Meeting-makers make meaning: alcoholics anonymous participation and personal meaningfulness.

AIMS: The central aim of this study was to determine whether intentional, voluntary alcoholics anonymous (AA) participation showed any independent association with affect, over and above that which has been observed in association with other recovery-related behaviors, such as abstinence, among individuals with a history of alcohol use disorder. Additionally, we sought to determine the nature of the affective changes associated with specific dimensions of AA participation (i.e. meeting  attendance, fellowship  involvement, 12-step  work). METHODS: Thirty abstinent alcohol use disorder individuals were recruited and evaluated. Multivariate linear regressions were used to examine associations between dimensions of AA participation, measured using the Multidimensional Mutual-Help Assessment Scale and standardized measures of affective experiences, including the Profile of Mood States, Subjective Happiness Scale, and the Twelve Promises Scale. RESULTS AND CONCLUSIONS: Increase in AA participation was associated with higher positive affective experiences. These associations were observed independently with AA meeting  attendance and fellowship  involvement, but not 12-step work. This study's findings suggest that greater AA meeting  attendance and fellowship  involvement are correlated with enhancements in the meta-emotional experience of personal meaningfulness. This study extends evidence on AA-related changes by considering affective improvements as a primary clinical outcome, thereby laying the foundation for subsequent, more comprehensive research into the relationship between dimensions of AA participation and recovery-related affective changes.

Brain, behavioral, affective, and sex correlates of recovery from alcohol use disorders.

BACKGROUND: Recovery from alcohol use disorders (AUDs) consists of salutary changes in behavior and affect. While evidence suggests that recovery-related behavioral changes, such as abstinence, emerge in tandem with both neural and affective changes, the precise relationships among these changes are unknown. To understand these relationships, we examined associations between the duration of abstinence (DOA), affective states, and neuroimaging-based structural measures of the brain reward system (BRS) in AUD men (AUDM ) and AUD women (AUDW ). METHODS: Participants were community respondents from the Boston area comprising right-handed abstinent individuals with AUD (n = 60; 30 men) and controls without AUD (NC; n = 60; 29 men). Multivariate linear regressions compared short-/mid-term abstainers (≤5 years), long-term abstainers (>5 years), and the NC group on measures of BRS volume (3T magnetic resonance imaging scans) and measures of affect (Profile of Mood States [POMS]; Multiple Affect Adjective Check List [MAACL]; Hamilton Rating Scale for Depression [HRSD]). Analyses contrasted sex differences and accounted for age, education, drinking severity, and verbal IQ. RESULTS: Compared to the NC group, short-/mid-term abstainers exhibited larger posterior insular volume (total (ß = 0.019, 95% CI: 0.004, 0.034)), higher negative affect (POMS Mood Disturbance (ß = 27.8, 95% CI: 11.56, 44.04), and lower positive affect (POMS Vigor (ß = -4.89, 95% CI: -9.06, -0.72)). Compared to the NC group, Long-term abstainers exhibited significantly smaller volumes of aggregate anterior cingulate cortex (ß = -0.06, 95% CI: -0.113, -0.008) and higher HRSD scores (ß = 1.56, 95% CI: 0.14, 2.98). Relative to AUDM , AUDW exhibited significantly larger right anterior insular volumes (ß = 0.03, 95% CI: 0.01, 0.06) and significantly greater MAACL Positive Affect scores (ß = 7.56, 95% CI: 0.59, 11.55) in association with DOA. CONCLUSIONS: We found that differences in abstinence from alcohol were correlated with differences in both neural recovery and affective dimensions of recovery from AUDs. The observed sex differences extend evidence of dimorphic effects of AUDs and recovery on brain structure and function. Future longitudinal research will test inferences concerning the directionality of these relationships.

Post-traumatic Headache and Mild Traumatic Brain Injury: Brain Networks and Connectivity.

PURPOSE OF REVIEW: Post-traumatic headache (PTH) consequent to mild traumatic brain injury (mTBI) is a complex, multidimensional, chronic neurological disorder. The purpose of this review is to evaluate the current neuroimaging studies on mTBI and PTH with a specific focus on brain networks and connectivity patterns. RECENT FINDINGS: We present findings on PTH incidence and prevalence, as well as the latest neuroimaging research findings on mTBI and PTH. Additionally, we propose a new strategy in studying PTH following mTBI. The diversity and heterogeneity of pathophysiological mechanisms underlying mild traumatic brain injury pose unique challenges on how we interpret neuroimaging findings in PTH. Evaluating alterations in the intrinsic brain network connectivity patterns using novel imaging and analytical techniques may provide additional insights into PTH disease state and therefore inform effective treatment strategies.

Molecular mechanisms of anticancer effect of rutin.

Because of the extensive biological functions of natural substances such as bioflavonoids, and their high safety and low costs, they could have high priority application in the health care system. The antioxidant properties of rutin, a polyphenolic bioflavonoid, have been well documented and demonstrated a wide range of pharmacological applications in cancer research. Since chemotherapeutic drugs have a wide range of side effects and rutin is a safe anticancer agent with minor side effects so recent investigations are performed for study of mechanisms of its anticancer effect. Both in-vivo and in-vitro examinations on anticancer mechanisms of this natural agent have been widely carried out. Regulation of different cellular signaling pathways such as Wnt/ß-catenin, p53-independent pathway, PI3K/Akt, JAK/STAT, MAPK, p53, apoptosis as well as NF-ĸB signaling pathways helps to mediate the anticancer impacts of this agent. This study tried to review the molecular mechanisms of rutin anticancer effect on various types of cancer. Deep exploration of these anticancer mechanisms can facilitate the development of this beneficial compound for its application in the treatment of different cancers.

Longitudinal course of vasomotor symptoms in perimenopausal migraineurs.

OBJECTIVE: To examine the longitudinal course of vasomotor symptoms (VMS) in women with a history of migraine in comparison to women without a history of migraine disease. METHODS: The study sample consisted of 467 women with a self-reported prior migraine diagnosis and 2,466 women without prior migraine diagnosis who were assessed longitudinally during menopausal transition as part of the Study of Women's Health Across the Nation. Linear mixed regression models with backward elimination were used to evaluate longitudinal associations between VMS and migraine while adjusting for baseline and time-varying demographic, socioeconomic, psychological, and reproductive factors. Additional analyses were performed to further assess the specificity of the association between migraine and VMS that included evaluating the association between migraine and vaginal dryness and between back pain and VMS. RESULTS: A history of migraine predicted an increased frequency of VMS but not vaginal dryness during menopausal transition. Significant interaction between history of migraine and menopausal status for the prediction of VMS was also identified. Burden of VMS was found to be higher during late-stage perimenopause in women with migraine. In contrast, the history of back pain did not predict the frequency of VMS. INTERPRETATION: This is the first study to delineate that a history of migraine predicts an increased frequency of VMS in women during menopausal transition. Hypothalamic abnormalities and thermoregulatory dysfunction against a milieu of decreasing estradiol concentrations during menopausal transition may explain the increased frequency of VMS in migraineurs during menopausal transition. ANN NEUROL 2019;85:865-874.

A novel sensitive laccase biosensor using gold nanoparticles and poly L-arginine to detect catechol in natural water.

In this study, the simple, green, and fast layer-by-layer modification of the glassy carbon electrode was mainly performed by electrodeposition of gold nanoparticles and then, poly-l-arginine, and finally, laccase was covalently bonded to poly-l-arginine using glutaraldehyde. This type of fabrication is used for the first time for catechol detection, which provides a bioelectrocatalytic cycle for electron transport in the presence of laccase that results in sensitive and fast detection of catechol. The scanning electron microscopy, Fourier-transform infrared spectroscopy, and electrochemical studies were performed to confirm successful immobilization of the enzyme. The biosensor response was linear in a wide range of catechol trace concentrations, 24.90-274.00 nM, with the detection limit of 18.00 nM. Values of Km , α, n, and Ks for the immobilized enzyme were calculated to be 1.25 × 10-2  µM, 0.56, 3.19, and 0.28 Sec-1 , respectively. It was examined in real sample successfully confirming it is capable of measuring catechol in natural water.

A novel intracellular pH-responsive formulation for FTY720 based on PEGylated graphene oxide nano-sheets.

OBJECTIVE: This study was performed to investigate a novel pH-responsive nanocarrier based on modified nano graphene oxide (nGO) to promote the acid-triggered intracellular release of a poorly soluble drug, FTY720. METHODS: To synthesize a drug conjugated to modified nGO, first the polyethylene glycol (PEG) was conjugated to nGO, then the produced PEG-nGO was functionalized with the anticancer drug, FTY720, through amide bonding. It was characterized by the scanning electron microscopy (SEM), the atomic force microscopy (AFM), the Fourier transform infrared (FTIR) spectroscopy and the UV-vis spectroscopy. In vitro drug release of the FTY720-conjugated PEG-nGO was evaluated at pH 7.4 and 4.6 PBS at 37 °C. Furthermore, the antineoplastic action of unloaded and drug-loaded carrier against the human breast adenocarcinoma cell line MCF7 was explored using MTT and BrdU assays. RESULTS: Characterization methods indicated successful drug deposition on the surface of nGO. In vitro, drug release results revealed a significantly faster release of FTY720 from PEG-nGO at acidic pH, compared with physiological pH. The proliferation assays proved that the unloaded nGO had no significant cytotoxicity against MCF7 cells, while free FTY720- and FTY720-loaded PEG-nGO had an approximately equal cytotoxic effect on the MCF7 cells. It was found that the extended release characteristic of FTY720 was well fitted to Korsmeyer-Peppas model and the release profile of FTY720 from PEG-nGO is diffusion controlled. CONCLUSION: PEGylated GO can act as a pH-responsive drug carrier to improve the efficacy of anticancer drug delivery.

Sex-related influences in migraine.

Migraine is a common neurological disorder with significantly higher incidence and prevalence in women than men. The presentation of the disease in women is modulated by changes in sex hormones from adolescence to pregnancy and menopause. Yet, the effect of sex influences has often been neglected in both basic and clinical and in clinical management of the disease. In this review, evidence from epidemiological, clinical, animal, and neuroimaging studies on the significance of the sex-related influences in migraine is presented, and the unmet needs in each area are discussed. © 2016 Wiley Periodicals, Inc.

Age at menarche and risk of developing migraine or non-migraine headaches by young adulthood: A prospective cohort study.

Importance Migraine is a highly prevalent and disabling primary headache disorder that is two to three times more prevalent in young women. Among females, there is a steep increase in incidence from puberty to young adulthood, but the mechanisms for the increase are unknown. Objective To determine if age of menarche is a risk factor for developing migraine headache vs. non-migraine headache by young adulthood. Design A prospective cohort study, The Growing Up Today Study (GUTS), of adolescents who have been followed since 1996, when they were nine, to 14 years of age. Headache questions were included on the 2007 and 2010 surveys. Setting Youth from across the United States who are offspring of women participating in the Nurses' Health Study II. Participants 6112 female participants who had provided data on headache symptoms, age at menarche and family history of migraine and were followed through 2007 or 2010 were included in this analysis. Main outcomes Migraine or non-migraine headache. Results Many females had a history of headaches, with approximately equal numbers reporting symptoms consistent with migraine (29.7%) and non-migraine headaches (25.3%). We found that, independent of age and family history of migraine, each one-year delay in onset of menarche decrease the odds of migraine by 7% (odds ratio (OR) = 0.93, 95% confidence interval (CI) 0.89-0.97), but was not related to non-migraine headaches. Conclusions and relevance The findings of this study suggest that early puberty increases the risk of developing migraines by young adulthood. As such, the study emphasizes the need for understanding the pathophysiological links between puberty and developmental changes that occur in the brain during that period and the mechanisms of onset of the migraine disease and its trajectory.

What Have We Learned From Brain Functional Connectivity Studies in Migraine Headache?

Over the past 20 years, headache syndromes, especially migraine, have benefited significantly from the knowledge gained through neuroimaging studies. This article is focused on the neuroimaging studies of the functional organization and connectivity of the migraine brain. First, data sources and the study design elements in functional neuroimaging studies of the brain connectivity in migraine headaches are discussed. Then, the article reviews the findings to date and discusses how functional connectivity studies have contributed to a better understanding of the mechanisms of the migraine disease by extending the focus from a single region or structure to a network of regions and structures and the interactions among them. Finally, the potential scenarios for the translation of connectivity knowledge to the benefit for patients are discussed.

A new electronic diary tool for mapping and tracking spatial and temporal head pain patterns in migraine.

AIM: We present an electronic tool for collecting data on the patterns of migraine headache onset and progression. METHODS: A digitized map consisting of 44 color-coded segments was defined based on previous reports of migraine pain and the distribution of nerves in the face, head and neck. The map was overlaid on a schematic map of the face, head and neck nerves. Thirty-six patients (N = 36, 28 female/eight male), who met ICDH-II criteria for episodic migraine and had headaches for at least three years, identified all regions where pain typically started and how pain spread and subsequently progressed. RESULTS: Consistent with previous findings, throbbing was the most prevalent quality of migraine pain, always present in 70% of patients surveyed. For the 70% of the patients with throbbing pain, the temple was the onset site of throbbing pain, with no significant difference in the laterality of onset site (58.3% on the right vs. 55.6% on the left hemisphere). The tool was able to capture patterns of pain distribution for throbbing and pressure headache pain and also may be used to assess the change in the pattern of the pain distribution as the disease progresses. DISCUSSION: The pain map survey may be a useful tool for recording and tracking the temporal pattern of migraine onset both for clinical and research purposes. The tool could be used to create maps of pain locations on a large population scale and thus will be a very useful tool in correlating the temporal nature of headache symptoms with potential mechanisms of disease evolution.

Pain response measured with arterial spin labeling.

The majority of functional MRI studies of pain processing in the brain use the blood oxygenation level-dependent (BOLD) imaging approach. However, the BOLD signal is complex as it depends on simultaneous changes in blood flow, vascular volume and oxygen metabolism. Arterial spin labeling (ASL) perfusion imaging is another imaging approach in which the magnetically labeled arterial water is used as an endogenous tracer that allows for direct measurement of cerebral blood flow. In this study, we assessed the pain response in the brain using a pulsed-continuous arterial spin labeling (pCASL) approach and a thermal stimulation paradigm. Using pCASL, response to noxious stimulation was detected in somatosensory cortex, anterior cingulate cortex, anterior insula, hippocampus, amygdala, thalamus and precuneus, consistent with the pain response activation patterns detected using the BOLD imaging approach. We suggest that pCASL is a reliable alternative for functional MRI pain studies in conditions in which blood flow, volume or oxygen extraction are altered or compromised.

Her versus his migraine: multiple sex differences in brain function and structure.

Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.

Exposure to Alcohol-Related Content on Social-Media.

Objective: Exposure to alcohol-related content is unavoidable on social media. In this study level of exposure to alcohol marketing content on Twitter and Instagram for those in recovery was examined, and the effectiveness of privacy settings to mitigate exposing content was assessed. Methods: Four fictitious accounts were created on Instagram and Twitter in a case-control design in Spring 2022. All accounts followed 19 alcohol brands, with two accounts (1 male, 1 female) following only alcohol brand accounts while the other two (1 male, 1 female) additionally followed recovery resources. Four weeks of data collection were done with default privacy and advertisement settings, followed by two additional weeks of data collection with advertisement and privacy settings for blocking alcohol content. Results: Privacy settings did not help with blocking the alcoholic brand-related photographic content on either platform, meaning that the accounts received the same amount of alcohol-related content from the accounts they were following with and without changing the privacy settings. However, Twitter algorithms were more effective in suppressing alcohol-related content for accounts following recovery resources and alcohol brands. Conclusions: These results suggest that risks of exposure to triggering/cueing photographic alcohol content may outweigh the benefits of social media for social connection if an individual is considering seeking recovery.

A model for irritable bowel syndrome and anxiety comorbidities in relation to alcohol use disorders.

About 95% of human body serotonin synthesis occurs in the gastrointestinal tract (GI). Lack of sufficient serotonin levels is thought to play a key role in mood disorders, including anxiety disorders. In this study, we looked at a disorder affecting the GI tract, irritable bowel syndrome (IBS), and aimed to determine whether IBS is differentially associated with anxiety disorders in 252 chronic pain patients in the presence of a history of alcohol use disorders (AUD) given that alcohol is an extremely aggressive substance for the GI mucosa. We found that while the prevalence of IBS was not affected by the presence of AUD in chronic pain patients, IBS had significantly higher comorbidity with anxiety disorders in chronic pain patients with comorbid alcohol use disorders. We argue that these findings highlight mechanistic differences in the comorbidity of anxiety disorders with chronic pain and AUD, implicating a central role for GI problems stemming from chronic alcohol use. The findings may have important implications for the treatment of IBS patients with AUD who commonly present with anxiety disorders which could motivate the continuation of problematic drinking and impede recovery success. We propose that addressing GI problems in patients with AUD may help manage AUD and recovery more effectively.

Trends in Alcohol-Related Deaths by Sex in the US, 1999-2020.

Importance: Alcohol consumption rates have been increasing among women in the US, which may affect mortality rates and sex gaps. Therefore, conducting a comprehensive assessment of sex differences in alcohol-related deaths is essential to inform targeted interventions and policies aimed at reducing the burden of alcohol-related harm among the population. Objective: To examine sex differences in the burden and trends of alcohol-related mortality in the US from 1999 to 2020. Design, Setting, and Participants: This cross-sectional time series study used Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data on alcohol-related deaths from 1999 to 2020. Alcohol-related deaths were identified from the underlying cause of death files using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes, including alcohol-related poisoning, liver disease, gastritis, cardiomyopathy, myopathy, polyneuropathy, and pseudo-Cushing syndrome, among others. Main Outcomes and Measures: Age-adjusted mortality rates (AAMRs) were analyzed by sex and substratified by race and ethnicity, age, and census region. Rate ratios and 95% CIs calculated by Taylor series were used to assess sex differences in mortality burden. Joinpoint regression was used to assess temporal trends. Results: A total of 605 948 alcohol-attributed deaths were identified in the US from 1999 through 2020 (AAMR, 8.3 per 100 000 persons; 95% CI, 8.3-8.3 per 100 000 persons). The mortality burden was higher among male individuals than female individuals, with male individuals being 2.88 (95% CI, 2.86-2.89) times more likely to die compared with female individuals. However, temporal trends showed an increase in alcohol-related deaths for both male and female individuals in recent years, with higher rates of increase among female individuals relative to male individuals. The AAMR increased by 12.5% (95% CI, 6.4%-19.1%) per year among male individuals from 2018 to 2020 but increased by 14.7% (95% CI, 9.1%-20.5%) per year among female individuals during the same period. Trend differences were observed across subtypes of age, race and ethnicity, cause, and region. Conclusions and Relevance: This study of alcohol-related mortality in the US suggests there has been a significantly higher rate of increase in deaths among female individuals in recent years. These findings underscore the need for further research to understand the specific factors associated with this trend. The development of targeted interventions and evidence-based treatments for alcohol use among female individuals becomes imperative in effectively addressing the increasing rates of alcohol-related deaths.

Racial and Ethnic Disparities in Alcohol-Attributed Deaths in the United States, 1999-2020.

The disparities in alcohol-attributed death rates among different racial and ethnic groups in the United States (US) have received limited research attention. Our study aimed to examine the burden and trends in alcohol-attributed mortality rates in the US by race and ethnicity from 1999 to 2020. We used national mortality data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database and employed the ICD-10 coding system to identify alcohol-related deaths. Disparity rate ratios were calculated using the Taylor series, and Joinpoint regression was used to analyze temporal trends and calculate annual and average annual percentage changes (APCs and AAPCs, respectively) in mortality rates. Between 1999 and 2020, 605,948 individuals died from alcohol-related causes in the US. The highest age-adjusted mortality rate (AAMR) was observed among American Indian/Alaska Natives, who were 3.6 times more likely to die from alcohol-related causes than Non-Hispanic Whites (95% CI: 3.57, 3.67). An examination of trends revealed that recent rates have leveled among American Indians/Alaska Natives (APC = 17.9; 95% CI: -0.3, 39.3) while increasing among Non-Hispanic Whites (APC = 14.3; 95% CI: 9.1, 19.9), Non-Hispanic Blacks (APC = 17.0; 95% CI: 7.3, 27.5), Asians/Pacific Islanders (APC = 9.5; 95% CI: 3.6, 15.6), and Hispanics (APC = 12.6; 95% CI: 1.3, 25.1). However, when the data were disaggregated by age, sex, census region, and cause, varying trends were observed. This study underscores the disparities in alcohol-related deaths among different racial and ethnic groups in the US, with American Indian/Alaska Natives experiencing the highest burden. Although the rates have plateaued among this group, they have been increasing among all other subgroups. To address these disparities and promote equitable alcohol-related health outcomes for all populations, further research is necessary to gain a better understanding of the underlying factors and develop culturally sensitive interventions.

Alcohol-Induced Mortality in the USA: Trends from 1999 to 2020.

This study comprehensively examined trends in alcohol-induced overdose mortality in the USA between 1999 and 2020 by age, sex, race/ethnicity, census region, and type of injury. Using the CDC WONDER database, 605,948 alcohol-induced deaths were recorded. Mortality increased by 14.1% per year (95% CI 8.2, 20.3) from 2018 to 2020, with the highest rates among males, non-Hispanic Whites, individuals aged 55-64, and the Western census region. Rising trends were observed across racial/ethnic subgroups, except for American Indians/Alaska Natives, with annual increases of 17% among non-Hispanic Blacks, 14.3% among non-Hispanic Whites, 9.5% among Asian/Pacific Islanders, and 12.6% among Hispanics. Males, females, all age groups, and census regions also experienced increasing trends. In conclusion, this study underscores worsening alcohol-induced mortality in the recent two decades and the need for research to identify its determinants. Such research can guide evidence-based public health interventions to reduce excessive alcohol use consequences. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-023-01083-1.