This study aimed to assess the longitudinal association between PCB exposure and the subsequent occurrence of hypertension in a highly polluted area. The study subjects had at least one PCB serum ...measurement between 2003 and 2014 and were followed up to the end of 2017. Hypertension cases were obtained from the Brescia Health Protection Agency database. Risk ratios of hypertension for total PCBs, high-, middle- and low-chlorinated groups and some common congeners were estimated using Poisson regression models. 1031 subjects were included (43.4% males, mean age 45.3 years). 229 subjects developed hypertension during the follow-up. Total PCBs, middle- and high-chlorinated PCBs, and particularly PCB congeners 138, 153 and 180 were associated with an about 2-fold increased risk of hypertension comparing the third with first tertile of distribution. After lipid-standardization of PCB serum values, the excess risk showed only a slight attenuation. A dose-response linear relationship of the risk of hypertension by PCB serum concentrations as continuous variables was also observed. The PCBs-hypertension association was stronger in overweight/obese subjects than those with normal body mass index. In this prospective cohort study the serum levels of total and middle to high chlorinated (≥6 Cl) PCBs were associated with an increased risk of hypertension, particularly among overweight/obese subjects.
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•The aim was to assess the PCB-hypertension association in a highly PCB polluted area.•A prospective cohort study (n = 1031, mean follow-up = 6.8 years) was carried out.•An increased risk of hypertension was found for middle and high chlorinated PCBs.•Non-dioxin like PCBs 138, 153 and 180 were associated with higher risk of hypertension.•The risk of hypertension did not vary controlling for serum lipids and other major risk factors.
Highlights • In this retrospective observational study carried out in Italy, 62 patients with refractory epilepsy of various origins (8 patients aged < 12 years) started treatment with perampanel as ...add-on therapy with exclusion of primary idiopathic generalized epilepsy. • At a median follow-up of 6.6 months, treatment with perampanel was associated with an overall response rate (reduction in seizures frequency ≥ 50% vs. baseline) in half of patients with 5% of patients becoming seizure free. The overall number of seizures significantly decreased from baseline to follow-up. • Adverse events (mainly consisting of behavioral disturbances, dizziness and sedation) occurred in 19 patients (30.6%). • Four patients (9.7%) stopped medication beacause of lack of efficacy and 10 for adverse events, 6 of them for aggravation of seizures. • These preliminary data indicate that perampanel was effective in children and adolescents with refractory epilepsies, and exhibited an acceptable safety profile.
Serum polychlorinated biphenyls (PCBs) have been associated with some chronic diseases, but little evidence exists on their possible relationship with neurodegenerative diseases. We aimed to assess ...the relationship between PCB exposure and the occurrence of dementia and Parkinson disease in a prospective cohort study in a highly polluted area (Brescia-Caffaro).
PCB exposure was assessed by measuring serum levels of 24 congeners. Data on the onset of dementia and Parkinson disease were retrieved by the Brescia Health Protection Agency Database. We used Poisson regression models adjusted for possible confounders to calculate rate ratios (RRs). A mediation analysis was performed to evaluate the mediatory role of cardiovascular diseases.
699 subjects without neurologic diseases at baseline were enrolled (48.1% males, 63.2 years of mean age) in 2001–2013 and followed up to 2018. During a mean follow-up of 8.8 years, 36 and 20 subjects developed dementia and Parkinson disease. Subjects in the 2nd and 3rd tertiles of the total PCBs distribution, compared with those in the 1st tertile, had a higher risk of dementia (RR = 2.30 and RR = 4.35). The estimates for Parkinson disease included the null value with wide confidence intervals. In the mediation analysis, the association between PCB exposure and dementia was dominated by the direct pathway and not by the hypertension-mediated pathway.
We observed a positive association between total PCBs serum levels and the onset of dementia not mediated by hypertension. For Parkinson, the unstable risk estimates did not allow to draw a conclusion on a possible association.
•PCB exposure was associated with higher risk of dementia independently of other risk factors.•These finding were confirmed using a dose-response analyses and controlling for lipids.•No conclusion can be made about the association between PCB exposure and Parkinson disease due to very few cases.
Sclerosing polycystic adenoma (SPA) is a rare salivary gland neoplasm originally thought to represent a non-neoplastic lesion. Recently we have encountered an index case of apocrine intraductal ...carcinoma of parotid gland of 62-year-old man with invasive salivary duct carcinoma component arising from SPA, a combination of tumor entities that has never been published so far. Here, we further explore the nature of SPA by evaluating 36 cases that were identified from the authors' consultation files. The patients were 25 females and 11 males aged 11 to 79 years (mean, 47.8 y). All tumors originated from the parotid gland. Their size ranged from 11 to 70 mm (mean, 28 mm). Histologically, all cases revealed characteristic features of SPA, such as lobulated well-circumscribed growth, focal hyalinized sclerosis, presence of large acinar cells with abundant brightly eosinophilic intracytoplasmic granules, and ductal components with variable cytomorphologic characteristics, including foamy, vacuolated, apocrine, mucous, clear/ballooned, squamous, columnar and oncocyte-like cells. In all cases, there were foci of intraluminal solid and cribriform intercalated duct-like epithelial proliferations with variable dysplasia which were positive for S100 protein and SOX10, and fully enveloped by an intact layer of myoepithelial cells. In addition, 14/36 cases (39%) had focal intraductal cribriform and micropapillary apocrine-type dysplastic epithelial structures composed of cells positive for androgen receptors and negative for S100/SOX10. The intraductal proliferations of both types showed focal mild to severe dysplasia in 17 cases (17/36; 47%). Two cases showed overt malignant morphology ranging from high-grade intraductal carcinoma to invasive carcinoma with an apocrine ductal phenotype. Next generation sequencing using ArcherDX panel targeting RNA of 36 pan-cancer-related genes and/or a TruSight Oncology 170/500 Kit targeting a selection of DNA from 523 genes and RNA from 55 genes was performed. Tumor tissue was available for molecular analysis in 11 cases, and 9 (9/11; 82%) of them harbored genetic alterations in the PI3K pathway. Targeted sequencing revealed HRAS mutations c.37G>C, p.(Gly13Arg) (2 cases) and c.182A>G, p.(Gln61Arg) (2 cases), and PIK3CA mutations c.3140A>G, p.(His1047Arg) (3 cases), c.1633G>A, p.(Glu545Lys) (1 case), and c.1624G>A, p.(Glu542Lys) (1 case). Moreover, mutations in AKT1 c.49G>A, p.(Glu17Lys) and c.51dup, p.(Tyr18ValfsTer15); c.49_50delinsAG, p.(Glu17Arg) (as a double hit) were found (2 cases). In addition, germinal and somatic mutation of PTEN c.1003C>T, p.(Arg335Ter); c.445C>T, p.(Gln149Ter), respectively, were detected. Gene fusions were absent in all cases. These prevalent molecular alterations converging on one major cancer-related pathway support the notion that SPA is a true neoplasm with a significant potential to develop intraluminal epithelial proliferation with apocrine and/or intercalated duct-like phenotype. The name SPA more correctly reflects the true neoplastic nature of this enigmatic lesion.
Silvoarable agroforestry could promote use of trees on farms in Europe, but its likely effect on production, farm profitability, and environmental services is poorly understood. Hence, from 2001 to ...2005, the Silvoarable Agroforestry for Europe project developed a systematic process to evaluate the biophysical and economic performance of arable, forestry, and silvoarable systems in Spain, France, and The Netherlands. A biophysical model called “Yield-SAFE” was developed to predict long-term yields for the different systems and local statistics and expert opinion were used to derive their revenue, costs, and pre- and post-2005 grant regimes. These data were then used in an economic model called “Farm-SAFE” to predict plot- and farm-scale profitability. Land equivalent ratios were greater than one, showing Yield-SAFE predicted that growing trees and crops in silvoarable systems was more productive than growing them separately. Pre-2005 grants in Spain and The Netherlands penalised silvoarable systems, but post-2005 grants were more equitable. In France, walnut and poplar silvoarable systems were consistently the most profitable system under both grant regimes. In Spain, holm oak and stone pine silvoarable systems were the least profitable system under pre-2005 grants, but only marginally less profitable than arable systems under post-2005 grants. In The Netherlands, low timber values and the opportunity cost of losing arable land for slurry manure application made silvoarable and forestry systems uncompetitive with arable systems under both grant regimes.
•Annual evapotranspiration of E. globulus and P. radiata plantations was the same.•Evapotranspiration by plantations was 100 mm more per year than for native forests.•Transpiration was about 100 mm ...greater in plantations than native forest.•The cause of greater transpiration differed between the plantation species.•E. globulus was 50% more water use efficient than than P. radiata.•Plantations were at least 5 times more water use efficient than native forests.
The water-use of plantations compared to alternative land uses is an important natural resource management issue in central Chile. The need for local data is heightened by a drying trend in the local climate, the potential for planted forests to store carbon and local plans to replace plantations of Pinus radiata D. Don with Eucalyptus globulus Labill. This paper compares the growth and water balance of P. radiata and native forest (Hualo – Nothofagus glauca (Phil.) Krasser) at a low rainfall site (1016 mm) and of P. radiata, E. globulus and native forest (Roble – N. obliqua Mirb.) at a medium rainfall (1395 mm) site.
Evapotranspiration of plantations of P. radiata in the north and of P. radiata and E. globulus further south was greater than in the local native forest by about 100 mm per year. This difference in total water use was due to greater transpiration by the plantation species; the sum of interception and soil evaporation was very similar for all forest types. Pinus radiata used more water than native forest throughout the year, owing to a more than two-fold greater stand sapwood area in the P. radiata. The difference between E. globulus and native forest was due to much higher sap flux density in the E. globulus during spring and early summer. Although there was no annual difference between the water use of E. globulus and P. radiata, the much greater transpiration of E. globulus in spring may result in earlier drying of soils and catchments planted with E. globulus than P. radiata species.
The annual growth rate of all forest types increased in the years after the end of Chilean mega drought. During the first year of this period, E. globulus produced significantly more wood per unit of water used (3.5 g wood kg−1) than P. radiata (2.1 g kg−1) which was, in turn, more than five times more efficient then the native forest (0.4 g kg−1).
Genome-wide association studies (GWAS) have successfully identified several risk loci for Alzheimer's disease (AD). Nonetheless, these loci do not explain the entire susceptibility of the disease, ...suggesting that other genetic contributions remain to be identified. Here, we performed a meta-analysis combining data of 4,569 individuals (2,540 cases and 2,029 healthy controls) derived from three publicly available GWAS in AD and replicated a broad genomic region (>248,000 bp) associated with the disease near the APOE/TOMM40 locus in chromosome 19. To detect minor effect size contributions that could help to explain the remaining genetic risk, we conducted network-based pathway analyses either by extracting gene-wise p-values (GW), defined as the single strongest association signal within a gene, or calculated a more stringent gene-based association p-value using the extended Simes (GATES) procedure. Comparison of these strategies revealed that ontological sub-networks (SNs) involved in glutamate signaling were significantly overrepresented in AD (p<2.7×10(-11), p<1.9×10(-11); GW and GATES, respectively). Notably, glutamate signaling SNs were also found to be significantly overrepresented (p<5.1×10(-8)) in the Alzheimer's disease Neuroimaging Initiative (ADNI) study, which was used as a targeted replication sample. Interestingly, components of the glutamate signaling SNs are coordinately expressed in disease-related tissues, which are tightly related to known pathological hallmarks of AD. Our findings suggest that genetic variation within glutamate signaling contributes to the remaining genetic risk of AD and support the notion that functional biological networks should be targeted in future therapies aimed to prevent or treat this devastating neurological disorder.
Helicobacter pylori is a common component of the human stomach microbiota, possibly dating back to the speciation of Homo sapiens. A history of pathogen evolution in allopatry has led to the ...development of genetically distinct H. pylori subpopulations, associated with different human populations, and more recent admixture among H. pylori subpopulations can provide information about human migrations. However, little is known about the degree to which some H. pylori genes are conserved in the face of admixture, potentially indicating host adaptation, or how virulence genes spread among different populations. We analyzed H. pylori genomes from 14 countries in the Americas, strains from the Iberian Peninsula, and public genomes from Europe, Africa, and Asia, to investigate how admixture varies across different regions and gene families. Whole-genome analyses of 723 H. pylori strains from around the world showed evidence of frequent admixture in the American strains with a complex mosaic of contributions from H. pylori populations originating in the Americas as well as other continents. Despite the complex admixture, distinctive genomic fingerprints were identified for each region, revealing novel American H. pylori subpopulations. A pan-genome Fst analysis showed that variation in virulence genes had the strongest fixation in America, compared with non-American populations, and that much of the variation constituted non-synonymous substitutions in functional domains. Network analyses suggest that these virulence genes have followed unique evolutionary paths in the American populations, spreading into different genetic backgrounds, potentially contributing to the high risk of gastric cancer in the region.
Mangroves act as buffer areas for marine systems, providing a barrier to contamination from continental sources by retaining metal pollutants. This study evaluates metal and semimetal contamination ...in the water column and sediments of four mangroves located on the volcanic island of São Tomé. Several metals had a widespread distribution, with occasional high concentrations, linked to potential sources of contamination. However, the two smaller mangroves, located in the northern part of the island, tended to have high metal concentrations. Arsenic and chromium concentrations were notably concerning, particularly if we consider this is an isolated and non-industrialized island. This work highlights the need for further assessments and a better understanding of processes and implications of metal contamination in mangroves. This assumes a particular relevance in areas that have specific geochemical compositions (i.e., volcanic origin) and in developing countries, where people often rely directly and heavily on resources obtained from these ecosystems.
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•High concentrations of Cu and Ni in São Tomé mangroves have a lithogenic origin.•Contamination by As and Cr suggest a strong contribution from human activities.•Smallest systems had higher metal content in water, but no sediment contamination.•Higher water contamination represents the continuous input from waste and chemicals.•Non-industrialized landscapes may also show severe contamination by human activities.
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