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Golf carts are increasingly used off the golf course and are often viewed as innocuous modes of transportation. However, research has shown they can cause significant injuries, particularly to children.Analyze golf cart related head and neck injuries in children and adults from a national database.The National Electronic Injury Surveillance System (NEISS) was queried for golf cart injuries. The NEISS tracks consumer product related injuries from a sampling of approximately 100 emergency departments across the United States. Age, general diagnosis (concussion, fracture, laceration), body-part injured, disposition (hospitalized, discharged), location injury occurred, and mechanism of injury were analyzed.Over an 11-year period, a total of 3433 total patients were identified. There were 1471 children (16 years old or younger), which compromised 42.9% of the cohort. Children were injured at home or on the road 44.7% of the time compared to only 16.6% of adults (p 0.003). Children injured their head or neck 42.6% of the time compared to 28.6% of adults (p 0.0001). Adults who were hit by a car while riding a golf cart or were ejected from the golf cart 44.6% of the time compared to 61.7% of children (p 0.0001). There were 3.9% of children with a face, head, or neck fracture compared to only 2.4% of adults (p = 0.01).Children are more vulnerable to golf cart related injuries, specifically to the head and neck.

Prostate cancer (PCa) is the second most common cancer in American men, with higher incidence and death rates in African Americans (AA) relative to Caucasian Americans (CA); nevertheless, these disparities are still poorly understood. MHC class I polypeptide related sequence A (MICA) is a cell surface protein able to promote activation of natural killer cells. Cleavage of MICA and generation of its soluble form (sMICA) has been described as an immunoevasion mechanism presented by different types of aggressive tumors. In agreement with the role of MICA on tumor immunoevasion, recent studies correlated better prognosis for patients expressing higher levels of MICA in different types of cancer. We speculated that MICA expression would be different between AA and CA PCa tumors. To access MICA expression in PCa patients, we stained a TMA containing 30 AA and 27 CA tumor cores. Our results showed that CA PCa tumor cores had higher expression of MICA than the AA (p=0.0019). In order to establish an in vitro system to study the biologic effects of MICA in the context of disparity in PCa, we assessed the expression of surface MICA and release rate of sMICA in different PCa cell lines: MDA-PCa-2b and E006AA-hT, derived from AA, and DU-145 and LNCaP, derived from CA. Flow cytometry analysis showed baseline cell fraction expression positive for surface MICA of 3% in MDA-PCa-2b, 18% in E006AA-hT, 54% in DU-145, and 67% in LNCaP, with significant difference between each cell line (p Citation Format: Charles R. Pound, Marcelo J. Sakiyama, Amit Reddy, Ingrid Espinoza, Eldrin Bhanat, Krista Syrigos, Roya Gordji, Deepak Kumar, Jack Lewin, Xinchun Zhou, Jesus Monico, Christian Gomez. MHC class I polypeptide related sequence A (MICA) race-related differential expression in prostate cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C038.

Biofloc technology (BFT) relies on adding organic carbon, often in the form of sugars or starches, to encourage heterotrophic bacteria that convert otherwise toxic ammonia/nitrite into potentially consumable biomass known as ‘bioflocs’. The subsequently higher turbidity may be inappropriate for more carnivorous fish, but research in this area is limited. In this study, largemouth bass Micropterus salmoides juveniles (7.27 g) were cultured in either a clear-water system (CWS) or BFT system. Each week, a sub-sample of M. salmoides was measured for length, weight, hepatosomatic index (HSI) and hemoglobin. After 4 weeks, M. salmoides were measured for productivity, muscle/liver biochemical composition, gill Na+/K+-ATPase/H+-ATPase activities, plasma cortisol, as well as the histomorphology of the gills and liver. Within 7 days, Bacillus spp., Acinetobacter spp. and Enterobacter spp. were detcted in the BFT tanks, but were replaced with Planococcus spp. by week 4. Despite consistently lower nitrogenous waste levels in BFT, growth became significantly reduced, which was likely due to elevated circulating cortisol depressing feed intake. Livers from fish in BFT showed some local inflammation while nearly all the secondary gill lamellae on the gills were shorter. This latter finding may have contributed to significantly elevated and depressed hemoglobin level and gill Na+/K+-ATPase activity in BFT, respectively, after 4 weeks. Although survival was similar between treatments, long-term culture of M. salmoides with BFT is not advisable likely due to excessive suspended solids accumulation, including mucus. However, BFT may be a short-term strategy to reduce excessive nitrogenous waste levels in times of limited access to water.

Various strategies exist to control noxious cyanobacterial populations, although the application of a newly developed granular compound (sodium carbonate peroxyhydrate 'SCP', trade name 'PAR (R) 27' algaecide) containing hydrogen peroxide (H2O2) as the active ingredient, has been recently proven as an effective and eco-friendly treatment. However, in aquaculture settings the application of SCP to treat cynobacterial blooms may affect non-targeted biota, such as fish due to H2O2 being known to elicit toxic oxidative stress. Consequently, a better understanding of the side effects as a function of dosing concentrations would help to improve treatment efficacy and fish welfare. Thus, the aim of the current study is to assess the potential risks of SCP to largemouth bass (Micropterus salmoides), a high priced fish in the U.S. To this end, fish were exposed to two recommended doses of SCP corresponding to either 2.5 or 4.0 mg/L H2O2 for 6 days, with a control group in parallel. After 6 days, the effect of SCP exposure on oxidative stress, histopathological changes and anti-oxidant potential in the brain, liver, gills and muscle were investigated. Results show that exposure to 4.0 mg/L H2O2-SCP incited oxidative damage, evidenced by an over-accumulation of H2O2 and malondialdehyde (MDA) in the brain and liver, which were accompanied by an increment in xanthine oxidase activity. Unlike 4.0 mg/L H2O2, these oxidative stress biomarkers in the brain and liver tissue of 2.5 mg/L H2O2-SCP exposed fish were restrained within control levels and concomitant with an increase in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-s-transferase (GST) activity. In contrast, many of these anti-oxidants sentinels in the 4.0 mg/L H2O2 exposed fish were either unaffected or significantly inhibited, which resulted in over-accumulation of H2O2 and MDA. In addition, a series of histopathological alterations were observed, and the most severe brain injuries and liver inflammation were recorded in 4.0 mg/L H2O2-SCP exposed fish. Based on oxidative parameters, both SCP doses resulted in a relatively mild oxidative stress in gills but no effect in muscle, probably explaining the modest anti-oxidative responses in the former and almost complete lack of anti-oxidative responses in the latter. Overall, our findings suggests that the application of SCP at 4.0 mg/L H2O2 to control cyanobacterial blooms in aquaculture settings can possess potential risks to the farmed fish.

Objective This study investigated the role of intravenous acetaminophen for alleviation of postoperative pain after surgical resection of head and neck cancers. Methods A single-center study was conducted, which investigated a prospective group of 48 participants who underwent surgery between April 2016 and May 2017 and postoperatively received scheduled IV acetaminophen (1 g every 6 hours for 4 doses) plus the standard opioid PCA and breakthrough narcotics. These were compared to a similar retrospective cohort of 51 patients who had surgery between January 2014 to March 2015 and only received an opioid patient controlled analgesia (PCA) pump and breakthrough narcotics. Outcome measures included averaged pain scores, total amount of narcotics received (in morphine equivalents), and number of PCA attempts measured in 8-hour intervals over the first 24 hours, as well as duration of PCA and length of stay. Statistical measures included descriptive analysis and gamma regression analysis. Results The acetaminophen group achieved equally low pain scores (0.8 ± 1.2 vs. 1.0 ± 1.3, P = .408) with significantly less total narcotics in the first 8 hours after surgery (13.5 ± 13.3 vs. 22.5 ± 21.5 MEs, P = .014). This group had a significantly decreased length of stay (7.8 ± 4.6 vs. 10.6 ± 7.6 days, P = .03). Conclusion This study demonstrates that intravenous acetaminophen may play a role in reducing the total narcotic requirement in the first 8 hours after surgery and contribute to a decreased length of stay and potentially decrease cost to the patient and hospital overall. Future research should be aimed at comparing these groups in a randomized control study/setting. Level of Evidence 3.

Fibroblast growth factor receptor 1 (FGFR1) has been noted to be amplified in a variety of squamous cell carcinomas (SCCa) of the head, neck, and lung and increased copy number (CN) is a predictor of poor outcomes. FGFR1 is a therapeutic target for lung SCCa and inhibition therapy is currently in clinical trials. Absolute quantification of FGFR1 from formalin fixed paraffin embedded (FFPE) tissue of laryngeal SCCa was examined in this retrospective study. A droplet digital polymerase chain reaction (ddPCR) was used for absolute quantitation of the FGFR1 gene CN. Of the 74 samples analyzed, FGFR1 CN analysis revealed 54% of samples had CN greater than 2 copies/cell (1.8-2.2 copies/cell), and 38% had CN values greater than 3. The mean and standard deviation FGFR1 CN was 4.17 ± 1.46 CN for African American patients (n = 41) and 3.78 ±1.85 CN for Caucasian patients (n = 31). Further, 60.9% of specimens from African Americans demonstrated increased FGFR1 CN compared to 48.4% of Caucasians. Two SCCA samples from Native American demonstrated increased FGFR1 CN (4.19 and 3.01 CN). The level of FGFR1 amplification did not correlate with tumor stage, lymph node staging, or metastasis. In this population, the proportion of patient samples with an FGFR1 amplification was three times higher than in reported for SCCA of the head and neck. Further, increased FGFR1 CN was observed in two racial groups not previously reported: African Americans and Native Americans. However, FGFR1 amplification is not prognostic in laryngeal squamous cell carcinomas.

According to the cancer stem-like cell (CSC) hypothesis, neoplastic clones are maintained by a small fraction of cells with stem cell properties. Also, melanoma resistance to chemo- and radiotherapy is thought to be attributed to melanoma stem-like cells (MSCs). Caffeic acid phenethyl ester (CAPE) is a bioactive molecule, whose antitumor activity is approved in different tumor types. CAPE induced both apoptosis and E2F1 expression in CD133(-), but not in CD133(+) melanoma subpopulations. The resistance of CD133(+) melanoma subpopulation is attributed to the enhanced drug efflux mediated by ATP-binding cassette sub-family B member 5 (ABCB5), since the knockdown of ABCB5 was found to sensitize CD133(+) cells to CAPE. CAPE-induced apoptosis is mediated by E2F1 as evidenced by the abrogation of apoptosis induced in response to the knockdown of E2F1. The functional analysis of E2F1 in CD133(+) melanoma subpopulation demonstrated the ability of E2F1 gene transfer to trigger apoptosis of CD133(+) cells and to enhance the activation of apoptosis signal-regulating kinase (ASK1), c-Jun N-terminal kinase and p38, and the DNA-binding activities of the transcription factors AP-1 and p53. Also, the induction of E2F1 expression was found to enhance the expression of the pro-apoptotic proteins Bax, Noxa and Puma, and to suppress the anti-apoptotic protein Mcl-1. Using specific pharmacological inhibitors we could demonstrate that E2F1 overcomes the chemo-resistance of MSCs/CD133(+) cells by a mechanism mediated by both mitochondrial dysregulation and ER-stress-dependent pathways. In conclusion, our data addresses the mechanisms of CAPE/E2F1-induced apoptosis of chemo-resistant CD133(+) melanoma subpopulation.

Genome-wide association studies (GWAS) have achieved great success in identifying common variants associated with increased risk of developing breast cancer. However, GWAS do not typically provide information about the broader context in which genetic variants operate in different subtypes of breast cancer. The objective of this study was to determine whether genes containing single nucleotide polymorphisms (SNPs, herein called genetic variants) are associated with different subtypes of breast cancer. Additionally, we sought to identify gene regulator networks and biological pathways enriched for these genetic variants. Using supervised analysis, we identified 201 genes that were significantly associated with the six intrinsic subtypes of breast cancer. The results demonstrate that integrative genomics analysis is a powerful approach for linking GWAS information to distinct disease states and provide insights about the broader context in which genetic variants operate in different subtypes of breast cancer.

BackgroundThe scarcity of tissues from racial and ethnic minorities at biobanks poses a scientific constraint to research addressing health disparities in minority populations.MethodsTo address this gap, the Minority Biospecimen/Biobanking Geographic Management Program for region 3 (BMaP-3) established a working infrastructure for a “biobanking” hub in the southeastern United States and Puerto Rico. Herein we describe the steps taken to build this infrastructure, evaluate the feasibility of collecting formalin-fixed, paraffin-embedded tissue blocks and associated data from a single cancer type (breast), and create a web-based database and tissue microarrays (TMAs).ResultsCancer registry data from 6 partner institutions were collected, representing 12,408 entries from 8,279 unique patients with breast cancer (years 2001–2011). Data were harmonized and merged, and deidentified information was made available online. A TMA was constructed from formalin-fixed, paraffin-embedded samples of invasive ductal carcinoma (IDC) representing 427 patients with breast cancer (147 African Americans, 168 Hispanics, and 112 non-Hispanic whites) and was annotated according to biomarker status and race/ethnicity. Biomarker analysis of the TMA was consistent with the literature.ConclusionsContributions from participating institutions have facilitated a robust research tool. TMAs of IDC have now been released for 5 projects at 5 different institutions.

Prostate cancer (PCa) is the second most common cancer in American men, with higher incidence and death rates in African American men (AAM) relative to Caucasian American men (CAM). MHC class I polypeptide-related sequence A (MICA) is a protein expressed in the membrane of tumor cells that binds to the NKG2D receptors in NK cells and subtypes of CD8+T cells, activating its cytotoxic effects. Aggressive tumors cleave MICA from the membrane, release the soluble form (sMICA) into the plasma and downregulate the NKG2D receptor from the immune cells. Reports in PCa show loss of MICA expression from the cell surface is associated to a more aggressive phenotype. Likewise, increased levels of sMICA were linked to patients with Gleason score (GS) greater than 7. We hypothesized that conditions related to tumor aggressiveness in the microenvironment, would modify the levels of MICA in PCa. We also speculated that, when compared to CAM, MICA would be differentially expressed in tumors from AAM. To access the different expression of MICA in AAM and CAM PCa patients we stained a TMA containing 41 CAM and 44 AAM tumor cores for MICA expression. Our results showed that CAM PCa tumor cores had higher proportion of high expression of MICA than the AAM (38% vs 7% respectively, p=0.008). Moreover, the association between race and MICA expression was more profound with GS greater than 7 (p=0.001). Next, we explored the effect of hypoxia, a condition known to be associated with tumor aggressiveness, on MICA surface expression. We stained our TMA for hypoxia-inducible factor 1-alpha (HIF1-α), the master regulator of cellular and developmental response to hypoxia. Similar to MICA expression, HIF1- α expression was observed in tumor cores compared to normal tissue cores (43% vs 17% respectively, p=0.021). In CAM there was a positive correlation between MICA and HIF1-α immunostaining (rs= 0.50, p= 0.004), while in AAM correlation was weak (rs= 0.32, p= 0.081). FACS analysis on C4-2B cells revealed that 1% O2 (hypoxia) reduced MICA expression by 24.1%, relative to 20% O2 (normoxia). Likewise, incubation of PCa cells in the presence of 100µM cobalt chloride, a compound that mimics hypoxia by inducing HIF-1/3 α, reduced MICA by 16.7%, relative to control conditions. Altogether, our results indicate that expression of MICA is modified by disease aggressiveness and hypoxic conditions. Experiments to validate our results in minorities are currently in progress. Of equal interest is the progress of experiments focused on elucidation of the mechanistic involvement of tumor microenvironment on MICA-mediated tumorigenesis and immunoevasion. Funding acknowledgements: PCRP W81XWH-14-1-0151 (CRG), UMMC Department of Pathology (CRG), CAPES (MJS). Citation Format: Marcelo J. Sakiyama, Ingrid Espinoza, Amit Reddy, Jack R. Lewin, Xinchun Zhou, Xu Zhang, Jesus Monico, Charles R. Pound, Christian R. Gomez. MHC class I polypeptide related sequence A (MICA) in context of aggressive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2007. doi:10.1158/1538-7445.AM2017-2007

The diagnosis of colorectal cancer (CRC) is based on tumor-node-metastasis staging, a weak staging system due to different genetic and epigenetic backgrounds. Biological markers improve early detection and guide clinicians in subsequent therapies. Stemness molecules have the potential to identify patients at high risk of developing aggressive cancers. Herein, Zinc finger E-box binding homeobox 1 (ZEB1), Trefoil factor 3 (TFF3), Hepatoma Up-Regulate Protein (HURP), Mucin 2 (MUC2), and Cystic fibrosis transmembrane regulator (CFTR) are assessed as potential prognostic biomarkers in CRC. There were a total of (N=56) cases included in this study which were assessed by a pathologist, out of them 32 were African Americans (AA) and 24 Caucasian Americans (CA). The median follow-up for 42 surviving patients were noted to be 4.5 years (range 2.5 - 7.5 years). A tissue tumor microarray (TMA) was created using tumor stage-matched CRC tissues from AA and CA. The TMA was stained with each biomarker using immunohistochemistry (IHC) and consisted of 132 cores including both controls and tumors. The individual staining score ranged from (0-3) for both area and intensity. The product of area and intensity was used as the final score which ranged from (0-9) with 0 defining no expression and 9 as high expression. We evaluated the association for expression of all the five biomarkers with disease-free survival (DFS) in AA and CA separately. Stratification of the cohort by race revealed that in CA, high ZEB1 expression (nuclear and cytoplasmic) was associated with poor DFS (p= 0.015 for cytoplasm, p= 0.116 for nucleus). ZEB1 expression was not found to be a significant predictor of DFS in AA who are usually known to have worse CRC outcomes. These findings suggest that expression of ZEB1 may represent a marker for CRC prognosis, particularly in CA. High nuclear TFF3 expression in AA was found to be marginally associated with poorer DFS (p=0.089). However, the cytoplasmic expression of TFF3 was not significantly associated with DFS. Both the cytoplasmic and nuclear expression of HURP, MUC2, and CFTR among the AA and CA did not significantly correlate with DFS. Overall, we have identified two stemness molecules, ZEB1 and TFF3, with potential as markers for aggressiveness in CRC. Our findings also provide evidence of a possible biological basis for ethnicity-related differences with regards to stemness and regulatory factors of CRC aggressiveness. ZEB1 can contribute to be a novel biomarker to predict the prognosis of CRC in CA, and TFF3 will be a prognostic marker for AA. Future goals include collecting additional samples and follow-up of the patients to accurately estimate the prognosis. In addition, we will expand the project to the cellular and molecular basis underlining our findings. Funding sources: PCRP W81XWH-14-1-0151, UMMC Medical Student Research Program, and UMMC Office of Research. Citation Format: Ingrid C. Espinoza, Amit Reddy, Xu Zhang, Eldrin Bhanat, Logan Fair, Joy King, Elizabeth Tarsi, Tara Craft, Jesus Monico, Charulochana Subramony, Xinchun Zhou, Roy Duhe, Christopher Lahr, Christian Gomez. Stemness markers in colorectal cancer: Analysis in a racially-diverse population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4716. doi:10.1158/1538-7445.AM2017-4716

Genome-wide association studies (GWAS) have identified genetic variants associated with an increased risk of developing breast cancer. However, the association of genetic variants and their associated genes with the most aggressive subset of breast cancer, the triple-negative breast cancer (TNBC), remains a central puzzle in molecular epidemiology. The objective of this study was to determine whether genes containing single nucleotide polymorphisms (SNPs) associated with an increased risk of developing breast cancer are connected to and could stratify different subtypes of TNBC. Additionally, we sought to identify molecular pathways and networks involved in TNBC. We performed integrative genomics analysis, combining information from GWAS studies involving over 400,000 cases and over 400,000 controls, with gene expression data derived from 124 breast cancer patients classified as TNBC (at the time of diagnosis) and 142 cancer-free controls. Analysis of GWAS reports produced 500 SNPs mapped to 188 genes. We identified a signature of 159 functionally related SNP-containing genes which were significantly ( P < 10−5) associated with and stratified TNBC. Additionally, we identified 97 genes which were functionally related to, and had similar patterns of expression profiles, SNP-containing genes. Network modeling and pathway prediction revealed multi-gene pathways including p53, NFkB, BRCA, apoptosis, DNA repair, DNA mismatch, and excision repair pathways enriched for SNPs mapped to genes significantly associated with TNBC. The results provide convincing evidence that integrating GWAS information with gene expression data provides a unified and powerful approach for biomarker discovery in TNBC.