نتائج البحث

1

A cellular approach to understanding and treating Gulf War Illness

المؤلفون: Alessia Niceforo, Philip L Yates, Alvin V. Terry, Kimberly Sullivan, Emanuela Piermarini, Ramnik S. Gill, Peter W. Baas, Ankita Patil, Liang Qiang, Wayne D. Beck, Patrick M. Callahan, Xiaohuan Sun

المصدر: Cell Mol Life Sci

الوصف: Gulf War Illness (GWI), a disorder suffered by approximately 200,000 veterans of the first Gulf War, was caused by exposure to low-level organophosphate pesticides and nerve agents in combination with battlefield stress. To elucidate the mechanistic basis of the brain-related symptoms of GWI, human-induced pluripotent stem cells (hiPSCs) derived from veterans with or without GWI were differentiated into forebrain glutamatergic neurons and then exposed to a Gulf War (GW) relevant toxicant regimen consisting of a sarin analog and cortisol, a human stress hormone. Elevated levels of total and phosphorylated tau, reduced microtubule acetylation, altered mitochondrial dynamics/transport, and decreased neuronal activity were observed in neurons exposed to the toxicant regimen. Some of the data are consistent with the possibility that some veterans may have been predisposed to acquire GWI. Wistar rats exposed to a similar toxicant regimen showed a mild learning and memory deficit, as well as cell loss and tau pathology selectively in the CA3 region of the hippocampus. These cellular responses offer a mechanistic explanation for the memory loss suffered by veterans with GWI and provide a cell-based model for screening drugs and developing personalized therapies for these veterans.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::163fc2fc8710b0410b2c07dce4604bf9Test
https://doi.org/10.1007/s00018-021-03942-3Test

2

Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics

المؤلفون: Julie T. Marchesan, Grant J. Egnatz, Kevin Moss, Mustafa Saadat Girnary, Karen V. Swanson, Eugenia Monaghan, Yizu Jiao, Shaoping Zhang, James D. Beck

المصدر: Periodontology 2000

الوصف: Inflammasomes are a group of multimolecular intracellular complexes assembled around several innate immune proteins. Recognition of a diverse range of microbial, stress and damage signals by inflammasomes results in direct activation of caspase‐1, which subsequently induces the only known form of secretion of active interleukin‐1β and interleukin‐18. Although the importance of interleukin‐1β in the periodontium is not questioned, the impact of inflammasomes in periodontal disease and its potential for therapeutics in periodontology is still in its very early stages. Increasing evidence in preclinical models and human data strongly implicate the involvement of inflammasomes in a number of inflammatory, autoinflammatory and autoimmune disorders. Here we review: (a) the currently known inflammasome functions, (b) clinical/preclinical data supporting inflammasome involvement in the context of periodontal and comorbid diseases and (c) potential therapies targeting inflammasomes. To clarify further the inflammasome involvement in periodontitis, we present analyses of data from a large clinical study (n = 5809) that measured the gingival crevicular fluid‐interleukin‐1β and grouped the participants based on current periodontal disease classifications. We review data on 4910 European‐Americans that correlate 16 polymorphisms in the interleukin‐1B region with high gingival crevicular fluid‐interleukin‐1β levels. We show that inflammasome components are increased in diseased periodontal tissues and that the caspase‐1 inhibitor, VX‐765, inhibits ~50% of alveolar bone loss in experimental periodontitis. The literature review further supports that although patients clinically present with the same phenotype, the disease that develops probably has different underlying biological pathways. The current data indicate that inflammasomes have a role in periodontal disease pathogenesis. Understanding the contribution of different inflammasomes to disease development and distinct patient susceptibility will probably translate into improved, personalized therapies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9579f4d169267c1f53884561de09720Test
http://europepmc.org/articles/PMC6927484Test

3

Quetiapine Augmentation of Cognitive Processing Therapy in Veterans with Posttraumatic Stress Disorder. Design and Methodology of a Pilot Study

المؤلفون: Adeel Meraj, Jennifer L. Wilson, Jennifer A. Lemmer, Alan L. Peterson, Jim Mintz, Muhammad R. Baig, John D. Roache, Eric C. Meyer, Robert D. Beck, Anna Hernandez

مصطلحات موضوعية: Posttraumatic stress, business.industry, medicine, Cognitive processing therapy, Quetiapine, business, behavioral disciplines and activities, medicine.drug, Clinical psychology

الوصف: BackgroundThe limited efficacy of first-line treatment of posttraumatic stress disorder (PTSD) with selective serotonergic reuptake inhibitors commonly leads to the use of multiple medications that still fail to achieve symptomatic remission. VA/DOD guidelines identify trauma-focused psychotherapies as the evidence-based treatment for PTSD, but overall effectiveness is limited by reduced levels of patient engagement. Cognitive processing therapy (CPT) is the most widely-used trauma-focused therapy in the VA system for Veterans with PTSD. Our previous results based on a case series suggested that quetiapine monotherapy, but not risperidone or valproate, could increase engagement in CPT, thereby improving clinical outcomes through direct medication effects and indirectly through greater engagement in CPT.Methods & ResultsWe report the study protocol of a pilot study. This randomized, double blind placebo-controlled study was designed to evaluate the feasibility, safety, and preliminary efficacy of completing a randomized trial of quetiapine vs. placebo as an adjunct to promote patient engagement in CPT treatment for PTSD.ConclusionsWe expect that the success of this ongoing study should provide us with the preliminary data necessary to design a full-scale randomized trial.Trial Registration:NCT04280965

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::42342897c9891065b00ff041ff0f37e5Test
https://doi.org/10.21203/rs.3.rs-812267/v1Test

4

Unusual presentation of CREST retinal vasculitis

المؤلفون: Corey Waldman, Effie Z. Rahman, Kinley D. Beck, Jeong-Hyeon Sohn

المصدر: American Journal of Ophthalmology Case Reports
American Journal of Ophthalmology Case Reports, Vol 23, Iss, Pp 101172-(2021)

الوصف: Purpose To report a case of CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) syndrome-induced retinal vasculitis in the setting of ocular inflammation soon after recent micropulse cyclophotocoagulation (mTS-CPC). Observations Our patient developed CREST associated retinal vasculitis in both eyes (right > left) eight days after receiving mTS-CPC in her left eye. There was initial concern for sympathetic ophthalmia due to the resulting bilateral inflammation. The patient was treated with prednisone with resolution of her symptoms. Conclusions This is the first case of CREST retinal vasculitis that appears to be directly triggered by inflammation caused by mTS-CPC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e55163d9a3ba4d531790096c129f0da0Test
http://europepmc.org/articles/PMC8326344Test

5

Time course of renal sodium transport in the pregnant rat

المؤلفون: Shyama M. E. Masilamani, Steven D. Beck, Crystal A. West

المصدر: Current Research in Physiology
Current Research in Physiology, Vol 4, Iss, Pp 229-234 (2021)

الوصف: Progressive sodium retention and cumulative plasma volume expansion occur to support the developing fetus during pregnancy. Sodium retention is regulated by individual tubular transporters and channels. An increase or decrease in any single transporter could cause a change in sodium balance. Understanding the time-course for changes in each sodium transporter during pregnancy will enable us to understand progressive sodium retention seen in pregnancy. Here, we examined the activity of the major apical sodium transporters found in the nephron using natriuretic response tests in virgin, early pregnant, mid-pregnant, and late pregnant rats. We also measured renal and serum aldosterone levels. We found that furosemide sensitive sodium transport (NKCC2) is only increased during late pregnancy, thiazide sensitive sodium transport (NDCBE/pendrin) is increased in all stages of pregnancy, and that benzamil sensitive sodium transport (ENaC) is increased beginning in mid-pregnancy. We also found that serum aldosterone levels progressively increased throughout gestation and kidney tissue aldosterone levels increased only during late pregnancy. Here we have shown progressive turning on of specific sodium transport mechanisms to help support progressive sodium retention through the course of gestation. These mechanisms contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.
Highlights • NKCC2 activity is only increased during late pregnancy. • Thiazide sensitive sodium transport, likely mediated by NDCBE/pendrin, is increased in all stages of pregnancy. • ENaC activity is increased beginning in mid-pregnancy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f5ef4013e0ee2bf8dfcd931d9f33db10Test
https://pubmed.ncbi.nlm.nih.gov/34988469Test

6

The Carbamate, Physostigmine does not Impair Axonal Transport in Rat Cortical Neurons

المؤلفون: Peter W. Baas, Wayne D. Beck, Guangyu Wu, Sean X. Naughton, Alvin V. Terry, Zhe Wei

المصدر: Neuroscience Insights
Neuroscience Insights, Vol 16 (2021)

الوصف: Among the various chemicals that are commonly used as pesticides, organophosphates (OPs), and to a lesser extent, carbamates, are most frequently associated with adverse long-term neurological consequences. OPs and the carbamate, pyridostigmine, used as a prophylactic drug against potential nerve agent attacks, have also been implicated in Gulf War Illness (GWI), which is often characterized by chronic neurological symptoms. While most OP- and carbamate-based pesticides, and pyridostigmine are relatively potent acetylcholinesterase inhibitors (AChEIs), this toxicological mechanism is inadequate to explain their long-term health effects, especially when no signs of acute cholinergic toxicity are exhibited. Our previous work suggests that a potential mechanism of the long-term neurological deficits associated with OPs is impairment of axonal transport (AXT); however, we had not previously evaluated carbamates for this effect. Here we thus evaluated the carbamate, physostigmine (PHY), a highly potent AChEI, on AXT using an in vitro neuronal live imaging assay that we have previously found to be very sensitive to OP-related deficits in AXT. We first evaluated the OP, diisopropylfluorophosphate (DFP) (concentration range 0.001-10.0 µM) as a reference compound that we found previously to impair AXT and subsequently evaluated PHY (concentration range 0.01-100 nM). As expected, DFP impaired AXT in a concentration-dependent manner, replicating our previously published results. In contrast, none of the concentrations of PHY (including concentrations well above the threshold for impairing AChE) impaired AXT. These data suggest that the long-term neurological deficits associated with some carbamates are not likely due to acute impairments of AXT.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8cde810801e806fe5df26000ec02558dTest
http://europepmc.org/articles/PMC8155748Test

7

The effects of temporary intraocular pressure spikes after intravitreal dexamethasone implantation on the retinal nerve fiber layer

المؤلفون: Nathan Gresores, Roberto Diaz-Rohena, Edward R Chu, Kinley D. Beck, Jeong-Hyeon Sohn, Jordan M. Comstock, Chelsey Krambeer, Rishi Das, Michael A Singer, Sarah Kenny, Aaron Mendlovitz, Daniel Nolan, Kendall Wannamaker, Daniel Kermany, Sepehr Bahadorani

المصدر: Clinical Ophthalmology. 13:1079-1086

الوصف: Background and objective: The dexamethasone (DEX) implant is known to cause temporary intraocular pressure (IOP) spikes after implantation. The purpose of this study is to determine if IOP spikes after DEX implant cause significant thinning in the retinal nerve fiber layer (RNFL). Study design, patients, and methods: A total of 306 charts were reviewed with 48 and 21 patients meeting inclusion criteria for the cross-sectional and prospective groups, respectively. Cross-sectional inclusion criteria: IOP spike ≥22 mmHg up to 16 weeks after DEX implant, DEX implant in only 1 eye per patient, and spectral-domain optical coherence tomography (OCT) RNFL imaging of both eyes ≥3 months after IOP spike. Prospective inclusion criteria: OCT RNFL performed within 1 year prior to DEX implantation, IOP spike ≥22 mmHg up to 16 weeks after DEX implant, and OCT RNFL performed ≥3 months after IOP spike. The average RNFL thickness in the contralateral eye was used as the control in the cross-sectional group. Institutional review board approval was obtained. Results: In the cross-sectional group, there was no statistically significant difference in the mean RNFL thicknesses in the treated vs untreated eyes (80.4±15.5 μm and 82.6±15.8 μm, respectively; P=0.33) regardless of treatment diagnosis, magnitude of IOP spike, or history of glaucoma. In the prospective group, mean RNFL thicknesses before and after IOP spikes ≥22 mmHg were similar (78.0±14.8 μm and 75.6±13.6 μm, respectively; P=0.13). Conclusion and relevance: Temporary elevation of IOP after DEX implantation when treated with topical IOP lowering drops does not appear to lead to a meaningful change in RNFL thickness.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::c8a0da42fd9a6bff85592aafff67a706Test
https://doi.org/10.2147/opth.s201395Test

8

Enhancing Completion of Cognitive Processing Therapy for Posttraumatic Stress Disorder with Quetiapine in Veterans with Mild Traumatic Brain Injury: a Case Series

المؤلفون: Alan L. Peterson, Jennifer A. Lemmer, Muhammad R. Baig, Jennifer L. Wilson, Robert D. Beck, John D. Roache

المصدر: Psychiatric Quarterly. 90:431-445

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Traumatic brain injury, medicine.medical_treatment, Arousal, Stress Disorders, Post-Traumatic, Quetiapine Fumarate, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, 030212 general & internal medicine, Brain Concussion, Veterans, Combat Disorders, Rehabilitation, Risperidone, Cognitive Behavioral Therapy, business.industry, Middle Aged, medicine.disease, Combined Modality Therapy, Polytrauma, 030227 psychiatry, Treatment Adherence and Compliance, Psychiatry and Mental health, Cognitive processing therapy, Quetiapine, Female, Psychopharmacology, business, Antipsychotic Agents, medicine.drug

الوصف: To evaluate the outcomes of the antiarousal medications valproate, risperidone, and quetiapine on completion of treatment of cognitive processing therapy (CPT) for PTSD. A case series of fifty treatment-seeking adult (≥18 years) veterans with mild traumatic brain injury and combat-related PTSD who had unsuccessful trials of 2 or more first-line agents and previously declined treatment with trauma-focused therapy, seen at the psychiatric outpatient services of the local Polytrauma Rehabilitation Center from January 1, 2014, through December 31, 2017. Patients were prescribed valproate (n = 8), risperidone (n = 17), or quetiapine (n = 25) and were referred for individual weekly treatment with CPT. Outcome measurements of interest were measures of engagement and completion rate of CPT, PTSD Checklist total score (range, 0-80; higher scores indicate greater PTSD severity) and arousal subscale score (range, 0-24; higher scores indicate greater arousal severity), and clinical observations of sleep variables. Of the 50 patients included in the study, 48 (96%) were men; mean (SD) age was 36 (8) years. Eighteen (86%) patients initially receiving quetiapine and none taking valproate or risperidone became adequately engaged in and completed CPT. Among patients who completed CPT, the mean decrease in the PTSD Checklist score was 25 [95% CI, 30 to 20] and 9 (50%) patients no longer met criteria for PTSD. These preliminary findings support quetiapine as an adjunctive medication to facilitate CPT. A pragmatic trial is needed to evaluate the efficacy, safety, and feasibility of quetiapine to improve engagement in and completion rate of CPT.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d092a73089480396d7fbdc00241135c9Test
https://doi.org/10.1007/s11126-019-09638-zTest

9

The severity and associated comorbidities of retinopathy of prematurity among micro-premature infants with birth weights less than 750 grams

المؤلفون: Clio Armitage Harper, Sarah P. Read, Jennifer Desireddi, Kinley D. Beck, Ryan C. Young, H. Harper

المصدر: Journal of Neonatal-Perinatal Medicine. 12:41-45

الوصف: Objectives To evaluate the characteristics and comorbidities associated with ROP in micro-premature infants and their results. Methods This is a retrospective chart review involving multiple intensive care units in Central Texas from 2011 to 2016. Infants were included if birth weight (BW) was≤750 g with confirmed ROP by the International Classification of Retinopathy of Prematurity (ICROP). Neonates were examined and treated with laser ablation or intravitreal ranibizumab (IVR) with subsequent laser treatment, guided by fluorescein angiography, if met treatment criteria defined as type 1 ROP by the Early Treatment of Retinopathy of Prematurity standards. Time to regression was defined clinically. Results were analyzed using chi-squared test. Results 100 neonates were included in the study. Mean BW was 599 grams and mean gestational age was 24.2 weeks. Forty neonates were classified as type 1 ROP and therefore required intervention; of them 21 received laser alone and 19 required IVR with subsequent laser. Only 2 patients received more than one IVR injection. None of the patients progressed to stage 4 or 5 ROP. Conclusions Despite such low birth weights, none of these neonates progressed to stage 4 or 5 ROP likely because of prompt examination and treatment with laser or with IVR and subsequent laser. IVR might serve as a bridge to laser in type 1 ROP allowing some retinal vessel development prior to definitive laser treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::340eb472dea5ac83792c3f6ff44814e5Test
https://doi.org/10.3233/npm-17158Test

10

Intraocular Pressure Control for Patients Undergoing Combination Intravitreal Anti-VEGF and Dexamethasone Therapy for Macular Edema from Retinal Vein Occlusion

المؤلفون: Darren Bell, Petar Yanev, Lyndon Tyler, Tyson Jergensen, Joshua Singer, Michael A Singer, Paul Woods, Joshua Michael Iltis, Kinley D. Beck

المصدر: Journal of Pharmaceutics and Therapeutics. 4:234-237

مصطلحات موضوعية: Anti vegf, medicine.medical_specialty, Intraocular pressure, Retinal Vein, genetic structures, business.industry, medicine.disease, eye diseases, Ophthalmology, Occlusion, medicine, sense organs, business, Macular edema, Dexamethasone, medicine.drug

الوصف: Background and Objective: Sustained-release dexamethasone intravitreal implant is an effective treatment for macular edema secondary to retinal vein occlusion (RVO) but ocular hypertension is a side effect. This study evaluated whether the addition of a single combination IOP-lowering medication will reliably control intraocular pressure (IOP) for those patients. Study Design/Patients and Methods: Retrospective chart review of 62 patients that underwent multiple injections of combination anti-VEGF and sustained-release dexamethasone intravitreal implant for macular edema secondary to RVO. IOP spikes were treated with brimonidine 0.2% - timolol 0.5%. IRB approval was obtained. Results: The average elevated IOP requiring treatment was 28.6 mmHg. The average IOP after adding brimonidine 0.2% - timolol 0.5% was 16.7 mmHg. 100 percent of treatment cycles had an IOP< 30 mmHg after starting treatment. Conclusions: Using one combination IOP-lowering drop can reliably control the ocular hypertension that occurs secondary to combination therapy for macular edema in RVO.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::31be963cfa4828d7fbe1459daa2714afTest
https://doi.org/10.18314/jpt.v4i1.1433Test

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