BackgroundAberrant DNA methylation in gene promoters is associated with aging and cancer, but the circumstances determining methylation change are unknown. We investigated the impact of lifestyle modulators of colorectal cancer (CRC) risk on the stability of gene promoter methylation in the colonic mucosa.MethodsWe measured genome-wide promoter CpG methylation in normal colon biopsies (n = 1092) from a female screening cohort, investigated the interaction of lifestyle factors with age-dependent increase in methylation with log-linear multivariable regression, and related their modifying effect to hypermethylation in CRC. All statistical tests were two-sided.ResultsOf 20025 promoter-associated CpGs analyzed, 1713 showed statistically significant age-dependent methylation gains. Fewer CpGs acquired methylation in users of aspirin (≥2 years) and hormonal replacement therapy (HRT age ≥50 years) compared with nonusers (43 vs 1355; 1 vs1377, respectively), whereas more CpGs were affected in smokers (≥20 years) and individuals with a body mass index (BMI) of 25kg/m2 and greater compared with control groups (180 vs 39; 554 vs 144, respectively). Fifty percent of the CpGs showing age-dependent methylation were found hypermethylated in CRC (odds ratio [OR] = 20; 95% confidence interval [CI] = 18 to 23; P < 2×10–16). These loci gained methylation with a higher median rate compared with age-only methylated sites (P = 2×10–76) and were enriched for polycomb regions (OR = 3.67). Importantly, aspirin (P < .001) and HRT use (P < .001) reduced the methylation rate at these cancer-related genes, whereas smoking (P < .001) and high BMI (P = .004) increased it.ConclusionsLifestyle, including aspirin use, modulates age-associated DNA methylation change in the colonic epithelium and thereby impacts the evolution of cancer methylomes.

Epidural analgesia is a well-recognised method of labour pain relief. It is associated with the parturient's higher satisfaction when compared to parenteral opioids. EA does not directly increase the caesarean section delivery rate, yet it can lead to instrumental deliveries (vacuum-assisted, obstetrics forceps) and a need to pharmacologically support the uterine contractile function. Further studies are required to evaluate the effect of EA on the course of labour, and methods of minimising its adverse effects.

This study aimed to assess knowledge about non-pharmacological pain-relief methods in labor among women who have given birth at least once. This cross-sectional study was conducted using an online survey among 466 adult women. The minimum sample size was estimated based on the number of labor admissions in the year before the study in Poland. The survey included questions about respondents’ sociodemographics and knowledge of pain-relief methods. The knowledge score was calculated using the sum of correct answers. Non-parametric Spearman’s correlation, Kruskal–Wallis and Wilcoxon variance tests were used. Antenatal classes (313/68.9%) and the Internet (248/54.6%) were the most common sources of knowledge. The most popular pharmacological pain-relief methods included epidural anesthesia (386/85.0%) and nitrous oxide (301/66.3%). Massage and breathing techniques were the most commonly known non-pharmacological methods (405/89.2% and 400/88.1%, respectively). The knowledge score about non-pharmacological methods was significantly higher as compared to the pharmacological methods score (rc = 0.85; p < 0.001). Respondents’ age correlated with knowledge about non-pharmacological methods (rs = −0.10,p = 0.026) but did not correlate with knowledge about pharmacological methods. Educational level correlated with knowledge about pharmacological (rs = −0.13,p = 0.007) and non-pharmacological (rs = 0.14, p = 0.003) methods concerning pain relief in labor. No correlation was found between respondents’ knowledge and gravidity, number of vaginal or cesarean deliveries, and hospital referral levels for previous deliveries. Our findings support the need to implement educational programs to increase evidence-based knowledge about pain-relief methods during labor in women.

Introduction: Pain experienced during labor is a symptom of contractile activity and is a physiological feature of the uterus that occurs at the appropriate stages of labor. For the majority of women, labor pain is the most severe pain they will ever experience, and therefore should be relieved. Objective: (1) To evaluate labor pain intensity before and after using non-pharmacological and pharmacological interventions; (2) to assess women’s satisfaction of labor pain management. Methods: A multicenter cross-sectional survey study was performed on 500 women who gave birth in different reference level hospitals (i.e., I, II, III). Pain intensity was assessed according the Numeric Rating Scale (range 0–10), whereas women’s satisfaction was measured with a 5 point Likert scale. Results: The use of both non-pharmacological (median 6.7 (5; 8) vs. 4.5 (3.3; 5.5)) and pharmacological methods (median 8 (7; 9) vs. 5 (3; 6)) resulted in a significant reduction in pain (p < 0.01). Water immersion and epidural anesthesia proved to be the most effective non-pharmacological and pharmacological methods, respectively. In hospitals of reference I, analgesic management was based primarily on the use of non-pharmacological techniques, less often mixed, i.e., non-pharmacological and pharmacological techniques (27.5%). On the other hand, in hospitals with higher referentiality, mixed methods were used more often (level II—65.8%; level III—81.2%). Pain intensity was significantly higher (p < 0.0001) in hospitals with reference level I (median 5 (4; 6)) than in the hospitals with reference level II (median 4.2 (3; 5)) or level III (median 4.2 (3.3; 5.4)). Epidural anesthesia was most often performed (60%) in the hospital of reference II. Women’s satisfaction (median 4 (3; 5)), inter alia, was associated with the effectiveness of applied methods. Conclusions: The study findings suggest that women giving birth in hospitals of higher referentiality have better control of labor pain due to access to pharmacological methods. Epidural anesthesia remains the gold standard for relieving labor pain. The choice of a specific method is determined by the degree of hospital and associated with the pain referentiality.

The present studies were desgined to examine the effect of local anesthetics (benzyl alcohol, lidocaine, and procainamide) on the secretory response of parietal cells to histamine, dbcAMP, and carbachol. Studies were performed in vitro using isolated cells from rat stomachs, and acid production was determined by ¹⁴C-aminopyrine accumulation. In addition, the (H⁺-K⁺)-ATPase activity of microsomal vesicles isolated from parietal cells was determined. Lower concentrations of the drugs studied increased the basal aminopyrine accumulation and potentiated the secretory response of parietal cells to histamine and dbcAMP. At higher concentrations local anesthetics progressively inhibited both the basal ¹⁴C-aminopyrine accumulation and that stimulated by histamine, dbcAMP or carbachol. While a low concentration of local anesthetics increased gastric microsomal (H⁺-K⁺)-ATPase activity, higher concentrations inhibited enzyme activity to about 80% of those activities found in resting parietal cells. We conclude that increased aminopyrine accumulation may reflect the activation of membrane-bound enzyme(s) involved in the cAMP-dependent signal transduction pathway mediating acid secretion by parietal cells. In turn, it is possible that the inhibition of aminopyrine accumulation by local anesthetics at higher concentrations can relate to two different mechanisms: (1) the nonspecific effect of local anesthetics that causes simple proton neutralization (as weak bases), and (2) to a minor extent their inhibitory effect on proton pump activity.