Reduction in ionic permeability of a silicone hydrogel contact lenses after one month of daily wear

[EN] Purpose. To compare the ionic permeability using the ionoflux method of new and worn samples of a silicone hydrogel contact lens material. Methods. An ionoflux experimental setup was established to measure the ionic permeability (NaCl) of soft contact lenses. Samples of a silicone hydrogel lens (Comfilcon A, Coopervision, Pleasanton, CA) with optical powers of -1.00, -1.50 and -4.75 diopters (D) were used in this study. Three samples of each power were measured after being worn for one month on a daily wear basis. Lenses were cleaned and disinfected every night using multipurpose disinfecting solutions. Three samples of new lenses from the same batch and the same optical power were also measured to evaluate the effect of lens wear on the ionic permeability of the lens material. Before measurement, the lenses were equilibrated with a 1 M NaCl solution during one week before of each measurement. Results. Lens power had minimal effect on the ionic permeability of a modern silicone hydrogel contact lens with the -1.00 lens having a 15% lower permeability compared to the other two lenses. After one month of lens wear the apparent ionic permeability for lenses with -1.50 D decreased by 15%. In the case of -1.00 and -4.75 D lenses there was a decrease of 26%. Conclusions. The ionic permeability of silicone hydrogel lenses of different optical powers was not significantly different. Worn lenses present a significant reduction of the ionic permeability after a month of wear. The potential effect this reduction on lens movement and discomfort associated to lens wear should be further evaluated.The authors have no proprietary interest in any of the materials mentioned in this article. This work was funded in part by FEDER through the COMPTETE Program and by the Portuguese Foundation for Science and Technology (FCT) in the framework of projects PTDC/SAU-BEB/098391/2008, PTDC/SAU-BEB/098392/2008 and the Strategic Project PEST-C/FIS/UI607/2011.Ferreira Da Silva, AR.; Compañ Moreno, V.; Gonzalez-Meijome, JM. (2015). Reduction in ionic permeability of a silicone hydrogel contact lenses after one month of daily wear. Materials Research Express. 2(6). https://doi.org/10.1088/2053-1591/2/6/065007S26Yoon, S. C., & Jhon, M. S. (1982). The transport phenomena of some model solutes through postcrosslinked poly(2-hydroxyethyl methacrylate) membranes with different tactic precursors. Journal of Applied Polymer Science, 27(8), 3133-3149. doi:10.1002/app.1982.070270834Yasuda, H., Lamaze, C. E., & Ikenberry, L. D. (1968). Die Makromolekulare Chemie, 118(1), 19-35. doi:10.1002/macp.1968.021180102MURPHY, S., HAMILTON, C., & TIGHE, B. (1988). Synthetic hydrogels: 5. Transport processes in 2-hydroxyethyl methacrylate copolymers. Polymer, 29(10), 1887-1893. doi:10.1016/0032-3861(88)90407-7Nicolson, P. C., & Vogt, J. (2001). Soft contact lens polymers: an evolution. Biomaterials, 22(24), 3273-3283. doi:10.1016/s0142-9612(01)00165-xMonticelli, M. V., Chauhan, A., & Radke, C. J. (2005). The Effect of Water Hydraulic Permeability on the Settling of a Soft Contact Lens on the Eye. Current Eye Research, 30(5), 329-336. doi:10.1080/02713680590934085Guan, L., Jiménez, M. E. G., Walowski, C., Boushehri, A., Prausnitz, J. M., & Radke, C. J. (2011). Permeability and partition coefficient of aqueous sodium chloride in soft contact lenses. Journal of Applied Polymer Science, 122(3), 1457-1471. doi:10.1002/app.33336Cheng, M.-L., & Sun, Y.-M. (2005). Observation of the solute transport in the permeation through hydrogel membranes by using FTIR-microscopy. Journal of Membrane Science, 253(1-2), 191-198. doi:10.1016/j.memsci.2005.01.017CHHABRA, M., PRAUSNITZ, J., & RADKE, C. (2007). A single-lens polarographic measurement of oxygen permeability (Dk) for hypertransmissible soft contact lenses. Biomaterials, 28(30), 4331-4342. doi:10.1016/j.biomaterials.2007.06.024González-Méijome, J. M., López-Alemany, A., Almeida, J. B., & Parafita, M. A. (2009). Surface AFM microscopy of unworn and worn samples of silicone hydrogel contact lenses. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 88B(1), 75-82. doi:10.1002/jbm.b.31153González-Méijome, J. M., López-Alemany, A., Almeida, J. B., & Parafita, M. A. (2008). Dynamic in vitro dehydration patterns of unworn and worn silicone hydrogel contact lenses. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 90B(1), 250-258. doi:10.1002/jbm.b.31279Pozuelo, J., Compañ, V., González-Méijome, J. M., González, M., & Mollá, S. (2014). Oxygen and ionic transport in hydrogel and silicone-hydrogel contact lens materials: An experimental and theoretical study. Journal of Membrane Science, 452, 62-72. doi:10.1016/j.memsci.2013.10.010Wolffsohn, J. S., Hunt, O. A., & Basra, A. K. (2009). Simplified recording of soft contact lens fit. Contact Lens and Anterior Eye, 32(1), 37-42. doi:10.1016/j.clae.2008.12.00

Prognostic and Diagnostic Potential of the Structural Neuroanatomy of Depression

Background Depression is experienced as a persistent low mood or anhedonia accompanied by behavioural and cognitive disturbances which impair day to day functioning. However, the diagnosis is largely based on self-reported symptoms, and there are no neurobiological markers to guide the choice of treatment. In the present study, we examined the prognostic and diagnostic potential of the structural neural correlates of depression. Methodology and Principal Findings Subjects were 37 patients with major depressive disorder (mean age 43.2 years), medication-free, in an acute depressive episode, and 37 healthy individuals. Following the MRI scan, 30 patients underwent treatment with the antidepressant medication fluoxetine or cognitive behavioural therapy (CBT). Of the patients who subsequently achieved clinical remission with antidepressant medication, the whole brain structural neuroanatomy predicted 88.9% of the clinical response, prior to the initiation of treatment (88.9% patients in clinical remission (sensitivity) and 88.9% patients with residual symptoms (specificity), p = 0.01). Accuracy of the structural neuroanatomy as a diagnostic marker though was 67.6% (64.9% patients (sensitivity) and 70.3% healthy individuals (specificity), p = 0.027). Conclusions and Significance The structural neuroanatomy of depression shows high predictive potential for clinical response to antidepressant medication, while its diagnostic potential is more limited. The present findings provide initial steps towards the development of neurobiological prognostic markers for depression

The role of the BDNF Val66Met polymorphism for the synchronization of error-specific neural networks

Behavioral adaptation depends on the recognition of response errors and processing of this error-information. Error processing is a specific cognitive function crucial for behavioral adaptation. Neurophysiologically, these processes are reflected by an event-related potential (ERP), the error negativity (Ne/ERN). Even though synchronization processes are important in information processing, its role and neurobiological foundation in behavioral adaptation are not understood. The brain-derived neurotrophic factor (BDNF) strongly modulates the establishment of neural connectivity that determines neural network dynamics and synchronization properties. Therefore altered synchronization processes may constitute a mechanism via which BDNF affects processes of error-induced behavioral adaptation. We investigate how variants of the BDNF gene regulate EEG-synchronization processes underlying error processing. Subjects (n = 65) were genotyped for the functional BDNF Val66Met polymorphism (rs6265). We show that Val/Val genotype is associated with stronger error-specific phase-locking, compared with Met allele carriers. Posterror behavioral adaptation seems to be strongly dependent on these phase-locking processes and efficacy of EEG-phase-locking-behavioral coupling was genotype dependent. After correct responses, neurophysiological processes were not modulated by the polymorphism, underlining that BDNF becomes especially necessary in situations requiring behavioral adaptation. The results suggest that alterations in neural synchronization processes modulated by the genetic variants of BDNF Val66Met may be the mechanism by which cognitive functions are affected.Christian Beste, Vasil Kolev, Juliana Yordanova, Katharina Domschke, Michael Falkenstein, Bernhard T. Baune, and Carsten Konra

Examining links between anxiety, reinvestment and walking when talking by older adults during adaptive gait

Falls by older adults often result in reduced quality of life and debilitating fear of further falls. Stopping walking when talking (SWWT) is a significant predictor of future falls by older adults and is thought to reflect age-related increases in attentional demands of walking. We examine whether SWWT is associated with use of explicit movement cues during locomotion, and evaluate if conscious control (i.e., movement specific reinvestment) is causally linked to falls-related anxiety during a complex walking task. We observed whether twenty-four older adults stopped walking when talking when asked a question during an adaptive gait task. After certain trials, participants completed a visual-spatial recall task regarding walkway features, or answered questions about their movements during the walk. In a subsequent experimental condition, participants completed the walking task under conditions of raised postural threat. Compared to a control group, participants who SWWT reported higher scores for aspects of reinvestment relating to conscious motor processing but not movement self-consciousness. The higher scores for conscious motor processing were preserved when scores representing cognitive function were included as a covariate. There were no group differences in measures of general cognitive function, visual spatial working memory or balance confidence. However, the SWWT group reported higher scores on a test of external awareness when walking, indicating allocation of attention away from task-relevant environmental features. Under conditions of increased threat, participants self-reported significantly greater state anxiety and reinvestment and displayed more accurate responses about their movements during the task. SWWT is not associated solely with age-related cognitive decline or generic increases in age-related attentional demands of walking. SWWT may be caused by competition for phonological resources of working memory associated with consciously processing motor actions and appears to be causally linked with fall-related anxiety and increased vigilance.This research was supported by The Royal Society (IE131576) and British Academy (SG132820)

Cost-effectiveness of financial incentives to promote adherence to depot antipsychotic medication: economic evaluation of a cluster-randomised controlled trial

Background: Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. Methods: Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of ‘good’ adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). Findings: Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4 533, £5 730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8 020, £14 000). The extra cost per patient of achieving 'good' adherence was £2 950 (CI -£19 400, £27 800). Probability of cost-effectiveness exceeded 97.5%at willingness-to-pay values of £14 000 for a 20% increase in adherence and £27 800 for good adherence. Interpretation: Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention. Trial Registration: ISRCTN.com 7776928

Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT)

<p>Abstract</p> <p>Background</p> <p>The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, which has been linked to anxiety and depression, but previous results are not conclusive. The aim of the present study was to examine the relationship between the Val158Met COMT gene polymorphism and anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS) in the general adult population.</p> <p>Methods</p> <p>In the Nord-Trøndelag Health Study (HUNT) the association between the Val158Met polymorphism and anxiety and depression was evaluated in a random sample of 5531 individuals. Two different cut off scores (≥ 8 and ≥ 11) were used to identify cases with anxiety (HADS-A) and depression (HADS-D), whereas controls had HADS-A <8 and HADS-D <8.</p> <p>Results</p> <p>The COMT genotype distribution was similar between controls and individuals in the groups with anxiety and depression using cut-off scores of ≥ 8. When utilizing the alternative cut-off score HADS-D ≥ 11, Met/Met genotype and Met allele were less common among men with depression compared to the controls (genotype: p = 0.017, allele: p = 0.006). In the multivariate analysis, adjusting for age and heart disease, depression (HADS-D ≥ 11) was less likely among men with the Met/Met genotype than among men with the Val/Val genotype (OR = 0.37, 95% CI = 0.18–0.76).</p> <p>Conclusion</p> <p>In this population-based study, no clear association between the Val158Met polymorphism and depression and anxiety was revealed. The Met/Met genotype was less likely among men with depression defined as HADS-D ≥ 11, but this may be an incidental finding.</p

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Transdiagnostic risk of mental disorders in offspring of affected parents:a meta-analysis of family high-risk and registry studies

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I2 statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.</p

Computational Approaches and Analysis for a Spatio-Structural-Temporal Invasive Carcinoma Model

Spatio-temporal models have long been used to describe biological systems of cancer, but it has not been until very recently that increased attention has been paid to structural dynamics of the interaction between cancer populations and the molecular mechanisms associated with local invasion. One system that is of particular interest is that of the urokinase plasminogen activator (uPA) wherein uPA binds uPA receptors on the cancer cell surface, allowing plasminogen to be cleaved into plasmin, which degrades the extracellular matrix and this way leads to enhanced cancer cell migration. In this paper, we develop a novel numerical approach and associated analysis for spatio-structuro-temporal modelling of the uPA system for up to two-spatial and two-structural dimensions. This is accompanied by analytical exploration of the numerical techniques used in simulating this system, with special consideration being given to the proof of stability within numerical regimes encapsulating a central differences approach to approximating numerical gradients. The stability analysis performed here reveals instabilities induced by the coupling of the structural binding and proliferative processes. The numerical results expound how the uPA system aids the tumour in invading the local stroma, whilst the inhibitor to this system may impede this behaviour and encourage a more sporadic pattern of invasion.PostprintPeer reviewe