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Containers are fundamental elements for the development of international trade; however, it is estimated that there are more than 17 million retired containers stacked in ports around the world. Considering the high costs involved in the process of storing, transporting, or destroying these materials, in addition to their non-degradable nature, it is urgent to develop strategies for the sustainable use of these decommissioned containers. In this context, repurposing these containers into permanent structures is becoming a predominant trend. One solution is converting steel shipping structures into habitable spaces. However, due to the urgency with which Container Houses (CHs) are demanded in case of disasters, they are usually planned to be built as quickly as possible, serving as many people as possible, and do not consider the basic principles of energy efficiency. The performance of the CHs is, then, impaired, including risks of overheating, corrosion, and rust, among others, during service, making them an even more stressful experience for their users who are already in a vulnerable situation. Therefore, the objective of this study is to compare the performance of two thermal insulators applied to a temporary shelter container designed to promptly serve vulnerable populations. The model was developed in Building Information Modeling (BIM) software and simulated in Building Energy Simulation (BES) software, aiming to obtain subsidies for its technical and economic viability analysis. The results indicated that thermal insulators are able to generate significant savings in energy consumption, with mineral wool presenting better long-term performance.

An association between the R990G polymorphism of the CaSR gene, coding for calcium-sensing receptor, and primary hypercalciuria was found in kidney stone formers. To confirm this relationship, we investigated hypercalciuric women without stones and studied the effect of CaSR gene in human embryonic kidney cells (HEK-293). We genotyped for CaSR A986S, R990G, and Q1011E polymorphisms, 119 normocalciuric and 124 hypercalciuric women with negative history of kidney stones. Homozygous (n=2) or heterozygous (n=21) women for the 990G allele considered as one group had an increased risk to be hypercalciuric (odds ratio=5.2; P=0.001) and higher calcium excretion (P=0.005) in comparison with homozygous women for the 990R allele (n=220). HEK-293 cells were transfected with the variant allele at the three CaSR gene polymorphisms and with the most common allele with no variants. The transient increment of intracellular calcium caused by the stepwise increase of extracellular calcium was evaluated in stable transfected cells loaded with fura-2AM. The extracellular calcium concentration producing the half-maximal intracellular calcium response was lower in HEK-293 cells transfected with the 990G allele than in those transfected with the wild-type allele (P=0.0001). Our findings indicate that R990G polymorphism results in a gain-of-function of the calcium-sensing receptor and increased susceptibility to primary hypercalciuria.

BackgroundUric acid has been associated with blood pressure and hypertension. During the final stage of purine metabolism xanthine oxidoreductase (XOR) produces uric acid, while at the same time reactive oxygen species are formed. We hypothesized that uric acid production, as assessed indirectly from XOR variants, is associated with hypertension (figure 1).ObjectivesThe aim of the present study is to investigate the association of variants in the XOR gene with blood pressure and the development of hypertension.MethodsAnalyses were conducted in the prospective Flemish FLEMENGHO and European EPOGH study. Among 2769 participants (48.3% men; mean age 40.7 years) we genotyped 25 XOR SNPs and measured blood pressure at baseline and follow-up (median 8.8 years). The relation between variants of the XOR gene with changes in pulse pressure and mean arterial pressure over time; and incidence of hypertension, were analysed using multivariable mixed models and cox-regression, respectively.ResultsCompared with major allele homozygotes, pulse pressure increased approximately 2 mm Hg more in minor allele carriers of rs11904439 (P=value 0.01), whereas mean arterial pressure and diastolic blood pressure increased approximately 1 mm Hg less in minor allele carriers of rs2043013 (P=0.01). In 2050 participants normotensive at baseline, hazard ratios contrasting risk of hypertension in minor allele carriers vs. major allele homozygotes was 1.31 (95% confidence interval [CI] 1.03–1.68) for rs11904439 and 1.69 (95% CI 1.11–2.57) for rs148756340. With the false discovery rate set at 0.25, the aforementioned associations retained significance. The changes in systolic blood pressure from baseline to follow-up and the serum levels of uric acid at baseline (n=1949) were not associated with XOR.ConclusionsIn conclusion, pending confirmation in appropriately powered cohort studies, our findings suggest that variation in uric acid production, as captured by genetic variation in XOR, might be a predictor of changes in pulse pressure, mean arterial pressure and in the risk of hypertension.AcknowledgementThe authors gratefully acknowledge the clerical assistance of Mrs Renilde Wolfs.Disclosure of InterestNone declared

We recently identified rs3918226 as a hypertension susceptibility locus (-665 C>T), TThomozygosity being associated with higher hypertension risk. T compared with C allele transfected cells had lower endothelial nitric oxide synthase (eNOS) expression. In the family-based Flemish Study on Environment, Genes and Health Outcomes (50.9% women; mean age 40.3 years), we investigated whether 32 TT homozygotes had worse outcomes than 2787 C allele carriers. Over 15 years (median), total and cardiovascular mortality and cardiovascular and coronary events amounted to 269 (9.5%), 98 (3.5%), 247 (8.8%) and 120 (4.3%), respectively. While accounting for family clusters, the hazard ratios associated with TT homozygosity were 4.11 (P = 0.0052) for cardiovascular mortality (4 deaths), 2.75 (P = 0.0067) for cardiovascular events (7 endpoints) and 3.10 (P = 0.022) for coronary events (4 endpoints). With adjustment for cardiovascular risk factors, these hazard ratios were 6.01 (P = 0.0003), 2.64 (P = 0.0091) and 2.89 (P = 0.010), respectively. Analyses unadjusted for blood pressure and antihypertensive treatment produced consistent results. For all fatal plus nonfatal cardiovascular events, the positive predictive value, attributable risk and population-attributable risk associated with TT homozygosity were 21.9, 61.5 and 2.0%, respectively. In conclusion, TT homozygosity at the position -665 in the eNOS promoter predicts adverse outcomes, independent of blood pressure and other risk factors. Journal of Human Hypertension (2015) 29, 167-172; doi: 10.1038/jhh.2014.66; published online 7 August 2014

We recently identified rs3918226 as a hypertension susceptibility locus ( −665 C>T ), TT homozygosity being associated with higher hypertension risk. T compared with C allele transfected cells had lower endothelial nitric oxide synthase ( eNOS ) expression. In the family-based Flemish Study on Environment, Genes and Health Outcomes (50.9% women; mean age 40.3 years), we investigated whether 32 TT homozygotes had worse outcomes than 2787 C allele carriers. Over 15 years (median), total and cardiovascular mortality and cardiovascular and coronary events amounted to 269 (9.5%), 98 (3.5%), 247 (8.8%) and 120 (4.3%), respectively. While accounting for family clusters, the hazard ratios associated with TT homozygosity were 4.11 ( P =0.0052) for cardiovascular mortality (4 deaths), 2.75 ( P =0.0067) for cardiovascular events (7 endpoints) and 3.10 ( P =0.022) for coronary events (4 endpoints). With adjustment for cardiovascular risk factors, these hazard ratios were 6.01 ( P =0.0003), 2.64 ( P =0.0091) and 2.89 ( P =0.010), respectively. Analyses unadjusted for blood pressure and antihypertensive treatment produced consistent results. For all fatal plus nonfatal cardiovascular events, the positive predictive value, attributable risk and population-attributable risk associated with TT homozygosity were 21.9, 61.5 and 2.0%, respectively. In conclusion, TT homozygosity at the position − 665 in the eNOS promoter predicts adverse outcomes, independent of blood pressure and other risk factors.

Complement receptor 1 (CR1) levels have been associated with malarial susceptibility and/or severity of the disease in different population groups, and CR1 is a receptor for Plasmodium falciparum . In this study, multiple CR1 single-nucleotide polymorphisms (SNPs) showed strong evidence of population differentiation between Sardinian and other European ethnic groups. Cross population algorithms comparing haplotype structure and differences in haplotype and allele frequency distribution provided additional support for natural selection of CR1 in Sardinia. The predominant Sardinian CR1 haplotype included SNPs that are associated with decreased CR1 levels in Europeans and other population groups. Previous studies have shown that the SNPs within the dominant Sardinian haplotype have a significantly higher frequency in a malaria endemic compared with non-endemic regions in India. Together with the historical evidence of the prevalence of malaria in Sardinia, these data support the role of malaria leading to positive selection of this CR1 haplotype in Sardinia.

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469 410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case–control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case–control analysis, the lowest two P -values were located within DLGAP1 ( P =2.49 × 10 −6 and P =3.44 × 10 −6 ), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3 , exceeded the genome-wide significance threshold with a P -value=3.84 × 10 −8 . However, when trios were meta-analyzed with the case–control samples, the P -value for this variant was 3.62 × 10 −5 , losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio–case–control sample, a significant enrichment of methylation QTLs ( P <0.001) and frontal lobe expression quantitative trait loci (eQTLs) ( P =0.001) was observed within the top-ranked SNPs ( P <0.01) from the trio–case–control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

A third of patients with the DiGeorge syndrome have congenital kidney and urinary tract anomalies. This study provides evidence that haploinsufficiency of CRKL is associated with such anomalies in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Deletions on chromosome 22q11.2 are the most common cause of the DiGeorge syndrome (Online Mendelian Inheritance in Man [OMIM] number, 188400) and the velocardiofacial syndrome (OMIM number, 192430) and constitute the most common microdeletion disorder in humans, with an estimated prevalence of 1 in 2000 to 4000 live births. 1 – 3 The DiGeorge syndrome is a debilitating, multisystemic condition that features (with variable expressivity) cardiac malformations, velopharyngeal insufficiency, hypoparathyroidism with hypocalcemia, and thymic aplasia with immune deficiency. Additional phenotypes include neurodevelopmental defects and urogenital malformations. 4 – 7 The long arm of chromosome 22 contains multiple segmental duplications (low-copy repeats) that confer a . . .

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution. Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

We compared a standard antihypertensive losartan treatment with a pharmacogenomics-guided rostafuroxin treatment in never-treated Caucasian and Chinese patients with primary hypertension. Rostafuroxin is a digitoxigenin derivative that selectively disrupts the binding to the cSrc-SH2 domain of mutant α-adducin and of the ouabain-activated Na-K pump at 10–11 M. Of 902 patients screened, 172 were enrolled in Italy and 107 in Taiwan. After stratification for country and genetic background, patients were randomized to rostafuroxin or losartan, being the difference in the fall in office systolic blood pressure (OSBP) after 2-month treatment the primary endpoint. Three pharmacogenomic profiles (P) were examined, considering: P1, adding to the gene variants included in the subsequent P2, the variants detected by post-hoc analysis of a previous trial; P2, variants of genes encoding enzymes for endogenous ouabain (EO) synthesis (LSS and HSD3B1), EO transport (MDR1/ABCB1), adducin (ADD1 and ADD3); P3, variants of the LSS gene only. In Caucasians, the group differences (rostafuroxin 50 μg minus losartan 50 mg in OSBP mmHg) were significant both in P2 adjusted for genetic heterogeneity (P2a) and P3 LSS rs2254524 AA [9.8 (0.6–19.0), P = 0.038 and 13.4 (25.4–2.5), P = 0.031, respectively]. In human H295R cells transfected with LSS A and LSS C variants, the EO production was greater in the former (P = 0.038); this difference was abolished by rostafuroxin at 10–11 M. Chinese patients had a similar drop in OSBP to Caucasians with losartan but no change in OSBP with rostafuroxin. These results show that genetics may guide drug treatment for primary hypertension in Caucasians.