Weight Gain in Early Infancy Impacts Appetite Regulation in the First Year of Life. A Prospective Study of Infants Living in Cyprus.

BACKGROUND: Eating behavior is associated with weight gain in infancy and childhood. Few studies found a bidirectional association between weight gain and eating behavior development in childhood, but there is little data on the association in early infancy, a period critical for the programming of obesity risk. OBJECTIVE: We investigated the bidirectional association between appetite traits and weight gain during the first year of life. METHODS: Participants were part of a cohort of 432 infants born in Cyprus. Appetite traits were measured using the Baby Eating Behavior Questionnaire or the Child Eating Behavior Questionnaire at age 2 to 4 wk, 6 mo, and 12 mo. Weight and length were collected at birth, 4 wk, 6 mo, and 12 mo. Multivariable linear regression was used to analyze associations between appetite traits at 2 to 4 wk and 6 mo and weight for age z-score change (WFAZC) between 4 wk and 6 mo and 6 and 12 mo. Associations were also analyzed in the opposite direction, between WFAZC from birth to 4 wk, 4 wk to 6 mo, and 6 mo to 12 mo and appetite traits at 4 wk, 6 mo, and 12 mo. RESULTS: Satiety responsiveness (SR) at 2 to 4 wk was associated with lower WFAZC from 4 wk to 6 mo (ß: -0.17; 95% CI: -0.30, -0.04) and SR at age 6 mo was associated with lower WFAZC from 6 to 12 mo (ß: -0.09; 95% CI: -0.17, -0.02). WFAZC from 4 wk to 6 mo was associated with higher enjoyment of food at 12 mo (ß: 0.11; 95% CI: 0.01, 0.20), higher food responsiveness at 12 mo (ß: 0.17; 95% CI: 0.04, 0.30), and lower SR at both 6 mo (ß: -0.11; 95% CI: -0.21, -0.01) and 12 mo (ß: -0.14; 95% CI: -0.24, -0.03). CONCLUSIONS: We found a bidirectional association between weight gain and appetite traits in infancy, suggesting that the effect of postnatal weight gain on obesity development is partly mediated by programming of appetite traits.

Relative validity and reproducibility of the CyFFQ semiquantitative food frequency questionnaire for assessing dietary intake in Cypriot adults.

BACKGROUND: Assessment of dietary intake is fundamental for evaluating the interrelationships between diet and disease. The present study aimed to develop and validate the semiquantitative Cypriot food frequency questionnaire (CyFFQ). METHODS: A 171-item paper-and-pencil semiquantitative interview-administered FFQ was developed, including local foods and culturally specific meals commonly consumed among Cypriot adults. FFQ reproducibility was assessed by comparing the energy-adjusted daily macro- and micronutrients intake at baseline (FFQ1) and 1 year later (FFQ2) using a Wilcoxon matched pairs signed rank test and intraclass correlation coefficients (ICCs) in a random sample of Cypriot adults. FFQ relative validity was evaluated by comparing the intake as estimated by FFQ2 with that obtained from the average of three 24-h recalls taken over the year between FFQ1 and FFQ2. Associations between nutrient intakes estimated using FFQ2 and the 24-h recalls were assessed using Spearman rank correlation and Bland-Altman plots were used to assess agreement between the FFQ and the 24-h recalls. RESULTS: Among eligible participants, 68 (78%) completed the study (44.1% males, aged 30.5-47.5 years). The energy-adjusted intakes of macro- and micronutrients did not significantly differ between the two FFQs, excluding magnesium. The FFQ2 and the averaged 24-h recalls were significantly correlated for most macro- and micronutrients. The median (interquartile) ICC for all macro- and micronutrients was 0.46 (0.38-0.52) (p < 0.05). Agreement was satisfactory (>30%) for most micro- and macronutrients. Bland-Altman plots also confirmed good agreement between the two methods. CONCLUSIONS: The CyFFQ is a valid and reliable tool for assessing dietary consumption in Cypriot adults.

Temporal trends in COVID-19 outcomes in people with rheumatic diseases in Ireland: data from the COVID-19 Global Rheumatology Alliance registry.

OBJECTIVES: Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. METHODS: Data entered into the C19-GRA provider registry from Ireland between 24 March 2020 and 9 July 2021 were analysed. Differences in the likelihood of hospitalization and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher's exact test, as appropriate. Trends in odds of hospitalization and mortality over time were investigated using logistic regression with the time period as a categorical variable. RESULTS: Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13-96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities and specific comorbidities of cancer, cardiovascular and pulmonary disease were more common in those hospitalized. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalized. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalization or mortality did not change over time. CONCLUSION: No temporal trend was observed in either COVID-19-related hospitalization or mortality outcomes for people with rheumatic disease in Ireland.

Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January-August 2020.

BACKGROUND: Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). METHODS: Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. RESULTS: As of August 2020, 442,677 (range: 18-185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112-1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. CONCLUSIONS: Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of premature mortality.

Effect of vaccination on SARS-CoV-2 reinfection risk: a case-control study in the Republic of Cyprus.

OBJECTIVES: We explored the effectiveness of COVID-19 vaccines in preventing reinfection in the Republic of Cyprus. STUDY DESIGN: This was a matched case-control study (1:2). METHODS: Cases were adults with a first episode of SARS-CoV-2 infection in 2020 and a second episode (i.e. reinfection) between June and August 2021. Controls were adults with only one infection episode in 2020 (i.e. not reinfected). Matching was performed by age, gender, and week of diagnosis for the first episode. The reinfection date of a case was applied to the matched controls for estimating full or partial vaccination status. Cases and controls were classified as unvaccinated, partially vaccinated (i.e. vaccination series not completed or final dose received ≤14 days before the reinfection date), or fully vaccinated (i.e. final dose received >14 days before the reinfection date). Conditional logistic regression was performed to calculate odds ratios and 95% confidence intervals for full or partial vaccination, against no vaccination, between controls and cases. RESULTS: This study showed that controls were more likely to be vaccinated (odds ratio for full vaccination: 5.51, 95% confidence interval: 2.43-12.49) than cases. CONCLUSIONS: This finding answers a pressing question of the public and supports the offer of vaccination to people with previous SARS-CoV-2 infection.

Lifestyle habits of adults during the COVID-19 pandemic lockdown in Cyprus: evidence from a cross-sectional study.

BACKGROUND: The COVID-19 pandemic and the widespread adoption of virus control measures have inevitably disrupted efforts to address lifestyle risk factors for non-communicable diseases (NCD). This study aimed to explore the effects of COVID-19 lockdown on all lifestyle medicine pillars, namely diet, physical activity, sleep, stress, social support and use of risky substances. METHODS: This was a cross-sectional study on a convenient sample of adults who resided in Cyprus during the Spring 2020 lockdown. Participants completed an anonymous online questionnaire comprised of six validated tools regarding the following lifestyle behaviours before and during lockdown: adherence to the Mediterranean diet, physical activity, stress and social support levels, sleep pattern and use of risky substances such as smoking and alcohol. Paired before and during lockdown comparisons for each lifestyle pillar were undertaken using Wilcoxon Signed-Rank test and Bowker symmetry Test where response was numerical (non-parametric data) and categorical respectively. Furthermore, stratified analyses for sociodemographic characteristics were performed. RESULTS: Out of 745 participants, 74% were female and median age was 39 years. Overall participants reported significantly higher perceived stress score (22 v 25, p <  0.01), lower social support score (71 v 68, p <  0.001), and worse sleep quality score (4 v 5, p <  0.01) during lockdown. Mediterranean diet (MD) adherence was moderate and increased significantly only in those practicing religious fasting (score of 6 v 7, p <  0.01). Total minutes spent sitting increased (120 v 180, p <  0.01) although overall physical activity score did not significantly change. Smoking intensity increased during lockdown whilst frequency of alcohol consumption decreased (ptrend = 0.03 and <  0.01, respectively). CONCLUSION: Various lifestyle factors were adversely affected by the COVID-19 lockdown in Cyprus. Evidence from this study supports development of holistic lifestyle interventions during and following the pandemic to reduce short and long-term NCD risks by building on lifestyle behaviour strengths and addressing longstanding and emerging gaps and needs.

Provider Misinterpretation, Documentation, and Follow-Up of Definitive Urine Drug Testing Results.

BACKGROUND: Urine drug testing (UDT) is an essential tool to monitor opioid misuse among patients on chronic opioid therapy. Inaccurate interpretation of UDT can have deleterious consequences. Providers' ability to accurately interpret and document UDT, particularly definitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) results, has not been widely studied. OBJECTIVE: To examine whether providers correctly interpret, document, and communicate LC-MS/MS UDT results. DESIGN: This is a retrospective chart review of 160 UDT results (80 aberrant; 80 non-aberrant) between August 2017 and February 2018 from 5 ambulatory clinics (3 primary care, 1 oncology, 1 pain management). Aberrant results were classified into one or more of the following categories: illicit drug use, simulated compliance, not taking prescribed medication, and taking a medication not prescribed. Accurate result interpretation was defined as concordance between the provider's documented interpretation and an expert laboratory toxicologist's interpretation. Outcome measures were concordance between provider and laboratory interpretation of UDT results, documentation of UDT results, results acknowledgement in the electronic health record, communication of results to the patient, and rate of prescription refills. KEY RESULTS: Aberrant results were most frequently due to illicit drug use. Overall, only 88 of the 160 (55%) had any documented provider interpretations of which 25/88 (28%) were discordant with the laboratory toxicologist's interpretation. Thirty-six of the 160 (23%) documented communication of the results to the patient. Communicating results was more likely to be documented if the results were aberrant compared with non-aberrant (33/80 [41%] vs. 3/80 [4%], p < 0.001). In all cases where provider interpretations were discordant with the laboratory interpretation, prescriptions were refilled. CONCLUSIONS: Erroneous provider interpretation of UDT results, infrequent documentation of interpretation, lack of communication of results to patients, and prescription refills despite inaccurate interpretations are common. Expert assistance with urine toxicology interpretations may be needed to improve provider accuracy when interpreting toxicology results.

Investigating the Transition of Pre-Symptomatic to Symptomatic Huntington's Disease Status Based on Omics Data.

Huntington's disease is a rare neurodegenerative disease caused by a cytosine-adenine-guanine (CAG) trinucleotide expansion in the Huntingtin (HTT) gene. Although Huntington's disease (HD) is well studied, the pathophysiological mechanisms, genes and metabolites involved in HD remain poorly understood. Systems bioinformatics can reveal synergistic relationships among different omics levels and enables the integration of biological data. It allows for the overall understanding of biological mechanisms, pathways, genes and metabolites involved in HD. The purpose of this study was to identify the differentially expressed genes (DEGs), pathways and metabolites as well as observe how these biological terms differ between the pre-symptomatic and symptomatic HD stages. A publicly available dataset from the Gene Expression Omnibus (GEO) was analyzed to obtain the DEGs for each HD stage, and gene co-expression networks were obtained for each HD stage. Network rewiring, highlights the nodes that change most their connectivity with their neighbors and infers their possible implication in the transition between different states. The CACNA1I gene was the mostly highly rewired node among pre-symptomatic and symptomatic HD network. Furthermore, we identified AF198444 to be common between the rewired genes and DEGs of symptomatic HD. CNTN6, DEK, LTN1, MST4, ZFYVE16, CEP135, DCAKD, MAP4K3, NUPL1 and RBM15 between the DEGs of pre-symptomatic and DEGs of symptomatic HD and CACNA1I, DNAJB14, EPS8L3, HSDL2, SNRPD3, SOX12, ACLY, ATF2, BAG5, ERBB4, FOCAD, GRAMD1C, LIN7C, MIR22, MTHFR, NABP1, NRG2, OTC, PRAMEF12, SLC30A10, STAG2 and Y16709 between the rewired genes and DEGs of pre-symptomatic HD. The proteins encoded by these genes are involved in various biological pathways such as phosphatidylinositol-4,5-bisphosphate 3-kinase activity, cAMP response element-binding protein binding, protein tyrosine kinase activity, voltage-gated calcium channel activity, ubiquitin protein ligase activity, adenosine triphosphate (ATP) binding, and protein serine/threonine kinase. Additionally, prominent molecular pathways for each HD stage were then obtained, and metabolites related to each pathway for both disease stages were identified. The transforming growth factor beta (TGF-ß) signaling (pre-symptomatic and symptomatic stages of the disease), calcium (Ca2+) signaling (pre-symptomatic), dopaminergic synapse pathway (symptomatic HD patients) and Hippo signaling (pre-symptomatic) pathways were identified. The in silico metabolites we identified include Ca2+, inositol 1,4,5-trisphosphate, sphingosine 1-phosphate, dopamine, homovanillate and L-tyrosine. The genes, pathways and metabolites identified for each HD stage can provide a better understanding of the mechanisms that become altered in each disease stage. Our results can guide the development of therapies that may target the altered genes and metabolites of the perturbed pathways, leading to an improvement in clinical symptoms and hopefully a delay in the age of onset.

Filling the gap between chemical carcinogenesis and the hallmarks of cancer: A temporal perspective.

BACKGROUND: Cancer is believed to arise through the perturbation of pathways and the order of pathway perturbation events can enhance understanding and evaluation of carcinogenicity. This order has not been examined so far, and this study aimed to fill this gap by attempting to gather evidence on the potential temporal sequence of events in carcinogenesis. DESIGN: The methodology followed was to discuss first the temporal sequence of hallmarks of cancer from the point of view of pathological specimens of cancer (essentially branched mutations) and then to consider the hallmarks of cancer that one well-known carcinogen, benzo(a)pyrene, can modify. RESULTS: Even though the sequential order of driving genetic alterations can vary between and within tumours, the main cancer pathways affected are almost ubiquitous and follow a generally common sequence: resisting cell death, insensitivity to antigrowth signals, sustained proliferation, deregulated energetics, replicative immortality and activation of invasion and metastasis. The first 3 hallmarks can be regarded as almost simultaneous while angiogenesis and avoiding immune destruction are perhaps the only hallmarks with a varying position in the above sequence. CONCLUSIONS: Our review of hallmarks of cancer and their temporal sequence, based on mutational spectra in biopsies from different cancer sites, allowed us to propose a hypothetical temporal sequence of the hallmarks. This sequence can add molecular support to the evaluation of an agent as a carcinogen as it can be used as a conceptual framework for organising and evaluating the strength of existing evidence.

Epidemiology of Amyotrophic Lateral Sclerosis in the Republic of Cyprus: A 25-Year Retrospective Study.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare, rapidly progressive neurodegenerative disease. Despite wide variability in the incidence and prevalence of ALS, there is evidence of positive temporal trends and an increase in incidence with age. The aim of this study was to conduct a detailed epidemiological investigation of ALS in Cyprus. METHODS: All registered Cypriot ALS patients in the Republic of Cyprus from January 1985 until December 2014 were included. Socio-demographic information was extracted from patient files. RESULTS: The study identified 179 ALS patients, of whom 7 had a positive family history. The mean age at onset was 58.6 years and a slight male predominance was observed. Average annual crude incidence was 1.26 cases/100,000 person-years and at the beginning of 2015, prevalence of ALS was 7.9 cases/100,000 population. Both incidence and prevalence displayed an increasing trend, even after age-standardization of incidence rates. CONCLUSIONS: Incidence, prevalence and main socio-demographic characteristics of ALS in Cyprus were similar to those of other European countries, without any geographic clustering of the disease. Additionally, an increased incidence through the years was confirmed. However, observations such as a higher male prevalence and a younger mean age of onset compared to published literature require further investigation.

The synergistic effect between the Mediterranean diet and GSTP1 or NAT2 SNPs decreases breast cancer risk in Greek-Cypriot women.

PURPOSE: Xenobiotic metabolism is related to the interplay between diet and breast cancer (BC) risk. This involves detoxification enzymes, which are polymorphic and metabolise various dietary metabolites. An important characteristic of this pathway is that chemoprotective micronutrients can act not only as substrates but also as inducers for these enzymes. We investigated whether functional GSTP1 (p.Ile105Val-rs1695), NAT2 (590G>A-rs1799930) SNPs and GSTM1 and GSTT1 deletion polymorphisms could modulate the effect of the Mediterranean diet (MD) on BC risk, in Greek-Cypriot women. METHODS: Genotyping was performed on women from the MASTOS case-control study of BC in Cyprus. A 32-item food-frequency questionnaire was used to obtain dietary intake information. A dietary pattern, which closely resembles the MD (high loadings of vegetables, fruit, legumes and fish), was previously derived with principal component analysis and was used as our dietary variable. RESULTS: GSTT1 null genotype increased BC risk compared with the homozygous non-null GSTT1 genotype (OR 1.21, 95 % CI 1.01-1.45). Increasing adherence to the MD reduced BC risk in women with at least one GSTP1 Ile allele (OR for Ile/Ile = 0.84, 95 % CI 0.74-0.95, for Ile/Val = 0.73, 95 % CI 0.62-0.85) or one NAT2 590G allele (OR for 590 GG = 0.73, 95 % CI 0.63-0.83, for 590 GA = 0.81, 95 % CI 0.70-0.94). p interaction values were not, however, statistically significant. CONCLUSION: The homozygous null GSTT1 genotype could be a risk allele for BC among Greek-Cypriot women. The anticarcinogenic effects of the high adherence to MD against BC risk could also be further enhanced when combined with the wild-type alleles of the detoxification GSTP1 or NAT2 SNPs.

Sex-specific age association with primary DNA transfer.

Practicing forensic scientists who are called to provide expert witness testimony are often asked to explain both the presence and the absence of DNA on objects that have been handled by perpetrators with bare hands. Unwashed hands, depending on what they have come in contact with previously, may become the vehicle of both primary and secondary transfer of DNA. In this study, we investigated the propensity of primary and secondary transfer of DNA from unwashed bare hands of 128 individuals onto plastic tubes. Our experiments, carried out in triplicate, have shown that DNA was not detected on all the touched tubes, secondary transfer of DNA, through unwashed hands, was small, and in the majority of cases primary DNA transfer could be distinguished from secondary DNA transfer. A statistically significant association was demonstrated between percent DNA profile deposited on plastic tubes, through unwashed hands, and the age of male individuals.

Association between Echinococcus granulosus infection and cancer risk - a pilot study in Cyprus.

BACKGROUND: Infections from microorganisms and parasites have been connected with either increased or decreased cancer risk. The objective of this study was to investigate whether infection by Echinococcus granulosus is associated with cancer risk. METHODS: We assembled a pilot retrospective cohort of patients who were diagnosed as being infected by E. granulosus in Cyprus between 1930 and 2011. Age/gender-matched non-infected family members and neighbors were selected as references. Medical history was ascertained from each study subject through in-person interview. Cox proportional hazards regression analysis was performed to assess the association of being infected by E. granulosus with cancer risk. RESULTS: Individuals with prior infection by E. granulosus (n=249) were more likely to have cancer compared to those without infection (n=753), 11.65% vs. 8.37% (p=0.0492). Survival analysis also showed that subjects with prior infection had a higher risk for developing cancer. The hazards ratio (HR) was 1.595, [95% confidence interval (CI) between 1.008 and 2.525]. The risk ratio did not change significantly (HR=1.536; 95% CI: 0.965-2.445) after adjusting for gender, year of birth, smoking status, alcohol consumption, and family history of cancer. CONCLUSIONS: Our study suggests that infection by E. granulosus may increase cancer risk. If this observation can be confirmed independently, further investigation of the mechanisms underlying the association is warranted.

MnSOD and CAT polymorphisms modulate the effect of the Mediterranean diet on breast cancer risk among Greek-Cypriot women.

PURPOSE: Oxidative stress arises due to a cellular imbalance in oxidants and antioxidants and/or due to an altered activity of antioxidant enzymes, caused by SNPs. Oxidative stress increases susceptibility to breast cancer (BC) risk, and we previously showed that the Mediterranean diet (MD), which is rich in antioxidants, reduces BC risk in Greek-Cypriot women. Here, we investigated the effect of MnSOD (p.Val16Ala, rs4880) and CAT (-262C>T, rs1001179) SNPs on the association between the MD and BC risk in the case-control study of BC MASTOS in Cyprus. METHODS: Dietary intake data were obtained using a 32-item food frequency questionnaire, from which a dietary pattern was previously derived, using principal component analysis. This pattern included high loadings of vegetables, fruit, legumes and fish, a combination that closely resembles the MD and was used as our dietary variable. RESULTS: High vegetable intake lowered BC risk in women with at least one MnSOD Val allele (ORHigh vs. Low for Val/Val = 0.56, 95 % CI 0.35-0.88, for Val/Ala = 0.57, 95 % CI 0.39-0.82), or one CAT -262C allele (ORHigh vs. Low for -262CC = 0.66, 95 % CI 0.47-0.92, for -262CT = 0.53, 95 % CI 0.35-0.81). High fish intake conferred a decreased BC risk of CAT -262CC women (ORQ4 vs. Q1 0.66, 95 % CI 0.47-0.92) compared with the CAT -262TT women and low fish intake (ORQ2 vs. Q1 2.79, 95 % CI 1.08-7.17). Additionally, high fish intake reduced BC risk in MnSOD Val/Val women (ORQ4 vs. Q1 0.63, 95 % CI 0.40-0.98). p interaction values were, however, not statistically significant. CONCLUSION: Our results demonstrate that the antioxidative effects of the MD against BC risk may be enhanced by the wild-type alleles of the MnSOD or CAT SNPs among Greek-Cypriot women.

Biological embedding of early-life exposures and disease risk in humans: a role for DNA methylation.

BACKGROUND: Following wider acceptance of 'the thrifty phenotype' hypothesis and the convincing evidence that early-life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early-life exposures become biologically embedded. MATERIALS AND METHODS: In this review, we summarize the current literature regarding biological embedding of early-life experiences. To this end, we conducted a literature search to identify studies investigating early-life exposures in relation to DNA methylation changes. In addition, we summarize the challenges faced in investigations of epigenetic effects, stemming from the peculiarities of this emergent and complex field. A proper systematic review and meta-analyses were not feasible given the nature of the evidence. RESULTS: We identified seven studies on early-life socio-economic circumstances, 10 studies on childhood obesity and six studies on early-life nutrition all relating to DNA methylation changes that met the stipulated inclusion criteria. The pool of evidence gathered, albeit small, favours a role of epigenetics and DNA methylation in biological embedding, but replication of findings, multiple comparison corrections, publication bias and causality are concerns remaining to be addressed in future investigations. CONCLUSIONS: Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early-life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early-life exposures might become biologically embedded through epigenetic effects.

Cause-Specific Excess Mortality During the COVID-19 Pandemic (2020-2021) in 12 Countries of the C-MOR Consortium.

BACKGROUND: This study investigated cause-specific mortality rates in 12 countries during the COVID-19 pandemic in 2020 and 2021. METHODS: We collected weekly cause-specific mortality data from respiratory disease, pneumonia, cardiovascular disease (CVD) and cancer from national vital statistic databases. We calculated excess mortality for respiratory disease (excluding COVID-19 codes), pneumonia, and CVD in 2020 and 2021 by comparing observed weekly against expected mortality based on historical data (2015-2019), accounting for seasonal trends. We used multilevel regression models to investigate the association between country-level pandemic-related variables and cause-specific mortality. RESULTS: Significant reductions in cumulative mortality from respiratory disease and pneumonia were observed in 2020 and/or 2021, except for Georgia, Northern Ireland, Kazakhstan, and Ukraine, which exhibited excess mortality for one or both causes. Australia, Austria, Cyprus, Georgia, and Northern Ireland experienced excess cumulative CVD mortality in 2020 and/or 2021. Australia, Austria, Brazil, Cyprus, Georgia, Northern Ireland, Scotland and Slovenia, experienced increased crude cumulative cancer mortality during 2020 and/or 2021 compared to previous years. Among pandemic-related variables, reported COVID-19 incidence was negatively associated with increased cancer mortality, excess respiratory, (2020) and pneumonia (2021) mortality, and positively associated with respiratory and CVD mortality (2021). Stringency of control measures were negatively associated with excess respiratory disease, CVD, and increased cancer mortality (2021). CONCLUSIONS: This study provides evidence of substantial excess mortality from CVD, and notable reductions in respiratory disease and pneumonia in both years across most countries investigated. Our study also highlights the beneficial impact of stringent control measures in mitigating excess mortality from most causes in 2021.

Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project.

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation.

Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and various fields of biomedical research. The result is a broader appreciation of epigenetic phenomena in the a etiology of common human diseases, most notably cancer. These advances also represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, are expected to generate information for establishing the 'normal' epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Recently, epigenetic events have emerged as key mechanisms in cancer development, and while our search of the Monograph Volume 100 revealed that epigenetics have played a modest role in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs so far, epigenetic data might play a pivotal role in the future. Here, we review (i) the current status of incorporation of epigenetics in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences and (v) critical technological and biological issues in assessment of epigenetic carcinogens. We also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation. Although the application of epigenetic assays in carcinogen evaluation is still in its infancy, important data are being generated and valuable scientific resources are being established that should catalyse future applications of epigenetic testing.

The Role of Social Work for Emergency Medical Services (EMS): A Systematic Review.

INTRODUCTION: Emergency Medical Services (EMS) are integrated services involving doctors, paramedics, nurses, and social workers. This research was carried out to synthesize the evidence concerning social work roles for EMS. The aim of this study was to synthesize literature on the social worker's role in EMS settings. METHODS: The study was a systematic review. Data were collected through selected databases. The researcher used Scopus, Sociology Database, Social Science Database, and Public Health Database related to EMS and social work settings. English papers were selected, without restrictions on publication time, place, and year. The searched keywords were: "Social Work AND Emergency Medical Services AND Ambulance Services," "Social Worker AND Emergency Medical Systems AND Ambulance Services," "Social Work AND EMS," "Social Worker AND EMS," "Social Work OR Social Worker," "Social Work Role AND EMS," Social Worker AND EMS," "Emergency Medical Services OR/AND Emergency Medical Systems." RESULTS: The study synthesized the literature about the social work role in pre-EMS, during emergency, and post-EMS. The following themes were highlighted: social workers act as cultural liaisons, effective communicators, emergency workers, and mental health practitioners, collaborating with other disciplines and researchers, for this study. In pre-emergency stages, social workers have roles as educators, communicators, advocates, and awareness builders. During an emergency, social workers act as search and rescue workers, advocates, facilitators, networkers, psychosocial assessors, consultants, counselors, and liaisons for referral activities. And in the post-emergency period, social workers have roles as planners, liaisons, interdisciplinary collaborators, researchers, evaluators, and individuals responsible for follow up. CONCLUSION: This study synthesizes the roles of social workers in EMS settings. It is the first study on this topic, aiming to produce new knowledge, evidence, and an EMS practice framework for the social worker.

Investigating the Dietary Intake Using the CyFFQ Semi-Quantitative Food Frequency Questionnaire in Cypriot Huntington's Disease Patients.

Huntington's disease (HD) is a rare progressive neurodegenerative disease characterised by autosomal dominant inheritance. The past decade saw a growing interest in the associations between the Mediterranean Diet (MD) and HD risk and outcomes. The aim of this case-control study was to assess the dietary intake and habits of Cypriot HD patients, comparing them to gender and age-matched controls, using the Cyprus Food Frequency Questionnaire (CyFFQ) and to assess adherence to the MD by disease outcomes. The method relied on the validated CyFFQ semi-quantitative questionnaire to assess energy, macro- and micronutrient intake over the past year in n = 36 cases and n = 37 controls. The MedDiet Score and the MEDAS score were used to assess adherence to the MD. Patients were grouped based on symptomatology such as movement and cognitive and behavioral impairment. The two-sample Wilcoxon rank-sum (Mann-Whitney) test was used to compare cases vs. controls. Statistically significant results were obtained for energy intake (kcal/day) (median (IQR): 4592 (3376) vs. 2488 (1917); p = 0.002) from cases and controls. Energy intake (kcal/day) (median (IQR): 3751 (1894) vs. 2488 (1917); p = 0.044) was also found to be significantly different between asymptomatic HD patients and controls. Symptomatic patients were also different from controls in terms of energy intake (kcal/day) (median (IQR): 5571 (2907) vs. 2488 (1917); p = 0.001); % energy monounsaturated fatty acids (median (IQR): 13.4 (5.2) vs. 15.5 (5.7); p = 0.0261) and several micronutrients. A significant difference between asymptomatic and symptomatic HD patients was seen in the MedDiet score (median (IQR): 31.1 (6.1) vs. 33.1 (8.1); p = 0.024) and a significant difference was observed between asymptomatic HD patient and controls (median (IQR): 5.5 (3.0) vs. 8.2 (2.0); p = 0.014) in the MEDAS score. This study confirmed previous findings that HD cases have a significantly higher energy intake than controls, revealing differences in macro and micronutrients and adherence to the MD by both patients and controls and by HD symptom severity. These findings are important as they are an effort to guide nutritional education within this population group and further understand diet-disease associations.