Valacyclovir in the treatment of acute retinal necrosis

Background: To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN). Methods: This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline) and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA) at final follow-up, retinal detachment and development of recurrent or second eye disease. Results: Retinitis resolved in ten of ten (100%) affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60%) of eyes. 3/10 eyes (30%) developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks). Conclusions: Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovi

Risk factors for posttraumatic stress reactions among chinese students following exposure to a snowstorm disaster

<p>Abstract</p> <p>Background</p> <p>It is important to understand which factors increase the risk of posttraumatic stress disorder (PTSD) in adolescents. Previous studies have shown that the most important risk factors for PTSD include the type, severity, and duration of exposure to the traumatic events.</p> <p>Methods</p> <p>A cross-sectional survey was used to investigate the psychological symptoms associated with the aftermath of a snowstorm disaster in the Hunan province of China in January 2008. Students living in Hunan were surveyed at a three<b>-</b>month follow-up after the disaster. The questionnaire battery included the Impact of Event Scale-Revised (IES-R, trauma and symptoms associated with PTSD), the Chinese version of the Life Orientation Test-Revised (LOT-R, optimism and pessimism), the Chinese version of the Eysenck Personality Questionnaire (EPQ, neuroticism and extraversion), the Chinese Trait Coping Style Questionnaire (TCSQ, positive and negative coping styles), and a range of questions addressing social demographic characteristics and factors relating to the snowstorm. The survey was administered in school, and 968 students completed and returned the questionnaires.</p> <p>Results</p> <p>The results showed that 14.5% of the students had a total IES-R score ≥20. Students with greater school-to-home distances showed higher levels of posttraumatic stress symptoms than students who lived shorter distances from school. Students with emotional support from their teachers reported higher levels of posttraumatic stress symptoms (21.20%) than students without a teacher's emotional support (11.07%). The IES-R total and subscale scores correlated with all variables except extraversion. The binary logistic regression analysis results showed that the teacher's emotional support [odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.13-2.62], school-to-home distance (OR = 1.01, 95% CI = 1.00-1.01), negative coping (OR = 1.05; 95% CI = 1.02-1.08), and neuroticism (OR = 1.04, 95% CI = 1.02-1.06) were risk factors that predicted PTSD frequency and severity (percentage correct = 85.5%).</p> <p>Conclusions</p> <p>The risk factors that significantly impacted the onset of posttraumatic stress reactions in students living in Hunan, China following a snowstorm disaster were the school-to-home distance, negative coping, neuroticism, and teacher's emotional support.</p

Absence of XMRV in Peripheral Blood Mononuclear Cells of ARV-Treatment Naïve HIV-1 Infected and HIV-1/HCV Coinfected Individuals and Blood Donors

<div><h3>Background</h3><p>Xenotropic murine leukemia virus-related virus (XMRV) has been found in the prostatic tissue of prostate cancer patients and in the blood of chronic fatigue syndrome patients. However, numerous studies have found little to no trace of XMRV in different human cohorts. Based on evidence suggesting common transmission routes between XMRV and HIV-1, HIV-1 infected individuals may represent a high-risk group for XMRV infection and spread.</p> <h3>Methodology/Principal Findings</h3><p>DNA was isolated from the peripheral blood mononuclear cells (PBMCs) of 179 HIV-1 infected treatment naïve patients, 86 of which were coinfected with HCV, and 54 healthy blood donors. DNA was screened for XMRV provirus with two sensitive, published PCR assays targeting XMRV <em>gag</em> and <em>env</em> and one sensitive, published nested PCR assay targeting <em>env</em>. Detection of XMRV was confirmed by DNA sequencing. One of the 179 HIV-1 infected patients tested positive for <em>gag</em> by non-nested PCR whereas the two other assays did not detect XMRV in any specimen. All healthy blood donors were negative for XMRV proviral sequences. Sera from 23 HIV-1 infected patients (15 HCV⁺) and 12 healthy donors were screened for the presence of XMRV-reactive antibodies by Western blot. Thirteen sera (57%) from HIV-1⁺ patients and 6 sera (50%) from healthy donors showed reactivity to XMRV-infected cell lysate.</p> <h3>Conclusions/Significance</h3><p>The virtual absence of XMRV in PBMCs suggests that XMRV is not associated with HIV-1 infected or HIV-1/HCV coinfected patients, or blood donors. Although we noted isolated incidents of serum reactivity to XMRV, we are unable to verify the antibodies as XMRV specific.</p> </div

The Tempered Polymerization of Human Neuroserpin

Neuroserpin, a member of the serpin protein superfamily, is an inhibitor of proteolytic activity that is involved in pathologies such as ischemia, Alzheimer's disease, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). The latter belongs to a class of conformational diseases, known as serpinopathies, which are related to the aberrant polymerization of serpin mutants. Neuroserpin is known to polymerize, even in its wild type form, under thermal stress. Here, we study the mechanism of neuroserpin polymerization over a wide range of temperatures by different techniques. Our experiments show how the onset of polymerization is dependent on the formation of an intermediate monomeric conformer, which then associates with a native monomer to yield a dimeric species. After the formation of small polymers, the aggregation proceeds via monomer addition as well as polymer-polymer association. No further secondary mechanism takes place up to very high temperatures, thus resulting in the formation of neuroserpin linear polymeric chains. Most interesting, the overall aggregation is tuned by the co-occurrence of monomer inactivation (i.e. the formation of latent neuroserpin) and by a mechanism of fragmentation. The polymerization kinetics exhibit a unique modulation of the average mass and size of polymers, which might suggest synchronization among the different processes involved. Thus, fragmentation would control and temper the aggregation process, instead of enhancing it, as typically observed (e.g.) for amyloid fibrillation

Patient empowerment in long-term conditions: development and preliminary testing of a new measure

BACKGROUND: Patient empowerment is viewed by policy makers and health care practitioners as a mechanism to help patients with long-term conditions better manage their health and achieve better outcomes. However, assessing the role of empowerment is dependent on effective measures of empowerment. Although many measures of empowerment exist, no measure has been developed specifically for patients with long-term conditions in the primary care setting. This study presents preliminary data on the development and validation of such a measure. METHODS: We conducted two empirical studies. Study one was an interview study to understand empowerment from the perspective of patients living with long-term conditions. Qualitative analysis identified dimensions of empowerment, and the qualitative data were used to generate items relating to these dimensions. Study two was a cross-sectional postal study involving patients with different types of long-term conditions recruited from general practices. The survey was conducted to test and validate our new measure of empowerment. Factor analysis and regression were performed to test scale structure, internal consistency and construct validity. RESULTS: Sixteen predominately elderly patients with different types of long-term conditions described empowerment in terms of 5 dimensions (identity, knowledge and understanding, personal control, personal decision-making, and enabling other patients). One hundred and ninety seven survey responses were received from mainly older white females, with relatively low levels of formal education, with the majority retired from paid work. Almost half of the sample reported cardiovascular, joint or diabetes long-term conditions. Factor analysis identified a three factor solution (positive attitude and sense of control, knowledge and confidence in decision making and enabling others), although the structure lacked clarity. A total empowerment score across all items showed acceptable levels of internal consistency and relationships with other measures were generally supportive of its construct validity. CONCLUSION: Initial analyses suggest that the new empowerment measure meets basic psychometric criteria. Reasons concerning the failure to confirm the hypothesized factor structure are discussed alongside further developments of the scale

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: A systematic review and meta-analysis of individual participant data

Contains fulltext : 174490.pdf (publisher's version ) (Open Access)Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.10 p