Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.

INTRODUCTION: The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. METHODS: 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. RESULTS: Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P < 0.05) associations with gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. CONCLUSION: There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases expression of IL-1β - the multiplicative interaction with CARD8 would be consistent with a synergy of greater inflammasome activity (resulting from reduced CARD8) combined with higher levels of pre-IL-1β expression leading to increased production of mature IL-1β in gout.

Prescription médicamenteuse inappropriée: les nouveaux critères STOPP/START [Prescribing inappropriate medication: the new STOPP/START criteria].

Prescribing inappropriate medication (PIM) is a common public health problem. Mainly due to associated adverse drugs events (ADE), it results in major morbidity and mortality, as well as increased healthcare utilization. For a long time, the systematic review of medications prescribed appeared as a solution for limiting PIM and the ADE associated with such prescriptions. With this aim and since 2008, the list of STOPP-START criteria has appeared as attractive in its design, as well as logical and easy to use. The initial version has just been updated and improved. After having detailed all improvements provided to the 2008 version, we present the result of its adaptation into French language by a group of French-speaking expert from Belgium, Canada, France, and Switzerland.

Pleiotropy and the low cost of individual traits promote cooperation.

The evolution of cooperation is thought to be promoted by pleiotropy, whereby cooperative traits are coregulated with traits that are important for personal fitness. However, this hypothesis faces a key challenge: what happens if mutation targets a cooperative trait specifically rather than the pleiotropic regulator? Here, we explore this question with the bacterium Pseudomonas aeruginosa, which cooperatively digests complex proteins using elastase. We empirically measure and theoretically model the fate of two mutants-one missing the whole regulatory circuit behind elastase production and the other with only the elastase gene mutated-relative to the wild-type (WT). We first show that, when elastase is needed, neither of the mutants can grow if the WT is absent. And, consistent with previous findings, we show that regulatory gene mutants can grow faster than the WT when there are no pleiotropic costs. However, we find that mutants only lacking elastase production do not outcompete the WT, because the individual cooperative trait has a low cost. We argue that the intrinsic architecture of molecular networks makes pleiotropy an effective way to stabilize cooperative evolution. Although individual cooperative traits experience loss-of-function mutations, these mutations may result in weak benefits, and need not undermine the protection from pleiotropy.

Variation in Current Management of Term and Late-preterm Neonates at Risk for Early-onset Sepsis: An International Survey and Review of Guidelines.

BACKGROUND: Uncertainty about the presence of infection results in unnecessary and prolonged empiric antibiotic treatment of newborns at risk for early-onset sepsis (EOS). This study evaluates the impact of this uncertainty on the diversity in management. METHODS: A web-based survey with questions addressing management of infection risk-adjusted scenarios was performed in Europe, North America, and Australia. Published national guidelines (n = 5) were reviewed and compared with the results of the survey. RESULTS: 439 Clinicians (68% were neonatologists) from 16 countries completed the survey. In the low-risk scenario, 29% would start antibiotic therapy and 26% would not, both groups without laboratory investigations; 45% would start if laboratory markers were abnormal. In the high-risk scenario, 99% would start antibiotic therapy. In the low-risk scenario, 89% would discontinue antibiotic therapy before 72 hours. In the high-risk scenario, 35% would discontinue therapy before 72 hours, 56% would continue therapy for 5-7 days, and 9% for more than 7 days. Laboratory investigations were used in 31% of scenarios for the decision to start, and in 72% for the decision to discontinue antibiotic treatment. National guidelines differ considerably regarding the decision to start in low-risk and regarding the decision to continue therapy in higher risk situations. CONCLUSIONS: There is a broad diversity of clinical practice in management of EOS and a lack of agreement between current guidelines. The results of the survey reflect the diversity of national guidelines. Prospective studies regarding management of neonates at risk of EOS with safety endpoints are needed.

Exposure to Tobacco Smoke and Markers of Subclinical Atherosclerosis in Children and Adolescents. The STRIP Study.

Background: Measurement of serum cotinine, a major metabolite of nicotine, provides a valid marker for quantifying exposure to tobacco smoke. Exposure to tobacco smoke causes vascular damage by multiple mechanisms, and it has been acknowledged as a risk factor for atherosclerosis. Multifactorial atherosclerosis begins in childhood, but the relationship between exposure to tobacco smoke and arterial changes related to early atherosclerosis have not been studied in children. Aims: The aim of the present study was to evaluate exposure to tobacco smoke with a biomarker, serum cotinine concentration, and its associations with markers of subclinical atherosclerosis and lipid profile in school-aged children and adolescents. Subjects and Methods: Serum cotinine concentration was measured using a gas chromatographic method annually between the ages 8 and 13 years in 538-625 children participating since infancy in a randomized, prospective atherosclerosis prevention trial STRIP (Special Turku coronary Risk factor Intervention Project). Conventional atherosclerosis risk factors were measured repeatedly. Vascular ultrasound studies were performed among 402 healthy 11-year-old children and among 494 adolescents aged 13 years. Results: According to serum cotinine measurements, a notable number of the school aged children and adolescents were exposed to tobacco smoke, but the exposure levels were only moderate. Exposure to tobacco smoke was associated with decreased endothelial function as measured with flow-mediated dilation of the brachial artery, decreased elasticity of the aorta, and increased carotid and aortic intima-media thickness. Longitudinal exposure to tobacco smoke was also related with increased apolipoprotein B and triglyceride levels in 13-year-old adolescents, whose body mass index and nutrient intakes did not differ. Conclusions: These findings suggest that exposure to tobacco smoke in childhood may play a significant role in the development of early atherosclerosis. Key Words: arterial elasticity, atherosclerosis, children, cotinine, endothelial function, environmental tobacco smoke, intima-media thickness, risk factors, ultrasound

De confessione Evae, ex Gen. IV, 1

Invocatio: [Alpha et Omega].

Karjalainen rapsodia

Soitinnus: orkesteri.

Spectrophotometric determination of metronidazole through Schiff's base system using vanillin and PDAB reagents in pharmaceutical preparations

Two simple sensitive and reproducible spectrophotometric methods have been developed for the determination of metronidazole either in pure form or in their tablets. The proposed methods are based on the reduction of the nitro group to amino group of the drug. The reduction of metronidazole was carried out with zinc powder and 5 N hydrochloric acid at room temperature in methanol. The resulting amine was then subjected to a condensation reaction with aromatic aldehyde namely, vanillin and p-dimethyl amino benzaldehyde (PDAB) to yield yellow colored Schiff's bases. The formed Schiff's bases are quantified spectrophotometrically at their absorption maxima at 422 nm for vanillin and 494 nm for PDAB. Beer's law was obeyed in the concentration ranges 10 to 65 µg mL-1 and 5 to 40 µg mL-1 with a limit of detection (LOD) of 0.080 µg mL-1 and 0.090 µg mL-1 for vanillin and PDAB, respectively. The mean percentage recoveries were found to be 100.05 ± 0.37 and 99.01 ± 0.76 for the two methods respectively. The proposed methods were successfully applied to determine the metronidazole in their tablet formulations and the results compared favorably to that of reference methods. The proposed methods are recommended for quality control and routine analysis.

Resolubilidade da estratégia saúde da família e unidades básicas de saúde tradicionais: contribuições do Pet-Saúde

O Programa de Educação pelo Trabalho para a Saúde (PET-Saúde) materializa uma política indutora de novas relações entre instituições de ensino de nível superior e a rede assistencial à saúde. A Universidade de São Paulo - Campus de Ribeirão Preto e a Secretaria de Saúde do município, selecionadas pelo PET-Saúde/2009, avaliaram a resolubilidade das Unidades Básicas de Saúde (UBS) e das Unidades de Estratégia Saúde da Família (ESF), como forma de contribuir para a qualificação da Atenção Básica. Foi realizado um estudo transversal em 13 Unidades de Saúde (oito ESF e cinco UBS), com a participação de 216 alunos dos cursos da área da saúde, 30 preceptores (profissionais) da rede pública de saúde e cinco tutores (docentes). Foram coletados dados de 12.494 atendimentos, sendo 7.129 (58,9%) em ESF e 4.963 (41,1%) em UBS, compostos por 4.059 (33,6%) pessoas do sexo masculino e 8.035 (66,4%) do feminino.As UBS referenciaram mais pacientes do que as Unidades de ESF (OR = 1,67; IC 95% 1,46 - 1,90; [p < 0,05]). As especialidades com maior demanda por encaminhamentos foram oftalmologia, cardiologia e ortopedia. A ESF apresenta-se como modelo assistencial com maior resolubilidade, e o PET-Saúde é uma iniciativa importante, considerando-se que estimula a ampliação desse modelo.

L'Univers

1868/08/31 (Numéro 494).

Viabilidade econômica da utilização do biogás produzido em granja suínícola para geração de energia elétrica

A produção de biogás por meio de biodigestão anaeróbia representa um avanço para equacionar o problema dos dejetos produzidos pela suinocultura e disponibilidade de energia no meio rural. Este trabalho teve como objetivo estimar a viabilidade econômica de um sistema biointegrado para geração de eletricidade a partir do aproveitamento de dejetos de suínos. Os dados para este estudo foram coletados em uma agroindústria, onde são realizadas diversas atividades agrícolas; entretanto, a suinocultura foi selecionada para o processo de análise de biodigestão anaeróbia, pelo fato de gerar uma grande quantidade de dejetos, com dificuldade de disposição no meio ambiente, configurando um estudo de caso. O biodigestor analisado é um modelo tubular contínuo, com calha de água em alvenaria e com uma manta plástica como gasômetro, onde são depositados diariamente os dejetos de 2.300 suínos em fase de terminação. O investimento inicial para implantação foi estimado em R$ 51.537,17, e os custos anuais do sistema foram de R$ 5.708,20 com manutenção, R$ 4.390,40 com depreciação e R$ 1.366,77 com juros. Concluiu-se que o sistema de produção de biogás é viável do ponto de vista econômico, se o consumo de energia elétrica for de 35 kWh por dia, em média, onde o valor presente líquido (VLP) é de R$ 9.494,90, e a taxa interna de retorno (TIR) é de 9,34% ao ano.

Traqueostomia a beira de leito na uti: estudo prospectivo de 70 casos

A traqueostomia apresenta uma série de vantagens em relação à entubação endotraqueal prolongada: conforto e maior possibilidade de comunicação para o paciente, diminuição da resistência respiratória, melhor controle de via aérea e facilidade de aspiração. No período de setembro de 1996 a dezembro de 1997 foram realizadas setenta traqueostomias à beira de leito na UTI, sob anestesia local, com tempo operatório médio de 30,5 minutos. A principal indicação foi ventilação mecânica prolongada, com uma média de 6,5 dias. Os pacientes foram acompanhados durante a internação por 1.494 dias. No terceiro dia de pós-operatório foi colhida cultura de secreção traqueal em 49 pacientes, predominando Pseudomonas aeruginosa em 40,8% dos casos. Houve 11 casos (15,7%) de complicações maiores: uma fístula traqueoesofágica, uma fasciíte necrotizante, uma úlcera traqueal, duas infecções e seis sangramentos, que necessitaram reintervenção. Um óbito foi relacionado ao procedimento, devido à fasciíte necrotizante cervical. Tendo em vista a gravidade dos pacientes, a traqueostomia à beira de leito demonstrou ser um procedimento seguro e com baixo índice de complicações maiores. Além disso, evita o transporte de doente crítico dentro do hospital, e os custos são menores do que a traqueostomia no centro cirúrgico.

Kaakkois-Suomen ekotehokkuusindikaattorit 2010

Kaakkois-Suomen ELY-keskus, Kymenlaakson liitto ja Etelä-Karjalan liitto toteuttivat vuoden 2011 aikana ECOREG-hankkeessa valittujen ekotehokkuusindikaattorien viidennen vuosipäivityksen molemmille maakunnille. Tässä raportissa esitetään Kaakkois-Suomen ympäristö-, talous- ja sosiaalis-kulttuuristen indikaattorien kehittyminen indikaattorikohtaisesti valittuina aikasarjoina. Indikaattorien lisäksi raportissa käydään läpi vuosiraportoinnin käytännöt ja aikataulut sekä päivitysprosessin aikana esiin tulleet kehitystavoitteet. Tässä raportissa esitetään myös indikaattoriryhmäkohtaiset yhteenvedot sekä arviot alueellisen ekotehokkuuden kehittymisestä ja tilasta Kaakkois-Suomessa.