Faculty Bibliography

Traumatic brain injury (TBI) is associated with adverse effects on brain functions, including sensation, language, emotions and/or cognition. Therapies for improving outcomes following TBI are limited. A better understanding of the pathophysiological mechanisms of TBI may suggest novel treatment strategies to facilitate recovery and improve treatment outcome. Aberrant activation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neuronal injury and neurodegeneration. Cdk5 is a neuronal protein kinase activated via interaction with its cofactor p35 that regulates numerous neuronal functions, including synaptic remodeling and cognition. However, conversion of p35 to p25 via Ca(2+) -dependent activation of calpain results in an aberrantly active Cdk5/p25 complex that is associated with neuronal damage and cell death. Here, we show that mice subjected to controlled cortical impact (CCI), a well-established experimental TBI model, exhibit increased p25 levels and consistently elevated Cdk5-dependent phosphorylation of microtubule-associated protein tau and retinoblastoma (Rb) protein in hippocampal lysates. Moreover, CCI-induced neuroinflammation as indicated by increased astrocytic activation and number of reactive microglia. Brain-wide conditional Cdk5 knockout mice (Cdk5 cKO) subjected to CCI exhibited significantly reduced edema, ventricular dilation, and injury area. Finally, neurophysiological recordings revealed that CCI attenuated excitatory post-synaptic potential field responses in the hippocampal CA3-CA1 pathway 24 h after injury. This neurophysiological deficit was attenuated in Cdk5 cKO mice. Thus, TBI induces increased levels of p25 generation and aberrant Cdk5 activity, which contributes to pathophysiological processes underlying TBI progression. Hence, selectively preventing aberrant Cdk5 activity may be an effective acute strategy to improve recovery from TBI. Traumatic brain injury (TBI) increases astrogliosis and microglial activation. Moreover, TBI deregulates Ca(2+) -homeostasis triggering p25 production. The protein kinase Cdk5 is aberrantly activated by p25 leading to phosphorylation of substrates including tau and Rb protein. Loss of Cdk5 attenuates TBI lesion size, indicating that Cdk5 is a critical player in TBI pathogenesis and thus may be a suitable therapeutic target for TBI.

To date, the value of fasting plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) as potential novel biomarkers in patients with neuroendocrine tumors (NETs) is unknown. The aims of this study are to (i) compare fasting AG and UAG levels between nonobese, nondiabetic NET patients (N=28) and age- (±3 years) and sex-matched nonobese, nondiabetic controls (N=28); and (ii) study the relationship between AG, UAG, and AG/UAG ratios and biochemical (chromogranin-A (CgA) and neuron-specific enolase (NSE) levels) and clinical parameters (age at diagnosis, sex, primary tumor location, carcinoid syndrome, ENETS TNM classification, Ki-67 proliferation index, grading, prior incomplete surgery) in NET patients. Fasting venous blood samples (N=56) were collected and directly stabilized with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride after withdrawal. Plasma AG and UAG levels were determined by ELISA. Expression of ghrelin was examined in tumor tissue by immunohistochemistry. There were no significant differences between NET patients and controls in AG (median: 62.5 pg/mL, IQR: 33.1-112.8 vs median: 57.2pg/mL, IQR: 26.7-128.3, P=0.66) and UAG in levels (median: 76.6pg/mL, IQR: 35.23-121.7 vs median: 64.9, IQR: 27.5-93.1, P=0.44). No significant correlations were found between AG, UAG, and AG/UAG ratios versus biochemical and clinical parameters in NET patients with the exception of age at diagnosis (AG: ρ= -0.47, P=0.012; AG/UAG ratio: ρ= -0.50, P=0.007) and baseline chromogranin-A levels (AG/UAG ratio: ρ= -0.44, P=0.019). In our view, fasting plasma acylated and unacylated ghrelin appear to have no value as diagnostic biomarkers in the clinical follow-up of patients with NETs.

Paclitaxel is a widely used chemotherapy agent that has rarely been associated with ophthalmic toxicities. Cystoid macular edema is one such rare side effect of paclitaxel therapy. Its pathophysiology remains poorly understood. Here, we report on a 69-year-old woman who developed cystoid macular edema associated with the albumin-bound formulation of paclitaxel after several months of therapy for breast cancer. After 2 months of drug withdrawal, her vision improved and there was a significant improvement in the macular edema by imaging with spectral-domain optical coherence tomography. Oncologists using taxane agents should be aware of this rare adverse outcome for timely patient referral to an ophthalmologist and appropriate treatment to preserve a patient's visual acuity.

Geosocial-networking smartphone applications are commonly used by gay, bisexual, and other men who have sex with men (MSM) to meet sexual partners. The purpose of the current study was to evaluate awareness of and willingness to use pre-exposure prophylaxis (PrEP) among MSM who use geosocial-networking smartphone applications residing in New York City. Recruitment utilizing broadcast advertisements on a popular smartphone application for MSM yielded a sample of 152 HIV-uninfected MSM. Multivariable models were used to assess demographic and behavioral correlates of awareness of and willingness to use PrEP. Most participants (85.5 %) had heard about PrEP but few (9.2 %) reported current use. Unwillingness to use PrEP was associated with concerns about side effects (PR = 0.303; 95 % CI 0.130, 0.708; p = 0.006). Given that more than half (57.6 %) of participants were willing to use PrEP, future research is needed to elucidate both individual and structural barriers to PrEP use among MSM.

OBJECTIVES: To examine uptake of screening for all individuals born between 1945 and 1965 (referred to by the Centers for Disease Control and Prevention as the "birth cohort") and outline preliminary HCV prevalence data in the New York City jail system. METHODS: Data were extracted from electronic health records for all individuals screened for HCV between June 13, 2013, and June 13, 2014, in New York City jails. We used the Abbott EIA 2.0 HCV antibody assay for testing. RESULTS: In the year of study, 56 590 individuals were incarcerated; 15.1% were born between 1945 and 1965, and 84.6% were born after 1965. HCV screening was completed for 64.1% of the birth cohort and for 11.1% born after 1965, with 55.1% and 43.8% of cases found in these groups, respectively. The overall seropositivity rate was 20.6%. CONCLUSIONS: Birth cohort screening in a large jail system identified many HCV cases, but HCV infection was common among younger age groups. Public Health Implications. Universal screening may be warranted pending further study including cost-effectiveness analyses. (Am J Public Health. Published online ahead of print May 19, 2016: e1-e2. doi:10.2105/AJPH.2016.303163).

BACKGROUND: No study has examined the longitudinal trends in National Council Licensure Exam for Registered Nurse (NCLEX-RN) applicants and pass rates among internationally-educated nurses (IENs) seeking to work in the United States, nor has any analysis explored the impact of specific events on these trends, including changes to the NCLEX-RN exam, the role of the economic crisis, or the passing of the WHO Code on the International Recruitment of Health Personnel. This study seeks to understand the impact of the three aforementioned factors that may be influencing current and future IEN recruitment patterns in the United States. METHODS: In this random effects panel data analysis, we analyzed 11 years (2003-2013) of annual IEN applicant numbers and pass rates for registered nurse credentialing. Data were obtained from publicly available reports on exam pass rates. With the global economic crisis and NCLEX-RN changes in 2008 coupled with the WHO Code passage in 2010, we sought to compare if (1) the number of applicants changed significantly after those 2 years and (2) if pass rates changed following exam modifications implemented in 2008 and 2011. RESULTS: A total of 177 countries were eligible for inclusion in this analysis, representing findings from 200,453 IEN applicants to the United States between 2003 and 2013. The majority of applicants were from the Philippines (58 %) and India (11 %), with these two countries combined representing 69 % of the total. Candidates from Sub-Saharan African countries totalled 7133 (3 % of all applications) over the study period, with half of these coming from Nigeria alone. No significant changes were found in the number of candidates following the 2008 economic crisis or the 2010 WHO Code, although pass rates decreased significantly following the 2008 exam modifications and the WHO Code implementation. CONCLUSION: This study suggests that, while the WHO Code has had an influence on overall IEN migration dynamics to the United States by decreasing candidate numbers, in most cases, the WHO Code was not the single cause of these fluctuations. Indeed, the impact of the NCLEX-RN exam changes appears to exert a larger influence.