Dynamic time warp analysis of individual symptom trajectories in patients with bipolar disorder

Stress and Psychopatholog

Філософія популізму як варіант сучасної філософії

We have previously reported on the functional interaction of Lipid II with human alpha-defensins, a class of antimicrobial peptides. Lipid II is an essential precursor for bacterial cell wall biosynthesis and an ideal and validated target for natural antibiotic compounds. Using a combination of structural, functional and in silico analyses, we present here the molecular basis for defensin-Lipid II binding. Based on the complex of Lipid II with Human Neutrophil peptide-1, we could identify and characterize chemically diverse low-molecular weight compounds that mimic the interactions between HNP-1 and Lipid II. Lead compound BAS00127538 was further characterized structurally and functionally; it specifically interacts with the N-acetyl muramic acid moiety and isoprenyl tail of Lipid II, targets cell wall synthesis and was protective in an in vivo model for sepsis. For the first time, we have identified and characterized low molecular weight synthetic compounds that target Lipid II with high specificity and affinity. Optimization of these compounds may allow for their development as novel, next generation therapeutic agents for the treatment of Gram-positive pathogenic infections

Cohort study ON Neuroimaging, Etiology and Cognitive consequences of Transient neurological attacks (CONNECT): Study rationale and protocol

Background: Transient ischemic attacks (TIA) are characterized by acute onset focal neurological symptoms and complete recovery within 24hours. Attacks of nonfocal symptoms not fulfilling the criteria for TIA but lacking a clear alternative diagnosis are called transient neurological attacks (TNA). Although TIA symptoms are transient in nature, cognitive complaints may persist. In particular, attacks consisting of both focal and nonfocal symptoms (mixed TNA) have been found to be associated with an increased risk of dementia. We aim to study the prevalence, etiology and risk factors of cognitive impairment after TIA or TNA. Methods/Design: CONNECT is a prospective cohort study on cognitive function after TIA and TNA. In total, 150 patients aged ≤45years with a recent (<7days after onset) TIA or TNA and no history of stroke or dementia will be included. We will classify events as: TIA, nonfocal TNA, or mixed TNA. Known short lasting paroxysmal neurological disorders like migraine aura, seizures and Ménière disease are excluded from the diagnosis of TNA. Patients will complete a comprehensive neuropsychological assessment and undergo MRI <7days after the qualifying event and again after six months. The primary clinical outcomes will be cognitive function at baseline and six months after the primary event. Imaging outcomes include the prevalence and evolution of DWI lesions, white matter hyperintensities and lacunes, as well as resting state networks functionality and white matter microstructural integrity. Differences between types of event and DWI, as well as determinants of both clinical and imaging outcomes, will be assessed. Discussion: CONNECT can provide insight in the prevalence, etiology and risk factors of cognitive impairment after TIA and TNA and thereby potentially identify a new group of patients at increased risk of cognitive impairment

Omineca Herald, October, 04, 1979

The relation between progression of cerebral small vessel disease (SVD) and gait decline is uncertain, and diffusion tensor imaging (DTI) studies on gait decline are lacking. We therefore investigated the longitudinal associations between (micro) structural brain changes and gait decline in SVD using DTI. 275 participants were included from the Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort (RUN DMC), a prospective cohort of participants with cerebral small vessel disease aged 50–85years. Gait (using GAITRite) and magnetic resonance imaging measures were assessed during baseline (2006–2007) and follow-up (2011−2012). Linear regression analysis was used to investigate the association between changes in conventional magnetic resonance and diffusion tensor imaging measures and gait decline. Tract-based spatial statistics analysis was used to investigate region-specific associations between changes in white matter integrity and gait decline. 56.2% were male, mean age was 62.9years (SD8.2), mean follow-up duration was 5.4years (SD0.2) and mean gait speed decline was 0.2m/s (SD0.2). Stride length decline was associated with white matter atrophy (β=0.16, p=0.007), and increase in mean white matter radial diffusivity and mean diffusivity, and decrease in mean fractional anisotropy (respectively, β=−0.14, p=0.009; β=−0.12, p=0.018; β=0.10, p=0.049), independent of age, sex, height, follow-up duration and baseline stride length. Tract-based spatial statistics analysis showed significant associations between stride length decline and fractional anisotropy decrease and mean diffusivity increase (primarily explained by radial diffusivity increase) in multiple white matter tracts, with the strongest associations found in the corpus callosum and corona radiata, independent of traditional small vessel disease markers. White matter atrophy and loss of white matter integrity are associated with gait decline in older adults with small vessel disease after 5years of follow-up. These findings suggest that progression of SVD might play an important role in gait decline. Keywords: Cerebral small vessel disease (SVD), MRI, Diffusion tensor imaging (DTI), Tract-based spatial statistics (TBSS), Gai

Salivary markers of stress system activation and social withdrawal in humans

Social withdrawal is an early and common feature of psychiatric disorders. Hypothalamic-pituitary-adrenal (HPA)-axis activation through increased salivary cortisol (sC) and sympathetic activation through increased salivary alpha-amylase (sAA) may play a role. We aimed to study whether the link between increased sC and sAA on the one hand and depression on the other hand is mediated by social withdrawal. In this cross-sectional, observational study, sC and sAA measures were measured in seven saliva samples in 843 participants (231 psychiatric patients and 612 healthy controls). Social withdrawal was assessed through the Brief Symptom Inventory (BSI)-, the Short Form 36-, and the Dutch Dimensional Assessment of Personality Pathology social withdrawal subscales, and analyzed using linear regression and mediation analyses. On average, participants were 44.0 years old (SD = 12.8; 64.1% female). Basal and diurnal sAA were unrelated to any social withdrawal scale and depression. Certain sC measures were positively associated with the BSI social withdrawal subscale (i. e., area under the curve with respect to the increase, beta = 0.082, p = 0.02; evening sC value: beta = 0.110, p = 0.003; and mean sC value: beta = 0.097; p = 0.01). We found limited support for statistical mediation by social withdrawal (measured using a composite social withdrawal score) on the relationship between evening sC and depression. Thus, although we found no support for a role of basal and diurnal sAA in social withdrawal, HPAaxis activation may partly aggravate social withdrawal in depressive disorders.Stress-related psychiatric disorders across the life spa