Search

Antisynthease syndrome (ASSD) is a rare, complex and understudied autoimmune disease. Internet-based studies can overcome barriers of traditional on-site research and are therefore very appealing for rare diseases. The aim of this study was to investigate patient-reported symptoms, diagnostic delay, symptoms, medical care, health status, working status, disease knowledge and willingness to participate in research of ASSD patients by conducting an international web-based survey. The multilingual questionnaire was created by an international group of rheumatologists and patients and distributed online. 236 participants from 22 countries completed the survey. 184/236 (78.0%) were female, mean age (SD) was 49.6 years (11.3) and most common antisynthetase antibody was Jo-1 (169/236, 71.6%). 79/236 (33.5%) reported to work full-time. Median diagnostic delay was one year. The most common symptom at disease onset was fatigue 159/236 (67.4%), followed by myalgia 130/236 (55.1%). The complete triad of myositis, arthritis and lung involvement verified by a clinician was present in 42/236 (17.8%) at disease onset and in 88/236 (37.3%) during the disease course. 36/236 (15.3%) reported to have been diagnosed with fibromyalgia and 40/236 (16.3%) with depression. The most reported immunosuppressive treatments were oral corticosteroids 179/236 (75.9%), followed by rituximab 85/236 (36.0%). 73/236 (30.9%) had received physiotherapy treatment. 71/236 (30.1%) reported to know useful online information sources related to ASSD. 223/236 (94.5%) were willing to share health data for research purposes once a year. Our results reiterate that internet-based research is invaluable for cooperating with patients to foster knowledge in rare diseases. [ABSTRACT FROM AUTHOR]

Background: Labor pain is difficult to measure. The aim of this proof-of-concept study is to implement and test a questionnaire assessing pain sensation during and after vaginal deliveries. Its key aspect is a highly standardized survey of patient-reported outcome (PRO) by staff not involved in routine care. Methods: Between January and November 2015 339 women were assessed 24–48 h after spontaneous or operative-vaginal delivery of a singleton. German language skills were a prerequisite to participate. The test–retest reliability was calculated in 38 women 24–36 and 48–72 h postpartum between July and October 2017. Primiparae after spontaneous delivery and multiparae with no history of operative deliveries were compared in a subgroup analysis. Results: Maximum labor pain and post-partum pain were reported a median of 9 [8–10] and 4 [3–6]. Higher ratings were associated with younger age, higher gestational ages, infant's biometrics, and the duration of laboring. Only regional analgesia tended to reduce pain perception (NRS 8 vs. 9). Higher-degree injuries were associated with less pain postpartum. The questionnaire proved to be reliable in most aspects (Cronbach's α > 0.6 for 19/21 questions) and showed an acceptable content and criterion validity (Cohen correlation > ± 0.3, interrelation between items). Conclusion: Labor is a very painful experience, irrespective of previous obstetric history. Ratings indicate inadequateness of treatment except for patients receiving preventive postoperative pain management. Systematic postpartum pain assessment, hence, is still a pending issue. Adjustments will be made concerning language skills and specific questions on effectiveness of analgesia otherwise good reliability and validity of the questionnaire were proven. [ABSTRACT FROM AUTHOR]

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Herz-, Thorax- und Gefaesschirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Immunoglobulin (Ig)G4-related disease is classified as an immune-mediated disease. The etiology of this condition has not been explained to date. Manifestations of the disease are diverse, and simultaneous involvement of multiple organs is not unusual. Case report: We report the case of a patient referred to us after multiple unsuccessful paranasal sinus operations who presented with enophthalmos and a resultant migratory keratitis with a suspected diagnosis of silent sinus syndrome. Preservation of the orbit was no longer feasible. After five years without a definitive diagnosis, we ascertained that this was a case of IgG4-related disease. Discussion: IgG4-related disease represents an important element in the differential diagnosis of chronic advanced diseases of the orbit and paranasal sinuses. The diagnosis should be considered in the case of unclear disease presentations. Typical histological findings include a storiform pattern of fibrosis, vasculopathy, and tissue infiltration by IgG4 plasma cells. [ABSTRACT FROM AUTHOR]

Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8∆int) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity. Here, we found that pharmacological Notch inhibition with dibenzazepine (DBZ) is able to essentially rescue the loss of Paneth cells, deescalate the inflammatory phenotype, and reduce intestinal permeability in casp8∆int mice. The secretory cell metaplasia in DBZ-treated casp8∆int animals is proliferative, indicating for Notch activities partially insensitive to gamma-secretase inhibition in a casp8∆int background. Our data suggest that casp8 acts in the intestinal Notch network. [ABSTRACT FROM AUTHOR]

Introduction: Due to increasing cost pressures and structural changes in the pharmaceutical industry in recent years, pharmaceutical manufacturers have been forced to focus on the optimization of their production processes. Therefore, operational excellence is receiving broader attention throughout the pharmaceutical industry. However, too many of these practices are attempting to reduce the cycle time or increase the output of single-process steps rather than optimizing the overall process from a holistic perspective. Objective: This paper addresses the concept of a 'Takt-time' analysis for pharmaceutical manufacturing. A Takt-time diagram is a tool to identify bottlenecks in a production process. It visualizes the cycle time of a product and the times per process step and relates it to customer demand (Takt time). Thus, the bottlenecks in the production flow are revealed, and production can be reorganized. However, the application of the Takt-time analysis to pharmaceutical manufacturers shows specific challenges because of their manufacturing characteristics, such as batch processing. Methods: The concept for a Takt-time analysis was developed while working on a project with a CMO of an imaging agent to address the practical challenges in implementing its concept in pharmaceutical manufacturing. Results: The concept creates the basis for a process redesign at a multiproduct production site. It lays the foundation that customer demands can be matched with an aligned production process, and that a seamless production flow driven by customer demands can be realized. [ABSTRACT FROM AUTHOR]

Copyright of Der Gynäkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Cartilage repair of full-thickness chondral defects in the knees of Goettinger minipigs was assessed by treatment with cell-free collagen type-I gel plugs of three different sizes. Methods: In 6 adult Goettinger minipigs, three full-thickness chondral defects were created in the trochlear groove of one knee of the hind leg. These defects were treated with a cell-free collagen type-I gel plug of 8, 10, or 12 mm diameter. All animals were allowed unlimited weight bearing. After 1 year, the animals were killed. Immediately after recovery, a non-destructive biomechanical testing was performed. The repair tissue quality was evaluated immunohistologically, collagen type-II protein was quantified, and a semiquantitative score (O'Driscoll score) was calculated. Results: After 1 year, a high number of cells migrated into the initially cell-free collagen gel plugs and a hyaline-like repair tissue had been created. The O'Driscoll scores were: 8 mm, 21.2 (SD, 2.8); 10 mm, 21.5 (SD, 1.6); and 12 mm, 22.3 (SD, 1.0). The determination of the e-modulus, creep and relaxation revealed that mechanical properties of the two smaller defects were closer to unaffected hyaline cartilage. Conclusions: As cell-free collagen type-I gel plugs of all three different sizes created hyaline-like repair tissue, this system seems suitable for the treatment of even larger defects. [ABSTRACT FROM AUTHOR]

Copyright of Der Orthopäde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Gynäkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The importance of the physician-patient relationship for the health care market is beyond controversy. Recent work emphasizes a two-sided asymmetric information relationship between physician and patient. In contrast to most work looking only at the physician's perspective, our paper concentrates on the patient's view. Estimation results support the hypotheses that physician consultation and health relevant behavior are not stochastically independent. In the recursive bivariate probit model, patient's health relevant behavior has a significant influence on the probability of a physician visit. This means that health care demand and not only the contact decision is determined by both, patient and physician. [ABSTRACT FROM AUTHOR]

Persistence of RNA viruses is frequently associated with non-uniform terminal nucleotide deletions at both ends of the viral genome, which are believed to restrict viral replication and transcription during persistent infection. Borna disease virus (BDV), a negative strand RNA virus with no recognizable acute phase, quickly establishes persistence. We recently demonstrated that the vast majority of BDV genomes and antigenomes possess uniformly trimmed 5′ termini, even if the virus is recovered from complementary DNA encoding a hypothetical full-length viral genome. Here we discuss different mechanisms which might lead to the selective 5′-terminal trimming of the BDV genome and subsequent retrieval of the lost genetic information. We further discuss possible benefits of genome trimming in the light of recent findings that terminal RNA structures are recognized by intracellular sensors which trigger innate immunity. We hypothesize that 5′-terminal genome trimming might represent a smart strategy of BDV to evade the antiviral host response. [ABSTRACT FROM AUTHOR]

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language–semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) – perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.Molecular Psychiatry (2007) 12, 206–220. doi:10.1038/sj.mp.4001907; published online 10 October 2006 [ABSTRACT FROM AUTHOR]

Noise in a quantum system is fundamentally governed by the statistics and the many-body state of the underlying particles. The correlated noise observed for bosonic particles (for example, photons or bosonic neutral atoms) can be explained within a classical field description with fluctuating phases; however, the anticorrelations (‘antibunching’) observed in the detection of fermionic particles have no classical analogue. Observations of such fermionic antibunching are scarce and have been confined to electrons and neutrons. Here we report the direct observation of antibunching of neutral fermionic atoms. By analysing the atomic shot noise in a set of standard absorption images of a gas of fermionic 40K atoms released from an optical lattice, we find reduced correlations for distances related to the original spacing of the trapped atoms. The detection of such quantum statistical correlations has allowed us to characterize the ordering and temperature of the Fermi gas in the lattice. Moreover, our findings are an important step towards revealing fundamental fermionic many-body quantum phases in periodic potentials, which are at the focus of current research. [ABSTRACT FROM AUTHOR]

The effects of uranium and its progeny radium are known to be harmful and their measurements in drinking water are necessary for careful monitoring. Fast and accurate methods for determination of uranium and radium in water samples with various salinity and activities concentrations have been developed. High Resolution Inductively Coupled Plasma Mass Spectrometry is used for direct measurement of uranium. Calibration is performed with 238U standards and 209Bi is used as internal standard to correct the matrix effects and plasma instability. The radium is determined by photon electron rejected alpha liquid spectrometry after a chemical separation procedure that includes co-precipitation of radium with barium sulphate, transformation of the sulphate to carbonate and extraction of radium in the scintillation cocktail. The minimal detectable activities of 3.5×10−8 Bq kg−1 for uranium and 2.3×10−4 Bq kg−1 for radium are obtained. [ABSTRACT FROM AUTHOR]

The relevance of the complexity of fetal heart rate fluctuations with regard to the classification of fetal behavioural states has not been satisfyingly clarified so far. Because of the short behavioural states, the permutation entropy provides an advantageous complexity estimation leading to the Kullback–Leibler entropy (KLE). We test the hypothesis that parameters derived from KLE can improve the classification of fetal behaviour states based on classical heart rate fluctuation parameters (SDNN, RMSSD, ln(LF), ln(HF)). From measured heartbeat sequences (35 healthy fetuses at a gestational age between 35 and 40 completed weeks) representative intervals of 256 heartbeats were visually preclassified into fetal behavioural states. Employing discriminant analysis to separate the states 1F, 2F and 4F, the best classification result by classical parameters was 80.0% (SDNN). After additionally considering KLE parameters it was improved significantly ( p<0.0005) to 94.3% (ln(LF), KLE_Mean). It could be confirmed that KLE can improve the state classification. This might reflect the consideration of different physiological aspects by classical and complexity measures. [ABSTRACT FROM AUTHOR]

Numerous studies have focused on the significance of modern marker proteins in the synovial fluid of the knee joint and in the serum both, for osteoarthritis (OA) and rheumatoid arthritis (RA). The relationship between the serum concentrations and the concentrations in the synovial fluid is still unclear. Synovial fluid and serum samples were obtained from 13 patients with advanced OA and from 8 patients with severe RA and concentrations of MMP-1, MMP-3, MMP-13, TIMP-1, COMP and MIA/CD-RAP were determined. All values were normalized against the total protein concentrations. Serum concentrations of MMP-13 in the RA-group were statistically higher than the synovial values ( P<0.05). MMP-13 was the only marker protein that revealed distinct higher levels in the serum than in the synovial fluid. The study design allows only conclusions about advanced stages of RA and OA. Longitudinal investigations may provide further information about the value of MMP-13 as a potential marker to monitor the course of RA and OA. [ABSTRACT FROM AUTHOR]

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary. Borna disease virus (BDV) polymerase can be reconstituted by co-expression of the viral genes N, P and L. N codes for two proteins, p39 and p38, resulting from alternative translation initiation. Using a viral minireplicon system we observed that unlike p39, p38 was almost completely inactive when expressed with P and L alone. Since BDV polymerase requires a 10–20 fold excess of N protein over P for high activity, we determined whether p38 might serve as buffer that influences the viral N:P ratio. We demonstrate that p38 efficiently rescued BDV polymerase activity in cells expressing unfavorably high amounts of P. [ABSTRACT FROM AUTHOR]

Introduction. Anterior knee pain is one of the major causes of knee pain in an adolescent population. It has been suggested that raised intraosseous pressure may play an important role in the development of anterior knee pain in the young patient. Material and methods. A prospective clinical multicentre study with 27 adolescent patients presenting with anterior knee pain was performed. After failure to respond to conservative treatment, all patients agreed to undergo minimally invasive intraosseous pressure measurements in local anaesthesia. All 27 patients demonstrated a positive "pain provocation test" as a response to increased intrapatellar pressure and were decompressed with a new intraosseous drilling technique. Results. The repeat intraosseous pressure measurement in 27 patients 1 year postoperatively revealed a significant reduction from 43.3±13.4 preoperatively to 24.1±4.2 mmHg (p<0.001). The pain relief was documented in the form of a reduced VAS from 7.6±1.4 to 2.1±1.1 cm after 3 years (p<0.001). Conclusion. Patients with anterior knee pain and a positive "pain provocation test" were diagnosed as suffering from a hypertension syndrome of the patella. We conclude that simple extraarticular patellar decompression may offer a valuable new form of treatment in this select group of adolescent patients with anterior knee pain. [ABSTRACT FROM AUTHOR]

Recombinant adenoviruses are presently the most efficient in vivo gene transfer system available. Targeting single organs or large tumors by adenoviral vectors requires an intravascular route of application. During the first pass of viral particles through the vascular bed of the target tissue, virus uptake is not quantitative and undefinite amounts of particles leak into circulation. To determine the amount of leaking particles and to calculate organ-specific uptake (in-/outflow ratio), it is necessary to titrate virus particles directly in blood. In preclinical and clinical trials titration is currently mostly done with blood plasma instead of full blood. However, this technique provides valid results only as long as there is no affinity between adenovirus particles and erythrocytes. In this study we demonstrate that Ad5 particles, as mostly employed for gene therapy, have a strong affinity to human erythrocytes. At 60 min after coincubation of human erythrocytes and Ad5 particles, more than 98% of the particles are attached to the surface of erythrocytes. Therefore, ignoring the amount of red cell bound particles by performing titration in plasma leads to severe miscalculation of organ-specific transfer rates or virus circulation half-life. The biological impact of an increased affinity between virus particles and erythrocytes will be discussed. [ABSTRACT FROM AUTHOR]

Copyright of Der Orthopäde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Different treatment options for penile curvature exist, such as the Nesbit procedure with complete excision of the tunica albuginea or the simple plication. We prefer a modification with only superficial excision, not opening the corpora cavernosa. From January 1997 to June 2000, 68 patients were treated surgically due to penile curvature. Data was obtained from 48 patients by telephone interview. The mean penile deviation was 46°. Excision of the tunica was performed only superficially and non-absorbable inverted sutures were used. The mean follow-up time in this study was 25 months. A total of 36 (75%) patients were satisfied postoperatively, 12 were unsatisfied. Eleven (23%) patients described a complete straightening, 37 (77%) a rest-curvature of 5-50° (mean 14°) and 21 (44%) described a shortening of 0.5-5 cm (mean 1.2 cm). Six patients reported a recurrence. No new erectile dysfunction occurred. Superficial excision of the tunica albuginea offers the advantage of tissue-contraction due to scaring without destroying the integrity of the corpora, leading in combination with non-absorbable inverted sutures to good functional and cosmetic results. [ABSTRACT FROM AUTHOR]

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Unfallchirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)