Gold nanoparticles-conjugation of irisin enhances therapeutic effect by improving cardiac function and attenuating inflammation in sepsis.

Irisin is considered to be a promising therapeutic approach for cardiac depression and inflammatory disorders. The short half-life of irisin impeded its use and drug efficacy in the treatment. This study aimed to examine if pegylated gold nanoparticles-conjugated to irisin would improve therapeutic effects in cecal ligation and puncture (CLP)-induced sepsis in mice. Recombinant irisin were conjugated to a pegylated gold nanoparticle, which was given to mice exposed to CLP. The cecal ligation procedure and sham on mice were operated and assigned to one of following five groups: (I) CLP group: The mouse models underwent the CLP surgical procedure and received only vehicle saline treatment (n = 5); (II) CLP + soluble Irisin: The mouse underwent the CLP and received an intramuscular injection (i.m) (TA) injection of 1 ug of soluble irisin into each tibialis anterior (TA) leg (n = 5); (III) CLP + Gold nanoparticle-conjugated to Irisin: The mouse models underwent the CLP and received an i.m (TA) injection of 1 µg of Gold nanoparticle-irisin via intramuscular injection (TA) into each leg (n = 5); (IV) CLP + Gold nanoparticles- conjugated to IgG: The mouse underwent the CLP and received an i.m (TA) injection of gold nanoparticles conjugated to IgG (n = 5). (V) Sham: The mouse underwent the surgical operation without conducting the CLP (n = 10). The post-operated animals were observed for one week, and survival rates were estimated. Echocardiography was performed to measure cardiac function at 12 h following CLP. TUNEL was employed to detect apoptosis in both cardiac and skeletal muscles; histology was conducted to assess tissue injury in muscles. Enzyme linked immunosorbent assay (ELISA) was conducted to examine release of interleukin 6 (IL6) and the tumor necrosis factor (TNF) alpha. Compared to the CLP control, soluble irisin treatment improved cardiac function recovery, as indicated by the fractional shortening (FS) and ejection fraction (EF). Irisin treatment exhibited reduced IL6 and TNF-alpha release in association with less apoptosis, lower muscle injury index and improved survival post-CLP. However, compared to soluble irisin treatment, gold nanoparticles-conjugated to irisin showed a significant improvement in cardiac function, suppression of apoptosis, reduced IL6 and TNF-alpha releases, decreased muscle injury and an improved survival rate of post-CLP. This study reveals that gold nanoparticles-conjugated irisin can serve to improve irisin's therapeutic effects over a longer course of treatment.

Integrated Service Delivery Model in Primary Care to Improve Frailty in Older Malaysians: GeKo Integrated Service Delivery.

BACKGROUND: This study aimed to evaluate the implementation stage of Malaysia's GeKo-Integrated Service Delivery (ISD) model for frailty management in primary care and explore its effectiveness in improving frailty scores. METHODS: The implementation stage of Malaysia's first three GeKo- ISD clinics was assessed using the WHO-ICOPE (Integrated Care of the Older Persons) scorecard. This involved evaluating documents related to the GeKo services and conducting in-depth interviews with key informants identified from those documents. The efficacy of GeKo-ISD was assessed by documenting the change in mean frailty scores between baseline and 3 months post intervention, measured by the Pictorial Fit Frail Scale Malay Version (PFFS-M), in patients who received GeKo-ISD care from October 2022 to April 2023. RESULTS: All three GeKo clinics achieved the sustaining implementation level, scoring a total of 50 out of 52. The paired t-test reported a significant reduction (p= 0.001) in the PFFS-M scores from baseline to 3 months after the GeKo-ISD intervention. The mean (SD) scores were 8.6 (4.6) at baseline and 7.0 (4.1) at 3 months post-intervention. CONCLUSION: GeKo-ISD is a comprehensive approach of integrated care for older people, leveraging existing public funded primary care infrastructure. It shows promise, was impacted by the pandemic but now, with support from the government, exists in 32 centers across one state in Malaysia.

Adherence to dietary guidelines associated with lower medical service utilization in preschoolers: a longitudinal study.

OBJECTIVE: We aimed to evaluate the association between dietary guideline adherence and overall, outpatient, and emergency medical service utilization in Taiwanese preschoolers. METHODS: We selected 614 preschoolers (2-6 years) who had one day of 24-h dietary recall data from the 2013-2016 Nutrition and Health Survey in Taiwan. The Taiwanese Children Healthy Eating Index (TCHEI) was developed on the basis of Taiwanese Food-Based Dietary Guidelines; it assesses dietary adequacy and eating behavior. Data on the participants' outpatient and emergency medical service utilization were obtained for 2013-2018 from the National Health Insurance Research Database. A multivariable generalized linear model was used to evaluate the association between the TCHEI and medical service utilization for all disease and respiratory diseases. RESULTS: After adjustment for confounding factors, children aged 2-3 years in the Tertile (T) 2 and T3 groups of the TCHEI exhibited 25% (95% CI 0.69-0.83) and 16% (95% CI 0.77-0.92) lower overall medical visits, respectively. The same pattern was noted in the outpatient and emergency visits for all diseases and respiratory diseases. The children aged 4-6 years in the T2 group exhibited 15% (95% CI 0.80-0.91) and 11% (95% CI 0.82-0.97) lower overall visits and visits for respiratory diseases, respectively. Moreover, preschoolers in the T2 group exhibited lower overall medical expenditures than did those in the T1 group. CONCLUSIONS: TCHEI score was positively correlated with better nutritional status. Optimal dietary intake associated with lower medical service utilization among Taiwan preschoolers.