Mineralocorticoid receptor and heat shock protein expression levels in peripheral lymphocytes from war trauma-exposed men with and without PTSD

Alterations in the number and functional status of mineralocorticoid (MR) and glucocorticoid receptors (GR) may contribute to vulnerability to posttraumatic stress disorder (PTSD). Corticosteroid receptors are chaperoned by heat shock proteins Hsp90 and Hsp70. We examined relations between corticosteroid receptor and heat shock protein expression levels, and related them with war trauma exposure, PTSD and resilience to PTSD. Relative levels of MR, Hsp90 and Hsp70 were determined by immunoblotting in lymphocytes from war trauma-exposed men with current PTSD (current PTSD group, n=113), with life-time PTSD (life-time PTSD group, n=61) and without PTSD (trauma control group, n=88), and from non-traumatized healthy controls (healthy control group, n=85). Between-group differences in MR, Hsp90 and Hsp70 levels and in MR/GR ratio were not observed. The level of MR was correlated with both Hsp90 and Hsp70 levels in trauma control and healthy control groups. On the other hand, GR level was correlated only with Hsp90 level, and this correlation was evident in current PTSD and trauma control groups. In conclusion, PTSD and exposure to trauma are not related to changes in lymphocyte MR, Hsp90 or Hsp70 levels, but may be associated with disturbances in corticosteroid receptors interaction with heat shock proteins.     

Significance of uroplakin III expression in recurrence of solitary muscle non-invasive bladder cancer

Numerous immunohistochemical biomarkers for patients with urothelial bladder cancer have been identified in order to predict their biological behavior. The aim of this present study was to examine the uroplakin III (UPIII) expression in homogenous group of non-muscle invasive bladder cancer and to correlate its value with clinico-pathological characteristics of patients and moreover with COX-2 expression and tumor infiltrating lymphocytes (TILs).     

New Drugs on the Block—Emerging Treatments for Nonalcoholic Steatohepatitis

Patients with nonalcoholic steatohepatitis (NASH) are at higher risk of progression to advanced stages of fibrosis, cirrhosis, hepatocellular carcinoma and othe...     

Seasonal distribution of multiclass pesticide residues in the surface waters of northwest Croatia

As part of our OPENTOX project, we evaluated the incidence and mass concentrations of multiclass pesticide residues in 23 river/stream water samples collected in urban and agricultural areas of northwest Croatia at various points of the pesticide application season in 2015. The study included 16 compounds of five herbicide classes and seven compounds of three insecticide classes. Pesticide residues were accumulated from water by solid-phase extraction and analysed using high performance liquid chromatography with UV-diode array detection and/or gas chromatography-mass spectrometry. Herbicide residues were more common than the insecticide ones, and, as expected, they peaked in the middle of the application season. Metolachlor showed the highest concentrations and was found in 91 % of all samples, followed by terbuthylazine, found in 70 % of the samples. The highest total mass concentration of detected pesticides was measured in the water samples of the Krapina (3992 ng/L) and Sutla (3455 ng/L) collected in rural areas with intensive agriculture. Our findings strongly speak in favour of continued monitoring of surface waters and possibly extending the list of priority water pollutants.KEY WORDS: degradation products, herbicides, insecticides, pesticide residues, river water, seasonal variations     

Chronic pelvic pain syndrome: Highlighting medicinal plants toward biomolecules discovery for upcoming drugs formulation

Chronic pelvic pain syndrome (CPPS) can be triggered by a various types of gynecological, gastrointestinal, urological, and musculoskeletal disorders. Recently, the role of the central nervous system has proven to be an integral part on the development of any chronic pain syndrome, including CPPS. However, owing to the complex and heterogeneous etiology and pathophysiology of CPPS, the establishment of effective therapeutic interventions remains challenging for both physicians and patients. Nonetheless, recent studies have pointed that medicinal plants and their secondary metabolites can be effectively used in CPPS therapy, besides contributing to restore the patients' quality of life and potentiate the conventional CPPS management. In this sense, this review aims to provide a careful overview on the biomedical data for the use of medicinal plants use and their secondary metabolites on CPPS management.     

Vemurafenib and cobimetinib‐induced toxic epidermal necrolysis in a patient with metastatic melanoma

Combination therapy in the treatment of metastatic melanoma has been associated with more durable response rate compared to monotherapy. However, previous studies have shown that combined target therapy commonly causes a wide spectrum of adverse events. These adverse reactions are usually manageable, however, it is always necessary to compare drug efficacy with its potential adverse effects. Toxic epidermal necrolysis represents severe mucocutaneous reaction, usually triggered by medications and characterized by extensive necrosis and detachment of the epidermis. Here we present a first case of toxic epidermal necrolysis induced by combined target therapy (vemurafenib plus cobimetinib). The case was observed in a young patient with BRAF mutant melanoma who was started on first‐line metastatic immunotherapy with pembrolisumab.     

Actinic keratosis and surrounding skin exhibit changes in corneocyte surface topography and decreased levels of filaggrin degradation products

Actinic keratosis (AK) is a frequent premalignant skin lesion mainly caused by chronic sun exposure. AK lesions are often surrounded by invisible, subclinical alterations, called field of cancerization (FoC). Definition of FoC is of importance for therapy management; however, the criteria and non-invasive tools to characterize FoC are lacking. Atomic force microscopy (AFM) proved to be a suitable tool for detection of changes in the corneocyte surface topography in inflammatory skin diseases, which share similar clinical features with AK such as hyper- and parakeratosis. Therefore, in this study we applied AFM to investigate AK and surrounding skin obtained by non-invasive collection of the stratum corneum (SC) with adhesive tapes. Furthermore, we determined degradation products of structural protein filaggrin (natural moisturizing factor, NMF), which previously showed association with the changes in corneocyte surface topography. Ten patients with multiple AK on the face were recruited from the outpatient clinic. SC samples were collected from the AK lesion, skin sites adjacent to the AK, 5 cm from the AK and retroauricular area. Corneocyte surface topography was determined by AFM, and NMF by liquid chromatography. The AK lesion showed alterations of the corneocyte surface topography characterized by an increased number of nanosize protrusions, which gradually decreased with the distance from the lesion. NMF levels show an inverse pattern. Atomic force microscopy showed to be a suitable tool to detect changes in the corneocyte surface topography on the AK lesion and surrounding skin in a non-invasive manner.     

MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages. Hum Brain Mapp 38:5180–5194, 2017. © 2017 Wiley Periodicals, Inc.     

Heritability of the limbic networks

Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum (‘medial default-mode network’), the ventral cingulum and the fornix (‘hippocampal-diencephalic-retrosplenial network’) and the uncinate fasciculus (‘temporo-amygdala-orbitofrontal network’). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition, and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, for example, fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing.