Feedback and Analysis System to Improve Partial Weight Bearing and Bone Healing Following Fractures and Osteotomies of the Lower Limb: Technical Note.

PURPOSE OF THE STUDY After the surgical treatment of injuries of the lower extremities or osteotomies, patients are frequently asked to partially load the affected leg during the first weeks of rehabilitation. The patient's compliance to the prescribed weight bearing limit and their ability to regain a physiological gait as soon as possible are necessary for a fast rehabilitation without complications. MATERIAL AND METHODS/RESULTS To support patients during this important phase of recovery, we developed a feedback and analysis system that is able to provide feedback concerning loading and roll over behavior to the patient. The system is based on sensor insoles to measure the amount of pressure and pressure distribution and on a smartphone application to provide realtime visual and acoustic feedback. CONCLUSIONS This newly developed device has the potential to monitor the rehabilitation phase and assist patients with lower leg injuries therefore decrease the complication rate and enable faster rehabilitation. Key words: lower limb fracture osteotomy around the knee, partial weight bearing, realtime feedback, smartphone application.

Infective endocarditis on ICU: risk factors, outcome and long-term follow-up.

OBJECTIVE: To identify factors associated with short-term, intermediate and long-term outcome in patients with infective endocarditis (IE) and the need for treatment on intensive care unit (ICU). DESIGN AND SETTING: Retrospective analysis and long-term follow-up by questionnaire in the two medical ICUs of our university hospital. PATIENTS: We conducted a retrospective analysis of all consecutive patients with IE and need for ICU treatment in our department between 2002 and 2009. All patients fulfilled the modified Duke criteria for definite diagnosis of IE. MEASUREMENTS AND MAIN RESULTS: Data of 216 patients (aged 62 ± 14 years, 31 % female) were analyzed, 15.7 % of whom had prosthetic valve endocarditis. Infectious agent (IA) was identified in 74 % and surgery was performed in 57 %. 56 patients (24.9 %) died on ICU, 9 patients were sent to palliative care units and died several days later. During follow-up, another 44 patients died. Multivariate Cox-regression analysis identified the following independent risk factors: High initial SAPS II for 30d-, multiple organ failure and high maximum SAPS II for 100d- and high maximum leukocyte count for long-term mortality. Surgical intervention during ICU was an independent predictor of a better 30d outcome. CONCLUSIONS: In contrast to general IE populations, IA and the type of infected impaired valve are not main predictors of survival in critically ill IE-patients. Biomarker of acute infection and markers for severity of illness (scores and organ failure) are independent risk factors for mortality. The surgical clearance of infected valve, device or abscesses is an independent predictor of 30d outcome.

Endothelial function in contemporary patients with repaired coarctation of aorta.

OBJECTIVE: Previous studies have suggested endothelial dysfunction in adult patients after repair of aortic coarctation (CoA). It has been proposed to play a key role in the pathogenesis of arterial hypertension in the absence of re-coarctation. We aimed to assess the presence of endothelial dysfunction, the number of endothelial progenitor cells (EPC), and the levels of proinflammatory cytokines associated with endothelial injury in contemporary patients after CoA repair. METHODS: For this prospective observational study, 20 CoA patients and 22 healthy controls were recruited. Digital reactive hyperaemia was measured by peripheral arterial tonometry. Flow cytometry was used to quantify EPCs, and a comprehensive panel of laboratory markers of endothelial dysfunction was measured. RESULTS: Half the patients had known arterial hypertension requiring medical treatment. Indices of reactive hyperaemia showed no significant difference between CoA patients (1.96±0.32) and controlss (1.765±0.48) (p=0.82). Circulating EPCs, defined by the number of CD34(+), CD34(+)/KDR(+), CD34(+)/AC133(+), CD34(+)/AC133(+)/KDR(+) or CD34(+)/CD45(-) labelled cells were equally not significantly different between the groups. Furthermore, plasma levels of inflammatory mediators and markers of endothelial function (IL-6, IL-8, ICAM1 and VCAM1) were not significantly different between the groups, as were vascular endothelial growth factor levels (p>0.05, for all). CONCLUSIONS: By contrast with earlier reports, no clinically significant difference in endothelial function between adult patients with coarctation repair and healthy controls could be demonstrated. Therefore, endothelial dysfunction may not necessarily be present in this population. Further studies are required to identify mechanisms and to develop strategies to avoid arterial hypertension in these patients.

Occludin is required for apoptosis when claudin-claudin interactions are disrupted.

Disruption of tight junctions is often seen during pathogen infection, inflammation, and tumor progression. Mislocalization of the tight junction proteins occludin and claudin in mammary epithelial monolayers leads to apoptosis through the extrinsic pathway. To further investigate the mechanism of this response, a normal mammary epithelial cell line (EpH4) as well as primary mammary epithelial cells were treated with a claudin-disrupting mimic peptide, DFYNP (aspartic acid-phenylalanine-tyrosine-asparagine-proline). Using fluorescent indicators, we found that caspase-3 activation, resulting from treatment with DFYNP, was restricted to EpH4 and primary mammary epithelial cells with mislocalized claudin-4. Mislocalized claudin-4 and occludin were colocalized in non-junctional puncta, and both molecules were found in the death-inducing signaling complex (DISC) where they colocalized with Fas, fas-associated protein with death domain (FADD), active caspase-8 and caspase-3 at distinct apical domains. Importantly, caspase-3 activation was totally repressed in primary mammary epithelial cells from occludin null mice. Thus, the apoptotic response appears to be initiated by the movement of occludin to the DISC suggesting that this molecule has signaling properties that initiate cell death when its tight junction location is disrupted.

Comparison between transcatheter and surgical prosthetic valve implantation in patients with severe aortic stenosis and reduced left ventricular ejection fraction.

BACKGROUND: Patients with severe aortic stenosis and reduced left ventricular ejection fraction (LVEF) have a poor prognosis with conservative therapy but a high operative mortality when treated surgically. Recently, transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement (SAVR) for patients considered at high or prohibitive operative risk. The objective of this study was to compare TAVI and SAVR with respect to postoperative recovery of LVEF in patients with severe aortic stenosis and reduced LV systolic function. METHODS AND RESULTS: Echocardiographic data were prospectively collected before and after the procedure in 200 patients undergoing SAVR and 83 patients undergoing TAVI for severe aortic stenosis (aortic valve area ≤1 cm(2)) with reduced LV systolic function (LVEF ≤50%). TAVI patients were significantly older (81±8 versus 70±10 years; P<0.0001) and had more comorbidities compared with SAVR patients. Despite similar baseline LVEF (34±11% versus 34±10%), TAVI patients had better recovery of LVEF compared with SAVR patients (ΔLVEF, 14±15% versus 7±11%; P=0.005). At the 1-year follow-up, 58% of TAVI patients had a normalization of LVEF (>50%) as opposed to 20% in the SAVR group. On multivariable analysis, female gender (P=0.004), lower LVEF at baseline (P=0.005), absence of atrial fibrillation (P=0.01), TAVI (P=0.007), and larger increase in aortic valve area after the procedure (P=0.01) were independently associated with better recovery of LVEF. CONCLUSION: In patients with severe aortic stenosis and depressed LV systolic function, TAVI is associated with better LVEF recovery compared with SAVR. TAVI may provide an interesting alternative to SAVR in patients with depressed LV systolic function considered at high surgical risk.

Pulmonary arterial hypertension in adults with congenital heart disease.

Pulmonary arterial hypertension (PAH) is a common problem in adult patients with congenital heart disease. We review available data on aetiology, clinical presentation, prognosis and management of PAH in this setting. In addition, we discuss general management strategies and emerging disease-targeting therapies.

Probability of metastable configurations in spherical three-dimensional Yukawa crystals.

Recently the occurrence probabilities of ground and metastable states of three-dimensional Yukawa clusters with 27 and 31 particles have been analyzed in dusty plasma experiments [D. Block, Phys. Plasmas 15, 040701 (2008)]. There it was found that, in many cases, the ground state appeared substantially less frequently than excited states. Here we analyze this question theoretically by means of molecular dynamics (MD) and Monte Carlo simulations and an analytical method based on the canonical partition function. We confirm that metastable states can occur with a significantly higher probability than the ground state. The results strongly depend on the screening parameter of the Yukawa interaction and the damping coefficient used in the MD simulations. The analytical method allows one to gain insight into the mechanisms being responsible for the occurrence probabilities of metastable states in strongly correlated finite systems.

Melting of trapped few-particle systems.

In small confined systems predictions for the melting point strongly depend on the choice of quantity and on the way it is computed, even yielding divergent and ambiguous results. We present a very simple quantity that allows us to control these problems-the variance of the block averaged interparticle distance fluctuations.

Moderate patient-prosthesis mismatch after valve replacement for severe aortic stenosis has no impact on short-term and long-term mortality.

BACKGROUND: The importance of moderate patient-prosthesis mismatch (PPM) for the prognosis of patients who undergo aortic valve replacement is unclear. METHODS: The presence of PPM was assessed in 361 consecutive patients undergoing valve replacement for isolated severe aortic stenosis and related to perioperative and postoperative mortality. Indexed effective orifice areas (EOAi) were estimated for each type and size of prosthesis. RESULTS: Using the previously proposed cut-off of EOAi

Myocardial blood flow in patients with low-flow, low-gradient aortic stenosis: differences between true and pseudo-severe aortic stenosis. Results from the multicentre TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study.

BACKGROUND: Impairment of myocardial flow reserve (MFR) in aortic stenosis (AS) with normal left ventricular function relates to the haemodynamic severity. OBJECTIVES: To investigate whether myocardial blood flow (MBF) and MFR differ in low-flow, low-gradient AS depending on whether there is underlying true-severe AS (TSAS) or pseudo-severe AS (PSAS). METHODS: In 36 patients with low-flow, low-gradient AS, dynamic [13N]ammonia PET perfusion imaging was performed at rest (n = 36) and during dipyridamole stress (n = 20) to quantify MBF and MFR. Dobutamine echocardiography was used to classify patients as TSAS (n = 18) or PSAS (n = 18) based on the indexed projected effective orifice area (EOA) at a normal flow rate of 250 ml/s (EOAI(proj )0.55 cm(2)/m(2)). RESULTS: Compared with healthy controls (n = 14), patients with low-flow, low-gradient AS had higher resting mean (SD) MBF (0.83 (0.21) vs 0.69 (0.09) ml/min/g, p = 0.001), reduced hyperaemic MBF (1.16 (0.31) vs 2.71 (0.50) ml/min/g, p<0.001) and impaired MFR (1.44 (0.44) vs 4.00 (0.91), p<0.001). Resting MBF and MFR correlated with indices of AS severity in low-flow, low-gradient AS with the strongest relationship observed for EOAI(proj) (r(s) = -0.50, p = 0.002 and r(s) = 0.61, p = 0.004, respectively). Compared with PSAS, TSAS had a trend to a higher resting MBF (0.90 (0.19) vs 0.77 (0.21) ml/min/g, p = 0.06), similar hyperaemic MBF (1.16 (0.31) vs 1.17 (0.32) ml/min/g, p = NS), but a significantly smaller MFR (1.19 (0.26) vs 1.76 (0.41), p = 0.003). An MFR <1.8 had an accuracy of 85% for distinguishing TSAS from PSAS. CONCLUSIONS: Low-flow, low-gradient AS is characterised by higher resting MBF and reduced MFR that relates to the AS severity. The degree of MFR impairment differs between TSAS and PSAS and may be of value for distinguishing these entities.

[Geriatric health promotion and prevention for independently living senior citizens: programmes and target groups]. / Geriatrische Gesundheitsförderung und Prävention für selbstständig lebende Senioren: Angebote und Zielgruppen.

BACKGROUND: Nearly all diseases in old age that are epidemiologically important can be reduced or prevented successfully through consequent changes in individual lifestyle, a systematic provision of measures in primary prevention (i.e. vaccination programmes) and the creation of health promoting settings. However, at the moment the amount of potential for preventative interventions is neither systematically nor sufficiently utilised in Germany. METHODS: Two different preventative approaches: a) multidimensional advice session in small groups through an interdisciplinary team at a geriatric centre (seniors come to seek advice offered at a centre) or b) multidimensional advice at the seniors home through one member of the interdisciplinary team from the geriatric centre (expert takes advice to seniors home) were tested simultaneously with a well-described study sample of 804 independent community-dwelling senior citizens aged 60 years or over, without need of care and cognitive impairments recruited from general practices. Information about target group specific approaches in health promotion and prevention for senior citizens were retrieved from analyses of sociodemographic, medical, psychological and spacial characteristics of this study sample. RESULTS: The majority of the study sample (580 out of 804 or 72.1%) decided to participate: a) 86.7% (503 out of 580) attended at the geriatric centre and sought advice in group sessions and b) 13.3% (77 out of 580) decided to receive advice in a preventive home visit. A total of 224 seniors (224 out of 804 or 27.9%) refused to participate at all. These three target groups were characterised on the basis of their age, gender, education, social background, health status, health behaviour, use of preventive care, self perceived health, functional disabilities, social net and social participation and distance or accessibility of preventative approaches. The 503 senior citizens who participated in small group sessions at the geriatric centre were characterised as "investors into their health resources". They were mobile and participated actively in their environment. They were open for health promoting advice and capable of understanding and incorporating it into their daily routines (health literacy). Those 224 seniors who refused any participation were characterised as "consumers of their health resources". They did not differ in age and gender from the health investors, but showed less self-efficacy and less self-responsibility and typical behaviour that endangers health in an active way, i.e. smokers or in a passive way, i.e. low physical activity. The 77 seniors who received a preventive home visit were characterised as "people with exhausted health resources". Their mobility was clearly restricted and autonomy was confined to their home environment. This group represented frail elderly people with many risk factors in different domains. CONCLUSION: The strongest reason to refuse participation in health promoting programmes was the personal attitude related to one's own personal health. Taking account of needs and wants of the seniors who refused to participate more people expressed the reason "no interest" in the preventive home visit than in the small group session at the geriatric centre. To strengthen the integration of the GP as a trustworthy person would seem to be more successful to motivate senior citizens to participate in health promoting and preventative programmes in the future. This could succeed in a cooperation with geriatric centres to establish community centres for generally healthy senior citizens.

Calcium signalling and pancreatic cell death: apoptosis or necrosis?

Secretagogues, such as cholecystokinin and acetylcholine, utilise a variety of second messengers (inositol trisphosphate, cADPR and nicotinic acid adenine dinucleotide phosphate) to induce specific oscillatory patterns of calcium (Ca(2+)) signals in pancreatic acinar cells. These are tightly controlled in a spatiotemporal manner, and are coupled to mitochondrial metabolism necessary to fuel secretion. When Ca(2+) homeostasis is disrupted by known precipitants of acute pancreatitis, for example, hyperstimulation or non-oxidative ethanol metabolites, Ca(2+) stores (endoplasmic reticulum and acidic pool) become depleted and sustained cytosolic [Ca(2+)] elevations replace transient signals, leading to severe consequences. Sustained mitochondrial depolarisation, possibly via opening of the mitochondrial permeability transition pore (MPTP), elicits cellular ATP depletion that paralyses energy-dependent Ca(2+) pumps causing cytosolic Ca(2+) overload, while digestive enzymes are activated prematurely within the cell; Ca(2+)-dependent cellular necrosis ensues. However, when stress to the acinar cell is milder, for example, by application of the oxidant menadione, release of Ca(2+) from stores leads to oscillatory global waves, associated with partial mitochondrial depolarisation and transient MPTP opening; apoptotic cell death is promoted via the intrinsic pathway, when associated with generation of reactive oxygen species. Apoptosis, induced by menadione or bile acids, is potentiated by inhibition of an endogenous detoxifying enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), suggesting its importance as a defence mechanism that may influence cell fate.

Structural properties of screened Coulomb balls.

Small three-dimensional strongly coupled charged particles in a spherical confinement potential arrange themselves in a nested shell structure. By means of experiments, computer simulations, and theoretical analysis, the sensitivity of their structural properties to the type of interparticle forces is explored. While the normalized shell radii are found to be independent of shielding, the shell occupation numbers are sensitive to screening and are quantitatively explained by an isotropic Yukawa model.

Ground state of a confined Yukawa plasma.

The ground state of an externally confined one-component Yukawa plasma is derived analytically. In particular, the radial density profile is computed. The results agree very well with computer simulations of three-dimensional spherical Coulomb crystals. We conclude in presenting an exact equation for the density distribution for a confinement potential of arbitrary geometry.

What influences the outcome of valve replacement in critical aortic stenosis?

Even patients with severely reduced left ventricular function and critical aortic stenosis can improve notably following valve replacement.

Cyclooxygenase 1 is required for pH control at the mouse gastric surface.

BACKGROUND: Endogenous cyclooxygenase (COX) activity is required to maintain a relatively alkaline surface pH at the gastric luminal surface. AIMS: The purpose of this study was to determine which COX isoform, COX-1 or COX-2, is responsible for regulating the protective surface pH gradient and to test if COX inhibitors also had non-COX mediated effects in vivo. METHODS: Immunofluorescence and western blot analysis showed constitutive expression of both COX isoforms in the normal mouse stomach. We used in vivo confocal microscopy to measure pH near the mucosal surface of anaesthetised COX-1 (-/-), COX-2 (-/-), or wild-type mice of the same genetic background. RESULTS: When the gastric mucosal surface was exposed and superfused (0.2 ml/min) with a weakly buffered saline solution (pH 3) containing the pH indicator Cl-NERF, the pH directly at the gastric surface and thickness of the pH gradient were similar in wild-type and COX-2 (-/-) mice, but COX-1 (-/-) mice had a significantly thinner pH gradient. Addition of indomethacin had minimal effects on the residual surface pH gradient in COX-1 (-/-) mice, suggesting no role for COX-2 in surface pH regulation. Whole stomach perfusion studies demonstrated diminished net alkali secretion in COX-1 (-/-) mice, and application of SC-560 or rofecoxib to wild-type mice and mutant mice confirmed that only COX-1 inhibition reduced alkali secretion. CONCLUSION: COX-1 is the dominant isoform regulating the normal thickness of the protective surface pH gradient in mouse stomach.