Bursts and oscillations as independent properties of neural activity in the parkinsonian globus pallidus internus

Bursts and oscillatory modulations in firing rate are hallmark features of abnormal neuronal activity in the parkinsonian Globus Pallidus internus (GPi). Although often implicated together in the pathophysiology of parkinsonian signs, little is known about how burst discharges and oscillatory firing (OF) relate to each other. To investigate this question, extracellular single-unit neuronal activity was recorded from 132 GPi cells in 14 Parkinson's disease patients. We found that burst firing was equally prevalent in OF and non-oscillatory firing (NOF) cells (p > 0.5). More than half of the cells were characterized by either aperiodic bursty activity or OF, but not both. OF and NOF cells had statistically-indistinguishable levels of mean burstiness (p = 0.8). Even when bursting and OF co-existed in individual cells, levels of burstiness and oscillatory power were seldom correlated across time. Interestingly, however, the few OF cells with spectral peaks between 8–13 Hz (α-range) were substantially burstier than other cells (p < 0.01) and showed an unique burst morphology and stronger temporal correlations between oscillatory power and burstiness. We conclude that independent mechanisms may underlie the burst discharges and OF typical of most neurons in the parkinsonian GPi.     

Risk Factors for Varicella Susceptibility Among Refugees to Toronto,Canada

Several outbreaks of varicella have occurred among refugees. We aimed to estimate the prevalence of varicella susceptibility among refugees, and identify risk factors for varicella susceptibility. All refugees rostered at Crossroads Clinic in Toronto, Canada in 2011–2014 were included in our study. Varicella serology was assessed at the initial visit. Refugees’ age, sex, education, time since arrival, and climate and population density of birth country were abstracted from the chart. Multivariate logistic regression was used to identify risk factors for varicella susceptibility. 1063 refugees were rostered at Crossroads Clinic during the study; 7.9 % (95 % CI 6.1, 9.7) were susceptible to varicella. Tropical climate (OR 3.20, 95 % CI 1.53, 6.69) and younger age (OR_{per year of age} 0.92, 95 % CI 0.88–0.96) were associated with increased varicella susceptibility. These risk factors for varicella susceptibility should be taken into account to maximize the cost-effectiveness of varicella prevention strategies among refugees.     

Analysis of junior doctor supervision in Australasian emergency departments

Background: Supervision of junior doctors in ED is vital but limited literature exists on how it is provided. Objective: To assess Australasian ED supervision and review regional legislature supervision requirements. Methods: Between December 2008 and June 2009 emails containing a link to a cross‐sectional survey were sent to Directors of Emergency Medicine Training in all Australasian ED accredited for advanced training. Non‐responding ED were subsequently contacted by telephone or email. Regional legislature supervision requirements were obtained from postgraduate medical councils. Results: A total of 103 (98.1%) of 105 ED participated. Senior review in person was mandatory in 43.2% of ED for patients of PGY1 (postgraduate year 1 doctors) and 6.1% of ED for patients of PGY2 (P < 0.001). Of ED without mandatory review, 13% had written guidelines detailing which patients required review. When ED consultants were on‐site, they most commonly provided supervision in 60.2% of ED and shared supervision equally with registrars in 35.7% of ED; when consultants were off‐site registrars most commonly provided supervision in 87.6% of ED. Fewer major regional/rural base hospitals had 24 h PGY3 or above supervision than major referral and urban district hospitals (82.6% vs 100% and 100%, P < 0.01). Regional legislature requirements varied with no universal guidelines. Conclusion: There are significant differences between supervision requirements for PGY1 and PGY2. A minority of ED in Australasia do not have 24 h supervision by PGY3 or higher. Few ED have written guidelines for supervising PGY1 and PGY2. The majority of registrar supervision occurs without consultant oversight. Legislature requirements for supervision in ED are variable between regions.     

Investigating the predictive value of whole-brain structural MR scans in autism: A pattern classification approach

Autistic spectrum disorder (ASD) is accompanied by subtle and spatially distributed differences in brain anatomy that are difficult to detect using conventional mass-univariate methods (e.g., VBM). These require correction for multiple comparisons and hence need relatively large samples to attain sufficient statistical power. Reports of neuroanatomical differences from relatively small studies are thus highly variable. Also, VBM does not provide predictive value, limiting its diagnostic value.Here, we examined neuroanatomical networks implicated in ASD using a whole-brain classification approach employing a support vector machine (SVM) and investigated the predictive value of structural MRI scans in adults with ASD. Subsequently, results were compared between SVM and VBM. We included 44 male adults; 22 diagnosed with ASD using “gold-standard” research interviews and 22 healthy matched controls.SVM identified spatially distributed networks discriminating between ASD and controls. These included the limbic, frontal-striatal, fronto-temporal, fronto-parietal and cerebellar systems. SVM applied to gray matter scans correctly classified ASD individuals at a specificity of 86.0% and a sensitivity of 88.0%. Cases (68.0%) were correctly classified using white matter anatomy. The distance from the separating hyperplane (i.e., the test margin) was significantly related to current symptom severity. In contrast, VBM revealed few significant between-group differences at conventional levels of statistical stringency.We therefore suggest that SVM can detect subtle and spatially distributed differences in brain networks between adults with ASD and controls. Also, these differences provide significant predictive power for group membership, which is related to symptom severity.     

Prognostic Implications of Declining Hemoglobin Content in Patients Hospitalized With Acute Coronary Syndromes

BackgroundContemporary definitions of bleeding endpoints are restricted mostly to clinically overt events. Whether hemoglobin drop per se, with or without overt bleeding, adversely affects the prognosis of patients with acute coronary syndrome (ACS) remains unclear.ObjectivesThe aim of this study was to examine in the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial the incidence, predictors, and prognostic implications of in-hospital hemoglobin drop in patients with ACS managed invasively stratified by the presence of in-hospital bleeding.MethodsPatients were categorized by the presence and amount of in-hospital hemoglobin drop on the basis of baseline and nadir hemoglobin values and further stratified by the occurrence of adjudicated in-hospital bleeding. Hemoglobin drop was defined as minimal (<3 g/dl), minor (≥3 and <5 g/dl), or major (≥5 g/dl). Using multivariate Cox regression, we modeled the association between hemoglobin drop and mortality in patients with and without overt bleeding.ResultsAmong 7,781 patients alive 24 h after randomization with available hemoglobin data, 6,504 patients (83.6%) had hemoglobin drop, of whom 5,756 (88.5%) did not have overt bleeding and 748 (11.5%) had overt bleeding. Among patients without overt bleeding, minor (hazard ratio [HR]: 2.37; 95% confidence interval [CI]: 1.32 to 4.24; p = 0.004) and major (HR: 2.58; 95% CI: 0.98 to 6.78; p = 0.054) hemoglobin drop were independently associated with higher 1-year mortality. Among patients with overt bleeding, the association of minor and major hemoglobin drop with 1-year mortality was directionally similar but had wider CIs (minor: HR: 3.53 [95% CI: 1.06 to 11.79]; major: HR: 13.32 [95% CI: 3.01 to 58.98]).ConclusionsAmong patients with ACS managed invasively, in-hospital hemoglobin drop ≥3 g/dl, even in the absence of overt bleeding, is common and is independently associated with increased risk for 1-year mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox; NCT01433627)     

Detection of Lymphatic Micrometastases in Patients With Stages I and II Colorectal Cancer: Impact on Five-Year Survival

PURPOSE: Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer.METHODS: This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test.RESULTS: Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11–160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients (P = 0.489).CONCLUSIONS: The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.Supported by the Apertus Research Program (Andromaco Pharmaceutical Company) and by The National Public Grant (FONDECYT #1000556).     

Acrylamide does not induce tumorigenesis or major defects in mice in vivo

Chronic administration of acrylamide has been shown to induce thyroid tumors in rat. In vitro acrylamide also causes DNA damage, as demonstrated by the comet assay, in various types of cells including human thyroid cells and lymphocytes, as well as rat thyroid cell lines. In this work, mice were administered acrylamide in their drinking water in doses comparable with those used in rats, i.e., around 3-4 mg/kg per day for mice treated 2, 6, and 8 months. Some of the mice were also treated with thyroxine (T(4)) to depress the activity of the thyroid. Others were treated with methimazole that inhibits thyroid hormone synthesis and consequently secretion and thus induces TSH secretion and thyroid activation. These moderate treatments were shown to have their known effect on the thyroid (e.g. thyroid hormone and thyrotropin serum levels, thyroid gland morphology...). Besides, T(4) induced an important polydipsia and degenerative hypertrophy of adrenal medulla. Acrylamide exerted various discrete effects and at high doses caused peripheral neuropathy, as demonstrated by hind-leg paralysis. However, it did not induce thyroid tumorigenesis. These results show that the thyroid tumorigenic effects of acrylamide are not observed in another rodent species, the mouse, and suggest the necessity of an epidemiological study in human to conclude on a public health policy.