Building the health-economic case for scaling up the WHO-HEARTS hypertension control package in low- and middle-income countries.

Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in low- and middle-income countries.

Economic evaluation of Health Extension Program packages in Ethiopia.

Background: Ethiopia launched the Health Extension Program (HEP) in 2004, aimed at ensuring equitable community-level healthcare services through Health Extension Workers. Despite the program's being a flagship initiative, there is limited evidence on whether investment in the program represents good value for money. This study assessed the cost and cost-effectiveness of HEP interventions to inform policy decisions for resource allocation and priority setting in Ethiopia.

Cost-effectiveness of facility-based, stand-alone and mobile-based voluntary counseling and testing for HIV in Addis Ababa, Ethiopia.

Background: Globally, there is a consensus to end the HIV/AIDS epidemic by 2030, and one of the strategies to achieve this target is that 90% of people living with HIV should know their HIV status. Even if there is strong evidence of clients' preference for testing in the community, HIV voluntary counseling and testing (VCT) continue to be undertaken predominantly in health facilities. Hence, empirical cost-effectiveness evidence about different HIV counseling and testing models is essential to inform whether such community-based testing are justifiable compared with additional resources required.

Direct CDKN2 Modulation of CDK4 Alters Target Engagement of CDK4 Inhibitor Drugs.

The interaction of a drug with its target is critical to achieve drug efficacy. In cases where cellular environment influences target engagement, differences between individuals and cell types present a challenge for prediction of drug efficacy. As such, characterization of environments conducive to achieving the desired pharmacologic outcome is warranted.

Correction: Identification of a Tumor Specific, Active-Site Mutation in Casein Kinase 1α by Chemical Proteomics.

[This corrects the article DOI: 10.1371/journal.pone.

Chemoproteomic Evaluation of Target Engagement by the Cyclin-Dependent Kinase 4 and 6 Inhibitor Palbociclib Correlates with Cancer Cell Response.

Palbociclib is a cyclin-dependent kinase (CDK) 4/CDK6 inhibitor approved for breast cancer that is estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative. We profiled palbociclib in cells either sensitive or resistant to the drug using an ATP/ADP probe-based chemoproteomics platform. Palbociclib only engaged CDK4 or CDK6 in sensitive cells.

Identification of a Tumor Specific, Active-Site Mutation in Casein Kinase 1α by Chemical Proteomics.

We describe the identification of a novel, tumor-specific missense mutation in the active site of casein kinase 1α (CSNK1A1) using activity-based proteomics. Matched normal and tumor colon samples were analyzed using an ATP acyl phosphate probe in a kinase-targeted LC-MS2 platform. An anomaly in the active-site peptide from CSNK1A1 was observed in a tumor sample that was consistent with an altered catalytic aspartic acid.

Monitoring native p38α:MK2/3 complexes via trans delivery of an ATP acyl phosphate probe.

Here we describe a chemical proteomics strategy using ATP acyl phosphates to measure the formation of a protein:protein complex between p38α and mapkap kinases 2 and/or 3. Formation of the protein:protein complex results in a new probe labeling site on p38α that can be used to quantify the extent of interaction in cell lysates and the equilibrium binding constant for the interaction in vitro. We demonstrate through RNA interference that the labeling site is dependent on formation of the protein:protein complex in cells.

Profiling native kinases by immuno-assisted activity-based profiling.

The protocols in this unit describe efficient and cost-effective approaches to determine the interaction of small-molecule inhibitors with native kinases, and also analyze the interactions between kinases and their binding partners in a cellular setting. The combined attributes of activity-based probes and western blotting procedures provide for quantitative measurement of inhibitor efficacy, isoform selectivity, and post-translational modifications. We further demonstrate the ability to identify protein-protein interactions between a probe-labeled protein and its noncovalent binding partners.