Sleep duration, sleep quality and obesity in the Canadian Armed Forces.

Background: Research has identified an association between sleep and obesity in the general population. It is also important to examine this association in a military population. Data and methods: Data from the 2019 Canadian Armed Forces Health Survey (CAFHS) were used to estimate the prevalence of sleep duration, sleep quality characteristics, overweight and obesity for Regular Force members. The relationship of sleep duration and sleep quality with obesity was assessed with multivariable logistic regression that controlled for sociodemographic, work and health characteristics. Results: Females were significantly more likely than males to report meeting recommended sleep duration (7 hours to less than 10 hours; 48.7% vs. 40.4%), trouble falling or staying asleep (32.3% vs. 23.5%), or that sleep was not refreshing (64.0% vs. 57.7%). Difficulty staying awake did not differ significantly between males and females (6.3% vs. 5.4%). Obesity, but not being overweight, was significantly more prevalent among those who had short (less than 6 hours) or borderline (6 hours to less than 7 hours) sleep duration, or poor sleep quality. Compared with recommended sleep duration, short sleep duration (adjusted odds ratio [AOR] 1.3; 95% confidence interval [CI]: 1.2 to 1.6) and borderline sleep duration (AOR 1.2; 95% CI: 1.1 to 1.4) were associated with obesity for males, but not females, in fully controlled models. Sleep quality indicators were not independently associated with obesity. Interpretation: This study adds to the body of evidence that identifies an association between sleep duration and obesity. The results emphasize the importance of sleep as one of the components of the Canadian Armed Forces Physical Performance Strategy.

Cervical intervertebral disc disease in 60 Yorkshire terriers.

Intervertebral disc extrusion (IVDE) is a common neurological condition in many dog breeds. This study aimed to describe this condition in Yorkshire terriers (YT) and calculate the prevalence of this condition amongst the YTs with neurological diseases. This is a double-centre retrospective study which was conducted in two arms. The first part of the study, describing the clinical features and prognosis of cervical (C) IVDE in YTs, is based on data from 2005 to 2021. The second part of the study calculated the prevalence of C IVDE amongst the YTs with neurological diseases based on data from 2016 to 2021. A retrospective search through the medical records was conducted. YTs with C IVDE diagnosed with MRI and confirmed surgically were eligible for inclusion in this study. Sixty YTs were included in the first part of the study. There were 48 (80%) dogs with acute onset and 12 (20%) with chronic onset with acute deterioration. Ambulation was preserved in 31 (51.7%) dogs on admission, and the remaining 29 (48.3%) dogs were non-ambulatory. No significant association was found between ambulation on admission and recovery status (p = 0.547). Seventy-three intervertebral spaces were treated during the surgical intervention. Relapses were seen in seven (11.7%) dogs. Forty-nine (81.7%) dogs were ambulatory at discharge. A complete recovery was observed in 46 (76.7%) dogs; the remaining dogs (14, 23.3%) were classified as incomplete recovery. A significant difference was found in time to ambulation (p = 0.0238) and time to discharge (p = 0.0139) between the on-admission ambulatory and non-ambulatory dogs. Three hundred and eight YTs were diagnosed with neurological diseases between 2016 and 2021 in one referral centre. C IVDE was diagnosed in 31 (10.06%) dogs. This is the first study explicitly describing the C IVDE in YTs and establishing the prevalence of this condition amongst YTs with other neurological disorders.

Myocarditis or Pericarditis Events After BNT162b2 Vaccination in Individuals Aged 12 to 17 Years in Ontario, Canada.

Importance: The risk of myocarditis or pericarditis after COVID-19 messenger RNA vaccines varies by age and sex, and there is some evidence to suggest increasing risk with shorter intervals between dose 1 and 2 (ie, interdose interval). Objective: To estimate the incidence of reported myocarditis or pericarditis after BNT162b2 vaccine among adolescents and to describe the clinical information associated with these events. Design, Setting, and Participants: This was a population-based cohort study using passive vaccine safety surveillance data linked to the provincial COVID-19 vaccine registry. Included in the study were all adolescents aged 12 to 17 years in Ontario, Canada, who received 1 or more doses of BNT162b2 vaccine between December 14, 2020, and November 21, 2021, and reported an episode of myocarditis or pericarditis. Data were analyzed from December 15, 2021, to April 22, 2022. Exposure: Receipt of BNT162b2 (Comirnaty [Pfizer-BioNTech]) vaccine. Main Outcomes and Measure: Reported incidence of myocarditis or pericarditis meeting level 1 to 3 of the Brighton Collaboration case definition per 100 000 doses of BNT162b2 administered by age group (12-15 years vs 16-17 years), sex, dose number, and interdose interval. All clinical information associated with symptoms, health care usage, diagnostic test results, and treatment at the time of the acute event were summarized. Results: There were approximately 1.65 million doses of BNT162b2 administered and 77 reports of myocarditis or pericarditis among those aged 12 to 17 years, which met the inclusion criteria during the study period. Of the 77 adolescents (mean [SD] age, 15.0 [1.7] years; 63 male individuals [81.8%]), 51 (66.2%) developed myocarditis or pericarditis after dose 2 of BNT162b2. Overall, 74 individuals (96.1%) with an event were assessed in the emergency department, and 34 (44.2%) were hospitalized (median [IQR] length of stay, 1 [1-2] day). The majority of adolescents (57 [74.0%]) were treated with nonsteroidal anti-inflammatory drugs only, and 11 (14.3%) required no treatment. The highest reported incidence was observed among male adolescents aged 16 to 17 years after dose 2 (15.7 per 100 000; 95% CI, 9.7-23.9). Among those aged 16 to 17 years, the reporting rate was highest in those with a short (ie, ≤30 days) interdose interval (21.3 per 100 000; 95% CI, 11.0-37.2). Conclusions and Relevance: Results of this cohort study suggest that there was variation in the reported incidence of myocarditis or pericarditis after BNT162b2 vaccine among adolescent age groups. However, the risk of these events after vaccination remains very rare and should be considered in relation to the benefits of COVID-19 vaccination.

Successful Treatment of Vertebral Osteosarcoma in a Cat Using Marginal Surgical Excision and Chemotherapy.

A three-year-old male neutered Norwegian Forest cat was referred for bilateral ambulatory paraparesis and spinal pain. On magnetic resonance imaging (MRI), a mass involving the right epaxial muscles with vertebral canal invasion and causing marked extradural spinal cord compression was identified. At surgery, the mass was debulked and a right hemilaminectomy was performed. Histopathology was diagnostic of fibroblastic osteosarcoma. Residual osteolytic lesions of the osteosarcoma were present at the level of the spinous process of the second lumbar vertebra. Four cycles of adjuvant doxorubicin chemotherapy were administered followed by oral toceranib phosphate. Neurological signs improved gradually over weeks to months and the lesion in the spinous process was no longer visible on radiographs. At one year from diagnosis, an MRI of the T3-L3 (3rd thoracic vertebra to the 3rd lumbar vertebra) spinal region and a whole-body computer tomography (CT) scan found no evidence of the osteosarcoma in the spine or of any metastasis. All medications were stopped and, at the time of writing 16 months later, the patient is neurologically normal with no signs of cancer recurrence. This is the first case report documenting the complete resolution of vertebral osteosarcoma lesions after treatment with doxorubicin followed by toceranib phosphate. The treatment also prevented tumor recurrence and was associated with an exceptionally long-term survival time.

Epidemiology of Myocarditis and Pericarditis Following mRNA Vaccination by Vaccine Product, Schedule, and Interdose Interval Among Adolescents and Adults in Ontario, Canada.

Importance: Increased rates of myocarditis or pericarditis following receipt of COVID-19 mRNA vaccines have been observed. However, few available data are associated with differences in rates of myocarditis or pericarditis specific to vaccine products, which may have important implications for vaccination programs. Objective: To estimate rates of reported myocarditis or pericarditis following receipt of a COVID-19 mRNA vaccine by product, age, sex, dose number, and interdose interval. Design, Setting, and Participants: This population-based cohort study was conducted in Ontario, Canada (population: 14.7 million) from December 2020 to September 2021 and used data from Ontario's COVID-19 vaccine registry and passive vaccine-safety surveillance system. All individuals in Ontario, Canada, who received at least 1 dose of COVID-19 mRNA vaccine between December 14, 2020, and September 4, 2021, and had a reported episode of myocarditis or pericarditis following receipt of the COVID-19 vaccine during this period were included. We obtained information on all vaccine doses administered in the province to calculate reported rates of myocarditis or pericarditis. Exposures: Receipt of a COVID-19 mRNA vaccine (mRNA-1273 [Moderna Spikevax] or BNT162b2 [Pfizer-BioNTech Comirnaty]). Main Outcomes and Measures: All reports of myocarditis or pericarditis meeting levels 1 to 3 of the Brighton Collaboration case definitions were included. Rates and 95% CIs of reported cases of myocarditis or pericarditis per 1 000 000 mRNA vaccine doses administered were calculated by age, sex, dose number, vaccine product, and interdose interval. Results: Among 19 740 741 doses of mRNA vaccines administered, there were 297 reports of myocarditis or pericarditis meeting the inclusion criteria; 228 (76.8%) occurred in male individuals, and the median age of individuals with a reported event was 24 years (range, 12-81 years). Of the reported cases, 207 (69.7%) occurred following the second dose of the COVID-19 mRNA vaccine. When restricted to individuals who received their second dose during the period of enhanced passive surveillance (on or after June 1, 2021), the highest rate of myocarditis or pericarditis was observed in male individuals aged 18 to 24 years following mRNA-1273 as the second dose (299.5 cases per 1 000 000 doses; 95% CI, 171.2-486.4 cases per 1 000 000 doses); the rate following BNT162b2 as the second dose was 59.2 cases per 1 000 000 doses (95% CI, 19.2-138.1 cases per 1 000 000 doses). Overall rates for both vaccine products were significantly higher when the interdose interval was 30 or fewer days (BNT162b2: 52.1 cases per 1 000 000 doses [95% CI, 31.8-80.5 cases per 1 000 000 doses]; mRNA-1273: 83.9 cases per 1 000 000 doses [95% CI, 47.0-138.4 cases per 1 000 000 doses]) compared with 56 or more days (BNT162b2: 9.6 cases per 1 000 000 doses [95% CI, 6.5-13.6 cases per 1 000 000 doses]; mRNA-1273: 16.2 cases per 1 000 000 doses [95% CI, 10.2-24.6 cases per 1 000 000 doses]). Conclusions and Relevance: The findings of this population-based cohort study of Ontario adolescents and adults with myocarditis or pericarditis following mRNA COVID-19 vaccination suggest that vaccine products and interdose intervals, in addition to age and sex, may be associated with the risk of myocarditis or pericarditis after receipt of these vaccines. Vaccination program strategies, such as age-based product considerations and longer interdose intervals, may reduce the risk of myocarditis or pericarditis following receipt of mRNA vaccines.

The role of Force Health Protection in the Canadian Armed Forces' response to the COVID-19 pandemic.

Within the Canadian Armed Forces (CAF), public health is managed by the Directorate of Force Health Protection (DFHP), a branch of the Canadian Forces Health Services Group. Since the emergence of the novel coronavirus (SARS-CoV-19), DFHP has become heavily involved in health surveillance, outbreak monitoring, policy development, providing evidence-based guidance and advice, liaising with other national, provincial and territorial, municipal and international public health agencies, and ensuring environmental safety of CAF members. Some specific activities include supporting operations and deployments, amending policies and training and promoting hand hygiene, physical distancing and personal protective equipment use. In addition to taking measures to protect its members, CAF-Department of National Defence has contributed to Canada's national response to coronavirus disease 2019 (COVID-19). The DFHP will be developing training for allied health professionals to assist with contact tracing and follow-up, and will ensure adequate resources are in place to manage surge capacity for COVID-19. With these ongoing efforts, initiatives and lessons learned, DFHP is well placed to carry on with its mandate to protect and promote the health and well-being of CAF members and National Defence civilian employees, assisting Canadians and ensuring that CAF members are ready to serve their missions at home and abroad.

Three sequential outbreaks of Group A Streptococcus over a two-year period at the Canadian Forces Leadership and Recruit School, St. Jean Garrison, Québec.

BACKGROUND: Since December 2016, the basic military training (BMT) facility for the Canadian Armed Forces (CAF) has experienced repeated outbreaks of Group A Streptococcus (GAS). In 2018, a voluntary mass antibiotic prophylaxis (MAP) program was implemented to interrupt GAS transmission among recruits. The objective of this study was to describe the epidemiology of three GAS outbreaks and a period of increased pharyngitis infections at the CAF BMT facility in Québec over a two-year span, and to detail the prevention and control measures implemented to mitigate the risk to recruit health. METHODS: Descriptive data were collected on invasive and severe GAS cases along with laboratory data including genotyping of throat swabs from recruits presenting with pharyngitis. A laboratory-based acute respiratory infection surveillance system was used to aid in monitoring and decision-making. Close contacts of recruits were assessed for asymptomatic GAS carriage and MAP adverse events surveillance was conducted. RESULTS: Three distinct GAS outbreaks occurred at the Canadian Forces Leadership and Recruit School totaling eight invasive (iGAS) and 13 severe (sGAS) cases over two years. All iGAS/sGAS cases, apart from one instructor, were among recruits. The predominant strain in all three outbreaks was type emm6.4. A total of 11,293 recruits received MAP (penicillin G benzathine or azithromycin) between March 7, 2018 and November 18, 2019. There were eight reported serious adverse events related to penicillin administration. CONCLUSION: The CAF BMT facility experienced three GAS outbreaks over the course of two years, and despite the use of enhanced hygiene measures, only MAP has been effective in quelling these outbreaks.

Adverse events following mass antibiotic prophylaxis during a Group A Streptococcus outbreak in the Canadian Forces Leadership and Recruit School.

BACKGROUND: Between December 2016 and March 2018, two outbreaks of Group A Streptococcus (GAS) infection occurred at the Canadian Forces Leadership and Recruit School. A voluntary mass antibiotic prophylaxis (MAP) program was implemented in March 2018, to interrupt an ongoing GAS outbreak, and to prevent future outbreaks. METHODS: Instructors and recruits were offered a one-time intramuscular injection of 1.2 million units penicillin G benzathine (PGB). Individuals with a penicillin allergy were offered azithromycin; 500 mg orally once weekly for four consecutive weeks. Instructors and recruits were also asked to complete a voluntary and anonymous survey one week after receipt of MAP, to detect MAP-related adverse events. RESULTS: MAP was offered to 2,749 individuals; 2,707 of whom agreed to receive it (98.5% uptake). The majority of personnel experienced adverse events in the days following MAP; 92.3% of personnel who received PGB reported localized pain at the injection site, and 70.2% of personnel who received azithromycin reported gastrointestinal symptoms. However, only five cases of serious adverse events were reported, and less than 1% of recruits could not complete their basic military training course because of MAP-related adverse events. CONCLUSION: The MAP program implemented in March 2018 was the first of its kind in the Canadian Armed Forces, and the largest single use of PGB in a defined group in Canada. It resulted in very few serious adverse events and with minimal impact on military recruits' successful completion of recruit training.

Cribriform pattern and perineural invasion on MR/US fusion biopsy predict failure of selection criteria for prostatic hemigland ablation.

OBJECTIVES: To assess clinicopathologic factors on MR/US fusion biopsy that might predict failure of theoretical selection criteria for prostatic hemigland ablation (HA). SUBJECTS AND METHODS: A retrospectively maintained single institution multiparametric MRI database (n = 1667) was queried to identify 355 patients who underwent MR/US fusion biopsy, including both targeted biopsy and concurrent systematic biopsy from December 1, 2014 to June 1, 2018. Clinical, pathological, and imaging variables were assessed on fusion biopsy (Table 1) to determine who met theoretical selection criteria for HA, defined as unilateral intermediate-risk prostate cancer per NCCN criteria (Grade Group [GG] 2 or 3 with prostate-specific antigen <20) and no evidence of extraprostatic extension (EPE) on multiparametric MRI. Predictors of selection criteria failure were then assessed in patients who also underwent radical prostatectomy (RP). Failure of the theoretical HA selection criteria was defined as presence of GG ≧ 2 on the contralateral (untreated) side, or the presence of high-risk disease (any GG ≧ 4 or EPE) in the RP specimen. RESULTS: Of the 355 patients who underwent fusion biopsy, 84 patients met the theoretical selection criteria for HA. Of those patients eligible, 54 underwent RP, 37 (68.5%) of which represented unsuccessful HA selection criteria. Patients no longer met HA selection criteria on the basis of upgrading alone in 6/54 (11.1%), EPE alone in 9/54 (16.7%), bilateral GG 2 or 3 in 16/54 (29.6%) or combined EPE and bilateral GG 2 or 3 in 6/54 (11.1%) cases. In the HA selection failures due to upgrading, three also had EPE, one of whom also had missed contralateral GG ≧ 2 disease. The only factor independently associated with HA failure was any presence of cribriform pattern (HR 7.01, P = 0.021). Perineural invasion on systematic biopsyalso appeared to improve the performance of our multivariable model (HR 5.33, P = 0.052), though it was not statistically significant when using a cutoff of <0.05. Accuracy for predicting successful HA was 0.32 and improved to 0.74 if PNI or cribriform were excluded and 0.84 if both were excluded. CONCLUSIONS: In a retrospective analysis of RP patients who underwent preoperative MRI/US fusion biopsy, current selection criteria for prostatic HA based on NCCN intermediate-risk stratification failed to accurately identify appropriate candidates in 68.5% of patients. Cribriform pattern and PNI detected on biopsy reduced the failure of hemigland selection criteria to 43%. These criteria should be routinely reported on biopsy pathology and taken into consideration when selecting patients for HA in prospective clinical trials.

Robot-Assisted Simple Prostatectomy: Illustration of a Simplified Extraperitoneal Transcapsular Technique.

Introduction and Objectives: Robot-assisted simple prostatectomy (RASP) performed with the extraperitoneal (EP) technique (RASP-EP) minimizes the risk of bowel injury, particularly when bowel adhesions may be expected to be prominent, by negating the need to be in the transperitoneal space. However, there is a perception of its technical difficulty owing to the limited space that can be expanded within the space of Retzius. We aimed to describe, in the accompanying video, the step-by-step approach for a technically proficient procedure. Methods: From January 2010 to July 2018, 33 consecutive patients who had undergone RASP-EP were identified from our institutional database. Procedures were performed as described stepwise in the accompanying video. In RASP-EP, a 3 cm paraumbilical incision is made, anterior rectus sheath incised, muscle pushed laterally, and the EP space is entered. The EP space is expanded in the retropubic area using a balloon dilator and a blunt ended trocar, enabling the placement of further three ports for robot docking. A transverse capsulotomy, 2 cm from the bladder neck, is performed a la Millin's. Prostate adenoma is resected circumferentially. Electrocautery hemostasis is performed. Posterior bladder neck and urethra are sutured onto the prostatic fossa with 2-0 Vicryl. A 22F three-way catheter is placed. Anterior capsulotomy is closed in two layers with 2-0 and 0-0 Vicryl sutures. A drain is left in the retropubic space. Patient is discharged within 1-2 days with the catheter in situ, which is then removed 10 days later. Results: Of the 33 patients, median values were age (68), American Society of Anesthesiology (3), Charlson Comorbidity Index (3), and body mass index (28.5 kg/m2). Eight (24.2%) patients had prior abdominal surgeries. Twenty-five (75.8%) patients were catheter dependent. Adjunctive procedures were cystolithotomy (5), umbilical hernia repair (2), and ureteroscopy (1). Median values were operative time (178 minutes), estimated blood loss (200 mL), hemoglobin change (2.8 g/dL), and hematocrit change (9%); only one patient (3.0%) required 1 U transfusion. Median length of stay was 2 days. Clavien-Dindo complications were 0 (21), I (7), II (3), IIIa (1), IIIb (1), IV, and V (0). Median resected prostate weight was 122 g. Incidental prostate cancer was found in three patients (9%); one patient required adjuvant radiotherapy. No patients were catheter-dependent postoperatively; mean postvoid residual was 29 mL (range 0-250 mL). Median follow-up was 4 months. Conclusions: RASP-EP is a safe and efficacious technique that should form the repertoire of a urologist's armamentarium when dealing with large adenomas, particularly when entry into the peritoneal cavity is to be avoided. No competing financial interests exist. Runtime of video: 7 mins 5 secs.

Group A Streptococcus Outbreak in a Canadian Armed Forces Training Facility.

Between December 2016 and April 2017, two cases of invasive Group A Streptococcus (GAS) infections were reported at a Canadian military training facility. An outbreak was declared and a field investigation was launched to characterize the outbreak and identify associated risk factors to limit transmission. Throat culture data from military personnel at the garrison were analyzed. Investigators tracked invasive GAS cases and non-invasive hospitalized GAS cases, and conducted site visits and case interviews. Sensitivity and specificity for a rapid antigen detection test were evaluated. Molecular typing and phylogenomic relationships of outbreak isolates were analyzed using whole-genome sequencing. During this outbreak, four invasive cases were reported and six non-invasive cases were hospitalized. In a sample of 705 throat cultures examined, 35.2% were GAS-positive. Among 65 platoon contacts of one invasive case, 30.2% were GAS-positive. Reluctance to seek medical care, challenges in following cough etiquette, and low compliance with antibiotics were identified among recruits. The rapid antigen detection test had low sensitivity (31.6%) during the outbreak. The outbreak sequence type was emm6.4 and outbreak isolates were highly related phylogenetically, differing by 0-4 single nucleotide variants. This is the first report of a GAS outbreak among Canadian military trainees. Increased surveillance of GAS infections, increased control measures and outbreak-specific clinical guidelines were implemented in-garrison. No further invasive GAS cases were identified. A GAS surveillance system was implemented and efforts to improve antibiotic compliance and medical consultation were recommended.

Intravesical chemotherapy use after radical nephroureterectomy: A national survey of urologic oncologists.

To determine the use of prophylactic intravesical chemotherapy (pIVC) following radical nephroureterectomy (RNU) and barriers to utilization in a survey study of urologic oncologists. METHODS: A survey instrument was constructed, which queried respondents on professional experience, practice environment, pIVC use, and reasons for not recommending pIVC when applicable. The survey was electronically distributed to members of the Society of Urologic Oncology over an 8-week period. Survey software was used for analysis. RESULTS: The survey response rate was 22% (158 of 722). Half of the respondents were in practice for ≤10 years, while 90% performed ≤10 RNU cases annually. Of the 144 urologists regularly performing RNU, only 51% reported administering pIVC, including 22 exclusively in patients with a prior history of bladder cancer. One-third administered pIVC intraoperatively, whereas the remainder instilled pIVC at ≤3 (7%), 4 to 7 (37%), 8 to 14 (20%), and>14 (3%) days postoperatively. Almost all urologists noted giving a single instillation of pIVC. Agents included mitomycin-C (88%), thiotepa (7%), doxorubicin (3%), epirubicin (1%), and BCG (1%). Among respondents who did not administer pIVC, the most common reasons cited included lack of data supporting use (44%), personal preference (19%), and office infrastructure (17%). CONCLUSION: Only 51% of urologic oncologists report using pIVC in patients undergoing RNU. Reasons underlying this underutilization are multifactorial, thereby underscoring the need for continued dissemination of existing data and additional studies to support its benefits. Moreover, improving the logistics of pIVC administration may help to increase utilization rates.

Strategies for prevention of ultrasound-guided prostate biopsy infections.

Prostate cancer is the most common cancer in male patients and the second leading cause of cancer-related mortality in males. To confirm the diagnosis of prostate cancer, an ultrasound-guided needle biopsy is necessary to obtain prostate tissue sufficient for histologic analysis by pathologists. Ultrasound-guided prostate needle biopsy can be accomplished via a transperineal or transrectal approach. The latter biopsy technique involves placing an ultrasound probe into the rectum, visualizing the prostate located just anterior to it, and then obtaining 12-14 biopsies. Each biopsy core requires piercing of the rectal mucosa which can inherently contribute to infection. The increasing infectious risk of prostate needle biopsy requires refinement and re-evaluation of the process in which the technique is performed. Such processes include (but are not limited to) prebiopsy risk stratification, antibiotic prophylaxis, use of rectal preparations, and equipment processing. In the subsequent review, we highlight the current available information on different strategies to reduce the risk of infection following prostate needle biopsy.

Repressor element 1 silencing transcription factor (REST) controls radial migration and temporal neuronal specification during neocortical development.

Neurogenesis requires mechanisms that coordinate early cell-fate decisions, migration, and terminal differentiation. Here, we show that the transcriptional repressor, repressor element 1 silencing transcription factor (REST), regulates radial migration and the timing of neural progenitor differentiation during neocortical development, and that the regulation is contingent upon differential REST levels. Specifically, a sustained presence of REST blocks migration and greatly delays--but does not prevent--neuronal differentiation, resulting in a subcortical band heterotopia-like phenotype, reminiscent of loss of doublecortin. We further show that doublecortin is a direct gene target of REST, and that its overexpression rescues, at least in part, the aberrant phenotype caused by persistent presence of REST. Our studies support the view that the targeted down-regulation of REST to low levels in neural progenitors, and its subsequent disappearance during neurogenesis, is critical for timing the spatiotemporal transition of neural progenitor cells to neurons.

Developing and pre-testing a decision board to facilitate informed choice about delivery approach in uncomplicated pregnancy.

BACKGROUND: The rate of caesarean sections is increasing worldwide, yet medical literature informing women with uncomplicated pregnancies about relative risks and benefits of elective caesarean section (CS) compared with vaginal delivery (VD) remains scarce. A decision board may address this gap, providing systematic evidence-based information so that patients can more fully understand their treatment options. The objective of our study was to design and pre-test a decision board to guide clinical discussions and enhance informed decision-making related to delivery approach (CS or VD) in uncomplicated pregnancy. METHODS: Development of the decision board involved two preliminary studies to determine women's preferred mode of risk presentation and a systematic literature review for the most comprehensive presentation of medical risks at the time (VD and CS). Forty women were recruited to pre-test the tool. Eligible subjects were of childbearing age (18-40 years) but were not pregnant in order to avoid raising the expectation among pregnant women that CS was a universally available birth option. Women selected their preferred delivery approach and completed the Decisional Conflict Scale to measure decisional uncertainty before and after reviewing the decision board. They also answered open-ended questions reflecting what they had learned, whether or not the information had helped them to choose between birth methods, and additional information that should be included. Descriptive statistics were used to analyse sample characteristics and women's choice of delivery approach pre/post decision board. Change in decisional conflict was measured using Wilcoxon's sign rank test for each of the three subscales. RESULTS: The majority of women reported that they had learned something new (n = 37, 92%) and that the tool had helped them make a hypothetical choice between delivery approaches (n = 34, 85%). Women wanted more information about neonatal risks and personal experiences. Decisional uncertainty decreased (p < 0.001) and perceived effectiveness of decisions increased (p < 0.001) post-intervention. CONCLUSION: Non-pregnant women of childbearing age were positive about the decision board and stated their hypothetical delivery choices were informed by risk presentation, but wanted additional information about benefits and experiences. This study represents a preliminary but integral step towards ensuring women considering delivery approaches in uncomplicated pregnancies are fully informed.

Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans.

Ceramide engagement in apoptotic pathways has been a topic of controversy. To address this controversy, we tested loss-of-function (lf) mutants of conserved genes of sphingolipid metabolism in Caenorhabditis elegans. Although somatic (developmental) apoptosis was unaffected, ionizing radiation-induced apoptosis of germ cells was obliterated upon inactivation of ceramide synthase and restored upon microinjection of long-chain natural ceramide. Radiation-induced increase in the concentration of ceramide localized to mitochondria and was required for BH3-domain protein EGL-1-mediated displacement of CED-4 (an APAF-1-like protein) from the CED-9 (a Bcl-2 family member)/CED-4 complex, an obligate step in activation of the CED-3 caspase. These studies define CEP-1 (the worm homolog of the tumor suppressor p53)-mediated accumulation of EGL-1 and ceramide synthase-mediated generation of ceramide through parallel pathways that integrate at mitochondrial membranes to regulate stress-induced apoptosis.

Rural intentions: factors affecting the career choices of family medicine graduates.

OBJECTIVE: To investigate the reasons for family medicine graduates' career choices. DESIGN: Qualitative study using focus groups and one-on-one interviews. SETTING: University of Calgary in Alberta. PARTICIPANTS: Seventeen male and female second-year family medicine residents, representing a range of ages and areas of origin, enrolled in the 2004 urban and rural south streams of the family medicine residency program at the University of Calgary. METHOD: During the final month of training, 2 focus groups were conducted to determine graduating students' career choices and the reasons for them. After focus-group data were analyzed, a questionnaire was constructed and subsequently administered to participants during face-to-face or telephone interviews. MAIN FINDINGS: Most residents initially planned to do urban locums in order to gain experience. In the long term, they planned to open practices in urban areas for lifestyle and family reasons. Many residents from the rural stream had no long-term plans to establish rural practices. Most residents said they felt prepared for practice, but many indicated that an optional third year of paid training, with an emphasis on emergency medicine, obstetrics, and pediatrics, would be desirable. Reasons cited for not practising in rural areas were related to workload, lifestyle issues, family obligations, and perceived lack of medical support in the community. Only 4 female graduates and 1 male graduate intended to practise obstetrics. The main reason residents gave for this was inadequate training in obstetrics during residency. Finances were cited as a secondary reason for many choices, and might in fact be more important than at first apparent. CONCLUSION: Despite its intention to recruit family medicine graduates to rural areas and to obstetrics, the University of Calgary residency training program was not successful in recruiting physicians to these areas. The program likely needs to re-examine the effectiveness of current approaches. If other programs are having similar difficulties recruiting graduates to obstetrics and rural practice, perhaps changes in policies should be considered.

REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis.

Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its co-repressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli.