The lived experiences of a COVID-19 immunization programme: vaccine hesitancy and vaccine refusal.

BACKGROUND: The COVID-19 pandemic has resulted in a global health emergency and lock-down measures to curb the uncontrolled transmission chain. Vaccination is an effective measure against COVID-19 infections. In Malaysia amidst the national immunisation programme (NIP) which started in February 2021, there were rising concerns regarding the prevalence of vaccine hesitancy and refusal, and therefore, vaccine uptake among Malaysians. Although there are many quantitative studies on COVID-19 vaccination, the subjective experience of individuals was understudied. This study aims to explore the lived experiences of Malaysians regarding vaccine hesitancy and refusal, and facilitating factors that could enhance vaccine acceptance and uptake. METHODS: This qualitative study employed the hermeneutic phenomenological study design. Purposive sampling strategies were used to recruit Malaysians that had direct experiences with friends, family members and their community who were hesitating or refusing to accept the COVID-19 vaccines. A semi-structured interview guide was developed based on the expert knowledge of the investigators and existing literature on the topic. A series of focus group interviews (FGIs) was conducted online facilitated by a multidisciplinary team of experts. The group interviews were transcribed verbatim and analysed. RESULTS: Fifty-nine participants took part in seven FGIs. We found that "incongruence" was the overall thematic meaning that connected all the 3 main themes. These themes comprise firstly, the incongruence between the aims and implementation of the National Immunization Program which highlighted the gap between realities and needs on the ground. Secondly, the incongruence between Trust and Mistrust revealed a trust deficit in the government, COVID-19 news, and younger people's preference to follow the examples of local vaccination "heroes". Thirdly, the incongruence in communication showed the populace's mixed views regarding official media and local social media. CONCLUSIONS: This study provided rich details on the complex picture of the COVID-19 immunization program in Malaysia and its impact on vaccine hesitancy and refusal. The inter-related and incongruent factors explained the operational difficulty and complexity of the NIP and the design of an effective health communication campaign. Identified gaps such as logistical implementation and communication strategies should be noted by policymakers in implementing mitigation plans.

Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by ampk activation.

Chlorogenic acid (CGA) has been shown to stimulate glucose uptake in skeletal muscle through the activation of AMPK. However, its effect on other metabolic pathways and likewise its effects after long-term consumption have yet to be understood. We investigated the effects of CGA on glucose tolerance, insulin sensitivity, hepatic gluconeogenesis, lipid metabolism and skeletal muscle glucose uptake in Lepr(db/db) mice. Hepatoma HepG2 was used to investigate CGA's effect on hepatic glucose production and fatty acid synthesis. Subsequently, we attempted to evaluate whether these effects of CGA are associated with the activation of AMPK. In Lepr(db/db) mice, acute treatment with CGA lowered AUCglucose in an OGTT. Chronic administration of CGA inhibited hepatic G6Pase expression and activity, attenuated hepatic steatosis, improved lipid profiles and skeletal muscle glucose uptake, which in turn improved fasting glucose level, glucose tolerance, insulin sensitivity and dyslipidemia in Lepr(db/db) mice. CGA activated AMPK, leading to subsequent beneficial metabolic outcomes, such as suppression of hepatic glucose production and fatty acid synthesis. Inhibition and knockdown of AMPK abrogated these metabolic alterations. In conclusion, CGA improved glucose and lipid metabolism, via the activation of AMPK.

Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes.

Chlorogenic acid (CGA) has been shown to delay intestinal glucose absorption and inhibit gluconeogenesis. Our aim was to investigate the role of CGA in the regulation of glucose transport in skeletal muscle isolated from db/db mice and L6 skeletal muscle cells. Oral glucose tolerance test was performed on db/db mice treated with CGA and soleus muscle was isolated for 2-deoxyglucose transport study. 2DG transport was also examined in L6 myotubes with or without inhibitors such as wortmannin or compound c. AMPK was knocked down with AMPKα1/2 siRNA to study its effect on CGA-stimulated glucose transport. GLUT 4 translocation, phosphorylation of AMPK and Akt, AMPK activity, and association of IRS-1 and PI3K were investigated in the presence of CGA. In db/db mice, a significant decrease in fasting blood sugar was observed 10 minutes after the intraperitoneal administration of 250 mg/kg CGA and the effect persisted for another 30 minutes after the glucose challenge. Besides, CGA stimulated and enhanced both basal and insulin-mediated 2DG transports in soleus muscle. In L6 myotubes, CGA caused a dose- and time-dependent increase in glucose transport. Compound c and AMPKα1/2 siRNA abrogated the CGA-stimulated glucose transport. Consistent with these results, CGA was found to phosphorylate AMPK and ACC, consistent with the result of increased AMPK activities. CGA did not appear to enhance association of IRS-1 with p85. However, we observed activation of Akt by CGA. These parallel activations in turn increased translocation of GLUT 4 to plasma membrane. At 2 mmol/l, CGA did not cause any significant changes in viability or proliferation of L6 myotubes. Our data demonstrated for the first time that CGA stimulates glucose transport in skeletal muscle via the activation of AMPK. It appears that CGA may contribute to the beneficial effects of coffee on Type 2 diabetes mellitus.

Polyphenols-rich Vernonia amygdalina shows anti-diabetic effects in streptozotocin-induced diabetic rats.

AIM OF THE STUDY: This study aims to investigate the hypoglycemic properties of Vernonia amygdalina Del. (VA) and its possible mechanisms of action in a single-dose STZ induced diabetic rat model. MATERIALS AND METHODS: A dose-response study was conducted to determine optimum dose for the hypoglycemic effect of VA in STZ-induced diabetic rats. The optimum dose (400 mg/kg) was used throughout the 28-day chronic study. Body weight, food and water intakes of the rats were monitored daily. Fasting blood serum, pancreas, liver and soleus muscle were collected for biochemical analyses. Chemical composition of VA was analysed using HPLC and LC-ESI-MS. RESULTS: The study reveals that ethanolic extract of VA contains high level of polyphenols mainly 1,5-dicaffeoyl-quinic acid, dicaffeoyl-quinic acid, chlorogenic acid and luteolin-7-O-glucoside. In an oral glucose tolerance test, 400 mg/kg VA exhibited a significant improvement in glucose tolerance of the STZ-induced diabetic rats. 28-day treatment with 400 mg/kg VA resulted in 32.1% decrease in fasting blood glucose compared to diabetic control. VA also caused significant decrease (18.2% and 41%) in triglyceride and total cholesterol level. Besides, VA showed protective effect over pancreatic ß-cells against STZ-induced damage, causing a slight increase in insulin level compared to diabetic control. VA administration also showed positive regulation of the antioxidant system, both enzymatic and non-enzymatic. Furthermore, VA was found to increase expression of GLUT 4 (24%) in rat skeletal muscle. Further tissue fractionation revealed that it can increase the GLUT 4 translocation (35.7%) to plasma membrane as well, suggesting that VA may stimulate skeletal muscle's glucose uptake. This observation is in line with the restoration in skeletal muscle glycogenesis of VA-treated group. However, no alteration was observed in GLUT 1 expression. In addition, VA also suppressed (40% inhibition) one of the key hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase). CONCLUSIONS: VA possesses antihyperglycemic effect, most probably through increasing GLUT 4 translocation and inhibiting hepatic G6Pase. The polyphenols in the extract may be the candidates that are responsible for the above-mentioned biological activities.

A modified in situ RT-PCR method for localizing fungal-specific gene expression in Candida-infected mice renal cells.

In situ Reverse Transcriptase PCR (in situ RT-PCR) can amplify mRNA and localize gene expression in cells. However, this method is not feasible in fungi as the thick fungal cell wall constitutes a barrier to this procedure. We developed a two step in situ RT-PCR procedure which enabled the detection and localization of Candida tropicalis mRNA expression in formalin-fixed, paraffin-embedded (FFPE) mouse kidney sections. This in situ hybridization study revealed the first direct evidence for deposition of Candida tropicalis secreted aspartic proteinase 2 (CtSAP2) in the tip of pseudohyphae and its involvement in acute systemic candidiasis. We conclude that in situ RT-PCR can be successfully applied to FFPE tissues and will offer new perspectives in studying gene expression in Candida species.