Magnetic properties of artificially designed magnetic stray field landscapes in laterally confined exchange-bias layers.

Magnetic stray fields generated by domain walls (DWs) have attracted significant attention as they might be employed for precise positioning and active control of micro- and nano-sized magnetic objects in fluids or in the field of magnonics. The presented work intends to investigate the near-field response of magnetic stray field landscapes above generic types of charged DWs as occurring in thin films with in-plane anisotropy and preferential formation of Néel type DWs when disturbed by external magnetic fields. For this purpose, artificial magnetic stripe domain patterns with three defined domain configurations, i.e. head-to-head (tail-to-tail), head-to-side, and side-by-side, were fabricated via ion bombardment induced magnetic patterning of an exchange-biased IrMn/CoFe bilayer. The magnetic stray field landscapes as well as the local magnetization reversal of the various domain configurations were analyzed in an external magnetic field by scanning magnetoresistive microscopy and compared to micromagnetic simulations.

Among the S100 proteins, S100A12 is the most significant marker for psoriasis disease activity.

BACKGROUND: Psoriasis is a chronic skin disease with deregulation of proteins in the immune system. These proteins include members of the heterogeneous S100 family, which have been discussed as potential biomarkers for disease severity. OBJECTIVE: The aim of this study was to evaluate the impact of S100A7, S100A8, S100A9 and S100A12 as possible markers for disease activity in patients with psoriasis skin disease. PATIENTS AND METHODS: S100A7, S100A8, S100A9 and S100A12 mRNA expression was determined in the skin of patients with psoriasis and controls (N = 341) by gene expression analyses. In addition, S100 serum levels were investigated by ELISA in an independent cohort of psoriasis patients (i) untreated, with different manifestations (skin/joints), (ii) under treatment (etanercept) and (iii) healthy controls, (N = 55). RESULTS: All S100-subtypes included are significantly upregulated in psoriasis skin lesions when compared with atopic dermatitis, lichen ruber and healthy donors. In untreated psoriasis patients, S100A12-serum levels showed the closest association with disease activity (PASI) (r = 0.542; P < 0.01). Serum levels decreased under treatment with etanercept (P < 0.05). CONCLUSION: Among the investigated S100-proteins, S100A12 showed the closest association with disease activity and therapeutic response and might therefore provide a valuable biomarker for psoriasis.

[Biomarkers for chronic inflammatory diseases]. / Biomarker für chronisch-entzündliche Erkrankungen.

Inflammatory disorders of childhood, such as juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) are a challenge for laboratory diagnostics. Firstly, the classical inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) often inadequately reflect disease activity but on the other hand there are few specific biomarkers that can be helpful in managing these diseases. Acute phase proteins reflect the systemic inflammatory response insufficiently as their increase is only the indirect result of local inflammatory processes. Modern inflammation diagnostics aim to reflect these local processes and to allow precise monitoring of disease activity. Experimental biomarkers, such as S100 proteins can detect subclinical inflammatory activity. In addition, established laboratory parameters exist for JIA [antinuclear antibodies (ANA), rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (anti-CCP)] and for chronic IBD (fecal calprotectin) that are useful in the treatment of these diseases.

Biological evidence for a causal role of HPV16 in a small fraction of laryngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV) is a causal factor in virtually all cervical and a subset of oropharyngeal squamous cell carcinoma (OP-SCC), whereas its role in laryngeal squamous cell carcinoma (L-SCC) is unclear. METHODS: Formalin-fixed paraffin-embedded (N=154) and deep-frozen tissues (N=55) of 102 L-SCC patients were analysed for the presence of 51 mucosal HPV types. HPV DNA-positive (HPV DNA+) cases were analysed for E6*I mRNA transcripts of all high risk (HR)/probably/possibly (p)HR-HPV identified, and for HPV type 16 (HPV16) viral load. Expression of p16(INK4a), pRb, cyclin D1 and p53 was analysed by immunohistochemistry. RESULTS: Ninety-two patients were valid in DNA analysis, of which 32 (35%) had at least one HPV DNA+ sample. Among the 29 single infections, 22 (76%) were HPV16, 2 (7%) HPV56 and 1 each (4%) HPV45, HPV53, HPV70, HPV11 and HPV42. Three cases harboured HPV16 with HPV33 (twice) or HPV45. Only 32% of HPV DNA+ findings were reproducible. Among HPV16 DNA+ L-SCC, 2 out of 23 (9%) had high viral loads, 5 out of 25 (21%) expressed E6*I mRNA and 3 out of 21 (14%) showed high p16(INK4a) and low pRb expression (all three HPV16 RNA-positive), immunohistochemical marker combination not identified in any other HPV DNA+ or HPV DNA-negative (HPV DNA-) L-SCC, respectively. CONCLUSION: HPV type 16 has a causative role in a small subgroup of L-SCC (<5% in this German hospital series).

Genotype-phenotype and genotype-origin correlations in children with mediterranean fever in Germany - an AID-net study.

Familial Mediterranean fever (FMF) is the most inherited common autoinflammatory disease (AID) with mutations in the MEFV (MEditerraneanFeVer) gene.The Mor- and Pras-Score modified for children and C-reactive protein (CRP) were used to assess FMF disease severity in Germany. We evaluate the applicability of the 2 severity scores and the correlations between ethnic origin, phenotype, and genotype.Among 242 children (median 5 age at diagnosis), we detected 431 pyrin mutations and 22 different sequence variants, including one new mutation (p.Gly488Asp). The 5 most -frequent alterations were p.Met694Val (55.2%), p.Met680lle (11.8%), p.Val726Ala (10%), p.Glu148Gln (7.9%) and p.Met694IIe (2.3%). The prevailing ancestries of 223 cases were Turkish (82.5%) and Lebanese (8.1%). Homozygous p.Met694Val substitution (30.2%) was associated with a more severe disease activity by Mor-Score, as well as with a higher mean CRP (74 mg/l) compared to patients with other mutations. Indeed, Mor- and Pras-Score were inconsistent with each other. A typical distribution of mutations in different ethnic populations was obvious, but not statistically verifiable due to the low number of cases.The homozygous p.Met694Val substitution was associated with a more severe disease activity in our German cohort. The common severity scores were inconsistent in -children.

[Genetic fever syndromes. Hereditary recurrent (periodic) fever syndromes]. / Genetische Fiebersyndrome. Hereditäre rekurrierende (periodische) Fiebersyndrome.

Genetic fever syndromes or hereditary recurrent fever syndromes (HRF) are considered to be part of the autoinflammatory diseases (AID) which result from errors in the innate immune system. Patients typically have self-limiting episodes of fever and high levels of inflammation markers. The mode of inheritance is autosomal recessive or autosomal dominant. The diseases of the HRF include familial Mediterranean fever, tumor necrosis factor receptor 1-associated periodic syndrome, hyper-IgD syndrome and cryopyrin-associated periodic fever syndromes. The disease known as deficiency of interleukin 1 (IL1) receptor antagonist does not fully belong to this group because fever is not a typical symptom. The therapy depends on the type and severity of the disease. Effective prophylaxis is possible for FMF. Biologicals, especially IL1 blocking agents are highly effective in very severe fever syndromes. In order to collect more information on AID, to establish a biobank and coordinate research in this field the AID-Net project was founded. Currently 606 patients with AID are registered of whom 381 have HRF.

[Interleukin-1-mediated diseases]. / Interleukin-1-vermittelte Erkrankungen.

Interleukin-1 (IL-1)-mediated diseases are caused by an inappropriately high production and release of IL-1 beta which results in a multitude of symptoms, e.g. arthritis, exanthema, conjunctivitis, serositis, fever and loss of hearing. If IL-1-mediated diseases remain unrecognized or are recognized and treated too late, long-term complications, such as amyloidosis may occur. In recent years the diagnostic and therapeutic options with respect to IL-1-mediated diseases have drastically improved. These diseases often manifesting in childhood can now be treated with monoclonal antibodies against IL-1 or with IL-1 receptor antagonists. Increased IL-1 secretion does not only play a role in relatively rare hereditary diseases, such as cryopyrin-associated periodic fever syndromes or familial Mediterranean fever but also in widespread diseases, such as gout or type 2 diabetes. This article will focus on pathogenic, diagnostic and therapeutic aspects of IL-1-mediated inflammatory diseases.

Assessment of Autism Spectrum Disorder in Deaf Adults with Intellectual Disability: Feasibility and Psychometric Properties of an Adapted Version of the Autism Diagnostic Observation Schedule (ADOS-2).

This study describes the adaptation of the autism diagnostic observation schedule (ADOS-2) to assess autism spectrum disorder (ASD) in adults with intellectual disability (ID) and hearing loss who communicate primarily visually. This adapted ADOS-2 was applied to residents of specialized therapeutic living communities (n = 56). The internal consistency of the adapted ADOS-2 was excellent for the Social Affect of modules 2 and 3 and acceptable for Restricted and Repetitive Behaviors subscale of module 2, but poor for module 3. Interrater reliability was comparable to standard ADOS-2 modules 1-3. Results suggest that autism symptoms of deaf adults with ID can be reliably identified by an adapted ADOS-2, provided adequate expertise in deafness, ID, ASD and proficiency in signed language by the administrator.

Screening for autism spectrum disorder in deaf adults with intellectual disability: Feasibility and accuracy of two autism screening instruments.

BACKGROUND: There is a lack of autism screening instruments for deaf or hard of hearing (DHH) adults with intellectual disability. AIMS: This study examined the diagnostic validity of the Pervasive Developmental Disorder in Mental Retardation Scale and the Diagnostic Behavioral Assessment for autism spectrum disorder - Revised in this rare population. METHODS AND PARTICIPANTS: 56 DHH adults with intellectual disability living in three specialized therapeutic communities were examined, 9 of whom met criteria for autism. OUTCOMES AND RESULTS: With minimal adaptions regarding item interpretation, both tools showed good diagnostic and high convergent validity. Items probing for difficulties in reciprocal social interaction and restricted interests were discriminant between individuals with and without autism. CONCLUSION: These data suggest that both autism screening tools are feasible and psychometrically sound when used with appropriate adaptations for DHH adults with intellectual disability.

[Methotrexate in the therapy of juvenile idiopathic arthritis]. / Methotrexat bei der Therapie der juvenilen idiopathischen Arthritis.

Treatment with low-dose methotrexate (MTX) is an important element in the therapy of juvenile idiopathic arthritis (JIA). It could be demonstrated in placebo-controlled trials that MTX is a safe and effective drug which is generally well tolerated by children and adolescents. MTX is usually used at a dose of 10-15 mg/m(2)/week, whereby oral administration is preferred for children. Side effects occur mainly in the form of gastro-intestinal discomfort such as nausea and vomiting or raised transaminases, which can be effectively treated with folic-acid supplementation.There are no general recommendations to date regarding in particular duration and discontinuation of MTX treatment or combination treatment with other disease-modifying antirheumatic drugs or biologics. These unresolved questions are the subject of current trials in which biomarkers have an increasingly important role.

Surgically assisted rapid maxillary expansion: a systematic review of complications.

A systematic review of the literature on the complications of surgically assisted maxillary expansion (SARME) was performed. The search strategy was based on the PRISMA guidelines. The PubMed, SCOPUS, and Cochrane Library databases were searched. Data were extracted from the full texts after screening of the abstracts and titles. Human clinical studies encompassing 'maxillary expansion', 'palatal expansion', 'SARME', or 'SARPE' and that reported sufficient data for 'complication' were included. In vitro studies, case reports, meta-analyses, reviews, book chapters, animal studies, and studies with missing or insufficient data were excluded. The final selection included 12 articles for data extraction. A total of 851 patients underwent SARME, with 187 reported complications (21.97%). Epistaxis (2.47%) and postoperative pain (2.00%) were the most often reported minor complications, and asymmetric or inadequate expansion presented an occurrence rate of 4.47%. Minor complications were equally distributed between surgical (49.30%) and orthodontic complications (50.70%). The technique without pterygomaxillary disjunction increased the occurrence of minor complications (29.95% vs. 16.87%), and the expansion pattern with less than 0.5 mm/day increased the occurrence of orthodontic complications (30.93% vs. 1.83%), i.e. asymmetric expansion. In conclusion, SARME procedures mostly present minor complications. Although several types of complication are described in the literature, occurrence rates are low, and technical issues such as pterygomaxillary disjunction and the pattern of distraction can be predictors of the complication risk.

The impact of language skills on mental health in teenagers with hearing impairments.

OBJECTIVE: The aim of this study was to examine the relationship of language competence level and mental distress in teenagers with hearing impairments. METHOD: 43 pupils were given a battery of linguistic tests and the Strengths and Difficulties Questionnaire (SDQ), which was also completed by 40 parents. Comparisons were made between the group of 33 children in mainstream education and 10 who were in a segregated school for the deaf. RESULTS: The children had impaired language skills relative to published norms, especially marked in segregated schools. Parents rated children as having more distress than published norms. Those with superior level of spoken language had fewer peer relationship problems in mainstream education, but significantly more in segregated schools. The reverse was almost significant for those proficient in signed language. CONCLUSION: Peer relationship problems are associated with the language competence levels in the way that children at school communicate with one another.

Failure to detect deaf-blindness in a population of people with intellectual disability.

BACKGROUND: Early identification of deaf-blindness is essential to ensure appropriate management. Previous studies indicate that deaf-blindness is often missed. We aim to discover the extent to which deaf-blindness in people with intellectual disability (ID) is undiagnosed. METHOD: A survey was made of the 253 residents of an institute offering residential and occupational facilities for people with IDs. Data are included for the 224 individuals who were able to complete both auditory and visual assessments. Otoacoustic emissions were used to screen for hearing impairment; those who did not pass were assessed by behavioural audiometry. Visual acuity was assessed with one of the following: EH-Optotypes, LH-Optotypes, Teller Acuity Cards, Cardiff Acuity Cards or the Stycar Ball Vision Test. RESULTS: Prior to the study hearing impairment had been diagnosed in 12.5% of the 224 subjects, and visual impairment in 17%. Upon completion of the study these figures rose to 46% and 38.4% respectively. Deaf-blindness was diagnosed in 3.6% of the subjects before, and in 21.4% after, the study. Most (87.5%) of the deaf-blind individuals had profound ID. CONCLUSION: Deaf-blindness is most often not identified either by standard medical screening or by care staff. Individuals with this disability, however, require provision of special kinds of care. Four categories of deaf-blindness are proposed, according to the severity of sensory impairment in each modality. The tests used in this study are non-invasive and are appropriate for individuals with ID and children. Early and periodic screening for visual and hearing impairment in individuals with ID is recommended.

Webinars for continuing education in oral and maxillofacial surgery: The Austrian experience.

The aim of the present study was to evaluate the acceptance of a webinar series for continuing medical education hosted by the Austrian Society for Oral and Maxillofacial Surgery (ÖGMKG). A series of twelve webinars was streamed via the Internet and the participants' satisfaction was evaluated by an online questionnaire. 51 out of 140 participants (36.4%) completed the questionnaire completely and were included into the study for further analysis. The mean age of the participants was 37.9 ± 8.9 and did not vary significantly between gender (p = 0.53). The results of the questionnaire revealed a positive attitude of the participants towards this kind of webinar. The participants found that the webinars allowed for an adequate transfer of knowledge. Continuing medical education by webinars in oral and maxillofacial surgery is well accepted by the participants. Although both male and female participants had a positive attitude towards the webinars, females gave even better ratings than their male counterparts did.

A Personalized Approach to Biological Therapy Using Prediction of Clinical Response Based on MRP8/14 Serum Complex Levels in Rheumatoid Arthritis Patients.

OBJECTIVES: Measurement of MRP8/14 serum levels has shown potential in predicting clinical response to different biological agents in rheumatoid arthritis (RA). We aimed to develop a treatment algorithm based on a prediction score using MRP8/14 measurements and clinical parameters predictive for response to different biological agents. METHODS: Baseline serum levels of MRP8/14 were measured in 170 patients starting treatment with infliximab, adalimumab or rituximab. We used logistic regression analysis to develop a predictive score for clinical response at 16 weeks. MRP8/14 levels along with clinical variables at baseline were investigated. We also investigated how the predictive effect of MRP8/14 was modified by drug type. A treatment algorithm was developed based on categorizing the expected response per drug type as high, intermediate or low for each patient and optimal treatment was defined. Finally, we present the utility of using this treatment algorithm in clinical practice. RESULTS: The probability of response increased with higher baseline MRP8/14 complex levels (OR = 1.39), differentially between the TNF-blockers and rituximab (OR of interaction term = 0.78), and also increased with higher DAS28 at baseline (OR = 1.28). Rheumatoid factor positivity, functional disability (a higher HAQ), and previous use of a TNF-inhibitor decreased the probability of response. Based on the treatment algorithm 80 patients would have been recommended for anti-TNF treatment, 8 for rituximab, 13 for another biological treatment (other than TNFi or rituximab) and for 69 no recommendation was made. The predicted response rates matched the observed response in the cohort well. On group level the predicted response based on the algorithm resulted in a modest 10% higher response rate in our cohort with much higher differences in response probability in individual patients treated contrary to treatment recommendation. CONCLUSIONS: Prediction of response using MRP8/14 levels along with clinical predictors has potential in personalizing treatment for RA patients starting biological anti-rheumatic treatment, and might increase cost-effectiveness.

Mental distress and quality of life in the hard of hearing.

OBJECTIVE: This study aims to compare levels of psychological distress and the quality of life in the hard of hearing with levels reported by the signing deaf, and the hearing population. METHOD: A total of 373 members of the Hard of Hearing Association completed the brief WHO's Quality of Life, 12-item General Health Questionnaire and Brief Symptom Inventory, and provided details about their initial and current deafness. RESULTS: The hard of hearing have worse social relationships than the signing deaf, and are disadvantaged relative to the hearing in all areas measured. Quality of life is related to the level of satisfaction with the hearing achieved by hearing aids. CONCLUSION: General psychiatrists need to be aware that patients who are hard of hearing may be even more isolated than deaf people in a signing community. Hard of hearing patients with unsatisfactory hearing aids can be greatly assisted by cochlear implants.

[Psychosocial characteristics of deaf people: evaluation of data from a special outpatient clinic for the deaf]. / Psychosoziale Merkmale bei Gehörlosen Daten aus einer Spezialambulanz für Gehörlose.

In this publication, data from a special outpatient clinic for deaf patients in a general hospital are presented. All members of the treatment team have competency in sign language. From the patients who consecutively attended the outpatient clinic, 352 were investigated for medical and psychosocial problems. In social contacts, there is a strong orientation towards other deaf people, and communication is mainly based on sign language. Of the deaf patients, 85% of their partners are also deaf, whereas only 10.1% of children of the deaf group are also deaf. The prevalence of selected psychiatric disorders (ICD 10 F1, F2, F3, F4, F6) in deaf people was found to be similar to that in hearing populations, with the exception of somatoform disorders, which seem to be more frequent in the deaf. Deaf people also more often present with somatic and other complaints such as nervousness, anxiety, and stress. With specific outpatient clinics for the deaf in which members of the therapeutic team are competent in sign language, access to health services is equally possible for deaf people.

[Competence in verbal communication of deaf adults in Austria. I: On the intelligibility of spoken language]. / Kommunikativ-sprachliche Kompetenz gehörloser Erwachsener in Osterreich. Teil I: Zur Verständlichkeit gesprochener Sprache.

Intelligibility of spoken language of deaf adults was assessed by hearing persons. The test procedure was intended to get as close as possible to an authentic communication situation. 5 of 6 deaf speakers are not intelligible to naive listeners. Furthermore, the listeners tend to highly overestimate their understanding of the meaning of the utterances heard. Distorting written reproductions are frequent. There are significant differences between the ability of comprehension of each of the hearing persons. The necessity of visual communication systems and -helps is stressed by the deficits in spoken language found by the study at hand.