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Objectives: The aim was to construct validity and reliability of the Hearing Implant Sound Quality Index Questionnaire (HISQUI19) in Turkish., Methods: This study was a methodologic study to validate HISQUI19 in Turkish. The study included 62 cochlear implant users. Guttman's split half-coefficient and Cronbach's alpha tests were used for construct validity and internal consistency. Pearson correlation test was used to assess the relationship of the HISQUI19 total score to the SSQ49 scales for CI users and to show test - retest reliability., Results: The Cronbach's α value was 0.94 overall score with high internal consistency (Guttman's split-half-coefficient: 0.912). Test-retest reliability results showed high repeatability and consistency of the measure across time ( r  = 0.708; P  = 0.002). Support for conducting factor analysis was provided by the KMO test, with a value of 0.876, which is 'great'., Discussion: Subjective evaluation of cochlear implant users' daily life experiences is a useful tool to reveal the auditory benefits of cochlear implant usage., Conclusion: Turkish version of the HISQUI19 is a reliable and valid assessment tool for adults with CIs. This questionnaire provides clinicians with a valuable, reliable, and valid tool for determining the subjective benefit of CI for patients.

Introduction: The treatment concept for slipped capital femoral epiphysis is still controversial. According to studies, there is currently no recommendation for a universal approach. Therefore, the aim of this study is to analyze the care reality of children with ECF in Germany., Methods: The evaluation of the study is performed based on a questionnaire sent to physicians tending to ECF in 2021. Data is compared to the literature., Results: 36 of 47 questionnaires sent out were included. Overall, no significant difference in ECF care was proven in terms of annual caseload or the size of hospital., Conclusion: A high variance in operative SCFE treatment is reported. According to current literature, the modified Dunn procedure is considered the best therapeutic option to date, especially for patients with severe or chronic ECF. However, compared with alternative care options, this is not feasible in every hospital due to its complicating and challenging nature. Central registration, minimum volume regulation, and expansion of continuing education measures can contribute to optimization., (© 2023. The Author(s).)

Objectives: Clinical laboratory results are required for critical medical decisions, underscoring the importance of quality results. As part of total quality management, external quality assessment (EQA) is a vital component to ensure laboratory accuracy. The goal of this survey was to evaluate the current status of global laboratory quality systems and assess the need for implementation, expansion, or harmonization of EQA programs (EQAP) for Clinical Chemistry and Laboratory Medicine., Methods: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on Global Laboratory Quality (TF-GLQ) conducted a survey of IFCC full and affiliate members (n=110) on laboratory quality practice. A total of 41 (37.3%) countries representing all IFCC regions except North America provided responses about EQA availability and practices., Results: All 41 countries perform EQA, 38 reported that their laboratories had EQA policies and procedures, and 39 further act/evaluate unacceptable EQA results. 39 countries indicated they have international and/or national EQAP and 30 use alternative performance assessments. EQA frequency varied among countries. Generally, an EQAP provided the EQA materials (40/41) with four countries indicating that they did not have an EQAP in their country., Conclusions: Globally, most laboratories participate in an EQAP and have defined quality procedures for EQA. There remain gaps in EQA material availability and implementation of EQA as a part of a total laboratory quality system. This survey highlights the need for education, training, and harmonization and will guide efforts of the IFCC TF-GLQ in identifying areas for enhancing global laboratory quality practices., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

The study aimed to develop a consensus classification system for the reporting of sound localization testing results, especially in the field of cochlear implantation. Against the background of an overview of the wide variations present in localization testing procedures and reporting metrics, a novel classification system was proposed to report localization errors according to the widely accepted International Classification of Functioning, Disability and Health (ICF) framework. The obtained HEARRING_LOC_ICF scale includes the ICF graded scale: 0 (no impairment), 1 (mild impairment), 2 (moderate impairment), 3 (severe impairment), and 4 (complete impairment). Improvement of comparability of localization results across institutes, localization testing setups, and listeners was demonstrated by applying the classification system retrospectively to data obtained from cohorts of normal-hearing and cochlear implant listeners at our institutes. The application of our classification system will help to facilitate multi-center studies, as well as allowing better meta-analyses of data, resulting in improved evidence-based practice in the field.

Introduction: Humoral immunity after SARS-CoV-2 vaccination has been extensively investigated in blood. Aim of this study was to develop an ELISA method in order to determine the prevalence of IgG and IgA SARS-CoV-2 domain 1 spike-protein (S) specific antibodies (Abs) in buccal and nasal mucosal surfaces of vaccinees., Methods: To this end, we analyzed 69 individuals who received their first vaccine dose between February and July 2021. Vaccines administered were BNT162b2, mRNA-1273 or ChAdOx1-nCoV-19. Detection of IgG and IgA Abs was performed using commercial ELISA kits for both blood and swab samples after protocol modification for the latter., Results: Anti-spike IgG and IgA Abs in the buccal and/or nasal swabs were detectable in >81% of the study subjects after the second dose. The IgG measurements in buccal swabs appeared to correlate in a more consistent way with the respective measurements in blood with a correlation coefficient of r=0.74. It is of note that IgA Abs appeared to be significantly more prevalent in the nasal compared to the buccal mucosa. Optimal selection of the assay cut-off for the IgG antibody detection in buccal swabs conferred a sensitivity of 91.8% and a specificity of 100%. Last, individuals vaccinated with mRNA-based vaccines exhibited higher antibody levels in both blood and mucosal surfaces compared to those receiving ChAdOx1-nCoV-19 confirming previously reported results., Conclusion: In conclusion, our findings show a differential prevalence of anti-S Abs on mucosal surfaces after vaccination for SARS-CoV-2, while they also set the basis for potential future use of IgG antibody detection in buccal swabs for extended immunity screening in large populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tsamadou, Ludwig, Scholz, Proffen, Hägele, Rode, Körper, Fabricius, Jahrsdörfer, Neuchel, Amann, Schrezenmeier and Fürst.)

Objective: The Audio Processor Satisfaction Questionnaire (APSQ) is a standardized tool to measure a user's satisfaction with their audio processor(s). It was first developed and validated in the German language. The purpose of the current study was to validate the English version of the APSQ., Design: The 15 items of the APSQ were translated into English. Item and scale analyses assessed the quality of individual items and of the questionnaire in its entirety., Study Sample: Sixty-seven adults with hearing implants participated. Forty-six of them completed the questionnaire twice within 2-4 weeks., Results: High mean values were obtained with total scores and with scores of the comfort, social life, and usability domains, indicating that users are generally satisfied with their audio processors. The questionnaire achieved good test-retest reliability with high internal consistency. A significant positive correlation between time since implantation and user satisfaction was found., Conclusion: Results of the item and reliability analyses suggest that the English version of the APSQ is a valid and reliable tool to assess user satisfaction with their audio processor(s)., Competing Interests: The authors are employed by a commercial company, MED-EL GmbH and MED-EL Corporation. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors have made all data fully available within the manuscript and Supporting information files.

Objectives: The 59-item Work Rehabilitation Questionnaire (WORQ) was developed based on the International Classification of Functioning, Disability and Health (ICF) core set for vocational rehabilitation to assess work related functioning. It was revised to include 17 questions, assigned to 14 ICF categories relevant to cochlear implant (CI) users. This cross-sectional multicenter study aimed to evaluate CI users' responses on the WORQ questions to describe and generate ICF qualifiers for the revised WORQ in CI users, forming part of a broader framework of CI outcome measures linked to the ICF., Methods: One hundred seventy-seven adults over the age of 18 years with a minimum of one year's device experience were included in the analysis. The WORQ was completed by the participants at a routine visit to the clinic, via email, or via post., Results: Most of the CI users perceived no problem on the WORQ questions (53.7%-91%), finished secondary school (54.2%) or obtained a college or university degree (32.8%) and are either employed (41.2%) or retired (34.5%). CI users that are currently working mostly have a full-time position (34.5%). Subjects reported no problem (91%) with sensation of falling, while handling communication devices and techniques (10.9%) and tinnitus (9.6%) showed the highest number of subjects reporting a complete problem., Conclusions: Overall, most of the CI users experienced no impairment, restriction or limitation on the WORQ questions and their assigned ICF categories. Their education level resembles the education level of the general population and they seem to integrate or reintegrate well in professional life postoperatively., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Lesions involving the osteochondral unit are difficult to treat. Biomimetic scaffolds are previously shown as promising alternative. Such devices often lack multiple functional layers that mimic bone, cartilage, and the interface. In this study, multilayered scaffolds are developed based on the use of natural extracellular matrix (ECM)-like biopolymers. Particular attention is paid to obtain a complex matrix that mimics the native osteochondral transition. Porous, sponge-like chitosan-collagen-octacalcium phosphate (OCP) scaffolds are obtained. Collagen content increases while the amount of OCP particles decreases toward the cartilage layer. The scaffolds are bioactive as a mineral layer is deposited containing hydroxyapatite at the bony side. The scaffolds stimulate proliferation of human adipose-derived mesenchymal stem cells, but the degree of proliferation depends on the cell seeding density. The scaffolds give rise to a zone-specific gene expression. RUNX2, COL1A1, BGLAP, and SPP1 are upregulated in the bony layer of the scaffold. SOX9 is upregulated concomitant with COL2A1 expression in the cartilage zone. Mineralization in presence of the cells is prominent in the bone area with Ca and P steadily increasing over time. These results are encouraging for the fabrication of biomimetic scaffolds using ECM-like materials and featuring gradients that mimic native tissues and their interface., (© 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Objective: The satisfaction experienced with using an audio processor is very important to hearing implant system users. Currently there are no measures that can be used to assess user satisfaction with an audio processor. This study aims to develop and validate a specific and standardised questionnaire that focuses on user satisfaction with their audio processor. Design: A preliminary version of the questionnaire was initially developed by experts in the field. Following validation of these results, the final version of the Audio Processor Satisfaction Questionnaire (APSQ) was developed consisting of 15 items. Item analyses and questionnaire validation measurements were assessed. Study sample: Sixty-nine subjects were recruited and asked to complete the APSQ twice within 2-4 weeks. Results : Subjects reported a high user satisfaction with the questionnaire and with their audio processor. The questionnaire had good reliability and results for test-retest reliability were high and significant across all items and across subscale analyses. Conclusion: Item analyses and reliability analyses show that the questionnaire is a valid and reliable tool to assess user satisfaction across different audio processors and hearing implant systems. The APSQ is a quick and easy tool to measure user satisfaction with their audio processor.

Following publication of the original article [1], the authors reported an added data on Table 1 in their paper. The original article [1] has been updated.

Background: Evaluation of core needle biopsies (CNB) is a standard procedure for the diagnosis of breast cancer. However, tissue processing and image preparation is a time- consuming procedure and instant on-site availability of high-quality images could substantially improve the efficacy of the diagnostic procedure. Conventional microscopic methods, such as frozen section analysis (FSA) for detection of malignant cells still have clear disadvantages. In the present study, we tested a confocal microscopy scanner on fresh tissue from CNB with intention to develop an alternative device to FSA in clinical practice., Patients and Methods: In 24 patients with suspicious breast lesions standard of care image-guided biopsies were performed. Confocal images have been obtained using the Histolog™ Scanner and evaluated by two independent pathologists. Hematoxylin-Eosin (H&E) histological sections of the biopsies were routinely processed in a blinded fashion with respect to the confocal images., Results: In total 42 confocal images were generated from 24 biopsy specimens, and available for analysis within a few minutes of taking the biopsy. This resulted in 2 × 42 = 84 pathologic evaluations. In four cases, a pathologic diagnosis was not possible with confocal microscopy. An exact correlation based on the B-classification was reached in 41 out of 80 examinations and in another 35 cases in a broader sense of correspondence definition (i.e. malignant vs. benign)., Conclusions: As a reliable on-site method, the Histolog™ Scanner provides a visualization of cellular details equivalent to the H&E standards, permitting rapid and accurate diagnosis of malignant and benign breast lesions. Furthermore, this device offers great potential for immediate margin analysis of specimen in breast conserving therapy.

Objective: This study was designed to investigate the presence of residual breast tissue (RBT) after skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) and to analyse patient- and therapy-related factors associated with RBT. Skin-sparing mastectomy and NSM are increasingly used surgical procedures. Prospective data on the completeness of breast tissue resection is lacking. However, such data are crucial for assessing oncologic safety of risk-reducing and curative mastectomies., Methods: Between April 2016 and August 2017, 99 SSM and 61 NSM were performed according to the SKINI-trial protocol, under either curative (n = 109) or risk-reducing (n = 51) indication. After breast removal, biopsies from the skin envelope (10 biopsies per SSM, 14 biopsies per NSM) were taken in predefined radial localizations and assessed histologically for the presence of RBT and of residual disease., Results: Residual breast tissue was detected in 82 (51.3%) mastectomies. The median RBT percentage per breast was 7.1%. Of all factors considered, only type of surgery (40.4% for SSM vs. 68.9% for NSM; P < 0.001) and surgeon (P < 0.001) were significantly associated with RBT. None of the remaining factors, e.g., skin flap necrosis, was associated significantly with RBT. Residual disease was detected in three biopsies., Conclusions: Residual breast tissue is commonly observed after SSM and NSM. In contrast, invasive or in situ carcinomas are rarely found in the skin envelope. Radicality of mastectomy in this trial is not associated with increased incidence of skin flap necrosis. ClinicalTrials.gov Identifier NCT03470909.

Given the significance of wastewater treatment and disposal for society and the economy together with the omnipresence of standards in the sector, we studied the development and prospects of the rules governing standardization in the German municipal wastewater sector. We thereby provide a detailed description of sector-specific committee-based standardization and significantly contribute to the understanding of this complex arena. We find that the German Association for Water Wastewater and Waste (DWA) has significantly improved its rules on standardization over time by aligning them closer to the generally accepted superordinate standardization principles. However, by focusing on theoretical findings of committee decision-making and committee composition, we argue that there is still scope for improvement with respect to rule reading and rule compliance. We show that the incentives at work in standardization committees are manifold, whereas the representation of the different stakeholder groups needs' remains unbalanced. Due to vested interests and potential strategic behavior of the various agents involved in standardization rule compliance does not necessarily happen naturally. To this end, we claim that the implementation of monitoring mechanisms can be a significant contribution to the institutional design of standardization and briefly discuss the advantages and disadvantages of different schemes. Finally, we show that there is ample need for future research on the optimal design of such a scheme. Even though the analysis relates specifically to the DWA our claims apply to a wide range of standards development organizations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To analyse language development of children with a cochlear implant (CI) in relation to length of CI use and age at implantation and to examine the suitability of the TEDIL as an assessment tool for measuring early language development in Turkish children., Methods: A total of 119 children implanted with a CI before 5 years of age were assessed acutely on sound field thresholds, speech recognition thresholds, open-set and closed-set monosyllabic word tests, the TEDIL, categories of auditory performance (CAP), and speech intelligibility rating (SIR). The outcome scores were analysed in relation to length of CI use (3, 4, and 5 years) and age at implantation (<24 months vs. >24 months). The TEDIL scores were compared to all other outcome measures., Results: Scores significantly increased with CI experience. CAP and SIR were significantly higher in the younger implanted group. No significant difference was observed between the younger and older implanted group on the closed-set and open-set monosyllabic tests and the TEDIL. The TEDIL scores significantly correlated with CAP, SIR, and the closed-set and open-set word scores. The mean TEDIL standard score was close to average., Conclusions: Performance of CI users improves with increased CI experience. CI users implanted <24 months tend to have better auditory skills and clearer speech than CI users implanted >24 months. CI users implanted between 24 months and 60 months tend to develop language similarly to CI users implanted <24 months. The TEDIL is a suitable tool for assessing early receptive and expressive language development in Turkish children.

Clinical success on cartilage regeneration could be achieved by using available biomaterials and cell-based approaches. In this study, we have developed a composite gel based on collagen/hyaluronic acid (Coll-HA) as ideal, physiologically representative 3D support for in vitro chondrogenesis of human adipose-derived mesenchymal stem cells (hAMSCs) co-cultured with human articular chondrocytes (hAC). The incorporation of hyaluronic acid (HA) attempted to provide an additional stimulus to the hAMSCs for chondrogenesis and extracellular matrix deposition. Coll-HA gels were fabricated by directly mixing different amounts of HA (0-5%) into collagen solution before gelation. hACs and hAMSCs were co-cultured at different ratios from 100% to 0% in steps of 25%. Thus, five different co-culture groups were tested in the various Coll-HA 3D matrices. HA greatly impacted the cell viability and proliferation as well as the mechanical properties of the Coll-HA gel. The effective Young's modulus changed from 5.8 to 9.0kPa with increasing concentrations of HA in the gel. In addition, significantly higher amounts of glycosaminoglycan (GAG) were detected that seemed to be dependent on HA content. The highest HA concentration used (5%) resulted in the lowest Collagen type X (Col10) expression for most of the cell culture groups. Unexpectedly, culturing in these gels was also associated with decreased SOX9 and Collagen type II (Col2) expression, while Collagen type III (Col3) and metalloproteinase 13 notably increased. By using 1% HA, a positive effect on SOX9 expression was observed in the co-culture groups. In addition, a significant increase in GAGs production was also detected. Regarding co-culturing, the group with 25% hAMSCs+75% hACs was the most chondrogenic one considering SOX9 and Col2 expression as well as GAGs production. This group showed negligible Col10 expression after 35days of culture independently of the gel used. It also featured the highest effective Young's modulus (9.9kPa) when cultivated in the 1% HA matrix. Concerning the level of dissolved oxygen in situ, the groups with a higher amount of hAMSCs showed lower oxygen levels (40-58% O 2 ) compared to hACs (63-74% O 2 ). This might be attributed to the higher cellular metabolism and proliferation rate of the hAMSCs. Interestingly, lower oxygen was detected in the HA-containing gels when compared to plain collagen. This may contribute to the better chondrogenesis observed in these groups. Altogether, our results indicated that HA may favor chondrogenesis, but its effect highly depends on the concentration used. Additionally, co-culture of hACs with hAMSCs also favors chondrogenesis and especially increases extracellular matrix production and decreases hypertrophy., Statement of Significance: In the clinical situation, large cartilage defects can be treated with MACT. However, this is a two-stage procedure, which increases the risk for the patient. Moreover, culturing chondrocytes leads to dedifferentiation. The matrix used for MACT is a collagen-based scaffold. In this study, it was demonstrated that hyaluronic acid, a natural component of the extracellular matrix, supplementation to a collagen hydrogel stimulates chondrogenic differentiation in a dose dependent manner. 1% HA showed the best overall results. Furthermore, exchanging 25% of human articular chondrocytes with adipose-derived mesenchymal stem cells didn't change the chondrogenic potential, but reduced going in unwanted pathways and improved biomechanical properties. This could translate to a one-step procedure and shows the potential of inducing differentiation by natural biomaterials., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Universal Newborn Hearing Screening programs, now instituted throughout the German-speaking countries, allow hearing loss to be detected and treated much earlier than ever before. With this earlier detection, arises the need for tools fit for assessing the very early speech and language production development of today's younger (0-18 month old) children. We have created the LittlEARS ® Early Speech Production Questionnaire, with the aim of meeting this need., Methods: 600 questionnaires of the pilot version of the LittlEARS ® Early Speech Production Questionnaire were distributed to parents via pediatricians' practices, day care centers, and personal contact. The completed questionnaires were statistically analyzed to determine their reliability, predictive accuracy, internal consistency, and to what extent gender or unilingualism influenced a child's score. Further, a norm curve was generated to plot the children's increased expected speech production ability with age., Results: Analysis of the data from the 352/600 returned questionnaires revealed that scores on LittlEARS ® Early Speech Production Questionnaire correlate positively with a child's age, with older children scoring higher than do younger children. Further, the questionnaire has a high measuring reliability, high predictability, high unidemensionality of scale, and is not significantly gender or uni-/multilingually biased. A norm curve for expected development with age was created., Conclusions: The LittlEARS ® Early Speech Production Questionnaire (LEESPQ) is a valid tool for assessing the most important milestones in very early development of speech and language production of German language children with normal hearing aged 0-18 months old. The questionnaire is a potentially useful tool for long-term infant screening and follow-up testing and for children with normal hearing and those who would benefit from or use hearing devices., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Ventilated preterm infants frequently develop bronchopulmonary dysplasia (BPD) which is associated with elevated inflammatory mediators in their tracheal aspirates (TA). In animal models of BPD, inhaled nitric oxide (iNO) has been shown to reduce lung inflammation, but data for human preterm infants is missing., Methods: Within a European multicenter trial of NO inhalation for preterm infants to prevent BPD (EUNO), TA was collected to determine the effects of iNO on pulmonary inflammation. TA was collected from 43 premature infants randomly assigned to receive either iNO or placebo gas (birth weight 530-1230 g, median 800 g, gestational age 24 to 28 2/7 weeks, median 26 weeks). Interleukin (IL)-1β, IL-6, IL-8, transforming growth factor (TGF)-β1, interferon γ-induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1α, acid sphingomyelinase (ASM), neuropeptide Y and leukotriene B4 were measured in serial TA samples from postnatal day 2 to 14. Furthermore, TA levels of nitrotyrosine and nitrite were determined under iNO therapy., Results: The TA levels of IP-10, IL-6, IL-8, MIP-1α, IL-1β, ASM and albumin increased with advancing postnatal age in critically ill preterm infants, whereas nitrotyrosine TA levels declined in both, iNO-treated and placebo-treated infants. The iNO treatment generally increased nitrite TA levels, whereas nitrotyrosine TA levels were not affected by iNO treatment. Furthermore, iNO treatment transiently reduced early inflammatory and fibrotic markers associated with BPD development including TGF-β1, IP-10 and IL-8, but induced a delayed increase of ASM TA levels., Conclusion: Treatment with iNO may have played a role in reducing several inflammatory and fibrotic mediators in TA of preterm infants compared to placebo-treated infants. However, survival without BPD was not affected in the main EUNO trial., Trial Registration: NCT00551642., Competing Interests: The authors have declared that no competing interests exist.

Availability of the semiessential amino acid arginine is fundamental for the efficient function of human T lymphocytes. Tumor-associated arginine deprivation, mainly induced by myeloid-derived suppressor cells, is a central mechanism of tumor immune escape from T-cell-mediated antitumor immune responses. We thus assumed that transmembranous transport of arginine must be crucial for T-cell function and studied which transporters are responsible for arginine influx into primary human T lymphocytes. Here, we show that activation via CD3 and CD28 induces arginine transport into primary human T cells. Both naïve and memory CD4(+) T cells as well as CD8(+) T cells specifically upregulated the human cationic amino acid transporter-1 (hCAT-1), with an enhanced and persistent expression under arginine starvation. When hCAT-1 induction was suppressed via siRNA transfection, arginine uptake, and cellular proliferation were impaired. In summary, our results demonstrate that hCAT-1 is a key component of efficient T-cell activation and a novel potential target structure to modulate adaptive immune responses in tumor immunity or inflammation., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Identifying seizures with prolonged duration during video-electroencephalographic (EEG) monitoring is of importance to inform clinicians when to start emergency treatment of seizures to prevent status epilepticus. The aims of this study were to assess the clinical and EEG seizure duration (SD) in consecutive patients with epilepsy who underwent prolonged video-EEG monitoring and to identify a seizure type-dependent time point to start emergency treatment based on the likelihood that seizures will not stop spontaneously. Furthermore, we sought to determine predictors of SD and explored the relationship between antiepileptic drug (AED) serum levels and SD., Material and Methods: We retrospectively analyzed 1796 seizures in 200 patients undergoing video-EEG monitoring between January 2006 and March 2008., Results: Focal simple seizures lasted significantly shorter (clinical SD: 28s, EEG SD: 42 s) compared with focal complex seizures (clinical SD: 64 s, EEG SD: 62 s), and both seizure types lasted significantly shorter compared with secondarily generalized tonic-clonic seizures (GTCSs; clinical SD: 90 s, EEG SD: 96 s). There was no difference between the duration of the convulsive phase of primary GTCSs (defined as nonfocal) and that of secondarily GTCSs (each 65 s). Cumulative clinical SD (99%) was 7 min in focal complex seizures and 11 min in focal simple seizures. Mixed linear regression model demonstrated that history of status epilepticus (P = 0.034), temporal lobe seizure onset (P = 0.040), and MRI lesions (P = 0.013) were significantly associated with logarithmic EEG SD in focal epilepsies recorded with scalp electrodes. We found significant negative correlations between the AED serum level and the EEG SD in patients treated with monotherapy: carbamazepine (P < 0.001), levetiracetam (P = 0.001), oxcarbazepine (P = 0.001), and valproic acid (P = 0.038) but not with lamotrigine monotherapy and EEG SD., Discussion: Based on the results of this study, we propose 2 min of convulsive seizure activity (irrespective of focal or generalized onset) as a prolonged seizure, which could serve as a time point to consider treatment to prevent status epilepticus. In focal complex seizures, we suggest an upper limit of 7 min, and in focal simple seizures 11 min, as definition of prolonged seizures. History of status epilepticus, temporal seizure onset, and lesional MRI findings are factors associated with significantly longer SD. Negative correlations of carbamazepine, levetiracetam, oxcarbazepine, and valproic acid serum levels and SD suggest a prolonging effect on seizures during withdrawal of these AEDs during video-EEG monitoring sessions. This article is part of a Special Issue entitled "Status Epilepticus"., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Conclusions: The Hearing Implant Sound Quality Index (HISQUI19) seems to be a valid tool for quantifying the self-perceived level of auditory benefit that cochlear implant (CI) users experience in everyday listening situations. Additional research is, however, required., Objectives: To develop and validate a user-friendly instrument for quantifying the self-perceived level of auditory benefit that CI users experience in everyday listening situations., Methods: This was an explorative, uncontrolled, single-group, cross-sectional study. Items for the HISQUI19 were decided upon using user input and verified by professionals. The HISQUI19 was assessed on 75 CI users from hearing implant centres in Germany and Austria to determine the questions., Results: The HISQUI19, consisting of 19 items scored on a 7-point Likert scale, was validated. Subjects older than 60 years at time of implantation did not have significantly higher mean values than subjects younger than 60 years. Gender and whether subjects are unilateral or bilateral implant CI users did not influence self-perceived functioning. Subjects with ≤20 years of hearing loss reported no significantly higher functioning than those with >20 years of hearing loss.

This review presents results from the project "The Impact of Overweight/Obesity on Breast Cancer: data from Switzerland". Swiss data is interesting because the general female population is distinctive in two areas when compared to that of most other industrialized countries: Switzerland has comparatively low rates of overweight (22-23%) and obesity (7-8%) and has rather stable rates of overweight and obesity. The entire project comprised three major issues: (I) etiology of breast cancer (BC). There is a consistently shown association between obesity and postmenopausal BC risk in countries with high obesity prevalence rates in the literature. In our Swiss study group, however, we did not find higher rates of overweight and obesity in postmenopausal BC cases than in the general population. A possible explanation for this observation may be a curvilinear dose-response relationship between BMI and postmenopausal BC risk, so that an increased risk may only be observed in populations with a high prevalence of obese/very obese women; (II) tumor characteristics. BMI was significantly associated with tumor size; this applied not only to the cases where the tumor was found by self-detection, but also to lesions detected by radiological breast examinations. In addition, a higher BMI was positively correlated with advanced TNM stage, unfavorable grading and a higher St. Gallen risk score. No associations were observed between BMI and histological subtype, estrogen receptor status, HER2 status and triple negative BC; (III) patient compliance and persistence towards adjuvant BC therapy. Many studies found that the prognosis of overweight/obese BC patients was significantly lower than that of normal weight patients. However, failure of compliance and persistence towards therapy on the part of the patient is not a contributing factor for this observed unfavorable prognosis. In most therapy modes, patients with increasing BMI demonstrated greater motivation and perseverance towards the recommended treatment.

Background: The study evaluates the frequency of and indications for bone-metastases (BM)-related surgery and/or radiotherapy in the palliative breast cancer (BC) situation and analyzes in which phase of the palliative disease course surgery and/or radiotherapy was applied., Methods: 340 patients who developed distant metastatic disease (DMD) and died (i.e. patients with completed disease courses) were analyzed., Results: From the entire study cohort, 237 patients (69.7%) were diagnosed with BM. Out of these, 116 patients (48.9%) received BM-related radiotherapy and/or surgery during the palliative situation., Radiotherapy: 108 patients (45.6%) received 161 series (range: 1-5) with 217 volumina (range: 1-8) on 300 osseous sites. At 75.3% of the radiated sites, the spine was the most frequent radiated location. Eighty-eight series (54.7%) were performed in the first third of the metastatic disease survival (MDS) period. The median survival after radiotherapy was 14 months (range: 0.2-121 months)., Surgery: In 37 patients (15.6%), 50 procedures (range: 1-4) were necessary to stabilize BM. The femur predominated with 56.0% of the procedures. Twenty procedures (40.0%) were performed in the first third of survival follow-up. The median survival after surgery was 13.5 months (range: 0.5-49 months). BC patients with BM had a significantly improved MDS when radiotherapy and/or surgery for skeletal metastases was embedded in the palliative approach (27.5 months vs. 19.5 months, p<0.001). From the 118 patients who had a MDS of ≥24 months, the majority (54.2%) had BM-related radiotherapy and/or surgery during the palliative course., Conclusions: Metastatic BC has become increasingly viewed as a chronic disease process. In a general palliative therapy approach, which allows for treatment according to the principles of a chronic disease, non-systemic therapy for BM, in particular radiotherapy, has a clearly established role in the therapy concept.

Aim: The LEESPQ validated on hearing, German infants is a standardized tool examining preverbal speech development. This study aims to validate the LEESPQ on hearing, Turkish infants., Materials and Methods: This is a prospective, cross-sectional validation study using the LEESPQ in Turkish. The LEESPQ was filled in once for each hearing infant. Data for ≥10 infants was collected at 19 test intervals, ≥ 0-1, ≥ 1-2……, ≥18-19 months. Psychometric validation was performed through confirmatory factor analysis, item response analysis, item analysis, and analysis of reliability and validity., Results: The LEESPQ was found to be gender independent, have high predictive accuracy and almost exclusively assess speech production ability. A very high correlation between total score and chronological age means score can be interpreted as child's speech production developmental age. Expected and minimum scores were defined for each monthly interval., Conclusion: The LEESPQ (Turkish) has clinical value to confirm typical speech production development and detect potential problems.

Introduction: Research on early cochlear implantation and first language milestones is limited. To compare language performance in cochlear implant (CI) users and hearing children, the establishment of normative data for both groups would be of benefit. To aid the data collection for Turkish hearing children and children with a CI diaries can be used., Aims: This study aimed to document the first 100-word lexicon acquired by Turkish hearing children and children with a CI during the first 2 years of hearing experience, to determine the distribution of the first 100-word lexicon per word category, the rate of acquisition of words and the effects of age at implantation on language performance., Methods: First word data was collected from 63 Turkish hearing children and 71 CI users implanted under 36 months of chronological age using a diary. The mean number of words recorded at each time interval was calculated. The time taken to achieve the first 100-word lexicon and the categories of the first words were documented. Performance under 18 months and over 24 months of age at first fitting was compared., Results: By 19-21 months of hearing age both hearing and CI user's vocabularies were of similar size. CI users developed a lexicon earlier than hearing children, but once hearing children started to acquire words their acquisition rate was faster. The distribution of words acquired per category were similar. 83% of first words were shared by both groups. No significant difference in performance was found between: hearing versus: implanted children; or earlier (<18 months) versus later (≥24 months) implanted children., Conclusions: The vocabulary of hearing children compared to CI users are similar in size and the category. Early access to auditory stimuli facilitates children with a hearing loss to develop vocabularies similar to hearing children in the short term., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: This study evaluates the frequency of and indications for disease-related surgical procedures in the palliative breast cancer (BC) situation., Patients & Methods: Based on a cohort of women who were treated for newly diagnosed BC during a 20-year period (1990-2009), we analyzed 340 patients who developed distant metastatic disease (DMD) until 2011 and died (i.e. still ongoing palliative disease courses were not included)., Results: One hundred and twenty-seven surgical procedures were performed in 100 patients (29.4% of all patients with metastatic disease). The most common site for surgery was breast (n = 60, 47.2%). The primary tumor was removed at first diagnosis of DMD in 43 patients (33.9%); sixteen operations (12.6%) were performed for local recurrence. In 37 patients, 50 surgical procedures (39.4%) were necessary to stabilize osseous structures due to metastases. Procedures were rarely performed on other common metastatic sites: lung: n = 1 (0.8%); liver: n = 1 (0.8%), brain: n = 4 (3.1%). When excluding surgery for primary breast tumors at initial diagnosis of DMD from analysis, 34 of 84 surgeries (40.4%) were performed in the first third of survival follow-up (i.e. period of metastatic disease survival); operations in the last two-thirds each totaled 29.8% (n = 25). The median survival after surgery was 16 months (range: 0.5-89 months)., Conclusions: In a cohort of BC patients who had primary or developed secondary DMD, nearly one third of the patients received disease-related surgical procedures during their palliative disease course. This high rate of operations shows that surgery has a clearly established role in the palliative therapy concept., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: This study aims to assess the usefulness of the LittlEARS(®) Auditory Questionnaire (LEAQ) in determining the audiological development of Turkish children who have received a cochlear implant., Methods: 20 children received a cochlear implant before their 3rd birthday. Each child's progress was evaluated with the LittlEARS(®) Auditory Questionnaire at first device fitting and then at 3-month intervals for 2 years. Scores were compared with the age-related norms established by hearing children., Results: All children showed a significant increase in LittlEARS(®) Auditory Questionnaire scores over time. Nearly all children showed a growth in auditory skills similar to that of hearing children. Children without additional needs showed more development than did children with additional needs., Conclusions: The LittlEARS(®) Auditory Questionnaire is useful for monitoring the audiological development of young children with a cochlear implant. Confirmation that a cochlear implant user is achieving typical auditory milestones serves to boost parental morale during a child's pre-verbal stage when parents may be anxious about their child's ability to talk. The questionnaire could also be useful as an early warning system. Poor scores likely indicate that something is impeding the child's development. This should prompt professionals to try to identify the impediment, whether technical, medical, social or educational and, possibly, eliminate/mitigate its effects while the child is still in his/her critical development stages., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Vulvar lichen sclerosus (LS) is a chronic inflammatory and mutilating disease, which goes often undetected for years. Advanced disease severely affects quality of life like sexual disorders and is also associated with an increased risk of vulvar cancer., Aim: To develop and validate a patient-administered symptom score and a physician-administered clinical score for the diagnosis and evaluation of vulvar LS., Methods: We included 24 patients with established LS diagnosis and 49 with other vulvar disease. The physician-administered score was based on six clinical features and the patient-administered score was a symptom-based four-item composite score. We determined inter-item correlations and internal consistency of both scores, and estimated sensitivities, specificities, likelihood ratios, and posttest probabilities for different cutoffs of the physician-administered score., Main Outcome Measures: Characteristics of patients with and without LS were compared using χ(2) and unpaired t-test as required. We then determined Cronbach's alpha as a measure of the overall consistency of scores and calculated positive and negative likelihoods., Results: Lack of redundancy of items (correlation coefficients < 0.90) and internal consistency (Cronbach's α ≥ 0.70) suggested that final composite scores were valid and yielded excellent power to rule in LS., Conclusion: Scores may be useful for assessing symptoms of vulvar disorders, to ease diagnosis of LS and to evaluate treatment response over time., (© 2012 International Society for Sexual Medicine.)

The "Comprehensive ICF Core Set for Low Back Pain (LBP)" is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning for patients with LBP. The aim of this study was to validate the Comprehensive ICF Core Set for low back pain from the perspective of physical therapists. Physical therapists experienced in LBP treatment were asked about the patients' problems, patients' resources and aspects of environment treated by physical therapists in a three-round survey using the Delphi technique. Responses were linked to the ICF. Eighty-four physical therapists in 32 countries named 1955 concepts that covered all ICF components. Fourteen ICF categories were not represented in the Comprehensive ICF Core Set for LBP although at least 75% of the participants have rated them as important. Most of them belonged to the ICF component "Body Functions". Twenty-eight concepts were linked to the not-yet-developed ICF component personal factors. Further, 21 issues were not covered by the ICF. The validity of the ICF components "Body Structures", "Activities and Participation" and "Environmental Factors" was largely supported by the physical therapists. However, several body functions were identified which are not covered and need further investigation., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: The "Extended ICF Core Set for stroke" is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning of people with stroke., Objective: The objective of this study was to validate this ICF Core Set from the perspective of physical therapists., Design and Methods: Physical therapists experienced in stroke intervention were asked about their patients' problems and resources and about aspects of the environment that physical therapists treat in people with stroke in a 3-round electronic-mail survey using the Delphi technique. The responses were linked to the ICF. The degree of agreement was calculated using the kappa statistic., Results: One hundred twenty-five physical therapists from 24 countries named 4,793 problems treated by physical therapists in people with stroke. They identified 10 second-level ICF categories that currently are not represented in the Extended ICF Core Set for stroke. Twelve responses of the participants were linked to the ICF component personal factors, and 15 responses were not covered by the current version of the classification. The kappa coefficient for the linking agreement was 0.39 (95% bootstrapped confidence interval=0.34-0.41)., Limitations: Two World Health Organization regions were not represented in the sample of physical therapists., Conclusions: According to the physical therapists, the current version of the Extended ICF Core Set for stroke largely covers the types of problems that their interventions address. However, some aspects of functioning emerged that are not yet covered and may need further investigation.

Background: Patient-Reported Outcomes (PROs) are considered important outcomes because they reflect the patient's experience in clinical trials. PROs have been included in the field of haemophilia only recently., Purpose: Comparing the contents of PROs measures used in haemophilia, based on the ICF/ICF-CY as frame of reference., Methods: Haemophilia-specific PROs for adults and children were selected on the grounds of international accessibility. The content of the selected instruments were examined by linking the concepts within the items of these instruments to the ICF/ICF-CY., Results: Within the 5 selected instruments 365 concepts were identified, of which 283 concepts were linked to the ICF/ICF CY and mapped into 70 different categories. The most frequently used categories were "b152: Emotional functions" and "e1101: Drugs"., Conclusions: The present paper provides an overview on current PROs in haemophilia and facilitates the selection of appropriate instruments for specific purposes in clinical and research settings. This work was made possible by the grant of the European Murinet Project (Multidisciplinary Research Network on Health and Disability in Europe).

The objective of the study is to analyze plasma amino acid concentrations in propionic acidemia (PA) for the purpose of elucidating possible correlations between propionyl-CoA carboxylase deficiency and distinct amino acid behavior. Plasma concentrations of 19 amino acids were measured in 240 random samples from 11 patients (6 families) with enzymatically and/or genetically proven propionic acidemia (sampling period, January 2001-December 2007). They were compared with reference values from the literature and correlated with age using the Pearson correlation coefficient test. Decreased plasma concentrations were observed for glutamine, histidine, threonine, valine, isoleucine, leucine, phenylalanine and arginine. Levels of glycine, alanine and aspartate were elevated, while values of serine, asparagine, ornithine and glutamate were normal. For lysine, proline and methionine a clear association was not possible. Significant correlations with age were observed for 13 amino acids (positive correlation: asparagine, glutamine, proline, alanine, histidine, threonine, methionine, arginine; negative correlation: leucine, phenylalanine, ornithine, glutamate and aspartate). This study gives new insight over long-term changes in plasma amino acid concentrations and may provide options for future therapies (e.g., substitution of anaplerotic substances) in PA patients.

Objective: The aim of this prospective study was to evaluate the feasibility and outcome of an adjustable sling system AMI in patients with recurrent urinary stress incontinence after failed suburethral sling insertion., Patients and Methods: Twenty-five patients with recurrent urinary stress incontinence treated with an adjustable sling system AMI were analyzed for feasibility and outcome. Patients' incontinence bother was quantified using the Visual Analogue Scale (VAS) from 0 to 10. Multichannel urodynamics and pad tests were pre- and postoperatively performed. Time of adjustment, time of the surgical intervention, and clinical outcome were also recorded., Results: Twenty-five patients were treated with the adjustable sling system AMI. Median time of adjustment was 3 days (range 1-8) and a median follow up time of 12 months. Twenty-one out of 25 patients were continent, four patients suffered from persisting incontinence. One patient was put on clean intermittent self-catheterization (CISC). Detrusor pressure at maximum flow rate (pdet/Qmax) increased significantly as did the maximum urethral closure pressure (MUCP). Patient satisfaction improved significantly., Conclusion: Adjustable slings in women with stress urinary incontinence might be indicated in difficult situations after surgical failure. As we present a selective group of patients these findings may not apply to other patients with recurrent stress incontinence., ((c) 2009 Wiley-Liss, Inc.)

Background: Recent studies indicate an increased mortality of anemic patients with renal failure when near-normal hemoglobin levels are aimed for by treatment with erythropoiesis stimulating agents. Aortic pulse wave velocity (aPWV) is a strong predictor of all-cause and cardiovascular mortality in patients with end-stage renal disease. The relationships between aPWV, hemoglobin levels and erythropoiesis stimulating agent dosage have not been evaluated to date., Methods: In 75 patients, aPWV was measured by applanation tonometry. Associations of aPWV and a broad range of clinical, laboratory and therapeutic parameters were determined by stepwise linear regression analysis., Results: aPWV was positively correlated to age (r = 0.55, p < 0.001), whereas the association with hemoglobin was significant, but negative (r = -0.31, p = 0.01). Multivariate analysis determined age (beta = 0.513, p < 0.001), mean blood pressure (beta = 0.255, p = 0.01), the presence of heart failure (beta = 0.188, p = 0.03), hemoglobin (beta = -0.226, p = 0.01), daily calcium load (beta = -0.230, p = 0.01) and the presence of diabetes mellitus (beta = 0.179, p = 0.04) to have a significant and independent influence on aPWV., Conclusions: This study demonstrates that in hemodialysis patients, aPWV is significantly but negatively associated with the serum hemoglobin concentration, even after multiple adjustments for other covariates., (Copyright (c) 2009 S. Karger AG, Basel.)

Objectives: To identify the concepts contained in treatment outcomes of randomized controlled trials (RCTs) for interventions in patients with fibromyalgia (FM) using the International Classification of Functioning, Disability, and Health (ICF) as external reference., Methods: RCTs between 1992 and 2001 were located in MEDLINE and selected according to predefined eligibility criteria. The outcome measures were extracted and the concepts within the outcome measures were identified and linked to the ICF using a content-analytical approach., Results: Forty-two trials on FM were included. Twenty-seven different questionnaires were extracted. Of all, 79.2% (N=236) of the clinical and physiologic outcomes could be linked to 31 different ICF categories and 84.7% (N=964) of the concepts contained in the health-status questionnaire to 113 ICF categories., Conclusions: The ICF provides a useful external reference to identify the concepts contained in outcome measures used in RCTs in FM.

Objective: To compare the content covered by twelve obesity-specific health status measures using the International Classification of Functioning, Disability and Health (ICF)., Design: Obesity-specific health status measures were identified and then linked to the ICF separately by two trained health professionals according to standardized guidelines. The degree of agreement between health professionals was calculated by means of the kappa (kappa) statistic. Bootstrapped confidence intervals (CI) were calculated. The obesity-specific health-status measures were compared on the component and category level of the ICF., Measurements: welve condition-specific health-status measures were identified and included in this study, namely the obesity-related problem scale, the obesity eating problems scale, the obesity-related coping and obesity-related distress questionnaire, the impact of weight on quality of life questionnaire (short version), the health-related quality of life questionnaire, the obesity adjustment survey (short form), the short specific quality of life scale, the obesity-related well-being questionnaire, the bariatric analysis and reporting outcome system, the bariatric quality of life index, the obesity and weight loss quality of life questionnaire and the weight-related symptom measure., Results: In the 280 items of the eight measures, a total of 413 concepts were identified and linked to the 87 different ICF categories. The measures varied strongly in the number of concepts contained and the number of ICF categories used to map these concepts. Items on body functions varied form 12% in the obesity-related problem scale to 95% in the weight-related symptom measure. The estimated kappa coefficients ranged between 0.79 (CI: 0.72, 0.86) at the component ICFs level and 0.97 (CI: 0.93, 1.0) at the third ICF's level., Conclusion: The ICF proved highly useful for the content comparison of obesity-specific health-status measures. The results may provide clinicians and researchers with new insights when selecting health-status measures for clinical studies in obesity.

Functioning is recognized as an important study outcome in rheumatoid arthritis (RA). The Comprehensive ICF Core Set for RA is an application of the International Classification of Functioning, Disability and Health (ICF) of the World Health Organisation with the purpose of representing the typical spectrum of functioning of patients with RA. To strengthen the patient perspective, persons with RA were explicitly involved in the validation of the Comprehensive ICF Core Set for RA using qualitative methodology. The objective of the study was twofold: to come forward with a proposal for the most appropriate methodology to validate Comprehensive ICF Core Sets from the patient perspective; and to add evidence to the validation of the Comprehensive ICF Core Set for RA from the perspective of patients. The specific aims were to explore the aspects of functioning and health important to patients with RA using two different focus group approaches (open approach and ICF-based approach) and to examine to what extent these aspects are represented by the current version of the Comprehensive ICF Core Set for RA. The sampling of patients followed the maximum variation strategy. Sample size was determined by saturation. The focus groups were digitally recorded and transcribed verbatim. The meaning condensation procedure was used for the data analysis. After qualitative data analysis, the resulting concepts were linked to ICF categories according to established linking rules. Forty-nine patients participated in ten focus groups (five in each approach). Of the 76 ICF categories contained in the Comprehensive ICF Core Set for RA, 65 were reported by the patients based on the open approach and 71 based on the ICF-based approach. Sixty-six additional categories (open approach, 41; ICF-based approach, 57) that are not covered in the Comprehensive ICF Core Set for RA were raised. The existing version of the Comprehensive ICF Core Set for RA could be confirmed almost entirely by the two different focus group approaches applied. Focus groups are a highly useful qualitative method to validate the Comprehensive ICF Core Set for RA from the patient perspective. The ICF-based approach seems to be the most appropriate technique.

Background and Objectives: A closed-system technology (ACP-215, Haemonetics, Braintree, MA) enables automated washing and extended storage of frozen red blood cells (RBC). This technology was applied to wash banked RBC for removal of undesirable protein and metabolites before transfusion. We studied protein and metabolite depletion as well as RBC metabolism and viability up to 14 days postwash with regard to various pre-storage times., Materials and Methods: Thirty RBC units were collected by means of apheresis and subdivided into three arms based on prewash storage time period (6 days/group 1, 14 days/group 2, 21 days/group 3). Wash efficacy (protein depletion, IgA), RBC metabolism (pH, lactate, potassium, haemolysis) and cell viability (ATP) were analysed immediately and 14 days after washing., Results: Total protein and IgA postwash were lowered by automated wash in all groups and uniformly met EC guidelines. Potassium (mmol/l) was below 1.2 mmol/l postwash and significantly below prewash values in all groups, even after 14 days of storage (prewash vs. postwash; P < 0.05). RBCs washed after 14 and 21 days, respectively, showed significantly lower pH values and lower ATP content than RBCs washed after only 6 days of storage. Haemolysis rate remained significantly below 0.8%, the maximum level recommended by the EC guidelines, immediately and 14 days after washing in all units., Conclusion: Our data confirm that RBC units banked up to 21 days can be effectively protein- and potassium-depleted with the ACP-215 independent from prewash storage time. With respect to high ATP levels and pH, postwash storage of 2 weeks should be limited to units not older than 7 days before wash. This new washing technology ensures better standardization in washed RBC and provides blood centres with a logistical alternative to 24-h washed RBC products.

Objectives: To identify the most typical and relevant categories of the International Classification of Functioning, Disability and Health (ICF) for patients with low back pain, osteoporosis, rheumatoid arthritis, osteoarthritis, chronic generalized pain, stroke, depression, obesity, chronic ischaemic heart disease, obstructive pulmonary disease, diabetes mellitus, and breast cancer., Methods: An international expert survey using the Delphi technique was conducted. Data were collected in 3 rounds. Answers were linked to the ICF and analysed for the degree of consensus., Results: Between 21 (osteoporosis, chronic ischaemic heart disease, and obstructive pulmonary disease) and 43 (stroke) experts responded in each of the conditions. In all conditions, with the exception of depression, there were categories in all ICF components that were considered typical and/or relevant by at least 80% of the responders. While all conditions had a distinct typical spectrum of relevant ICF categories, there were also some common relevant categories throughout the majority of conditions., Conclusion: Lists of ICF categories that are considered relevant and typical for specific conditions by international experts could be created. This is an important step towards identifying ICF Core Sets for chronic conditions.

Objectives: The objective of this study was to link the Western Ontario and McMaster Universities (WOMAC) and Lequesne-Algofunctional indices to the ICF on the basis of linking rules developed specifically to accomplish this aim. The linking process enables the understanding of the relationship between health-status measures and the ICF., Methods: Since the fifth World Health Organisation/International Liege Against Rheumatism (WHO/ILAR) Task Force and the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group recommend the use of WOMAC and the Lequesne-Algofunctional indices in patients with osteoarthritis of the hip and knee in clinical trials, these two health-status measures have been used in this study. Both health-status measures were linked to the ICF separately by two trained health professionals. Consensus between health professionals was used to decide which ICF category should be linked to each item/concept of the two questionnaires. To resolve disagreements between the two health professionals, a third person trained in the linking rules was consulted., Results: Except for the concept of 'morning stiffness', both health professionals agreed on the ICF category chosen to link all the items/concepts of both questionnaires. Altogether, 29 different ICF categories have been linked. Five ICF categories belong to the ICF component 'body functions', 23 categories to the component 'activities and participation', and one category to 'environmental factors'. Both questionnaires have 10 ICF categories in common., Conclusions: The results of the linking process reflect both the structure of the two questionnaires studied and the relationship between them, showing that the ICF classification can become the cardinal reference for existing health-status measures.

Purpose: We determine the sensitivity and specificity of cytokeratin 20 (CK-20) and mucin 7 (MUC7) gene expression in voided urine samples taken from patients with bladder tumor and from control groups to investigate putative, noninvasive urinary markers for bladder tumor detection and monitoring., Materials and Methods: Voided urine samples were collected from 50 patients with histologically proven bladder neoplasms (pTaN0M0G1-3 in 19 and pTisN0M0G3-pT4pN1M1G3 in 31), 20 patients with urolithiasis, 20 patients with urinary tract infection, 20 patients with other urological neoplasms and 20 healthy volunteers. Total RNA was extracted from exfoliated cells collected from 200 ml. voided urine. All RNA samples were investigated by a specific CK-20 and MUC7 nested reverse transcriptase polymerase chain reaction., Results: The overall sensitivity of CK-20 gene expression in voided urine samples for the detection of bladder neoplasms was 78%. In contrast, voided urine samples from control patients and healthy volunteers showed a high rate of false-positive CK-20 detection resulting in a low specificity of 36%. The overall sensitivity of the MUC7 test for all bladder tumor cases was 66%. The sensitivity for papillary urothelial neoplasms (pTaN0M0G1-3) was 42% whereas analysis of the carcinoma in situ and invasive bladder cancer group (pTisN0M0G3-pT4pN1M1G3) yielded a sensitivity of 81%. The overall specificity of the MUC7 nested reverse transcriptase polymerase chain reaction method in the control groups was 80%., Conclusions: A high positive CK-20 detection rate was found not only in voided urine samples from patients with bladder tumor, but also in urine specimens from control groups. Therefore, CK-20 is not a reliable urinary tumor marker for bladder neoplasms. In contrast to CK-20, analysis of MUC7 demonstrated a high sensitivity and high specificity for carcinoma in situ and invasive bladder cancer, thus fulfilling the criteria of a urinary tumor marker.

The human tumour associated cancer antigen CA 125 is a glycoprotein with high molecular weight. The determination of this antigen has been proven to be useful in the monitoring of patients with ovarian cancer. OPUS OV, the tumour marker assay for the ovarian cancer antigen CA 125 is an ELISA that was developed for the family of fully automated random-access analyzers, OPUS, OPUS Plus and OPUS I Magnum. The assay uses a double monoclonal sandwich format (antibodies B27.1 and B43.13, Biomira/Canada). The first antibody is immobilized on the solid phase of the OPUS modules. Sample is automatically added and incubated for 5 minutes. The addition of a solution of the second antibody conjugated to the enzyme alkaline phosphatase leads to the formation of a sandwich complex within 5 minutes. The last step, the addition of the fluorogenic substrate 4-methylumbelliferyl phosphate, serves both as washing procedure and for the development of the fluorescence signal (kinetic measurement). OPUS OV has an assay range from 0-1000 kU/L with a detection limit of 5 kU/L. Within run cv's are 6-8%. A good correlation was found to commercially available kits for the determination of CA 125. We conclude that this new OPUS OV assay is a valid alternative for use in the routine determination of the cancer associated antigen CA 125 and allows more reliable determinations in terms of random access, speed, and ease of operation.

The properties of Sf9 and Tn5 insect cells were analyzed comparatively under serum-free culture conditions. Sf9 cells in SF900II medium apparently utilized sucrose as a primary nutrient both before and after virus infection, yielding small amounts of lactate and ammonia. Tn5 cells in Excell 401 medium consumed all the nutrients examined, including sucrose. The productivity of a recombinant glycoprotein, OSF-2, by Tn5 cells, was moderate in both monolayer and spinner cultures, but the ability to secrete it was compromised in the former case. Relative to the Tn5 cultures, Sf9 produced 30-fold more OSF-2 in either culture mode. (c) 1996 John Wiley & Sons, Inc.

Osteoblast-specific factor 2 (OSF-2) is a approximately 90-kDa protein selectively expressed in bone. OSF-2 cDNA was recently isolated from mouse and human cDNA libraries and shows limited sequence homology with fasciclin I, a cell adhesion protein expressed in insect nerve cells. Here we describe the expression of recombinant murine OSF-2 (rmOSF-2) in a baculovirus/insect cell system. Western blotting analysis employing polyclonal antiserum raised against a C-terminal synthetic OSF-2 peptide detected a protein of approximately 90-kDa as early as 2 days after infection of Sf9 cells with the recombinant virus. Tunicamycin treatment of infected cells resulted in a mobility shift of OSF-2 (approximately 90-kDa band) on Western blots. N-Glycanase digestion resulted in the same mobility shift of OSF-2, indicating that rmOSF-2 expressed in insect cells is N-glycosylated. However, OSF-2 was insensitive to endoglycosidase H digestion while a major fraction of this protein had affinity for concanavalin A. Finally, it was demonstrated that rmOSF-2 was able to bind to heparin. This finding suggests that OSF-2 might be associated with the bone extracellular matrix after secretion by osteoblasts and participate in cell adhesion and/or cell communication. The establishment of the baculovirus expression system with a high productivity of recombinant OSF-2 (around 40 micrograms/ml at maximum) and its heparin binding properties should allow us to obtain large amounts of rmOSF-2.

The cDNAs encoding the porcine 65- and 67-kDa glutamic acid decarboxylases (GAD65 and GAD67, respectively) were cloned by the PCR method. The 2246-nucleotide (nt) GAD65 cDNA contained an open reading frame (ORF) coding for a protein of 585 amino acids (aa), and the 3262-nt GAD67 cDNA contained an ORF coding for a protein of 594 aa. A remarkable conservation was shown when the deduced aa sequences of porcine GAD65 and GAD67 were compared with those of other mammalian species (human, cat and rat). Porcine GAD65 is 96% identical to human and rat GAD65, and porcine GAD67 is more than 95% identical to human, cat and rat GAD67 at the aa level.

A genetically-engineered strain of Saccharomyces cerevisiae employed for the industrial production of the human coagulation Factor XIIIa (rhFXIIIa) was used for a survival study under simulated environmental conditions. The homologous strain devoid of the recombinant plasmid and the homologous strain bearing the 2 microns-based vector plasmid without the rhFXIIIa-encoding DNA insert were compared. The strains were introduced into natural soil/water suspension, into soil/medium suspension and into waste water. After intervals, samples of cell suspensions were taken and viable cell numbers were determined by plating on antibiotic-containing medium. In addition, a non-radioactive technique involving enhanced chemiluminescence was employed to detect plasmid-bearing yeast cells. The rhFXIIIa expression plasmid showed a high stability during the simulated environmental condition. No differences in survival rates, however, could be detected for the plasmid-bearing and plasmid-less strains under the three conditions tested, suggesting that the presence of plasmid does not confer selective advantages on the survival of the yeast cells. It is concluded that, even after accidental release of the engineered yeast cells into the environment, elimination rates would be comparable to those for non-recombinant yeast strains.

The preferential screening of cDNA libraries derived from the mouse osteoblastic cell line MC3T3-E1 has yielded a cDNA clone encoding 796 amino acids including the typical 24-residue-long signal sequence. The predicted amino acid sequence revealed that this protein constitutes a new member of the cadherin family. We propose the name OB-cadherin (OB for osteoblast) for this new protein. RNA analyses revealed that the OB-cadherin gene is selectively expressed in osteoblastic cell lines, precursor cell lines of osteoblasts, and primary osteoblastic cells from calvaria, as well as in lung, testis, and brain tissues at low levels. Transfection of OB-cadherin cDNA into L cells resulted in the acquisition of the Ca(2+)-dependent adhesive property. Two different forms of the human OB-cadherin cDNA were subsequently cloned; one is a counterpart of mouse OB-cadherin gene, and the other encodes a protein with a truncated cytoplasmic domain. The results suggest that the newly found OB-cadherin might have an important role in bone formation.

A cDNA library prepared from the mouse osteoblastic cell line, MC3T3-E1, was screened for the presence of specifically expressed genes by employing subtraction hybridization/differential screening methods. A cDNA clone was identified and sequenced, encoding a protein designated as osteoblast specific factor 3 (OSF-3) comprising 199 amino acids. RNA dot blot analysis indicated weak OSF-3 expression in thymus, spleen, brain, lung, testis, and heart, and high expression in kidney and liver. A homology search of an amino acid sequence database revealed a strong relationship of OSF-3 to the MER5 (gene preferentially expression in murine erythroleukemia cells) protein and human pag (proliferation associated gene) product. This indicates that OSF-3 plays an intrinsic role in the proliferation and/or differentiation of bone cells.

Anti-P-glycoprotein (P-gp) monoclonal antibody, MRK16, and its F(ab')2 fragment were evaluated for its therapeutic efficacy to P-gp-mediated multidrug resistant human colorectal carcinoma cell lines in a nude mouse model. In a blood clearance experiment, 125I-labeled MRK16 had a half-life (16 h) 7 times longer than its F(ab')2 fragment (half-life of 1.8 h) in circulation in nude mice, and approximately 16 and 5% of MRK16 were retained on days 10 and 20 after injection, respectively. In biodistribution experiments using nude mice bearing HCT-15, an intrinsically resistant cell line, 125I-labeled MRK16 accumulated at the tumor site significantly higher than its F(ab')2 fragment as revealed by the percentage of injected dose/g of tissue values (7.4 versus 0.6%) on day 3 after injection. In contrast, the tissue to blood ratio at the tumor site of the MRK16 was significantly lower than that of its F(ab')2 fragment (1.2 versus 10.5). Specific targeting of the MRK16 F(ab')2 fragment to the P-gp-positive tumor (HCT-15) but not to the P-gp-negative tumor (COLO 205) was observed in the nude mice bearing both tumors. In the therapeutic efficacy tests, when administered i.v. 3 times on days 1, 4, and 7 after tumor s.c. inoculation, MRK16 alone showed the significant inhibition of tumor growth of P-gp-positive cell lines, HCT-15, DLD-1, SW480, and SW1417 in contrast to cases of P-gp-negative cell lines, COLO 205 and KM20L2. This inhibitory effect of MRK16 was enhanced in combination with Adriamycin, which alone hardly inhibited the tumor growth. However, MRK16 F(ab')2 fragment alone, even at 1 mg/mouse, had little inhibitory effect on the growth of HCT-15 in the same treatment schedule. When administered at early palpable stage, the degree of HCT-15 tumor growth suppression depended on the number of MRK16 injections. At more progressed stages, treatment with MRK16 alone showed little antitumor activity but when combined with Adriamycin resulted in significant suppression of tumor growth. The present results suggest that MRK16 may be useful for in vivo immunoscintigraphy and immunotherapy of multidrug-resistant colorectal carcinoma.

Five human nuclear antigens, RNP 70 kD, SS-A, SS-B, Sm-B and Sm-D, were produced in E. coli using the expression vector pSEM. cDNAs encoding these antigens were ligated to a truncated lacZ' gene of the vector and the beta-galactosidase fusion proteins were efficiently expressed as intracellular inclusion bodies after isopropyl-beta-thiogalactopyranoside induction. The antibody reactivities of these fusion proteins were evaluated by Western blot and by ELISA employing panel sera from patients with autoimmune diseases such as systemic lupus erythematosus, Sjögren's syndrome or mixed connective tissue disease. The three fusion proteins, RNP 70 kD, SS-B, and Sm-B, showed good reactivities in both systems, whereas the other two fusion proteins, SS-A and Sm-D, showed poor and no reactivity in both systems, respectively. It can be concluded that RNP 70 kD, SS-B and Sm-B recombinant antigens are useful reagents for the differential diagnosis of the autoimmune diseases.