Effects of Computerized Decision Support Systems on Management of Atrial Fibrillation: A Scoping Review

Background: Potential role of computerized decision support system on management of atrial fibrillation is not well understood. Objectives: To systematically review studies that evaluate the effects of computerized decision support systems and decision aids on aspects pertaining to atrial fibrillation. Data sources: We searched Medline, Scopus and Cochrane database. Last date of search was 2016, January 10. Selection criteria: Computerized decision support systems that help manage atrial fibrillation and decision aids that provide useful knowledge for patients with atrial fibrillation and help them to self-care. Data collection and analysis: Two reviewers extracted data and summarized findings. Due to heterogeneity, meta-analysis was not feasible; mean differences of outcomes and confidence intervals for a difference between two Means were reported. Results: Seven eligible studies were included in the final review. There were one observational study without controls, three observational studies with controls, one Non-Randomized Controlled Trial and two Randomized Controlled Trials. The interventions were three decision aids that were used by patients and four computerized decision support systems. Main outcomes of studies were: stroke events and major bleeding (one article), Changing doctor-nurse behavior (three articles), Time in therapeutic International Normalized Ratio range (one article), decision conflict scale (two articles), patient knowledge and anxiety about stroke and bleeding (two articles). Conclusions: A computerized decision support system may decrease decision conflict and increase knowledge of patients with atrial fibrillation (AF) about risks of AF and AF treatments. Effect of computerized decision support system on outcomes such as changing doctor-nurse behavior, anxiety about stroke and bleeding and stroke events could not be shown.We need more studies to evaluate the role of computerized decision support system in patients with atrial fibrillation

Noninvasive temporal detection of early retinal vascular changes during diabetes

Diabetes associated complications, including diabetic retinopathy and loss of vision, are major health concerns. Detecting early retinal vascular changes during diabetes is not well documented, and only few studies have addressed this domain. The purpose of this study was to noninvasively evaluate temporal changes in retinal vasculature at very early stages of diabetes using fundus images from preclinical models of diabetes.Non-diabetic and Akita/+ male mice with different duration of diabetes were subjected to fundus imaging using a Micron III imaging system. The images were obtained from 4 weeks- (onset of diabetes), 8 weeks-, 16 weeks-, and 24 weeks-old male Akita/+ and non-diabetic mice. In total 104 fundus images were subjected to analysis for various feature extractions. A combination of Canny Edge Detector and Angiogenesis Analyzer plug-ins in ImageJ were utilized to quantify various retinal vascular changes in fundus images. Statistical analyses were conducted to determine significant differences in the various extracted features from fundus images of diabetic and non-diabetic animals. Our novel image analysis method led to extraction of over 20 features. These results indicated that some of these features were significantly changed with a short duration of diabetes, and others remained the same but changed after longer duration of diabetes. These patterns likely distinguish acute (protective) and chronic (damaging) associated changes with diabetes. We show that with a combination of various plugging one can extract over 20 features from retinal vasculature fundus images. These features change during diabetes, thus allowing the quantification of quality of retinal vascular architecture as biomarkers for disease progression. In addition, our method was able to identify unique differences among diabetic mice with different duration of diabetes. The ability to noninvasively detect temporal retinal vascular changes during diabetes could lead to identification of specific markers important in the development and progression of diabetes mediated-microvascular changes, evaluation of therapeutic interventions, and eventual reversal of these changes in order to stop or delay disease progression

Adenosine Receptors Expression in Human Retina and Choroid with Age-related Macular Degeneration

Purpose: Adenosine signaling modulates ocular inflammatory processes, and its antagonism mitigates neovascularization in both newborns and preclinical models of ocular neovascularization including age-related macular degeneration (AMD). The adenosine receptor expression patterns have not been well characterized in the human retina and choroid. Methods: Here we examined the expression of adenosine receptor subtypes within the retina and choroid of human donor eyes with and without AMD. Antibodies specifically targeting adenosine receptor subtypes A1, A2A, A2B, and A3 were used to assess their expression patterns. Quantitative real-time PCR analysis was used to confirm gene expression of these receptors within the normal human retina and choroid. Results: We found that all four receptor subtypes were expressed in several layers of the retina, and within the retinal pigment epithelium and choroid. The expression of A1 receptors was more prominent in the inner and outer plexiform layers, where microglia normally reside, and supported by RNA expression in the retina. A2A and A2B showed similar expression patterns with prominent expression in the vasculature and retinal pigment epithelium. No dramatic differences in expression of these receptors were observed in eyes from patients with dry or wet AMD compared to control, with the exception A3 receptors. Eyes with dry AMD lost expression of A3 in the photoreceptor outer segments compared with eyes from control or wet AMD. Conclusion: The ocular presence of adenosine receptors is consistent with their proposed role in modulation of inflammation in both the retina and choroid, and their potential targeting for AMD treatment

Effects of electrical stimulation of dorsal raphe nucleus on neuronal response properties of barrel cortex layer IV neurons following long-term sensory deprivation

Abstract: Objective To evaluate the effect of electrical stimulation of dorsal raphe nucleus (DRN) on response properties of layer IV barrel cortex neurons following long-term sensory deprivation. Methods: Male Wistar rats were divided into sensory-deprived (SD) and control (unplucked) groups. In SD group, all vibrissae except the D2 vibrissa were plucked on postnatal day one, and kept plucked for a period of 60 d. After that, whisker regrowth was allowed for 8-10 d. The D2 principal whisker (PW) and the D1 adjacent whisker (AW) were either deflected singly or both deflected in a serial order that the AW was deflected 20 ms before PW deflection for assessing lateral inhibition, and neuronal responses were recorded from layer IV of the D2 barrel cortex. DRN was electrically stimulated at inter-stimulus intervals (ISIs) ranging from 0 to 800 ms before whisker deflection. Results: PW-evoked responses increased in the SD group with DRN electrical stimulation at ISIs of 50 ms and 100 ms, whereas AW-evoked responses increased at ISI of 800 ms in both groups. Whisker plucking before DRN stimulation could enhance the responsiveness of barrel cortex neurons to PW deflection and decrease the responsiveness to AW deflection. DRN electrical stimulation significantly reduced this difference only in PW-evoked responses between groups. Besides, no DRN stimulation-related changes in response latency were observed following PW or AW deflection in either group. Moreover, condition test (CT) ratio increased in SD rats, while DRN stimulation did not affect the CT ratio in either group. There was no obvious change in 5-HT2A receptor protein density in barrel cortex between SD and control groups. Conclusion: These results suggest that DRN electrical stimulation can modulate information processing in the SD barrel cortex

Biochemistry and Molecular Biology b2-Adrenergic Receptor Antagonism Attenuates CNV Through Inhibition of VEGF and IL-6 Expression

Citation: Lavine JA, Farnoodian M, Wang S, et al. b2-adrenergic receptor antagonism attenuates CNV through inhibition of VEGF and IL-6 expression. Invest Ophthalmol Vis Sci. 2017;58:299-308. DOI:10.1167/ iovs.16-20204 PURPOSE. The role of b-adrenergic receptor (AR) signaling in neovascular ocular diseases has recently emerged. We have previously reported that intraperitoneal propranolol inhibits choroidal neovascularization (CNV) in vivo and b2-AR blockade reduces vascular endothelial growth factor (VEGF) expression in mouse retinal pigment epithelium and choroidal endothelial cells in culture. Here we tested the hypothesis that the b2-AR regulates CNV through modulation of VEGF and inflammatory cytokine expression. METHODS. Mice were subjected to laser burns, inducing CNV, and were treated with an intravitreal b2-AR antagonist. After 3 and 5 days, total eye interleukin-6 (IL-6) and VEGF protein levels were measured, respectively. After 14 days, CNV was measured on choroidalscleral flatmounts. The effects of b-AR signaling on VEGF and IL-6 expression were investigated in various mouse retinal and human RPE cells by using specific b-AR agonists and antagonists. RESULTS. b2-Adrenergic receptor signaling increased Vegf mRNA expression by approximately 3-to 4-fold in mouse retinal microglia and pericytes in culture. b2-Adrenergic receptor signaling upregulated IL-6 mRNA expression between 10-and 60-fold in mouse retinal microglia, pericytes, RPE, and choroidal endothelial cells in culture. Intravitreal injection of b2-AR antagonist ICI 118,551 reduced CNV by 35% and decreased IL-6 protein levels by approximately 50%. In primary human RPE cells, b2-AR activation also stimulated VEGF and IL-6 mRNA expression by 2-and 10-fold, respectively. CONCLUSIONS. Anti-VEGF therapy for CNV is highly effective; however, some patients are resistant to therapy while others undergo repeated, frequent treatments. b2-Adrenergic receptor signaling is a potential therapeutic target because of its angiogenic and inflammatory properties

Investigating the effects of adult neural stem cell transplantation by lumbar puncture in transient cerebral ischemia

Stem cells have the ability to self renew and are therefore a good source for cell therapy following ischemia. In this study, we transplanted adult rat neural stem cells (NSCs) by lumbar puncture (LP) to investigate whether these cells can migrate and differentiate into neurons or glial cells, thereby improving functional outcome in cerebral ischemia. Transient ischemia was induced in adult rats (n = 16) for 1 h. Three days after the induction of ischemia, NSCs obtained from the subventricular zone of adult rats were injected into ischemic animals (n = 8) by LP at the level of L6–S1. Improved recovery of the coordination of movement on the 1st, 7th, 14th, 21st and 28th days after the injury was examined by the Rotarod test and compared with non-transplanted ischemic animals (n = 8). The presence of NSCs in the brain tissue of the animals was examined by immunohistofluorscence and immunohistochemical techniques. The coordination of movement in ischemic animals that received neural stem cells was improved significantly (P < 0.05) compared with untreated ischemic animals. Cells labeled with PKH26 were observed in the ischemic area of brain tissue sections. The alkaline phosphatase test and immunohistochemical techniques demonstrated a gathering of NSCs in the lateral ventricle. A number of cells which expressed neuronal and astrocytic cell markers had migrated from the lateral ventricle to the subjacent brain parenchyma. NSCs injected by LP were able to migrate to the ischemic tissue and differentiate into neural-like cells. These differentiated cells may have improved the coordination in movement in the ischemic animals injected with NSCs

Customized clinical practice guidelines for management of adult cataract in Iran

Purpose: To customize clinical practice guidelines (CPGs) for cataract management in the Iranian population. Methods: First, four CPGs (American Academy of Ophthalmology 2006 and 2011, Royal College of Ophthalmologists 2010, and Canadian Ophthalmological Society 2008) were selected from a number of available CPGs in the literature for cataract management. All recommendations of these guidelines, together with their references, were studied. Each recommendation was summarized in 4 tables. The first table showed the recommendation itself in clinical question components format along with its level of evidence. The second table contained structured abstracts of supporting articles related to the clinical question with their levels of evidence. The third table included the customized recommendation of the internal group respecting its clinical advantage, cost, and complications. In the fourth table, the internal group their recommendations from 1 to 9 based on the customizing capability of the recommendation (applicability, acceptability, external validity). Finally, customized recommendations were sent one month prior to a consensus session to faculty members of all universities across the country asking for their comments on recommendations. Results: The agreed recommendations were accepted as conclusive while those with no agreement were discussed at the consensus session. Finally, all customized recommendations were codified as 80 recommendations along with their sources and levels of evidence for the Iranian population. Conclusion: Customization of CPGs for management of adult cataract for the Iranian population seems to be useful for standardization of referral, diagnosis and treatment of patients. © 2015 Journal of Ophthalmic and Vision Research | Published by Wolters Kluwer - Medknow

Bringing an end to the silence: identifying priorities and solutions to addressing the mental health consequences of child marriage

Despite its inclusion in Sustainable Development Goal 5 to end all harmful gendered practices by 2030, child, early and forced marriages continue to be a pervasive problem globally. While there is consistent evidence on the physical health consequences of child marriage, there is a lack of evidence and inquiry into the mental health consequence. We completed a change-oriented Delphi study to establish consensus on priority areas of research and intervention in relation to the mental health consequences of child, early and forced marriages. Invited experts (n = 11), survivors (n = 27) and professionals (n = 30) participated in our Delphi. Four rounds of data collection included: a blended in-person and online workshop with invited experts, an online mixed-methods questionnaire, focus groups in Zimbabwe with women who are survivors of child marriage and a repeat questionnaire sent to the first round of experts. Quantitative data were analysed using descriptive statistics and ranking methods, consistent with other Delphi studies. Qualitative data were analysed using thematic network analysis. Findings coalesced around three areas: perspectives on the relationship between mental health and child marriage, policy actions and treatment-driven solutions. Consensus was reached on 16 items across these areas which included the need to prioritize psychosocial and social interventions to improve mental health outcomes for women and girls in existing marriages. They also called for new approaches to advocacy to drive awareness of this issue in policy circles. Implications for future practice are discussed

Inhibition study on insulin fibrillation and cytotoxicity by paclitaxel

Alzheimer, a neurodegenerative disease, and a large variety of pathologic conditions are associated with a form of protein aggregation known as amyloid fibrils. Since fibrils and prefibrillar intermediates are cytotoxic, numerous attempts have been made to inhibit fibrillation process as a therapeutic strategy. Peptides, surfactants and aromatic small molecules have been used as fibrillation inhibitors. Here we studied the effects of paclitaxel, a polyphenol with a high tendency for interaction with proteins, on fibrillation of insulin as a model protein. The effects of paclitaxel on insulin fibrillation were determined by Thioflavin T fluorescence, Congo red absorbance, circular dichroism and atomic force microscopy. These studies indicated that paclitaxel considerably hindered nucleation, and therefore, fibrillation of insulin in a dose-dependant manner. The isothermal titration calorimetry studies showed that the interaction between paclitaxel and insulin was spontaneous. In addition, the van der Waal's interactions and hydrogen bonds were prominent forces contributing to this interaction. Computational results using molecular dynamic simulations and docking studies revealed that paclitaxel diminished the polarity of insulin dimer and electrostatic interactions by increasing the hydrophobicity of its dimer state. Furthermore, paclitaxel reduced disrupting effects of insulin fibrils on PC12 cell's neurite outgrowth and complexity, and enhanced their survival. © 2014 The Authors 2014