A coordinated preventive care approach for healthy ageing in five European cities: A mixed methods study of process evaluation components.

AIMS: To evaluate specific process components of the Urban Health Centres Europe (UHCE) approach; a coordinated preventive care approach aimed at healthy ageing by decreasing falls, polypharmacy, loneliness and frailty among older persons in community settings of five cities in the United Kingdom, Greece, Croatia, the Netherlands and Spain. DESIGN: Mixed methods evaluation of specific process components of the UHCE approach: reach of the target population, dose of the intervention actually delivered and received by participants and satisfaction and experience of main stakeholders involved in the approach. METHODS: The UHCE approach intervention consisted of a preventive assessment, shared decision-making on a care plan and enrolment in one or more of four coordinated care-pathways that targeted falls, polypharmacy, loneliness and frailty. Quantitative data from a questionnaire and quantitative/qualitative data from logbooks were collected among older persons involved in the approach. Qualitative data from focus groups were collected among older persons, informal caregivers and professionals involved in the approach. Quantitative data were analysed by means of descriptive statistics and multilevel logistic regression models. Qualitative data were analysed through thematic analysis. RESULTS: Having limited function was associated with non-enrolment in falls and loneliness care-pathways (both p < .01). The mean rating of the approach was 8.3/10 (SD 1.9). Feeling supported by a care professional and meeting people were main benefits for older persons. Mistrust towards unfamiliar care providers, lack of confidence to engage in care activities and health constraints were main barriers towards engagement in care. CONCLUSIONS: Although the UHCE approach was received generally positively, health constraints and psychosocial barriers prevented older person's engagement in care. IMPACT: Coordinated preventive care approaches for older community-dwelling persons should address health constraints and psychosocial barriers that hinder older person's engagement in care. TRIAL REGISTRATION: ISRCTN registry number is ISRCTN52788952. Date of registration is 13/03/2017.

Increased Risk-Taking Behaviour and Brain-Derived Neurotrophic Factor Val66Met Polymorphism Correlates to Decreased Serum Brain-Derived Neurotrophic Factor Level in Heroin Users.

BACKGROUND: This study has examined the relationships and interactions between serum brain-derived neurotrophic factor (BDNF) levels, BDNF Val66Met polymorphism and self-reported risk-taking behaviour in individuals with a history of heroin use undergoing outpatient treatment in comparison to healthy individuals. METHODS: We enrolled 167 heroin users and 86 healthy subjects and examined serum BDNF levels, Val66Met polymorphism, and personal characteristics using Connor Davidson Resilience Scale, Risk-taking (RT) propensity questionnaire, and Personality Assessment Inventory. RESULTS: Heroin users had significantly higher serum BDNF levels than controls. In addition, serum BDNF levels were significantly higher in Val/Val carriers than in Met/Val or Met/Met in all recruited subjects. Furthermore, a stepwise multiple regression analysis of serum BDNF levels as a dependent variable with related factors showed that in heroin users, Alcohol Use Disorder Identification Test score, anxiety and RT score were found as independent contributors to serum BDNF levels. When performing gene-environment interaction it was additionally found that heroin users with self-reported high risk-taking behaviour had significantly lower levels of serum BDNF among heroin users with the Met allele. CONCLUSIONS: These results indicate that genetic variant Met66 decreased the serum BDNF levels in combination with self-reported risk-taking propensity among heroin users. If results of future work confirm the influence of this combined effect between neurotrophic genotype and risk-taking behaviour, 66Met carriers might require higher levels of intervention to overcome their drug use pattern and risky behaviour.

Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice.

The aim of this study was to investigate the therapeutic potential of rosmarinic acid (RA), a natural phenolic, in the treatment of acute liver toxicity. RA at 10, 25 and 50mg/kg was administered by gavage once daily for 2 consecutive days, 6h after CCl(4) intoxication. CCl(4) intoxication caused hepatic necrosis and increased serum ALT activity. In the livers, oxidative/nitrosative stress was evidenced by increased 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances (TBARS) formation and a significant decrease in Cu/Zn superoxide dismutase (SOD) activity. CCl(4) administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). RA improved histological and serum markers of liver damage and significantly ameliorated oxidative/nitrosative stress and inflammatory response in liver tissue. Additionally, RA prevented transforming growth factor-beta1 (TGF-ß1) and alpha-smooth muscle actin (α-SMA) expression, suggesting suppression of profibrotic response. Furthermore, RA significantly inhibited the CCl(4)-induced apoptosis, which was evident from decreased cleavage of caspase-3. The hepatoprotective activity of RA coincided with enhanced NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. The results of this study indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity.

Differential hepatoprotective mechanisms of rutin and quercetin in CCl(4)-intoxicated BALB/cN mice.

AIM: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl(4)-induced liver damage in mice. METHODS: BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl(4) in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. RESULTS: Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl(4)-intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl(4)-intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl(4)-induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-ß1 (TGF-ß1) than rutin. CONCLUSION: Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and anti-inflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.