Piercedemant7162

AMP-activated protein kinase (AMPK) is a fundamental component of a protein kinase cascade that is an energy sensor. AMPK maintains energy homeostasis in the cell by promoting catabolic and inhibiting anabolic pathways. Activation of AMPK requires phosphorylation by the liver kinase B1 or by the Ca2+ /calmodulin-dependent protein kinase kinase 2 (CaMKK2). The scaffold protein IQGAP1 regulates intracellular signaling pathways, such as the mitogen-activated protein kinase and AKT signaling cascades. Recent work implicates the participation of IQGAP1 in metabolic function, but the molecular mechanisms underlying these effects are poorly understood. Here, using several approaches including binding analysis with fusion proteins, siRNA-mediated gene silencing, RT-PCR, and knockout mice, we investigated whether IQGAP1 modulates AMPK signaling. In vitro analysis reveals that IQGAP1 binds directly to the α1 subunit of AMPK. In addition, we observed a direct interaction between IQGAP1 and CaMKK2, which is mediated by the IQ domain of IQGAP1. Both CaMKK2 and AMPK associate with IQGAP1 in cells. The ability of metformin and increased intracellular free Ca2+ concentrations to activate AMPK is reduced in cells lacking IQGAP1. Importantly, Ca2+-stimulated AMPK phosphorylation was rescued by re-expression of IQGAP1 in IQGAP1-null cell lines. Comparison of the fasting response in wild-type and IQGAP1-null mice revealed that transcriptional regulation of the gluconeogenesis genes PCK1 and G6PC and the fatty acid synthesis genes FASN and ACC1 is impaired in IQGAP1-null mice. Our data disclose a previously unidentified functional interaction between IQGAP1 and AMPK and suggest that IQGAP1 modulates AMPK signaling.

Philip Morris International has made efforts to expand the sale of its heated tobacco product, IQOS, into new domestic markets globally. In Australia, where heated tobacco products are prohibited, the company recently attempted to overturn Australian legislation in order to permit their sale. In light of this recent move, this study presents a case study of the company's strategies to legalise and distribute IQOS in the Australian market.

To assess Philip Morris' lobbying activities and corporate strategies, a case study approach was used by triangulating data from three sources interviews with former Philip Morris employees, news articles reporting Philip Morris' lobbying activities or plans for IQOS in Australia, and submissions to relevant government inquiries and reviews from 2015 to 2020.

Philip Morris has actively lobbied Australian policy-makers to overturn bans on nicotine-containing products. Information obtained from key informants and Philip Morris' government submissions indicates that the cer countries where Philip Morris may be replicating similar strategies to weaken tobacco control legislation.

In Ethiopia, community-level knowledge about the current COVID-19 pandemic has not been well studied. This study is aimed to assess knowledge level and factors influencing the prevention of the COVID-19 pandemic among residents of Dessie and Kombolcha city administrations, Ethiopia.

Community-based cross-sectional study.

Dessie and Kombolcha city administrations.

Participants were household heads or members (n=828, >18 years) who have lived in the study area for at least 2 months preceding the survey.

Binary logistic regression was used for a single outcome and multiple response variables. In the multivariable regression model, a value of p<0.05 and adjusted OR (AOR) with 95% CI were used to identify factors associated with knowledge level of the community. Epi Info V.7.2 and SPSS V.20 software were used for data entry and analysis, respectively.

Knowledge level.

A total of 828 participants was involved with a response rate of 98%. Women were 61.7%. Participants' mean (±SD) age was 39 (±14 knowledge about COVID-19. It highlights the need for widespread awareness campaigns about COVID-19 through mass media, healthcare professionals and social media as sources of information. House-to-house awareness creation is recommended to address older adults who are more vulnerable to the pandemic.

To investigate individual, practice and area level variation in patient-reported unmet need among those with long-term conditions, in the context of general practice (GP) appointments and support from community-based services in England.

Cross-sectional study using data from 199 150 survey responses.

Primary care and community-based services.

Respondents to the 2018 English General Practice Patient Survey with at least one long-term condition.

The primary outcomes were the levels of unmet need in GP and local services among patients with multiple long-term conditions. Secondary outcomes were the proportion of variation explained by practice and area-level factors.

There was no relationship between needs being fully met in patients' last practice appointment and number of long-term conditions once sociodemographic characteristics and health status were taken into account (5+conditions-OR=1.04, 95% CI 0.99 to 1.09), but there was a relationship for having enough support from local services to managey living. Younger patients and certain ethnic groups with multimorbidity are also more likely to have unmet needs. Oxaliplatin Increased personalisation and coordination of care among these groups may help in addressing their needs.

To determine the use and expenditure associated with cystic fibrosis (CF) modulator therapies in Ireland since their reimbursement in 2013.

A retrospective analysis of a national drug claims database.

The data included in this study are nationally representative (Ireland).

Data on all persons receiving CF modulator therapies were included.

We obtained national claims data for CF therapies from the Health Service Executive's Primary Care Reimbursement Service. We determined the use and expenditure associated with CF therapies from January 2012 to March 2020.

The increased prescribing of CF modulator therapies was associated with an approximate fivefold increase in expenditure from €23 million in 2013 to €113 million in 2019. Many patients who initiated lumacaftor/ivacaftor in 2017 went on to receive symptomatic therapies, and subsequently initiated tezacaftor/ivacaftor in 2019.

Despite none of these modulator therapies demonstrating value for money when subjected to health technology assessment, the associated Irish expenditure reached €113 million in 2019 alone.