Trends in the Number of Authors and Institutions in Papers Published in AJPE 2015-2019.

Objective. To investigate the number of authors and unique institutions per paper published in the American Journal of Pharmaceutical Education (AJPE) in 2015 through 2019, and to examine the number of authors and unique institutions for papers that were nominated for the Rufus A. Lyman Award in the same period.Methods. Articles published in AJPE from 2015 through 2019 were reviewed. Data collected for each article included article type, number of authors, and number of institutions.Results. Of the 811 articles published in AJPE during this period, the number of authors increased significantly from a mean (SD) of 3.5 (1.8) to 4.5 (2.2). The number of unique institutions also increased significantly from 1.7 (1.1) to 2.4 (1.8).Conclusion. There is a trend toward a greater number of authors and unique institutions for the publications in one pharmacy education journal. Explanations for this trend may include pressure to publish, increased research complexity, and expanded interprofessional collaboration.

Disulfiram: A Repurposed Drug in Preclinical and Clinical Development for the Treatment of Infectious Diseases.

This article reviews preclinical and clinical studies on the repurposed use of disulfiram (Antabuse) as an antimicrobial agent. Preclinical research covered on the alcohol sobriety aid includes uses as an anti-MRSA agent, a carbapenamase inhibitor, antifungal drug for candidiasis, and treatment for parasitic diseases due to protozoa (e.g., giardiasis, leishmaniasis, malaria) and helminthes (e.g., schistosomiasis, trichuriasis). Past, current, and pending clinical studies on disulfiram as a post-Lyme disease syndrome (PTLDS) therapy, an HIV latency reversal agent, and intervention for COVID-19 infections are also reviewed..

Murine hepatitis virus nonstructural protein 4 regulates virus-induced membrane modifications and replication complex function.

Positive-strand RNA viruses induce modifications of cytoplasmic membranes to form replication complexes. For coronaviruses, replicase nonstructural protein 4 (nsp4) has been proposed to function in the formation and organization of replication complexes. Murine hepatitis virus (MHV) nsp4 is glycosylated at residues Asn176 (N176) and N237 during plasmid expression of nsp4 in cells. To test if MHV nsp4 residues N176 and N237 are glycosylated during virus replication and to determine the effects of N176 and N237 on nsp4 function and MHV replication, alanine substitutions of nsp4 N176, N237, or both were engineered into the MHV-A59 genome. The N176A, N237A, and N176A/N237A mutant viruses were viable, and N176 and N237 were glycosylated during infection of wild-type (wt) and mutant viruses. The nsp4 glycosylation mutants exhibited impaired virus growth and RNA synthesis, with the N237A and N176A/N237A mutant viruses demonstrating more profound defects in virus growth and RNA synthesis. Electron microscopic analysis of ultrastructure from infected cells demonstrated that the nsp4 mutants had aberrant morphology of virus-induced double-membrane vesicles (DMVs) compared to those infected with wt virus. The degree of altered DMV morphology directly correlated with the extent of impairment in viral RNA synthesis and virus growth of the nsp4 mutant viruses. The results indicate that nsp4 plays a critical role in the organization and stability of DMVs. The results also support the conclusion that the structure of DMVs is essential for efficient RNA synthesis and optimal replication of coronaviruses.

A novel mutation in murine hepatitis virus nsp5, the viral 3C-like proteinase, causes temperature-sensitive defects in viral growth and protein processing.

Sequencing and reversion analysis of murine hepatitis virus (MHV) temperature-sensitive (ts) viruses has identified putative ts mutations in the replicase nonstructural proteins (nsp's) of these coronaviruses. In this study, reverse transcriptase PCR sequencing of the RNA genome of an isolate of the MHV ts virus Alb ts6, referred to as Alb/ts/nsp5/V148A, identified a putative ts mutation in nsp5 (T10651C, Val148Ala), the viral 3C-like proteinase (3CLpro). The introduction of the T10651C mutation into the infectious MHV clone resulted in the recovery of a mutant virus, the nsp5/V148A virus, that demonstrated reduced growth and nsp5 proteinase activity identical to that of Alb/ts/nsp5/V148A at the nonpermissive temperature. Sequence analysis of 40 degrees C revertants of Alb/ts/nsp5/V148A identified primary reversion to Ala148Val in nsp5, as well as two independent second-site mutations resulting in Ser133Asn and His134Tyr substitutions in nsp5. The introduction of the Ser133Asn or His134Tyr substitution into the cloned nsp5/V148A mutant virus background resulted in the recovery of viruses with increased growth fitness and the partial restoration of nsp5 activity at the nonpermissive temperature. Modeling of the nsp5 structure of Alb/ts/nsp5/V148A predicted that the Val148Ala mutation alters residue 148 interactions with residues of the substrate binding S1 subsite of the nsp5 active-site cavity. This study identifies novel residues in nsp5 that may be important for regulating substrate specificity and nsp5 proteinase activity.

Prospective comparison of the pneumatic cuff and manual compression methods in diagnosing lower extremity venous reflux.

AIM: To compare pneumatic cuff with manual compression in diagnosing reflux in patients with chronic venous insufficiency (CVI). PATIENTS AND METHODS: Eighteen patients (Clinical Etiologic Anatomic Pathophysiologic [CEAP 2-5], median Venous Clinical Severity Score [VCSS 6.5]) were studied. The VenaPulse device (ACI Medical, San Marcos, California) was used for cuff inflation. The hemodynamic performance of the 2 methods was tested in the first 9 patients, while their diagnostic value was tested in the last 9 patients. RESULTS: Both methods induced equal compression with median peak velocity of the antegrade flow (PVA) being 86 cm/s (P = .65). Coefficient of variation (CV) for PVA in the superficial veins was significantly higher with the manual method (16.8%) compared to the VenaPulse method (9.5%, P <.001), while sensitivity and specificity were 85% and 100%, and 78% (kappa .68, P <.001) and 100%, respectively. CONCLUSIONS: Pneumatic cuff and manual compression were shown to be equally effective in diagnosing venous reflux. Cost-effectiveness and ease-of-use studies comparing these methods are justified.

SARS coronavirus replicase proteins in pathogenesis.

Much progress has been made in understanding the role of structural and accessory proteins in the pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) infections. The SARS epidemic also brought new attention to the proteins translated from ORF1a and ORF1b of the input genome RNA, also known as the replicase/transcriptase gene. Evidence for change within the ORF1ab coding sequence during the SARS epidemic, as well as evidence from studies with other coronaviruses, indicates that it is likely that the ORF1ab proteins play roles in virus pathogenesis distinct from or in addition to functions directly involved in viral replication. Recent reverse genetic studies have confirmed that proteins of ORF1ab may be involved in cellular signaling and modification of cellular gene expression, as well as virulence by mechanisms yet to be determined. Thus, the evolution of the ORF1ab proteins may be determined as much by issues of host range and virulence as they are by specific requirements for intracellular replication.

A randomized controlled trial of abdominal binders for the management of postoperative pain and distress after cesarean delivery.

OBJECTIVE: To determine whether abdominal binders effectively control pain and distress after cesarean delivery. METHODS: A prospective randomized controlled trial was conducted between April and November, 2014, among women undergoing cesarean delivery (low-transverse skin incision) at two US hospitals. Participants were randomly allocated to either the abdominal binder or control groups on entry to the operating suite. Masking was not possible. Patients in the abdominal binder group were fitted with a device before leaving the operating room and were encouraged to wear it constantly, although breaks were allowed. The primary outcomes were postoperative distress (measured by the Symptom Distress Scale [SDS]) and pain (measured by a visual analog scale [VAS]). Individuals who asked to be removed from the study within 6hours of surgery were excluded from analyses. RESULTS: Analyses included 87 patients in the abdominal binder group and 68 in the control group. The abdominal binder and control groups did not differ in postoperative day 1 VAS (3.1±2.1 vs 3.4±2.3; P=0.33), postoperative day 2 VAS (3.0±1.9 vs 3.8±2.2; P=0.16), postoperative day 1 SDS (21.5±5.4 vs 21.8±5.1; P=0.87), and postoperative day 2 SDS (19.4±4.8 vs 19.9±5.0; P=0.53). CONCLUSION: Postoperative pain and distress scores after cesarean delivery were not affected by abdominal binders. ClinicalTrials.gov:NCT02129894.

Assessing and Documenting the Cognitive Performance of Family Medicine Residents Practicing Outpatient Medicine.

BACKGROUND: Development of cognitive skills for competent medical practice is a goal of residency education. Cognitive skills must be developed for many different clinical situations. INNOVATION: We developed the Resident Cognitive Skills Documentation (CogDoc) as a method for capturing faculty members' real-time assessment of residents' cognitive performance while they precepted them in a family medicine office. The tool captures 3 dimensions of cognitive skills: medical knowledge, understanding, and its application. This article describes CogDoc development, our experience with its use, and its reliability and feasibility. METHODS: After development and pilot-testing, we introduced the CogDoc at a single training site, collecting all completed forms for 14 months to determine completion rate, competence development over time, consistency among preceptors, and resident use of the data. RESULTS: Thirty-eight faculty members completed 5021 CogDoc forms, documenting 29% of all patient visits by 33 residents. Competency was documented in all entrustable professional activities. Competence was statistically different among residents of different years of training for all 3 dimensions and progressively increased within all residency classes over time. Reliability scores were high: 0.9204 for the medical knowledge domain, 0.9405 for understanding, and 0.9414 for application. Almost every resident reported accessing the individual forms or summaries documenting their performance. CONCLUSIONS: The CogDoc approach allows for ongoing assessment and documentation of resident competence, and, when compiled over time, depicts a comprehensive assessment of residents' cognitive development and ability to make decisions in ambulatory medicine. This approach meets criteria for an acceptable tool for assessing cognitive skills.

Entrustable professional activities in family medicine.

BACKGROUND: The Accreditation Council for Graduate Medical Education Outcome Project intended to move residency education toward assessing and documenting resident competence in 6 dimensions of performance important to the practice of medicine. Although the project defined a set of general attributes of a good physician, it did not define the actual activities that a competent physician performs in practice in the given specialty. These descriptions have been called entrustable professional activities (EPAs). OBJECTIVE: We sought to develop a list of EPAs for ambulatory practice in family medicine to guide curriculum development and resident assessment. METHODS: We developed an initial list of EPAs over the course of 3 years, and we refined it further by obtaining the opinion of experts using a Delphi Process. The experts participating in this study were recruited from 2 groups of family medicine leaders: organizers and participants in the Preparing the Personal Physician for Practice initiative, and members of the Society of Teachers of Family Medicine Task Force on Competency Assessment. The experts participated in 2 rounds of anonymous, Internet-based surveys. RESULTS: A total of 22 experts participated, and 21 experts participated in both rounds of the Delphi Process. The Delphi Process reduced the number of competency areas from 91 to 76 areas, with 3 additional competency areas added in round 1. CONCLUSIONS: This list of EPAs developed through our Delphi process can be used as a starting point for family medicine residency programs interested in moving toward a competency-based approach to resident education and assessment.

Genetic analysis of Murine hepatitis virus nsp4 in virus replication.

Coronavirus replicase polyproteins are translated from the genomic positive-strand RNA and are proteolytically processed by three viral proteases to yield 16 mature nonstructural proteins (nsp1 to nsp16). nsp4 contains four predicted transmembrane-spanning regions (TM1, -2, -3, and -4), demonstrates characteristics of an integral membrane protein, and is thought to be essential for the formation and function of viral replication complexes on cellular membranes. To determine the requirement of nsp4 for murine hepatitis virus (MHV) infection in culture, engineered deletions and mutations in TMs and intervening soluble regions were analyzed for effects on virus recovery, growth, RNA synthesis, protein expression, and intracellular membrane modifications. In-frame partial or complete deletions of nsp4; deletions of TM1, -2, and -3; and alanine substitutions of multiple conserved, clustered, charged residues in nsp4 resulted in viruses that were nonrecoverable, viruses highly impaired in growth and RNA synthesis, and viruses that were nearly wild type in replication. The results indicate that nsp4 is required for MHV replication and that while putative TM1, -2, and -3 and specific charged residues may be essential for productive virus infection, putative TM4 and the carboxy-terminal amino acids K(398) through T(492) of nsp4 are dispensable. Together, the experiments identify important residues and regions for studies of nsp4 topology, function, and interactions.

Severe acute respiratory syndrome coronavirus group-specific open reading frames encode nonessential functions for replication in cell cultures and mice.

SARS coronavirus (SARS-CoV) encodes several unique group-specific open reading frames (ORFs) relative to other known coronaviruses. To determine the significance of the SARS-CoV group-specific ORFs in virus replication in vitro and in mice, we systematically deleted five of the eight group-specific ORFs, ORF3a, OF3b, ORF6, ORF7a, and ORF7b, and characterized recombinant virus replication and gene expression in vitro. Deletion of the group-specific ORFs of SARS-CoV, either alone or in various combinations, did not dramatically influence replication efficiency in cell culture or in the levels of viral RNA synthesis. The greatest reduction in virus growth was noted following ORF3a deletion. SARS-CoV spike (S) glycoprotein does not encode a rough endoplasmic reticulum (rER)/Golgi retention signal, and it has been suggested that ORF3a interacts with and targets S glycoprotein retention in the rER/Golgi apparatus. Deletion of ORF3a did not alter subcellular localization of the S glycoprotein from distinct punctuate localization in the rER/Golgi apparatus. These data suggest that ORF3a plays little role in the targeting of S localization in the rER/Golgi apparatus. In addition, insertion of the 29-bp deletion fusing ORF8a/b into the single ORF8, noted in early-stage SARS-CoV human and civet cat isolates, had little if any impact on in vitro growth or RNA synthesis. All recombinant viruses replicated to wild-type levels in the murine model, suggesting that either the group-specific ORFs play little role in in vivo replication efficiency or that the mouse model is not of sufficient quality for discerning the role of the group-specific ORFs in disease origin and development.