Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles.

The Dietary Approach to Stop Hypertension (DASH) diet, with its low sodium and high potassium content, acts like a diuretic by reducing sodium reabsorption in the kidney's distal convoluted tubule but without the side effects. Previous studies based on animal models didn't explore changes in human ion channel proteins. Recent insights into urinary extracellular vesicles (uEVs) suggest they reflect kidney tissue and physiological modifications. In our inpatient study, we shifted hypertensive volunteers from an American diet to the DASH diet, examining changes in those with stage 1 untreated hypertension. We analyzed a large range of pure uEVs, from small to large, in urine samples from nine volunteers over three time points. Mass spectrometry of these uEVs identified 1,800 proteins, revealing an increase in SCL12A3 (NCC) and a decrease in aquaporin 2 (AQP2). Immunoblotting showed an increase in activated (phosphorylated) NCC ratio to total NCC and a decrease in AQP2 from day 5 to 11, indicating the DASH diet induces measurable kidney responses via uEV protein abundance changes. This non-invasive method offers new insights into the diet's renal mechanism. Future studies should confirm these findings in a larger cohort, clarify the drivers behind NCC and AQP2 changes, their impact on hypertension, and investigate if uEVs also act as a waste pathway for inactive proteins, expanding our understanding of dietary effects on kidney physiology.

Empowering the Participant Voice (EPV): Design and implementation of collaborative infrastructure to collect research participant experience feedback at scale.

Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.

Factor structure of the alcohol expectancies questionnaire among adolescents in rural Ghana.

INTRODUCTION: Children's early experiences with alcohol inform the development of alcohol-related beliefs which are known to predict alcohol consumption during the critical stage of adolescence. Yet, there has been considerably less research into these alcohol-related cognitions in low- and middle-income countries (LMIC) and existing measures of these beliefs are highly reflective of Western contexts, which may not be fully appropriate for use in LMICs. The aim is to ascertain the construct validity of the Alcohol Expectancies Questionnaire (AEQ) in a non-Western sample. METHODS: A cross-sectional diagnostic accuracy study involving 500 adolescents aged 10 to 18 years randomly selected from the database of the Navrongo Health and Demographic Surveillance System. Participants were administered the locally back translated version of the 34-item AEQ. Confirmatory factor analysis using the lavaan package in R was conducted to generate indices for the factor structure of the AEQ. RESULTS: Confirmatory factor analyses showed that while groupings of positive and negative expectancies were similar to those observed when expectancies have been assessed previously in Western studies, these formed a single 'alcohol expectancy' factor. Questions relating to positive tension reduction and negative physical expectancies showed inconsistent responses in this study. DISCUSSION AND CONCLUSIONS: Commonly used tools for the assessment of alcohol expectancies may not be suitable for use in Ghana, possibly owing to their development and validation in Western contexts. These findings have implications for the assessment of alcohol-related beliefs in LMIC settings and begin to map out a research agenda to develop more contextually and culturally attune alcohol assessments.

GalNAc-conjugated siRNA targeting the DNAJB1-PRKACA fusion junction in fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer caused by a dominant recurrent fusion of the heat shock protein (DNAJB1) and the catalytic subunit of protein kinase A (PRKACA). Current therapies such as chemotherapy and radiation have limited efficacy, and new treatment options are needed urgently. We have previously shown that FLC tumors are dependent on the fusion kinase DNAJB1::PRKACA, making the oncokinase an ideal drug target. mRNA degrading modalities such as antisense oligonucleotides or small interfering RNAs (siRNAs) provide an opportunity to specifically target the fusion junction. Here, we identify a potent and specific siRNA that inhibits DNAJB1::PRKACA expression. We found expression of the asialoglycoprotein receptor in FLC to be maintained at sufficient levels to effectively deliver siRNA conjugated to the GalNAc ligand. We observe productive uptake and siRNA activity in FLC patient-derived xenografts (PDX) models in vitro and in vivo. Knockdown of DNAJB1::PRKACA results in durable growth inhibition of FLC PDX in vivo with no detectable toxicities. Our results suggest that this approach could be a treatment option for FLC patients.

Catching a smile from individuals and crowds: Evidence for distinct emotional contagion processes.

Research examining how crowd emotions impact observers usually requires participants to engage in an atypical mental process whereby (static) arrays of individuals are cognitively integrated to represent a crowd. The present work sought to extend our understanding of how crowd emotions may spread to individuals by assessing self-reported emotions, attention and muscle movement in response to emotions of dynamic, virtually modeled crowd stimuli. Self-reported emotions and attention from thirty-six participants were assessed when foreground and background crowd characters exhibited homogeneous (Study 1) or heterogeneous (Study 2) positive, neutral, or negative emotions. Results suggested that affective responses in observers are shaped by crowd emotions even in the absence of direct attention. Thirty-four participants supplied self-report and facial electromyography responses to the same homogeneous (Study 3) or heterogeneous (Study 4) crowd stimuli. Results indicated that positive crowd emotions appeared to exert greater attentional pull and objective responses, while negative crowd emotions also elicited affective responses. Study 5 (n = 67) introduced a control condition (stimuli containing an individual person) to examine if responses are unique to crowds and found that emotional contagion from crowds was more intense than from individuals. These studies present methodological advances in the study of crowd emotional contagion and have implications for our broader understanding of how people process, attend, and affectively respond to crowds. Advancing theory by suggesting that emotional contagion from crowds is distinct from that elicited by individuals, findings may have applications for refining crowd management approaches. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Developing a simple risk metric for the effect of sport-related concussion and physical pain on mental health.

Risk factors associated with depression in athletes include biological sex, physical pain, and history of sport-related concussion (SRC). Due to the well-documented benefits of sport and physical activity on mental health, athletes and non-athletes were recruited to assess any differences. Beyond this, athletes were also grouped by sport-type (contact/non-contact sports) due to the increased prevalence of pain and SRC in contact sports. To our knowledge, there has been no research on how these factors influence the likelihood of depression. In the current study, 144 participants completed a short survey on the above factors and the Center for Epidemiological Studies Depression Scale. Sixty-two of these reported a history of concussion. Logistic regression revealed all the above predictors to be significantly associated with the depression scale. Individuals that had previously sustained SRC, were experiencing greater physical pain and females were more likely to display poor mental health. However, we provide further evidence for the benefits of engaging in sport and physical activity as those that took part in sport were less likely to report depression. Therefore, this study provides a simple risk metric whereby sportspeople can make a better informed choice of their sporting participation, making their own cost/reward judgement.

UK alcohol consumption during the COVID-19 pandemic: The role of drinking motives, employment and subjective mental health.

Background Previous investigations suggest that the COVID-19 pandemic effects on alcohol consumption were heterogenous and may vary as a function of structural and psychological factors. Research examining mediating or moderating factors implicated in pandemic-occasioned changes in drinking have also tended to use single-study cross-sectional designs and convenience samples. AIMS: First, to explore structural (changed employment or unemployment) and psychological (subjective mental health and drinking motives) correlates of consumption reported during the COVID-19 pandemic using a UK nationally representative (quota sampled) dataset. Second, to determine whether population-level differences in drinking during the COVID-19 pandemic (versus pre-pandemic levels) could be attributable to drinking motives. METHOD: Data collected from samples of UK adults before and during the pandemic were obtained and analysed: Step1 carried out structural equation modelling (SEM) to explore data gathered during a period of social restrictions after the UK's first COVID-19-related lockdown (27 August-15 September, 2020; n = 3,798). It assessed whether drinking motives (enhancement, social, conformity, coping), employment and the perceived impact of the pandemic on subjective mental health may explain between-person differences in self-reported alcohol consumption. Step 2 multigroup SEM evaluated data gathered pre-pandemic (2018; n = 7,902) in concert with the pandemic data from step 1, to test the theory that population-level differences in alcohol consumption are attributable to variances in drinking motives. RESULTS: Analyses of the 2020 dataset detected both direct and indirect effects of subjective mental health, drinking motives, and employment matters (e.g., having been furloughed) on alcohol use. Findings from a multigroup SEM were consistent with the theory that drinking motives explain not only individual differences in alcohol use at both time points, but also population-level increases in use during the pandemic. CONCLUSION: This work highlights socioeconomic and employment considerations when seeking to understand COVID-19-related drinking. It also indicates that drinking motives may be particularly important in explaining the apparent trend of heightened drinking during the pandemic. Limitations related to causal inference are discussed.

In people who drink more, facets of theory of mind may be impaired by alcohol stimuli.

BACKGROUND: Theory of mind (ToM) - the ability to understand others' beliefs, mental states, and knowledge - is an important part of successful social interaction. There is a growing (albeit mixed) evidence base suggesting that individuals with substance use disorder or who are intoxicated (relative to sober controls) perform worse on a number of ToM tasks. The aim of this study was to explore the hitherto little explored notion that ToM-related capabilities such as the ability to see the world from another person's perspective (termed Visual Perspective Taking; VPT), may be impacted by alcohol-related stimuli. METHOD: In this pre-registered study, 108 participants (M age = 25.75, SD age = 5.67) completed a revised version of the director task where they followed the instructions of an avatar to move both alcohol beverages and soft drinks that were mutually visible (target objects) while avoiding those only visible to the participant (distractor items). RESULTS: Contrary to predictions, accuracy was lower when the target drink was alcohol and the distractor was a soft drink, although higher AUDIT scores were associated with significantly lower accuracy when alcohol drinks were the distractor items. CONCLUSIONS: There may be some contexts when being able to see alcohol beverages makes it harder to take another person's perspective. It also appears that poorer VPT and perhaps ToM capacity may be evident in individuals who consume more alcohol. Future research is warranted to examine how alcohol beverages, alcohol consumption behaviours, and intoxication interact to impact VPT capacity.

A cross-national study of predrinking motives in Spain and the UK: Cross-sectional associations with risk-taking and alcohol consumption.

This study contrasts young people's predrinking in two European cultural contexts: Spain and the UK. Whilst UK predrinking typically occurs amongst small groups of individuals who already know one another, the distinctive Spanish context of the Botellón details a far larger gathering in which participants may be less likely to know each other. As such, predrinking motives which drive consumption and risk-taking may be expected to vary between these cultures. An online questionnaire (N = 397; UK = 167, Spain = 230) was used to examine a variety of drinking behaviours and associated beliefs/motivations including predrinking motivations, drinking behaviour, and risk taking. Path analysis was used to analyse both direct and indirect relationships between the measures with the aim of predicting problem alcohol consumption with the most parsimonious model. Varying (in)direct paths were observed between predrinking motives and alcohol consumption between the cultures. Most notably and pointing towards inconsistency in the drivers of young adults' drinking, fun predrinking motives featured prominently among Spanish respondents and predicted their reported consumption (not so in the UK), while conviviality was a more prevalent predrinking motive in the UK sample and associated with alcohol consumption (not the case in Spain). Further, (personal) risky behaviour and risk-taking predicted consumption in both samples, suggesting the importance of group norms and behaviours in predrinking activity, irrespective of alcohol consumption. These findings highlight the potential importance of the environment in which young people predrink. Given their importance in shaping alcohol consumption and risk taking in young people, cultural differences in predrinking contexts and motives warrant further investigation.

Oncogenic Addiction of Fibrolamellar Hepatocellular Carcinoma to the Fusion Kinase DNAJB1-PRKACA.

PURPOSE: Gene fusions are drivers of many pediatric tumors. In fibrolamellar hepatocellular carcinoma (FLC), a fusion of DNAJB1 and PRKACA is the dominant recurrent mutation. Expression of the DNAJB1-PRKACA fusion gene in mice results in a tumor that recapitulates FLC. However, it is not known whether transient expression of DNAJB1-PRKACA is sufficient only to trigger tumor formation or whether ongoing expression is necessary for maintenance and progression. EXPERIMENTAL DESIGN: We screened short hairpin RNAs (shRNA) tiled over the fusion junction and identified several potent and specific candidates in vitro and two independent FLC patient-derived xenografts (PDX). RESULTS: We show that continued DNAJB1-PRKACA expression is not only required for continued tumor growth, but additionally its inhibition results in cell death. Inhibition of DNAJB1-PRKACA by an inducible shRNA in cells of PDX of FLC resulted in cell death in vitro. Induction of the shRNA inhibits FLC tumors growing in mice with no effect on xenografts from a hepatocellular carcinoma cell line engineered to express DNAJB1-PRKACA. CONCLUSIONS: Our results validate DNAJB1-PRKACA as the oncogene in FLC and demonstrate both a continued requirement for the oncogene for tumor growth as well as an oncogenic addiction that can be exploited for targeted therapies. We anticipate our approach will be useful for investigations of other fusion genes in pediatric cancers and spur development of precision therapies.

Affect and alcohol consumption: An ecological momentary assessment study during national lockdown.

Coronavirus disease (COVID-19)-related lockdown provided an opportunity to examine the relationship between affect and alcohol consumption in a historically unique context. To shed light on mixed findings regarding the interplay between affective states and alcohol consumption, the present study examined how affective states and affect fluctuations impact drinking during confinement of people to their homes. It also examined the extent to which the social context moderated the affect-consumption relationship. Having preregistered study protocols, methods, and hypotheses, 87 U.K. participants (34% male, Mage = 29.33) used their smartphones to respond to thrice daily prompts, recording their affective states, alcohol consumption, and social context over 1 week. Multilevel modeling suggested that being with someone (vs. alone) was associated with increased alcohol consumption. Increased drinking on the previous day was associated with increased next day negative affect, and the number of household occupants was associated with decreased negative affect. Preconsumption affect was not associated with subsequent drinking. These findings point to a complex relationship between alcohol consumption, social context, and negative affect. The opportunity to interact with others during lockdown was generally associated with decreased negative affect in the moment. However, the presence of others was associated with increased consumption which, in turn, predicted elevated next-day negative affect. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Validation of the revised Alcohol Expectancy Task [rAET].

Alcohol expectancies are well-established determinants of alcohol consumption. Traditionally, expectancies were assessed using self-report questionnaires. However, researchers have increasingly begun to explore the use of pictographic assessments, for example, the revised Alcohol Expectancy Task [rAET]. The current research aimed to examine the factor structure of the task in relation to the hypothesised expectancy dimensions, participants' endorsement of these dimensions, and whether rAET scores are associated with drinking patterns. The rAET presents participants with several illustrated scenarios in which people are displaying emotions, following the Circumplex Model of Affect. For each scenario, participants select which type of drink the person presented in the illustration was most likely to have drunk. The rAET was administered online to a convenience sample (n = 1,192, female: 50.7%, Mage = 36.8, SD = 13.7). The confirmatory factor analysis demonstrated adequate fit of the hypothesised four-factor model. Mean comparisons demonstrated that positive expectancies were more pronounced than negative expectancies, and a distinction between arousal and sedation expectancies was found. Results of a structural equation model found that positive sedation and positive arousal were related to high drinking frequency. There were no links between usual quantity of alcohol use or binge drinking. It appears that the rAET can be successfully used to assess alcohol expectancies in terms of the emotions that are expected to occur from alcohol consumption. Future research is needed to establish the tool's assessment properties in different settings, and its utility in predicting alcohol consumption in different age groups, particularly children and young adolescents. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Dark Nudges: Branding Magnifies the Decoy Effect in Alcohol Purchasing Decisions.

OBJECTIVE: Public health policies aim to reduce alcohol consumption and related harms by controlling the cost and availability of alcohol, yet industry actors seek to position branded beverages appealingly vis-à-vis other products. To inform the development of regulatory strategies, it is important to understand how alcohol branding interacts with seductive pricing strategies to influence purchasing decisions. Toward this aim, the current study examines how the "decoy effect" may operate to modify purchasing decisions for branded alcoholic beverages. METHOD: Social drinkers (n = 98, 66.6% female; M AUDIT = 5.00, SD = 4.42) completed an online Decoy Assessment, choosing from a range of (non)branded, (non)alcoholic beverage offers based on price and quantity. These initial purchasing decisions were then re-assessed when a decoy product--offering a quantity in between the two original offers but at a significantly higher price--was introduced into the choice array. RESULTS: The decoy modified initial purchasing decisions for alcoholic compared with nonalcoholic beverages, and this effect was exacerbated by alcohol branding. Increases in self-reported alcohol consumption were associated with a greater change from choices for branded alcoholic beverages. CONCLUSIONS: When faced with a choice conflict, individuals who consume alcohol may be nudged into selecting more expensive branded alcoholic beverages. These findings may inform the development of alcohol control policies relating to branding and relative pricing/product placement.

Implementing DASH-Aligned Meals and Self-Measured Blood Pressure to Reduce Hypertension at Senior Centers: A RE-AIM Analysis.

Low-income, minority seniors face high rates of hypertension that increase cardiovascular risk. Senior centers offer services, including congregate meals, that can be a valuable platform to reach older adults in underserved communities. We implemented two evidence-based interventions not previously tested in this setting: DASH-aligned congregate meals and Self-Measured Blood Pressure (SMBP), to lower blood pressure (BP) at two senior centers serving low-income, racially diverse communities. The study enrolled congregate meal program participants, provided training and support for SMPB, and nutrition and BP education. DASH-aligned meals delivered 40% (lunch) or 70% (breakfast and lunch) of DASH requirements/day. Primary outcomes were change in BP, and BP control, at Month 1. Implementation data collected included client characteristics, menu fidelity, meal attendance, SMBP adherence, meal satisfaction, input from partner organizations and stakeholders, effort, and food costs. We used the RE-AIM framework to analyze implementation. Study Reach included 94 older, racially diverse participants reflecting neighborhood characteristics. Effectiveness: change in systolic BP at Month 1 trended towards significance (-4 mmHg, p = 0.07); change in SMBP reached significance at Month 6 (-6.9 mmHg, p = 0.004). We leveraged existing community-academic partnerships, leading to Adoption at both target sites. The COVID pandemic interrupted Implementation and Maintenance and may have attenuated BP effectiveness. DASH meals served were largely aligned with planned menus. Meal attendance remained consistent; meal satisfaction was high. Food costs increased by 10%. This RE-AIM analysis highlights the acceptability, feasibility, and fidelity of this DASH/SMBP health intervention to lower BP at senior centers. It encourages future research and offers important lessons for organizations delivering services to older adults and addressing cardiovascular risk among vulnerable populations.

Clinical and demographic predictors of survival for fibrolamellar carcinoma patients-A patient community, registry-based study.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer that affects primarily adolescents and young adults. It is associated with a poor overall prognosis. There is a need to better define risk factors, but small sample size has limited such studies. An FLC patient registry now provides data sufficient for statistically robust inferences. We leveraged a unique patient community-based FLC registry to analyze the prognostic impact of demographic and clinical characteristics evident at diagnosis. Variables were analyzed using Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariable models of 149 patients (88 females and 61 males), female gender was associated with statistically significant improved survival with HR of 0.52 (95% CI 0.29-0.93). Factors evident at diagnosis that are associated with worse survival included the presence of 10 or more tumors within the liver (HR 7.1; 95% CI 2.4-21.04), and metastases at diagnosis (HR 2.17; 95% CI 1.19-3.94). Positive lymph nodes at diagnosis, despite being found significantly associated with worse survival in a univariate analysis, did not remain significant when adjusted for covariates in a multivariable analysis. We found no statistically significant effect of age at diagnosis nor tumor size at diagnosis on survival. Female gender may confer a favorable prognosis in FLC. Established high-risk prognostic factors that we confirmed in this Registry included the diagnostic presence of numerous intrahepatic tumors, and metastases. This is the first study derived from a FLC patient community-based registry, and highlights how registries of rare tumors can empower patients to meaningfully advance clinical and scientific discoveries.

Targeting BCL-XL in fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare and often lethal liver cancer with no proven effective systemic therapy. Inhibition of the antiapoptotic protein BCL-XL was found to synergize with a variety of systemic therapies in vitro using cells dissociated from patient-derived xenografts (PDX) of FLC or cells dissociated directly from surgical patient resections. As BCL-XL is physiologically expressed in platelets, prior efforts to leverage this vulnerability in other cancers have been hampered by severe thrombocytopenia. To overcome this toxicity, we treated FLC models with DT2216, a proteolysis targeting chimera (PROTAC) that directs BCL-XL for degradation via the von Hippel-Lindau (VHL) E3 ligase, which is minimally expressed in platelets. The combination of irinotecan and DT2216 in vitro on cells directly acquired from patients or in vivo using several xenografts derived from patients with FLC demonstrated remarkable synergy and at clinically achievable doses not associated with significant thrombocytopenia.

Serum aldosterone and urine electrolytes dynamics in response to DASH diet intervention - An inpatient mechanistic study.

Background: Dietary approach to stop hypertension (DASH) diet reduces blood pressure (BP) as effectively as one antihypertensive drug, yet its mechanism of action was never fully characterized. Methods: We designed a translational inpatient trial to elucidate the biological pathway leading from nutritional change, through hormonal response, reversal of urine electrolytes ratio, to BP reduction. Results: A single-center open-label interventional trial. Volunteers were admitted for 14 days, transitioning from an American-style diet to DASH diet. Vital signs, blood, and urine samples were collected daily. Participants completed two 24-hour ambulatory BP measurements (ABPM) and two 24-hour urine collections on days 1 and 10. Nine volunteers completed the protocol. During inpatient stay, serum aldosterone increased from day 0 (mean 8.3 ± 5.0) to day 5 (mean 17.8 ± 5.8) after intervention and decreased on day 11 (mean 11.5 ± 4.7) despite continuous exposure to the same diet (p-value = 0.002). Urine electrolyte ratio ([Na]/[K]) decreased significantly from a mean of 3.5 to 1.16 on day 4 (p < 0.001). BP by 24-hour ABPM decreased by a mean of 3.7 mmHg systolic BP and 2.3 mmHg diastolic BP from day 1 to 10. Conclusion: Shifting from a high-sodium/low-potassium diet to the opposite composition leads to aldosterone increase and paradoxical BP reduction. Urine electrolyte ratio reflects nutritional changes and should guide clinicians in assessing adherence to lifestyle modification.

Implementing DASH-aligned Congregate Meals and Self-Measured Blood Pressure in two senior centers: An open label study.

BACKGROUND AND AIMS: Cardiovascular Disease (CVD) poses significant health risks for seniors, especially among low-income and minority communities. Senior centers offer multiple services. We tested whether implementing two evidence-based interventions- DASH-aligned meals provided through an existing congregate meal program, and support for home Self-Measured Blood Pressure (SMBP) monitoring-lowers blood pressure among participants at two senior centers serving low-income, racially diverse communities. METHODS AND RESULTS: Open-label study, enrolling clients aged ≥60, eating ≥4 meals/week at two NYC senior centers. Participants received DASH-aligned congregate meals, and training in nutrition, BP management education, and personal SMBP device. Co-Primary outcomes: a) change in systolic BP measured by independent health professionals, and b) change in percent with "controlled BP" (Eighth Joint National Committee (JNC-8) Guidelines), at Month 1 compared to Baseline. SECONDARY OUTCOMES: Changes in BP at Months 3 and 5/6 (last measure). We enrolled 94 participants; COVID closures interrupted implementation mid-study. Mean systolic BP at Month-1 changed by -4.41 mmHg (n = 61 p = 0.07) compared to Baseline. Participants with controlled BP increased (15.7%) at Month 1. Change in mean BP at Month 1 was significantly correlated with BMI (p = 0.02), age (p = 0.04), and baseline BP (p < 0.001). Mean systolic SMBP changed by -6.9 mmHg (p = 0.004) at Months 5/6. CONCLUSIONS: Implementing an evidence-based multi-component BP-lowering intervention within existing congregate meal programs at senior centers serving minority and low-income communities is feasible, and early findings show promising evidence of effectiveness. This approach to cardiovascular risk reduction should be further tested for widespread adoption and impact. Registered on ClinicalTrials.gov NCT03993808 (June 21st, 2019).

Elevated ad libitum alcohol consumption following continuous theta burst stimulation to the left-dorsolateral prefrontal cortex is partially mediated by changes in craving.

Previous research indicates that following alcohol intoxication, activity in prefrontal cortices is reduced, linking to changes in associated cognitive processes, such as inhibitory control, attentional bias (AB), and craving. While these changes have been implicated in alcohol consumption behaviour, it has yet to be fully illuminated how these frontal regions and cognitive processes interact to govern alcohol consumption behaviour. The current preregistered study applied continuous theta burst transcranial magnetic stimulation (cTBS) to examine directly these relationships while removing the wider pharmacological effects of alcohol. A mixed design was implemented, with cTBS stimulation to right and left dorsolateral prefrontal cortex (DLPFC), the medial orbital frontal cortex (mOFC) and Vertex, with measures of inhibitory control, AB, and craving taken both pre- and post-stimulation. Ad libitum consumption was measured using a bogus taste task. Results suggest that rDLPFC stimulation impaired inhibitory control but did not significantly increase ad libitum consumption. However, lDLPFC stimulation heightened craving and increased consumption, with findings indicating that changes in craving partially mediated the relationship between cTBS stimulation of prefrontal regions and ad libitum consumption. Medial OFC stimulation and AB findings were inconclusive. Overall, results implicate the left DLPFC in the regulation of craving, which appears to be a prepotent cognitive mechanism by which alcohol consumption is driven and maintained.

Intoxication without anticipation: Disentangling pharmacological from expected effects of alcohol.

BACKGROUND: The pharmacological effects of alcohol on executive function, craving and subsequent alcohol-seeking have been well documented. Yet, insufficient methodological controls within existing alcohol administration paradigms have meant that the relative importance of alcohol's pharmacological and anticipatory effects remains in need of further elucidation. AIM: The objective of this study is to disentangle alcohol's pharmacological effects from its anticipatory effects on alcohol-related cognitions and subsequent consumption. METHODS: Inhibitory control, attentional bias and craving were assessed pre- and post-consumption in 100 participants who were randomly allocated to one of four beverage conditions in a two by two design: (1) alcohol aware (alcohol with participant knowledge (pharmacological/anticipation effects)), (2) alcohol blind (alcohol without participant knowledge; in a novel grain alcohol masking condition (pharmacological/no anticipation effects)), (3) placebo (no alcohol but participants were deceived (anticipation/non-pharmacological effects)) and (4) pure control (no alcohol with participant knowledge (no anticipation/non-pharmacological effects)). RESULTS: Findings suggest that the pharmacological effects of alcohol result in greater inhibitory control impairments compared with anticipated effects. Anticipatory but not the pharmacological effects of alcohol were found to increase attentional bias. Both pharmacology and anticipation resulted in increased craving, though higher levels of craving were observed due to alcohol's pharmacology. Furthermore, alcohol pharmacology resulted in heightened ad libitum consumption; however, anticipation did not. Changes in craving partially mediated the relationship between initial intoxication and subsequent drinking, while inhibitory control impairments did not. CONCLUSIONS: Successive alcohol consumption appears driven primarily by the pharmacological effects of alcohol which are exerted via changes in craving.