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In the last decade, cardiovascular tissue engineering has made great progress developing new strategies for regenerative medicine applications. However, while tissue engineered heart valves are already entering the clinical routine, tissue engineered myocardial substitutes are still restrained to experimental approaches. In contrast to the heart valves, tissue engineered myocardium cannot be repopulated in vivo because of its biological complexity, requiring elaborate cultivation conditions ex vivo. Although new promising approaches—like the whole-heart decellularization concept—have entered the myocardial tissue engineering field, bioreactor technology needed for the generation of functional myocardial tissue still lags behind in the sense of user-friendly, flexible and low cost systems. Here, we present a novel customizable modular bioreactor system that can be used for whole-heart cultivation. Out of a commercially obtainable original equipment manufacturer platform we constructed a modular bioreactor system specifically aimed at the cultivation of decellularized whole-hearts through perfusion and controlled 3D biomechanical stimulation with a simple but highly flexible operation platform based on LabVIEW ® . The modular setup not only allows a wide range of variance regarding medium conditioning under controlled 3D myocardial stretching but can also easily be upgraded for e.g. electrophysiological monitoring or stimulation, allowing for a tailor-made low-cost myocardial bioreactor system.

Purpose: To evaluate the time course of late rectal mucosal changes after prostate cancer radiotherapy (RT). Patients and Methods: A rectosigmoidoscopy was performed at 12, 24, and 65 months after RT in 20 patients. Rectal mucosal changes (telangiectasia, congested mucosa, ulceration, stricture, and necrosis) were scored and documented according to the Vienna Rectoscopy Score (VRS, score 0–3). Results: VRS of 0 and 3, were found in 20% of patients (n = 4) and 5% of patients (n = 1), respectively at all time points. A shift of the VRS from 2 to 1 was found with incidence rates of 60% at 12 months and 20% at 65 months, which is equivalent to an improvement rate of 67%. Laser coagulation was required in 3 patients (15%) with rectal bleeding due to telangiectasia grade ≥2. Conclusion: Late rectal mucosal changes are frequent after pelvic RT. Generally only the incidence rates corresponding to the initial diagnosis of the complications, independent of subsequent recovery, are reported. The results reported in the present study show that complications often improve over time. Hence, the usual reports of complication rates overestimate the proportion of patients presenting with side effects of certain grades.

The aim of the study was to assess the effect of structured strength and balance training on cognitive function in frail, geriatric, long-term care facility residents, aged 75 years or older, and additionally to evaluate the influence of training on various functional, physical and psychological parameters. Participants were randomly assigned to a training group or a control group. Physical training was performed three times a week for ten weeks in the training group. Muscle function was assessed by manual examination on a scale of 0-5. Cognitive function was tested with the Mini Mental State Examination (MMSE). In addition, scores for activities of daily living, mobility and depression were assessed. 30 subjects with a mean age of 86.8 years completed the study. After 10 weeks of intervention in the training group, muscle strength increased from a mean of 3.75 to 4.44 points (p<0.001) and the mean MMSE score increased from 20.9 to 23.9 points (p=0.023). In the training group, the change in the MMSE score correlated significantly with change in muscle function, with a Pearson correlation coefficient of 0.750 (p=0.002). An increase in mean BMI from 23.8 to 25.0 kg/m2 (p=0.013) was also found in the training group, but no significant changes in scores for activities of daily living, mobility or depression. Compared with the control group, the change in the mean scores over the ten-week training period was significantly higher for the trained group with regard to muscle scores, BMI and lean body mass, but not for MMSE scores. Our findings reinforce the recommendation that structured strength and balance training should be implemented in long-term care facilities. Besides the well-known benefits of physical training, our findings showed that an improvement in cognitive function may also be possible.

Introduction Cerebral small vessel disease (cSVD) is one of the most prevalent neurological disorders. The progressive remodeling of brain microvessels due to arterial hypertension or other vascular risk factors causes subtle, but constant cognitive decline through to manifest dementia and substantially increases the risk for stroke. Preliminary evidence suggests the contribution of the immune system to disease initiation and progression, but a more detailed understanding is impaired by the unavailability of appropriate animal models. Here, we introduce the spontaneously hypertensive rat (SHR) as a model for early onset cSVD and unveiled substantial immune changes in conjunction with brain abnormalities that resemble clinical findings. Results In contrast to age-matched normotensive Wistar Kyoto (WKY) rats, male SHR exhibited non-spatial memory deficits. Magnetic resonance imaging showed brain atrophy and a reduction of white matter volumes in SHR. Histological analyses confirmed white matter demyelination and unveiled a circumscribed blood brain barrier dysfunction in conjunction with micro- and macrogliosis in deep cortical regions. Flow cytometry and histological analyses further revealed substantial disparities in cerebral CD45high leukocyte counts and distribution patterns between SHR and WKY. SHR showed lower counts of T cells in the choroid plexus and meningeal spaces as well as decreased interleukin-10 levels in the cerebrospinal fluid. On the other hand, both T and NK cells were significantly augmented in the SHR brain microvasculature. Conclusions Our results indicate that SHR share behavioral and neuropathological characteristics with human cSVD patients and further undergird the relevance of immune responses for the initiation and progression of cSVD.

Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing.

The objective was to examine the effect of BMI on the incidence of various infectious diseases in institutionalised, geriatric subjects. In a retrospective cohort study we analysed medical records of 619 patients aged 75 years and older (mean age 87·6 (sd 6·4) years) who were treated in a geriatric hospital in Vienna, Austria. The total incidence rate of infection in this population was 0·80 per person-year. The most frequent infections were urinary tract infections (0·30 per person-year), followed by infections of the lower respiratory tract (0·19 per person-year), diarrhoea (0·12 per person-year) and other infections (0·20 per person-year). Incidence risk ratios were obtained by a multiplicative Poisson regression model. There was a J-shaped curve in the incidence of infections recorded by BMI with a nadir at 27–28 kg/m2. Compared with the reference group with a BMI of 24–27·9 kg/m2, subjects with a lower BMI had a higher incidence rate of infections. The incidence risk ratios, adjusted for sex, age and chronic diseases, were 1·62 (95 % CI 1·21, 2·17) for those with a BMI of < 20 kg/m2 and 1·84 (95 % CI 1·40, 2·42) for those with a BMI of 20–23·9 kg/m2. However, also patients with a BMI of 28 kg/m2 and above had a higher incidence rate of infections, with an incidence risk ratio of 1·54 (95 % CI 1·07, 2·22). These results show that both underweight and obesity are associated with a higher risk of infections in institutionalised geriatric patients.

Arterial hypertension is not only the leading risk factor for stroke, but also attributes to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood-brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were subjected to photothrombotic stroke. One and 3 days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines along with the post-stroke inflammatory response were analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains 4 days after stroke. Although comparable at day 1, lesion volumes were significantly larger in SHR at day 3. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and P-selectin (CD62P) was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte-leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may finally be responsible for larger infarct volumes. These findings provide an immunological explanation for the epidemiological observation that existing hypertension negatively affects stroke outcome and mortality.

CT and MR imaging techniques are frequently used for the diagnosis and progress monitoring of ischemic stroke in clinical practice and research. After stroke, both methods are characterized by a transient pseudo-normalized imaging signal, the so-called fogging phenomenon. This study evaluates potential pathophysiological changes associated with fogging, as well as its influence on the correct determination of the ischemic lesion in a rat stroke model. Male spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion. Ischemic lesion volume, brain edema and gray scale value spread within the ischemic lesion were determined on T2-weighted MR sequences at days 1, 4, 8, 11 and 29 after stroke onset, and compared with immunohistochemistry for astrogliosis, microglia/macrophage infiltration and angiogenesis. All animals showed MR fogging at days 4, 8 and 11 after stroke. The transient normalization of T2 signals occurred independently from the development of infarct volumes, but coincided well with the spatio–temporal occurrence of necrosis, angiogenesis and microglia/macrophage infiltration. Our results suggest that the fogging effect reflects the clearance of necrotic tissue within the ischemic lesion and is thus not relevant for the determination of the lesion volume. ► After stroke, MR sequences frequently show a transiently normalized imaging signal. ► MR fogging was also evident after permanent middle cerebral artery occlusion in rats. ► The infarct volume was not influenced by MR fogging. ► The pattern of MR fogging coincided with necrosis, angiogenesis and macrophage infiltration.

Background HPV-infection, p16 positivity, and EGFR expression have been correlated with favorable responses of head and neck cancer patients treated with radiotherapy (RT) with or without chemotherapy. However, a possible correlation of HPV/p16 and EGFR status on the effect of RT in combination with cetuximab has not been sufficiently investigated. Materials and methods We analyzed tumor samples for p16 and EGFR expression and correlated these variables with treatment outcome. Cox-proportional-hazard regression models were applied to compare the risk of death among patients stratified according to risk factors. Survival was estimated by the Kaplan–Meier method. Results were compared with an institutional historical control group treated without cetuximab and with published data. Results Expression of p16 was predominantly found in oropharyngeal squamous cell cancer patients (OPSCC; 36.6 % positivity; 92 % of all cases), while EGFR was expressed at high levels in all tumor subsites (82 %). p16 expression was associated with improved overall survival in irradiated OPSCC patients (2-year overall survival of 80 % in p16-positive vs. 33 % overall survival in p16-negative patients). In a multivariable analysis covering all tumor sites, nodal stage (> N2a vs. ≤ N2a) and tumor site (OPSSC vs. non-OPSCC) had an impact on overall survival. Conclusion Our results show that p16 positivity is associated with a favorable outcome in OPSCC patients treated with RT and cetuximab.

Although tissue-engineering approaches have led to significant progress in the quest of finding a viable substitute for dysfunctional myocardium, the vascularization of such bioartificial constructs still remains a major challenge. Hence, there is a need for model systems that allow us to study and better understand cardiac and vascular biology to overcome current limitations. Therefore, in this study, in toto decellularized rat hearts with a patent vessel system were processed into standardized coronary artery tissue flaps adherent to the ascending aorta. Protein diffusivity analysis and blood perfusion of the coronary arteries showed proper sealing of the de-endothelialized vessels. Retrograde aortic perfusion allowed for selective seeding of the coronary artery system, while surface seeding of the tissue flaps allowed for additional controlled coculture with cardiac cells. The coronary artery tissue-flap model offers a patent and perfusable coronary vascular architecture with a preserved cardiac extracellular matrix, therefore mimicking nature's input to the highest possible degree. This offers the possibility to study re-endothelialization and endothelial function of different donor cell types and their interaction with cardiac cells in a standardized biologically derived cardiac in vitro model, while establishing a platform that could be used for in vitro drug testing and stem cell differentiation studies.