Triclosan (TCS) and triclocarban (TCC) are widely used broad spectrum bactericides that are common pollutants of waterways and soils. Methyl triclosan (mTCS) is the predominant bacterial TCS metabolite. Previous studies have shown that TCS disrupts thyroid hormone (TH) action; however, the effects of mTCS or TCC are not known. The present study uses the cultured frog tadpole tail fin biopsy (C-fin) assay and the TH-responsive rat pituitary GH3 cell line to assess the effects of these three chemicals (1-1000 nM) on TH signaling and cellular stress within 48 h. mRNA abundance of TH receptor β, Rana larval keratin type I (TH-response), heat shock protein 30, and catalase (stress-response) was measured using quantitative real-time polymerase chain reaction in the C-fin assay. The TH-responsive gene transcripts encoding growth hormone, deiodinase I, and prolactin were measured in GH3 cells with the heat shock protein 70 transcript acting as a cellular stress indicator. We found alteration of stress indicators at a wide range of concentrations of TCS, mTCS, and TCC in both test systems. mTCS and TCC affected TH-responsive gene transcripts at the highest concentration in mammalian cells, whereas a modest effect included lower concentrations in the C-fin assay. In contrast, TCS did not affect TH-responsive transcripts. These results identify nontarget biological effects of these bacteriocides on amphibian and mammalian cells and suggest the TH-disrupting effects observed for TCS could be mediated through its metabolite.
Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.
Nanometals are manufactured to particle sizes with diameters in the nanometer range and are included in a variety of consumer and health products. There is a lack of information regarding potential effects of these materials on aquatic organisms. Amphibians are regarded as environmental sentinels and demonstrate an exquisite sensitivity to thyroid hormone action, a hormone that is essential for human health. This present study assessed the effect of exposure to nanometals on stress and thyroid hormone signaling in frog tissue using a cultured tail fin biopsy (C-fin) assay derived from Rana catesbeiana tadpoles. The C-fin assay maintains tissue complexity and biological replication while multiple chemical responses can be assessed from the same individual. We tested the ability of nanosilver (0.06 μg/L-5.5 mg/L), quantum dots (0.25 μg/L-22 mg/L), and nanozinc oxide (0.19-10 mg/L) to alter gene expression in the presence or absence of 3,3',5'-triiodothyronine (T(3)) using quantitative real-time polymerase chain reaction. Results were compared to exposure to micrometer-silver, silver nitrate, and micrometer-cadmium telluride. Nanosilver (≥2.75 mg/L) and quantum dots (≥0.22 mg/L) altered the expression of transcripts linked to T(3)- and stress-mediated pathways, while nanozinc oxide had no effect. Lower concentrations of nanosilver (0.6 to 550 μg/L) perturbed T(3)-mediated signaling while not inducing cell stress. The observed effects were orders of magnitude below acute toxicity levels and occurred at or below the current North American water quality guidelines for metals, underscoring the need for evaluating nanoparticles separately from their constituent chemicals.
There is a need for the development of a rapid method for identifying chemicals that disrupt thyroid hormone (TH) action while maintaining complex tissue structure and biological variation. Moreover, no assay to date allows a simultaneous screen of an individual's response to multiple chemicals. A cultured tail fin biopsy or C-fin assay was developed using Rana catesbeiana tadpoles. Multiple tail fin biopsies were taken per tadpole, cultured in serum-free medium, and then each biopsy was exposed to a different treatment condition. The effects of known disruptors of TH action were evaluated in the C-fin assay. Chemical exposure was performed +/- 10 nM 3,3',5-triiodothyronine and real-time quantitative polymerase chain reaction (QPCR) of two TH-responsive transcripts, TH receptor beta (TRbeta) and the Rana larval keratin type I (RLKI), was performed. Within 48 h of exposure to Triac (1-100 nM), roscovitine (0.6-60 microM), or genistein (1-100 microM), perturbations in TH signaling were detected. Tetrabromobisphenol A (TBBPA) (10-1,000 nM) showed no effect. Acetochlor (1-100 nM) elicited a modest effect on the TH-dependent induction of TRbeta transcript. These data reveal that a direct tissue effect may not be critical for TBBPA and acetochlor to disrupt TH action previously observed in intact tadpoles.
Background There are a number of studies in the literature that describe the prevalence, causes, and factors associated with chronic postoperative opioid use, but there is a lack of synthesis of the literature to guide clinicians in optimally managing postoperative pain while avoiding opioid dependence. Thus, the goal of this study was to perform a systematic review of the literature to investigate the prevalence of chronic postoperative opioid use and the associated risk factors. Materials and methods A systematic search was performed using Ovid Medline and Embase according to PRISMA guidelines. Data were collected on the following outcomes of interest: prevalence of opioid use at 3, 6, and 12 months postoperatively, and risk factors associated with chronic postoperative opioid use. Results Forty-three articles were included in the final analysis. The mean prevalence of chronic postoperative opioid use in all populations at 3, 6, and 12 months postoperatively was 30.5%, 25.6%, and 25.2%, respectively. The prevalence of patients who developed chronic opioid use at 3, 6, and 12 months postoperatively was 10.4%, 8.5%, and 9.8%, respectively. Forty of the articles analyzed risk factors associated with chronic postoperative opioid use. The most common associated risk factor identified was preoperative opioid use with 27 articles demonstrating a significant association with chronic postoperative opioid use. Discussion The current opioid crisis is in part secondary to the prevalence of chronic opioid use following surgery. This study identified associated risk factors with chronic postoperative opioid use, which may help identify patients at risk for developing chronic postoperative opioid use.
BackgroundOur study quantifies the effectiveness of perioperative pain control in a cohort of patients undergoing major head and neck surgery with free flap reconstruction. Our long-term goal is to improve pain control and thereby increase mobility, decrease postoperative complications and decrease hospital stay.MethodsA retrospective analysis was performed at a tertiary, academic head and neck surgical oncology program in Calgary, Alberta, Canada from January 1, 2015 – December 31, 2015. Pain scores were recorded prospectively. Primary outcomes were frequency of postoperative pain assessments and pain intensity using the numeric rating scale.ResultsThe cohort included 41 patients. Analysis was limited to pain scores recorded from postoperative days 1–14. There was an average of 7.3 pain measurements per day (SD 4.6, range 1–24) with the most frequent monitoring on postoperative days 1–4.Median pain scores ranged from 0 to 4.5 with the highest median score on postoperative day 6. The daily maximum pain scores recorded ranged from 8 to 10 with scores of 10 recorded on postoperative days 1, 2, 3, 5, 7, 8, and 10.Patients most frequently had inadequate pain control on postoperative days 1, 2, 4, and 5 with the majority occurring on postoperative day 1.ConclusionsPostoperative pain control could be improved at our centre. The frequency of pain assessments is also highly variable. Ongoing measurement, audit, and feedback of analgesic protocol effectiveness is an excellent first step in improving perioperative pain management in patients undergoing major head and neck cancer surgery with free flap reconstruction.
Nitrate and nitrite are common aqueous pollutants that are known to disrupt the thyroid axis. In amphibians, thyroid hormone (TH)-dependent metamorphosis is affected, although whether the effect is acceleration or deceleration of this developmental process varies from study to study. One mechanism of action of these nitrogenous compounds is through alteration of TH synthesis. However, direct target tissue effects on TH signaling are hypothesized. The present study uses the recently developed cultured tail fin biopsy (C-fin) assay to study possible direct tissue effects of nitrate and nitrite. Tail biopsies obtained from premetamorphic Rana catesbeiana tadpoles were exposed to 5 and 50 mg/L nitrate (NO3–N) and 0.5 and 5 mg/L nitrite (NO2–N) in the absence and presence of 10 nM T3. Thyroid hormone receptor β (TRβ) and Rana larval keratin type I (RLKI), both of which are TH-responsive gene transcripts, were measured using quantitative real time polymerase chain reaction. To assess cellular stress which could affect TH signaling and metamorphosis, heat shock protein 30, and catalase (CAT) transcript levels were also measured. We found that nitrate and nitrite did not significantly change the level of any of the four transcripts tested. However, nitrate exposure significantly increased the heteroscedasticity in response of TRβ and RLKI transcripts to T3. Alteration in population variation in such a way could contribute to the previously observed alterations of metamorphosis in frog tadpoles, but may not represent a major mechanism of action.
Postoperative opioid use has been linked to the subsequent development of opioid dependency. Multimodal analgesia (MMA) can reduce the use of opioids in the postoperative period, but MMA has not been well-studied after major head and neck surgery. Our goal is to explore the association between MMA and postoperative opioid use and pain control in patients undergoing major head and neck surgery. We performed a retrospective study in adult (age 18 years) patients undergoing primary head and neck cancer resection with free-flap reconstruction. All patients were treated using an established care pathway. The baseline group was treated between January 2015–December 2015 (n = 41), prior to the implementation of MMA, and were compared to an MMA-treated cohort treated between December 2017–June 2019 (n = 97). The primary outcome was the proportion of opioids prescribed and oral morphine equivalents (OMEs) consumed during the hospitalization. The secondary outcome was pain control. We found that the post-MMA group consumed fewer opioids in the postoperative period compared to the pre-MMA group. Prior to post-operative day (POD) 6, pain control was better in the post-MMA group; however, the pain control lines intersect on POD 6 and the pre-MMA group appeared to have better pain control from PODs 7–10. In conclusion, our data suggest MMA is an effective method of pain control and opioid reduction in patients undergoing surgery for head and neck cancer with free flap reconstruction. MMA use was associated with a significant decrease in the quantity of opioids consumed postoperatively. The MMA protocol was associated with improved pain management early in the postoperative course. Finally, the MMA protocol is a feasible method of pain control and may reduce the adverse side effects associated with opioid use.
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