Unique Aspects of Impulsive Traits in Substance Use and Overeating: Specific Contributions of Common Assessments of Impulsivity

Part of this work was supported by grants from NIDA for marijuana studies (K01 DA021632-01A1 to FMF) and The Mind Research Network for control, nicotine, and obesity studies (Institutional Grant to FMF). FMF and DB are currently supported by NIDA (R01 DA030344-01 and F31 DA035039-01A1, respectively). DB and HA createdRunning Head: UNIQUE IMPULSE IN SUBSTANCE USE AND OVEREATING 2 some of the open source software used for analysis in this manuscript (TExPosition and TInPosition). The authors have no other declarations of interest. The American Journal of Drug and Alcohol Abus

Intrinsic Frontolimbic Connectivity and Mood Symptoms in Young Adult Cannabis Users.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f 2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02). Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions

Preparo da veia safena na cirurgia de revascularização miocárdica: uma nova técnica -no touch- que mantém a parede da veia íntegra e proporciona uma alta perviabilidade imediata

BACKGROUND: The technique of harvesting the saphenous vein (SV) for coronary artery bypass grafting (CABG) influences the fate of vein grafts. A new no touch (NT) technique of SV preparation was developed where the vein is harvested with a pedicle of surrounding tissue, which protects the vein from spasms therefore obviating the need for distension. METHOD: A prospective randomized study in 156 patients who underwent CABG was performed comparing three SV harvesting techniques. The techniques were conventional (c) (adventitial stripping of the vein, manual distention and storing in saline solution); Intermediate (I) (after adventitial stripping, the vein was left in situ, covered with a papaverine-soaked compress, and stored in heparinized blood); and no touch (SV dissected with its surrounding tissue was left in situ, covered with a saline-soaked compress and stored in heparinized blood). A morphological study of the endothelium was preformed using scanning electronic microscopy and an angiographic assessment of the vein graft patency was performed at 18 months mean follow-up time. Also an immunohistochemistry assessment was performed to identify the enzyme, nitric oxide synthase (NOS) in the vein wall. RESULTS: The preservation of the endothelial cell integrity was greater with the no touch technique than with the other procedures. At angiographic follow up, the patency for NT was 95.4%, 88.9% for grafts in group C and 86.2% for grafts in group I. The immunohistochemistry assessment revealed NOS in all three layers of the vein wall that was prepared by the no touch technique. However, a great reduction of this enzyme in veins treated by the conventional technique was observed. CONCLUSION: The endothelial integrity and NOS activity were better preserved when using the no touch technique for vein graft harvesting. The vasorelaxation and thrombo-resistant activities of nitric oxide (NO) may be responsible for the reduced of vasospasms and improved patency rate. Furthermore, the mechanical properties provided by the cushion of surrounding tissue in graft harvested by NT technique may contribute to the observed high patency rate.OBJETIVO: O objetivo deste trabalho é apresentar uma nova técnica no touch de preparo da veia safena e sua importância clínica. Esta nova técnica consiste na retirada da veia safena do seu leito, juntamente com um pedículo de tecido adiposo, protegendo a veia contra espasmos e, conseqüentemente, da necessidade de distendê-la durante a operação. MÉTODO: O estudo foi realizado em dois tempos: 1) Inicialmente, foi realizado um estudo prospectivo e randomizado, envolvendo 156 pacientes que foram submetidos à operação de revascularização miocárdica. Neste estudo nós comparamos a técnica no touch (NT) com duas outras: a convencional (C) e a intermediária (I). Foi feita uma avaliação detalhada da morfologia endotelial, utilizando a microscopia eletrônica, enquanto que a perviabilidade das pontes foi determinada com um exame angiográfico executado num período médio de 18 meses após a operação. 2) Finalmente, a enzima óxido nítrico síntase (NOS) foi identificada com ajuda do estudo imunohistoquímico e também pela localização auto-radiográfica de (3H)-L- Nitro-Arginina (NOARG). RESULTADOS: A avaliação morfológica mostrou integridade endotelial de 97% nas veias que foram tratadas pela técnica NT; enquanto quase metade da superfície endotelial das veias tratadas pelas outras duas técnicas exibiu ausência de células endoteliais. O exame angiográfico revelou perviabilidade de 95,4% para as pontes do grupo NT, 88,9% para as pontes do grupo (C) e 86,2% para as pontes do grupo (I). O estudo imunohistoquímico revelou a presença de NOS nas três camadas que compõem a parede da veia quando, as mesmas, foram tratadas pela técnica NT. Por outro lado, foi observada uma elevada redução desta enzima nas veias que foram tratadas pela técnica (C). A análise auto-radiográfica confirmou os resultados imunohistoquímicos. CONCLUSÃO: A integridade endotelial e a atividade da enzima óxido nítrico síntase foram melhor mantidas com o uso da técnica NT no preparo da veia safena. A atividade vasodilatadora e bloqueadora da agregação plaquetária causada pelo óxido nítrico (NO) pode ser a responsável pela proteção da veia contra o espasmo, como também pela alta perviabilidade imediata da mesma. Além disso, as propriedades mecânicas providas pelo tecido gorduroso em volta da veia, contribuíram para o melhor resultado desta nova técnica.University Hospital of Örebro Cardiothoracic Surgery DivisionUniversity Hospital Royal Free College Medical School Molecular Pathology and Biochemical DivisionHospital do Servidor Público EstadualUNIFESP Paulista Medical School Cardiothoracic Surgery DivisionHospital Oswaldo Cruz Cardiothoracic Surgery DivisionUNIFESP, Paulista Medical School Cardiothoracic Surgery DivisionSciEL

A structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells

Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host

Determining Risks for Cannabis Use Disorder in the Face of Changing Legal Policies

Purpose of Review: This review aims to summarize and critically evaluate the current literature on the associations between individual and socio-cultural factors that increase risk for cannabis use disorder (CUD), and policy change. Recent findings: Epidemiological studies show that areas with permissive legal cannabis climates are associated with greater individual risk factors for CUD. This includes (1) higher rates of edible consumption and vaping, (2) higher delta-9-tetrahydrocannabinol (THC) potency and lower cannabidiol (CBD) levels, and (3) younger age of initiation of use. Summary: A change in the socio-cultural level, such as shifts in the legalization of cannabis, could interact with individual-level factors in their associations with CUD. There is currently a lack of empirical studies that evaluate this interaction. We propose that future research consider a bioecological framework for CUD to allow for a comprehensive understanding of the effects of legal climate that could inform policy and clinical practice

Explicit processing of verbal and spatial features during letter-location binding modulates oscillatory activity of a fronto-parietal network.

The present study investigated the binding of verbal and spatial features in immediate memory. In a recent study, we demonstrated incidental and asymmetrical letter-location binding effects when participants attended to letter features (but not when they attended to location features) that were associated with greater oscillatory activity over prefrontal and posterior regions during the retention period. We were interested to investigate whether the patterns of brain activity associated with the incidental binding of letters and locations observed when only the verbal feature is attended differ from those reflecting the binding resulting from the controlled/explicit processing of both verbal and spatial features. To achieve this, neural activity was recorded using magnetoencephalography (MEG) while participants performed two working memory tasks. Both tasks were identical in terms of their perceptual characteristics and only differed with respect to the task instructions. One of the tasks required participants to process both letters and locations. In the other, participants were instructed to memorize only the letters, regardless of their location. Time–frequency representation of MEG data based on the wavelet transform of the signals was calculated on a single trial basis during the maintenance period of both tasks. Critically, despite equivalent behavioural binding effects in both tasks, single and dual feature encoding relied on different neuroanatomical and neural oscillatory correlates. We propose that enhanced activation of an anterior–posterior dorsal network observed in the task requiring the processing of both features reflects the necessity for allocating greater resources to intentionally process verbal and spatial features in this task

Time to acknowledge the mixed effects of cannabis on health: a summary and critical review of the NASEM 2017 report on the health effects of cannabis and cannabinoids

This is a summary and critical review of the National Academies of Sciences, Engineering and Medicine (NASEM) report of the health effects of cannabis. The report stated that effects of cannabis are understudied, and research findings are mixed. It concluded that the under‐developed evidence base poses a public health risk and rightly addressed complexities of cannabis research that need to be resolved collaboratively. We support NASEM's urgent call for research, but add that the mixed evidence base cannot be attributed solely to research limitations. Rather, we propose a need to acknowledge the heterogeneity in the effects of cannabis to advance the field

Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory task

Introduction: The APOE e4 allele has been linked to poorer cognitive aging and enhanced dementia risk. Previous imaging studies have used subsequent memory paradigms to probe hippocampal function in e4 carriers across the age range, and evidence suggests a pattern of hippocampal overactivation in young adult e4 carriers. Methods: In this study, we employed a word-based subsequent memory task under fMRI; pupillometry data were also acquired as an index of cognitive effort. Participants (26 non-e4 carriers and 28 e4 carriers) performed an incidental encoding task (presented as word categorization), followed by a surprise old/new recognition task after a 40 minute delay. Results: In e4 carriers only, subsequently remembered words were linked to increased hippocampal activity. Across all participants, increased pupil diameter differentiated subsequently remembered from forgotten words, and neural activity covaried with pupil diameter in cuneus and precuneus. These effects were weaker in e4 carriers, and e4 carriers did not show greater pupil diameter to remembered words. In the recognition phase, genotype status also modulated hippocampal activity: here, however, e4 carriers failed to show the conventional pattern of greater hippocampal activity to novel words. Conclusions: Overall, neural activity changes were unstable in e4 carriers, failed to respond to novelty, and did not link strongly to cognitive effort, as indexed by pupil diameter. This provides further evidence of abnormal hippocampal recruitment in young adult e4 carriers, manifesting as both up and downregulation of neural activity, in the absence of behavioral performance differences

Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin (THCv) on food reward and aversion in healthy volunteers

Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity and eating disorders. We previously showed that the cannabis receptor subtype (CB1) inverse agonist rimonabant, an antiobesity drug withdrawn due to depressogenic side effects, diminished neural reward responses yet increased aversive responses (Horder et al., 2010). Unlike rimonabant, tetrahydrocannabivarin is a neutral CB1 receptor antagonist (Pertwee, 2005) and may therefore produce different modulations of the neural reward system. We hypothesized that tetrahydrocannabivarin would, unlike rimonabant, leave intact neural reward responses but augment aversive responses. Methods: We used a within-subject, double-blind design. Twenty healthy volunteers received a single dose of tetrahydrocannabivarin (10mg) and placebo in randomized order on 2 separate occasions. We measured the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (picture of moldy strawberries and/or a less pleasant strawberry taste) using functional magnetic resonance imaging. Volunteers rated pleasantness, intensity, and wanting for each stimulus. Results: There were no significant differences between groups in subjective ratings. However, tetrahydrocannabivarin increased responses to chocolate stimuli in the midbrain, anterior cingulate cortex, caudate, and putamen. Tetrahydrocannabivarin also increased responses to aversive stimuli in the amygdala, insula, mid orbitofrontal cortex, caudate, and putamen. Conclusions: Our findings are the first to show that treatment with the CB1 neutral antagonist tetrahydrocannabivarin increases neural responding to rewarding and aversive stimuli. This effect profile suggests therapeutic activity in obesity, perhaps with a lowered risk of depressive side effects. Keywords: reward, THCv, obesity, fMRI, cannabinoi