Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Human C1q Deficiency: The Karolinska Experience.

Human C1q deficiency is associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections. These patients require extensive medical therapy and some develop treatment-resistant disease. Because C1q is produced by monocytes, it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure this disorder

Self-rated walking disability and dynamic ankle joint stiffness in children and adolescents with Juvenile Idiopathic Arthritis receiving intraarticular corticosteroid joint injections of the foot

Background: Children and adolescents with Juvenile Idiopathic Arthritis (JIA) exhibit deviations in ankle dynamic joint stiffness (DJS, or moment-angle relationship) compared to healthy peers, but the relationship between ankle DJS and self-reported walking impairments has not been studied. This secondary analysis aimed to investigate the relationship between ankle DJS and self-reported walking disability in juveniles with JIA, and to determine whether intraarticular corticosteroid foot injections (IACI) were associated with long term changes in ankle DJS. Research questions: Is ankle DJS altered in children with JIA reporting walking difficulties compared to children with JIA reporting no walking difficulties? Are IACIs associated with persistent alterations in ankle DJS? Methods: Gait dynamics (DJS), foot pain, and foot-related disability were assessed in 33 children with JIA before intraarticular corticoid foot injection (IACI), and three months after IACI. Using self-reported walking capacity scores, children were classified as either having no walking difficulties (ND) or having walking difficulties (WD). Inferential statistics were used to compare demographics, pain, impairment scores, and ankle DJS between the groups. Results: Before treatment, in the WD group, ankle DJS was significantly decreased both in the early rising phase (ERP = 0.03+0.02 vs. 0.05+0.02 Nm(kg*deg)− 1) and late rising phase (LRP = 0.11+0.06 vs. 0.24+0.22 Nm(kg*deg)-1) compared to the ND group. At three months, the ERP was still significantly decreased in the WD group (ERP = 0.03+0.01 vs. 0.05+0.03 Nm(kg*deg)-1). Significance: Among children and adolescents with JIA who reported walking difficulties prior to IACIs, alterations in DJS in early stance phase (decreased ERP) remained three months after IACI suggesting persistent gait adaptations, possibly related to pain. Pre-treatment gait analysis may aid in identifying children who will not have long term benefit from IACIs in terms of improved gait, and therefore, may be informed and have the choice to be spared the risk of side effects associated with this treatment

Temporomandibular involvement in children and adolescents with juvenile idiopathic arthritis: a 2-year prospective cohort study

Abstract This study aimed to clinically evaluate temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA) and the ability to identify and/or predict development of TMJ-deformities over time using cone beam computed tomography (CBCT). The predictive value of self-reported TMJ pain was also assessed. A prospective longitudinal cohort study comprising 54 children with JIA, 39 girls and 15 boys, was performed. All children had active disease at baseline, 50% with the subtype oligoarthritis. Repeated clinical orofacial and CBCT examinations were performed over a two-year period. At baseline, 39% had radiographic TMJ deformities (24% unilateral, 15% bilateral), at 2-year follow-up, 42% (p > 0.05). Both progressing and improving TMJ deformities were observed. An association was found between TMJ-deformities and self-reported TMJ pain at baseline (p = 0.01). Maximum unassisted mouth opening (MUO) was smaller for children with TMJ-deformities (p < 0.05). The prevalence of palpatory muscle pain was high (48–59%) but not predictive of development of TMJ-deformities. TMJ noises increased over time and crepitations were associated with TMJ-deformities (p < 0.05). In conclusion, in children with JIA, self-reported TMJ pain and dysfunction were common and predictive of TMJ deformities. TMJ deformities were associated with smaller MUO and palpatory TMJ pain as well as crepitations. Trial registration. ClinicalTrials.gov Protocol id: 2010/2089-31/2

Vegetation changes and human settlement of Easter Island during the last millennia: a multiproxy study of the Lake Raraku sediments

Earlier palynological studies of lake sediments from Easter Island suggest that the island underwent a recent and abrupt replacement of palm-dominated forests by grasslands, interpreted as a deforestation by indigenous people. However, the available evidence is inconclusive due to the existence of extended hiatuses and ambiguous chronological frameworks in most of the sedimentary sequence studied. This has given rise to an ongoing debate about the timing and causes of the assumed ecological degradation and cultural breakdown. Our multiproxy study of a core recovered from Lake Raraku highlights the vegetation dynamics and environmental shifts in the catchment and its surroundings during the late Holocene. The sequence contains shorter hiatuses than in previously recovered cores and provides a more continuous history of environmental changes. The results show a long, gradual and stepped landscape shift from palm dominated forests to grasslands. This change started c. 450 BC and lasted about two thousand years. The presence of Verbena litoralis , a common weed, which is associated with human activities in the pollen record, the signi ficant correlation between shifts in charcoal influx, and the dominant pollen types suggest human disturbance of the vegetation. Therefore, human settlement on the island occurred c. 450 BC, some 1500 years earlier than is assumed. Climate variability also exerted a major influence on environmental changes. Two sedimentary gaps in the record are interpreted as periods of droughts that could have prevented peat growth and favoured its erosion during the Medieval Climate Anomaly and the Little Ice Age, respectively. At c. AD 1200, the water table rose and the former Raraku mire turned into a shallow lake, suggesting higher precipitation/evaporation rates coeval with a cooler and wetter Pan-Pacific AD 1300 event. Pollen and diatom records show large vegetation changes due to human activities c. AD 1200. Other recent vegetation changes also due to human activities entail the introduction of taxa (e.g. Psidium guajava, Eucalyptus sp.) and the disappearance of indigenous plants such as Sophora toromiro during the two last centuries. Although the evidence is not conclusive, the American origin of V.litoralis re-opens the debate about the possible role of Amerindians in the human colonisation of Easter Island

Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency.

Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can be restored by allogeneic hematopoietic stem cell transplantation. Current literature lacks information on disease progression and quality of life of C1q deficient persons which is of major importance to guide clinicians taking care of patients with this rare disease

Updated orbital monitoring and dynamical masses for nearby M-dwarf binaries

International audienceYoung M-type binaries are particularly useful for precise isochronal dating by taking advantage of their extended pre-main sequence evolution. Orbital monitoring of these low-mass objects becomes essential in constraining their fundamental properties, as dynamical masses can be extracted from their Keplerian motion. Here, we present the combined efforts of the AstraLux Large Multiplicity Survey, together with a filler sub-programme from the SpHere INfrared Exoplanet (SHINE) project and previously unpublished data from the FastCam lucky imaging camera at the Nordical Optical Telescope (NOT) and the NaCo instrument at the Very Large Telescope (VLT). Building on previous work, we use archival and new astrometric data to constrain orbital parameters for 20 M-type binaries. We identify that eight of the binaries have strong Bayesian probabilities and belong to known young moving groups (YMGs). We provide a first attempt at constraining orbital parameters for 14 of the binaries in our sample, with the remaining six having previously fitted orbits for which we provide additional astrometric data and updated Gaia parallaxes. The substantial orbital information built up here for four of the binaries allows for direct comparison between individual dynamical masses and theoretical masses from stellar evolutionary model isochrones, with an additional three binary systems with tentative individual dynamical mass estimates likely to be improved in the near future. We attained an overall agreement between the dynamical masses and the theoretical masses from the isochrones based on the assumed YMG age of the respective binary pair. The two systems with the best orbital constrains for which we obtained individual dynamical masses, J0728 and J2317, display higher dynamical masses than predicted by evolutionary models

Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping anti-inflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent. METHODS: Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn. The phagocyte activation markers S100A12 and myeloid-related proteins 8/14 (MRP8/14) were compared as well as the acute phase reactant high-sensitivity C reactive protein (hsCRP) as predictive biomarkers for the risk of a flare within a time frame of 6 months. RESULTS: 35 of 188 enrolled patients experienced a flare within 6 months. Clinical or standard laboratory parameters could not differentiate between patients at risk of relapse and those not at risk. S100A12 and MRP8/14 levels were significantly higher in patients who subsequently developed flares than in patients with stable remission. The best single biomarker for the prediction of flare was S100A12 (HR 2.81). The predictive performance may be improved if a combination with hsCRP is used. CONCLUSIONS: Subclinical disease activity may result in unstable remission (ie, a status of clinical but not immunological remission). Biomarkers such as S100A12 and MRP8/14 inform about the activation status of innate immunity at the molecular level and thereby identify patients with unstable remission and an increased risk of relapse