Coordinated activity of a central pathway drives associative opioid analgesic tolerance.

Opioid analgesic tolerance, a root cause of opioid overdose and misuse, can develop through an associative learning. Despite intensive research, the locus and central pathway subserving the associative opioid analgesic tolerance (AOAT) remains unclear. Using a combination of chemo/optogenetic manipulation with calcium imaging and slice physiology, here we identify neuronal ensembles in a hierarchically organized pathway essential for AOAT. The association of morphine-induced analgesia with an environmental condition drives glutamatergic signaling from ventral hippocampus (vHPC) to dorsomedial prefrontal cortex (dmPFC) cholecystokininergic (CCKergic) neurons. Excitation of CCKergic neurons, which project and release CCK to basolateral amygdala (BLA) glutamatergic neurons, relays AOAT signal through inhibition of BLA µ-opioid receptor function, thereby leading to further loss of morphine analgesic efficacy. This work provides evidence for a circuit across different brain regions distinct for opioid analgesic tolerance. The components of this pathway are potential targets to treat opioid overdose and abuse.

Effect of nutritional risk on cognitive function in patients with chronic obstructive pulmonary disease.

OBJECTIVE: We aimed to clarify the cognitive function of patients with chronic obstructive pulmonary disease (COPD) and different nutritional status. METHODS: Among 95 patients with COPD in this retrospective study, we administered the Nutritional Risk Screening 2002 (NRS 2002) and Mini-Mental State Examination (MMSE). We recorded patients' clinical characteristics, comorbidities, and laboratory measurements. According to NRS 2002 scores, patients were divided into two groups: no nutritional risk with NRS 2002 < 3 (n = 54) and nutritional risk, with NRS 2002 ≥ 3 (n = 41). RESULTS: We found a negative correlation between NRS 2002 and MMSE scores in participants with COPD (r = -0.313). Patients with nutritional risk were more likely to be cognitively impaired than those with no nutritional risk. Multivariate logistic regression analysis indicated that malnutrition was an independent risk factor for cognitive impairment, after adjusting for confounders (odds ratio [OR] = 4.120, 95% confidence interval [CI]: 1.072-15.837). We found a similar association between NRS 2002 and MMSE scores at 90-day follow-up using a Pearson's correlation test (r = -0.493) and logistic regression analysis (OR = 7.333, 95% CI: 1.114-48.264). CONCLUSIONS: Patients with COPD at nutritional risk are more likely to have cognitive impairment.

Experimental Study on Wet Skid Resistance of Asphalt Pavements in Icy Conditions.

In this research, the durability of skid resistance during the ice melting process with temperature increasing from -5 °C to 10 °C was characterized by means of a British Pendulum Skid Tester. Four types of pavement surfaces were prepared and tested. The difference between two antiskid layers prepared with bitumen emulsion was the aggregate. The detailed angularity and form 2D index of fine aggregates used for antiskid surfaces, characterized by means of the Aggregate Image Measure System (AIMS) with micro image analysis methods, were then correlated with British Pendulum Number (BPN) values. Results indicate that skid resistance has the lowest value during the ice-melting process. The investigated antiskid layers can increase the surface friction during icy seasons. In icy conditions, the skid resistance behavior first worsens until reaches the lowest value, and then increases gradually with increasing temperature. Results from ice-melting conditions on four investigated pavement surfaces give the same temperature range where there will be lowest skid resistance. That temperature range is from 3 °C to 5 °C. A thicker ice layer will result in a lower skid resistance property and smaller "lowest BPN".