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Bestrophinopathies are a group of clinically distinct inherited retinal dystrophies that typically affect the macular region, an area synonymous with central high acuity vision. This spectrum of disorders is caused by mutations in bestrophin1 ( BEST1 ), a protein thought to act as a Ca 2+ -activated Cl - channel in the retinal pigment epithelium (RPE) of the eye. Although bestrophinopathies are rare, over 250 individual pathological mutations have been identified in the BEST1 gene, with many reported to have various clinical expressivity and incomplete penetrance. With no current clinical treatments available for patients with bestrophinopathies, understanding the role of BEST1 in cells and the pathological pathways underlying disease has become a priority. Induced pluripotent stem cell (iPSC) technology is helping to uncover disease mechanisms and develop treatments for RPE diseases, like bestrophinopathies. Here, we provide a comprehensive review of the pathophysiology of bestrophinopathies and highlight how patient-derived iPSC-RPE are being used to test new genomic therapies in vitro.

Introduction: Dysphagia can lead to morbidity including weight loss and aspiration pneumonia. Effective triage of patients and streamlining of pathways to expedite diagnosis and treatment is therefore imperative., Objectives: The goals of this research were to measure the referral to treatment time for dysphagia patients in a newly established pathway and compare with existing UK national and local referral to treatment times, and to evaluate patient feedback., Methods: Speech and language therapy advanced clinical practitioners were trained in nasendoscopy and assessment of swallow. Referral to treatment times were measured and patient satisfaction questionnaires completed., Results: A decrease in triage to treatment time (from 24 to 6 weeks). Patients reported high understanding of the condition and minimal discomfort during assessments. Radiation exposure was reduced (2 per cent of patients undergoing soluble contrast swallows, previously 100 per cent)., Conclusion: The new pathway expedites treatment and achieves high patient satisfaction. It empowers speech and language therapy in efficiently managing low-complexity cases and supports multidisciplinary care for dysphagia patients.

Importance: The association between radiotherapy (RT) timing after radical prostatectomy and long-term patient-reported health-related quality of life (HRQOL) in men with prostate cancer is unknown., Objective: To measure long-term HRQOL in men with prostate cancer up to 15 years after prostatectomy with or without RT and examine whether early vs late postprostatectomy RT is associated with differences in sexual, urinary, and bowel HRQOL., Design, Setting, and Participants: A prospective, multicenter, longitudinal cohort analysis using HRQOL data from the PROST-QA (2003-2006) and RP2 consortium (2010-2013) studies was conducted. Men with localized prostate cancer undergoing radical prostatectomy were included. Data were analyzed between May 8, 2023, and March 1, 2024. The study was conducted in 12 high-volume academic medical centers in the US., Exposures: Men were stratified based on receipt and timing of postprostatectomy RT: prostatectomy only, early RT (<12 months), and late RT (≥12 months)., Main Outcomes and Measures: Longitudinal sexual, incontinence, urinary irritation, bowel, and hormonal/vitality HRQOL were measured via the Expanded Prostate Cancer Index Composite at baseline; months 2, 6, and 12; and annually thereafter. Treatment groups were compared using multivariable linear mixed-effects models of change in longitudinal domain scores. Pad use for incontinence was measured longitudinally among men receiving postprostatectomy RT., Results: A total of 1203 men were included in the study: prostatectomy only (n = 1082), early RT (n = 57), and late RT (n = 64). Median age for the entire cohort was 60.5 (range, 38.8-79.7) years, and 1075 men (92.0%) were White. Median follow-up was 85.6 (IQR, 35.8-117.2) months. Compared with men receiving prostatectomy alone, those receiving postprostatectomy RT had significantly greater decreases in sexual, incontinence, and urinary irritation HRQOL. However, timing of postprostatectomy RT, specifically early vs late, was not associated with a long-term decrease in any HRQOL domain. There was evidence of improved recovery of sexual, continence, and urinary irritation scores among men receiving early RT compared with those receiving late RT after prostatectomy. Before the start of postprostatectomy RT, 39.3% of men in the early RT cohort and 73.4% of men in the late RT cohort were pad-free. By the sixth visit post-RT, 67.4% in the early RT cohort and 47.6% in the late RT cohort were pad-free., Conclusions and Relevance: In this multicenter, prospective analysis, postprostatectomy RT appeared to be negatively associated with long-term HRQOL across all domains. However, receipt of early vs late postprostatectomy RT may result in similar long-term HRQOL outcomes.

Current knowledge about the fate and transport behaviors of per- and polyfluoroalkyl substances (PFASs) in urban stormwater biofilter facilities is very limited. C5-14,16 perfluoroalkyl carboxylic acids [perfluorinated carboxylic acids (PFCAs)], C4,8,10 perfluoroalkanesulfonic acids (PFSAs), methyl-perfluorooctane sulfonamide acetic acid (MeFOSAA, a PFSA precursor), and unknown C6-8 PFCA and perfluorooctanesulfonic acid precursors were frequently found in bioretention media and forebay sediments at Σ 35 PFAS concentrations of <0.03-19 and 0.064-16 μg/kg-DW, respectively. Unknown C6-8 PFCA precursor concentrations were up to ten times higher than the corresponding PFCAs, especially at forebays and biofilters' top layer. No significant trend could be attributed to PFAS and precursor concentrations versus depth of filter media, though PFAS concentrations were 2-3 times higher in the upper layers on average (significant difference between the upper (0-5 cm) and deepest (35-50 cm) layer). PFASs had a similar spatial concentration distribution in each filter media (no clear difference between short- and long-chain PFASs). Commercial land use and organic matter were important factors explaining the concentration variations among the biofilters and between the sampling depths, respectively. Given the comparable PFAS accumulations in deeper and superficial layers and possible increased mobility after precursor biotransformation, designing shallow-depth, nonamended sand biofilters or maintaining only the top layer may be insufficient for stormwater PFAS management.

Introduction: Following the COVID-19 pandemic, telehealth usage increased. Virtual visits minimize exposure risk while also addressing barriers to care. Telehealth offers the ability to increase patient access and provider efficiency. However, patient satisfaction with telehealth has not been fully determined. This study evaluated patient-perceived quality and satisfaction of virtual vs face-to-face visits during consultation with a dietician in the management of nephrolithiasis., Methods: Ninety-six patients with previous diagnosis of nephrolithiasis underwent an initial, in-person nutrition consultation between May 2019 to February 2021. A follow-up with a dietician was randomized to in-person or telehealth. The telehealth group used an application called MDLive. The telehealth group used MDLive on a hospital computer during their follow-up with the urologist, whereas the in-person group had a separate appointment scheduled at a different location. Patient satisfaction following telehealth visits was assessed by the Telemedicine Satisfaction Questionnaire. Patient satisfaction following in-person visits was assessed with an 8-question modified Telemedicine Satisfaction Questionnaire, which lacked technology-related questions., Results: Fifty patients were randomized to in-person follow-up and 46 to virtual follow-up. Within the virtual follow-up group more than 90% "agreed" or "strongly agreed" that they were satisfied with the quality of service provided through telemedicine. Greater than 82% reported intention to use telemedicine services again. There was no significant difference in patient satisfaction between telemedicine and face-to-face visits. Sixty-seven percent of patients in the telemedicine group reported better access to health care services and time saved and 89% reported independence accessing the telehealth system without assistance., Conclusions: This study supports the idea that telemedicine may be a successful alternative in the follow up of patients undergoing nutritional counseling for stone prevention. Future studies regarding telehealth use should evaluate which other urologic conditions are amenable to virtual management.

Disuse is associated with reduced muscle oxygen saturation (SmO 2 ). Improving oxygen delivery to tissues is important for healing, preventing muscle atrophy, and reducing the risk of deep vein thrombosis. Mobility devices are used during disuse periods to ambulate and protect the injured limb. This study examined SmO 2 in walking and ambulation with various mobility devices. Thirty-eight participants randomly completed four, ten-minute trials which included: (1) walking, (2) medical kneeling scooter (MKS), (3) hands-free crutch (HFC), and (4) axillary crutch (AC). During each trial, near infrared spectroscopy sensors were placed on the vastus lateralis (VL), biceps femoris (BF), and lateral gastrocnemius (LG) of the right limb. Compared to walking, all mobility devices showed a decline in SmO 2 in the VL of ∼10% (mean ± SD; 75% ± 12%-65% ± 17%, P  < 0.05). In the BF, SmO 2 declined ∼9% in AC compared to walking (76% ± 12%-67% ± 17%, P  = 0.025). In the LG, SmO 2 declined in AC (64% ± 16%) compared to MKS (70% ± 15%, P  = 0.005). There were no differences in LG SmO 2 compared to walking (69% ± 13%) in MKS ( P  > 0.05) or HFC (65% ± 15%, P  > 0.05). In young, healthy volunteers, the use of mobility devices altered muscle oxygenation in several muscles. AC reduced muscle oxygenation in the VL, BF, and LG; while MKS and HFC maintained BF and LG muscle oxygenation at a level consistent with ambulatory walking., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bradley, Roehl, Smith, McGrath and Hackney.)

Femtosecond-laser-assisted material restructuring employs extreme optical intensities to localize the ablation regions. To overcome the minimum feature size limit set by the wave nature of photons, there is a need for new approaches to tailored material processing at the nanoscale. Here, we report the formation of deeply-subwavelength features in silicon, enabled by localized laser-induced phase explosions in prefabricated silicon resonators. Using short trains of mid-infrared laser pulses, we demonstrate the controllable formation of high aspect ratio (>10:1) nanotrenches as narrow as [Formula: see text]. The trench geometry is shown to be scalable with wavelength, and controlled by multiple parameters of the laser pulse train, such as the intensity and polarization of each laser pulse and their total number. Particle-in-cell simulations reveal localized heating of silicon beyond its boiling point and suggest its subsequent phase explosion on the nanoscale commensurate with the experimental data. The observed femtosecond-laser assisted nanostructuring of engineered microstructures (FLANEM) expands the nanofabrication toolbox and opens exciting opportunities for high-throughput optical methods of nanoscale structuring of solid materials., (© 2023. Springer Nature Limited.)

PEERs in Parasitology (PiP) is a global scientific grassroots organization founded in 2021 to promote equity and inclusion for persons (currently and) historically excluded from science because of ethnicity and/or race. The article details systemic obstacles PEER parasitologists face and current and future strategies of PiP to overcome them., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Bioretention systems are designed for quality treatment of stormwater. Particulate contaminants are commonly treated efficiently and accumulate mainly in the surface layer of the bioretention filter material. However, concerns exist that microplastic particles may not show equal accumulation behavior as other sediment particles. So far only two field and two laboratory studies are available on the fate of microplastics in few relatively newly built bioretention systems. Therefore, this study investigated the abundance and distribution of microplastics in nine 7-12 years old stormwater bioretention systems. It was found that microplastics generally accumulate on the surface of bioretention systems. Microplastic median particle concentrations decreased significantly from the surface layer (0-5 cm) of the filter material to the 10-15 cm depth layer from 448 to 136 particles/100 g, respectively. The distance to the inlet did not significantly affect the surface accumulation of microplastic particles, suggesting modest spatial variability in microplastics accumulation in older bioretention systems. Further, this study investigated the polymer composition in bioretention systems. It was shown that PP, EVA, PS and EPDM rubber are the most abundant polymer types in bioretention systems. Also, it was found that large percentages of microplastic particles are black particles (median percentage of black particles: 39%) which were found in 28 of the 33 investigated samples. This underlines the importance of including black particles in microplastic studies on stormwater, which has been overlooked in most previous studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the efficacy of fibroblast growth factor-18 (FGF-18) augmentation for improving articular cartilage healing following surgical repair in preclinical ( in vivo ) animal models., Design: A systematic review was performed evaluating the efficacy of FGF-18 augmentation with cartilage surgery compared with cartilage surgery without FGF-18 augmentation in living animal models. Eligible intervention groups were FGF-18 treatment in conjunction with orthopedic procedures, including microfracture, osteochondral auto/allograft transplantation, and cellular-based repair. Outcome variables were: International Cartilage Repair Society (ICRS) score, modified O'Driscoll histology score, tissue infill score, qualitative histology, and adverse events. Descriptive statistics were recorded and summarized for each included study., Results: In total, 493 studies were identified and 4 studies were included in the final analysis. All studies were randomized controlled trials evaluating in vivo use of recombinant human FGF-18 (rhFGF-18). Animal models included ovine ( n = 3) and equine ( n = 1), with rhFGF-18 use following microfracture ( n = 3) or osteochondral defect repair ( n = 1). The rhFGF-18 was delivered via intra-articular injection ( n = 2), collagen membrane scaffold ( n = 1), or both ( n = 1). All studies reported significant, positive improvements in cartilage defect repair with rhFGF-18 compared with controls based on ICRS score ( n = 4), modified O'Driscoll score ( n = 4), tissue infill ( n = 3), and expression of collagen type II ( n = 4) ( P < 0.05). No adverse events were reported with the intra-articular administration of this growth factor, indicating short-term safety and efficacy of rhFGF-18 in vivo ., Conclusion: This systematic review provides evidence that rhFGF-18 significantly improves cartilage healing at 6 months postoperatively following microfracture or osteochondral defect repair in preclinical randomized controlled trials.

Background: Ambulation devices may differ in their utility, muscle activation patterns, and how they affect regional blood flow. This study aimed to evaluate popliteal blood flow and vessel dimensions in response to ambulation with a hands-free crutch (HFC), axillary crutches (AC), a medical kneeling scooter (MKS), and regular walking in healthy adults., Methods: HFC, AC, MKS, and regular walking were completed in a random order by 40 adults aged 18-45 years. Participants ambulated at a comfortable pace for 10 minutes with each device. At baseline and immediately following each trial, a trained operator used diagnostic ultrasonography to capture popliteal vein and artery dimensional and flow characteristics., Results: Significant increases were observed from baseline (0.65 ± 0.23 cm) in venous diameter following walking (0.71 ± 0.21 cm, P = .012) and MKS (0.73 ± 0.21 cm, P = .003). Venous blood flow was also significantly different between conditions ( P = .009) but was only greater following walking (124 ± 79 mL/min) compared to MKS (90 ± 64 mL/min, P = .021). No differences were observed in arterial dimensions between ambulation conditions. Significant increases were found in arterial blood flow from baseline (107 ± 69 mL/min) following walking (184 ± 97 mL/min, P < .001) and HFC (163 ± 86 mL/min, P < .001). Arterial blood flow following walking was greater than AC (132 ± 72 mL/min, P = .016) and MKS (128 ± 74 mL/min, P = .003)., Conclusion: We found an average decrease in venous time-averaged mean velocity between walking and use of the MKS, but no such decrease with either HFCs or use of ACs in this healthy experimental cohort., Level of Evidence: Level III, diagnostic comparative study., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Adam P. Bradley, MS, Alexis S. Roehl, and Kyle J. Hackney, PhD, report research grant from IwalkFree, Inc, grant to institution (North Dakota State University [NDSU]); medical knee scooter, axillary crutches, and IwalkFree devices were provided for study via grant (1), and devices provided to institution (NDSU). ICMJE forms for all authors are available online., (© The Author(s) 2022.)

Background: A Hands-Free crutch (HFC) is a relatively new device that can be used during the nonweightbearing period to increase mobility. The primary aim of this investigation was to examine aerobic oxygen consumption (V.o 2 ) and substrate utilization with HFC compared to conventional ambulation devices as well as normal ambulation. A secondary purpose was to quantify perceived exertion, pain, and performance during each ambulation condition., Methods: Forty participants completed 4 separate 10-minute ambulation conditions around a rectangular course. The order of the ambulation conditions was randomized and consisted of (1) walking, (2) medical knee scooter (MKS), (3) HFC, and (4) axillary crutch (AC). Indirect calorimetry was used to determine V.o 2 and the respiratory exchange ratio (RER), an indicator of substrate utilization. Perceived exertion and pain were also assessed using questionnaires., Results: All mobility devices significantly elevated V.o 2 (+35%) compared to walking (13.14 ± 1.70 mL/kg/min; P < .001). AC had significantly greater V.o 2 requirements (20.26 ± 2.62 mL/kg/min) compared to both the MKS (15.28 ± 2.29 mL/kg/min; P < .001) and HFC (15.88 ± 2.03 mL/kg/min; P < .001). There was no difference in average V.o 2 between MKS and HFC ( P = .368). Compared to walking (0.78 ± 0.43), RER was significantly elevated in MKS (0.81 ± 0.05, P < .001) and AC (0.84 ± 0.06, P < .001), but not in HFC (0.79 ± 0.04, P = .350). RPE and pain were elevated in all ambulatory conditions (all P values <.001). Pain was significantly greater in AC compared with MKS ( P < .001) and HFC ( P < .001)., Conclusion: HFC and MKS share similar V.o 2 requirements over a 10-minute ambulation interval and are below those needed in AC. Substrate utilization in HFC was similar to regular walking with a greater reliance on lipid utilization for energy as evidenced by a lower RER. Exertion and pain scores were the most tolerable in HFC and MKS., Level of Evidence: Level II, prospective comparative study., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Kyle J. Hackney, PhD, Adam P. Bradley, MS, and Alexis S. Roehl report reseach grant from IwalkFree, Inc, grant to institution (NDSU; FAR0034987), as well as receipt of, medical knee scooter, axillary crutches, and iwalkfree devices with consultation on proper fitting provided for study via grant (devices provided to institution [NDSU]). ICMJE forms for all authors are available online., (© The Author(s) 2022.)

Images captured from a long distance suffer from dynamic image distortion due to turbulent flow of air cells with random temperatures, and thus refractive indices. This phenomenon, known as image dancing, is commonly characterized by its refractive-index structure constant C n 2 as a measure of the turbulence strength. For many applications such as atmospheric forecast model, long-range/astronomy imaging, and aviation safety, optical communication technology, C n 2 estimation is critical for accurately sensing the turbulent environment. Previous methods for C n 2 estimation include estimation from meteorological data (temperature, relative humidity, wind shear, etc.) for single-point measurements, two-ended pathlength measurements from optical scintillometer for path-averaged C n 2, and more recently estimating C n 2 from passive video cameras for low cost and hardware complexity. In this paper, we present a comparative analysis of classical image gradient methods for C n 2 estimation and modern deep learning-based methods leveraging convolutional neural networks. To enable this, we collect a dataset of video capture along with reference scintillometer measurements for ground truth, and we release this unique dataset to the scientific community. We observe that deep learning methods can achieve higher accuracy when trained on similar data, but suffer from generalization errors to other, unseen imagery as compared to classical methods. To overcome this trade-off, we present a novel physics-based network architecture that combines learned convolutional layers with a differentiable image gradient method that maintains high accuracy while being generalizable across image datasets.

Introduction: Handgrip strength (HGS) asymmetry may help identify the functional asymmetries that contribute to mobility limitations. We sought to determine the associations of HGS asymmetry on gait speed and standing balance in older Americans., Materials and Methods: The analytic sample included 8,396 adults aged ≥65-years for the last wave in which they participated in the 2006-2016 Health and Retirement Study. Participants were categorized into asymmetry groups based on the degree of HGS asymmetry. Persons with gait speed <0.8 meters/second were slow. Balance scores ranged from 0-4 with lower scores representing poorer standing balance., Results: Older Americans with 20.1%-30.0% asymmetry had 1.22 (95% confidence interval (CI): 1.05-1.42) greater odds for slow gait speed, while those with >30.0% asymmetry had 1.23 (CI: 1.05-1.44) greater odds. Persons with 10.1%-20.0%, 20.1%-30.0%, and >30% asymmetry had 1.09 (CI: 1.07-1.22), 1.23 (CI: 1.07-1.42) and 1.40 (CI: 1.22-1.61) greater odds for poorer static balance, respectively. Those in each individual asymmetry group had greater odds for slow gait speed: 1.14 (CI: 1.03-1.26) for >10.0%, 1.19 (CI: 1.07-1.33) for >20.0%, and 1.16 (CI: 1.01-1.35) for >30.0%. Similar results were observed for poorer balance: 1.20 (CI: 1.09-1.32) for >10.0%, 1.27 (CI: 1.15-1.41) for >20.0%, and 1.31 (CI: 1.16-1.49) for >30.0%. Every 10% asymmetry increase was associated with 1.62 (CI: 1.32-1.99) greater odds for poorer balance., Conclusions: The bimanual aspects of HGS asymmetry may reflect the bilateral movements required for mobility, and the relationship between upper and lower extremity strength and function may elucidate our findings., (Copyright © 2022. Published by Elsevier B.V.)

Cats and kittens in animal shelters and catteries regularly suffer from severe gastrointestinal coccidiosis, which can be fatal, and there are no drugs labeled for feline coccidiosis in the United States. Ponazuril, a triazine-class drug, is increasingly used at a dose of 50 mg/kg/d, orally, for three to five days in shelter environments for coccidiosis. A single oral dose of ponazuril paste 15% (Marquis ® ; Merial) at 50 mg/kg was administered to six healthy adult cats. Sample analysis was completed via high-performance liquid chromatography. Plasma concentrations peaked at 7.49 ± 2.06 µg/ml at 14.67 ± 7.45 hr post-administration. This study shows that ponazuril achieved a plasma concentration that inhibits growth of similar organisms after a single oral dose in cats. Further studies are necessary to optimize dosing for the treatment of clinical coccidiosis in cats., (© 2022 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.)

Background: Patients with chronic obstructive pulmonary disease (COPD) commonly experience dyspnea, which may limit activities of daily living. Pursed-lip breathing improves dyspnea for COPD patients; however, access to pursed-lip breathing training is limited., Methods: The proposed MELodica Orchestra for DYspnea (MELODY) study will be a single-site pilot study to assess the safety, feasibility, and efficacy of a music-based approach to teach pursed-lip breathing. Patients with COPD and moderate-severe dyspnea are randomized to intervention, education-control, or usual care control groups. Intervention patients meet twice weekly for eight weeks for melodica instruction, group music-making, and COPD education. Safety, feasibility, and efficacy is assessed qualitatively and quantitatively., Results: This manuscript describes the rationale and methods of the MELODY pilot project., Conclusions: If pilot data demonstrate efficacy, then a multi-site randomized control trial will be conducted to evaluate program effectiveness and implementation.

Abstract: Klawitter, L, Vincent, BM, Choi, BJ, Smith, J, Hammer, KD, Jurivich, DA, Dahl, LJ, and McGrath, R. Handgrip strength asymmetry and weakness are associated with future morbidity accumulation in americans. J Strength Cond Res 36(1): 106-112, 2022-Identifying strength asymmetries in physically deconditioned populations may help in screening and treating persons at risk for morbidities linked to muscle dysfunction. Our investigation sought to examine the associations between handgrip strength (HGS) asymmetry and weakness on accumulating morbidities in aging Americans. The analytic sample included 18,506 Americans aged ≥50 years from the 2006-2016 Health and Retirement Study. Handgrip strength was measured on each hand with a handgrip dynamometer, and persons with an imbalance in strength >10% between hands had HGS asymmetry. Men with HGS <26 kg and women with HGS <16 kg were considered as weak. Subjects reported the presence of healthcare provider-diagnosed morbidities: hypertension, diabetes, cancer, chronic lung disease, cardiovascular disease, stroke, arthritis, and psychiatric problems. Covariate-adjusted ordinal generalized estimating equations analyzed the associations for each HGS asymmetry and weakness group on future accumulating morbidities. Of those included in our study, subjects at baseline were aged 65.0 ± 10.2 years, 9,570 (51.7%) had asymmetric HGS, and 996 (5.4%) were weak. Asymmetry alone and weakness alone were associated with 1.09 (95% confidence interval [CI]: 1.04-1.14) and 1.27 (CI: 1.11-1.45) greater odds for future accumulating morbidities, respectively. Having both HGS asymmetry and weakness was associated with 1.46 (CI: 1.29-1.65) greater odds for future accumulating morbidities. Handgrip-strength asymmetry, as another potential indicator of impaired muscle function, is associated with future morbidity status during aging. Exercise professionals and related practitioners should consider examining asymmetry and weakness with handgrip dynamometers as a simple and noninvasive screening method for helping to determine muscle dysfunction and future chronic disease risk., (Copyright © 2021 National Strength and Conditioning Association.)

In this era of global environmental change and rapid regime shifts, managing core areas that species require to survive and persist is a grand challenge for conservation. Wildlife monitoring data are often limited or local in scale. The emerging ability to map and track spatial regimes (i.e., the spatial manifestation of state transitions) using advanced geospatial vegetation data has the potential to provide earlier warnings of habitat loss because many species of conservation concern strongly avoid spatial regime boundaries. Using 23 yr of data for the lek locations of Greater Prairie-Chicken (Tympanuchus cupido; GPC) in a remnant grassland ecosystem, we demonstrate how mapping changes in the boundaries between grassland and woodland spatial regimes provide a spatially explicit early warning signal for habitat loss for an iconic and vulnerable grassland-obligate known to be highly sensitive to woody plant encroachment. We tested whether a newly proposed metric for the quantification of spatial regimes captured well-known responses of GPC to woody plant expansion into grasslands. Resource selection functions showed that the grass:woody spatial regime boundary strength explained the probability of 80% of relative lek occurrence, and GPC strongly avoided grass:woody spatial regime boundaries at broad scales. Both findings are consistent with well-known expectations derived from GPC ecology. These results provide strong evidence for vegetation-derived delineations of spatial regimes to serve as generalized signals of early warning for state transitions that have major consequences to biodiversity conservation. Mapping spatial regime boundaries over time provided interpretable early warnings of habitat loss. Woody plant regimes displaced grassland regimes starting from the edges of the study area and constricting inward. Correspondingly, the relative probability of lek occurrence constricted in space. Similarly, the temporal trajectory of spatial regime boundary strength increased over time and moved closer to the observed limit of GPC lek site usage relative to grass:woody boundary strength. These novel spatial metrics allow managers to rapidly screen for early warning signals of spatial regime shifts and adapt management practices to defend and grow habitat cores at broad scales., (© 2021 by the Ecological Society of America.)

Objective: We compared pain medication use in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA) versus matched control over 2 years; a subgroup analysis assessed changes in pain medication use in patients who initiated a biologic during 12 months before and after., Methods: This was a retrospective observational cohort study using an administrative claims database. Newly diagnosed adult patients with AS, PsA, or RA identified between 1/1/2014 and 7/31/2017 were included. Demographics, baseline characteristics, and pain medication use were described using descriptive statistics. Differences in pain medication use were assessed using McNemar's/Wilcoxon signed-rank test for categorical/continuous variables., Results: The study included 2180 AS, 5681 PsA, and 34,047 RA patients to assess overall pain medication use over 2 years; 188 AS, 921 PsA, and 1599 RA patients were included to assess changes in pain medication use 12 months before and after initiation of biologic. Demographics and baseline characteristics were balanced. In the overall cohort, 74.6% AS, 75.0% PsA, and 83.0% RA patients used any pain medication at baseline versus matched control; pain medications use 2 years after diagnosis date was reported in 73.5% AS, 74.1% PsA, and 81.3% RA patients. Among AS, PsA, and RA patients, use of prescribed NSAIDs (AS: 68.1 vs. 51.1%; PsA: 51.1 vs. 42.5%; RA: 61.1 vs. 41.5%; P < 0.05), glucocorticoids (AS: 56.4 vs. 41.5%; PsA: 57.4 vs. 46.9%; RA: 88.2 vs. 75.3%; P < 0.05), and opioids (AS: 42.6 vs. 36.2% [non-significant]; PsA: 38.1 vs. 33.8%; RA: 52.0 vs. 40.4%; P < 0.05) significantly decreased 12 months after biologic initiation versus prior., Conclusions: Use of NSAIDs, glucocorticoids, and opioids are common among patients with AS, PsA, or RA, although the reported use of these co-medications after biologic initiation significantly decreases in the first year of treatment., (© 2021. The Author(s).)

The purpose of this study was to evaluate the pharmacokinetics of tulathromycin in the plasma and maternal and fetal tissues of pregnant ewes when administered within 24 hours of a single, IV Campylobacter jejuni (C. jejuni) challenge. Twelve, pregnant ewes between 72-92 days of gestation were challenged IV with C. jejuni IA3902 and then treated with 1.1 ml/45.36 kg of tulathromycin subcutaneously 18 hours post-challenge. Ewes were bled at predetermined time points and euthanized either at a predetermined time point or following the observation of vaginal bleeding or abortion. Following euthanasia, tissues were collected for bacterial culture, pharmacokinetics and histologic examination. The maximum (geometric) mean tulathromycin plasma concentration was estimated at 0.302 μg/mL, with a peak level observed at around 1.2 hours. The apparent systemic clearance of tulathromycin was estimated at 16.6 L/h (or 0.28 L/kg/h) with an elimination half-life estimated at approximately 22 hours. The mean tissue concentrations were highest in the uterus (2.464 μg/g) and placentome (0.484 μg/g), and were lowest in fetal liver (0.11 μg/g) and fetal lung (0.03 μg/g). Compared to previous reports, results of this study demonstrate that prior IV administration of C. jejuni appeared to substantially alter the pharmacokinetics of tulathromycin, reducing both the peak plasma concentrations and elimination half-life. However, additional controlled trials are required to confirm those observations., Competing Interests: The authors have declared that no competing interests exist.

Background: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR)., Methods: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed., Results: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up., Conclusions: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings., (Copyright © 2020. Published by Elsevier Inc.)

myo -Inositol (mI) is widely distributed in all domains of life and is important for several cellular functions, including bacterial survival. The enzymes responsible for the bacterial catabolism of mI, encoded in the iol operon, can vary from one organism to another, and these pathways have yet to be fully characterized. We previously identified a new scyllo -inositol dehydrogenase (sIDH) in the iol operon of Lactobacillus casei that can oxidize mI in addition to the natural substrate, scyllo -inositol, but the product of mI oxidation was not determined. Here we report the identification of these metabolites by monitoring the reaction with 13 C nuclear magnetic resonance. We prepared all six singly 13 C-labeled mI isotopomers through a biocatalytic approach and used these labeled inositols as substrates for sIDH. The use of all six singly labeled mI isotopomers allowed for metabolite characterization without isolation steps. sIDH oxidation of mI produces 1l-5- myo -inosose preferentially, but also two minor products, 1d- chiro -inosose and 1l- chiro -inosose. Together with previous crystal structure data for sIDH, we were able to rationalize the observed oxidation preference. Our relatively simple procedure for the preparation of isotopically labeled mI standards can have broad applications for the study of mI biotransformations.

Introduction: Academic medicine has long faced the challenge of addressing health inequities, reflecting on how these contribute to structural racism, and perpetuating negative social determinants of health. Most recently, we have constructed opportunities for dialogues about racism, discrimination, and microaggressions (RDM). As such, we created a professional development program that encouraged participants to (1) openly discuss RDM and the impact they have in academia, (2) learn about tools to address and respond to RDM, and (3) move towards the creation of inclusive environments. The target audience included institutional leaders, faculty, trainees, professional staff, and health care teams., Methods: We sought to meet workshop goals by integrating anti-racist dramaturgical teaching, introducing concepts knowledge, and practicing communication tools. To assess learning and evaluate our workshops, participants completed a pre- and postsurvey., Results: Results showed that 30 participants were more comfortable with discussing issues related to race/ethnicity, gender identity/expression, sexual orientation, and spirituality after participating in the workshops. Prior to the two workshops, the percentage of learners who felt confident initiating conversations ranged from 29% to 54%. After the workshops, the percentage of learners who felt confident ranged from 58% to 92%. The greatest increase, 100%, was observed in the levels of confidence in initiating conversations related to race/ethnicity., Discussion: Despite medical education's commitment to cultural competence and institutional mission statements that value diversity, equity, inclusion, and justice, professional development opportunities are limited. Participants strongly agreed their participation in such a workshop was relevant and important to their professional work., (© 2020 Sotto-Santiago et al.)

Resistance to androgen receptor (AR) targeting therapeutics in prostate cancer (PC) is a significant clinical problem. Mechanisms by which this is accomplished include AR amplification and expression of AR splice variants, demonstrating that AR remains a key therapeutic target in advanced disease. For the first time we show that IKBKE drives AR signalling in advanced PC. Significant inhibition of AR regulated gene expression was observed upon siRNA-mediated IKBKE depletion or pharmacological inhibition due to inhibited AR gene expression in multiple cell line models including a LNCaP derivative cell line resistant to the anti-androgen, enzalutamide (LNCaP-EnzR). Phenotypically, this resulted in significant inhibition of proliferation, migration and colony forming ability suggesting that targeting IKBKE could circumvent resistance to AR targeting therapies. Indeed, pharmacological inhibition in the CWR22Rv1 xenograft mouse model reduced tumour size and enhanced survival. Critically, this was validated in patient-derived explants where enzymatic inactivation of IKBKE reduced cell proliferation and AR expression. Mechanistically, we provide evidence that IKBKE regulates AR levels via Hippo pathway inhibition to reduce c-MYC levels at cis-regulatory elements within the AR gene. Thus, IKBKE is a therapeutic target in advanced PC suggesting repurposing of clinically tested IKBKE inhibitors could be beneficial to castrate resistant PC patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: There is a need for low power, scalable photoelectronic devices and systems for emerging optogenetic needs in neuromodulation. Conventional light emitting diodes (LEDs) are constrained by power and lead-counts necessary for scalability. Organic LEDs (OLEDs) offer an exciting approach to decrease power and lead-counts while achieving high channel counts on thin, flexible substrates that conform to brain surfaces or peripheral neuronal fibers. In this study, we investigate the potential for using OLEDs to modulate neuronal networks cultured in vitro on a transparent microelectrode array (MEA) and subsequently validate neurostimulation in vivo in a transgenic mouse model., Approach: Cultured mouse cortical neurons were transfected with light-sensitive opsins such as blue-light sensitive channel-rhodopsin (ChR2) and green-light sensitive chimeric channel-rhodopsin (C1V1tt) and stimulated using blue and green OLEDs (with 455 and 520 nm peak emission spectra respectively) at a power of ~1 mW mm -2 under pulsed conditions., Main Results: We demonstrate neuromodulation and optostimulus-locked, single unit-neuronal activity in neurons expressing stimulating opsins (34 units on n = 4 MEAs, each with 16 recordable channels). We also validated the optostimulus-locked response in preliminary experiments in a channel-rhodopsin expressing transgenic mouse model, where at least three isolatable single neuronal cortical units respond to OLED stimulation., Significance: The above results indicate the feasibility of generating sufficient luminance from OLEDs to perform neuromodulation both in vitro and in vivo. This opens up the possibility of developing thin, flexible OLED films with multiple stimulation sites that can conform to the shape of the neuronal targets in the brain or the peripheral nervous system. However, stability of these OLEDs under chronic conditions still needs to be carefully assessed with appropriate packaging approaches.

An estimated 2.4 million children play baseball in 80 countries. The majority of these children have experienced pain with throwing. A key component to a successful rehabilitation after an upper extremity injury for a baseball player is an interval throwing program, which allows a youth athlete to increase the demands of throwing in a progressive and controlled manner. Numerous interval throwing programs are designed for baseball players of high school age and older, but few exist for the baseball player who is skeletally immature. Our interval throwing programs take into consideration various field dimensions, injury types, and position requirements for youth. Our goal is to create a guide for rehabilitation specialists and players to return to throwing as quickly and safely as possible.

Emergency Room (ER) crowding is one of the more complex issues in the healthcare system worldwide. Crowding gives rise to long ER waiting times, patient dissatisfaction, and negative effects on a healthcare systems' performance. This paper focuses on the utilization of the Collective System Design (CSD) methodology to optimize the performance of an ER, which is of principal importance both from a life-threatening and an economic standpoint. The CSD technique is applied to detect areas of deficiency and to identify the functional requirements of the system to address those issues. The ER and system engineering specialists' team gathered data from the electronic medical center log and their system observation. The team determined the functional requirements and effective solutions, and implemented a continuous improvement plan to enhance ER performance. From a statistical standpoint, a significant decrease in the median of the door-to-doctor time measure (27 min vs 13 min) and a substantial improvement in the patients' level of satisfaction with the quality of health care (20th percentile vs 41th percentile) were observed after the implementation of the CSD methodology. The CSD methodology augments the implementation of lean tools by providing a language for defining the requirements and corresponding solutions for a system design. Using the CSD methodology, results in a significant increase in the ER's capacity to treat patients efficiently.