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.

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.

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.

TEACHING MUST GO ON: flexibility and advantages of peer assisted learning during the COVID-19 pandemic for undergraduate medical ultrasound education - perspective from the "sonoBYstudents" ultrasound group.

Background: Facing the global COVID-19 pandemic University teaching has been digitalized and German medical faculties took great effort to offer curricular contents online as they agreed that semesters during pandemic should not be suspended. Skill training is an essential part of medical education and cannot be fully digitalized nor should it be omitted. The pandemic demonstrates that skills like ultrasound are essential when treating critical ill patients. Medical faculties use peer assisted learning (PAL) concepts to teach skills, like ultrasound through specially trained student tutors. Aim: Here, we would like to share our experiences and elaborate how ultrasound teaching can be safely performed during the pandemic with an emphasis on adjustment of an existing PAL teaching concept. Method: At the hospital of Saarland University, we implemented a PAL teaching concept for abdominal, including emergency, ultrasound, and echocardiography, called "sonoBYstudents" to teach sonography to undergraduate medical students. Students are generally taught in small groups of 5 people in 90min sessions over a time of 8 weeks with an objective structured clinical exam (OSCE) at the end of the course program. Each semester nearly 50 students are taught in abdominal and emergency ultrasound and 30 students in echocardiography. Over five years, more than 600 students have been taught with at least 30 students being trained as student tutors. Given the pandemic, course size, course interval and total course time and total course time were adapted to the hygienic precautions. Results: 45 and 30 students were taught in abdominal ultrasound and echocardiography respectively achieving their learning goals measured via OSCE at the end of the courses. OSCE results were the same when compared to previous semesters. Conclusion: PAL as a teaching concept lives out of sustained educational strategies like practical and didactical trainings and an ongoing recruitment of new student tutors. Suspending PAL and its skill teaching would require starting from the beginning which is a time and cost consuming process. With sonoBYstudents we were able to demonstrate that an existing PAL concept can, with some effort, be adjusted to changing teaching circumstances. Apart from this ultrasound is a non-omittable part of medical skill training with easily appliable hygienic precautions during teaching sessions.

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.

Discussing modern poultry farming systems-insights into citizen's lay theories.

A growing public concern, especially about animal welfare problems in poultry farming systems in the EU, has been addressed by numerous (mostly quantitative) studies. However, in-depth research about the underlying reasons for the lack of acceptance concerning modern poultry farming is rare. Debates on animal welfare are often polarized. Thus, this study involved 8 exploratory focus group discussions in 4 German cities. To understand the different positions and to simulate controversial debates on animal welfare, the study includes vegetarians/vegans (as a critical and involved group) and meat eaters. The actual level of knowledge about modern poultry production among participants was heterogeneous, varying between detailed specialized knowledge and misinformation. It was found that improvements for poultry animal welfare that have already been achieved, such as the ban of conventional cages for laying hens in the EU, were not yet recognized by the wider public. A central finding was that participants mostly use lay theories and conclude that the actual poultry husbandry systems make a high use of antibiotics necessary, which has a negative influence on the meat products and, thus, endangers consumer health. The results also indicate that an industrialized agri-food system (rather than farmers) is held primarily responsible for the perceived problems in the poultry value chain. Furthermore, participants are aware of their responsibility and also blame their buying behavior.

Impaired post-irradiation survival of cyclooxygenase-2-deficient mice.

We investigated and evaluated post-irradiation survival in cyclooxygenase-2-deficient (COX-2 KO) mice. Thirty-day survival following exposure of COX-2 KO mice to a lethal dose of 8.5 Gy of gamma-rays was observed to be statistically significantly lower in both males and females, as well as when the sexes were merged, in comparisons with their wild-type counterparts. These findings were related to the previous observations concerning the detrimental influence of the COX-2 genetic disruption on hematopoiesis in sublethally irradiated mice. Deteriorated post-irradiation survival of COX-2 KO mice confirmed the previously anticipated conclusion regarding negative influence of the antiinflammatory action of COX-2 deficiency under the conditions of exposure of the animals to ionizing radiation.

Hematological findings in non-treated and gamma-irradiated mice deficient for MIC-1/GDF15.

Several members of the TGF-beta family are known to effectively regulate the fate of hematopoietic progenitor cells in a complex and context-dependent manner. Growth differentiation factor-15 (GDF15) is a divergent member of the TGF-beta family. This stress-induced cytokine has been proposed to possess immunomodulatory functions and its high expression is often associated with progression of a variety of pathological conditions. GDF15 is also induced by chemotherapy and irradiation. Very few fundamental studies have been published regarding the effect of GDF15 in hematopoiesis. In this study, we analyzed the hematological status of untreated and gamma-irradiated mice deficient for GDF15 as a result of genetic knock-out (KO), in order to clarify the regulatory role of GDF15 in hematopoiesis. Significant differences between GDF15 KO mice and their pertinent WT controls were found in the parameters of blood monocyte numbers, blood platelet size, and distribution width, as well as in the values of bone marrow granulocyte/macrophage progenitor cells. Different tendencies of some hematological parameters in the GDF15 KO mice in normal conditions and those under exposure of the mice to ionizing radiation were registered. These findings are discussed in the context of the GDF15 gene function and its lack under conditions of radiation-induced damage.

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.

Quality of life in patients with unilateral vestibular schwannoma on wait and see - strategy.

OBJECTIVE: A 'wait and see' strategy is an option when managing patients with small vestibular schwannomas (VS). A risk of growth and worsening of hearing may influence a patient's daily quality of life (QOL). Therefore, the present study focused on QOL parameters in patients who are on a 'wait and see' strategy following magnetic resonance imaging (MRI)-based diagnosis of small unilateral VS. PATIENTS AND METHODS: Sixty-five patients (mean age 64.4 years; male:female, 32:33) who suffered from a small unilateral VS (9.34 mm, range 1.5-23 mm) between 2013 and 2016 were included in a prospective single center study. During follow-up, in addition to clinical and neurological examinations and MRI imaging, all patients answered the Short Form 36 questionnaire once to characterize QOL. Additionally, the severity of tinnitus was determined by the Mini-TQ-12 from Hiller and Goebel. RESULTS: It was found during follow-up that there was no lowering of QOL in patients with small VS who were on 'wait and see' strategy compared with Germany's general population and no tumor growth was detected in 53 patients (81.5%). Patients with a tumor diameter larger than 10 mm did not suffer from stronger tinnitus, vertigo or unsteadiness than the group with an average tumor size, which is smaller than 10 mm. Sixty-two patients (95.4%) showed ipsilateral hearing loss and three of these reported deafness (4.6%). Severe vertigo or tinnitus is connected with lower levels of mental component scale and physical component scale. These findings reduced the QOL (p = 0.05). CONCLUSION: In our series, QOL is not influenced in patients with unilateral untreated small VS in comparison to Germany's general population. This is helpful information when advising patients during follow-up and finding out the optimal timing of individual treatment.

Equine papillomavirus type 2: An equine equivalent to human papillomavirus 16?

In horses, squamous cell carcinomas (SCC) commonly affect the external genitals. There is growing evidence that equine papillomavirus type 2 (EcPV2) infection promotes disease development. To assess the possible association of EcPV2 with equine SCCs of the head (HSCC), 15 HSCC DNA samples were screened by E6/E7, E2, and LCR PCR and amplicons were analysed for sequence variations. The physical form of EcPV2 in HSCC, genital lesions, and smegma from horses with SCC was then addressed using EcPV2 immunocapture PCR (IC/PCR) for detection of virion, and E6 vs. E2 qPCR to investigate possible integration events. Four of 15 HSCC tested positive for EcPV2 DNA and harboured known or novel genetic variants of E6, E7, E2 and the LCR. Eighteen of 35 sample extracts including 3/4 smegma samples scored positive by IC/PCR, suggesting that about 51% of tested extracts harboured virions. E6/E2 qPCR from tumour DNA revealed E2/E6 copies/cell ranging between <1 (E2; E6) and 797 (E2) or 1434 (E6). IC/PCR-positive smegma samples contained higher E2 and E6 copy numbers, ranging between 1490 and 4.95×105 (E2) or 2227 and 8.54×105 (E6) copies/cell. Together with IC/PCR results, this finding suggests that smegma can serve as a rich EcPV2 reservoir. HSCCs harboured significantly lower viral DNA amounts (<1-25 copies/cell) than most genital tumour and smegma DNA isolates. The majority of samples contained more E6 than E2 DNA, with E6:E2 ratios ranging between 0.88 and 4.12. Although not statistically significant (P>0.05), this finding suggests that EcPV2 can integrate into the equine host cell genome.

OR.NET: multi-perspective qualitative evaluation of an integrated operating room based on IEEE 11073 SDC.

PURPOSE: Clinical working environments have become very complex imposing many different tasks in diagnosis, medical treatment, and care procedures. During the German flagship project OR.NET, more than 50 partners developed technologies for an open integration of medical devices and IT systems in the operating room. The aim of the present work was to evaluate a large set of the proposed concepts from the perspectives of various stakeholders. METHOD: The demonstration OR is focused on interventions from the head and neck surgery and was developed in close cooperation with surgeons and numerous colleagues of the project partners. The demonstration OR was qualitatively evaluated including technical as well as clinical aspects. In the evaluation, a questionnaire was used to obtain feedback from hospital operators. The clinical implications were covered by structured interviews with surgeons, anesthesiologists and OR staff. RESULTS: In the present work, we qualitatively evaluate a subset of the proposed concepts from the perspectives of various stakeholders. The feedback of the clinicians indicates that there is a need for a flexible data and control integration. The hospital operators stress the need for tools to simplify risk management in openly integrated operating rooms. CONCLUSION: The implementation of openly integrated operating rooms will positively affect the surgeons, the anesthesiologists, the surgical nursing staff, as well as the technical personnel and the hospital operators. The evaluation demonstrated the need for OR integration technologies and identified the missing tools to support risk management and approval as the main barriers for future installments.

Hematological profile of untreated or ionizing radiation-exposed cyclooxygenase-2-deficient mice.

We investigated hematopoiesis in untreated and ionizing radiation-exposed cyclooxygenase-2-deficient (COX-2 KO) mice. We performed a complex hematological analysis of 16 parameters in untreated COX-2 KO male mice or COX-2 KO male mice irradiated with the dose of 4 Gy of gamma-rays and their wildtype littermates. At baseline, hematopoiesis was increased in COX-2-deficient mice, but attenuated by irradation in COX-2-deficient mice compared to wildtype. To conclude, the anti-inflammatory action of the COX-2 genetic disruption plays a positive role in hematopoiesis under basal conditions but is detrimental following radiation exposure.

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.

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.

[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.

Immunoinflammatory diseases of the central nervous system - the tale of two cytokines.

Cytokines are potent mediators of cellular communication that have crucial roles in the regulation of innate and adaptive immunoinflammatory responses. Clear evidence has emerged in recent years that the dysregulated production of cytokines may in itself be causative in the pathogenesis of certain immunoinflammatory disorders. Here we review current evidence for the involvement of two different cytokines, IFN-α and IL-6, as principal mediators of specific immunoinflammatory disorders of the CNS. IFN-α belongs to the type I IFN family and is causally linked to the development of inflammatory encephalopathy exemplified by the genetic disorder, Aicardi-Goutières syndrome. IL-6 belongs to the gp130 family of cytokines and is causally linked to a number of immunoinflammatory disorders of the CNS including neuromyelitis optica, idiopathic transverse myelitis and genetically linked autoinflammatory neurological disease. In addition to clinical evidence, experimental studies, particularly in genetically engineered mouse models with astrocyte-targeted, CNS-restricted production of IFN-α or IL-6 replicate many of the cardinal neuropathological features of these human cytokine-linked immunoinflammatory neurological disorders giving crucial evidence for a direct causative role of these cytokines and providing further rationale for the therapeutic targeting of these cytokines in neurological diseases where indicated.