Prelimbic cortex is a common brain area activated during cue‐induced reinstatement of cocaine and heroin seeking in a polydrug self‐administration rat model

Many preclinical studies examined cue‐induced relapse to heroin and cocaine seeking in animal models, but most of these studies examined only one drug at a time. In human addicts, however, polydrug use of cocaine and heroin is common. We used a polydrug self‐administration relapse model in rats to determine similarities and differences in brain areas activated during cue‐induced reinstatement of heroin and cocaine seeking. We trained rats to lever press for cocaine (1.0 mg/kg per infusion, 3‐hr/day, 18 day) or heroin (0.03 mg/kg per infusion) on alternating days (9 day for each drug); drug infusions were paired with either intermittent or continuous light cue. Next, the rats underwent extinction training followed by tests for cue‐induced reinstatement where they were exposed to either heroin‐ or cocaine‐associated cues. We observed cue‐selective reinstatement of drug seeking: the heroin cue selectively reinstated heroin seeking and the cocaine cue selectively reinstated cocaine seeking. We used Fos immunohistochemistry to assess cue‐induced neuronal activation in different subregions of the medial prefrontal cortex, dorsal striatum, nucleus accumbens, and amygdala. Fos expression results indicated that only the prelimbic cortex (PL) was activated by both heroin and cocaine cues; in contrast, no significant cue‐induced neuronal activation was observed in other brain areas. RNA in situ hybridization indicated that the proportion of glutamatergic and GABAergic markers in PL Fos‐expressing cells was similar for the heroin and cocaine cue‐activated neurons. Overall, the results indicate that PL may be a common brain area involved in both heroin and cocaine seeking during polydrug use.     

A pilot trial of RNS60 in amyotrophic lateral sclerosis

Introduction: RNS60 is a novel immune-modulatory agent that has shown neuroprotective effects in amytrophic lateral sclerosis (ALS) preclinical models. RNS60 is administered by weekly intravenous infusion and daily nebulization. The objective of this pilot open-label trial was to test the feasibility, safety, and tolerability of long-term RNS60 administration in ALS patients. Methods: The planned treatment duration was 23 weeks and the primary outcomes were safety and tolerability. Secondary outcomes included PBR28 positron emission tomography (PET) imaging and plasma biomarkers of inflammation. Results: Sixteen participants with ALS received RNS60 and 13 (81%) completed 23 weeks of RNS60 treatment. There were no serious adverse events and no participants withdrew from the trial due to drug-related adverse events. There were no significant changes in the biomarkers. Discussion: Long-term RNS60 administration was safe and well-tolerated. A large, multicenter, phase II trial of RNS60 is currently enrolling participants to test the effects of RNS60 on ALS biomarkers and disease progression. Muscle Nerve 59 :303–308, 2019     

Fifty shades of graft: How to improve the efficacy of faecal microbiota transplantation for decolonization of antibiotic-resistant bacteria

Background

Spontaneous decolonization of antibiotic-resistant bacteria (ARB) takes time: approximately 25% after 30 days for carbapenem-producing Enterobacteriaceae or extended-spectrum beta-lactamase-producing Enterobacteriaceae. Faecal microbiota transplantation (FMT) has been proposed as a new strategy to promote decolonization in order to reduce the risk of superinfection due to these ARB. This paper discusses the literature on the use of FMT for this indication, and the improvement levers available to promote its efficacy.

Factors that predict diagnostic stability in neurodegenerative dementia

Journal of Neurology - To determine the frequency and characteristics of clinical diagnostic change in frontotemporal dementia (FTD)-spectrum syndromes and Alzheimer’s disease (AD)-type...     

Weight loss and co-morbidity resolution between different races and ethnicities after gastric bypass

BackgroundSeveral studies have demonstrated that minorities and Hispanic ethnicities have disproportionally greater burden of morbid obesity in the United States. However, the majority of bariatric procedures are performed in the non-Hispanic white population.ObjectivesThe objective of this study was to investigate the weight loss and remission of obesity-related co-morbidities based on race and ethnicity.SettingThe Longitudinal Assessment of Bariatric Surgery prospective, multicenter, observational study was used to collect patients from 10 different health centers across the United States.MethodsRetrospective analysis of a prospective, multicenter, observational study over a 5-year follow-up.ResultsAll patients who underwent primary gastric bypass and provided racial/ethnic information were included in the study (n = 1695). Regardless of race or ethnicity, total weight loss was maintained over a 5-year follow-up, which included 87% of the original cohort. However, whites had on average 1.94% higher adjusted total weight loss compared with blacks (P < .0001). After adjusting for confounders there were no significant differences in resolution of co-morbidities, including diabetes.ConclusionAll patients regardless of race or ethnicity have significant and sustained total weight loss and resolution of co-morbidities after gastric bypass at 5-year follow-up.