Faculty Bibliography

OBJECTIVE:Presenting the diagnosis of psychogenic nonepileptic seizures (PNES) can be a difficult task, but disclosing this information effectively is important to optimize patient outcomes. We sought to develop a standardized method to teach neurology residents how to introduce the diagnosis of PNES via an objective structured clinical examination (OSCE) with a standardized patient (SP). METHODS:In conjunction with the New York University School of Medicine Simulation Center (NYSIM), we designed an OSCE in which a resident had to inform a SP of her diagnosis of PNES and discuss a treatment plan. The SP was provided with details to gradually disclose depending on what the resident said about the history of her episodes, triggers for her episodes and her history of sexual abuse. Each encounter was observed by an attending physician who provided real-time feedback to the resident after the session. Additionally, the SP completed an objective written checklist of items the resident should have covered in the session and gave them verbal feedback. RESULTS:Twenty-six adult neurology (n = 22), child neurology (n = 3), and neuropsychiatry (n = 1) residents participated in this OSCE in 2018 and 2019, with full data available for 25 participants. Residents reported the OSCE was very useful (mean Likert score of 4.9/5). They felt moderately prepared (mean Likert score 3.8/5) and rated their performance as a mean of 3.3/5. On the SP's checklist, most residents were rated as Well Done in the domains of information gathering, relationship development, and education and counseling. Only in the domain of psychosocial assessment were most residents rated as Not Done (only 7/25 inquired about past trauma as a risk factor for PNES). SIGNIFICANCE/CONCLUSIONS:The OSCEs are a feasible and useful way to teach neurology residents about discussing PNES, as they allow for provision of real-time practice and feedback in a safe environment without real patients.

Since at least T. H. Marshall, scholars have recognized military service as a form of sacrifice that warrants compensation from the state. War-widow pensions, expansion of the franchise, and subsidized higher education are all examples of rights and benefits "bestowed" in return for wartime mobilization. Similarly, in the United States, governments have hired veterans preferentially for civilian public jobs as recompense for active military service. Although oft overlooked, those policies seem influential: the percentage of job holders identifying as veterans in the civilian US executive branch exceeds the proportion in the wider population by several multiples. This century-old pattern suggests another way that wartime mobilization has influenced the state. Yet, efforts to understand it have struggled to rule out the possibility that those who serve in the armed forces are predisposed to work for the state in both military and civilian capacities. Here, we rule out this possibility by examining whether birthdates randomly called for induction in the Vietnam-Era Selective Service Lotteries (VSSL) appear disproportionately in the population of nonsensitive personnel records of the civilian US executive branch. We find that birthdates called for induction appear with unusually high frequency among employees who were draft eligible and at risk for induction but not among other employees. This finding suggests a treatment effect from military service, thus dovetailing with the hypothesis that wartime mobilization has substantially and continually influenced who works in the contemporary administrative state.

The treatment of bacterial infections is hindered by the presence of biofilms and metabolically inactive persisters. Here, we report the synthesis of an enantiomeric block co-beta-peptide, poly(amido-D-glucose)-block-poly(beta-L-lysine), with high yield and purity by one-shot one-pot anionic-ring opening (co)polymerization. The co-beta-peptide is bactericidal against methicillin-resistant Staphylococcus aureus (MRSA), including replicating, biofilm and persister bacterial cells, and also disperses biofilm biomass. It is active towards community-acquired and hospital-associated MRSA strains which are resistant to multiple drugs including vancomycin and daptomycin. Its antibacterial activity is superior to that of vancomycin in MRSA mouse and human ex vivo skin infection models, with no acute in vivo toxicity in repeated dosing in mice at above therapeutic levels. The copolymer displays bacteria-activated surfactant-like properties, resulting from contact with the bacterial envelope. Our results indicate that this class of non-toxic molecule, effective against different bacterial sub-populations, has promising potential for the treatment of S. aureus infections.

Carfilzomib-lenalidomide-dexamethasone (KRd) therapy has yielded promising results in patients with newly diagnosed multiple myeloma (NDMM). Cereblon (CRBN) is the direct molecular target of lenalidomide and genetic polymorphisms in CRBN have been associated with lenalidomide efficacy. In this study, we assessed the correlation of five single nucleotide variants (SNVs) in the CRBN gene with clinical response and outcomes in patients with NDMM administered KRd therapy with lenalidomide maintenance, achieving favorable trial endpoints in a prospective Phase II study (NCT01402284). Of the observed SNVs, no associations with KRd therapy response were found in this patient cohort, although strong trends in hypoalbuminemia grade and hyperbilirubinemia grade emerged across the CRBN rs1672753 genotype (P = 0.0008) and the rs1714327 genotype (P = 0.0010), respectively. Our results do not provide conclusive support for the predictive utility of CRBN gene polymorphisms as potential biomarkers of clinical response to lenalidomide-based therapy in our patient population. However, these findings remain to be validated in prospective studies using larger patient populations.

Staphylococcus aureus (S. aureus) is an important pathogen causing various limited or systemic infections. Methicillin resistant S. aureus (MRSA) in particular presents a major clinical and public health problem. Toxic shock syndrome toxin-1 (TSST-1) encoded by the gene tst is an important virulence factor of tst positive S. aureus, leading to multi-organ malfunction. However, the mechanism of TSST-1 in pathogenesis is only partly clear. In this study, we investigated the prevalence of the tst gene in clinical isolates of S. aureus. Then, animal experiments were performed to further evaluate the influence of the presence of the tst gene associated Staphylococcus aureus Pathogenicity Island (SaPI) on body weight, serum cytokine concentrations and the bacterial load in different organs. In addition, macrophages were used to analyze the secretion of cytokines in vitro and bacterial survival in the cytoplasm. Finally, pathological analysis was carried out to evaluate organ tissue impairment. The results demonstrated that the prevalence of tst gene was approximately 17.8% of the bacterial strains examined. BALB/c mice infected with tst gene associated SaPI positive isolates exhibited a severe loss of body weight and a high bacterial load in the liver, heart, kidney and spleen. Pathological analysis demonstrated that tissue impairment was more severe after infection with tst gene associated SaPI positive isolates. Moreover, the secretion of IL-6, IL-2 and IL17A by macrophages infected with tst gene associated SaPI positive isolates clearly increased. Notably, IL-6 secretion in BALB/c mice infected with tst gene associated SaPI positive isolates was higher than that in BALB/c mice infected with negative ones. Together, these results indicated that the tst gene associated SaPI may play a critical role in the pathological process of infection via a direct and persistent toxic function, and by promoting the secretion of inflammatory cytokines that indirectly induce immune suppression.

BACKGROUND:Prior studies have found that rescue and recovery workers exposed to the 9/11 World Trade Center (WTC) disaster have evidence of increased persistent hearing and other ear-related problems. The potential association between WTC disaster exposures and post-9/11 persistent self-reported hearing problems or loss among non-rescue and recovery survivors has not been well studied. METHODS:We used responses to the World Trade Center Health Registry (Registry) enrollment survey (2003-2004) and first follow-up survey (2006-2007) to model the association between exposure to the dust cloud and persistent hearing loss (n = 22,741). RESULTS:The prevalence of post-9/11 persistent hearing loss among survivors was 2.2%. The adjusted odds ratio (aOR) of hearing loss for those who were in the dust cloud and unable to hear was 3.0 (95% CI: 2.2, 4.0). Survivors with persistent sinus problems, headaches, PTSD and chronic disease histories had an increased prevalence of reported hearing problems compared to those without symptoms or chronic problems. CONCLUSIONS:In a longitudinal study, we observed an association between WTC-related exposures and post-9/11 self-reported hearing loss among disaster survivors.

Background:Gut microbes influence the development several chronic conditions marking them as targets for holistic care, prevention strategies, and potential treatments. Microbiome studies are relatively new to health research and present unfamiliar terms to clinicians and researchers. "Dysbiosis" often refers to an alteration in the gut microbiome, but conceptual clarification is rarely provided. Purpose: The purpose of this study is to refine a conceptual definition of dysbiosis based on a review of nursing literature. Method: A Rodgerian approach to concept analysis was used. CINAHL, PubMed, and Web of Science were queried using "dysbiosis" through December 2018. Each article was analyzed with regard to the antecedents, attributes, and consequences of dysbiosis. Essential elements were tabulated and compared across studies to determine recurring themes and notable outliers. Findings: Analysis revealed several important antecedences, attributes, and consequences of dysbiosis. The findings also elucidated notable gaps and highlighted the co-evolving nature of the proposed definition with advances in microbiome research. Conclusion: This article adds a proposed definition of dysbiosis, offering a contribution of conceptual clarity upon which to enhance dialogue and build research. The definition emphasizes risk factors and consequences of dysbiosis as implications for holistic nursing practice.