Altered hippocampal function in major depression despite intact structure and resting perfusion

Background: Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation. Method: A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed. Results: The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow. Conclusions: Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression

Pharyngeal Oxygen Delivery Device Sustains Manikin Lung Oxygenation Longer Than High-Flow Nasal Cannula

PURPOSE: Hypoxemia during a failed airway scenario is life threatening. A dual-lumen pharyngeal oxygen delivery device (PODD) was developed to fit inside a traditional oropharyngeal airway for undisrupted supraglottic oxygenation and gas analysis during laryngoscopy and intubation. We hypothesized that the PODD would provide oxygen as effectively as high-flow nasal cannula (HFNC) while using lower oxygen flow rates. METHODS: We compared oxygen delivery of the PODD to HFNC in a preoxygenated, apneic manikin lung that approximated an adult functional residual capacity. Four arms were studied: HFNC at 20 and 60 liters per minute (LPM) oxygen, PODD at 10 LPM oxygen, and a control arm with no oxygen flow after initial preoxygenation. Five randomized 20-minute trials were performed for each arm (20 trials total). Descriptive statistics and analysis of variance were used with statistical significance of RESULTS: Mean oxygen concentrations were statistically different and decreased from 97% as follows: 41 ± 0% for the control, 90 ± 1% for HFNC at 20 LPM, 88 ± 2% for HFNC at 60 LPM, and 97 ± 1% (no change) for the PODD at 10 LPM. CONCLUSION: Oxygen delivery with the PODD maintained oxygen concentration longer than HFNC in this manikin model at lower flow rates than HFNC

A comparison of the hypoglycemic effect of insulin with systemic venous and portal venous administration

The hyperglycemic effect of insulin by prolonged intraportal and systemic infusion was measured in unanesthetized dogs with a modified portacaval transposition. There was no significant difference in response with the two routes of administration. The relation of these results to research directed to surgical therapy of diabetes is discussed. © 1963 W. B. Saunders Company

Identifying the nature of episodic memory deficits in Major Depressive Disorder using a Real-World What-Where-When task

Deficits in episodic memory have been reported in various psychiatric conditions, including Major Depressive Disorder (MDD). Many widely used episodic memory tests do not have the ability to distinguish between impaired memory of separate components of a real-life event (e.g. what happened, where it happened and when), and impaired binding of such real-life features. To address this issue, a naturalistic, real-world What-Where-When memory task was employed to assess the nature of episodic memory impairments in MDD. A validation study established that the task is sensitive to age-related episodic memory changes, and that intentional encoding does not invalidate the task. The main study then compared the performance of patients with depression and control participants on the intentionally encoded WWW task. Patients with MDD presented an overall episodic memory impairment arising from deficits in object memory and the ability to bind objects to temporal context. Taken together, our study confirms the episodic memory impairment in MDD, by providing evidence of deficient object memory and reduced ability to bind temporal context to objects in patients. Our naturalistic WWW task presents a promising approach for thorough identification of the nature of episodic memory impairments, under a real-world environment, in various conditions, including MDD

Lectures in Honor of the Alexander Campbell Bicentennial

In 1984, the Disciples of Christ Historical Society set forth a program to celebrate the 200th birthday of Alexander Campbell. This book launched a renewed interest in Stone-Campbell history and inspired research that shaped numerous historical projects. Contributors include T. Dwight Bozeman, Robert O. Fife, Richard L. Harrison, Samuel S. Hill, Thomas Olbricht, William J. Richardson, D. Newell Williams, Eva Jean Wrather, and Barbara Brown Zickmund.https://digitalcommons.acu.edu/acu_library_books/1018/thumbnail.jp

When who and how matter: explaining the success of referendums in Europe

This article aims to identify the institutional factors that make a referendum successful. This comparative analysis seeks to explain the success of top-down referendums organized in Europe between 2001 and 2013. It argues and tests for the main effect of three institutional factors (popularity of the initiator, size of parliamentary majority, and political cues during referendum campaigns) and controls for the type of referendum and voter turnout. The analysis uses data collected from referendums and electoral databases, public opinion surveys, and newspaper articles. Results show that referendums proposed by a large parliamentary majority or with clear messages from political parties during campaign are likely to be successful

Reconceptualising treatment-resistant depression as difficult-to-treat depression

We are heartened that our consensus statement1 on difficult-to-treat depression has provoked robust debate. As pointed out by Lisa Cosgrove and colleagues,2 our proposed definition and model of care for difficult-to-treat depression is not derived from a systematic review or a Delphi technique. The term difficult-to-treat depression had previously been proposed to address semantic and conceptual issues with the so-called treatment-resistant depression model, for patients where achieving sustained remission proves elusive.3 We aimed to extend the discussion regarding this proposal, focusing on practical clinical advice. As the concept of difficult-to-treat depression is new, there is no literature to systematically review. The literature around the management of so-called treatment-resistant depression has been reviewed on many occasions, but this literature was only of partial relevance to our aims. Not only is there no universally accepted definition of treatment-resistant depression, but those that are used rarely if ever take into account psychotherapeutic or neurostimulatory treatments, or how to account for differential efficacy among treatments.4, 5 At the core of the proposed difficult-to-treat depression model is the importance of taking a holistic approach and considering all treatment options available. A systematic review of all treatments for depression was not practical. As a result, our consensus was based on the culmination of extensive discussion and deliberation among 15 international experts in the management of depression from across three continents, and the national guidelines for the treatment of depression from the countries represented. Rather than through a Delphi technique, we arrived at a consensus through many iterative reviews of the manuscript until all 15 contributors were comfortable with all the statements being discussed. However, we wish to clarify two key points that we feel Cosgrove and colleagues might have misunderstood

Huntington’s disease age at motor onset is modified by the tandem hexamer repeat in TCERG1

Huntington’s disease is caused by an expanded CAG tract in HTT. The length of the CAG tract accounts for over half the variance in age at onset of disease, and is influenced by other genetic factors, mostly implicating the DNA maintenance machinery. We examined a single nucleotide variant, rs79727797, on chromosome 5 in the TCERG1 gene, previously reported to be associated with Huntington’s disease and a quasi-tandem repeat (QTR) hexamer in exon 4 of TCERG1 with a central pure repeat. We developed a method for calling perfect and imperfect repeats from exome-sequencing data, and tested association between the QTR in TCERG1 and residual age at motor onset (after correcting for the effects of CAG length in the HTT gene) in 610 individuals with Huntington’s disease via regression analysis. We found a significant association between age at onset and the sum of the repeat lengths from both alleles of the QTR (p = 2.1 × 10−9), with each added repeat hexamer reducing age at onset by one year (95% confidence interval [0.7, 1.4]). This association explained that previously observed with rs79727797. The association with age at onset in the genome-wide association study is due to a QTR hexamer in TCERG1, translated to a glutamine/alanine tract in the protein. We could not distinguish whether this was due to cis-effects of the hexamer repeat on gene expression or of the encoded glutamine/alanine tract in the protein. These results motivate further study of the mechanisms by which TCERG1 modifies onset of HD