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Background Differential diagnosis in children with signs of unprovoked inflammation can be challenging. In particular, differentiating systemic juvenile idiopathic arthritis (SJIA) from other diagnoses is difficult. We have recently validated the complex of myeloid-related proteins 8/14 (MRP8/14, also known as S100A8/A9 complex or serum calprotectin) as a helpful biomarker supporting the diagnosis of SJIA. The results were subsequently confirmed with a commercial ELISA. However, further optimization of the analytical technology is important to ensure its feasibility for large-scale use in routine laboratory settings. Methods To evaluate the accuracy in identifying children with SJIA, the performance of a particle-enhanced immuno-turbidimetric assay for serum calprotectin (sCAL turbo) on an automated laboratory instrument was analyzed. Samples from 615 children were available with the diagnoses SJIA ( n  = 99), non-systemic JIA ( n  = 169), infections ( n  = 51), other inflammatory diseases ( n  = 126), and acute lymphoblastic leukemia (ALL, n  = 147). In addition, samples from 23 healthy controls were included. Results The sCAL turbo assay correlated well with the MRP8/14 ELISA used in previous validation studies ( r  = 0.99, p  < 0.001). It could reliably differentiate SJIA from all other diagnoses with significant accuracy (cutoff at 10,500 ng/ml, sensitivity 84%, specificity 94%, ROC area under curve 0.960, p  < 0.001). Conclusions Serum calprotectin analyses are a helpful tool supporting the diagnosis of SJIA in children with prolonged fever or inflammatory disease. Here, we show that an immuno-turbidimetric assay for detection of serum calprotectin on an automated laboratory instrument can be implemented in clinical laboratory settings to facilitate its use as a diagnostic routine test in clinical practice.

Background The evaluation of patients with abdominal discomfort is challenging and patient selection for endoscopy based on symptoms is not reliable. We evaluated the diagnostic value of fecal calprotectin in patients with abdominal discomfort. Methods In an observational study, 575 consecutive patients with abdominal discomfort referred for endoscopy to the Department of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland, were enrolled in the study. Calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. The presence of a clinically significant finding in the gastrointestinal tract was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values. Results Median calprotectin levels were higher in patients with significant findings (N = 212, median 97 μg/g, IQR 43-185) than in patients without (N = 326, 10 μg/g, IQR 10-23, P < 0.001). The area under the receiver operating characteristics curve (AUC) to identify a significant finding was 0.877 (95% CI, 0.85-0.90). Using 50 μg/g as cut off yielded a sensitivity of 73% and a specificity of 93% with good positive and negative likelihood ratios (10.8 and 0.29, respectively). Fecal calprotectin was useful as a diagnostic parameter both for findings in the upper intestinal tract (AUC 0.730, 0.66-0.79) and for the colon (AUC 0.912, 0.88-0.94) with higher diagnostic precision for the latter (P < 0.001). In patients > 50 years, the diagnostic precision remained unchanged (AUC 0.889 vs. 0.832, P = 0.165). Conclusion In patients with abdominal discomfort, fecal calprotectin is a useful non-invasive marker to identify clinically significant findings of the gastrointestinal tract, irrespective of age.

Fission yeast, Schizosaccharomyces pombe, is a natural inositol auxotroph. We show here that the amount of exogenous inositol added to the medium is critical for the control of its life cycle. Above growth-limiting concentrations inositol stimulates mating and sporulation in minimal medium. The effect of inositol is also observed on yeast-extract-medium plates. We selected a mutant, IM49, which mates and sporulates only poorly and show that it is defective in inositol transport. Its defect is in a gene (itr2) coding for a putative 12 membrane-spanning protein. The polypeptide contains the two sugar-transport motifs typical for hexose transporters and shows good homology to the two Saccharomyces cerevisiae inositol transporters. The itr2 gene is essential for cell growth and its mRNA level is repressed by glucose. Mutant IM49 is also complemented by a multicopy suppressor gene (itr1) which codes for a putative hexose transporter with unknown substrate specifity.

High-speed boat operators (HSBO) are exposed to high-impact forces and unstable platforms that are linked to spine pain and musculoskeletal injury risk. This study sought to determine the effects of different military occupational specialties (MOS) on spine kinematics in 86 active-duty personnel (64 HSBO and 22 Marines). The relationships between spine postures, pain, and disability were also examined. Upright MRI scans were performed in sitting and standing positions to determine sagittal cobb angle, angle with respect to the horizontal plane, sacral slope, T1 slope, and intervertebral angles of the lumbar and cervical spine. Disability and pain were assessed with the Oswestry Disability Index (ODI), Neck Disability Index (NDI), and a Visual Analog Scale (VAS). A two-way repeated measures ANOVA analyzed the effects of MOS and position on spine kinematics, and a stepwise linear regression analyzed the influence of pain and disability. Main effects of position were found for lumbar sagittal cobb angle, sacral slope, and intervertebral angles from L2-S1 (p < 0.0001), and cervical sagittal cobb angle (p = 0.02). MOS significantly affected sagittal cobb angle (p = 0.05) and angle w.r.t horizontal (p < 0.0001). Neck disability explained 4 % of the variance in cervical cobb angle, T1 slope, and the intervertebral angle at C5-C6. Pain did not predict lumbar or cervical spine posture. Position has a significant impact on spine kinematics in all groups, with MOS-related differences in cervical spine posture. Subjective pain measures did not reliably predict spine posture, underscoring the necessity for objective diagnostic approaches and targeted interventions to mitigate injury risk in HSBO.

Here we report a simple and cost-effective approach for the electroless plating of platinum onto mesoporous cellulosic structures to obtain catalytically active free-standing hybrid materials. Pt nanoparticles are reduced onto native cellulosic supports through wet chemical reduction of cis -[PtCl 2 (sty) 2 ] (sty = styrene). The decoration of solid cellulosic films by Pt nanoparticles was followed by Fourier transform infrared spectroscopy, reflectance mode ultraviolet–visible spectroscopy, thermogravimetric analysis, X-ray powder diffraction and scanning electron microscopy. An induction period is observed for the reduction of cis -[PtCl 2 (sty) 2 ] to spherical Pt nanoparticles onto cellulosic supports, after which the amount of deposited Pt increases rapidly. Upon coating a commercially available cellulose fabric with Pt, the Brunauer–Emmett–Teller surface area increases by a factor of 4. Catalytic properties of obtained materials are examined for two model reactions; the reduction of 4-nitrophenol to 4-aminophenol and the hydrosilylation of styrene with triethylsilane. Catalysis was particularly efficient using previously synthesized mesoporous cellulose nanocrystal films as supports due to their high specific surface area up to 177 m 2  g −1 . Free-standing Pt-decorated mesoporous cellulose films could be potentially used in catalytic applications for the production of industrially relevant compounds and wastewater treatment. Graphical abstract An approach for the electroless plating of platinum onto mesoporous cellulosic structures to obtain catalytically active free-standing hybrid materials is here reported. Obtained materials show a potential application for novel production procedures applied to industrially relevant compounds.

IntroductionChronic headache due to the overuse of medication for the treatment of migraine attacks has a prevalence of 0.5–2.0%. This guideline provides guidance for the management of medication overuse (MO) and medication overuse headache (MOH). RecommendationsTreatment of headache due to overuse of analgesics or specific migraine medications involves several stages. Patients with medication overuse (MO) or medication overuse headache (MOH) should be educated about the relationship between frequent use of symptomatic headache medication and the transition from episodic to chronic migraine (chronification), with the aim of reducing and limiting the use of acute medication. In a second step, migraine prophylaxis should be initiated in patients with migraine and overuse of analgesics or specific migraine drugs. Topiramate, onabotulinumtoxinA and the monoclonal antibodies against CGRP or the CGRP-receptor are effective in patients with chronic migraine and medication overuse. In patients with tension-type headache, prophylaxis is performed with amitriptyline. Drug prophylaxis should be supplemented by non-drug interventions. For patients in whom education and prophylactic medication are not effective, pausing acute medication is recommended. This treatment can be performed in an outpatient, day hospital or inpatient setting. Patients with headache due to overuse of opioids should undergo inpatient withdrawal. The success rate of the stepped treatment approach is 50–70% after 6 to 12 months. A high relapse rate is observed in patients with opioid overuse. Tricyclic antidepressants, neuroleptics (antiemetics) and the administration of steroids are recommended for the treatment of withdrawal symptoms or headaches during the medication pause. Consistent patient education and further close monitoring reduce the risk of relapse.

Allergen exposure via the respiratory tract and in particular via the nasal mucosa boosts systemic allergen-specific IgE production. Intranasal corticosteroids (INCS) represent a first line treatment of allergic rhinitis but their effects on this boost of allergen-specific IgE production are unclear. Here we aimed to determine in a double-blind, placebo-controlled study whether therapeutic doses of an INCS preparation, i.e., nasal fluticasone propionate, have effects on boosts of allergen-specific IgE following nasal allergen exposure. Subjects (n = 48) suffering from grass and birch pollen allergy were treated with daily fluticasone propionate or placebo nasal spray for four weeks. After two weeks of treatment, subjects underwent nasal provocation with either birch pollen allergen Bet v 1 or grass pollen allergen Phl p 5. Bet v 1 and Phl p 5-specific IgE, IgG1-4, IgM and IgA levels were measured in serum samples obtained at the time of provocation and one, two, four, six and eight weeks thereafter. Nasal allergen provocation induced a median increase to 141.1% of serum IgE levels to allergens used for provocation but not to control allergens 4 weeks after provocation. There were no significant differences regarding the boosts of allergen-specific IgE between INCS- and placebo-treated subjects. In conclusion, the application of fluticasone propionate had no significant effects on the boosts of systemic allergen-specific IgE production following nasal allergen exposure. http://clinicaltrials.gov/NCT00755066.

The respiratory epithelium is a barrier against pathogens and allergens and a target for therapy in respiratory allergy, asthma and chronic obstructive pulmonary disease (COPD). We investigated barrier-damaging factors and protective factors by real-time measurement of respiratory cell barrier integrity. Barrier integrity to cigarette smoke extract (CSE), house dust mite (HDM) extract, interferon-γ (IFN-γ) or human rhinovirus (HRV) infection alone or in combination was assessed. Corticosteroids, lipopolysaccharide (LPS), and nasal mucus proteins were tested for their ability to prevent loss of barrier integrity. Real-time impedance-based measurement revealed different patterns of CSE-, HDM-, IFN-γ- and HRV-induced damage. When per se non-damaging concentrations of harmful factors were combined, a synergetic effect was observed only for CSE and HDM. Betamethasone prevented the damaging effect of HRV and CSE, but not damage caused by HDM or IFN-γ. Real-time impedance-based measurement of respiratory epithelial barrier function is useful to study factors, which are harmful or protective. The identification of a synergetic damaging effect of CSE and HDM as well as the finding that Betamethasone protects against HRV- and CSE-induced damage may be important for asthma and COPD.

Purpose Optimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols. Methods A systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted. Results Out of 200 identified publications, 43 studies (28 retrospective, 15 prospective) were selected, encompassing 7447 patients (study sizes from 24 to 728 patients). Recurrence rates in the urinary bladder varied between 14–52%; 3–16% were muscle-invasive while 11–36% were non-muscle invasive. Nodal recurrence occurred at 13–16% and distant metastases at 15–35%. After 5 and 10 years of follow-up, around 60–85% and 45–75% of patients could preserve their bladder, respectively. Various prognostic risk factors associated with relapse and inferior survival were proposed, including higher disease stage (> c/pT2), presence of extensive/multifocal carcinoma in situ (CIS), hydronephrosis, multifocality, histological subtypes, incomplete transurethral resection of bladder tumor (TURBT) and incomplete response to radio-chemotherapy. The analyzed follow-up guidelines varied slightly in terms of the number, timing, and types of investigations, but overall, the recommendations were similar. Conclusion Randomized prospective studies should focus on evaluating the impact of specific follow-up protocols on oncological and functional outcomes following trimodal treatment for muscle-invasive bladder cancer. It is crucial to evaluate personalized adaption of follow-up protocols based on established risk factors, as there is potential for improved patient outcomes and resource allocation.

Opinion statement Allergic diseases are among the most common health issues worldwide. Specific immunotherapy has remained the only disease-modifying treatment, but it is not effective in all patients and may cause side effects. Over the last 25 years, allergen molecules from most prevalent allergen sources have been isolated and produced as recombinant proteins. Not only are these molecules useful in improved allergy diagnosis, but they also have the potential to revolutionize the treatment of allergic disease by means of immunotherapy. Panels of unmodified recombinant allergens have already been shown to effectively replace natural allergen extracts in therapy. Through genetic engineering, several molecules have been designed with modified immunological properties. Hypoallergens have been produced that have reduced IgE binding capacity but retained T cell reactivity and T cell peptides which stimulate allergen-specific T cells, and these have already been investigated in clinical trials. New vaccines have been recently created with both reduced IgE and T cell reactivity but retained ability to induce protective allergen-specific IgG antibodies. The latter approach works by fusing per se non-IgE reactive peptides derived from IgE binding sites of the allergens to a virus protein, which acts as a carrier and provides the T-cell help necessary for immune stimulation and protective antibody production. In this review, we will highlight the different novel approaches for immunotherapy and will report on prior and ongoing clinical studies.