Assessment of lisdexamfetamine on executive function in rats: A translational cognitive research.

Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.

Development of a comprehensive assessment tool to measure the quality of care for individuals with traumatic spinal cord injuries.

OBJECTIVE: To develop a comprehensive assessment tool to evaluate the Quality of Care (QoC) in managing individuals with traumatic spinal cord injuries (TSCI). METHOD: At first, the concepts of QoC for TSCI were identified by conducting a qualitative interview along with re-evaluation of the results of a published scoping review (conceptualization). After operationalization of indicators, they were valued by using the expert panel method. Afterward, the content validity index (CVI) and content validity ratio (CVR) were calculated and served as cut-offs for indicator selection. Then specific questions were developed for each indicator and classified into three categories: pre-hospital, in-hospital, and post-hospital. Data availability of the National Spinal Cord Injury Registry of Iran (NSCIR-IR) was subsequently used to design questions that represent indicators in an assessment tool format. The comprehensiveness of the tool was evaluated using a 4-item Likert scale by the expert panel. RESULT: Twelve experts participated in conceptualization and 11 experts participated in operationalization phase. Overall, 94 concepts for QoC were identified from published scoping review (87 items) and qualitative interviews (7 items). The process of operationalization and indicator selection led to the development of 27 indicators with acceptable content validity. Finally, the assessment tool contained three pre-hospital, twelve in-hospital, nine post-hospital, and three mixed indicators. Ninety-one percent of experts evaluated the entire tool as comprehensive. CONCLUSION: Our study presents a health-related QoC tool that contains a comprehensive set of indicators to assess the QoC for individuals with TSCI. However, this tool should be used in various situations to establish construct validity further.

Sulfur autotrophic denitrification filter and heterotrophic denitrification filter: Comparison on denitrification performance, hydrodynamic characteristics and operating cost.

Sulfur autotrophic denitrification (SAD) process, as an alternative to heterotrophic denitrification (HD) filter, receives growing interest in polishing the effluent from secondary sewage treatment. Although individual studies have indicated several advantages of SAD over HD, rare study has compared these two systems under identical condition and by using real secondary effluent. In this study, two small pilot scale filters (SAD and HD) were designed with identical configuration and operated parallelly by feeding the real secondary effluent from a WWTP. The results showed SAD filter can be started up without the addition of soluble electron donor, although the time (14 days) was about 3 times longer than that of HD filter. The nitrate removal rate of SAD filter at HRT of 1.4 h was measured as 0.268 ± 0.047 kg N/(m3∙d). Similar value was observed in HD filter with supplementing 90 mg/L COD. The COD concentration of effluent always kept lower than that of influent in SAD filter but not in HD filter. In addition, SAD filter could maintain a stable denitrification performance without backwash for 15 days, while decline of nitrate removal rate was observed in HD filter just 2 days after stopping the backwash. This different behavior was further confirmed as the SAD filter had a better hydraulic flow pattern. Analysis according to high-throughput 16S rRNA gene-based Illumina MiSeq sequencing clearly showed the microbial community evolution and differentiation among the samples of seed sludge, SAD and HD filters. Finally, the economic assessment was carried out, showing the operation cost of SAD filter was over 50% lower than that of HD filter.

Test of the stress process model of family caregivers of people living with schizophrenia in China.

Across the world, people living with schizophrenia (PLS) are often cared for by family caregivers. This is especially true in China where community-based systems of care for PLS are underdeveloped. Thus, family caregivers of PLS may experience emotional distress and burden in the absence of community-based services. Pearlin (1990) proposed a highly influential model for understanding the stress process and its relationship to health and wellbeing. Although the model has been examined worldwide, it has yet to be studied in China for caregivers of PLS. In the present study, we use Pearlin's stress process model to examine the mediating effect of perceived caregiver burden, family functioning, and caregivers' positive feelings about caregiving on PLS global functioning and caregiver depressive symptoms. We also examine whether the model differs for parent and spouse caregivers. A total of 327 primary family caregivers of PLS in Hunan province, China, were assessed cross-sectionally using culturally-validated measures. Bootstrap methods with Hayes's PROCESS Macro were used to test multiple mediation models of global functioning scores of PLS and caregiver depressive symptoms. In this first study of the stress process model of family caregivers of PLS in China, the results generally support the model. Caregiver perceived burden, family functioning, and positive caregiver feelings about caregiving all mediate the relationship between PLS global functioning and caregiver depression, with perceived caregiver burden having the strongest indirect effect. Analyses also show that the stress process differs between parent and spouse caregivers, with perceived caregiver burden a mediator for both groups but family functioning only a mediator for parent depressive symptoms. We discuss implications of these findings for extending the stress process model cross-culturally; suggest hypotheses for future research to examine parent and spouse differences; and discuss fruitful directions for intervention.

Therapeutic efficacy of PCSK9 monoclonal antibodies in statin-nonresponsive patients with hypercholesterolemia and dyslipidemia: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Heterozygous familial hypercholesterolemia and dyslipidemia are the predominant causes for cardiovascular disease (CVD). Clinical guidelines for lowering CVD risk have advocated that low density lipoprotein-cholesterol (LDL-C) must be reduced. The primary choice of therapy for controlling lipidemia has been statins, which are not completely effective. Proprotein convertase subtilisin/kexin type-9 (PCSK9), which interferes with LDL clearance from circulation, inversely relates to the LDL-C levels. The loss of statin efficacy is likely due to increased circulating PCSK9 and antibody therapy against PCSK9 has been found to be efficacious in lowering LDL-C. In this study, we evaluated the efficacy of PCSK9-mAbs for lowering LDL-C, in statin non-responsive hypercholesterolemia patients. STUDY DESIGN AND METHODS: PubMed, EMBASE, Scholar, Web of Science and Scopus databases were searched to identify randomized controlled trials of PCSK9 antibody-statin combination vs statin, published till 2015. Two reviewers independently screened the articles, and a collective decision was reached about the included studies in the metaanalysis. Parameters analyzed: change from baseline in LDL-C, high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC); ApoB and ApoA1 levels. RESULTS: A total of 12 studies with 4909 patients were selected. Overall, add-on therapy with PCSK9-mAb to the ongoing statin therapy was found to achieve greater reduction in LDL-C, ApoB, TC, compared to statin therapy. There were no major treatment emergent adverse effects due to PCSK9-mAb therapy. CONCLUSIONS: In adult patients with heterozygous familial hypercholesterolemia and dyslipidemia, PCSK9-mAb therapy in combination with statins was able to achieve the goal of lowering LDL-C.