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AIMS: Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention. SUBJECTS AND METHODS: In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the 'weight loss phase' (0-6 months) and the 'weight maintenance/regain phase' (7-24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP). RESULTS: Mean weight reduction was -5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7-24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0- to 6-month weight loss (ß = -0.222, P-value = 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (ß = 0.505, P-value < 0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (ß = -0.131, P-value < 0.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin (+3.4% (95% confidence interval 2.1-4.8)) as compared with those in the lowest combined tertiles (+0.2% (95% confidence interval -1.1 to 1.4)); P-value < 0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P = 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%. CONCLUSION: Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with greater weight loss in the short term, plasma leptin reduction, combined with the degree of initial weight loss and with genetic variations in the LEP gene, constitutes a significant predictor of subsequent long-term weight regain.
Assuntos
Leptina/genética , Obesidade/genética , Aumento de Peso/genética , Biomarcadores/metabolismo , Índice de Massa Corporal , Dieta Redutora/métodos , Feminino , Variação Genética , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Fenótipo , Aumento de Peso/fisiologiaRESUMO
BACKGROUND AND AIM: Hypercholesterolaemia is a major risk factor for atherosclerosis. Cholesterol is modulated by genetic and environmental factors. An important regulatory pathway is controlled by the sterol-regulatory element-binding proteins (SREBPs) and the SREBP cleavage-activating protein (SCAP). Both SREBP-2 and SCAP are candidates to contribute to the development of atherosclerosis. We investigated the possible effects of the variability of proteins involved in this regulatory pathway on plasma lipids among familial hypercholesterolaemia patients. METHODS AND RESULTS: Single nucleotide polymorphisms (SNPs) in the genes encoding SREBP-2 and SCAP causing amino acid changes at positions 595 (595G/A) and 796 (796I/V), respectively, were genotyped in 801 FH individuals originating from Israel, The Netherlands, and Switzerland. A linear regression model to examine the associations between SREBP-2 and SCAP isoforms and lipid and lipoprotein levels was used. In females, homozygosity either for the SREBP-2-595A or for the SCAP-796I isoform was associated with higher LDL-cholesterol plasma concentrations (14.7 mg/dl and 20.3 mg/dl, respectively). Surprisingly, heterozygosity for the combination SREBP-2-595A/SCAP-796I was associated with a decrease of 30.28 mg/dl in LDL-C (p-value for gene-gene interaction=0.09). No such effect was observed among FH males. Subgroup analysis considering the most frequent (N>/=24) LDL receptor mutations (del191-2, ins313+1-2, C660X, E207K, S285L) revealed further gene-dosage- and gender-dependent effects of the SCAP mutations on LDL-cholesterol concentrations (p=0.0345). These effects were, however, not present when less frequent LDL receptor mutations were investigated. CONCLUSIONS: These results suggest a possible gene-gene interaction between the genes encoding SREBP-2 and SCAP that modulate plasma lipids in a strictly gender-specific fashion. Further investigation is needed to confirm this effect. A study in a larger FH group or in non-FH hypercholesterolaemic subjects may further define the role of this regulatory mechanism in determining plasma lipid concentration.
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DNA/genética , Hiperlipoproteinemia Tipo II/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipídeos/sangue , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Aterosclerose/sangue , Aterosclerose/etiologia , Aterosclerose/genética , Feminino , Genótipo , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/complicações , Israel , Masculino , Mutação , Países Baixos , Reação em Cadeia da Polimerase , Fatores Sexuais , SuíçaRESUMO
The copper vapor laser is a pulsed gas laser which emits energy in two wavelengths simultaneously: 510.6 nm (green) and 578.2 nm (yellow). Each pulse has a duration of 15 nsec, maximal energy of 3 mJ and a peak power of more than 100 kW. It is a variably high repetition rate laser, in the range between 1 kHz and more than 20 kHz. We studied its interaction with the rabbit retina, while using two different repetition rates, 4 kHz and 18 kHz. The histological analysis of the lesion produced by 4 kHz repetition rate showed undesired retinal effects, similar to those caused by other pulsed lasers. On the other hand, the histological examination of the lesion produced by the 18 kHz repetition rate showed a desired coagulation effect, limited to the outer retinal layers, and comparable to a lesion produced by a continuous wave (CW) laser.
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Lasers , Retina/efeitos da radiação , Animais , Cobre , Terapia a Laser , Fotocoagulação , Oftalmologia/instrumentação , Células Fotorreceptoras/patologia , Células Fotorreceptoras/efeitos da radiação , Células Fotorreceptoras/ultraestrutura , Epitélio Pigmentado Ocular/patologia , Epitélio Pigmentado Ocular/ultraestrutura , Retina/patologiaRESUMO
A two-crystal double axis x-ray spectrometer, capable of goniometric accuracy on the order of 0.1", has been developed. Some of its unique design features are presented. These include (1) a modified commercial thrust bearing which furnishes a precise, full circle theta:2theta coupling, (2) a new tangent drive system design in which a considerable reduction of the lead screw effective pitch is achieved, and (3) an automatic step scanning control which eliminates most of the mechanical deficiencies of the tangent drive by directly reading the tangent arm displacement.
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Cristalografia/métodos , Eletrônica/instrumentação , Processamento de Sinais Assistido por Computador/instrumentação , Espectrometria por Raios X/instrumentação , Transdutores , Espectrometria por Raios X/métodosRESUMO
BACKGROUND: Schizophrenia and bipolar disorder are associated with impairments in insight, leading to a poorer clinical outcome and functioning. Earlier studies comparing the two disorders on the basis of insight included inpatients or patients who were clinically symptomatic. The current study therefore assessed patients in remission of affective symptoms and positive symptoms of schizophrenia. METHODS: Schizophrenia and bipolar disorder patients (n=32, n=34; respectively) underwent clinical and functional evaluations. Insight was assessed using the Scale to assess Unawareness of Mental Disorder (SUMD) and the positive and negative syndrome scale (PANSS). Attention was assessed using a continuous performance task (CANTAB's rapid visual information processing). RESULTS: Schizophrenia patients displayed poorer insight into having a mental disorder and into the social consequences thereof compared to the bipolar disorder patients. They were also less aware of their anhedonia-asociality. Age, however, was significantly correlated with insight and differences in insight between the patient groups became nonsignificant when age was used as a covariate in the statistical analyses. Age was not a moderating variable of the relationship between diagnosis and insight. CONCLUSIONS: Significant differences in insight held by the two patient groups might be related to age disparities between patient groups. Earlier studies did not adequately address these age differences, their cause and their potential effects on findings. These issues are explored with regard to the findings of the current study, as well as earlier studies, emphasizing the need for further research of the relationship between age and insight.
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Sintomas Afetivos/fisiopatologia , Atenção/fisiologia , Conscientização/fisiologia , Transtorno Bipolar/fisiopatologia , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Sintomas Afetivos/diagnóstico , Transtorno Bipolar/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto JovemRESUMO
UNLABELLED: Atherosclerosis is a systemic process, and the leading cause of morbidity and mortality in the developed world. HMG-CoA reductase inhibitors ('statins') are potent lipid lowering drugs, which have been shown to reduce morbidity and mortality in patients with coronary atherosclerosis. OBJECTIVE: To present the up-to-date data concerning statin use in the prevention and treatment of extra-coronary atherosclerosis. METHODS: Clinical trials with statins in patients with extra-coronary atherosclerosis were searched for via PUBMED. FINDINGS AND CONCLUSIONS: The different forms of peripheral arterial disease (e.g. cerberovascular disease, lower extremity peripheral arterial disease) are associated with significant cardiovascular morbidity and mortality, and hence constitute a coronary artery disease equivalent in terms of published practice guidelines. There is some evidence from small randomized controlled trials that statin therapy decreases cardiovascular morbidity and mortality in patients with peripheral arterial disease. The mechanism of action of statins may derive from their lipid lowering properties, or from other, pleiotropic effects. Further, larger randomized controlled studies with statins are needed to evaluate the efficacy of statin therapy in patients with stable peripheral arterial disease and in those undergoing vascular or endovascular surgery.
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Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doenças Vasculares Periféricas/tratamento farmacológico , Humanos , Morbidade/tendências , Doenças Vasculares Periféricas/epidemiologia , Resultado do TratamentoRESUMO
The majority of patients with breast carcinoma are being treated with breast conservation therapy (BCT): lumpectomy and postoperative radiation. Local recurrence reported at 8% to 11% is often treated with salvage mastectomy. This has led to a growing group of patients requiring breast reconstruction after failed BCT. Reluctance to use the latissimus dorsi flap (LDF) has resulted from reports of high implant capsular contracture rates. We present a series of 12 patients who underwent LDF reconstruction after the development of recurrent breast cancer after BCT. All 12 patients had a satisfactory esthetic result. Despite previous radiation, the capsular contracture rate was 12.5% (median follow up, 50 months; range, 20-93 months). The most common complication was donor site seroma in 25% (3 of 12) of cases. The LDF yielded satisfactory esthetic results with a low capsular contracture rate. Despite prior radiation, LDF remains a good option for breast reconstruction after failure of BCT.
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Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia , Retalhos Cirúrgicos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de TratamentoRESUMO
Latissimus dorsi flap has been unfairly relegated to a second option in breast reconstruction. One hundred consecutive latissimus dorsi muscle flaps (LDMF) with tissue-expander reconstruction were studied, mean follow-up 34.5 months (range, 1-175), 50 immediate, 50 delayed. With attention to a few technical details, excellent esthetic, soft reconstructions were achieved. Complications included 1 partial flap loss; 2 patients required inframammary fold revision; and 6 patients required surgery for capsular contracture. Donor-site seroma occurred in 34 patients; 6 required operative revision. Results were similar in the immediate versus the delayed groups. LDMF remains an esthetic, reliable, safe reconstructive choice.
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Mamoplastia/métodos , Músculo Esquelético/transplante , Retalhos Cirúrgicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estética , Feminino , Humanos , Pessoa de Meia-Idade , Necrose , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Retalhos Cirúrgicos/patologiaRESUMO
The information content of a contour map is calculated and compared with the information required for determining the relative position of the contours. We have found that usually the information required for arranging the contours in the right order is small as compared with that of producing the map. To demonstrate this finding we introduce two novel methods for ordering the contours. The first makes use of two colors, double exposure, moire mapping. The second analyzes the relative motion of hills and valleys, while the relative angle of two transparencies photographed in the grid projection technique is changed.
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A thermal model has been used for the interaction of an annular laser beam of a high-repetition-rate pulsed laser (copper-vapor laser) with the retina of a rabbit. The model predicts the temperature rise at each retinal point, during and after the laser exposure, as a function of pulse energy, exposure time, and pulse repetition rate. The retinal effects for each set of treatment parameters were estimated according to the predicted temperature rise and were found to be identical with our previous experimental results. The character of the interaction between the copper-vapor laser and the retina can be pretuned by the laser pulse repetition rate to fit the requirements of various treatments, permitting multiple uses of this laser for ophthalmic treatments.
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Fotocoagulação , Retina/cirurgia , Animais , Lasers , Modelos Biológicos , Coelhos , Retina/fisiologia , TemperaturaRESUMO
A convenient method to measure beam divergence of laser beams is described. The apparatus is compact and accurate due to the use of a telescope to focus the beam. Incorporation of a Fabry-Perot etalon permits focusing and in situ calibration. Measurement of single-pulse beam divergence is performed with a CCTV system which includes a video tape recorder.
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A new case is reported of müllerian adenosarcoma, presenting as a 'benign cervical polyp' protruding through the vulva of a 44 year-old woman admitted with abnormal vaginal bleeding. This report emphasizes the importance of a careful examination of the stroma and special features of the entrapped glands in order to contribute to an earlier and proper diagnosis. The literature is reviewed and the probable histogenesis of this tumor and differential diagnosis with embryonal rhabdomysarcoma (sarcoma botryoides), adenofibroma, malignant mesodermal tumor and carcinosarcoma is discussed.