Non-smoking Women Research Articles

Alterations in the placental proteome in association with the presence of black carbon particles: A discovery study

BackgroundExposure to ambient air pollution is known to cause direct and indirect molecular expression changes in the placenta, on the DNA, mRNA, and protein levels. Ambient black carbon (BC) particles can be found in the human placenta already very early in gestation. However, the effect of in utero BC exposure on the entire placental proteome has never been studied to date. ObjectivesWe explored whether placental proteome differs between mothers exposed to either high or low BC levels throughout the entire pregnancy. MethodsWe used placental tissue samples from the ENVIRONAGE birth cohort, of 20 non-smoking, maternal- and neonate characteristic-matched women exposed to high (n = 10) or low (n = 10) levels of ambient BC throughout pregnancy. We modeled prenatal BC exposure levels based on the mother's home address and measured BC levels in the fetal side of the placenta. The placental proteome was analyzed by nano-liquid chromatography Q-TOF mass spectrometry. PEAKS software was used for protein identification and label-free quantification. Protein-protein interaction and functional pathway enrichment analyses were performed with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) software. ResultsThe accumulation of BC particles in placenta was 2.19 times higher in the high versus low exposure group (20943.4 vs 9542.7 particles/mm³; p = 0.007). Thirteen proteins showed a ≥2-fold expression difference between the two exposure groups, all overexpressed in the placentas of women prenatally exposed to high BC levels. Three protein-protein interactions were enriched within this group, namely between TIMP3 and COL4A2, SERPINE2 and COL4A2, and SERPINE2 and GP1BB. Functional pathway enrichment analysis put forward pathways involved in extracellular matrix-receptor interaction, fibrin clot formation, and sodium ion transport regulation. DiscussionPrenatal BC exposure affects the placental proteome. Future research should focus on the potential consequences of these alterations on placental functioning, and health and disease during early childhood development.

The state of rheological properties of blood in pregnant smokers with chronic nonspecific bronchial inflammation

Aim. To evaluate the effect of smoking on the blood rheology of pregnant smokers with chronic nonspecific bronchial inflammation. Materials and methods. The prospective study included 107 pregnant smoking patients and 136 non-smoking pregnant women who were observed in a polyclinic. The control group consisted of 42 non-smoking women without chronic diseases. The patients were examined according to the clinical guidelines for the treatment of chronic obstructive pulmonary disease. The speed and volume indicators of the function of external respiration, indicators of blood rheology were studied. The reliability of the results was assessed using the methods of parametric and nonparametric statistics. Before applying all statistical research methods, it was checked whether the sample obeys the Gaussian (normal) distribution law. A single-factor analysis of variance was used to determine whether there was a statistically significant difference between the averages of three or more independent groups. Results. Having refuted the null hypothesis about the absence of the effect of smoking on hemoglobin, using the Student's t-test method for dependent samples, it was established. Conclusion. The longer the period of tobacco use lasted, the more likely it was to develop changes in the viscosity qualities of blood, which undoubtedly affected the condition of patients and the fetus.

Modern problems of bronchial tuberculosis in the world and the Russian Federation: A review

In the Russian Federation there is a positive trend in reducing the incidence of tuberculosis. However, there is a tendency to increase the prevalence of tuberculosis in the bronchi. According to foreign authors, the prevalence of bronchial tuberculosis ranges from 10% to 40%. There are no official statistics on the incidence of bronchial tuberculosis in the Russian Federation. The main contingent of bronchial tuberculosis lesions are young non-smoking women. At the same time, the most common target is the left main bronchus. Currently, no additional methods have been developed in the scheme of specific treatment of patients with pulmonary tuberculosis complicated by bronchial tuberculosis. It is important to understand that the eradication of MBT after an effective course of chemotherapy does not prevent the formation of cicatricial bronchial stenosis. It is also important to note that bacterial excretion in patients with bronchial tuberculosis is much more common than in patients with a comparable process in the lungs, but without bronchial damage. Consequently, tuberculosis of the trachea and bronchi has not only clinical, but also great epidemiological significance.

Daily snuff use during pregnancy, gestational length and birth weight; register-based study

BackgroundSnuff is a smokeless source of nicotine that is common in Scandinavia and increasingly used by women of fertile age. Persistent use of snuff during pregnancy has been associated with adverse pregnancy outcomes. Emerging data from the Medical Birth Registry of Norway distinguishes between occasional use and daily use. We provide preliminary estimates of associations between frequency of snuff and gestational length and birth weight.MethodsData on snuff use during pregnancies delivered in 2020 and 2021 were available for the west and central regions of Norway. Associations of snuff use with gestational length and birth weight at term (39–41 weeks) were estimated using quantile regression at the 25th, the 50th and the 75th percentiles, with adjustments for mother’s age, pre-pregnancy weight, and parity. We compared associations with the pregnancy outcomes according to maternal snuff and cigarette use.Results12.4% of 18 042 non-smoking women reported daily use of snuff before pregnancy, and 4.6% reported continuing use during pregnancy, with 1.2% still reporting daily use in the last trimester. Women with daily use through the last trimester delivered babies with a median gestational length reduced by 3.4 days (95% CI: -5.0 to -1.7 days) compared with women who never used snuff. The reduction was even stronger at the 25th percentile of gestational age. The median term birth weight was reduced by 44 g (95% CI: -134 to 46 g). These associations were much weaker for women who quit snuff at some point during pregnancy or used snuff only occasionally. Mothers who smoked daily through the last trimester had a median gestational length reduced by 2.1 days (95% CI: -2.7 to -1.4) and a median term birth weight reduced by 294 g (95% CI: -325 to -262) compared with never-smokers.ConclusionsDaily snuff use through the last trimester reduced the median gestational length by more than three days. Snuff reduced birth weight, but not as much as smoking, suggesting that the predominant effect of smoking on fetal growth is not through nicotine but through the additional toxic chemicals in cigarettes or by reduced oxygen supply to the fetus.

A clinically applicable model more suitable for predicting malignancy or benignity of pulmonary ground glass nodules in women patients

BackgroundIn recent years, clinicians often encounter patients with multiple pulmonary nodules in their clinical practices. As most of these ground glass nodules (GGNs) are small in volume and show no spicule sign, it is difficult to use Mayo Clinic Model to make early diagnosis of lung cancer accurately, especially in large numbers of nonsmoking women who have no tumor history. Other clinical models are disadvantaged by a relatively high false-positive or false-negative rate. Therefore, there is an urgent need to establish a new model of predicting malignancy or benignity of pulmonary GGNs for the sake of making accurate and early diagnosis of lung cancer.MethodsIncluded in this study were GGNs surgically resected from patients who were admitted to Yiwu Central Hospital from January 2018 to March 2024, including both male and female patients, there is no gender specific issue. The nature of all these GGN tissues was confirmed pathologically. The case data were statistically analyzed to establish a mathematical prediction model, the prediction performance of which was verified by the pathological results.ResultsAltogether 261 GGN patients met the inclusion criteria. Using the results of logistic regression analysis, a mathematical prediction equation was established as follows: Malignant probability (mP) = ex/ (1 + ex); when mP was > 0.5, the GGN was considered as malignant, and when mP was ≤ 0.5, it was considered as benign. x= -2.46 + 1.032*gender + 1.85*mGGN + 1.40*VCS-0.0027*mean CT value of the nodule + 0.078*maximum diameter of the nodule, where e represents the natural logarithm; if the patient was a female, gender = 1 (otherwise = 0); if the pulmonary nodule was a mixed GGN, mGGN = 1 (otherwise = 0); if the pulmonary nodule had vascular convergence sign, VCS = 1 (otherwise = 0). The prediction performance of the mathematical prediction model was verified as follows: the negative prediction value was 0.97156 and the positive prediction value was 0.3800 in the model group versus 1 and 0.25 in the verification group.ConclusionIn this study, we identified female gender, mGGN, VCS, mean CT value and maximum nodule diameter as five key factors for predicting malignancy or benignity of pulmonary nodules, based on which we established a mathematical prediction model. This novel innovation may provide a useful auxiliary tool for predicting malignancy and benignity of pulmonary nodules, especially in women patients.

Association of rs401681 (C > T) and rs402710 (C > T) polymorphisms in the CLPTM1L region with risk of lung cancer: a systematic review and meta-analysis.

Although many genome-wide association studies (GWAS) have confirmed the negative associations between rs401681[T] / rs402710[T] in the Cleft lip and cleft palate transmembrane protein 1 (CLPTM1L) region and lung cancer (LC) susceptibility in Caucasian and Asian populations, some other studies haven't found these negative associations. The purpose of this study is to clarify the associations between them and LC, as well as the differences in these associations between patients of different ethnicities (Caucasians and Asians), LC subtypes and smoking status. Relevant literatures published before July 7, 2023 in PubMed, EMbase, Web of Science, MEDLINE were searched through the Internet. Statistical analysis of data was performed in Revman 5.3, including drawing forest plots, funnel plots and so on. Sensitivity and publication bias were performed in Stata 14.0. TSA software was performed for the trial sequential analysis (TSA) tests to assess the stability of the results. Registration number: CRD42023407890. A total of 41 literatures (containing 44 studies: 16 studies in Caucasians and 28 studies in Asians) were included in this meta-analysis, including 126476 LC patients and 191648 healthy controls. The results showed that the T allele variants of rs401681 and rs402710 were negatively associated with the risk of LC (rs401681[T]: [OR] = 0.87, 95% CI [0.86, 0.88]; rs402710[T]: [OR] = 0.88, 95% CI [0.86, 0.89]), and the negative associations were stronger in Caucasians than in Asians (Subgroup differences: I2 > 50%). In LC subtypes, the rs401681[T] was negatively associated with the risk of Non-small-cell lung carcinoma (NSCLC), Lung adenocarcinoma (LUAD) and Lung squamous cell carcinoma (LUSC) (P < 0.05), and these negative associations were stronger in Caucasians than in Asians (Subgroup differences: I2 > 50%). The rs402710[T] was negatively associated with the risk of NSCLC, LUAD and LUSC (P < 0.05), and these negative associations in Caucasians were the same as in Asians (Subgroup differences: I2 < 50%). The rs401681[T] was negatively associated with the risk of LC in both smokers and non-smokers (P < 0.05), and the negative association for smokers equals to that of non-smokers (Subgroup differences: P = 0.25, I2 = 24.2%). In LC subtypes, the rs401681[T] was negatively associated with the risks of NSCLC and LUAD in both Caucasian smokers and Asian non-smokers (P < 0.05). The rs402710[T] was negatively associated with the risk of LC in both smokers and non-smokers (P < 0.05), and there was no difference in the strength of this negative risk association between them in Caucasians (Subgroup differences: I2 = 0%). In Asians, this negative association was found to be predominantly among smokers ([OR] = 0.80, 95%CI [0.65, 0.99]). In LC subtypes, the rs402710[T]was negatively associated with the risk of NSCLC in non-smokers, and this negative association was found to be predominantly among non-smokers in Asians ([OR] = 0.75, 95%CI [0.60, 0.94]). The T allele variants of rs401681 and rs402710 are both negatively associated with the risk of developing LC, NSCLC (LUAD, LUSC) in the Caucasian and Asian populations, and the negative associations with the risk of LC are higher in Caucasians. Smoking is an important risk factor for inducing the rs401681 and rs402710 variants and causes LC development in both populations. Other factors like non-smoking are mainly responsible for inducing the development of NSCLC in Asians, and is concentrated in LUAD among Asian non-smoking women.

The Concentration of Follistatin and Activin A in Serum and Selected Biochemical Parameters in Women with Polycystic Ovary Syndrome: Stratification by Tobacco Smoke Exposure, Insulin Resistance, and Overweight/Obesity.

Background/Objectives: The aim of the study was to investigate the concentrations of follistatin and activin A in the serum of women with polycystic ovary syndrome (PCOS) and to assess their relationship with selected biochemical parameters, specifically stratifying the analysis based on tobacco smoke, insulin resistance, and abnormal weight. Methods: The research was carried out within a cohort of 88 women (60 women with and 28 without PCOS). Results: We observed significant differences (p < 0.05) in follistatin concentrations between women with PCOS stratified by homeostatic model assessment for insulin resistance (HOMA-IR) values. These differences were consistent across both smoking and non-smoking subgroups with PCOS. Similar results were observed when comparing normal-weight women with PCOS to those with overweight or obesity. Additionally, activin A concentrations were significantly increased by higher body mass index (BMI) and HOMA-IR values in non-smoking women with PCOS. Moreover, we identified a negative correlation (r = -0.30; p < 0.023) between cotinine levels and Anti-Müllerian hormone. Among smoking women with PCOS, we noted decreased concentrations of sex hormone-binding globulin and high-density lipoproteins, alongside increased fasting glucose, insulin, HOMA-IR, and free androgen index values. Conclusions: Our findings suggest that activin A and follistatin concentrations are more strongly influenced by disruptions in glucose metabolism and BMI than by tobacco smoke exposure. The observed changes were more pronounced in follistatin than in activin A level.

Obesity-associated non-oxidative genotoxic stress alters trophoblast turnover in human first-trimester placentas.

Placental growth is most rapid during the first trimester (FT) of pregnancy, making it vulnerable to metabolic and endocrine influences. Obesity, with its inflammatory and oxidative stress, can cause cellular damage. We hypothesized that maternal obesity increases DNA damage in the FT placenta, affecting DNA damage response and trophoblast turnover. Examining placental tissue from lean and obese non-smoking women (4-12 gestational weeks), we observed higher overall DNA damage in obesity (COMET assay). Specifically, DNA double-strand breaks were found in villous cytotrophoblasts (vCTB; semi-quantitative γH2AX immunostaining), while oxidative DNA modifications (8-hydroxydeoxyguanosine; FPG-COMET assay) were absent. Increased DNA damage in obese FT placentas did not correlate with enhanced DNA damage sensing and repair. Indeed, obesity led to reduced expression of multiple DNA repair genes (mRNA array), which were further shown to be influenced by inflammation through in vitro experiments using tumor necrosis factor-α treatment on FT chorionic villous explants. Tissue changes included elevated vCTB apoptosis (TUNEL assay; caspase-cleaved cytokeratin 18), but unchanged senescence (p16) and reduced proliferation (Ki67) of vCTB, the main driver of FT placental growth. Overall, obesity is linked to heightened non-oxidative DNA damage in FT placentas, negatively affecting trophoblast growth and potentially leading to temporary reduction in early fetal growth.

Exploring the Disparity in Indoor/Outdoor Time and Radon Exposure as Possible Factors Contributing to the Unexpected Increase in Lung Cancer Risk among Non-Smoking Women.

According to a NIH study, Lung cancer among individuals who have never smoked is more prevalent in women and occurs at an earlier age than in smokers. The rise in lung cancer rates among female non-smokers might be linked to radon inhalation and should be further investigated. Our theory is based on the differences in radon exposure between males and females, which can be attributed to the variations in time spent indoors versus outdoors. Over the past few years, the smoking rates have shown a steady decline in the United States and other developed countries. This decrease in smoking prevalence has led to a new shift in the primary risk factors associated with lung cancer. Although tobacco smoke historically served as the primary cause of lung cancer, the reduction in smoking rates has allowed other risk factors, such as radon exposure, to come to the forefront. Given that women in certain countries, on average, might spend more time indoors compared to men, they are potentially exposed to higher levels of radon. This increased exposure could explain the rising rates of lung cancer among female non-smokers. The theory is still in its nascent stages and requires further research and validation. However, if proven correct, it could significantly alter our understanding of lung cancer risk factors and lead to new prevention. It is therefore crucial to expedite the review and publication of this theory, given its potential implications for public health.

Association Between Smoking with a Molecular Profile of Breast Cancer

Background: Female breast cancer is one of the causes of the highest cancer mortality and morbidity in the world. It is already known that there is a strong association between smoking and breast cancer. However, the association between smoking and tumor severity is not very clear. The objective of this study was to assess the severity of the breast tumor, using the tumor's molecular classification as a tool according to its immunohistochemical profile in smoking and non-smoking women. Methods: This is a longitudinal study in which 208 women with a diagnosis of breast cancer were followed for 17 months, 80 of whom were smokers and all underwent anatomopathological diagnosis by core biopsy and subsequent immunohistochemistry, followed by treatment indicated according to the type and the clinical staging of the tumor. The severity of the tumor was assessed by its molecular classification according to its immunohistochemical profile. Results: Smoking was associated with higher mortality. The tumor with the most severe immunohistochemical profile was found in younger smokers. 19.7% of smokers had a triple negative tumor and 10% of non-smokers. The age of female smokers with triple negative was 48.2 years and of non-smoking women was 52.6 years (p = 0.005). In 17 months of follow-up, mortality among smokers was 39.5% and for nonsmokers, 20%. Survival was statistically significantly lower among the group of smokers (p=0.01). Conclusion: smoking is associated with greater breast cancer severity, risk for cancer severity was OR 5.5 times higher for the smoking group survival was statistically significantly lower among the group of smokers

Polymorphic variants of the hOGG1, APEX1, XPD, SOD2, and CAT genes involved in DNA repair processes and antioxidant defense and their association with breast cancer risk.

Breast cancer is one of the leading causes of mortality among women. The most frequently encountered tumors are luminal tumors. Associations of polymorphisms in the hOGG1 (rs1052133), APEX1 (rs1130409), XPD (rs13181), SOD2 (rs4880), and CAT (rs1001179) genes were studied in 313 nonsmoking postmenopausal patients with luminal B subtype breast cancer. The control group consisted of 233 healthy nonsmoking postmenopausal women. Statistically significant associations of the XPD and APEX1 gene polymorphisms with the risk of developing luminal B Her2-negative subtype of breast cancer were observed in a log-additive inheritance model, while the CAT gene polymorphism showed an association in a dominant inheritance model (OR = 1.41; CI 95 %: 1.08-1.85; Padj.= 0.011; OR = 1.39; CI 95 %: 1.07-1.81; Padj = 0.013 и OR = 1.70; CI 95 %: 1.19-2.43; Padj = 0.004, respectively). In the group of elderly women (aged 60-74 years), an association of the CAT gene polymorphism with the risk of developing luminal B subtype of breast cancer was found in a log-additive inheritance model (OR = 1.87; 95 % CI: 1.22-2.85; Padj = 0.0024). Using MDR analysis, the most optimal statistically significant 3-locus model of gene-gene interactions in the development of luminal B Her2-negative subtype breast cancer was found. MDR analysis also showed a close interaction and mutual enhancement of effects between the APEX1 and SOD2 loci and the independence of the effects of these loci from the CAT locus in the formation of luminal B subtype breast cancer.

Exposure to second-hand smoke and breast cancer risk in non-smoking women: a comprehensive systematic review and meta-analysis.

Through the use of an innovative method to identify original publications, we conducted ameta-analysis of all epidemiological studies evaluating the association between second-hand smoke (SHS) exposure and breast cancer risk among female non-smokers published in English up to October 2022. Pooled relative risks (RR) were obtained through the use of random-effects models. Dose-response relationships were derived using log-linear functions. Out of 73 identified eligible studies, 63 original articles were included in the meta-analysis. The pooled RR for breast cancer for overall exposure to SHS was 1.24 (95% confidence interval, CI, 1.15-1.34, number of articles, n = 52). Regarding the setting of exposure, RRs were 1.17 (95% CI 1.08-1.27, n = 37) for SHS exposure at home, 1.03 (95% CI 0.98-1.08, n = 15) at the workplace, 1.24 (95% CI 1.11-1.37, n = 16) at home or workplace, and 1.45 (95% CI 1.16-1.80, n = 13) for non-specified settings. The risk of breast cancer increased linearly with higher duration (RR 1.29;95% CI 1.04-1.59 for 40 years of SHS exposure, n = 12), intensity (RR 1.38;95% CI 1.14-1.67 for 20 cigarettes of SHS exposure per day, n = 6), and pack-years (RR 1.50;95% CI 0.92-2.45 for 40 SHS pack-years, n = 6) of SHS exposure. This meta-analysis shows a statistically significant excess risk of breast cancer in women exposed to SHS.

A Qualitative Study of Barriers and Motivators to Prevent Secondhand Smoke Exposure Among Pregnant Women and Children in Egypt: Identifying Appropriate Approaches for Change.

The prevalence of daily secondhand smoke (SHS) exposure among pregnant nonsmoking women and children in Egypt is estimated to be about 50% and 55%, respectively. This study aimed to explore barriers to preventing SHS exposure among pregnant women/children and smoking in the home in Egypt. Six focus group discussions with pregnant women or mothers of children residing in urban-rural areas (n = 61) were conducted. Data were managed and analyzed using the Framework Method. Sixty-one participants aged 18-49 were recruited. They reported being never smokers and SHS exposure for themselves and their children was mainly at home. Pregnant women or mothers had some general knowledge of the dangers of SHS, but their knowledge appeared incomplete. The most commonly reported barriers to preventing SHS exposure/adopting a smoke-free home or workplace were social acceptance of smoking and SHS exposure, masculinity and gender norms of accepting smoking among men as a normative behavior, fear among women of damaging a relationship with family or even divorce, women resigning themselves to SHS exposure, and doctors not being supportive of smoking cessation. The majority of interviewees' families were reported to allow smoking anywhere in the home. Others implemented some measures to prevent SHS; however, these tended to be inconsistently implemented. Changing the norm of accepting smoking among men as a normative behavior within Egyptian society and better enforcement of smoke-free policies, will help to protect pregnant women and children from SHS. This study suggests promising approaches to support the promotion of smoke-free homes and the prevention of SHS exposure among pregnant women and children in public places in Egypt. Better enforcement of smoke-free policies is needed. Healthcare professionals should support smoking cessation services in primary health centers. SHS policy, practice, and research should focus on husbands/fathers as they are the main source of SHS. There is a need for denormalization of SHS exposure in Egyptian society.

Results of Lung Cancer Screening with Low-dose Computed Tomography and Exploration of Risk Factors in Guangzhou

Both of lung cancer incidence and mortality rank first among all cancers in China. Previous lung cancer screening trials were mostly selective screening for high-risk groups such as smokers. Non-smoking women accounted for a considerable proportion of lung cancer cases in Asia. This study aimed to evaluate the outcome of community-based mass screening in Guangzhou and identify the high-risk factors for lung cancer. Residents aged 40-74 years in Guangzhou were screened with low-dose computed tomography (LDCT) for lung cancer and the pulmonary nodules were classified and managed according to China National Lung Cancer Screening Guideline with Low-dose Computed Tomography (2018 version). The detection rate of positive nodules was calculated. Before the LDCT examination, residents were required to complete a "lung cancer risk factors questionnaire". The risk factors of the questionnaire were analyzed by least absolute shrinkage and selection operator (LASSO) penalized Logistic regression analysis. A total of 6256 residents were included in this study. 1228 positive nodules (19.63%) and 117 lung cancers were confirmed, including 6 cases of Tis, 103 cases of stage I (accounting for 88.03% of lung cancer). The results of LASSO penalized Logistic regression analysis indicated that age ≥50 yr (OR=1.07, 95%CI: 1.06-1.07), history of cancer (OR=3.29, 95%CI: 3.22-3.37), textile industry (OR=1.10, 95%CI: 1.08-1.13), use coal for cooking in childhood (OR=1.14, 95%CI: 1.13-1.16) and food allergy (OR=1.10, 95%CI: 1.07-1.13) were risk factors of lung cancer for female in this district. This study highlighted that numerous early stages of lung cancer cases were detected by LDCT, which could be applied to screening of lung cancer in women. Besides, age ≥50 yr, personal history of cancer, textile industry and use coal for cooking in childhood are risk factors for women in this district, which suggested that it's high time to raise the awareness of early lung cancer screening in this group.

Female smoking does not affect live birth rate after frozen thawed blastocyst transfer cycle

PurposeThe development of vitrification and blastocyst culture have recently led to a rapidly growing number of single frozen thawed blastocyst transfer (FBT) cycles worldwide. Although the impact of female smoking on spontaneous fertility is well established, its effect on assisted reproductive technologies (ART) outcome is still controversial, and no study has specifically evaluated its effect on FBT cycles’ outcome. MethodsThis retrospective study was conducted in all consecutive FBT cycles conducted between 2012 and 2021 in a single University-based ART centre. Endometrial preparation was standard and based on hormonal replacement therapy. One or two blastocysts were transferred according to couple's history and embryo quality. Female smoking status was recorded for each cycle, and the association between female smoking status and Live Birth Rate (LBR) after FBT cycle was evaluated with univariate and multivariate analysis. ResultsA total of 1537 FBT cycles performed in non-smoking women and 397 FBT cycles performed in smoking women were included in the analysis. No independent association between female smoking status and LBR in FBT cycles was found after logistic regression (OR=1.07 [0.79–1.45], p = 0.649). ConclusionOur study suggests that female smoking might not impair endometrial receptiveness in non-stimulated FBT cycles. Further studies should nevertheless consider assessing more precisely the current smoking exposure.

Effects of Heavy Alcohol Use on Nighttime Blood Pressure, Sleep Quality, and Urine Catecholamines

Heavy alcohol drinking habits contribute to the development of hypertension; this is partly due to overactivation of the sympathetic nervous system and the increased release of catecholamines. Recently, heavy alcohol drinking has been linked to poor sleep quality, but the underlying mechanisms remain unclear. We postulated that long-term frequent heavy alcohol use could increase catecholamine levels and cause blood pressure dysregulation at night, altogether influencing sleep quality. Therefore, the purpose of this study is to test the following hypothesis that compared to non-heavy drinkers, heavy drinkers have a higher level of nighttime catecholamines, a higher levels of nighttime blood pressure, and poorer sleep quality. A total of 44 men and postmenopausal women non-smokers, free of major clinical diseases, were included in this study. Heavy drinkers were defined as those having a dried blood spot phosphatidylethanol (PEth, a biomarker to detect heavy alcohol drinking) level ≥ 20 ng/mL. Participants wore an ambulatory blood pressure monitor for 24 hours and catecholamines were measured from urine samples collected in the same 24-hour period. Sleep quality was measured by using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. There were 21 heavy drinkers (mean±SEM for age: 58±1 and BMI: 26.2±0.7 kg/m2) and 23 non-heavy drinkers (age: 58±1 and BMI: 27.5±0.8 kg/m2; P≥0.3 vs. heavy drinkers). Compared to non-heavy drinkers, heavy drinkers had a higher nighttime systolic blood pressure (SBP), higher diastolic blood pressure (DBP), and a lower SBP dipping ratio (heavy drinkers vs. non-heavy drinkers for nighttime SBP: 118±3 vs. 109±2 mmHg, P=0.02; nighttime DBP: 70±2 vs. 65±2 mmHg, P=0.04; and SBP dipping ratio: 10.6±1.4% vs. 14.5±1.6%, P=0.04). No differences were found in nighttime urine catecholamines between heavy drinkers and non-heavy drinkers (P≥0.3). A total of 13 participants had a PSQI score higher than 5, indicating poor sleep quality; however, PSQI scores were similar between heavy and non-heavy drinkers (P=0.8). These findings indicate that heavy drinkers had a higher nighttime blood pressure and are consistent with the observation that heavy drinking is associated with an increased risk of hypertension in mid-life adults. Interestingly, the increase in nighttime blood pressure does not appear to be related to catecholamines and sleep quality in apparently healthy mid-life adults does not appear to be influenced by heavy drinking habits. This work was supported by NIAAA AA028537 to CLH and AHA 1266805160 to TH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Factors associated with miscarriage in Nepal: Evidence from Nepal Demographic and Health Surveys, 2001-2016.

Miscarriage is a major public health concern in low and middle-income countries (LMICs) like Nepal. This study aims to examine the factors associated with miscarriage among pregnant women of reproductive age (15-49 years) in the past 15 years. There were a total of weighted sample of 26,376 cross-sectional pregnancy data from Nepal Demographic and Health Surveys (NDHS) 2001, 2006, 2011, and 2016 combined together, which was used in the study. Multilevel logistic regression analysis that adjusted for cluster and survey weights was used to identify factors associated with miscarriage among pregnant women of reproductive age in Nepal. The results showed that maternal age, contraception, tobacco smoking, wealth index, respondents' educational status, and, caste/ethnicity were found to be strong factors of miscarriage in Nepal. The likelihood of having a miscarriage among older women (≥40 years) was more than 100% (aOR = 2.12, 95% CI [1.73, 2.59]), among non-users of contraception was 88.9% (aOR = 1.88, 95% CI [1.68, 2.11]) (p<005) and non-smoking women had a 19% lower odds of miscarriage (aOR = 0.81, 95% CI [0.69, 0.95]). Respondents from the richest wealth index had 50% (aOR = 1.50, 95% CI [1.22, 1.85]) higher likelihood of miscarriage. Mothers with only primary education had a 25% higher chance of miscarriage (aOR = 1.25, 95% CI [1.09, 1.44]) compared to those with secondary and higher secondary education. In relation to caste/ethnicity, Dalits had 13% lesser likelihood (aOR = 0.87, 95% CI [0.74, 1.02]) and Janajatis had 26% lower chances of a miscarriage than Brahmin/Chettri (aOR = 0.74, 95% CI [0.64, 0.85]). Findings from this study show that miscarriages are associated with maternal age, use of contraception, smoking, wealth index, caste, and ethnicity. Interventions aimed to improve use of contraceptives, avoiding smoking and pregnancy planning on the basis of maternal age, are needed to prevent miscarriage. Also, women from Brahmin ethinicity and those with the highest income index require greater attention when it comes to miscarriage prevention strategies in Nepal.

ВЕРОЯТНОСТЬ ФОРМИРОВАНИЯ НИКОТИНОВОЙ ЗАВИСИМОСТИ У КУРЯЩИХ ПАЦИЕНТОК С ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЕГКИХ С УЧЕТОМ СТАЖА КУРЕНИЯ И КОЛИЧЕСТВА ВЫКУРИВАЕМЫХ СИГАРЕТ

Introduction. This paper presents the results of assessing the likelihood of developing nicotine addiction, depending on smoking history and on the number of cigarettes smoked per day by women of fertile age. The aim is to establish the prognostic probability of nicotine addiction development in smokers, depending on smoking history and on the number of cigarettes smoked. Materiаls and Methods. The prospective study included 107 smoking female patients with chronic obstructive pulmonary disease and nicotine addiction of different stages (hereinafter referred to as nicotine addiction). The patients were divided into 2 groups, depending on their secondhand smoke: 53 smoking patients with and 54 smoking patients without secondhand smoke. The observational group consisted of 42 non-smoking women without any chronic diseases. Chronic obstructive pulmonary disease was diagnosed based on the clinical recommendations of the Russian Respiratory Society (2021). Reliability of the outcomes was assessed using the methods of parametric and nonparametric statistics. Prior to the application of all statistical research methods, we checked whether our sam- pling complied with the Gaussian (normal) distribution law. The distribution law was described using the Kolmogorov- Smirnov and Lilliefors normality criteria, and a single-sample Shapiro-Wilco normality test. Nonlinear links of binary features with quantitative or qualitative features were evaluated using logistic regression. Logistic regression analysis made it possible to create a statistical model for predicting the probability of an event based on available data. Results and Discussion. With an average smoking activity of 14 cigarettes per day, the onset of nicotine addiction in the first group (a combination of active and secondhand smoke) began with the smoking experience of 12 years, reaching the maximum probability with the experience of 15 years. In the second group, nicotine addiction appeared and reached its maximum (100 %) four years later than in the first group. With an increase in the number of cigarettes up to 16 per day, an identical pattern was observed within the course of earlier nicotine addiction. Conclusions. Secondhand smoke, in addition to active smoking, increases the nicotine load with the development of more pronounced prerequisites for the pathogenetic processes of chronic obstructive pulmonary disease development.

АНАЛИЗ ВЗАИМОСВЯЗИ НИКОТИНОВОЙ ЗАВИСИМОСТИ И ПАССИВНОГО КУРЕНИЯ СО СТЕПЕНЬЮ ТЯЖЕСТИ ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНИ ЛЕГКИХ У КУРЯЩИХ ЖЕНЩИН РЕПРОДУКТИВНОГО ВОЗРАСТА

Introduction. We studied the nicotine addiction stage and secondhand smoke interrelationships with the chronic obstructive pulmonary disease severity in smokers of reproductive age. Aim of the study was to research in the nicotine addiction and secondhand smoke impact upon the development of chronic obstructive pulmonary disease severity in smoking women of reproductive age. Materials and Methods. Using the questionnaire methodology developed, the nicotine addiction stage was analyzed in reproductive women with and without secondhand smoke (based on questionnaire survey outcomes). There were 107 smoking female patients of reproductive age divided into two groups: Those with secondhand smoke and those without it. Observational group consisted of 42 non-smoking women without any chronic diseases. Chronic obstructive pulmonary disease was diagnosed based on the clinical recommendations of the Russian Respiratory Society (2021). The data obtained during the study were analyzed followed by the comparison of the outcomes between the groups of smoking patients with secondhand and non-secondhand smoking, against the observational group. The outcomes led us to determine whether there is a statistically significant relationship between secondhand smoke and nicotine addiction stage in the development of chronic obstructive pulmonary disease. The reliability of the outcomes was assessed using the methods of parametric and nonparametric statistics. Before using all statistical research methods, we checked whether the sampling complied with the Gaussian (normal) distribution law. Variables that did not obey the normal distribution law or those with the uncertain distribution law were analyzed using a nonparametric statistical method, i. e., Pearson criterion. Results and Discussion. Average age of the smoking patients is 26.5 years. Average index of smokers was 6.59 pack-years. The smokers’ index exceeded the middle of the indicator contributing to the chronic obstructive pulmonary disease development (10 pack – years), which is typical for a young age and their smoking experience. It was found that the nicotine addiction stage correlates with the chronic obstructive pulmonary disease severity with a statistically significant reliability. Conclusions. Secondhand smoke in addition to active smoking, reduces the temporal characteristics of chronic obstructive pulmonary disease severity.

Abstract 3427: Serum metabolites and pancreatic ductal adenocarcinoma in two prospective cohorts

Abstract Objective: Metabolomics may provide insight to understand the etiology and potential mechanisms for pancreatic ductal adenocarcinoma (PDAC) development beyond established risk factors of smoking, diabetes, and adiposity. We extended our previous metabolomic study by including additional participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) with the aim to examine prospective associations between serum metabolites and incident PDAC. Method: We measured 1483 known metabolites in pre-diagnostic serum (up to 24 years) in two PDAC nested case-control studies within the PLCO (360 cases-control pairs) of mostly non-smoker men and women and Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC, 372 cases-control pairs) male smokers using liquid chromatography, high resolution/accurate mass spectrometry. Controls were incidence-density sampled and matched to cases by age, blood draw date, sex, race/ethnicity, and cohort. We used conditional logistic regression to calculate odds ratios and 95% confidence intervals for PDAC per standard deviation increase in log10-metabolite levels in each cohort and combined using fixed-effect meta-analyses and stratified by follow-up time. We also performed ElasticNet regression in each cohort to identify metabolites. We assessed associations of 72 predefined metabolic pathways with PDAC by comparing Fisher’s statistic of metabolite p-values per pathway with a null distribution based on 500,000 permutations. Results: Sixty-six metabolites were associated with PDAC at a false discovery rate (FDR)&amp;lt;0.05 with 26 below the Bonferroni threshold (P&amp;lt;3.4 × 10−5). Among the 66 metabolites, 14 and 15 were selected in ElasticNet regressions in ATBC and PLCO, respectively, with two in both cohorts. Notable findings include: fibrinopeptide B(1-9); seven modified, di- or poly-peptides; eight xenobiotics related to tobacco smoke; amino acids, carbohydrates, and TCA cycle metabolites known to be regulated by mutant KRAS (aspartate, glutamate, lactate, pyruvate, and α-ketoglutarate); four secondary bile acids and three aromatic amino acids (tryptophan, phenylalanine, and tyrosine) that were positively, while four fibrinogen cleavage peptides were inversely associated with PDAC. Among the top identified metabolites, aspartate, α-glutamyltyrosine, pyroglutamylglutamine, and Glu-Gly-Asn-Val showed time-varying associations overall (P≤0.05) with greater magnitudes within the first 5 years after blood draw. Thirteen metabolic pathways were associated with PDAC (Bonferroni P≤0.05). Conclusion: Our study suggests pre-diagnostic circulating metabolites, particularly those potentially related to subclinical disease, microbiome, and tobacco metabolism are associated with PDAC. The identified metabolites along with other known risk factors might be useful in algorithms to model disease risk and progression. Citation Format: Ting Zhang, Steven C. Moore, Sheng Fu, Kevin Wang, Demetrius Albanes, Stephanie J. Weinstein, Kai Yu, Rachael Z. Stolzenberg-Solomon. Serum metabolites and pancreatic ductal adenocarcinoma in two prospective cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3427.