Oxidative stress, histopathological alterations and anti-oxidant capacity in different tissues of largemouth bass (Micropterus salmoides) exposed to a newly developed sodium carbonate peroxyhydrate granular algaecide formulated with hydrogen peroxide.

Various strategies exist to control noxious cyanobacterial populations, although the application of a newly developed granular compound (sodium carbonate peroxyhydrate 'SCP', trade name 'PAK® 27' algaecide) containing hydrogen peroxide (H2O2) as the active ingredient, has been recently proven as an effective and ecofriendly 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.

The role of intravenous acetaminophen in post-operative pain control in head and neck cancer patients.

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 amplification in laryngeal squamous cell carcinoma.

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.

Construction and Validation of a Multi-Institutional Tissue Microarray of Invasive Ductal Carcinoma From Racially and Ethnically Diverse Populations.

BACKGROUND: The scarcity of tissues from racial and ethnic minorities at biobanks poses a scientific constraint to research addressing health disparities in minority populations. METHODS: To 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). RESULTS: Cancer 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. CONCLUSIONS: Contributions from participating institutions have facilitated a robust research tool. TMAs of IDC have now been released for 5 projects at 5 different institutions.

Pediatric head and neck injuries due to golf cart trauma.

INTRODUCTION: 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. OBJECTIVES: Analyze golf cart related head and neck injuries in children and adults from a national database. METHODS: 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. RESULTS: 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). CONCLUSION: Children are more vulnerable to golf cart related injuries, specifically to the head and neck.

CD133⁺ melanoma subpopulation acquired resistance to caffeic acid phenethyl ester-induced apoptosis is attributed to the elevated expression of ABCB5: significance for melanoma treatment.

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.

Novel Integrative Genomics Approach for Associating GWAS Information with Intrinsic Subtypes of Breast Cancer.

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.

An Integrative Genomics Approach for Associating GWAS Information with Triple-Negative Breast Cancer.

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.