On alert for Ebola: public health risk assessment of travellers from Uganda to the USA during the 2022 outbreak.

BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.

Investigating impacts of the mycothiazole chemotype as a chemical probe for the study of mitochondrial function and aging.

Small molecule inhibitors of the mitochondrial electron transport chain (ETC) hold significant promise to provide valuable insights to the field of mitochondrial research and aging biology. In this study, we investigated two molecules: mycothiazole (MTZ) - from the marine sponge C. mycofijiensis and its more stable semisynthetic analog 8-O-acetylmycothiazole (8-OAc) as potent and selective chemical probes based on their high efficiency to inhibit ETC complex I function. Similar to rotenone (Rote), MTZ, a newly employed ETC complex I inhibitor, exhibited higher cytotoxicity against cancer cell lines compared to certain non-cancer cell lines. Interestingly, 8-OAc demonstrated greater selectivity for cancer cells when compared to both MTZ and Rote, which has promising potential for anticancer therapeutic development. Furthermore, in vivo experiments with these small molecules utilizing a C. elegans model demonstrate their unexplored potential to investigate aging studies. We observed that both molecules have the ability to induce a mitochondria-specific unfolded protein response (UPRMT) pathway, that extends lifespan of worms when applied in their adult stage. We also found that these two molecules employ different pathways to extend lifespan in worms. Whereas MTZ utilizes the transcription factors ATFS-1 and HSF1, which are involved in the UPRMT and heat shock response (HSR) pathways respectively, 8-OAc only required HSF1 and not ATFS-1 to mediate its effects. This observation underscores the value of applying stable, potent, and selective next generation chemical probes to elucidate an important insight into the functional roles of various protein subunits of ETC complexes and their regulatory mechanisms associated with aging.

Investigating impacts of marine sponge derived mycothiazole and its acetylated derivative on mitochondrial function and aging.

Small molecule inhibitors of the mitochondrial electron transport chain (ETC) hold significant promise to provide valuable insights to the field of mitochondrial research and aging biology. In this study, we investigated two molecules: mycothiazole (MTZ) - from the marine sponge C. mycofijiensis and its more stable semisynthetic analog 8-O-acetylmycothiazole (8-OAc) as potent and selective chemical probes based on their high efficiency to inhibit ETC complex I function. Similar to rotenone (Rote), a widely used ETC complex I inhibitor, these two molecules showed cytotoxicity to cancer cells but strikingly demonstrate a lack of toxicity to non-cancer cells, a highly beneficial feature in the development of anti-cancer therapeutics. Furthermore, in vivo experiments with these small molecules utilizing C.elegans model demonstrate their unexplored potential to investigate aging studies. We observed that both molecules have the ability to induce a mitochondria-specific unfolded protein response (UPRMT) pathway, that extends lifespan of worms when applied in their adult stage. Interestingly, we also found that these two molecules employ different pathways to extend lifespan in worms. Whereas MTZ utilize the transcription factors ATFS-1 and HSF-1, which are involved in the UPRMT and heat shock response (HSR) pathways respectively, 8-OAc only required HSF-1 and not ATFS-1 to mediate its effects. This observation underscores the value of applying stable, potent, and selective next generation chemical probes to elucidate an important insight into the functional roles of various protein subunits of ETC complexes and their regulatory mechanisms associated with aging.

Examining the effects of soil entrainment during nuclear cloud rise on fallout predictions using a multiscale atmospheric modeling framework.

Current operational models for nuclear cloud rise over land were developed and validated using observations from shallow-buried or surface detonations, where lofted soil quickly mixed with fission products from the detonation. These models poorly predict fallout from elevated detonations near the fallout-free height of burst (FFHOB), where interactions with the ground are limited and the mixing of fission products and lofted soil is incomplete. Fallout-free is a misnomer at this HOB, as fallout was observed in these cases, but was below the levels of concern, especially off-grounds of the nuclear test site. To correctly characterize and model fallout from detonations near the FFHOB, models must be developed which can capture the stratified nature of the particle and activity-size distributions within the cloud. Previously, it was shown that the Weather Research and Forecasting (WRF) model can accurately simulate nuclear cloud rise for airbursts with little to no ground interactions (Arthur et al., 2021). That work is expanded here by (1) using a radiation-hydrodynamics code to improve the fireball initialization in WRF, (2) further developing an aerosol package from WRF-Chem to simulate lofted soil, and (3) combining the WRF cloud rise simulations with the operational models used at the National Atmospheric Release Advisory Center (NARAC) for fallout modeling. Using this combination of codes, the Upshot-Knothole Grable detonation, which was just below the FFHOB, is simulated from seconds after detonation through cloud rise and fallout, and results are compared to historical test data. The results show improved prediction of dose rate and highlight the need to correctly characterize the entrainment of material into the cloud and the subsequent mixing of fission products with entrained material.

Comparing open-ended question methods to vignette methods to explore willingness to obtain pre-exposure prophylaxis access in pharmacies among black men who have sex with men.

Black men who have sex with men (BMSM) are at higher risk of HIV transmission than any other group; however, their uptake of the highly effective HIV prevention medication, pre-exposure prophylaxis (PrEP), is low. In collaboration with a communitybased organization in Atlanta, Georgia, we explored ten HIV-negative BMSM's willingness to obtain PrEP in pharmacies using standard open-ended and vignette qualitative methods. Three overarching themes were identified: privacy, patient-pharmacist interactions, and HIV/STI screening. While open-ended questions allowed participants to provide broad answers on their willingness to receive prevention services at a pharmacy, the vignette drew out specific responses to facilitate in-pharmacy PrEP delivery. Using both openended questions and vignette data collection strategies, BMSM reported high willingness to screen for and uptake PrEP in pharmacies. However, the vignette method allowed for greater depth. Open-ended questions elicited responses that highlighted general barriers and facilitators of PrEP dispensing in pharmacies. However, the vignette allowed participants to customize a plan of action that would best fit their needs. Vignette methods are underutilized in HIV research and may be helpful in supplementing standard open-ended interview questions to uncovering unknown challenges about health behaviors and obtain more robust data on highly sensitive research topics in HIV research.

In Vivo Evaluation of (-)-Zampanolide Demonstrates Potent and Persistent Antitumor Efficacy When Targeted to the Tumor Site.

Microtubule-stabilizing agents (MSAs) are a class of compounds used in the treatment of triple-negative breast cancer (TNBC), a subtype of breast cancer where chemotherapy remains the standard-of-care for patients. Taxanes like paclitaxel and docetaxel have demonstrated efficacy against TNBC in the clinic, however new classes of MSAs need to be identified due to the rise of taxane resistance in patients. (-)-Zampanolide is a covalent microtubule stabilizer that can circumvent taxane resistance in vitro but has not been evaluated for in vivo antitumor efficacy. Here, we determine that (-)-zampanolide has similar potency and efficacy to paclitaxel in TNBC cell lines, but is significantly more persistent due to its covalent binding. We also provide the first reported in vivo antitumor evaluation of (-)-zampanolide where we determine that it has potent and persistent antitumor efficacy when delivered intratumorally. Future work on zampanolide to further evaluate its pharmacophore and determine ways to improve its systemic therapeutic window would make this compound a potential candidate for clinical development through its ability to circumvent taxane-resistance mechanisms.

Re-evaluation of the Fijianolide/Laulimalide Chemotype Suggests an Alternate Mechanism of Action for C-15/C-20 Analogs.

Herein, we report on naturally derived microtubule stabilizers with activity against triple negative breast cancer (TNBC) cell lines, including paclitaxel, fijianolide B/laulimalide (3), fijianolide B di-acetate (4), and two new semisynthetic analogs of 3, which include fijianolide J (5) and fijianolide L (6). Similar to paclitaxel, compound 3 demonstrated classic microtubule stabilizing activity with potent (GI50 = 0.7-17 nM) antiproliferative efficacy among the five molecularly distinct TNBC cell lines. Alternatively, compounds 5 or 6, generated from oxidation of C-20 or C-15 and C-20 respectively, resulted in a unique profile with reduced potency (GI50 = 4-9 µM), but improved efficacy in some lines, suggesting a distinct mechanism of action. The C-15, C-20 di-acetate, and dioxo modifications on 4 and 6 resulted in compounds devoid of classic microtubule stabilizing activity in biochemical assays. While 4 also had no detectable effect on cellular microtubules, 6 promoted a reorganization of the cytoskeleton resulting in an accumulation of microtubules at the cell periphery. Compound 5, with a single C-20 oxo substitution, displayed a mixed phenotype, sharing properties of 3 and 6. These results demonstrate the importance of the C-15/C-20 chiral centers, which appear to be required for the potent microtubule stabilizing activity of this chemotype and that oxidation of these sites promotes unanticipated cytoskeletal alterations that are distinct from classic microtubule stabilization, likely through a distinct mechanism of action.

HIV care outcomes among transgender persons with HIV infection in the United States, 2006-2021.

OBJECTIVES: HIV prevalence is an estimated 14% among transgender women (TW) and 3% among transgender men (TM). HIV care is vital for viral suppression but is hindered by transphobia and HIV stigma. We assessed HIV care outcomes among transgender persons (TG) with HIV in the United States. DESIGN: Systematic review and meta-analysis of peer-reviewed journal articles. METHODS: We searched multiple electronic databases and Centers for Disease Control and Prevention's HIV Prevention Research Synthesis database for 2006-September 2020. Eligible reports were US-based studies that included TG and reported HIV care outcomes. Random-effects models were used to calculate HIV care outcome rates. The protocol is registered with PROSPERO (CRD42018079564). RESULTS: Few studies reported outcomes for TM; therefore, only TW meta-analysis results are reported. Fifty studies were identified having low-to-medium risk-of-bias scores. Among TW with HIV, 82% had ever received HIV care; 72% were receiving care, and 83% of those were retained in HIV care. Sixty-two percent were currently virally suppressed. Among those receiving HIV care or antiretroviral therapy (ART), 67% were virally suppressed at last test. Sixty-five percent were linked to HIV care 3 months or less after diagnosis. Seventy-one percent had ever been prescribed ART. Approximately 66% were taking ART, and 66% were ART-adherent. Only 56% were currently adherent the previous year. CONCLUSIONS: HIV care outcomes for TW were not ideal, and research gaps exists for TM. High heterogeneity was observed; therefore, caution should be taken interpreting the findings. Integrating transgender-specific health needs are needed to improve outcomes of transgender persons across the HIV care continuum.

Linking Big Five Personality Domains and Facets to Alcohol (Mis)Use: A Systematic Review and Meta-Analysis.

AIMS: The goal of this investigation was to synthesize (un)published studies linking Big Five personality domains and facets to a range of alcohol use outcomes. Meta-analyses were conducted to quantify the unique associations between alcohol use outcomes and each Big Five personality domains over and above other domains. Within each domain, meta-analyses also were conducted to examine the unique contribution of each personality facet in predicting alcohol use outcomes. METHODS: Systematic literature reviews were performed in PsycINFO and PubMed using keywords related to alcohol use and personality. Peer-reviewed and unpublished studies were screened and coded for the meta-analyses. A total of 80 independent samples were subjected to correlated effects meta-regressions. RESULTS: Over and above other Big Five personality domains, both conscientiousness and agreeableness were negatively correlated with alcohol consumption, risky/hazardous drinking and negative drinking-related consequences. Facet-level analyses indicated that deliberation and dutifulness were uniquely associated with alcohol (mis)use over and above other conscientiousness facets, and compliance and straightforwardness were uniquely associated with alcohol (mis)use over and above other agreeableness facets. Extraversion-namely excitement seeking-was correlated with alcohol consumption, whereas neuroticism-namely impulsiveness and angry hostility-was correlated with negative drinking-related consequences. CONCLUSIONS: Personality characteristics are robust correlates of alcohol (mis)use. Examining relevant narrowband traits can inform mechanisms by which personality affects drinking behaviors and related problems, and ways to enhance clinical interventions for alcohol use disorder. Gaps in this literature and future research directions are discussed.

Using the Think-Aloud Method to Assess the Feasibility and Acceptability of Network Canvas Among Black Men Who Have Sex With Men and Transgender Persons: Qualitative Analysis.

BACKGROUND: Characteristics of an individual's social network have been important factors in understanding infectious disease transmission patterns. Social network data collection is generally time and resource intensive, yet it is crucial to our understanding of the complex epidemiologic landscape of human behaviors among stigmatized social groups. OBJECTIVE: We sought to evaluate the feasibility and acceptability of a self-administered social network data collection tool, Network Canvas, among Black men who have sex with men (BMSM) and transgender persons using the think-aloud method, which is a robust and flexible research technique used to perform usability testing. METHODS: We piloted a self-administered network interview within the Network Canvas Software Suite. Participants aged 18 years and older were recruited through a community-based organization in Atlanta, GA, and were included based upon their willingness to share information on sexual behaviors and drug use for themselves and their social networks. A semistructured interview guide was used to document cognitive decision-making processes while using the tool. Recorded interviews were transcribed verbatim, and thematic analyses were performed. RESULTS: Among 7 BMSM and transgender participants, three main themes were identified from cognitive processes: (1) the utility, (2) navigation, and (3) intuitive design of Network Canvas. Overall, Network Canvas was described as "easy to use," with suggestions mainly directed toward improving navigation tools and implementing an initial tutorial on the program prior to use. Participants were willing to use Network Canvas to document their social networks and characteristics. In general, observed verbal responses from participants matched their behavior, although there were some discrepancies between verbal affirmations of use and understanding versus external observation. CONCLUSIONS: We found Network Canvas to be a useful new tool to capture social network data. Self-administration allowed participants the opportunity to provide sensitive information about themselves and their social networks. Furthermore, automated name generation and visualization of an individuals' social network in the app has the potential to reduce cognitive burden during data collection. More efficient methods of social network data collection have the potential to provide epidemiologic information to guide prevention efforts for populations with stigmatized health conditions or behaviors.

An interesting case of progressive dyspnoea and diffuse mediastinal adenopathy in a 25-year-old man.

Mediastinal adenopathy, septal line thickening, centrilobular ground glass opacities on CT and a markedly reduced T LCO in a young patient with pulmonary hypertension, should alert the clinician to this potential diagnosis https://bit.ly/3cfe9pX.

Intravascular lithotripsy-assisted balloon angioplasty to facilitate transfemoral transcatheter aortic valve implantation in a patient with coral reef aorta.

This case describes the management of a woman in her 70s with severe symptomatic aortic stenosis and concomitant severe stenosis of the suprarenal abdominal aorta due to 'coral reef' calcification of the aortic wall and lumen (CRA). Due to her religious beliefs as a Jehovah's Witness regarding the use of blood products, she rejected the option of surgical aortic valve replacement. Transfemoral (TF) delivery of a transcatheter aortic valve was challenged by the presence of CRA. A successful TF transcatheter aortic valve implantation (TAVI) was achieved by the treatment of the CRA with intravascular lithotripsy-assisted angioplasty, followed by delivery and deployment of a self-expanding TAVI valve.

Support and perceived barriers to implementing pre-exposure prophylaxis screening and dispensing in pharmacies: Examining concordance between pharmacy technicians and pharmacists.

OBJECTIVES: Recent legislation to expand pre-exposure prophylaxis (PrEP) screening and dispensing in pharmacies may significantly improve PrEP access for people at a high risk of human immunodeficiency virus (HIV) transmission. Studies have shown that pharmacists show wide support for PrEP expansion in pharmacies. However, pharmacy technicians are often the first point of contact for patients in pharmacies and are required to implement many of the tasks to ensure patients of a pharmacy receive adequate services. The purpose of this study was to assess pharmacists' and pharmacy technicians' perspectives regarding the implementation of PrEP screening and dispensing. METHODS: We qualitatively examined whether pharmacy technicians' (n = 6) support and perceived barriers to screening and dispensing PrEP in pharmacies were concordant with those of pharmacists (n = 7). Pharmacy staff were recruited from high-risk HIV neighborhoods in Atlanta, GA using AIDSVu (Atlanta, GA). Two independent coders used MAXQDA (Berlin, Germany) and performed thematic data analysis and unitization to determine agreement. RESULTS: Pharmacists and pharmacy technicians expressed strong willingness and support for screening and dispensing PrEP in pharmacies. Both groups expressed concerns about the time and the resources needed to perform PrEP screening and dispensing. Technicians, however, also reported concerns about privacy for patients, the need for community support and awareness of pharmacy-based PrEP screening, and recommended scheduling of PrEP screening activities during a limited part of the day to facilitate screening. Pharmacists reported fewer barriers but reported a need for more training of pharmacy staff to assist with PrEP screening and dispensing implementation. CONCLUSION: Pharmacy technicians discussed more barriers compared with pharmacists who were largely centered around practical considerations (i.e., logistics and workflow) that may affect the success of PrEP screening and dispensing. Given technicians' pivotal role in the pharmacy, implementation of pharmacy-based PrEP services should address technicians' perceived barriers in addition to those of pharmacists.

Willingness to Discuss and Screen for Pre-Exposure Prophylaxis in Pharmacies Among Men Who Have Sex With Men.

OBJECTIVE: To determine the willingness to discuss and be screened for pre-exposure prophylaxis (PrEP) in pharmacies among MSM. METHODS: Led by Georgia's Fulton County Board of Health, this study surveyed individuals who attended 2 Atlanta-based Gay Pride events in 2018. This analysis was limited to those who identified as men who have sex with men (MSM) who were not HIV positive and reported never using PrEP. Multivariable regression was used to determine the correlates of willingness to discuss and be screened for PrEP in-pharmacy. RESULTS: Most (69%) were willing to discuss PrEP with pharmacy staff and 61.35% were willing to be screened for PrEP in-pharmacy. Those who were interested in PrEP were significantly more willing to discuss PrEP in-pharmacy compared to those not interested in PrEP (prevalence ratio [PR]: 1.65; 95% confidence interval [95% CI]: 1.11-2.48). Race was not associated with willingness to discuss PrEP with pharmacy staff. However, black MSM (BMSM) were less willing to be screened in pharmacies than white MSM, until we accounted for interest in PrEP (PR: 1.27; 95% CI: 1.09-1.48). DISCUSSION: Pharmacies may be an optimal setting to expand PrEP access to reach racial minorities who have the highest need but are not being reached. Pharmacy-based PrEP discussions and screening could improve awareness of HIV status and increase PrEP knowledge and uptake. Future studies should determine optimal pharmacy conditions under which PrEP screening and uptake are acceptable for BMSM.

Reinvestigation of Mycothiazole Reveals the Penta-2,4-dien-1-ol Residue Imparts Picomolar Potency and 8S Configuration.

Reinvestigation of mycothiazole (1) revealed picomolar potency (IC50 = 0.00016, 0.00027, 0.00035 µM) against pancreatic, (PANC-1), liver (HepG2), and colon (HCT-116) tumor cell lines. Reevaluation of 1 provided [α]D data indicating Vanuatu specimens of C. mycofijiensis contain the 8S enantiomer of 1 and not the 8R configuration previously reported. Semisynthesis provided 8-O-acetylmycothiazole (2), 8-oxomycothiazole (8), mycothiazole nitrosobenzene derivatives (MND1, MND2: 9a, 9b), and MND3 (10) with IC50 = 0.00129, >1.0, >1.0, >1.0, >1.0 µM, respectively, against PANC-1 cell lines. These results highlight the significance of the penta-2,4-dien-1-ol residue as a key structural feature of 1 required for its cytotoxicty against tumor cell lines.

Pharmacy-based pre-exposure prophylaxis support among pharmacists and men who have sex with men.

OBJECTIVE: To understand the perceptions and support for pharmacy-based pre-exposure prophylaxis (PrEP) delivery among pharmacists and men who have sex with men (MSM). DESIGN: A qualitative study from April 2017 to December 2018. SETTING AND PARTICIPANTS: The researchers used purposive sampling to identify MSM participants and AIDSVu to identify pharmacists in high-human immunodeficiency virus (HIV) zip codes in the metropolitan Atlanta area. Eight MSM and 6 pharmacists consented to participate in the study. OUTCOME MEASURES: Perceptions and support for PrEP delivery in pharmacies. RESULTS: Both MSM and pharmacists expressed strong support for in-pharmacy PrEP screening and dissemination. MSM reported that pharmacies were more convenient and accessible compared with physician's offices. However, they also noted that privacy and training of pharmacy staff were important for them to consider being screened for PrEP in a pharmacy. Pharmacists also believed training was important and felt comfortable counseling on HIV prevention for their current patients. CONCLUSION: These data support early evidence that pharmacies are a promising venue to improve PrEP access for MSM. To implement PrEP screening in pharmacies, proper training of pharmacy staff and a designated space to ensure privacy are critical. Future studies should test the feasibility of screening for PrEP in pharmacies for black MSM.

"Knowing Your Status and Knowing Your Partner's Status Is Really Where It Starts": A Qualitative Exploration of the Process by Which a Sexual Partner's HIV Status Can Influence Sexual Decision Making.

Gay and bisexual men are at disproportionate risk for human immunodeficiency virus (HIV) infection. While prevention efforts often emphasize consistent condom use, there is growing evidence that men are using seroadaptive safer-sex strategies, such as serosorting and seropositioning. This qualitative analysis of 204 HIV-negative and HIV-positive gay and bisexual men explored the ways that a sexual partner's HIV status can influence safer-sex strategies and sexual decisions. The majority of the respondents reported that they were influenced by their partners' HIV status. Those respondents who reported no influence discussed adhering to safer-sex rules that were not dependent on partner status and a lack of concern about HIV. Conversely, respondents who reported influence identified three primary areas of influence: psychological impacts, partner preference and selection, and specific behavioral intentions and strategies. A conceptual model explicating a potential process by which respondents use partner serostatus information in shaping sexual decisions is presented.

Granulomatous interstitial nephritis secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma.

Granulomatous interstitial nephritis (GIN) is an uncommon pathologic lesion encountered in 0.5% to 5.9% of renal biopsies. Drugs, sarcoidosis, and infections are responsible for most cases of GIN. Malignancy is not an established cause of GIN. Here, we report a series of 5 patients with GIN secondary to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients were mostly elderly white males with an established history of CLL/SLL who presented with severe renal impairment (median peak serum creatinine, 7.3 mg/dL), leukocyturia, and mild proteinuria. One had nephromegaly. In 2 patients, the development and relapse of renal insufficiency closely paralleled the level of lymphocytosis. Kidney biopsy in all patients showed GIN concomitant with CLL/SLL leukemic interstitial infiltration. Granulomas were nonnecrotizing and epithelioid and were associated with giant cells. One biopsy showed granulomatous arteritis. One patient had a granulomatous reaction in lymph nodes and skin. Steroids with/without CLL/SLL-directed chemotherapy led to partial improvement of kidney function in all patients except 1 who had advanced cortical scarring on biopsy. In conclusion, we report an association between CLL/SLL and GIN. Patients typically present with severe renal failure due to both GIN and leukemic interstitial infiltration, which tends to respond to steroids with/without CLL/SLL-directed chemotherapy. The pathogenesis of GIN in this clinical setting is unknown but may represent a local hypersensitivity reaction to the CLL/SLL tumor cells.

Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic behavior: a novel ex vivo and biophysical approach.

Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics systems; however, PCa may utilize the extensive innervation of the prostate for glandular egress. The interaction of PCa and its nerve fibers is observed in 80% of PCa and is termed perineural invasion (PNI). PCa cells have been observed traveling through the endoneurium of nerves, although the underlying mechanisms have not been elucidated. Voltage sensitive sodium channels (VSSC) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two auxiliary beta (ß) subunits with inherent cell adhesion molecule (CAM) functions. The beta-2 isoform (gene SCN2B) interacts with several neural CAMs, while interacting putatively with other prominent neural CAMs. Furthermore, beta-2 exhibits elevated mRNA and protein levels in highly metastatic and castrate-resistant PCa. When overexpressed in weakly aggressive LNCaP cells (2BECFP), beta-2 alters LNCaP cell morphology and enhances LNCaP cell metastasis associated behavior in vitro. We hypothesize that PCa cells use beta-2 as a CAM during PNI and subsequent PCa metastasis. The objective of this study was to determine the effect of beta-2 expression on PCa cell neurotropic metastasis associated behavior. We overexpressed beta-2 as a fusion protein with enhanced cyan fluorescence protein (ECFP) in weakly aggressive LNCaP cells and observed neurotropic effects utilizing our novel ex vivo organotypic spinal cord co-culture model, and performed functional assays with neural matrices and atomic force microscopy. With increased beta-2 expression, PCa cells display a trend of enhanced association with nerve axons. On laminin, a neural CAM, overexpression of beta-2 enhances PCa cell migration, invasion, and growth. 2BECFP cells exhibit marked binding affinity to laminin relative to LNECFP controls, and recombinant beta-2 ectodomain elicits more binding events to laminin than BSA control. Functional overexpression of VSSC beta subunits in PCa may mediate PCa metastatic behavior through association with neural matrices.