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Introduction Osteoarthritis is a chronic pathology that involves multidisciplinary management. Self-management for patients is an essential element, present in all international guidelines. During the time of the spa therapy, the patient is receptive to take the advantage of self-management workshops. The aim of this study is to assess the effects of 18 days spa therapy associated with a self-management intervention in patients with knee osteoarthritis in comparison with spa therapy alone on a priority objective, personalized and determined with the patient, chosen in the list of 5 objectives determined during the self-management initial assessment. Methods and analysis Two hundred fifty participants with knee osteoarthritis will participate to this multicenter, prospective, randomized, controlled study. All patients will benefit 18 days of spa therapy and patients randomized in the intervention group will participate to 6 self-management workshops. Randomization will be centralized. The allocation ratio will be 1:1. Data analysts and assessor will be blinded. The primary outcome is the effectiveness of the educational workshops associated with spa therapy in comparison with spa therapy alone on a priority objective, measured by Goal Attainment Scaling (GAS). The secondary outcomes are disability, health-related quality of life, and pain intensity. Ethics and dissemination Ethics were approved by the CPP Sud-Méditerranée II . The results will be disseminated in a peer-reviewed journal and disseminated at PRM, rheumatology, and orthopedics conferences. The results will also be disseminated to patients. Trial registration Trial registration number NCT03550547. Registered 8 June 2018. Date and version identifier of the protocol. Version N°6 of March 12, 2018.

Objective To determine whether spa therapy, plus home exercises and usual medical treatment provides any benefit over exercises and usual treatment, in the management of knee osteoarthritis. Methods Large multicentre randomised prospective clinical trial of patients with knee osteoarthritis according to the American College of Rheumatology criteria, attending French spa resorts as outpatients between June 2006 and April 2007. Zelen randomisation was used so patients were ignorant of the other group and spa personnel were not told which patients were participating. The main endpoint criteria were patient self-assessed. All patients continued usual treatments and performed daily standardised home exercises. The spa therapy group also received 18 days of spa therapy (massages, showers, mud and pool sessions). Main Endpoint The number of patients achieving minimal clinically important improvement (MCII) at 6 months, defined as ≥19.9 mm on the visual analogue pain scale and/or ≥9.1 points in a normalised Western Ontario and McMaster Universities osteoarthritis index function score and no knee surgery. Results The intention to treat analysis included 187 controls and 195 spa therapy patients. At 6 months, 99/195 (50.8%) spa group patients had MCII and 68/187 (36.4%) controls (χ2=8.05; df=1; p=0.005). However, no improvement in quality of life (Short Form 36) or patient acceptable symptom state was observed at 6 months. Conclusion For patients with knee osteoarthritis a 3-week course of spa therapy together with home exercises and usual pharmacological treatments offers benefit after 6 months compared with exercises and usual treatment alone, and is well tolerated. Trial registration number NCT00348777.

Natural mineral water (NMWs) intake has been traditionally used in the treatment of various gastrointestinal diseases. We investigated the effect of two French NMWs, one a calcium and magnesium sulphate, sodium chloride, carbonic, and ferruginous water (NMW1), the other a mainly bicarbonate water (NMW2) on the prevention of intestinal inflammation. Intestinal epithelial cells stimulated with heat inactivated Escherichia coli or H2O2 were treated with NMWs to evaluate the anti-inflammatory effects. Moderate colitis was induced by 1% dextran sulfate sodium (DSS) in Balbc/J mice drinking NMW1, NWW2, or control water. General signs and histological features of colitis, fecal lipocalin-2 and pro-inflammatory KC cytokine levels, global mucosa-associated microbiota, were analyzed. We demonstrated that both NMW1 and NMW2 exhibited anti-inflammatory effects using intestinal cells. In induced-colitis mice, NMW1 was effective in dampening intestinal inflammation, with significant reductions in disease activity scores, fecal lipocalin-2 levels, pro-inflammatory KC cytokine release, and intestinal epithelial lesion sizes. Moreover, NMW1 was sufficient to prevent alterations in the mucosa-associated microbiota. These observations, through mechanisms involving modulation of the mucosa-associated microbiota, emphasize the need of investigation of the potential clinical efficiency of such NMWs to contribute, in human beings, to a state of low inflammation in inflammatory bowel disease.

Dense and narrow rings have been discovered recently around the small Centaur object Chariklo1 and the dwarf planet Haumea2, while being suspected around the Centaur Chiron3, although this point is debated4. They are the first rings observed in the Solar System elsewhere than around giant planets. In contrast to giant planets, gravitational fields of small bodies may exhibit large non-axisymmetric terms that create strong resonances between the spin of the object and the mean motion of ring particles. Here we show that modest topographic features or elongations of Chariklo and Haumea explain why their rings are relatively far away from the central body, when scaled to those of the giant planets5. Resonances actually clear on decadal timescales an initial collisional disk that straddles the corotation resonance (where the particles' mean motion matches the spin rate of the body). Quite generically, the disk material inside the corotation radius migrates onto the body, while the material outside the corotation radius is pushed outside the 1/2 resonance, where the particles complete one revolution while the body completes two rotations. Consequently, the existence of rings around non-axisymmetric bodies requires that the 1/2 resonance resides inside the Roche limit of the body, favouring faster rotators for being surrounded by rings.Chariklo, Haumea and potentially Chiron are the only known ringed Solar System objects that are not giant planets. The rings of these minor bodies are relatively further from their hosts than those around giant planets; this increase is shown to be due to resonances driven by modest topographic features or elongations.

Objective: To investigate the effect of tizanidine (an α2 noradrenergic agonist) on transmission in the interneuronal pathway coactivated by group I and group II afferents in post-stroke patients with spastic hemiplegia. Methods: Early and late facilitation of the quadriceps H reflex elicited in the common peroneal nerve—attributed to non-monosynaptic group I and group II excitation, respectively—was investigated in 14 spastic hemiplegic patients. All received a single dose of tizanidine (150 μg/kg) or placebo in randomised order at 10 day intervals. Repeated measurements were made at baseline (T0), 45–90 min, and 120 min after drug intake. Spasticity was assessed by modified Ashworth score in the quadriceps muscle and by a leg tone score calculated by the sum of the modified Ashworth score in five muscle groups. Results: On the spastic side a decrease in late group II and, to a lesser extent, early group I common peroneal nerve induced quadriceps H reflex facilitation occurred with tizanidine (group II, mean (SEM) difference T0–T90: 34.3 (10.2)%, p<0.001; group I, T0–T120: 19.8 (9)%, p<0.05), but not with placebo (group II, difference T0–T90: 12.5 (8)%, NS; group I, T0–T120: 3.2 (7)%, NS). Tizanidine but not placebo decreased the quadriceps muscle and global lower limb Ashworth scores (2.9 (0.2) to 1.9 (0.3), p<0.001; and 12 (0.7) to 9.5 (0.8), p<0.0001, respectively). Conclusions: Enhancement of group II–group I facilitation of the quadriceps motor neurones on the spastic side of hemiplegic patients is modulated by α2 noradrenergic agonists. This strengthens the view that late facilitation of quadriceps motor neurones is mediated by group II afferents and suggests that group II pathways may be involved in lower limb spasticity.

To assess the one-year effectiveness on weight loss of a 3-week balneotherapy program (BT). Method. A Zelen double consent randomised controlled trial to compare one-year BMI loss between a 3-week BT program versus usual care (UC) for overweight or obese patients (BMI: 27–35 kg/m2), associated or not with a dietary motivational interview (DMI) during the follow-up, using a 2 × 2 factorial design. Main analysis was a per protocol analysis comparing patients attending BT to patients managed by UC, matched on sex, overweight or obese status, DMI randomisation and a propensity score to attend BT or to be managed by UC. Results. From the 257 patients who completed the follow-up, 70 patients of each group could be matched. Mean BMI loss was 1.91 kg/m2 [95%CI: 1.46; 2.35] for the BT patients and 0.20 kg/m2 [−0.24; 0.64] for the UC patients (P<0.001), corresponding to a significant BT benefit of 1.71 kg/m2 [1.08; 2.33]. There was no significant effect of DMI and no interaction with BT or UC. No adverse reaction was observed for patients attending BT. Conclusion. A 3-week BT program provided a significant one-year benefit over the usual GP dietary advice for overweight and obese patients.

OBJECTIVE A potent heteronymous group II excitation of quadriceps motor neurons has been recently demonstrated in normal subjects. The present study was undertaken to investigate whether this heteronymous group II excitation also contributes to spasticity in hemiplegic patients. METHOD The early and late facilitations of the quadriceps H reflex elicited by a conditioning volley to the common peroneal nerve at three times motor threshold, attributed to non-monosynaptic group I and group II excitations respectively, were investigated. The comparison was drawn between results obtained in 20 patients after stroke, with hemiplegia due to a vascular lesion in the territory of the middle cerebral artery, and 20 age and sex matched normal subjects. RESULTS A significant increase in the group I as well as in the group II common peroneal nerve induced facilitation of the quadriceps H reflex was seen on the spastic side of the patients (group I: 159 (SEM 10)% of control H reflex; group II: 165 (SEM 8)%) compared with their unaffected side (group I: 126 (SEM 4)%; group II: 128 (SEM 5)%) (Wilcoxon signed rank test, p<0.01), or to the right (group I: 132 (SEM 4)%; group II: 131 (SEM 5)%) or left (group I: 130 (SEM 3)%; group II: 135 (SEM 6)%) side of controls (Mann-Whitney U test, p<0.01). No significant correlation (Spearman rank test) was found between the degree of group I and group II induced facilitations on the spastic side of the patients and the degree of clinically assessed spasticity (Ashworth scale). CONCLUSION These results reflect a facilitation of the transmission in the interneuronal pathway coactivated by group I and group II afferents, probably resulting from a change in their descending control in spastic hemiplegic patients.

According to the latest forecasts of the INSEE (1) — Institut National de la Statistique et des Etudes Economiques (National Statistics and Economic Studies Institute), ageing of the French population will increase between 2005 and 2050: whereas 20.8% of the population living in continental France reached the age of 60 years or more in 2005, this proportion would be of 30.6% in 2035 and 31.9% in 2050. In 2050, 22.3 million persons will have reached the age of 60 years or more compared to 12.6 million in 2005, increasing by 80% in a 45-year period. In line with the actual age pyramid, ageing is unavoidable, as those who will reach 60 years of age in 2050 are already born (in 1989 or before). This expansion will be most important between 2006 and 2035, when the numerous “baby-boom“ generations born between 1946 and 1975, will reach these ages. In future years, lifespan improvement will only emphasize this increase. Even if life expectancy stabilizes at the 2005 level, the number of seniors reaching 60 years or more would still increase to 50% between 2005 and 2050. This issue is identical in all countries of the European Union. Ageing is a major risk factor for dementia that will considerably worsen in the next years, if no curative therapies are found. Today, 25 million persons in the world suffer from Alzheimer's disease (AD). In France, it is estimated that 860 000 persons are affected and that 225 000 news cases are annually diagnosed. After 75 years of age, more than 20% of women and 13% of men are concerned. Forecasts for the coming years are frightening. Considering ageing of the population, the number of Alzheimer's disease cases should raise to 1.3 million in 2020 (20 patients for 1000 inhabitants) ant 2.1 million in 2040 (30 patients for 1000 inhabitants) (2).

Observations of a stellar occultation of Haumea, one of the four known trans-Neptunian dwarf planets, constrain its size, shape and density, and reveal a ring coplanar with Haumea’s largest moon. A ring around Haumea Haumea is a dwarf planet beyond the orbit of Neptune. It is rapidly rotating and very elongated, unlike the other three known trans-Neptunian dwarf planets. Jose Ortiz and collaborators obtained observations from multiple Earth-based telescopes as Haumea passed in front of a background star. This occultation enabled the team to constrain the density of Haumea to an upper limit of about 1,885 kilograms per cubic metre. They also constrained its ellipsoid shape and albedo (0.51). They did not detect an atmosphere around the planet, but found a ring circling it. They determined that the ring is 70 kilometres wide, has a radius of about 2,287 kilometres and lies in the same orbital plane as Haumea's equator and largest moon. It has an orbital period that is three times the spin period of Haumea. The ring absorbed roughly half of the star light coming through, giving it an opacity of 0.5. Haumea—one of the four known trans-Neptunian dwarf planets—is a very elongated and rapidly rotating body 1 , 2 , 3 . In contrast to other dwarf planets 4 , 5 , 6 , its size, shape, albedo and density are not well constrained. The Centaur Chariklo was the first body other than a giant planet known to have a ring system 7 , and the Centaur Chiron was later found to possess something similar to Chariklo’s rings 8 , 9 . Here we report observations from multiple Earth-based observatories of Haumea passing in front of a distant star (a multi-chord stellar occultation). Secondary events observed around the main body of Haumea are consistent with the presence of a ring with an opacity of 0.5, width of 70 kilometres and radius of about 2,287 kilometres. The ring is coplanar with both Haumea’s equator and the orbit of its satellite Hi’iaka. The radius of the ring places it close to the 3:1 mean-motion resonance with Haumea’s spin period—that is, Haumea rotates three times on its axis in the time that a ring particle completes one revolution. The occultation by the main body provides an instantaneous elliptical projected shape with axes of about 1,704 kilometres and 1,138 kilometres. Combined with rotational light curves, the occultation constrains the three-dimensional orientation of Haumea and its triaxial shape, which is inconsistent with a homogeneous body in hydrostatic equilibrium. Haumea’s largest axis is at least 2,322 kilometres, larger than previously thought, implying an upper limit for its density of 1,885 kilograms per cubic metre and a geometric albedo of 0.51, both smaller than previous estimates 1 , 10 , 11 . In addition, this estimate of the density of Haumea is closer to that of Pluto than are previous estimates, in line with expectations. No global nitrogen- or methane-dominated atmosphere was detected.

BackgroundOsteoporosis is a major public health issue with 5 million of French affected. Overall, she seriously underestimated, and costs are barely covered in France. Considering this situation, AFLAR were urged to create the so-called National Osteoporosis Alliance made up of 15 various stakeholders and patients.MethodsNational consultations on osteoporosis rely methodologically on 2 pillars:First the bottom-up reporting on patient needs and expectations. Second the conduct of coordination meetings with various osteoporosis key stakeholders and patients as part of regional panel-discussions. The aim is to provide an overview of real obstacles contributing to the lack of government subsidies for osteoporosis and write consensual proposals compiled into a white paper.ResultsAn online survey along with a citizen’s panel were key to provide feedbacks on difficulties, knowledges and believes but also patient needs. From November 2016 to June 2017, 10 days of dialogue and debate covering 5 various topics were convened in 10 different cities: Consultation and consolidation work regarding proposals made during various panel-discussions allowed synthesis around one call: the creation of a real public health plan against osteoporosis-related fractures relying on 7 key axis.ConclusionsThe human and medico-economic rational considering dramatic fallouts caused by osteoporosis has been illustrated many times over. The policy makers mobilization made by stakeholders through white paper release, a real manifesto for public health plan against osteoporosis-related fracture, remain a significant challenge to face.Disclosure of InterestL. Grange Grant/research support from: ucb Lilly Amgen expanscience Roche company, B. Cortet : None declared, T. Thomas : None declared, F. Srour : None declared, P. Guggenbuhl : None declared, C. Roux : None declared, P. Monod: None declared, J. M. Feron: None declared, F. Alliot- launois: None declared, F. Tremollières : None declared, G. Chalés : None declared, J. Giraud : None declared, E. Senbel: None declared, G. Thibaud: None declared, P. Niemczynski: None declared, D. R. Bertholon : None declared, C. F. Roques : None declared, D. Buchon: None declared, C. Bonnet : None declared, H. Blain : None declared, C. Rolland : None declared, D. Lafarge : None declared, L. Carton: None declared