Brain activity and connectivity in response to negative affective stimuli: Impact of dysphoric mood and sex across diagnoses

Negative affective stimuli elicit behavioral and neural responses which vary on a continuum from adaptive to maladaptive, yet are typically investigated in a dichotomous manner (healthy controls vs. psychiatric diagnoses). This practice may limit our ability to fully capture variance from acute responses to negative affective stimuli to psychopathology at the extreme end. To address this, we conducted a functional magnetic resonance imaging study to examine the neural responses to negative valence/high arousal and neutral valence/low arousal images as a function of dysphoric mood and sex across individuals (n = 99) who represented traditional categories of healthy controls, major depressive disorder, bipolar psychosis, and schizophrenia. Observation of negative (vs. neutral) stimuli elicited blood oxygen‐level dependent responses in the following circuitry: periaqueductal gray, hypothalamus (HYPO), amygdala (AMYG), hippocampus (HIPP), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and greater connectivity between AMYG and mPFC. Across all subjects, severity of dysphoric mood was associated with hyperactivity of HYPO, and, among females, right (R) AMYG. Females also demonstrated inverse relationships between severity of dysphoric mood and connectivity between HYPO ‐ R OFC, R AMYG ‐ R OFC, and R AMYG ‐ R HIPP. Overall, our findings demonstrated sex‐dependent deficits in response to negative affective stimuli increasing as a function of dysphoric mood state. Females demonstrated greater inability to regulate arousal as mood became more dysphoric. These findings contribute to elucidating biosignatures associated with response to negative stimuli across disorders and suggest the importance of a sex‐dependent lens in determining these biosignatures. Hum Brain Mapp 37:3733–3744, 2016. © 2016 Wiley Periodicals, Inc .     

Left atrial systolic function is depressed in idiopathic and preserved in ischemic dilated cardiomyopathy

BACKGROUND: Left atrial systolic dysfunction, unexplained by altered loading conditions, has been reported in idiopathic dilated cardiomyopathy suggesting left atrial involvement in the myopathic process. MATERIALS AND METHODS: Seventeen patients with idiopathic dilated cardiomyopathy, 16 with ischemic dilated cardiomyopathy and 18 normal controls were studied with transthoracic echocardiography and cardiac catheterization. Transmitral diastolic flow was evaluated with pulsed Doppler. Left atrial volume (cm3/m2) at mitral valve opening (maximal, Vmax.), onset of atrial systole (P wave of the electrocardiogram, Vp), and mitral valve closure (minimal, Vmin. ) was determined with two-dimensional echocardiography using the biplane area-length method. The left atrial active emptying fraction (ACTEF = [Vp-Vmin.] x 100/Vp) served as an index of systolic function. RESULTS: The peak early diastolic transmitral flow velocity (cm/sec) was similar in the three groups (idiopathic: 60 +/- 16, ischemic: 58 +/- 20, control: 56 +/- 22; P = NS), whereas the late diastolic transmitral flow velocity was lower but not significantly different in idiopathic compared to ischemic cardiomyopathy, and in both was lower than control (26 +/- 12 vs. 34 +/- 13 vs. 44 +/- 14, respectively; P < 0.05). Vmax. and Vp were similar in idiopathic and ischemic cardiomyopathy and greater than control (44.6 +/- 13.6 vs. 48.2 +/- 18.3 vs. 26.9 +/- 6.2; P < 0.05, and 34.6 +/- 13.4 vs. 30.8 +/- 10.9 vs. 16.7 +/- 3.7, respectively; P < 0.05). ACTEF was lower in idiopathic than in ischemic cardiomyopathy and in the latter it was similar to control (18 +/- 10% vs. 32 +/- 10% vs. 36 +/- 10%, respectively; P < 0.05). Moreover, ACTEF was inversely related to left atrial tension at end-of atrial systole both in idiopathic and in ischemic cardiomyopathy (r2 = 0.52, P = 0.001 and r2 = 0.57, P = 0.0007, respectively). However, at any given level of left atrial tension at end of atrial systole, ACTEF was lower in idiopathic than ischemic cardiomyopathy. CONCLUSION: Left atrial systolic function is depressed in idiopathic and preserved in ischemic dilated cardiomyopathy despite similar left atrial loading conditions. This finding suggests left atrial myopathy in the former, and may be related to the differences in the response to medical treatment and clinical outcome observed between the two conditions.     

Continuing education course #3: current practices and future trends in neuropathology assessment for developmental neurotoxicity testing

The continuing education course on Developmental Neurotoxicity Testing (DNT) was designed to communicate current practices for DNT neuropathology, describe promising innovations in quantitative analysis and noninvasive imaging, and facilitate a discussion among experienced neuropathologists and regulatory scientists regarding suitable DNT practices. Conventional DNT neuropathology endpoints are qualitative histopathology and morphometric endpoints of particularly vulnerable sites (e.g., cerebral, cerebellar, or hippocampal thickness). Novel imaging and stereology measurements hold promise for automated analysis of factors that cannot be effectively examined in routinely processed specimens (e.g., cell numbers, fiber tract integrity). The panel recommended that dedicated DNT neuropathology data sets be acquired on a minimum of 8 sections (for qualitative assessment) or 3 sections (for quantitative linear and stereological analyses) using a small battery of stains to examine neurons and myelin. Where guidelines permit discretion, immersion fixation is acceptable for younger animals (postnatal day 22 or earlier), and peripheral nerves may be embedded in paraffin. Frequent concerns regarding DNT data sets include false-negative outcomes due to processing difficulties (e.g., lack of concordance among sections from different animals) and insensitive analytical endpoints (e.g., qualitative evaluation) as well as false-positive results arising from overinterpretation or misreading by inexperienced pathologists.     

Roux-en-Y Reconstruction for Failed Fundoplication

Background

Redo fundoplication has acceptable outcomes in patients with failed previous fundoplications. However, a subset of patients require Roux-en-Y (RNY) reconstruction for symptom relief.

Aim

The aim of this study was to demonstrate safety and efficacy of RNY reconstruction for failed fundoplications.

Method

Retrospective review of data on patients who underwent short-limb RNY gastrojejunostomy (GJ) or esophagojejunostomy (EJ) between the years 2005 and 2007 was performed.

Results

Twenty-two patients underwent RNY reconstructions. Fourteen (64%) patients had one, six (27%) patients had two, and 2 (9%) patients had three previous anti-reflux procedures. RNY GJ was performed in 18 patients and EJ in four patients. Gastrectomy was performed in 13 of these patients. Seven patients (32%) had ten major or minor complications within the 30-day postoperative period, without any mortality observed. At a mean follow-up of 23 months, completed in 21 of these patients (95%), the average heartburn score was 0.38 (range, 0–2). The average regurgitation score was 0.23 (range, 0 to2) and the average dysphagia score was 0.7 (range, 0–2). The mean postoperative BMI was 25.4 compared to a preoperative BMI of 31.

Conclusion

RNY reconstruction with GJ or EJ for failed anti-reflux procedures is a safe, valid surgical option in difficult situations, where a redo fundoplication is either non-feasible or expected to fail. However, it is associated with higher morbidity.     

Tracheobronchial stenting and central airway replacement

PURPOSE OF REVIEW: The present paper reviews the recent literature on the management of malignant large airway obstruction using tracheobronchial stenting and airway replacement by aortic allografts. RECENT FINDINGS: Airway stenting is a valuable adjunct to therapeutic bronchoscopy to relieve malignant airway obstruction. Over 80% of patients with obstructing lesions who were treated by airway stenting presented immediate symptom improvement in recent series. Stenting may also function as a bridge until further curative treatment can be used. Different stent models are available; their advantages and disadvantages depend on materials and constructions; clinical experience is larger with silicon-based models than with metallic stents. An alternative strategy for the management of nonresectable primary tracheal tumors aiming to replace the central airway with an allogenic aortic allograft has been proposed. Experimental studies showed that an aortic allograft produced a respiratory conduit that shared fundamental elements of the trachea and newly formed cartilage rings were observed. SUMMARY: Airway stenting provides efficient palliation of symptoms in patients with malignant central airway obstruction. Evidence-based studies are needed to identify patients who may have the greatest benefit from stenting. Tracheal replacement with allogenic aortic allografts is a novel technique which brings hope to the management of extensive tracheal lesions.     

Role of the medial temporal lobes in relational memory: neuropsychological evidence from a cued recognition paradigm

In this study, we examined the role of the hippocampus in relational memory by comparing item recognition performance in amnesic patients with medial temporal lobe (MTL) damage and their matched controls. Specifically, we investigated the contribution of associative memory to item recognition using a cued recognition paradigm. Control subjects studied cue-target pairs once, whereas amnesic patients studied cue-target pairs six times. Following study, subjects made recognition judgments about targets that were presented either alone (no cue), with the originally presented cue (same cue), or with a cue that had been presented with a different target (recombined cue). Controls had higher recognition scores in the same cue than in the recombined cue condition, indicating that they benefited from the associative information provided by the same cue. By contrast, amnesic patients did not. This was true even for a subgroup of patients whose recognition performance in the no cue condition was matched to that of the controls. These data provide further support for the idea that the hippocampus plays a critical role in relational memory, even when associative information need not be retrieved intentionally.