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This study seeks to give an overview of academic research on internet-based interventions that are used to address problem gambling. The rate of treatment seeking has been demonstrated to be low across several research environments. This is in part because of the systemic barriers that treatment seekers face to accessing traditional face-to-face treatment. Making treatment resources for problem gambling available through the internet is one way to reduce the impact of those systemic barriers. The use of internet-based resources to address problem gambling has been growing, and a field of research evaluating it has developed as well. However, little has been done to summarize this collection of research. This study aimed to provide a scoping review of the use of internet-based interventions for problem gambling treatment and prevention to provide an understanding of the current state of the field. A scoping review was performed for 6 peer-reviewed research databases (Web of Science, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Social Science Abstracts, and Scopus) and 3 gray literature databases (MedEdPortal, Proquest: Dissertations, and OpenGrey). Article inclusion criteria were as follows: published over the 10-year period of 2007 to 2017, including an intervention for problem gambling, and involving the use of internet to deliver that intervention. A total of 27 articles were found that met the review criteria. Studies were found from several different areas, with particularly strong representation for Australia, New Zealand, and Scandinavia. Cognitive behavioral therapy was the most common form of internet-based intervention. Internet-based interventions were generally shown to be effective in reducing problem gambling scores and gambling behaviors. A wide range of interventions that made use of internet resources included text-based interactions with counselors and peers, automated personalized and normative feedback on gambling behaviors, and interactive cognitive behavioral therapies. A lack of diversity in samples, little comparison with face-to-face interventions, and issues of changes in the treatment dynamic are identified as areas that require further investigation. Internet-based interventions are a promising direction for treatment and prevention of problem gambling, particularly in reducing barriers to accessing professional help. The state of the current literature is sparse, and more research is needed for directly comparing internet-based interventions and their traditional counterparts.

Although cognitive-behavioural therapy (CBT) is a well-established treatment for adult depression, its efficacy and efficiency may be enhanced by better understanding its mechanism(s) of action. According to the theoretical model of CBT, symptom improvement occurs via reductions in maladaptive cognition. However, previous research has not established clear evidence for this cognitive mediation model. The present study investigated the cognitive mediation model of CBT in the context of a randomized controlled trial of CBT v. antidepressant medication (ADM) for adult depression. Participants with major depressive disorder were randomized to receive 16 weeks of CBT (n = 54) or ADM (n = 50). Depression symptoms and three candidate cognitive mediators (dysfunctional attitudes, cognitive distortions and negative automatic thoughts) were assessed at week 0 (pre-treatment), week 4, week 8 and week 16 (post-treatment). Longitudinal associations between cognition and depression symptoms, and mediation of treatment outcome, were evaluated in structural equation models. Both CBT and ADM produced significant reductions in maladaptive cognition and depression symptoms. Cognitive content and depression symptoms were moderately correlated within measurement waves, but cross-lagged associations between the variables and indirect (i.e. mediated) treatment effects were non-significant. The results provide support for concurrent relationships between cognitive and symptom change, but not the longitudinal relationships hypothesized by the cognitive mediation model. Results may be indicative of an incongruence between the timing of measurement and the dynamics of cognitive and symptom change.

The epithelial sodium channel (ENaC) can increase the colonic absorptive capacity for salt and water. Campylobacter concisus is a common pathogenic epsilonproteobacterium, causing enteritis and diarrhea. It can induce barrier dysfunction in the intestine, but its influence on intestinal transport function is still unknown. Therefore, our study aimed to characterize C. concisus effects on ENaC using the HT-29/B6-GR/MR (epithelial cell line HT-29/B6 transfected with glucocorticoid and mineralocorticoid receptors) cell model and mouse colon. In Ussing chambers, C. concisus infection inhibited ENaC-dependent Na+ transport as indicated by a reduction in amiloride-sensitive short circuit current (−55%, n = 15, p < 0.001). This occurred via down-regulation of β- and γ-ENaC mRNA expression and ENaC ubiquitination due to extracellular signal-regulated kinase (ERK)1/2 activation, predicted by Ingenuity Pathway Analysis (IPA). In parallel, C. concisus reduced the expression of the sealing tight junction (TJ) protein claudin-8 and induced claudin-8 redistribution off the TJ domain of the enterocytes, which facilitates the back leakage of Na+ ions into the intestinal lumen. In conclusion, C. concisus caused ENaC dysfunction via interleukin-32-regulated ERK1/2, as well as claudin-8-dependent barrier dysfunction—both of which contribute to Na+ malabsorption and diarrhea.

Campylobacter jejuni (C. jejuni) is the most common cause of foodborne gastroenteritis worldwide. The bacteria induce diarrhea and inflammation by invading the intestinal epithelium. Curcumin is a natural polyphenol from turmeric rhizome of Curcuma longa, a medical plant, and is commonly used in curry powder. The aim of this study was the investigation of the protective effects of curcumin against immune-induced epithelial barrier dysfunction in C. jejuni infection. The indirect C. jejuni-induced barrier defects and its protection by curcumin were analyzed in co-cultures with HT-29/B6-GR/MR epithelial cells together with differentiated THP-1 immune cells. Electrophysiological measurements revealed a reduction in transepithelial electrical resistance (TER) in infected co-cultures. An increase in fluorescein (332 Da) permeability in co-cultures as well as in the germ-free IL-10−/− mouse model after C. jejuni infection was shown. Curcumin treatment attenuated the C. jejuni-induced increase in fluorescein permeability in both models. Moreover, apoptosis induction, tight junction redistribution, and an increased inflammatory response—represented by TNF-α, IL-1β, and IL-6 secretion—was observed in co-cultures after infection and reversed by curcumin. In conclusion, curcumin protects against indirect C. jejuni-triggered immune-induced barrier defects and might be a therapeutic and protective agent in patients.

Human infections with the food-borne enteropathogen are responsible for increasing incidences of acute campylobacteriosis cases worldwide. Since antibiotic treatment is usually not indicated and the severity of the enteritis directly correlates with the risk of developing serious autoimmune disease later-on, novel antibiotics-independent intervention strategies with non-toxic compounds to ameliorate and even prevent campylobacteriosis are utmost wanted. Given its known pleiotropic health-promoting properties, curcumin constitutes such a promising candidate molecule. In our actual preclinical placebo-controlled intervention trial, we tested the anti-microbial and anti-inflammatory effects of oral curcumin pretreatment during acute experimental campylobacteriosis. Therefore, secondary abiotic IL-10 mice were challenged with synthetic curcumin via the drinking water starting a week prior oral infection. To assess anti-pathogenic, clinical, immune-modulatory, and functional effects of curcumin prophylaxis, gastrointestinal bacteria were cultured, clinical signs and colonic histopathological changes quantitated, pro-inflammatory immune cell responses determined by immunohistochemistry and intestinal, extra-intestinal and systemic pro-inflammatory mediator measurements, and finally, intestinal epithelial barrier function tested by electrophysiological resistance analysis of colonic biopsies in the Ussing chamber. Whereas placebo counterparts were suffering from severe enterocolitis characterized by wasting symptoms and bloody diarrhea on day 6 post-infection, curcumin pretreated mice, however, were clinically far less compromised and displayed less severe microscopic inflammatory sequelae such as histopathological changes and epithelial cell apoptosis in the colon. In addition, curcumin pretreatment could mitigate pro-inflammatory innate and adaptive immune responses in the intestinal tract and importantly, rescue colonic epithelial barrier integrity upon infection. Remarkably, the disease-mitigating effects of exogenous curcumin was also observed in organs beyond the infected intestines and strikingly, even systemically given basal hepatic, renal, and serum concentrations of pro-inflammatory mediators measured in curcumin pretreated mice on day 6 post-infection. In conclusion, the anti- and disease-mitigating including anti-inflammatory effects upon oral curcumin application observed here highlight the polyphenolic compound as a promising antibiotics-independent option for the prevention from severe acute campylobacteriosis and its potential post-infectious complications.

Background Proenkephalin A 119–159 (penKid) is a novel blood biomarker for real-time assessment of kidney function and was found to be independently associated with worsening kidney function and mortality. A novel penKid-based estimated glomerular filtration rate equation (eGFRPENK-Crea), outperforms current creatinine-based eGFR equations in predicting iohexol or iothalamate plasma clearance-based measured GFR. In this study, we aimed to evaluate the predictive value of penKid and eGFRPENK-Crea for all-cause mortality in stable patients at high cardiovascular risk. Methods Circulating penKid levels were assessed in 615 stable patients hospitalized at the Department of Cardiology at University Hospital Aachen, Germany. The endpoint was all-cause mortality; follow up was 3 years. Results penKid levels were higher in 46 non-survivors [58.8 (IQR 47.5–85.0) pmol/l] compared to 569 survivors [43.8 (IQR 34.0–58.0) pmol/l; P < .0001]. Univariable Cox regression analyses found penKid and eGFRPENK-Crea to be associated with all-cause mortality (C index 0.703, χ2 33.27, P < .00001; C index 0.716, χ2 36.51, P < .00001). This association remained significant after adjustment for significant baseline parameters including age, smoking, chronic heart failure, use of diuretics, leucocytes, body mass index, sex, and creatinine (C index 0.799, χ2 72.06, P < .00001). Importantly, penKid provided significant added value on top of eGFRCKD-EPI 2021 (eGFRCKD-EPI 2021: C index 0.716, χ2 34.21; eGFRCKD-EPI 2021 + penKid: C index 0.727, χ2: 40.02; Delta χ2 5.81; all P < .00001) for all-cause mortality prediction in our cohort. Conclusions penKid levels and eGFRPENK-Crea is associated with all-cause mortality within a 3-year follow-up period and the addition of penKid on top of eGFRCKD-EPI 2021 provided significant added value in mortality prediction.

Human infections are progressively rising and of high socioeconomic impact. In the present preclinical intervention study we investigated anti-pathogenic, immuno-modulatory, and intestinal epithelial barrier preserving properties of vitamin D applying an acute campylobacteriosis model. Therefore, secondary abiotic IL-10 mice were perorally treated with synthetic 25-OH-cholecalciferol starting 4 days before peroral infection. Whereas, 25-OH-cholecalciferol application did not affect gastrointestinal pathogen loads, 25-OH-cholecalciferol treated mice suffered less frequently from diarrhea in the midst of infection as compared to placebo control mice. Moreover, 25-OH-cholecalciferol application dampened induced apoptotic cell responses in colonic epithelia and promoted cell-regenerative measures. At day 6 post-infection, 25-OH-cholecalciferol treated mice displayed lower numbers of colonic innate and adaptive immune cell populations as compared to placebo controls that were accompanied by lower intestinal concentrations of pro-inflammatory mediators including IL-6, MCP1, and IFN-γ. Remarkably, as compared to placebo application synthetic 25-OH-cholecalciferol treatment of infected mice resulted in lower cumulative translocation rates of viable pathogens from the inflamed intestines to extra-intestinal including systemic compartments such as the kidneys and spleen, respectively, which was accompanied by less compromised colonic epithelial barrier function in the 25-OH-cholecalciferol as compared to the placebo cohort. In conclusion, our preclinical intervention study provides evidence that peroral synthetic 25-OH-cholecalciferol application exerts inflammation-dampening effects during acute campylobacteriosis.

The polyphenolic compound resveratrol has been shown to exert health-beneficial properties. Given globally emerging Campylobacter infections in humans, we addressed potential anti-pathogenic, immuno-modulatory and intestinal epithelial barrier preserving properties of synthetic resveratrol in the present preclinical intervention study applying a murine acute campylobacteriosis model. Two days following peroral C. jejuni infection, secondary abiotic IL-10−/− mice were either subjected to resveratrol or placebo via the drinking water. Whereas placebo mice suffered from acute enterocolitis at day 6 post-infection, resveratrol treatment did not only lead to improved clinical conditions, but also to less pronounced colonic epithelial apoptosis as compared to placebo application. Furthermore, C. jejuni induced innate and adaptive immune cell responses were dampened in the large intestines upon resveratrol challenge and accompanied by less colonic nitric oxide secretion in the resveratrol versus the placebo cohort. Functional analyses revealed that resveratrol treatment could effectively rescue colonic epithelial barrier function in C. jejuni infected mice. Strikingly, the disease-alleviating effects of resveratrol could additionally be found in extra-intestinal and also systemic compartments at day 6 post-infection. For the first time, our current preclinical intervention study provides evidence that peroral resveratrol treatment exerts potent disease-alleviating effects during acute experimental campylobacteriosis.

Background Point of care ultrasound (POCUS) education has grown significantly over the past two decades. Like most curricular items, POCUS education is siloed within individual graduate medical education (GME) programs. The purpose of this study was to evaluate the effectiveness of a shared GME POCUS curriculum between five GME programs at a single institution. Methods Post-graduate-year-1 (PGY-1) residents from emergency medicine (EM), family medicine (FM), internal medicine (IM), combined internal medicine-pediatrics (IM-Peds) and combined emergency medicine-pediatrics (EM-Peds) residency programs were enrolled in a core POCUS curriculum. The curriculum included eleven asynchronous online learning modules and ten hands-on training sessions proctored by sonographers and faculty physicians with POCUS expertise. Data was gathered about the curriculum’s effectiveness including participation, pre- and post-curricular surveys, pre- and post-knowledge assessments, and an objective skills assessment. Results Of the 85 residents enrolled, 61 (72%) participated in the curriculum. Engagement varied between programs, with attendance at hands-on sessions varying the most (EM 100%, EM-Peds 100%, FM 40%, IM 22%, Med-Peds 11%). Pre- and post-knowledge assessment scores improved for all components of the curriculum. Participants felt significantly more confident with image acquisition, anatomy recognition, interpreting images and incorporating POCUS findings into clinical practice ( p  < 0.001) after completing the curriculum. Conclusion In this shared GME POCUS curriculum, we found significant improvement in POCUS knowledge, attitudes, and psychomotor skills. This shared approach may be a viable way for other institutions to provide POCUS education broadly to their GME programs.

Risky decision-making is characteristic of depression and of addictive disorders, including pathological gambling. However it is not clear whether a propensity to risky choices predisposes to depressive symptoms or whether the converse is the case. Here we tested the hypothesis that rats showing risky decision-making in a rat gambling task (rGT) would be more prone to depressive-like behaviour in the learned helplessness (LH) model. Results showed that baseline rGT choice behaviour did not predict escape deficits in the LH protocol. In contrast, exposure to the LH protocol resulted in a significant increase in risky rGT choices on retest. Unexpectedly, control rats subjected only to escapable stress in the LH protocol showed a subsequent decrease in riskier rGT choices. Further analyses indicated that the LH protocol affected primarily rats with high baseline levels of risky choices and that among these it had opposite effects in rats exposed to LH-inducing stress compared to rats exposed only to the escape trials. Together these findings suggest that while baseline risky decision making may not predict LH behaviour it interacts strongly with LH conditions in modulating subsequent decision-making behaviour. The suggested possibility that stress controllability may be a key factor should be further investigated.