Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex.

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric "RCR-complex". We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically.

Post-intensive cardiac care outpatient long-term outreach clinic (PICCOLO clinic): Defining health care needs and outcomes among coronary care unit survivors.

Objective: Patients who survive critical illness endure complex physical and mental health conditions, referred to as post-intensive care syndrome (PICS). The University of Michigan's post-intensive cardiac care outpatient long-term outreach (PICCOLO) clinic is designed for patients recently admitted to the coronary care unit (CCU). The long-term goal of this clinic is to understand post-CCU patients' needs and design targeted interventions to reduce their morbidity and mortality post-discharge.

Cardiac Metastatic Melanoma Causing Ventricular Arrhythmias Through Impaired Coronary Artery Vasodilation.

Melanoma is an aggressive malignant disease with a high rate of cardiac metastasis. There is a reported association between myocardial tumor invasion and ventricular arrhythmias. We present a case of cardiac metastatic melanoma causing ventricular arrhythmias through a novel mechanism of encasement of coronary arteries leading to reduced myocardial perfusion.

An ultrafast brain MRI technique for evaluating acute neurologic deficits in the emergency department.

Herein we share our preliminary experience with an ultrafast brain MRI technique for use in the ED consisting of axial T1-weighted (40 s), axial T2-weighted (62 s), axial diffusion-weighted (80 s), axial FLAIR (96 s), axial T2* (6 s), and axial susceptibility-weighted (108 s) imaging for a total scan time of 6 min and 53 s. Utilization of this ultrafast technique yields an efficient assessment of the brain, decreases ED length of stay and inpatient observation admissions, and may obviate the need for vascular imaging with either CTA or MRA in the ED.

A step-by-step guide to implementing a multidisciplinary endocarditis team.

Over the last several years multiple studies, primarily from European centers have demonstrated the clinical and outcomes benefits of multidisciplinary endocarditis teams. Despite this literature, adoption of this approach to patient care has been slower in the United States. While there is literature outlining the optimal composition of an endocarditis team, there is little information to guide providers as they attempt to transform practice from a fragmented, disjointed process to an efficient, collaborative care model.

Convenient Synthesis of Benziodazolone: New Reagents for Direct Esterification of Alcohols and Amidation of Amines.

Hypervalent iodine heterocycles represent one of the important classes of hypervalent iodine reagents with many applications in organic synthesis. This paper reports a simple and convenient synthesis of benziodazolones by the reaction of readily available iodobenzamides with -chloroperoxybenzoic acid in acetonitrile at room temperature. The structure of one of these new iodine heterocycles was confirmed by X-ray analysis.

Impact of a pharmacist in an interdisciplinary post-cardiac intensive care unit clinic.

Background: The complex needs of cardiac patients shortly after discharge from a cardiac intensive care unit (CICU) provides a unique opportunity for a pharmacist to help optimize medication management and guideline-directed medical therapy (GDMT).

Objective: This study describes the impact of a pharmacist in a multidisciplinary post-CICU clinic.

Methods: We performed a retrospective cohort study of patients ≥18 years of age who completed a visit in the University of Michigan Post Intensive Cardiac Care Outpatient Long-Term Outreach (PICCOLO) Clinic from July 2018 to May 2020.

Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm.

Thoracic aortic aneurysm (TAA) is characterized by dilation of the aortic root or ascending/descending aorta. TAA is a heritable disease that can be potentially life threatening. While 10%-20% of TAA cases are caused by rare, pathogenic variants in single genes, the origin of the majority of TAA cases remains unknown.

The Clinical Impact of Implementation of a Multidisciplinary Endocarditis Team.

Background: Infectious endocarditis is associated with substantial in-hospital mortality of 15%-20%. Effective management requires coordination between multiple medical and surgical subspecialties, which can often lead to disjointed care. Previous European studies have identified multidisciplinary endocarditis teams as a tool for reducing endocarditis mortality.

Prolactin synergizes with canonical Wnt signals to drive development of ER+ mammary tumors via activation of the Notch pathway.

Prolactin (PRL) cooperates with other factors to orchestrate mammary development and lactation, and is epidemiologically linked to higher risk for breast cancer. However, how PRL collaborates with oncogenes to foster tumorigenesis and influence breast cancer phenotype is not well understood. To understand its interactions with canonical Wnt signals, which elevate mammary stem cell activity, we crossed heterozygous NRL-PRL mice with Apc mice and treated pubertal females with a single dose of mutagen.

How Oncologists Perceive the Availability and Quality of Information Generated From Patient-Reported Outcomes (PROs).

Background: Despite increased incorporation of patient-reported outcome (PRO) measures into clinical trials, information generated from PROs remains largely absent from drug labeling and electronic health records, giving rise to concerns that such information is not adequately informing clinical practice.

Objective: To evaluate oncologists' perceptions concerning the availability and quality of information generated from PRO measures. Additionally, to identify whether an association exists between perceptions of availability and attitudes concerning quality.

The Role of Coronary Catheterization with Angiography in Surgically Managed Infectious Endocarditis.

Background: Coronary catheterization with angiography is often performed prior to surgical valve replacement in infectious endocarditis. There are no existing data as to whether this intervention is clinically necessary or leads to a change in surgical management. In order to determine the frequency with which coronary angiography impacts surgical management in infectious endocarditis, we conducted a retrospective review of surgically managed endocarditis cases at a tertiary care medical center.

Physician perceptions of a multidisciplinary endocarditis team.

Infectious endocarditis is a highly morbid infection that requires coordination of care across medical and surgical specialties, often through the use of a multidisciplinary team model. Multiple studies have demonstrated that such conferences can improve clinical outcomes. However, little is known about physicians' impressions of these groups.

Functional Comparison of Blood-Stage Malaria Vaccine Candidate Antigens.

The malaria genome encodes over 5,000 proteins and many of these have also been proposed to be potential vaccine candidates, although few of these have been tested clinically. RH5 is one of the leading blood-stage malaria vaccine antigens and Phase I/II clinical trials of vaccines containing this antigen are currently underway. Its likely mechanism of action is to elicit antibodies that can neutralize merozoites by blocking their invasion of red blood cells (RBC).

Sulfonylimino Group Transfer Reaction Using Imino-λ³-iodanes with I₂ as Catalyst Under Metal-free Conditions.

A new practical procedure of imination for sulfide has been developed. The treatment of (-tosylimino)-phenyl-λ³-iodane, PhINTs, with various sulfides in the presence of a catalytic amount of I₂ under metal-free conditions affords the corresponding -tosylsulfilimine compounds with moderate to good yields. This facile transfer procedure of the sulfonylimino group can also be applied to triphenylphosphine to produce the respective iminotriphenylphosphoranes in high yields.

Preparation and structure of phenolic aryliodonium salts.

Phenol based aryliodonium salts were prepared by the reaction of [hydroxy(tosyloxy)iodo]arenes with aryl silyl ethers in the presence of trifluoromethanesulfonic acid. Structures of several aryliodonium salts with the hydroxy group in the para-position of the phenyl ring were established by single crystal X-ray crystallography. Under basic conditions, 4-hydroxyphenyl(phenyl)iodonium salts form a dimeric hypervalent iodine(iii) complex, oxyphenyl(phenyl)iodonium ylidic salt, the solid structure of which was confirmed by X-ray crystallography.

Preparation, structure, and reactivity of bicyclic benziodazole: a new hypervalent iodine heterocycle.

A new bicyclic organohypervalent iodine heterocycle derivative of benziodazole was prepared by oxidation of 2-iodo-diisopropylisophthalamide with -chloroperoxybenzoic acid under mild conditions. Single crystal X-ray crystallography of this compound revealed a five-membered bis-heterocyclic structure with two covalent bonds between the iodine atom and the nitrogen atoms. This novel benziodazole is a very stable compound with good solubility in common organic solvents.

High collagen density augments mTOR-dependent cancer stem cells in ERα+ mammary carcinomas, and increases mTOR-independent lung metastases.

Metastatic estrogen receptor alpha positive (ERα+) cancers account for most breast cancer mortality. Cancer stem cells (CSCs) and dense/stiff extracellular matrices are implicated in aggression and therapy resistance. We examined this interplay and response to mTOR inhibition using ERα+ adenocarcinomas from NRL-PRL females in combination with Col1a1 (mCol1a1) mice, which accumulate collagen-I around growing tumors.

Outdated Prescription Drug Labeling: How FDA-Approved Prescribing Information Lags Behind Real-World Clinical Practice.

Background: Prescription drug labeling is an authoritative source of information that guides the safe and effective use of approved medications. In many instances, however, labeling may fail to be updated as new information about drug efficacy emerges in the postmarket setting. When labeling becomes outdated, it loses its value for prescribers and undermines a core part of the FDA's mission to communicate accurate and reliable information to patients and physicians.

What is the Impact of Placement Type on Educational and Health Outcomes of Unaccompanied Refugee Minors? A Systematic Review of the Evidence.

Record numbers of unaccompanied refugee minors have been arriving in high-income countries since 2015. Child welfare agencies and non-governmental organisations tasked with providing services have struggled to cope with demands on their services as a result. Despite this, there is little research on how best to meet their needs and in particular what services can mitigate the psychological difficulties they face.

Antiestrogen Therapy Increases Plasticity and Cancer Stemness of Prolactin-Induced ERα Mammary Carcinomas.

Although antiestrogen therapies are successful in many patients with estrogen receptor alpha-positive (ERα) breast cancer, 25% to 40% fail to respond. Although multiple mechanisms underlie evasion of these treatments, including tumor heterogeneity and drug-resistant cancer stem cells (CSC), further investigations have been limited by the paucity of preclinical ERα tumor models. Here, we examined a mouse model of prolactin-induced aggressive ERα breast cancer, which mimics the epidemiologic link between prolactin exposure and increased risk for metastatic ERα tumors.

Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action.

Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood.

Healthcare provider compliance with the 2013 ACC/AHA Adult Cholesterol Guideline recommendation for high-intensity dose statins for patients with coronary artery disease.

Background: Atherosclerotic cardiovascular disease is the foremost cause of death for U.S. adults.