bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does aerobic exercise training alter responses to opioid analgesics in individuals with chronic low back pain? A randomized controlled trial
Authors: Bruehl Stephen , Burns John W. , Koltyn Kelli , Gupta Rajnish , Buvanendran Asokumar , Edwards David , Chont Melissa , Wu Yung Hsuan , Stone Amanda 
Published: December 2020

Abstract
We tested whether aerobic exercise training altered morphine analgesic responses or reduced morphine dosages necessary for adequate analgesia. Patients with chronic back pain were randomized to an 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 45). Before and after the intervention, participants underwent 3 laboratory sessions (double-blinded, crossover) to assess effects of saline placebo, i.v. morphine (0.09 mg/kg), and i.v. naloxone (12 mg) on low back pain and evoked heat pain responses. Differences in evoked and back pain measures between the placebo and morphine conditions indexed morphine analgesia, with pre-post intervention changes the primary outcome. Endogenous opioid analgesia was indexed by differences in evoked and low back pain measures between the naloxone and placebo conditions. A Sex X Intervention interaction on the analgesic effects of morphine on visual analogue scale back pain intensity was observed (P = 0.046), with a similar trend for evoked pain threshold (P = 0.093). Male exercisers showed reduced morphine analgesia pre-post intervention, whereas male controls showed increased analgesia (with no differences in females). Of clinical significance were findings that relative to the control group, aerobic exercise produced analgesia more similar to that observed after receiving ≈7 mg morphine preintervention (P < 0.045). Greater pre-post intervention increases in endogenous opioid function (from any source) were significantly associated with larger pre-post intervention decreases in morphine analgesia (P < 0.046). The overall pattern of findings suggests that regular aerobic exercise has limited direct effects on morphine responsiveness, reducing morphine analgesia in males only.
Oral potentially malignant disorders: new insights for future treatment
Authors: Gurizzan Crisitna , Lorini Luigi , Bossi Paolo 
Published: December 2020

Purpose of review
The purpose of this review is to define the issues regarding oral potentially malignant disorders (OPMDs) and provide an overview of currently available treatments and ongoing clinical trials for future opportunities.

Recent findings
Nowadays, the treatment of choice of OPMD is surgery, whose role in preventing malignant transformation is however limited because of the high rate of recurrence and field cancerization. There have been several attempts of combining systemic therapies with surgery to reduce risk of malignant transformation. The identification of biomarkers that could predict malignant transformation is crucial in better tailoring the risk profile and possible therapeutic approaches.

Summary
Loss of heterozygosity remains the most predictive marker of malignant transformation; however, role of specific microRNA and OPMD immune infiltration are emerging as potential biomarkers. Given the failure of previous trials with various chemopreventive strategies, new strategies should be defined to address the issue of systemic prevention of malignant transformation. Recent updates about immune infiltration and the immune-equilibrium concept for OPMD could shed light into new preventive approaches.
Pre-therapeutic Biomarkers for Ranibizumab Therapy among Type 2 Diabetic Patients with Diabetic Macular Edema
Authors: Paine Suman K. , Bhattacharjee Chandra K. , Bhaduri Gautam , Pramanik Subhasish , Borah Prasanta K. , Mahanta Jagadish , Basu Analabha , Mondal Lakshmi K. 
Published: December 2020

SIGNIFICANCE
A differential outcome in randomized controlled trials of anti–vascular endothelial growth factor (anti-VEGF) therapy, including ranibizumab, for diabetic macular edema is a major dilemma for planning, optimizing, and managing clinical usage. The variable outcome of the therapeutics necessitates the importance of finding a predictive biomarker for anti-VEGF therapy to improve subject selection.

PURPOSE
Our study correlates the baseline pro- and anti-VEGF isoforms and its three receptors (VEGFReceptor1, VEGFReceptor2, and VEGFReceptor3) for circulatory candidate protein molecules among diabetic patients with macular edema, with the clinical outcome of ranibizumab therapy.

METHODS
This study included 86 individuals who were anti-VEGF naive at the time of ascertainment but have completed the standardized therapy regimen of the clinic. Plasma proteins for pro- and anti-VEGF isoforms and its three receptors were determined in replicate by an enzyme-linked immunosorbent assay.

RESULTS
The study demonstrated that 56 (65.12%) individuals benefited from the therapy in terms of letter gain (Snellen chart). Baseline plasma soluble VEGF receptor 2 (sVEGFR-2) was significantly higher among responders (65.10 pg/mL; 95% confidence interval, 55.41 to 74.80 pg/mL) compared with nonresponders (46.38 pg/mL; 95% confidence interval, 38.69 to 54.07 pg/mL; P
FDR = .03). Diffuse diabetic macular edema with proliferative diabetic retinopathy increases the risk of nonresponse to the therapy by 3.03-fold (P
FDR = .04).

CONCLUSIONS
The present study postulates that diffuse diabetic macular edema with proliferative diabetic retinopathy and baseline circulatory soluble VEGF receptor 2 may be potential candidates as therapy-stratifying markers for ranibizumab treatment among patients with diabetic macular edema.
Case Report: Successful Corneal Crosslinking in a Patient with Corneal Ectasia Associated with Stevens-Johnson Syndrome
Authors: Li Ye , Lu Lucy M. , Gokul Akilesh , Ziaei Mohammed 
Published: December 2020

SIGNIFICANCE
Corneal ectasia can be a complication of Stevens-Johnson syndrome. When detected in a timely manner, corneal crosslinking can be a safe treatment. This is an important association to highlight that early diagnosis and treatment can prevent the need for invasive surgical procedures such as keratoplasty.

PURPOSE
This study aimed to report a successful accelerated epithelium-off corneal crosslinking in a rare case of corneal ectasia secondary to Stevens-Johnson syndrome.

CASE REPORT
A 25-year-old Indian man presented with a progressive visual acuity decline 5 years after an acute episode of Stevens-Johnson syndrome secondary to penicillin ingestion. Serial tomography scans confirmed the diagnosis of corneal ectasia. After the preparation of the ocular surface, which was deemed to have a mild degree of limbal stem cell deficiency, with frequent preservative-free lubrication and steroid use, accelerated epithelium-off crosslinking was performed with 4 minutes of continuous ultraviolet-A exposure at 30 mW/cm2 and a total energy dose of 7.2 J/cm2. Complete re-epithelialization was observed at 72 hours after crosslinking with no complications. Corneal tomography 15 months after treatment showed stabilization of ectasia, with improvement in visual acuity.

CONCLUSIONS
Corneal ectasia is a rare but important complication of Stevens-Johnson syndrome. Accelerated epithelium-off crosslinking treatment can be considered in patients with a compromised ocular surface after Stevens-Johnson syndrome. Pre-operative optimization of the ocular surface and vigilant monitoring in the early post-operative period are recommended for the prevention of complications.
Subjective Evaluation of Defocus and Astigmatism Combinations Using Image Simulation in Presbyopes
Authors: Vincent Marc , Marin Gildas , Legras Richard 
Published: December 2020

SIGNIFICANCE
Image simulation is a useful and efficient tool to explore the impact of defocus and astigmatism combinations on visual acuity and image quality score when accommodation is taken into account.

PURPOSE
The goal of this experiment was to determine if a simulation is able to predict visual acuity and image quality score (IQS) with defocus and astigmatism combinations in presbyopes.

METHODS
We measured visual acuity and IQS in five defocus and astigmatism combinations in either real or simulated conditions. In real conditions, the subjects viewed a stimulus through an ophthalmic lens or a deformable mirror. In simulated conditions, subjects viewed images of the same stimulus with simulated blur. The amounts of defocus and astigmatism combinations of a progressive addition lens in near vision were generated through a static correction of the subject's aberrations. We simulated three levels of accommodation: subject could not accommodate (FOC0), subject could accommodate to the less hyperopic focal point (FOC1), or subject could accommodate to the circle of least confusion (FOC2).

RESULTS
Visual acuity or IQS did not differ between mirror and progressive addition lens conditions. Visual acuity measured in real blur conditions differed significantly from that in FOC0 simulated blur condition but were similar to that in FOC1 and FOC2 simulated blur conditions. Image quality score obtained in real conditions were between scores measured with the FOC0 and FOC1 simulated conditions, suggesting that the subjects were able to produce a low level of accommodation.

CONCLUSIONS
Accommodation may play a role when comparing optical and simulated defocus and astigmatism combinations. Presbyopic subjects are able to produce a low level of accommodation that may counterbalance a part of the deleterious effect of the astigmatism on image quality. Simulation remains a useful tool if the correct accommodation state is taken into account.
Uncorrected Refractive Error and Distance Visual Acuity in Children Aged 6 to 14 Years
Authors: Kleinstein Robert N. , Mutti Donald O. , Sinnott Loraine T. , Jones-Jordan Lisa A. , Cotter Susan A. , Manny Ruth E. , Twelker J. Daniel , Zadnik Karla ,   for the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study Group
Published: December 2020

SIGNIFICANCE
This study presents the relationship between distance visual acuity and a range of uncorrected refractive errors, a complex association that is fundamental to clinical eye care and the identification of children needing refractive correction.

PURPOSE
This study aimed to analyze data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study to describe the relationship between distance uncorrected refractive error and visual acuity in children.

METHODS
Subjects were 2212 children (51.2% female) 6 to 14 years of age (mean ± standard deviation, 10.2 ± 2.1 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study between 2000 and 2010. Uncorrected distance visual acuity was measured using a high-contrast projected logMAR chart. Cycloplegic refractive error was measured using the Grand Seiko WR-5100K autorefractor. The ability of logMAR acuity to detect various categories of refractive error was examined using receiver operating characteristic curves.

RESULTS
Isoacuity curves show that increasing myopic spherical refractive errors, increasing astigmatic refractive errors, or a combination of both reduces distance visual acuity. Visual acuity was reduced by approximately 0.5 minutes of MAR per 0.30 to 0.40 D of spherical refractive error and by approximately 0.5 minutes of MAR per 0.60 to 0.90 D of astigmatism. Higher uncorrected hyperopic refractive error had little effect on distance visual acuity. Receiver operating characteristic curve analysis suggests that a logMAR distance acuity of 0.20 to 0.32 provides the best balance between sensitivity and specificity for detecting refractive errors other than hyperopia. Distance acuity alone was ineffective for detecting hyperopic refractive errors.

CONCLUSIONS
Higher myopic and/or astigmatic refractive errors were associated with predictable reductions in uncorrected distance visual acuity. The reduction in acuity per diopter of cylindrical error was about half that for spherical myopic error. Although distance acuity may be a useful adjunct to the detection of myopic spherocylindrical refractive errors, accommodation presumably prevents acuity from assisting in the detection of hyperopia. Alternate procedures need to be used to detect hyperopia.
A Randomized Trial of Objective Spectacle Prescriptions for Adults with Down Syndrome: Baseline Data and Methods
Authors: Anderson Heather A. , Benoit Julia S. , Marsack Jason D. , Manny Ruth E. , Ravikumar Ayeswarya , Fern Karen D. , Trast Kelsey R. 
Published: December 2020

SIGNIFICANCE
It is difficult to determine the most efficacious refractive correction for individuals with Down syndrome using routine clinical techniques. New objective methods that optimize spectacle corrections for this population may reduce limitations on daily living by improving visual quality.

PURPOSE
This article describes the methods and baseline characteristics of study participants in a National Eye Institute–sponsored clinical trial to evaluate objectively derived spectacle corrections in adults with Down syndrome. Intersession repeatability of the primary outcome measure (distance visual acuity) is also reported.

METHODS
Adults with Down syndrome were enrolled into a nine-visit study to compare clinically derived spectacle corrections and two different objective spectacle corrections derived from wavefront aberration data. Spectacle corrections were randomized and dispensed for 2 months each. Distance visual acuity was measured with a Bailey-Lovie–style chart. Intersession repeatability of acuity was established by performing difference versus mean analysis from binocular acuity measures obtained through habitual corrections at visits 1 and 2.

RESULTS
Thirty adults (mean ± standard deviation age, 29 ± 10 years) with a large range of refractive errors were enrolled. Presenting visual acuity at visit 1 was reduced (right eye, 0.47 ± 0.20 logMAR; left eye, 0.42 ± 0.17 logMAR). The mean difference between visits 1 and 2 was 0.02 ± 0.06 logMAR, with a coefficient of repeatability (1.96 × within-subject standard deviation) of 0.12 logMAR.

CONCLUSIONS
This study seeks to investigate new strategies to determine optical corrections that may reduce commonly observed visual deficits in individuals with Down syndrome. The good intersession repeatability of acuity found in this study (six letters) indicates that, despite the presence of reduced acuity, adults with Down syndrome performed the outcome measure for this clinical trial reliably.
Targeting Uric Acid Prevents Brain Injury and Anxiety in a Rat Model of Hemorrhagic Shock
Authors: L’Ecuyer Sydnée , Gilbert Kim , Brochu Benjamin , Beyrouthy Joseph , Liu Chao , Bouchard Caroline , Gagné Marc-André , Khazoom François , Bernard Francis , Rousseau Guy , Charbonney Emmanuel 
Published: December 2020

ABSTRACT
Secondary brain injury following hemorrhagic shock (HS) is a frequent complication in patients, even in the absence of direct brain trauma, leading to behavioral changes and more specifically anxiety and depression. Despite preclinical studies showing inflammation and apoptosis in the brain after HS, none have addressed the impact of circulating mediators. Our group demonstrated an increased uric acid (UA) circulation in rats following HS. Since UA is implicated in endothelial dysfunction and inflammatory response, we hypothesized UA could alter the blood–brain barrier (BBB) and impact the brain. Male Wistar rats were randomly assigned to: SHAM, HS (hemorrhagic shock) and HS + U (hemorrhagic shock + 1.5 mg/kg of uricase). The uricase intervention, specifically targeting UA, was administered during fluid resuscitation. It prevented BBB dysfunction (fluorescein sodium salt permeability and expression of intercellular adhesion molecule-1) following HS. As for neuroinflammation, all of the results obtained (MPO activity; Iba1 and GFAP expression) showed a significant increase after HS, also prevented by the uricase. The same pattern was observed after quantification of apoptosis (caspase-3 activity and TUNEL) and neurodegeneration (Fluoro-Jade). Finally, the forced swim, elevated plus maze, and social interaction tests detected anxiety-like behavior after HS, which was blunted in rats treated with the uricase. In conclusion, we have identified UA as a new circulatory inflammatory mediator, responsible for brain alterations and anxious behavior after HS in a murine model. The ability to target UA holds the potential of an adjunctive therapeutic solution to reduce brain dysfunction related to hemorrhagic shock in human.
Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients
Authors: Keyloun John W. , Le Tuan D. , Pusateri Anthony E. , Ball Robert L. , Carney Bonnie C. , Orfeo Thomas , Brummel-Ziedins Kathleen E. , Bravo Maria C. , McLawhorn Melissa M. , Moffatt Lauren T. , Shupp Jeffrey W. 
Published: December 2020

ABSTRACT

Objective:
The aim of this study is to evaluate the association between burn injury and admission plasma levels of Syndecan-1 (SDC-1) and Tissue Factor Pathway Inhibitor (TFPI), and their ability to predict 30-day mortality.

Background:
SDC-1 and TFPI are expressed by vascular endothelium and shed into the plasma as biomarkers of endothelial damage. Admission plasma biomarker levels have been associated with morbidity and mortality in trauma patients, but this has not been well characterized in burn patients.
Methods: This cohort study enrolled burn patients admitted to a regional burn center between 2013 and 2017. Blood samples were collected within 4 h of admission and plasma SDC-1 and TFPI were quantified by ELISA. Demographics and injury characteristics were collected prospectively. The primary outcome was 30-day in-hospital mortality.

Results:
Of 158 patients, 74 met inclusion criteria. Most patients were male with median age of 41.5 years and burn TBSA of 20.5%. The overall mortality rate was 20.3%. Admission SDC-1 and TFPI were significantly higher among deceased patients. Plasma SDC-1 >34 ng/mL was associated with a 32-times higher likelihood of mortality [OR: 32.65 (95% CI, 2.67–399.78); P = 0.006] and a strong predictor of mortality (area under the ROC [AUROC] 0.92). TFPI was associated with a nine-times higher likelihood of mortality [OR: 9.59 (95% CI, 1.02–89.75); P = 0.002] and a fair predictor of mortality (AUROC 0.68).

Conclusions:
SDC-1 and TFPI are associated with a higher risk of 30-day mortality. We propose the measurement of SDC-1 on admission to identify burn patients at high risk of mortality. However, further investigation with a larger sample size is warranted.
Low Microcirculatory Perfused Vessel Density and High Heterogeneity are Associated With Increased Intensity and Duration of Lactic Acidosis After Cardiac Surgery with Cardiopulmonary Bypass
Authors: Greenwood John C. , Jang David H. , Spelde Audrey E. , Gutsche Jacob T. , Horak Jiri , Acker Michael A. , Kilbaugh Todd J. , Shofer Frances S. , Augoustides John G.T. , Bakker Jan , Abella Benjamin S. 
Published: December 2020

ABSTRACT

Introduction:
Lactic acidosis after cardiac surgery with cardiopulmonary bypass is common and associated with an increase in postoperative morbidity and mortality. A number of potential causes for an elevated lactate after cardiopulmonary bypass include cellular hypoxia, impaired tissue perfusion, ischemic-reperfusion injury, aerobic glycolysis, catecholamine infusions, and systemic inflammatory response after exposure to the artificial cardiopulmonary bypass circuit. Our goal was to examine the relationship between early abnormalities in microcirculatory convective blood flow and diffusive capacity and lactate kinetics during early resuscitation in the intensive care unit. We hypothesized that patients with impaired microcirculation after cardiac surgery would have a more severe postoperative hyperlactatemia, represented by the lactate time-integral of an arterial blood lactate concentration greater than 2.0 mmol/L.

Methods:
We measured sublingual microcirculation using incident darkfield video microscopy in 50 subjects on intensive care unit admission after cardiac surgery. Serial measurements of systemic hemodynamics, blood gas, lactate, and catecholamine infusions were recorded each hour for the first 6 h after surgery. Lactate area under the curve (AUC) was calculated over the first 6 h. The lactate AUC was compared between subjects with normal and low perfused vessel density (PVD < 18 mm/mm2), high microcirculatory heterogeneity index (MHI > 0.4), and low vessel-by-vessel microvascular flow index (MFIv < 2.6).

Results:
Thirteen (26%) patients had a low postoperative PVD, 20 patients (40%) had a high MHI, and 26 (52%) patients had a low MFIv. Patients with low perfused vessel density had higher lactate AUC compared with subjects with a normal PVD (22.3 [9.4–31.0] vs. 2.6 [0–8.8]; P < 0.0001). Patients with high microcirculatory heterogeneity had a higher lactate AUC compared with those with a normal MHI (2.5 [0.1–8.2] vs. 13.1 [3.7–31.1]; P < 0.001). We did not find a difference in lactate AUC when comparing high and low MFIv.

Conclusion:
Low perfused vessel density and high microcirculatory heterogeneity are associated with an increased intensity and duration of lactic acidosis after cardiac surgery with cardiopulmonary bypass.
Mechanical Ventilation with Moderate Tidal Volume Exacerbates Extrapulmonary Sepsis-Induced Lung Injury via IL33-WISP1 Signaling Pathway
Authors: Liu Shuai , Deng Meihong , Pan Pinhua , Turnquist Heth R. , Pitt Bruce R. , Billiar Timothy R. , Zhang Li-Ming 
Published: December 2020

ABSTRACT
IL-33 and WNT1-inducible secreted protein (WISP1) play central roles in acute lung injury (ALI) induced by mechanical ventilation with moderate tidal volume (MTV) in the setting of sepsis. Here, we sought to determine the inter-relationship between IL-33 and WISP1 and the associated signaling pathways in this process.
We used a two-hit model of cecal ligation puncture (CLP) followed by MTV ventilation (4 h 10 mL/kg) in wild-type, IL-33−/− or ST2−/− mice or wild-type mice treated with intratracheal antibodies to WISP1. Macrophages (Raw 264.7 and alveolar macrophages from wild-type or ST2-/- mice) were used to identify specific signaling components.
CLP + MTV resulted in ALI that was partially sensitive to genetic ablation of IL-33 or ST2 or antibody neutralization of WISP1. Genetic ablation of IL-33 or ST2 significantly prevented ALI after CLP + MTV and reduced levels of WISP1 in the circulation and bronchoalveolar lung fluid. rIL-33 increased WISP1 in alveolar macrophages in an ST2, PI3K/AKT, and ERK dependent manner. This WISP1 upregulation and WNT β-catenin activation were sensitive to inhibition of the β-catenin/TCF/CBP/P300 nuclear pathway.
We show that IL-33 drives WISP1 upregulation and ALI during MTV in CLP sepsis. The identification of this relationship and the associated signaling pathways reveals a number of possible therapeutic targets to prevent ALI in ventilated sepsis patients.