Sesaminol alters phospholipid metabolism and alleviates obesity-induced NAFLD.

The prevalence of obesity-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance is increasing worldwide. We previously demonstrated that sesaminol increases thermogenesis in adipocytes, improves insulin sensitivity, and mitigates obesity in mice. In this study, we demonstrated that sesaminol increased mitochondrial activity and reduced ROS production in hepatocytes. Therefore, we delve into the metabolic action of sesaminol in obesity-induced NAFLD or metabolic dysfunction-associated liver disease (MAFLD). Here, we report that sesaminol induces OXPHOS proteins and mitochondrial function in vivo. Further, our data suggest that sesaminol administration reduces hepatic triacylglycerol accumulation and LDL-C levels. Prominently, the lipidomics analyses revealed that sesaminol administration decreased the major phospholipids such as PC, PE, PI, CL, and PS to maintain membrane lipid homeostasis in the liver upon HFD challenge. Besides, SML reduced ePC and SM molecular species and increased PA levels in the HFD-fed mice. Also, sesaminol renders anti-inflammatory properties and dampens fibrosis markers in the liver. Remarkably, SML lowers the hepatic levels of ALT and AST enzymes and alleviates NAFLD in diet-induced obese mice. The molecular docking analysis identifies peroxisome proliferator-activated receptors as potential endogenous receptors for sesaminol. Together, our study demonstrates plant lignan sesaminol as a potential small molecule that alters the molecular species of major phospholipids, including sphingomyelin and ether-linked PCs in the liver tissue, improves metabolic parameters, and alleviates obesity-induced fatty liver disease in mice.

Ensuring vaccine potency and availability: how evidence shaped Gavi's Immunization Supply Chain Strategy.

BACKGROUND: In 2014, Gavi and partners developed a global Immunization Supply Chain (iSC) Strategy, 2015-2020, which prioritized functioning cold chain equipment (CCE) and additional storage capacity. In 2016, Gavi launched the Cold Chain Equipment Optimization Platform (CCEOP) as a funding mechanism to improve CCE availability. In 2018, Gavi commissioned an evaluation of CCEOP in Guinea, Kenya and Pakistan. The global iSC Strategy has recently been revised, drawing on findings from effective vaccine management assessments and practical experiences. This case study presents the CCEOP evaluation and how its findings reinforced the revision of the iSC strategy. METHODS: The CCEOP evaluation used a prospective mixed-methods research design in all three countries involving key informant interviews at multiple levels of the health system, document reviews, direct observation (as and when possible), and a health facility assessment. RESULTS: Results show that CCEOP was effective at increasing the number of available and reliable CCE, and establishing improved management processes using the project management team (PMT) approach for country management systems and the service bundle provider approach for installation and maintenance. CCEOP also extended the iSC and immunization services in countries. The evaluation results also show gaps in the overall supply chain system, including CCE maintenance. DISCUSSION: Gavi has recently revised its iSC strategy, which has addressed gaps identified through assessments and practical experiences from stakeholders. Results of the CCEOP evaluation reinforce many of these findings. The strategy now provides more emphasis on supporting the fundamental infrastructure and establishing strong processes for maintenance. It also emphasizes strategic planning and forward thinking for iSC decisions, building on the processes established for the PMT through CCEOP. The original iSC strategy was an impetus for the establishment of CCEOP. The new strategy reflects shifting trends and priorities to fill gaps identified through practical experience, advocated for by stakeholders and thought leaders engaged in the iSC, and validated by the evaluation. It demonstrates the importance of aligning stakeholders with clear objectives and a sound strategy.

Moving forward with strengthening routine immunization delivery as part of measles and rubella elimination activities.

The Global Vaccine Action Plan includes a goal of meeting global and regional measles and rubella elimination targets, noting that such efforts should not operate in silos but be coordinated with other immunization efforts. Similarly, the Global Measles and Rubella Strategic Plan for 2012-2020 emphasizes the need for integrated approaches to achieve and maintain very high levels of population immunity using both routine immunization and supplemental immunization activities (SIAs). The strategic plan also includes routine vaccination coverage targets, highlighting the critical role of strong routine immunization systems as a cornerstone for sustainable measles control/elimination efforts. It encourages exploiting the resources and visibility of SIAs to strengthen routine immunization, thereby reducing the frequency with which SIAs are needed. Documented examples of doing so include training health workers, procuring cold chain equipment, and improving injection safety and adverse events management. However, the concept has been put into practice only to a limited extent and missed opportunities persist regarding this aspect of SIA planning and execution. This paper draws on recent studies of the interaction between measles activities and health systems as well as country experiences in using SIAs to strengthen routine immunization. It identifies obstacles and enabling factors to doing so and proposes options for systematically strengthening routine immunization as part of a best practice SIA.

Routine immunisation in India.

Vaccine preventable diseases have been reduced in the country since the routine immunisation programme started in 1978 as the Expanded Programme on Immunisation, then in 1985 renamed as Universal Immunisation Programme. Re-emergence of some vaccine preventable disease is a concern to all and the Government of India has launched a new multiyear plan to strengthen the routine immunisation. A number of recommendations was made to address the weaknesses in the programme. Some newer initiatives were also made under the multiyear plan and National Rural Health Mission to strengthen the routine immunisation. The general practitioners can play a positive role while immunising children as per Universal Immunisation Programme. Routine immunisation is one of the key components of polio eradication.