Somatic Comorbidity in Chronic Constipation: More Data from the GECCO Study

Background. Comorbidity in chronic constipation has rarely been investigated, despite the fact that constipation can occur as one symptom in a number of neurological, systemic, and other nonintestinal and intestinal disorders. Methods. Of 1037 individuals with constipation identified during a telephone survey, 589 returned a postal questionnaire with valid data, asking for sociographic data, clinical symptoms, comorbid conditions, medication intake, and health care behavior related to constipation. Among them, 245 reported some somatic diagnoses and another 120 regular medication intake. They were compared to individuals without comorbid condition and presumed functional constipation (n=215). Results. Individuals reporting a somatic comorbid condition and/or regular medication were significantly older than those with functional constipation (63.8±15.8 and 43.7±15.5 years, resp., p<0.001) and had lower health and social status (both p<0.001), but similar general life satisfaction (n.s.). Their quality-of-life was lower for the physical (p<0.001) but not for the mental health domain (n.s.), while among those with functional constipation, the mental health domain distinguished IBS-C individuals from those with functional constipation but without pain (p<0.001). Conclusion. In an unselected population sample with constipated individuals, those with a somatic comorbid condition outnumber those with functional constipation alone and are distinctly different with respect to age and health status

Somatic Comorbidity in Chronic Constipation: More Data from the GECCO Study

Background. Comorbidity in chronic constipation has rarely been investigated, despite the fact that constipation can occur as one symptom in a number of neurological, systemic, and other nonintestinal and intestinal disorders. Methods. Of 1037 individuals with constipation identified during a telephone survey, 589 returned a postal questionnaire with valid data, asking for sociographic data, clinical symptoms, comorbid conditions, medication intake, and health care behavior related to constipation. Among them, 245 reported some somatic diagnoses and another 120 regular medication intake. They were compared to individuals without comorbid condition and presumed functional constipation ( = 215). Results. Individuals reporting a somatic comorbid condition and/or regular medication were significantly older than those with functional constipation (63.8 ± 15.8 and 43.7 ± 15.5 years, resp., &lt; 0.001) and had lower health and social status (both &lt; 0.001), but similar general life satisfaction (n.s.). Their quality-of-life was lower for the physical ( &lt; 0.001) but not for the mental health domain (n.s.), while among those with functional constipation, the mental health domain distinguished IBS-C individuals from those with functional constipation but without pain ( &lt; 0.001). Conclusion. In an unselected population sample with constipated individuals, those with a somatic comorbid condition outnumber those with functional constipation alone and are distinctly different with respect to age and health status

Photo-Induced Depletion of Binding Sites in DNA-PAINT Microscopy

The limited photon budget of fluorescent dyes is the main limitation for localization precision in localization-based super-resolution microscopy. Points accumulation for imaging in nanoscale topography (PAINT)-based techniques use the reversible binding of fluorophores and can sample a single binding site multiple times, thus elegantly circumventing the photon budget limitation. With DNA-based PAINT (DNA-PAINT), resolutions down to a few nanometers have been reached on DNA-origami nanostructures. However, for long acquisition times, we find a photo-induced depletion of binding sites in DNA-PAINT microscopy that ultimately limits the quality of the rendered images. Here we systematically investigate the loss of binding sites in DNA-PAINT imaging and support the observations with measurements of DNA hybridization kinetics via surface-integrated fluorescence correlation spectroscopy (SI-FCS). We do not only show that the depletion of binding sites is clearly photo-induced, but also provide evidence that it is mainly caused by dye-induced generation of reactive oxygen species (ROS). We evaluate two possible strategies to reduce the depletion of binding sites: By addition of oxygen scavenging reagents, and by the positioning of the fluorescent dye at a larger distance from the binding site

Prognostische und diagnostische Bedeutung von macrophage migration inhibitory factor in der nichtischämischen Kardiomyopathie

MIF ist ein inflammatorisches Zytokin mit zahlreichen Funktionen sowohl in akuten als auch in chronischen entzündlichen Erkrankungen. Die Bedeutung von MIF in der NICM wurde bisher nicht untersucht.[5] In dieser Studie untersuchten wir an einem Patientenkollektiv von 324 Patienten mit nicht-ischämischer Kardiomyopathie die Bedeutung von myokardialer MIF-Expression hinsichtlich seiner diagnostischen und prognostischen Bedeutung.[5] Alle 324 Patienten des Patientenkollektivs wurden endomyokardbiopsiert. Die Endomyokardbiopsien wurden histopathologisch untersucht und immunhistochemisch analysiert. Neben MIF wurde das Myokardgewebe auf die Expression der weiteren inflammatorischen Marker MHC II, CD3 und CD68 untersucht. Desweiteren wurden etablierte Risikofaktoren wie die LVEF, NYHA-Stadium, BNP und TnI erfasst. Der primäre Studienendpunkt wurde bei Tod jedweder Ursache erreicht. Der sekundäre Studienendpunkt wurde erreicht bei Eintreten eines der folgenden Ereignisse innerhalb des Nachverfolgungszeitraums von 3 Jahren: Tod jedweder Ursache, Herztransplantation, herzinsuffizienzbedingte Rehospitalisierung oder Verschlechterung der LVEF.[5] Die Ergebnisse der Studie zeigen, dass MIF im Myokard von Patienten mit NICM exprimiert wird und myokardiale MIF-Expression mit einem schlechten klinischen Outcome assoziiert ist. MIF ist somit geeignet, ein schlechtes klinisches Outcome von Patienten mit NICM vorherzusagen.[5] Außerdem korreliert die myokardiale MIF-Expression mit dem Grad myokardialer Fibrosierung. MIF scheint an den pathophysiologischen Mechanismen des kardialen Remodelings beteiligt zu sein.[5] Die myokardiale MIF-Expression ist somit von hoher diagnostischer und 49 prognostischer Relevanz für Patienten mit NICM. Eine routinemäßige MIFAnalyse des Myokards ergänzend zu der Untersuchung bereits etablierter Risikofaktoren von Patienten mit NICM könnte insbesondere in der präventiven Patientenversorgung hilfreich sein, Risikopatienten für kardiale Ereignisse zu identifizieren und diese einer intensivierten Überwachung und Therapie zuzuführen.[5

Functional Constipation and Constipation-Predominant Irritable Bowel Syndrome in the General Population: Data from the GECCO Study

Background. The prevalence of constipation in the (German) population has been shown to be 14.9% in a telephone survey, but more detailed data are required to characterize the sociographics and clinical characteristics of persons with different types of functional constipation, either constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation with or without meeting Rome criteria. Methods. Of 2239 constipated individuals identified during the telephone interview, 1037 (46.3%) were willing to provide a postal address for a questionnaire, of which 589 (56.8%) returned the questionnaire, inquiring about sociographic data, clinical symptoms, and health care behavior related to constipation, as well as health-related quality-of-life (SF12). Subgroups of functionally constipated individuals were compared. Results. More than 50% of the respondents reported a somatic comorbid condition and/or regular medication intake that may contribute to constipation. We split the remaining individuals (N=214) into three groups, matching Rome-criteria for IBS (IBS-C, n=64) and for functional constipation (FC-R, n=36) and FC not matching Rome criteria (n=114). Nearly all sociographic and clinical characteristics were equal among them, and all individuals with constipation had similar and lowered QOL on the SF-12 physical health domain, but in IBS-C the scores were also significantly lower in comparison to FC-R and FC, in both the physical health and the mental health domain. Conclusion. Only a fraction of individuals with chronic constipation match Rome criteria for IBS-C or FC, but subgroups do not differ with respect to most other measures except quality-of-life profiles

Dual-color DNA-PAINT single-particle tracking enables extended studies of membrane protein interactions

Abstract DNA-PAINT based single-particle tracking (DNA-PAINT-SPT) has recently significantly enhanced observation times in in vitro SPT experiments by overcoming the constraints of fluorophore photobleaching. However, with the reported implementation, only a single target can be imaged and the technique cannot be applied straight to live cell imaging. Here we report on leveraging this technique from a proof-of-principle implementation to a useful tool for the SPT community by introducing simultaneous live cell dual-color DNA-PAINT-SPT for quantifying protein dimerization and tracking proteins in living cell membranes, demonstrating its improved performance over single-dye SPT

3D printed protein-based robotic structures actuated by molecular motor assemblies

Three-dimensional printed protein-based robotic structures are actuated by exoskeleton-like coats of molecular motor assemblies upon the spatially targeted release of chemical fuel, resulting in micrometre-scale shape-morphing activity. Upscaling motor protein activity to perform work in man-made devices has long been an ambitious goal in bionanotechnology. The use of hierarchical motor assemblies, as realized in sarcomeres, has so far been complicated by the challenges of arranging sufficiently high numbers of motor proteins with nanoscopic precision. Here, we describe an alternative approach based on actomyosin cortex-like force production, allowing low complexity motor arrangements in a contractile meshwork that can be coated onto soft objects and locally activated by ATP. The design is reminiscent of a motorized exoskeleton actuating protein-based robotic structures from the outside. It readily supports the connection and assembly of micro-three-dimensional printed modules into larger structures, thereby scaling up mechanical work. We provide an analytical model of force production in these systems and demonstrate the design flexibility by three-dimensional printed units performing complex mechanical tasks, such as microhands and microarms that can grasp and wave following light activation

Comparison of Ventricular Inducibility with Late Gadolinium Enhancement and Myocardial Inflammation in Endomyocardial Biopsy in Patients with Dilated Cardiomyopathy.

Risk stratification of patients with non-ischemic dilated cardiomyopathy remains a matter of debate in the era of device implantation.We investigated associations between histopathological findings, contrast-enhanced cardiac MRI and the inducibility of ventricular tachycardia (VT) or fibrillation (VF) in programmed ventricular stimulation.56 patients with impaired left ventricular ejection fraction (LVEF≤50%, mean 36.6±10.5%) due to non-ischemic dilated cardiomyopathy underwent cardiac MRI, programmed ventricular stimulation, and endomyocardial biopsy and were retrospectively investigated. Inducibility was defined as sustained mono- or polymorphic VT or unstable VT/VF requiring cardioversion/defibrillation. Primary study endpoint was defined as the occurrence of hemodynamically relevant VT/VF and/or adequate ICD-therapy during follow-up.Endomyocardial biopsy detected cardiac fibrosis in 18 (32.1%) patients. Cardiac MRI revealed 35 (62.5%) patients with positive late gadolinium enhancement. VT/VF was induced in ten (17.9%) patients during programmed ventricular stimulation. Monomorphic VT was inducible in 70%, while 20% of patients showed polymorphic VT. One patient (10%) presented with VF. Inducibility correlated significantly with the presence of positive late gadolinium enhancement in cardiac MRI (p<0.01). We could not find a significant association between inducibility and the degree of cardiac inflammation and fibrosis in non-site directed routine right ventricular endomyocardial biopsy. During a mean follow-up of 2.6 years, nine (16.1%) patients reached the primary endpoint. Monomorphic VTs were found in 66.7% patients and were terminated by antitachycardia pacing therapy. One patient with polymorphic VT and two patients with VF received adequate therapy by an ICD-shock. However, inducibility did not correlate with the occurrence of endpoints.Inducibilty during programmed ventricular stimulation is associated with positive late gadolinium enhancement in cardiac MRI of patients with non-ischemic dilated cardiomyopathy. The presence of myocardial fibrosis or inflammation in undirected endomyocardial biopsy does not seem to be sufficient to predict future ventricular arrhythmias

Professional burnout among medical students: Systematic literature review and meta-analysis

<p><b>Background:</b> This systematic review and meta-analysis aim to summarize the available evidence on the prevalence of professional burnout among medical students.</p> <p><b>Methods:</b> The review was performed according to the PRISMA guidelines. Databases were systematically searched for peer-reviewed articles, reporting burnout among medical students published between 2000 and 2017. The meta-analysis was conducted on the available data on burnout rates in medical students measured with the Maslach Burnout Inventory (MBI-HSS).</p> <p><b>Results:</b> Fifty-eight out of 3006 studies were found eligible for inclusion. Twelve of these studies met the criteria for meta-analysis. Weighted mean values for the three sub-dimensions of the MBI–HSS were M = 22.93 (SD = 10.25) for Emotional Exhaustion, M = 8.88 (SD = 5.64) for Depersonalization, and M = 35.11 (SD = 8.03) for Personal Accomplishment. Prevalence rates for professional burnout ranged from 7.0% to 75.2%, depending on country-specific factors, applied instruments, cutoff-criteria for burnout symptomatology.</p> <p><b>Conclusion:</b> This review underlines the burden of burnout among medical students. Future research should explicitly focus on specific context factors and student group under investigation. Such efforts are necessary to control for context-dependent confounders in research on medical students’ mental health impairment to enable more meaningful comparisons and adequate prevention strategies.</p