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.

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.

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.

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.

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.

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.

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.

Brain activation during emotion regulation in women with premenstrual dysphoric disorder.

BACKGROUND: Difficulties in regulating emotions are linked to the core symptoms of premenstrual dysphoric disorder (PMDD). We therefore investigated the neural substrates of emotion-regulation problems in women with PMDD. METHODS: On the basis of self-evaluations over 2 months on the Daily Record of Severity of Problems, eligible participants were assigned to two groups: PMDD and control (18 per group). Functional magnetic resonance imaging (fMRI) and a well-validated task were used to assess brain function during emotion regulation. Participants were tested twice, once during the follicular (asymptomatic) and once in the late luteal (symptomatic) phase of the menstrual cycle. RESULTS: Women with PMDD gave higher ratings of negative affect in the luteal phase than in the follicular phase, and compared with healthy control participants during the luteal phase. A region-of-interest fMRI analysis indicated that during the late luteal phase, women with PMDD had hypoactivation in right dorsolateral prefrontal cortex (dlPFC) during all conditions of the emotion-regulation task, not only in the contrast that isolated emotion regulation. An exploratory whole-brain, voxel-wise analysis showed that women with PMDD had less activation in the precentral gyrus during the luteal phase than the follicular phase, and less activation in the postcentral gyrus compared with control participants. CONCLUSIONS: During the luteal phase of the menstrual cycle, women with PMDD experience difficulty regulating emotions. Hypoactivation in the right dlPFC may contribute to this problem, but may be related more generally to other affective symptoms of PMDD. Hypofunction in the right pre- and postcentral gyri warrants additional study.

Impact of different concentrations of an octenidine dihydrochloride mouthwash on salivary bacterial counts: a randomized, placebo-controlled cross-over trial.

OBJECTIVES: This bi-centric, placebo-controlled, randomized, evaluator-blinded, incomplete cross-over clinical phase II trial was initialized to identify the most appropriate concentration of octenidine dihydrochloride (OCT) in mouth rinses. MATERIALS AND METHODS: Rinses of 0.10, 0.15, and 0.20% OCT were compared to a saline placebo rinse regarding the reduction of salivary bacterial counts (SBCs) in 90 gingivitis patients over 4 days. Changes in plaque (PI) and gingival index (GI), taste perception, and safety issues were evaluated. RESULTS: At baseline, the first OCT (0.10, 0.15, 0.20%) rinse resulted in a decrease of SBC (reduction by 3.63-5.44 log10 colony forming units [CFU]) compared to placebo (p < 0.001). Differences between OCT concentrations were not verified. After 4 days, the last OCT rinse again resulted in a significant SBC decrease (3.69-4.22 log10 CFU) compared to placebo (p < 0.001). Overall, SBC reduction between baseline and day 4 was significantly higher in OCT 0.15 and 0.20% groups compared to OCT 0.10% and placebo. Mean GI/PIs were significantly lower in OCT groups than in the placebo group (p < 0.001). Differences in GI/PI between OCT groups were not verified. Adverse effects increased with increasing OCT concentrations. CONCLUSIONS: Considering antibacterial efficacy, frequency of adverse events, and user acceptance, 0.10% OCT was identified as the preferred concentration to be used in future clinical trials. CLINICAL RELEVANCE: Due to its low toxicity and pronounced antibacterial properties, octenidine dihydrochloride (OCT) is a promising candidate for the use in antiseptic mouth rinses. OCT concentrations of 0.10% are recommended for future clinical trials evaluating the plaque-reducing properties of OCT mouth rinses. ( www.clinicaltrials.gov , NCT022138552).

Stimulation of the nitrate-nitrite-NO-metabolism by repeated lettuce juice consumption decreases gingival inflammation in periodontal recall patients: a randomized, double-blinded, placebo-controlled clinical trial.

AIM: This prospective, parallel group, two-armed, double-blind, placebo-controlled randomized trial evaluated the impact of dietary nitrate consumption on gingival inflammation in periodontal recall patients. MATERIAL AND METHODS: Forty-four (23 test/21 placebo) periodontal recall patients with chronic gingivitis were enrolled. At baseline, gingival index (GI), plaque control record (PCR) and salivary nitrate level (SNL) were recorded, followed by sub- and supragingival debridement. Subsequently, participants were randomly provided with 100 ml bottles of a lettuce juice beverage to be consumed 3× daily over 14 days, containing either a standardized amount of nitrate resulting in an intake of approximately 200 mg nitrate per day (test) or being devoid of nitrate (placebo). RESULTS: At baseline, mean GI, PCR and SNL did not differ significantly between the groups. At day 14, mean GI of the test group was significantly reduced compared to baseline and significantly lower (p = 0.002) than in the placebo group (GI 0.3 versus 0.5). Also, mean SNL in the test group was significantly higher than in the placebo group (54.0 µg/ml versus 27.8 µg/ml; p < 0.035). Mean PCR did not change significantly in both groups. CONCLUSIONS: Dietary nitrate consumption may be a useful adjunct in the control of chronic gingivitis.

Emotion regulation in women with premenstrual dysphoric disorder.

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.

False memories in highly superior autobiographical memory individuals.

The recent identification of highly superior autobiographical memory (HSAM) raised the possibility that there may be individuals who are immune to memory distortions. We measured HSAM participants' and age- and sex-matched controls' susceptibility to false memories using several research paradigms. HSAM participants and controls were both susceptible to false recognition of nonpresented critical lure words in an associative word-list task. In a misinformation task, HSAM participants showed higher overall false memory compared with that of controls for details in a photographic slideshow. HSAM participants were equally as likely as controls to mistakenly report they had seen nonexistent footage of a plane crash. Finding false memories in a superior-memory group suggests that malleable reconstructive mechanisms may be fundamental to episodic remembering. Paradoxically, HSAM individuals may retrieve abundant and accurate autobiographical memories using fallible reconstructive processes.

Oral contraceptive pill use is associated with localized decreases in cortical thickness.

Oral contraceptive pills (OCs), which are used to prevent pregnancy by the majority of women in the United States, contain steroid hormones that may affect the brain's structure and function. In this investigation, we tested the hypothesis that OC use is associated with differences in brain structure using a hypothesis-driven, surface-based approach. In 90 women, (44 OC users, 46 naturally-cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. Further investigations are needed to determine if cortical thinning in these regions are associated with behavioral changes, and also to identify whether OC use is causally or only indirectly related to these changes in brain morphology.

On the relationship between gingival biotypes and gingival thickness in young Caucasians.

OBJECTIVES: To evaluate a possible relationship between gingival biotypes and gingival thickness, papilla height and gingival width. MATERIAL AND METHODS: Thirty-six adult subjects were stratified by their gingival biotype (GB), as defined by transparency of a periodontal probe through the buccal gingival margin, into "thin" (18 subjects) and "thick" (18 subjects) GB. Out of these, extreme cases (6 "very thin", 6 "very thick") were identified. Four different parameters were assessed: gingival thickness (GT), papilla height (PH), probing depth (PD) and gingival width (GW). RESULTS: When comparing "thin" and "thick" GB, midfacial GT (0.40 ± 0.07 vs. 0.72 ± 0.11 mm; P < 0.0001), PH (3.76 ± 0.50 vs. 3.95 ± 0.41 mm, P = 0.02) and GW (3.01 ± 1.26 vs. 4.63 ± 0.86 mm, P = 0.04) were lower in the "thin" GB group. Further stratification into moderately and extremely "thin"/"thick" GB eliminated the differences between the moderate groups. CONCLUSION: Our data support the traditional hypothesis that two different gingival biotypes with concomitant properties distinguishable by gingival transparency exist. In addition, we provide evidence that an alternative classification into "very thick", "moderate" and "very thin" biotypes might be advantageous, because the unique properties were seemingly primarily driven by subjects with extreme values.

Decreased susceptibility to false memories from misinformation in hormonal contraception users.

Sex hormones are increasingly implicated in memory formation. Recent literature has documented a relationship between hormones and emotional memory and sex differences, which are likely related to hormones, have long been demonstrated in a variety of mnemonic domains, including false memories. Hormonal contraception (HC), which alters sex hormones, has been associated with a bias towards gist memory and away from detailed memory in women who use it during an emotional memory task. Here, we investigated whether HC was associated with changes in susceptibility to false memories, which may be related to the formation of gist memories. We tested false memory susceptibility using two well-validated false memory paradigms: the Deese-Roediger-McDermott (DRM) task, and a story-based misinformation task. We found that hormonal contraceptive users were less susceptible to false memories compared to non-users in the misinformation task, and no differences were seen between groups on the DRM task. We hypothesise that the differences in false memories from the misinformation task may be related to hormonal contraceptive users' memory bias away from details, towards gist memory.

Oral contraceptive pill use and menstrual cycle phase are associated with altered resting state functional connectivity.

At rest, brain activity can be characterized not by an absence of organized activity but instead by spatially and temporally correlated patterns of activity. In this experiment, we investigated whether and to what extent resting state functional connectivity is modulated by sex hormones in women, both across the menstrual cycle and when altered by oral contraceptive pills. Sex hormones have been shown to have important effects on task-related activity, but few studies have investigated the extent to which they can influence the behavior of functional networks at rest. These hormones are dramatically altered by the use of hormonal contraception, which is used by approximately 100 million women worldwide. However, potential cognitive side effects of hormonal contraception have been given little attention. Here, we collected resting state data for naturally-cycling women (n=45) and women using combined oral contraceptive pills (n=46) and evaluated the differences in resting state activity between these two groups using independent component analysis. We found that in the default mode network and in a network associated with executive control, resting state dynamics were altered both by the menstrual cycle and by oral contraceptive use. Specifically, the connectivity of the left angular gyrus, the left middle frontal gyrus, and the anterior cingulate cortex were different between groups. Because the anterior cingulate cortex and left middle frontal gyrus are important for higher-order cognitive and emotional processing, including conflict monitoring, changes in the relationship of these structures to the functional networks with which they interact may have important consequences for attention, affect, and/or emotion regulation.

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.