Antimicrobial bianthrones from the crinoid sp.

Antimicrobial resistance is a global public health problem and identification of new chemical scaffolds is important to overcoming this threat. In a recent high-throughput discovery campaign, fractions derived from the organic extract of crinoid, sp. (Echinodermata), showed antibacterial activity.

Discovery of a nasal spray steroid, tixocortol, as an inhibitor of SARS-CoV-2 main protease and viral replication.

Coronaviruses rely on the viral-encoded chymotrypsin-like main protease (M or 3CL) for replication and assembly. Our previous research on M of SARS-CoV-2 identified cysteine 300 (Cys300) as a potential allosteric site of M inhibition. Here, we identified tixocortol (TX) as a covalent modifier of Cys300 which inhibits M activity as well as in a cell-based M expression assay.

Structure elucidation, absolute configuration, and biological evaluation of cyclic peroxides from the sponge Plakinastrella sp.

Two cyclic peroxides, plakortides V (1) and W (2) were purified from the organic extract of the sponge Plakinastrella sp. Their planar structures were established based on extensive NMR and MS analysis and the absolute configurations of the three stereogenic centers of the 1,2-dioxane moiety were determined to be 3R,4S,6S by comparative analysis of the H NMR spectral data of the R- or S-MTPA Mosher esters. Compounds 1 and 2 exhibited potent cytotoxic activity against LOX IMVI (melanoma), UO-31 (renal), and HL-60 (TB) (leukemia) cell lines in the NCI-60 cytotoxicity assay.

Use of Virtual Interactive Patient Encounters to Prepare First-Year Medical Students for Clinical Practice.

Problem: With the dissolution of the Step 2 Clinical Skills exam, medical programs have a greater responsibility to teach and assess clinical skills in the preclerkship years. Clinical teaching this early has traditionally been avoided because of insufficient integration with biomedical sciences, curricular time constraints, and concerns about overwhelming novice learners with clinical learning objectives. To overcome these barriers, the authors created a clinical framework for the biomedical science curriculum by integrating a series of virtual interactive patient (VIP) videos.

Screen for New Antimicrobial Natural Products from the NCI Program for Natural Product Discovery Prefractionated Extract Library.

The continuing emergence of antibiotic-resistant microbes highlights the need for the identification of new chemotypes with antimicrobial activity. One of the most prolific sources of antimicrobial molecules has been the systematic screening of natural product samples. The National Institute of Allergy and Infectious Diseases and the National Cancer Institute here report a large screen of 326,656 partially purified natural product fractions against a panel of four microbial pathogens, resulting in the identification of >3000 fractions with antifungal and/or antibacterial activity.

Decreased DNA Damage and Improved p53 Specificity of RITA Analogs.

Reactivation of p53 tumor-suppressor function by small molecules is an attractive strategy to defeat cancer. A potent p53-reactivating molecule RITA, which triggers p53-dependent apoptosis in human tumor cells in vitro and in vivo, exhibits p53-independent cytotoxicity due to modifications by detoxification enzyme Sulfotransferase 1A1 (SULT1A1), producing a reactive carbocation. Several synthetic modifications to RITA's heterocyclic scaffold lead to higher energy barriers for carbocation formation.

Training in the Era of EHR: Examining the Experience of Medical Student Documentation in the Ambulatory Care Setting.

This article was migrated. The article was marked as recommended. Documenting clinical encounters in the electronic health record has become an important component of medical student training.

Physician Preceptor Satisfaction and Productivity Across Curricula: A Comparison Between Longitudinal Integrated Clerkships And Traditional Block Rotations.

Physicians are under intense pressure to improve clinical productivity. High clinical load, limited availability, and decreased clinical efficiency are well-documented barriers to precepting medical students and threaten clinical productivity. In an era of increasing medical student enrollment, these barriers have already led to a decreased availability of clinical teachers and training sites across the United States.

Specific RITA Modification Produces Hyperselective Cytotoxicity While Maintaining Antitumor Efficacy.

The preclinical antitumor agent RITA (2,5-bis[5-hydroxymethyl-2-thienyl] furan, NSC 652287), an analog of the natural product α-terthiophene, failed during the development phase due to acute pulmonary toxicity in animal models. A series of synthetic modifications to RITA's heterocyclic scaffold resulted in activity ranging from broadly cytotoxic to highly selective. In the NCI 60-cell line screen, these "hyperselective" agents (e.

The North Carolina Community Preceptor Experience: Third Study of Trends Over 12 Years.

Purpose: To measure community-based preceptors' overall satisfaction and motivations, the influence of students on preceptors' practices, and compare with 2005 and 2011 studies.

Method: North Carolina primary care preceptors across disciplines (physicians, pharmacists, advanced practice nurses, physician assistants) received survey invitations via e-mail, fax, postcard, and/or full paper survey. Most questions in 2017 were the same as questions used in prior years, including satisfaction with precepting, likelihood to continue precepting, perceived influence of teaching students in their practice, and incentives for precepting.

A Dinner-Table Approach to a Unique Interactive Nutrition Curriculum for Healthcare Professional Students.

Nutrition education is significantly lacking from healthcare provider educational curricula despite its proven benefit for some of the most chronic and challenging diseases facing Americans today. We successfully developed and implemented an interprofessional, experiential nutrition education course for healthcare professional students that emphasizes evidence-based nutrition interventions for patient care.

Effects of Delivering SLCO1B1 Pharmacogenetic Information in Randomized Trial and Observational Settings.

Background: Outcomes of tailoring statin-type based on solute carrier organic anion transporterfamily member 1B1 ( SLCO1B1)pharmacogenetic toxicity information on patient, provider, and pharmacological outcomes are unknown.

Methods: The trial randomized 159 patients not taking statins because of prior statin myalgia 1:1 to receiving SLCO1B1 GIST (Genotype Informed Statin Therapy) versus usual care (UC) and followed for up to 8 months. The UC arm received their SLCO1B1 results post-trial.

Diffusion of innovation and longitudinal integrated clerkships: Results of the clerkship directors in internal medicine annual survey.

Purpose: Longitudinal integrated clerkships (LICs) are innovative educational models that emphasize medical student continuity with patients, preceptors, peers, and health systems. We characterize LIC growth in the US and interpret the growth using Rogers' Diffusion of Innovation Theory.

Methods: In 2015, we surveyed 123 US allopathic medical schools affiliated with Clerkship Directors in Internal Medicine (CDIM).

A threonine turnstile defines a dynamic amphiphilic binding motif in the AAA ATPase p97 allosteric binding site.

The turnstile motion of two neighboring threonines sets up a dynamic side chain interplay that can accommodate both polar and apolar ligands in a small molecule allosteric protein binding site. A computational model based on SAR data and both X-ray and cryo-EM structures of the AAA ATPase p97 was used to analyze the effects of paired threonines at the inhibitor site. Specifically, the Thr side chain hydroxyl groups form a hydrogen bonding network that readily accommodates small, highly polar ligand substituents.

SRC family kinase inhibitors antagonize the toxicity of multiple serotypes of botulinum neurotoxin in human embryonic stem cell-derived motor neurons.

Botulinum neurotoxins (BoNTs), the causative agents of botulism, are potent inhibitors of neurotransmitter release from motor neurons. There are currently no drugs to treat BoNT intoxication after the onset of the disease symptoms. In this study, we explored how modulation of key host pathways affects the process of BoNT intoxication in human motor neurons, focusing on Src family kinase (SFK) signaling.

Enlisting New Teachers in Clinical Environments (ENTICE); novel ways to engage clinicians.

Purpose: To explore the barriers and incentives that affect primary care providers who precept students in outpatient clinics in the US.

Method: In 2013, leadership of our large primary care group sent a 20-question survey via e-mail to all of the 180 providers within the network. The survey assessed provider demographics, precepting history, learner preferences, and other issues that might affect future decisions about teaching.

The Primary Care Leadership Track at the Duke University School of Medicine: creating change agents to improve population health.

Problem: Physicians need training in community engagement, leadership, and population health to prepare them to work with partners within the community and to adapt medical care to address population health needs.

Approach: With an overall goal of training primary care practitioners to be change agents for improving population health, the Duke University School of Medicine launched the Primary Care Leadership Track (PCLT) in 2011. The four-year PCLT curriculum requires students to contribute to existing community health initiatives, perform community-engaged research, and participate in leadership training.

Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV). Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors.

High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells.

The clinical development of drug combinations is typically achieved through trial-and-error or via insight gained through a detailed molecular understanding of dysregulated signaling pathways in a specific cancer type. Unbiased small-molecule combination (matrix) screening represents a high-throughput means to explore hundreds and even thousands of drug-drug pairs for potential investigation and translation. Here, we describe a high-throughput screening platform capable of testing compounds in pairwise matrix blocks for the rapid and systematic identification of synergistic, additive, and antagonistic drug combinations.

Delivering pharmacogenetic testing in a primary care setting.

Pharmacogenetic testing refers to a type of genetic test to predict a patient's likelihood to experience an adverse event or not respond to a given drug. Despite revision to several labels of commonly prescribed drugs regarding the impact of genetic variation, the use of this testing has been limited in many settings due to a number of factors. In the primary care setting, the limited office time as well as the limited knowledge and experience of primary care practitioners have likely attributed to the slow uptake of pharmacogenetic testing.

Integrating high-content imaging and chemical genetics to probe host cellular pathways critical for Yersinia pestis infection.

The molecular machinery that regulates the entry and survival of Yersinia pestis in host macrophages is poorly understood. Here, we report the development of automated high-content imaging assays to quantitate the internalization of virulent Y. pestis CO92 by macrophages and the subsequent activation of host NF-κB.

Identification of essential filovirion-associated host factors by serial proteomic analysis and RNAi screen.

An assessment of the total protein composition of filovirus (ebolavirus and marburgvirus) virions is currently lacking. In this study, liquid chromatography-linked tandem mass spectrometry of purified ebola and marburg virions was performed to identify associated cellular proteins. Host proteins involved in cell adhesion, cytoskeleton, cell signaling, intracellular trafficking, membrane organization, and chaperones were identified.

Reduced levels of protein tyrosine phosphatase CD45 protect mice from the lethal effects of Ebola virus infection.

Ebola virus (EBOV) infection of humans is a lethal but accidental dead-end event. Understanding resistance to EBOV in other species may help establish the basis of susceptibility differences among its hosts. Although rodents are resistant to EBOV, a murine-adapted variant is lethal when injected intraperitoneally into mice.