Extinction blunts paraventricular thalamic contributions to heroin relapse.

Here, we use optogenetics and chemogenetics to investigate the contribution of the paraventricular thalamus (PVT) to nucleus accumbens (NAc) pathway in aversion and heroin relapse in two different heroin self-administration models in rats. In one model, rats undergo forced abstinence in the home cage prior to relapse testing, and in the other, they undergo extinction training, a procedure that is likened to cognitive behavioral therapy. We find that the PVT→NAc pathway is both sufficient and necessary to drive aversion and heroin seeking after abstinence, but not extinction. The ability of extinction to reduce this pathway's contribution to heroin relapse is accompanied by a loss of synaptic plasticity in PVT inputs onto a specific subset of NAc neurons. Thus, extinction may exert therapeutic reductions in opioid seeking by altering synaptic plasticity within the PVT→NAc pathway, resulting in reduced aversion during opioid withdrawal as well as reduced relapse propensity.

Methamphetamine seeking after prolonged abstinence is associated with activated projections from anterior intralaminar nucleus of thalamus to dorsolateral striatum in female rats.

Methamphetamine (Meth) seeking progressively increases after cessation from drug self-administration (incubation of Meth craving). We have previously shown that both dorsomedial and dorsolateral striatum (DMS and DLS) play critical roles in this incubation in male rats. Moreover, our recent anatomical tracing study examined afferent projections into DMS and demonstrated a novel role of projections from anterior intralaminar nucleus of thalamus (AIT) to DMS in incubation of Meth craving in male rats. Here we investigated projection-specific activation of afferent glutamate projections into DLS associated with incubated Meth seeking in female rats. We trained female rats to self-administer Meth (6-h/d for 10 d). On abstinence day 12, we injected cholera toxin subunit B (CTb, a retrograde tracer) unilaterally into DLS. On abstinence day 26, we tested rats for relapse to Meth seeking and measured Fos (a neuronal activity marker), and double-labeling of CTb and Fos in anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, basolateral amygdala, AIT, and parafascicular nuclei of thalamus. We observed neuronal activation in both cortical and thalamic regions associated with incubated Meth seeking. At the circuit level, AIT➔DLS projections were strongly activated, followed by other corticostriatal projections. Overall our results suggest that AIT to DLS may play a role in Meth seeking after prolonged abstinence in female rats.

Risk Factors for Medication Nonadherence to Self-Injectable Biologic Therapy in Adult Patients With Inflammatory Bowel Disease.

BACKGROUND: In inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), nonadherence to biologic therapy increases risk of disease flare. The aim of this study was to identify risk factors for nonadherence. METHODS: This was a single-center retrospective study evaluating patients with IBD treated at a tertiary care center and prescribed self-injectable biologic therapy using the center's specialty pharmacy. Adherence was defined using medication possession ratio (MPR). Nonadherence was defined as MPR <0.86. RESULTS: Four hundred sixty patients (n = 393 with CD and n = 67 with UC) were evaluated with mean MPR (interquartile range) equaling 0.89 (0.48-1). Overall, 69% of patients were adherent (defined as MPR ≥0.86), 66% of patients with CD and 87% of patients with UC. In univariate analysis, several factors increased risk of nonadherence: CD diagnosis, insurance type, psychiatric history, smoking, prior biologic use, and narcotic use (P < 0.05). In multivariable analysis, Medicaid insurance (odds ratio [OR], 5.5; 95% confidence interval [CI], 1.85-15.6) and CD diagnosis (OR, 2.8; 95% CI, 1.3-6.0) increased risk of nonadherence. In CD, as the number of risk factors increased (narcotic use, psychiatric history, prior biologic use, and smoking), the probability of nonadherence increased. Adherence was 72% in patients with 0-1 risk factors, decreasing to 62%, 61%, and 42% in patients with 2, 3, and 4 risk factors, respectively (P < 0.05). CONCLUSIONS: This study identified risk factors for nonadherence to biologic therapy. In patients with CD, the probability of nonadherence increased as the number of risk factors increased.

Self-Administered Auricular Acupressure Integrated With a Smartphone App for Weight Reduction: Randomized Feasibility Trial.

BACKGROUND: Obesity is a common global health problem and increases the risk of many chronic illnesses. Given the adverse effects of antiobesity agents and bariatric surgeries, the exploration of noninvasive and nonpharmacological complementary methods for weight reduction is warranted. OBJECTIVE: The study aimed to determine whether self-administered auricular acupressure (AA) integrated with a smartphone app was more effective than using AA alone or the controls for weight reduction. METHODS: This study is a 3-arm randomized waitlist-controlled feasibility trial. A total of 59 eligible participants were randomly divided into either group 1 (AA group, n=19), group 2 (AA plus smartphone app, n=19), or group 3 (waitlist control, n=21). A total of 6 reflective zones or acupoints for weight reduction were chosen. The smartphone app could send out daily messages to the subjects to remind them to perform self-pressing on the 6 ear acupoints. A "date picker" of the 8-week treatment course was used to enable the users to input the compliance of pressing and the number of bowel movement daily instead of using the booklet for recordings. The app also served as a reminder for the subjects regarding the dates for returning to the center for acupoint changing and assessments. Treatment was delivered 2 times a week, for 8 weeks. Generalized estimating equations were used to examine the interactions among the groups before and after intervention. RESULTS: Subjects in group 2 expressed that the smartphone app was useful (7.41 out of 10). The most popular features were the daily reminders for performing self-pressing (88%), the ear diagram indicating the locations and functions of the 6 ear points (71%), and ear pressing method demonstrated in the video scripts (47%). Nearly 90% of the participants completed the 8-week intervention, with a high satisfaction toward the overall arrangement (8.37 out of 10). The subjects in group 1 and 2 achieved better therapeutic effects in terms of body weight, body mass index (BMI), waist circumference, and hip circumference and perceived more fullness before meals than the waitlist controls. Although no significant differences in the pairwise comparisons between the 2 groups were detected (P>.05), the decrease in body weight, BMI, body fat, visceral fat rating and leptin level, and increase in adiponectin level were notable in group 2 before and after the intervention. CONCLUSIONS: The high compliance rate and high satisfaction toward the trial arrangement indicate that AA can be used to achieve weight reduction and applied in future large-scale studies. AA integrated with the smartphone app has a more notable effect than using AA alone for weight reduction. Larger sample size should be considered in future trials to determine the causal relationship between treatment and effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT03442712; https://clinicaltrials.gov/ct2/show/NCT03442712 (Archived by WebCite at http://www.webcitation.org/78L2tO8Ql).

Practices and outcomes of self-treatment with helminths based on physicians' observations.

The successful use of helminths as therapeutic agents to resolve inflammatory disease was first recorded 40 years ago. Subsequent work in animal models and in humans has demonstrated that the organisms might effectively treat a wide range of inflammatory diseases, including allergies, autoimmune disorders and inflammation-associated neuropsychiatric disorders. However, available information regarding the therapeutic uses and effects of helminths in humans is limited. This study probes the practices and experiences of individuals 'self-treating' with helminths through the eyes of their physicians. Five physicians monitoring more than 700 self-treating patients were interviewed. The results strongly support previous indications that helminth therapy can effectively treat a wide range of allergies, autoimmune conditions and neuropsychiatric disorders, such as major depression and anxiety disorders. Approximately 57% of the self-treating patients observed by physicians in the study had autism. Physicians reported that the majority of patients with autism and inflammation-associated co-morbidities responded favourably to therapy with either of the two most popular organisms currently used by self-treaters, Hymenolepis diminuta and Trichuris suis. However, approximately 1% of paediatric patients experienced severe gastrointestinal pains with the use of H. diminuta, although the symptoms were resolved with an anti-helminthic drug. Further, exposure to helminths apparently did not affect the impaired comprehension of social situations that is the hallmark of autism. These observations point toward potential starting points for clinical trials, and provide further support for the importance of such trials and for concerted efforts aimed at probing the potential of helminths, and perhaps other biologicals, for therapeutic use.

Effects of an acute cannabidiol treatment on cocaine self-administration and cue-induced cocaine seeking in male rats.

Cannabidiol is a non-psychoactive compound that is the second most abundant component of cannabis. It has been shown to have a potential therapeutic value for a wide range of disorders, including anxiety, psychosis, and depression. Recently, it was suggested that cannabidiol might be a potential treatment for heroin craving and relapse. Here we investigated the effects of an acute treatment with cannabidiol on cocaine self-administration and cue-induced cocaine seeking in rats. Rats were trained to press a lever to self-administer cocaine (0.5 mg/kg/infusion), first under a fixed interval 20 s (FI-20 s) and then under a progressive ratio (PR) schedule of reinforcement. Cocaine self-administration under a PR schedule of reinforcement was not attenuated by cannabidiol injections (5.0 mg/kg and 10.0 mg/kg; i.p.) when tested 30 min and 24 h after treatment. Cannabidiol treatment (5.0 mg/kg or 10.0 mg/kg) also did not attenuate cue-induced cocaine seeking in rats after a withdrawal period of 14 days. In contrast, treatment with cannabidiol (10.0 mg/kg; i.p.) resulted in a statistically significant anxiolytic effect in the elevated plus-maze. Our findings suggest that, under the conditions described here, an acute cannabidiol treatment has a minimal effect on a rat model of cocaine intake and relapse.

Glucose-responsive neurons of the paraventricular thalamus control sucrose-seeking behavior.

Feeding behavior is governed by homeostatic needs and motivational drive to obtain palatable foods. Here, we identify a population of glutamatergic neurons in the paraventricular thalamus of mice that express the glucose transporter Glut2 (encoded by Slc2a2) and project to the nucleus accumbens. These neurons are activated by hypoglycemia and, in freely moving mice, their activation by optogenetics or Slc2a2 inactivation increases motivated sucrose-seeking but not saccharin-seeking behavior. These neurons may control sugar overconsumption in obesity and diabetes.

[Addison's disease : Primary adrenal insufficiency]. / Morbus Addison : Primäre Nebenniereninsuffizienz.

Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease. Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH. Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises. Patients with adrenal insufficiency should carry an emergency card and emergency kit with them.

Sensitivity to self-administered cocaine within the lateral preoptic-rostral lateral hypothalamic continuum.

The lateral preoptic-rostral lateral hypothalamic continuum (LPH) receives projections from the nucleus accumbens and is believed to be one route by which nucleus accumbens signaling affects motivated behaviors. While accumbens firing patterns are known to be modulated by fluctuating levels of cocaine, studies of the LPH's drug-related firing are absent from the literature. The present study sought to electrophysiologically test whether drug-related tonic and slow-phasic patterns exist in the firing of LPH neurons during a free-access cocaine self-administration task. Results demonstrated that a majority of neurons in the LPH exhibited changes in both tonic and slow-phasic firing rates during fluctuating drug levels. During the maintenance phase of self-administration, 69.6% of neurons exhibited at least a twofold change in tonic firing rate when compared to their pre-drug firing rates. Moreover, 54.4% of LPH neurons demonstrated slow-phasic patterns, specifically "progressive reversal" patterns, which have been shown to be related to pharmacological changes across the inter-infusion interval. Firing rate was correlated with calculated drug level in 58.7% of recorded cells. Typically, a negative correlation between drug level and firing rate was observed, with a majority of neurons showing decreases in firing during cocaine self-administration. A small percentage of LPH neurons also exhibited correlations between locomotor behavior and firing rate; however, correlations with drug level in these same neurons were always stronger. Thus, the weak relationships between LPH firing and locomotor behaviors during cocaine self-administration do not account for the observed changes in firing. Overall, these findings suggest that a proportion of LPH neurons are sensitive to fluctuations in cocaine concentration and may contribute to neural activity that controls drug taking.

Análisis de conocimientos, hábitos y destrezas en una población diabética infantil: Intervención de Enfermería / Analysis of knowledge, habits and skills in a diabetic population childhood: nursing intervention

Introducción: Numerosos estudios han tratado de verificar la eficacia de una intervención educativa en pacientes diabéticos tipo 1 (DM1). Objetivos: Analizar los conocimientos previos a la intervención educativa sobre hábitos alimentarios y ejercicio físico, comprobar una posible mejora del nivel de estos conocimientos tras la intervención y verificar la adquisición de destrezas relacionadas con el autoanálisis y la autoinyección. Metodología: Se incluyeron 32 pacientes con DM1 de entre 4 y 14 años de Melilla. Mediante un cuestionario se analizaron los conocimientos sobre alimentación y ejercicio físico, y los hábitos sobre los mismos, mediante cuestionario KrecePlus. Se realizó una intervención educativa y se analizaron nuevamente dichos conocimientos, así como las destrezas adquiridas sobre autoanálisis y autoinyección con un nuevo cuestionario. Resultados: En relación a los conocimientos sobre dieta y ejercicio físico, se alcanzó una mejora significativa (p<0,0001) tras la intervención. Igualmente, los resultados mostraron una mejora en los hábitos de alimentación y ejercicio físico. El estudio de destrezas sobre autoanálisis y autoinyección reveló que los sujetos eran independientes en los procesos de autoanálisis de glucemia y autoinyección de insulina tras la intervención. Conclusión: Una intervención educativa llevada a cabo por enfermeras especializadas constituye un procedimiento efectivo para mejorar y aumentar los conocimientos de pacientes con DM1 sobre alimentación, ejercicio físico y sobre la propia enfermedad, así como un incentivo para adquirir hábitos saludables respecto a alimentación y ejercicio físico (AU)

Introduction: Large researches have tried to verify the efficiency of the educational intervention in patients suffering from type 1 diabetes (T1D). Objectives: Analyzing the initial knowledge about diet habits and physical exercise, confirming a possible improvement of the level of this knowledge after the educational intervention and verifying the acquisition of skills related to self-analysis and self-injection. Methodology: 32 subjects with T1D, from 4 to 14 years old in Melilla were included. The knowledge about diet and physical exercise were analyzed using a questionnaire. Diet habits were evaluated using the KrecePlus questionnaire. An educational intervention was offered and that knowledge was analysed again, as well as the skills acquired about self-analysis and self-injection with a new questionnaire. Results: After the intervention, the knowledge about diet and physical exercise significantly improved (p <0,0001). The results also showed an improvement in diet habits and physical exercise. The study of self-analysis and self-injection skills evidenced that the subjects were independent in the processes of blood glucose self-analysis and insulin self-injection. Conclusion: An educational intervention developed by a nurse is an effective procedure to improve and increase the knowledge about diet, physical exercise and about the disease in diabetic type 1 diabetic, as well as an incentive to acquire healthy habits about diet and physical exercise (AU)