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Intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy usually starts with a 2.0 g/kg induction dose followed by 1.0 g/kg maintenance doses every 3 weeks. No dose-ranging studies with intravenous immunoglobulin maintenance therapy have been published. The Progress in Chronic Inflammatory Demyelinating polyneuropathy (ProCID) study was a prospective, double-blind, randomized, parallel-group, multicentre, phase III study investigating the efficacy and safety of 10% liquid intravenous immunoglobulin (Panzyga®) in patients with active chronic inflammatory demyelinating polyneuropathy. Patients were randomized 1:2:1 to receive the standard intravenous immunoglobulin induction dose and then either 0.5, 1.0 or 2.0 g/kg maintenance doses every 3 weeks. The primary end point was the response rate in the 1.0 g/kg group, defined as an improvement ≥1 point in adjusted Inflammatory Neuropathy Cause and Treatment score at Week 6 versus baseline and maintained at Week 24. Secondary end points included dose response and safety. This trial was registered with EudraCT (Number 2015–005443-14) and clinicaltrials.gov (NCT02638207). Between August 2017 and September 2019, the study enrolled 142 patients. All 142 were included in the safety analyses. As no post-infusion data were available for three patients, 139 were included in the efficacy analyses, of whom 121 were previously on corticosteroids. The response rate was 80% (55/69 patients) [95% confidence interval (CI): 69–88%] in the 1.0 g/kg group, 65% (22/34; CI: 48–79%) in the 0.5 g/kg group, and 92% (33/36; CI: 78–97%) in the 2.0 g/kg group. While the proportion of responders was higher with higher maintenance doses, logistic regression analysis showed that the effect on response rate was driven by a significant difference between the 0.5 and 2.0 g/kg groups, whereas the response rates in the 0.5 and 2.0 g/kg groups did not differ significantly from the 1.0 g/kg group. Fifty-six per cent of all patients had an adjusted Inflammatory Neuropathy Cause and Treatment score improvement 3 weeks after the induction dose alone. Treatment-related adverse events were reported in 16 (45.7%), 32 (46.4%) and 20 (52.6%) patients in the 0.5, 1.0 and 2.0 g/kg dose groups, respectively. The most common adverse reaction was headache. There were no treatment-related deaths. Intravenous immunoglobulin (1.0 g/kg) was efficacious and well tolerated as maintenance treatment for patients with chronic inflammatory demyelinating polyneuropathy. Further studies of different maintenance doses of intravenous immunoglobulin in chronic inflammatory demyelinating polyneuropathy are warranted.

Background For a better understanding of the factors underlying the Post-Acute COVID Syndrome, we studied the relationship between symptoms and functional alterations in COVID-19 patients 10 months after hospitalization. Methods One-hundred-one patients hospitalized between March 1st and June 30th 2020 participated in a follow-up visit for an assessment of clinical history, comorbidities, lung function, physical capacity and symptoms, including the SGRQ for health-related quality of life, PHQ-9-D for depression, and SOMS-2 J for somatoform disorders. Data were analyzed by univariate comparisons and multiple logistic regression analyses. Results Median age was 60 years, 42% were female, 76% had at least one comorbidity, the median length of the hospital stay was 8 days, 19% had been on the ICU. The most prevalent symptoms included shortness of breath (49%), fatigue (49%) and cognitive impairment (39%). Signs of major depression (PHQ-9-D ≥ 10) occurred in 28%/2% (p

Background: The aim of this study was to provide a comprehensive overview of German nationwide data including (i) the number of hospitalized Post-COVID Syndrome (PCS) cases including in-hospital mortality rates and intensive care unit treatments, (ii) the main common concomitant diagnoses associated with PCS, (iii) the most frequently performed treatment procedures, and (iv) the annual direct healthcare costs. Methods: The incidence was calculated based on annual ICD-10 diagnosis codes “U09.9!, Post-COVID-19 condition”. Data on concomitant diagnoses, treatment procedures, treatment in an intensive care unit (ICU), in-hospital mortality, the proportion of G-DRGs, and cumulative costs were assessed based on the Institute for the Hospital Remuneration System (InEK) data for 2019. Results: A total of 29,808 PCS inpatients could be identified yielding a prevalence of 5.5%. In total, 1330 (4.5%) in-hospital deaths were recorded, and 5140 (17.2%) patients required ICU treatment. The majority of patients (18.6%) were aged 65–74 years. The most common concomitant diagnoses included pneumonia, critical illness polyneuropathy, dyspnea, chronic fatigue syndrome, and pulmonary embolisms. The most frequently performed procedures were computed tomography of the thorax with contrast medium, whole-body plethysmography, and the monitoring of respiration, heart, and circulation. The cost per case of the G-DRG codes that were analyzed ranged from € 620 ± 377 (E64D, Respiratory insufficiency, one day of occupancy) to € 113,801 ± 27,939 (A06B, Ventilation > 1799 h with complex OR procedure). Total cumulative direct healthcare costs of € 136,608,719 were calculated, resulting in mean costs of € 4583 per case. Conclusion: Post-COVID Syndrome is of major public health importance with substantial financial implications. The present article can support stakeholders in health care systems to foresee future needs and adapt their resource management. Consensus diagnostic criteria and rehabilitation guidelines are highly warranted.

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human-nonhuman chimeric research. Led by bioethics researchers working closely with an interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human-nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics' previous focus on human-centered questions about the ethics of "humanization" and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less-siloed governance and oversight and more-comprehensive public communication.

Background The 2020 postpolypectomy surveillance guideline update of European Society for Gastrointestinal Endoscopy defines a more restrictive group of individuals in need for surveillance 3 years after colonoscopy. Aim The aim of this cohort study was to validate the new guideline recommendation. Methods Based on a national quality assurance program, we compared the 2020 risk group definition with the previous 2013 recommendations for their strength of association with (1) colorectal cancer death, and (2) all‐cause death. Results A total of 265,608 screening colonoscopies were included in the study. Mean age was 61.1 years (SD ±9.0), and 50.6% were women. During a mean follow‐up of 59.3 months (SD ±35.0), 170 CRC deaths and 7723 deaths of any cause were identified. 62.4% of colonoscopies were negative and 4.9% were assigned to surveillance after 3 years according to the 2020 guidelines versus 10.4% following the 2013 guidelines, which corresponds to a relative reduction in colonoscopies by 47%. The strength of association with CRC mortality was markedly higher with the 2020 surveillance group as compared to the 2013 guidelines (HR 2.56, 95% CI 1.62–4.03 vs. HR 1.73, 95% CI 1.13–2.62), while the magnitude of association with CRC mortality for low risk individuals was lower (HR 1.17, 95% CI 0.83–1.63 vs. 1.25, 95% CI 0.88–1.76). Conclusions Adherence to the updated guidelines reduces the burden of surveillance colonoscopies by 47% while preserving the efficacy of surveillance in preventing CRC mortality., Key summary Summarize the established knowledge on this subject Individuals who had colorectal polyps removed are advised to undergo surveillance; intervals are based on the number, size, and histopathological features of the resected lesions.In 2020, the European Society for Gastrointestinal Endoscopy (ESGE) updated their postpolypectomy surveillance guideline. What are the significant and/or new findings of this study? The risk stratification introduced in the new guideline leads to a substantial reduction (by 47%) in the number of individuals in need for surveillance while preserving the efficacy of surveillance in preventing colorectal cancer mortality.

Non-union after fracture depicts a devastating complication in trauma surgery and studies assessing patient-reported outcome measures after stable bone consolidation are rare. Therefore, we aimed to evaluate the long-term impact of aseptic long bone non-union on the patients' physical health state and psychological wellbeing. For this purpose, quality of life after successful surgical treatment of long bone non-union was assessed.Sixty-one patients with aseptic long bone non-union surgically treated in our department between November 2009 and March 2019 with achieved bone consolidation were included. Quality of life was evaluated with the EQ-5D and SF-36 outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data.With a minimum follow-up time of one year after the last surgery (mean 4.7 ± 2.7 years) the mean physical health component score of the SF-36 was 38.9 ± 13.7 and the mean mental health component score of the SF-36 was 49.0 ± 5.9, indicating lower quality of life compared to German normative values of 48.4 ± 9.4 (p .001) and 50.9 ± 8.8 (p = 1.61), respectively. The mean EQ-5D index value reached 0.827 ± 0.18 with an EQ-5D VAS rating of 64.4 ± 21.5 compared to scores of 0.922 (p .001) and 72.9 ± 1.1 (p .001) obtained from an age-matched reference population. Mean scores of the ISR did not reveal significant psychological symptom burden in any scale, while an individual analysis showed moderate to severe impairments in 11.5% of the patients in total.Even 4.7 years on average after surgically successful treatment of aseptic long bone non-union, patients still report significant lower quality of life in comparison to normative data. Future clinical studies on non-unions should focus on patient-related outcome measures. Newly emerging treatment strategies and interdisciplinary approaches should be implemented to improve the overall quality of life of non-union patients.

Periprosthetic joint infection (PJI) is a devastating complication in orthopedics and trauma surgery. A potential increase in PJI diagnoses, especially in combination with psychological comorbidities may become a significant challenge for healthcare stakeholders. So far, the prevalence for Germany is unknown, which makes it difficult to estimate future treatment demand or to predict developments that can be influenced by adapting prevention and treatment measures.The present study provides a detailed overview of the epidemiology of periprosthetic joint infections and psychological comorbidities.A dataset provided by the Federal Statistical Office (Destatis) consisting of annual, Germany-wide ICD-10 diagnosis codes from 2009 through 2019 was analyzed. Incidences of the code "T84.5-Infection and inflammatory reaction due to joint arthroplasty" were quantified, and a detailed breakdown of this data by age group and gender was performed. Prevalence rates of secondary diagnoses of the ICD-10 chapter F were determined.PJI diagnoses have been steadily increasing since 2009. The incidence declined in 2018. In 2019, 16,174 cases were registered, corresponding to a prevalence of 23.8/100,000 population. A trend towards more diagnoses in elderly patients became evident. Twenty-five percent of all patients had a secondary diagnosis regarding mental and behavioural disorders. The number of patients with psychological comorbidities doubled in the last decade.Guidelines on prevention strategies as well as psychological support services should be implemented in trauma surgery.HINTERGRUND: Die periprothetische Gelenkinfektion (PJI) ist eine gefürchtete Komplikation in der Orthopädie und Unfallchirurgie. Ein potenzieller Anstieg an PJI-Diagnosen, insbesondere in Verbindung mit psychologischen Komorbiditäten, kann zu einer besonderen Herausforderung für Akteure im Gesundheitswesen werden. Bisher ist die Prävalenz für Deutschland unbekannt. Dies erschwert es, den zukünftigen Behandlungsbedarf abzuschätzen und Entwicklungen vorherzusehen, die durch eine Anpassung von Präventions- und Therapiemaßnahmen beeinflusst werden können.Die vorliegende Arbeit gibt eine detaillierte Übersicht über die Epidemiologie periprothetischer Gelenkinfektionen und psychologischer Komorbiditäten.Ein Datensatz vom Statistischen Bundesamt (Destatis) aus jährlichen, deutschlandweiten ICD-10-Diagnosekodes von 2009 bis 2019 wurde analysiert. Prävalenzraten des Kodes „T84.5 – Infektion und entzündliche Reaktion durch eine Gelenkendoprothese“ wurden nach Altersgruppe, Geschlecht und in Verbindung mit einer Nebendiagnose des Kapitels F quantifiziert und aufgeschlüsselt.Seit 2009 steigen die PJI-Diagnosen kontinuierlich an, die Häufigkeit war im Jahr 2018 rückläufig. Im Jahr 2019 wurden 16.174 Fälle entsprechend einer Prävalenz von 23,8/100.000 Einwohner verzeichnet. Eine Entwicklung hinsichtlich mehr Diagnosen bei älteren Patienten wurde evident. Ein Viertel aller Patienten wiesen eine Nebendiagnosen im Bereich psychischer Störungen und Verhaltensstörungen auf, wobei sich die Anzahl an Patienten mit psychologischen Komorbiditäten im letzten Jahrzehnt verdoppelte.Richtlinien zu Präventionsstrategien und psychologische Unterstützungsangebote sollten in der Unfallchirurgie implementiert werden.

Background In Patients suffering from post-COVID syndrome, in addition to physical limitations, cognitive limitations, fatigue, dyspnea as well as depression and anxiety disorders may also be present. Up to now (as of May 2022), approx. 514 million people worldwide have been infected with SARS-CoV-2, in Germany this affects approx. 25 million. In Germany, 2.5 million people could potentially be affected by post-COVID syndrome. Post-COVID is thus a highly relevant public health issue. So far, there is no specific causal therapy for the post-COVID syndrome, but with multimodal symptom-oriented rehabilitation, the course can be favourably influenced. However, there is no study yet that focuses on patients in different rehabilitation indications and compares the focal symptomatology and coping strategies as well as the patients' benefit per indication. Methods/design As first objective, pulmonal, cardiac, neurological, cognitive or/and psychological functional impairments in rehabilitation patients after COVID-19 disease will be described. The second objective is the differentiated review of the specific rehabilitation measures, in the short term and in the longer term for the purpose of future prognoses and optimisation of therapeutic interventions. This prospective, non-randomised, controlled longitudinal study, plus multi-group comparisons will take place in seven rehabilitation clinics of different specialisations: cardiological rehab, pneumological rehab, neurological rehab, psychosomatic rehab. Within 12 months, 1000 cases across all participating centres will be included. Somatic and psychological testing will be conducted at three measurement points: Admission (t0), discharge (t1), 6-montas Catamnesis (t2). The patients receive the usual care according to the respective rehabilitation priorities, adapted to the special challenges of post-COVID symptoms. Patients of the post-COVID outpatient clinic without rehabilitation will be used as a control group. Discussion This study will precisely assess the extent to which subclinical neurological or/and psychological impairments are present in post-COVID-19 rehabilitation and the results will help, developing, providing and evaluating appropriate treatment concepts. This may also have relevant implications for the improvement of physical ability and quality of life in post-COVID-19 patients and increase the probability of return to work. Trial registration Z-2022-1749-8, registered 03. February 2022, https://studienanmeldung.zks-regensburg.de

ObjectivePostscreening colorectal cancer (PSCRC) after screening colonoscopy is associated with endoscopists’ performance and characteristics of resected lesions. Prior studies have shown that adenoma detection rate (ADR) is a decisive factor for PSCRC, but correlations with other parameters need further analysis and ADR may change over time.DesignCohort study including individuals undergoing screening colonoscopy between 1/2008 and 12/2019 performed by physicians participating in a quality assurance programme in Austria. Data were linked with hospitalisation data for the diagnosis of PSCRC (defined as CRC diagnosis >6 months after colonoscopy). ADR was defined dynamically in relation to the time point of subsequent colonoscopies; high-risk groups of patients were those with an adenoma ≥10 mm, or with high-grade dysplasia, or villous or tubulovillous histology, or a serrated lesion ≥10 mm or with dysplasia, or colonoscopies with ≥3 lesions. Main outcome was PSCRC for each risk group (negative colonoscopy, hyperplastic polyps, low-risk and high-risk group of patients) after colonoscopy by endoscopists with an ADR Results352 685 individuals were included in the study (51.0% women, median age 60 years) of which 10.5% were classified as high-risk group. During a median follow-up of 55.4 months, 241 (0.06%) PSCRC were identified; of 387 participating physicians, 19.6% had at least one PSCRC (8.4% two or more). While higher endoscopist ADR decreased PSCRC incidence (HR per 1% increase 0.97, 95% CI 0.95 to 0.98), affiliation to the high-risk group of patients was also associated with higher PSCRC incidence (HR 3.27, 95% CI 2.36 to 4.00). Similar correlations were seen with regards to high-risk, and advanced adenomas. The risk for PSCRC was significantly higher after colonoscopy by an endoscopist with an ADR ConclusionA dynamic calculation of the ADR takes into account changes over time but confirms the correlation of ADR and interval cancer. Both lesion characteristics and endoscopists ADR may play a similar role for the risk of PSCRC. This should be considered in deciding about appropriate surveillance intervals in the future.

Background and Objectives: In recent years, singing bowl sound interventions have been progressively implemented in the fields of well-being, therapy and education; however, the effectiveness has only scarcely been investigated. Therefore, this study was aimed at determining neurophysiological effects of a singing bowl massage. Materials and Methods: In this prospective cohort study 64-channel EEG, ECG and respiration was recorded from 34 participants (mean age 36.03 ± 13.43 years, 24 females/10 males) before, during and after a professional singing bowl massage. Further, subjective changes in well-being were assessed. EEG data were analyzed by determining the effect sizes of distinct frequency bands. Significant differences were calculated by a two-tailed t-test corrected for multiple comparisons. Heart rate variability metrics, heart rate and respiration rate were estimated and compared. Results: Overall EEG power decreased during the sound condition compared to a task-free resting state (d = −0.30, p = 0.002). After the intervention, global EEG power was further reduced (d = −0.46, p < 0.001), revealing a decrease in the beta 2 (d = −0.15, p = 0.002) and the gamma frequency band (d = −0.21, p = 0.004). The mean heart rate was significantly lower after the intervention (75.5 ± 19.8 vs. 71.5 ± 17.9, p < 0.001) and the respiration rate higher (13.5 ± 5.3 vs. 15.2 ± 6.3, p = 0.018). 91.2% of the participants felt more integrated, 97.1% more balanced and 76.5% more vitalized. Conclusions: The neurophysiological effects of a singing bowl sound massage may be interpreted as a shift towards a more mindful, meditative state of consciousness. The intervention was perceived as beneficial for the wellbeing.

Research suggests that stays in a forest promote relaxation and reduce stress compared to spending time in a city. The aim of this study was to compare stays in a forest with another natural environment, a cultivated field. Healthy, highly sensitive persons (HSP, SV12 score > 18) aged between 18 and 70 years spent one hour in the forest and in the field at intervals of one week. The primary outcome was measured using the Change in Subjective Self-Perception (CSP-14) questionnaire. Secondary outcomes were measured using the Profile Of Mood States (POMS) questionnaire and by analyzing salivary cortisol. We randomized 43 participants. Thirty-nine were allocated and included in the intention-to-treat analysis (90% female, mean age 45 years). CSP-14 in part showed significant differences—total score (p = 0.054, Cohen’s d = 0.319), item “integration” (p = 0.028, Cohen’s d = 0.365)—favoring the effects of the forest. These effects were more pronounced in summer (August). In October, during rainfall, we detected no relevant differences. POMS only showed a significant difference in the subcategory “depression/anxiety” in favor of the field. The amount of cortisol in saliva was not different between the groups. A short-term stay in a forest in summer caused a greater improvement in mood and well-being in HSP than in a field. This effect was not detectable during bad weather in the fall.

Neuronal interactions coupled by phase synchronization have been studied in a wide range of frequency bands, but fluctuations below the delta frequency have often been neglected. In the present study, phase synchrony in slow cortical potentials (SCPs, 0.01–0.1 Hz) was examined during two different mental states; a resting state and a breath-focused mindfulness meditation. SCP phase synchrony in 9 long-term expert meditators (on average 22 years of experience) were compared with the data obtained from 11 novices. Additionally, after the novices attended an 8-week mindfulness-based stress reduction (MBSR) program, SCP phase synchrony was measured again. While expert meditators and novices exhibited the same amount of SCP phase synchrony in the resting state, decreased synchronization was found during meditation among expert meditators as well as novices who had participated in the MBSR program (but not prior to the program). These findings suggest that phase synchrony in slow cortical activity is context-dependent and could provide crucial information in the study of the human mind.

Hot snare (HS) is widely used for the resection of adenomas5 mm. The cold snare (CS) has a better safety profile and is more cost-effective. The aims of this study were to evaluate effectiveness and safety of CS polypectomy (CSP) compared to HS polypectomy (HSP) for adenomas sized 5-10 mm and 11-20 mm.4018 colonoscopies performed within "quality certificate for screening colonoscopy" with one polypectomy of an adenoma sized 5-20 mm each were included. Retrieval rates, complete resection rates and complication rates were assessed and compared between CSP and HSP for adenomas sized 5-10 mm and 11-20 mm. Histologic subgroups were additionally assessed.Complete resection rates (5-10 mm: CSP: 89.4% vs. HSP: 87.9%, p = 0.33; 11-20 mm: CSP: 81.8% vs. 80.9%; p = 1), retrieval rates (5-10 mm: CSP: 99.5% vs. HSP: 99.4%, p = 0.76; 11-20 mm: CSP: 100% vs. HSP: 99%, p = 1) and complication rates (5-10 mm: CSP: 0.2% vs. HSP: 0.2%; p = 1; 11-20 mm: CSP: 0% vs. HSP: 1%, p = 1) were equal between CSP and HSP for adenomas sized 5-10 mm as well as 11-20 mm. For serrated adenomas sized 5-10 mm, HSP was superior to CSP (88.7% vs. 77.2%, p 0.05) regarding the complete resection rate, but not for advanced adenomas (HSP: 89.1% vs. 87.3%, p = 0.69) or adenomas with high-grade dysplasia (HSP: 76.7% vs. 75%, p = 1).This study further supports the use of CSP for polyps sized 5-10 mm and additionally suggests also using CSP for polyps sized 11-20 mm. These findings, as well as the best method for resection of serrated polyps should be validated in further studies.

The primary aim of this study was to evaluate adenomas per positive participant (APP) and adenomas per colonoscopy (APC) as new quality parameters in screening colonoscopy. Furthermore, we wanted to assess whether these parameters differ depending on the setting or profession.Colonoscopy records were obtained from the database of the Austrian certificate of quality for screening colonoscopy. The Spearman correlation was calculated to compare the adenoma detection rate (ADR), APC, APP, and advanced ADR. The parameters were compared between surgeons and internists and between private practices and hospitals by using the t test.A total of 44,142 colonoscopies performed by 202 endoscopists were included. APC showed a strong correlation with ADR (r = 0.94; P .01), and both showed a similar correlation with the advanced ADR (ADR: r = 0.47; P0.01, APC: r = 0.46; P .01). APP showed weaker correlations compared with all other parameters (ADR: r = 0.36; P .01; advanced ADR: r = 0.19; P .01). Private practices did not differ in ADR, APP or APC from hospitals. Among endoscopists with ADRs of ≥25%, 7 (10.3%) had an APP in the lowest quartile, whereas no endoscopists had an APC in the lowest quartile.APC did not reveal additional information to ADR, and thus there is no need to use it instead of or additionally to ADR. Although the APP identifies endoscopists who find few adenomas per procedure despite acceptable ADRs, this additional information might not be important in regard to sufficient colorectal cancer prevention, because these endoscopists still had high advanced ADRs.

The adenoma detection rate (ADR) and characteristics of previously resected adenomas are associated with colorectal cancer (CRC) incidence and mortality. However, the combined effect of both factors on CRC mortality is unknown.Using data of the Austrian quality assurance program for screening colonoscopy, we evaluated the combined effect of ADR and lesion characteristics on subsequent risk for CRC mortality. We analyzed mortality rates for individuals with low-risk adenomas (1-2 adenomas10 mm), individuals with high-risk adenomas (advanced adenomas or ≥3 adenomas), and after negative colonoscopy (negative colonoscopy or small hyperplastic polyps) performed by endoscopists with an ADR25% compared with ≥25%. Cox regression was used to determine the association of combined risk groups with CRC mortality, adjusted for age and sex.We evaluated 259,885 colonoscopies performed by 361 endoscopists. A total of 165 CRC-related deaths occurred during the follow-up period, up to 12.2 years. In all risk groups, CRC mortality was higher when colonoscopy was performed by an endoscopist with an ADR25%. Compared with negative colonoscopy with an ADR ≥25%, CRC mortality was similar for individuals with low-risk adenomas irrespective of ADR (for ADR ≥25%: adjusted hazard ratio [HR], 1.22; 95% confidence interval [CI], 0.59-2.49; for ADR25%: adjusted HR, 1.25; 95% CI, 0.64-2.43) and after negative colonoscopy with ADR25% (adjusted HR, 1.27; 95% CI, 0.81-2.00). Individuals with high-risk adenomas were at significantly higher risk for CRC death if colonoscopy was performed by an endoscopist with an ADR25% (adjusted HR, 2.25; 95% CI, 1.18-4.31) but not if performed by an endoscopist with an ADR ≥25% (adjusted HR, 1.35; 95% CI, 0.61-3.02).Our study adds important evidence for mandatory assessment and monitoring of performance quality in screening colonoscopy. High-quality colonoscopy was associated with a lower risk for CRC death, and the impact of ADR was strongest for individuals with high-risk adenomas.

Objectives We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori . Methods Therapy-naive patients ( n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. Results H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. Conclusions Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

Background: Mindfulness meditation (MM) can be regarded as a practice for calming the mind, while the focus on their breathing can help meditators maintain a state of mindful presence. We have developed and evaluated an alternative method for reaching conscious states of pure being without the aid of a focus of attention. Methods: Skin conductance feedback was provided in real-time during meditation sessions (SCFM) and the practicability of this novel approach was evaluated. 30 participants - 15 meditation experts and 15 non-meditators - attended 6 sessions of meditation over the course of 3 days; 4 SCFM and 2 ordinary MM sessions were conducted. Each session was evaluated with physiological measures and a feedback questionnaire assessing subjective changes in body-related, emotional, and mental self-perception. Results: On average, 78.3% of the participants felt more integrated and connected, 84.2% perceived themselves as more calm and balanced, and 50% felt vitalized after SCFM sessions, while only 5% or less felt more agitated or depressed after the sessions. SCFM was not significantly different from MM. The positive effect of SCFM correlated positively with mindfulness self-ratings. Conclusion: The study demonstrates that SCFM is a viable method for performing a satisfying and consciousness-expanding meditation session.

Biofeedback-treatment for primary headache is highly recommended. Its expenses are mostly not or not completely covered by health funds, hindering the implementation in the care system. This randomized controlled study aimed at evaluating the efficacy of a biofeedback-treatment for primary headache in the outpatient care system all over Germany.The participants were divided into a direct treatment-group (n=41) and a waiting control-group (n=29). The treatment was carried out for 8-11 sessions with vasoconstriction-/vasodilation training for migraine, with electromyography training for headache of the tension type (diagnosis according to the criteria of the International Headache Association). Headache characteristics (frequency, duration, intensity) were collected via headache-diary before, during and after the treatment and headache specific disability using the Pain Disability Index before and after the treatment. The waiting group stated additional information of the questionnaires about 3 months before and again ultimately before the start of the treatment. Measurement of the headache specific self-efficacy (Headache Management Self-efficacy Scale) took place every second session. For the collected parameters the effect sizes fHeadache characteristics decreased during the time of the study significantly linearly with medium to strong effects (frequency fOverall the effects were comparable to already existing studies. Therefore biofeedback turned out to be efficient against migraine and tension-type headache in the out-patient care setting. By that a better integration in the care system seems to be qualified.Für die Behandlung primärer Kopfschmerzen mit Biofeedback liegen einige Empfehlungen vor. Dennoch werden die Kosten meist von den Kassen nicht oder nicht vollständig getragen und die Versorgung dadurch erschwert. In dieser randomisierten kontrollierten Studie wurde die Effektivität einer ambulanten Biofeedback-Therapie bei primärem Kopfschmerz deutschlandweit evaluiert.Die Teilnehmer wurden aufgeteilt in eine sofortige Behandlungsgruppe (n=41) und eine Wartekontrollgruppe (n=29). Die Behandlung erfolgte in 8–11 Sitzungen bei Migräne als Vasokonstriktions-/Vasodilatationstraining, bei Kopfschmerz vom Spannungstyp als Elektromyografietraining. Die Diagnose richtete sich nach den Kriterien der International Headache Society. Erhoben wurden Kopfschmerzcharakteristika (Häufigkeit, Dauer, Intensität) in Form eines Kopfschmerztagebuchs jeweils vor, während und nach der Behandlung und die kopfschmerzspezifische Beeinträchtigung mittels Pain-Disability-Index vor und nach der Behandlung. Die Wartegruppe machte zusätzlich etwa 3 Monate davor sowie nochmals vor Beginn der Behandlung Angaben zu den Fragebögen. Die Messung der kopfschmerzspezifischen Selbstwirksamkeit (Fragebogen zu Kopfschmerzmanagement und Selbstwirksamkeit) erfolgte zu jeder zweiten Sitzung. Für die erhobenen Parameter wurden die Effektstärken fDie Kopfschmerzcharakteristika sanken im Untersuchungszeitraum signifikant linear mit mittleren bis starken Effekten (Häufigkeit fInsgesamt zeigten sich zu bereits vorliegenden Studien vergleichbare Effekte. Biofeedback erwies sich demnach unter Bedingungen der ambulanten Versorgung als effektiv gegen Migräne und Kopfschmerz vom Spannungstyp. Eine bessere Einbindung in die Versorgungspraxis scheint dadurch gerechtfertigt.

Virus-based vaccines and appropriate costimulation potently enhance antigen-specific T cell immunity against cancer. Here we report the use of recombinant modified vaccinia virus Ankara (rMVA) encoding costimulatory CD40L against solid tumors. Therapeutic treatment with rMVA-CD40L-expressing tumor-associated antigens results in the control of established tumors. The expansion of tumor-specific cytotoxic CD8+ T cells is essential for the therapeutic antitumor effects. Strikingly, rMVA-CD40L also induces strong natural killer (NK) cell activation and expansion. Moreover, the combination of rMVA-CD40L and tumor-targeting antibodies results in increased therapeutic antitumor efficacy relying on the presence of Fc receptor and NK cells. We describe a translationally relevant therapeutic synergy between systemic viral vaccination and CD40L costimulation. We show strengthened antitumor immune responses when both rMVA-CD40L-induced innate and adaptive immune mechanisms are exploited by combination with tumor-targeting antibodies. This immunotherapeutic approach could translate into clinical cancer therapies where tumor-targeting antibodies are employed., CD40 agonists have been investigated as a strategy to awaken the immune system against cancers. Here, the authors use a virus encoding CD40L and tumour-associated antigens to enhance innate and adaptive immunity that together with tumour targeting antibodies controls the growth of tumours in mice.

Numerous methods for enhancing consciousness and well-being emphasize the role of breathing. For the first time, we have investigated the link between body rhythms and slow cortical brain dynamics during paced breathing. We present physiological data from 37 participants who performed paced breathing sessions with respiration rates (RRs) from 6 to 14 s/cycle (with 7 min for each task). Measures of respiration, heart rate variability (HRV) and 64-channel electroencephalogram (EEG) as well as subjective ratings were recorded and compared with each other. Both the respiratory sinus arrhythmia of the HRV and the slow cortical potentials (SCPs) of the EEG correlated with the respiration cycle. The highest correlations were observed at a RR of 10 s/cycle for the SCPs. A strong positive voltage deflection during inhalation is followed by a negative variation during exhalation. This decelerated breathing rhythm matches the frequency of baroreceptor sensitivity, leading to synchronization between breathing, HRV, baroreceptors and the brain. Subjectively, participants rated this RR as the most relaxing one. This study demonstrates the importance of the effect of speed of breathing on brain dynamics, which might help in understanding the role of breathing in mental health.

Adenoma detection rate (ADR) is the best established quality parameter for screening colonoscopy. Guidelines recommend a target ADR25% because previous studies have shown that patients of endoscopists with higher ADRs have a lower risk of postcolonoscopy interval cancers. However, studies have shown that improvement in ADR mainly results in increased detection of clinically irrelevant nonadvanced adenomas (NAAs). The impact of ADR on the detection of advanced adenomas (AAs) as well as adverse event rates has yet to be determined.A total of 218,193 screening colonoscopies performed between 2007 and 2010 by 262 endoscopists within the Austrian quality assurance program were analyzed. We divided endoscopists into quintiles based on ADRs and calculated mean advanced ADRs (AADRs), NAA detection rates (NAADRs), and adverse event rates for each quintile. Spearman rank-order was used to calculate overall correlations between ADRs and AADRs as well as adverse event rates. Endoscopists with an ADR 25% were compared with those with an ADR25%.Fifty-one percent of patients were women. Mean ADR was 23.03% (95% confidence interval [CI], 21.93-24.13), AADRs 7.72% (95% CI, 7.19-8.25), and NAADRs 15.31% (95% CI, 14.36-16.27). Overall, there was a significant correlation between ADR and AADR (rho = .51; P .001). When ADR was divided into quintiles, mean AADR increased with increasing ADR. Even in the highest ADR group (ADR, 31.36%-52.27%) there was a further increase in AADR with a mean of 10.75% (95% CI, 9.31-12.19). Importantly, NAADRs increased continuously with improvement in ADRs but never dissociated from a simultaneous improvement in AADRs. However, there was also a significant correlation of ADRs and endoscopic adverse events (rho = .26, P .001), even if the perforation rate of .028% (95% CI, .004-.052) in the highest ADR group still remained within the accepted limits based on guidelines.Increasing ADR is associated with improved detection of AAs and therefore is likely to prevent more cases of colorectal cancer. However, higher ADR was also associated with a higher rate of adverse events, although the adverse event rate was low.

The readiness potential is an ongoing negativity in the EEG preceding a self-initiated movement by approximately 1.5 s. So far it has predominantly been interpreted as a preparatory signal with a causal link to the upcoming movement. Here a different hypothesis is suggested which we call the selective slow cortical potential sampling hypothesis. In this review of recent research results we argue that the initiation of a voluntary action is more likely during negative fluctuations of the slow cortical potential and that the sampling and averaging of many trials leads to the observed negativity. That is, empirical evidence indicates that the early readiness potential is not a neural correlate of preconscious motor preparation and thus a determinant of action. Our hypothesis thereafter challenges the classic interpretation of the Libet experiment which is often taken as proof that there is no free will. We furthermore suggest that slow cortical potentials are related to an urge to act but are not a neural indicator of the decision process of action initiation.

The Sensorium is a multimodal neurofeedback environment that reflects a person's physiological state by presenting physiological signals via orchestral sounds from a speaker and multi-coloured lights projected onto a white surface. The software manages acquisition, real-time processing, storage, and sonification of various physiological signals such as the electroencephalogram (EEG) or electrocardiogram (ECG). Each of the 36 participants completed 6 interventional conditions consisting of three different Sensorium-phases with EEG and ECG feedback, a mindfulness meditation, a guided body scan exercise, and a Pseudo-Sensorium using pre-recorded data that did not reflect the subject's own physiology. During all phases EEG, ECG, skin conductance, and respiration were recorded. A feedback questionnaire assessed the participants' subjective reports of changes in well-being, perception, and life-spirit. The results indicate that the Sensorium sessions were not statistically inferior compared to their corresponding active control conditions with respect to improvements in subjective reports concerning well-being and perception. Additionally, the Sensorium was rated as being a more extraordinary experience, as compared to meditation. During the Sensorium conditions the EEG showed lower levels of theta2 (7-8.5 Hz), alpha (9-12 Hz) and beta (12.5-25 Hz) activity. Since participants reported benefit from the Sensorium experience regardless of any prior experience with meditation, we propose this novel method of meditative and extraordinary self-experience to be utilized as a modern alternative to more traditional forms of meditation.

An increase of extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) in various clinical specimens among intensive care unit patients (n = 7) initiated an outbreak investigation consisting of patient data analyses, control of adherence to infection control guidelines, microbiologic surveys, and molecular-based studies. XDR-PA was detected in a jointly used aroma-oil nursing bottle for aromatherapy. We implemented the restriction of oil sharing among patients. Hence, the outbreak was controlled successfully.

Background Vancomycin resistant enterococci (VRE) are an emerging problem in health care settings. The purpose of the investigation was to assess the extent of the outbreak including environmental contamination and to limit further transmission. Methods We used retrospective patient and laboratory data including pulse field gel electrophoresis (PFGE) typing and virulence and resistance gene analysis. For comparison of medians the Mann-Whitney and for comparison of proportions the Fisher exact tests were used. Results PFGE typing of VRE strains of an outbreak of 15 VRE cases in a solid transplant unit revealed that nine of the cases belonged to one identical pattern (A), which was only found twice in the environment. Eleven further positive environmental samples showed a different, but identical PFGE pattern E. Only one patient was infected with this environmental strain. Two of nine (22.2%) PFGE A, but nine of eleven (81.2%) PFGE E samples were positive for gelatinase E (p = 0.01), which is described as enhancing biofilm production, suggesting a survival benefit for this strain on inanimate surfaces. Conclusion Routine disinfection was not able to stop the cluster, but after repeated enforcement of the infection prevention and control (IPC) bundle such as training, strict adherence to hand hygiene and surface disinfection no further cases were observed. We conclude that certain VRE strains predominate in the environment whereas others predominate in humans. Enforcement of the IPC bundle is essential for controlling VRE outbreaks and reducing further transmission.

Alzheimer’s disease (AD) is the most common neurodegenerative disease and of continuously rising prevalence. The identification of easy-to-measure biomarkers capable to assist in the prediction and early diagnosis of AD is currently a main research goal. Lipid metabolites in peripheral blood of human patients have recently gained major attention in this respect. Here, we analyzed plasma of 174 participants (not demented at baseline; mean age: 75.70±0.44 years) of the Vienna Transdanube Aging (VITA) study, a longitudinal, population-based birth cohort study, at baseline and after 90 months or at diagnosis of probable AD. We determined the levels of specific choline phospholipids, some of which have been suggested as potential biomarkers for the prediction of AD. Our results show that during normal aging the levels of lysophosphatidylcholine, choline plasmalogen, and lyso-platelet activating factor increase significantly. Notably, we observed similar but more pronounced changes in the group that developed probable AD. Thus, our results imply that, in terms of choline-containing plasma phospholipids, the conversion to AD mimics an accelerated aging process. We conclude that age, even in the comparatively short time frame between 75 and 82.5 years, is a crucial factor in the quest for plasma lipid biomarkers for AD that must be carefully considered in future studies and trials.

ThetaHealing® (Vianna Stibal, Kalispell, MT) is a spiritual healing method in which the practitioner and client engage in joint meditations during several healing sessions. It is claimed that these meditation periods are characterized by a "theta state" in which the presence of theta-waves in the electroencephalograph (EEG) frequency spectrum of both the healer and the client is supposed. This study sought to test this hypothesis as well as the presence of synchronicities in the two EEGs.Measurements were obtained with a dual EEG system with 2 × 32 channels, allowing for simultaneous EEG measurements of healer and client. Ten healers and 10 clients performed 10 ThetaHealing sessions while the EEG was measured.Theta frequency band did not increase in healers or in clients. Rather, the contrary was found, with a significant decrease in theta-2 band during healing in healers. Small correlations were seen between the Fourier amplitudes of healer and client in the theta-2 band, as well as small phase synchronicities in theta frequencies.The hypothesis that ThetaHealing is associated with an enhanced generation of theta frequencies in the brain could not be confirmed. This finding makes no claim about whether ThetaHealing is beneficial from a clinical perspective.

Meditation practice involves attention regulation, and thus is thought to facilitate attention control mechanisms. Studies on meditation techniques using a behavioral measurement of the Attention Network Test (ANT) have shown enhanced attention control, but neural features remain unknown. In the present study, event-related potentials (ERPs) and behavioral data from twenty long-term meditators were examined, compared to data obtained from twenty matched controls. Results showed that meditators made fewer error responses than controls, especially during the incongruent target condition, suggesting higher accuracy in executive attention control among meditators. The P3 amplitude in the parietal area remained constant in the congruent and incongruent target conditions among meditators, indicating a higher parietal P3 amplitude during the incongruent target condition relative to matched controls. The findings that meditators exhibited fewer error responses on the ANT and a lack of parietal P3 modulation irrespective of reaction time are discussed in the context of attentional resource allocation.

Summary Thymic antigen-presenting cells (APCs) such as dendritic cells and medullary thymic epithelial cells (mTECs) use distinct strategies of self-antigen expression and presentation to mediate central tolerance. The thymus also harbors B cells; whether they also display unique tolerogenic features and how they genealogically relate to peripheral B cells is unclear. Here, we found that Aire is expressed in thymic but not peripheral B cells. Aire expression in thymic B cells coincided with major histocompatibility class II (MHCII) and CD80 upregulation and immunoglobulin class-switching. These features were recapitulated upon immigration of naive peripheral B cells into the thymus, whereby this intrathymic licensing required CD40 signaling in the context of cognate interactions with autoreactive CD4 + thymocytes. Moreover, a licensing-dependent neo-antigen selectively upregulated in immigrating B cells mediated negative selection through direct presentation. Thus, autoreactivity within the nascent T cell repertoire fuels a feed forward loop that endows thymic B cells with tolerogenic features.

Summary Background In intensive care units (ICUs), inanimate surfaces and equipment may be contaminated by nosocomial pathogens, including multi-drug-resistant micro-organisms. Aims To assess the degree of environmental contamination close to and distant from patients, and contamination of healthcare workers' (HCWs) hands with nosocomial pathogens under real-life conditions and to investigate potential transmission events. Methods Over the course of three weeks, agar contact samples were taken close to and distant from patient areas and from HCWs' hands in eight ICUs of a tertiary care hospital in Innsbruck, Austria. Each ICU was visited once without announcement. Species identification and antimicrobial susceptibility testing were performed according to standard methods, and corresponding strains from patient, environment and hand samples were genotyped using pulsed-field gel electrophoresis. Findings Among 523 samples, HCWs' hands were most frequently contaminated with potentially pathogenic bacteria (15.2%), followed by areas close to patients (10.9%) and areas distant from patients (9.1%). Gram-positive bacteria were identified most often (67.8%), with Enterococcus spp. being the most prevalent species (70% vancomycin sensitive and 30% vancomycin resistant) followed by Staphylococcus aureus, of which 64% were classified as meticillin-resistant Staphylococcus aureus. Molecular typing documented identical strains among patient, environment and hand isolates. Conclusion This study found widespread contamination of the ICU environment with clinically relevant pathogens, including multi-drug-resistant micro-organisms, despite cleaning and disinfection. The bioburden might not be restricted to areas close to patients. The role of extended environmental disinfection of areas distant from patients in order to improve infection prevention needs further discussion.

16 patients with transfusion-dependent, life-threatening bone marrow failure (14 with severe aplastic anaemia, 1 with systemic lupus erythematosus and 1 with pure red cell aplasia) were treated with cyclosporin-A (Cy-A) after either lack of response to conventional immunosuppression with antithymocyte-globulin/high-dose methylpred-nisolone for 95 to 1190 days (median 186.5) (group I, 8 patients) or as a primary treatment due to ineligibility for conventional immunosuppression (group II, 8 pat.). Cyclosporin-A was given orally to maintain trough levels of 200 to 300 ng/ml (RIA). In group I, 6 out of 8 patients responded 30 to 480 d (median 53) and are currently alive 627 to 1482 d (median 731) after initiation of Cy-A, respectively. In 3 of the responders Cy-A has been withdrawn, without relapse. In group II, 5 of 8 patients responded 26 to 170 d (median 63) and are currently alive 142 to 697 (median 420) d following initiation of Cy-A, respectively. These data indicate a place for cyclosporin-A in the management of patients with life-threatening bone marrow failure in whom a) immunosuppressive therapy with antithymocyte-globulin and high-dose methylprednisolone had failed and b) who are not candidates for vigorous immunosuppression or bone marrow transplantation, for medical or other reasons.

The belief in free will has been frequently challenged since Benjamin Libet published his famous experiment in 1983. Although Libet’s experiment is highly dependent upon subjective reports, no study has been conducted that focused on a first-person or introspective perspective of the task. We took a neurophenomenological approach in an N = 1 study providing reliable and valid measures of the first-person perspective in conjunction with brain dynamics. We found that a larger readiness potential (RP) is attributable to more frequent occurrences of self-initiated movements during negative deflections of the slow cortical potentials (SCP). These negative deflections occur in parallel with an inner impulse reported by an expert meditator which may in turn lead to a voluntary act. We demonstrate in this proof-of-principle approach that the first-person perspective obtained by an expert meditator in conjunction with neural signal analysis can contribute to our understanding of the neural underpinnings of voluntary acts.

Background A 1-day point prevalence study evaluated hand hygiene compliance, yeast colonization, and contamination, focusing on the hands of health care workers (HCWs) and patient-oriented surfaces. Methods Hand hygiene compliance was evaluated by applying the direct observation technique and the World Health Organization's compliance program, “My Five Moments for Hand Hygiene.” A total of 128 samples from HCWs working in intensive care (n = 11) and intermediate care (n = 2) units and 65 environmental samples from Innsbruck Medical University Hospital were investigated. Results Hand hygiene compliance was superior for nurses (83.5%) and moderate for medical doctors (45.2%). In general, fungal growth was unique; only 9 of 128 HCW samples and only 4 of 65 environmental samples yielded positive results. The genetic relatedness of yeasts from the same species was investigated by random amplified polymorphic DNA (RAPD) typing. RAPD profiles exhibited the potential for cross-transmission of yeasts. Conclusion In general, the fungal colonization and contamination rate was low, but a high level of hand hygiene compliance was lacking.

It has been repeatedly shown that specific brain activity related to planning movement develops before the conscious intention to act. This empirical finding strongly challenges the notion of free will. Here, we demonstrate that in the Libet experiment, spontaneous fluctuations of the slow electro-cortical potentials (SCPs) account for a significant fraction of the readiness potential (RP). The individual potential shifts preceding self-initiated movements were classified as showing a negative or positive shift. The negative and positive potential shifts were analyzed in a self-initiated movement condition and in a no-movement condition. Comparing the potential shifts between both conditions, we observed no differences in the early part of the potential. This reveals that the apparently negative RP emerges through an unequal ratio of negative and positive potential shifts. These results suggest that ongoing negative shifts of the SCPs facilitate self-initiated movement but are not related to processes underlying preparation or decision to act.

Association of telomere shortening with overall dementia or Alzheimer’s disease is described controversially and the pathophysiologic relevance is unclear. Whether patients, suffering from pure probable Alzheimer’s disease or pure vascular dementia, have shorter leukocyte telomeres than cognitively healthy controls was determined. Leukocyte telomere lengths (LTLs) of 597 participants of the VITA study (longitudinal community-based age-cohort [mean 75.7 (±0.45) years] study: 243 male; 578 non-demented at baseline) were compared with different aspects of cognition, risk factors of dementia and survival. LTLs of 264 persons cognitively healthy at baseline (mild cognitive impaired excluded) and all follow-ups (mean = 5643 bp, SD = 736) did not show any difference to LTLs of 43 incident pure possible (mean = 5548 bp; SD = 666) or 34 incident pure probable Alzheimer’s diseases (mean = 5712 bp; SD = 695; post hoc Dunnett test: MD = −95; SE = 119; p = 0.67 and MD =+68.3; SE = 132; p = 0.84, res.). 264 stably cognitively healthy showed a trend to longer telomeres than 6 incident vascular dementias (mean = 5643 bp, SD = 736 vs mean = 5101 bp, SD = 510; t test: T = 1.8; df = 268; p = 0.07). Males (n = 243; mean = 5470 bp; SD = 684) had significantly shorter telomeres than females (n = 354; mean = 5686 bp; SD = 714; t test: T = −3.7; df = 595; p = 0.0001) and died significantly earlier (113.7 vs 130.1 months: Log Rank Chi square = 12.2; p = 0.0001). Shorter telomeres were associated with prevalence of more than one vascular risk factor (n = 587; mean = 5728; SD = 723 vs mean = 5533; SD = 691; t test: T = 3.1; df = 576; p = 0.002) and, as a trend, with poorer survival (Cox Regression: Wald = 4.9; p = 0.026; OR = 0.98; 95% CI 0.96–0.99). In 75.7 years old persons, no association of LTL with incident pure Alzheimer’s disease was found. Significantly shorter telomeres were associated with sum of vascular risk factors, males and early mortality in males. Exclusion of mixed dementias may improve the search for risk factors more specific for Alzheimer’s disease.

INTRODUCTION: The objective was to investigate the association between chorionicity-specific intertwin birthweight discordance and adverse outcomes including long-term follow up at 6, 18, and 48-60 months after term via Ages and Stages Questionnaire.MATERIAL AND METHODS: In this secondary analysis of a cohort study (Oldenburg et al., n = 1688) and a randomized controlled trial (PREDICT study, n = 1045) twin pairs were divided into three groups according to chorionicity-specific birthweight discordance: 90th percentile. Information on infant mortality, admittance to neonatal intensive care units, and gestational age at delivery was available for all pairs. Detailed neonatal outcomes were available for 656 pairs from PREDICT, of which 567 pairs had at least one Ages and Stages Questionnair follow-up. Logistic regression models were used for dichotomous outcomes. Ages and Stages Questionnair scores were compared using the method of generalized estimating equation to account for the correlation within twins.RESULTS: The 75th and 90th percentiles for birthweight discordance were 14.8 and 21.4% for monochorionic and 16.0 and 23.8% for dichorionic twins. After adjustment for small for gestational age and gender, birthweight discordance >75th and >90th percentile was associated with induced delivery 75th-percentile was associated with an increased risk of infant mortality after 28 days [odds ratio 4.69 (95% confidence interval 1.07-20.45)] but not with major neonatal complications or with low mean Ages and Stages Questionnair scores at 6, 18, and 48-60 months after term.CONCLUSION: Chorionicity-specific intertwin birthweight discordance is a risk factor for induced preterm delivery and infant mortality, but not for lower scores for neurophysiological development at 6, 18, and 48-60 months.

Improving laboratory animal science and welfare requires both new scientific research and insights from research in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the '3Rs'), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they design research programmes, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on methods employed by other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including on issues around: international harmonisation, openness and public engagement, 'cultures of care', harm-benefit analysis and the future of the 3Rs. The process outlined below underlines the value of interdisciplinary exchange for improving communication across different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy.

BACKGROUND: Retinol-binding protein (RBP) 4, a human adipokine that specifically binds to retinol, has been reported to provide a link between obesity and insulin resistance. Plasma RBP4 concentration may be under the influence of age and obesity, but only a few studies has investigated this link in elderly individuals. Consequently, we tested the correlation between RBP4 concentrations and type 2 diabetes/metabolic syndrome (MetS) components in a large population based cohort study (VITA) of elderly [1, 2]. Using a single birth cohort, this investigation could exclude the influence of age. METHODS: We evaluated the correlation of RBP4 with type 2 diabetes and MetS components including Body Mass Index (BMI), blood pressure, lipid parameters, fasting glucose insulin, homeostasis model assessment insulin resistance (HOMA-IR), and smoking in exclusively 75–76 year old participants (N = 232). RESULTS: In the present study, RBP4 concentrations were associated with type 2 diabetes and metabolic syndrome (MetS) components. Of all the individual components of metabolic syndrome that were associated with RBP4 concentrations, the correlations of RBP4 with serum triglycerides and a negative correlation with HDL were the strongest ones observed in our study cohort (p

Hypnosis can be seen as a guided induction of various states of consciousness. This article details a time-series analysis that visualized the electrophysiological state changes during a session as a correlate to the instructions. Sixty-four channels of EEG and peripheral physiological measures were recorded in 1 highly susceptible subject. Significant state changes occurred synchronously with specific induction instructions. Some patterns could be physiologically explained, such as sensorimotor desynchronization over the right hemispheric hand area during left arm levitation. There was a highly significant increase in broadband activity during the stepwise trance induction that may point to a deep hypnotic state. This study provides illustrated proof for the detectability of physiological state changes as correlates to different states of awareness, consciousness, or cognition during hypnosis.

Globally, cardiovascular diseases (CVDs) are the number one cause of all mortalities. Of these deaths, 7.6 million are due to heart attacks, and 5.7 millions are due to stroke. The Vienna Transdanube Aging Study (VITA), a population-based cohort study, enabled us to evaluate associations between the known major risk factors for cerebrovascular and CVDs and their appearance beyond age 75 years. Using a single birth cohort, age was excluded as confounding factor. In the baseline investigations in the Danube Hospital, 606 individuals took part and were examined completely at baseline. After 60 months, 508 patients were re-examined. Each participant underwent an indepth investigation with the duration of 7 h, including neuropsychological testing, as well as analyses of biochemical, clinical chemical and genetic parameters, and magnetic resonance imaging (MRI) of the brain. In the present study, only a history of cerebral and cardiovascular events at the baseline or smoking was associated significantly with the appearance of CVDs. In a multiple model both risk factors—history of cerebral and cardiovascular events at the baseline (p = 0.0003, OR 2.36, 95% CI 1.49–3.76) and smoking (p = 0.0005, OR 1.57, 95% CI 1.22–2.03)—remained significant. However, the predictive value of this assessment model was low. The rescaled r 2 of the model was 0.088. A significant correlation was found only between exposure to cigarette smoke or a history of previous CVDs, such as stroke or myocardial infarction. Smoking or earlier CVDs greatly increase the risk for further cerebral and cardiovascular events in persons after 75 years.

Soluble cytokeratin 18 fragments (M30, M65) are released from human cancer cells during cell death and hold potential as biomarkers in colorectal cancer characterized by frequent metastatic spread. A total of 62 colorectal cancer and 27 control patients were included in the study. M65 (necrosis and apoptosis) and M30 (apoptosis) were quantified preoperatively (n = 62) and postoperatively (n = 31) using specific enzyme-linked immunosorbent assays. Presence of disseminated tumor cells (DTC) in the bone marrow was assessed by staining of A45-B/B3-positive cells in aspirates. M65 was significantly elevated in patients with International Union against Cancer stage I and IIA tumors compared to controls. A subgroup (19/31) exhibited a significant (p0.05) decrease of M65 after tumor surgery (503.9 +/- 230.7 to 342.6 + 94.8 U/l; -32.0 +/- 16.5%), in contrast to 12 patients who revealed higher M65 levels postoperatively (386.5 +/- 128.5 to 519.1 +/- 151 U/l; +37.4 +/- 32.3%). DTC in bone marrow were found in 10% (2/19) of patients with decreasing and 50% (6/12) of the patients with increasing M65 serum concentrations after surgery (p = 0.028). In conclusion, M65 as marker is likely to be valuable to identify patients with a high incidence of systemic disease.

OBJECTIVE To evaluate whether a prolonged time interval between dilation and curettage (D&C) and hysterectomy has an effect on survival in patients with surgically treated endometrial cancer. METHODS In this multicenter study, time between D&C and hysterectomy was correlated to clinical data in 344 surgically staged patients with endometrioid endometrial cancer. RESULTS The median (interquartile range) interval between D&C and hysterectomy in patients with endometrial cancer was 23 (13-34) days. In a univariable survival analysis, International Federation of Gynecology and Obstetrics (FIGO) tumor stage (P

Brain–computer interfaces (BCIs) can be used for communication in writing without muscular activity or for learning to control seizures by voluntary regulation of brain signals such as the electroencephalogram (EEG). Three of five patients with epilepsy were able to spell their names with electrocorticogram (ECoG) signals derived from motor-related areas within only one or two training sessions. Imagery of finger or tongue movements was classified with support-vector classification of autoregressive coefficients derived from the ECoG signals. After training of the classifier, binary classification responses were used to select letters from a computer-generated menu. Offline analysis showed increased theta activity in the unsuccessful patients, whereas the successful patients exhibited dominant sensorimotor rhythms that they could control. The high spatial resolution and increased signal-to-noise ratio in ECoG signals, combined with short training periods, may offer an alternative for communication in complete paralysis, locked-in syndrome, and motor restoration.

Duramycin (Moli1901) is being developed for the treatment of reduced mucociliary clearance in cystic fibrosis. This study was conducted to estimate lung residence time and systemic exposure and to assess whether duramycin causes an inflammatory response. Six volunteers were administered a single dose (7.5 mg) of nebulized duramycin and underwent bronchoscopies to obtain a composite data set for pharmacokinetic analysis; duramycin was measured in the cellular fraction of bronchoalveolar lavage fluid (BALF) (mainly alveolar macrophages) and brush biopsies (bronchial epithelial cells). The estimated t(1/2) of duramycin was approximately 5 days in brush biopsies and 25 to 91 days in BALF cells. Levels of duramycin in BALF (C (max) 800 ng/mg) exceeded those in brush biopsies by approximately 20-fold. Duramycin was absent from plasma and did not cause any detectable inflammatory response in pulmonary tissue as judged from the BALF profile of 14 relevant cytokines. Our data suggest that duramycin qualifies for intrapulmonary administration in cystic fibrosis (CF) patients.

Background: Few prospective community-based cohort studies have so far concentrated specifically on the risk factors for Alzheimer dementia (AD) with onset after the age of 75 years. Methods: We prospectively investigated a birth cohort of 585 nondemented inhabitants in the area on the East bank of the river Danube who were born between 1925 and 1926. They were investigated at the age of 75 years and followed up after 30 months. The follow-up was possible with 488 probands; 36 died, and 61 refused to participate. Results: In multivariate analysis an elevated risk for late-onset AD could be found for (1) history of depressive episodes (OR = 2.09; 95% CI = 1.25–3.48); (2) the Ε4 allele of the APOE gene (OR = 1.86; 95% CI = 1.08–3.23); (3) lower serum level of folate (OR = 0.92; 95% CI = 0.87–0.98); (4) no chronic use of nonsteroidal anti-inflammatory drugs (OR = 0.40; 95% CI = 0.20–0.81), and (5) lower education (OR = 1.43; 95% CI = 1.03–2.00). Conclusions: Five risk factors for late-onset AD could be confirmed, which might be targets for preventive strategies.

The H3K9me3-specific histone methyltransferase Setdb1 impacts on transcriptional regulation by repressing both developmental genes and retrotransposons. How impaired retrotransposon silencing may lead to developmental phenotypes is currently unclear. Here we show that loss of Setdb1 in pro-B cells completely abrogates B cell development. In pro-B cells, Setdb1 is dispensable for silencing of lineage-inappropriate developmental genes. Instead, we detect strong derepression of endogenous Murine Leukemia Virus (MLV) copies. This activation coincides with an unusual change in chromatin structure with only partial loss of H3K9me3 and unchanged DNA methylation, but strongly increased H3K4me3. Production of MLV proteins leads to activation of the unfolded protein response pathway and apoptosis. Thus, our data demonstrate that B cell development critically depends on the proper repression of retrotransposon sequences through Setdb1.

The sensitivity and specificity of MDCT for depiction and localization of urothelial carcinoma (UC) was determined retrospectively. Axial and coronal four-row MDCT of the urinary tract (unenhanced, contrast-enhanced nephrographic, CT urography) was independently reviewed for UC by a radiologist (R1) and a urologist (R2), without other patient information, in 27 patients (22 male, five female; age, 72 +/- 11 years) with previous UC and/or painless macroscopic haematuria. Urinary tract segments included bladder, right and left upper, middle, and lower caliceal groups, renal pelvis, uretero-pelvic junction, upper, middle, and lower ureter. MDCT findings were corroborated by surgery, other invasive procedures, and 1-year follow-up, including MDCT, intravenous urography, and cystoscopy. Receiver-operating characteristic analysis was undertaken and the the area under the curve (AUC) calculated. Eighteen of 27 patients had evidence of UC (pTa, n = 3; pT1-pT3, n = 15; TNM 2002). Tumor was correctly located by both R1 and R2 in 17 patients (sensitivity, 94%; 95% confidence interval, 84-100%) and ruled out in seven (specificity, 78%; 95% confidence interval, 51-100%), with complete agreement. Each detected ten of 11 upper urinary tracts affected by UC. For 35 urinary tract segments with UC and 308 without, the AUC was 0.910 +/- 0.035 (R1) and 0.74 +/- 0.055 (R2), z = 2.4772, Bonferroni-corrected P = 0.022. MDCT depicts urinary tracts affected by UC with high sensitivity and substantial agreement between readers with different training.

Behavioral and cognitive improvements in children with ADHD have been consistently reported after neurofeedback-treatment. However, neurofeedback has not been commonly accepted as a treatment for ADHD. This study addresses previous methodological shortcomings while comparing a neurofeedback-training of Theta-Beta frequencies and training of slow cortical potentials (SCPs). The study aimed at answering (a) whether patients were able to demonstrate learning of cortical self-regulation, (b) if treatment leads to an improvement in cognition and behavior and (c) if the two experimental groups differ in cognitive and behavioral outcome variables. SCP participants were trained to produce positive and negative SCP-shifts while the Theta/Beta participants were trained to suppress Theta (4-8 Hz) while increasing Beta (12-20 Hz). Participants were blind to group assignment. Assessment included potentially confounding variables. Each group was comprised of 19 children with ADHD (aged 8-13 years). The treatment procedure consisted of three phases of 10 sessions each. Both groups were able to intentionally regulate cortical activity and improved in attention and IQ. Parents and teachers reported significant behavioral and cognitive improvements. Clinical effects for both groups remained stable six months after treatment. Groups did not differ in behavioural or cognitive outcome.

Objective: Segmentectomy has recently been suggested as alternative to lobectomy for curative treatment of early-stage non-small cell lung cancer (NSCLC). This study was performed to investigate if localisation of the resected segment or width of resection margins influence local recurrence following complete segmentectomy of stage IA NSCLC. Methods: Between 1987 and 2002, 49 segmentectomies and 150 lobectomies were performed in patients with pT1pN0cM0-NSCLC in our institution. Indications for segmentectomy were a limited pulmonary function or severe comorbidity. The median follow-up duration was 54 months. Local recurrence was distinguished from secondary primary lung cancer and was defined as tumour within the same lung or in the ipsilateral mediastinum. Segment localisation, width of resection margins, tumour size, tumour type,grading andage wereanalysed concerningtheirinfluence onlocalrecurrence.Results:Localrecurrence occurred in16% of patients with segmentectomy and was significantly more frequent than in patients with lobectomy (5%; p = 0.005; log-rank test). Segmentectomy in the S1—3 region tended more frequently to local recurrence than segmentectomy in the remaining segments (p = 0.08; log-rank test): There was no recurrence following segmentectomy in the S7—10 region (n = 6) or of S4—5 (n = 5). Recurrence occurred in 7 (23%) out of 30 patients with segmentectomy in the S1—3 region and in 1 (12%) out of 8 patients with S6-segmentectomy. Also, resection margins 1 cm tended to be associated with local recurrence (p = 0.06; log-rank test). Conclusions: The frequency of local recurrence following segmentectomy might be influenced by segment localisation and width of resection margins. Segmentectomy within the S1—3 region should be avoided whenever possible. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Research findings link rolandic beta-band activity to voluntary movements, but a linkage with the decision time to move remains unknown. We found that beta-band (16-28Hz) activity shortly before the movement onset is relevant for the decision time to move: the more pronounced the decrease in beta-band synchronization, the earlier the subjective experience of the decision to move. The linkage was relevant regarding 'decision', but not regarding 'intention' timing that has been often applied in the study of free will. Our findings suggest that oscillatory neural activity in the beta-band is an important neural signature pertaining to the subjective experience of making a decision to move.