Association of e-Cigarette Use and Postpartum Depression: Pregnancy Risk Assessment Monitoring System 2016-2019.

Background: Postpartum depression (PPD) is a prevalent public health concern. Combustible cigarette use is associated with increased risk of PPD. While electronic cigarette (e-cigarette) use during pregnancy is linked to increased risk of depressive symptoms during pregnancy, the relationship between e-cigarette use and PPD is not well understood. We sought to examine the association of e-cigarette use with PPD. Materials and Methods: Using Pregnancy Risk Assessment Monitoring System 2016-2019 data, unadjusted and adjusted logistic regression analyses for PPD were conducted via three analyses where e-cigarette use (any vs. none) was retrospectively self-reported (1) in past 2-year, (2) prepregnancy (i.e., 3 months before pregnancy), and (3) during pregnancy (i.e., last 3 months of pregnancy). We conducted an additional past 2-year e-cigarette use analysis excluding those who used combustible cigarette and/or hookah. Covariates included age, race, ethnicity, combustible cigarette, and/or hookah use, prenatal care during the last trimester, health insurance coverage during pregnancy, physical abuse during pregnancy, income, and survey type. Results: Only unadjusted odds ratios from past 2-year e-cigarette use (1.63, 95% confidence interval [CI]: 1.42-1.87) and past 2-year e-cigarette use excluding individuals with cigarette and/or hookah use (1.78, 95% CI: 1.30-2.38) were statistically associated with PPD. No adjusted analyses were statistically significant. Conclusion: Any e-cigarette use, as compared to no use, does not appear to be an independent risk factor of PPD, though it may be a useful clinical marker of increased risk of PPD. Future studies are warranted to advance our knowledge of impact of e-cigarette use on PPD.

Unraveling Neural Complexity: Exploring Brain Entropy to Yield Mechanistic Insight in Neuromodulation Therapies for Tobacco Use Disorder.

Neuromodulation therapies, such as repetitive transcranial magnetic stimulation (rTMS), have shown promise as treatments for tobacco use disorder (TUD). However, the underlying mechanisms of these therapies remain unclear, which may hamper optimization and personalization efforts. In this study, we investigated alteration of brain entropy as a potential mechanism underlying the neural effects of noninvasive brain stimulation by rTMS in people with TUD. We employed sample entropy (SampEn) to quantify the complexity and predictability of brain activity measured using resting-state fMRI data. Our study design included a randomized single-blind study with 42 participants who underwent 2 data collection sessions. During each session, participants received high-frequency (10Hz) stimulation to the dorsolateral prefrontal cortex (dlPFC) or a control region (visual cortex), and resting-state fMRI scans were acquired before and after rTMS. Our findings revealed that individuals who smoke exhibited higher baseline SampEn throughout the brain as compared to previously-published SampEn measurements in control participants. Furthermore, high-frequency rTMS to the dlPFC but not the control region reduced SampEn in the insula and dlPFC, regions implicated in TUD, and also reduced self-reported cigarette craving. These results suggest that brain entropy may serve as a potential biomarker for effects of rTMS, and provide insight into the neural mechanisms underlying rTMS effects on smoking cessation. Our study contributes to the growing understanding of brain-based interventions for TUD by highlighting the relevance of brain entropy in characterizing neural activity patterns associated with smoking. The observed reductions in entropy following dlPFC-targeted rTMS suggest a potential mechanism for the therapeutic effects of this intervention. These findings support the use of neuroimaging techniques to investigate the use of neuromodulation therapies for TUD.

Smoking, tobacco dependence, and neurometabolites in the dorsal anterior cingulate cortex.

Cigarette smoking has a major impact on global health and morbidity, and positron emission tomographic research has provided evidence for reduced inflammation in the human brain associated with cigarette smoking. Given the consequences of inflammatory dysfunction for health, the question of whether cigarette smoking affects neuroinflammation warrants further investigation. The goal of this project therefore was to validate and extend evidence of hypoinflammation related to smoking, and to examine the potential contribution of inflammation to clinical features of smoking. Using magnetic resonance spectroscopy, we measured levels of neurometabolites that are putative neuroinflammatory markers. N-acetyl compounds (N-acetylaspartate + N-acetylaspartylglutamate), glutamate, creatine, choline-compounds (phosphocholine + glycerophosphocholine), and myo-inositol, have all been linked to neuroinflammation, but they have not been examined as such with respect to smoking. We tested whether people who smoke cigarettes have brain levels of these metabolites consistent with decreased neuroinflammation, and whether clinical features of smoking are associated with levels of these metabolites. The dorsal anterior cingulate cortex was chosen as the region-of-interest because of previous evidence linking it to smoking and related states. Fifty-four adults who smoked daily maintained overnight smoking abstinence before testing and were compared with 37 nonsmoking participants. Among the smoking participants, we tested for associations of metabolite levels with tobacco dependence, smoking history, craving, and withdrawal. Levels of N-acetyl compounds and glutamate were higher, whereas levels of creatine and choline compounds were lower in the smoking group as compared with the nonsmoking group. In the smoking group, glutamate and creatine levels correlated negatively with tobacco dependence, and creatine correlated negatively with lifetime smoking, but none of the metabolite levels correlated with craving or withdrawal. The findings indicate a link between smoking and a hypoinflammatory state in the brain, specifically in the dorsal anterior cingulate cortex. Smoking may thereby increase vulnerability to infection and brain injury.

Impact of the uninstructed use of a herbal, ayurvedic toothpaste on parameters of gingival health in periodontal aftercare patients: A randomized, double-blinded, two-arm parallel-group study.

AIM: The aim of this study was to evaluate the impact of the uninstructed use of a toothpaste containing herbal ayurvedic ingredients on parameters of gingival health in a cohort of periodontal aftercare patients affected by gingival inflammation compared to the use of a standard, non-herbal toothpaste. MATERIALS AND METHODS: The monocentric, randomized, double-blinded, two-arm parallel-group intervention was performed in a cohort of 88 periodontal aftercare patients with clinical signs of gingival inflammation. At baseline, bleeding on probing (BoP), gingival index (GI) and Quigley-Hein plaque index (QHI) were recorded. Subsequently, the study patients were randomly provided with a herbal ayurvedic toothpaste (n = 44) or a conventional, non-ayurvedic control toothpaste (n = 44) and without additional oral hygiene training instructed to use it 2× daily for the next 28 days. On day 28, BoP, GI and QHI were recorded again. RESULTS: At baseline, there were no significant differences between both groups. On day 28, mean GI and BoP scores were significantly lower (p < 0.001) compared to baseline in both groups. Differences between the groups could not be verified. Mean QHI scores did not change significantly between day 0 and day 28 in both groups. CONCLUSIONS: The impact of uninstructed toothbrushing with an ayurvedic toothpaste on the manifestation of gingival inflammation in periodontal aftercare patients is not significantly different to the use of a conventional, non-herbal toothpaste.

F-erythrocytes promote Plasmodium falciparum proliferation in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) remains prevalent because heterozygous carriers (HbAS) are partially resistant to Plasmodium falciparum malaria. Sickle hemoglobin (HbS) polymerization in low and intermediate oxygen (O2 ) conditions is the main driver of HbAS-driven resistance to P. falciparum malaria. However, epidemiological studies have reported mixed malaria morbidity and mortality outcomes in individuals with sickle cell disease (SCD). While maximum-tolerated dose hydroxyurea has been shown to lower malaria incidence, fetal hemoglobin (HbF), an inhibitor of HbS polymerization that is variably packaged in F-erythrocytes, might provide hemoglobin that is accessible to the parasite for feeding. METHODS: To explore that risk, we examined the effect of variable mean corpuscular fetal hemoglobin (MCHF) on P. falciparum proliferation, invasion, and development in HbSS RBCs. RESULTS: We found that greater MCHF in HbSS red blood cells (RBCs) is associated with increased P. falciparum proliferation in O2 environments comparable with the microcirculation. Moreover, both parasite invasion and intracellular growth, the major components of proliferation, occur predominantly in F-erythrocytes and are augmented with increasing MCHF. CONCLUSIONS: HbF modifies P. falciparum infection in HbSS RBCs, further highlighting the complexity of the molecular interactions between these two diseases. Other inhibitors of HbS polymerization that do not increase HbF or F-erythrocytes should be independently assessed for their effects on P. falciparum malaria proliferation in HbSS RBCs.

Impact of Dietary Nitrate on the Recovery of Therapy-related Vascular Health Impairments Following Standard Periodontal Aftercare Therapy: a Hypothesis-generating Subanalysis.

This follow-up study assessed the impact of a nitrate-rich diet on salivary nitrate/nitrite levels and the recovery of therapy-induced vascular impairments in a cohort of 39 periodontitis patients treated by standard subgingival mechanical plaque removal (PMPR). At baseline, saliva samples for nitrate/nitrite analysis were collected, and peripheral/central blood and augmentation pressure was documented using the Arteriograph recording system. Immediately after, PMPR vascular parameters were reassessed. All study patients received a randomly allocated supply of a lettuce beverage to be consumed for 14 days, containing either a daily dosage of 200 mg nitrate (test group, n = 20) or being void of nitrate (placebo group, n = 19). At day 14, salivary and vascular parameters were reassessed. Initial salivary and vascular parameters did not differ significantly between the groups. PMPR impaired all vascular parameters in both groups with no differences between the groups. At day 14, salivary nitrate/nitrite levels of the test group were significantly elevated compared to baseline. All vascular parameters had significantly recovered from the impairment inflicted by PMPR. In the placebo group, by contrast, salivary parameters did not differ significantly from baseline, and the recovery of impaired vascular parameters was restricted to a significant improvement of diastolic blood pressure. Correlation analysis identified a significant inverse correlation between salivary nitrate/nitrite sum and central/peripheral blood pressure and augmentation pressure. In conclusion, the data of this subanalysis suggest that increasing salivary nitrate/nitrite levels by a diet rich in nitrate may improve recovery of therapy-induced vascular impairments after PMPR.

Hormone-based models for comparing menstrual cycle and hormonal contraceptive effects on human resting-state functional connectivity.

Oral contraceptives (OCs) are widely used yet understudied given their potential for public health consequences. Emerging investigations scaling from single-subject, dense-sampling neuroimaging studies to population-level metrics have linked OCs to altered brain structure and function. Modeling the hypogonadal, hypergonadal, or mixed state effects of OCs in terms of their impact on hormone action in the brain is a valuable approach to synthesizing results across neuroimaging studies and comparing OC effects to companion findings from research on menstrual cycle phase effects on brain anatomy and function. Resting-state functional connectivity studies provide a powerful tool to evaluate the role of OCs on the intrinsic network connectivity that underlies multiple behavioral domains. The preponderance (but not consensus) of the current literature indicates that (1) as the menstrual cycle proceeds from a low to high progesterone state, prefrontal connectivity increases and parietal connectivity decreases; (2) OCs tend to mimic this connectivity pattern; therefore (3) OCs may produce a hyperprogestogenic state in the brain, in spite of overall reductions in endogenous steroid hormone levels. Alternative models are also considered.

Electronic Nicotine Delivery Systems (ENDS) Use and Pregnancy I: ENDS Use Behavior During Pregnancy.

PURPOSE OF REVIEW: This review examines Electronic Nicotine Delivery Systems (ENDS) use behavior during pregnancy, including the prevalence of and transitions in use during pregnancy. RECENT FINDINGS: Twenty-two papers addressed the prevalence of and/or transitions in ENDS use during pregnancy. Findings show a complex landscape of ENDS use. A minority (0.4%-7.0%) of pregnant persons use ENDS; most commonly this occurs in the form of dual use (ENDS and combustible cigarettes (CC); 75%). Many pregnant persons report using ENDS because they perceive them to be a lower-risk alternative and/or potential cessation aide for CC smoking. However, while a subset of those who use ENDS do quit all tobacco product use during pregnancy, only a small proportion switch from exclusive CC smoking to exclusive ENDS use. SUMMARY: ENDS are a somewhat new addition to the tobacco product landscape. The perception of ENDS as a lower-risk alternative may contribute to ENDS use in pregnancy. There is insufficient evidence to support the notion that ENDS facilities the cessation of tobacco product use during pregnancy.

Sex Differences in the Association of Cigarette Craving With Insula Structure.

BACKGROUND: Cigarette craving, which can negatively impact smoking cessation, is reportedly stronger in women than in men when they initiate abstinence from smoking. Identifying approaches to counteract craving in people of different sexes may facilitate the development of personalized treatments for Tobacco Use Disorder, which disproportionately affects women. Because cigarette craving is associated with nicotine dependence and structure of the insula, this study addressed whether a person's sex influences these associations. METHODS: The research participants (n = 99, 48 women) reported daily cigarette smoking and provided self-reports of nicotine dependence. After overnight abstinence from smoking, they underwent structural magnetic resonance imaging scanning to determine cortical thickness of the left and right anterior circular insular sulcus, and self-rated their cigarette craving before and after their first cigarette of the day. RESULTS: Women reported stronger craving than men irrespective of smoking condition (i.e., pre- and post-smoking) (P = .048), and smoking reduced craving irrespective of sex (P < .001). A 3-way interaction of sex, smoking condition, and right anterior circular insular sulcus thickness on craving (P = .033) reflected a negative association of cortical thickness with pre-smoking craving in women only (P = .012). No effects of cortical thickness in the left anterior circular insular sulcus were detected. Nicotine dependence was positively associated with craving (P < .001) across groups and sessions, with no sex differences in this association. CONCLUSIONS: A negative association of right anterior insula thickness with craving in women only suggests that this region may be a relevant therapeutic target for brain-based smoking cessation interventions in women.

Striatal dopamine D2-type receptor availability and peripheral 17ß-estradiol.

Research using rodent models has established a relationship between the steroid hormone estrogen and dopamine function, by revealing changes throughout the estrous cycle and by directly manipulating neuroendocrine signaling through ovariectomy and administration of estrogen. However, a direct link between estrogen levels and dopamine signaling had not been established in humans. The goal of this study, therefore, was to assess the relationship between circulating 17ß-estradiol and dopamine signaling in the human brain by testing for a relationship between two proxies for these variables: peripheral 17ß-estradiol and striatal dopamine D2-type receptor availability, measured with [18F]fallypride and positron emission tomography (PET). Sixteen (23-45 years of age) women were tested on 2 days of the menstrual cycle estimated prospectively to occur during (a) the early follicular phase, when estrogen levels are near their nadir, and (b) the periovulatory phase, when estrogen levels peak. PET scans with [18F]fallypride were performed on these 2 days, and serum 17ß-estradiol was measured using radioimmunoassay. Dopamine D2-type receptor availability did not differ significantly in the whole striatum or the caudate, putamen, or accumbens subregions during the high-estrogen vs. the low-estrogen phases of the menstrual cycle. We conclude that circulating estrogen levels do not affect dopamine D2-type receptor availability in the human striatum although other indices of dopaminergic function may be affected.

Effects of oral contraceptive pills on mood and magnetic resonance imaging measures of prefrontal cortical thickness.

Gonadal hormones influence neuronal organization and plasticity. Yet the consequences of altering their concentrations by administering contraceptive agents, which are used by most reproductive-age women in the United States, are unclear. Cross-sectional studies have found both larger and smaller cortical regions alongside a variety of mood alterations in women who use oral contraceptive pills (OCPs) compared to naturally-cycling women. The goal of this study, therefore, was to determine whether there is an effect of OCPs on MRI measures of prefrontal cortical brain structure that may influence regulation of mood. We performed a double-blind, placebo-controlled, randomized crossover study comparing effects of OCPs (0.15 mg levonorgestrel + 0.30 µg ethinyl estradiol) vs placebo (N = 26) on MRI measures of prefrontal cortical thickness and on mood, as indicated by self-report on the Daily Record of Severity of Problems, which also includes one item related to somatic symptoms. MRI measures that reflect cortical thickness were smaller bilaterally in the pars triangularis and in the pars opercularis and frontal pole of the right hemisphere during the OCP arm vs. placebo. Only the effect in the right pars triangularis survived multiple comparisons correction. Right pars triangularis MRI measures of cortical thickness were not related to mood symptoms, but negatively correlated across conditions with severity of somatic symptoms on the DSRP. The somatic symptoms and MRI measures may be independently related to the actions of steroid hormones in OCPs, with OCPs simultaneously inducing both more effects on MRI measures of cortical thickness and somatic symptoms.

Electronic Nicotine Delivery Systems (ENDS) Use and Pregnancy II: Perinatal Outcomes Following ENDS Use During Pregnancy.

Purpose of Review: This review examines the risk of adverse perinatal outcomes following electronic nicotine delivery system (ENDS) use during pregnancy, and considers whether there are sufficient data to support ENDS as a harm reduction approach during pregnancy. Recent Findings: Seven papers assessed perinatal outcomes following ENDS use during pregnancy. There was evidence that ENDS use was associated with increased risk for some adverse perinatal outcomes (e.g., small for gestational age). However, the repeated use of data sets, insufficient data (e.g., timing of ENDS use, type of ENDS products used), and limited samples size, contributed to mixed findings on the degree to which ENDS use (alone or in combination with combustible cigarettes (CC)) impacts the risk of adverse perinatal outcomes relative to CC smoking alone. Summary: The current data are still insufficient to support ENDS as a harm reduction approach, though findings do warrant concern and more detailed investigation of ENDS use during pregnancy. Future research directions, as well as implications for clinical recommendations and tobacco regulatory science are discussed.

Impulsivity across substance use categories: Consideration of sex/gender.

PURPOSE OF REVIEW: The goal was to review recent (1/2015-2/2020) evidence of impulsivity as a feature of substance use disorders or use of substances (alcohol, cannabis, nicotine, opioids, stimulants) in males compared to females in terms of: a) impulsivity in substance-using groups (or substance-using compared to control groups), and b) relationship between impulsivity and substance use behavior, clinical severity, or treatment outcomes. RECENT FINDINGS: Of 361 papers identified by the searches, 69 met inclusion criteria, and 39 were highlighted for considering sex/gender in relation to impulsivity in substance-using populations. Taken together, findings supported higher impulsivity in males and females who use substances, relative to controls; and higher impulsivity was linked with more substance use/severity in both sex/genders. There were mixed findings regarding male versus female differences in impulsivity among individuals who use substances, or in the magnitude of the relationship between impulsivity and substance use severity. SUMMARY: The current body of evidence does not point to a consistent sex/gender difference in the role of impulsivity within and across substance use disorders. Impulsivity is a clinically-relevant construct for male and female individuals who use substances, across a range of substances.

Resting-state functional connectivity in women with PMDD.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is an understudied, debilitating disorder of women. Given evidence for prefrontal cortical and limbic dysfunction in PMDD, we compared intrinsic connectivity of the executive control network (ECN), default mode network (DMN), and amygdala in women with PMDD vs. controls. METHODS: Thirty-six women (18 PMDD, 18 control) participated in fMRI during the follicular and luteal phases of the menstrual cycle. At each time, resting-state functional connectivity was evaluated both before and after participants performed an emotion regulation task. The ECN was identified using independent components analysis, and connectivity of left and right amygdala seeds was also evaluated. RESULTS: Nonparametric permutation testing identified a cluster in the left middle temporal gyrus (MTG) with significantly stronger connectivity to the left ECN in women with PMDD vs. controls in all four fMRI sessions. Women with PMDD exhibited no difference in functional connectivity between menstrual cycle phases. Amygdala connectivity did not differ between the groups but differed significantly with menstrual phase, with left amygdala connectivity to cingulate cortex being significantly stronger during the follicular vs. luteal phase. Right amygdala connectivity to the middle frontal gyrus was also stronger during the follicular vs. luteal phase, with no group differences. These findings suggest that women with PMDD have different intrinsic network dynamics in the left executive control network compared to healthy controls.

Subjective response to intranasal nicotine administration in oral contraceptive users and naturally-cycling women.

INTRODUCTION: Approximately half of premenopausal women who smoke cigarettes also use hormonal contraceptives, with most using oral contraceptives (OCs). While research on the effects of endogenous hormones on smoking-related outcomes continues to expand, little is known about the influence of OCs on similar outcomes. We sought to explore differences in the subjective response to nicotine by OC use after stratifying by testing condition (e.g., smoking status). METHODS: Participants were regular (≥5 cigarettes/day) smokers, classified into OC and naturally cycling (NC) groups. All participants completed four total lab sessions by smoking status (ad libitum smoking, acute smoking abstinence) and anticipated progesterone level (low progesterone week (LPW), high progesterone week (HPW)). Each lab session included self-administration of intranasal nicotine (Time 0 min), assessment of subjective response via the Subjective State Scale (-30 and + 5 min). RESULTS: Compared to the NC group (n = 28), the OC group (n = 14) was younger (26.2 ±â€¯1.1 versus 24.2 ±â€¯1.1; p < 0.001) and had a lower Fagerström Test for Nicotine Dependence score (3.4 ±â€¯0.5 versus 2.6 ±â€¯0.5; p = 0.011). Progesterone-to-estradiol ratios varied significantly by group at three of the four time points (p < 0.05). During ad libitum smoking, the OC group had significantly lower craving after nicotine administration than the NC group (1.93 ±â€¯0.33 versus 2.89 ±â€¯0.23; p = 0.024). No other significant differences in subjective response were identified. CONCLUSIONS: Despite significantly different hormone levels, group differences in subjective response to nicotine were relatively few. Additional research is needed to elucidate the mechanisms involved in these observations, as well as explore how they may influence cessation in women.

Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition.

Sickle cell trait (AS) confers partial protection against lethal Plasmodium falciparum malaria. Multiple mechanisms for this have been proposed, with a recent focus on aberrant cytoadherence of parasite-infected red blood cells (RBCs). Here we investigate the mechanistic basis of AS protection through detailed temporal mapping. We find that parasites in AS RBCs maintained at low oxygen concentrations stall at a specific stage in the middle of intracellular growth before DNA replication. We demonstrate that polymerization of sickle hemoglobin (HbS) is responsible for this growth arrest of intraerythrocytic P. falciparum parasites, with normal hemoglobin digestion and growth restored in the presence of carbon monoxide, a gaseous antisickling agent. Modeling of growth inhibition and sequestration revealed that HbS polymerization-induced growth inhibition following cytoadherence is the critical driver of the reduced parasite densities observed in malaria infections of individuals with AS. We conclude that the protective effect of AS derives largely from effective sequestration of infected RBCs into the hypoxic microcirculation.