E-consults between primary care and internal medicine: implementation, accessibility, benefits, and implications.

AIM: This work aims to evaluate whether electronic consultations (e-consults) are a clinically useful, safe tool for assessing patients between primary care and internal medicine. METHODS: This is a retrospective cohort study of all e-consults ordered by the Primary Care Department to the Internal Medicine Department between September 2019 and December 2023. The results of initial consultations, emergency department visits and subsequent admissions, and survival were assessed and complaints and claims filed were reviewed. RESULTS: A total of 11,434 e-consults were recorded (55.4% women) with a mean age of 62.1 (SD19.4) years and a wide range (15-102 years). The mean response time was 2.55 (SD 1.6) days. As a result of the e-consults, 5645 patients (49.4%) were given an in-person appointment. For the remaining 5789 (50.6%), a written response was provided. Among those given appointments, the time between the response and in-person appointment was less than five days (95% of cases). Compared to those not given appointments, in-person appointments were older (p < 0.0001), visited the emergency department more times (one month: p = 0.04; three months: p = 0.001), were admitted to the hospital more times (one month: p = 0.0001; three months: p = 0.0001), and had higher mortality at one year (12.7% vs. 9.8% p = 0.0001). In the Cox analysis, only in-person appointments (RR = 1.11; p = 0.04)) and age (RR = 1.09; p < 0.01) were independent factors of mortality. No complaints or claims of any kind were registered. CONCLUSIONS: These data suggest that e-consults are a clinically useful, safe tool for assessing patients referred from primary care to internal medicine departments.

Zygomorphic flowers last longer: the evolution of floral symmetry and floral longevity.

Floral longevity, the length of time a flower remains open and functional, is a phylogenetically conserved trait that balances floral costs against the rate at which flowers are pollinated. Floral symmetry has long been considered a key trait in floral evolution. Although zygomorphic (bilaterally symmetric) flowers typically receive fewer floral visitors than actinomorphic (radially symmetric) flowers, it is yet to be determined whether this could be associated with longer floral longevity. Using newly collected field data combined with data from the literature on 1452 species in 168 families, we assess whether floral longevity covaries with floral symmetry in a phylogenetic framework. We find that zygomorphic flowers last on average 1.1 days longer than actinomorphic flowers, a 26.5% increase in longevity, with considerable variation across both groups. Our results provide a basis to discuss the ecological and evolutionary costs of zygomorphy for plants. Despite these costs, zygomorphy has evolved numerous times throughout angiosperm history, and we discuss which rewards may outweigh the costs of slower pollination in zygomorphic flowers.

Clinical suspicion, diagnosis and management of cardiac amyloidosis: update document and executive summary.

In recent years, the interest in cardiac amyloidosis has grown exponentially. However, there is a need to improve our understanding of amyloidosis in order to optimise early detection systems. Therefore, it is crucial to incorporate solutions to improve the suspicion, diagnosis and follow-up of cardiac amyloidosis. In this sense, we designed a tool following the different phases to reach the diagnosis of cardiac amyloidosis, as well as an optimal follow-up: a) clinical suspicion, where the importance of the "red flags" to suspect it and activate the diagnostic process is highlighted; 2) diagnosis, where the diagnostic algorithm is mainly outlined; and 3) follow-up of confirmed patients. This is a practical resource that will be of great use to all professionals caring for patients with suspected or confirmed cardiac amyloidosis, to improve its early detection, as well as to optimise its accurate diagnosis and optimal follow-up.

Effects of internet and smartphone addiction on cognitive control in adolescents and young adults: A systematic review of fMRI studies.

BACKGROUND: Internet Addiction (IA) refers to excessive or uncontrolled behaviors related to Internet access, causing impairment or distress. Similarly, Smartphone Addiction (SPA) involves the excessive use of smartphones, disrupting users' daily lives. Cognitive control plays a relevant role in the development of IA and SPA, with executive functions and rewards processing being particularly important. OBJECTIVE: This study aims to provide a synthesis of scientific evidence on the differential effects of IA and SPA on cognition in young adults and adolescents, using fMRI. METHODS: Relevant articles published between 2013 and May 2023 were identified following the PRISMA protocol. RESULTS: Included studies (n = 21) revealed that both behavioral addictions were associated with impairments in cognitive control related to reward processing (ACC, insula, amygdala) and executive function (DLPFC, frontal, parietal lobes) in adolescents and young adults. CONCLUSION: These findings provide evidence for neuroanatomical similarities between IA and SPA in young adults and adolescents related to executive functions and rewards processing. However, differential effects of SPA and IA on cognitive control were not found in this study. Future research should explore the relationship between these addictions with other cognitive domains to further expand our understanding within this field. While both IA and SPA involve the excessive use of online technology, SPA could involve a higher risk, given that smartphones allow internet connectivity anytime.

Meningoencephalitis caused by Non-O1, non-O139 Vibrio cholerae in an infant from southern Spain.

Non-O1, non-O139 Vibrio cholerae (NOVC) is an emergent pathogen that mainly causes gastroenteritis. Also, it causes ear, wound infections, and bacteremia but the nervous system is rarely affected. We report on a case of NOVC meningoencephalitis in an infant that recovered after antimicrobial therapy but later presented neurologic sequelae.

Biting rhythms and infection rates of anthropophilic sand fly species (Diptera: Phlebotominae) in sites with different land use in southern Mexico.

Could tropical forest conversion shape sand fly (Diptera: Phlebotominae) biting rhythms and Leishmania infection rates? Using a Shannon trap, we estimated the bite rate and infection prevalence among anthropophilic sand flies at sites with different land use in southern Mexico. We estimated the expected monthly infection rate of the Leishmania parasite along the gradient and generated information on the biting rhythm of sand flies in a poorly characterized cutaneous leishmaniasis endemic region. We used generalized mixed linear and mixed additives models to evaluate differences in the biting rate, nocturnal activity, and inoculation rate of female sand flies, as well as their relationship with the loss of forest cover and environmental disparities recorded throughout the study area. Our results show that the loss of forest cover influences the biting rhythm of sand fly species and the potential number of infectious bites with Leishmania, but the greatest entomological and potential epidemiological risk continues to be associated with sylvatic areas (amplification events). Despite this, we detected that the effect of forest cover (%) on the entomological exposure seems to be also dependent on the sand fly species, and that, albeit to a lesser extent, Leishmania parasite is circulating in disturbed landscapes through generalist and competent sand fly vector species. We also found that land use change did not affect the nocturnal activity, however we detected that important vector species were active most of the time. Contrary to our expectation, temperature and humidity did not shape the biting rhythm of sand fly species. We discuss the limitations and epidemiological implications of our findings regarding the risk of contracting leishmaniasis in southern Mexico.

REALMS: Resilient exploration and lunar mapping system.

Space resource utilisation is opening a new space era. The scientific proof of the presence of water ice on the south pole of the Moon, the recent advances in oxygen extraction from lunar regolith, and its use as a material to build shelters are positioning the Moon, again, at the centre of important space programs. These worldwide programs, led by ARTEMIS, expect robotics to be the disrupting technology enabling humankind's next giant leap. However, Moon robots require a high level of autonomy to perform lunar exploration tasks more efficiently without being constantly controlled from Earth. Furthermore, having more than one robotic system will increase the resilience and robustness of the global system, improving its success rate, as well as providing additional redundancy. This paper introduces the Resilient Exploration and Lunar Mapping System, developed with a scalable architecture for semi-autonomous lunar mapping. It leverages Visual Simultaneous Localization and Mapping techniques on multiple rovers to map large lunar environments. Several resilience mechanisms are implemented, such as two-agent redundancy, delay invariant communications, a multi-master architecture different control modes. This study presents the experimental results of REALMS with two robots and its potential to be scaled to a larger number of robots, increasing the map coverage and system redundancy. The system's performance is verified and validated in a lunar analogue facility, and a larger lunar environment during the European Space Agency (ESA)-European Space Resources Innovation Centre Space Resources Challenge. The results of the different experiments show the efficiency of REALMS and the benefits of using semi-autonomous systems.

Relevance of subclinical right ventricular dysfunction measured by feature-tracking cardiac magnetic resonance in non-ischemic dilated cardiomyopathy.

BACKGROUND: Right ventricular (RV) dysfunction in patients with non-ischemic dilated cardiomyopathy (NICM) is associated with cardiovascular events. To analyze the feasibility of assessing RV myocardial deformation by feature tracking (FT)-cardiac magnetic resonance (CMR), and its usefulness as a prognostic marker. METHODS: Retrospective study of NICM patients undergoing CMR. Longitudinal FT-RV free wall (LFT-RVFW) and fractional area change (FAC) were obtained. Correlation with standard RV parameters was studied. An association with combined event (heart failure (HF), ICD implantation or cardiovascular death) was assessed using a logistic regression model. RESULTS: 98 patients (64 ± 13 years) were included. Left ventricular (LV) systolic function (LVEF 29.5 ± 9.6%, 47% with LVEF ≥ 30%) and RV (RVEF 52.2 ± 14.6%, 72% with RVEF ≥ 45%). Follow-up of 38 ± 17 months, 26.5% presented at least one admission for HF. An excellent correlation of LFT-RVFW (r = 0.82) and FAC (r = 0.83) with RVEF was evident. No association of RV-FT parameters with prognosis entire study population was found. However, in patients with LVEF ≥ 30%, admissions for HF were associated with lower LFT-RVFW (-21.6 ± 6.6% vs -31.3 ± 10%; p = 0.006) and FAC (36.6 ± 9.6% vs 50.5 ± 13.4%; p < 0.001) values. Similar differences were observed when only patients with RVEF ≥ 45% were considered. An LFT-RVFW cut-off point of -19.5% and FAC of 36.5% showed good prognostic performance. Decreased LFT-RVFW or FAC represented an independent predictor of combined event in patients with LVEF ≥ 30%. CONCLUSIONS: In NICM patients without severe LV dysfunction, decreased values of LFT-RVFW and/or FAC were associated with HF admissions, independently of RVEF.

Pain extent is associated with Central Sensitization Inventory but not widespread pressure pain sensitivity or psychological variables in women with fibromyalgia.

OBJECTIVE: To investigate the relationship between pain extent, as a clinical sign of central sensitization, and clinical, psychological, and pressure sensitivity in women with fibromyalgia syndrome (FMS). METHOD: In this study, 126 females with FMS completed demographic (age, gender, body mass index, height, weight), clinical (pain history, and pain intensity at rest and during daily living activities), psychological (depression and anxiety levels), and neurophysiological [pressure pain threshold (PPT)] assessments. The Central Sensitization Inventory (CSI) was also used to collect self-reported symptoms of sensitization. Pain extent and frequency maps were obtained from pain drawings using customized software. After conducting a multivariable correlation analysis to determine the relationships between variables, a stepwise linear regression model analysis was performed to identify variables associated with pain extent. RESULTS: Pain extent was positively associated with age (r = 0.17), years with pain (r = 0.27), pain during daily life activities (r = 0.27), and CSI (r = 0.42) (all p < 0.05). The stepwise regression analysis revealed that 27.8% of the pain extent was explained by CSI, age, and years with pain. CONCLUSIONS: This study found that larger pain extent was associated with self-reported outcomes, i.e. CSI, but not neurophysiological outcomes, i.e. PPTs, of sensitization in women with FMS. Older age and a longer history with pain symptoms were also associated with larger pain extent.

Effect of growing forage legumes on the migration and survival in the pasture of gastrointestinal nematodes of sheep.

In order to identify types of forage that inhibit pasture contamination, an evaluation was performed of the effect of the forage legumes Trifolium repens (white clover), Trifolium pratense (red clover) and Lotus corniculatus (bird's-foot-trefoil) on the survival and migration of infective larvae (L3) of gastrointestinal nematodes (GIN) of sheep. An experimental area of 441 m2 was divided into four blocks, subdivided into areas of 1.20 × 1.20 in which the three forage legumes were separately overseeded. After growth of the forage in each subdivision, experimental units were established that were later artificially contaminated with sheep faeces containing GIN eggs. Between October and December 2018, pasture, faecal and soil samples were collected on four occasions during weeks 1, 2, 4 and 8 after the deposition of faeces. In week 6, the forage legumes in all the experimental units were mown to simulate grazing. The number of L3 was quantified to determine their survival in the pasture, faeces and soil. In addition, the horizontal migration of L3 was measured at two distances from the faecal pellets (10 and 30 cm), as well as their vertical migration at two heights of the plant stems, that is, lower half and upper half. Larvae vertical migration was affected by the forage species (P < 0.001), in that bird's-foot-trefoil contained fewer larvae in the upper stratum. Bird's-foot-trefoil restricted the migration of L3 to the upper stratum of the plant, which could potentially decrease the risk of infection by intestinal nematodes in grazing sheep.

EMMPRIN is an emerging protein capable of regulating cancer hallmarks.

EMMPRIN, also known as Basigin or CD147, is a transmembrane glycoprotein member of the immunoglobulin superfamily. It is expressed basally in cells that regulate physiological processes of the cardiovascular, nervous, and immune systems. However, EMMPRIN is also capable of interacting with different proteins, like VEGFR, SMAD4, Integrin, MCT, CyPA, GLUT1, CAIV, Annexin II, Cav-1, CAML, etc., and regulating signaling pathways that stimulate the cell processes of proliferation, apoptosis, metabolism, adhesion, invasion, migration, metastasis, tumor immune response, and angiogenesis processes, which favors the development of different types of cancer. EMMPRIN is the first protein reported that favors cancer development due to its ability to interact with extracellular, intracellular, and membrane proteins. In conclusion, EMMPRIN regulates several proteins associated with the development of tumor processes. Therefore, blocking the expression of EMMPRIN can be a therapeutic target, and the analysis of its expression can be used as an important biomarker in cancer.

Telemedicine in retinopathy of prematurity: Crossing borders in pediatric vision health. TELEROP study.

GENERAL OBJECTIVE: To evaluate the accuracy and validity of images with smartphone compared to the RetCam® system for the diagnosis of retinopathy of prematurity (ROP). METHODOLOGY: Observational, longitudinal and masked study carried out at the Dr. Elías Santana hospital. Infants with birth weight ≤1500 g, gestational age ≤30 weeks and/or patients exposed to risk factors or complications linked to ROP were included. These subjects were screened using images with smartphone or RetCam®, both compared to conventional fundoscopy. The ICROP classification was used for staging. The main results analyzed were sensitivity, specificity, positive predictive values and kappa index. RESULTS: 915 images (n = 121) were obtained, distributed in smartphone group (50.4%) and RetCam® group (49.6%) between August 2020 and March 2021. Subjects with ROP had lower gestational age (30.2 sem ± 2.8), birth weight (1361 g ± 398), and greater exposure to oxygen therapy (12.8 days ± 11.3). The RetCam® group presented sensitivity = 80%, specificity = 78%, positive predictive value = 90% and kappa index = 0.70. The smartphone group presented sensitivity = 88%, specificity = 90%, positive predictive value = 93.75% and kappa index = 0.81. CONCLUSIONS: Both diagnostic methods were accurate to identify ROP. The smartphone group obtained superior results with excellent resolution, representing a cost-effective method to create a global impact on reducing preventable blindness in the pediatric population.

Biomechanical characteristics of the ovarian cortex in POI patients and functional outcomes after drug-free IVA.

PURPOSE: There is increasing evidence that the ovarian extracellular matrix (ECM) plays a critical role in follicle development. The rigidity of the cortical ECM limits expansion of the follicle and consequently oocyte maturation, maintaining the follicle in its quiescent state. Quiescent primordial, primary, and secondary follicles still exist in primary ovarian insufficiency (POI) patients, and techniques as in vitro activation (IVA) and drug-free IVA have recently been developed aiming to activate these follicles based on the Hippo signaling disruption that is essential in mechanotransduction. In this context, we analyze the effect of drug-free IVA in POI patients, comparing the relationship between possible resumption ovarian function and biomechanical properties of ovarian tissue. METHODS: Nineteen POI patients according to ESHRE criteria who underwent drug-free IVA by laparoscopy between January 2018 and December 2019 and were followed up for a year after the intervention. A sample of ovarian cortex taken during the intervention was analyzed by atomic force microscopy (AFM) in order to quantitatively measure tissue stiffness (Young's elastic modulus, E) at the micrometer scale. Functional outcomes after drug-free were analyzed. RESULTS: Resumption of ovarian function was observed in 10 patients (52.6%) and two of them became pregnant with live births. There were no differences in clinical characteristics (age and duration of amenorrhea) and basal hormone parameters (FSH and AMH) depending on whether or not there was activation after surgery. However, ovarian cortex stiffness was significantly greater in patients with ovarian activity after drug-free IVA: median E = 5519 Pa (2260-11,296) vs 1501 (999-3474); p-value < 0.001. CONCLUSIONS: Biomechanical properties of ovarian cortex in POI patients have a great variability, and higher ovarian tissue stiffness entails a more favorable status when drug-free IVA is applied in their treatment. This status is probably related to an ovary with more residual follicles, which would explain a greater possibility of ovarian follicular reactivations after treatment.

BoviPure® density-gradient centrifugation procedure enhances the quality of fresh and cryopreserved dog epididymal spermatozoa.

BoviPure® is a salt solution containing colloidal silica particles coated with silane used to select sperm (e.g., ruminants) by density-gradient centrifugation (DGC). This research assessed the suitability of the BoviPure-DGC and swim-up methods for selecting dog epididymal sperm in fresh, chilled and frozen-thawed samples on post-treatment sperm quality. Sperm samples (n = 60 epididymides) were recovered by retrograde flushing from thirty orchiectomized adult dogs. Thereafter, 20 sperm pools, containing sperm aliquots of three randomly selected animals, were used for chilling (at 5 ºC for 24 h) and freezing (in liquid nitrogen vapors). Sperm selection by BoviPure-DCG and swim-up was performed in both individual and pooled samples, including non-selected samples as controls. Overall, after BoviPure-DGC selection a higher sperm retrieval rate was obtained than the swim-up selection in both individual (P < 0.05) and pooled (P < 0.01) samples. BoviPure-DGC improved (P < 0.05) the total (TM) and progressive (PSM) sperm motilities, curvilinear (VCL) and straight-line (VSL) velocities, linearity (LIN), wobble (WOB), beat-cross frequency (BCF), and integrity of plasmatic (IPM) and acrosomal (IAM) membranes of individual samples in comparison with non-selected samples. In pooled samples, however, the BoviPure-DGC improved (P < 0.05) the PSM, VCL, WOB, and IPM of chilled and frozen-thawed samples. The swim-up method improved (P < 0.05) only some kinematic variables of the individual (VCL, WOB and BCF) and cryopreserved pooled samples (VCL and ALH) in comparison with non-selected samples. In conclusion, BoviPure-DGC was more effective for recovering and selecting both fresh and cryopreserved dog epididymal sperm than the swim-up procedure improving the kinematic variables, and membranes intactness.

Dose-responses for solar radiation exposure reveal high sensitivity of microbial decomposition to changes in plant litter quality that occur during photodegradation.

Plant litter decomposition is a key process for carbon (C) turnover in terrestrial ecosystems. Sunlight has been shown to cause and accelerate C release in semiarid ecosystems, yet the dose-response relationships for these effects have not been evaluated. We conducted a two-phase experiment where plant litter of three species was subjected to a broad range of cumulative solar radiation (CSR) exposures under field conditions. We then evaluated the relationships between CSR exposure and abiotic mass loss, litter quality and the subsequent biotic decomposition and microbial activity in litter. Dose-response relationships demonstrated that CSR exposure was modestly correlated with abiotic mass loss but highly significantly correlated with lignin degradation, saccharification, microbial activity and biotic decay of plant litter across all species. Moreover, a comparison of these dose-response relationships suggested that small reductions in litter lignin due to exposure to sunlight may have large consequences for biotic decay. These results provide strong support for a model that postulates a critical role for lignin photodegradation in the mechanism of photofacilitation and demonstrate that, under natural field conditions, biotic degradation of plant litter is linearly related with the dose of solar radiation received by the material before coming into contact with decomposer microorganisms.

Results from the INMUNOSUN-SOGUG trial: a prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy.

BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.

A persistent ultraviolet outflow from an accreting neutron star binary transient.

All disc-accreting astrophysical objects produce powerful disc winds. In compact binaries containing neutron stars or black holes, accretion often takes place during violent outbursts. The main disc wind signatures during these eruptions are blue-shifted X-ray absorption lines, which are preferentially seen in disc-dominated 'soft states'1,2. By contrast, optical wind-formed lines have recently been detected in 'hard states', when a hot corona dominates the luminosity3. The relationship between these signatures is unknown, and no erupting system has as yet revealed wind-formed lines between the X-ray and optical bands, despite the many strong resonance transitions in this ultraviolet (UV) region4. Here we report that the transient neutron star binary Swift J1858.6-0814 exhibits wind-formed, blue-shifted absorption lines associated with C IV, N V and He II in time-resolved UV spectroscopy during a luminous hard state, which we interpret as a warm, moderately ionized outflow component in this state. Simultaneously observed optical lines also display transient blue-shifted absorption. Decomposing the UV data into constant and variable components, the blue-shifted absorption is associated with the former. This implies that the outflow is not associated with the luminous flares in the data. The joint presence of UV and optical wind features reveals a multi-phase and/or spatially stratified evaporative outflow from the outer disc5. This type of persistent mass loss across all accretion states has been predicted by radiation-hydrodynamic simulations6 and helps to explain the shorter-than-expected duration of outbursts7.

Post-traumatic osteoarthritis progression is diminished by early mechanical unloading and anti-inflammatory treatment in mice.

OBJECTIVE: Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease initiated by injury. Early phase (0-7 days) treatments often include rest (unloading) and anti-inflammatory medications, but how those early interventions impact PTOA progression is unknown. We hypothesized that early unloading and anti-inflammatory treatment would diminish joint inflammation and slow PTOA progression. DESIGN: Mice were injured with non-invasive ACL rupture followed by hindlimb unloading (HLU) or normal cage activity (ground control: GC) for 7 days, after which all mice were allowed normal cage activity. HLU and GC mice were treated with daily celecoxib (CXB; 10 mg/kg IP) or vehicle. Protease activity was evaluated using in vivo fluorescence imaging, osteophyte formation and epiphyseal trabecular bone were quantified using micro-computed tomography, and synovitis and articular cartilage were evaluated using whole-joint histology at 7, 14, 21, and 28 days post-injury. RESULTS: HLU significantly reduced protease activity (-22-30% compared to GC) and synovitis (-24-50% relative to GC) at day 7 post-injury (during unloading), but these differences were not maintained at later timepoints. Similarly, trabecular bone volume was partially preserved in HLU mice at during unloading (-14-15% BV/TV for HLU mice, -21-22% for GC mice relative to uninjured), but these differences were not maintained during reloading. Osteophyte volume was reduced by both HLU and CXB, but there was not an additive effect of these treatments (HLU: -46%, CXB: -30%, HLU + CXB: -35% relative to vehicle GC at day 28). CONCLUSIONS: These data suggest that early unloading following joint injury can reduce inflammation and potentially slow PTOA progression.