The-2518 bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil

Mucosal leishmaniasis (ML) follows localized cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Proinflammatory responses mediate CL self-healing but are exaggerated in ML Proinflammatory monocyte chemoattractant protein 1 (MCP-1; encoded by CCL2) is associated with CL We explore its role in CL/ML through analysis of the regulatory CCL2 -2518 bp promoter polymorphism in CL/ML population samples and families from Brazil. Genotype frequencies were compared among ML/CL cases and control groups using logistic regression and the family-based association test (FBAT). MCP-1 was measured in plasma and macrophages. The GG recessive genotype at CCL2 -2518 bp was more common in patients with ML (N = 67) than in neighborhood control (NC; N = 60) subjects (OR 1.78; 95% Cl 1.01-3.14; P = 0.045), than in NC combined with leishmanin skin-test positive (N = 60) controls (OR 4.40; 95% CI 1.42-13.65; P = 0.010), and than in controls combined with CL (N = 60) patients (OR 2.78; 95% CI 1.13-6.85; P = 0.045). No associations were observed for CL compared to any groups. FBAT (91 ML and 223 CL cases in families) confirmed recessive association of ML with allele G (Z = 2.679; P = 0.007). Higher levels of MCP-1 occurred in plasma (P = 0.03) and macrophages (P < 0.0001) from GG compared to AA individuals. These results suggest that high MCP-1 increases risk of ML (C) 2010 Elsevier B.V. All rights reserved.

Effects of Caffeoylquinic Acid Derivatives and C-Flavonoid from Lychnophora ericoides on in vitro Inflammatory Mediator Production

In this study we aimed at evaluating the effect of the major polar constituents of the medicinal plant Lychnophora ericoides on the production of inflammatory mediators produced by LPS-stimulated U-937 cells. The 6,8-di-C-beta-glucosylapigenin (vicenin-2) presented no effect on tumor necrosis factor (TNF)-alpha production, but inhibited, in a dose-dependent manner, the production of prostaglandin (PG) E(2) without altering the expression of cyclooxygenase (COX) -2 protein. 3,5-Dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid, at lower concentrations, had small but significant effects on reducing PG E, levels; at higher doses these compounds stimulated PGE(2) and also TNF-alpha production by the cells. All the caffeoylquinic acid derivatives, in a dose-dependent fashion, were able to inhibit monocyte chemoattractant protein-3 synthesis/release, with 4,5-DCQ being the most potent at the highest tested concentration. These results add important information on the effects of plant natural polyphenols, namely vicenin-2 and caffeoylquinic acid derivatives, on the production of inflammatory mediators by cultured cells.

Hábitos alimentares aterogênicos de grupos populacionais em área metropolitana da região sudeste do Brasil

Em amostra representativa da população de duas áreas de estudo (568 indivíduos), Município de Cotia, SP, Brasil, foi realizado inquérito alimentar, baseado na história alimentar do indivíduo. Os objetivos foram: identificar o potencial aterogênico de dietas de diferentes agrupamentos humanos, estratificados em classes sociais e analisar diferenciais de consumo de alguns nutrientes, que conferem aterogenicidade à dieta entre esses agrupamentos. Foram analisados diferenciais de consumo, entre homens e mulheres, segundo classes sociais e tomando-se como referência o percentil 50 (P50) da amostra, dos seguintes constituintes da dieta: energia, proteínas totais, proteínas de origem animal, percentagem de calorias protéicas (P%), ácidos graxos, gorduras, carboidratos. Seguindo esse critério, foram analisados perfis de dieta em relação às recomendações do National Cholesterol Education Program (NEP) no que diz respeito às calorias fornecidas pelas gorduras (G >30%), ac. graxos saturados (AGS> 10%), carboidratos (HC>60%) e colesterol (>300mg/dia). Os resultados mostraram que os diferenciais de consumo foram mais pronunciados entre os homens do que entre as mulheres. As classes sociais, entre os homens, que apresentaram maiores percentuais acima do P50 da amostra, no que diz respeito à energia , proteínas totais, gorduras e carboidratos, foram as representadas pelos trabalhadores não qualificados, que se dedicam a trabalhos braçais com alto consumo energético e a dos pequenos proprietários e comerciantes. A classe de maior poder aquisitivo e nível educacional apresentou consumo moderado desses constituintes. O consumo de proteínas de origem animal, acima do P50, entre homens e mulheres, guardou relação direta com o nível socioeconômico da classe . A participação calórica das gorduras (G%) e proteínas (P%) foi diretamente proporcional ao poder aquisitivo da classe, ao passo que a dos carboidratos (HC%) guardou relação inversa. Por outro lado, o consumo de colesterol acima de 300mg/dia situou-se nas faixas de 37 a 50% e de 20 a 32% para os homens e mulheres, respectivamente. A percentagem de dietas com calorias provenientes das gorduras (G%) acima de 30% variou de 25 a 40%, para os homens e de 45 a 50% para as mulheres. A participação dos ácidos graxos saturados (AGS%) em proporções maiores ou iguais a 10 foi relativamente baixa para ambos os sexos: de 5 a 17% para os homens e menos de 10% para as mulheres. Os percentuais de casos em que a relação ácidos graxos saturados e insaturados (AGS/AGI) guardou valores menores ou iguais a 1, também foi baixa para a população em geral; situou-se entre 7 e 22% para os homens e em proporções abaixo de 10%, para as mulheres. Concluiu-se que a dieta se apresenta como provável fator de risco de doenças cardiovasculares, dislipidemias, obesidade e hipertensão, para grande parte da população.

Antropometria de idosos residentes em instituições geriátricas, Fortaleza, CE

OBJETIVO: Fornecer informações antropométricas e de composição corporal de idosos residentes em instituições geriátricas. MÉTODOS: Foram avaliados 305 idosos, de ambos os sexos, residentes em seis instituições geriátricas de Fortaleza, Estado do Ceará. As variáveis antropométricas utilizadas foram: peso, estatura, índice de massa corporal, perímetro do braço, dobra cutânea tricipital, circunferência muscular do braço e área muscular do braço corrigida. O índice de massa corporal foi calculado a partir de equação que utiliza as variáveis peso e estatura. A circunferência muscular do braço e área muscular do braço corrigida foram calculadas utilizando-se equações específicas. Os dados são apresentados sob a forma de média, desvio-padrão e percentil (P5, P10, P25, P50, P75, P90 e P95). Foi realizado o teste t-Student para verificar a diferença dos valores médios das variáveis entre os sexos. Foi realizada análise de variância (ANOVA) para verificar o efeito da idade nas variáveis. RESULTADOS: Em todas as variáveis, o valor médio dos homens foi superior ao das mulheres, exceto para dobra cutânea tricipital. As diferenças de média das variáveis índice de massa corporal e perímetro do braço entre os sexos não foram estatisticamente significativas (p>0,05). A idade mostrou ser fator importante na diminuição dos valores de algumas variáveis, o que implica a necessidade de padrões de referência específicos para idosos. CONCLUSÕES: Apesar da população estudada ser institucionalizada, a tendência de diminuição das variáveis antropométricas segue a mesma de outros estudos com população idosa, no entanto os valores diferem. Dessa forma, sugere-se que esses valores possam ser usados para auxiliar na avaliação nutricional de idosos institucionalizados.

Anti-vibration gloves and the forearm efforts during tools operations

The objective of this paper is to analyze the forearm muscular contraction levels associated to the use of anti-vibration gloves, by comparing the contraction levels with gloves and without gloves. Two different vibration tools were used in a simulated work environment: (1) A compact Duty Multi-Cutter Bosch and (2) and a Percussion Drill with a drill bit Ø20 mm. Standard operations were performed by each subject in the following materials: (1) Performing cross- sectional cuts in 80x40 mm pine section and (2) performing 20 mm diameter holes in a concrete slab 2 x 2 m, 70 mm thick. The forearm contraction level were measured by surface electromyography in four different muscles: Flexor Digitorum Superficialis (FDS), Flexor Carpi Ulnaris (FCU), Extensor Carpi Radialis Longus (ECRL) e Extensor Carpi Ulnaris (ECU). For the flexor muscles (FDS, FCU), an increase tendency in muscular contraction was observed when the operations are performed without gloves (2-5% MVE increase in the FDS and 3-9% MVE increase in the FCU). For the extensor muscles ECU a decrease tendency in muscular contraction was observed when the operations are performed without gloves (1-10% MVE decrease). Any tendency was found in the ECRL muscle. ECU was the muscle with the highest contraction level for 79% and 71% of the operators, during the operations respectively with the multi-cutter (P50= 27-30%MVE) and with the percussion drill (P50=46-55%MVE). As a final conclusion from this study, anti- vibration gloves may increase the forearm fatigue in the posterior region of the forearm (ECU muscle) during operations with the mentioned tools

Upper Arm Measurements of Healthy Neonates Comparing Ultrasonography and Anthropometric Methods

Objective: To compare measurements of the upper arm cross-sectional areas (total arm area,arm muscle area, and arm fat area of healthy neonates) as calculated using anthropometry with the values obtained by ultrasonography. Materials and methods: This study was performed on 60 consecutively born healthy neonates: gestational age (mean6SD) 39.661.2 weeks, birth weight 3287.16307.7 g, 27 males (45%) and 33 females (55%). Mid-arm circumference and tricipital skinfold thickness measurements were taken on the left upper mid-arm according to the conventional anthropometric method to calculate total arm area, arm muscle area and arm fat area. The ultrasound evaluation was performed at the same arm location using a Toshiba sonolayer SSA-250AÒ, which allows the calculation of the total arm area, arm muscle area and arm fat area by the number of pixels enclosed in the plotted areas. Statistical analysis: whenever appropriate, parametric and non-parametric tests were used in order to compare measurements of paired samples and of groups of samples. Results: No significant differences between males and females were found in any evaluated measurements, estimated either by anthropometry or by ultrasound. Also the median of total arm area did not differ significantly with either method (P50.337). Although there is evidence of concordance of the total arm area measurements (r50.68, 95% CI: 0.55–0.77) the two methods of measurement differed for arm muscle area and arm fat area. The estimated median of measurements by ultrasound for arm muscle area were significantly lower than those estimated by the anthropometric method, which differed by as much as 111% (P,0.001). The estimated median ultrasound measurement of the arm fat was higher than the anthropometric arm fat area by as much as 31% (P,0.001). Conclusion: Compared with ultrasound measurements using skinfold measurements and mid-arm circumference without further correction may lead to overestimation of the cross-sectional area of muscle and underestimation of the cross-sectional fat area. The correlation between the two methods could be interpreted as an indication for further search of correction factors in the equations.

Changes in peripheral refractive profile after orthokeratology for different degrees of myopia

Purpose: The purpose of this study was to evaluate the effect of orthokeratology for different degrees of myopia correction in the relative location of tangential (FT) and sagittal (FS) power errors across the central 70 of the visual field in the horizontal meridian. Methods: Thirty-four right eyes of 34 patients with a mean age of 25.2 ± 6.4 years were fitted with Paragon CRT (Mesa, AZ) rigid gas permeable contact lenses to treat myopia (2.15 ± 1.26D, range: 0.88 to 5.25D). Axial and peripheral refraction were measured along the central 70 of the horizontal visual field with the Grand Seiko WAM5500 open-field auto-refractor. Spherical equivalent (M), as well as tangential (FT) and sagittal power errors (FS) were obtained. Analysis was stratified in three groups according to baseline spherical equivalent: Group 1 [MBaseline = 0.88 to 1.50D; n = 11], Group 2 [MBaseline = 1.51 to 2.49D; n = 11], and Group 3 [MBaseline = 2.50 to 5.25D; n = 12]. Results: Spherical equivalent was significantly more myopic after treatment beyond the central 40 of the visual field (p50.001). FT became significantly more myopic for all groups in the nasal and temporal retina with 25 (p 0.017), 30 (p 0.007) and 35 (p 0.004) of eye rotation. Myopic change in FS was less consistent, achieving only statistical significance for all groups at 35 in the nasal and temporal retina (p 0.045). Conclusions: Orthokeratology changes significantly FT in the myopic direction beyond the central 40 of the visual field for all degrees of myopia. Changes induced by orthokeratology in relative peripheral M, FT and FS with 35 of eye rotation were significantly correlated with axial myopia at baseline. Keywords: Field

Abnormalities in the processing of emotional prosody from single words in schizophrenia

Background: Abnormalities in emotional prosody processing have been consistently reported in schizophrenia and are related to poor social outcomes. However, the role of stimulus complexity in abnormal emotional prosody processing is still unclear. Method: We recorded event-related potentials in 16 patients with chronic schizophrenia and 16 healthy controls to investigate: 1) the temporal course of emotional prosody processing; and 2) the relative contribution of prosodic and semantic cues in emotional prosody processing. Stimuli were prosodic single words presented in two conditions: with intelligible (semantic content condition—SCC) and unintelligible semantic content (pure prosody condition—PPC). Results: Relative to healthy controls, schizophrenia patients showed reduced P50 for happy PPC words, and reduced N100 for both neutral and emotional SCC words and for neutral PPC stimuli. Also, increased P200 was observed in schizophrenia for happy prosody in SCC only. Behavioral results revealed higher error rates in schizophrenia for angry prosody in SCC and for happy prosody in PPC. Conclusions: Together, these data further demonstrate the interactions between abnormal sensory processes and higher-order processes in bringing about emotional prosody processing dysfunction in schizophrenia. They further suggest that impaired emotional prosody processing is dependent on stimulus complexity.

The music of language: an ERP investigation of the effects of musical training on emotional prosody processing

Recent studies have demonstrated the positive effects of musical training on the perception of vocally expressed emotion. This study investigated the effects of musical training on event-related potential (ERP) correlates of emotional prosody processing. Fourteen musicians and fourteen control subjects listened to 228 sentences with neutral semantic content, differing in prosody (one third with neutral, one third with happy and one third with angry intonation), with intelligible semantic content (semantic content condition--SCC) and unintelligible semantic content (pure prosody condition--PPC). Reduced P50 amplitude was found in musicians. A difference between SCC and PPC conditions was found in P50 and N100 amplitude in non-musicians only, and in P200 amplitude in musicians only. Furthermore, musicians were more accurate in recognizing angry prosody in PPC sentences. These findings suggest that auditory expertise characterizing extensive musical training may impact different stages of vocal emotional processing.

Pressão arterial: efeito do índice de massa corporal e da circunferência abdominal em adolescentes

FUNDAMENTO: Aumento do índice de massa corporal (IMC) e da circunferência abdominal (CA) tem sido associado a elevação da pressão arterial. OBJETIVO: Avaliar o efeito do IMC e da CA sobre a pressão arterial (PA) de adolescentes. MÉTODOS: Estudo analítico de corte transversal. Selecionados 536 adolescentes, alunos de escolas públicas e privadas. Foram calculados IMC, classificado como normal alto (>p50 p85 p95). Mediu-se a CA, aumentada se>p75 e a PA, elevada se >p90. RESULTADOS: Trezentos e dezenove (59,5%) indivíduos eram meninas, idade de 14,0± 1,99 anos, peso normal alto em 39,6%, sobrepeso em 37,1% e obesidade em 23,3%. O percentual de PAS e PAD elevadas acompanhou a elevação do IMC (p=0,000), alcançando 46,4% nos meninos e 39,3% nas meninas obesas (PAS) e 42,0% e 44,6% (PAD), respectivamente. PAS e PAD elevadas foram 3,9 a 3,4 vezes mais freqüente nos meninos, e 2,2 a 2,0 vezes mais nas meninas com CA > p75, respectivamente. Pela análise de regressão linear simples cada aumento no IMC aumentaria a PAS em 1,198 mmHg e da CA em 0,622 mmHg. A razão de prevalência (RP) de PAS e PAD elevadas em razão do IMC>p85 foi 3,9(I.C. 95% 2,0-7,4[p=0,000]) e 4,3(I.C. 95% 2,2-8,5[p=0,000]), respectivamente, e em razão da CA>p75 de 1,8(IC 95% 1,0 a 3,0 [p=0,036]) e 1,4(IC 95% 0,8 a 2,4). Encontrou-se em 16/181(8,8%) dos adolescentes com peso normal alto, PA>P90 com CA>p75. CONCLUSÃO: Os valores do IMC e da CA têm forte influência sobre os valores da PA de adolescentes.

Associação entre peso de nascimento e fatores de risco cardiovascular em adolescentes

FUNDAMENTO: Peso ao nascer (PN) é um determinante de risco a médio e longo prazo de fatores de risco cardiovascular. OBJETIVO: Estudar a associação entre peso ao nascer e fatores de risco cardiovascular em adolescentes de Salvador. MÉTODOS: Estudo de corte transversal com grupos de comparação por PN. Amostra composta de 250 adolescentes, classificados segundo IMC: normal alto (>p50 e

Canakinumab Reduces The Risk Of Acute Gouty Arthritis Flares During Initiation Of Allopurinol Therapy: Results Of A Double-blind, Randomised Study

RATIONALE: This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin-1beta monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating uratelowering therapy.METHODS: In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol therapy were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously (sc); four 4-weekly doses of canakinumab (50150125125 mg sc); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks.RESULTS: A dose-response for canakinumab was not apparent with any of the four pre-defined dose-responsemodels. The estimated canakinumab dose with equivalent efficacy to colchicinewas belowthe range of doses tested.At 16 weeks, therewas a 62-72% reduction in themean number of flares per patient for canakinumab doses >50 mg vs colchicine based on a negative binomial model (rate ratio: 0.28-0.38, p50.0083), and the percentage of patients experiencing >1 flarewas significantly lower for all canakinumab doses (15- 27%) vs colchicine (44%, p<0.05). Therewas a 64-72%reduction in the risk of experiencing >1 flare for canakinumab doses >50 mg vs colchicine at 16 weeks (hazard ratio: 0.28-0.36, p50.05). The incidence of adverse events was similar across treatment groups.CONCLUSIONS: Single canakinumab doses >50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.

De novo lipogenesis in adipose tissue is associated with course of morbid obesity after bariatric surgery.

OBJECTIVE De novo lipogenesis is involved in fatty acid biosynthesis and could be involved in the regulation of the triglyceride storage capacity of adipose tissue. However, the association between lipogenic and lipolytic genes and the evolution of morbidly obese subjects after bariatric surgery remains unknown. In this prospective study we analyze the association between the improvement in the morbidly obese patients as a result of bariatric surgery and the basal expression of lipogenic and lipolytic genes. METHODS We study 23 non diabetic morbidly obese patients who were studied before and 7 months after bariatric surgery. Also, we analyze the relative basal mRNA expression levels of lipogenic and lipolytic genes in epiploic visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT). RESULTS When the basal acetyl-CoA carboxylase 1 (ACC1), acetyl-CoA synthetase 2 (ACSS2) and ATP citrate lyase (ACL) expression in SAT was below percentile-50, there was a greater decrease in weight (P = 0.006, P = 0.034, P = 0.026), body mass index (P = 0.008, P = 0.033, P = 0.034) and hip circumference (P = 0.033, P = 0.021, P = 0.083) after bariatric surgery. In VAT, when the basal ACSS2 expression was below percentile-50, there was a greater decrease in hip circumference (P = 0.006). After adjusting for confounding variables in logistic regression models, only the morbidly obese patients with SAT or VAT ACSS2 expression ≥ P50 before bariatric surgery had a lower percentage hip circumference loss (<P50) after bariatric surgery (SAT: P = 0.039; VAT: P = 0.033). CONCLUSIONS A lower basal ACSS2, ACC1 and ACL expression, genes involved in de novo lipogenesis, is associated with a better evolution of anthropometric variables after bariatric surgery. Thus, the previous state of the pathways involved in fatty acid metabolism may have repercussions on the improvement of these patients.

Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING Transnational registry in Spain. SUBJECTS We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES All-cause death. RESULTS Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.

Intronic variants in the NFKB1 gene may influence hearing forecast in patients with unilateral sensorineural hearing loss in Meniere's disease.

Meniere's disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-κB pathway, such as REL, TNFAIP3, NFKB1 and TNIP1, have been associated with two or more immune-mediated diseases and allelic variations in the TLR10 gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10(-8)), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and p = 0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL.