Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain.

Background: Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM). There is a wide variation in the prevalence of MTHFR polymorphisms and homocysteine (Hcy) plasma levels among populations around the world. The present study was undertaken to investigate the possible association between hyperhomocysteinemia and its causative genetic or acquired factors and RM in Catalonia, a Mediterranean region in Spain. Methods: Sixty consecutive patients with ≥ 3 unexplained RM and 30 healthy control women having at least one child but no previous miscarriage were included. Plasma Hcy levels, MTHFR gene mutation, red blood cell (RBC) folate and vitamin B12 serum levels were measured in all subjects. Results: No significant differences were observed neither in plasma Hcy levels, RBC folate and vitamin B12 serum levels nor in the prevalence of homozygous and heterozygous MTHFR gene mutation between the two groups studied. Conclusions: In the present study RM is not associated with hyperhomocysteinemia, and/or the MTHFR gene mutation.

Role of vitamin D deficiency in extraskeletal complications : predictor of health outcome or marker of health status?

The relationship of vitamin D with extraskeletal complications, such as cardiovascular disease, cancer, and autoimmune disease, is of major interest considering its roles in key biological processes and the worldwide high prevalence of vitamin D deficiency. However, the causal relationships between vitamin D and most extraskeletal complications are weak. Currently, a heated debate over vitamin D is being conducted according to two hypotheses. In this review, we first present the different arguments that suggest a major role of vitamin D in a very broad type of extraskeletal complications (hypothesis #1). We then present results from recent meta-analyses of randomized controlled trials indicating a lack of association of vitamin D with major extraskeletal complications (hypothesis #2). We discuss different issues (e.g., causality, confounding, reverse causation, misclassification, and Mendelian randomization) that contribute to the favoring of one hypothesis over the other. While ultimately only one hypothesis is correct, we anticipate that the results from the ongoing randomized controlled trials will be unlikely to reconcile the divided experts.

Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry.

BACKGROUND: Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. METHODS: 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow-up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analysed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40 ng/ml during 12 months of follow-up and several dosage regimens were evaluated by simulation. RESULTS: A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/ritonavir and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the inter-individual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates, and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300,000 IU two times per year. CONCLUSIONS: This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

Gériatrie [Review in geriatric medicine 2014].

Several studies contributed to improving the diagnostic and prognostic assessment of delirium in hospitalized older patients. Direct patient education proved efficient in benzodiazepines withdrawal. A position statement of the American Geriatrics Society does not recommend tube feeding when eating difficulties arise in older persons suffering from advanced dementia. Several studies emphasized once again the potential importance of preventative interventions (in particular physical activity) to prevent or delay dementia occurrence. Two randomized controlled trials of monoclonal antibodies that bind amyloid did not show benefit in patients with mild-to-moderate Alzheimer's dementia (AD). In contrast, vitamin E reduced functional decline in these patients, and citalopram reduced agitation among AD patients as well as their caregiver's stress.

Chemical, physico-chemical and sensory characterization of mixed açai (Euterpe oleracea) and cocoa´s honey (Theobroma cacao) jellies

Four formulations of mixed açaí (Euterpe oleracea) (A) and cocoa´s honey (Theobroma cacao) (CH) jellies were prepared according to the following proportions: T1 (40% A:60% CH), T2 (50% A:50% CH), T3 (60% A: 40% CH) and T4 (100% A - control). All formulations were prepared using a rate 60:40 (w/w) of sucrose and pulp, plus 0.5% pectin and the products reached to average of 65% soluble solids content. The jellies were analyzed by chemical and physicochemical (titratable acidity, pH, soluble solid content, dry matter, total protein, lipids, vitamin C and calories) and sensory characteristics; also were evaluated levels of P, K, Ca, Mg, Fe, Zn, Cu and Mn. It was used a hedonic scale of 7 points to evaluate the attributes: overall impression, spreadability, brightness, flavor, texture and color, and also was verified the purchase intention score. The titratable acidity and pH ranged from 0.46 to 0.64% and 3.35 to 3.64, respectively, that are within the range found at most fruit jellies. The soluble solids content ranged between 65.2 and 65.5 ºBrix. The sensory acceptance results showed that all treatments (T1, T2, T3 and T4) presented means of sensory attributes above 4, demonstrating good acceptance of the product, but the treatment T1 presented the higher scores for the evaluated attributes. Cocoa´s honey added a positive influence on the attributes of color, texture and spreadability.

Nutrição mineral e produção de abacaxizeiro 'Pérola', em função das relações K/N na adubação

A adubação do abacaxizeiro deve contemplar a reposição das quantidades de N e K absorvidas pela planta e exportadas pelos frutos e mudas, e o estabelecimento de relações adequadas entre as doses destes nutrientes. Este trabalho objetivou avaliar o efeito de diferentes relações K/N na adubação sobre a nutrição mineral e a produção de abacaxizeiro 'Pérola', em solos de Tabuleiros Costeiros da Paraíba. O experimento foi conduzido em delineamento experimental em blocos casualizados com 13 tratamentos e três repetições. Os tratamentos resultaram da combinação de quatro relações K/N (0,85:1; 1:1; 2:1 e 3:1), duas doses de N (7,2 e 10,8 g planta-1), quatro tratamentos adicionais (relação K/N de 2:1 na maior dose de N, variando-se a fonte, o parcelamento, a época e a forma de aplicação das doses de N e K) e uma testemunha absoluta (sem adubação). O aumento das relações K/N eleva o peso da folha 'D', os teores de K e os valores das relações K/N e K/Mg; reduz os teores de N e não afeta os teores de P, Ca e a relação K/Ca. O aumento das relações K/N não influencia no peso médio, na produtividade e no percentual de frutos das classes I, II e III. A utilização de sulfato de K, o parcelamento das doses de N e K, na forma de KCl, em cinco aplicações, e a aplicação de metade das doses de N e K via foliar na relação 2:1 aumentam o peso da folha 'D', o teor foliar de N e os valores de peso médio, produtividade e percentual de frutos da classe II.

Avaliação nutricional, produção e incidência do mal-do-panamá em bananeira 'Prata-Anã' (AAB) adubada com K, no quarto ciclo

O presente trabalho teve como objetivos estimar a dose de K para obter a máxima eficiência física e econômica, estimar o nível crítico foliar de K e relacionar o equilíbrio nutricional da bananeira 'Prata-Anã' com a incidência de plantas com mal-do-panamá no 4º ciclo. O experimento foi realizado em Latossolo Vermelho-Amarelo (LVA), textura média, na região semiárida do norte de Minas Gerais, Brasil. Os tratamentos consistiram nas aplicações de quatro doses de K (0; 400; 800 e 1.200 kg ha-1 ano de K2O). Estes foram distribuídos em blocos ao acaso, com cinco repetições. A adubação com K promoveu aumento na produção da bananeira no 4º ciclo. A máxima eficiência física (31 Mg ha-1) e a econômica (30,5 Mg ha-1) foram obtidas com as aplicações de 969 e 707 kg ha-1 ano-1 de K2O, respectivamente. Os níveis críticos foliares de K obtidos foram 29,5 e 27,1 g kg-1, para a máxima eficiência física e econômica, respectivamente. O aumento das doses de K proporcionou melhor equilíbrio nutricional à bananeira e reduziu a porcentagem de plantas infestadas com o mal-do-panamá.

Materiaalimallin määrityksestä kylmämuovattujen putkipalkkien K-liitosten FE-analyysissä

Työssä on tutkittu kylmämuovattujen nelikulmaisten putkipalkkien K-liitosten mallinnusta epälineaarisella elementtimenetelmällä. Työn tärkeimpänä tavoitteena on ollut kehittää putkipalkin osien materiaalimalleja siten, että liitosten kestävyyttä voidaan tutkia laboratoriokokeiden ohella luotettavasti myös elementtimenetelmällä. Toisena tavoitteena on ollut tutkia, voidaanko putkipalkkien liitosten mitoitusohjeita turvallisesti soveltaa kylmämuovatuille putkipalkeille, joissa valmistusprosessi aiheuttaa muutoksia materiaaliominaisuuksiin, erityisesti muodonmuutoskykyyn. Työssä tehtyjen laboratoriokokeiden ja elementtianalyysien perusteella elementti-menetelmä on käyttökelpoinen työkalu putkipalkkiliitosten staattista kestävyyttä määritettäessä, kun materiaalimallit on määritetty oikein. Erityisesti liitoksen käyttö-rajatilan mukaisen kestävyyden laskennassa elementtimenetelmällä saadaan hyvin laboratoriokokeita vastaavia tuloksia. Tehdyt laboratoriokokeet osoittavat myös, että Eurocode 3:n mukaisia putkipalkkien liitosten mitoitusohjeita voi turvallisesti käyttää kylmämuovatuille putkipalkeille.

Oncogenic K-Ras segregates at spatially distinct plasma membrane signaling platforms according to its phosphorylation status

Activating mutations in the K-Ras small GTPase are extensively found in human tumors. Although these mutations induce the generation of a constitutively GTP-loaded, active form of K-Ras, phosphorylation at Ser181 within the C-terminal hypervariable region can modulate oncogenic K-Ras function without affecting the in vitro affinity for its effector Raf-1. In striking contrast, K-Ras phosphorylated at Ser181 shows increased interaction in cells with the active form of Raf-1 and with p110α, the catalytic subunit of PI 3-kinase. Because the majority of phosphorylated K-Ras is located at the plasma membrane, different localization within this membrane according to the phosphorylation status was explored. Density-gradient fractionation of the plasma membrane in the absence of detergents showed segregation of K-Ras mutants that carry a phosphomimetic or unphosphorylatable serine residue (S181D or S181A, respectively). Moreover, statistical analysis of immunoelectron microscopy showed that both phosphorylation mutants form distinct nanoclusters that do not overlap. Finally, induction of oncogenic K-Ras phosphorylation - by activation of protein kinase C (PKC) - increased its co-clustering with the phosphomimetic K-Ras mutant, whereas (when PKC is inhibited) non-phosphorylated oncogenic K-Ras clusters with the non-phosphorylatable K-Ras mutant. Most interestingly, PI 3-kinase (p110α) was found in phosphorylated K-Ras nanoclusters but not in non-phosphorylated K-Ras nanoclusters. In conclusion, our data provide - for the first time - evidence that PKC-dependent phosphorylation of oncogenic K-Ras induced its segregation in spatially distinct nanoclusters at the plasma membrane that, in turn, favor activation of Raf-1 and PI 3-kinase.