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Baird Daniels opublikował 5 miesięcy, 1 tydzień temu
Inflammation and ferroptosis in astrocytes can be induced by external injuries, which results in excessive production of inflammatory factors and further injury on neurons. Alleviating ferroptosis might be an effective way to protect the brain from external injuries. The present study aims to explore the protective effects of Ferrostatin-1 against ferroptosis induced by Angiotensin II and the underlying mechanism.
The mouse primary astrocytes were isolated from the cortices of mice. The astrocytes were stimulated using 10µM angiotensin II in the presence or absence of 1 or 2μM Ferrostatin-1. The gene expression levels of AT1R, IL-6, IL-1β, COX-2, GFAP, and GPx4 were evaluated using qRT-PCR. Western Blot was used to determine the protein levels of AT1R, COX-2, GFAP, GPx4, Nrf2, and HO-1 and ELISA was used to detect the concentrations of IL-6, IL-1β, and PGE
. The ROS levels were evaluated using DHE staining and the reduced GSH level was determined using GSH detection kits.
The expression levels of AT1R, IL-6, IL-1β, COX-2, and GFAP in the astrocytes were significantly elevated by stimulation with Ang II and greatly suppressed by the introduction of Ferrostatin-1 in a dose-dependent manner. The promoted ROS level and inhibited GSH level in the astrocytes by the stimulation with Ang II were significantly reversed by Ferrostatin-1. Down-regulated GPx4, Nrf2, and HO-1 in the astrocytes induced by Ang II were extremely up-regulated by the treatment of Ferrostatin-1 in a dose-dependent manner.
Ferrostatin-1 alleviates angiotensin II (Ang II)- induced inflammation and ferroptosis by suppressing the ROS levels and activating the Nrf2/HO-1 signaling pathway.
Ferrostatin-1 alleviates angiotensin II (Ang II)- induced inflammation and ferroptosis by suppressing the ROS levels and activating the Nrf2/HO-1 signaling pathway.There has not been a comprehensive comparison of differences between men and women with body dysmorphic disorder (BDD) for approximately two decades. Major social and technological changes over this time may have changed patterns of bodily concerns and symptom profile among men and women with BDD, thus warranting an updated assessment of gender differences. BDD symptomatology, insight, and associated clinical and sociodemographic characteristics were compared between 49 women and 27 men with BDD. Skin was the most common concern for both men and women. Women showed more concerns than men about the appearance of their legs. Men were more concerned about muscularity/body build. Women demonstrated significantly more severe distress associated with BDD behaviours, and poorer illness insight than men. Age at BDD onset, illness duration, as well as mean severity of depression, anxiety, stress, and social anxiety were similar across the genders. These data suggest that the most common body areas of concern in people with BDD have not dramatically changed over the past two decades. However, the finding of worse insight among women is novel, and suggests a need for further investigation.While digital psychiatric interventions reduce treatment barriers, not all persons benefit from this type of treatment. Research is needed to preemptively identify who is likely to benefit from these digital treatments in order to redirect those people to a higher level of care. The current manuscript used an ensemble of machine learning methods to predict changes in major depressive and generalized anxiety disorder symptoms from pre to 9-month follow-up in a randomized controlled trial of a transdiagnostic digital intervention based on participants’ (N=632) pre-treatment data. The results suggested that baseline characteristics could accurately predict changes in depressive symptoms in both treatment groups (r=0.482, 95% CI[0.394, 0.561]; r=0.477, 95% CI[0.385, 0.560]) and anxiety symptoms in both treatment groups (r=0.569, 95% CI[0.491, 0.638]; r=0.548, 95% CI[0.464, 0.622]). These results suggest that machine learning models are capable of preemptively predicting a person’s responsiveness to digital treatments, which would enable personalized decision-making about which persons should be directed towards standalone digital interventions or towards blended stepped-care.Cognitive effects of tobacco use among women with schizophrenia, bipolar disorder or depression have not been studied extensively as most studies focussed on men smokers. As part of a study on prevalence and cognitive effects of tobacco use, women with schizophrenia, bipolar disorder and depression were assessed for cognitive functioning using an information questionnaire derived from the Indian Post Graduate Institute Battery of Brain Dysfunction (PGIBBD) and the Trail Making Tests (TMT) A and B. The community dwelling women were clinically diagnosed and recruited from the outpatient department of a free tertiary care teaching hospital in India. The sample consisted of 321 women, 141 with schizophrenia (SZ), 80 with Bipolar Disorder (BD) and 100 with Recurrent Depressive Disorder (RDD). Tobacco users answered statistically significantly fewer questions on the PGIBBD Information Questionnaire. Users also took significantly more time to complete both TMT-A and TMT-B. Age, years of schooling and tobacco use were all significant co-variates for performance on cognitive tests. Tobacco users had lower motor speed and lesser visual scanning, poorer flexibility of thinking and working memory. Women with schizophrenia performed the worst. Tobacco use may exacerbate the cognitive dysfunction associated with major mental illnesses among women.The Multiple Sclerosis Data Alliance (MSDA), a global multi-stakeholder collaboration, is working to accelerate research insights for innovative care and treatment for people with multiple sclerosis (MS) through better use of real-world data (RWD). Despite the increasing reliance on RWD, challenges and limitations complicate the generation, collection, and use of these data. MSDA aims to tackle sociological and technical challenges arising with scaling up RWD, specifically focused on MS data. MSDA envisions a patient-centred data ecosystem in which all stakeholders contribute and use big data to co-create the innovations needed to advance timely treatment and care of people with MS.
This study examines the relationship between meniscus tear presentations and failure rates following all-inside repair in isolation and in conjunction with an anterior cruciate ligament (ACL) reconstruction.
Eighty seven consecutive patients undergoing all-inside meniscal repair at a single institution from July 2016 to June 2018 were retrospectively reviewed. Details of patient presentation, tear type and location, the presence or absence of simultaneous ACL reconstruction, and surgical repair details were recorded to evaluate the relationship between patient characteristics and the primary endpoint of repair failure.
Patients were followed for an average of 2.7±0.8years. Three patients (3.4%) experienced 30-day complications including 1 deep vein thrombosis and 2 joint aspirations. Within the study time frame, 15 repairs (17.2%) failed, with 10 (11.5%) failing within one year of the initial procedure; the average time to failure was 12.3±9.0months. Patients undergoing concurrent ACL reconstruction were less likely to experience repair failure (9.7% vs. 36.0%, p=.009), while bucket-handle repairs were more likely to fail during the study period (45.0% vs. 9.0%, p=.001). These trends remained after controlling for tear location, body mass index, and number of sutures (ACL reconstruction Odds Ratio [OR] 0.229, p=.029; Bucket-handle OR 9.400, p=.003).
Our findings suggest concurrent ACL reconstruction at the time of meniscal repair is associated with increased repair survival. The all-inside technique may be successfully used across a variety of tear types and locations, although further study of its efficacy in repairing bucket-handle tears is warranted.
Our findings suggest concurrent ACL reconstruction at the time of meniscal repair is associated with increased repair survival. The all-inside technique may be successfully used across a variety of tear types and locations, although further study of its efficacy in repairing bucket-handle tears is warranted.
The purpose of this study was to evaluate the extent to which individuals with knee articular cartilage defects (ACDs) have kinesiophobia and pain catastrophizing, and how these psychological factors relate to self-reported knee outcomes.
Thirty-five individuals seeking surgical consultation for an ACD in the knee confirmed with 3.0T MRI and 18 controls without history of knee injury participated in the study. Kinesiophobia was measured with the Tampa Scale of Kinesiophobia (TSK), and scored using the modified 11-item (TSK-11) methods. Pain catastrophizing was measured with the Pain Catastrophizing Scale (PCS). Data were analyzed using descriptive statistics, independent t-tests, chi-squared tests and Spearman’s correlation coefficients, as appropriate (α=0.05).
Participants with ACDs reported higher TSK-11 scores (median 27 [IQR 25-29]) and higher PCS scores (median 10 [IQR 4-18]) than controls (median TSK-11 16 [IQR 14-17], p<0.001; median PCS 0 [IQR 0-9], p<0.001). Within those with knee ACDs, higher TSK-11 scores were associated with worse knee pain, function on activities of daily living, sports/recreation, and knee-related quality of life scores (rho=-0.38 to -0.61). Higher pain catastrophizing was associated with worse function with activities of daily living and knee-related quality of life (rho=-0.37 to -0.40).
Kinesiophobia and pain catastrophizing in people with knee ACDs were higher than controls. Higher kinesiophobia and pain catastrophizing were associated with worse function and quality of life. Further study of the impact of these psychological factors on outcomes and prognosis in people with knee ACDs is warranted.
Kinesiophobia and pain catastrophizing in people with knee ACDs were higher than controls. Higher kinesiophobia and pain catastrophizing were associated with worse function and quality of life. Further study of the impact of these psychological factors on outcomes and prognosis in people with knee ACDs is warranted.
There has been increased use of adjustable suspensory fixation (ASF) for anterior cruciate ligament reconstruction (ACLR). Potential benefits are the ability to use a shorter graft and to prevent graft displacement and damage. The purpose of this study was to establish the efficacy of this fixation method and assess whether it leads to less tunnel widening, and avoids known complications of screw fixation.
Thirty-eight patients who underwent ACLR with ASF on both the femoral and tibial sides met the inclusion criteria and were propensity matched demographically with 38 patients who underwent hybrid fixation with femoral suspensory and tibial screw and sheath. At one-year, KT-1000 knee laxity measurements were recorded and detailed MRI analysis looking at tunnel aperture widening, tunnel appearance, graft integration within the tunnels, and graft healing.
MRI comparison between ASF and hybrid cohorts revealed no significant differences in graft signal or integration, and clinically there were no differences in knee laxity between cohorts (mean 1.