Task-Dependent Differences in Operant Behaviors of Rats With Acute Exposure to High Ambient Temperature: A Potential Role of Hippocampal Dopamine Reuptake Transporters.

Behavioral or cognitive functions are known to be influenced by thermal stress from the change in ambient temperature (Ta). However, little is known about how increased Ta (i.e., when the weather becomes warm or hot) may affect operant conditioned behavior and the neural substrates involved. The present study thus investigated the effects of high Ta on operant behaviors maintained on a fixed-ratio 1 (FR1) and a differential reinforcement for low-rate responding 10 s (DRL 10-s) schedule of reinforcement. The rats were randomly assigned to three groups receiving acute exposure to Ta of 23°C, 28°C, and 35°C, respectively, for evaluating the effects of high Ta exposure on four behavioral tests. Behavioral responses in an elevated T-maze and locomotor activity were not affected by Ta treatment. Regarding operant tests, while the total responses of FR1 behavior were decreased only under 35°C when compared with the control group of 23°C, those of DRL 10-s behavior were significantly reduced in both groups of 28°C and 35°C. Distinct patterns of inter-response time (IRT) distribution of DRL behavior appeared among the three groups; between-group differences of behavioral changes produced by high Ta exposure were confirmed by quantitative analyses of IRT data. Western blot assays of dopamine (DA) D1 and D2 receptor, DA transporter (DAT) and brain-derived neurotrophic factor (BDNF) were conducted for the sample tissues collected in six brain areas from all the subjects after acute high Ta exposure. Significant Ta-related effects were only revealed in the dorsal hippocampus (dHIP). In which, the DAT levels were increased in a Ta-dependent fashion that was associated with operant behavior changes under high Ta exposure. And, there as an increased level of D1 receptors in the 28°C group. In summary, these data indicate that the performance of operant behavior affected by the present high Ta exposure is task-dependent, and these changes of operant behaviors cannot be attributed to gross motor function or anxiety being affected. The regulation of dHIP DAT may be involved in this operant behavioral change under high Ta exposure.

Prognostic factors of health care-associated bloodstream infection in adult patients ≥40 years of age.

We investigated 401 geriatric patients and 453 middle-aged patients with health care-associated bloodstream infection (HABSI) at a medical center during January-December 2014. Compared with middle-aged patients, the geriatric group had higher 30-day mortality (31.2% vs 23.4%, P = .01). Body mass index, serum albumin concentration, Charlson comorbidity index score, vancomycin-resistant Enterococcus bacteremia, and high C-reactive protein levels predict poor outcomes for HABSI among adult patients.

Predicting Multidrug-Resistant Gram-Negative Bacterial Colonization and Associated Infection on Hospital Admission.

OBJECTIVE Isolation of multidrug-resistant gram-negative bacteria (MDR-GNB) from patients in the community has been increasingly observed. A prediction model for MDR-GNB colonization and infection risk stratification on hospital admission is needed to improve patient care. METHODS A 2-stage, prospective study was performed with 995 and 998 emergency department patients enrolled, respectively. MDR-GNB colonization was defined as isolates resistant to 3 or more classes of antibiotics, identified in either the surveillance or early (≤48 hours) clinical cultures. RESULTS A score-assigned MDR-GNB colonization prediction model was developed and validated using clinical and microbiological data from 995 patients enrolled in the first stage of the study; 122 of these patients (12.3%) were MDR-GNB colonized. We identified 5 independent predictors: age>70 years (odds ratio [OR], 1.84 [95% confidence interval (CI), 1.06-3.17]; 1 point), assigned point value in the model), residence in a long-term-care facility (OR, 3.64 [95% CI, 1.57-8.43); 3 points), history of cerebrovascular accidents (OR, 2.23 [95% CI, 1.24-4.01]; 2 points), hospitalization within 1 month (OR, 2.63 [95% CI, 1.39-4.96]; 2 points), and recent antibiotic exposure (OR, 2.18 [95% CI, 1.16-4.11]; 2 points). The model displayed good discrimination in the derivation and validation sets (area under ROC curve, 0.75 and 0.80, respectively) with the best cutoffs of<4 and ≥4 points for low- and high-risk MDR-GNB colonization, respectively. When applied to 998 patients in the second stage of the study, the model successfully stratified the risk of MDR-GNB infection during hospitalization between low- and high-risk groups (probability, 0.02 vs 0.12, respectively; log-rank test, P<.001). CONCLUSION A model was developed to optimize both the decision to initiate antimicrobial therapy and the infection control interventions to mitigate threats from MDR-GNB. Infect Control Hosp Epidemiol 2017;38:1216-1225.

Nanostructured lipid carriers containing a high percentage of a Pluronic copolymer increase the biodistribution of novel PDE4 inhibitors for the treatment of traumatic hemorrhage.

Although the application of nanotechnology to drug therapy has been widely investigated, very few nanomedicine-based treatments for traumatic hemorrhage have been reported so far. The aim of this work was to develop nanostructured lipid carriers (NLCs) loaded with phosphodiesterase 4 (PDE4) inhibitors to treat acute inflammation in peripheral organs. The pharmacokinetics and biodistribution of DSM-RX78 and EFB-1, two novel PDE4 inhibitors, were examined using rats as an animal model. Entrapment by NLCs resulted in sustained drug release. The plasma concentrations of DSM-RX78 and EFB-1 in NLCs were lower, and their half-lives were much shorter in the NLC condition than in the control condition. PDE4 inhibitors delivered in NLCs accumulated with high abundance in many organs, especially the brain and lungs. Polyethylene glycol (PEG) coating on the particulate surface (P-NLCs) significantly reduced brain delivery of the drugs. P-NLCs enhanced drug distribution to the lungs by 5-fold compared to free control. In vivo real-time imaging confirmed rapid escape of nanoparticles from the blood circulation. Histological examination and aminotransferase measurement revealed that P-NLCs containing EFB-1 improved hemorrhagic shock-induced injuries in the lungs, intestines, and liver. P-NLCs even reversed acute lung inflammation to the level observed in an uninjured condition. Our results indicate that NLC-based delivery of PDE4 inhibitors is a candidate treatment for traumatic hemorrhage.