Multivariate meta-analysis of the association of G-protein beta 3 gene (GNB3) haplotypes with cardiovascular phenotypes

The objective of the present study was to review previous investigations on the association of haplotypes in the G-protein β3 subunit (GNB3) gene with representative cardiovascular risk factors/phenotypes: hypertension, overweight, and variation in the systolic and diastolic blood pressures (SBP and DBP, respectively) and as well as body mass index (BMI). A comprehensive literature search was undertaken in Pubmed, Web of Science, EMBASE, Biological Abstracts, LILACS and Google Scholar to identify potentially relevant articles published up to April 2011. Six genetic association studies encompassing 16,068 participants were identified. Individual participant data were obtained for all studies. The three most investigated GNB3 polymorphisms (G-350A, C825T and C1429T) were considered. Expectation–maximization and generalized linear models were employed to estimate haplotypic effects from data with uncertain phase while adjusting for covariates. Study-specific results were combined through a random-effects multivariate meta-analysis. After carefully adjustments for relevant confounding factors, our analysis failed to support a role for GNB3 haplotypes in any of the investigated phenotypes. Sensitivity analyses excluding studies violating Hardy–Weinberg expectations, considering gender-specific effects or more extreme phenotypes (e.g. obesity only) as well as a fixed-effects “pooled” analysis also did not disclose a significant influence of GNB3 haplotypes on cardiovascular phenotypes. We conclude that the previous cumulative evidence does not support the proposal that haplotypes formed by common GNB3 polymorphisms might contribute either to the development of hypertension and obesity, or to the variation in the SBP, DBP and BMI.     

Lactate threshold and performance adaptations to 4 weeks of training in untrained swimmers: volume vs. intensity

The purpose of this study was to investigate the impact of 4 weeks of high-intensity vs. high-volume swim training on lactate threshold (LT) characteristics and performance. Thirteen untrained swimmers with a mean age of 19.0 ± 0.5 undertook an incremental swimming test before and after 4 weeks of training for the determination of LT. Performance was evaluated by a 50-m maximum freestyle test. The swimmers were assigned to 1 of each of 2 training groups. The high-intensity group (n = 6) focused on sprint training (SP) and swam a total of 1,808 ± 210 m. The high-volume group (n = 7) followed the same program as the SP group but swam an additional 1,100 m (38% more) of endurance swimming (SP + End). A training effect was evident in both groups as seen by the similar improvements in sprint performance of the 50-m maximum time (p < 0.01), peak velocity increases and the lower value of lactate at the individual LTs (p < 0.01). Lactate threshold velocity improved only in the SP + End group from 1.20 ± 0.12 m·s(-1) pretraining to 1.32 ± 0.12 m·s(-1) posttraining (p = 0.77, effect size = 1, p < 0.01), expressed by the rightward shifts of the individual lactate-velocity curves, indicating an improvement in the aerobic capacity. Peak lactate and lactate concentrations at LT did not significantly change. In conclusion, this study was able to demonstrate that 4 weeks of either high-intensity or high-volume training was able to demonstrate similar improvements in swimming performance. In the case of lack of significant changes in lactate profiling in response to high-intensity training, we could suggest a dissociation between the 2.     

The impact of climate suitability,urbanisation, and connectivity on the expansion of dengue in 21st century Brazil

Dengue is hyperendemic in Brazil, with outbreaks affecting all regions. Previous studies identified geographical barriers to dengue transmission in Brazil, beyond which certain areas, such as South Brazil and the Amazon rainforest, were relatively protected from outbreaks. Recent data shows these barriers are being eroded. In this study, we explore the drivers of this expansion and identify the current limits to the dengue transmission zone. We used a spatio-temporal additive model to explore the associations between dengue outbreaks and temperature suitability, urbanisation, and connectivity to the Brazilian urban network. The model was applied to a binary outbreak indicator, assuming the official threshold value of 300 cases per 100,000 residents, for Brazil’s municipalities between 2001 and 2020. We found a nonlinear relationship between higher levels of connectivity to the Brazilian urban network and the odds of an outbreak, with lower odds in metropoles compared to regional capitals. The number of months per year with suitable temperature conditions for Aedes mosquitoes was positively associated with the dengue outbreak occurrence. Temperature suitability explained most interannual and spatial variation in South Brazil, confirming this geographical barrier is influenced by lower seasonal temperatures. Municipalities that had experienced an outbreak previously had double the odds of subsequent outbreaks. We identified geographical barriers to dengue transmission in South Brazil, western Amazon, and along the northern coast of Brazil. Although a southern barrier still exists, it has shifted south, and the Amazon no longer has a clear boundary. Few areas of Brazil remain protected from dengue outbreaks. Communities living on the edge of previous barriers are particularly susceptible to future outbreaks as they lack immunity. Control strategies should target regions at risk of future outbreaks as well as those currently within the dengue transmission zone.     

Concerted and nonconcerted evolution of the Hsp70 gene superfamily in two sibling species of nematodes

We have identified the Hsp70 gene superfamily of the nematode Caenorhabditis briggsae and investigated the evolution of these genes in comparison with Hsp70 genes from C. elegans, Drosophila, and yeast. The Hsp70 genes are classified into three monophyletic groups according to their subcellular localization, namely, cytoplasm (CYT), endoplasmic reticulum (ER), and mitochondria (MT). The Hsp110 genes can be classified into the polyphyletic CYT group and the monophyletic ER group. The different Hsp70 and Hsp110 groups appeared to evolve following the model of divergent evolution. This model can also explain the evolution of the ER and MT genes. On the other hand, the CYT genes are divided into heat-inducible and constitutively expressed genes. The constitutively expressed genes have evolved more or less following the birth-and-death process, and the rates of gene birth and gene death are different between the two nematode species. By contrast, some heat-inducible genes show an intraspecies phylogenetic clustering. This suggests that they are subject to sequence homogenization resulting from gene conversion-like events. In addition, the heat-inducible genes show high levels of sequence conservation in both intra-species and inter-species comparisons, and in most cases, amino acid sequence similarity is higher than nucleotide sequence similarity. This indicates that purifying selection also plays an important role in maintaining high sequence similarity among paralogous Hsp70 genes. Therefore, we suggest that the CYT heat-inducible genes have been subjected to a combination of purifying selection, birth-and-death process, and gene conversion-like events.     

A methodological approach to assess and compare the sustainability level of agricultural plant production systems

A large number of indicators have been developed, in order to assess agricultural sustainability. However, there is no unified theoretical basis for the creation of a scientifically substantiated system of indicators and especially for data collection, analysis, scale and final goal. This paper proposes a methodological approach to assess and to compare the sustainability level of agricultural plant production systems on regional scale combining the three pillars of sustainability environment, economy and society. The combination of 21 individual indicators expressed a unique indicator was realized using the Multiattribute Value Theory (MAVT). The proposed methodology was testified on two geographical regions in Greece, through an empirical study, utilizing questionnaires completed during interviews with farm managers. The questionnaire was designed to gather data on current agricultural practices applied in each particular region and was separated into three broad groups of questions concerning (a) crop management practices, (b) economic performance and (c) social characteristics of each farm. The results of our study demonstrate the overall status of the studied regions, regarding their level of agricultural sustainability. Finally, findings related to the acceptability of the proposed methodological framework were discussed.     

Use of Fibrates and Cancer Risk: A Systematic Review and Meta-Analysis of 17 Long-Term Randomized Placebo-Controlled Trials

Background

Fibrates comprise a class of well-established antilipidemic agents that significantly reduce cardiovascular events. Given the concerns of cancer with fibrate therapy, we undertook a systematic review and meta-analysis to investigate the effects of fibrates on cancer outcomes.

Methods

We systematically searched Medline, Scopus, SCI Expanded, and the Cochrane Library for studies published up to 2012. We included randomized controlled trials (RCTs) that evaluated a fibrate therapy compared with placebo, had a minimum duration of two years, and reported data on the incidence of and/or deaths from cancer during the trial. Reviews of each study were performed and the relative data were abstracted. Pooled relative risk estimates (RR) and 95% confidence intervals (CIs) were calculated using the inverse variance weighted approach. Subgroup, sensitivity and meta-regression analyses were also conducted.

Results

Seventeen RCTs, involving 44,929 participants with an average follow-up of 5.2 years, contributed to the analysis. The degree of variability between trials was consistent with what would be expected to occur by chance alone. The quantitative synthesis of data retrieved from the RCTs was not indicative of a fibrate effect on cancer incidence (780 [fibrate] vs 814 [control]; RR = 1.02, 95% CI 0.92–1.12) or cancer death (385 [fibrate] vs 377 [control]; RR = 1.06, 95% CI: 0.92–1.22). When the analysis was restricted to major RCTs, the results did not substantially change. Similarly, we found no evidence of differential effects by length of follow-up or type of fibrate. Insignificant results were also obtained for the role of fibrates in cancers of the respiratory tract, breast, colon, gastrointestinal tract, prostate, genitourinary tract, or in melanoma.

Conclusion

Our findings demonstrate that fibrates have a neutral effect on cancer outcomes. However, it is important to continue monitoring their long-term safety profiles.     

Discussion on Spatial and Time Averaging Restrictions Within the Electromagnetic Exposure Safety Framework in the Frequency Range Above 6 GHz for Pulsed and Localized Exposures

Both the current and newly proposed safety guidelines for local human exposure to millimeter-wave frequencies aim at restricting the maximum local temperature increase in the skin to prevent tissue damage. In this study, we show that the application of the current and proposed limits for pulsed fields can lead to a temperature increase of 10°C for short pulses and frequencies between 6 and 30 GHz. We also show that the proposed averaging area of 4 cm², that is greatly reduced compared with the current limits, does not prevent high-temperature increases in the case of narrow beams. A realistic Gaussian beam profile with a 1 mm radius can result in a temperature increase about 10 times higher than the 0.4°C increase the same averaged power density would produce for a plane wave. In the case of pulsed narrow beams, the values for the time and spatial-averaged power density allowed by the proposed new guidelines could result in extreme temperature increases. Bioelectromagnetics. 2020;41:164–168. © 2019 Bioelectromagnetics Society.