Persistent neuronal firing in the medial temporal lobe supports performance and workload of visual working memory in humans

The involvement of the medial temporal lobe (MTL) in working memory is controversially discussed. Recent findings suggest that persistent neural firing in the hippocampus during maintenance in verbal working memory is associated with workload. Here, we recorded single neuron firing in 13 epilepsy patients (7 male) while they performed a visual working memory task. The number of coloured squares in the stimulus set determined the workload of the trial. Performance was almost perfect for low workload (1 and 2 squares) and dropped at high workload (4 and 6 squares), suggesting that high workload exceeded working memory capacity. We identified maintenance neurons in MTL neurons that showed persistent firing during the maintenance period. More maintenance neurons were found in the hippocampus for trials with correct compared to incorrect performance. Maintenance neurons increased and decreased firing in the hippocampus and increased firing in the entorhinal cortex for high compared to low workload. Population firing predicted workload particularly during the maintenance period. Prediction accuracy of workload based on single-trial activity during maintenance was strongest for neurons in the entorhinal cortex and hippocampus. The data suggest that persistent neural firing in the MTL reflects a domain-general process of maintenance supporting performance and workload of multiple items in working memory below and beyond working memory capacity. Persistent neural firing during maintenance in the entorhinal cortex may be associated with its preference to process visual-spatial arrays

Is Internal Rotation Measurement of the Hip Useful for Ruling in Cam or Pincer Morphology in Asymptomatic Males? A Diagnostic Accuracy Study.

BACKGROUND Cam and pincer morphologies are associated with limited internal rotation. However, the routine clinical examination for hip rotation has limited reliability. A more standardized method of measuring hip rotation might increase test-retest and interobserver reliability and might be useful as a screening test to detect different hip morphologies without the need for imaging. We developed an examination chair to standardize the measurement of internal hip rotation, which improved interobserver reliability. However, the diagnostic test accuracy for this test is unknown. QUESTION/PURPOSE Is a standardized method of determining internal hip rotation using an examination chair useful in detecting cam and pincer morphology with MRI as a reference standard? METHODS A diagnostic test accuracy study was conducted in a sample of asymptomatic males. Using an examination chair with a standardized seated position, internal rotation was measured in 1080 men aged 18 to 21 years who had been conscripted for the Swiss army. The chair prevents compensatory movement by stabilizing the pelvis and the thighs with belts. The force to produce the internal rotation was standardized with a pulley system. Previous results showed that the measurements with the examination chair are similar to clinical assessment but with higher interobserver agreement. A random sample of 430 asymptomatic males was invited to undergo hip MRI. Of those, 244 White European males responded to the invitation and had a mean age of 20 ± 0.7 years and a mean internal rotation of the hip of 33° ± 8.5°. Using MRI as the reference standard, 69% (169 of 244) had a normal hip, 24% (59 of 244) a definite cam morphology (Grades 2 and 3), 3% (8 of 244) an increased acetabular depth, and 3% (8 of 244) a combination of both. One experienced radiologist graded cam morphology as follows: 0 = normal, 1 = mild, 2 = moderate, and 3 = severe. Pincer morphology was defined by increased acetabular depth (≤ 3 mm distance between the center of the femoral neck and the line connecting the anterior and posterior acetabular rims). The intraobserver agreement was substantial (weighted κ of 0.65). A receiver operating characteristic (ROC) curve was fitted, and sensitivity, specificity, and likelihood ratios were estimated for different internal rotation cutoffs. RESULTS For cam morphology, the area under the ROC curve was 0.75 (95% CI 0.67 to 0.82). Internal hip rotation of less than 20° yielded a positive likelihood ratio of 9.57 (sensitivity 0.13, specificity 0.99), and a value of 40° or more resulted in a negative likelihood ratio of 0.36 (sensitivity 0.93, specificity 0.20). The area under the curve for detecting the combination of cam and pincer morphologies was 0.87 (95% CI 0.74 to 1.0). A cutoff of 20° yielded a positive likelihood ratio of 9.03 (sensitivity 0.33, specificity 0.96). CONCLUSION This examination chair showed moderate-to-good diagnostic value to rule in hip cam morphology in White European males. However, at the extremes of the 95% confidence intervals, diagnostic performance would be poor. Nonetheless, we believe this test can contribute to identifying cam morphologies, and we hope that future, larger studies-ideally in more diverse patient populations-will seek to validate this to arrive at more precise estimates of the diagnostic performance of this test. LEVEL OF EVIDENCE Level III, diagnostic study

Bromocriptine treatment associated with recovery from peripartum cardiomyopathy in siblings: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Peripartum cardiomyopathy is a rare form of cardiomyopathy, with heterogeneous presentation occurring in women between one-month antepartum and six months postpartum. It carries a poor prognosis and a high risk of mortality.</p> <p>Case presentation</p> <p>We report the development of peripartum cardiomyopathy in two sisters, 27- and 35-year-old African women, one of whom presented with a large left ventricular thrombus. Subsequently, both patients were treated with bromocriptine, heparin and standard therapy for heart failure (angiotensin converting enzyme inhibitors, beta-blockers and diuretics). During follow-up, the left ventricular thrombus observed in one patient degraded. Neither patient experienced a thrombotic event, and both experienced continuous improvements in cardiac function and New York Heart Association stage.</p> <p>Conclusion</p> <p>The development of peripartum cardiomyopathy in two sisters indicates that there may be a genetic basis for this type of cardiomyopathy, and that women with a positive family history for peripartum cardiomyopathy may have an increased risk of developing the disease. This is also the first report of a patient experiencing degradation of a large left ventricular thrombus under standard therapy for heart failure with bromocriptine. It suggests that the use of bromocriptine in association with adequate anti-coagulation and heart failure therapy may be beneficial and safe.</p

Long-term prognosis, subsequent pregnancy, contraception and overall management of peripartum cardiomyopathy: practical guidance paper from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy

Peripartum cardiomyopathy is an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause for heart failure is identified. Outcome varies from full recovery to residual left ventricular systolic dysfunction and even death. Many women return to their physician to acquire information on their long‐term prognosis, to seek medical advice regarding contraception, or when planning a subsequent pregnancy. This position paper summarizes current evidence for long‐term outcome, risk stratification of further pregnancies and overall management. Based on the best available evidence, as well as the clinical experience of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy members, a consensus on pre‐ and postpartum management algorithms for women undergoing a subsequent pregnancy is presented

Protective Function of STAT3 in CVB3-Induced Myocarditis

The transcription factor signal transducer and activator of transcription 3 (STAT3) is an important mediator of the inflammatory process. We investigated the role of STAT3 in viral myocarditis and its possible role in the development to dilated cardiomyopathy. We used STAT3-deficent mice with a cardiomyocyte-restricted knockout and induced a viral myocarditis using Coxsackievirus B3 (CVB3) which induced a severe inflammation during the acute phase of the viral myocarditis. A complete virus clearance and an attenuated inflammation were examined in both groups WT and STAT3 KO mice 4 weeks after infection, but the cardiac function in STAT3 KO mice was significantly decreased in contrast to the infected WT mice. Interestingly, an increased expression of collagen I was detected in STAT3 KO mice compared to WT mice 4 weeks after CVB3 infection. Furthermore, the matrix degradation was reduced in STAT3 KO mice which might be an explanation for the observed matrix deposition. Consequently, we here demonstrate the protective function of STAT3 in CVB3-induced myocarditis. Since the cardiomyocyte-restricted knockout leads to an increased fibrosis, it can be assumed that STAT3 signalling in cardiomyocytes protects the heart against increased fibrosis through paracrine effects

Machine Learning Techniques for Personalized Detection of Epileptic Events in Clinical Video Recordings

Continuous patient monitoring is essential to achieve an effective and optimal patient treatment in the intensive care unit. In the specific case of epilepsy it is the only way to achieve a correct diagnosis and a subsequent optimal medication plan if possible. In addition to automatic vital sign monitoring, epilepsy patients need manual monitoring by trained personnel, a task that is very difficult to be performed continuously for each patient. Moreover, epileptic manifestations are highly personalized even within the same type of epilepsy. In this work we assess two machine learning methods, dictionary learning and an autoencoder based on long short-term memory (LSTM) cells, on the task of personalized epileptic event detection in videos, with a set of features that were specifically developed with an emphasis on high motion sensitivity. According to the strengths of each method we have selected different types of epilepsy, one with convulsive behaviour and one with very subtle motion. The results on five clinical patients show a highly promising ability of both methods to detect the epileptic events as anomalies deviating from the stable/normal patient status

Pathophysiology and risk factors of peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is a potentially fatal form of idiopathic heart failure with variable prevalence across different countries and ethnic groups. The cause of PPCM is unclear, but environmental and genetic factors and pregnancy-associated conditions such as pre-eclampsia can contribute to the development of PPCM. Furthermore, animal studies have shown that impaired vascular and metabolic function might be central to the development of PPCM. A better understanding of the pathogenic mechanisms involved in the development of PPCM is necessary to establish new therapies that can improve the outcomes of patients with PPCM. Pregnancy hormones tightly regulate a plethora of maternal adaptive responses, including haemodynamic, structural and metabolic changes in the cardiovascular system. In patients with PPCM, the peripartum period is associated with profound and rapid hormonal fluctuations that result in a brief period of disrupted cardiovascular (metabolic) homeostasis prone to secondary perturbations. In this Review, we discuss the latest studies on the potential pathophysiological mechanisms of and risk factors for PPCM, with a focus on maternal cardiovascular changes associated with pregnancy. We provide an updated framework to further our understanding of PPCM pathogenesis, which might lead to an improvement in disease definition

In peripartum cardiomyopathy plasminogen activator inhibitor-1 is a potential new biomarker with controversial roles

Aims Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease occurring in previously heart-healthy women. A common pathomechanism in PPCM involves the angiostatic 16 kDa-prolactin (16 kDa-PRL) fragment, which via NF-kappa B-mediated up-regulation of microRNA-(miR)-146a induces vascular damage and heart failure. We analyse whether the plasminogen activator inhibitor-1 (PAI-1) is involved in the pathophysiology of PPCM. Methods and results In healthy age-matched postpartum women (PP-Ctrl, n = 53, left ventricular ejection fraction, LVEF > 55%), PAI-1 plasma levels were within the normal range (21 +/- 10 ng/mL), but significantly elevated (64 +/- 38 ng/mL, P <0.01) in postpartum PPCM patients at baseline (BL, n = 64, mean LVEF: 23 +/- 8%). At 6-month follow-up (n = 23), PAI-1 levels decreased (36 +/- 14 ng/mL, P <0.01 vs. BL) and LVEF (49 +/- 11%) improved. Increased N-terminal pro-brain natriuretic peptide and Troponin T did not correlate with PAI-1. C-reactive protein, interleukin (IL)-6 and IL-1 beta did not differ between PPCM patients and PP-Ctrl. MiR-146a was 3.6-fold (P <0.001) higher in BL-PPCM plasma compared with PP-Ctrl and correlated positively with PAI-1. In BL-PPCM serum, 16 kDa-PRL coprecipitated with PAI-1, which was associated with higher (P <0.05) uPAR-mediated NF-kappa B activation in endothelial cells compared with PP-Ctrl serum. Cardiac biopsies and dermal fibroblasts from PPCM patients displayed higher PAI-1 mRNA levels (P <0.05) than healthy controls. In PPCM mice (due to a cardiomyocyte-specific-knockout for STAT3, CKO), cardiac PAI-1 expression was higher than in postpartum wild-type controls, whereas a systemic PAI-1-knockout in CKO mice accelerated peripartum cardiac fibrosis, inflammation, heart failure, and mortality. Conclusion In PPCM patients, circulating and cardiac PAI-1 expression are up-regulated. While circulating PAI-1 may add 16 kDa-PRL to induce vascular impairment via the uPAR/NF-kappa B/miR-146a pathway, experimental data suggest that cardiac PAI-1 expression seems to protect the PPCM heart from fibrosis. Thus, measuring circulating PAI-1 and miR-146a, together with an uPAR/NF-kappa B-activity assay could be developed into a specific diagnostic marker assay for PPCM, but unrestricted reduction of PAI-1 for therapy may not be advised