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Background: Few methods are available for transparently combining different evidence streams for chemical risk assessment to reach an integrated conclusion on the probability of causation. Hence, the UK Committees on Toxicity (COT) and on Carcinogenicity (COC) have reviewed current practice and developed guidance on how to achieve this in a transparent manner, using graphical visualisation., Methods/approach: All lines of evidence, including toxicological, epidemiological, new approach methodologies, and mode of action should be considered, taking account of their strengths/weaknesses in their relative weighting towards a conclusion on the probability of causation. A qualitative estimate of the probability of causation is plotted for each line of evidence and a combined estimate provided., Discussion/conclusions: Guidance is provided on integration of multiple lines of evidence for causation, based on current best practice. Qualitative estimates of probability for each line of evidence are plotted graphically. This ensures a deliberative, consensus conclusion on likelihood of causation is reached. It also ensures clear communication of the influence of the different lines of evidence on the overall conclusion on causality. Issues on which advice from the respective Committees is sought varies considerably, hence the guidance is designed to be sufficiently flexible to meet this need., 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 © 2024 Elsevier Inc. All rights reserved.)

Epidemiological studies performed in low- and middle-income countries have shown a positive association between solid fuel burning exposure and adverse health effects, including respiratory effects in adults. However, the evidence is less clear in other countries. We performed a systematic review of epidemiological studies conducted in Europe, North America (Canada and USA only), Australia and New Zealand on the association between outdoor and indoor exposure to solid fuel (biomass and coal) combustion and respiratory outcomes in adults. We identified 34 articles. The epidemiological evidence is still limited. Positive associations were found between indoor coal, wood and combined solid fuel combustion exposure and lung cancer risk, although based on a limited number of studies. A significant association was found between indoor solid fuel exposure and COPD risk. Inconsistent results were found considering indoor coal, wood and mixed solid fuel burning exposure and other respiratory outcomes (i.e. lower respiratory infections, upper respiratory infections and other upper respiratory tract diseases, asthma and respiratory symptoms). Inconsistent results were found considering the relationship between the exposure to outdoor wood burning exposure and overall respiratory mortality, asthma, COPD and respiratory symptoms in adults. The available epidemiological evidence between outdoor exposure to residential coal burning and respiratory outcomes suggests an increased risk of adverse respiratory effects. The studies considering the impact of the introduction of measures in order to reduce solid fuel burning on air quality and health showed an improvement in air quality resulting in a reduction of adverse respiratory effects. The identified epidemiological studies have several limitations. Additional and better conducted epidemiological studies are needed to establish whether exposure occurring indoors and outdoors to solid fuel combustion pollutants is associated with adverse respiratory outcomes in adults., (Crown Copyright © 2022. Published by Elsevier GmbH. All rights reserved.)

Background: Coffee contains many bioactive substances that can play a role on colorectal cancer. Epidemiological evidence of coffee intake and colorectal cancer is, however, inconsistent., Aim: To provide further information on the risk of colorectal cancer in relation to coffee consumption., Methods: Data derive from two companion case-control studies conducted in Italy and Spain within the European Union Project on Health Impacts of long-term exposure to disinfection by-products in Drinking Water and the Spanish Multi-Case Control study on Cancer. These included a total of 2289 incident cases with colorectal cancer and 3995 controls with information on coffee intake. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were derived from unconditional logistic regression models, adjusted for study centre, sex, age, education, smoking, and other covariates., Results: Compared with never coffee drinkers, the OR was 0.99 (95% CI 0.95-1.02) for total coffee consumption. There was no significant trend in risk with dose or duration, the ORs being 0.95 (95% CI 0.72-1.25) for an amount of five or more cups per day of coffee and 0.95 (95% CI 0.75-1.19) for a duration of consumption of 50 years or longer. The OR was 1.04 (95% CI 0.87-1.25) for two or more cups per day of decaffeinated coffee. There were no heterogeneity across strata of various covariates, as well as no apparent differences between various anatomical subsites., Conclusion: This large pooled analysis of two studies shows no association of coffee and decaffeinated coffee with colorectal cancer risk., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

A systematic literature review was carried out to examine the impact of portable air purifiers (PAPs) on indoor air quality (PM 2.5 ) and health, focussing on adults and children in indoor environments (homes, schools and offices). Analysed studies all showed reductions in PM 2.5 of between 22.6 and 92.0% with the use of PAPs when compared to the control. Associations with health impacts found included those on blood pressure, respiratory parameters and pregnancy outcomes. Changes in clinical biochemical markers were also identified. However, evidence for such associations was limited and inconsistent. Health benefits from a reduction in PM 2.5 would be expected as the cumulative body of scientific evidence from various cohort studies shows positive impacts of long-term reduction in PM 2.5 concentrations. The current evidence demonstrates that using a PAP results in short-term reductions in PM 2.5 in the indoor environment, which has the potential to offer health benefits., 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., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Dementia is arguably the most pressing public health challenge of our age. Since dementia does not have a cure, identifying risk factors that can be controlled has become paramount to reduce the personal, societal and economic burden of dementia. The relationship between exposure to air pollution and effects on cognitive function, cognitive decline and dementia has stimulated increasing scientific interest in the past few years. This review of the literature critically examines the available epidemiological evidence of associations between exposure to ambient air pollutants, cognitive performance, acceleration of cognitive decline, risk of developing dementia, neuroimaging and neurological biomarker studies, following Bradford Hill guidelines for causality. The evidence reviewed has been consistent in reporting associations between chronic exposure to air pollution and reduced global cognition, as well as impairment in specific cognitive domains including visuo-spatial abilities. Cognitive decline and dementia incidence have also been consistently associated with exposure to air pollution. The neuro-imaging studies reviewed report associations between exposure to air pollution and white matter volume reduction. Other reported effects include reduction in gray matter, larger ventricular volume, and smaller corpus callosum. Findings relating to ischemic (white matter hyperintensities/silent cerebral infarcts) and hemorrhagic (cerebral microbleeds) markers of cerebral small vessel disease have been heterogeneous, as have observations on hippocampal volume and air pollution. The few studies available on neuro-inflammation tend to report associations with exposure to air pollution. Several effect modifiers have been suggested in the literature, but more replication studies are required. Traditional confounding factors have been controlled or adjusted for in most of the reviewed studies. Additional confounding factors have also been considered, but the inclusion of these has varied among the different studies. Despite all the efforts to adjust for confounding factors, residual confounding cannot be completely ruled out, especially since the factors affecting cognition and dementia are not yet fully understood. The available evidence meets many of the Bradford Hill guidelines for causality. The reported associations between a range of air pollutants and effects on cognitive function in older people, including the acceleration of cognitive decline and the induction of dementia, are likely to be causal in nature. However, the diversity of study designs, air pollutants and endpoints examined precludes the attribution of these adverse effects to a single class of pollutant and makes meta-analysis inappropriate., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Epidemiological studies have shown a positive association between exposure to outdoor and indoor solid fuel combustion and adverse health effects. We reviewed the epidemiological evidence from Europe, North America, Australia and New Zealand on the association between outdoor and indoor exposure to solid fuel combustion and respiratory outcomes in children. We performed a systematic review and meta-analysis. Pooled relative risks (RRs) and 95% confidence intervals (CI) were calculated using random-effects models. We identified 74 articles. Due to limited evidence on other exposures and outcomes, we performed meta-analyses on the association between indoor wood burning exposure and respiratory outcomes. The RR for the highest vs the lowest category of indoor wood exposure was 0.90 (95% CI 0.77-1.05) considering asthma as an outcome. The corresponding pooled RRs for lower respiratory infection (LRI) and upper respiratory infection (URI) were 1.11 (95% CI 0.88, 1.41) and 1.11 (95% CI 0.85, 1.44) respectively. No association was found between indoor wood burning exposure and risk of wheeze and cough. Inconsistent and limited results were found considering the relationship between indoor wood burning exposure and other respiratory outcomes (rhinitis and hay fever, influenza) as well as indoor coal burning exposure and respiratory outcomes in children. Results from epidemiological studies that evaluated the relationship between the exposure to outdoor emissions derived from indoor combustion of solid fuels are too limited to allow firm conclusions. We found no association between indoor wood burning exposure and risk of asthma. A slight, but not significant, increased risk of LRI and URI was identified, although the available evidence is limited. Epidemiological studies evaluating the relationship between indoor coal burning exposure and respiratory outcomes, as well as, studies considering exposure to outdoor solid fuels, are too limited to draw any firm conclusions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Huge reductions in incinerators' emissions occurred over time, and results of older studies cannot be directly generalized to modern plants. We conducted a systematic review of the epidemiologic evidence of the health effects of incinerators, classifying plants in three generations, according to emission limits. A systematic search identified 63 epidemiologic studies, published in English, investigating health effects of incinerators on humans. We focused on cancer, cardio-cerebrovascular diseases (CVD) and respiratory diseases, pregnancy outcomes and congenital anomalies. Only six studies in the general population were on third generation incinerators providing data on pregnancy outcomes and congenital anomalies. Given the heterogeneity of methods, the abundance of ecological/semi-ecological studies and the lack of reliable quantitative measures of exposure in several studies we did not perform any meta-analysis. No excesses emerged concerning all cancers and lung cancer. An excess of non-Hodgkin lymphoma was reported in some earlier studies, but not for second generation plants. Possible excesses of soft tissue sarcomas were confined to earlier incinerators and the areas closer to the plants. No clear association emerged for CVD and diseases of the respiratory system. Several different pregnancy outcomes were considered, and no consistent association emerged, in spite of a few positive results. Studies were negative for congenital anomalies as a whole. Sporadic excesses were reported in a few studies for specific types of anomalies, but no consistent pattern emerged. Evaluation of the evidence was hindered by heterogeneity in reporting and classification of outcomes across studies. Direct evidence from third generation plants is scarce. Methodological issues in study design (mainly related to exposure assessment, confounding and ecological design) and analysis make interpretation of results complex. In spite of this, the overall evidence suggests that, if there were any excesses at all for older incinerators, they were modest at most. Additional monitoring of third generation plants needs to overcome methodological weaknesses., 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. Published by Elsevier Inc.)

Background: Soft tissue sarcoma (STS) is a heterogeneous group of rare neoplasms whose aetiology is largely unknown. Dioxin and dioxin-like compounds, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and polychlorinated biphenyls (PCBs), are potential risk factors for STS., Objectives: To investigate the relation of 17 PCBs congeners, assessed in human plasma, with STS risk., Methods: We conducted a case-control study in Italy, including 52 STS cases and 99 hospital-based controls. Selected PCB were extracted by high-performance liquid chromatography (HPLC) and measured with gas chromatography-mass spectrometry (GC-MS). Odds ratios (OR), and the corresponding 95% confidence intervals (CI), were estimated through multivariate logistic regression models., Results: The most frequently detected PCB congeners were 138, 170, 180 and 149 (detected in 40-77% of controls). The OR for the sum of all 17 PCB congeners was 1.20 (95% CI 0.50-2.92). In categorical analysis no consistent association was found for individual congeners and for groups based on Wolff's classification or the degree of chlorination. For continuous estimates, borderline positive associations emerged for Wolff's groups 2A (OR 1.23, 95% CI 0.97-1.55), 2B (OR 1.34, 95% CI 1.00-1.77, and 3 (OR 1.19, 95% CI 0.96-1.49), for moderately (OR 1.20, 95% CI 0.96-1.51) and highly (OR 1.18, 95% CI 0.99-1.41) chlorinated PCBs, and for congeners 170 (OR 1.26, 95% CI 0.98-1.63), 180 (OR 1.26, 95% CI 0.97-1.64) and 138 (OR 1.45, 95% CI 1.02-2.04)., Discussion: Most associations between PCBs and STS risk were not significant, but, given the limited sample size, we cannot exclude moderate associations.

In this article, we critically evaluate the evidence relating to the effects of the Mediterranean diet (MD) on the risk of cardiovascular disease (CVD). Strong evidence indicating that the MD prevents CVD has come from prospective cohort studies. However, there is only weak supporting evidence from randomized controlled trials (RCTs) as none have compared subjects who follow an MD and those who do not. Instead, RCTs have tested the effect of 1 or 2 features of the MD. This was the case in the Prevenciόn con Dieta Mediterránea (PREDIMED) study: the major dietary change in the intervention groups was the addition of either extravirgin olive oil or nuts. Meta-analyses generally suggest that the MD causes small favorable changes in risk factors for CVD, including blood pressure, blood glucose, and waist circumference. However, the effect on blood lipids is generally weak. The MD may also decrease several biomarkers of inflammation, including C-reactive protein. The 7 key features of the MD can be divided into 2 groups. Some are clearly protective against CVD (olive oil as the main fat; high in legumes; high in fruits/vegetables/nuts; and low in meat/meat products and increased in fish). However, other features of the MD have a less clear relationship with CVD (low/moderate alcohol use, especially red wine; high in grains/cereals; and low/moderate in milk/dairy). In conclusion, the evidence indicates that the MD prevents CVD. There is a need for RCTs that test the effectiveness of the MD for preventing CVD. Key design features for such a study are proposed.

The aim of this study was to investigate the relation between bladder cancer risk and the use of selected drugs for cardiovascular disease (CVD) prevention, such as aspirin, statins, and calcium channel blockers (CCBs). We analyzed data from a multicentric case-control study carried out in Italy between 2003 and 2014, including 690 bladder cancer cases and 665 hospital controls. Odds ratios (ORs) of bladder cancer and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models. The ORs for bladder cancer were 1.21 (95% CI: 0.87-1.68) for regular use of aspirin, 0.72 (95% CI: 0.54-0.97) for use of any CCBs, and 1.32 (95% CI: 0.87-1.99) for use of any statins. A slight inverse association was found with duration of use of CCBs, whereas no consistent association was found with duration of use, age at first use, and frequency for aspirin and statin use, or with indication of use for aspirin (as an analgesic or, for CVD prevention). No significant association was found for various combinations of drugs or for all drugs combined (OR=1.23, 95% CI: 0.31-4.85). Our data indicate the lack of a relevant association between the use of selected drugs for CVD prevention and bladder cancer risk, although suggest a potential favorable role for CCBs.

Purpose: To provide evidence of the relationship of Mediterranean diet (MD) on incidence/mortality for cardiovascular disease (CVD), coronary/ischemic heart disease (CHD)/acute myocardial infarction (AMI) and stroke (ischemic/hemorrhagic) by sex, geographic region, study design and type of MD score (MDS)., Methods: We performed a systematic review and meta-analysis of observational studies. Pooled relative risks (RRs) were calculated using random-effects models., Results: We identified 29 articles. The RR for the highest versus the lowest category of the MDS was 0.81 (95% CI 0.74-0.88) for the 11 studies that considered unspecified CVD, consistent across all strata. The corresponding pooled RR for CHD/AMI risk was 0.70 (95% CI 0.62-0.80), based on 11 studies. The inverse relationship was consistent across strata of study design, end point (incidence and mortality), sex, geographic area, and the MDS used. The overall RR for the six studies that considered unspecified stroke was 0.73 (95% CI 0.59-0.91) for the highest versus the lowest category of the MDS. The corresponding values were 0.82 (95% CI 0.73-0.92) for ischemic (five studies) and 1.01 (95% CI 0.74-1.37) for hemorrhagic stroke (four studies)., Conclusions: Our findings indicate and further quantify that MD exerts a protective effect on the risk of CVD. This inverse association includes CHD and ischemic stroke, but apparently not hemorrhagic stroke.

Proanthocyanidins are polymers of monomeric unit flavan-3-ols with antioxidant, anti-inflammatory and free radical scavenging activities. We investigated the association between proanthocyanidin intake and prostate cancer risk through data that were collected between 1991 and 2002 in an Italian case-control study, including a total of 1,294 incident, histologically confirmed cases of prostate cancer and 1,451 controls admitted to hospital for acute, non-neoplastic, and non-hormone-related diseases. We estimated odds ratios (ORs) and their 95% confidence intervals (CIs) using multiple logistic regression models, and computed energy-adjusted proanthocyanidin intakes using the residual method. The ORs for the highest versus the lowest tertile were 0.80 (95% CI 0.83-1.00) for energy-adjusted monomers and dimers combined, 0.72 (95% CI 0.59-0.87) for polymers with ≥ 3 mers, and 0.72 (95% CI 0.59-0.88) for total proanthocyanidins. The inverse relation was stronger among cases with a Gleason score ≥ 7, with the ORs of 0.56 (95% CI 0.40-0.78) for monomers and dimers, 0.62 (95% CI 0.40-0.78) for polymers with ≥ 3 mers, and 0.57 (95% CI 0.42-0.77) for total proanthocyanidins. These risk estimates were consistent across strata of age, education, body mass index, and family history of prostate cancer. Our data indicate an inverse association between proanthocyanidins and prostate cancer risk.

Toxicological and epidemiological evidence on the association between perfluorooctanoic acid (PFOA) or perfluorooctane sulfonic acid (PFOS) and birth/fetal weight was assessed. An extensive search for toxicological information in rats and mice, and a systematic search for epidemiological evidence were conducted. The linear regression coefficient (LRC) of birth weight (BrthW) on PFOA/PFOS was considered, and separate random effects meta-analyses for untransformed (i.e. not mathematically transformed) and log-transformed values were performed. Toxicological evidence: PFOA: 12 studies (21 datasets) in mice showed statistically significant lower birth/fetal weights from 5 mg/kg body weight per day. PFOS: most of the 13 studies (19 datasets) showed lower birth/fetal weights following in utero exposure. Epidemiological evidence: Sixteen articles were considered. The pooled LRC for a 1 ng/mL increase in untransformed PFOA (12 studies) in maternal plasma/serum was -12.8 g (95% CI -23.2; 2.4), and -27.1 g (95% CI -50.6; -3.6) for an increase of 1 log e ng/mL PFOA (nine studies). The pooled LRC for untransformed PFOS (eight studies) was -0.92 g (95%CI -3.4; 1.6), and for an increase of 1 log e ng/mL was -46.1(95% CI -80.3; -11.9). No consistent pattern emerged for study location or timing of blood sampling., Conclusions: Epidemiological and toxicological evidence suggests that PFOA and PFOS elicit a decrease in BrthW both in humans and rodents. However, the effective animal extrapolated serum concentrations are 10 2 -10 3 times higher than those in humans. Thus, there is no quantitative toxicological evidence to support the epidemiological association, thus reducing the biological plausibility of a causal relationship.

Background: Adherence to the Mediterranean diet (MD) is associated with a reduced risk of several cancers. However, studies conducted in Mediterranean regions are scanty., Methods: To investigate the relation between MD and colorectal cancer risk in Italy, we pooled data from three case-control studies, including a total of 3745 colorectal cancer cases and 6804 hospital controls. Adherence to the MD was assessed using an a priori Mediterranean Diet Score (MDS), based on nine components., Results: Compared with the lowest adherence to the MD (0-2 MDS), the odds ratio (OR) was 0.52 (95% confidence interval (CI) 0.43-0.62) for the highest adherence (7-9 MDS), with a significant inverse trend in risk (P<0.0001). The OR for a 1-point increment in the MDS was 0.89 (95% CI 0.86-0.91). The inverse association was consistent across studies, cancer anatomical subsites and strata of selected covariates., Conclusions: This Italian study confirms a favourable role of MD on colorectal cancer risk.

Rapid population aging has become a major challenge in the industrialized world and progressive aging is a key reason for making improvement in vaccination a cornerstone of public health strategy. An increase in age-related disorders and conditions is likely to be seen in the near future, and these are risk factors for the occurrence of a number of vaccine-preventable diseases. An improvement in infectious diseases prevention specifically aimed at adults and the elderly can therefore also decrease the burden of these chronic conditions by reducing morbidity, disability, hospital admissions, health costs, mortality rates and, perhaps most importantly, by improving the quality of life. Among adults, it is necessary to identify groups at increased risk of vaccine-preventable diseases and highlight the epidemiological impact and benefits of vaccinations using an evidence-based approach. This document provides clinical practice guidance on immunization for adults in order to provide recommendations for decision makers and healthcare workers in Europe. Although immunization is considered one of the most impactful and cost-effective public health measures that can be undertaken, vaccination coverage rates among adults are largely lower than the stated goal of ≥ 95% among adults, and stronger efforts are needed to increase coverage in this population. Active surveillance of adult vaccine-preventable diseases, determining the effectiveness of the vaccines approved for marketing in the last 5 y, the efficacy and safety of vaccines in immunocompromised patients, as well as in pregnant women, represent the priorities for future research.

Scope: To provide updated quantitative overall estimations of the relation between total allium, garlic, and onion intake on the risk of cancer of the upper aerodigestive tract (UADT)., Methods and Results: We combined data of published observational studies (21 case-control and four cohort studies), using a meta-analytic approach and random effects models. The overall relative risks (RR) and 95% confidence intervals (CIs) for the squamous cell carcinoma of the UADT were 0.79 (95% CI 0.56-1.11) for total allium, 0.74 (95% CI 0.57-0.95) for garlic, and 0.72 (95% CI 0.57-0.91) for onion for the highest versus the lowest consumption. The inverse relation was apparently stronger in case-control studies (RR 0.56, 95% CI 0.38-0.83 for total allium), in Chinese studies (RR 0.67, 95% CI 0.45-0.98 for garlic intake), and for esophageal than for head and neck cancers. Apparently, there was no relation between allium vegetable intake and adenocarcinoma of the esophagus., Conclusion: We found a moderate inverse association between allium vegetable intake and the risk of squamous cell carcinoma of the UADT in case-control studies. The relation was unclear in cohort studies and for adenocarcinoma of the esophagus., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Only a few studies analyzed the role of allium vegetables with reference to head and neck cancers (HNC), with mixed results. We investigated the potential favorable role of garlic and onion within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium., Methods and Results: We analyzed pooled individual-level data from eight case-control studies, including 4590 cases and 7082 controls. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between garlic and onion intakes and HNC risk. Compared with no or low garlic use, the ORs of HNC were 0.95 (95% CI 0.71-1.27) for intermediate and 0.74 (95% CI 0.55-0.99) for high garlic use (p for trend = 0.02). The ORs of HNC for increasing categories of onion intake were 0.91 (95% CI 0.68-1.21) for >1 to ≤3 portions per week, and 0.83 (95% CI 0.60-1.13) for >3 portions per week (p for trend = 0.02), as compared to <1 portion per week. We found an inverse association between high onion intake and laryngeal cancer risk (OR = 0.69; 95% CI 0.54-0.88), but no significant association for other subsites., Conclusion: The results of this pooled-analysis support a possible moderate inverse association between garlic and onion intake and HNC risk., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: To provide new epidemiological data and summarize evidence on the association between allium vegetable intake and gastric cancer risk., Methods and Results: Data were from an Italian case-control study including 230 cases and 547 controls. Odds ratios were derived using multiple logistic regression. We combined results from all published studies using random-effect models. In our case-control study, the odds ratios were 0.59 (95% confidence interval, CI, 0.25-1.41) for ≥2 portions of onion per week, 0.69 (95% CI, 0.41-1.15) for high garlic intake, and 0.70 (95% CI, 0.39-1.28) for frequent use of both onion and garlic. Besides our study, 22 case-control and four cohort studies were included in the meta-analyses (>10 000 cases). The pooled relative risks for the highest versus lowest intake category were 0.78 (95% CI, 0.67-0.91) for allium vegetables (ten case-control and four cohort studies), 0.60 (95% CI, 0.47-0.76) for garlic (12 case-control studies), and 0.55 (95% CI, 0.41-0.73) for onion (13 case-control studies). The pooled relative risk for high allium vegetable intake from the four cohorts was 1.02 (95% CI, 0.88-1.18)., Conclusion: High allium vegetable consumption is likely to reduce gastric cancer risk. This evidence is derived mainly from case-control studies. Further data from large cohorts are desirable for conclusive confirmation., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: To provide updated quantitative estimates of the associations between allium vegetables intake and risk of colorectal cancer and colorectal adenomatous polyps., Methods and Results: We combined all published data on the issue, using a meta-analytic approach. Pooled relative risks (RRs) were calculated using random-effects models. Sixteen studies (13 333 cases) were included in the meta-analyses of colorectal cancer. Seven studies provided information on garlic, six on onion, and four on total allium vegetables. The pooled RRs of colorectal cancer for the highest versus the lowest category of intake were 0.85 (95% confidence interval; CI, 0.72-1.00) for garlic (0.76 for case-control, 0.99 for cohort studies), 0.85 (95% CI, 0.70-1.04) for onion (0.74 for case-control, 1.04 for cohort studies), and 0.78 (95% CI, 0.56-1.08) for total allium vegetables. Significant heterogeneity was found for the three meta-analyses. The pooled RR of colorectal adenomatous polyps for the highest versus the lowest category of total allium vegetables intake was 0.88 (95% CI, 0.80-0.98, three studies), with no heterogeneity., Conclusion: High garlic intake may reduce the risk of colorectal cancer. However, evidence of such protection derived mainly from case-control studies. High intake of total allium vegetables may be associated with a risk reduction of colorectal adenomatous polyps., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

There are suggestions of an anticancerogenic effect of allium vegetables and their associated organosulfur components against several cancer types, including gastric cancer, but the issue remains open to discussion and quantification. The present critical review discussed the history, the health properties, the chemistry, the anticancerogenic evidences from experimental studies, and the anticancer mechanisms of allium vegetables. We also summarized findings from epidemiological studies concerning the association between different types of allium vegetables and gastric cancer risk, published up to date. Available data, derived mainly from case-control studies, suggested a favorable role of high intakes of allium vegetables, mainly garlic and onion, in the etiology of gastric cancer. In particular, of 10 studies, 7 suggested a favorable role of high intake of total allium vegetables and gastric cancer. All 14 studies on garlic and most studies on onion (more than 80%) reported a beneficial role of these allium types against gastric cancer. However several limitations, including possible publication bias and the difficulty to establish a dose-risk relationship, suggest caution in the interpretation. Evidences on other types of allium vegetables, as well as on the influence of different gastric cancer anatomical and histological types, are less consistent.

Objective: To determine efficacy of a single intra-articular injection of an autologous platelet concentrate for treatment of osteoarthritis in dogs., Design: Randomized, controlled, 2-center clinical trial., Animals: 20 client-owned dogs with osteoarthritis involving a single joint., Procedures: Dogs were randomly assigned to a treatment or control group. In all dogs, severity of lameness and pain was scored by owners with the Hudson visual analog scale and the University of Pennsylvania Canine Brief Pain Inventory, respectively, and peak vertical force (PVF) was determined with a force platform. Dogs in the treatment group were then sedated, and a blood sample (55 mL) was obtained. Platelets were recovered by means of a point-of-use filter and injected intra-articularly within 30 minutes. Control dogs were sedated and given an intra-articular injection of saline (0.9% NaCl) solution. Assessments were repeated 12 weeks after injection of platelets or saline solution., Results: Dogs weighed between 18.3 and 63.9 kg (40.3 and 140.6 lb) and ranged from 1.5 to 8 years old. For control dogs, lameness scores, pain scores, and PVF at week 12 were not significantly different from pretreatment values. In contrast, for dogs that received platelet injections, lameness scores (55% decrease in median score), pain scores (53% decrease in median score), and PVF (12% increase in mean PVF) were significantly improved after 12 weeks, compared with pretreatment values., Conclusions and Clinical Relevance: Results suggested that a single intra-articular injection of autologous platelets resulted in significant improvements at 12 weeks in dogs with osteoarthritis involving a single joint.

The detection of IgM antibodies for Schistosoma mansoni using gut-associated antigens (IgM-IFT) was compared to the parasitological Kato-Katz method for study of the transmission of schistosomiasis in an urban area in Campinas. About 400 schoolchildren whose ages ranged from 6 to 18 years, were observed for a period of two years. Blood samples on filter paper and fecal samples were collected, at intervals of six months. Serological (IgM-IFT) prevalence rates of 1.2%, 4.3%, 3.6%, 2.9% and 3.4% were obtained in five surveys carried out. S. mansoni eggs were detected in only one child out of the 225 children (0.4%) who were submitted to the Kato-Katz method (three slides for each fecal sample) in the 1st survey. Sixty eight children who submitted five blood samples, one for each survey, were found IFT negative throughout the study. No child was found to be IFT positive in all five surveys, and only four children showed IFT positive results in at least four surveys. Seroconversion from IFT negative to positive was observed from the 1st to the 2nd survey in six children, from the 2nd to the 3rd survey in three children, from the 3rd to the 4th survey in four children, and from the 4th to the 5th survey in two cases. However, confirmation of S. mansoni infection using the fecal examination was not possible in any of the cases. Also, in most of them the IFT result oscillated from negative to positive and vice versa. Our data implied that recent transmission of schistosomiasis in the study area was not possible.

Cases of Brasilian spotted fever (BSF) have been occurred since 1985, in the rural area of Pedreira town, situated 160 km away from the city of São Paulo (longitude 46 degrees 54'07", latitude 22 degrees 44'21"). Aiming at evaluating the prevalence of Brasilian spotted fever in this endemic area, single-serum samples were collected from 473 healthy persons, amongst city-dwellers and the local china industry workers. The obtained samples were tested by indirect immunofluorescence (IFA), in order to determine the antibodies titer for the group of Brasilian spotted fever. Twenty-five (5.3%) were considered positive (titer 3 1:64) and thirty-one (6.5%) were taken as "borderline" (titer 1:32). The results show a serologically positivity rate similar to other areas, known as endemic ones within the country.

A crude extract of Brucella melitensis was obtained by sonication, centrifugation and dialysis, and analyzed by quantitative immunoelectrophoresis. CIE analysis, using a high titer purified rabbit antibody anti-brucella fraction, showed that the Brucella melitensis extract contained at least 22 antigens that all moved towards the anode. The antigens of the crude extract able to interact with IgG of patients affected by brucellosis, were identified by means of CRIE using sheep 125I-anti human IgG. Fifteen sera of patients affected by brucellosis were analyzed by CRIE and three (Ag6, Ag12, Ag15) of the 22 antigens were able to bind specific human IgG to their corresponding immunoprecipitates. Ag6 was the only one present after one day of the CRIE plate exposure. After treatment of brucellosis patients with antibiotics for two weeks, the three antigens were still able to bind the specific IgG, after two months of treatment the antigens were reduced to two (Ag6, Ag15), while after ten months only one antigen (Ag6) was still able to bind specific human IgG. The brucellosis titer determined with common methods gave normal values after ten months of therapy. These results suggest that Ag6 is the most important antigen specific for human IgG. A preliminary determination of the molecular weight range of these antigens was carried out by a combination of size exclusion chromatography and CIE analysis. The Kav values were all above 66 kD.