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The neocortex and striatum are topographically organized for sensory and motor functions. While sensory and motor areas are lateralized for touch and motor control, respectively, frontal areas are involved in decision-making, where lateralization of function may be less important. This study contrasted the topographic precision of cell-type-specific ipsilateral and contralateral cortical projections while varying the injection site location in transgenic mice of both sexes. While sensory cortical areas had strongly topographic outputs to the ipsilateral cortex and striatum, they were weaker and not as topographically precise to contralateral targets. The motor cortex had somewhat stronger projections but still relatively weak contralateral topography. In contrast, frontal cortical areas had high degrees of topographic similarity for both ipsilateral and contralateral projections to the cortex and striatum. Corticothalamic organization is mainly ipsilateral, with weaker, more medial contralateral projections. Corticostriatal computations might integrate input outside closed basal ganglia loops using contralateral projections, enabling the two hemispheres to act as a unit to converge on one result in motor planning and decision-making. [ABSTRACT FROM AUTHOR]

Background Hospital patients who use illicit opioids such as heroin may use drugs during an admission or leave the hospital in order to use drugs. There have been reports of patients found dead from drug poisoning on the hospital premises or shortly after leaving the hospital. This study examines whether hospital admission and discharge are associated with increased risk of opioid-related death. Methods and findings We conducted a case-crossover study of opioid-related deaths in England. Our study included 13,609 deaths between January 1, 2010 and December 31, 2019 among individuals aged 18 to 64. For each death, we sampled 5 control days from the period 730 to 28 days before death. We used data from the national Hospital Episode Statistics database to determine the time proximity of deaths and control days to hospital admissions. We estimated the association between hospital admission and opioid-related death using conditional logistic regression, with a reference category of time neither admitted to the hospital nor within 14 days of discharge. A total of 236/13,609 deaths (1.7%) occurred following drug use while admitted to the hospital. The risk during hospital admissions was similar or lower than periods neither admitted to the hospital nor recently discharged, with odds ratios 1.03 (95% CI 0.87 to 1.21; p = 0.75) for the first 14 days of an admission and 0.41 (95% CI 0.30 to 0.56; p < 0.001) for days 15 onwards. 1,088/13,609 deaths (8.0%) occurred in the 14 days after discharge. The risk of opioid-related death increased in this period, with odds ratios of 4.39 (95% CI 3.75 to 5.14; p < 0.001) on days 1 to 2 after discharge and 2.09 (95% CI 1.92 to 2.28; p < 0.001) on days 3 to 14. 11,629/13,609 deaths (85.5%) did not occur close to a hospital admission, and the remaining 656/13,609 deaths (4.8%) occurred in hospital following admission due to drug poisoning. Risk was greater for patients discharged from psychiatric admissions, those who left the hospital against medical advice, and those leaving the hospital after admissions of 7 days or more. The main limitation of the method is that it does not control for time-varying health or drug use within individuals; therefore, hospital admissions coinciding with high-risk periods may in part explain the results. Conclusions Discharge from the hospital is associated with an acute increase in the risk of opioid-related death, and 1 in 14 opioid-related deaths in England happens in the 2 weeks after the hospital discharge. This supports interventions that prevent early discharge and improve linkage with community drug treatment and harm reduction services., Author(s): Dan Lewer 1,2,3,*, Brian Eastwood 2, Martin White 2, Thomas D. Brothers 1,3,4, Martin McCusker 5, Caroline Copeland 6,7, Michael Farrell 3, Irene Petersen 8 Introduction People who use [...]

An analog of the trans3,4-dimethyl-4-(3-hydroxyphenyl)piperidine series (LY255582) exhibits high in vitro binding affinity and antagonist potency for the Ix-, [delta]-, and [kappa]-opioid receptors. In vivo, LY255582 exhibits potent effects in reducing food intake and body weight in several rodent models of obesity. In the present study, we evaluated the effects of LY255582 to prevent the consumption of a highly palatable (HP) diet (a high-fat/ high-carbohydrate diet) both when the food was novel and following daily limited access to the HP diet. Additionally, we examined the effects of consumption of the HP diet and of LY255582 treatment on mesolimbic dopamine (DA) signaling by in vivo microdialysis. Consumption of the HP diet increased extracellular DA levels within the nucleus accumbens (NAc) shell. Increased DA in the NAc shell was not related to the quantity of the HP diet consumed, and the DA response did not habituate following daily scheduled access to the HP diet. Interestingly, treatment with LY255582 inhibited consumption of the HP diet and the HP diet-associated increase in NAc shell DA levels. Moreover, the increased HP diet consumption observed following daily limited access to the HP diet was completely prevented by LY255582 treatment. LY255582 may be a useful tool in understanding the neural mechanisms involved in the reinforcement mechanisms regulating food intake. opiate; nucleus accumbens; obesity; food intake; microdialysis

In this article, the authors compare the assay performance measures, signal window, Z' factor, and assay variability ratio. They examine their mathematical formulae for similarities and differences, describe their statistical [...]

The authors show by illustration that procedures used to validate the reliability of single-concentration high-throughput screens such as the signal window and Z' factor do not ensure sufficient reliability in [...]

Agonists to opioid receptors induce a positive energy balance, whereas antagonists at these receptors reduce food intake and body weight in rodent models of obesity. An analog of 3,4-dimethyl-4-(3-hydroxyphenyl)piperidine, LY255582, is a potent non-morphinan antagonist for [mu]-, [kappa]-, and [delta]-receptors ([K.sub.i] of 0.4, 2.0, and 5.2 nM, respectively). In the present study, we examined the effects of oral LY255582 treatment on caloric intake, calorie expenditure, and body composition in dietary-induced obese rats. Acute oral treatment of LY255582 produced a dose-dependent decrease in energy intake and respiratory quotient (RQ), which correlated with the occupancy of central opioid receptors. Animals receiving chronic oral treatment with LY255582 for 14 days maintained a negative energy balance that was sustained by increased lipid use. Analysis of body composition revealed a reduction in fat mass accretion, with no change in lean body mass, in animals treated with LY255582. Therefore, chronic treatment with LY255582 reduces adipose tissue mass by reducing energy intake and stimulating lipid use. respiratory quotient; body composition; dual-energy X-ray absorptiometry; indirect calorimetry; ex vivo receptor binding

A 7-day treatment with erythromycin appears to be just as effective as a 14-day treatment in patients with whooping cough. Whooping cough is a respiratory infection which still occurs despite the widespread use of the DPT vaccine. Researchers compared a 7-day and 14-day antibiotic treatment in 168 patients with whooping cough. Nasal cultures were taken at various times during treatment to test for the bacterium that causes whooping cough. The cure rate in the 74 patients treated for 7 days was as high as the rate in the 94 patients treated for 14 days., ABSTRACT. Objective and Methods. Although 14 days of erythromycin is recommended for the treatment of Bordetella pertussis infection, there have been no prospective controlled studies to support the contention that this long course of therapy is required to eradicate the microorganism from the nasopharynx or to prevent bacteriological relapse. We randomly allocated children and adults with culture-positive community-acquired pertussis to either 7 or 14 days of erythromycin estolate treatment (40 mg/kg/d; maximum dose 1 g/d). Nasopharyngeal aspirate cultures were obtained by study nurses during home visits before and at the end of treatment, and 1 week after the completion of treatment. B pertussis-specific antibodies were measured before treatment and 1 month later. Information about clinical symptoms, adverse reactions, and compliance were collected at each scheduled contact. Results and Conclusions. A total of 168 participants were eligible for analysis (74 treated for 7 days and 94 treated for 14 days). Bacteriological persistence (positive end of therapy culture) occurred once in each group, and bacteriological relapse (positive culture 1 week after completion of treatment) occurred in one participant treated for 7 days. The overall failure rate (persistence plus relapse) of 2.70% in the 7-day group was not different than the rate of 1.06% in the 14-day group. The study had a power of 99.99% at the 5% level to detect a difference in failure rates of 10% and a power of 80% to detect a difference of 5%. We conclude that 7 days of erythromycin estolate is as effective as 14 days for the eradication of B pertussis. Pediatrics 1997;100:65-71; pertussis, whooping cough, Bordetella pertussis, antimicrobial therapy, erythromycin estolate., Pertussis (whooping cough) is an acute respiratory infection caused by Bordetella pertussis and characterized by a paroxysmal cough which often ends in an inspiratory whoop and/or vomiting. Through the widespread [...]

Mental imagery manipulations are used to treat several psychological disorders, but their utility in treating cocaine use disorder (CUD) is unknown. Using prompted re‐experiences and simulations with contrasting valence, we assessed the acute impact of a deliberate mental imagery task on cocaine craving. Design A quantitative–qualitative 'mixed‐methods' analysis of data collected for a randomized controlled trial that was stopped prematurely. Setting: UK National Health Service addictions treatment clinic and outpatient clinical research facility (laboratory). Participants: Adults with CUD. The original target sample was 120. All participants enrolled at the point the original trial was stopped were included (38 enrolled, 31 completed study). Interventions: Personalized (3‐minute) cue–exposure (handling cocaine paraphernalia and watching video of drug preparation), immediately followed by a single 5‐minute, audio‐recorded, self‐guided and verbally described imagery task with random assignment to one of four conditions: two mental imagery memory re‐experiences (positive image before initiation to cocaine use or a negative image of a 'worst time' adverse cocaine use episode) or two future simulations (positive theme of recovery from CUD or negative theme of worsened CUD). Measurements Task transcripts were rated for imagery detail using five dimensions using a six‐point scale of imagery detail (ID) (total score = 0–25) and thematically coded. The outcome measure was cocaine craving using the Craving Experiences Questionnaire—strengths version (CEQ–S11; score = 0–110) reported at baseline, arrival at the laboratory, and immediately after the cue–exposure and mental imagery tasks. Findings A mixed‐effects, longitudinal, restricted linear regression, with the past‐positive imagery condition as referent, showed main effects of reduced craving after the imagery task (b = –29.2, 95% confidence interval (CI) = –45.3 to −13.1, P‐value < 0.001) and increased craving for the future‐negative task (b = 14.2, 95% CI = 0.1–28.4, P‐value 0.049). There was a future‐negative task by post‐imagery craving interaction (b = 28.1, 95% CI = 0.1–56.1, P‐value 0.049). A theory‐driven, deductive/inductive qualitative analysis of the transcripts revealed six major themes: sensory characteristics, CUD vicious cycle, self‐care, emotions and appraisals, social role and CUD recovery. Positively themed simulations included interpersonal connections and rewarding activity; negative images included personal adversity, with appraisals of self‐criticism and hopelessness. Transcripts with more imagery detail were not associated with significantly greater reductions in craving in the positive or negative imagery task (r = –0.32, 95% CI = –0.69 to 0.13 and r = 0.06, 95% CI = –0.58 to 0.53, respectively). Conclusion: In people with cocaine use disorder, after cue–exposure, a self‐guided imagery task with positive themes reduced craving, whereas mental imagery simulating worsened cocaine use disorder did not appear to. [ABSTRACT FROM AUTHOR]