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3.
Eur J Clin Nutr ; 72(1): 117-123, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28901337

RESUMO

BACKGROUND/OBJECTIVES: The objective of this sudy was to assess the relationship between dietary intake and fatty liver as scored by the validated Fatty Liver Index (FLI) in a large cross-sectional study among a general Dutch adult population. Diet is known to affect liver fat accumulation in humans. SUBJECTS/METHODS: 1128 men and women aged 20-70 years were included. Dietary intake was assessed using a validated semiquantitative food frequency questionnaire. FLI was derived from body mass index (BMI), waist circumference, triglycerides and gamma-glutamyltransferase. Associations were adjusted for energy intake, alcohol intake, age, sex, education, smoking and prevalence of hypertension and diabetes. RESULTS: In this population (mean age 53.0±11.4 years; BMI 25.9±4.0 kg/m2; FLI 35.0±27.7), the prevalence of fatty liver as indicated by an FLI>60 was 21.5%. Subjects in the highest FLI category were more likely to be male, older and less physically active. Total protein intake and animal protein intake were positively associated with the highest FLI score versus the lowest (odds ratio (OR) 1.25 per 1 en%, 95% confidence interval (CI) 1.15-1.37 and OR 1.27, 95% CI 1.17-1.38, respectively); for vegetable protein, an inverse association was observed (OR 0.81, 95% CI 0.69-0.94). A similar positive association with FLI was observed when carbohydrates and fat were iso-calorically exchanged for total and animal proteins. CONCLUSIONS: Subjects in the high FLI group consumed more protein, especially from animal origin, less carbohydrates and less dietary fibre. The presence of fatty liver was associated with a higher intake of animal protein and total fat, soft drinks and snacks.


Assuntos
Biomarcadores/análise , Dieta , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Bebidas Gaseificadas , Estudos Transversais , Registros de Dieta , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Hepatopatia Gordurosa não Alcoólica/sangue , Razão de Chances , Fatores Sexuais , Lanches , Inquéritos e Questionários , Triglicerídeos/sangue , Circunferência da Cintura , gama-Glutamiltransferase/sangue
4.
Int J Obes (Lond) ; 40(5): 731-46, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26443336

RESUMO

BACKGROUND: Yoghurt is part of the diet of many people worldwide and is commonly recognised as a 'health food'. Epidemiological studies suggest that yoghurt may be useful as part of weight management programs. In the absence of comprehensive systematic reviews, this systematic review investigated the effect of yoghurt consumption by apparently healthy adults on weight-related outcomes. METHODS: An extensive literature search was undertaken, as part of a wider scoping review, to identify yoghurt studies. A total of 13 631 records were assessed for their relevance to weight-related outcomes. RESULTS: Twenty-two publications were eligible according to the review protocol. Cohort studies (n=6) and cross-sectional studies (n=7) all showed a correlation between yoghurt and lower or improved body weight/composition. Six randomised controlled trials (RCTs) and one controlled trial had various limitations, including small size and short duration. One RCT showed significant effects of yoghurt on weight loss, but was confounded by differences in calcium intake. One trial showed nonsignificant weight gain and the remaining five trials showed nonsignificant weight losses that were greater in yoghurt consumers. CONCLUSIONS: Yoghurt consumption is associated with lower body mass index, lower body weight/weight gain, smaller waist circumference and lower body fat in epidemiological studies. RCTs suggest weight reduction effects, but do not permit determination of a cause-effect relationship. Well-controlled, adequately powered trials in research and community settings appear likely to identify a modest but beneficial effect of yoghurt consumption for prevention of weight gain and management of obesity. The ready availability of yoghurt (a nutrient-dense food) and its ease of introduction to most diets suggests that educating the public to eat yoghurt as part of a balanced and healthy diet may potentially contribute to improved public health. Future carefully designed RCTs could provide proof of principle and large community-based studies could determine the practical impact of yoghurt on body weight/composition.


Assuntos
Dieta Saudável , Dieta Redutora/estatística & dados numéricos , Iogurte , Peso Corporal , Estudos Transversais , Ingestão de Energia , Humanos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Circunferência da Cintura
5.
Mol Psychiatry ; 21(8): 1125-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26416544

RESUMO

The genetic basis of intellectual disability (ID) is extremely heterogeneous and relatively little is known about the role of autosomal recessive traits. In a field study performed in a highly inbred area of Northeastern Brazil, we identified and investigated a large consanguineous family with nine adult members affected by severe ID associated with disruptive behavior. The Genome-Wide Human SNP Array 6.0 microarray was used to determine regions of homozygosity by descent from three affected and one normal family member. Whole-exome sequencing (WES) was performed in one affected patient using the Nextera Rapid-Capture Exome kit and Illumina HiSeq2500 system to identify the causative mutation. Potentially deleterious variants detected in regions of homozygosity by descent and not present in either 59 723 unrelated individuals from the Exome Aggregation Consortium (Browser) or 1484 Brazilians were subject to further scrutiny and segregation analysis by Sanger sequencing. Homozygosity-by-descent analysis disclosed a 20.7-Mb candidate region at 8q12.3-q21.2 (lod score: 3.11). WES identified a homozygous deleterious variant in inositol monophosphatase 1 (IMPA1) (NM_005536), consisting of a 5-bp duplication (c.489_493dupGGGCT; chr8: 82,583,247; GRCh37/hg19) leading to a frameshift and a premature stop codon (p.Ser165Trpfs*10) that cosegregated with the disease in 26 genotyped family members. The IMPA1 gene product is responsible for the final step of biotransformation of inositol triphosphate and diacylglycerol, two second messengers. Despite its many physiological functions, no clinical phenotype has been assigned to this gene dysfunction to date. Additionally, IMPA1 is the main target of lithium, a drug that is at the forefront of treatment for bipolar disorder.


Assuntos
Deficiência Intelectual/genética , Monoéster Fosfórico Hidrolases/genética , Adulto , Brasil , Consanguinidade , Exoma/genética , Família , Feminino , Genoma Humano/genética , Genótipo , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Monoéster Fosfórico Hidrolases/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA/métodos
6.
Public Health ; 129(12): 1585-90, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26506453

RESUMO

OBJECTIVES: To describe the registration, management and characteristics of patients with tuberculosis (TB) in north-west China, and investigate whether patients with TB were diagnosed and treated in a timely manner. STUDY DESIGN: Health-facility-based retrospective data were collected from district patient registers and case reports for all patients with TB registered from January 2009 to December 2011 in Xinjiang Uygur Autonomous Region, north-west China. METHODS: Patient characteristics and clinical data were collected from the national TB epidemic reporting system using standardized case reporting forms for diagnosis, treatment and outcome. Data were collected and entered by trained health staff in the regional TB clinics. RESULTS: In total, data for 20,396 patients with TB were collected; of these, 78.5% were farmers. The age peaks were 20-44 years and 60-74 years. Average health-seeking and diagnostic delays were 32 days and two days, respectively. More than half (54.7%) of the patients with smear-negative TB were diagnosed by chest x-ray. Moreover, 94.3% of patients with TB were treated successfully. From 2009 to 2011, the health-seeking delay decreased significantly (P < 0.05), and the diagnostic delay increased significantly (P < 0.05). A significant decreasing trend in smear-positive TB was observed (P < 0.05), along with an increasing trend in treatment success (P < 0.05). CONCLUSIONS: In north-west China, there is a need to focus on key high-risk populations for prevention and control of TB, such as those aged 20-44 years and 60-74 years, males and farmers. Delays in diagnosis and treatment have a negative effect on cure rates and make it more difficult to control the propagation of TB.


Assuntos
Serviços de Saúde Comunitária , Sistema de Registros , Tuberculose/diagnóstico , Tuberculose/terapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China/epidemiologia , Diagnóstico Tardio/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Tuberculose/epidemiologia , Adulto Jovem
7.
Eur Rev Med Pharmacol Sci ; 19(11): 2016-25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26125264

RESUMO

OBJECTIVE: The tuberculosis (TB) program was carried out in the Changji zone in northwest of China. Directly Observed Treatment, Short-Course (DOTS) is a modern control strategy against tuberculosis recommended by World Health Organization. The purpose of this work is to describe the survival of post-treatment TB (PTB) patients and to identify the risk factors associated with mortality and treatment outcomes, so that effective measures and interventions could be used to decrease the mortality rate. PATIENTS AND METHODS: Registry of 4501 TB patients at Center for Disease Control and Prevention (CDC) treated from 2007 to 2014 were collected. Mortality was used as an outcome measure and calculated per 100 person years of observation (PYO) from the date of completion of the treatment to the date of interview if the patients were alive or to the date of death. Kaplan-Meier and Cox regression methods were used to determine the survival and hazard ratios. An indirect method of standardization was used to calculate the standard mortality ratio (SMR). RESULTS: The average PYO was 5.0 and the total was 21851. Mortality per 100 PYO was 1.9/100 PYO [223/11871] for smear-positive, 3.4/100 PYO [305/9048] for smear-negative and 2.4/100 PYO [22/932] for EPTB cases. Univariate and Cox regression analysis showed that age (p < 0.01), education (p < 0.01), occupation (p < 0.01) and economic status (p < 0.01) were associated with increased mortality. DISCUSSION: Since the mortality rate was higher in Post-treatment TB patients than the general population these patients need special health care. An integrated survival and associated mortality risk factors and information system is necessary for TB surveillance, personal health status and treatment management. Further studies are required to identify the causes of death in these patients.


Assuntos
Fatores de Risco , Resultado do Tratamento , Tuberculose/epidemiologia , Tuberculose/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ocupações , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores Socioeconômicos , Tuberculose/prevenção & controle , Organização Mundial da Saúde , Adulto Jovem
8.
Dev Cell ; 32(1): 97-108, 2015 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-25533206

RESUMO

The widespread availability of programmable site-specific nucleases now enables targeted gene disruption in the zebrafish. In this study, we applied site-specific nucleases to generate zebrafish lines bearing individual mutations in more than 20 genes. We found that mutations in only a small proportion of genes caused defects in embryogenesis. Moreover, mutants for ten different genes failed to recapitulate published Morpholino-induced phenotypes (morphants). The absence of phenotypes in mutant embryos was not likely due to maternal effects or failure to eliminate gene function. Consistently, a comparison of published morphant defects with the Sanger Zebrafish Mutation Project revealed that approximately 80% of morphant phenotypes were not observed in mutant embryos, similar to our mutant collection. Based on these results, we suggest that mutant phenotypes become the standard metric to define gene function in zebrafish, after which Morpholinos that recapitulate respective phenotypes could be reliably applied for ancillary analyses.


Assuntos
Desoxirribonucleases/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes/métodos , Morfolinos/farmacologia , Mutação/genética , Oligonucleotídeos Antissenso/farmacologia , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Western Blotting , Desoxirribonucleases/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Fenótipo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/antagonistas & inibidores
9.
Mol Genet Metab Rep ; 2: 34-37, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28649523

RESUMO

Mucolipidosis II and III alpha/beta (ML II/III alpha/beta) are rare autosomal recessive lysosomal storage diseases that are caused by a deficiency of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, the enzyme responsible for the synthesis of the mannose 6-phosphate targeting signal on lysosomal hydrolases. A Brazilian patient suspected of having a very mild ML III was investigated using whole next-generation sequencing (NGS). Two mutations in the GNPTAB gene were detected and confirmed to be in trans status by parental analysis: c.1208T>C (p.Ile403Thr), previously reported as being pathogenic, and the novel mutation c.1723G>A (p.Gly575Arg). This study demonstrates the effectiveness of using whole NGS for the molecular diagnosis of very mild ML III alpha/beta patients.

10.
Eur J Clin Nutr ; 68(9): 973-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24986822

RESUMO

Dietary proteins have an insulinotropic effect and thus promote insulin secretion, which indeed leads to enhanced glucose clearance from the blood. In the long term, however, a high dietary protein intake is associated with an increased risk of type 2 diabetes. Moreover, branched-chain amino acids (BCAA), a prominent group of amino acids, were recently identified to be associated with diabetes. Observational data and intervention studies do not point in the same direction regarding the effect of protein intake on insulin sensitivity and diabetes risk. Therefore, the first aim of this review will be to discuss human studies addressing high dietary protein intake and insulin action, with special attention for BCAA. In the second part, we will highlight the (patho) physiological consequences of high-protein diets regarding insulin action, in particular the role of the mechanistic target of the rapamycin pathway.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Glicemia/metabolismo , Dieta , Proteínas Alimentares/administração & dosagem , Resistência à Insulina/fisiologia , Insulina/sangue , Serina-Treonina Quinases TOR/metabolismo , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Proteínas Alimentares/farmacologia , Humanos
11.
Oncogene ; 32(48): 5439-48, 2013 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-23563182

RESUMO

Anti-apoptotic Bcl-2 family members can contribute to tumorigenesis and may convey resistance to anti-cancer regimens. Therefore, they are important targets for novel therapeutics, particularly Bcl-2 homology (BH)3 mimetics. Bcl-B (BCL-2-like protein-10) is a relatively understudied member of the Bcl-2 protein family. Its physiological function is unknown, but it has been proven to have an anti-apoptotic activity and to act as a tumor promoter in mice. In human, high Bcl-B protein expression levels correlate with poor prognosis in various carcinomas and predict treatment resistance in acute myeloid leukemia. We here report that protein expression level and anti-apoptotic activity of Bcl-B are dictated by its ubiquitination. We demonstrate that Bcl-B is polyubiquitinated at steady state, in a unique loop between the BH1 and BH2 domains. Mutagenesis identified lysine (K)128 as an acceptor site for polyubiquitin chains, and K119 and K120, but not K181, as potential ubiquitination sites. Mass spectrometry confirmed K128 as a ubiquitination site and defined the polyubiquitin chains as K48-linked, which was confirmed by linkage-specific antibodies. Accordingly, Bcl-B proved to be an instable protein that is subject to ubiquitin-dependent proteasomal degradation at steady state. At equal mRNA expression, protein expression of a lysineless, nonubiquitinated Bcl-B mutant was fivefold higher than that of wild-type Bcl-B, demonstrating that ubiquitination is a key determinant for Bcl-B protein expression levels. Ubiquitination controlled the anti-apoptotic capacity of Bcl-B, in response to a variety of conventional and novel anti-cancer drugs. Certain anti-cancer drugs, known to reduce Mcl-1 protein levels, likewise downregulated Bcl-B. Together, these data demonstrate that polyubiquitination and proteasomal turnover dictate the expression level and anti-apoptotic capacity of Bcl-B.


Assuntos
Apoptose , Poliubiquitina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ubiquitinação , Sequência de Aminoácidos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Meia-Vida , Humanos , Lisina/metabolismo , Modelos Moleculares , Terapia de Alvo Molecular , Conformação Proteica , Transporte Proteico/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/química , Ubiquitinação/efeitos dos fármacos
12.
Osteoporos Int ; 24(5): 1567-77, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23229471

RESUMO

UNLABELLED: On September 29, 2011, acknowledged experts in the field of vitamin D, mainly European, were brought together in order to discuss the recent scientific advances in relation to vitamin D: the current requirements and associations with various health outcomes. In this article, the discussions resulting from the meeting are summarized. INTRODUCTION: Several groups at risk for developing vitamin D insufficiency have been identified. Accordingly, reviews indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l. In addition to the role of vitamin D in bone health, recent studies suggest that it may play a pivotal role in other systems, e.g., the cardiovascular system, pancreas, muscle, immune system and brain. Most evidence, however, is obtained from observational studies and yet inconclusive. METHODS: To exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes, a workshop entitled "Vitamin D Expert Meeting: Do we get enough?", was organized. RESULTS: Despite low vitamin D levels worldwide, consensus on the definition of deficiency is not yet reached. In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects, randomized controlled trials in these fields are warranted. The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation, in most studies co-administered with calcium, reduces fracture risk in the senior population. CONCLUSION: To reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged ≥65 years are therefore recommended to meet a mean daily vitamin D intake of 20 µg (800 IU), which is best achieved with a supplement.


Assuntos
Dieta/normas , Suplementos Nutricionais , Deficiência de Vitamina D/diagnóstico , Vitamina D/administração & dosagem , Europa (Continente) , Medicina Baseada em Evidências/métodos , Saúde Global , Humanos , Valores de Referência , Luz Solar , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue
13.
Clin Genet ; 83(2): 169-74, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22320281

RESUMO

PLP1 (proteolipid protein1 gene) mutations cause Pelizaeus-Merzbacher disease (PMD), characterized by hypomyelination of the central nervous system, and affecting almost exclusively males. We report on a girl with classical PMD who carries an apparently balanced translocation t(X;22)(q22;q13). By applying array-based comparative genomic hybridization (a-CGH), we detected duplications at 22q13 and Xq22, encompassing 487-546 kb and 543-611 kb, respectively. The additional copies were mapped by fluorescent in situ hybridization to the breakpoint regions, on the derivative X chromosome (22q13 duplicated segment) and on the derivative 22 chromosome (Xq22 duplicated segment). One of the 14 duplicated X-chromosome genes was PLP1.The normal X chromosome was the inactive one in the majority of peripheral blood leukocytes, a pattern of inactivation that makes cells functionally balanced for the translocated segments. However, a copy of the PLP1 gene on the derivative chromosome 22, in addition to those on the X and der(X) chromosomes, resulted in two active copies of the gene, irrespective of the X-inactivation pattern, thus causing PMD. This t(X;22) is the first constitutional human apparently balanced translocation with duplications from both involved chromosomes detected at the breakpoint regions.


Assuntos
Cromossomos Humanos Par 22 , Cromossomos Humanos X , Duplicação Gênica , Proteína Proteolipídica de Mielina/genética , Doença de Pelizaeus-Merzbacher/genética , Hibridização Genômica Comparativa , Humanos , Hibridização in Situ Fluorescente , Doença de Pelizaeus-Merzbacher/diagnóstico , Translocação Genética
14.
Eur J Clin Nutr ; 66(7): 869-70, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22473043
15.
Eur Psychiatry ; 27(7): 506-12, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21920707

RESUMO

PURPOSE: The aim of this study is to evaluate the effectiveness of 12-week treatment with aripiprazole in a broad range of patients suffering from schizophrenia by using a variety of physicians, caregivers and patients scales. SUBJECTS AND METHODS: A total of 361 in- or outpatients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia received open-label aripiprazole (10-30 mg per day) in this 12-week, prospective, multicentre, uncontrolled study. The primary endpoint was the Clinical Global Impression-Improvement (CGI-I) scale which measured effectiveness of study medication, including efficacy, safety and tolerability. A variety of physician-, patient- and caregiver-rated parameters were measured to gain a complete view of the effectiveness of aripiprazole. RESULTS: The effectiveness of aripiprazole treatment was demonstrated in a broad range of schizophrenia patients (CGI-I score of 3.0; 95% confidence interval: 2.8, 3.2: last observation carried forward [LOCF]) as the upper bound of the 95% CI was less than 4 (score of "no change"). Both patient and caregiver PGI-I scores (LOCF: 95% CI: 2.79, 3.09 and, 95% CI: 2.74, 3.17, respectively) corroborate this finding. Aripiprazole had a positive effect on disease severity by study end, as assessed by an increase of the (physician-rated) CGI-S scores, with 57.3% of patients having improved disease, one-third maintaining their condition (30.8%) and 11.3% with worsening symptoms (LOCF). The Investigator Assessment Questionnaire (IAQ) showed a great improvement (>50% of patients). Patients reported significantly improved quality of life and overall, 71% of patients and 67% of caregivers preferred aripiprazole to their previous antipsychotic medication (LOCF; P<0.0001 over time). CONCLUSION: Aripiprazole was effective in a broad range of patients with schizophrenia.


Assuntos
Antipsicóticos/uso terapêutico , Piperazinas/uso terapêutico , Quinolonas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Aripiprazol , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Piperazinas/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Quinolonas/efeitos adversos , Esquizofrenia/diagnóstico , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento
16.
J Med Genet ; 49(2): 104-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22180640

RESUMO

BACKGROUND: Congenital deletions affecting 3q11q23 have rarely been reported and only five cases have been molecularly characterised. Genotype-phenotype correlation has been hampered by the variable sizes and breakpoints of the deletions. In this study, 14 novel patients with deletions in 3q11q23 were investigated and compared with 13 previously reported patients. METHODS: Clinical data were collected from 14 novel patients that had been investigated by high resolution microarray techniques. Molecular investigation and updated clinical information of one cytogenetically previously reported patient were also included. RESULTS: The molecular investigation identified deletions in the region 3q12.3q21.3 with different boundaries and variable sizes. The smallest studied deletion was 580 kb, located in 3q13.31. Genotype-phenotype comparison in 24 patients sharing this shortest region of overlapping deletion revealed several common major characteristics including significant developmental delay, muscular hypotonia, a high arched palate, and recognisable facial features including a short philtrum and protruding lips. Abnormal genitalia were found in the majority of males, several having micropenis. Finally, a postnatal growth pattern above the mean was apparent. The 580 kb deleted region includes five RefSeq genes and two of them are strong candidate genes for the developmental delay: DRD3 and ZBTB20. CONCLUSION: A newly recognised 3q13.31 microdeletion syndrome is delineated which is of diagnostic and prognostic value. Furthermore, two genes are suggested to be responsible for the main phenotype.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 3 , Deficiências do Desenvolvimento/genética , Fácies , Genitália Masculina/anormalidades , Transtornos do Crescimento/genética , Deficiências do Desenvolvimento/diagnóstico , Feminino , Estudos de Associação Genética , Humanos , Masculino , Proteínas do Tecido Nervoso/genética , Receptores de Dopamina D3/genética , Síndrome , Fatores de Transcrição/genética
17.
Eur J Neurol ; 19(2): 248-52, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21771203

RESUMO

BACKGROUND AND PURPOSES: Anti-aquaporin 4 antibodies are specific markers for Devic's disease. This study aimed to test if this high specificity holds in the context of a large spectrum of systemic autoimmune and non-autoimmune diseases. METHODS: Anti-aquaporin-4 antibodies (NMO-IgG) were determined by indirect immunofluorescence (IIF) on mouse cerebellum in 673 samples, as follows: group I (clinically defined Devic's disease, n=47); group II [inflammatory/demyelinating central nervous system (CNS) diseases, n=41]; group III (systemic and organ-specific autoimmune diseases, n=250); group IV (chronic or acute viral diseases, n=35); and group V (randomly selected samples from a general clinical laboratory, n=300). RESULTS: MNO-IgG was present in 40/47 patients with classic Devic's disease (85.1% sensitivity) and in 13/22 (59.1%) patients with disorders related to Devic's disease. The latter 13 positive samples had diagnosis of longitudinally extensive transverse myelitis (n=10) and isolated idiopathic optic neuritis (n=3). One patient with multiple sclerosis and none of the remaining 602 samples with autoimmune and miscellaneous diseases presented NMO-IgG (99.8% specificity). The autoimmune disease subset included five systemic lupus erythematosus individuals with isolated or combined optic neuritis and myelitis and four primary Sjögren's syndrome (SS) patients with cranial/peripheral neuropathy. CONCLUSIONS: The available data clearly point to the high specificity of anti-aquaporin-4 antibodies for Devic's disease and related syndromes also in the context of miscellaneous non-neurologic autoimmune and non-autoimmune disorders.


Assuntos
Aquaporina 4/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Sensibilidade e Especificidade
18.
J Nutr Health Aging ; 15(10): 912-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22159782

RESUMO

OBJECTIVE: Aging and oxidative stress may lead to enhanced cellular damage and programmed cell death. To study the association of intrinsic apoptosis with age and the effect of antioxidant supplementation on intrinsic and UV-induced apoptosis in children, young and elderly people. METHODS: The study was a 2 months, double-blind, randomized trial. Three age groups were studied: children, young adults and elderly people. A total of 274 healthy subjects were allocated to a group supplemented with moderate amounts of retinol, ß-carotene, α-tocopherol, ascorbic acid and selenium or placebo. Plasma oxidative stress parameters were detected and apoptosis of lymphocytes was evaluated with TUNEL staining. RESULTS: At baseline, percentages of intrinsic apoptosis were 13.8% and 11.1% in elderly and young people, respectively, both significantly higher than children (6.3%). A decrease of 1.7% and 2.3% in intrinsic apoptosis of lymphocytes was found in the supplemented groups of young and elderly people compared with their control groups (all p values <0.001), but no significant decrease in children. Moreover, percentages UV-induced apoptosis significantly decreased by 1.4%, 1.9% and 3.1% in children, young and elderly people, respectively, compared with control groups after the trial. There were considerable increments in concentrations of plasma ß-carotene, retinol, tocopherol, ascorbic acid and selenium in all three treated groups after the supplementation. CONCLUSIONS: Young and elderly people have a higher intrinsic apoptosis than children, which was improved by antioxidant supplementation. UV-induced damage was attenuated by the supplementation in all three age groups.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Suplementos Nutricionais , Linfócitos/efeitos dos fármacos , Micronutrientes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Raios Ultravioleta , Adolescente , Adulto , Idoso , Antioxidantes/metabolismo , Ácido Ascórbico/sangue , Ácido Ascórbico/farmacologia , Criança , Método Duplo-Cego , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Contagem de Linfócitos , Linfócitos/efeitos da radiação , Masculino , Micronutrientes/metabolismo , Pessoa de Meia-Idade , Selênio/sangue , Selênio/farmacologia , Vitamina A/sangue , Vitamina A/farmacologia , Adulto Jovem , beta Caroteno/sangue , beta Caroteno/farmacologia
19.
J Nutr Health Aging ; 14(5): 347-51, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20424800

RESUMO

OBJECTIVES: Age-related hearing loss is a common social and health problem in the older adult population. Up until now, very little scientific attention has been given to the potential role of fatty acids in age-related hearing loss. In this study we investigated whether plasma very long-chain n-3 polyunsaturated fatty acids (PUFAs) are associated with age-related hearing loss over three years. DESIGN: Cross-sectional and 3-year longitudinal analyses. SETTING: Wageningen, the Netherlands. PARTICIPANTS: 720 men and postmenopausal women (50-70 years of age) without middle ear dysfunction or unilateral hearing loss. MEASUREMENTS: Fatty acid proportions were measured in plasma cholesteryl esters. Hearing thresholds (in decibels, dB) at baseline and after three years were measured with pure-tone audiometry. Hearing loss was calculated as the increase in mean hearing thresholds in the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies over three years. RESULTS: Subjects in the highest quartile of plasma very long-chain n-3 PUFA had less hearing loss in the low frequencies over three years than subjects in the lowest quartile (p < 0.01, ANCOVA, difference in mean adjusted hearing thresholds= -1.2 dB). There were no significant differences between the quartiles of plasma very long-chain n-3 PUFA in hearing loss in the high frequencies (p=0.49, ANCOVA). These associations are adjusted for baseline mean hearing thresholds, age, sex, level of education and alcohol consumption. CONCLUSION: This study is the first to show an inverse association between plasma very long-chain n-3 PUFAs and age-related hearing loss. These results are encouraging, but require confirmation from future studies.


Assuntos
Envelhecimento/fisiologia , Limiar Auditivo/fisiologia , Ácidos Graxos Ômega-3/sangue , Presbiacusia/sangue , Idoso , Audiometria , Estudos Transversais , Ácidos Graxos Ômega-3/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Presbiacusia/etiologia
20.
J Clin Ultrasound ; 38(3): 128-34, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20127966

RESUMO

BACKGROUND: The purpose of this study was to evaluate the inter- and intra-observer reliability and accuracy of sonographic (US) acromiohumeral distance (AHD) measurement for both experienced and novice operators in US in patients suffering from subacromial impingement syndrome. METHOD: A total of 43 patients (50 shoulders) diagnosed with subacromial impingement syndrome were recruited from an orthopedic outpatient clinic. The US measurement of AHD was obtained consecutively in a neutral position and in a 60 degrees abduction position. A total of 300 blinded measurements were taken. RESULT: In the neutral abduction group the intra- observer interclass correlation coefficient (ICC) was 0.94 for the experienced operator and 0.92 for the novice operator. The inter-observer ICC was 0.70 and the accuracy was 1.1 mm. In the 60 degrees abduction group, the intra-observer ICC was 0.90 for the experienced operator and 0.87 for the novice operator. The inter-observer ICC was 0.64 and the accuracy was 1.4 mm. All ICCs were significant at a level of p < 0.0001. CONCLUSION: The inaccuracy of the method was 1 mm regardless of the experience of the observer. US AHD measurement in patients with shoulder complaints is not as accurate as reported in healthy subjects. This may have important implications for the clinical use of this parameter.


Assuntos
Acrômio/diagnóstico por imagem , Pesos e Medidas Corporais/métodos , Úmero/diagnóstico por imagem , Síndrome de Colisão do Ombro/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Ultrassonografia
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