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Thirty people (mostly children) experienced an episode of skin rash days after a sand sifting beach operation at Porto Pim Beach in Faial, Azores during June 2019. An environmental and epidemiologic investigation was conducted to identify the cause of the outbreak of skin rash. The epidemiologic investigation found that some of the patients experiencing symptoms had never entered the beach water. During the pollution period and throughout the epidemiologic investigation, faecal indicator bacteria levels (94 CFU/100 ml for intestinal enterococci and 61 CFU/100 ml for Escherichia coli) in water remained under the limits used for the ninety-five percentile calculation of an Excellent coastal and transitional bathing water defined in the Portuguese Legislation (100 CFU/100 ml for intestinal enterococci and 250 CFU/100 ml for Escherichia coli). Thus sand contact was considered as a likely primary exposure route. Sand microbiological analysis for faecal indicator organisms and electron microscopy strongly suggested faecal contamination. Chemical analysis of the sand also revealed a concomitant substance compatible with sodium-hypochlorite as analysed using gas chromatography and subsequently confirmed by free chlorine analysis. Inspection of the toilet facilities and sewage disposal system revealed a leaking sewage distribution box. Collectively, results suggest that the cause of the outbreak was the leaking underground sewage distribution box that serviced the beach toilet facilities (40 m from beach), where sodium-hypochlorite was used for cleaning and disinfection. This sewage then contaminated the surficial sands to which beach goers were exposed. Chlorine being an irritant substance, was believed to have been the cause of the symptoms given the sudden presentation and dissipation of skin rashes. No gastro-intestinal illness was reported during this episode and during the following 30 days. Like water, beach sand should also be monitored for safety, especially for areas serviced by aged infrastructure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Growth factors are thought to modulate neurological function in stroke recovery through effects in angiogenesis, neurogenesis, and neuroprotection., Methods: We tested the association of variants in the brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) genes, and epistatic interactions between them, with functional outcome in a sample of 546 stroke patients., Results: While none of the tested genes was independently associated with stroke outcome, two significant gene-gene interaction models were identified. One model combined one BDNF and three FGF2 markers, with a global odds ratio (OR) (95% confidence interval [CI]) of 4.15 [2.86-6.04]. The second model included one FGF2 and two VEGFA markers with a global OR [95% CI] = 2.54 [1.76-3.67]., Conclusions: The results provide evidence for gene interactions in stroke outcome, highlighting the complexity of the recovery mechanisms after a stroke event., (© 2012 The Author(s). European Journal of Neurology © 2012 EFNS.)

We hereby propose a novel approach to the identification of ischemic stroke (IS) susceptibility genes that involves converging data from several unbiased genetic and genomic tools. We tested the association between IS and genes differentially expressed between cases and controls, then determined which data mapped to previously reported linkage peaks and were nominally associated with stroke in published genome-wide association studies. We first performed gene expression profiling in peripheral blood mononuclear cells of 20 IS cases and 20 controls. Sixteen differentially expressed genes mapped to reported whole-genome linkage peaks, including the TTC7B gene, which has been associated with major cardiovascular disease. At the TTC7B locus, 46 tagging polymorphisms were tested for association in 565 Portuguese IS cases and 520 controls. Markers nominally associated in at least one test and defining associated haplotypes were then examined in 570 IS Spanish cases and 390 controls. Several polymorphisms and haplotypes in the intron 5-intron 6 region of TTC7B were also associated with IS risk in the Spanish and combined data sets. Multiple independent lines of evidence therefore support the role of TTC7B in stroke susceptibility, but further work is warranted to identify the exact risk variant and its pathogenic potential.

Objective: Animal studies have allowed important insights into the role of the nitric oxide synthase (NOS) enzymes in atherosclerosis and hypertension, as well as in stroke. In this study we tested the hypothesis that the NOS1 and NOS3 genes, respectively encoding neuronal NOS (nNOS) and endothelial NOS (eNOS), influence stroke susceptibility and outcome after a stroke event., Methods: We conducted a case-control association study in 551 ischemic stroke patients and 530 controls to assess the role of NOS1 and NOS3 variants in stroke susceptibility. The same genes were tested for association with stroke outcome in a subset of 431 patients., Results: Four NOS1 single nucleotide polymorphisms (SNPs) (rs2293050, rs2139733, rs7308402 and rs1483757) and four haplotypes were significantly associated with stroke susceptibility after adjusting for demographic, clinical and life-style risk factors, and correcting for multiple testing using the false discovery rate (FDR) method (SNPs: 0.004<(uncorrected)P<0.007 and 0.036

There is substantial evidence that inflammation within the central nervous system contributes to stroke risk and recovery. Inflammatory conditions increase stroke risk, and the inflammatory response is of major importance in recovery and healing processes after stroke. We investigated the role of inflammatory genes IL1B, IL6, MPO, and TNF in stroke susceptibility and recovery in a population sample of 672 patients and 530 controls, adjusting for demographic, clinical and lifestyle risk factors, and stroke severity parameters. We also considered the likely complexity of inflammatory mechanisms in stroke, by assessing the combined effects of multiple genes. Two interleukin 6 (IL6) and one myeloperoxidase (MPO) single-nucleotide polymorphisms were significantly associated with stroke risk (0.022<(corrected)P<0.042), highlighting gene variants of low to moderate effect in stroke risk. An epistatic interaction between the IL6 and MPO genes was also identified in association with stroke susceptibility (P=0.031 after 1,000 permutations). In a subset of 546 patients, one IL6 haplotype was associated with stroke outcome at 3 months ((corrected)P=0.024), an intriguing finding warranting further validation. Our findings support the association of the IL6 gene and present novel evidence for the involvement of MPO in stroke susceptibility, suggesting a modulation of stroke risk by main gene effects, clinical and lifestyle factors, and gene-gene interactions.

Background: Multiple lines of evidence suggest that genetic factors contribute to stroke recovery. The matrix metalloproteinases -2 (MMP-2) and -9 (MMP-9) are modulators of extracellular matrix components, with important regulatory functions in the Central Nervous System (CNS). Shortly after stroke, MMP-2 and MMP-9 have mainly damaging effects for brain tissue. However, MMPs also have a beneficial activity in angiogenesis and neurovascular remodelling during the delayed neuroinflammatory response phase, thus possibly contributing to stroke functional recovery., Methods: In the present study, the role of MMP-2 and MMP-9 genetic variants in stroke recovery was investigated in 546 stroke patients. Functional outcome was assessed three months after a stroke episode using the modified Rankin Scale (mRS), and patients were classified in two groups: good recovery (mRS 1). Haplotype tagging single nucleotide polymorphisms (SNPs) in the MMP-2 (N = 21) and MMP-9 (N = 4) genes were genotyped and tested for association with stroke outcome, adjusting for significant non-genetic clinical variables., Results: Six SNPs in the MMP-2 gene were significantly associated with stroke outcome (0.0018

Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases.

The aim of this work was to study the distribution of apolipoprotein E (APOE) genotypes and their association with some atherosclerotic risk factors, all of them modifiable: total, HDL and LDL cholesterol, triglycerides, systolic and diastolic blood pressure, BMI, waist circumference and smoking. The sample population was constituted of 672 healthy subjects recruited in the Lisbon area. Lipids were quantified by usual automatic enzymatic methods and the APOE genotypes performed in accordance with Hixson and Vernier. Blood pressure measurement and hypertension classification followed international specifications. The frequency distribution of APOE alleles was: epsilon2 = 6.4%, epsilon3 = 83.6% and epsilon4 = 10.0% and the more prevalent genotypes were epsilon2/epsilon3, epsilon3/epsilon3 and epsilon3/epsilon4 respectively 11.0%, 70.1% and 16.1%. We could only observe associations among the most prevalent genotypes and lipids, always statistically significant, specially when the epsilon4 allele was present which was even proved by an higher prevalence of epsilon4 in dyslipidemic subjects with the only exception of those with low HDL-c values. A stronger intervention in the epsilon4 carriers is so recommended through appropriate intervention measures on the connected modifiable risk factors.

Background: The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk., Methods: We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk., Results: Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45-0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41-7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13-7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect., Conclusion: Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.

The objective of this work was to study the distribution of apolipoprotein E (APOE) genotypes in a sample of the Portuguese population, and its association with the dyslipidemias observed. Study participants were healthy users of local Public Health Laboratories in six regions of mainland Portugal (Porto, Vila Real, Viseu, Lisboa, Portalegre and Faro). A total of 779 men and 1153 women aged 15-74 years agreed to participate. Fasting lipid levels and APOE genotypes were determined centrally at the National Institute of Health in Lisboa. The frequency distribution of APOE alleles was: epsilon2=5.3%, epsilon3=84.9% and epsilon4=9.8%. Dyslipidemias were present in 66.6% of men and 60.7% of women. Comparison of APOE genotypes and relative allele frequencies showed that in dyslipidemic compared to normolipidemic subjects, the epsilon4 allele was more frequent in both sexes, although in a more pronounced way in men than in women due to higher frequencies of epsilon3/epsilon4 and epsilon4/epsilon4 genotypes. The known association of the epsilon4 allele with high cholesterol levels, the association of the epsilon2 allele with low cholesterol levels, and the association of the epsilon2 allele with high levels of triglycerides and low levels of high-density lipoprotein-cholesterol were confirmed in this study.