Glucagon-like peptide-1 (GLP-1) is a gut peptide that regulates food intake and glucose metabolism. GLP-1 is also produced and released in the brain, and GLP-1 receptors are expressed in brain ...regions important for alcohol and drug reward, and for the development of addiction. GLP-1 receptor agonists can decrease alcohol intake acutely in rodents. However, alcohol use disorder is a chronic condition that requires treatments to be effective in promoting abstinence from excessive alcohol consumption over time. Here, we assessed the effect of daily treatment with the GLP-1 receptor agonist Exendin-4 in an assay of relapse-like drinking in socially housed mice. Male C57BL/6NTac mice were allowed continuous access to alcohol without tastant in the home cage for 37days. Then, alcohol bottles were removed and Exendin-4 (1.5μg/kg/day) or saline was administered subcutaneously for 8days during alcohol deprivation. Treatment continued for 8 additional days after reintroducing access to alcohol. A high-precision automated fluid consumption system was used to monitor intake of alcohol and water, drinking kinetics, and locomotor activity. Exendin-4 prevented the deprivation-induced increase in alcohol intake observed in control mice, without significantly affecting total fluid intake, body weight, or locomotor activity. The reduced alcohol intake was caused by a protracted latency to the first drink of alcohol and a reduced number of drinking bouts, while bout size and duration were not affected. The effect was maintained undiminished throughout the treatment period. These findings support the possible use of GLP-1 receptor agonists in the treatment of alcohol use disorder.
•Repeated daily Exendin-4 prevented deprivation-induced increase in alcohol drinking.•Exendin-4 increased latency to first alcohol drink and decrease drink frequency, not size.•Treatment did not affect total fluid intake, body weight, or locomotor activity.
The chemoselective functionalization of polyfunctional aryl linchpins is crucial for rapid diversification. Although well-explored for Csp2 and Csp nucleophiles, the chemoselective introduction of ...Csp3 groups remains notoriously difficult and is virtually undocumented using Ni catalysts. To fill this methodological gap, a “haloselective” cross-coupling process of arenes bearing two halogens, I and Br, using ammonium alkylbis(catecholato)silicates, has been developed. Utilizing Ni/photoredox dual catalysis, Csp3 –Csp2 bonds can be forged selectively at the iodine-bearing carbon of bromo(iodo)arenes. The described high-yielding, base-free strategy accommodates various protic functional groups. Selective electrophile activation enables installation of a second Csp3 center and can be done without the need for purification of the intermediate monoalkylated product.
Interdisciplinary pain rehabilitation programs (IPRPs) help people with chronic pain improve their health and manage their work; however, the way IPRPs address sick leave could be improved. Although ...work interventions can be a part of IPRP, it is not well known how and to what extent.
This study explores the frequency of work interventions and the characteristics of patients who participate in work interventions as part of IPRP at specialist pain rehabilitation departments in Sweden. In addition, this study explores the association between participation in work interventions and change in patients' self-rated work ability after IPRP.
Data from the Swedish quality registry for pain rehabilitation (SQRP), which includes 3809 patients between 2016 and 2018, were analysed with descriptive statistics and regression analyses.
The results indicate a high participation rate in work interventions (90%). Some differences were evident concerning characteristics of patients who participated in different work interventions. The return-to-work (RTW) plan, the most frequently used work intervention, had the strongest association with change in self-rated work ability after IPRP. However, the effect sizes were small, and the initial score best explained the change. Furthermore, there were differences between employed and unemployed patients and employment had a positive association with change in self-rated work ability.
More research is needed to understand IPRP's mechanisms and work interventions to support patients with chronic pain, reduce sick leave, and manage work. Employment status needs to be considered and interventions should be tailored to match the individual needs.
The palladium-catalyzed borylation of aryl and heteroaryl halides with a novel borylating agent, tetrakis(dimethylamino)diboron (Me2N)2B–B(NMe2)2, is reported. The method is complementary to the ...previously reported method utilizing bis-boronic acid (BBA) in that certain substrates perform better under one set of optimized reaction conditions than the other. Because tetrakis(dimethylamino)diboron is the synthetic precursor to both BBA and bis(pinacolato)diboron (B2Pin2), the new method represents a more atom-economical and efficient approach to current borylation methods.
A method has been developed for the Pd-catalyzed synthesis of α-(hetero)aryl esters and amides through a Suzuki-Miyaura cross-coupling reaction. This method avoids the use of strong base, does not ...necessitate inert or low temperature formation of reagents, and does not require the use of a large excess of organometallic reagent. Utilization of organotrifluoroborate salts as nucleophilic partners allows a variety of functional groups and heterocyclic compounds to be tolerated.
Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental ...trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components.
This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned.
This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group.
Objectives:
Chronic diseases have an impact on and change patient’s lives which means that they need to find ways to cope with the new situation. The aim was to describe how the chronic disease has ...influenced patients’ views of their life situation.
Methods:
The study was quantitative in design with data collected using a semi-structured questionnaire. Descriptive statistics were used to compare similarities and differences between patients with asthma-allergy, diabetes mellitus, cancer and inflammatory rheumatoid arthritis.
Results:
Changes in their life were experienced as a negative outcome for the majority of participants. Support can be in the form of interpersonal support from various persons, but also from activities and beliefs/religion. Family and friends as well as healthcare professionals were identified as being most supportive. Sadness and worry were the most common emotions among the participants and their surrounding networks.
Conclusion:
People with a chronic disease have to live with the consequences the disease has for their life situation. They need to find strategies to cope with the negative outcome in their new life. Support from their own network and healthcare professionals can be helpful in the new life situation.
The synthesis and utilization of a class of 2,1-borazaronaphthyltrifluoroborate reagents that provide a general solution to the challenge of N-functionalization of the 2,1-borazaronaphthalene core is ...described. By adorning the nitrogen of this core with a trifluoroboratomethyl unit, a suite of odd-electron processes can be executed, installing motifs that would otherwise be inaccessible using a two-electron approach. In addition, this process enables rapid annulation, furnishing a heretofore unknown polycyclic B–N species.
Tinnitus is the experience of sounds without an appropriate external auditory source. These auditory sensations are intertwined with emotional and attentional processing. Drawing on theories of ...mental control, we predicted that suppressing an affectively negative sound mimicking the psychoacoustic features of tinnitus would result in decreased persistence in a mentally challenging task (mental arithmetic) that required participants to ignore the same sound, but that receiving a mindfulness exercise would reduce this effect. Normal hearing participants (N = 119) were instructed to suppress an affectively negative sound under cognitive load or were given no such instructions. Next, participants received either a mindfulness induction or an attention control task. Finally, all participants worked with mental arithmetic while exposed to the same sound. The length of time participants could persist in the second task served as the dependent variable. As hypothesized, results indicated that an auditory suppression rationale reduced time of persistence relative to no such rationale, and that a mindfulness induction counteracted this detrimental effect. The study may offer new insights into the mechanisms involved in the development of tinnitus interference. Implications are also discussed in the broader context of attention control strategies and the effects of emotional sound on task performance. The ironic processes of mental control may have an analog in the experience of sounds.
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