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.     

Cross-Sectional and Prospective Associations between Physical Activity and C-Reactive Protein in Males

BackgroundThere is conflicting evidence about the association between physical activity and inflammatory markers. Few prospective studies are available, particularly from low and middle-income countries. This study was aimed at assessing the cross-sectional and prospective associations between physical activity and C-reactive protein (CRP) levels in males belonging to the 1982 Pelotas (Brazil) Birth Cohort Study.MethodsThe sample comprised 2,213 males followed up at the ages of 18 and 23 years. We performed high sensitivity CRP assays; we used a cut-off of 3 mg/L in categorical analyses. We measured physical activity by self-report at ages 18 and 23 years. Body mass index and waist circumference were studies as possible mediators.ResultsCRP levels above the 3mg/L cut-off were found in 13.3% (95%CI: 11.7; 14.8) of the individuals. We found no evidence for an association between physical activity (leisure-time or all-domains) and either continuous (geometrical mean) or categorical CRP. We confirmed these null findings in (a) prospective and cross-sectional analyses; (b) trajectories analyses.ConclusionsThere was no association between CRP levels and physical activity levels in early adulthood in a large birth cohort. Little variability in CRP at this early age is the likely explanation for these null findings.     

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.     

A meta-analysis on pyrogenic organic matter induced priming effect

Pyrogenic organic matter (PyOM) is considered an important soil carbon (C) sink. However, there are evidences that its addition to soil may induce a priming effect (PE) thus influencing its C abatement potential. The direction, the size and the mechanisms responsible for PyOM induced PE are far from being understood. We collected approximately 650 data points from 18 studies to analyse the characteristics of the PE induced by PyOM. The database was divided between the PE induced on the native soil organic matter and on fresh organic matter. Most of the studies were short-term incubation therefore the projections of findings on the long term may be critical. Our findings indicate that over 1 year PyOM induces an average positive PE of 0.3 mg C g⁻¹ soil on native soil organic matter and a PE of approximately the same size but opposite direction on fresh organic matter. We studied the correlation of PE with several properties of soil, of the added PyOM, and time after PyOM addition. We found that PyOM primes positively the native soil organic matter in the first 20 days while negative PE appears in a later stage. Negative PE was correlated with the soil C content. PyOM characterized by a low C content induced a higher positive PE on native soil organic carbon. No correlation was found between the factors record in our database and the PE induced on the fresh organic matter. We reviewed the mechanisms proposed in literature to explain PE and discussed them based on findings from our meta-analysis. We believe that the presence of a labile fraction in PyOM may trigger the activity of soil microorganisms on the short term and therefore induce a positive PE, while on the long term PyOM may induce a negative PE by promoting physical protection mechanisms.     

Human Metapneumovirus Is Capable of Entering Cells by Fusion with Endosomal Membranes

Human metapneumovirus (HMPV), a member of the Paramyxoviridae family, is a leading cause of lower respiratory illness. Although receptor binding is thought to initiate fusion at the plasma membrane for paramyxoviruses, the entry mechanism for HMPV is largely uncharacterized. Here we sought to determine whether HMPV initiates fusion at the plasma membrane or following internalization. To study the HMPV entry process in human bronchial epithelial (BEAS-2B) cells, we used fluorescence microscopy, an R18-dequenching fusion assay, and developed a quantitative, fluorescence microscopy assay to follow virus binding, internalization, membrane fusion, and visualize the cellular site of HMPV fusion. We found that HMPV particles are internalized into human bronchial epithelial cells before fusing with endosomes. Using chemical inhibitors and RNA interference, we determined that HMPV particles are internalized via clathrin-mediated endocytosis in a dynamin-dependent manner. HMPV fusion and productive infection are promoted by RGD-binding integrin engagement, internalization, actin polymerization, and dynamin. Further, HMPV fusion is pH-independent, although infection with rare strains is modestly inhibited by RNA interference or chemical inhibition of endosomal acidification. Thus, HMPV can enter via endocytosis, but the viral fusion machinery is not triggered by low pH. Together, our results indicate that HMPV is capable of entering host cells by multiple pathways, including membrane fusion from endosomal compartments.     

Regularity of Cardiac Rhythm as a Marker of Sleepiness in Sleep Disordered Breathing

Aim

The present study aimed to analyse the autonomic nervous system activity using heart rate variability (HRV) to detect sleep disordered breathing (SDB) patients with and without excessive daytime sleepiness (EDS) before sleep onset.

Methods

Two groups of 20 patients with different levels of daytime sleepiness -sleepy group, SG; alert group, AG- were selected consecutively from a Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT) research protocol. The first waking 3-min window of RR signal at the beginning of each nap test was considered for the analysis. HRV was measured with traditional linear measures and with time-frequency representations. Non-linear measures -correntropy, CORR; auto-mutual-information function, AMIF- were used to describe the regularity of the RR rhythm. Statistical analysis was performed with non-parametric tests.

Results

Non-linear dynamic of the RR rhythm was more regular in the SG than in the AG during the first wakefulness period of MSLT, but not during MWT. AMIF (in high-frequency and in Total band) and CORR (in Total band) yielded sensitivity > 70%, specificity >75% and an area under ROC curve > 0.80 in classifying SG and AG patients.

Conclusion

The regularity of the RR rhythm measured at the beginning of the MSLT could be used to detect SDB patients with and without EDS before the appearance of sleep onset.     

Genomic Ancestry,Self-Rated Health and Its Association with Mortality in an Admixed Population: 10 Year Follow-Up of the Bambui-Epigen (Brazil) Cohort Study of Ageing

Background

Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification.

Materials/Methods

We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality.

Results

European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups.

Conclusions

Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry—and the inverse for European ancestry—were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality.     

Effect of P144? (Anti-TGF-β) in an “In Vivo” Human Hypertrophic Scar Model in Nude Mice

Background

Hypertrophic scars are one of the most important complications in surgery due to their cosmetic and functional impairments. Previous studies in tissue fibrotic disorders have shown promising results by inhibiting the biological activity effect of Transforming Growth Factor-beta 1 (TGF-β1). The aim of the current study was to determine the clinical effect of the inhibition of TGF-β1 signaling in human hypertrophic scars implanted in nude mice by topical application of an inhibitor of TGF-β1 (P144®).

Material and Methods

A total of 30 human hypertrophic scars were implanted in 60 nude mice. The animals were divided in two groups, group A (placebo) and group B (treatment). Group C (basal) was considered as the preimplanted scar samples and they were not implanted in the nude mice. After the shedding period, topical application of a lipogel containing placebo (group A) or P144 (group B) was daily administered during two weeks. The animals were sacrificed upon completion of the study. Total area, thickness and collagen fibers area were measure and compared across all groups. Immunohistochemistry was also performed in order to quantify collagen type I and type III and elastic fiber expressions present in the dermis.

Results

Successful shedding was achieved in 83,3% of the xenografts. The mean time for shedding was 35±5.4 days. Statistically significant differences were found in the total area, collagen fibers area and thickness between the groups. Increased elastic fibers and decreased collagen I were found in the P144-treated group compared to the basal group.

Conclusion

Topical application of an inhibitor of TGF-β1 may promote scar maturation and clinical improvement of hypertrophic scar morphology features in an “in vivo” model in nude mice after two weeks of treatment.     

Prevalence of the dhfr and dhps Mutations among Pregnant Women in Rural Burkina Faso Five Years after the Introduction of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine

Background

The emergence and spread of drug resistance represents one of the biggest challenges for malaria control in endemic regions. Sulfadoxine-pyrimethamine (SP) is currently deployed as intermittent preventive treatment in pregnancy (IPTp) to prevent the adverse effects of malaria on the mother and her offspring. Nevertheless, its efficacy is threatened by SP resistance which can be estimated by the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations. This was measured among pregnant women in the health district of Nanoro, Burkina Faso.

Methods

From June to December 2010, two hundred and fifty six pregnant women in the second and third trimester, attending antenatal care with microscopically confirmed malaria infection were invited to participate, regardless of malaria symptoms. A blood sample was collected on filter paper and analyzed by PCR-RFLP for the alleles 51, 59, 108, 164 in the pfdhfr gene and 437, 540 in the pfdhps gene.

Results

The genes were successfully genotyped in all but one sample (99.6%; 255/256) for dhfr and in 90.2% (231/256) for dhps. The dhfr C59R and S108N mutations were the most common, with a prevalence of 61.2% (156/255) and 55.7% (142/255), respectively; 12.2% (31/255) samples had also the dhfr N51I mutation while the I164L mutation was absent. The dhps A437G mutation was found in 34.2% (79/231) isolates, but none of them carried the codon K540E. The prevalence of the dhfr double mutations NRNI and the triple mutations IRNI was 35.7% (91/255) and 11.4% (29/255), respectively.

Conclusion

Though the mutations in the pfdhfr and pfdhps genes were relatively common, the prevalence of the triple pfdhfr mutation was very low, indicating that SP as IPTp is still efficacious in Burkina Faso.     

Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome

SCYX-7158, an oxaborole, is currently in Phase I clinical trials for the treatment of human African trypanosomiasis. Here we investigate possible modes of action against Trypanosoma brucei using orthogonal chemo-proteomic and genomic approaches. SILAC-based proteomic studies using an oxaborole analogue immobilised onto a resin was used either in competition with a soluble oxaborole or an immobilised inactive control to identify thirteen proteins common to both strategies. Cell-cycle analysis of cells incubated with sub-lethal concentrations of an oxaborole identified a subtle but significant accumulation of G2 and >G2 cells. Given the possibility of compromised DNA fidelity, we investigated long-term exposure of T. brucei to oxaboroles by generating resistant cell lines in vitro. Resistance proved more difficult to generate than for drugs currently used in the field, and in one of our three cell lines was unstable. Whole-genome sequencing of the resistant cell lines revealed single nucleotide polymorphisms in 66 genes and several large-scale genomic aberrations. The absence of a simple consistent mechanism among resistant cell lines and the diverse list of binding partners from the proteomic studies suggest a degree of polypharmacology that should reduce the risk of resistance to this compound class emerging in the field. The combined genetic and chemical biology approaches have provided lists of candidates to be investigated for more detailed information on the mode of action of this promising new drug class.