Exposure to air pollution during the first 1000 days of life (from conception to the 2nd year of life) might be of particular relevance for long-term child health. Changes in molecular markers such ...as DNA methylation and telomere length could underlie the association between air pollution exposure and pollution-related diseases as well as serve as biomarkers for past exposure. The objective of this systematic review was to assess the association between air pollution exposure during pregnancy and the first two years of life and changes in DNA methylation or telomere length in children.
PubMed was searched in October 2020 by using terms relative to ambient air pollution exposure, DNA methylation, telomere length and the population of interest: mother/child dyads and children. Screening and selection of the articles was completed independently by two reviewers. Thirty-two articles matched our criteria. The majority of the articles focused on gestational air pollution exposure and measured DNA methylation/telomere length in newborn cord blood or placental tissue, to study global, candidate-gene or epigenome-wide methylation patterns and/or telomere length. The number of studies in children was limited.
Ambient air pollution exposure during pregnancy was associated with global loss of methylation in newborn cord blood and placenta, indicating the beginning of the pregnancy as a potential period of susceptibility. Candidate gene and epigenome-wide association studies provided evidence that gestational exposure to air pollutants can lead to locus-specific changes in methylation, in newborn cord blood and placenta, particularly in genes involved in cellular responses to oxidative stress, mitochondrial function, inflammation, growth and early life development. Telomere length shortening in newborns and children was seen in relation to gestational pollutant exposure.
Ambient air pollution during pregnancy is associated with changes in both global and locus-specific DNA methylation and with telomere length shortening. Future studies need to test the robustness of the association across different populations, to explore potential windows of vulnerability and assess the role of the methylation and telomere length as mediators in the association between early exposure to ambient air pollutants and specific childhood health outcomes.
•32 studies were identified that measured mostly air pollution exposure in pregnancy.•Air pollution exposure is associated with global DNA hypomethylation in newborns.•Air pollution exposure is associated with locus-specific methylation in newborns.•Air pollution exposure is associated with telomere length shortening in newborns.•These changes might be relevant for child’s health.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In high income countries one in five children still lives in poverty, which is known to adversely shape the life course health trajectory of these children. However, much less is understood on ...whether social and fiscal policies have the capacity to reverse this damage, which intervention is likely to be most effective and when these interventions should be delivered to maximise their impact. This systematic review attempts to address these questions by looking at the impact of income-support interventions, delivered during the first 1,000 days of life, on cardiovascular, metabolic, respiratory and mental health outcomes.
The review was restricted to experimental or quasi experimental studies conducted in high income countries. Studies were retrieved from multidisciplinary databases as well as health, economic, social sciences-specific literature browsers. All papers retrieved through the search strategy were double screened at title, abstract and full text stage. Relevant data of the selected studies were extracted and collected in tables, then summarised via narrative synthesis approach. Robustness of findings was assessed by tabulating impact by health outcome, type of intervention and study design.
Overall, 16 relevant papers were identified, including 15 quasi-experimental studies and one randomized control trial (RCT). Income-support interventions included were unconditional/conditional cash transfers, income tax credit and minimum wage salary policies. Most studies were conducted in United States and Canada. Overall, the evidence suggested limited effect on mental health indicators but a positive, albeit small, effect of most policies on birth weight outcomes. Despite this, according to few studies that tried to extrapolate the results into public health terms, the potential number of negative outcomes averted might be consistent.
Income-support interventions can positively affect some of the health outcomes of interest in this review, including birth weight and mental health. Given the large number of people targeted by these programs, one could infer that - despite small - the observed effect may be still relevant at population level. Nonetheless, the limited generalisability of the evidence gathered hampers firm conclusions. For the future, the breadth and scope of this literature need to be broadened to fully exploit the potential of these interventions and understand how their public health impact can be maximised.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To estimate the sensitivity and specificity of posterior elevation in discriminating keratoconus and subclinical keratoconus from normal corneas.
Prospective case-control study.
Seventy-five patients ...with keratoconus, 25 with subclinical keratoconus, and 64 refractive surgery candidates with normal corneas.
In one eye of each patient, posterior corneal elevation was measured in the central 5 mm using the Pentacam rotating Scheimpflug camera (Oculus, Wetzlar, Germany). Posterior corneal elevation in keratoconus and subclinical keratoconus were compared with that in normal corneas in separate analyses. Receiver operating characteristic (ROC) curves were used to determine the test's overall predictive accuracy (area under the curve) and to identify optimal posterior corneal elevation cutoff points to maximize sensitivity and specificity in discriminating keratoconus and subclinical keratoconus from normal corneas. Logistic regression was used to support cutoff points identified through ROC curve analysis, and to check for model validity; model goodness-of-fit was estimated using r(2), and its internal validation was by bootstrapping analysis.
Posterior corneal elevation in keratoconus, subclinical keratoconus, and normal corneas.
Mean posterior corneal elevation was statistically higher in keratoconus (100.7+/-49.2 microm; P<0.001), and subclinical keratoconus (39.9+/-15.0 microm; P = 0.01) versus normal corneas (19.8+/-6.37 microm). ROC curve analyses showed high overall predictive accuracy of posterior elevation for both keratoconus and subclinical keratoconus (area under the curve 0.99 and 0.93, respectively). Optimal cutoff points were 35 microm for keratoconus and 29 microm for subclinical keratoconus. These values were associated with sensitivity and specificity of 97.3% and 96.9%, respectively, for keratoconus, and 68% and 90.8% for subclinical keratoconus. Similar cutoff points were obtained with logistic regression analysis (38 microm for keratoconus and 32 microm for subclinical keratoconus). The models showed good fit to the data, including after internal validation.
Posterior corneal elevation very effectively discriminates keratoconus from normal corneas. Its efficacy is lower for subclinical keratoconus, and thus data concerning posterior elevation should not be used alone to stratify patients with this condition.
Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ...ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age‐adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8–143.2) for SqCC, 111.3 (95% CI: 69.8–177.5) for SCLC and 21.9 (95% CI: 16.6–29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5–124.6), 108.6 (95% CI: 50.7–232.8) and 16.8 (95% CI: 9.2–30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The exposome represents the totality of life course environmental exposures (including lifestyle and other non-genetic factors), from the prenatal period onwards. This holistic concept of exposure ...provides a new framework to advance the understanding of complex and multifactorial diseases. Prospective pregnancy and birth cohort studies provide a unique opportunity for exposome research as they are able to capture, from prenatal life onwards, both the external (including lifestyle, chemical, social and wider community-level exposures) and the internal (including inflammation, metabolism, epigenetics, and gut microbiota) domains of the exposome. In this paper, we describe the steps required for applying an exposome approach, describe the main strengths and limitations of different statistical approaches and discuss their challenges, with the aim to provide guidance for methodological choices in the analysis of exposome data in birth cohort studies. An exposome approach implies selecting, pre-processing, describing and analyzing a large set of exposures. Several statistical methods are currently available to assess exposome-health associations, which differ in terms of research question that can be answered, of balance between sensitivity and false discovery proportion, and between computational complexity and simplicity (parsimony). Assessing the association between many exposures and health still raises many exposure assessment issues and statistical challenges. The exposome favors a holistic approach of environmental influences on health, which is likely to allow a more complete understanding of disease etiology.
Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the ...repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998-2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen's kappa and Bland and Altman's limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Extracorporeal membrane oxygenation (ECMO) has become an established rescue therapy for severe acute respiratory distress syndrome (ARDS) in several etiologies including influenza A H1N1 pneumonia. ...The benefit of receiving ECMO in coronavirus disease 2019 (COVID-19) is still uncertain. The aim of this analysis was to compare the outcome of patients who received veno-venous ECMO for COVID-19 and Influenza A H1N1 associated ARDS.
This was a multicenter retrospective cohort study including adults with ARDS, receiving ECMO for COVID-19 and influenza A H1N1 pneumonia between 2009 and 2021 in seven Italian ICU. The primary outcome was any-cause mortality at 60 days after ECMO initiation. We used a multivariable Cox model to estimate the difference in mortality accounting for patients' characteristics and treatment factors before ECMO was started. Secondary outcomes were mortality at 90 days, ICU and hospital length of stay and ECMO associated complications.
Data from 308 patients with COVID-19 (N = 146) and H1N1 (N = 162) associated ARDS who had received ECMO support were included. The estimated cumulative mortality at 60 days after initiating ECMO was higher in COVID-19 (46%) than H1N1 (27%) patients (hazard ratio 1.76, 95% CI 1.17-2.46). When adjusting for confounders, specifically age and hospital length of stay before ECMO support, the hazard ratio decreased to 1.39, 95% CI 0.78-2.47. ICU and hospital length of stay, duration of ECMO and invasive mechanical ventilation and ECMO-associated hemorrhagic complications were higher in COVID-19 than H1N1 patients.
In patients with ARDS who received ECMO, the observed unadjusted 60-day mortality was higher in cases of COVID-19 than H1N1 pneumonia. This difference in mortality was not significant after multivariable adjustment; older age and longer hospital length of stay before ECMO emerged as important covariates that could explain the observed difference.
NCT05080933 , retrospectively registered.
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•In an Italian birth cohort three indirect methods to assess pesticide exposure during pregnancy were used.•The association of each of the maternal exposure variables with infant ...wheezing occurrence was evaluated.•Self-reported pesticide use during pregnancy was weakly associated with infant wheezing.•Involvement in agricultural activities during pregnancy was not associated with infant wheezing.•In rural areas, living in proximity of crops, especially fruit trees, during pregnancy was associated with infant wheezing.
Pesticide exposure in pregnancy may have health effects in the offspring. We studied whether maternal pesticides exposure during pregnancy is associated with infant wheezing.
The study involved 5997 children from the Italian NINFEA birth cohort, whose mothers were recruited during pregnancy between 2005 and 2016. We used questionnaires completed during pregnancy and 6 months after delivery to derive the following indirect measures of exposure: i) Self-reported pesticide use during the first and the third trimester of pregnancy; (ii) Agricultural activities during the same trimesters. We also evaluated the exposure to agricultural pesticides applied near home using the Corine Land Cover inventory to derive the proportion of a 200-metre buffer area around maternal home address covered by agricultural crops and specific crop types (arable land, fruit trees, heterogeneous cultivations). Questionnaires completed when the child turned 18 months reported information on wheezing between 6 and 18 months of age. We estimated the odds ratios of wheezing adjusting for the following maternal characteristics: age, education, parity, asthma, atopy, smoking in pregnancy, region and area of residence, pet ownership during pregnancy. Crops proximity analyses were restricted to residents in rural areas (N = 1674).
Agricultural activities during pregnancy were not associated with infant wheezing. Compared to no pesticide use, there was a weak positive association for self-reported use in the third trimester (POR: 1.30; 95 %CI 0.95–1.78) and a stronger association for use in both trimesters (POR: 1.72; 95 %CI 1.11–2.65). The relationship between the proportion of crops around the home address and the risk of infant wheezing, was J-shaped, in particular for fruit trees with the lowest risk for mid values and elevated risk for higher values.
We found some evidence of association for maternal pesticide use in pregnancy and residential proximity to fruit trees cultivations with infant wheezing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Testicular cancer is one of the most treatable cancers, with a 10-year survival of more than 95%. Many patients will be long-term survivors and this disease strikes men in an important phase of their ...lives, therefore the quality of life (QoL) among these patients is an area of particular interest. We aimed to study whether QoL in testicular cancer survivors depends on the time since cancer diagnosis. Data were collected from the EPSAM (Esposizioni postnatali e salute maschile) study, a case-control study on patients with testicular cancer, diagnosed between 1997 and 2008 in the province of Turin, Northern Italy, and interviewed between 2008 and 2010 (response rate among cases 57%). Patients were contacted through their oncologist at the San Giovanni Batista Hospital in Turin or through their general practitioner (GP) in the rest of the Province of Turin. QoL was assessed cross-sectionally using the short form 12 (SF-12) questionnaire, a generic short-form health survey that produces two summary scores, PCS (physical component score) and MCS (mental component score), to evaluate physical and mental health, respectively. Out of 234 study patients, 125 cases were seminomas and 109 cases were nonseminomas. The mean age at diagnosis was 34.5 years. After adjusting for age, time since diagnosis was not associated with PCS and MCS scores. Among nonseminomas, the median PCS slightly increased (adjusted OR (odds ratio) for 5+ vs < 2 years since cancer diagnosis: 1.78 (1.17-2.73), p = 0.008) and MCS slightly decreased (adjusted OR per 1-year increase since cancer diagnosis: 0.92, 95% CI: 0.82-1.05, p = 0.23) with time. Similar findings of no association between time since diagnosis and PCS and MCS were found when the analyses were restricted to the subgroup of cancer patients contacted through their oncologist, whose response proportion was 82%. In a study of testicular cancer patients interviewed cross-sectionally at 1 to more than 10 years since diagnosis, time since cancer diagnosis was not associated with QoL when we considered all germ-cell testicular cancer patients together. When stratified by histology type, we found certain evidence that nonseminoma cases report higher PCS over time since cancer diagnosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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