Is there a causal role for homocysteine concentration in blood pressure?:A Mendelian randomization study

Background: An understanding of whether homocysteine is a cause or a marker of increased blood pressure is relevant because blood homocysteine can be effectively lowered by safe and inexpensive interventions (e.g., vitamin B-6, B-9, and B-12 supplementation). Objective: The aim was to assess the causal influence of homocysteine on systolic and diastolic blood pressure (SBP and DBP, respectively) in adults with the use of Mendelian randomization (MR). Design: Data from the 1982 Pelotas Birth Cohort (Brazil) were used. A total of 4297 subjects were evaluated in 2004–2005 (mean age: 22.8 y). The association of homocysteine concentration with SBP and DBP was assessed by conventional ordinary least-squares (OLS) linear regression and 2-stage least-squares (2SLS) regression (MR analysis). The single nucleotide polymorphism (SNP) methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) was used as proxy for homocysteine concentration. We also applied MR to data from the International Consortium for Blood Pressure (ICBP) genomewide association studies (>69,000 participants) using rs1801133 and additional homocysteine-associated SNPs as instruments. Results: In OLS regression, a 1-SD unit increase in log homocysteine concentration was associated with an increase of 0.9 (95% CI: 0.4, 1.4) mm Hg in SBP and of 1.0 (95% CI: 0.6, 1.4) mm Hg in DBP. In 2SLS regression, for the same increase in homocysteine, the coefficients were −1.8 mm Hg for SBP (95% CI: −3.9, 0.4 mm Hg; P = 0.01) and 0.1 mm Hg for DBP (95% CI: −1.5, 1.7 mm Hg; P = 0.24). In the MR analysis of ICBP data, homocysteine concentration was not associated with SBP (β = 0.6 mm Hg for each 1-SD unit increase in log homocysteine; 95% CI: −0.8, 1.9 mm Hg) but was positively associated with DBP (β = 1.1 mm Hg; 95% CI: 0.2, 1.9 mm Hg). The association of genetically increased homocysteine with DBP was not consistent across different SNPs. Conclusion: Overall, the present findings do not corroborate the hypothesis that homocysteine has a causal role in blood pressure, especially in SBP

SIMULATION OF THE ALCOHOL-OIL MIXTURE IN A T-SHAPED MICROCHANNEL USING THE DISSIPATIVE PARTICLE DYNAMICS METHOD ON GPU DEVICES

Multiphase fluid motion in microchannnels involves complicated fluid dynamics and is fundamentally important to diverse practical engineering applications. Among several applications, the alcohol-oil mixture is particularly important due to its application for biodiesel production. In this work, the mixture of immiscible fluids alcohol-oil in a square T-shaped microchannel was investigated using the Dissipative Particle Dynamics (DPD) method available in the HOOMD simulator, which runs on a single graphic processing unit (GPU). The immiscible fluids were achieved by increasing the repulsive force between species. The fluid properties and hydrodynamic behavior were discussed in function of model parameters. The simulation results agree with data published in the literature showing that the DPD is appropriate for simulation of mass transport on complex geometries in microscale on a single GPU

MOTHER-TO-CHILD TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INFECTION

Introdução: A Infeção pelo Vírus da Imunodeficiência Humana do tipo 1 (VIH1) na criança ocorre quase exclusivamente por transmissão mãe-filho (TMF). Sem profilaxia ocorrem taxas de transmissão de 15-25%, diminuindo para <2% quando são adotadas medidas adequadas. Objetivo: Avaliar a TMF da Infeção VIH numa maternidade. Material e Métodos: Estudo retrospetivo, com consulta do processo clínico, de crianças de mães com Infeção VIH1, nascidas na Maternidade Júlio Dinis de Janeiro de 2006 a Dezembro de 2011. Definida não Infeção se 2 testes virológicos negativos (um após os 4 meses) e ausência de clínica. Analise estatística – programa Epi-InfoR v.3.5.1 (Teste Fisher, p <0,05). Resultados: Nasceram 77 crianças com risco de transmissão VIH1, 45 do sexo masculino (58.4%) e 15 (19.5%) prematuros. Diagnostico de Infeção materna ocorreu na gestação em 24 (31.6%) e no parto numa (1.3%). Sete (9.2%) Não efetuaram terapêutica anti retrovirica (TARV) na gravidez e 9 (12.3%) apresentavam carga vírica >1.000 copias no parto. Nasceram por parto eutocico 4 (5.2%) e 10 (13%) tiveram rotura membranas (RM) ≥4h. Nenhum efetuou leite materno e todos fizeram profilaxia no periodo neonatal; 17 (22.1%) efetuaram profilaxia com 3 fármacos, associado a ausência de TARV na gravidez e parto, carga vírica materna >1.000 copias, RM≥4h, RM espontânea e prematuridade. Um recém-nascido (1.3%) faleceu. Nenhuma criança foi infetada. Cerca de um terço (35.5%) apresentou alterações hematológicas e 23 (30.3%) na função hepática, ambas reversíveis. Conclusão: Na população estudada não ocorreu TMF da Infeção VIH1, apesar de apresentar fatores que aumentam o risco de transmissão numa elevada percentagem de casos.Introduction: Human Immunodeficiency Virus type 1 (HIV1) infection in children is almost related to mother-to-child transmission (MTCT). Without prophylaxis transmission rates are 15-25%. With appropriate prophylaxis <2% rates are achieved. Objective: Evaluate the MTCT of HIV infection in a maternity. Materials and Methods: Retrospective study, with review of clinical files of children whose mothers have HIV1 infection, born at Julio Dinis Maternity from January 2006 to December 2011. Not infected was defined if 2 virologic tests were negative (one after 4 months of age) with no clinical signs of infection. Statistical analysis was performed with Epi-Info R v.3.5.1 (Fisher test, p <0.05). Results: Seventy seven children were born from HIV1 infected mothers, 45 (58.4%) males and 15 (19.5%) preterm infants. Diagnosis of maternal infection during pregnancy occurred in 24 (31.6%) and one at childbirth (1.3%). Seven (9.2%) hadn’t had antiretroviral therapy (ART) during pregnancy and 9 (12.3%) had viral load> 1,000 copies at childbirth. Normal delivery occurred in 4 (5.2%) and 10 (13%) had rupture of membranes (RM) ≥ 4h. None was breastfed. All received prophylaxis in the neonatal period; 17 (22.1%) with 3 drugs, associated with absence of ART in pregnancy and at childbirth, maternal viral load> 1,000 copies, RM ≥ 4h, spontaneous RM and prematurity. One newborn (1.3%) died. No child became infected. Almost a third (35.5%) had hematological toxicity and 23 (30.3%) had hepatic toxicity, both reversible. Conclusion: In the population studied no MTCT of HIV1 infection occurred, despite the presence of factors that increase the risk of transmission in a high percentage of cases

Origin and function of short-latency inputs to the neural substrates underlying the acoustic startle reflex

The acoustic startle reflex (ASR) is a survival mechanism of alarm, which rapidly alerts the organism to a sudden loud auditory stimulus. In rats, the primary ASR circuit encompasses three serially connected structures: cochlear root neurons (CRNs), neurons in the caudal pontine reticular nucleus (PnC), and motoneurons in the medulla and spinal cord. It is well-established that both CRNs and PnC neurons receive short-latency auditory inputs to mediate the ASR. Here, we investigated the anatomical origin and functional role of these inputs using a multidisciplinary approach that combines morphological, electrophysiological and behavioral techniques. Anterograde tracer injections into the cochlea suggest that CRNs somata and dendrites receive inputs depending, respectively, on their basal or apical cochlear origin. Confocal colocalization experiments demonstrated that these cochlear inputs are immunopositive for the vesicular glutamate transporter 1 (VGLUT1). Using extracellular recordings in vivofollowed by subsequent tracer injections, we investigated the response of PnC neurons after contra-, ipsi-, and bilateral acoustic stimulation and identified the source of their auditory afferents. Our results showed that the binaural firing rate of PnC neurons was higher than the monaural, exhibiting higher spike discharges with contralateral than ipsilateral acoustic stimulations. Our histological analysis confirmed the CRNs as the principal source of short-latency acoustic inputs, and indicated that other areas of the cochlear nucleus complex are not likely to innervate PnC. Behaviorally, we observed a strong reduction of ASR amplitude in monaural earplugged rats that corresponds with the binaural summation process shown in our electrophysiological findings. Our study contributes to understand better the role of neuronal mechanisms in auditory alerting behaviors and provides strong evidence that the CRNs-PnC pathway mediates fast neurotransmission and binaural summation of the ASR. © 2014 Gómez-Nieto, Horta-Júnior, Castellano, Millian-Morell, Rubio and López

Pedometers to enhance physical activity in COPD: a randomised controlled trial

Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality. Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD. COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme. Assessments were performed by investigators blinded to treatment allocation. Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups. 102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean±sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV1) 66.1±19.4% and FEV1/forced vital capacity 55.2±9.5%. Both groups had comparable characteristics at baseline. The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day−1 versus 138.3±1950 steps·day−1 (p<0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only. A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients

Measuring the proton spectrum in neutron decay - latest results with aSPECT

The retardation spectrometer aSPECT was built to measure the shape of the proton spectrum in free neutron decay with high precision. This allows us to determine the antineutrino electron angular correlation coefficient a. We aim for a precision more than one order of magnitude better than the present best value, which is Delta_a /a = 5%. In a recent beam time performed at the Institut Laue-Langevin during April / May 2008 we reached a statistical accuracy of about 2% per 24 hours measurement time. Several systematic effects were investigated experimentally. We expect the total relative uncertainty to be well below 5%.Comment: Accepted for publication in the Conference Proceedings of the International Workshop on Particle Physics with Slow Neutrons 2008 held at the ILL, France. To be published in Nuclear Instruments and Methods in Physics Research, Section

A simultaneous assessment of multiple ecosystem services and disservices in vineyards and orchards on Terceira Island, Azores

Monitoring ecosystem processes resulting in ecosystem services (ESs) and disservices (EDs) is crucial in agricultural ecosystems. Traditionally, ESs/EDs provided by arthropods have been estimated indirectly by measuring arthropod abundance and diversity, overlooking the recognised limitations of such approach. Using a consistent methodology based on the sentinel approach, we quantified the intensity of five ecological processes leading to four ESs and two EDs in vineyards and citrus orchards on Terceira Island, Azores. We assessed herbivory rates on lettuce plants (ED), predation rates on green plasticine caterpillars by vertebrates and invertebrates (ES), the intensity of insect pollination on strawberry plants (ES), the rates of predation on wheat and dandelion seeds (ED and ES, respectively) by rodents and invertebrates, and decomposition rates using tea and rooibos leaves (ES). Herbivory rates after 2 weeks were significantly lower in vineyards (mean ± SD; 0.5 ± 0.6%) than in citrus orchards (3.6 ± 2.9%). Vertebrate predation rates in vineyards (4.0 ± 13.6% d⁻¹) were significantly higher than in citrus orchards (2.4 ± 10.7% d⁻¹), while no differences were observed for overall and invertebrate predation rates. Pollination efficiency in vineyards (214.5 ± 23.9 seeds/fruit) was significantly higher than in citrus orchards (162.0 ± 14.7 seeds/fruit). Seed predation rates were higher, although not significantly so, in citrus orchards (2.0 ± 5.8% d⁻¹) than in vineyards (0.3 ± 0.8% d⁻¹). Decomposition was significantly higher on tea than on rooibos leaves, both in vineyards (1.15 ± 0.11 g vs. 0.72 ± 0.16 g) and citrus orchards (1.34 ± 0.06 g vs. 0.78 ± 0.13 g); no differences between mass loss in the two habitats were observed. Our results demonstrated the suitability of simple, direct monitoring tools for a quantitative comparison of agricultural habitats, confirm that landscape complexity does not always support ESs, and that the same agro-ecosystem characteristics that support ESs could occasionally also favour EDs.This work was financed by FEDER (European Regional Development Fund) in 85% and by Azorean Public Funds by 15% through Operational Program Azores 2020, under the project AGRO-ECOSERVICES (ACORES-01-0145-FEDER-000073).info:eu-repo/semantics/publishedVersio

New sulphated flavonoids from Wissadula periplocifolia (L.) C. Presl (Malvaceae)

Wissadula periplocifolia (L.) C. Presl (Malvaceae) is commonly used in Brazil to treat bee stings and as an antiseptic. The antioxidant properties of its extracts have been previously demonstrated, thus justifying a phytochemical investigation for its bioactive phenolic constituents. This has yielded five new sulphated flavonoids: 8-O-sulphate isoscutellarein (yannin) (1a); 4'-O-methyl-7-O-sulphate isoscutellarein (beltraonin) (1b); 7-O-sulphate acacetin (wissadulin) (2a); 4'-O-methyl-8-O-sulphate isoscutellarein (caicoine) (2b) and 3'-O-methyl-8-O-sulphate hypolaetin (pedroin) (3b) along with the known flavonoids 7,4'-di-O-methyl-8-O-sulphate isoscutellarein (4), acacetin, apigenin, isoscutellarein, 4´-O-methyl isoscutellarein, 7,4'-di-O-methylisoscutellarein, astragalin and tiliroside. The compounds were isolated by column chromatography and identified by NMR (¹H, (13)C, HMQC, HMBC and COSY) and LC-HRMS. A cell based assay was carried out to evaluate the preliminary cytotoxic properties of the flavonoids against UVW glioma and PC-3M prostate cancer cells as well as non-tumour cell lines. The obtained results showed that acacetin, tiliroside, a mixture of acacetin + apigenin and the sulphated flavonoids 2a + 2b exhibited inhibitory activity against at least one of the cell lines tested. Among the tested flavonoids acacetin and tiliroside showed lower IC50 values, presenting promising antitumor effects