Prevalent lightning sferics at 600 megahertz near Jupiter's poles.

Lightning has been detected on Jupiter by all visiting spacecraft through night-side optical imaging and whistler (lightning-generated radio waves) signatures1-6. Jovian lightning is thought to be generated in the mixed-phase (liquid-ice) region of convective water clouds through a charge-separation process between condensed liquid water and water-ice particles, similar to that of terrestrial (cloud-to-cloud) lightning7-9. Unlike terrestrial lightning, which emits broadly over the radio spectrum up to gigahertz frequencies10,11, lightning on Jupiter has been detected only at kilohertz frequencies, despite a search for signals in the megahertz range 12 . Strong ionospheric attenuation or a lightning discharge much slower than that on Earth have been suggested as possible explanations for this discrepancy13,14. Here we report observations of Jovian lightning sferics (broadband electromagnetic impulses) at 600 megahertz from the Microwave Radiometer 15 onboard the Juno spacecraft. These detections imply that Jovian lightning discharges are not distinct from terrestrial lightning, as previously thought. In the first eight orbits of Juno, we detected 377 lightning sferics from pole to pole. We found lightning to be prevalent in the polar regions, absent near the equator, and most frequent in the northern hemisphere, at latitudes higher than 40 degrees north. Because the distribution of lightning is a proxy for moist convective activity, which is thought to be an important source of outward energy transport from the interior of the planet16,17, increased convection towards the poles could indicate an outward internal heat flux that is preferentially weighted towards the poles9,16,18. The distribution of moist convection is important for understanding the composition, general circulation and energy transport on Jupiter.

Oral as compared to intravenous tranexamic acid to limit peri-operative blood loss associated with primary total hip arthroplasty: A randomised noninferiority trial.

BACKGROUND: Oral as compared to intravenous tranexamic acid (TXA) is an attractive option, in terms of cost and safety, to reduce blood loss and transfusion in total hip arthroplasty. Exclusion criteria applied in the most recent randomised trials may have limited the generalisability of oral tranexamic acid in this indication. Larger and more inclusive studies are needed to definitively establish oral administration as a credible alternative to intravenous administration. OBJECTIVES: To assess the noninferiority of oral to intravenous TXA at reducing intra-operative and postoperative total blood loss (TBL) in primary posterolateral approached total hip arthroplasty (PLTHA). DESIGN: Noninferiority, single centre, randomised, double-blind controlled study. SETTING: Patients scheduled for primary PLTHA. Data acquisition occurred between May 2021 and November 2022 at the University Hospital of Liège, Belgium. PATIENTS: Two hundred and twenty-eight patients, randomised in a 1 : 1 ratio from a computer-generated list, completed the trial. INTERVENTIONS: Administration of 2 g of oral TXA 2 h before total hip arthroplasty and 4 h after incision (Group oral) was compared to the intravenous administration of 1 g of TXA 30 min before surgery and 4 h after incision (Group i.v.). MAIN OUTCOME MEASURES: TBL (measured intra-operative and drainage blood loss up to 48 h after surgery, primary outcome), decrease in haemoglobin concentration, D-Dimer at day 1 and day 3, transfusion rate (secondary outcomes). RESULTS: Analyses were performed on 108 out of 114 participants (Group i.v.) and 104 out of 114 participants (Group oral). Group oral was noninferior to Group i.v. with regard to TBL, with a difference between medians (95% CI) of 35 ml (-103.77 to 33.77) within the noninferiority margins. Median [IQR] of estimated TBL was 480 ml [350 to 565] and 445 ml [323 to 558], respectively. No significant interaction between group and time was observed regarding the evolution of TBL and haemoglobin over time. CONCLUSIONS: TXA as an oral premedication before PLTHA is noninferior to its intravenous administration regarding peri-operative TBL. TRIAL REGISTRATION: European Clinical Trial Register under EudraCT-number 2020-004167-29 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-004167-29/BE ).

[Large excoriated pleomorphic liposarcoma]. / L'image du mois. Volumineux liposarcome pléomorphe excorié.

Pleomorphic liposarcoma is a rare and aggressive tumour developed from mesenchymal tissue. The clinical presentation is most often a subcutaneous mass syndrome. The surgical excision of such lesions has both a therapeutic and diagnostic confirmation value. We here report the case of a 41-year-old woman with a voluminous gluteal lesion that required surgical treatment.

Les liposarcomes pléomorphes sont des tumeurs malignes rares et agressives d'origine mésenchymateuse. Ces lésions se présentent le plus souvent sous la forme d'un syndrome de masse sous-cutanée. L'exérèse de ces lésions a un intérêt à la fois thérapeutique et de confirmation diagnostique. Nous rapportons le cas d'une patiente de 41 ans présentant une volumineuse lésion fessière redevable d'un traitement chirurgical.

Probing Jovian Broadband Kilometric Radio Sources Tied to the Ultraviolet Main Auroral Oval With Juno.

Observations of Jovian broadband kilometric (bKOM) radiation and ultraviolet (UV) auroras were acquired with the Waves and Juno-UVS instruments for ∼2 hr over the northern and southern polar regions during Juno's perijoves 4, 5, and 6 passes (PJ4, PJ5, and PJ6). During all six time periods, Juno traversed auroral magnetic field lines connecting to the UV main auroral ovals, matching the estimates of bKOM radio source footprints. The localized bKOM radio sources for the PJ4 north pass map to magnetic field lines having distances of 10 to 12 Jovian radii (R J) at the magnetic equator, whereas the extended bKOM radio sources for the other events map to field lines extending to 20-61 R J. We found the peak bKOM intensities during Juno's potential radio source crossings show positive, negative, and no correlations with the UV main oval brightness and color ratio. Only the positive correlations suggest wave-particle energy transport.

Profile of osteoarthritic patients undergoing hip or knee arthroplasty, a step toward a definition of the "need for surgery".

AIMS: The objective of this study is to characterize, based on clinical, radiographic, health-related, quality-of-life-related, and demographic variables, the profile of a large, homogeneous, cohort of patients undergoing knee or hip arthroplasty, in a public hospital. Current regulatory guidelines for structure-modifying agent are not clear regarding hard clinical endpoint. The "need for surgery" has been suggested as a potential relevant outcome, but, until now, it is poorly defined. By characterizing a large number of patients who undergo total hip or total knee replacement, this paper aims at providing a contribution to the better definition of the "need for surgery" in advanced OA of the lower limbs. METHODS: Consecutive patients who underwent primary knee arthroplasty (KA) or hip arthroplasty (HA) between December 2008 and February 2013, in an academic hospital, and who were diagnosed with hip or knee osteoarthritis (OA) (ACR criteria). Data collected at baseline included demographic and clinical data; Kellgren-Lawrence radiological grading; Western Ontario and Mc Master Universities Arthritis Index (WOMAC); EuroQol five dimensions questionnaire and EuroQol visual analog scale; and 36-item Short Form Health Survey. RESULTS: 626 subjects were included, 346 with hip OA and 280 with knee OA. Significant differences between subjects in need of an HA or of a KA were seen in terms of age (66.5 years versus 65 for hip), duration of complaints (2188 days versus 1146.5 for hip), BMI (28.68 kg/m² versus 27.07), radiological status (severe OA were found in 79.85% in knee group and 68.73% in hip group), comorbidities (FCI higher in knee group), traumatic of surgical history (37 versus 6%), and health-related quality of life and function (patients with HA had a poorer clinical status regarding WOMAC and WOMAC subscale). CONCLUSION: Significant differences were observed between patients undergoing KA or HA. These differences might be useful to better understand the "need for surgery" status in these indications. This concept may help to define responders and failures to pharmacological treatment of OA.

Unilateral Hypertrophy of the Tensor Fascia Lata.

A 57-year-old woman presented with right hip pain. The initial diagnosis was an inflammatory tendinopathy of the gluteus medius without signs of rupture, and the patient underwent an ultrasound-guided corticosteroid injection. However, 1 month later, she presented with a painful swelling on the anterior-external aspect of the right hip/thigh, with a clinical suspicion of malignancy. Magnetic resonance imaging (MRI) scan and ultrasound confirmed the diagnosis of hypertrophy of the tensor fascia lata (TFL) muscle . It is included in the differential diagnosis of soft tissue masses of the anterolateral proximal part of the thigh. The etiology is likely to be associated with gluteal muscle dysfunction. Teaching point: Unilateral hypertrophy of the fascia lata consists of an association with hypertrophy of the tensor fascia lata muscle and pathology of the minimus and medius gluteus muscles.

Radar for Europa Assessment and Sounding: Ocean to Near-Surface (REASON).

The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry, reflectometry, sounding, interferometry, plasma characterization, and ranging. Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world.

(111)Indium-oxine labelling for evaluating the homing process of autologous osteoblasts implanted percutaneously in atrophic nonunion fractures.

PURPOSE: The aim of the study was to control the in vivo localisation of implanted cells in cell-based therapies. Labelling cells with (111)indium-oxine is one of the most interesting methods proposed. We evaluated this method in the setting of autologous osteoblast implantation in nonunion fractures. METHODS: An in vitro study of osteoblasts was conducted after (111)indium-oxine labelling. Radioactivity retention and viability, proliferation and the ability to produce alkaline phosphatase were evaluated in a seven-day culture. In vivo labelling of implanted osteoblastic cells was conducted during a therapeutic trial of atrophic nonunion fractures, with the leakage outside the nonunion site and local uptake evolution at four, 24 and 48 hour being studied. RESULTS: The mean labelling efficiency for osteoprogenitors was 78.8 ± 4.6 %. The intracellular retention was 89.4 ± 2.1 % at three hours and 67.3 ± 4.7 % at 18 hours. The viability assessed at three hours was 93.7 ± 0.6 %. After seven days of culture, morphology and alkaline phosphatase staining were similar for both labelled and unlabelled control cells, although the proliferation rate was decreased in the labelled cells. Some local intraosseous leakage was observed in four of 17 cases. All patients showed uptake at the injection site, with four having no other uptake. Four patients showed additional uptake in the bladder, liver and spleen, while 11 patients had additional uptake in the lungs in addition to the bladder, liver and spleen. The activity ratios (injection site/body) were 48 ± 28 % at four hours, 40 ± 25 % at 24 hours and 35 ± 25 % at 48 hours. After correcting for decay, the activity within the injection site was 82 ± 15 % at 24 hours and 69 ± 11 % at 48 hours compared with the activity measured at four hours. No relationship was found between uptake and radiological bone repair. CONCLUSIONS: The (111)indium-oxine labelling appears to be a good method for monitoring the behaviour of the osteoblastic cells after their implantation in atrophic nonunion fractures.

Lightning at Jupiter pulsates with a similar rhythm as in-cloud lightning at Earth.

Our knowledge about the fine structure of lightning processes at Jupiter was substantially limited by the time resolution of previous measurements. Recent observations of the Juno mission revealed electromagnetic signals of Jovian rapid whistlers at a cadence of a few lightning discharges per second, comparable to observations of return strokes at Earth. The duration of these discharges was below a few milliseconds and below one millisecond in the case of Jovian dispersed pulses, which were also discovered by Juno. However, it was still uncertain if Jovian lightning processes have the fine structure of steps corresponding to phenomena known from thunderstorms at Earth. Here we show results collected by the Juno Waves instrument during 5 years of measurements at 125-microsecond resolution. We identify radio pulses with typical time separations of one millisecond, which suggest step-like extensions of lightning channels and indicate that Jovian lightning initiation processes are similar to the initiation of intracloud lightning at Earth.

Effect of suprainguinal fascia iliaca compartment block on postoperative opioid consumption and functional recovery in posterolateral-approached total hip arthroplasty: a single-blind randomized controlled trial.

INTRODUCTION: Posterolateral-approached total hip arthroplasty (PLTHA) is followed by moderate to severe postoperative pain. Suprainguinal fascia iliaca compartment block (SFICB) has been proposed as a promising analgesia technique. METHODS: Data from 86 patients scheduled for PLTHA with spinal anesthesia were analyzed in this prospective randomized controlled trial. Patients were randomly divided into two groups of 43 patients each. As opposed to the control group (group C), ropivacaine group (group R) received additional SFICB using 40 mL of 0.375% ropivacaine. As primary endpoint, blind observers noted total morphine consumption at postoperative 48 hours. Secondary endpoints were pain at rest and mobilization on 0-10 Numeric Rating Scale (rest and dynamic NRS) at fixed time points (1 hour and 6 hours after surgery, and at day 1 and day 2 at 8:00, 13:00 and 18:00 hours), walking performance at day 1 and day 2; postoperative complications including morphine-related side effects or orthostatic intolerance symptoms such as dizziness, nausea, blurred vision or vasovagal syncope. RESULTS: A 48-hour morphine consumption (mg; median (IQR)) was significantly lower in group R than in group C (11 (8.5-15.5)) vs 26 (21-33.5), p<0001), as well as incidence of morphine-related side effects such as nausea at day 1 (p=0.04) and day 2 (p<0.01). Rest and dynamic NRS were globally significantly lower in group R than in group C (p<0.01). Group R showed less orthostatic intolerance at day 1 (p<0.001) and day 2 (p<0.01) and better functional walking performance at day 1 (<0.001) and day 2 (<0.001). DISCUSSION: In PLTHA, SFICB provides opioid sparing, improved postoperative pain control, and enhanced functional recovery. TRIAL REGISTRATION NUMBER: NCT04574479.

Properties of Ion-Inertial Scale Plasmoids Observed by the Juno Spacecraft in the Jovian Magnetotail.

We expand on previous observations of magnetic reconnection in Jupiter's magnetosphere by constructing a survey of ion-inertial scale plasmoids in the Jovian magnetotail. We developed an automated detection algorithm to identify reversals in the B θ component and performed the minimum variance analysis for each identified plasmoid to characterize its helical structure. The magnetic field observations were complemented by data collected using the Juno Waves instrument, which is used to estimate the total electron density, and the JEDI energetic particle detectors. We identified 87 plasmoids with "peak-to-peak" durations between 10 and 300 s. Thirty-one plasmoids possessed a core field and were classified as flux-ropes. The other 56 plasmoids had minimum field strength at their centers and were termed O-lines. Out of the 87 plasmoids, 58 had in situ signatures shorter than 60 s, despite the algorithm's upper limit being 300 s, suggesting that smaller plasmoids with shorter durations were more likely to be detected by Juno. We estimate the diameter of these plasmoids assuming a circular cross section and a travel speed equal to the Alfven speed in the surrounding lobes. Using the electron density inferred by Waves, we contend that these plasmoid diameters were within an order of the local ion-inertial length. Our results demonstrate that magnetic reconnection in the Jovian magnetotail occurs at ion scales like in other space environments. We show that ion-scale plasmoids would need to be released every 0.1 s or less to match the canonical 1 ton/s rate of plasma production due to Io.

Persistent plasma waves in interstellar space detected by Voyager 1.

In 2012, Voyager 1 became the first in situ probe of the very local interstellar medium1. The Voyager 1 Plasma Wave System has given point estimates of the plasma density spanning about 30 au of interstellar space, revealing a large-scale density gradient2,3 and turbulence4 outside the heliopause. Previous studies of the plasma density relied on the detection of discrete plasma oscillation events triggered ahead of shocks propagating outwards from the Sun and used to infer the plasma frequency and hence density5,6. We present the detection of a class of very weak, narrowband plasma wave emission in the Voyager 1 data that persists from 2017 onwards and enables the first steadily sampled measurement of the interstellar plasma density over about 10 au with an average sampling distance of 0.03 au. We find au-scale density fluctuations that trace interstellar turbulence between episodes of previously detected plasma oscillations. Possible mechanisms for the narrowband emission include thermally excited plasma oscillations and quasi-thermal noise, and could be clarified by new findings from Voyager or a future interstellar mission. The emission's persistence suggests that Voyager 1 may be able to continue tracking the interstellar plasma density in the absence of shock-generated plasma oscillation events.

A Preliminary Study of Magnetosphere-Ionosphere-Thermosphere Coupling at Jupiter: Juno Multi-Instrument Measurements and Modeling Tools.

The dynamics of the Jovian magnetosphere are controlled by the interplay of the planet's fast rotation, its main iogenic plasma source and its interaction with the solar wind. Magnetosphere-Ionosphere-Thermosphere (MIT) coupling processes controlling this interplay are significantly different from their Earth and Saturn counterparts. At the ionospheric level, they can be characterized by a set of key parameters: ionospheric conductances, electric currents and fields, exchanges of particles along field lines, Joule heating and particle energy deposition. From these parameters, one can determine (a) how magnetospheric currents close into the ionosphere, and (b) the net deposition/extraction of energy into/out of the upper atmosphere associated to MIT coupling. We present a new method combining Juno multi-instrument data (MAG, JADE, JEDI, UVS, JIRAM and Waves) and modeling tools to estimate these key parameters along Juno's trajectories. We first apply this method to two southern hemisphere main auroral oval crossings to illustrate how the coupling parameters are derived. We then present a preliminary statistical analysis of the morphology and amplitudes of these key parameters for eight among the first nine southern perijoves. We aim to extend our method to more Juno orbits to progressively build a comprehensive view of Jovian MIT coupling at the level of the main auroral oval.

Revealing the source of Jupiter's x-ray auroral flares.

Jupiter's rapidly rotating, strong magnetic field provides a natural laboratory that is key to understanding the dynamics of high-energy plasmas. Spectacular auroral x-ray flares are diagnostic of the most energetic processes governing magnetospheres but seemingly unique to Jupiter. Since their discovery 40 years ago, the processes that produce Jupiter's x-ray flares have remained unknown. Here, we report simultaneous in situ satellite and space-based telescope observations that reveal the processes that produce Jupiter's x-ray flares, showing surprising similarities to terrestrial ion aurora. Planetary-scale electromagnetic waves are observed to modulate electromagnetic ion cyclotron waves, periodically causing heavy ions to precipitate and produce Jupiter's x-ray pulses. Our findings show that ion aurorae share common mechanisms across planetary systems, despite temporal, spatial, and energetic scales varying by orders of magnitude.

Total joint replacement improves pain, functional quality of life, and health utilities in patients with late-stage knee and hip osteoarthritis for up to 5 years.

OBJECTIVES: To study and identify the determinants of the impact on pain, function, and quality of life of a prosthetic replacement surgery after 5 years of survival in patients with osteoarthritis (OA) of the lower limb. METHOD: In total, 626 osteoarthritic patients from a University Hospital, divided in 2 groups (according to surgical site), were prospectively followed for 5 years after hip (n = 346) or knee (n = 280) replacement. Validated specific Western Ontario and McMaster Universities Arthritis Index (WOMAC) and generic (SF-36 and EQ) instruments assessing quality of life were used prior to surgery and yearly, thereafter. We defined a good outcome as a clinically relevant improvement in WOMAC greater than or equal to the minimally important difference (MID). Regressions showed the relationships among preoperative, perioperative, and postoperative measures and the evolution of WOMAC scores after 5 years (percent change). We also examined any predictors of good outcomes. RESULTS: The beneficial effect on quality of life observed during the first year after hip and knee arthroplasty (HA and KA) was maintained for up to 5 years. More than 3/4 of the patients in our study experienced a good outcome (86.04% in HA group and 79.91% in KA group). Both the good outcome and the 5-year change in WOMAC are predicted by preoperative (i.e., radiological severity, comorbidities, disability, and level of education), perioperative (i.e., length of hospital stay and place of discharge), and postoperative (i.e., complications) variables in the two groups. CONCLUSIONS: Joint arthroplasty is a highly valuable therapeutic strategy for hip or knee OA patients who do not respond to pharmacological management. These results represent a step towards the collection of robust, scientifically sound data that will facilitate the completion of health economic analyses in the field of OA. KEY POINTS: • This study reports the long term outcomes of hip and knee replacement surgery in late-stage OA.• We identified pre-, per-, and post-operative determinants which contribute to a greater improvement in pain and function, hence increasing patients' satisfaction.• These results could contribute to select an OA population which has a high probability to get an optimal benefit from total joint replacement.

Magnetotail Reconnection at Jupiter: A Survey of Juno Magnetic Field Observations.

At Jupiter, tail reconnection is thought to be driven by an internal mass loading and release process called the Vasyliunas cycle. Galileo data have shown hundreds of reconnection events occurring in Jupiter's magnetotail. Here we present a survey of reconnection events observed by Juno during its first 16 orbits of Jupiter (July 2016-October 2018). The events are identified using Juno magnetic field data, which facilitates comparison to the Vogt et al. (2010, https://doi.org/10.1029/2009JA015098) survey of reconnection events from Galileo magnetometer data, but we present data from Juno's other particle and fields instruments for context. We searched for field dipolarizations or reversals and found 232 reconnection events in the Juno data, most of which featured an increase in |B θ |, the magnetic field meridional component, by a factor of 3 over background values. We found that most properties of the Juno reconnection events, like their spatial distribution and duration, are comparable to Galileo, including the presence of a ~3-day quasi-periodicity in the recurrence of Juno tail reconnection events and in Juno JEDI, JADE, and Waves data. However, unlike with Galileo we were unable to clearly define a statistical x-line separating planetward and tailward Juno events. A preliminary analysis of plasma velocities during five magnetic field reconnection events showed that the events were accompanied by fast radial flows, confirming our interpretation of these magnetic signatures as reconnection events. We anticipate that a future survey covering other Juno datasets will provide additional insight into the nature of tail reconnection at Jupiter.

CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes.

CEMIP (for "Cell migration-inducing protein" also called KIAA1199 and Hybid for "Hyaluronan-binding protein") expression is increased in cancers and described as a regulator of cell survival, growth and invasion. In rheumatoid arthritis, CEMIP is referred to as an angiogenic marker and participates in hyaluronic acid degradation. In this study, CEMIP expression is investigated in healthy and osteoarthritis (OA) cartilage from human and mouse. Its role in OA physiopathology is deciphered, specifically in chondrocytes proliferation and dedifferentiation and in the extracellular matrix remodeling. To this end, CEMIP, αSMA and types I and III collagen expressions were assessed in human OA and non-OA cartilage. CEMIP expression was also investigated in a mouse OA model. CEMIP expression was studied in vitro using a chondrocyte dedifferentiation model. High-throughput RNA sequencing was performed on chondrocytes after CEMIP silencing. Results showed that CEMIP was overexpressed in human and murine OA cartilage and along chondrocytes dedifferentiation. Most of genes deregulated in CEMIP-depleted cells were involved in cartilage turnover (e.g., collagens), mesenchymal transition and fibrosis. CEMIP regulated ß-catenin protein level. Moreover, CEMIP was essential for chondrocytes proliferation and promoted αSMA expression, a fibrosis marker, and TGFß signaling towards the p-Smad2/3 (Alk5/PAI-1) pathway. Interestingly, CEMIP was induced by the pSmad1/5 (Alk1) pathway. αSMA and type III collagen expressions were overexpressed in human OA cartilage and along chondrocytes dedifferentiation. Finally, CEMIP was co-expressed in situ with αSMA in all OA cartilage layers. In conclusion, CEMIP was sharply overexpressed in human and mouse OA cartilage and along chondrocytes dedifferentiation. CEMIP-regulated transdifferentiation of chondrocytes into "chondro-myo-fibroblasts" expressing α-SMA and type III collagen, two fibrosis markers. Moreover, these "chondro-myo-fibroblasts" were found in OA cartilage but not in healthy cartilage.

15-Deoxy-Δ-12, 14-prostaglandin J2 acts cooperatively with prednisolone to reduce TGF-ß-induced pro-fibrotic pathways in human osteoarthritis fibroblasts.

BACKGROUND/AIMS: Synovial fibrosis is a pathological process that is observed in several musculoskeletal disorders and characterized by the excessive deposition of extracellular matrix, as well as cell migration and proliferation. Despite the fact that glucocorticoids are widely employed in the treatment of rheumatic pathologies such as osteoarthritis (OA) and rheumatoid arthritis, the mechanisms by which glucocorticoids act in the joint and their impacts on pro-fibrotic pathways are still unclear. MATERIALS: Human OA synovial fibroblasts were obtained from knee and hip joints. Cells were treated with prednisolone (1 mM) or transforming growth factor-beta 1 (TGF-ß1) (10 ng/ml) for 1 and 7 days for quantification of RNA and protein expression (by real-time quantitative reverse transcription-PCR and western blot, respectively), 72 h for immunocytochemistry analysis, and 48 h for proliferation (by BrdU assay) and migration (by wound assay) studies. In addition, cells were preincubated with prednisolone and/or the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) for 6 h before adding TGF-ß1. pSmad1/5, pSmad2 and ß-catenin levels were analyzed by Western blot. The activin receptor-like kinase-5 (ALK-5) inhibitor (SB-431542) was employed for the mechanistic assays. RESULTS: Prednisolone showed a predominant anti-fibrotic impact on fibroblast-like synoviocytes as it attenuated the spontaneous and TGF-ß-induced gene expression of pro-fibrotic markers. Prednisolone also reduced α-sma protein and type III collagen levels, as well as cell proliferation and migration after TGF-ß stimulation. However, prednisolone did not downregulate the gene expression of all the pro-fibrotic markers tested and did not restore the reduced PPAR-γ levels after TGF-ß stimulation. Interestingly, anti-fibrotic actions of the glucocorticoid were reinforced in the presence of the PPAR-γ agonist 15d-PGJ2. Combined pretreatment modulated Smad2/3 levels and, similar to the ALK-5 inhibitor, blocked ß-catenin accumulation elicited by TGF-ß. CONCLUSIONS: Prednisolone, along with 15d-PGJ2, modulates pro-fibrotic pathways activated by TGF-ß in synovial fibroblasts at least partially through the inhibition of ALK5/Smad2 signaling and subsequent ß-catenin accumulation. These findings shed light on the potential therapeutic effects of glucocorticoids treatment combined with a PPAR-γ agonist against synovial fibrosis, although future studies are warranted to further evaluate this concern.

Evidence for low density holes in Jupiter's ionosphere.

Intense electromagnetic impulses induced by Jupiter's lightning have been recognised to produce both low-frequency dispersed whistler emissions and non-dispersed radio pulses. Here we report the discovery of electromagnetic pulses associated with Jovian lightning. Detected by the Juno Waves instrument during its polar perijove passes, the dispersed millisecond pulses called Jupiter dispersed pulses (JDPs) provide evidence of low density holes in Jupiter's ionosphere. 445 of these JDP emissions have been observed in snapshots of electric field waveforms. Assuming that the maximum delay occurs in the vicinity of the free space ordinary mode cutoff frequency, we estimate the characteristic plasma densities (5.1 to 250 cm-3) and lengths (0.6 km to 1.3 × 105 km) of plasma irregularities along the line of propagation from lightning to Juno. These irregularities show a direct link to low plasma density holes with ≤250 cm-3 in the nightside ionosphere.

Origin of two-band chorus in the radiation belt of Earth.

Naturally occurring chorus emissions are a class of electromagnetic waves found in the space environments of the Earth and other magnetized planets. They play an essential role in accelerating high-energy electrons forming the hazardous radiation belt environment. Chorus typically occurs in two distinct frequency bands separated by a gap. The origin of this two-band structure remains a 50-year old question. Here we report, using NASA's Van Allen Probe measurements, that banded chorus waves are commonly accompanied by two separate anisotropic electron components. Using numerical simulations, we show that the initially excited single-band chorus waves alter the electron distribution immediately via Landau resonance, and suppress the electron anisotropy at medium energies. This naturally divides the electron anisotropy into a low and a high energy components which excite the upper-band and lower-band chorus waves, respectively. This mechanism may also apply to the generation of chorus waves in other magnetized planetary magnetospheres.