CEMIP (KIAA1199) regulates inflammation, hyperplasia and fibrosis in osteoarthritis synovial membrane.

Osteoarthritis (OA) synovial membrane is mainly characterized by low-grade inflammation, hyperplasia with increased cell proliferation and fibrosis. We previously underscored a critical role for CEMIP in fibrosis of OA cartilage. However, its role in OA synovial membrane remains unknown. An in vitro model with fibroblast-like synoviocytes from OA patients and an in vivo model with collagenase-induced OA mice were used to evaluate CEMIP-silencing effects on inflammation, hyperplasia and fibrosis. Our results showed that i. CEMIP expression was increased in human and mouse inflamed synovial membrane; ii. CEMIP regulated the inflammatory response pathway and inflammatory cytokines production in vitro and in vivo; iii. CEMIP induced epithelial to mesenchymal transition pathway and fibrotic markers in vitro and in vivo; iv. CEMIP increased cell proliferation and synovial hyperplasia; v. CEMIP expression was increased by inflammatory cytokines and by TGF-ß signaling; vi. anti-fibrotic drugs decreased CEMIP expression. All these findings highlighted the central role of CEMIP in OA synovial membrane development and underscored that targeting CEMIP could be a new therapeutic approach.

Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes.

Osteoarthritis (OA) is recognized as being a cellular senescence-linked disease. Intra-articular injections of glucocorticoids (GC) are frequently used in knee OA to treat synovial effusion but face controversies about toxicity. We investigated the influence of GC on cellular senescence hallmarks and senescence induction in fibroblast-like synoviocytes (FLS) from OA patients and mesenchymal stem cells (MSC). METHODS: Cellular senescence was assessed via the proliferation rate, ß-galactosidase staining, DNA damage and CKI expression (p21, p16INK4A). Experimental senescence was induced by irradiation. RESULTS: The GC prednisolone did not induce an apparent senescence phenotype in FLS, with even higher proliferation, no accumulation of ß-galactosidase-positive cells nor DNA damage and reduction in p21mRNA, only showing the enhancement of p16INK4A. Prednisolone did not modify experimental senescence induction in FLS, with no modulation of any senescence parameters. Moreover, prednisolone did not induce a senescence phenotype in MSC: despite high ß-galactosidase-positive cells, no reduction in proliferation, no DNA damage and no CKI enhancement was observed. CONCLUSIONS: We provide reassuring in vitro data about the use of GC regarding cellular senescence involvement in OA: the GC prednisolone did not induce a senescent phenotype in OA FLS (the proliferation ratio was even higher) and in MSC and did not worsen cellular senescence establishment.

TFEB phosphorylation on Serine 211 is induced by autophagy in human synovial fibroblasts and by p62/SQSTM1 overexpression in HEK293 cells.

Autophagy receptor p62/SQSTM1 signals a complex network that links autophagy-lysosomal system to proteasome. Phosphorylation of p62 on Serine 349 (P-Ser349 p62) is involved in a cell protective, antioxidant pathway. We have shown previously that P-Ser349 p62 occurs and is rapidly degraded during human synovial fibroblasts autophagy. In this work we observed that fingolimod (FTY720), used as a medication for multiple sclerosis, induced coordinated expression of p62, P-Ser349 p62 and inhibitory TFEB form, phosphorylated on Serine 211 (P-Ser211 TFEB), in human synovial fibroblasts. These effects were mimicked and potentiated by proteasome inhibitor MG132. In addition, FTY720 induced autophagic flux, LC3B-II up-regulation, Akt phosphorylation inhibition on Serine 473 but down-regulated TFEB, suggesting stalled autophagy. FTY720 decreased cytoplasmic fraction contained TFEB but induced TFEB in nuclear fraction. FTY720-induced P-Ser211 TFEB was mainly found in membrane fraction. Autophagy and VPS34 kinase inhibitor, autophinib, further increased FTY720-induced P-Ser349 p62 but inhibited concomitant expression of P-Ser211 TFEB. These results suggested that P-Ser211 TFEB expression depends on autophagy. Overexpression of GFP tagged TFEB in HEK293 cells showed concomitant expression of its phosphorylated form on Serine 211, that was down-regulated by autophinib. These results suggested that autophagy might be autoregulated through P-Ser211 TFEB as a negative feedback loop. Of interest, overexpression of p62, p62 phosphorylation mimetic (S349E) mutant and phosphorylation deficient mutant (S349A) in HEK293 cells markedly induced P-Ser211 TFEB. These results showed that p62 is involved in regulation of TFEB phosphorylation on Serine 211 but that this involvement does not depend on p62 phosphorylation on Serine 349.

Investigating Magma Ocean Solidification on Earth Through Laser-Heated Diamond Anvil Cell Experiments.

We carried out a series of silicate fractional crystallization experiments at lower mantle pressures using the laser-heated diamond anvil cell. Phase relations and the compositional evolution of the cotectic melt and equilibrium solids along the liquid line of descent were determined and used to assemble the melting phase diagram. In a pyrolitic magma ocean, the first mineral to crystallize in the deep mantle is iron-depleted calcium-bearing bridgmanite. From the phase diagram, we estimate that the initial 33%-36% of the magma ocean will crystallize to form such a buoyant bridgmanite. Substantial calcium solubility in bridgmanite is observed up to 129 GPa, and significantly delays the crystallization of the calcium silicate perovskite phase during magma ocean solidification. Residual melts are strongly iron-enriched as crystallization proceeds, making them denser than any of the coexisting solids at deep mantle conditions, thus supporting the terrestrial basal magma ocean hypothesis (Labrosse et al., 2007).

Modulation of αVß6 integrin in osteoarthritis-related synovitis and the interaction with VTN(381-397 a.a.) competing for TGF-ß1 activation.

Osteoarthritis is characterized by structural alteration of joints. Fibrosis of the synovial tissue is often detected and considered one of the main causes of joint stiffness and pain. In our earlier proteomic study, increased levels of vitronectin (VTN) fragment (amino acids 381-397) were observed in the serum of osteoarthritis patients. In this work, the affinity of this fragment for integrins and its putative role in TGF-ß1 activation were investigated. A competition study determined the interaction of VTN(381-397 a.a.) with αVß6 integrin. Subsequently, the presence of αVß6 integrin was substantiated on primary human fibroblast-like synoviocytes (FLSs) by western blot and flow cytometry. By immunohistochemistry, ß6 was detected in synovial membranes, and its expression showed a correlation with tissue fibrosis. Moreover, ß6 expression was increased under TGF-ß1 stimulation; hence, a TGF-ß bioassay was applied. We observed that αVß6 could mediate TGF-ß1 bioavailability and that VTN(381-397 a.a.) could prevent TGF-ß1 activation by interacting with αVß6 in human FLSs and increased α-SMA. Finally, we analyzed serum samples from healthy controls and patients with osteoarthritis and other rheumatic diseases by nano-LC/Chip MS-MS, confirming the increased expression of VTN(381-397 a.a.) in osteoarthritis as well as in lupus erythematosus and systemic sclerosis. These findings corroborate our previous observations concerning the overexpression of VTN(381-397 a.a.) in osteoarthritis but also in other rheumatic diseases. This fragment interacts with αVß6 integrin, a receptor whose expression is increased in FLSs from the osteoarthritic synovial membrane and that can mediate the activation of the TGF-ß1 precursor in human FLSs.

Toward diagnostic relevance of the αVß5, αVß3, and αVß6 integrins in OA: expression within human cartilage and spinal osteophytes.

We previously reported 18FPRGD2 uptake by the coxofemoral lining, intervertebral discs and facet joint osteophytes in OA using PET/SCAN imaging. However, the molecular mechanism by which the PRGD2 tracer interacts with joint tissues and osteophytes in OA remains unclear. As PRGD2 ligands are expected to belong to the RGD-specific integrin family, the purpose of this study was (i) to determine which integrin complexes display the highest affinity for PRGD2-based ligands, (ii) to analyze integrin expression in relevant tissues, and (iii) to test integrin regulation in chondrocytes using OA-related stimuli to increase the levels of fibrosis and ossification markers. To this end, the affinity of PRGD2-based ligands for five heterodimeric integrins was measured by competition with 125I-echistatin. In situ analyses were performed in human normal vs. OA cartilage and spinal osteophytes. Osteophytes were characterized by (immuno-)histological staining. Integrin subunit expression was tested in chondrocytes undergoing dedifferentiation, osteogenic differentiation, and inflammatory stimulation. The integrins αVß5, αVß3, and αVß6 presented the highest affinity for PRGD2-based ligands. In situ, the expression of these integrins was significantly increased in OA compared to normal cartilage. Within osteophytes, the mean integrin expression score was significantly higher in blood vessels, fibrous areas, and cells from the bone lining than in osteocytes and cartilaginous zones. In vitro, the levels of integrin subunits were significantly increased during chondrocyte dedifferentiation (except for ß6), fibrosis, and osteogenic differentiation as well as under inflammatory stimuli. In conclusion, anatomical zones (such as OA cartilage, intervertebral discs, and facet joint osteophytes) previously reported to show PRGD2 ligand uptake in vivo expressed increased levels of αVß5, αVß3, and ß6 integrins, whose subunits are modulated in vitro by OA-associated conditions that increase fibrosis, inflammation, and osteogenic differentiation. These results suggest that the increased levels of integrins in OA compared to normal tissues favor PRGD2 uptake and might explain the molecular mechanism of OA imaging using the PRGD2-based ligand PET/CT.

Preoperative planning of Total Hip Arthroplasty. Must this essential part of the procedure be necessarily performed by the orthopedic surgeon? A prospective study about 100 Corail ® Hip System.

Currently, patients who undergo total hip arthroplasty want a complete restoration of their hip function and not only pain relief. Templating in THA is essential for accurately predicting the optimal size of the implants required. It also reduces the risk of potential complications. To check the reproducibility of our preoperative planning, to compare the accuracy of templating between orthopedic surgeon (OS), orthopedic resident (OR) and data manager (DM), to determine the learning curve between the different planners and to evaluate the effect of body mass index impact on digital templating for THA. One hundred uncemented Corail ® Hip System using a ceramic on ceramic bearing surface were included into the study. The software used for templating was IMPAX-Orthopaedic-Tools. A calibration marker (28-mm ball) was used for calibration. All the anteroposterior pelvis radiographs were planned by three participants (OS, OR, DM). We systematically collected the precisely planned size measurements as well as the variation by 1 or 2 sizes of prostheses. At +/- 1 size, we did not find any significant difference between the participants with respectively 94%, 96% and 93% concordance for the cup, 88%, 90% and 90% for the stem and 85%, 84% and 83% for the neck. Our preoperative templating was accurate in predicting the required implant size and results were similar to those available in the literature. We did not find any difference between the planners and we were unable to objectivate a learning curve period. We conclude that this essential part of the planning procedure can be performed by the surgeon himself or an orthopedic resident or a data manager who has anatomical knowledge if the surgeon is unable to perform templating himself.

Clinical and radiological results with a 36-mm cobalt-chrome prosthetic head, cross-linked Durasul liners associated with Allofit cups: a more than 10-year follow-up period.

BACKGROUND: Highly cross-linked polyethylene is currently a common articulation surface used for total hip arthroplasty (THA). AIM: The aim of the present study is in vivo assessment of highly cross-linked Durasul polyethylene linear and volumetric wear when associated with a 36-mm prosthetic femoral head. METHODS: We retrospectively reviewed clinical and radiographic data of 78 patients (81 hips) having primary THAs using Durasul liner combined with a 36-mm CoCr prosthetic head. All of them were followed for more than 10 years. Patient outcome was assessed with the Harris Hip Score (HHS) preoperatively and at last follow-up. 2-D prosthetic head penetration into polyethylene, 3D wear rates and cup migration were evaluated. RESULTS: The preoperative and last follow-up HHS were 50.43 +/- 10.42 and 97.44 +/- 5.51 respectively. The annual penetration of the prosthetic head into Durasul® liner was 0.029 +/- 0.003 mm. The annual linear penetration and volumetric wear extrapolation rates using Charnley and Ilchmann formulas were 37.84% and 57.76% respectively of that seen with conventional polyethylene liner. At last follow-up, the total loss of material in Durasul represents only 0.15% of the initial polyethylene mass. We did not observe any significant cup migration in the study group. CONCLUSIONS: Results are promising, and we believe that these data authorise the continued use of highly cross-linked polyethylene liner associated with a 36-mm prosthetic head for total hip arthroplasties in older patients. More long-term follow-up studies are mandatory before we feel comfortable with the project of using cross-linked polyethylene in young and active patients instead of ceramic-on-ceramic bearings.

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.

Observation of methane filled hexagonal ice stable up to 150 GPa.

Gas hydrates consist of hydrogen-bonded water frameworks enclosing guest gas molecules and have been the focus of intense research for almost 40 y, both for their fundamental role in the understanding of hydrophobic interactions and for gas storage and energy-related applications. The stable structure of methane hydrate above 2 GPa, where CH4 molecules are located within H2O or D2O channels, is referred to as methane hydrate III (MH-III). The stability limit of MH-III and the existence of a new high-pressure phase above 40 to 50 GPa, although recently conjectured, remain unsolved to date. We report evidence for a further high-pressure, room-temperature phase of the CH4-D2O hydrate, based on Raman spectroscopy in diamond anvil cell and ab initio molecular dynamics simulations including nuclear quantum effects. Our results reveal that a methane hydrate IV (MH-IV) structure, where the D2O network is isomorphic with ice Ih, forms at ∼40 GPa and remains stable up to 150 GPa at least. Our proposed MH-IV structure is fully consistent with previous unresolved X-ray diffraction patterns at 55 GPa [T. Tanaka et al., J. Chem. Phys. 139, 104701 (2013)]. The MH-III → MH-IV transition mechanism, as suggested by the simulations, is complex. The MH-IV structure, where methane molecules intercalate the tetrahedral network of hexagonal ice, represents the highest-pressure gas hydrate known up to now. Repulsive interactions between methane and water dominate at the very high pressure probed here and the tetrahedral topology outperforms other possible arrangements in terms of space filling.

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.

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.

Serum starvation raises turnover of phosphorylated p62/SQSTM1 (Serine 349), reveals expression of proteasome and N-glycanase1 interactive protein RAD23B and sensitizes human synovial fibroblasts to BAY 11-7085-induced cell death.

Phosphorylation of p62/SQSTM1 (p62) on Serine 349 (P-Ser349 p62) as well as proteasome dysfunction have been shown to activate the cell protective Keap1/Nrf2 pathway. We showed previously that BAY 11-7085-induced human synovial fibroblast cell death includes autophagy and p62 downregulation. In this work, we have studied expression of P-Ser349 p62 in human synovial fibroblasts. Results showed that P-Ser349 p62 was not detected in synovial cell extracts unless cells were cultured in the presence of proteasome inhibitor (MG132). MG132 revealed P-Ser349 p62 turnover, that was further increased by concomitant autophagy inhibition and markedly enhanced in serum starved cells. Starvation sensitized synovial fibroblasts to BAY 11-7085 while MG132 protected both non-starved and starved cells from BAY 11-7085-induced cell death. Lentivirus mediated overexpression of phosphorylation-mimetic p62 mutant S349E markedly protected synovial fibroblasts from BAY 11-7085. Inhibitor of Keap1-P-S349 p62 interaction, K67, had synergistic effect with MG132. Starvation increased p62 molecular weight, that was reversed by serum and bovine serum albumin re-feeding. Furthermore, starvation markedly induced RAD23B. Increased endo-ß-N-acetylglucosaminidase (ENGase) turnover was detected in starved synovial fibroblasts. PNGase F treatment produced faster migration p62 form in human synovial tissue extracts but starvation-like p62 form of higher molecular weight in synovial cell extracts. Co-transfection of NGLY1, with p62 or p62 mutants S349A and S349E markedly stabilized p62 expressions in HEK293 cells. Tunicamycin upregulated p62 and protected synovial fibroblasts from BAY 11-7085-induced cell death. These results showed that P-Ser349 p62 has pro-survival role in human synovial fibroblasts and that de-glycosylation events are involved in p62 turnover.

Photo-based External Quality Assessment of Malaria rapid diagnostic tests in a non-endemic setting.

INTRODUCTION: In non-endemic settings, expertise in malaria microscopy is limited and rapid diagnostic tests (RDTs) are an adjunct to malaria diagnosis. AIM: We performed an External Quality Assessment (EQA) on reading and interpretation of malaria RDTs in a non-endemic setting. METHODS: Participants were medical laboratories in Belgium and the Grand Duchy of Luxembourg using malaria RDTs; they received (i) 10 high-resolution photographs presenting test line combinations of RDTs with interpretations listed in a multiple choice format and (ii) a questionnaire about their practices of malaria diagnosis. RESULTS: Among 135 subscribing laboratories, 134 (99.3%) used 139 RDT products (11 different products from 8 brands). After exclusion of the results of one laboratory, analysis was done for 133 laboratories using 137 RDT products. Scores of 10/10, 9/10 and 8/10 were achieved for 58.4%, 13.1% and 8.0% of 137 RDT products respectively. For three-band P. falciparum-pan-Plasmodium RDTs (113 (82.5%) products, 6 brands), most frequent errors were (1) disregarding faint test lines (18.6%), (2) reporting invalid instead of P. falciparum (16.8%) and (3) reporting "Plasmodium spp., no further differentiation possible" without mentioning the presence or absence of P. falciparum (11.5%). For four-band RDTs (21 (15.3%) products, 1 brand), errors were (4) disregarding faint P. vivax test lines (47.6%) and (5) reporting "Plasmodium spp., no further differentiation possible" without mentioning the presence of P. falciparum and P. vivax (28.6%). Instructions for use (IFU) of only 4 out of 10 RDT products mentioned to interpret faint-intensity test lines as positive (conducive to errors 1 and 4) and IFU of 2 products displayed incorrect information (conducive to errors 2 and 5). Outside of office hours, 36.1% of participants relied on RDTs as the initial diagnostic test; 13.9% did not perform microscopic confirmation. CONCLUSION: Reading and interpretation of malaria RDTs was satisfactory, but errors were embedded in the instructions for use of the products. Relying on RDTs alone for malaria diagnosis (about one third of participants) is not a recommended practice.

Where there is no brain imaging: Safety and diagnostic value of lumbar puncture in patients with neurological disorders in a rural hospital of Central Africa.

Analysis of cerebrospinal fluid (CSF) obtained by lumbar puncture (LP) is an essential step for the diagnostic approach of neurological disorders, in particular neuro-infections. In low-resource settings, it is even often the only available diagnostic method. Despite its key contribution, little is known on the risks and benefits of LP in the large tropical areas where hospital-based neuroimaging is not available. The objectives of this study were to assess the safety and diagnostic yield of LP in a rural hospital of central Africa and to identify predictors of CSF pleocytosis (white blood cell count >5/µL) as surrogate marker of neuro-infections. From 2012 to 2015, 351 patients admitted for neurological disorders in the rural hospital of Mosango, Kwilu province, Democratic Republic of Congo, were evaluated using a systematic clinical and laboratory workup and a standard operating procedure for LP. An LP was successfully performed in 307 patients (87.5%). Serious post-LP adverse events (headache, backache or transient confusion) were observed in 23 (7.5%) of them but were self-limiting, and no death or long-term sequelae were attributable to LP. CSF pleocytosis was present in 54 participants (17.6%), almost always associated with neuro-infections. Presenting features strongly and independently associated with CSF pleocytosis were fever, altered consciousness, HIV infection and positive screening serology for human African trypanosomiasis. In conclusion, the established procedure for LP was safe in this hospital setting with no neuroimaging and CSF analysis brought a substantial diagnostic contribution. A set of presenting features may help accurately selecting the patients for whom LP would be most beneficial.

A large planetary body inferred from diamond inclusions in a ureilite meteorite.

Planetary formation models show that terrestrial planets are formed by the accretion of tens of Moon- to Mars-sized planetary embryos through energetic giant impacts. However, relics of these large proto-planets are yet to be found. Ureilites are one of the main families of achondritic meteorites and their parent body is believed to have been catastrophically disrupted by an impact during the first 10 million years of the solar system. Here we studied a section of the Almahata Sitta ureilite using transmission electron microscopy, where large diamonds were formed at high pressure inside the parent body. We discovered chromite, phosphate, and (Fe,Ni)-sulfide inclusions embedded in diamond. The composition and morphology of the inclusions can only be explained if the formation pressure was higher than 20 GPa. Such pressures suggest that the ureilite parent body was a Mercury- to Mars-sized planetary embryo.

An Original Approach to Evaluating the Quality of Blood Donor Selection: Checking Donor Questionnaires and Analyzing Donor Deferral Rate.

Blood donor selection is a cornerstone for blood transfusion safety, designed to safeguard the health of both donors and recipients. In the Service du Sang, Belgian Red Cross, French and German-speaking part of Belgium (SFS), health professionals (HPs) are allowed to interview donors on their own after formal qualification. This qualification is afterward evaluated by means of two complementary quality indicators: monitoring of donor health questionnaires (DHQs) and analysis of donor deferral rate. The study aims to evaluate the degree to which both quality indicators may be useful and appropriate tools to evaluate the quality of blood donor selection. An analysis performed on 2016 data showed that noncompliance detected by means of DHQ monitoring seems to be more frequent in HPs who conduct a low number of interviews compared to all HPs as a group (5.67 vs. 3.23%; p < 0.001). Deferral rates are also higher in HPs with a lower activity compared to HPs who interview more donors (14.80 vs. 13.00%, p < 0.001). Furthermore, statistically differences are observed between the type of blood donation venue in terms of the global deferral rate (for instance fixed site vs. schools: 11.9 vs. 19.5%; p < 0.001), and specific reasons for deferral (such as sexual risk behavior and travel in at-risk areas, the differences being highly significant between each category of blood donation venue; p < 0.001). Providing the HPs with feedback on these findings was an opportunity to draw their attention to some aspects of the selection process in order to improve it.

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.