Addressing food insecurity in HIV care: perspectives from healthcare and social service providers in New York state.

Ending the HIV epidemic in the United States will require addressing social determinants contributing to poor care engagement among people living with HIV (PLH), such as food insecurity. Food insecurity is associated with poor care engagement among PLH. Yet, few studies have examined the perspectives of healthcare and social services providers on addressing food insecurity in HIV care. Guided by the Social Ecological Model, we conducted semi-structured interviews with 18 providers in New York State to understand barriers and facilitators to addressing food insecurity in HIV care. Thematic analysis illustrated eight themes across various levels of the Social Ecological Model. At the patient-level, providers perceived patients' feelings of embarrassment, shame, and judgement, and low health literacy as barriers. At the provider-level, challenges included limited time. Facilitators included fostering strong, patient-provider relationships. Barriers at the clinic-level included limited funding, while clinic resources served as facilitators. At the community-level, challenges included intersecting stigmas arising from community norms towards PLH and people who receive food assistance and limited access to healthy food. Findings suggest the need to incorporate their insights into the development of interventions that address food insecurity in HIV care.

Neural Stem Cell-Derived Extracellular Vesicles Counteract Insulin Resistance-Induced Senescence of Neurogenic Niche.

Neural stem and progenitor cell (NSPC) depletion may play a crucial role in the cognitive impairment observed in many age-related non-communicable diseases. Insulin resistance affects brain functions through a plethora of mechanisms that remain poorly understood. In an experimental model of insulin resistant NSPCs, we identified a novel molecular circuit relying on insulin receptor substrate-1 (IRS-1)/ Forkhead box O (FoxO) signaling cascade and inhibiting the recruitment of transcription factors FoxO1 and FoxO3a on the promoters of genes regulating proliferation and self-renewal. Insulin resistance also epigenetically increased the expression of cyclin-dependent kinase inhibitor 1 (p21) and accelerated NSPC senescence. Of note, we found that stimulation of NSPCs with NSPC-derived exosomes (exo-NSPC) rescued IRS-1/FoxO activation and counteracted both the reduced proliferation and senescence of stem cells. Accordingly, intranasal administration of exo-NSPC counteracted the high-fat diet-dependent impairment of adult hippocampal neurogenesis in mice by restoring the balance between proliferating and senescent NSPCs in the hippocampus. Our findings suggest a novel mechanism underlying the metabolic control of NSPC fate potentially involved in the detrimental effects of metabolic disorders on brain plasticity. In addition, our data highlight the role of extracellular vesicle-mediated signals in the regulation of cell fate within the adult neurogenic niche.

Feasibility and implementation of a grocery shopping intervention for adults diagnosed with or at-risk for type 2 diabetes.

OBJECTIVE: To examine the feasibility and implementation of an optimal defaults intervention designed to align grocery purchases with a diet recommended for people with or at-risk for type 2 diabetes. DESIGN: This was a 5-week pilot randomised trial with three groups: in-person grocery shopping, shopping online and shopping online with 'default' carts. Participants were asked to shop normally in Week One, according to group assignment in Weeks Two-Four (intervention period), and as preferred in Week Five. All groups received diabetes-friendly recipes via email each intervention week. SETTING: Participants grocery shopped in person or online. Grocery receipt forms, enrolment information and exit surveys were collected remotely and used to assess feasibility and implementation. PARTICIPANTS: Sixty-five adults with or at-risk for type 2 diabetes. RESULTS: Sixty-two participants completed the exit survey and fifty-five submitted receipts all 5 weeks. Forty utilised recipes, 95 % of whom indicated recipes were somewhat or very useful. Orange chicken, quesadillas and pork with potato and apples were the most liked recipes. Most Defaults group participants accepted at least some default cart items. Recipes with the highest default acceptance were whole grain pasta and chicken, quesadillas with black beans and chicken with olives. Participants' primary concerns about the intervention were costs associated with online shopping, inability to select preferred foods and some recipes including ingredients household members would not eat. CONCLUSIONS: The study had high retention, data were successfully collected remotely and the intervention was acceptable to most participants. Tailoring recipes to household preferences may be beneficial in future studies.

Chronic mild stress alters synaptic plasticity in the nucleus accumbens through GSK3ß-dependent modulation of Kv4.2 channels.

Although major depressive disorder (MDD) is highly prevalent, its pathophysiology is poorly understood. Recent evidence suggests that glycogen-synthase kinase 3ß (GSK3ß) plays a key role in memory formation, yet its role in mood regulation remains controversial. Here, we investigated whether GSK3ß activity in the nucleus accumbens (NAc) is associated with depression-like behaviors and synaptic plasticity. We performed whole-cell patch-clamp recordings of medium spiny neurons (MSNs) in the NAc and determined the role of GSK3ß in spike timing-dependent long-term potentiation (tLTP) in the chronic unpredictable mild stress (CUMS) mouse model of depression. To assess the specific role of GSK3ß in tLTP, we used in vivo genetic silencing by an adeno-associated viral vector (AAV2) short hairpin RNA against GSK3ß. In addition, we examined the role of the voltage-gated potassium Kv4.2 subunit, a molecular determinant of A-type K+ currents, as a potential downstream target of GSK3ß. We found increased levels of active GSK3ß and augmented tLTP in CUMS mice, a phenotype that was prevented by selective GSK3ß knockdown. Furthermore, knockdown of GSK3ß in the NAc ameliorated depressive-like behavior in CUMS mice. Electrophysiological, immunohistochemical, biochemical, and pharmacological experiments revealed that inhibition of the Kv4.2 channel through direct phosphorylation at Ser-616 mediated the GSK3ß-dependent tLTP changes in CUMS mice. Our results identify GSK3ß regulation of Kv4.2 channels as a molecular mechanism of MSN maladaptive plasticity underlying depression-like behaviors and suggest that the GSK3ß-Kv4.2 axis may be an attractive therapeutic target for MDD.

Operational challenges that may affect implementation of evidence-based mobile market interventions.

INTRODUCTION: Mobile produce markets are becoming an increasingly prevalent, accepted, and effective strategy for improving fruit and vegetable (F&V) access and consumption across underserved and lower-income communities. However, there is limited published research on mobile market operations. The goal of this research is to identify the challenges mobile markets face and ways to potentially mitigate those challenges. We will also discuss implications of our findings for future implementation of evidence-based food access interventions. METHODS: We conducted 21 semi-structured key informant (KI) interviews to assess common practices of mobile market organizations that had been operating for 2 + years. We asked KIs about their organizational structure, operations, procurement and logistics, evaluation efforts, marketing and community engagement, success and challenges. A primary qualitative analysis involved deductive coding using qualitative software. A secondary qualitative analysis identified subthemes related to common challenges and remedial practices. A deductive coding process was applied to match identified challenges to the appropriate Consolidated Framework for Implementation Research (CFIR). RESULTS: The leading challenges cited by KIs correspond to the CFIR domains of inner setting (e.g., funding and resources), outer setting (e.g., navigating regulations), and process (e.g., engaging community partnership). Practices that may mitigate challenges include maximizing ancillary services, adopting innovative volunteer and staffing structures, and formalizing agreements with community partners. CONCLUSION: Common and persistent challenges ought to be addressed to ensure and enhance the positive public health impacts of mobile produce markets. Contextual factors, particularly organizational factors, that impact implementation should also be considered when implementing an evidence-based intervention at a mobile market. Further research is needed to determine which innovative solutions are the most effective in mitigating challenges, improving implementation, and enhancing sustainability of mobile markets.

Evaluating the implementation and impact of a healthier checkout programme at a regional convenience store chain.

OBJECTIVE: To test the feasibility of implementing and evaluating a healthier checkout pilot study in a convenience store chain. DESIGN: A quasi-experimental study was conducted comparing a 3-month 'healthier checkouts' intervention in ten convenience stores which stocked eight healthier items in the checkout space and ten comparison stores assigned to continue stocking their current checkout space product mix. All aspects of the intervention were implemented by the retailer. The research team conducted in-person fidelity checks to assess implementation. Sales data were collected from the retailer in order to compare mean baseline to intervention sales of the eight healthier items in intervention and comparison groups while controlling for overall store sales. SETTING: Convenience store chain. PARTICIPANTS: Twenty convenience stores in New Hampshire. RESULTS: The increases in sales of healthier items between the baseline and intervention periods among the intervention and comparison stores were not statistically significant; however, the overall pattern of the results showed promising changes that should be expanded on in future studies. Intervention fidelity checks indicated that results may have been attenuated by variability in intervention implementation. CONCLUSIONS: This study advances the evidence for effective promotion of healthier food purchases in the convenience store chain setting and adds to the current literature on retail checkout space interventions. Additional research is needed to confirm and expand these results.

Herpes Simplex Virus Type-1 Infection Impairs Adult Hippocampal Neurogenesis via Amyloid-ß Protein Accumulation.

We previously reported that Herpes simplex virus type-1 (HSV-1) infection of cultured neurons triggered intracellular accumulation of amyloid-ß protein (Aß) markedly impinging on neuronal functions. Here, we demonstrated that HSV-1 affects in vitro and in vivo adult hippocampal neurogenesis by reducing neural stem/progenitor cell (NSC) proliferation and their neuronal differentiation via intracellular Aß accumulation. Specifically, cultured NSCs were more permissive for HSV-1 replication than mature neurons and, once infected, they exhibited reduced proliferation (assessed by 5'-bromo-deoxyuridine incorporation, Ki67 immunoreactivity, and Sox2 mRNA expression) and impaired neuronal differentiation in favor of glial phenotype (evaluated by immunoreactivity for the neuronal marker MAP2, the glial marker glial fibrillary astrocyte protein, and the expression of the proneuronal genes Mash1 and NeuroD1). Similarly, impaired adult neurogenesis was observed in the subgranular zone of hippocampal dentate gyrus of an in vivo model of recurrent HSV-1 infections, that we recently set up and characterized, with respect to mock-infected mice. The effects of HSV-1 on neurogenesis did not depend on cell death and were due to Aß accumulation in infected NSCs. Indeed, they were: (a) reverted, in vitro, by the presence of either ß/γ-secretase inhibitors preventing Aß production or the specific 4G8 antibody counteracting the action of intracellular Aß; (b) not detectable, in vivo, in HSV-1-infected amyloid precursor protein knockout mice, unable to produce and accumulate Aß. Given the critical role played by adult neurogenesis in hippocampal-dependent memory and learning, our results suggest that multiple virus reactivations in the brain may contribute to Alzheimer's disease phenotype by also targeting NSCs. Stem Cells 2019;37:1467-1480.

GSK3ß Modulates Timing-Dependent Long-Term Depression Through Direct Phosphorylation of Kv4.2 Channels.

Spike timing-dependent plasticity (STDP) is a form of activity-dependent remodeling of synaptic strength that underlies memory formation. Despite its key role in dictating learning rules in the brain circuits, the molecular mechanisms mediating STDP are still poorly understood. Here, we show that spike timing-dependent long-term depression (tLTD) and A-type K+ currents are modulated by pharmacological agents affecting the levels of active glycogen-synthase kinase 3 (GSK3) and by GSK3ß knockdown in layer 2/3 of the mouse somatosensory cortex. Moreover, the blockade of A-type K+ currents mimics the effects of GSK3 up-regulation on tLTD and occludes further changes in synaptic strength. Pharmacological, immunohistochemical and biochemical experiments revealed that GSK3ß influence over tLTD induction is mediated by direct phosphorylation at Ser-616 of the Kv4.2 subunit, a molecular determinant of A-type K+ currents. Collectively, these results identify the functional interaction between GSK3ß and Kv4.2 channel as a novel mechanism for tLTD modulation providing exciting insight into the understanding of GSK3ß role in synaptic plasticity.

Neural Stem Cell-Derived Exosomes Revert HFD-Dependent Memory Impairment via CREB-BDNF Signalling.

Overnutrition and metabolic disorders impair cognitive functions through molecular mechanisms still poorly understood. In mice fed with a high fat diet (HFD) we analysed the expression of synaptic plasticity-related genes and the activation of cAMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signalling. We found that a HFD inhibited both CREB phosphorylation and the expression of a set of CREB target genes in the hippocampus. The intranasal administration of neural stem cell (NSC)-derived exosomes (exo-NSC) epigenetically restored the transcription of Bdnf, nNOS, Sirt1, Egr3, and RelA genes by inducing the recruitment of CREB on their regulatory sequences. Finally, exo-NSC administration rescued both BDNF signalling and memory in HFD mice. Collectively, our findings highlight novel mechanisms underlying HFD-related memory impairment and provide evidence of the potential therapeutic effect of exo-NSC against metabolic disease-related cognitive decline.

Cluster randomized controlled trial of a mobile market intervention to increase fruit and vegetable intake among adults in lower-income communities in North Carolina.

BACKGROUND: Poorer diets and subsequent higher rates of chronic disease among lower-income individuals may be partially attributed to reduced access to fresh fruits and vegetables (F&V) and other healthy foods. Mobile markets are an increasingly popular method for providing access to F&V in underserved communities, but evaluation efforts are limited. The purpose of this study was to determine the impact of Veggie Van (VV), a mobile produce market, on F&V intake in lower-income communities using a group randomized controlled trial. METHODS: VV is a mobile produce market that sells reduced-cost locally grown produce and offers nutrition and cooking education. We recruited 12 sites in lower-income communities in North Carolina (USA) to host VV, randomizing them to receive VV immediately (intervention) or after the 6-month study period (delayed intervention control). Participants at each site completed baseline and follow-up surveys including F&V intake, perceived access to fresh F&V and self-efficacy for purchasing, preparing and eating F&V. We used multiple linear regression to calculate adjusted differences in outcomes while controlling for baseline values, education and clustering within site. RESULTS: Among 142 participants who completed the follow-up, baseline F&V intake was 3.48 cups/day for control and 3.33 for intervention. At follow-up, adjusted change in F&V consumption was 0.95 cups/day greater for intervention participants (p = 0.005), but was attenuated to 0.51 cups per day (p = 0.11) after removing extreme values. VV customers increased their F&V consumption by 0.41 cups/day (n = 30) compared to a 0.25 cups/day decrease for 111 non-customers (p = 0.04). Intervention participants did not show significant improvements in perceived access to fresh F&V, but increased their self-efficacy for working more F&V into snacks (p = 0.02), making up a vegetable dish with what they had on hand (p = 0.03), and cooking vegetables in a way that is appealing to their family (p = 0.048). CONCLUSIONS: Mobile markets may help improve F&V intake in lower-income communities. TRIAL REGISTRATION: Clinicaltrials.gov ID# NCT03026608 retrospectively registered January 2, 2017.

Examining the relationship between the food environment and adult diabetes prevalence by county economic and racial composition: an ecological study.

BACKGROUND: Inequitable access to healthy food may contribute to health disparities. This study examines the relationship between the prevalence of adult diabetes and food access in the U.S. by county economic/racial composition. METHODS: An ecological study from 2012 was used to estimate the relationship between diabetes and retail food outlet access. County diabetes prevalence was measured based on individual responses to the Behavioral Risk Factor Surveillance Survey question, "Have you ever been told by a doctor that you have diabetes?" If the answer was "yes" individuals were classified as having diabetes. Retail food outlets included grocery stores, supercenters, farmer's markets, full-service restaurants, fast food restaurants and convenience stores. Counties were categorized as "high-poverty" or "low-poverty". Counties were categorized as low (< 4.6%), medium (4.6%-31.0%), and high (> 31.0%) percent minority residents. Multiple linear regression models estimated the association between retail food outlets and diabetes, controlling for confounders, and testing for interactions between retail food outlets and county racial composition. Regression models were conditioned on county economic composition. Data were analyzed in 2016. RESULTS: Density of retail foods outlets varied greatly by county economic and racial composition; counties with medium-minority populations had the least access to grocery stores and the highest access to fast food restaurants and convenience stores. Low poverty/low-minority population counties had the greatest access to farmer's markets and grocery stores. For low poverty/low-minority counties, grocery stores were associated with decreased of diabetes prevalence. Supercenters were associated with an increase in diabetes prevalence for high-poverty/low-minority counties. Only low poverty/medium-minority counties had a statistically significant relationship between farmer's markets and diabetes prevalence. Fast food restaurants were found to be positively associated with diabetes prevalence in all counties except high poverty/medium-minority. However, only low poverty/low-minority counties had a statistically significant relationship. Across all models, access to full service restaurants were significantly associated with lower prevalence of diabetes. Generally, access to convenience stores were associated with increased diabetes prevalence, except for high poverty/low-minority counties. CONCLUSIONS: The food environment is more strongly associated with diabetes prevalence for wealthier counties with a lower proportion of minority residents. This is important given efforts to increase food access in vulnerable communities. Availability of healthier food may not be enough to change health outcomes.

Recruiting Community Partners for Veggie Van: Strategies and Lessons Learned From a Mobile Market Intervention in North Carolina, 2012-2015.

BACKGROUND: Food access interventions are promising strategies for improving dietary intake, which is associated with better health. However, studies examining the relationship between food access and intake are limited to observational designs, indicating a need for more rigorous approaches. The Veggie Van (VV) program was a cluster-randomized intervention designed to address the gap between food access and intake. In this article, we aim to describe the approaches involved in recruiting community partners to participate in VV. COMMUNITY CONTEXT: The VV mobile market aimed to improve access to fresh fruits and vegetables by providing subsidized, high-quality, local produce in low-resource communities in North Carolina. This study describes the strategies and considerations involved in recruiting community partners and individual participants for participation in the VV program and evaluation. METHODS: To recruit partners, we used various strategies, including a site screener to identify potential partners, interest forms to gauge future VV use and prioritize enrollment of a high-need population, marketing materials to promote VV, site liaisons to coordinate community outreach, and a memorandum of understanding between all invested parties. OUTCOME: A total of 53 community organizations and 725 participants were approached for recruitment. Ultimately, 12 sites and 201 participants were enrolled. Enrollment took 38 months, but our approaches helped successfully recruit a low-income, low-access population. The process took longer than anticipated, and funding constraints prevented certain strategies from being implemented. INTERPRETATION: Recruiting community partners and members for participation in a multi-level, community-based intervention was challenging. Strategies and lessons learned can inform future studies.

Effects of exposure to gradient magnetic fields emitted by nuclear magnetic resonance devices on clonogenic potential and proliferation of human hematopoietic stem cells.

This study investigates effects of gradient magnetic fields (GMFs) emitted by magnetic resonance imaging (MRI) devices on hematopoietic stem cells. Field measurements were performed to assess exposure to GMFs of staff working at 1.5 T and 3 T MRI units. Then an exposure system reproducing measured signals was realized to expose in vitro CD34+ cells to GMFs (1.5 T-protocol and 3 T-protocol). CD34+ cells were obtained by Fluorescence Activated Cell Sorting from six blood donors and three MRI-exposed workers. Blood donor CD34+ cells were exposed in vitro for 72 h to 1.5 T or 3 T-protocol and to sham procedure. Cells were then cultured and evaluated in colony forming unit (CFU)-assay up to 4 weeks after exposure. Results showed that in vitro GMF exposure did not affect cell proliferation but instead induced expansion of erythroid and monocytes progenitors soon after exposure and for the subsequent 3 weeks. No decrease of other clonogenic cell output (i.e., CFU-granulocyte/erythroid/macrophage/megakaryocyte and CFU-granulocyte/macrophage) was noticed, nor exposed CD34+ cells underwent the premature exhaustion of their clonogenic potential compared to sham-exposed controls. On the other hand, pilot experiments showed that CD34+ cells exposed in vivo to GMFs (i.e., samples from MRI workers) behaved in culture similarly to sham-exposed CD34+ cells, suggesting that other cells and/or microenvironment factors might prevent GMF effects on hematopoietic stem cells in vivo. Accordingly, GMFs did not affect the clonogenic potential of umbilical cord blood CD34+ cells exposed in vitro together with the whole mononuclear cell fraction.

Monitoring the Response of Hyperbilirubinemia in the Mouse Brain by In Vivo Bioluminescence Imaging.

Increased levels of unconjugated bilirubin are neurotoxic, but the mechanism leading to neurological damage has not been completely elucidated. Innovative strategies of investigation are needed to more precisely define this pathological process. By longitudinal in vivo bioluminescence imaging, we noninvasively visualized the brain response to hyperbilirubinemia in the MITO-Luc mouse, in which light emission is restricted to the regions of active cell proliferation. We assessed that acute hyperbilirubinemia promotes bioluminescence in the brain region, indicating an increment in the cell proliferation rate. Immunohistochemical detection in brain sections of cells positive for both luciferase and the microglial marker allograft inflammatory factor 1 suggests proliferation of microglial cells. In addition, we demonstrated that brain induction of bioluminescence was altered by pharmacological displacement of bilirubin from its albumin binding sites and by modulation of the blood-brain barrier permeability, all pivotal factors in the development of bilirubin-induced neurologic dysfunction. We also determined that treatment with minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, or administration of bevacizumab, an anti-vascular endothelial growth factor antibody, blunts bilirubin-induced bioluminescence. Overall the study supports the use of the MITO-Luc mouse as a valuable tool for the rapid response monitoring of drugs aiming at preventing acute bilirubin-induced neurological dysfunction.

A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction.

Calorie restriction delays brain senescence and prevents neurodegeneration, but critical regulators of these beneficial responses other than the NAD(+)-dependent histone deacetylase Sirtuin-1 (Sirt-1) are unknown. We report that effects of calorie restriction on neuronal plasticity, memory and social behavior are abolished in mice lacking cAMP responsive-element binding (CREB)-1 in the forebrain. Moreover, CREB deficiency drastically reduces the expression of Sirt-1 and the induction of genes relevant to neuronal metabolism and survival in the cortex and hippocampus of dietary-restricted animals. Biochemical studies reveal a complex interplay between CREB and Sirt-1: CREB directly regulates the transcription of the sirtuin in neuronal cells by binding to Sirt-1 chromatin; Sirt-1, in turn, is recruited by CREB to DNA and promotes CREB-dependent expression of target gene peroxisome proliferator-activated receptor-γ coactivator-1α and neuronal NO Synthase. Accordingly, expression of these CREB targets is markedly reduced in the brain of Sirt KO mice that are, like CREB-deficient mice, poorly responsive to calorie restriction. Thus, the above circuitry, modulated by nutrient availability, links energy metabolism with neurotrophin signaling, participates in brain adaptation to nutrient restriction, and is potentially relevant to accelerated brain aging by overnutrition and diabetes.

Extremely low-frequency electromagnetic fields enhance the survival of newborn neurons in the mouse hippocampus.

In recent years, much effort has been devoted to identifying stimuli capable of enhancing adult neurogenesis, a process that generates new neurons throughout life, and that appears to be dysfunctional in the senescent brain and in several neuropsychiatric and neurodegenerative diseases. We previously reported that in vivo exposure to extremely low-frequency electromagnetic fields (ELFEFs) promotes the proliferation and neuronal differentiation of hippocampal neural stem cells (NSCs) that functionally integrate in the dentate gyrus. Here, we extended our studies to specifically assess the influence of ELFEFs on hippocampal newborn cell survival, which is a very critical issue in adult neurogenesis regulation. Mice were injected with 5-bromo-2'-deoxyuridine (BrdU) to label newborn cells, and were exposed to ELFEFs 9 days later, when the most dramatic decrease in the number of newly generated neurons occurs. The results showed that ELFEF exposure (3.5 h/day for 6 days) enhanced newborn neuron survival as documented by double staining for BrdU and doublecortin, to identify immature neurons, or NeuN labeling of mature neurons. The effects of ELFEFs were associated with enhanced spatial learning and memory. In an in vitro model of hippocampal NSCs, ELFEFs exerted their pro-survival action by rescuing differentiating neurons from apoptotic cell death. Western immunoblot assay revealed reduced expression of the pro-apoptotic protein Bax, and increased levels of the anti-apoptotic protein Bcl-2, in the hippocampi of ELFEF-exposed mice as well as in ELFEF-exposed NSC cultures, as compared with their sham-exposed counterparts. Our results may have clinical implications for the treatment of impaired neurogenesis associated with brain aging and neurodegenerative diseases.

Reduced D-serine levels in the nucleus accumbens of cocaine-treated rats hinder the induction of NMDA receptor-dependent synaptic plasticity.

Cocaine seeking behaviour and relapse have been linked to impaired potentiation and depression at excitatory synapses in the nucleus accumbens, but the mechanism underlying this process is poorly understood. We show that, in the rat nucleus accumbens core, D-serine is the endogenous coagonist of N-methyl-D-aspartate receptors, and its presence is essential for N-methyl-D-aspartate receptor-dependent potentiation and depression of synaptic transmission. Nucleus accumbens core slices obtained from cocaine-treated rats after 1 day of abstinence presented significantly reduced D-serine concentrations, increased expression of the D-serine degrading enzyme, D-amino acid oxidase, and downregulated expression of serine racemase, the enzyme responsible for D-serine synthesis. The D-serine deficit was associated with impairment of potentiation and depression of glutamatergic synaptic transmission, which was restored by slice perfusion with exogenous D-serine. Furthermore, in vivo administration of D-serine directly into the nucleus accumbens core blocked behavioural sensitization to cocaine. These results provide evidence for a critical role of D-serine signalling in synaptic plasticity relevant to cocaine addiction.

Development of the Fit&Fab Exercise Intervention for Women With Obesity: A Community Advisory Board Informed Process.

BACKGROUND: Women with higher body mass index report low rates of and face unique barriers to exercise. Increasing exercise participation can improve mental and physical health independent of weight loss; however, most exercise programs targeting this population focus predominately on losing weight. This paper aims to describe the development of Fit&Fab, a community-based exercise intervention focused on increasing exercise participation and enjoyment for women with obesity. METHODS: In partnership with the YMCA, we recruited women ages 35-64 years (body mass index ≥ 30) to participate in 4 focus groups to understand exercise preferences. Formative work was used to identify theory constructs and associated intervention components. Women from the focus groups were recruited for a community advisory board that finalized the intervention design, recruitment, and evaluation plan. RESULTS: Focus groups participants (N = 29) preferred to exercise without men and wanted a cohort-style class that included women of similar exercise levels and body types, incorporated social support, fun activities, and broke exercise into smaller bouts. They wanted a supportive instructor who was fit but understood weight-related challenges. The community advisory board and research team used focus group findings to inform design of the final intervention including group exercise classes, psychosocial support sessions, personalized training, exercise tracking, outcome monitoring, and rewards. CONCLUSIONS: Our findings emphasize the need to focus on exercise enjoyment and benefits other than losing weight to improve exercise participation among women with higher body mass index. In addition to having outcomes other than weight loss, exercise interventions with this population should also consider group composition, instructor, and class format.

Optimal Defaults in Online Grocery Shopping: A Secondary Analysis to Explore Impacts in Multiresident Households and Families.

OBJECTIVE: To examine whether household type (eg, families with children) moderated the effects of an optimal defaults grocery intervention and examine intervention effects on grocery purchases to be consumed by the participant vs others in the household. METHODS: Participants (n = 65) diagnosed with or at risk for type 2 diabetes were recruited and randomized into an optimal default online grocery intervention or an online or in-person control group. Grocery receipt data were coded into Dietary Approaches to Stop Hypertension nutritional quality scores, and energy, carbohydrate, and sugar content were calculated. Repeated measures analysis of variance examined household types (eg, single vs multi-resident) as moderators of intervention effects. Parallel models explored foods purchased for the participant and foods purchased for other household members separately. RESULTS: Household type was not a significant moderator of intervention effects on nutritional quality or other nutrients of interest (P > 0.10). The default intervention significantly increased the nutritional quality of groceries purchased across household types and for other household members besides the participant (P < 0.05). CONCLUSIONS AND IMPLICATIONS: Optimal defaults may improve grocery purchases across different household types and extend to others in the household, supporting use across household types.