Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF -270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =-2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

BACKGROUND AND STUDY AIMS: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. PATIENTS AND METHODS: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800-1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. RESULTS: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. CONCLUSIONS: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era.

Vitamina C, Cancro e Cittoxidade: Marcação e estabilidade in vitro e in vivo

A vitamina C é uma substância essencial apresentando inúmeras propriedades fisiológicas. Ela apresenta-se sob duas formas, a reduzida e a oxidada. O ácido asc��rbico (AA), a forma reduzida da vitamina C, é um potente antioxidante hidrossolúvel, na medida em que neutraliza os radicais livres, constituindo um potencial mecanismo anticancerígeno. O AA actua também como pró-oxidante, promovendo a formação de espécies reactivas de oxigénio (ROS), como o peróxido de hidrogénio (H2O2), que comprometem a viabilidade celular. Por outro lado, a maioria das células tumorais não transporta directamente o AA para o seu interior, razão pela qual as células obtêm a vitamina C na sua forma oxidada, o ácido dehidroasc��rbico (DHA). As células tumorais demonstram ainda outra particularidade, a diminuição da catalase (enzima responsável pela destoxificação do H2O2), num factor entre 10 e 100, relativamente às células normais. Assim, o aumento da produção de H2O2, acoplado à deficiência da actividade da catalase nas células neoplásicas e à presença de metais de transição, poderá redundar na citotoxicidade selectiva da vitamina C e na consequente revelação do seu potencial terapêutico.

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Distribución, concentración y biomasa de los principales recursos pelágicos peruanos a principios del otoño de 1997. Crucero BIC Humboldt 9704, Callao - Paita

Las condiciones oceanográficas observadas durante el crucero describen una intromisión de Aguas Ecuatoriales Superficiales (la extensión sur de la Corriente de Cromwell) que ha provocado el repliegue, sobre la zona litoral, del stock de anchoveta y la migración al sur de la sardina y la dispersión de los recursos jurel y caballa. Este fenómeno constituyó el inicio del evento cálido denominado El Niño. Esta condiciones se caracterizaron por presentar anomalías positivas de cerca de 2° C, en promedio en el área prospectada, así como grandes capturas de anchoveta por parte de la flota industrial debido al alto índice promedio de concentración de esta especie (408,15 t/mn2 ). Los estimados de biomasa para las principales especies pelágicas, utilizando el método hidroacústico son los siguientes: anchoveta 6,59 x 106 t ±18,49%; sardina 2,48 x 106 t ±22,16%; jurel 1,25 x 106 t ±29,73%; caballa 1,1 x 106 t ±13,64%. Sin embargo, para el caso de la anchoveta, la biomasa total estimada entre Tacna y Paita es de 9 a 10 x 106 t debido a la migración sur-norte de buena parte del stock que estuvo ubicado entre el Callao y Tacna entre los meses febrero-marzo de 1997, desplazamiento provocado por la intromisión, en casi toda la zona sur de aguas cálidas subtropicales, situación que fuera evaluada por el Crucero 9702-03 a bordo del BIC SNP-1; en esa ocasión una biomasa de 6,4 x 106 t para dicha zona. Esta cifra final ha sido calculada comparando los resultados del Análisis de Población Virtual (IMARPE-DIRP, 1997) con el método hidroacústico.

Multiple sclerosis-related trigeminal neuralgia: a prospective series of 43 patients treated with gamma knife surgery with more than one year of follow-up.

BACKGROUND: Trigeminal neuralgia (TN) related to multiple sclerosis (MS) is more difficult to manage pharmacologically and surgically. OBJECTIVE: This article aims to evaluate the safety and efficacy of Gamma Knife surgery (GKS) in this special group of patients. METHODS: Between July 1992 and November 2010, 43 cases with more than 1 year of follow-up were operated with GKS for TN related to MS and prospectively evaluated in the Timone University Hospital, Marseille, France. Radiosurgery using the Gamma Knife (model B or C or Perfexion) was performed. A single 4-mm isocenter was positioned at a median distance of 8 mm (range 5.7-14.7) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range 75-90) was delivered. RESULTS: The median follow-up period was 53.8 months (12-157.1). Thirty-nine patients (90.7%) were initially pain free. Their actuarial probability of remaining pain free without medication at 6 months, 1, 3, 5 and 10 years was 87.2, 71.8, 43.1, 38.3 and 20.5%, respectively, and remained stable till 12 years. The hypoesthesia actuarial rate at 6 months, 1 and 2 years was 11.5, 11.5 and 16%, and remained stable till 12 years. CONCLUSIONS: GKS proved safe and effective in this special group of patients.

Evaluación poblacional de Chondracanthus chamissoi (C. Agardh 1820) en las bahías de Pisco y Paracas, Otoño 2010.

Entre mayo y junio 2010, se desarrolló la evaluación poblacional de la macroalga Chondracanthus chamissoi “yuyo” de las praderas en las bahías de Pisco y Paracas. Las biomasas medias fluctuaron entre 2,2 y 67,0 g.m-2, con promedio de 43,6 g.m-2. Se estimó una biomasa total de 211,96 toneladas (±56,8%); de los cuales 179,74 t correspondieron a Atenas; 30,1 t a Puerto Nuevo y 2,1 t a Playa Lobería. El sustrato de fijación estuvo compuesto, principalmente, por piedras, conchuela y arena media. En las praderas de Atenas ocupó la mayor parte del área evaluada, en las praderas de Puerto Nuevo y Playa Lobería se encontraron reducidas, respecto al 2007. Se encontró ejemplares entre 1 y 25 cm de longitud. El peso total individual varió de 0,1 a 94,6 g. Se registró biodiversidad asociada conformada por moluscos. Las condiciones oceanográficas se registraron normales, lo que permite suponer que la disminución poblacional respondería a las actividades de extracción.

IL28B polymorphisms, IP-10 and viral load predict virological response to therapy in chronic hepatitis C.

Aliment Pharmacol Ther 2011; 33: 1162-1172 SUMMARY: Background  Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma and the identification of the predictors of response to antiviral therapy is an important clinical issue. Aim  To determine the independent contribution of factors including IL28B polymorphisms, IFN-gamma inducible protein-10 (IP-10) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) score in predicting response to therapy in chronic hepatitis C (CHC). Methods  Multivariate analysis of factors predicting rapid (RVR) and sustained (SVR) virological response in 280 consecutive, treatment-naive CHC patients treated with peginterferon alpha and ribavirin in a prospective multicentre study. Results  Independent predictors of RVR were HCV RNA <400 000 IU/mL (OR 11.37; 95% CI 3.03-42.6), rs12980275 AA (OR 7.09; 1.97-25.56) and IP-10 (OR 0.04; 0.003-0.56) in HCV genotype 1 patients and lower baseline γ-glutamyl-transferase levels (OR = 0.02; 0.0009-0.31) in HCV genotype 3 patients. Independent predictors of SVR were rs12980275 AA (OR 9.68; 3.44-27.18), age <40 years (OR = 4.79; 1.50-15.34) and HCV RNA <400 000 IU/mL (OR 2.74; 1.03-7.27) in HCV genotype 1 patients and rs12980275 AA (OR = 6.26; 1.98-19.74) and age <40 years (OR 5.37; 1.54-18.75) in the 88 HCV genotype 1 patients without a RVR. RVR was by itself predictive of SVR in HCV genotype 1 patients (OR 33.0; 4.06-268.32) and the only independent predictor of SVR in HCV genotype 2 (OR 9.0, 1.72-46.99) or genotype 3 patients (OR 7.8, 1.43-42.67). Conclusions  In HCV genotype 1 patients, IL28B polymorphisms, HCV RNA load and IP-10 independently predict RVR. The combination of IL28B polymorphisms, HCV RNA level and age may yield more accurate pre-treatment prediction of SVR. HOMA-IR score is not associated with viral response.

Definição da dimensão do indivíduo solo e determinação do número de amostras simples necessário à sua representação

Uma população é composta por indivíduos, e a amostragem correta dos indivíduos estima adequadamente as características da população. Porém, para avaliar a fertilidade do solo, quem seria o indivíduo solo (unidades de amostra) e qual sua dimensão? Com o objetivo de definir a dimensão do indivíduo solo componente de determinada população, sob plantio direto (PD) ou sob plantio convencional antes (PCAA) ou depois da aração (PCDA), visando avaliar a fertilidade do solo e desenvolver um método de amostragem de solos, determinando o número de amostras simples necessário à formação de uma amostra composta que caracterize o indivíduo solo (unidade de amostra), foram coletadas amostras simples de solo (5,4 cm de diâmetro x 10 cm de profundidade) sobre as semidiagonais de cinco hexágonos delimitados sobre cada uma das áreas selecionadas para amostragem (PD, PCAA e PCDA). Os hexágonos de amostragem apresentavam 2 m de lado e, em cada uma das seis semidiagonais dos mesmos, foram coletadas dez amostras simples de solo (55 por hexágono) nas seguintes distâncias, a partir de uma amostra simples central, medidas até o centro do orifício de coleta: 12,5; 25,0; 37,5; 50,0; 75,0; 100,0; 112,5; 150,0 e 200,0 cm, sendo a amostra simples central comum às seis semidiagonais. Foram determinados o pH (H2O), os teores de P e K disponíveis e de Ca2+ e Mg2+, H + Al, P-rem e a matéria orgânica. As amostras simples foram agrupadas sucessivamente a partir do centro do hexágono, formando nove unidades de amostra: A (até 18,75), B (até 31,25), C (até 43,75), D (até 56,25), E (até 81,25), F (até 106,25), G (até 118,75), H (até 156,25) e I (até 206,25 cm). Foi realizada análise de regressão das médias e dos desvios-padrão das características avaliadas, considerando possíveis dimensões da unidade de amostra de solo. A partir dos resultados obtidos, pôde-se concluir que: para a caracterização do indivíduo solo (unidade de amostra), devem-se coletar 25 amostras simples, necessárias à formação de uma amostra composta representativa, num hexágono de 68,75 cm de lado e área de 1,228 m².

Dramatic decline of serogrup C meningococcal disease incidence in Catalonia (Spain) 24 months after a mass vaccination programme of children and young people

STUDY OBJECTIVES The objective of this study was to evaluate the effectiveness of a mass vaccination programme carried out in Catalonia (Spain) in the last quarter of 1997 in response to an upsurge of serogroup C meningococcal disease (SCMD). DESIGN Vaccination coverage in the 18 month to 19 years age group was investigated by means of a specific vaccination register. Vaccination effectiveness was calculated using the prospective cohort method. Cases of SCMD were identified on the basis of compulsory reporting and microbiological notification by hospital laboratories. Vaccination histories were investigated in all cases. Unadjusted and age adjusted vaccination effectiveness referred to the time of vaccination and the corresponding 95% confidence intervals (CI) were estimated at 6, 12, 18 and 24 months of follow up. SETTING All population aged 18 months to 19 years of Catalonia. MAIN RESULTS A total of seven cases of SCMD were detected at six months of follow up (one in the vaccinated cohort), 12 cases at 12 months (one in the vaccinated cohort), 19 cases at 18 months (two in the vaccinated cohort) and 24 at 24 months (two in the vaccinated cohort). The age adjusted effectiveness was 84% (95%CI 30, 97) at six months, 92% (95%CI 63, 98) at 12 months, 92% (95% CI 71, 98) at 18 months and 94% (95%CI 78, 98) at 24 months. In the target population, cases have been reduced by more than two thirds (68%) two years after the vaccination programme. In the total population the reduction was 43%. CONCLUSION Vaccination effectiveness has been high in Catalonia, with a dramatic reduction in disease incidence in the vaccinated cohort accompanied by a relevant reduction in the overall population. Given that vaccination coverage was only 54.6%, it may be supposed that this vaccination effectiveness is attributable, in part, to the herd immunity conferred by the vaccine.

The Gronnedal-Ika carbonatite-syenite complex, South Greenland: Carbonatite formation by liquid immiscibility

The Gronnedal-Ika complex is dominated by layered nepheline syenites which were intruded by a xenolithic syenite and a central plug of calcite to calcite-siderite carbonatite. Aegirine-augite, alkali feldspar and nepheline are the major mineral phases in the syenites, along with rare calcite. Temperatures of 680-910degreesC and silica activities of 0.28-0.43 were determined for the crystallization of the syenites on the basis of mineral equilibria. Oxygen fugacities, estimated using titanomagnetite compositions, were between 2 and 5 log units above the fayalite-magnetite-quartz buffer during the magmatic stage. Chondrite-normalized REE patterns of magmatic calcite in both carbonatites and syenites are characterized by REE enrichment (La-CN-Yb-CN = 10-70). Calcite from the carbonatites has higher Ba (similar to5490 ppm) and lower HREE concentrations than calcite from the syenites (54-106 ppm Ba). This is consistent with the behavior of these elements during separation of immiscible silicate-carbonate liquid pairs. epsilon(Nd)(T = 1.30 Ga) values of clinopyroxenes from the syenites vary between +1.8 and +2.8, and epsilon(Nd)(T) values of whole-rock carbonatites range from +2.4 to +2.8. Calcite from the carbonatites has delta(18)O values of 7.8 to 8.6parts per thousand and delta(13)C values of -3.9 to -4.6parts per thousand. delta(18)O values of clinopyroxene separates from the nepheline syenites range between 4.2 and 4.9parts per thousand. The average oxygen isotopic composition of the nepheline syenitic melt was calculated based on known rock-water and mineral-water isotope fractionation to be 5.7 +/- 0.4parts per thousand. Nd and C-O isotope compositions are typical for mantle-derived rocks and do not indicate significant crustal assimilation for either syenite or carbonatite magmas. The difference in delta(18)O between calculated syenitic melts and carbonatites, and the overlap in epsilon(Nd) values between carbonatites and syenites, are consistent with derivation of the carbonatites from the syenites via liquid immiscibility.