ROC analysis of dexamethasone suppression test threshold in suicide prediction after attempted suicide

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behavior. In suicide attempters with mood disorder, the non-suppressor status in the dexamethasone suppression test (DST) is associated with suicide indicating that HPA-axis hyperactivity is a biological risk factor for suicide and may be a useful predictor. The threshold of 5 microg/dl for cortisol levels measured at 08:00 a.m. or 4:00 p.m. following dexamethasone at 11:00 p.m. to define the DTS nonsuppression was derived as being optimal for the separation of melancholia and nonmelancholic conditions rather than the prediction of suicide. A different threshold may offer a better identification of suicide. The aim of this study was to find the optimal threshold level of post DST plasma cortisol at 4 p.m. for suicide prediction using receiver operating characteristics (ROC) analysis. A cohort of 106 depressed inpatients with an index suicide attempt admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000, were submitted to DST and followed up for causes of death. During the follow-up (mean 17 years), 25 suicides (24%) were identified. The ROC analysis revealed that a lower threshold of 3.3 microg/dl for the nonsuppressor status predicted 17 of 25 suicides (sensitivity of 68%) compared with 15 of 25 suicides (sensitivity 60%) with a conventional threshold of 5 microg/dl at 4:00 p.m. In male suicide attempters the lower threshold for pathological DST result (3.3 microg/dl) changed the Odds ratio from 6.7 till 18. In female suicide attempters a higher threshold (7.3 microg/dl) optimised the value of DST as a biological test for suicide prediction indicating a gender difference.     

Screening of Antifungal Azole Drugs and Agrochemicals with an Adapted alamarBlue-Based Assay Demonstrates Antibacterial Activity of Croconazole against Mycobacterium ulcerans

An alamarBlue-based growth inhibition assay has been adapted for the thermosensitive and slow-growing pathogen Mycobacterium ulcerans. The standardized test procedure enables medium-throughput screening of preselected compound libraries. Testing of a set of 48 azoles with known antifungal activity led to the identification of an imidazole antifungal displaying an inhibitory dose (ID) of 9 μM for M. ulcerans.     

Differential Degradation of Full-length and Cleaved Ataxin-7 Fragments in a Novel Stable Inducible SCA7 Model

Spinocerebellar ataxia type 7 (SCA7) is one of nine neurodegenerative disorders caused by expanded polyglutamine repeats, and a common toxic gain-of-function mechanism has been proposed. Proteolytic cleavage of several polyglutamine proteins has been identified and suggested to modulate the polyglutamine toxicity. In this study, we show that full-length and cleaved fragments of the SCA7 disease protein ataxin-7 (ATXN7) are differentially degraded. We found that the ubiquitin-proteosome system (UPS) was essential for the degradation of full-length endogenous ATXN7 or transgenic full-length ATXN7 with a normal or expanded glutamine repeat in both HEK 293T and stable PC12 cells. However, a similar contribution by UPS and autophagy was found for the degradation of proteolytically cleaved ATXN7 fragments. Furthermore, in our novel stable inducible PC12 model, induction of mutant ATXN7 expression resulted in toxicity and this toxicity was worsened by inhibition of either UPS or autophagy. In contrast, pharmacological activation of autophagy could ameliorate the ATXN7-induced toxicity. Based on our findings, we propose that both UPS and autophagy are important for the reduction of mutant ataxin-7-induced toxicity, and enhancing ATXN7 clearance through autophagy could be used as a potential therapeutic strategy in SCA7.     

First neuropathological description of a patient with Parkinson's disease and LRRK2 p.N1437H mutation

The c.4309A>C mutation in the LRRK2 gene (LRRK2 p.N1437H) has recently been reported as the seventh pathogenic LRRK2 mutation causing monogenic Parkinson's disease (PD). So far, only two families worldwide have been identified with this mutation. By screening DNA from seven brains of PD patients, we found one individual with seemingly sporadic PD and LRRK2 p.N1437H mutation. Clinically, the patient had levodopa-responsive PD with tremor, and developed severe motor fluctuations during a disease duration of 19 years. There was severe and painful ON-dystonia, and severe depression with suicidal thoughts during OFF. In the advanced stage, cognition was slow during motor OFF, but there was no noticeable cognitive decline. There were no signs of autonomic nervous system dysfunction. Bilateral deep brain stimulation of the subthalamic nucleus had unsatisfactory results on motor symptoms. The patient committed suicide. Neuropathological examination revealed marked cell loss and moderate alpha-synuclein positive Lewy body pathology in the brainstem. There was sparse Lewy pathology in the cortex. A striking finding was very pronounced ubiquitin-positive pathology in the brainstem, temporolimbic regions and neocortex. Ubiquitin positivity was most pronounced in the white matter, and was out of proportion to the comparatively weaker alpha-synuclein immunoreactivity. Immunostaining for tau was mildly positive, revealing non-specific changes, but staining for TDP-43 and FUS was entirely negative. The distribution and shape of ubiquitin-positive lesions in this patient differed from the few previously described patients with LRRK2 mutations and ubiquitin pathology, and the ubiquitinated protein substrate remains undefined.     

Is a Self-Monitoring App for Depression a Good Place for Additional Mental Health Information? Ecological Momentary Assessment of Mental Help Information Seeking among Smartphone Users

ABSTRACT

Mobile devices and apps offer promising opportunities for both patients and healthcare professionals, for example, to monitor and assess health status, and also to provide relevant health information. However, health information seeking within a mood-tracking app has not yet been addressed by research. To bridge this gap, the depression-related health information seeking of 6,675 users of a mood-tracking smartphone app was unobtrusively monitored. The study shows that self-monitored depressive symptoms are associated with higher depression-related information seeking within the app. Health information seeking was low in general, with differences across 12 depression-related topics (e.g., depressive thoughts, a depression diagnosis, or depression facts), but the findings are also promising as the smartphone app was shown to be a place where users can inform themselves about health topics related to the main purpose of the app. Smartphone apps would therefore seem to be a vehicle through which to provide additional health information about, for example, comorbidities, or pre- or post-interventions, even going beyond the original purposes of such mobile health (mHealth) monitoring apps.     

Pseudallescheria boydii infection in the acquired immunodeficiency syndrome.

Pulmonary and renal infection developed in a 44-year-old Hispanic man due to the fungus Pseudallescheria boydii. Pseudallescheria boydii has been associated with cutaneous infection known as mycetoma but occurs very infrequently in extracutaneous sites. To our knowledge, this is the second reported case of P boydii in a patient with the acquired immunodeficiency syndrome and the first case with pulmonary and/or renal involvement.