Sourcebook update: using near-infrared spectroscopy to assess skeletal muscle oxygen uptake.

Monitoring the metabolic cost or oxygen consumption associated with rest and exercise is crucial to understanding the impact of disease or physical training on the health of individuals. Traditionally, measuring the skeletal muscle oxygen cost associated with exercise/muscle contractions can be rather expensive or invasive (i.e., muscle biopsies). More recently, specific protocols designed around the use of near-infrared spectroscopy (NIRS) have been shown to provide a quick, noninvasive easy-to-use tool to measure skeletal muscle oxygen consumption ([Formula: see text]). However, the data and results from NIRS devices are often misunderstood. Thus the primary purpose of this sourcebook update is to provide several experimental protocols students can utilize to improve their understanding of NIRS technology, learn how to analyze results from NIRS devices, and better understand how muscle contraction intensity and type (isometric, concentric, or eccentric) influence the oxygen cost of muscle contractions.NEW & NOTEWORTHY Compared to traditional methods, near-infrared spectroscopy (NIRS) provides a relatively cheap and easy-to-use noninvasive technique to measure skeletal muscle oxygen uptake following exercise. This laboratory not only enables students to learn about the basics of NIRS and muscle energetics but also addresses more complex questions regarding skeletal muscle physiology.

Evaluating the performance of Bayesian geostatistical prediction with physical barriers in the Chesapeake Bay.

The Chesapeake Bay is one of the most widely studied bodies of water in the United States and around the world. Routine monitoring of water quality indicators (e.g., salinity) relies on fixed sampling stations throughout the Bay. Utilizing this rich monitoring data, various methods produce surface predictions of water quality indicators to further characterize the health of the Bay as well as to support wildlife and human health research studies. Bayesian approaches for geostatistical modelling are becoming increasingly popular and can be preferred over frequentist approaches because full and exact inference can be computed, along with more accurate characterization of uncertainty. Traditional geostatistical prediction methods assume a Euclidean distance between two points when characterizing spatial dependence as a function of distance. However, Euclidean approaches may not be appropriate in estuarine environments when water-land boundaries are crossed during the modelling process. In this study, we compare stationary and barrier INLA geostatistical models with a classic kriging geostatistical model to predict salinity in the Chesapeake Bay during 4 months in 2019. Cross-validation is conducted for each approach to evaluate model performance based on prediction accuracy and precision. The results provide evidence that the two Bayesian-based models outperformed ordinary kriging, especially when examining prediction accuracy (most notably in the tributaries). We also suggest that the non-Euclidean model accounts for the appropriate water-based distances between sampling locations and is likely better at characterizing the uncertainty. However, more complex bodies of water may better showcase the capabilities and efficacy of the physical barrier INLA model.

Equine fecal microbiota response to short term antibiotic administration.

Though generally safe, research continues to demonstrate negative side effects of antibiotic administration on the gastrointestinal (GIT) microbiota across species. In horses, antibiotic associated diarrhea (AAD) is a life-threatening condition linked to the GIT microbiota. This study tested the hypothesis that short term antibiotic administration to healthy horses would negatively impact the fecal microbiota as measured by their ability to digest nutrients and through fecal shedding of disease-associated-bacteria. Twenty-four horses were assigned to one of four treatment groups: control (CO); potassium penicillin/gentamicin sulfate (KPG); ceftiofur crystalline free acid (EX); trimethoprim/sulfamethoxazole (SMZ); and treated for 4 days. Fecal samples were collected before treatment began (S0), the day after treatment conclusion (S5), and at 10, 14, 21, and 28 days after initiating treatment. Horses had highly individualized responses to antibiotic administration. All horses receiving antibiotics experienced significantly softer stool compared to controls. Lactobacillus spp. were dramatically reduced in all antibiotic treated S5 samples. Horses receiving antibiotics were significantly more likely to test positive for C. difficile or C. perfringens on fecal qPCR. In conclusion, response to antibiotic administration displays high inter-individual variability, but shows changes to the functions of fecal microbiota that may depend on the antibiotic used.

Clonal hematopoiesis related TET2 loss-of-function impedes IL1ß-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells.

Clonal hematopoiesis (CH) is defined as a single hematopoietic stem/progenitor cell (HSPC) gaining selective advantage over a broader range of HSPCs. When linked to somatic mutations in myeloid malignancy-associated genes, such as TET2-mediated clonal hematopoiesis of indeterminate potential or CHIP, it represents increased risk for hematological malignancies and cardiovascular disease. IL1ß is elevated in patients with CHIP, however, its effect is not well understood. Here we show that IL1ß promotes expansion of pro-inflammatory monocytes/macrophages, coinciding with a failure in the demethylation of lymphoid and erythroid lineage associated enhancers and transcription factor binding sites, in a mouse model of CHIP with hematopoietic-cell-specific deletion of Tet2. DNA-methylation is significantly lost in wild type HSPCs upon IL1ß administration, which is resisted by Tet2-deficient HSPCs, and thus IL1ß enhances the self-renewing ability of Tet2-deficient HSPCs by upregulating genes associated with self-renewal and by resisting demethylation of transcription factor binding sites related to terminal differentiation. Using aged mouse models and human progenitors, we demonstrate that targeting IL1 signaling could represent an early intervention strategy in preleukemic disorders. In summary, our results show that Tet2 is an important mediator of an IL1ß-promoted epigenetic program to maintain the fine balance between self-renewal and lineage differentiation during hematopoiesis.

Ball Milling-Enabled Fe2.4+ to Fe3+ Redox Reaction in Prussian Blue Materials for Long-Life Aqueous Sodium-Ion Batteries.

Aqueous Na-ion batteries using Prussian blue materials have inherent advantages in safety, material sustainability, and economic cost. However, it is challenging to obtain long-term cycling stability because many redox reactions have poor intrinsic stability in water. Here, we demonstrate reversible Fe2.4+ to Fe3+ redox reaction of Prussian blue electrodes cycled in a 17 m NaClO4 water-in-salt electrolyte. The cubic phase c-Na1.17Fe[Fe(CN)6]·0.35H2O) derived from monoclinic Prussian blue (m-Na1.88Fe[Fe(CN)6]·0.7H2O) through ball milling delivers excellent cycling stability of >18,000 cycles with >90% capacity retention at the 10C rate. The specific capacity is ∼75 and ∼67 mAh/g at 1C and 10C rates, respectively. Systematic characterizations including electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy have verified the phase transition and iron oxidation state evolution, revealing the mechanism that enables the material's high rate and long durability as the battery cathode.

Efficacy of incisional negative pressure therapy in preventing post-sternotomy wound complications.

BACKGROUND: Sternal wound infections represent a source of significant morbidity and mortality following median sternotomy. The use of incisional negative pressure wound therapy in prevention has yet to be elucidated. METHODS: A retrospective study was conducted before and after a universal wound care protocol was implemented including the prophylactic use of negative pressure wound therapy (NPWT). The primary endpoint was sternal infections within 90 days of the index operation. RESULTS: In the control period, there was a 3.0% rate of sternal infection within 90 days compared to 0.8% in the intervention period (p < 0.001). An odds ratio of 0.25 (95% confidence interval 0.11, 0.57; p < 0.001) in the intervention period as compared to the control period was demonstrated. CONCLUSIONS: The use of a standardized wound care protocol including the universal application of NPWT for patients undergoing cardiac surgery with median sternotomy was an independent predictor of decreased rates of sternal infection.

Analysis of electrical stimulation and voluntary muscle contraction on skeletal muscle oxygen uptake and mitochondrial recovery using near-infrared spectroscopy.

PURPOSE: This investigation was to compare differences in skeletal muscle oxygen consumption ([Formula: see text]) and mitochondrial recovery between voluntary (VOL) and electrically stimulated (ES) plantarflexion contractions. METHODS: Twelve men and women (26 ± 4.0 years; 171.8 ± 5.1 cm; 74.0 ± 13.7 kg) were seated in a chair with their right knee fully extended and right foot secured to a force transducer. ES electrodes and a near-infrared spectroscopy device were placed on the gastrocnemius. Participants performed ES plantarflexion contractions across a range of stimulation intensities at frequencies of 1 and 2 Hz and similar VOL contractions. Cuff occlusion occurred immediately following each series of contractions to measure [Formula: see text]. A standardized mitochondrial function assessment protocol was also performed to calculate K-constants between work-matched ES and VOL contractions. RESULTS: For mitochondrial assessments, there were no significant differences between ES and VOL rate constants (2.03 ± 0.98 vs. 1.25 ± 1.35 min-1, p = 0.266). ES resulted in a significantly greater workrate-[Formula: see text] slope at 1 Hz (0.007 ± 0.007 vs. 0.001 ± 0.002% [Formula: see text]/s/N, p = 0.014) and 2 Hz (0.010 ± 0.010 vs. 0.001 ± 0.001% [Formula: see text]/s/N, p = 0.012), as well as a significantly greater workrate-[Formula: see text] Y-intercept at 2 Hz (1.603 ± 1.513 vs. 0.556 ± 0.564% [Formula: see text]/s, p = 0.035) but not 1 Hz (0.579 ± 0.448 vs. 0.442 ± 0.357% mV̇O2/s, p = 0.535) when compared to VOL. CONCLUSION: ES results in a significantly greater [Formula: see text] at similar work rates compared to VOL, however, the mitochondrial recovery rate constants were similar. The greater mVO2 with ES may partially contribute to the increased rate of fatigue during ES exercise in individuals with muscle paralysis.

A Matter of Taste: Roles of Taste Preference on Performance and Psychological Responses during Anaerobic Exercise.

Various tastes including sweet, bitter, and sour have been shown to differentially influence physiological and psychological processes. Furthermore, ingestion of bitter and sweet solutions has been shown to acutely enhance exercise performance. However, the taste is highly individualized, and it is unclear if preference influences the ergogenic potential of taste. The purpose of this study was to investigate the effects of preferred and non-preferred drink tastes on anaerobic performance and psychological responses thereof. Physically active females participated in two counterbalanced sprint trials each with a different condition: (1) non-preferred taste (NPT), (2) Preferred taste (PT). Participants self-reported taste preferences (sweet, sour, bitter) with the highest-ranked taste being used for the PT condition and the lowest-ranked for NPT. For each visit, participants completed a 15 s Wingate Anaerobic Test (WAnT) prior to (PRE) ingestion of ~20 mL of their NP or PREF taste. Following ingestion, participants completed 2 min of active recovery, rated their taste preference of the solution, and completed another 15 s WAnT. The rate of perceived exertion (RPE), motivation, and enjoyment were measured through a visual analog scale following each WAnT. Anaerobic performance measures and heart rate (HR) were also obtained at the succession of each WAnT. Findings revealed no differences between taste conditions for mean power (p = 0.455), peak power (p = 0.824), or HR (p = 0.847). RPE was significantly lower with PT versus NPT (p = 0.006). Exercise enjoyment (p = 0.022) was higher with PT compared to NPT. NPT resulted in worse motivation compared to PRE (p = 0.001) while no changes were observed between PT and PRE (p = 0.197). These findings suggest that preferred drink taste may not enhance acute performance but improves psychological responses to maximal anaerobic exercise which may have implications for improving exercise training and adherence.

A novel tool to quantify in vivo lumbar spine kinematics and 3D intervertebral disc strains using clinical MRI.

Medical imaging modalities that calculate tissue morphology alone cannot provide direct information regarding the mechanical behaviour of load-bearing musculoskeletal organs. Accurate in vivo measurement of spine kinematics and intervertebral disc (IVD) strains can provide important information regarding the mechanical behaviour of the spine, help to investigate the effects of injuries on the mechanics of the spine, and assess the effectiveness of treatments. Additionally, strains can serve as a functional biomechanical marker for detecting normal and pathologic tissues. We hypothesised that combining digital volume correlation (DVC) with 3T clinical MRI can provide direct information regarding the mechanics of the spine. Here, we have developed a novel non-invasive tool for in vivo displacement and strain measurement within the human lumbar spine and we used this tool to calculate lumbar kinematics and IVD strains in six healthy subjects during lumbar extension. The proposed tool enabled spine kinematics and IVD strains to be measured with errors that did not exceed 0.17 mm and 0.5%, respectively. The findings of the kinematics study identified that during extension the lumbar spine of healthy subjects experiences total 3D translations ranging from 1 mm to 4.5 mm for different vertebral levels. The findings of strain analysis identified that the average of the maximum tensile, compressive, and shear strains for different lumbar levels during extension ranged from 3.5% to 7.2%. This tool can provide base-line data that can be used to describe the mechanical environment of healthy lumbar spine, which can help clinicians manage preventative treatments, define patient-specific treatments, and to monitor the effectiveness of surgical and non-surgical interventions.

Neutron time-of-flight detectors (nTOF) used at Sandia's Z-Machine.

Neutron time-of-flight (nTOF) detectors have been used on Sandia National Laboratories' Z-Machine for inertial confinement fusion and magnetized liner fusion experiments to infer physics parameters including the apparent fuel-ion temperature, neutron yield, the magnetic-radius product (BR), and the liner rho-r. Single-paddle, dual-paddle, and co-axial scintillation nTOF detectors are used in axial lines-of-sight (LOS) and LOS that are 12° from the midplane. Detector fabrication, characterization, and calibration are discussed.

Insights into Sickle Cell Disease through the Retinal Microvasculature: Adaptive Optics Scanning Light Ophthalmoscopy Correlates of Clinical OCT Angiography.

Purpose: Clinical OCT angiography (OCTA) of the retinal microvasculature offers a quantitative correlate to systemic disease burden and treatment efficacy in sickle cell disease (SCD). The purpose of this study was to use the higher resolution of adaptive optics scanning light ophthalmoscopy (AOSLO) to elucidate OCTA features of parafoveal microvascular compromise identified in SCD patients. Design: Case series of 11 SCD patients and 1 unaffected control. Participants: A total of 11 eyes of 11 SCD patients (mean age, 33 years; range, 23-44; 8 female, 3 male) and 1 eye of a 34-year-old unaffected control. Methods: Ten sequential 3 × 3 mm parafoveal OCTA full vascular slab scans were obtained per eye using a commercial spectral domain OCT system (Avanti RTVue-XR; Optovue). These were used to identify areas of compromised perfusion near the foveal avascular zone (FAZ), designated as regions of interest (ROIs). Immediately thereafter, AOSLO imaging was performed on these ROIs to examine the cellular details of abnormal perfusion. Each participant was imaged at a single cross-sectional time point. Additionally, 2 of the SCD patients were imaged prospectively 2 months after initial imaging to study compromised capillary segments across time and with treatment. Main Outcome Measures: Detection and characterization of parafoveal perfusion abnormalities identified using OCTA and resolved using AOSLO imaging. Results: We found evidence of abnormal blood flow on OCTA and AOSLO imaging among all 11 SCD patients with diverse systemic and ocular histories. Adaptive optics scanning light ophthalmoscopy imaging revealed a spectrum of phenomena, including capillaries with intermittent blood flow, blood cell stasis, and sites of thrombus formation. Adaptive optics scanning light ophthalmoscopy imaging was able to resolve single sickled red blood cells, rouleaux formations, and blood cell-vessel wall interactions. OCT angiography and AOSLO imaging were sensitive enough to document improved retinal perfusion in an SCD patient 2 months after initiation of oral hydroxyurea therapy. Conclusions: Adaptive optics scanning light ophthalmoscopy imaging was able to reveal the cellular details of perfusion abnormalities detected using clinical OCTA. The synergy between these clinical and laboratory imaging modalities presents a promising avenue in the management of SCD through the development of noninvasive ocular biomarkers to prognosticate progression and measure the response to systemic treatment.

Efficacy of CRISPR-Based Gene Editing in a Sickle Cell Disease Patient as Measured through the Eye.

Sickle cell disease (SCD) exists on a phenotypic spectrum with variable genetic expressivity, making it difficult to assess an individual patient's risk of complications at any particular point in time. Current and emerging SCD treatments, including CRISPR-based gene editing, result in a variable proportion of affected red blood cells (RBCs) still vulnerable to sickling. Clinical serological indicators of disease such as hemoglobin, indirect bilirubin, and reticulocyte count and clinical metrics including number of emergency department visits and hospitalizations over time often fall short in their ability to objectively quantify ischemic disease activity and efficacy of treatments. Clearly, better clinical biomarkers are needed. The rapidly developing field of oculomics leverages the transparent nature of the ocular tissue to directly study the retinal microvasculature in order to characterize the status of systemic diseases. In this case report, we demonstrate the ability of optical coherence tomography angiography (OCT-A) to detect and measure micro-occlusive events within the retinal capillary bed before and after RBC exchange transfusion and following CRISPR-based gene editing, as an indicator of systemic ischemic disease activity and measure of treatment efficacy. The implications of these findings are discussed.

Social Media Marketing of Cosmetic Services in the United States: Examining Gender Disparities.

INTRODUCTION: Cosmetic surgery and other elective noninvasive aesthetic procedures have become significantly more popular throughout the 21st century. As these procedures have grown in popularity, more and more Americans have begun to research potential procedures via social media. However, it is unclear whether plastic surgery practices have done an adequate job advertising these services via social media to men. MATERIALS AND METHODS: A systematic search was conducted Google, Facebook, and Instagram in order to examine potential gender disparities in social media plastic surgery marketing in America. Each practice's Facebook and Instagram profile were analyzed in two separate fashions: the presence or absence of advertisement for male services in the last ten posts, and the proportion of specific procedures advertised.. Two Pearson chi-squared analyses comparing the statistical significance of differences in the Facebook and Instagram data were then performed. RESULTS: A total of 242 Facebook and 231 Instagram profiles were selected and subsequently analyzed. The number of both Facebook and Instagram profiles that advertised to male patients varied widely from state to state. Additionally, there was substantial disparity in the procedures most heavily marketed toward men and their actual popularity amongst the male demographic. CONCLUSIONS: Plastic surgery practices have not done an effective job in capitalizing upon the increased popularity of cosmetic procedures among men with their social media advertising. Although the industry has improved its presence on Instagram, the marketing efforts of plastic surgery practices geared toward capturing the interest and demand of the male demographic remain lacking.

Imaging of vitreous cortex hyalocyte dynamics using non-confocal quadrant-detection adaptive optics scanning light ophthalmoscopy in human subjects.

Vitreous cortex hyalocytes are resident macrophage cells that help maintain the transparency of the media, provide immunosurveillance, and respond to tissue injury and inflammation. In this study, we demonstrate the use of non-confocal quadrant-detection adaptive optics scanning light ophthalmoscopy (AOSLO) to non-invasively visualize the movement and morphological changes of the hyalocyte cell bodies and processes over 1-2 hour periods in the living human eye. The average velocity of the cells 0.52 ± 0.76 µm/min when sampled every 5 minutes and 0.23 ± 0.29 µm/min when sampled every 30 minutes, suggesting that the hyalocytes move in quick bursts. Understanding the behavior of these cells under normal physiological conditions may lead to their use as biomarkers or suitable targets for therapy in eye diseases such as diabetic retinopathy, preretinal fibrosis and glaucoma.

A Pilot Study of Subclinical Non-Capillary Peripapillary Perfusion Changes in Thyroid-Related Orbitopathy Detected Using Optical Coherence Tomography Angiography.

Purpose: Hemodynamic changes surrounding the optic nerve head are known to occur in thyroid-related orbitopathy (TRO). This pilot study explores the capillary and non-capillary peripapillary perfusion changes of the retina in TRO eyes without dysthyroid optic neuropathy (DON) using optical coherence tomography angiography (OCT-A). Methods: Non-capillary and capillary peripapillary perfusion densities were calculated using single 4.5 × 4.5mm en face "RPC layer" OCT-A scans of 8 TRO patients without DON (8 eyes, mean age 40.6 years, range 23-69 years). Results were compared to a previously published dataset of 133 healthy controls (133 eyes, mean 41.5 years, range 11-83 years). The strength of association was measured between OCT-A perfusion densities and clinical measures of TRO. Results: Non-capillary peripapillary perfusion density in TRO eyes was found to be significantly decreased compared to healthy controls (TRO group 15.4 ± 2.9% vs controls 21.5 ± 3.1%; p < 0.0001). Capillary peripapillary perfusion densities showed no significant difference (TRO group 42.5 ± 1.8% vs controls 42.5 ± 1.5%; p = 1.0). Clinical measures of disease did not correlate well with OCT-A perfusion densities (p>0.05). Conclusion: These findings may represent decreased blood flow and subclinical ischemia to the optic nerve. We discuss possible pathogenic mechanisms of thyroid-related vasculopathy, including vessel wall thickening due to immunologically-induced media enlargement.

3-D OCT angiographic evidence of Anti-VEGF therapeutic effects on retinal capillary hemangioma.

PURPOSE: To report the impact of intravitreal anti-vascular endothelial growth factor (VEGF) therapy on a retinal capillary hemangioma (RCH) using clinical OCT angiography (OCT-A) in addition to standard imaging modalities. OBSERVATIONS: A 25-year-old male patient with Von Hippel-Lindau (VHL) disease presented with a history of bilateral RCH. No view was present in the right eye. Examination of the left eye revealed six peripheral RCH, the smallest of which was temporal to the macula with active exudation. This RCH was thought to be the source of cystoid macular edema (CME) involving the fovea, and therefore, the source of vision decline. 11 injections of 1.25mg of Bevacizumab EA across 14-month was given. Comparison of the pre- and post-treatment OCT-A at the temporal RCH showed a reduction of CME and regression of RCH. CONCLUSION: Anti-VEGF therapy appeared to stabilize the visual acuity and produce partial regression of RCH. It offers a safe option when visual acuity is threatened. OCT and OCT-A have the ability to document the impact of antiangiogenic therapy on RCH. 3D renderings of OCT-A offer enhanced sensitivity to recognition of structural and functional changes of RCH which may prove useful for monitoring treatment response.

CDC field triage criteria accurately predicts outcomes in high impact trauma.

BACKGROUND: The precision of emergency medical services (EMS) triage criteria dictates whether an injured patient receives appropriate care. The trauma triage protocol is a decision scheme that groups patients into triage categories of major, moderate and minor. We hypothesized that there is a difference between trauma triage category and injury severity score (ISS). METHODS: This retrospective, observational study was conducted to investigate a difference between trauma triage category and ISS. Bivariate analysis was used to test for differences between the subgroup means. The differences between the group means on each measure were analyzed for direction and statistical significance using ANOVA for continuous variables and chi square tests for categorical variables. Logistic and linear regressions were performed to evaluate factors predicting mortality, ICU length of stay. RESULTS: With respect to trauma triage category, our findings indicate that minor and moderate triage categories are similar with respect to ISS, GCS, ICU LOS, hospital LOS, and mortality. However, after excluding for low impact injuries (falls), differences between the minor and moderate categories were evident when comparing to ISS, GCS, ICU LOS, and hospital LOS. Additionally, after excluding for low impact injures, ISS, ICU LOS, and hospital stay were found to correlate well with trauma triage category. CONCLUSIONS: In this retrospective, observational study significant differences were not seen when comparing ISS with the trauma triage categories of moderate and minor during our initial analysis. However, a difference was found after excluding for low impact injuries. These findings suggest that CDC criteria accurately predicts outcomes in high impact trauma.

Mitochondrial Dysfunction in Primary Open-Angle Glaucoma Characterized by Flavoprotein Fluorescence at the Optic Nerve Head.

PURPOSE: To investigate the presence of flavoprotein fluorescence (FPF) at the optic nerve head (ONH) rim as a marker of mitochondrial dysfunction in primary open-angle glaucoma (POAG) and control eyes. DESIGN: Retrospective cross-sectional study of patients recruited from the New York Eye and Ear Infirmary of Mount Sinai. PARTICIPANTS: A total of 86 eyes (50 eyes of 30 patients with POAG and 36 eyes of 20 control participants) were enrolled. The presence of POAG was defined by circumpapillary retinal nerve fiber layer thickness (cpRNFLT) of less than the bottom fifth percentile of the normative database, glaucomatous ONH changes, and visual field defects on 24-2 tests. METHODS: Primary open-angle glaucoma and control eyes were imaged using the OcuMet Beacon. A 23° × 23° infrared scan was obtained, and an FPF scan was performed within a capture field spanning 13° in diameter. The ONH margins on the infrared image were identified by software algorithms. Then, FPF was measured within an elliptical annulus around the ONH rim, with the inner and outer boundaries corresponding to 0.5 to 1.1 times the ONH rim size. MAIN OUTCOMES MEASURES: Flavoprotein fluorescence at the OHN rim in POAG and control eyes. RESULTS: Differences in FPF between POAG and control eyes were characterized through mixed-effects logistic regression, adjusted for age and interocular pressure. Flavoprotein fluorescence was significantly higher in POAG versus control eyes, with a mean ± SD of 46.4 ± 27.9 versus 28.0 ± 11.7 (P < 0.001), respectively. Among POAG eyes, FPF showed correlation to visual field mean deviation (P < 0.001), visual field pattern standard deviation (P = 0.003), and cpRNFLT (P = 0.001) on linear mixed-effects models. CONCLUSIONS: Higher FPF in POAG versus control eyes suggests the presence of mitochondrial dysfunction at the ONH rim in eyes with glaucomatous damage. The degree of FPF corresponds to disease severity, as measured by visual field and nerve fiber layer thickness metrics. Thus, FPF may represent a metabolic indicator of disease status that reveals the extent of injury in glaucoma.

Patient perspective on remission in rheumatoid arthritis: Validation of patient reported outcome instruments to measure absence of disease activity.

OBJECTIVE: Patients have identified pain, fatigue and independence as the most important domains that need to be improved to define remission in rheumatoid arthritis (RA). This study identified and validated instruments for these domains and evaluated their added value to the ACR/EULAR Boolean remission definition. METHODS: Patients with a 28-joint Disease Activity Score (DAS28) ≤3.2 or in self-perceived remission (declaring their disease activity 'as good as gone') from the Netherlands, Portugal, Australia, and Canada, were assessed at 0, 3 and 6 months for patient-reported outcomes and the WHO-ILAR RA core set. Instrument validity was evaluated cross-sectionally, longitudinally and for the ability to predict future good outcome in terms of physical functioning. Logistic regression quantified the added value to Boolean remission. RESULTS: Of 246 patients, 152 were also assessed at 3, and 142 at 6 months. Most instruments demonstrated construct validity and discriminative capacity. Pain and fatigue were best captured by a simple numerical rating scale (NRS). Measurement of independence proved more complex, but a newly developed independence NRS was preferred. NRS for pain, fatigue and independence, in addition to or instead of patient global assessment did not add enough information to justify modification of the current Boolean definition of remission in RA. CONCLUSION: Key elements of the patient perspective on remission in RA can be captured by NRS pain, fatigue, and independence. Although this study did not find conclusive evidence to improve the current definition of remission in RA, the information from these instruments adds value to the physician's assessment of remission and further bridges the gap between physician and patient.