Early life exposure to mercury and relationships with telomere length and mitochondrial DNA content in European children.

BACKGROUND: Telomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation, respectively. Methylmercury (MeHg), a common pollutant in fish, induces oxidative stress. We hypothesized that elevated oxidative stress from exposure to MeHg decreases mtDNAcn and shortens TL. METHODS: Study participants are 6-11-year-old children from the HELIX multi-center birth cohort study, comprising six European countries. Prenatal and postnatal total mercury (THg) concentrations were measured in blood samples, TL and mtDNAcn were determined in child DNA. Covariates and confounders were obtained by questionnaires. Robust regression models were run, considering sociodemographic and lifestyle covariates, as well as fish consumption. Sex, ethnicity, and fish consumption interaction models were also run. RESULTS: We found longer TL with higher pre- and postnatal THg blood concentrations, even at low-level THg exposure according to the RfD proposed by the US EPA. The prenatal association showed a significant linear relationship with a 3.46 % increase in TL for each unit increased THg. The postnatal association followed an inverted U-shaped marginal non-linear relationship with 1.38 % an increase in TL for each unit increased THg until reaching a cut-point at 0.96 µg/L blood THg, from which TL attrition was observed. Higher pre- and postnatal blood THg concentrations were consistently related to longer TL among cohorts and no modification effect of fish consumption nor children's sex was observed. No association between THg exposure and mtDNAcn was found. DISCUSSION: We found evidence that THg is associated with TL but the associations seem to be time- and concentration-dependent. Further studies are needed to clarify the mechanism behind the telomere changes of THg and related health effects.

Adherence to inhalers and comorbidities in COPD patients. A cross-sectional primary care study from Greece.

BACKGROUND: Comorbidities and adherence to inhaled therapy appears to have a major impact on treatment goals, health status and disease control in chronic obstructive pulmonary disease (COPD). Aim of the study was to assess levels of adherence to inhalers, comorbidities and associations with COPD outcomes in patients residing in rural and semi-urban areas of Greece. METHODS: Two hundred fifty-seven COPD patients were enrolled from primary health care in 2015-2016. Physicians used structured interviews and questionnaires to assess quality of life and disease status. Patients were classified into groups according to GOLD 2019 guidelines (based on CAT and mMRC). Adherence to inhalers was measured with the Test of Adherence to Inhalers (TAI). Multivariate linear and logistics regression models were used to assess associations between comorbidities and adherence to inhalers with COPD outcomes, including CAT and mMRC scores, exacerbations and GOLD A-D status. RESULTS: 74.1% of COPD patients reported poor adherence, while most of them were characterized as deliberate non-compliers (69.5%). 77.1% had ≥2 comorbidities, with overweight/obese (82.2%), hypertension (72.9%) and diabetes mellitus (58%) being the most prevalent. In multivariate analysis, COPD outcomes having significant associations with poor adherence included worse health status [OR (95% CI) 4.86 (1.61-14.69) and 2.93 (1.51-5.71) based on CAT and mMRC, respectively], having ≥2 exacerbations in the past year [4.68 (1.51-4.44)], and disease status e.g., be in groups C or D [3.13 (1.49-8.53) and 3.35 (1.24-9.09) based on CAT and mMRC, respectively). Subjects with gastroesophageal reflux showed better inhaler adherence [OR (95% CI) 0.17 (0.6-0.45)], but none of the comorbid conditions was associated with COPD outcomes after adjustments. CONCLUSIONS: Poor adherence to inhalers and comorbidities are both prevalent in COPD patients of primary care residing in rural/semi-urban areas of Greece, with adherence influencing COPD outcomes. Raising awareness of patients and physicians on the importance of comorbidities control and inhaler adherence may lead to interventions and improve outcomes.

Associations of sense of coherence and self-efficacy with health status and disease severity in COPD.

Sense of coherence and self-efficacy has been found to affect health-related quality of life in chronic diseases. However, research on respiratory diseases is limited. Here we report findings on quality of life (QoL) of COPD patients and the associations with coherence and self-efficacy. This study consists of the Greek national branch of the UNLOCK study, with a sample of 257 COPD patients. Coherence and self-efficacy are positively inter-correlated (Pearson rho = 0.590, p < 0.001). They are negatively correlated with the quality of life (CAT) [Pearson rho: coherence = -0.29, p < 0.001; self-efficacy = -0.29, p < 0.001) and mMRC (coherence = -0.37, p < 0.001; self-efficacy rho = -0.32, p < 0.001)]. Coherence is inversely associated with (Global Initiative for Chronic Obstructive Lung Disease) GOLD 2018-CAT and GOLD 2018-mMRC classification and "having at least one exacerbation in the past year". Findings are stressing the need for their incorporation in primary health care and COPD guidance as it maybe that enhancing coherence and self-efficacy will improve QoL.

Determinants of frailty in primary care patients with COPD: the Greek UNLOCK study.

BACKGROUND: Frailty is a state of increased vulnerability that has a significant risk of unfavorable outcomes such as increased dependency and/or death, but little is known about frailty in people with chronic obstructive pulmonary disease (COPD). METHOD: We aimed to determine the prevalence of frailty in COPD patients and to identify the associated risk factors. Two hundred fifty-seven COPD patients enrolled from primary care in Greece between 2015 and 2016. Physicians used structured interviews to collect cross-sectional data including demographics, medical history, symptoms and COPD Assessment Tool (CAT) or modified Medical Research Council Dyspnea scale (mMRC) score. Patients were classified into severity groups according to GOLD 2017 guidelines. Participants completed the The Frail Non-Disabled (FiND) questionnaire, exploring the frailty and disability domains. In the present analyses, frail patients with and without mobility disability were pooled and were compared to non-frail patients. Factors associated with frailty were analyzed using univariate and multivariate logistic regression. RESULTS: Mean (SD) age was 65 (12.3) with 79% males. The majority of patients suffered with frailty (82%) of which 76.8% had mobility disability. 84.2% were married/with partner and 55.4% retired. 55.6% were current smokers. Uncontrolled disease (≥10 CAT score) was reported in 91.1% and 37.2% of patients had ≥2 exacerbations in the past year. Dyspnea (38%) and cough (53.4%) were the main symptoms. Main comorbidities were hypertension (72.9%), hyperlipidaemia (24.6%) and diabetes (11%). Risk of frailty was significantly increased with age (OR; 95%CI: 1.05; 1.02-1.08), hypertension (2.25; 1.14-4.45), uncontrolled disease (≥10 CAT score 4.65; 1.86-11.63, ≥2 mMRC score 5.75 (2.79-11.85) or ≥ 2 exacerbations 1.73; 1.07-2.78), smoking cessation (ex compared to current smokers: 2.37; 1.10-5.28) and GOLD status (B&D compared to A&C groups: CAT-based 4.65; 1.86-11.63; mMRC-based: 5.75; 2.79-11.85). In multivariate regression smoking cessation and GOLD status remained significant. Gender, body mass index, occupational or marital status, symptoms and other comorbidities were not significant. CONCLUSIONS: Frailty with mobility disability is common in COPD patients and severity of disease increases the risk. It is possible that frail patients are more likely to quit smoking perhaps because of their disability and uncontolled disease. Routine assessment of frailty in addition to COPD control may allow early interventions for preventing or delaying progression of frailty and improvement in COPD disease.

Androgen Triggers the Pro-Migratory CXCL12/CXCR4 Axis in AR-Positive Breast Cancer Cell Lines: Underlying Mechanism and Possible Implications for the Use of Aromatase Inhibitors in Breast Cancer.

BACKGROUND/AIMS: Reports regarding the role of androgen in breast cancer (BC) are conflicting. Some studies suggest that androgen could lead to undesirable responses in the presence of certain BC tumor characteristics. We have shown that androgen induces C-X-C motif chemokine 12 (CXCL12) in BC cell lines. Our aim was to identify the mechanisms regulating the phenotypic effects of androgen-induced CXCL12 on Androgen Receptor (AR) positive BC cell lines. METHODS: We analyzed the expression of CXCL12 and its receptors with qPCR and ELISA and the role of Nuclear Receptor Coactivator 1 (NCOA1) in this effect. AR effects on the CXCL12 promoter was studied via Chromatin-immunoprecipitation. We also analyzed publically available data from The Cancer Genome Atlas to verify AR-CXCL12 interactions and to identify the effect or Aromatase Inhibitors (AI) therapy on CXCL12 expression and disease progression in AR positive cases. RESULTS: CXCL12 induction occurs only in AR-positive BC cell lines, possibly via an Androgen Response Element, upstream of the CXCL12 promoter. The steroid receptor co-regulator NCOA1 is critical for this effect. Androgen only induced the motility of p53-mutant BC cells T47D cells via upregulation of CXCR4 expression while they had no effect on wild-type p53 MCF-7 cells. Loss of CXCR4 expression and depletion of CXCL12 abolished the effect of androgen in T47D cells while inhibition of p53 expression in MCF-7 cells made them responsive to androgen and increased their motility in the presence to androgen. Patients with estrogen receptor positive (ER+)/AR+ BC treated with AIs were at increased risk of disease progression compared to ER+/AR+ non-AI treated and ER+/AR- AI treated cases. CONCLUSION: AIs may lead to unfavorable responses in some ER/AR positive BC cases, especially in patients with AR+, p53 mutant tumors.