Repetitive element hypermethylation in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is a complex disorder of the central nervous system whose cause is currently unknown. Evidence is increasing that DNA methylation alterations could be involved in inflammatory and neurodegenerative diseases and could contribute to MS pathogenesis. Repetitive elements Alu, LINE-1 and SAT-α, are widely known as estimators of global DNA methylation. We investigated Alu, LINE-1 and SAT-α methylation levels to evaluate their difference in a case-control setup and their role as a marker of disability. RESULTS: We obtained blood samples from 51 MS patients and 137 healthy volunteers matched by gender, age and smoking. Methylation was assessed using bisulfite-PCR-pyrosequencing. For all participants, medical history, physical and neurological examinations and screening laboratory tests were collected. All repetitive elements were hypermethylated in MS patients compared to healthy controls. A lower Expanded Disability Status Scale (EDSS) score was associated with a lower levels of LINE-1 methylation for 'EDSS = 1.0' and '1.5 ≤ EDSS ≤ 2.5' compared to an EDSS higher than 3, while Alu was associated with a higher level of methylation in these groups: 'EDSS = 1.0' and '1.5 ≤ EDSS ≤ 2.5'. CONCLUSIONS: MS patients exhibit an hypermethylation in repetitive elements compared to healthy controls. Alu and LINE-1 were associated with degree of EDSS score. Forthcoming studies focusing on epigenetics and the multifactorial pathogenetic mechanism of MS could elucidate these links further.

Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment.

BACKGROUND: Cancer patients are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment remain unclear. PATIENTS AND METHODS: In this interventional prospective multicohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Vaccine safety and efficacy (until 3 months post-booster) were assessed. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) antibody levels were followed over time (until 28 days after the booster) and in vitro SARS-CoV-2 50% neutralization titers (NT50) toward the wild-type Wuhan strain were analyzed 28 days after the booster. RESULTS: Local and systemic adverse events (AEs) were mostly mild to moderate (only 1%-3% of patients experienced severe AEs). Local, but not systemic, AEs occurred more frequently after the booster dose. Twenty-eight days after the booster vaccination of 197 cancer patients, RBD-binding antibody titers and NT50 were lower in the chemotherapy group {234.05 IU/ml [95% confidence interval (CI) 122.10-448.66] and 24.54 (95% CI 14.50-41.52), respectively} compared with healthy individuals [1844.93 IU/ml (95% CI 1383.57-2460.14) and 122.63 (95% CI 76.85-195.67), respectively], irrespective of timing of vaccination during chemotherapy cycles. Extremely low antibody responses were seen in hematology patients receiving rituximab; only two patients had RBD-binding antibody titers necessary for 50% protection against symptomatic SARS-CoV-2 infection (<200 IU/ml) and only one had NT50 above the limit of detection. During the study period, five cancer patients tested positive for SARS-CoV-2 infection, including a case of severe COVID-19 in a patient receiving rituximab, resulting in a 2-week hospital admission. CONCLUSION: The BNT162b2 vaccine is well-tolerated in cancer patients under active treatment. However, the antibody response of immunized cancer patients was delayed and diminished, mainly in patients receiving chemotherapy or rituximab, resulting in breakthrough infections.

Air pollution-induced placental alterations: an interplay of oxidative stress, epigenetics, and the aging phenotype?

According to the "Developmental Origins of Health and Disease" (DOHaD) concept, the early-life environment is a critical period for fetal programming. Given the epidemiological evidence that air pollution exposure during pregnancy adversely affects newborn outcomes such as birth weight and preterm birth, there is a need to pay attention to underlying modes of action to better understand not only these air pollution-induced early health effects but also its later-life consequences. In this review, we give an overview of air pollution-induced placental molecular alterations observed in the ENVIRONAGE birth cohort and evaluate the existing evidence. In general, we showed that prenatal exposure to air pollution is associated with nitrosative stress and epigenetic alterations in the placenta. Adversely affected CpG targets were involved in cellular processes including DNA repair, circadian rhythm, and energy metabolism. For miRNA expression, specific air pollution exposure windows were associated with altered miR-20a, miR-21, miR-146a, and miR-222 expression. Early-life aging markers including telomere length and mitochondrial DNA content are associated with air pollution exposure during pregnancy. Previously, we proposed the air pollution-induced telomere-mitochondrial aging hypothesis with a direct link between telomeres and mitochondria. Here, we extend this view with a potential co-interaction of different biological mechanisms on the level of placental oxidative stress, epigenetics, aging, and energy metabolism. Investigating the placenta is an opportunity for future research as it may help to understand the fundamental biology underpinning the DOHaD concept through the interactions between the underlying modes of action, prenatal environment, and disease risk in later life. To prevent lasting consequences from early-life exposures of air pollution, policy makers should get a basic understanding of biomolecular consequences and transgenerational risks.

Ten-year experience with early angioplasty in 759 patients with acute myocardial infarction.

OBJECTIVES: How effective and safe is rescue percutaneous transluminal coronary angioplasty [PTCA] compared with primary PTCA, and is it cost effective? BACKGROUND: In acute myocardial infarction (AMI), primary PTCA has been shown to be beneficial in terms of clinical outcome. In contrast, the value of rescue PTCA has not been established. METHODS: In a retrospective analysis, we compared the angiographic and clinical outcomes of 317 consecutive patients who had rescue PTCA approximately 90 min after failed thrombolysis and 442 patients treated with primary PTCA. An estimation of interventional costs was compared with the strategies of primary and rescue PTCA or with the strategy of thrombolysis with rescue PTCA, when indicated. RESULTS: Baseline characteristics between primary and rescue PTCA were comparable for most variables. Treatment delay was longer for patients who had rescue PTCA: 240 min. versus 195 min. Coronary patency after PTCA was comparable: 90.2% for rescue PTCA and 91.4% for primary PTCA (p = 0.67, power 71.9%). In-hospital mortality rates were 4.7% and 6.6%, respectively (p = 0.37). Also, the other complications were fairly similar during the in-hospital phase and during one-year follow-up. Predictors of death were age, infarct size, localization of AMI, failed PTCA and left main stem occlusion. The estimated interventional costs during one-year follow-up were $7,377 for primary PTCA and $8,246 for rescue PTCA: difference $869 (11.7%). CONCLUSIONS: In this retrospective analysis of 759 patients with AMI, rescue angioplasty early after failed thrombolysis seems to be as effective and safe as primary PTCA. In the present evaluation, interventional costs of primary PTCA are less than those of rescue PTCA (p = 0.0001).

Quality of life and psychosocial adjustment in patients after Roux-en-Y gastric bypass: a brief report.

BACKGROUND: While Roux-en-Y gastric bypass (RYGBP) appears to be the most effective procedure for weight loss in morbidly obese patients, objective outcome data regarding quality of life (QoL) and psychosocial status following surgery are lacking. METHODS: The present study examined the effects of RYGBP in 32 morbidly obese subjects on a variety of outcome measures including QoL and psychosocial functioning. Assessments were conducted before surgery, 1 to 3 weeks post-surgery, and at 6-month follow-up. RESULTS: In addition to weight loss, results show significant improvements in health-related QoL, depression, and self-esteem, as well as a significant reduction in eating pathology following surgery. Results also show that neither the presence of binge-eating disorder nor clinical depression predicted poorer outcome post-surgery. CONCLUSION: RYGBP results in a dramatic reduction in weight, and marked improvements in health-related QoL, depression, self-esteem, and eating pathology, including binge-eating in the short term. These findings need to be replicated in a larger cohort of patients and followed for a longer time before we can reach more definitive conclusions regarding the psychosocial outcome in RYGBP.