The skinny on skin: The role of skin-aware professionals in skin cancer surveillance.

Licensed nonmedical, skin-aware professionals (e.g., hairdressers, massage therapists, etc.

Chemoproteomics validates selective targeting of M1 alanyl aminopeptidase as an antimalarial strategy.

New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of M1 alanyl metalloaminopeptidase as an attractive drug target using the selective inhibitor, MIPS2673. MIPS2673 demonstrated potent inhibition of recombinant (A-M1) and (A-M1) M1 metalloaminopeptidases, with selectivity over other and human aminopeptidases, and displayed excellent in vitro antimalarial activity with no significant host cytotoxicity.

Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy.

New antimalarial drug candidates that act via novel mechanisms are urgently needed to combat malaria drug resistance. Here, we describe the multi-omic chemical validation of M1 alanyl metalloaminopeptidase as an attractive drug target using the selective inhibitor, MIPS2673. MIPS2673 demonstrated potent inhibition of recombinant ( A-M1) and ( A-M1) M1 metalloaminopeptidases, with selectivity over other and human aminopeptidases, and displayed excellent antimalarial activity with no significant host cytotoxicity.

On-target, dual aminopeptidase inhibition provides cross-species antimalarial activity.

To combat the global burden of malaria, development of new drugs to replace or complement current therapies is urgently required. Here, we show that the compound is a selective, nanomolar inhibitor of both and aminopeptidases M1 and M17, leading to inhibition of end-stage hemoglobin digestion in asexual parasites. can kill sexual-stage , is active against murine malaria, and does not show any shift in activity against a panel of parasites resistant to other antimalarials.

The reported impact of non-communicable disease investment cases in 13 countries.

Non-communicable diseases (NCDs) are a leading health and development challenge worldwide. Since 2015, WHO and the United Nations Development Programme have provided support to governments to develop national NCD investment cases to describe the socioeconomic dimensions of NCDs. To assess the impact of the investment cases, semistructured interviews and a structured process for gathering written feedback were conducted between July and October 2022 with key informants in 13 countries who had developed a national NCD investment case between 2015 and 2020.

A simeprevir-inducible molecular switch for the control of cell and gene therapies.

Chemical inducer of dimerization (CID) modules can be used effectively as molecular switches to control biological processes, and thus there is significant interest within the synthetic biology community in identifying novel CID systems. To date, CID modules have been used primarily in engineering cells for in vitro applications. To broaden their utility to the clinical setting, including the potential to control cell and gene therapies, the identification of novel CID modules should consider factors such as the safety and pharmacokinetic profile of the small molecule inducer, and the orthogonality and immunogenicity of the protein components.

Differential membrane binding of α/β-peptide foldamers: implications for cellular delivery and mitochondrial targeting.

The intrinsic pathway of apoptosis is regulated by the Bcl-2 family of proteins. Inhibition of the anti-apoptotic members represents a strategy to induce apoptotic cell death in cancer cells. We have measured the membrane binding properties of a series of peptides, including modified α/β-peptides, designed to exhibit enhanced membrane permeability to allow cell entry and improved access for engagement of Bcl-2 family members.

STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.

Prostate cancer (PCa) is a common and fatal type of cancer in men. Metastatic PCa (mPCa) is a major factor contributing to its lethality, although the mechanisms remain poorly understood. PTEN is one of the most frequently deleted genes in mPCa.

Human Tim8a, Tim8b and Tim13 are auxiliary assembly factors of mature Complex IV.

Human Tim8a and Tim8b are paralogous intermembrane space proteins of the small TIM chaperone family. Yeast small TIMs function in the trafficking of proteins to the outer and inner mitochondrial membranes. This putative import function for hTim8a and hTim8b has been challenged in human models, but their precise molecular function(s) remains undefined.

[Monitoring and evaluation platform for HEARTS in the Americas: improving population-based hypertension control programs in primary health carePlataforma de monitoramento e avaliação do programa HEARTS nas Américas: melhoria dos programas de controle da hipertensão de base populacional na atenção primária à saúde].

HEARTS in the Americas is the Pan American Health Organization flagship program to accelerate the reduction of the cardiovascular disease (CVD) burden by improving hypertension control and CVD secondary prevention in primary health care. A monitoring and evaluation (M&E) platform is needed for program implementation, benchmarking, and informing policy-makers. This paper describes the conceptual bases of the HEARTS M&E platform including software design principles, contextualization of data collection modules, data structure, reporting, and visualization.

Biochemical Characterization of Ferritins.

The nematode contains genes for two types of ferritin ( and ) that express FTN-1 and FTN-2. We have expressed and purified both proteins and characterized them by X-ray crystallography, cryo-electron microscopy, transmission electron microscopy, dynamic light scattering, and kinetically by oxygen electrode and UV-vis spectroscopy. Both show ferroxidase activity, but although they have identical ferroxidase active sites, FTN-2 is shown to react approximately 10 times faster than FTN-1, with L-type ferritin character over longer time periods.

TRIM24 controls induction of latent HIV-1 by stimulating transcriptional elongation.

Binding of USF1/2 and TFII-I (RBF-2) at conserved sites flanking the HIV-1 LTR enhancer is essential for reactivation from latency in T cells, with TFII-I knockdown rendering the provirus insensitive to T cell signaling. We identified an interaction of TFII-I with the tripartite motif protein TRIM24, and these factors were found to be constitutively associated with the HIV-1 LTR. Similar to the effect of TFII-I depletion, loss of TRIM24 impaired reactivation of HIV-1 in response to T cell signaling.

Structure-based development of potent Plasmodium falciparum M1 and M17 aminopeptidase selective and dual inhibitors via S1'-region optimisation.

Malaria remains a global health threat and growing resistance to artemisinin-based therapies calls for therapeutic agents with novel mechanisms of action. The Plasmodium spp M1 and M17 metalloaminopeptidases have been identified as attractive new antimalarial drug targets as inhibition of these enzymes results in antiplasmodial activity. Previously identified novel hydroxamic acid 2 as a moderate inhibitor of PfA-M1 and PfA-M17 and a potent inhibitor of P.

Adherence to topical glaucoma therapy in patients attending virtual clinics.

Background/objectives: Poor adherence to medical therapy is a major challenge to the effective treatment of chronic diseases including glaucoma. Potential factors influencing adherence include treatment complexity and patient understanding of disease and health beliefs. An increasing number of patients are seen in virtual clinics, where there is no face-to-face consultation, potentially reducing opportunities for patient education and reinforcement of the importance of treatment.

Improving cardiovascular health with the patient-centered, integrated primary care HEARTS model in Trinidad and Tobago.

This article describes the introduction of the Pan American Health Organization's HEARTS in the Americas program in Trinidad and Tobago and the successful experiences and challenges encountered in introducing and scaling it up as a strategy for strengthening the health system's response to cardiovascular diseases. Evidence about implementation of the HEARTS program in the World Health Organization's Region of the Americas was reviewed to identify the progress made, barriers, success factors and lessons learned. In 2019, the Ministry of Health commenced implementation of the program in 5 (4.

Monitoring and evaluation platform for HEARTS in the Americas: improving population-based hypertension control programs in primary health care.

HEARTS in the Americas is the Pan American Health Organization flagship program to accelerate the reduction of the cardiovascular disease (CVD) burden by improving hypertension control and CVD secondary prevention in primary health care. A monitoring and evaluation (M&E) platform is needed for program implementation, benchmarking, and informing policy-makers. This paper describes the conceptual bases of the HEARTS M&E platform including software design principles, contextualization of data collection modules, data structure, reporting, and visualization.

Genetic and chemical validation of aminopeptidase A-M17 as a drug target in the hemoglobin digestion pathway.

the causative agent of malaria, remains a global health threat as parasites continue to develop resistance to antimalarial drugs used throughout the world. Accordingly, drugs with novel modes of action are desperately required to combat malaria. parasites infect human red blood cells where they digest the host's main protein constituent, hemoglobin.

Utilization of the TRAIN Learning Network for Online Disaster Medicine and Public Health Training During the COVID-19 Pandemic.

Objective: The coronavirus disease 2019 (COVID-19) pandemic dramatically accelerated a growing trend toward online and asynchronous education and professional training, including in the disaster medicine and public health sector. This study analyzed the impact of the COVID-19 pandemic on the growth of the TRAIN Learning Network (TRAIN) for the year 2020 and evaluated pandemic-related changes in use patterns by disaster and public health professionals.

Methods: The TRAIN database was queried to determine the change in the number of registered users, total courses completed, and courses completed related to COVID-19 during 2020.

Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation Group.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control.

A metal ion-dependent conformational switch modulates activity of the Plasmodium M17 aminopeptidase.

The metal-dependent M17 aminopeptidases are conserved throughout all kingdoms of life. This large enzyme family is characterized by a conserved binuclear metal center and a distinctive homohexameric arrangement. Recently, we showed that hexamer formation in Plasmodium M17 aminopeptidases was controlled by the metal ion environment, although the functional necessity for hexamer formation is still unclear.

[Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation GroupFatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas].

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control.

[Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation GroupFactores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas].

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control.