Long-term outcomes of childhood-onset systemic lupus erythematosus.

OBJECTIVE: Data on the long-term outcome of patients with childhood-onset Systemic Lupus Erythematosus (cSLE) are scarce. Aims of this study were to describe the long-term outcomes of cSLE and to identify factors associated with the development of damage and persistent disease activity. METHODS: We conducted a retrospective multicentre study using data from the PEDIALUP registry of the Juvenile Inflammatory Rheumatism (JIR) cohort database. Demographic characteristics, clinical manifestations, laboratory, radiological, histological and treatment data were collected from medical records during follow-up. RESULTS: A total of 138 patients with cSLE, diagnosed between 1971 and 2015, were included. With a median follow-up of 15.4 [9.6-22.4] years, 51% of patients had a SLICC-Damage Index score ≥ 1 at last follow-up with the musculoskeletal, cutaneous, renal, neurological, and cardiovascular damage being the most common manifestations. The proportion of patients with a SLICC-DI score ≥ 1 increased significantly with the duration of the follow-up (p< 0.001). On multivariate analysis, duration of follow-up was associated with increased risk of cumulative damage (OR 1.08, 95% CI 1.01, 1.15, p= 0.035). At the last visit, 34% of patients still had active disease with a SLEDAI score of ≥ 6. On multivariate analysis, Sub-Saharan African ethnicity was associated with 7-fold increased odds of having active disease at the last visit compared with Caucasians (OR 7.44, 95% CI 2.24, 24.74, p= 0.0002). CONCLUSION: The prevalence of damage remains high in patients with cSLE even when the diagnosis of c-SLE has been made in the recent decades.

Exposure of maize seeds to liquid nitrogen modifies the morphology and hormonal response of young plants.

BACKGROUND: Cryopreservation currently represents the most suitable strategy for the long-term conservation of plant germplasm. While much effort has focused on the development of protocols to enable successful cryostorage, there are few, if any reports, that consider the effect of cryogenic temperatures on the phytohormone status of the seed and developing seedlings. OBJECTIVE: To investigate the effect of cryopreservation on external seed coat features as well as levels of indole-3-acetic acid (IAA), abscisic acid (ABA) and 1-aminocyclopropane-1-carboxylic acid (ACC) in maize. MATERIALS AND METHODS: Two groups of seeds at 6% moisture content were compared: one was maintained at 4 degree C (control) while the other was exposed to LN within cryo-vials. RESULTS: Seeds exposed to cryogenic temperatures were characterized by the presence of large cracks in the seed coat compared with control seeds. Cryogenic exposure also resulted in a reduction in biomass and plant height. Results from the phytohormone analysis showed an initial reduction in the levels of IAA, ABA and ACC after 7 days of growth followed by sharp increase in levels relative to the control by 14 days. Whilst the roles of ABA and ethylene (and by extension, its precursor ACC) are well studied as stress response molecules, much less is known about the potentially vital role of auxins in regulating plant growth under conditions of low temperature stress. CONCLUSION: It is postulated that the interaction of all three hormones modulate crosstalk between various stress responses and recovery pathways to ameliorate the damage caused by freezing stress and enable plant survival. Given the dearth of information on phytohormones in cryobiology, more studies are needed to fully elucidate these relationships in the context of freezing stress caused by liquid nitrogen. Doi.org/10.54680/fr23610110612.

Cryopreservation of seeds of the highly valued tropical timber species Swietenia mahagoni.

BACKGROUND: Swietenia mahagoni wood is one of the most valuable in world trade and, as a result, natural populations have been decimated due to unsustainable harvesting. The decline in natural population levels is being exacerbated by climate change. In order to ensure the preservation of valuable genotypes, there is an urgent need to develop strategies to conserve the genetic diversity present within this species. At present, cryopreservation is the most viable option for the long-term storage of plant germplasm, particularly for long-lived species which are challenging to maintain in the field. OBJECTIVE: To cryopreserve intact seeds of S. mahagoni, with the dual goal of retaining the biosynthetic capacity of plants, which is critical since this species is highly valued for medicinal purposes. MATERIALS AND METHODS: Seeds at a moisture content of 6% were immersed in liquid nitrogen (LN) before warming and recovery. Plantlet establishment and growth were assessed over a period of 70 days and anthraquinone synthesis was determined in roots, stems and leaves. RESULTS: The results showed an initial lag in the germination rate of cryopreserved seeds compared with control seeds; however, this difference disappeared over time. The lag in seedling emergence observed in cryostored seeds was also evident in the plant characteristics measured following 30 days of culture when all plant parameters measured were significantly higher in plants produced from control than cryostored seeds. However, after 70 days of growth, these differences were no longer apparent. Anthraquinone levels were also initially lower (at 30 days) in plants regenerated from cryopreserved seeds than those from control seeds, however, this difference was substantially reduced by 70 days thereby indicating the ability of these plants to accumulate secondary metabolites, albeit at a reduced rate, during the early stages of development. CONCLUSION: In S. mahagoni, the delay in anthraquinone production in plants regenerated from cryostored seeds during the early stages of development may have occurred as a consequence of the preferential allocation of resources towards the initiation of recovery processes in response to the stresses imposed by cryopreservation. Once the stresses were overcome and plant growth resumed, resources could be directed to secondary processes such as anthraquinone synthesis. doi.org/10.54680/fr22610110412.

Autonomy and competence satisfaction as resources for facing chronic pain disability in adolescence: a self-determination perspective.

This study aimed to test empirically the developmental goal pursuit model of paediatric chronic pain, which draws upon Self-Determination Theory for understanding risks and resources for living with chronic pain. This study examined the relationship between basic psychological need satisfaction (i.e. the satisfaction of the needs for autonomy, relatedness and competence) and the fear-avoidance model of pain in adolescents suffering from chronic pain. Hundred and twenty adolescents (mean age = 14.52, 71.6% female), receiving treatment through paediatric pain centres for chronic pain, were enrolled. Adolescents completed measures of basic psychological need satisfaction, fear and avoidance of pain, and pain-related functional impairment. Path analyses model indicated that higher levels of autonomy and competence satisfaction were associated with lower levels of functional disability, through the mediation of fear and avoidance of pain. Relatedness satisfaction was not significatively related to fear of pain, avoidance, and functional disability. The integration of Self-Determination Theory in the paediatric pain literature may further our understanding of potential resources for decreasing functional disability in children living with chronic pain.

Observation of Coherent Multiorbital Polarons in a Two-Dimensional Fermi Gas.

We report on the experimental observation of multiorbital polarons in a two-dimensional Fermi gas of ^{173}Yb atoms formed by mobile impurities in the metastable ^{3}P_{0} orbital and a Fermi sea in the ground-state ^{1}S_{0} orbital. We spectroscopically probe the energies of attractive and repulsive polarons close to an orbital Feshbach resonance and characterize their coherence by measuring the quasiparticle residue. For all probed interaction parameters, the repulsive polaron is a long-lived quasiparticle with a decay rate more than 2 orders of magnitude below its energy. We formulate a many-body theory, which accurately treats the interorbital interactions in two dimensions and agrees well with the experimental results. Our work paves the way for the investigation of many-body physics in multiorbital ultracold Fermi gases.

Localized Magnetic Moments with Tunable Spin Exchange in a Gas of Ultracold Fermions.

We report on the experimental realization of a state-dependent lattice for a two-orbital fermionic quantum gas with strong interorbital spin exchange. In our state-dependent lattice, the ground and metastable excited electronic states of ^{173}Yb take the roles of itinerant and localized magnetic moments, respectively. Repulsive on-site interactions in conjunction with the tunnel mobility lead to spin exchange between mobile and localized particles, modeling the coupling term in the well-known Kondo Hamiltonian. In addition, we find that this exchange process can be tuned resonantly by varying the on-site confinement. We attribute this to a resonant coupling to center-of-mass excited bound states of one interorbital scattering channel.

Transition from paediatric to adult care: what makes it easier for parents?

OBJECTIVE: To assess differences between parents of adolescents with chronic illness (CI) going through a self-reported easy or difficult transfer. METHODS: Seventy-two parents of CI youths who had already transferred to adult care were divided according to whether they considered that the transfer had been easy (n = 45) or difficult (n = 27). We performed a bivariate analysis comparing both groups and variables with a significance level < .1 were included in a logistic regression. Results are presented as adjusted odds ratio (aOR). RESULTS: Over one third of parents (27/72) reported a difficult transfer. At the multivariate level, higher socioeconomic status (aOR: 7.74), parents feeling ready for transfer (aOR: 6.54) and a good coordination between teams (aOR: 7.66) were associated with an easy transfer. CONCLUSIONS: An easy transfer for parents is associated with feeling ready and considering that the coordination between teams is good. Health providers should consider these requisites for a successful transfer.

Post-Streptococcal Uveitis: a Rare Entity.

Without appropriate treatment, Group A streptococcal infections can lead to post-streptococcal syndrome, including post-streptococcal uveitis. This should be kept in mind in young patients with acute bilateral non-granulomatous anterior uveitis, in order to avoid ocular and systemic complications. We report two cases of bilateral post-streptococcal anterior uveitis, in young men, of respectively 20 and 16 years old, that presented to Jules Gonin Eye Hospital.

[Surgery of the nose and paranasal sinuses]. / Chirurgie der Nase und Nasennebenhöhlen.

A compromised overview of surgical techniques regarding the nose (functional) and para nasal sinus inflammation surgical treatment is exposed in this article. The nasal septum is within the focus for function, form and stability for the nasal structure (especially for tip and back of the nose) and for success of a rhinoplasty. An important role play the lower nasal turbinates regulating nasal air flow and thus having a great effect after turbinate surgery (submucosal resection and lateral fracturing).The endonasal endoscopy is of utmost importance for diagnosis, therapy and detection of recurrence. In severe cases of nasal polyps, functional endoscopic sinus surgery (FESS) remains the ultimate therapy. However, the indication to operate will be carried out after exhaustion of medical treatment. The most important recurrent prophylaxis for rhino sinusitis and nasal polyps is an appropriate post operative nasal care.

Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry.

OBJECTIVE: To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. METHODS: A web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included. RESULTS: 136 patients were analysed. The median age at disease onset was 9 months, and the median duration of follow-up was 15 years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311 K and A439 V alleles. Early onset was predictive of severe neurological complications and hearing loss. CONCLUSIONS: Patients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6 months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions.

Observation of Scaling in the Dynamics of a Strongly Quenched Quantum Gas.

We report on the experimental observation of scaling in the time evolution following a sudden quench into the vicinity of a quantum critical point. The experimental system, a two-component Bose gas with coherent exchange between the constituents, allows for the necessary high level of control of parameters as well as the access to time-resolved spatial correlation functions. The theoretical analysis reveals that when quenching the system close to the critical point, the energy introduced by the quench leads to a short-time evolution exhibiting crossover reminiscent of the finite-temperature critical properties in the system's universality class. Observing the time evolution after a quench represents a paradigm shift in accessing and probing experimentally universal properties close to a quantum critical point and allows in a new way benchmarking of quantum many-body theory with experiments.

Observation of an Orbital Interaction-Induced Feshbach Resonance in (173)Yb.

We report on the experimental observation of a novel interorbital Feshbach resonance in ultracold (173)Yb atoms. This opens up the possibility of tuning the interactions between the (1)S(0) and (3)P(0) metastable state, both possessing zero total electronic angular momentum. The resonance is observed at experimentally accessible magnetic field strengths and occurs universally for all hyperfine state combinations. We characterize the resonance in the bulk via interorbital cross thermalization as well as in a three-dimensional lattice using high-resolution clock-line spectroscopy. Our measurements are well described by a generalized two-channel model of the orbital-exchange interactions.

Family Nurture Intervention in preterm infants alters frontal cortical functional connectivity assessed by EEG coherence.

AIM: To assess the impact of Family Nurture Intervention (FNI) on cortical function in preterm infants at term age. METHODS: Family Nurture Intervention is a NICU-based intervention designed to establish emotional connection between mothers and preterm infants. Infants born at 26-34 weeks postmenstrual age (PMA) were divided into two groups, standard care (SC, N = 49) and FNI (FNI, N = 56). Infants had EEG recordings of ~one hour duration with 124 lead nets between 37 and 44 weeks PMA. Coherence was measured between all pairs of electrodes in ten frequency bands. Data were summarised both within and between 12 regions during two sleep states (active, quiet). RESULTS: Coherence levels were negatively correlated with PMA age in both groups. As compared to SC infants, FNI infants showed significantly lower levels of EEG coherence (1-18 Hz) largely within and between frontal regions. CONCLUSION: Coherence in FNI infants was decreased in regions where we previously found robust increases in EEG power. As coherence decreases with age, results suggest that FNI may accelerate brain maturation particularly in frontal brain regions, which have been shown in research by others to be involved in regulation of attention, cognition and emotion regulation; domains deficient in preterm infants.

Treatment resistance in inclusion body myositis: the role of mast cells.

Inclusion body myositis is the commonest acquired myopathy in those over 50 years of age. Although it is classified as an idiopathic inflammatory myopathy and the most frequent finding on muscle biopsy in inclusion body myositis is an endomysial inflammatory infiltrate, it is clinically distinct from other myositis, including a lack of response to immunosuppressive medication. Neurogenic changes are commonly reported in inclusion body myositis and inflammatory changes are observed in muscle following neurogenic injury. The objective of our study was to explore whether neurogenic inflammation plays a role in the pathogenesis of inclusion body myositis, possibly explaining its resistance to immunosuppression. The number of mast cells and presence of neuropeptides, substance P and calcitonin gene-related peptide, were assessed in 48 cases of inclusion body myositis, 11 cases of steroid responsive myositis, two cases of focal myositis associated with neurogenic injury, and ten normal controls. The number of mast cells in inclusion body myositis focal and myositis associated to neurogenic injury were significantly greater than that observed in steroid responsive myositis. Our findings suggest that neurogenic inflammation mediated through mast cells may play a role in the pathogenesis of inclusion body myositis, and focal myositis associated to neurogenic injury, and thus, explain in some part its lack of response to immunosuppressive treatments.

Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Diagnostic and prognostic markers in gliomas - an update.

Gliomas are the most common primary central nervous system tumour seen in adults. There have been many advances over the last two decades as we widen our search for a molecular basis of gliomagenesis. Many biomarkers have been discovered to be important in the management of gliomas, including 1p19q co-deletion, MGMT promoter methylation, BRAF and IDH1 mutations. In this review, we attempt to summarise the available literature on these biomarkers and their use in the diagnosis and management of gliomas. We pay special attention to the recently discovered IDH1 mutation, which is already proving to be a valuable new marker for favourable prognosis and may also indicate a greater response to therapy. 1p19q co-deletions have been shown to delineate a clinically distinct tumour type and are now routinely tested for in certain situations and can help direct treatment. MGMT promoter methylation is one of the most commonly studied biomarkers in gliomas. It has been shown to be a strong positive prognostic marker in gliomas, with positive tumours being more sensitive to chemotherapy. However, a lack of alternatives means that it is not yet a routine mutation tested for clinically. BRAF mutations are new markers found in pilocytic astrocytomas. Although the prognostic value of such mutations is not yet known, they may play a significant role in the diagnosis and treatment of such tumours. IDH1 mutations are 'the new kid on the block' and seem to play a central role in the pathogenesis of gliomas. They represent an independent and favourable prognostic marker and are a new molecular marker for disease diagnosis. Its role in determining response to chemotherapy is still controversial but with further study, IDH1 mutations may prove to be an invaluable marker in the management of gliomas.

Breaking down the fences among registries on autoinflammatory diseases: the E-Merge project.

BACKGROUND: Among the various numbers of different autoinflammatory diseases (AIDs), the absolute majority of them remains rare, with a single representative in large populations. This project, endorsed by PRES, supported by the EMERGE fellowship program, and performed in line with the Metadata registry for the ERN RITA (MeRITA), has the objective of performing a data synchronization attempt of the most relevant research questions regarding clinical features, diagnostic strategies, and optimal management of autoinflammatory diseases. RESULTS: An analysis of three large European registries: Eurofever, JIR-cohort and AID-Net, with a total coverage of 7825 patients from 278 participating centers from different countries, was performed in the context of epidemiological and clinical data merging. The data collected and evaluated in the registries does not cover only pediatric patients, but also adults with newly diagnosed AIDs. General aspects of the existing epidemiological data have been discussed in the context of patient global distribution, potential diagnostic delays, access to genetic testing, and the availability of the treatment. CONCLUSIONS: In general, the results indicate a great potential for upcoming collaborative work using existing data in cohorts that enhance the quality of medical care performed for patients with autoinflammatory diseases.

Disease evolution in systemic juvenile idiopathic arthritis: an international, observational cohort study through JIRcohort.

BACKGROUND: Systemic juvenile idiopathic arthritis (systemic JIA) is a severe disease with both systemic and joint inflammation. This study aims to identify predictors of disease evolution within the systemic JIA population enrolled in the Juvenile Inflammatory Rheumatism cohort (JIRcohort). METHODS: Observational patient cohort study with 201 recruited children from 4 countries (3 European, 1 North Africa) from 2005 until 2019, using retrospectively (2005-2015) and prospectively (2015-2019) routine care collected data. RESULTS: Sixty-five patients with complete follow-up data for 24 months after first diagnosis were classified as monophasic (n = 23), polyphasic (n = 6) or persistent group (n = 36) corresponding to their evolution (unique flare, recurrent flares, or persistent disease activity respectively). The patients of the persistent group were more likely to have an earlier disease onset, before the age of 6 (OR 2.57, 95%-CI 0.70-9.46), persistence of arthritis at 12-months post-diagnosis (OR 4.45, 95%-CI 0.58-34.20) and higher use of synthetic DMARD (sDMARD, OR 5.28, 95%-CI 1.39-20.01). Other variables like global assessment by physician and by patient and C Reactive Protein levels at 12-months post-diagnosis were assessed but without any predictive value after adjusting for confounding factors. CONCLUSIONS: Our results suggest that the earlier disease onset, the persistence of arthritis throughout the first year of disease evolution and the need of sDMARD might predict a persistent disease course.

Compact x-ray microscope for the water window based on a high brightness laser plasma source.

We present a laser plasma based x-ray microscope for the water window employing a high-average power laser system for plasma generation. At 90 W laser power a brightness of 7.4 x 10(11) photons/(s x sr x µm(2)) was measured for the nitrogen Lyα line emission at 2.478 nm. Using a multilayer condenser mirror with 0.3 % reflectivity 10(6) photons/(µm(2) x s) were obtained in the object plane. Microscopy performed at a laser power of 60 W resolves 40 nm lines with an exposure time of 60 s. The exposure time can be further reduced to 20 s by the use of new multilayer condenser optics and operating the laser at its full power of 130 W.

Quality indicators for the development and didactics of ultrasound courses in continuing medical education.

PURPOSE: Based on evaluation data from participant feedback, a concept was to be developed for introductory abdominal ultrasound courses lasting several days. This approach was to be developed incrementally with the intent of maximizing the learning effect per time. MATERIALS AND METHODS: This concept has been modified annually over several years based on the findings of educational research and the scores on final examinations in OSCE format. It has been modified with the aid of detailed questionnaires completed by approximately 2000 participating physicians and has thus undergone incremental optimization. RESULTS: Analysis of the most recent 1005 questionnaires has shown that participants recommend a modular course design with only brief lectures on theory (average optimal duration of 20 min., SD 9.6 min.). These should alternate with longer practical "hands-on" ultrasound exercises (60 - 90 min., accounting for at least 50 - 60 % of the course time), consolidating drawing exercises, and breaks. 51 % of the physicians specified 5 participants as the ideal group size for practical exercises, while 43 % specified only 4. The discussion presents 10 specific quality indicators for efficient ultrasound courses. It elucidates the feasibility and logistical prerequisites of this model, and compares it with other basic course concepts. Furthermore, this article presents a model for an evaluation covering the course concept and tutors as well as discussing a training program for tutors including a cost analysis. CONCLUSION: In summary, the participants estimate the course design to represent a mature concept that has demonstrated its feasibility and broad acceptance among physicians in CME.