Kathleen A. McGann

Human immunodeficiency virus type 1 Tat activity in human neuronal cells: uptake and trans-activation

Neurological dysfunction in AIDS occurs in the absence of productive infection of neurons, and may involve modulation of neuronal cell function by viral or cellular products released from surrounding infected cells. The human immunodeficiency virus type 1 (HIV-1) trans-activator protein Tat may be one such factor, as it can act as a neurotoxin, induces marked morphological changes in neurons and astrocytes in primary embryonic rodent brain cultures, and is released by certain HIV-1-infected cells. In addition, Tat can alter expression of cellular genes in several non-neuronal cell types. To explore the possibility that Tat may also mediate neuronal dysfunction in AIDS through non-lethal effects on neurons, we determined the trans-activating ability of Tat in human neuronal cells. We generated human neuronal cell lines stably expressing several HIV-1 tat genes, and also tested human neuronal cells exposed to extracellular recombinant Tat protein. Both endogenously expressed Tat as well as exogenous recombinant Tat protein up-regulated HIV-1 long terminal region (LTR)-driven gene expression by several hundred-fold. Only brief exposure to recombinant Tat was necessary and no toxic effects were seen at levels sufficient for trans-activation. Furthermore, Tat significantly enhanced virus expression in neuronal cells transfected with molecular clones of HIV-1. These results show that Tat is trans-activationally active in human neuronal cells, and can be taken up from the extracellular compartment by these cells in a biologically active form. Neurons represent an important potential target for Tat-mediated cellular dysfunction.

The evolution of virus diseases: their emergence, epidemicity, and control

Abstract The evolution of virus diseases, both their emergence and disappearance, involves complex interactions between the agent, the host, and the environment. These themes are illustrated by three examples, poliomyelitis of humans, bovine spongiform encephalopathy of cattle, and AIDS of humans. Emergence may be due to evolution of the virus genome, such as probably occurred in parvovirus infection of dogs and human immunodeficiency virus infection of humans. However, emergence of some new viral diseases can be traced to host or environmental factors with no change in the agent. Poliomyelitis, an enteric infection, probably emerged as an epidemic disease due to improvements in personal hygiene and public sanitation which led to a delay in the occurrence of initial infections from the perinatal period (when maternal antibody protected against paralysis) to later childhood when passive immunity had waned. Bovine spongiform encephalopathy is a common source epidemic which was transmitted through nutritional supplements which became contaminated due to a change in the method of production of bone meal supplements in rendering plants. The reduction or disappearance of virus diseases usually involves human intervention, as exemplified by immunization for smallpox and other virus diseases of humans and animals. Naturally occurring immunity may lead to fadeout of a virus as seen with measles in isolated island populations. Evolution of a virus can also result in waning of a disease as seen with myxomatosis among rabbits in Australia. The evolution of virus diseases is a provocative scientific topic and carries lessons relevant to the control of important diseases of humans, animals, and plants.

Do pediatric residents prefer interactive learning? Educational challenges in the duty hours era

Background: The volume of information that physicians must learn is increasing; yet, trainee educational time is limited. Many experts propose using trainees’ learning preferences to guide teaching. However, data regarding predominant learning preferences within pediatrics are limited. Aim: Identify predominant learning preferences among pediatric residents in a Residency Training Program. Methods: The Visual–Aural–Read/Write–Kinesthetic (VARK) questionnaire and Kolb Learning Style Inventory (LSI) were administered anonymously to 50 pediatric residents. Results: Learning style assessments were completed by 50 pediatric residents. Residents were significantly more likely to be accommodating on the Kolb LSI, which is consistent with an interactive learning preference (p < 0.01); 30% demonstrated a multimodal preference on the Kolb LSI (Figure 1). VARK assessments demonstrated that 45 (90%) respondents were kinesthetic, which is also consistent with a significant preference for interactive learning (p < 0.01). Forty (80%) were found to be multimodal on the VARK (Figure 1). There was no association between learning preference and the residents’ anticipated career choice or level of training. Conclusions: The predominant learning preferences among a cohort of pediatric residents from a single training program were consistent with a preference for interactive learning, suggesting that some trainees may benefit from supplementation of educational curricula with additional interactive experiences. Continued investigation is needed in this area to assess the effectiveness of adapting teaching techniques to individual learning preferences.

Milestone-Based Assessments Are Superior to Likert-Type Assessments in Illustrating Trainee Progression

BACKGROUND The Pediatrics Milestone Project uses behavioral anchors, narrative descriptions of observable behaviors, to describe learner progression through the Accreditation Council for Graduate Medical Education competencies. Starting June 2014, pediatrics programs were required to submit milestone reports for their trainees semiannually. Likert-type scale assessment tools were not designed to inform milestone reporting, creating a challenge for Clinical Competency Committees. OBJECTIVE To determine if milestone-based assessments better stratify trainees by training level compared to Likert-type assessments. METHODS We compared assessment results for 3 subcompetencies after changing from a 5-point Likert scale to milestone-based behavioral anchors in July 2013. Program leadership evaluated the new system by (1) comparing PGY-1 mean scores on Likert-type versus milestone-based assessments; and (2) comparing mean scores on the Likert-type versus milestone-based assessments across PGY levels. RESULTS Mean scores for PGY-1 residents were significantly higher on the prior years Likert-type assessments than milestone-based assessments for all 3 subcompetencies (P < .01). Stratification by PGY level was not observed with Likert-type assessments (eg, interpersonal and communication skills 1 [ICS1] mean score for PGY-1, 3.99 versus PGY-3, 3.98; P  =  .98). In contrast, milestone-based assessments demonstrated stratification by PGY level (eg, the ICS1 mean score was 3.06 for PGY-1, 3.83 for PGY-2, and 3.99 for PGY-3; P < .01 for PGY-1 versus PGY-3). Significantly different means by trainee level were noted across 21 subcompetencies on milestone-based assessments (P < .01 for PGY-1 versus PGY-3). CONCLUSIONS Initial results indicate milestone-based assessments stratify trainee performance by level better than Likert-type assessments. Average PGY-level scores from milestone-based assessments may ultimately provide guidance for determining whether trainees are progressing at the expected pace.

Achromobacter xylosoxidans bacteremia.

Achromobacter xylosoxidans is a nonfermenting, oxidase-positive, gram-negative rod that prefers aqueous environmental reservoirs. A variety of such sources have been implicated in epidemic and sporadic A xylosoxidans infections, including the deionized water of a hemodialysis system, a swimming pool chlorhexidine solutions, intravascular pressure transducers and distilled water. Nuclear medicine tracer material prepared at our institution was implicated in a 1978 outbreak that involved four hospitals. Fourteen patients developed proven or suspected A xylosoxidans bacteremia following intravenous injection with this tracer for lung, liver and bone scans. Contaminated non-bacteriostatic saline used as a diluent for the radioactive material was the likely source. A xylosoxidans has been isolated from many different body sites, including the bloodstream, urinary tract, central nervous system, peritoneum, respiratory tract, biliary tree; bowel, eyes, ears, pharynx and surgical wounds. Many infected individuals have had compromised host defenses of varying types. Serious infections with this organism may be fatal, perhaps, in part, because of its resistance to multiple antibiotics.

An Innovative Process for Faculty Development in Residency Training

Background: For programs to accomplish the goals of the Accreditation Council of Graduate Medical Education (ACGME) Outcome Project, faculty must be trained to deliver and assess education that is level-specific, competency-based, standardized, integrated, and easily accessible. Description: An innovative faculty development model that accomplishes these goals is described. This model trained faculty to analyze curricular needs and then to design, disseminate, and evaluate their curricula. This model utilized guided experiential learning that promoted the creation of residency program curricula and faculty buy-in. Evaluation: Key outcomes included high levels of resident satisfaction and use of the curricula, improved tracking of rotation progress, improved faculty satisfaction with their role as educators, perceived improvement in resident evaluations, and increased involvement of faculty in creating and teaching to the curriculum. Conclusion: This process may be adapted by other programs based on their available resources to address faculty development needs. The process serves as a model for meeting ACGME requirements.

Complications of human immunodeficiency virus therapy

Nucleoside/Nucleotide Reverse Transcription Inhibitors (NRTIs). NRTIs, the first antiretroviral agents, are prodrugs that are phosphorylated to triphosphate nucleotides, compete with nucleotides for the active site of viral reverse transcription (RT) and cause premature DNA chain termination. NRTIs used in pediatrics include zidovudine (AZT), lamivudine (3TC), didanosine (ddI), stavudine (d4T), abacavir (ABC) and emtricitabine (FTC). Tenofovir (TFV) is under study in children. NRTIs also inhibit human mitochondrial DNA polymerase, resulting in mitochondrial DNA depletion thought to contribute to toxicity. Non-Nucleoside Reverse Transcription Inhibitors (NNRTIs). NNRTIs are noncompetitive RT inhibitors by binding at sites distinct from the nucleotide binding site. Nevirapine (NVP) and efavirenz (EFZ) are approved for pediatric use. Protease Inhibitors (PIs). PIs block the cleavage of critical HIV proteins and result in defective virions. PIs are extensively metabolized by the cytochrome P-450 complex, with potential drug interactions. PIs used in pediatrics are saquinavir (SQV), ritonavir (RTV), lopinavir-ritonavir (LPV/R), nelfinavir (NFV), indinavir (IDV) and amprenavir (APV). Fosamprenavir and atazanavir are under study. Fusion Inhibitor. T-20 (enfuvirtide) inhibits fusion of HIV-1 with the host target cell and is considered for patients who fail alternative regimens.

Can Tablet Computers Enhance Faculty Teaching

BACKGROUND Learner benefits of tablet computer use have been demonstrated, yet there is little evidence regarding faculty tablet use for teaching. OBJECTIVE Our study sought to determine if supplying faculty with tablet computers and peer mentoring provided benefits to learners and faculty beyond that of non-tablet-based teaching modalities. METHODS We provided faculty with tablet computers and three 2-hour peer-mentoring workshops on tablet-based teaching. Faculty used tablets to teach, in addition to their current, non-tablet-based methods. Presurveys, postsurveys, and monthly faculty surveys assessed feasibility, utilization, and comparisons to current modalities. Learner surveys assessed perceived effectiveness and comparisons to current modalities. All feedback received from open-ended questions was reviewed by the authors and organized into categories. RESULTS Of 15 eligible faculty, 14 participated. Each participant attended at least 2 of the 3 workshops, with 10 to 12 participants at each workshop. All participants found the workshops useful, and reported that the new tablet-based teaching modality added value beyond that of current teaching methods. Respondents developed the following tablet-based outputs: presentations, photo galleries, evaluation tools, and online modules. Of the outputs, 60% were used in the ambulatory clinics, 33% in intensive care unit bedside teaching rounds, and 7% in inpatient medical unit bedside teaching rounds. Learners reported that common benefits of tablet computers were: improved access/convenience (41%), improved interactive learning (38%), and improved bedside teaching and patient care (13%). A common barrier faculty identified was inconsistent wireless access (14%), while no barriers were identified by the majority of learners. CONCLUSIONS Providing faculty with tablet computers and having peer-mentoring workshops to discuss their use was feasible and added value.

Using an Innovative Curriculum Evaluation Tool to Inform Program Improvement: The Clinical Skills Fair

BACKGROUND Program evaluation is important for assessing the effectiveness of the residency curriculum. Limited resources are available, however, and curriculum evaluation processes must be sustainable and well integrated into program improvement efforts. INTERVENTION We describe the pediatric Clinical Skills Fair, an innovative method for evaluating the effectiveness of residency curriculum through assessment of trainees in 2 domains: medical knowledge/patient care and procedure. Each year from 2008 to 2011, interns completed the Clinical Skills Fair as rising interns in postgraduate year (PGY)-1 (R1s) and again at the end of the year, as rising residents in PGY-2 (R2s). Trainees completed the Clinical Skills Fair at the beginning and end of the intern year for each cohort to assess how well the curriculum prepared them to meet the intern goals and objectives. RESULTS Participants were 48 R1s and 47 R2s. In the medical knowledge/patient care domain, intern scores improved from 48% to 65% correct (P < .001). Significant improvement was demonstrated in the following subdomains: jaundice (41% to 65% correct; P < .001), fever (67% to 94% correct; P < .001), and asthma (43% to 62% correct; P  =  .002). No significant change was noted within the arrhythmia subdomain. There was significant improvement in the procedure domain for all interns (χ(2)  =  32.82, P < .001). CONCLUSIONS The Clinical Skills Fair is a readily implemented and sustainable method for our residency program curriculum assessment. Its feasibility may allow other programs to assess their curriculum and track the impact of programmatic changes; it may be particularly useful for program evaluation committees.

Molecular Basis of Virus Evolution: The evolution of virus diseases: their emergence, epidemicity and control

The evolution of virus diseases, both their emergence and disappearance, involves complex interactions between the agent, the host, and the environment. These themes are illustrated by three examples, poliomyelitis of humans, bovine spongiform encephalopathy of cattle, and AIDS of humans. Emergence may be due to evolution of the virus genome, such as probably occurred in parvovirus infection of dogs and human immunodeficiency virus infection of humans. However, emergence of some new viral diseases can be traced to host or environmental factors with no change in the agent. Poliomyelitis, an enteric infection, probably emerged as an epidemic disease due to improvements in personal hygiene and public sanitation which led to a delay in the occurrence of initial infections from the perinatal period (when maternal antibody protected against paralysis) to later childhood when passive immunity had waned. Bovine spongiform encephalopathy is a common source epidemic which was transmitted through nutritional supplements which became contaminated due to a change in the method of production of bone meal supplements in rendering plants. The reduction of disappearance of virus diseases usually involves human intervention, as exemplified by immunization for smallpox and other virus diseases of humans and animals. Naturally occurring immunity may lead to fadeout of a virus as seen with measles in isolated island populations. Evolution of a virus can also result in waning of a disease as seen with myxomatosis among rabbits in Australia. The evolution of virus diseases is a provocative scientific topic and carries lessons relevant to the control of important diseases of humans, animals, and plants.