methylation differences at the human leukocyte antigen (HLA) complex group 9 gene (HCG9) in bipolar disorder (BPD). Sodium bisulfite conversion coupled with pyrosequencing was used to interrogate 28 CpGs spanning ∼700 bp region of HCG9 in 1402 DNA samples from post-mortem brains, peripheral blood cells and germline (sperm) of bipolar disease patients and controls. The analysis of nearly 40 000 CpGs revealed complex relationships between DNA methylation and age, medication as well as DNA sequence variation (rs1128306). Two brain tissue cohorts exhibited lower DNA methylation in bipolar disease patients compared with controls at an extended HCG9 region (P=0.026). Logistic regression modeling of BPD as a function of rs1128306 genotype, age and DNA methylation uncovered an independent effect of DNA methylation in white blood cells (odds ratio (OR)=1.08, P=0.0077) and the overall sample (OR=1.24, P=0.0011). Receiver operating characteristic curve A prime statistics estimated a 69-72% probability of correct BPD prediction from a case vs control pool. Finally, sperm DNA demonstrated a significant association (P=0.018) with BPD at one of the regions demonstrating epigenetic changes in the post-mortem brain and peripheral blood samples. The consistent multi-tissue epigenetic differences at HCG9 argue for a causal association with BPD.


Assuntos
Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo , Metilação de DNA/genética , RNA não Traduzido/metabolismo , Adulto , Fatores Etários , Transtorno Bipolar/sangue , Encéfalo/metabolismo , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , RNA não Traduzido/genética , Espermatozoides/metabolismo
18.
J Microsc ; 241(2): 119-24, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21118215

RESUMO

Many multiphoton imaging applications would benefit from a larger field of view; however, large field of views (>mm) require low magnification objectives which have low light collection efficiencies. We demonstrate a light collection system mounted on a low magnification objective that increases fluorescence collection by as much as 20-fold in scattering tissues. This peripheral detector results in an effective numerical aperture of collection >0.8 with a 3-4 mm field of view.


Assuntos
Microscopia de Fluorescência/métodos , Patologia/métodos , Neoplasias Abdominais/patologia , Animais , Encéfalo/citologia , Carcinoma/patologia , Camundongos , Medula Espinal/citologia
19.
Br J Dermatol ; 163(4): 695-703, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20633012

RESUMO

BACKGROUND: Emollient molecules are widely used in skin care formulations to improve skin sensory properties and to alleviate dry skin but little is understood regarding their effects on skin biomechanical properties. OBJECTIVES: To investigate the effects of emollient molecules on drying stresses in human stratum corneum (SC) and how these stresses are related to SC components and moisture content. METHODS: The substrate curvature method was used to measure the drying stresses in isolated SC following exposure to selected emollient molecules. While SC stresses measured using this method have the same biaxial in vivo stress state and moisture exchange with the environment, a limitation of the method is that moisture cannot be replenished by the underlying skin layers. This provides an opportunity to study the direct effects of emollient treatments on the moisture content and the components of the SC. Attenuated total reflectance Fourier transform infrared spectroscopy was used to determine the effects of emollient molecules on SC lipid extraction and conformation. Results Emollient molecules resulted in a complex SC drying stress profile where stresses increased rapidly to peak values and then gradually decreased to significantly lower values compared with the control. The partially occlusive treatments also penetrated into the SC where they caused extraction and changes in lipid conformation. These effects together with their effects on SC moisture content are used to rationalize the drying stress profiles. CONCLUSIONS: Emollient molecules have dramatic effects on SC drying stresses that are related to their effects on intercellular lipids and SC moisture content.


Assuntos
Desidratação/fisiopatologia , Emolientes/farmacologia , Epiderme/efeitos dos fármacos , Água Corporal/metabolismo , Epiderme/metabolismo , Epiderme/fisiopatologia , Feminino , Humanos , Técnicas In Vitro , Metabolismo dos Lipídeos/efeitos dos fármacos , Pessoa de Meia-Idade , Manejo de Espécimes/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , Perda Insensível de Água/efeitos dos fármacos
20.
Br J Ophthalmol ; 94(1): 36-40, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19713199

RESUMO

AIMS: To compare post-operative pain following 25-gauge (25G) and 20-gauge (20G) vitrectomy in the first week following surgery. METHODS: The study was a pilot randomised controlled trial with patients masked to the treatment allocation. Post-operative pain was assessed using both a visual scale and verbal pain scores for 1 week following surgery. Additional data collected included intraocular pressure (IOP), time taken to perform the surgical procedure, per-operative and post-operative complications, and dropout rates. RESULTS: Forty patients were recruited for the study: 21 randomised to 20G vitrectomy and 19 to 25G. In the first 12 h following surgery, presence of significant post-operative pain (defined as >1 cm on a visual analogue scale) was similar in both 20G (50%) and 25G (53%) patients. In the first week following surgery, 38 of the 527 scores (7.2%) were >1 (median 2.1, IQR 1.3-3) cm; however, there was evidence that "significant pain" was experienced more commonly in the 20G group. There was no statistical difference in the time taken to complete the surgical procedure, although in the 25G group the time from first incision to the start of vitrectomy was significantly shorter (p = 0.043) and in the 20G group the time taken to complete the vitrectomy was less (p = 0.047). Post-operative hypotony (IOP <6 mmHg) was observed in 25% of patients in the 25G group. No patients required additional surgery for hypotony. CONCLUSION: There was evidence that 25G resulted in less patient discomfort. However, pain was not a prominent feature in either group. We failed to find a significant advantage in 25G for patients or surgeons.


Assuntos
Dor Pós-Operatória/etiologia , Vitrectomia/efeitos adversos , Vitrectomia/instrumentação , Idoso , Analgésicos/administração & dosagem , Esquema de Medicação , Membrana Epirretiniana/cirurgia , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Agulhas , Medição da Dor/métodos , Projetos Piloto , Perfurações Retinianas/cirurgia , Vitrectomia/métodos , Hemorragia Vítrea/cirurgia
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