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Although the increasing prevalence of thyroid nodular disease (TND) has been partially attributed to the more frequent usage of improved diagnostics, environmental factors, such as exposures to thyroid-disrupting chemicals may contribute to TND and altered thyroid function. We investigated the association between exposures to bisphenol A (BPA), its chlorinated derivatives (ClxBPA), and bisphenol F (BPF) with TND and thyroid measures in adult women. A case-control study in Cyprus and Romania (n = 212) was conducted, where cases were those with thyroid nodules (diameter >3mm), and controls without nodules. Serum TSH and free thyroxine and urinary levels of BPA, BPF and ClxBPA were measured using immunoassays and tandem mass spectrometry, respectively. The association between exposures to BPA compounds and TND, adjusting for age, BMI, thyroid hormones and urinary iodine was assessed using logistic regression. Linear regression was used to explore associations between urinary BPA, BPF and ClxBPA and serum thyroid hormones. With the exception of a chlorinated BPA compound (30%), the rest of bisphenols were quantified in 100% of urine samples. A positive and significant (p<0.05) association was observed between urinary BPA and serum TSH that remained after adjusting for urinary creatinine, age, BMI, study site and disease status; there was no significant association between BPF or ClxBPA with TSH. None of the BPA compounds were associated with higher odds of TND. Our study found associations of urinary BPA with TSH but not with BPF or ClxBPA. A larger study would be justified.

Despite suggestive observational epidemiology and laboratory studies, there is limited experimental evidence regarding the effect of organic diet on human health. A cluster-randomized 40-day-organic (vs. 40-day-conventional) crossover trial was conducted among children (11-12 years old) from six schools in Cyprus. One restaurant provided all organic meals, and adherence to the organic diet intervention was measured by parent-provided diet questionnaire/diary data. Biomarkers of pyrethroid and neonicotinoid pesticide exposures were measured using tandem mass spectrometry, and oxidative stress/inflammation (OSI) biomarkers using immunoassays or spectrophotometry. Associations were assessed using mixed-effect regression models including interactions of treatment with time. Seventy-two percent of neonicotinoid biomarkers were non-detectable and modeled as binary (whether detectable). In post-hoc analysis, we considered the outcome of age-and-sex-standardized BMI. Multiple comparisons were handled using Benjamini-Hochberg correction for 58 regression parameters. Outcome data were available for 149 children. Children had lower pesticide exposures during the organic period (pyrethroid geometric mean ratio, GMR = 0.297; [95% confidence interval (95% CI): 0.237, 0.373], Q-value<0.05); odds for detection of neonicotinoids (OR = 0.651; [95% CI: 0.463, 0.917), Q-value<0.05); and decreased OSI biomarker 8-OHdG (GMR = 0.888; [95% CI: 0.808, 0.976], Q-value<0.05). An initial increase was followed by a countervailing decrease over time in the organic period for OSI biomarkers 8-iso-PGF2a and MDA. BMI z-scores were lower at the end of the organic period (β = -0.131; [95% CI: 0.179, -0.920], Q-value<0.05). Energy intake during the conventional period was reported to be higher than the recommended reference levels. The organic diet intervention reduced children's exposure to pyrethroid and neonicotinoid pesticides and, over time lowered biomarkers of oxidative stress/inflammation (8-iso-PGF2a, 8-OHdG and MDA). The several-week organic diet intervention also reduced children's age-and-sex-standardized BMI z-scores, but causal inferences regarding organic diet's physiological benefits are limited by the confounding of the organic diet intervention with caloric intake reduction and possible lifestyle changes during the trial. Trial registration: This trial is registered with ClinicalTrials.gov, number: NCT02998203.

To counter the second COVID-19 wave in autumn 2020, the Italian government introduced a system of physical distancing measures organized in progressively restrictive tiers (coded as yellow, orange, and red) imposed on a regional basis according to real-time epidemiological risk assessments. We leverage the data from the Italian COVID-19 integrated surveillance system and publicly available mobility data to evaluate the impact of the three-tiered regional restriction system on human activities, SARS-CoV-2 transmissibility and hospitalization burden in Italy. The individuals’ attendance to locations outside the residential settings was progressively reduced with tiers, but less than during the national lockdown against the first COVID-19 wave in the spring. The reproduction number R(t) decreased below the epidemic threshold in 85 out of 107 provinces after the introduction of the tier system, reaching average values of about 0.95-1.02 in the yellow tier, 0.80-0.93 in the orange tier and 0.74-0.83 in the red tier. We estimate that the reduced transmissibility resulted in averting about 36% of the hospitalizations between November 6 and November 25, 2020. These results are instrumental to inform public health efforts aimed at preventing future resurgence of cases. Italy introduced a system of tiered SARS-CoV-2 control measures in November 2020. Here, the authors quantify the effect of these measures on SARS-CoV-2 transmissibility and hospitalisation, and find reductions across all tiers with the greatest impacts associated with the most restrictive level.

Excess weight is a public health challenge affecting millions worldwide, including younger age groups. The human exposome concept presents a novel opportunity to comprehensively characterize all non-genetic disease determinants at susceptible time windows. This study aimed to describe the association between multiple lifestyle and clinical exposures and body mass index (BMI) in adolescents using the exposome framework. We conducted an exposome-wide association (ExWAS) study using U.S. National Health and Nutrition Examination Survey (NHANES) 2003–2004 wave for discovery of associations between study population characteristics and zBMI, and used the 2013–2014 wave to replicate analysis. We included non-diabetic and non-pregnant adolescents aged 12–18 years. We performed univariable and multivariable linear regression analysis adjusted for age, sex, race/ethnicity, household smoking, and income to poverty ratio, and corrected for false-discovery rate (FDR). A total of 1899 and 1224 participants were eligible from 2003–2004 and 2013–2014 survey waves. Weighted proportions of overweight were 18.4% and 18.5% whereas those for obese were 18.1% and 20.6% in 2003–2004 and 2013–2014, respectively. Retained exposure agents included 75 laboratory (clinical and biomarkers of environmental chemical exposures) and 64 lifestyle (63 dietary and 1 physical activity) variables. After FDR correction, univariable regression identified 27 and 12 predictors in discovery and replication datasets, respectively, while multivariable regression identified 22 and 9 predictors in discovery and replication datasets, respectively. Six were significant in both datasets: alanine aminotransferase, gamma glutamyl transferase, segmented neutrophils number, triglycerides; uric acid and white blood cell count. In this ExWAS study using NHANES data, we described associations between zBMI, nutritional, clinical and environmental factors in adolescents. Future studies are warranted to investigate the role of the identified predictors as early-stage biomarkers of increased BMI and associated pathologies among adolescents and to replicate findings to other populations.

Enhanced laboratory-based surveillance of invasive meningococcal disease (IMD) in Italy was only assessed indirectly by numerically comparing surveillance data cases with hospital discharge records (HDR). In this study, we evaluated the completeness, timeliness and sensitivity of the IMD surveillance in Italy from 2015 to 2018. Completeness and timeliness were described at the national and subnational level. A capture-recapture analysis was conducted to evaluate the sensitivity and positive predictive value (PPV) using HDR as the external source with a combination of deterministic and probabilistic approaches. The characteristics of the unmatched vs. matched cases were compared using multivariable Poisson modeling. Overall, the completeness of data improved, except for specific variables. Timeliness of notifications also improved to a median of 4 days from onset to reporting. For the years 2015–2017, the sensitivity of the surveillance was estimated at 71.4% and the PPV at 77.5%, changing to 80.6% and 66.9% respectively after removing cases with a secondary meningitis diagnosis. We noted substantial sub-national differences. In 2018 sensitivity was 66.5% (135/203) and the PPV was 79.4% (135/170). The adjusted relative risk of being unmatched in 2015–2017 was higher in cases that were ≥60 years, had missing information or symptom onset in December. The IMD surveillance system overall performs well with completeness and timeliness improving in time. Specific challenges identified for individual variables should guide further improvement. Notwithstanding limitations posed by the comparison database, sensitivity and PPV are promising. The study highlights that promoting etiological ascertainment in people ≥60 years and addressing sub-national challenges are the main current challenges to address.

Embraced as a breaking through methodological framework, the exposome is accompanied by novel exposure assessment methods and data processing tools or models. However, systematic mapping of the landscape of exposome studies, including their characteristics, components, tools and language has not been done so far. We conducted a scoping review to answer the question: “Which main domains of the human exposome have been included in the literature and which metrics of exposure(s)/outcome(s) have been used?” We performed a comprehensive search of human studies containing the word “exposom*” and published up to March 8, 2019. We screened 1133 records and 82 studies were included in the analysis. Most studies took place in Europe. Data analysis showed the non-systematic use of the exposome term. Most studies had a longitudinal design ( n  = 30, 37%), were conducted on adults ( n  = 40, 51%), and had a clearly defined health outcome in methodology ( n  = 48, 61%). Omics tools, such as metabolomics were used in 38 studies (49%), while environment-wide association analysis was used in 9 studies (11%). Thirty-seven (48%) studies included all three exposome domains (general external, specific external and internal) while 33 (42%) studies included two. Despite the large number of environmental components that comprise each of the exposome domains, only a subset has been currently studied. An optimized consideration of the components from all exposome domains, as well as the standardization of the exposure and outcome assessment methods is warranted to advance the utility of the human exposome concept.

After Italy's first national restriction measures in 2020, a robust approach was needed to monitor the emerging epidemic of coronavirus disease 2019 (COVID-19) at subnational level and provide data to inform the strengthening or easing of epidemic control measures. We adapted the European Centre for Disease Prevention and Control rapid risk assessment tool by including quantitative and qualitative indicators from existing national surveillance systems. We defined COVID-19 risk as a combination of the probability of uncontrolled transmission of severe acute respiratory syndrome coronavirus 2 and of an unsustainable impact of COVID-19 cases on hospital services, adjusted in relation to the health system's resilience. The monitoring system was implemented with no additional cost in May 2020. The infectious diseases surveillance system in Italy uses consistent data collection methods across the country's decentralized regions and autonomous provinces. Weekly risk assessments using this approach were sustainable in monitoring the epidemic at regional level from 4 May 2020 to 24 September 2021. The tool provided reliable assessments of when and where a rapid increase in demand for health-care services would occur if control or mitigation measures were not increased in the following 3 weeks. Although the system worked well, framing the risk assessment tool in a legal decree hampered its flexibility, as indicators could not be changed without changing the law. The relative complexity of the tool, the impossibility of real-time validation and its use for the definition of restrictions posed communication challenges.

Evidence of bisphenols’ obesogenic effects on humans is mixed and inconsistent. We aimed to explore the presence of bisphenol A (BPA), bisphenol F (BPF) and chlorinated BPA (ClBPA), collectively called the bisphenols, in different brain regions and their association with obesity using post-mortem hypothalamic and white matter brain material from twelve pairs of obese (body mass index (BMI) >30 kg/m 2 ) and normal-weight individuals (BMI <25 kg/m 2 ). Mean ratios of hypothalamus:white matter for BPA, BPF and ClBPA were 1.5, 0.92, 0.95, respectively, suggesting no preferential accumulation of the bisphenols in the grey matter (hypothalamic) or white matter-enriched brain areas. We observed differences in hypothalamic concentrations among the bisphenols, with highest median level detected for ClBPA (median: 2.4 ng/g), followed by BPF (2.2 ng/g) and BPA (1.2 ng/g); similar ranking was observed for the white matter samples (median for: ClBPA-2.5 ng/g, BPF-2.3 ng/g, and BPA-1.0 ng/g). Furthermore, all bisphenol concentrations, except for white-matter BPF were associated with obesity ( p  < 0.05). This is the first study reporting the presence of bisphenols in two distinct regions of the human brain. Bisphenols accumulation in the white matter-enriched brain tissue could signify that they are able to cross the blood-brain barrier.

On March 11, 2020, Italy imposed a national lockdown to curtail the spread of severe acute respiratory syndrome coronavirus 2. We estimate that, 14 days after lockdown, the net reproduction number had dropped below 1 and remained stable at »0.76 (95% CI 0.67-0.85) in all regions for >3 of the following weeks.

ObjectivesWe aimed to review SARS-CoV-2 seroprevalence studies conducted in Europe to understand how they may be used to inform ongoing control strategies for COVID-19.DesignScoping review of peer-reviewed publications and manuscripts on preprint servers from January 2020 to 15 September 2020.Primary measureSeroprevalence estimate (and lower and upper CIs). For studies conducted across a country or territory, we used the seroprevalence estimate and the upper and lower CIs and compared them to the total number of reported infections to calculate the ratio of reported to expected infections.ResultsWe identified 23 population-based seroprevalence studies conducted in Europe. Among 12 general population studies, seroprevalence ranged from 0.42% among residual clinical samples in Greece to 13.6% in an area of high transmission in Gangelt, Germany. Of the eight studies in blood donors, seroprevalence ranged from 0.91% in North-Western Germany to 23.3% in a high-transmission area in Lombardy region, Italy. In three studies which recruited individuals through employment, seroprevalence ranged from 0.5% among factory workers in Frankfurt, Germany, to 10.2% among university employees in Milan, Italy. In comparison to nationally reported cases, the extent of infection, as derived from these seroprevalence estimates, is manyfold higher and largely heterogeneous.ConclusionExposure to the virus in Europe has not reached a level of infection that would prevent further circulation of the virus. Effective vaccine candidates are urgently required to deliver the level of immunity in the population.