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Background: The risks associated with medications and co-medications for chronic pain (CP) can influence a physician's choice of drugs and dosages, as well as a patient's adherence to the medication. High-quality care requires patients to participate in medication decisions. This study aimed to compare perceived risks of medications and co-medications between physicians and persons living with CP., Methods: This cross-sectional survey conducted in Quebec, Canada, included 83 physicians (snowball sampling) and 141 persons living with CP (convenience sampling). Perceived risks of adverse drug reaction of pain medications and co-medications were assessed using 0-10 numerical scales (0 = no risk, 10 = very high risk). An arbitrary cutoff point of 2-points was used to ease the interpretation of our data. Physicians scored the 36 medication subclasses of the Medication Quantification Scale 4.0 (MQS 4.0) through an online survey, while CP patients scored the medication subclasses they had taken in the last three months through telephone interviews., Results: Persons living with CP consistently perceived lower risks of adverse drug reaction compared to physicians. For eight subclasses, the difference in the mean perceived risk score was > 2 points and statistically significant (p < 0.05): non-specific oral NSAIDs, acetaminophen in combination with an opioid, short-acting opioids, long-acting opioids, tricyclic antidepressants, antipsychotics, benzodiazepines, and medical cannabis., Conclusions: Divergent risk perceptions between physicians and patients underscore the necessity of facilitating a more extensive discussion on medications and co-medications risks to empower patients to make informed decisions and participate in shared decision-making regarding their treatments., Competing Interests: Declarations. Ethics approval and consent to participate: Our research was conducted in accordance with the ethical principles of Canada’s Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, a policy informed by international ethics norms. Ethical approval was obtained from the Research Ethics Board of Université du Québec in Abitibi-Témiscamingue (#2020-01–Diallo, M.A.). Informed consent to participate was obtained from all participants. The physicians provided electronic informed consent via an online questionnaire, and the patients provided electronic consent via email with an attached consent letter. This consent was also reconfirmed orally at the beginning of the telephone questionnaire. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Abstract: Treatment of chronic pain should be multimodal and include pharmacological, physical, and psychological treatments. However, because various barriers to physical and psychological treatments (PPTs) exist, a better understanding of biopsychosocial factors leading to their use is relevant. This study aimed to explore the association between gender identity, gender-stereotyped personality traits, and the use of PPTs in chronic pain management. The ChrOnic Pain trEatment cohort, a self-reported data infrastructure resulting from a web-based recruitment of 1935 people living with chronic pain (Quebec, Canada) was analyzed. Gender identity was operationalized as women, men, and nonbinary. Gender-stereotyped personality traits were measured using the Bem Sex-Role Inventory (feminine, masculine, androgynous, undifferentiated). A checklist of 31 types of PPTs that can be used for chronic pain management was presented to participants (yes/no). From the 1433 participants, 85.5% reported using at least one PPT. Hot-cold therapies (43.4%), exercise (41.9%), and meditation (35.2%) were the most frequently used PPTs, but most popular PPTs were not the same among women and men. Women reported a significantly higher use of PPTs in general (87.2% vs 77.2%; P < 0.001). Multivariable and interaction analyses showed that identifying as a man decreased the odds of reporting the use of PPTs (odds ratio: 0.32, 95% confidence interval: 0.11-0.92) but only among participants who scored high on both masculine and feminine personality traits (those classified as androgynous). The high prevalence of PPTs use found in our study is positive. Our results are relevant for a more personalized promotion of PPTs for chronic pain management., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Objective: Where a person lives is a recognized socioeconomic determinant of health and influences healthcare access. This study aimed to compare the pain treatment profile of persons with chronic pain (CP) living in remote regions to those living in non-remote regions (near or in major urban centers)., Methods: A cross-sectional study was performed among persons living with CP across Quebec. In a web-based questionnaire, participants were asked to report in which of the 17 administrative regions they were living (six considered "remote"). Pain treatment profile was drawn up using seven variables: use of prescribed pain medications, over-the-counter pain medications, non-pharmacological pain treatments, multimodal approach, access to a trusted healthcare professional for pain management, excessive polypharmacy (≥10 medications), and use of cannabis for pain., Results: 1,399 participants completed the questionnaire (women: 83.4%, mean age: 50 years, living in remote regions: 23.8%). As compared to persons living in remote regions, those living in non-remote regions were more likely to report using prescribed pain medications (83.8% vs. 67.4%), a multimodal approach (81.5% vs. 75.5%), experience excessive polypharmacy (28.1% vs. 19.1%), and report using cannabis for pain (33.1% vs. 20.7%) (bivariable p  < 0.05). Only the use of prescribed medications as well as cannabis remained significantly associated with the region of residence in the multivariable models., Discussion: There are differences in treatment profiles of persons with CP depending on the region they live. Our results highlight the importance of considering remoteness, and not only rurality, when it comes to better understanding the determinants of pain management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Audet, Zerriouh, Nguena Nguefack, Julien, Pagé, Guénette, Blais and Lacasse.)

Shunt-dependent hydrocephalus (HC) is a common sequela following aneurysmal subarachnoid hemorrhage (aSAH). However, there is still poor evidence regarding the optimal timing of ventriculoperitoneal shunt (VPS) placement, particularly in the context of early aSAH-associated complications such as delayed cerebral ischemia (DCI). The purpose of this study was to compare the impact of early (< 21 days after aSAH) versus late (≥ 21 days after aSAH) VPS placement on the functional clinical outcome. We retrospectively analyzed data from 82 patients with VPS placement after aSAH enrolled in our institutional database between 2011 and 2021. We compared two groups, early VPS placement (< 21 days after aSAH) versus late VPS placement (≥ 21 days after aSAH) in terms of demographics, SAH grading, radiological parameters, externalized cerebrospinal fluid diversions, DCI, VPS variables, and functional outcome. We identified 53 patients with early and 29 patients with late VPS implantation. Baseline variables, such as the modified Rankin Scale (mRS), the World Federation of Neurological Surgeons Scale, the Glasgow Coma Scale, and Fisher grade were not significantly different between the groups. Postoperatively, the mRS (p = 0.0037), the Glasgow Outcome Scale (p = 0.0037), and the extended Glasgow Outcome Scale (p = 0.0032) showed significantly better functional results in patients with early cerebrospinal fluid diversion. The rate of DCI did not differ significantly between the groups (p = 0.53). There was no difference in the rate of VPS placement associated complications (p = 0.44) or overall mortality (p = 0.39). Early shunt implantation, within 21 days after aSAH and therefore during the timeframe of possible DCI, might not be harmful in patients developing HC after aSAH., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Over the past 25 years, we have demonstrated the feasibility of airway bioengineering using stented aortic matrices experimentally then in a first-in-human trial (n = 13). The present TRITON-01 study analyzed all the patients who had airway replacement at our center to confirm that this innovative approach can be now used as usual care. For each patient, the following data were prospectively collected: postoperative mortality and morbidity, late airway complications, stent removal and status at last follow-up on November 2, 2021. From October 2009 to October 2021, 35 patients had airway replacement for malignant (n = 29) or benign (n = 6) lesions. The 30-day postoperative mortality and morbidity rates were 2.9% (n = 1/35) and 22.9% (n = 8/35) respectively. At a median follow-up of 29.5 months (range 1-133 months), 27 patients were alive. There have been no deaths directly related to the implanted bioprosthesis. Eighteen patients (52.9%) had stent-related granulomas requiring a bronchoscopic treatment. Ten among 35 patients (28.6%) achieved a stent free survival. The actuarial 2- and 5-year survival rates (Kaplan-Meier estimates) were respectively 88% and 75%. The TRITON-01 study confirmed that airway replacement using stented aortic matrices can be proposed as usual care at our center. Clinicaltrials.gov Identifier: NCT04263129., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Traumatic brain injuries (TBIs) still put a high burden on public health worldwide. Medical and surgical treatment strategies are continuously being studied, but the role and indications of primary decompressive craniectomy (DC) remain controversial. In medically refractory intracranial hypertension after severe traumatic brain injury, secondary decompressive craniectomy is a last resort treatment option to control intracranial pressure (ICP). Randomized controlled studies have been extensively performed on secondary decompressive craniectomy and its role in the management of severe traumatic brain injuries. Indications, prognostic factors, and long-term outcomes in primary decompressive craniectomy during the evacuation of an epidural, subdural, or intracerebral hematoma in the acute phase are still a matter of ongoing research and controversy to this day. Prospective trials have been designed, but the results are yet to be published. In isolated epidural hematoma without underlying brain injury, osteoplastic craniotomy is likely to be sufficient. In acute subdural hematoma (ASDH) with relevant brain swelling and preoperative CT signs such as effaced cisterns, overly proportional midline-shift compared to a relatively small acute subdural hematoma, and accompanying brain contusions as well as pupillary abnormalities, intraventricular hemorrhage, and coagulation disorder, primary decompressive craniectomy is more likely to be of benefit for patients with traumatic brain injury. The role of intracranial pressure monitoring after primary decompressive craniectomy is recommended, but prospective trials are pending. More refined guidelines and hopefully class I evidence will be established with the ongoing trials: randomized evaluation of surgery with craniectomy for patients undergoing evacuation of acute subdural hematoma (RESCUE-ASDH), prospective randomized evaluation of decompressive ipsilateral craniectomy for traumatic acute epidural hematoma (PREDICT-AEDH), and pragmatic explanatory continuum indicator summary (PRECIS)., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Jost et al.)

Introduction: Recently, targeted therapies using BRAFV600E and MEK inhibitors (dabrafenib and trametinib, respectively) have been recommended in BRAF-mutated anaplastic thyroid carcinoma (ATC). Considering the fast development of ATC, droplet digital PCR (ddPCR) performed on fine-needle aspirate (FNA), which is a rapid, reliable, and low-cost method, appears interesting for the detection of BRAFV600E mutation in these patients and allows early initiation of targeted therapies., Results: In our two patients, both presenting extensive cervical masses inaccessible to surgery, ddPCR results were available in less than 24 h. Therefore, dabrafenib and trametinib were started only a few days after first contact., Conclusions: We suggest that ddPCR on FNA be used in non-resectable cervical masses for rapid BRAFV600E mutation detection in the hope that starting targeted therapies early might improve outcomes.

Background: Medical cannabis has been legal in Canada since 2001, and recreational cannabis was legalized in October 2018, which has led to a widespread increase in the accessibility of cannabis products., Aims: This study aimed to estimate the prevalence of cannabis use among adults living with chronic pain (CP) and investigate the relationship between age and cannabis use for CP management., Methods: A cross-sectional analysis of the COPE Cohort data set, a large Quebec sample of 1935 adults living with CP, was conducted. Participants completed a web-based questionnaire in 2019 that contained three yes/no questions about past-year use of cannabis (i.e., for pain management, management of other health-related conditions, recreational purposes)., Results: Among the 1344 participants who completed the cannabis use section of the questionnaire, the overall prevalence of cannabis use for pain management was 30.1% (95% confidence interval 27.7-32.7). Differences were found between age groups, with the highest prevalence among participants aged ≤26 years (36.5%) and lowest for those aged ≥74 years (8.8%). A multivariable logistic model revealed that age, region of residence, generalized pain, use of medications or nonpharmacological approaches for pain management, alcohol/drug consumption, and smoking were associated with the likelihood of using cannabis for pain management., Conclusions: Cannabis is a common treatment for the management of CP, especially in younger generations. The high prevalence of use emphasizes the importance of better knowledge translation for people living with CP, rapidly generating evidence regarding the safety and efficacy of cannabis, and clinicians' involvement in supporting people who use cannabis for pain management., Competing Interests: Marimée Godbout-Parent holds a Canadian Institutes of Health Research (CIHR) master’s degree scholarship. Adriana Angarita-Fonseca holds an FRQS postdoctoral scholarship. M. Gabrielle Pagé has a Junior 1 research scholarship from the FRQS and received honoraria from Canopy Growth for work unrelated to this study. Lucie Blais received research grants from AstraZeneca, TEVA, and Genentech, as well as consultation fees from AstraZeneca, TEVA, and Genentech for projects unrelated to this study. Anaïs Lacasse holds a Junior 2 research scholarship from the FRQS in partnership with the Quebec SUPPORT Unit (Support for People and Patient-Oriented Research and Trials). She leads the Chronic Pain Epidemiology Laboratory, which is funded by the Fondation de l’Université du Québec en Abitibi-Témiscamingue (FUQAT), in partnership with local businesses: the Pharmacie Jean-Coutu de Rouyn-Noranda (community pharmacy) and Glencore Fonderie Horne (copper smelter). All other authors have no conflicts of interest to report., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Hepatitis B virus has infected a third of the world's population, and 296 million people are living with chronic infection. Chronic infection leads to progressive liver disease, including hepatocellular carcinoma and liver failure, and there remains no reliable curative therapy. These gaps in our understanding are due, in large part, to a paucity of animal models of HBV infection. Here, we show that rhesus macaques regularly clear acute HBV infection, similar to adult humans, but can develop long-term infection if immunosuppressed. Similar to patients, we longitudinally detected HBV DNA, HBV surface antigen, and HBV e antigen in the serum of experimentally infected animals. In addition, we discovered hallmarks of HBV infection in the liver, including RNA transcription, HBV core and HBV surface antigen translation, and covalently closed circular DNA biogenesis. This pre-clinical animal model will serve to accelerate emerging HBV curative therapies into the clinic., (© 2022. The Author(s).)

The cameras in modern gaze-tracking systems suffer from fundamental bandwidth and power limitations, constraining data acquisition speed to 300 Hz realistically. This obstructs the use of mobile eye trackers to perform, e.g., low latency predictive rendering, or to study quick and subtle eye motions like microsaccades using head-mounted devices in the wild. Here, we propose a hybrid frame-event-based near-eye gaze tracking system offering update rates beyond 10,000 Hz with an accuracy that matches that of high-end desktop-mounted commercial trackers when evaluated in the same conditions. Our system, previewed in Figure 1, builds on emerging event cameras that simultaneously acquire regularly sampled frames and adaptively sampled events. We develop an online 2D pupil fitting method that updates a parametric model every one or few events. Moreover, we propose a polynomial regressor for estimating the point of gaze from the parametric pupil model in real time. Using the first event-based gaze dataset, we demonstrate that our system achieves accuracies of 0.45°-1.75° for fields of view from 45° to 98°. With this technology, we hope to enable a new generation of ultra-low-latency gaze-contingent rendering and display techniques for virtual and augmented reality.

Camera sensors rely on global or rolling shutter functions to expose an image. This fixed function approach severely limits the sensors' ability to capture high-dynamic-range (HDR) scenes and resolve high-speed dynamics. Spatially varying pixel exposures have been introduced as a powerful computational photography approach to optically encode irradiance on a sensor and computationally recover additional information of a scene, but existing approaches rely on heuristic coding schemes and bulky spatial light modulators to optically implement these exposure functions. Here, we introduce neural sensors as a methodology to optimize per-pixel shutter functions jointly with a differentiable image processing method, such as a neural network, in an end-to-end fashion. Moreover, we demonstrate how to leverage emerging programmable and re-configurable sensor-processors to implement the optimized exposure functions directly on the sensor. Our system takes specific limitations of the sensor into account to optimize physically feasible optical codes and we evaluate its performance for snapshot HDR and high-speed compressive imaging both in simulation and experimentally with real scenes.

Purpose: Occupational safety and health (OSH) professionals are often the point of contact for health and safety policies derived in the workplace, and the handling of incidents in their aftermath. As chronic pain affects 20% of people, many pain-awareness campaigns and educational activities target healthcare professionals. However, initiatives directed toward OSH professionals are also important to aid in prevention and rehabilitation efforts. The objective of this study was to describe knowledge and attitudes of OSH students with regard to chronic pain. Methods: A web-based cross-sectional study was conducted amongst a convenience sample of 88 students enrolled in the distance learning OSH undergraduate certificate program at the Université du Québec en Abitibi-Témiscamingue (Quebec, Canada). Results: Although 30% of students were already employed within OSH or human resources and 40% reported intervening in cases involving chronic pain in their line of work, 56% of respondents had received no training on chronic pain and its treatment in the past five years. Only 14% chose to take the optional 45 hr course dedicated to pain within the program. OSH students also exhibited poorer knowledge and more negative attitudes toward people suffering from chronic pain when compared to other groups assessed in the province of Quebec, including healthcare professionals, chronic pain patients, and people not suffering from chronic pain ( p ≤0.0002). Half of the respondents (51.9%) were not aware that chronic pain affects 1 in 5 adults. Conclusion: Our study demonstrates a need for pain education within OSH training programs and through continuing education., Competing Interests: This study was supported by the Fondation de l’Université du Québec en Abitibi-Témiscamingue (FUQAT). The authors report no further conflicts of interest in this work.

Background and Aims: Cardiovascular diseases (CVD) increase late morbidity and mortality in survivors of acute lymphoblastic leukaemia (ALL). We compared the risk of CVD in ALL survivors to siblings, examined time trends, quantified treatment-related risks, and investigated whether risk extends beyond patients treated with anthracyclines and chest radiotherapy., Methods: The Swiss Childhood Cancer Survivor Study assessed CVD by patient questionnaire in 5-year ALL survivors diagnosed between 1976 and 2005 and their siblings. Participants were asked whether a physician had ever told them that they had hypertension, arrhythmia, heart failure, myocardial infarction, angina pectoris, stroke, thrombosis or valvular problems. We investigated treatment-related risk factors for CVD using multivariable logistic regression, adjusting for demographic and socioeconomic factors, BMI, smoking, diabetes mellitus, alcohol consumption and physical activity., Results: We contacted 707 survivors and 1299 siblings, 511 (72%) and 709 (55%) of whom responded, respectively. Survivors had a higher risk of developing CVD than siblings (odds ratio [OR] 1.9, 95% confidence interval 1.3&ndash;2.8), in particular heart failure (OR 13.9, 1.8&ndash;107.4). Compared to patients treated 1976&ndash;85, the risk of CVD was 1.4 (0.7&ndash;2.8) for those treated 1985&ndash;1994 and 1.5 (0.6&ndash;3.7) for those treated 1995&ndash;2005. The overall CVD risks after anthracycline treatment (OR 3.1, 2.0&ndash;4.7), haematopoietic stem cell transplantation (OR 8.0, 2.4&ndash;26.9) or relapse (OR 4.1, 1.9&ndash;8.8) were increased compared to those of siblings, while the CVD risks of survivors treated without anthracycline or chest radiotherapy were similar (OR 1.0; 0.5&ndash;2.0)., Conclusions: Despite attempts to reduce cardiotoxicity in childhood cancer treatment, CVD risks in ALL survivors treated more recently do not seem to have declined.

Oncogene-induced replication stress (RS) promotes cancer development but also impedes tumor growth by activating anti-cancer barriers. To determine how cancer cells adapt to RS, we have monitored the expression of different components of the ATR-CHK1 pathway in primary tumor samples. We show that unlike upstream components of the pathway, the checkpoint mediators Claspin and Timeless are overexpressed in a coordinated manner. Remarkably, reducing the levels of Claspin and Timeless in HCT116 cells to pretumoral levels impeded fork progression without affecting checkpoint signaling. These data indicate that high level of Claspin and Timeless increase RS tolerance by protecting replication forks in cancer cells. Moreover, we report that primary fibroblasts adapt to oncogene-induced RS by spontaneously overexpressing Claspin and Timeless, independently of ATR signaling. Altogether, these data indicate that enhanced levels of Claspin and Timeless represent a gain of function that protects cancer cells from of oncogene-induced RS in a checkpoint-independent manner.

Ultraviolet (UV) induces distorting lesions to the DNA that can lead to stalling of the RNA polymerase II (RNAP II) and that are removed by transcription-coupled nucleotide excision repair (TC-NER). In humans, mutations in the TC-NER genes CSA and CSB lead to severe postnatal developmental defects in Cockayne syndrome patients. In Caenorhabditis elegans, mutations in the TC-NER genes csa-1 and csb-1, lead to developmental growth arrest upon UV treatment. We conducted a genetic suppressor screen in the nematode to identify mutations that could suppress the developmental defects in csb-1 mutants. We found that mutations in the ERK1/2 MAP kinase mpk-1 alleviate the developmental retardation in TC-NER mutants, while constitutive activation of the RAS-MAPK pathway exacerbates the DNA damage-induced growth arrest. We show that MPK-1 act via insulin/insulin-like signaling pathway and regulates the FOXO transcription factor DAF-16 to mediate the developmental DNA damage response.

Purpose of Review: The goal of this review is to evaluate the global supply and demand of opioids used for pain management and discuss how it relates to the utilization of opioids around the world. The purpose of the review is also to determine the factors that contribute to inappropriate pain management., Recent Findings: The total global production of opium for opioid manufacturing is enough to supply the growing global demands. However, licit opioids are only consumed by 20% of the world population. Most people throughout the world had no access to opioid analgesics for pain relief in case of need. Opioid misuse and abuse is not only a phenomena plague by the USA but globally across many countries. Many countries have a lack of availability of opioids, contributing factors being strict government regulations limiting access, lack of knowledge of the efficacy of opioid analgesics in treating acute and chronic pain and palliative care, and the stigma that opioids are highly addictive. For the countries in which opioids are readily available and prescribed heavily, diversion, misuse, abuse, and the resurgence of heroin have become problems leading to morbidity and mortality. It is pertinent to find a balance between having opioids accessible to patients in need, with ensuring that opioids are regulated along with other illicit drugs to decrease abuse potential.

Purpose: Aboriginal people in Canada are disproportionately affected by chronic illnesses, compared to non-Aboriginal Canadians. The purpose of this review was to determine whether differences exist between the two groups with respect to chronic non-cancer pain (CNCP) in order to better inform clinical practice and to identify research gaps., Data Sources: Four electronic databases were searched for the period of 1990-2015., Study Selection: Only English and French language original studies that examined CNCP prevalence, assessment tools and beliefs among Aboriginal people in Canada were considered., Data Extraction: Data extracted included Aboriginal group, geographic location, study setting and pain definition (for prevalence studies only)., Results of Data Synthesis: A total of 11 studies matched the selection criteria: 10 reported estimates of chronic pain prevalence among Aboriginal people in Canada, 1 was about a culturally adapted pain assessment tool, and no study was found about CNCP beliefs within Aboriginal people., Conclusion: CNCP among Aboriginal people is still a largely unexplored research field. The limited evidence available so far does not allow us to conclude that CNCP affects a higher proportion of Aboriginal than non-Aboriginal people in Canada. However, arthritis, a specific condition associated with chronic pain, is more prevalent in Aboriginal than non-Aboriginal people. Additional research is needed on other CNCP types and conditions. Furthermore, pain assessment tools are not culturally adapted and clinicians should inquire more about the beliefs of Aboriginal patients to make them feel safer and to better target interventions.

Objectives: The aim of the study was to stimulate the vagal and the recurrent laryngeal nerves during and after thyroidectomy or parathyroidectomy, to record muscle responses, interpret the electrophysiological modifications and identify prognostic factors for postoperative vocal fold mobility., Patients and Methods: A prospective study monitored 151 vagal nerves and 144 recurrent laryngeal nerves in 114 patients. Seven patients (14 vagal nerves) underwent continuous monitoring via an automatic periodic stimulation (APS ® ) electrode. In 15 patients (21 vagal nerves), the stimulation threshold was studied. Muscle response was recorded on direct vagal and/or recurrent laryngeal nerve stimulation by a monopolar electrode or direct repeated stimulation via an electrode on the vagal nerve. In case of signal attenuation on the first operated side, surgery was not extended to the contralateral side., Results: The vagal nerve stimulation checked inferior laryngeal nerve integrity and recurrent status, without risk of false negatives. The vagal nerve stimulation threshold, before and after dissection, that induced a muscle response of at least 100μV ranged from 0.1 to 0.8mA. Similarity between pre- and post-dissection responses to supramaximal stimulation, defined as 1mA, on the one hand, and between post-dissection vagal and laryngeal recurrent nerve responses on the other correlated with normal postoperative vocal cord mobility. Conversely, muscle response attenuation below 100μV and increased latency indicated a risk of vocal fold palsy., Conclusion: Vagal nerve stimulation allows suspicion or elimination of lesions on the inferior laryngeal nerve upstream of the stimulation point and detection of non-recurrent inferior laryngeal nerve. Intermittent monitoring assesses nerve function at the moment of stimulation, while continuous monitoring detects the first signs of nerve injury liable to induce postoperative recurrent nerve palsy. When total thyroidectomy is indicated, signal attenuation on the first operated side casts doubt on continuing surgery to the contralateral side in the same step., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Few studies have been conducted to explore physicians' prescription practices and attitudes toward the use of cannabinoids in Canada.We measured the prevalence and identified determinants of cannabinoid prescription for the management of chronic noncancer pain among physicians in southwestern Quebec., Methods: In February 2013, we conducted a postal survey using a modified Dillman method that involved physicians practising in the Abitibi-Témiscamingue region of Quebec. We used multivariate logistic regression models to identify determinants of cannabinoid prescription., Results: A total of 166 physicians of 318 practising in the region participated in the survey (response rate 52.2%). The prevalence of cannabinoid prescription was 27.3% (45/165) for any indication and 23.0% (38/165) for the management of chronic noncancer pain; 91.1% (41/45) of the physicians prescribed cannabinoids to 5 or fewer patients. Of the 38 physicians who prescribed cannabinoids for chronic noncancer pain, 35 (92.1%) prescribed nabilone, 7 (18.4%) medical marijuana and 2 (5.3%) nabiximols. The principal determinant of cannabinoid prescription was the physician's level of comfort with prescribing cannabinoids (adjusted odds ratio 1.25, 95% confidence interval 1.01-1.55, per 1-point increase in comfort level measured on 10-point scale). Respondents reported that continuing medical education (CME) activities could increase their comfort level. They also indicated a need for guidelines or algorithms that included cannabinoid use as well as more studies about the efficacy and safety of cannabinoids for the management of chronic noncancer pain., Interpretation: We found that cannabinoids were not often prescribed for the management of chronic noncancer pain and that survey respondents were not comfortable with prescribing this drug class. This degree of discomfort could be addressed by CME activities, more effective dissemination of guidelines and more evidence regarding cannabinoid use for the management of chronic noncancer pain.

The automatic reconstruction of neurons from stacks of electron microscopy sections is an important computer vision problem in neuroscience. Recent advances are based on a two step approach: First, a set of possible 2D neuron candidates is generated for each section independently based on membrane predictions of a local classifier. Second, the candidates of all sections of the stack are fed to a neuron tracker that selects and connects them in 3D to yield a reconstruction. The accuracy of the result is currently limited by the quality of the generated candidates. In this paper, we propose to replace the heuristic set of candidates used in previous methods with samples drawn from a conditional random field (CRF) that is trained to label sections of neural tissue. We show on a stack of Drosophila melanogaster neural tissue that neuron candidates generated with our method produce 30% less reconstruction errors than current candidate generation methods. Two properties of our CRF are crucial for the accuracy and applicability of our method: (1) The CRF models the orientation of membranes to produce more plausible neuron candidates. (2) The interactions in the CRF are restricted to form a bipartite graph, which allows a great sampling speed-up without loss of accuracy.

DNA combing is a powerful method developed by Bensimon and colleagues to stretch DNA molecules on silanized glass coverslips. This technique provides a unique way to monitor the activation of replication origins and the progression of replication forks at the level of single DNA molecules, after incorporation of thymidine analogs, such as 5-bromo-2'-deoxyuridine (BrdU), 5-iodo-2'-deoxyuridine (IdU) and 5-chloro-2'-deoxyuridine (CldU) in newly-synthesized DNA. Unlike microarray-based approaches, this assay gives access to the variability of replication profiles in individual cells. It can also be used to monitor the effect of DNA lesions on fork progression, arrest and restart. In this review, we propose standard DNA combing methods to analyze DNA replication in budding yeast and in human cells. We also show that 5-ethynyl-2'-deoxyuridine (EdU) can be used as a good alternative to BrdU for DNA combing analysis, as unlike halogenated nucleotides, it can be detected without prior denaturation of DNA., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to stimulate the recurrent laryngeal nerve during thyroidectomy or parathyroidectomy and to record the muscle responses in an attempt to predict postoperative vocal fold mobility., Patients and Methods: Intraoperative recurrent laryngeal nerve monitoring during general anaesthesia was performed by using an electrode-bearing endotracheal tube (nerve integrity monitor EMG endotracheal tube [Medtronic Xomed, Jacksonville, Flo, USA]). Two hundred and fifteen recurrent laryngeal nerves from 141 patients undergoing total thyroidectomy (n=74), hemithyroidectomy (n=63), or parathyroidectomy (n=4) were prospectively monitored. In each case, the muscle potential was recorded after stimulation of the recurrent laryngeal nerve by a monopolar probe., Results: The nerve stimulation threshold before and after dissection that induced a muscle response of at least 100 μV ranged from 0.1 to 0.85 mA (mean 0.4 mA). The supramaximal stimulation intensity was defined as 1 mA. The amplitude of muscle response varied considerably from one patient to another, but the similarity of the muscle response at supramaximal intensity between pre- and postdissection and between postdissection at the proximal and distal exposed portions of the nerve was correlated with normal postoperative vocal fold function. Inversely, alteration of the muscle response indicated a considerable risk of recurrent laryngeal nerve palsy, but was not predictive of whether or not this lesion would be permanent., Conclusions: Recurrent laryngeal nerve monitoring with a system using surface electrodes is a simple, non-invasive technique that is just as sensitive as monitoring by intramuscular electrodes. Monitoring is helpful for initial nerve identification and is useful to determine nerve function during and after surgery, and to adapt the surgical strategy accordingly., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: The boreal forest of Canada is home to several hundred thousands Aboriginal people who have been using medicinal plants in traditional health care systems for thousands of years. This knowledge, transmitted by oral tradition from generation to generation, has been eroding in recent decades due to rapid cultural change. Until now, published reviews about traditional uses of medicinal plants in boreal Canada have focused either on particular Aboriginal groups or on restricted regions. Here, we present a review of traditional uses of medicinal plants by the Aboriginal people of the entire Canadian boreal forest in order to provide comprehensive documentation, identify research gaps, and suggest perspectives for future research., Methods: A review of the literature published in scientific journals, books, theses and reports., Results: A total of 546 medicinal plant taxa used by the Aboriginal people of the Canadian boreal forest were reported in the reviewed literature. These plants were used to treat 28 disease and disorder categories, with the highest number of species being used for gastro-intestinal disorders, followed by musculoskeletal disorders. Herbs were the primary source of medicinal plants, followed by shrubs. The medicinal knowledge of Aboriginal peoples of the western Canadian boreal forest has been given considerably less attention by researchers. Canada is lacking comprehensive policy on harvesting, conservation and use of medicinal plants. This could be explained by the illusion of an infinite boreal forest, or by the fact that many boreal medicinal plant species are widely distributed., Conclusion: To our knowledge, this review is the most comprehensive to date to reveal the rich traditional medicinal knowledge of Aboriginal peoples of the Canadian boreal forest. Future ethnobotanical research endeavours should focus on documenting the knowledge held by Aboriginal groups that have so far received less attention, particularly those of the western boreal forest. In addition, several critical issues need to be addressed regarding the legal, ethical and cultural aspects of the conservation of medicinal plant species and the protection of the associated traditional knowledge.

Cullin 4 (Cul4)-based ubiquitin ligases emerged as critical regulators of DNA replication and repair. Over 50 Cul4-specific adaptors (DNA damage-binding 1 (Ddb1)-Cul4-associated factors; DCAFs) have been identified and are thought to assemble functionally distinct Cul4 complexes. Using a live-cell imaging-based RNAi screen, we analysed the function of DCAFs and Cul4-linked proteins, and identified specific subsets required for progression through G1 and S phase. We discovered C6orf167/Mms22-like protein (Mms22L) as a putative human orthologue of budding yeast Mms22, which, together with cullin Rtt101, regulates genome stability by promoting DNA replication through natural pause sites and damaged templates. Loss of Mms22L function in human cells results in S phase-dependent genomic instability characterised by spontaneous double-strand breaks and DNA damage checkpoint activation. Unlike yeast Mms22, human Mms22L does not stably bind to Cul4, but is degraded in a Cul4-dependent manner and upon replication stress. Mms22L physically and functionally interacts with the scaffold-like protein Nfkbil2 that co-purifies with histones, several chromatin remodelling and DNA replication/repair factors. Together, our results strongly suggest that the Mms22L-Nfkbil2 complex contributes to genome stability by regulating the chromatin state at stalled replication forks.

The Rad52 pathway has a central function in the recombinational repair of chromosome breaks and in the recovery from replication stress. Tolerance to replication stress also depends on the Mec1 kinase, which activates the DNA replication checkpoint in an Mrc1-dependent manner in response to fork arrest. Although the Mec1 and Rad52 pathways are initiated by the same single-strand DNA (ssDNA) intermediate, their interplay at stalled forks remains largely unexplored. Here, we show that the replication checkpoint suppresses the formation of Rad52 foci in an Mrc1-dependent manner and prevents homologous recombination (HR) at chromosome breaks induced by the HO endonuclease. This repression operates at least in part by impeding resection of DNA ends, which is essential to generate 3' ssDNA tails, the primary substrate of HR. Interestingly, we also observed that the Mec1 pathway does not prevent recombination at stalled forks, presumably because they already contain ssDNA. Taken together, these data indicate that the DNA replication checkpoint suppresses genomic instability in S phase by blocking recombination at chromosome breaks and permitting helpful recombination at stalled forks.

The main goal of this project was to identify the presence of fibromyalgia (FM) subgroups using a simple and frequently used clinical tool, the Fibromyalgia Impact Questionnaire (FIQ). A total of 61 women diagnosed with FM participated in this study. FM subgroups were created by applying a hierarchical cluster analysis on selected items of the FIQ (pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms). We also tested for group differences on experimental pain, psychosocial functioning and demographic characteristics. Two cluster profiles best fit our data. FM-Type I was characterized by the lowest levels of anxiety, depressive and morning tiredness symptoms, while FM-Type II was characterized by elevated levels of pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms. Both FM subgroups showed hyperalgesic responses to experimental pain. These results suggest that pain and stiffness are universal symptoms of the disorder but that psychological distress is a feature present only in some patients.

Background: Measurement of mid-gestation cervix length has become a common screening tool for preterm birth. Our study was designed to assess the value of cervix length and serum relaxin in the prediction of spontaneous preterm birth at < 35 and < 37 weeks' gestation in a general obstetric population., Methods: A prospective cohort of women with a singleton pregnancy had blood collected at 24 and 28 weeks' gestation for determination of serum relaxin immediately before transvaginal ultrasound measurement of cervical length. Patients and referring physicians were blinded to cervix length and relaxin levels to preclude changes in management. The primary outcomes were spontaneous delivery at < 35 and < 37 weeks' gestation., Results: A total of 1004 women entered the study. Delivery data were not available for 20 women who delivered elsewhere. Twenty women were excluded because preterm delivery was undertaken because of pregnancy abnormalities. Of the 964 women with known gestational age at delivery, 46 (4.8%) delivered at < 37 weeks and 16 (1.7%) at < 35 weeks' gestation. Mean cervix length at 28 weeks (36.7 +/- 7.3 mm) was significantly shorter than at 24 weeks (37.8 +/- 7.1 mm) (P < 0.001). Cervix length at 24 and 28 weeks' gestation was equally predictive of preterm birth. A cervix length of < or = 30 mm at 28 weeks had a sensitivity of 57.1%, a specificity of 81.8%, and a positive predictive value of 4.5% for birth at < 35 weeks. Serum relaxin levels were not correlated with cervix length at either 24 or 28 weeks. Serum relaxin at 24 and 28 weeks' gestation was not associated with preterm birth before or after controlling for patient characteristics and cervix length., Conclusion: Serum relaxin levels at 24 and 28 weeks' gestation are not associated with preterm birth. Although cervix length is associated with preterm birth, its positive predictive value is low. Given the lack of proven therapies for those at risk, cervix length does not appear to be a useful screening tool for preterm delivery in the general obstetric population.

In previous reports, we have shown that PBI-1393 (formerly BCH-1393), N,N-Dimethylaminopurine pentoxycarbonyl D-arginine, stimulates cytotoxic T-lymphocyte (CTL) responses both in vitro and in vivo in normal immune status and immunosuppressed mice. Additionally, PBI-1393 was tested for anticancer activity in syngeneic mouse experimental tumor models and it displayed significant inhibition of tumor outgrowths when given in combination with sub-therapeutic doses of cytotoxic drugs (cyclophosphamide, 5-fluorouracil, doxorubicin and cis-platinum). However, the mechanism of action of PBI-1393 was still unknown. Here, we report that PBI-1393 enhances IL-2 and IFN-gamma production in human activated T cells by 51% and 46% respectively. PBI-1393 increases also IL-2 and IFN-gamma mRNA expression as shown by RT-PCR. The physiological relevance of IL-2 and IFN-gamma gene modulation by PBI-1393 is illustrated by the advantageous increase of T cell proliferation (39+/-0.3% above control) and human CTL response against prostate (PC-3) cancer cells (42+/-0.03%). The enhancement of human T cell proliferation and CTL activation by PBI-1393 demonstrates that this compound potentiates the immune response and in this regard, it could be used as an alternative approach to IL-2 and/or IFN-gamma therapy against cancer.

Objectives: Previous studies have shown a reduction of diffuse noxious inhibitory controls (DNICs) in elderly adults compared with younger adults. Unfortunately, little is known regarding the developmental course of DNIC deficits and so it is still unclear whether middle-aged adults also show a DNIC deficit. The aims of the present study were to better characterize the developmental time course of the change in DNIC response by adding a middle-aged group. The role of expectations was also investigated., Methods: The pain thresholds (PTs) of 20 young, 20 middle-aged, and 20 healthy elderly volunteers were assessed before and during a cold pressor task (water at 7 degrees C). Acute nociceptive stimuli were administered using a thermode and consisted of a range of painless and painful heat pulses., Results: Analyses showed that thermal PTs increase by middle age but that the DNIC-induced increase in PT dampens progressively with advancing age. DNIC response was negatively correlated with advancing age, however, expectations regarding DNIC efficacy did not vary with age. This suggests that age-related changes in the size of the DNIC response are not best explained by an age-related change in expectation., Discussion: The findings tell us that changes in pain perception and endogenous pain modulation arrive earlier than previously suggested. Studies on aging and pain should include a middle-aged group when comparing pain measures across the adult lifespan.

We previously developed a spatial summation model and demonstrated that spatial summation of pain involves the activation of both excitatory and inhibitory systems. The aim of this study was to determine whether the endogenous pain inhibitory systems recruited by the spatial summation model are opioid-mediated by verifying if they could be blocked by the opioid antagonist naloxone. Twenty healthy volunteers (10 men, 10 women) participated in a randomized, four-session, cross-over study. Each session consisted of pain perception ratings (visual analog scale) taken during the immersion of different surfaces of the arm in circulating noxious cold water (12 degrees C). The arm was arbitrarily divided into eight segments from fingertips to shoulder. Two sessions were increasing (from fingertips to shoulder) and two sessions were decreasing (from shoulder to fingertips). All sessions consisted of eight consecutive 2-min immersions separated by 5-min resting periods. Intravenous injections of naloxone hydrochloride (0.14 mg/kg) or saline (NaCl, 0.9%) were administered under double-blind conditions. We found that during the control session (saline injection) there was a significant difference in pain intensity ratings between the increasing and decreasing sessions. The decreasing session resulted in lower pain intensity. As previously demonstrated, this lowering of the perception curve seems to be due to a large recruitment of inhibitory systems at the beginning of the decreasing session as opposed to a gradual recruitment during the increasing session. However, during the opioid inhibition session (naloxone injection) no differences were found between the increasing and decreasing sessions. Naloxone inhibited the endogenous pain inhibitory systems activated by the spatial summation model, suggesting that these systems have an opioid-mediated component, as previously reported for diffuse noxious inhibitory controls.

The aim of this study was to evaluate the functional outcome of facial nerve repair with fibrin glue in end-to-end anastomosis and intermediate nerve graft. Thirty-six patients undergoing facial nerve repair by end-to-end anastomosis or facial nerve grafting using exclusively fibrin glue between 1986 and 1999 were included in this retrospective study. The population comprised ten vestibular schwannomas (28%), nine temporal bone fractures (25%), seven facial nerve schwannomas (19%), four facial nerve hemangiomas (11%), two iatrogenic facial nerve interruptions (6%) and four miscellaneous facial nerve lesions (11%). Data were reviewed concerning etiology, location of the nerve interruption, type of repair and postoperative facial function according to the repaired facial nerve recovery scale (A: normal; B: independent movements of eyelid and mouth; C: strong closure of eyelids and mouth; D: incomplete eyelid closure; E: minimal movement; F: no movement). Eleven patients (31%) underwent end-to-end nerve anastomosis and 25 (69%) underwent intermediate facial nerve grafting. The mean follow-up period was 50 months (range: 3-95). Among patients followed-up more than 18 months (n = 20), a score of B or C was obtained in 16 patients (80%), a score D in 2 cases (10%) and a score E in 2 cases (10%). The type of repair and the site of interruption did not influence the results. Fibrin glue is a simple, rapid and efficient means of facial nerve repair. In case of intraoperative facial nerve interruption, this type of repair can be attempted in any location at the time of the tumor removal.

A deficit of endogenous pain inhibitory systems has been suggested to contribute to some chronic pain conditions, one of them being fibromyalgia. The aim of the investigation was to test whether endogenous pain inhibitory systems were activated by a spatial summation procedure in 30 fibromyalgia, 30 chronic low back pain, and 30 healthy volunteers who participated in a cross-over trial (two sessions). Each session consisted of visual analog scale ratings of pain during the immersion of different surfaces of the arm in circulating noxious cold (12 degrees C) water. The arm was arbitrarily divided into eight segments from the fingertips to the shoulder. One session was ascending (from the fingertips to the shoulder) and the other was descending (from the shoulder to the fingertips); they included eight consecutive 2-min immersions separated by 5-min resting periods. For healthy and low back pain subjects, pain was perceived differently during the ascending and descending sessions (P=0.0001). The descending session resulted in lower pain intensity and unpleasantness. This lowering of the perception curve seems to be due to a full recruitment of inhibitory systems at the beginning of the descending session as opposed to a gradual recruitment during the ascending session. For fibromyalgia subjects, no significant differences were found between the increasing and decreasing sessions (P>0.05). These data support a deficit of endogenous pain inhibitory systems in fibromyalgia but not in chronic low back pain. The treatments proposed to fibromyalgia patients should aim at stimulating the activity of those endogenous systems.

Objective: To investigate a new method in teaching and supervising tooth and denture brushing activities by employing occupational therapy techniques., Materials and Methods: Sixty-one residents, 44 women and 17 men, with an average age of 85.7 +/- 6.6 years (range 72-97 years) living in a Long-Term Care home (LTC) in Geneva were enrolled in a randomised controlled trial. They were divided at random into experimental (EG) and control groups (CG) with matched age and sex distribution. Two subjects passed away during the 3-month experimental period. Following medical history, plaque scores and tooth brushing habits were evaluated within the context of a comprehensive clinical assessment. Furthermore, a Mini Mental State and a vision test were taken. Based on the results of these health assessments both the EG and the CG were divided into an 'assisted' (IA) and an 'independent' (II) subgroup. In the EG, tooth brushing was initially taught and in the IA monitored and re-educated once a week by an occupational therapist. In contrast, the CG-IA group received a weekly placebo activity such as manicure by the same person., Results: From the individual movements taught and monitored by the occupational therapist, opening a tube of toothpaste (n.s.) and denture brushing (p < 0.05) were performed more independently after 3 months. Both the occupational therapy and the placebo activity led to a significant improvement in oral (p < 0.01 and 0.05) and in denture hygiene (p < 0.001 and 0.05). From all participants, the EG-IA subgroup presented the most significant amelioration in plaque (p < 0.01) and denture hygiene scores (p < 0.001). This group consisted mostly of subjects with an impaired cognitive state., Conclusions: Despite the marked placebo effect, the results indicate that occupational therapy is particularly useful to improve the oral and denture hygiene in dependent and cognitively impaired LTC residents and may promote their autonomy in the execution of activities of daily life such as denture brushing.

The aim of this work was to investigate whether the Penh index, measured using whole body barometric plethysmography, can be used as a screening parameter to evaluate the airway reactivity and the intensity of the pulmonary response to endotoxins. Penh was firstly recorded in non-sedated freely moving piglets exposed (1) to a nebulized acetylcholine (Ach) pre-treated or not with clenbuterol, or (2) to endotoxin challenge. To measure Penh simultaneously with total pulmonary resistance (R(L)), dynamic compliance (C(dyn)) and intrapleural pressure changes (Max Delta Ppl), an oesophageal balloon catheter technique was used and the piglets were anaesthetised. The recordings were performed during (1) an intravenous metacholine (Mch) challenge and (2) in endotoxin-exposed animals. In freely moving animals, Ach induced a significant dose-dependent increase in Penh, which was significantly blocked by clenbuterol. Endotoxin instillation also resulted in a significant rise in Penh while the corresponding response measured under anaesthesia was significantly and positively correlated with R(L) and Max Delta Ppl. Similar results were obtained during Mch challenge but the Penh was negatively correlated with C(dyn). We conclude that Penh could be used in freely moving piglets as a screening index for airway reactivity and pulmonary functional changes in cholinergic and endotoxin challenges.

Hypothesis: This study investigates the function of the diastrophic dysplasia sulfate transporter (DTDST) in otosclerotic bone and the effect on it of sodium fluoride (NaF)., Background: Otosclerosis is a localized bone dystrophy with increased bone turnover. DTDST is implicated in the regulation of the bone turnover., Materials and Methods: Primary cultures of cells were obtained from the stapes and external auditory canal (EAC) of 26 patients with otosclerosis and from nine control patients. Sulfate uptake was quantified under basal conditions and with NaF. The NaF signaling pathways were investigated using forskolin and verapamil., Results: The relative initial rates of sulfate uptake and the apparent Vmax values were: otosclerotic stapes > EAC > control stapes = control EAC. The sulfate uptake by the otosclerotic stapes was correlated with the loss of sensorineural hearing. The amounts of DTDST mRNA (RNase protection assay) in the four subgroups did not differ. NaF (10(-6)M, 1 hr) inhibited sulfate uptake by the otosclerotic stapes and EAC cells but not by control samples., Conclusion: The authors believe that whether the increased DTDST activity is a cause or an effect of otosclerosis, it appears to be a specific target for NaF treatment.

Vanadate, an inhibitor of tyrosine phosphatases, has insulin-mimetic properties. It has been shown that acute vanadate administration enhances glucose uptake independently of phosphatidylinositol (PI) 3-kinase and p38 MAPK. However, therapeutic vanadate use requires chronic administration, and this could potentially involve a different signaling pathway(s). Thus, we examined the mechanisms by which chronic vanadate exposure (16 h) stimulates glucose uptake in primary cultures of adult cardiomyocytes. The effect of vanadate on the activation of insulin-signaling molecules was evaluated 60 min after its withdrawal and in the absence of insulin. We therefore evaluated the persistent effect of vanadate on the insulin-signaling cascade. Our results demonstrate that preincubation with low vanadate concentrations (25-75 microM) induces a dose-dependent increase in glucose uptake. The augmentation of this process was not due to alterations in GLUT1 or GLUT4 protein levels, transcription, or de novo protein synthesis. Chronic vanadate exposure was associated with activation of the insulin receptor, insulin receptor substrate-1 (IRS-1), PKB/Akt, and p38 MAPK. Furthermore, inhibition of PI 3-kinase or p38 MAPK by wortmannin and PD-169316, respectively, significantly inhibited vanadate-mediated glucose uptake in cardiomyocytes. Thus, over time, different (albeit overlapping) signaling cascades may be activated by vanadate.

Introduction: In thyroid diseases, the place of fine needle aspiration biopsy still continues to be discussed: the sensibility and specificity vary greatly in the literature. Frozen section diagnosis is necessary to form a diagnostic strategy. The objective of this study was compare the results of fine needle aspiration biopsy, frozen section diagnosis, and definitive histologic results in a population of 163 patients and to draw conclusions about treatment., Material and Method: From 1994 to 1999, 163 patients (132 females and, 31 males) undergoing thyroid surgery were included in this retrospective study, after a standard preoperative work-up. Those with a single palpable nodule and hypofixation on scintigraphy underwent fine needle aspiration before surgery. These results were compared with the definitive histologic results., Results: A loboisthmectomy was performed in 88 cases (54%), a subtotal thyroidectomy in 34 cases (21%), and a total thyrodectomy in 41 cases (25%). In the latter group, an associated neck dissection was performed in 18 cases (11%); a frozen section diagnosis was obtained in all cases of thyroid nodules. This study demonstrated a single nodule in 97 cases (60%), multiple nodules in 27 cases (17%), multinodular goitre in 34 cases (21%), and 5 Basedow diseases (3%). Sixty-two cases (38%) of thyroid nodules underwent fine needle aspiration before surgery. In 25 cases (15%), definitive pathology showed a malignant lesion. The frozen section diagnosis had a sensitivity of 73% and a specificity of 99%, and the fine needle aspiration biopsy had a sensitivity of 40% and a specificity of 100%., Conclusion: The authors propose fine needle aspiration biopsy in the following cases: a single palpable nodule and hypofixation on scintigraphy or a surgical contra indication; and direct surgery in symptomatic thyroid disease or if there are one or several full nodules > 2 cm. In near future, these indications will be modified with the increasing reliability of fine needle aspiration biopsy.

Type 1 and type 2 diabetic patients often show elevated plasma ketone body concentrations. Because ketone bodies compete with other energetic substrates and reduce their utilization, they could participate in the development of insulin resistance in the heart. We have examined the effect of elevated levels of ketone bodies on insulin action in primary cultures of adult cardiomyocytes. Cardiomyocytes were cultured with the ketone body beta-hydroxybutyrate (beta-OHB) for 4 or 16 h, and insulin-stimulated glucose uptake was evaluated. Although short-term exposure to ketone bodies was not associated with any change in insulin action, our data demonstrated that preincubation with beta-OHB for 16 h markedly reduced insulin-stimulated glucose uptake in cardiomyocytes. This effect is concentration dependent and persists for at least 6 h after the removal of beta-OHB from the media. Ketone bodies also decreased the stimulatory effect of phorbol 12-myristate 13-acetate and pervanadate on glucose uptake. This diminution could not be explained by a change in either GLUT-1 or GLUT-4 protein content in cardiomyocytes. Chronic exposure to beta-OHB was associated with impaired protein kinase B activation in response to insulin and pervanadate. These results indicate that prolonged exposure to ketone bodies altered insulin action in cardiomyocytes and suggest that this substrate could play a role in the development of insulin resistance in the heart.

Objective: To define factors predictive of outcome after ossiculoplasty in adults., Material and Methods: From 1992 to 1998, 220 ossiculoplasties were performed for chronic otitis media in 200 patients (100 men and 90 women), average age 53 years, age range 17 - 82 years. Ninety-four patients (47%) had not undergone prior surgery (99 ossiculoplasties) and 106 (53%) underwent revision procedures (121 ossiculoplasties). Average follow-up was 20 months. All patients were reexamined at consultations 3 and 12 months after surgery and 100 patients (50%) were reexamined at two years. The operations were classified in type II tympanoplasty when the patient presented a normal stapes (n=120), and a type III tympanoplasty when the stapes arch was absent (n=100). Perforations (n=200) were repaired by temporal aponeurosis in 160 cases (80%) and a tragal perichondrium in 40 cases (20%). The materials used included 23 incus autografts (10%), 105 hydroxyapatite composite Goldenberg prosthesis (48%), 55 all-hydroxyapatite Xomed prosthesis (25%) including 20 covered with a thinned tragal cartilage, 19 teflon Klein prosthesis (9%), 12 Ionos prosthesis (5%) and 6 Malleus prosthesis (3%). The results were analyzed from the microscopic aspect and audiometric data for frequencies 0,5 to 3 KHz., Results: Twenty prosthesis luxed or extruded (9%) within an average of 6 months, 15 (12.4%) after a revision procedure and 5 (5%, p<0,05) after an initial procedure. Fifteen perforations (15/200, 7.5%) occurred, 9 with temporal aponeurosis grafts (9/160, 5.6%) and 6 with perichondrium grafts (6/40, 15%, NS). The residual air-bone gap (ABG) was equal to 23 +/- 12,5 dB with 57% of ABG<20 dB at 12 months follow-up. The gain in air conduction was 14 +/- 16,5 dB and the change in air-bone gap 13 +/- 12,3 dB. Some factors could significantly improve functional results: presence of the stapes arch (n=120, p<0,05), first-intention procedure (n=99, p<0,05), and use of all-hydroxyapatite prosthesis in type II (p<0,05) or type III tympanoplasties., Conclusion: Ossiculoplasty with all-hydroxyapatite prosthesis produced satisfactory results in type II or III tympaonoplasties.

Auricular malformations are frequently associated to malformations of the external, the middle, and the inner ear in variable degrees. Asystematic audiometry must be performed in case of unilateral facial microsomia. This test which can be performed in very young patients can detect bilateral ear malformations necessitating auditory rehabilitation by surgery or external hearing aids. In major ear aplasia, air conduction hearing aids can rarely be proposed. In this case, bone conduction hearing aids using a mastoid transducer of through a bone anchored device yield the best auditory results with an excellent local tolerance.

Purpose of Study: The aim of this retrospective survey was to define factors which may influence tympanic grafts results., Methods: 260 surgical procedures were retrospectively analyzed between 1992 and 1997 by studying anatomical and functional results with a mean follow-up of 18 months., Results: Global rate of tympanic grafts reperforation was 9.2%. At 18 months, the air conduction gain was 9.5 +/- 11.5 dB, with an 13 +/- 7.7 dB air-bone gap (ABG) and 80% ABG inferior to 20 dB, the change in air bone gap was 9 +/- 10.3 dB. Several factors influencing the results were identified: second hand surgical procedures (40%) had worse functional results than patients from first hand procedures, inflammatory atrial mucosa or obstruction of the eustachian tube (more graft retraction), retracted malleus handle and/or stuck to the promontory (worse auditory results), temporal aponeurosis placed under malleus handle (more reperforation of the graft without hearing difference as to graft placement above malleus handle), association of canal wall-down technique (poor auditory results), surgeon experience (better auditory results)., Conclusion: A first surgical procedure, normal malleus handle and atrial mucosa, no mastoidectomy or canal wall-up technique, a temporal aponeurosis graft placed above malleus handle are predictive factors for anatomical and/or functional good results.

Objectives: In order to evaluate the results of tympanoplasty in one stage middle ear cholesteatoma surgery, a retrospective study of 180 consecutive cholesteatomas operated on was undertaken., Methods: 150 single procedures and 30 revision surgeries realized between 1992 and 1997 were analysed by studying anatomical and functional results with a mean follow-up of 24 months., Results: Among the 150 adult patients, 85 (57%) were previously operated on in other centres and presented a recurrence of cholesteatoma. Closed technique was performed in 110 cases (61%) and opened one in the remaining cases (41%). Ossiculoplasty was made in 101 cases (56%) with different materials (15 incus autografts, 14 teflon prosthesis, 35 hydroxyapatite (HA) composite prosthesis and 37 all in HA prosthesis): 91 cases in a one-stage procedure but 10 worse functional results required a closed revision procedure. Twenty cases were also revised after one year of follow up at least: six recurrences of cholesteatoma were operated on by using canal down mastoidectomy (4%), 14 limited residual cholesteatomas (9.3%) had a revision closed technique procedure. CT Scan followed up all the patients operated on by a closed technique. Postoperative air-bone gap (ABG) was 20 +/- 11.3 dB and 27 +/- 10.1 dB in closed and opened techniques, respectively (p < 0.05). ABG was 20 +/- 9.2 dB and 26 +/- 13 dB in type II and type III tympanoplasty, respectively (p < 0.05)., Conclusion: If the tympanic and posterior cavities are reasonably safe, middle ear cholesteatoma in adults can be well cured by a one-stage procedure including ossicular chain reconstruction with hydroxylapatite prosthesis covered with cartilage graft who achieved a valuable hearing restoration.

Gentamicin-induced nephrotoxicity varies temporally, with a peak being observed when this antibiotic is administered during the resting period and a trough when given during the activity period of rats. These nychthemeral variations are modified by fasting and by restricted feeding schedules. In this study, food and water intakes of adult female Sprague-Dawley rats were measured during pretreatment (Days 1 to 5) and during treatment (Days 6 to 10) with gentamicin (80 mg/kg/day, i.p.) injected at 1300 or 0100h. A significantly higher level of serum creatinine was observed when gentamicin was administered at 1300 h compared to 0100 h, and a significantly lower creatinine clearance was found in rats treated with gentamicin at 1300 h compared to those treated with saline at the same time. Gentamicin treatment at 1300 or 0100 h resulted in a decrease in the 24-h food intake. In addition, in the gentamicin-treated group at 0100 h, the maximal food intake observed at late dark during the pretreatment period decreased during treatment, and early dark rather than late dark maximal intake occurred. Our data demonstrate that gentamicin induces a nephrotoxicity that varies temporally, and that gentamicin treatment inhibits food intake and alters its nocturnal variations.