Inhibitory effects of angiotensin II receptor blockade on human tenon fibroblast migration and reactive oxygen species production in cell culture

Purpose: We investigate the effect of angiotensin receptor blockade on the migration of human Tenon fibroblasts (HTF), using irbesartan, an angiotensin II receptor type 1 (AT1R) blocker (ARB) as a potential antifibrotic agent in glaucoma filtration surgery. Methods: Confluent HTF cultures were scratched with a 1 mL pipette tip and treated with either irbesartan (10, 50, and 100 μg/mL) or angiotensin II (2 μg/mL). The extent of HTF migration up to 30 hours, and cell number and morphology at 72 hours was evaluated. To assess the effect on reactive oxygen species (ROS) level, HTF were treated with either irbesartan (10 μg/mL) or angiotensin II (2 μg/mL) for 24 hours after scratching, and then stained with dihydroethidium (DHE) before evaluation by confocal microscopy. Results: Irbesartan inhibited HTF migration by 50% to 70% compared to controls (P < 0.05). Levels of ROS were almost completely attenuated by irbesartan (DHE fluorescence intensity of 5.68E-09) (P < 0.05). Irbesartan reduced cell numbers by 50% and induced morphologic changes with loss of pseudopods (P < 0.05). Conversely, angiotensin II increased cell numbers up to 4-fold while retaining cell viability. Conclusions: Irbesartan inhibited HTF migration and ROS production. It also reduced cell numbers and altered HTF morphology. Angiotensin II increased cell number without altering morphology. This initial study warrants future investigations for further potential antifibrotic effects of this drug. Translational Relevance: This in vitro study focused on investigations of irbesartan’s effects on HTF migration, ROS production, as well as HTF cell numbers and morphology. It suggests a potential therapeutic strategy worth further exploration with a view towards postoperative wound healing modulation in glaucoma filtration surgery

Trauma memory characteristics and the development of acute stress disorder and post-traumatic stress disorder in youth

Background & objectives: The present study addresses gaps in knowledge regarding the association between trauma memory processes and posttraumatic stress responses in youth. Our primary goal was to explore the relative contribution of perceptions of trauma memory quality versus narrative trauma memory characteristics to explain overall adjustment.  Methods: Children (N = 67) were interviewed within four weeks (T1) of an injury leading to hospital treatment and then again eight weeks later (T2). In each interview, the child told a trauma narrative (which were later coded), and answered the Trauma Memory Quality Questionnaire (Meiser-Stedman, Smith, Yule, & Dalgleish, 2007a), a self-report measure indexing the sensory, fragmented, and disorganised characteristics of trauma memory. They then completed measures of Acute Stress Disorder (ASD) symptoms and associated psychopathology at T1 and measures of Posttraumatic Stress (PTS) symptoms and associated psychopathology at T2.  Results: Self-reported trauma memory characteristics predicted ASD symptoms cross-sectionally at T1 and PTS symptoms prospectively over time. At both time points, self-reported trauma memory characteristics accounted for all of the unique variance in symptoms initially explained by narrative characteristics. A reduction in self-report ratings, but not the hypothesised narrative features (e.g., disorganised or lexical elements of the narrative), significantly predicted a reduction in PTS symptoms over time.  Limitations: The small sample size and the absence of a within-subjects narrative control were the main limitations of the study.  Conclusions: These findings underscore the importance of self-reported trauma memory characteristics to the aetiology of PTSD

Personality, posttraumatic stress and trauma type: factors contributing to posttraumatic growth and its domains in a Turkish community sample

Background: Posttraumatic growth (PTG) is conceptualized as a positive transformation resulting from coping with and processing traumatic life events. This study examined the contributory roles of personality traits, posttraumatic stress (PTS) severity and their interactions on PTG and its domains, as assessed with the Posttraumatic Growth Inventory Turkish form (PTGI-T). The study also examined the differences in PTG domains between survivors of accidents, natural disasters and unexpected loss of a loved one. Methods: The Basic Personality Traits Inventory, Posttraumatic Diagnostic Scale, and PTGI-T were administered to a large stratified cluster community sample of 969 Turkish adults in their home settings. Results: The results showed that conscientiousness, agreeableness, and openness to experience significantly related to the total PTG and most of the domains. The effects of extraversion, neuroticism and openness to experience were moderated by the PTS severity for some domains. PTG in relating to others and appreciation of life domains was lower for the bereaved group. Conclusion: Further research should examine the mediating role of coping between personality and PTG using a longitudinal design

Culturing Pancreatic Islets in Microfluidic Flow Enhances Morphology of the Associated Endothelial Cells

Pancreatic islets are heavily vascularized in vivo with each insulin secreting beta-cell associated with at least one endothelial cell (EC). This structure is maintained immediately post-isolation; however, in culture the ECs slowly deteriorate, losing density and branched morphology. We postulate that this deterioration occurs in the absence of blood flow due to limited diffusion of media inside the tissue. To improve exchange of media inside the tissue, we created a microfluidic device to culture islets in a range of flow-rates. Culturing the islets from C57BL6 mice in this device with media flowing between 1 and 7 ml/24 hr resulted in twice the EC-density and -connected length compared to classically cultured islets. Media containing fluorescent dextran reached the center of islets in the device in a flow-rate-dependant manner consistent with improved penetration. We also observed deterioration of EC morphology using serum free media that was rescued by addition of bovine serum albumin, a known anti-apoptotic signal with limited diffusion in tissue. We further examined the effect of flow on beta-cells showing dampened glucose-stimulated Ca2+-response from cells at the periphery of the islet where fluid shear-stress is greatest. However, we observed normal two-photon NAD(P)H response and insulin secretion from the remainder of the islet. These data reveal the deterioration of islet EC-morphology is in part due to restricted diffusion of serum albumin within the tissue. These data further reveal microfluidic devices as unique platforms to optimize islet culture by introducing intercellular flow to overcome the restricted diffusion of media components

Big GABA II: Water-referenced edited MR spectroscopy at 25 research sites

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels

Understanding adaptation to first episode psychosis through the creation of images

This article aims to understand and explore the meaning of adaptation to First Episode Psychosis (FEP). An innovative method of data collection was used with ten participants who experienced FEP which integrated drawings of their lived experience within semi-structured interviews. The data were analysed through Interpretative Phenomenological Analysis and hermeneutic-phenomenological image analysis. Participants’ experience was captured in four superordinate themes which identified that adaptation to FEP entailed: ‘Finding out how psychosis fits into my story’, ‘Breaking free from psychosis’, ‘Fighting my way through psychosis’, and ‘Finding a new way of being ‘me’’. The participants’ path of adaptation to FEP was an interplay of pains, challenges, and gains, and there was resonance with posttraumatic growth in their accounts. This article illustrates that creating images may offer a powerful way of conveying the multifaceted aspects of adaptation to FEP and could help individuals in communicating and processing their experience

Cognitive and Psychological Reactions of the General Population Three Months After the 2011 Tohoku Earthquake and Tsunami

BACKGROUND: The largest earthquake on record in Japan (magnitude 9.0) occurred on March 11, 2011, and the subsequent tsunami devastated the Pacific coast of Northern Japan. These further triggered the Fukushima I nuclear power plant accidents. Such a hugely complex disaster inevitably has negative psychological effects on general populations as well as on the direct victims. While previous disaster studies enrolled descriptive approaches focusing on direct victims, the structure of the psychological adjustment process of people from the general population has remained uncertain. The current study attempted to establish a path model that sufficiently reflects the early psychological adaptation process of the general population to large-scale natural disasters. METHODS AND FINDINGS: Participants from the primary disaster area (n = 1083) and other areas (n = 2372) voluntarily participated in an online questionnaire study. By constructing path models using a structural equation model procedure (SEM), we examined the structural relationship among psychological constructs known related to disasters. As post-traumatic stress symptoms (PTS) were significantly more present in people in the primarily affected area than in those in secondary- or non-affected areas, the path models were constructed for the primary victims. The parsimoniously depicted model with the best fit was achieved for the psychological-adjustment centered model with quality of life (QoL) as a final outcome. CONCLUSION: The paths to QoL via negative routes (from negative cognitive appraisal, PTS, and general stress) were dominant, suggesting the importance of clinical intervention for reducing negative cognitive appraisal, and for caring for general stress and PTS to maintain QoL at an early stage of psychological adaptation to a disaster. The model also depicted the presence of a positive route where positive cognitive appraisal facilitates post-traumatic growth (PTG) to achieve a higher QoL, suggesting the potential importance of positive psychological preventive care for unexpected natural disasters

Positive Psychology in Cancer Care: Bad Science, Exaggerated Claims, and Unproven Medicine

Claims of positive psychology about people with cancer enjoy great popularity because they seem to offer scientific confirmation of strongly held cultural beliefs and values. Our goal is to examine critically four widely accepted claims in the positive psychology literature regarding adaptational outcomes among individuals living with cancer. We examine: (1) the role of positive factors, such as a "fighting spirit" in extending the life of persons with cancer; (2) effects of interventions cultivating positive psychological states on immune functioning and cancer progression and mortality; and evidence concerning (3) benefit finding and (4) post-traumatic growth following serious illness such as cancer and other highly threatening experiences. Claims about these areas of research routinely made in the positive psychology literature do not fit with available evidence. We note in particular the incoherence of claims about the adaptational value of benefit finding and post-traumatic growth among cancer patients, and the implausibility of claims that interventions that enhance benefit finding improve the prognosis of cancer patients by strengthening the immune system. We urge positive psychologists to rededicate themselves to a positive psychology based on scientific evidence rather than wishful thinking