Carotid Intima-Media Thickness at Age 30, Birth Weight,Accelerated Growth during Infancy and Breastfeeding: A Birth Cohort Study in Southern Brazil

Objective

To examine the relationship between carotid intima-media thickness (IMT) at age 30 and birth characteristics, growth during infancy, and breastfeeding duration, among subjects who have been prospectively followed since birth.

Methods and Results

In 1982, all births in the city of Pelotas, southern Brazil, were identified and those children (n = 5,914) whose families lived in the urban area of the city have been followed and evaluated at several time points. The cohort participants were evaluated in 2012–13, and IMT was measured at the posterior wall of the right and left common carotid arteries in longitudinal planes using ultrasound imaging. We obtained valid IMT measurements for 3,188 individuals. Weight-for-age z-score (WAZ) at age 2 years, weight-for-height z-score (WHZ) at age 4, height-for-age z-score (HAZ) at 4 years, WAZ at age 4 and relative conditional weight at 4 years were positively associated with IMT, even after controlling for confounding variables. The beta-coefficient associated with ≥1 s.d. WAZ at age 2 (compared to those with a <–1 s.d.) was 3.62 μm (95% CI 0.86 to 6.38). The beta-coefficient associated with ≥1 s.d. WHZ at 4 (in relation to <–1 s.d) was 3.83 μm (95% CI 0.24 to 7.42). For HAZ at 4, the beta-coefficient for ≥1 s.d. in relation to <–1 s.d. was 4.19 μm (95% CI 1.14 to 7.25). For WAZ at 4, the beta-coefficient associated with ≥1 s.d. in relation to <–1 s.d. was 4.28 μm (95% CI 1.59 to 6.97). The beta-coefficient associated with conditional weight gain at age 2–4 was 1.26 μm (95% CI 0.49 to 2.02).

Conclusion

IMT at age 30 was positively associated with WAZ at age 2 years, WHZ at age 4, HAZ at age 4, WAZ at age 4 and conditional weight gain at age 4 years.     

Biomass,sugar, and bioethanol potential of sweet corn

Sweet corn is a widely distributed crop that generates agricultural waste without significant commercial value. In this study, we show that sweet corn varieties produce large amounts of residual biomass (10 t ha^?1) with high content of soluble sugars (25% of dry matter) in a short growing season (3 months). The potential ethanol production from structural and soluble sugars extracted from sweet corn stover reached up to 4400 l ha^?1 in the most productive hybrids, 33% of which (1500 l ha^?1) were obtained by direct fermentation of free sugars. We found wide genetic variation for biomass yield and soluble sugars content suggesting that those traits can be included as complementary traits in sweet corn breeding programs. Dual‐purpose sweet corn hybrids can have an added value for the farmers contributing to energy generation without affecting food supply or the environment.     

Enhanced Neuronal Glucose Transporter Expression Reveals Metabolic Choice in a HD Drosophila Model

Huntington’s disease is a neurodegenerative disorder caused by toxic insertions of polyglutamine residues in the Huntingtin protein and characterized by progressive deterioration of cognitive and motor functions. Altered brain glucose metabolism has long been suggested and a possible link has been proposed in HD. However, the precise function of glucose transporters was not yet determined. Here, we report the effects of the specifically-neuronal human glucose transporter expression in neurons of a Drosophila model carrying the exon 1 of the human huntingtin gene with 93 glutamine repeats (HQ93). We demonstrated that overexpression of the human glucose transporter in neurons ameliorated significantly the status of HD flies by increasing their lifespan, reducing their locomotor deficits and rescuing eye neurodegeneration. Then, we investigated whether increasing the major pathways of glucose catabolism, glycolysis and pentose-phosphate pathway (PPP) impacts HD. To mimic increased glycolytic flux, we overexpressed phosphofructokinase (PFK) which catalyzes an irreversible step in glycolysis. Overexpression of PFK did not affect HQ93 fly survival, but protected from photoreceptor loss. Overexpression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the PPP, extended significantly the lifespan of HD flies and rescued eye neurodegeneration. Since G6PD is able to synthesize NADPH involved in cell survival by maintenance of the redox state, we showed that tolerance to experimental oxidative stress was enhanced in flies co-expressing HQ93 and G6PD. Additionally overexpressions of hGluT3, G6PD or PFK were able to circumvent mitochondrial deficits induced by specific silencing of genes necessary for mitochondrial homeostasis. Our study confirms the involvement of bioenergetic deficits in HD course; they can be rescued by specific expression of a glucose transporter in neurons. Finally, the PPP and, to a lesser extent, the glycolysis seem to mediate the hGluT3 protective effects, whereas, in addition, the PPP provides increased protection to oxidative stress.     

Sex-Specific Mediating Role of Insulin Resistance and Inflammation in the Effect of Adiposity on Blood Pressure of Prepubertal Children

Objective

To evaluate the association between obesity indices and blood pressure (BP) at 4 years of age, in each sex, and to quantify to which extent this association is mediated by inflammation and insulin resistance (IR).

Materials and Methods

We studied 1250 4-year-old children selected from the population-based birth cohort Generation XXI. Associations between body mass index (BMI) z-score and waist-to-height ratio (WHtR), office BP, inflammation (high sensitivity C-reactive protein) and IR (HOMA-IR index) were assessed. Path Analysis, a modified multivariate regression approach, was applied to test causal models and quantify direct and indirect effects of predictors of systolic (SBP) and diastolic BP (DBP).

Results

SBP and DBP increased significantly with BMI and WHtR in both sexes. There was a strong direct association (explaining 74.1-93.2% of the total association) of both measures of adiposity with SBP, in both sexes. This association was additionally indirectly mediated by IR, particularly regarding WHtR (20.5% in girls and 9.4% in boys). Mediation by inflammation did not reach statistical significance in either sex. Regarding DBP, the direct effect of adiposity was strong (>95% for BMI and WHtR in boys) and the mediation by IR was much smaller in boys than in girls.

Discussion

The direct association between adiposity and BP in healthy 4-year-old children is strong and IR plays an important mediating role. The strength of effects of IR and inflammation suggests sex differences in the complex interplay between BP, adiposity and inflammation.     

Local IL-17 Production Exerts a Protective Role in Murine Experimental Glomerulonephritis

IL-17 is a pro-inflammatory cytokine implicated in the pathogenesis of glomerulonephritis and IL-17 deficient mice are protected from nephrotoxic nephritis. However, a regulatory role for IL-17 has recently emerged. We describe a novel protective function for IL-17 in the kidney. Bone marrow chimeras were created using wild-type and IL-17 deficient mice and nephrotoxic nephritis was induced. IL-17 deficient hosts transplanted with wild-type bone marrow had worse disease by all indices compared to wild-type to wild-type bone marrow transplants (serum urea p<0.05; glomerular thrombosis p<0.05; tubular damage p<0.01), suggesting that in wild-type mice, IL-17 production by renal cells resistant to radiation is protective. IL-17 deficient mice transplanted with wild-type bone marrow also had a comparatively altered renal phenotype, with significant differences in renal cytokines (IL-10 p<0.01; IL-1β p<0.001; IL-23 p<0.01), and macrophage phenotype (expression of mannose receptor p<0.05; inducible nitric oxide synthase p<0.001). Finally we show that renal mast cells are resistant to radiation and produce IL-17, suggesting they are potential local mediators of disease protection. This is a novel role for intrinsic cells in the kidney that are radio-resistant and produce IL-17 to mediate protection in nephrotoxic nephritis. This has clinical significance as IL-17 blockade is being trialled as a therapeutic strategy in some autoimmune diseases.     

"Healthy Men" and High Mortality: Contributions from a Population-Based Study for the Gender Paradox Discussion

Background

Inequalities between men and women in morbidity and mortality show a contrast, which has been called gender paradox. Most studies evaluating this paradox were conducted in high-income countries and, until now, few investigations have been performed in Brazil. This study aims to estimate the magnitude of inequalities between adult men and women in several dimensions: demographic and socioeconomic, health behaviors, morbidity, use of health services and mortality.

Methods

The data were obtained from population-based household survey carried out in Campinas (Campinas Health Survey 2008/09) corresponding to 957 people, and data from the Mortality Information System (MIS) between 2009 and 2011. Prevalences and prevalence ratios were analyzed in order to verify the differences between men and women regarding socioeconomic and demographic variables, health behaviors, morbidities and consultations in the last two weeks. Mortality rates and the ratio between coefficients considering the underlying causes of death were calculated.

Results

Women had a greater disadvantage in socioeconomic indicators, chronic diseases diagnosed by a health professional and referred health problems as well as make more use of health services, while men presented higher frequency of most unhealthy behaviors and excessive mortality for all causes investigated.

Conclusions

The findings contribute to the discussion of gender paradox and demonstrate the need to employ health actions that consider the differences between men and women in the various health dimensions analyzed. The premature male mortality from preventable causes was outstanding, making clear the need for more effective prevention and health promotion directed to this segment of the population.     

Pseudo-peptides derived from isomannide: inhibitors of serine proteases

In this paper, we describe the synthesis of a novel class of pseudo-peptides derived from isomannide and several oxazolones as potential inhibitors of serine proteases as well as preliminary pharmacological assays for hepatitis C. Hepatitis C, dengue and West Nile fever are among the most important flaviviruses that share one important serine protease enzyme. Serine proteases belong to the most studied class of proteolytic enzymes and are a primary target in the drug development field. Several pseudo-peptides were obtained in good yields from the reaction of isomannide and oxazolones, and their anti-HCV potential using the HCV replicon-based assay was shown.     

每搏量变异度在围手术期容量治疗监测中的应用

每搏量变异度是动态的容量监测指标.机械通气患者心肺的相互作用是每搏量变异度的产生基础,通过动脉压力波形分析技术可以进行连续监测.每搏量变异度能够准确预测容量治疗反应,与静态的血流动力学参数相比,对于优化心输出量和组织氧供更有优势,但也存在一定的局限性.每搏量变异度受多种因素影响且不能用于自主呼吸和心律失常的患者.临床应用时应该综合考虑其影响因素,结合其他的指标和方法指导容量治疗.     

Effect of chronic treatment with Rosiglitazone on Leydig cell steroidogenesis in rats: <Emphasis Type="Italic">In vivo</Emphasis> and <Emphasis Type="Italic">ex vivo</Emphasis> studies

Background  

The present study was designed to examine the effect of chronic treatment with rosiglitazone - thiazolidinedione used in the treatment of type 2 diabetes mellitus for its insulin sensitizing effects - on the Leydig cell steroidogenic capacity and expression of the steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc) in normal adult rats.