I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Suicidal thoughts and behaviors (STBs) are major public health problems that have not declined appreciably in several decades. One of the first steps to improving the prevention and treatment of STBs is to establish risk factors (i.e., longitudinal predictors). To provide a summary of current knowledge about risk factors, we conducted a meta-analysis of studies that have attempted to longitudinally predict a specific STB-related outcome. This included 365 studies (3,428 total risk factor effect sizes) from the past 50 years. The present random-effects meta-analysis produced several unexpected findings: across odds ratio, hazard ratio, and diagnostic accuracy analyses, prediction was only slightly better than chance for all outcomes; no broad category or subcategory accurately predicted far above chance levels; predictive ability has not improved across 50 years of research; studies rarely examined the combined effect of multiple risk factors; risk factors have been homogenous over time, with 5 broad categories accounting for nearly 80% of all risk factor tests; and the average study was nearly 10 years long, but longer studies did not produce better prediction. The homogeneity of existing research means that the present meta-analysis could only speak to STB risk factor associations within very narrow methodological limits-limits that have not allowed for tests that approximate most STB theories. The present meta-analysis accordingly highlights several fundamental changes needed in future studies. In particular, these findings suggest the need for a shift in focus from risk factors to machine learning-based risk algorithms. (PsycINFO Database Record

Risk factors for suicidal thoughts and behaviors: A meta-analysis of 50 years of research.

The International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support (ALS) Task Force performed detailed systematic reviews based on the recommendations of the Institute of Medicine of the National Academies1 and using the methodological approach proposed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group.2 Questions to be addressed (using the PICO [population, intervention, comparator, outcome] format)3 were prioritized by ALS Task Force members (by voting). Prioritization criteria included awareness of significant new data and new controversies or questions about practice. Questions about topics no longer relevant to contemporary practice or where little new research has occurred were given lower priority. The ALS Task Force prioritized 42 PICO questions for review. With the assistance of information specialists, a detailed search for relevant articles was performed in each of 3 online databases (PubMed, Embase, and the Cochrane Library).

By using detailed inclusion and exclusion criteria, articles were screened for further evaluation. The reviewers for each question created a reconciled risk of bias assessment for each of the included studies, using state-of-the-art tools: Cochrane for randomized controlled trials (RCTs),4 Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 for studies of diagnostic accuracy,5 and GRADE for observational studies that inform both therapy and prognosis questions.6

GRADE evidence profile tables7 were then created to facilitate an evaluation of the evidence in support of each of the critical and important outcomes. The quality of the evidence (or confidence in the estimate of the effect) was categorized as high, moderate, low, or very low,8 based on the study methodologies and the 5 core GRADE domains of risk of bias, inconsistency, indirectness, imprecision, and other considerations (including publication bias).9

These evidence profile tables were then used to create a …

/pdf/part-4-advanced-life-support-2015-international-consensus-on-3s0zzf6w8u.pdf

Part 4: Advanced life support: 2015 International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations

Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins

Multiple sources of evidence support a role for diminished dopaminergic neurotransmission in major depression. The physiological alterations underlying reduced dopamine(DA)signalingcouldresultfromeitherdiminishedDAreleasefrompresynaptic neuronsorimpairedsignaltransduction,eitherduetochangesinreceptornumberor functionand/oralteredintracellularsignalprocessing.Therearedatasupportingeachofthesemechanisms,althoughinterpretationofpreviousresearchisconfoundedbyissuesaroundstudypopulation, medication status, and technological limitations. In some patients with depression, DA-related disturbances improve by treatment with antidepressants, presumably by acting on serotonergic or noradrenergic circuits, which then affect DA function. However, most antidepressant treatments do not directly enhance DA neurotransmission, which may contribute to residual symptoms, including impaired motivation, concentration, and pleasure. Animal models of major depression show considerable responsiveness to manipulations of DA neurotransmission. Several studies, including postmortem investigations, particularly of subjects with severe depression, have demonstrated reduced concentrations of DA metabolites both in the cerebrospinal fluid and in brain regions that mediate mood and motivation. Although the neuroimaging findings are not unequivocal, several studies support the hypothesis that major depression is associated with a state of reduced DA transmission, possiblyreflectedbyacompensatoryup-regulationofD2receptors.ThesealterationsinDAsignalingmay underlie the findings of increased “liking” or “high” feelings reported by severely depressed subjects treated with d-amphetamine compared with the response of less severely ill and normal control subjects. The efficacy of medications that directly act on DA neurons or receptors, such as monoamine oxidase inhibitors and pramipexole, suggests that subtypes of depression stemming from a primary DA dysfunction exist. Further research on the contribution of DA to the pathophysiology of depressionisjustifiedtoimproveoutcomesforpatientswithtreatment-resistantandnonremittingdepression.

/pdf/the-role-of-dopamine-in-the-pathophysiology-of-depression-3c9024azkx.pdf

The role of dopamine in the pathophysiology of depression.

Serum S100 protein: A potential marker for cerebral events during cardiopulmonary bypass

Background: Sleep disturbance is common in intensive care patients. Aside from its unpleasantness, there is a correlation with intensive care unit (ICU) syndrome/delirium. Reasons for sleep deprivation appear to be multifactorial, including the underlying illness, an acute superimposed disturbance, medications, and the ICU environment itself. There are reasons to believe that alterations of the 'biological clock' might contribute. Melatonin secretion is one reflection of this internal sleep/wake mechanism. Melatonin levels are normally high during the night and low during daytime, being suppressed by bright light. Methods: Melatonin levels in blood and urine were studied over 3 consecutive days in eight critically ill patients during deep sedation and mechanical ventilation. Sedation was assessed with the sedation-agitation (SAS) scale and bispectral index (BIS) monitor. Results: The circadian rhythm of melatonin release was abolished in all but one patient, who recovered much more quickly than the others. There was no correlation between melatonin levels and levels of sedation. Conclusions: This study indicates that dyssynchronization of the melatonin secretion rhythm is common in critically ill and mechanically ventilated patients. It could be hypothesized that an impairment of the melatonin rhythm may play a role in the development of sleep disturbances and delirium in intensive care patients, and that melatonin supply could reduce the incidence of these phenomena.

Abolished circadian rhythm of melatonin secretion in sedated and artificially ventilated intensive care patients.

Purpose: This study of patients with minor head injury was designed to investigate the relation of S-100 protein measurements to computed tomograpy (CT) findings and patients outcomes. Increased serum levels of this protein were hypothetized to predict intracranial pathology and increased frequency of post-concussion symptoms. Methods: One hundred and eighty-two patients were studied with Glasgow Coma Scale scores of 13-15. The study recruited patients from three Scandinavian neurotrauma centres. Serum levels of S-100 protein were measured at admittance and CT scans of the brain were obtained within 24 hours postinjury in all patients. Outcome was evaluated with the Rivermead Postconcussion Symptoms Questionnaire (RPQ) 3 months after the injury. Results: Increased serum level of S-100 protein was detected in 69 (38%) patients, and CT scan demonstrated intracranial pathology in 10 (5%) (brain contusion in seven, epidural haematoma in two, traumatic subarachnoid haemorrhage in one). The proportion of patien...

Christer Alling

Papers

Serum S100 protein: A potential marker for cerebral events during cardiopulmonary bypass

Abolished circadian rhythm of melatonin secretion in sedated and artificially ventilated intensive care patients.

The clinical value of serum S-100 protein measurements in minor head injury : a Scandinavian multicentre study

Cerebral complications after cardiac surgery assessed by S-100 and NSE levels in blood

The Appearance of S-100 Protein in Serum During and Immediately After Cardiopulmonary Bypass Surgery: A Possible Marker for Cerebral Injury