The NCR1 transporter is an antimalarial target that exports cholesterol from the parasite's plasma membrane.

Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria, , has developed resistance to nearly all currently available antimalarial drugs. The Niemann-Pick type C1-related (PfNCR1) transporter has been identified as a druggable target, but its structure and detailed molecular mechanism are not yet available.

Implementation of a Telemedicine Direct Oral Anticoagulant Monitoring Program at a Safety-Net Hospital.

Direct oral anticoagulants (DOACs) are the preferred choice of anticoagulation therapy for nonvalvular atrial fibrillation and venous thromboembolism. Inadequate monitoring of patients on DOACs may lead to suboptimal outcomes and safety concerns. This project aimed to implement a standardized telemedicine-based DOAC monitoring service and track pharmacist-based interventions.

Structures of the mycobacterial MmpL4 and MmpL5 transporters provide insights into their role in siderophore export and iron acquisition.

The Mycobacterium tuberculosis (Mtb) pathogen, the causative agent of the airborne infection tuberculosis (TB), harbors a number of mycobacterial membrane protein large (MmpL) transporters. These membrane proteins can be separated into 2 distinct subclasses, where they perform important functional roles, and thus, are considered potential drug targets to combat TB. Previously, we reported both X-ray and cryo-EM structures of the MmpL3 transporter, providing high-resolution structural information for this subclass of the MmpL proteins.

Heart Failure in Older People Part 2: Guideline-Directed Medical Therapy.

Heart failure is a common cardiovascular disease that affects older people and has a high rate of mortality. Treatment for heart failure has evolved in the past 10 years to include novel evidence-based agents as well as changes in how medications are initiated and up-titrated. Despite evidence of the importance of using four guideline-directed medications, older people are often undertreated with these lifesaving therapies.

Cryo-EM structures of the human band 3 transporter indicate a transport mechanism involving the coupled movement of chloride and bicarbonate ions.

The band 3 transporter is a critical integral membrane protein of the red blood cell (RBC), as it is responsible for catalyzing the exchange of bicarbonate and chloride anions across the plasma membrane. To elucidate the structural mechanism of the band 3 transporter, detergent solubilized human ghost membrane reconstituted in nanodiscs was applied to a cryo-EM holey carbon grid to define its composition. With this approach, we identified and determined structural information of the human band 3 transporter.

Evaluating the Need for Competency-Based Pharmacy Education (CBPE): The Report of the 2023-2024 Academic Affairs Standing Committee.

The 2023-2024 Academic Affairs Committee was charged to create a sense of urgency around the concept of Competency-Based Pharmacy Education and develop a "readiness for change" instrument that is based on the 5 essential elements that make up the definition of Competency-Based Pharmacy Education. This report describes the process undertaken by the committee to determine the societal needs of pharmacists and current state of pharmacy practice and pharmacy education. The practice gaps in pharmacy education and the key drivers needed to close these gaps are evaluated.

The Need for Competency-Based Education.

Objectives: While pharmacy education updates learning as new information arises, changes to learning experiences can trail behind current practices and technology. There have been multiple calls for radical changes in how health professions education is delivered to ensure patients are receiving high-quality care. Competency-based education has been one way discussed in the literature for how to handle this need to develop students who have a willingness to learn and can problem-solve.

A common data model for the standardization of intensive care unit medication features.

Objective: Common data models provide a standard means of describing data for artificial intelligence (AI) applications, but this process has never been undertaken for medications used in the intensive care unit (ICU). We sought to develop a common data model (CDM) for ICU medications to standardize the medication features needed to support future ICU AI efforts.

Materials And Methods: A 9-member, multi-professional team of ICU clinicians and AI experts conducted a 5-round modified Delphi process employing conference calls, web-based communication, and electronic surveys to define the most important medication features for AI efforts.

Unsupervised machine learning analysis to identify patterns of ICU medication use for fluid overload prediction.

Introduction: Intravenous (IV) medications are a fundamental cause of fluid overload (FO) in the intensive care unit (ICU); however, the association between IV medication use (including volume), administration timing, and FO occurrence remains unclear.

Methods: This retrospective cohort study included consecutive adults admitted to an ICU ≥72 hours with available fluid balance data. FO was defined as a positive fluid balance ≥7% of admission body weight within 72 hours of ICU admission.

Enabling Factors for the Implementation of Competency-Based Curricula in Colleges and Schools of Pharmacy.

Objectives: To review the implementation drivers of competency-based pharmacy education (CBPE) and provide recommendations for enablers.

Findings: Competency-based education is an emerging model in the health professions, focusing on time-variable competency development and achievement compared with a time-bound, course-based, traditional model. CBPE is an outcomes-based organized framework of competencies enabling pharmacists to meet health care and societal needs.

Machine learning vs. traditional regression analysis for fluid overload prediction in the ICU.

Fluid overload, while common in the ICU and associated with serious sequelae, is hard to predict and may be influenced by ICU medication use. Machine learning (ML) approaches may offer advantages over traditional regression techniques to predict it. We compared the ability of traditional regression techniques and different ML-based modeling approaches to identify clinically meaningful fluid overload predictors.

Budget impact analysis of a bovine pericardial aortic bioprosthesis versus mechanical aortic valve replacement in adult patients with aortic stenosis in Romania.

Aims: An analysis of the budget impact of using a bovine pericardial aortic bioprosthesis (BPAB) or a mechanical valve (MV) in aortic stenosis (AS) patients in Romania.

Materials And Methods: A decision-tree with a partitioned survival model was used to predict the financial outcomes of using either a BPAB (the Carpentier-Edwards Perimount Magna Ease Valve) or MV in aortic valve replacement (AVR) procedure over a 5-year period. The budget impact of various resource consumption including disabling strokes, reoperations, minor thromboembolic events, major bleeding, endocarditis, anticoagulation treatment and monitoring, and echocardiogram assessments were compared for both types of valves.

Recommendations and Next Steps For Competency-Based Pharmacy Education.

In July 2021, the chairs of the American Association of Colleges of Pharmacy Council of Deans, Council of Faculties, and Council of Sections developed a task force to discuss potential ways to improve pharmacy education. The Competency-Based Education (CBE) Joint Task Force was created to explore the pros and cons of advancing a competency-based approach to pharmacy education (CBPE) and to determine ways to create more flexibility within pharmacy curricula to enable CBE. To achieve these goals, the Task Force systematically reviewed available resources and outlined the pros and cons of CBPE, best practices for implementation, strategies to minimize barriers, and recommendations on whether CBE should be implemented in pharmacy education.

Ten-year cost-consequence analysis of weight loss on obesity-related outcomes in privately insured adults with obesity in Saudi Arabia.

Aim: This study aimed to estimate the 10-year cost-consequence of weight loss on obesity-related outcomes in a sample of privately insured adults with obesity in Saudi Arabia (KSA).

Methods: We analyzed data of adults with obesity (BMI ≥ 30 kg/m) available in Nphies, the private health insurance platform of the Council of Health Insurance, KSA. A micro-costing analysis was used to obtain domestic cost estimates for obesity-related outcomes.

Pharmacophenotype identification of intensive care unit medications using unsupervised cluster analysis of the ICURx common data model.

Background: Identifying patterns within ICU medication regimens may help artificial intelligence algorithms to better predict patient outcomes; however, machine learning methods incorporating medications require further development, including standardized terminology. The Common Data Model for Intensive Care Unit (ICU) Medications (CDM-ICURx) may provide important infrastructure to clinicians and researchers to support artificial intelligence analysis of medication-related outcomes and healthcare costs. Using an unsupervised cluster analysis approach in combination with this common data model, the objective of this evaluation was to identify novel patterns of medication clusters (termed 'pharmacophenotypes') correlated with ICU adverse events (e.

Loss-of-function K2.2 mutations abolish channel activity.

Small-conductance Ca-activated potassium channels subtype 2 (K2.2, also called SK2) are operated exclusively by a Ca-calmodulin gating mechanism. Heterozygous genetic mutations of K2.

Cryo-EM Structures of AcrD Illuminate a Mechanism for Capturing Aminoglycosides from Its Central Cavity.

The Escherichia coli acriflavine resistance protein D (AcrD) is an efflux pump that belongs to the resistance-nodulation-cell division (RND) superfamily. Its primary function is to provide resistance to aminoglycoside-based drugs by actively extruding these noxious compounds out of E. coli cells.

Inhibition mechanism of NKCC1 involves the carboxyl terminus and long-range conformational coupling.

The Na-K-2Cl cotransporter-1 (NKCC1) is an electroneutral Na-dependent transporter responsible for simultaneously translocating Na, K, and Cl ions into cells. In human tissue, NKCC1 plays a critical role in regulating cytoplasmic volume, fluid intake, chloride homeostasis, and cell polarity. Here, we report four structures of human NKCC1 (hNKCC1), both in the absence and presence of loop diuretic (bumetanide or furosemide), using single-particle cryo-electron microscopy.

Evaluation of an Opt-Out Protocol for Antibiotic De-Escalation in Patients With Suspected Sepsis: A Multicenter, Randomized, Controlled Trial.

Background: Sepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. This randomized, controlled trial evaluated an opt-out protocol to decrease unnecessary antibiotics in patients with suspected sepsis.

Methods: We evaluated non-intensive care adults on broad-spectrum antibiotics despite negative blood cultures at 10 US hospitals from September 2018 through May 2020.

2020 rankings for US PharmD programs, research, and overall quality.

Background: US News and World Report (USNWR) publishes well-known rankings of graduate health programs. Medicine and nursing are ranked with weighted metrics using multiple criteria, and medical schools are ranked separately according to their focus (research or primary care). USNWR pharmacy school rankings are based on a single-question peer perception survey.

Channelopathy of small- and intermediate-conductance Ca-activated K channels.

Small- and intermediate-conductance Ca-activated K (K2.x/K3.1 also called SK/IK) channels are gated exclusively by intracellular Ca.