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Study Design: National Trauma Data Bank (NTDB) review and propensity-matched analysis., Objective: To evaluate differences in clinical outcomes by operative management., Summary of Background Data: Odontoid type II fractures are the most prevalent cervical fracture. Operative intervention on these fractures is frequently debated; surgical risks are compounded by clinical severity, patient age, and comorbidities., Methods: This registry review included index admissions for odontoid type II fractures [International Classification of Diseases (ICD)-10 codes beginning with S12.11] from 1/1/2017 to 1/1/2020; patients who died in the emergency department (ED) were excluded. Propensity score techniques were used to match patients 1:1 by surgical management, using a caliper distance of 0.05, after matching on the following covariates that differed significantly between surgical and nonsurgical patients: age, sex, race, cause of injury, transfer status, injury severity score, ED Glasgow coma score, ED systolic blood pressure, presence of transverse ligamentous injury, cervical dislocation, and 8 comorbidities. The following outcomes were analyzed with McNemar tests and Wilcoxon signed-rank tests: near-term survival (discharged from the hospital to locations other than morgue or hospice), intensive care unit (ICU) admission, hospital complications, median hospital length of stay (LOS), and median ICU LOS., Results: There were 16,607 patients, 2916 (17.6%) were operatively managed and 13,691 were nonoperatively managed. Before matching, survival was greater for patients managed operatively compared with nonoperatively (95.0% vs. 88.2%). The matched population consisted of 5334 patients: 2667 patients in the operative group (91.5% of this population) and 2667 well-matched patients in the nonoperative group. After matching, there was a survival benefit for patients who were operatively managed compared with nonoperative management (94.8% vs. 91.4% P <0.001). However, operative management was associated with greater development of complications, ICU admission, and longer hospital and ICU LOS., Conclusion: Compared with nonoperative management, operative management demonstrated a significant near-term survival benefit for patients with odontoid type II fractures in select patients., Level of Evidence: III., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Mild traumatic brain injuries (mTBIs) comprise 80% of all TBI, but conventional MRI techniques are often insensitive to the subtle changes and injuries produced in a concussion. Diffusion tensor imaging (DTI) is one of the most sensitive MRI techniques for mTBI studies with outcome and symptom associations described. The corpus callosum (CC) is one of the most studied fiber tracts in TBI and mTBI, but the comprehensive post-mTBI symptom relationship has not fully been explored., Methods: This is a retrospective observational study of how quantitative DTI data of the CC and its sub-regions may relate to clinical presentation of symptoms and timing of resolution of symptoms in patients diagnosed with uncomplicated mTBI. DTI and clinical data were obtained retrospectively from 446 (mean age 42 years, range 13-82) civilian patients. From patient medical charts, presentation of the following common post-concussive symptoms was noted: headache, balance issues, cognitive deficits, fatigue, anxiety, depression, and emotional lability. Also recorded was the time between injury and a visit to the physician when improvement or resolution of a particular symptom was reported. FA values from the total CC and 3 subregions of the CC (genu or anterior, mid body, and splenium or posterior) were obtained from hand tracing on the Olea Sphere v3.0 SP12 free-standing workstation. DTI data was obtained from 8 different 3T MRI scanners and harmonized via ComBat harmonization. The statistical models used to explore the association between regional Fractional Anisotropy (FA) values and symptom presentation and time to symptom resolution were logistic regression and interval-censored semi-parametric Cox proportional hazard models, respectively. Subgroups related to age and timing of first scan were also analyzed., Results: Patients with the highest FA in the total CC ( p = 0.01), anterior CC ( p < 0.01), and mid-body CC ( p = 0.03), but not the posterior CC ( p = 0.91) recovered faster from post-concussive cognitive deficits. Patients with the highest FA in the posterior CC recovered faster from depression ( p = 0.04) and emotional lability ( p = 0.01). There was no evidence that FA in the CC or any of its sub-regions was associated with symptom presentation or with time to resolution of headache, balance issues, fatigue, or anxiety. Patients with mTBI under 40 had higher FA in the CC and the anterior and mid-body subregions (but not the posterior subregion: p = 1.00) compared to patients 40 or over ( p ≤ 0.01). There was no evidence for differences in symptom presentation based on loss of consciousness (LOC) or sex ( p ≥ 0.18)., Conclusion: This study suggests that FA of the CC has diagnostic and prognostic value for clinical assessment of mTBI in a large diverse civilian population, particularly in patients with cognitive symptoms., Competing Interests: SA and TS were employed by company HCA Healthcare. AA, TK, AR, CV, and TS were employed by company Imgen Research Group. LG was employed by company Clinical Neurology Specialists. TS was employed by company SimonMed Imaging. The remaining 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., (Copyright © 2023 Asturias, Knoblauch, Rodriguez, Vanier, Le Tohic, Barrett, Eisenberg, Gibbert, Zimmerman, Parikh, Nguyen, Azad, Germin, Fazzini and Snyder.)

The mechanism of human immunodeficiency virus 1 (HIV-1) nuclear entry, required for productive infection, is not fully understood. Here, we report that in HeLa cells and activated CD4 + T cells infected with HIV-1 pseudotyped with VSV-G and native Env protein, respectively, Rab7 + late endosomes containing endocytosed HIV-1 promote the formation of nuclear envelope invaginations (NEIs) by a molecular mechanism involving the VOR complex, composed of the outer nuclear membrane protein VAP-A, hyperphosphorylated ORP3 and Rab7. Silencing VAP-A or ORP3 and drug-mediated impairment of Rab7 binding to ORP3-VAP-A inhibited the nuclear transfer of the HIV-1 components and productive infection. In HIV-1-resistant quiescent CD4 + T cells, ORP3 was not hyperphosphorylated and neither VOR complex nor NEIs were formed. This new cellular pathway and its molecular players are potential therapeutic targets, perhaps shared by other viruses that require nuclear entry to complete their life cycle., (© 2023. The Author(s).)

Metastases are responsible for the vast majority of cancer deaths, yet most therapeutic efforts have focused on targeting and interrupting tumor growth rather than impairing the metastatic process. Traditionally, cancer metastasis is attributed to the dissemination of neoplastic cells from the primary tumor to distant organs through blood and lymphatic circulation. A thorough understanding of the metastatic process is essential to develop new therapeutic strategies that improve cancer survival. Since Paget's original description of the "Seed and Soil" hypothesis over a hundred years ago, alternative theories and new players have been proposed. In particular, the role of extracellular vesicles (EVs) released by cancer cells and their uptake by neighboring cells or at distinct anatomical sites has been explored. Here, we will outline and discuss these alternative theories and emphasize the horizontal transfer of EV-associated biomolecules as a possibly major event leading to cell transformation and the induction of metastases. We will also highlight the recently discovered intracellular pathway used by EVs to deliver their cargoes into the nucleus of recipient cells, which is a potential target for novel anti-metastatic strategies.

Objective: The objective of this review is to investigate the short- and long-term effects of osteopathic manipulative treatment on cardiovascular function and its regulators in the nervous and endocrine systems., Introduction: A variety of pharmacological and lifestyle-based treatments are used to prevent or treat vascular diseases, yet vascular disease underpins the top 2 causes of death worldwide. There is a need for more preventative and therapeutic interventions in the management and prevention of vascular disease that are compatible with existing interventions. Osteopathic manipulative treatment has shown promise as a non-invasive approach to improve cardiovascular function, but it is currently utilized mostly for alleviating musculoskeletal symptoms. A comprehensive summary of the evidence on the effectiveness of osteopathic manipulative treatment in cardiovascular function will assist clinicians and guide future research directions., Inclusion Criteria: This review will consider randomized controlled trials, non-randomized controlled trials, and crossover studies. Participants must have received osteopathic manipulative treatment intervention. Comparators will include passive or active controls, including controls for body position, touch, and other potential interventions for vascular disease. Cardiovascular, nervous-system, or endocrine-system outcome variables must be measured at least once after treatment. Adverse events will also be considered., Methods: Searches will be conducted in the following sources: MEDLINE, the Journal of Osteopathic Medicine , Embase, Scopus, ProQuest One Academic, MedNar, the International Journal of Osteopathic Medicine , and CINAHL. Studies available in English, without date restrictions, will be considered for inclusion. Relevant studies will be selected by 2 independent reviewers, critically appraised, and extracted using a tool customized for the details of the study. If meta-analysis is possible, evidence will be summarized using standard techniques with subgroup analyses providing more insight into particular osteopathic manipulative treatment techniques, time frame of the treatment, and duration of effects, among others. Certainty of findings will be presented using GRADE., Systematic Review Registration Number: PROSPERO CRD42021225838., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 JBI.)

Objectives: Intracranial pressure (ICP) monitoring is recommended for severe traumatic brain injuries (TBI) but some data suggests it may not improve outcomes. The objective was to investigate the effect of ICP monitoring among TBI., Methods: This retrospective observational cohort study (1/1/2015-6/1/2020) included severe TBI patients. Outcomes [discharge destination, length of stay (LOS)] were compared by ICP monitoring and were stratified by GCS (3 vs. 4-8), α < 0.05., Results: Of the123 patients who met inclusion criteria, 47% received ICP monitoring. There were baseline differences in the two groups characteristics, ICP monitored patients were younger (p = 0.02), had a subarachnoid hemorrhage less often (p = 0.04), and a subdural hematoma more often (p = 0.04) than those without ICP monitors. ICP monitored patients had a significantly longer median LOS (12 vs. 3, p < 0.01) than patients without monitoring. There was a trend towards more ICP monitored patients discharged home (40% vs. 23%, p = 0.06). Among patients with GCS = 3, ICP monitored patients had a longer LOS (p < 0.01) with no significant differences in discharge destinations. For those with a GCS of 4-8, ICP monitoring was associated with a longer LOS (p = 0.01), but fewer were discharged to a skilled nursing facility or long-term care (p = 0.01)., Conclusions: For TBI patients, ICP monitoring was associated with an increased LOS, with no significant differences in discharge destinations when compared to those without ICP monitoring. However, among only those with a GCS of 4-8, ICP monitoring was associated with a decreased proportion of patients discharged to a skilled nursing facility or long-term acute care ., (© 2022. The Author(s).)

Purpose: Transgender individuals disproportionately face barriers to accessing and receiving health care. This study examines physician comfort in managing and caring for the unique health needs and barriers that transgender patients encounter. We predicted that increased exposure to a transgender person, prior treatment of a transgender patient, and transgender health education would increase comfort in providing care to transgender individuals., Methods: A Qualtrics ® survey link was sent through mail to actively licensed physicians within the state of Nevada. Questions related to perceived comfort level were measured on a 10-point scale (1=lowest level of comfort, 10=highest level of comfort) and dichotomized for analysis (1-5=not comfortable, 6-10=comfortable)., Results: Survey response was 62 of 1620 (4%). Comfort with providing transgender patients routine care (87%) and sex or gender-related care (68%) was high, whereas comfort with providing hormonal treatment (26%) was low. A majority (61%) of respondents either had no training or obtained their training through a nonformal avenue (e.g., self-study and literature review) regarding transgender health issues. Although there was no evidence that knowing a transgender person ( p >0.165) or having more education ( p >0.489) significantly improved comfortability with treatment, respondents who had previously treated a transgender patient had greater comfort providing routine ( p =0.059) and sex or gender-related care ( p =0.011)., Conclusion: Although the results show that a majority of physician respondents in Nevada feel comfortable providing routine care to transgender patients, they also reveal a need for education that incorporates experience with transgender patients and a need for widely available guidelines on hormonal treatment of transgender patients., (Copyright 2022, Mary Ann Liebert, Inc., publishers.)

Background: Traumatic falls among the elderly (≥ 65 years old) are the leading cause of injury, morbidity and mortality are increasing with rising medical costs., Methods: This is a retrospective medical record review of elderly mechanical fall patients (288 patients) admitted to an American College of Surgeons level II trauma center from January 2016 to January 2021. Demographics and comorbidities were determined, and physical/occupational therapy used to predict subsequent fall readmissions., Results: Out of 288 patients, 243 received therapy with 45 readmissions for subsequent falls. Age (P = .016), body mass index (P = .035), previous falls (P = .003), walker/cane use (P = .039), and dementia (P = .038) were predictive of readmission. Therapy was shown to benefit patients, but deferred therapy sessions were shown to be associated with prolonged hospitalization., Conclusion: Directed therapy may improve functionality and return autonomy to elderly mechanical fall patients admitted to trauma services., Competing Interests: We know of no conflicts of interests associated with the publication, and there has been no financial support for this work that could influence its outcome., (© 2022 Published by Elsevier Inc.)

Firearm related mortality in the USA surpassed all other developed countries. This study hypothesizes that injury patterns, weapon type, and mortality differ between suicide groups as opposed to homicide. The American College of Surgeons National Trauma Database was queried from January 2017 to December 2019. All firearm related injuries were included, and weapon type was abstracted. Differences between homicide and suicide groups by sex, age, race, and injury severity were compared using a Mann-Whitney test for numerical data and Fisher's exact test for categorical data. The association between weapon type and mortality relative to suicide as opposed to homicide was assessed in Fisher's exact tests. Significance was defined as p &lt; 0.05. There were 100,031 homicide and 11,714 suicide subjects that met inclusion criteria. Homicides were mostly assault victims (97.6%), male (88%), African-American (62%), had less severe injury (mean (ISS) 12.07) and a median age of 20 years old (IQR: 14, 30, p &lt; 0.01). Suicides were mostly male (83%), white (79%), had more severe injury (mean ISS 20.73), and a median age of 36 years old (IQR: 19, 54, p &lt; 0.01). Suicide group had higher odds of head/neck (OR = 13.6) or face (OR = 5.7) injuries, with lower odds of injury to chest (OR = 0.55), abdominal or pelvic contents (OR = 0.25), extremities or pelvic girdle (OR = 0.15), or superficial soft tissue (OR = 0.32). Mortality rate was higher for suicide group (44.8%; 95% confidence interval (CI) 43.9%, 45.7%) compared to the homicide group (11.5%; 95% CI 11.3%, 11.7%). Suicide had higher mortality, more severe injuries, and more head/neck/facial injuries than homicide. Majority of suicides were with handguns., (© 2022. The Author(s).)

Background: Apprehensions of undocumented immigrants in the Rio Grande Valley sector of the U.S.-Mexico border have grown to account for nearly half of all apprehensions at the border. The purpose of this study is to report the prevalence, mechanism, and pattern of traumatic injuries sustained by undocumented immigrants who crossed the U.S.-Mexico border at the Rio Grande Valley sector over a span of 5 years and were treated at a local American College of Surgeons verified Level II trauma center., Methods: A retrospective chart review was conducted from January 2014 to December 2019. Demographics, comorbidities, injury severity score (ISS), mechanism of injury, anatomical part of the body affected, hospital and ICU length of stay (LOS), and treatment costs were analyzed. Descriptive statistics for demographics, injury location and cause, and temporal trends are reported. The impact of ISS or surgical intervention on hospital LOS was analyzed using an analysis of covariance (ANCOVA)., Results: Of 178 patients, 65.2% were male with an average age of 31 (range 0-67) years old and few comorbidities (88.8%) or social risk factors (86%). Patients most commonly sustained injuries secondary to a border fence-related incident (33.7%), fleeing (22.5%), or motor vehicle accident (16.9%). There were no clear temporal trends in the total number of patients injured, or in causes of injury, between 2014 and 2019. The majority of patients (60.7%) sustained extremity injuries, followed by spine injuries (20.2%). Border fence-related incidents and fleeing increased risk of extremity injuries (Odds ratio (OR) > 3; p < 0.005), whereas motor vehicle accidents increased risk of head and chest injuries (OR > 4; p < 0.004). Extremity injuries increased the odds (OR: 9.4, p < 0.001) that surgery would be required. Surgical intervention was common (64%), and the median LOS of patients who underwent surgery was 3 days more than those who did not (p < 0.001)., Conclusion: In addition to border fence related injuries, undocumented immigrants also sustained injuries while fleeing and in motor vehicle accidents, among others. Extremity injuries, which were more likely with border fence-related incidents, were the most common type. This type of injury often requires surgical intervention and, therefore, a longer hospital stay for severe injuries., (© 2021. The Author(s).)

Time allocated to nutrition education in the medical school curriculum stands in contrast to high mortality rates attributable to poor diet in patients. Counseling patients on nutrition-related diseases is a critical skill for physicians, particularly those entering primary care. The crowded medical school curriculum has made adding hours of nutrition instruction difficult. This study evaluates the attitudes of undergraduate medical students at a single institution regarding the need for and relevance of nutrition education and reports on organization of and students' responses to a short experimental elective. Student attitudes regarding nutrition in medicine and a proposed nutrition elective were surveyed. Results helped formulate a short experimental elective. A two-session experimental course was completed, after which the participants were surveyed. Students agreed or strongly agreed with statements regarding the importance of nutrition in clinical practice. Greater than 60% of students surveyed in each class were interested in the proposed elective. All participants found the elective with culinary medicine sessions at least moderately useful to their needs as future healthcare providers. The majority of participants (more than 93%) reported being likely to both take and recommend the elective should it be offered in the future. Medical students consider nutrition an essential aspect of a patient encounter, but do not feel prepared to counsel future patients on dietary changes for management and/or prevention of nutrition linked diseases. There is strong student support for creating an elective in clinical nutrition with culinary medicine sessions to address the gap in their education and improve their confidence., Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-021-01346-3., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2021.)

Background: Minimally invasive techniques for Achilles tendon repair are increasing due to reports of similar rerupture rates using open and percutaneous techniques with fewer wound complications and quicker recovery with percutaneous methods. The goal of this study was to investigate quantitatively the relationship and risk of injury to the sural nerve during Achilles tendon repair when using the Percutaneous Achilles Repair System (PARS) (Arthrex®, Naples, FL), by recording the distance between the passed needles and the sural nerve as well identifying any direct violation of the nerve with needle passage or nerve entrapment within the suture after the jig was removed. The hypothesis of the study is that the PARS technique can be performed safely and without significant risk of injury to the sural nerve., Methods: A total of five needles were placed through the PARS jig in each of 10 lower extremity cadaveric specimens using the proximal portion after simulation of a midsubstance Achilles tendon rupture. Careful dissection was performed to measure the distance of the sural nerve in relation to the passed needles. The sutures were then pulled out through the incision as the jig was removed from the proximal portion of the tendon and observation of the suture in relation to the tendon was documented., Results: Of the 10 cadaveric specimens, none had violation of the sural nerve. Zero of the 50 (0%) needles directly punctured the sural nerve. In addition, upon retraction of the jig, all sutures were noted to reside within the tendon sheath with no entrapment of the sural nerve noted., Conclusion: This study demonstrated the variable course of the sural nerve and identifies the potential risk for sural nerve injury when using the PARS for Achilles tendon repair. However, this study provides additional evidence of safety from an anatomic standpoint that explains the outcomes demonstrated in the clinical trials. With this information the authors believe surgeons should feel comfortable they can replicate those outcomes while minimizing risk of sural nerve injury when the technique is used correctly., (Copyright © 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Objective: The goal of this review is to identify and summarize technology-assisted methods that are being used in clinical, research, or educational settings to assess non-verbal behaviors that have been identified as contributors to the quality of the therapeutic alliance between health care providers and patients., Introduction: A strong therapeutic alliance is a critical component of positive patient outcomes. A health care provider's non-verbal behaviors help build a strong therapeutic alliance, but practice with expert feedback is often required to develop desirable non-verbal behaviors. Advances in technology have been harnessed to assess and provide feedback to health care providers, but the technological tools can be difficult to find and compare. Technology-assisted feedback has the potential to help health care providers hone important clinical skills without requiring highly trained instructors, improving medical care overall., Inclusion Criteria: This review will consider quantitative and qualitative studies, as well as review articles. Participants must be health care providers (or students) who routinely conduct appointments with patients. Included studies must incorporate technology-assisted methods that are being used to collect or analyze information regarding at least one behavior associated with the therapeutic alliance in a clinical, research, or educational setting. Any type of patient encounter, whether actual, actor-based, virtual reality, or simulation-based, will be included., Methods: Five bibliographic databases will be searched, with results limited to English-language articles published from 2010 to the present. The search strategy yielded 404 results in PubMed. The proposed methodology follows the JBI methodology for scoping reviews., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 JBI.)

The purpose of this study was to explore patient perceptions of primary care providers and their offices relative to their physician's philosophy (medical degree [MD] vs doctorate in osteopathic medicine [DO]), specialty (internal medicine vs family medicine), US region, and gender (male vs female). Using the Healthgrades website, the average satisfaction rating for the physician, office parameters, and wait time were collected and analyzed for 1267 physicians. We found female doctors tended to have lower ratings in the Midwest, and staff friendliness of female physicians were rated lower in the northwest. In the northeast, male and female MDs were rated more highly than DOs. Wait times varied regionally, with northeast and northwest regions having the shortest wait times. Overall satisfaction was generally high for most physicians. Regional differences in perception of a physician based on gender or degree may have roots in local culture, including proximity to a DO school, comfort with female physicians, and expectations for waiting times., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Declining lecture attendance has been an ongoing concern for educators involved in undergraduate medical education. A survey was developed (a) to gain insight into the reasons students skipped class, (b) to identify the type of study materials they were using, and (c) to determine what they thought would motivate them to come to class. The survey was sent to 317 first-year and second-year medical students, and 145 (45%) responded. Only 63% of first-year students and 53% of second-year students attended any lectures that were not mandatory. The attendance was higher for students who aspired to less competitive specialties such as pediatrics and family medicine. The most popular reasons for not coming to class were related to the efficiency of information intake and instructor or class style. The most heavily used resources (> 60%) were materials or recorded lectures provided by the instructor. The second-year students also heavily used outside study materials for Board exams, such as Pathoma (50%). Students' ideas for what might increase their attendance suggest that they perceive that the lectures may not prepare them for Board exams, and they would like faculty to address Board related content more often in class and on assessments. Respondents also suggested that teaching practices might be improved through faculty development. Faculty awareness of and references to Board exam content, embedded in strong teaching practices, may help students find more value in live lectures. Carefully designed active learning sessions may change students' minds regarding the relevance and value of these sessions., Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-021-01236-8., Competing Interests: Conflict of InterestThe authors declare that they have no conflicts of interest., (© The Author(s) 2021.)

Objective: This study describes and assesses services, staffing practices, and trends in academic health sciences libraries that serve accredited college of osteopathic medicine (COM) programs in the United States., Methods: The study was conducted in three phases. In phase one, the investigators collected data on library services and staffing through the publicly facing websites of the COM libraries. In phase two, thirty-five COM library directors were invited to complete a survey regarding their services, staffing, supported programs, and students served. In phase three, seven COM library directors participated in phone interviews regarding services that increased their visibility, their motivation to offer expanded services, adequacy of staffing, and competencies required for new librarian roles. The investigators incorporated the Medical Library Association (MLA) competencies as a framework to structure the results., Results: Phase one identified 35 COM libraries serving between 162 and 8,281 students. In phase two, 30 out of a possible 35 survey respondents indicated that the top services offered or considered by COM libraries were in the MLA competency areas of "Instruction & Instructional Design" and "Evidence-Based Practice & Research." In addition, we discovered that COM libraries had a median of 10 full-time equivalent (FTE) staff per 1,000 students. Phase three data revealed that library directors attributed their libraries' success to the skills and talents of their staff, the wide range of resources and services they offered, and the desirability of their physical spaces. Library directors identified skills in the same MLA competency areas as phase two, as well as in the MLA competency areas of "Information Management" and "Leadership & Management," as being desirable for new staff., Conclusion: The study results provide information for medical school administrators and library directors to help identify trends across US osteopathic medical schools in order to justify the need for additional services and staffing. These results can assist medical and library leadership in COM schools in planning for their future academic health sciences libraries. Finally, the findings could assist programs in library and information sciences in redesigning their curriculums based on the MLA competencies for students who seek future careers in academic health sciences libraries., (Copyright © 2020 Joanne M. Muellenbach, Wendy C. Duncan, Cheryl Vanier, Lisa A. Ennis, Anna Yang.)

The intercellular communication mediated by extracellular vesicles (EVs) has gained international interest during the last decade. Interfering with the mechanisms regulating this cellular process might find application particularly in oncology where cancer cell-derived EVs play a role in tumour microenvironment transformation. Although several mechanisms were ascribed to explain the internalization of EVs, little is our knowledge about the fate of their cargos, which are crucial to mediate their function. We recently demonstrated a new intracellular pathway in which a fraction of endocytosed EV-associated proteins is transported into the nucleoplasm of the host cell via a subpopulation of late endosomes penetrating into the nucleoplasmic reticulum. Silencing tetraspanin CD9 both in EVs and recipient cells strongly decreased the endocytosis of EVs and abolished the nuclear transfer of their cargos. Here, we investigated whether monovalent Fab fragments derived from 5H9 anti-CD9 monoclonal antibody (referred hereafter as CD9 Fab) interfered with these cellular processes. To monitor the intracellular transport of proteins, we used fluorescent EVs containing CD9-green fluorescent protein fusion protein and various melanoma cell lines and bone marrow-derived mesenchymal stromal cells as recipient cells. Interestingly, CD9 Fab considerably reduced EV uptake and the nuclear transfer of their proteins in all examined cells. In contrast, the divalent CD9 antibody stimulated both events. By impeding intercellular communication in the tumour microenvironment, CD9 Fab-mediated inhibition of EV uptake, combined with direct targeting of cancerous cells could lead to the development of novel anti-melanoma therapeutic strategies., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

With the introduction of McMaster University's problem-based, self-directed learning and cognitive integration in the medical school curriculum, learning in small groups has been gaining popularity with medical schools worldwide. Problem-based learning (PBL) places emphasis on the value of basic medical sciences as the basis of learning medicine using clinical problems. For a successful outcome, a PBL curriculum needs to have a student-centered learning environment, problem-based design and facilitation, and assessment of learning in PBL domains. We describe a PBL program that has been used for undergraduate medical education, including changes made to learning resources and assessment. The changes required input from both faculty educators and students, and success depended on buy-in into the process. One of the changes included implementing the use of standard textbooks, which students use as the primary source of information during self-directed learning. Another change was the use of several reliable, valid, and cost-effective high-stakes written exams from internal and external sources, to promote spaced retrieval of biomedical facts and clinical contexts. By making these and other changes, we have been able to achieve pass rates and board scores which are consistently above the national average for 12 years. We conclude that in order to ensure sustainable successful outcomes, it is important to keep our program dynamic by making improvements in the PBL domains and assessment methods, taking into consideration students' course evaluations of the learning environment., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Association of Medical Science Educators 2019.)

Background: In 2013, Tel-jeunes created a text messaging intervention program to reach youth aged 12 to 17 years on their cell phones. Tel-jeunes was the first in the country to offer a text-based brief psychosocial interventions performed by professional counselors. Researchers were contacted to document and evaluate the program., Objectives: The research aimed to: 1) determine motives, contexts and issues that lead young people to use the SMS service; 2) document the characteristics of text-based brief intervention; and 3) assess the advantages and difficulties encountered by counselors who respounded to youth text-messages., Methods: We conducted a multimethod research from November 2013 to May 2014. We held four focus groups with 23 adolescents aged 15 to 17 who had or not used the SMS service, conducted a content analysis of a corpus of 13,236 text messages (or 601 conversations), and two focus groups with 11 Tel-jeunes counselors, just over a year after the implantation of the service., Results: Our findings show that the SMS service meets youth needs. They identify text messaging to be their prefered mode of communication with Tel-jeunes when they need support or information. Moreover, the service reaches young people who would not have felt confortable to contact Tel-jeunes by phone. We identified three dominant issues in youths demands: romantic relationships, psychological health and sexuality. Perceived benefits of the service include anonimity and privacy (cell phone providing the ability to text anywhere). Youth participants also appreciated writing to counselors as they felt they had more time to think abouth their questions and answers to the counselor. Counselors were more ambivalent. They considered text-based intervention to be very effective and satisfactory to adress youth information requests, but reported difficulties when dealing with more complex problems or with mental health issues. They reported that text-based communication makes it more difficult to assess youth emotional states, found the discontinuity of text-based conversations very frustrating, and experienced problems when dealing with several youth at the same time. They also struggled with some the computer-based platform features., Conclusions: Finding suggest that text-based intervention are now essential to reach out to youth seeking for information and help. But, Tel-jeunes text-based service required adaptations of the intervention model. Adjustment were made by the managment team when implementing the service which required taking into account youth needs, engaging in a continuous dialogue with counselors and working with the suppliers of the text-based platform to improve its features. Futur challenges include reaching out for boys, conducting interventions with younger youth who feel confortable contacting the service by SMS, and managing urgent requests initiated via web text-messaging apps rather than mobile phones.

The physiological role of a vacuolar ATPase subunit c1 (SaVHAc1) from a halophyte grass Spartina alterniflora was studied through its expression in rice. The SaVHAc1-expressing plants showed enhanced tolerance to salt stress than the wild-type plants, mainly through adjustments in early stage and preparatory physiological responses. In addition to the increased accumulation of its own transcript, SaVHAc1 expression led to increased accumulation of messages of other native genes in rice, especially those involved in cation transport and ABA signalling. The SaVHAc1-expressing plants maintained higher relative water content under salt stress through early stage closure of the leaf stoma and reduced stomata density. The increased K(+) /Na(+) ratio and other cations established an ion homoeostasis in SaVHAc1-expressing plants to protect the cytosol from toxic Na(+) and thereby maintained higher chlorophyll retention than the WT plants under salt stress. Besides, the role of SaVHAc1 in cell wall expansion and maintenance of net photosynthesis was implicated by comparatively higher root and leaf growth and yield of rice expressing SaVHAc1 over WT under salt stress. The study indicated that the genes contributing toward natural variation in grass halophytes could be effectively manipulated for improving salt tolerance of field crops within related taxa., (© 2012 Louisiana State University Agricultural Center. Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.)

Background: There is mixed support for the efficacy of the opioid antagonist naltrexone in the treatment of nicotine dependence. One potential unexplored mechanism underlying naltrexone's effects in smoking cessation may be in its ability to reduce alcohol consumption., Methods: Alcohol consumption and liver enzyme levels (aspartate aminotransferase and alanine transaminase) were examined in a sample of 78 nonalcoholic social drinking smokers (34 naltrexone, 44 placebo) enrolled in a double-blind randomized clinical trial of naltrexone in smoking cessation. Naltrexone or placebo began 3 days prior to the quit date (25 mg daily) and continued for 8 weeks (50 mg daily). All participants received nicotine patches and behavioral counseling up through 4 weeks after the quit date., Results: Naltrexone significantly reduced weekly heavy drinking rates. This effect was associated with greater nausea and pill taking adherence within the naltrexone group. Within heavy drinkers, naltrexone also directionally improved smoking quit rates compared with placebo. Liver enzyme levels did not differ during treatment with naltrexone compared with placebo., Conclusions: Naltrexone may reduce the frequency of heavy drinking in nonalcoholics attempting to quit smoking. Further, naltrexone may preferentially improve smoking quit rates within heavy drinkers who smoke, and further investigation in larger sample sizes is warranted.

Many studies use the number of fish meals as an estimate of Hg intake, although fish Hg concentrations, even within the same species, can greatly vary. Furthermore, most freshwater advisories only refer to local catch, while market fish advisories only focus on market fish, although both can contribute to Hg body burden. The present study, carried out in lakeside communities from 2 ecosystems in Quebec, Canada, sought to (i) estimate Hg intake from local freshwater sources, hunted waterfowl and market fish and seafood, and (ii) examine the relations between fish consumption, estimated Hg intake and biomarkers of exposure. A total of 238 adults (18-74 years), who had consumed local catch within the past three months, responded to an extensive interview-administered fish and waterfowl frequency questionnaire. Anthropometric measures were taken and a self-administered questionnaire was used to obtain socio-demographic information. Hg intake was estimated as microg Hg/kg body weight/day. Blood and hair samples were analyzed for Hg content. Results showed that persons from one ecosystem ate significantly more fish compared to those from the other (median: 52.1 g/day vs 38.9 g/day), but presented significantly lower concentrations of hair Hg (median: 448.0 ng/g vs 730.5 ng/g), blood organic Hg (median: 1.1 microg/L vs 3.4 microg/L) and inorganic Hg (median: 0.4 microg/L vs 0.8 microg/L). Median daily total Hg intake was 0.080 microg/kg bw/day for the former community and 0.141 microg/kg bw/day for the latter. Overall, 59.5% from the first ecosystem and 41.0% from the other, exceeded the US EPA RfD (0.1 microg/kg bw/day), while 13.2% and 6.0%, respectively, exceeded the Canadian tolerable daily intake (0.47 microg/kg bw/day) for adults. For the two groups, freshwater fish consumption frequency, but not total fish, was positively associated with bioindicators of Hg while estimated Hg intake from freshwater catch as well as from total fish consumption were positively related to Hg biomarkers. There was a positive relation between consumption and estimated Hg intake from freshwater fish and blood inorganic Hg. These findings indicate that the number of fish can be a poor surrogate for Hg exposure. The differences observed here for Hg intake and exposure reflect ecosystem disparities in fish diversity and Hg bioaccumulation. Studies and advisories need to consider Hg fish concentrations and fish-eating patterns in different ecosystems, as well as the contribution of market fish. The relation between fish consumption and inorganic Hg exposure, reported as well in other studies, needs to be further investigated.

Environmental chemicals can disrupt endocrine balance and in particular thyroid hormone (TH) homeostasis. However, studies differ with respect to thyroid profile changes and gender differences are rarely examined. This study investigated the THs, triodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH), in relation to serum organochlorines (OCs), bioindicators of mercury (Hg) and blood lead (Pb) in 211 freshwater fish consumers (124 men and 87 women) from two communities in Canada. Thyroid hormones were within the normal range and the bioindicators of exposure were low compared to other reports on fish consumers. Stratified analysis showed that for women, serum T3 concentrations were negatively related to serum concentrations of PCB 138, PCB 153, the non-coplanar congeners, Arochlor 1260, and SigmaPCB, as well as p,p'-DDE. No relations were observed between T4 and any of the chemicals measured, but TSH was negatively related to blood Pb. For men, serum T4 was inversely related to PCB 138, non-ortho-substituted (dioxin-like) PCBs and SigmaPCB. A significant positive relationship was observed between serum TSH and different PCB congeners (PCB 138, PCB 180, non-coplanar congeners, mono-ortho coplanar congeners, dioxin-like PCBs), as well as SigmaPCB. Serum TSH increased with hair and blood Hg concentrations and was highest among those in the highest 50th percentile for both Hg and dioxin-like PCB congeners compared to the others. No associations were observed for T3 in men. These findings suggest that even at low concentrations, these environmental contaminants can interfere with thyroid status and effects may differ by gender.

Background: In the most general sense, studies involving global analysis of gene expression aim to provide a comprehensive catalog of the components involved in the production of recognizable cellular phenotypes. These studies are often limited by the available technologies. One technology, based on microarrays, categorizes gene expression in terms of the abundance of RNA transcripts, and typically employs RNA prepared from whole cells, where cytoplasmic RNA predominates., Results: Using microarrays comprising oligonucleotide probes that represent either protein-coding transcripts or microRNAs (miRNA), we have studied global transcript accumulation patterns for the HepG2 (human hepatoma) cell line. Through subdividing the total pool of RNA transcripts into samples from nuclei, the cytoplasm, and whole cells, we determined the degree of correlation of these patterns across these different subcellular locations. The transcript and miRNA abundance patterns for the three RNA fractions were largely similar, but with some exceptions: nuclear RNA samples were enriched with respect to the cytoplasm in transcripts encoding proteins associated with specific nuclear functions, such as the cell cycle, mitosis, and transcription. The cytoplasmic RNA fraction also was enriched, when compared to the nucleus, in transcripts for proteins related to specific nuclear functions, including the cell cycle, DNA replication, and DNA repair. Some transcripts related to the ubiquitin cycle, and transcripts for various membrane proteins were sorted into either the nuclear or cytoplasmic fractions., Conclusion: Enrichment or compartmentalization of cell cycle and ubiquitin cycle transcripts within the nucleus may be related to the regulation of their expression, by preventing their translation to proteins. In this way, these cellular functions may be tightly controlled by regulating the release of mRNA from the nucleus and thereby the expression of key rate limiting steps in these pathways. Many miRNA precursors were also enriched in the nuclear samples, with significantly fewer being enriched in the cytoplasm. Studies of mRNA localization will help to clarify the roles RNA processing and transport play in the regulation of cellular function.

Background: Although high mercury concentrations in fish diets raise an alarm, fish can also be a healthy choice because it is the primary source of n-3 fatty acids (FAs). However, little information is available on the contribution of freshwater fish to serum FA concentrations., Objective: This study examined the FA pathway from fish to serum in 243 moderate consumers of freshwater fish., Design: A food-frequency questionnaire was used to determine the intakes of freshwater fish caught locally and not sold in markets and of fish purchased in markets (x +/- SD: 58 +/- 63 g/d). Locally caught freshwater fish accounted for an average of 45% of total fish intake. Fish were categorized as lean or fatty on the basis of the eicosapentaenoic acid + docosahexaenoic acid content estimated from published data. Serum FA concentrations were determined by gas chromatography., Results: The results showed no relation between total fish intake or estimated n-3 FA intake from all fish and serum n-3 FA concentrations. Only fatty fish intake, particularly salmonid, and estimated EPA + DHA intake from fatty fish were significantly associated with serum EPA + DHA (R2 = 0.41 and 0.40, respectively). No relation was observed between the quantity of locally caught fish (g/d) consumed or the estimated FA intake from locally caught fish and serum n-3 FAs. Age, sex, and lipid metabolism medication were associated with serum n-3 FA concentrations. Neither blood selenium nor blood mercury was associated with serum FAs., Conclusion: The relation between fatty fish consumption and serum n-3 FAs cannot be generalized to all fish intakes.

Platelet monoamine oxidase-B (MAO-B) has been considered a surrogate biochemical marker of neurotoxicity, as it may reflect changes in the monoaminergic system in the brain. Colour vision discrimination, in part a dopamine dependent process, has been used to identify early neurological effects of some environmental and industrial neurotoxicants. The objective of this cross-sectional study was to explore the relationship between platelet MAO-B activity and acquired colour discrimination capacity in fish-consumers from the St. Lawrence River region of Canada. Assessment of acquired dyschromatopsia was determined using the Lanthony D-15 desaturated panel test. Participants classified with dyschromatopsia (n=81) had significantly lower MAO-B activity when compared to those with normal colour vision (n=32) (26.5+/-9.6 versus 31.0+/-9.9 nmol/min/20 microg, P=0.030)). Similarly, Bowman's Colour Confusion Index (CCI) was inversely correlated with MAO-B activity when the vision test was performed with the worst eye only (r=-0.245, P=0.009), the best eye only (r=-0.188, P=0.048) and with both eyes together (r=-0.309, P=0.001). Associations remained significant after adjustment for age and gender when both eyes (P=0.003) and the worst eye (P=0.045) were tested. Adjustment for heavy smoking weakened the association between MAO-B and CCI in the worst eye (P=0.140), but did not alter this association for both eyes (P=0.006). Adjustment for blood-mercury concentrations did not change the association. This study suggests a relationship between reduced MAO-B activity and acquired colour vision loss and both are associated with tobacco smoking. Therefore, results show that platelet MAO-B may be used as a surrogate biochemical marker of acquired colour vision loss.

Mercury (Hg) is a widespread neurotoxic compound that bio-accumulates in fish and marine mammals. Monoamine oxidase (MAO; EC 1.4.3.4) regulates biogenic amine concentration in the brain and peripheral tissue and has been shown to be a molecular target of Hg compounds in animal models. Blood platelet monoamine oxidase-B (MAO-B) activity may reflect MAO function in the central nervous tissue. Therefore, the objective of this study was to evaluate the relationship between platelet MAO-B and Hg exposure in fish-eating adults (n=127) living along the St. Lawrence River (Lake St. Pierre, Que., Canada). Hg concentrations were determined in blood and hair samples. A significant negative association was observed between platelet MAO-B activity and blood-Hg (r=-0.193, p=0.029) but not with hair-Hg levels (r=-0.125, p=0.169). Multiple linear regression analysis demonstrated that blood-Hg (beta=-4.6, p=0.011) and heavy smoking (beta=-8.5, p=0.001) were associated with reduced platelet MAO activity in the total population. In addition, this reduction in MAO-B activity appeared to be associated with blood-Hg concentrations above 3.4 microg/L (75th percentile). Possible gender related differences were also observed and are discussed. Our results suggest that MAO-B activity in blood platelets may be a useful tool to assess biochemical effects of Hg exposure in human populations. These changes in platelet MAO-B may reflect enzymatic changes in nervous tissue and should be further investigated as a surrogate marker of neurotoxicity.

Epigenetic variation is a potential source of genomic and phenotypic variation among different individuals in a population, and among different varieties within a species. We used a two-tiered approach to identify naturally occurring epigenetic alleles in the flowering plant Arabidopsis: a primary screen for transcript level polymorphisms among three strains (Col, Cvi, Ler), followed by a secondary screen for epigenetic alleles. Here, we describe the identification of stable, meiotically transmissible epigenetic alleles that correspond to one member of a previously uncharacterized non-LTR retroposon family, which we have designated Sadhu. The pericentromeric At2g10410 element is highly expressed in strain Col, but silenced in Ler and 18 other strains surveyed. Transcription of this locus is inversely correlated with cytosine methylation and both the expression and DNA methylation states map in a Mendelian manner to stable cis-acting variation. The silent Ler allele can be converted by the epigenetic modifier mutation ddm1 to a meiotically stable expressing allele with an identical primary nucleotide sequence, demonstrating that the variation responsible for transcript level polymorphism among Arabidopsis strains is epigenetic. We extended our characterization of the Sadhu family members and show that different elements are subject to both genetic and epigenetic variation in natural populations. These findings support the view that an important component of natural variation in retroelements is epigenetic., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Leaf-level CO2 assimilation (A(area)) can largely be predicted from stomatal conductance (g(s)), leaf morphology (SLA) and nitrogen (N) content (N(area)) in species across biomes and functional groups. The effects of simulated global change scenarios, increased summer monsoon rain (+H2O), N deposition (+N) and the combination (+H2O +N), were hypothesized to affect leaf trait-photosynthesis relationships differently in the short- and long-term for the desert shrub Larrea tridentata. During the spring, +H2O and +H2O +N plants had lower A(area) and g(s), but similar shoot water potential (Psi(shoot)) compared with control and +N plants; differences in A(area) were attributed to lower leaf N(area) and g(s). During the summer, +H2O and +H2O +N plants displayed higher A(area) than control and +N plants, which was attributed to higher Psi(shoot), g(s) and SLA. Throughout the year, A(area) was strongly correlated with g(s) but weakly correlated with leaf N(area) and SLA. We concluded that increased summer monsoon had a stronger effect on the performance of Larrea than increased N deposition. In the short term, the +H2O and +H2O +N treatments were associated with increasing A(area) in summer, but also with low leaf N(area) and lower A(area) in the long term the following spring.

The goal of this study was to explore the applicability of surface plasmon resonance (SPR)-based fragment screening to identify compounds that bind to factor VIIa (FVIIa). Based on pharmacophore models virtual screening approaches, we selected fragments anticipated to have a reasonable chance of binding to the S1-binding pocket of FVIIa and immobilized these compounds on microarrays. In affinity fingerprinting experiments, a number of compounds were identified to be specifically interacting with FVIIa and shown to fall into four structural classes. The results demonstrate that the chemical microarray technology platform using SPR detection generates unique chemobiological information that is useful for de novo discovery and lead development and allows the detection of weak interactions with ligands of low molecular weight.

Suicide is known to vary according to season, with peaks in the spring and troughs in the winter. The presence of psychopathology is a significant predictor of suicidality, and it is possible that the seasonal variation of suicide completion may be related to seasonality in the manifestation of psychiatric disorders common to suicide completers. In the current study, we evaluated 115 French-Canadian male suicide completers from the Greater Montreal Area for DSM-IV psychiatric disorders using proxy-based diagnostic interviews. Subjects were assessed for seasonal differences in the prevalence of DSM-IV psychiatric diagnoses just before their deaths. Diagnoses of major depressive disorder (MDD) without comorbid cluster B personality disorders, and schizophrenia were differently distributed between seasons. Most (63.4%) subjects with MDD committed suicide in the spring/summer (P =.038). However, closer examination revealed that depressed suicides with comorbid cluster B personality disorders did not show seasonality, while 83.3% of depressed suicides without comorbid cluster B personality disorders committed suicide in the spring/summer (P =.019). 87.5% of those suicides with schizophrenia committed suicide in the fall/winter (P =.026), and the only suicide with schizophrenia who died in the spring/summer was also the only one without positive symptomology. Our study is limited to male suicide completers, and results should not be generalized to women. We conclude that seasonal variation in suicide manifests itself differently in patients with different psychopathology. These findings indicate that assessment of suicide risk may need to include consideration of possible seasonal effects, depending on psychopathology.

Resin-bound 4H-1,3-oxazines are synthesized by the stepwise condensation of an amide resin, an aldehyde, and an alkyne. Upon DDQ activation, oxazines are converted into oxazinium salts. When treated with hydrazines, these resin-bound beta-diketone equivalents yield pyrazoles through a functionalizing release process. This multicomponent capture strategy, tedious to handle in classical synthesis in solution, is well-suited to solid-supported chemistry. It facilitates the handling of sensitive and unstable intermediates, such as N-alpha-methoxyalkylamides and 1,3-oxazinium salts.

Background: Psychiatric co-morbidity is thought to be an important problem in suicide, but it has been little investigated. This study aims to investigate patterns of co-morbidity in a group of male suicide completers., Method: One hundred and fifteen male suicide completers from the Greater Montreal Area and 82 matched community controls were assessed using proxy-based diagnostic interviews. Patterns of co-morbidity were investigated using latent class analysis., Results: Three subgroups of male suicide completers were identified (L2 = 171.62, df = 2012, P < 0.05). they differed significantly in the amount of co-morbidity (Kruskal-Wallis chi2 = 71.227, df = 2. P < 0.000) and exhibited different diagnostic profiles. Co-morbidity was particularly found in subjects with disorders characterized by impulsive and impulsive-aggressive traits, whereas subjects without those traits had levels of co-morbidity which were not significantly different from those of controls (chi2 = 8.17, df = 4, P = 0.086)., Conclusions: Suicide completers can be divided into at least three subgroups according to co-morbidity: a low co-morbidity group, a substance-dependent group and a group exhibiting childhood onset of psychopathology.

There is evidence suggesting that subjects affected with the Wolfram syndrome (WFS) and normal carriers present an increased risk of psychiatric disorders, particularly depression and suicidal behavior. We investigated a possible role of the gene involved in WFS (WFS1) in the neurobiology of suicide and the potential modulatory effect on traits associated to suicidal behavior. Genetic variation at WFS1 (H611R, R456H, and I333V) was investigated in 111 suicide victims and 129 normal controls. Possible effects on psychopathology and behavioral traits were investigated in a subsample of suicide cases (N = 31) for whom phenotyping was carried out by means of structured psychiatric interviews and questionnaires adapted for psychological autopsies. We found a significantly higher frequency of the 611R/611R genotype in suicide completers as compared to controls (chi(2) = 19.21, df=2, P = 0.001). Suicide completers with this genotype had higher scores on measures of impulsivity (t = -3.15, df = 15.3, P = 0.006); novelty seeking (NS) (t = -3.35, df = 13.8, P = 0.005); and conversely, lower scores of persistence (t = 2.4, df = 16.6, P = 0.028). Scores of impulsivity and NS remained higher in subjects with the associated genotype after adjusting for age, gender, and psychopathology. These results suggest a role for WFS1 in the pathophysiology of impulsive suicide, and are consistent with previous clinical reports suggesting an increased risk of suicidal behavior in WFS homozygotes and heterozygotes. However, these findings are preliminary and should be confirmed in independent samples., (Copyright 2003 Wiley-Liss, Inc.)

Suicide is an important public health problem, accounting for a significant proportion of total mortality among young people, particularly males. There is growing and consistent evidence suggesting that genetic factors play an important role in the predisposition to suicide. Based on several lines of evidence supporting a reduced serotonergic neurotransmission in subjects who committed suicide, we investigated variation at genes that code for serotonin receptor 1B (5-HTR1B), 1Dalpha (5-HTR1Dalpha), 1E (5-HTR1E), 1F (5-HTR1F), 2C (5-HTR2C), 5A (5-HTR5A), and 6 (5-HTR6) in a total sample of 106 suicide completers and 120 normal controls. No differences were observed in allelic or genotypic distributions between groups for any of the loci investigated. Moreover, further analysis according to suicide method or psychopathology also failed to reveal differences between groups. Our results do not support a substantial role of these serotonergic receptors in suicide completion., (Copyright 2003 Wiley-Liss, Inc.)

Objective: As pressure mounts to reduce the number of costly acute care beds, governments and the literature propose top-down ratios. Is this reasonable and fair to the responsible medical officers who, as the key care providers, will need to admit patients and develop discharge plans in a reduced-beds environment?, Method: Treating physicians of all acute care inpatients on a given day (n = 212) and all new acute care admissions over a 2-week period (n = 125) completed an adapted version of the Nottingham Acute Beds Use Survey (NABUS) Questionnaire., Results: On a given day, only 62 of 212 inpatients were unsuited for any alternative to acute care hospitalization. A floor ratio of 18 acute care beds per 100,000 inhabitants seems adequate for the catchment area in question, provided that alternatives to hospitalization are fully and efficiently available. Alternatives essentially involve an array of the following: supervised residential settings, day hospitals, and intensive home care (2 to 6 hours weekly). The ratio of intensive home care workers required would be 25 per 100,000 inhabitants.

The applicability of the equilibrium partition theory (EPT) for PCB accumulation in submerged macrophyte shoots was investigated using field data. The equilibrium state of PCBs between macrophyte shoots and sediments was verified by testing the direct proportionality (slope = 1 in a log-log relationship) between congener concentrations in the lipids of macrophyte shoots (Cli) and in the organic fraction of sediments (Cso), using the slope-range method. A significant proportionality was found between Cli and Cso (slope of the log-log relationship: 0.978 +/- 0.041; R2 = 0.847; P < 0.001). The biota-sediment accumulation factor (BSAF) predicted from this relationship (3.74, SE: 1.14) was in the 1-4 range that is suggested in the literature. These results indicate that, in our study sites, EPT is applicable to PCBs in macrophyte shoots. This opens interesting perspectives in environmental monitoring.

The development of a new and efficient synthesis of resin-bound N-(alpha-methoxyalkyl)amides is described. The condensation of aldehydes on a supported amide in the presence of trimethyl orthoformate afforded, in acidic media, the resin-bound N-acyliminium ion precursors. Repeating the reaction a second time led to a great improvement in yields, demonstrating one advantage of the solid-phase chemistry for the handling of sensitive intermediates difficult to isolate.

Media reports connecting UN peacekeeping duties by Canadian soldiers to their subsequent suicide prompted this study of peacekeeping as suicide risk. In a case-control design we retrospectively compared 66 suicides in the Canadian military between 1990 and 1995 with two control groups: (a) 2,601 controls randomly selected from the electronic military database and (b) 66 matched controls with complete personnel and medical data. We found no increased risk of suicide in peacekeepers except among a subgroup of air force personnel. Here confounding individual factors, isolation from supports, and possibly inadequate preparation for deployment elucidated their suicides. Theater of deployment (e.g., Bosnia) did not affect the suicide rate. Military suicides experienced psychosocial stresses and psychiatric illness more often than their matched controls. We conclude that although peacekeeping per se does not increase overall suicide risk, military life-styles may strain interpersonal relationships, encourage alcohol abuse, and contribute to psychiatric illness and suicide in a minority of vulnerable individuals irrespective of peacekeeping assignment. Careful selection, and preparatory military training that encourages intragroup bonding and mutual support, may protect against suicide risk.

An association between the gene that codes for tryptophan hydroxylase (TPH)-the rate-limiting enzyme in the synthesis of serotonin-and suicidal behavior has been investigated with some detail in samples of living subjects who attempted suicide. In this study, we investigated TPH and suicide completion, the most severe form of suicidal behavior. A relatively large sample of suicide completers (n = 101) was genotyped at three TPH loci (two polymorphisms in the promoter region, A-6526G and G-5806T, and one in intron 7, A218C) and compared to psychiatrically normal living controls (n = 129). Although no significant differences were found between groups for genetic variation at single loci, haplotype analysis revealed that one haplotype (-6526G -5806T 218C) was significantly more frequent among suicide cases than in normal controls (chi(2) = 11.30, df = 2, P = 0.0008; OR = 2.0 CI: 1.30-3.6). Further analyses suggested that this haplotype is particularly more frequent among subjects who committed suicide using violent methods. Similar results were observed in recent haplotype analyses in suicide attempters, which found that the equivalent of haplotype -6526G -5806T 218C was more frequent in impulsive attempters (Rotondo et al, Mol Psychiatry 1999; 4: 360-368). Our results replicate in suicide completers previous data observed in suicide attempters. These and other results continue to point to the substantial role that the gene that codes for TPH may play in the neurobiology of suicidal behavior.

Objective: Postmortem studies have indicated that suicide victims have greater serotonin receptor 2A (5-HTR2A) binding in prefrontal brain regions. However, there remains some controversy regarding the biological specificity of these findings. The authors hypothesized that the variance observed in brain 5-HTR2A binding is genetically mediated, at least in part., Method: Postmortem data from 56 subjects who had committed suicide and 126 normal comparison subjects were studied; brain tissue was available from 11 subjects who committed suicide and 11 comparison subjects. Homogenate binding assays were carried out with [3H]ketanserin. Variation at the 5-HTR2A gene (HTR2A) was investigated by means of two polymorphisms: T102C and A-1438G., Results: 5-HTR2A binding was greater in the prefrontal cortex of the subjects who committed suicide. In addition, the findings suggest that HTR2A variation significantly affects 5-HTR2A binding. However, no interaction between suicidal behavior and this locus was observed., Conclusions: These results confirm previous reports of greater 5-HTR2A binding in subjects who committed suicide; they also provide preliminary evidence suggesting that the number of 5-HTR2A receptors is genetically mediated.

The objective of this exploratory research is to identify the main sources of work stress and burnout among community mental health workers and examine the social support they receive. Information has been collected through individual and group interviews with 19 community workers from three crisis centres in Montreal. The most stressing factors identified by participants are related to their intervention with users and their roles as intervention worker. Difficulties related specifically to community work are also reported. Social support received from colleagues and quality of relations with superiors stand out as important factors of protection against stress and burnout.

One hundred and nine adults were screened in the community using the abridged version of the CIDI (CIDIS). The subjects comprised DSM-III-R current cases (N = 48), lifetime cases (N = 31) and non-cases (N = 30). The interviews with the 109 subjects were conducted by one of two pairs of clinicians and videotaped. Each interviewer-pair included a psychiatrist and a clinical psychologist. They rated the community version of the Needs for Care (NFCAS-C) by consensus. The other pair of judges then viewed the video and rated the NFCAS-C independently. The agreement on overall needs was excellent (kappa = 0.75), and very good for four of the seven specific sections (from kappa = 0.61 to 0.81). One section could not be rated because of low prevalence, and agreement was less good for the remaining two sections. Agreement was good on specific interventions (medication, kappa = 0.60; specific psychotherapy, kappa = 0.55), but poor on non-specific interventions. The majority of disagreements were due to differences in clinical judgement rather than to technical errors. A new instruction manual has been produced and should help training as well as stabilizing reliability. In devising reliable and valid instruments based on clinical judgement, a balance must be achieved between enhancing reliability with more precise rules and constraining clinical judgement so tightly that validity is lost.

This article outlines a course on occupational therapy community practice offered at the University of Ottawa and discusses its assets and limitations in terms of preparing students for the shift to community-based health services. The shift to community services in the health care systems of Ontario and Québec is described. Then the curricular components needed to prepare students for community practice are summarized. Finally, the community practice course at the University of Ottawa including its goal, objectives, class topics and evaluations is outlined. The strength of the community practice course described is that it includes many of the curricular components needed for community practice. On the other hand, limitations include the lack of skill training in some areas, its place in the last year of the programme, and its optional nature. Changes planned for the course and other recommendations for curricula are also discussed.

Seventy five young male adults between the age of 18 and 35 who had committed suicide were compared with 75 male adults still alive matched for age, residence, marital and employment status. For each group a principal respondent was interviewed in order to reconstitute the psychological profile of each individual, as well as their utilisation of health services. This was completed by the study of the coroner's reports and the medical records when available. At six months the prevalence for all axis I diagnosis was 88.8% for the suicide group and 37.3% for the control group. Among the subjects who had committed suicide 38.7% were afflicted by major depression, 24% by alcohol dependency and 28.7% were dependent on drugs. Borderline personalities were present in 28% of the suicide group compared to 5% in the control group. Forty five percent (45%) of the subjects who had killed themselves had consulted a mental health professional in the year preceding the suicide compared to 5% in the control group. However, 78.5% of the suicide group had consulted during the same period a health professional compared to 73.3% of the controls.

Objective: By means of the psychological autopsy method and a case-control design, the authors examined the association of specific mental disorders and comorbidity with suicide among young men., Method: Seventy-five men aged 18-35 years whose deaths were adjudicated as completed suicides by coroners of greater Montreal and Quebec City were matched to 75 living young men for age, neighborhood, marital status, and occupation. For each subject in both groups a key respondent best acquainted with the subject was interviewed by clinicians using standardized schedules. Information from the coroner and medical records was also collected. Two experienced psychiatrists, blind to outcome, established best-estimate DSM-III-R diagnoses., Results: Six-month prevalence rates for all axis I diagnoses for the suicide and comparison groups were 88.0% and 37.3%, respectively; major depression was present in 38.7% and 5.3%, alcohol dependence in 24.0% and 5.3%, psychoactive substance dependence in 22.7% and 2.7%. Borderline personality disorder was identified in 28.0% and 4.0%, respectively. Of the suicide subjects, 28.0% had at least two of the following disorders: major depression, borderline personality disorder, and alcohol or drug dependence; the rate was 0.0% among the comparison subjects., Conclusions: In young men, completed suicide is linked to specific mental disorders, namely, major depression, borderline personality disorder, and substance abuse. Comorbidity involving any of these disorders is frequently associated with completed suicide.