Low-intensity noise exposure takes an essential part in the mechanism of late-onset hereditary hearing loss caused by Abcc1 mutation.

With the development of the social economy, we are exposed to increasing noise in our daily lives. Our previous work found an ABCC1(NM_004996.3:c.A1769G, NP_004987.2:p.N590S) variant which cosegregated with the patients in an autosomal dominant non-syndromic hearing loss family. At present, the specific mechanism of deafness caused by ABCC1 mutation is still not clear. Using the knock-in mouse model simulating human ABCC1 mutation, we found that the occurrence of family-related phenotypes was likely attributed to the combination of the mouse genotype and low-intensity noise. GSH and GSSG are important physiological substrates of ABCC1. The destruction of GSH-GSSG balance in the cochleae of both Abcc1N591S/+ mice and Abcc1N591S/N591S mice during low-intensity noise exposure may result in irreversible damage to the hair cells of the cochleae, consequently leading to hearing loss in mice. The findings offered a potential novel idea for the prevention and management of hereditary hearing loss within this family.

Prenatal triphenyl phosphate exposure impairs placentation and induces preeclampsia-like symptoms in mice.

Triphenyl phosphate (TPhP) is an organophosphate flame retardant that is widely used in many commercial products. The United States Environmental Protection Agency has listed TPhP as a priority compound that requires health risk assessment. We previously found that TPhP could accumulate in the placentae of mice and impair birth outcomes by activating peroxisome proliferator-activated receptor gamma (PPARγ) in the placental trophoblast. However, the underlying mechanism remains unknown. In this study, we used a mouse intrauterine exposure model and found that TPhP induced preeclampsia (PE)-like symptoms, including new on-set gestational hypertension and proteinuria. Immunofluorescence analysis showed that during placentation, PPARγ was mainly expressed in the labyrinth layer and decidua of the placenta. TPhP significantly decreased placental implantation depth and impeded uterine spiral artery remodeling by activating PPARγ. The results of the in vitro experiments confirmed that TPhP inhibited extravillous trophoblast (EVT) cell migration and invasion by activating PPARγ and inhibiting the PI3K-AKT signaling pathway. Overall, our data demonstrated that TPhP could activate PPARγ in EVT cells, inhibit cell migration and invasion, impede placental implantation and uterine spiral artery remodeling, then induce PE-like symptom and impair birth outcomes. Although the exposure doses used in this study was several orders of magnitude higher than human daily intake, our study highlights the placenta as a potential target organ of TPhP worthy of further research.

Triphenyl phosphate interferes with the synthesis of steroid hormones through the PPARγ/CD36 pathway in human trophoblast JEG-3 cells.

Triphenyl phosphate (TPhP), a chemical commonly found in human placenta and breast milk, has been shown to disturb the endocrine system. Our previous study confirmed that TPhP could accumulate in the placenta and interference with placental lipid metabolism and steroid hormone synthesis, as well as induce endoplasmic reticulum (ER) stress through PPARγ in human placental trophoblast JEG-3 cells. However, the molecular mechanism underlying this disruption remains unknown. Our study aimed to identify the role of the PPARγ/CD36 pathway in TPhP-induced steroid hormone disruption. We found that TPhP increased lipid accumulation, total cholesterol, low- and high-density protein cholesterol, progesterone, estradiol, glucocorticoid, and aldosterone levels, and genes related to steroid hormones synthesis, including 3ßHSD1, 17ßHSD1, CYP11A, CYP19, and CYP21. These effects were largely blocked by co-exposure with either a PPARγ antagonist GW9662 or knockdown of CD36 using siRNA (siCD36). Furthermore, an ER stress inhibitor 4-PBA attenuated the effect of TPhP on progesterone and glucocorticoid levels, and siCD36 reduced ER stress-related protein levels induced by TPhP, including BiP, PERK, and CHOP. These findings suggest that ER stress may also play a role in the disruption of steroid hormone synthesis by TPhP. As our study has shed light on the PPARγ/CD36 pathway's involvement in the disturbance of steroid hormone biosynthesis by TPhP in the JEG-3 cells, further investigations of the potential impacts on the placental function and following birth outcome are warranted.

Triphenyl phosphate disturbs placental tryptophan metabolism and induces neurobehavior abnormal in male offspring.

Epidemiological studies have shown that prenatal triphenyl phosphate (TPhP) exposure is related to abnormal neurobehavior in children. However, the neurodevelopmental toxicity of TPhP in mammals is limited. To study the neurodevelopmental toxicity of TPhP in mammals and investigate the underlying mechanism, we used a mouse intrauterine TPhP exposure model. We measured the inflammatory factors (IL-6, TNFα) and NFκB levels, and tryptophan metabolism in placentae, detected the fetal brain transcriptome, hippocampal neuron development and neurobehavioral in the male offspring. The results showed that the protein level of IL-6, TNFα and NFκB in the placenta of the TPhP treatment group (1, 5 mg/kg) were significantly increased. Change of the protein level of these pro-inflammatory factors in maternal serum or fetal brain was not observed. Expression of genes along tryptophan-serotonin metabolism pathway were significantly decreased. While, the concentration of 5-HT levels in the placenta or fetal brain were significantly increased. Consistent with the increased 5-HT, the Nissl body was reduced in the hippocampus of treatment group. The expression of serotonergic neuron gene markers including Tph2, Htr1A, Htr2A, Pet1 and Lmx1b in the hippocampus of treatment group was significantly decreased. The neurobehavioral test showed that TPhP decreased center time that represent anxiety-like behavior, and reduced learning and memory in male offspring. Meanwhile, expression of genes along tryptophan-kynurenine metabolism pathway were significantly increased. The result of the transcriptome analysis of fetal brain showed that the differentially expressed genes are mainly involved in the transcription regulation of DNA as a template in the nucleus, and the enriched pathways are mainly signal pathways regulated by axon guidance and neurotrophic factors, dopaminergic and cholinergic synapses, suggest that not only serotonergic neuronal was affected. Overall, this study demonstrates that TPhP has the potential to induce placental inflammatory response in the placenta, disturb placental tryptophan metabolism, compromise the neuronal development and synaptic transmission, and cause abnormal neurobehavior in male offspring.

Establishment of a risk index for early complications after trans-canal endoscopic ear surgery.

PURPOSE: This study aimed to determine the risk factors associated with early postoperative complications of trans-canal endoscopic ear surgery (TEES), then to develop a risk index. MATERIALS AND METHODS: This single-institution retrospective study reviewed TEESs from January 1, 2017, to December 31, 2019 in a tertiary hospital. In the derivation cohort, univariable and multivariable logistic regression were performed to identify factors significantly associated with early postoperative complications of TEES. Then these parameters were integrated into a trans-canal endoscopic ear surgery risk index (TEESRI). The performance of TEESRI was compared with that of the American Society of Anesthesiologists (ASA) classification using the validation cohort. RESULTS: 932 TEESs were enrolled in total and 151 (16.2%) developed early postoperative complications. In the derivation set, 8 factors including state of the opposite ear and presence of nasal or pharyngeal diseases were found to be independently associated with the occurrence of early postoperative complications on multivariable regression analysis [area under the curve (AUC), 0.806; 95% confidence interval (CI), 0.765-0.848]. Using the validation cohort, the AUC of the TEESRI was 0.776 [95%CI, 0.711-0.842], with a sensitivity of 82.2% and specificity of 65.5%, while the AUC of the ASA classification was 0.512 (95%CI, 0.421-0.603). The TEESRI outperformed the ASA classification when evaluating the risk for early postoperative complications of TEES. CONCLUSIONS: Based on the 8 risk factors, the TEESRI was established with satisfactory predicting capacity. Surgeons should pay extra attention to the risk factors in the TEESRI, when treating patients.

Does the public feel prepared to be substitute decision-makers? Gaps in preparedness and support for a high school curriculum: a national survey.

BACKGROUND: Substitute decision-makers (SDMs) make decisions on behalf of patients who do not have capacity, in line with previously expressed wishes, values and beliefs. However, miscommunications and poor awareness of previous wishes often lead to inappropriate care. Increasing public preparedness to communicate on behalf of loved ones may improve care in patients requiring an SDM. METHODS: We conducted an online survey in January 2019 with a representative sample of the Canadian population. The primary outcome was self-reported preparedness to be an SDM. The secondary outcome was support for a high school curriculum on the role of SDMs. The effect of socio-demographics, known enablers and barriers to acting as an SDM, and attitudes towards a high school curriculum were assessed using multivariate analysis. RESULTS: Of 1,000 participants, 53.1% felt prepared to be an SDM, and 75.4% stated they understood their loved one's values. However, only 55.6% reported having had a meaningful conversation with their loved one about values and wishes, and only 61.7% reported understanding the SDM role. Engagement in advance care planning for oneself was low (23.1%). Age, experience, training and comfort with communication were associated with preparedness in our multivariate analysis. A high school curriculum was supported by 61.1% of respondents, with 28.3% neutral and 10.6% against it. INTERPRETATION: There is a gap between perceived and actual preparedness to be an SDM. Many report understanding their loved one's values yet have not asked them about wishes in illness or end of life. The majority of respondents support high school education to improve preparedness.

Impact of physician-based palliative care delivery models on health care utilization outcomes: A population-based retrospective cohort study.

BACKGROUND: Increasing involvement of palliative care generalists may improve access to palliative care. It is unknown, however, if their involvement with and without palliative care specialists are associated with different outcomes. AIM: To describe physician-based models of palliative care and their association with healthcare utilization outcomes including: emergency department visits, acute hospitalizations and intensive care unit (ICU) admissions in last 30 days of life; and, place of death. DESIGN: Population-based retrospective cohort study using linked health administrative data. We used descriptive statistics to compare outcomes across three models (generalist-only palliative care; consultation palliative care, comprising of both generalist and specialist care; and specialist-only palliative care) and conducted a logistic regression for community death. SETTING/PARTICIPANTS: All adults aged 18-105 who died in Ontario, Canada between April 1, 2012 and March 31, 2017. RESULTS: Of the 231,047 decedents who received palliative services, 40.3% received generalist, 32.3% consultation and 27.4% specialist palliative care. Across models, we noted minimal to modest variation for decedents with at least one emergency department visit (50%-59%), acute hospitalization (64%-69%) or ICU admission (7%-17%), as well as community death (36%-40%). In our adjusted analysis, receipt of a physician home visit was a stronger predictor for increased likelihood of community death (odds ratio 9.6, 95% confidence interval 9.4-9.8) than palliative care model (generalist vs consultation palliative care 2.0, 1.9-2.0). CONCLUSION: The generalist palliative care model achieved similar healthcare utilization outcomes as consultation and specialist models. Including a physician home visit component in each model may promote community death.

Removal efficiencies and risk assessment of endocrine-disrupting chemicals at two wastewater treatment plants in South China.

Endocrine-disrupting chemicals (EDCs) in the effluent from wastewater treatment plants (WWTPs) are an important pollutant sources of the aquatic system. In this study, the removal efficiencies of eight typical EDCs at two domestic WWTPs in Dongguan City, China, are reported based on instrumental analysis and bioassay results. Bioactivities, including steroidogenesis-disrupting effects, estrogen receptor (ER)-binding activity, and aryl hydrocarbon receptor (AhR)-binding activity were evaluated using the H295R, MVLN, and H4IIE cell bioassays, respectively. The potential environmental risks of these residual EDCs were also evaluated. The results of instrumental analysis showed that nonylphenol was the major chemical type present among the eight tested EDCs. Meanwhile, concentrations of estrogen compounds including estrone, 17ß-estradiol (E2), estriol, 17α-ethinyl estradiol, and diethylstilbestrol were relatively low. The removal rates of all eight EDCs were relatively high. Although the chemical analysis indicated high removal efficiency, the bioassay results showed that steroidogenesis-disrupting effects as well as ER-binding and AhR-binding activities remained, with E2-equivalent values of effluent samples ranging from 0.16 to 0.9 ng·L-1, and 2,3,7,8-tetrachlorodibenzo-p-dioxin-equivalent values ranging from 0.61 to 4.09 ng L-1. Principal component analysis combined with regression analysis suggests that the chemicals analyzed in this study were partly responsible for these ER and AhR activities. Ecological risk assessment of the residual EDCs showed that estrone was the most hazardous chemical among the eight EDCs tested, with a risk quotient of 1.44-5.50. Overall, this study suggests that, despite high apparent removal efficiencies of typical EDCs, their bioactivities and potential ecological risks cannot be ignored.

ABCC1 deficiency potentiated noise-induced hearing loss in mice by impairing cochlear antioxidant capacity.

The ABCC1 gene belongs to the ATP-binding cassette membrane transporter superfamily, which plays a crucial role in the efflux of various endogenous and exogenous substances. Mutations in ABCC1 can result in autosomal dominant hearing loss. However, the specific roles of ABCC1 in auditory function are not fully understood. Through immunofluorescence, we found that ABCC1 was expressed in microvascular endothelial cells (ECs) of the stria vascularis (StV) in the murine cochlea. Then, an Abcc1 knockout mouse model was established by using CRISPR/Cas9 technology to elucidate the role of ABCC1 in the inner ear. The ABR threshold did not significantly differ between WT and Abcc1-/- mice at any age studied. After noise exposure, the ABR thresholds of the WT and Abcc1-/- mice were significantly elevated. Interestingly, after 14 days of noise exposure, ABR thresholds largely returned to pre-exposure levels in WT mice but not in Abcc1-/- mice. Our subsequent experiments showed that microvascular integrity in the StV was compromised and that the number of outer hair cells and the number of ribbons were significantly decreased in the cochleae of Abcc1-/- mice post-exposure. Besides, the production of ROS and the accumulation of 4-HNE significantly increased. Furthermore, StV microvascular ECs were cultured to elucidate the role of ABCC1 in these cells under glucose oxidase challenge. Notably, 30 U/L glucose oxidase (GO) induced severe oxidative stress damage in Abcc1-/- cells. Compared with WT cells, the ROS and 4-HNE levels and the apoptotic rate were significantly elevated in Abcc1-/- cells. In addition, the reduced GSH/GSSG ratio was significantly decreased in Abcc1-/- cells after GO treatment. Taken together, Abcc1-/- mice are more susceptible to noise-induced hearing loss, possibly because ABCC1 knockdown compromises the GSH antioxidant system of StV ECs. The exogenous antioxidant N-acetylcysteine (NAC) may protect against oxidative damage in Abcc1-/- murine cochleae and ECs.

Epidemiologic approaches to evaluating the potential for human papillomavirus type replacement postvaccination.

Currently, 2 vaccines exist that prevent infection by the genotypes of human papillomavirus (HPV) responsible for approximately 70% of cervical cancer cases worldwide. Although vaccination is expected to reduce the prevalence of these HPV types, there is concern about the effect this could have on the distribution of other oncogenic types. According to basic ecological principles, if competition exists between ≥2 different HPV types for niche occupation during natural infection, elimination of 1 type may lead to an increase in other type(s). Here, we discuss this issue of "type replacement" and present different epidemiologic approaches for evaluation of HPV type competition. Briefly, these approaches involve: 1) calculation of the expected frequency of coinfection under independence between HPV types for comparison with observed frequency; 2) construction of hierarchical logistic regression models for each vaccine-targeted type; and 3) construction of Kaplan-Meier curves and Cox models to evaluate sequential acquisition and clearance of HPV types according to baseline HPV status. We also discuss a related issue concerning diagnostic artifacts arising when multiple HPV types are present in specific samples (due to the inability of broad-spectrum assays to detect certain types present in lower concentrations). This may result in an apparent increase in previously undetected types postvaccination.

Endoscopist specialty is associated with colonoscopy quality.

BACKGROUND: Some studies have shown that endoscopist specialty is associated with colorectal cancers missed by colonoscopy. We sought to examine the relationship between endoscopist specialty and polypectomy rate, a colonoscopy quality indicator. Polypectomy rate is defined as the proportion of colonoscopies that result in the removal of one or more polyps. METHODS: A cross-sectional study was conducted of endoscopists and their patients from 7 Montreal and 2 Calgary endoscopy clinics. Eligible patients were aged 50-75 and covered by provincial health insurance. A patient questionnaire assessed family history of colorectal cancer, history of large bowel conditions and symptoms, and previous colonoscopy. The outcome, polypectomy status, was obtained from provincial health administrative databases. For each city, Bayesian hierarchical logistic regression was used to estimate the odds ratio for polypectomy comparing surgeons to gastroenterologists. Model covariates included patient age, sex, family history of colorectal cancer, colonoscopy indication, and previous colonoscopy. RESULTS: In total, 2,113 and 538 colonoscopies were included from Montreal and Calgary, respectively. Colonoscopies were performed by 38 gastroenterologists and 6 surgeons in Montreal, and by 31 gastroenterologists and 5 surgeons in Calgary. The adjusted odds ratios comparing surgeons to gastroenterologists were 0.48 (95% CI: 0.32-0.71) in Montreal and 0.73 (95% CI: 0.43-1.21) in Calgary. CONCLUSIONS: An association between endoscopist specialty and polypectomy was observed in both cities after adjusting for patient-level covariates. Results from Montreal suggest that surgeons are half as likely as gastroenterologists to remove polyps, while those from Calgary were associated with a wide, non-significant Bayesian credible interval. However, residual confounding from patient-level variables is possible, and further investigation is required.

Developing model-based algorithms to identify screening colonoscopies using administrative health databases.

BACKGROUND: Algorithms to identify screening colonoscopies in administrative databases would be useful for monitoring colorectal cancer (CRC) screening uptake, tracking health resource utilization, and quality assurance. Previously developed algorithms based on expert opinion were insufficiently accurate. The purpose of this study was to develop and evaluate the accuracy of model-based algorithms to identify screening colonoscopies in health administrative databases. METHODS: Patients aged 50-75 were recruited from endoscopy units in Montreal, Quebec, and Calgary, Alberta. Physician billing records and hospitalization data were obtained for each patient from the provincial administrative health databases. Indication for colonoscopy was derived using Bayesian latent class analysis informed by endoscopist and patient questionnaire responses. Two modeling methods were used to fit the data, multivariate logistic regression and recursive partitioning. The accuracies of these models were assessed. RESULTS: 689 patients from Montreal and 541 from Calgary participated (January to March 2007). The latent class model identified 554 screening exams. Multivariate logistic regression predictions yielded an area under the curve of 0.786. Recursive partitioning using the latent outcome had sensitivity and specificity of 84.5% (95% CI: 81.5-87.5) and 63.3% (95% CI: 59.7-67.0), respectively. CONCLUSIONS: Model-based algorithms using administrative data failed to identify screening colonoscopies with sufficient accuracy. Nevertheless, the approach of constructing a latent reference standard against which model-based algorithms were evaluated may be useful for validating administrative data in other contexts where there lacks a gold standard.

Feasibility of a call-in centre to deliver colorectal cancer screening in primary care.

OBJECTIVE: To evaluate the feasibility of a call-in centre to deliver colorectal cancer (CRC) screening in primary care through self-administered fecal occult blood testing (FOBT). DESIGN: Four-month intervention study (September 2010 to January 2011) with randomly selected follow-up interviews. SETTING: The family medicine clinics of 3 hospitals in Montreal, Que. PARTICIPANTS: Letters from doctors invited their patients to contact the call-in centre (N = 761). Eligible patients agreeing to FOBT were sent testing kits that could be returned by mail (N = 100). Randomly selected patients (N = 36) were interviewed to explore the reasons why they did not contact the call-in centre, or why they did or did not adhere to FOBT. MAIN OUTCOME MEASURES: Feasibility was assessed by the proportions of patients who contacted the call-in centre, who were eligible for FOBT, and who adhered to FOBT; and by the time between invitation mail-out and contact with the call-in centre, initial telephone contact and receipt of the signed consent form, and FOBT kit mail-out and receipt of the kit by the laboratory. Hierarchical logistic regression evaluated the effect of patient characteristics on feasibility indicators, adjusting for clustering by physician and centre. RESULTS: Of 761 patients (61.6% female, mean age 61.0 years), 250 (32.9%) contacted the call-in centre, of whom 100 (40.0%) were eligible for and consented to FOBT; 62 (62.0%) of these patients adhered to FOBT. Median (interquartile range) time from invitation mail-out to call-in centre contact was 21 (7 to 29) days, from initial telephone contact to receipt of the signed consent form was 24 (10 to 38) days, and from FOBT kit mail-out to receipt at the laboratory was 23 (18 to 32) days. With the exception of previous cancer diagnosis, patient characteristics were not associated with feasibility indicators. Of the 115 (46.0%) patients determined to be ineligible for FOBT screening, 111 (96.5%) were up to date with or already scheduled for screening. CONCLUSION: Feasibility of the call-in centre was demonstrated. Targeting screening-eligible individuals or coupling a call-in service with another evidence-based CRC screening improvement strategy might further improve uptake of fecal testing.

Novel ZnFe2O4/BC/ZnO photocatalyst for high-efficiency degradation of tetracycline under visible light irradiation.

Developing broad-spectrum light reactions, effective charge separation, and easily recoverable photocatalysts were considered cost-effective pollution remediation methods. The ZnFe2O4/BC/ZnO composite was prepared to achieve these objectives, where biochar (BC) was used as a conductive channel and ZnFe2O4 as a magnetic substance. Among them, the 0.6-ZBO composite performed the best, with photocatalytic removal of tetracycline (TC) reaching 85.6%. The photocatalytic degradation rated constant of 0.6-ZBO composite was 23.36 × 10-3 min-1, which was 7.6, 4.1, and 2.5 times higher than that of ZnFe2O4/BC, ZnO, and ZnFe2O4/ZnO samples, respectively. According to several characterization data, it was demonstrated that successful Z-scheme heterojunctions were constructed between ZnFe2O4 and ZnO. The 0.6-ZBO complex increased the range of light absorption and strengthened the separation of electron-hole pairs, thus improving the redox ability of the complex. In the different water matrices, the stability of 0.6-ZBO was excellent and its ability to remove TC decreased slightly to about 11% after 5 cycles. This work provided a valuable approach to design a novel and efficient system for degrading organic pollutants in wastewater using magnetic biochar.

Gestation and lactation triphenyl phosphate exposure disturbs offspring gut microbiota in a sex-dependent pathway.

Triphenyl phosphate (TPhP) is an Organophosphate flame retardant (OPFR) that has been widely used in many commercial products. Following its widely usage, its health risk has been concerned. In this study, mice were exposed to TPhP (1 mg/kg) during pregnancy and lactation (E0-PND21), the effect of TPhP on gut microbiota and its role in TPhP mediated lipid metabolism disturbance of offspring was investigated. Our results showed that TPhP disturbed the gut microbiota in dam or offspring at different extent, with male offspring experiencing major effects. Both the composition, abundance or network of gut microbiome was affected in male offspring. In male offspring, expression of genes along gut-liver axis including FXR, CYP7A1, SREBP-1c and ChREBP was significantly up-regulated, and expression of SHP, FGF15 and ASBT was significantly down-regulated. Consistent with this, lipid accumulation in the liver, and increased level of triglyceride, total cholestrol and total bile acid in the serum was observed. The changed abundance of Ruminococcaceae, Clostridiaceae, and Bacteroidaceae shows strong correlation with disturbed lipid metabolism in male offspring. Our research showed that indirect TPhP exposure during early life stage could affect the gut microbiota and gene expression along gut-liver axis in offspring at sex-dependent pathways, with males experiencing more effects.

Short-term effects of intravenous batroxobin in treatment of sudden sensorineural hearing loss: a propensity score-matched study.

Background: Sudden sensorineural hearing loss (SSNHL) can cause great panic in patients. Whether it is advantageous to add intravenous batroxobin in the treatment of SSNHL remains to be determined. This study aimed to compare the short-term efficacy of therapy combined with intravenous batroxobin and that without intravenous batroxobin in SSNHL patients. Methods: This retrospective study harvested the data of SSNHL patients hospitalized in our department from January 2008 to April 2021. The hearing levels on the admitted day (before treatment) and the discharge day were considered pre-treatment hearing and post-treatment hearing, respectively. The hearing gain was the difference value of pre-treatment hearing and post-treatment hearing. We used Siegel's criteria and the Chinese Medical Association of Otolaryngology (CMAO) criteria to evaluate hearing recovery. The complete recovery rate, overall effective rate, and hearing gain at each frequency were considered outcomes. Propensity score matching (PSM) was conducted to balance the baseline characteristics between the batroxobin group and the non-batroxobin group. Sensitivity analysis was carried out in flat-type and total-deafness SSNHL patients. Results: During the study period, 657 patients with SSNHL were admitted to our department. Among them, a total of 274 patients met the enrolled criteria of our study. After PSM, 162 patients (81 in each group) were included in the analysis. Once the hospitalized treatment was completed, the patients would be discharged the next day. Logistic regression analysis of the propensity score-matched cohort indicated that both the complete recovery rates [Siegel's criteria, OR: 0.734, 95% CI: 0.368-1.466, p = 0.381; CMAO criteria, OR: 0.879, 95% CI: 0.435-1.777, p = 0.720] and the overall effective rates [Siegel's criteria and CMAO criteria, OR: 0.741, 95% CI: 0.399-1.378, p = 0.344] were not significantly different between the two treatment groups. Sensitivity analysis has shown similar results. For flat-type and total-deafness SSNHL patients, no significant difference was found in post-treatment hearing gain at each frequency between the two groups after PSM. Conclusion: There was no significant difference in short-term hearing outcomes between treatment with batroxobin and treatment without batroxobin in SSNHL patients by Siegel's and CMAO criteria after PSM. Future studies for better therapy regimens of SSNHL are still needed.

Susceptibility of immature spiral ganglion neurons to aminoglycoside-induced ototoxicity is mediated by the TRPV1 channel in mice.

Aminoglycoside antibiotics are among the most common agents that can cause sensorineural hearing loss. From clinical experience, premature babies, whose inner ear is still developing, are more susceptible to aminoglycoside-induced ototoxicity, which is echoed by our previous study carried out in organotypic cultures. This study aimed to investigate whether a nonselective cation channel, TRPV1, contributes to the susceptibility of immature spiral ganglion neurons (SGNs) to the damage caused by aminoglycosides. Through western blotting and immunofluorescence, we found that the TRPV1 expression levels were much higher in immature SGNs than in their mature counterparts. In postnatal day 7 cochlear organotypic cultures, AMG-517 reduced reactive oxygen species generation and inhibited SGN apoptosis under aminoglycoside challenge. However, in adult mice, AMG-517 did not ameliorate the ABR threshold increase at high frequencies (16 kHz and 32 kHz) after aminoglycoside administration, and the SGNs within the cochleae had no morphological changes. By further regulating the function of TRPV1 in primary cultured SGNs with its inhibitor AMG-517 and agonist capsaicin, we demonstrated that TRPV1 is a major channel for aminoglycoside uptake: AMG-517 can significantly reduce, while capsaicin can significantly increase, the uptake of GTTR. In addition, TRPV1 knockdown in SGNs can also significantly reduce the uptake of GTTR. Taken together, our results demonstrated that aminoglycosides can directly enter immature SGNs through the TRPV1 channel. High expression of TRPV1 contributes to the susceptibility of immature SGNs to aminoglycoside-induced damage. The TRPV1 inhibitor AMG-517 has the potential to be a therapeutic agent for preventing aminoglycoside-induced ototoxicity in immature SGNs.

Different screening definitions have little impact on polypectomy rate estimates.

BACKGROUND: Polypectomy rate is a surrogate quality indicator for screening colonoscopy. Various methods for identifying screening colonoscopies have been used and it is unclear how different definitions affect the estimated polypectomy rate. OBJECTIVE: To estimate polypectomy rates and how they vary according to the definition of a screening colonoscopy, using patient- and endoscopist-reported indications. METHODS: A cross-sectional analysis of endoscopists and their patients 50 to 75 years of age who underwent colonoscopy was conducted. Based on questionnaire responses, four patient indications were derived: perceived screening; perceived nonscreening; medical history indicating nonscreening; and combination of the three indications. Endoscopist indication was derived from a questionnaire completed immediately after colonoscopy. Polypectomy status was obtained from provincial physician billing records. Polypectomy rates were computed, while accounting for physician and hospital level clustering, using all four patient indications, endoscopist indication, and the agreement between patient and endoscopist indications. The effect of indications on polypectomy rate was estimated adjusting for age, sex and family history of colorectal cancer. RESULTS: A total of 2134 patients and 45 endoscopists were included. The proportion of colonoscopies classified as screening according to the nine indications ranged from 32.2% to 70.9%. Polypectomy rates ranged between 22.6% and 26.2% for screening colonoscopy, and between 27.1% and 30.8% for nonscreening colonoscopy. Adjusted ORs for indication ranged between 0.74 and 0.94. DISCUSSION: Although the proportion of colonoscopies identified as screening varied considerably among the indications, the estimated polypectomy rates were similar. CONCLUSION: The findings suggest that the way screening is defined does not greatly affect the estimates of polypectomy rate.

Rate of serious complications of colonoscopy in Quebec.

BACKGROUND: The rate of serious complications is one marker of the quality of colonoscopy services. OBJECTIVE: To estimate the rate of serious complications of colonoscopy according to colonoscopy indication and polypectomy status. METHODS: A prospective cohort study of patients scheduled for colonoscopy who were recruited from seven endoscopy facilities across Montreal (Quebec) was conducted. Before colonoscopy, patients completed a brief questionnaire and provided their health insurance numbers. Colonoscopy indication was based on patient-reported medical history. Polypectomy status was obtained from provincial physician billing records (Régie de l'assurance maladie du Québec). Diagnoses and procedures associated with hospitalization in the 30 days following colonoscopy were obtained from the provincial hospitalization database (MedEcho). RESULTS: Of the 2134 patients enrolled (mean age 60.9 years, 50.1% male), 33 (1.55% [95% CI 1.06% to 2.16%]) were hospitalized within 30 days. One patient experienced bleeding following a colonoscopy that involved polypectomy and was diagnosed with carcinoma in situ of the rectum. Based on self-reported rectal bleeding in the previous six months, the colonoscopy was nonscreening. The provincial hospitalization data showed no occurrences of perforation, diverticulitis, myocardial infarction/stroke or death; thus, the rate of serious colonoscopy complications was 0.05% (95% CI 0.00% to 0.26%). DISCUSSION: The rate of serious colonoscopy complications requiring hospitalization was low and comparable with what is reported in the literature. The serious complication occurred subsequent to polypectomy and in a nonscreening colonoscopy. CONCLUSION: The findings support the relative safety of screening colonoscopy in persons without large bowel diseases and symptoms. However, future research to determine the rate of serious complications not requiring hospitalization is warranted to reassure decision makers of the safety of colonoscopy for colorectal cancer screening.

Report on the expert forum on using information technology to facilitate uptake and impact of colorectal cancer screening guidelines.

The present report summarizes the proceedings of the pan-Canadian Expert Forum on Using Information Technology to Facilitate Uptake and Impact of Colorectal Cancer Screening Guidelines, which was held in Montreal, Quebec, November 18 to 19, 2011. The meeting assembled a multidisciplinary group of family physicians, gastroenterologists, nurses, patients, foundation representatives, screening program administrators and researchers to discuss the development of a mechanism or strategy that would permit the collection of comparable data by all colorectal cancer (CRC) screening programs, which would not only support the needs of each program but also provide a national perspective. The overarching theme of the meeting was 'designing a national approach to computerized electronic data collection and dissemination for CRC screening that would improve knowledge transfer across the continuum of preventive health care'. The forum encouraged presentations on clinical, research and technical topics. The meeting fostered valuable cross-disciplinary communication and delivered the message that it is essential to develop a national health informatics approach for CRC screening data collection and dissemination to support provincial CRC screening programs.