Showing papers by "Danube University Krems published in 2012"

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Abstract: Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

Delaying progression to type 2 diabetes among high-risk Spanish individuals is feasible in real-life primary healthcare settings using intensive lifestyle intervention

Abstract: Aims/hypothesis To assess the feasibility and effectiveness of an active real-life primary care lifestyle intervention in preventing type 2 diabetes within a high-risk Mediterranean population.

Tissue Engineering for Total Meniscal Substitution: Animal Study in Sheep Model—Results at 12 Months

Abstract: The aim of the study was to investigate the use of a hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Eighteen skeletally mature sheep were treated. The animals were divided into three groups: cell-free scaffold, scaffold seeded with autologous chondrocytes, and meniscectomy alone. The implant was sutured to the capsule and to the meniscal ligament. At a 12-month gross assessment, histology and histomorphometry were used to assess the meniscus implant, knee joint, and osteoarthritis development. All implants showed excellent capsular ingrowth at the periphery. The implant gross assessment showed significant differences between cell-seeded and cell-free groups (p=0.011). The histological analysis indicated a cellular colonization throughout the implanted constructs. Avascular cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Joint gross assessment showed that sheep treated with scaffold implantation achieved a significant higher score than those underwent meniscectomy (p<0.0005), and the Osteoarthritis Research Society International score showed that osteoarthritic changes were significantly less in the cell-seeded group than in the meniscectomy group (p=0.047), even though results were not significantly superior to those of the cell-free scaffold. Seeding of the scaffold with autologous chondrocytes increases its tissue regeneration capacity, providing a better fibrocartilaginous tissue formation. The study suggests the potential of the novel hyaluronic acid/polycaprolactone scaffold for total meniscal substitution, although this approach has to be further improved before being applied into clinical practice.

Mitochondrial toxicity of antiepileptic drugs and their tolerability in mitochondrial disorders.

Abstract: Introduction: Epilepsy is a frequent CNS manifestation of mitochondrial disorders (MIDs). At present, patients with MID-related epilepsy are largely treated in the same way as any other epilepsy sufferer. The problem with this approach is that some antiepileptic drugs (AEDs) are mitochondrial toxic and care is, therefore, needed when administering these AEDs to patients with MIDs. Areas covered: This review summarizes and discusses the mitochondrial toxicity, tolerability and beneficial effects of AED in patients with MIDs. The literature for this article was retrieved through PubMed using the search terms: ‘mitochondrial disorder', ‘mitochondriopathy', ‘mitochondrial', ‘cytopathy', ‘metabolic disease', ‘epilepsy', ‘seizures' and various AEDs alone or in combination. Expert opinion: Mitochondrial-toxic AEDs may trigger or worsen an MID or may be even fatal in single cases. The AED with the most well-known mitochondrial toxicity is valproic acid (VPA), which has been known to exhibit a deleterious effect i...

Leukocyte telomere length in the Finnish Diabetes Prevention Study

Abstract: Leukocyte telomere length (TL) is considered a biomarker for biological aging. Shortened TL has been observed in many complex diseases, including type 2 diabetes (T2DM). Lifestyle intervention studies, e.g. the Diabetes Prevention Study (DPS), have shown a decrease in the incidence of T2DM by promoting healthy lifestyles in individuals with impaired glucose tolerance (IGT). Our aim was to study in the DPS the influence of the lifestyle intervention on TL. TL was measured by quantitative PCR-based method at two time points (N = 334 and 343) on average 4.5 years apart during the active intervention and post-intervention follow-up. TL inversely correlated with age. Our main finding was that TL increased in about two thirds of the individuals both in the intervention and in the control groups during follow-up; TL increased most in individuals with the shortest TL at the first measurement. TL was not associated with development of T2DM, nor did lifestyle intervention have an effect on TL. No association between insulin secretion or insulin resistance indices and TL was observed. We did not detect an association between TL and development of T2DM in the DPS participants. It could be due to all participants being overweight and having IGT at baseline, both of which have been found to be independently associated with shorter leukocyte TL in some earlier studies. TL had no substantial role in worsening of glucose tolerance in people with IGT. Our study confirms that leukocyte TL can increase with time even in obese people with impaired glucose metabolism.

Epilepsy in mitochondrial disorders

Abstract: Objectives Information about epilepsy in mitochondrial disorders is scarce although a number or syndromic and non-syndromic mitochondrial disorders frequently manifest with focal or generalized seizures. Aim of the review was to describe epilepsy in syndromic and non-syndromic mitochondrial disorders with epilepsy as a dominant or collateral feature of the phenotype. Methods Literature search via Pubmed using the key words "mitochondrial", "epilepsy", "seizures", and all acronyms of syndromic mitochondrial disorders. Results Syndromic mitochondrial disorders obligatory associated with epilepsy include Alpers-Huttenlocher-syndrome (AHS), ataxia neuropathy spectrum (ANS), Leigh-syndrome, MELAS-syndrome, myoclonic epilepsy, myopathy, and sensory ataxia (MEMSA) syndrome, and MERRF-syndrome, Occasionally, epilepsy is a phenotypic feature in IOSCA, KSS, LHON, LBSL, or NARP, All types of seizures occur but most frequently generalized tonic–clonic seizures, partial seizures, myoclonic jerks, or West-syndrome was reported. Treatment of epilepsy in patients with mitochondrial disorders is not at variance from epilepsy of other causes but mitochondrion-toxicity of various antiepileptic drugs, such as valproic acid, carbamazepine etc. has to be considered to avoid severe complications or deterioration of the underlying disease. Conclusions Epilepsy is a common phenotypic feature of syndromic as well as non-syndromic mitochondrial disorders. Treatment of epilepsy in mitochondrial disorders is not at variance from treatment of epilepsy due to other causes but mitochondrion-toxic drugs should be avoided.

Comparative effectiveness of second-generation antidepressants for accompanying anxiety, insomnia, and pain in depressed patients: a systematic review

Abstract: Background Patients with major depressive disorder (MDD) often suffer from accompanying symptoms that influence the choice of pharmacotherapy with second-generation antidepressants (SGAs). We conducted a systematic review to determine the comparative effectiveness of citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, desvenlafaxine, duloxetine, venlafaxine, bupropion, mirtazapine, nefazodone, and trazodone, for accompanying anxiety, insomnia, and pain in patients with MDD. Methods We conducted searches in multiple databases including MEDLINE®, Embase, the Cochrane Library, International Pharmaceutical Abstracts, and PsycINFO, from 1980 through August 2011 and reviewed reference lists of pertinent articles. We dually reviewed abstracts, full-text articles, and abstracted data. We included randomized, head-to-head trials of SGAs of at least 6 weeks’ duration. We grouped SGAs into three classes for the analysis: selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors, and others. We graded the strength of the evidence as high, moderate, low, or very low based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group (GRADE) approach. Results We located 19 head-to-head trials in total: 11 on anxiety, six on insomnia, and four on pain. For the majority of comparisons, the strength of the evidence was moderate or low: evidence is weakened by inconsistency and imprecision. For treating anxiety, insomnia, and pain moderate evidence suggests that the SSRIs do not differ. Conclusions Evidence guiding the selection of an SGA based on accompanying symptoms of depression is limited. Very few trials were designed and adequately powered to answer questions about accompanying symptoms; analyses were generally of subgroups in larger MDD trials.

Cognitive dysfunction in mitochondrial disorders

Abstract: Among the various central nervous system (CNS) manifestations of mitochondrial disorders (MIDs), cognitive impairment is increasingly recognized and diagnosed (mitochondrial cognitive dysfunction). Aim of the review was to summarize recent findings concerning the aetiology, pathogenesis, diagnosis and treatment of cognitive decline in MIDs. Among syndromic MIDs due to mitochondrial DNA (mtDNA) mutations, cognitive impairment occurs in patients with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes syndrome, myoclonus epilepsy with ragged-red fibres syndrome, mitochondrial chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome, neuropathy, ataxia and retinitis pigmentosa syndrome and maternally inherited diabetes and deafness. Among syndromic MIDs due to nuclear DNA (nDNA) mutations, cognitive decline has been reported in myo-neuro-gastro-intestinal encephalopathy, mitochondrial recessive ataxia syndrome, spinocerebellar ataxia with encephalopathy, Mohr-Tranebjaerg syndrome, leuko-encephalopathy; brain and spinal cord involvement and lactic acidosis, CMT2, Wolfram syndrome, Wolf-Hirschhorn syndrome and Leigh syndrome. In addition to syndromic MIDs, a large number of non-syndromic MIDs due to mtDNA as well as nDNA mutations have been reported, which present with cognitive impairment as the sole or one among several other CNS manifestations of a MID. Delineation of mitochondrial cognitive impairment from other types of cognitive impairment is essential to guide the optimal management of these patients. Treatment of mitochondrial cognitive impairment is largely limited to symptomatic and supportive measures. Cognitive impairment may be a CNS manifestation of syndromic as well as non-syndromic MIDs. Correct diagnosis of mitochondrial cognitive impairment is a prerequisite for the optimal management of these patients.

Clinical outcome after microfracture of the knee: a meta-analysis of before/after-data of controlled studies

Abstract: Purpose The aims of this study were to systematically review the medical literature, in order to find controlled studies about microfracture in the treatment of patients with full-thickness cartilage lesions of the knee, to statistically combine these studies in order to determine a best estimate of the average treatment effect, and to gather information to detect cartilage-specific and patient-specific factors that might have an influence on the clinical outcome

Robust Precision Position Detection With an Optical MEMS Hybrid Device

Abstract: For vibration and displacement sensors, robustness is one of the key requirements. Optical measurement concepts are among the most promising possibilities to achieve it. The presented microoptoelectromechanical system sensor modulates a light flux by means of two congruently placed aperture gratings: one etched into a seismic mass and the other fixed to the sensor package. Commercially available LED and photodetector components at the top and bottom of the sandwich structure generate and detect this modulated light flux and allow for a cost-effective implementation. The prototype used for experimental verification is actuated by inertial forces and exhibits a high sensitivity of 0.85 mV/nm for displacements of the seismic mass and a corresponding noise level of about 14 pm/√Hz. This sensitivity and noise level can be further improved, paving the way for small, lightweight, robust, and high-precision displacement sensors for a large variety of applications.

Methods for the Drug Effectiveness Review Project

Abstract: The Drug Effectiveness Review Project was initiated in 2003 in response to dramatic increases in the cost of pharmaceuticals, which lessened the purchasing power of state Medicaid budgets. A collaborative group of state Medicaid agencies and other organizations formed to commission high-quality comparative effectiveness reviews to inform evidence-based decisions about drugs that would be available to Medicaid recipients. The Project is coordinated by the Center for Evidence-based Policy (CEbP) at Oregon Health & Science University (OHSU), and the systematic reviews are undertaken by the Evidence-based Practice Centers (EPCs) at OHSU and at the University of North Carolina. The reviews adhere to high standards for comparative effectiveness reviews. Because the investigators have direct, regular communication with policy-makers, the reports have direct impact on policy and decision-making, unlike many systematic reviews. The Project was an innovator of methods to involve stakeholders and continues to develop its methods in conducting reviews that are highly relevant to policy-makers. The methods used for selecting topics, developing key questions, searching, determining eligibility of studies, assessing study quality, conducting qualitative and quantitative syntheses, rating the strength of evidence, and summarizing findings are described. In addition, our on-going interactions with the policy-makers that use the reports are described.

Indoor air in schools and lung function of Austrian school children

Abstract: The Children's Environment and Health Action Plan for Europe (CEHAPE) of WHO focuses (inter alia) on improving indoor environments where children spend most of their time. At present, only little is known about air pollution in schools and its effect on the lung function of school children. Our project was set up as an Austrian contribution to CEHAPE. In a cross-sectional approach, differences in indoor pollution in nine elementary all-day schools were assessed and 34 of these pollutants were analyzed for a relationship with respiratory health determined by spirometry using a linear regression model. Overall 596 children (aged 6–10 years) were eligible for the study. Spirometry was performed in 433 children. Socio-economic status, area of living (urban/rural), and smoking at home were included in the model as potential confounders with school-related average concentration of air pollutants as the variable of primary interest. A negative association with flow volumes (MEF75) was found for formaldehyde in air samples, benzylbutylphthalate and the sum of polybrominated diphenylethers in school dust. FVC and FEV1 were negatively associated with ethylbenzene and xylenes in air samples and tris(1,3-dichlor-2-propyl)-phosphate on particulates. Although, in general, the quality of school indoor air was not worse than that reported for homes, effects on the respiratory health of children cannot be excluded. A multi-faceted strategy to improve the school environment is needed.

Stroke and Stroke-like Episodes in Muscle Disease

Abstract: Background: Though not obvious at a first glance, myopathies may be associated with ischemic stroke. Stroke- like episodes resemble ischemic stroke only to some extent but are a unique feature of certain mitochondrial disorders with a pathogenesis at variance from that of ischemic stroke. Only limited data are available about ischemic stroke in pri- mary myopathies and the management of stroke-like episodes in mitochondrial disorders. This review aims to summarize and discuss current knowledge about stroke in myopathies and to delineate stroke-like episodes from ischemic stroke. Methods: Literature review via PubMED using the search terms "stroke", "cerebrovascular", "ischemic event", "stroke- like episode", "stroke-mimic", "mitochondrial disorder". Results: Stroke in myopathies is most frequently cardioembolic due to atrial fibrillation or atrial flutter, dilated cardio- myopathy, or left-ventricular hypertrabeculation (noncompaction). The second most frequent cause of stroke in myopathies is angiopathy from atherosclerosis or vasculitis, which may be a feature of inflammatory myopathies. Athero- sclerosis may either result from classical risk factors, such as diabetes, arterial hypertension, hyperlpidemia, or smoking, associated with muscle disease, or may be an inherent feature of a mitochondrial disorder. In case of severe heart failure from cardiomyopathy as a manifestation of muscle disease low flow infarcts may occur. Thrombophilic stroke has been described in polymyositis and dermatomyositis in association with anti-phospholipid syndrome. Stroke-like episodes oc- cur particularly in mitochondrial encephalopathy, lactacidosis and stroke-likeepisode syndrome but rarely also in Leigh- syndrome and other mitochondrial disorders. Stroke-like episodes are at variance from ischemic stroke, pathogenically, clinically and on imaging. They may be the manifestation of a vascular, metabolic or epileptic process and present with predominantly vasogenic but also cytotoxic edema on MRI. Differentiation between ischemic stroke and stroke-like epi- sodes is essential in terms of management and prognosis. Management of ischemic stroke in patients with myopathy is not at variance from the treatment of ischemic stroke in non-myopathic patients. There is no standardized treatment of stroke- like episodes but there is increasing evidence that these patients profit from the administration of L-arginine and conse- quent antiepileptic treatment if associated with seizure activity. Conclusions: Ischemic stroke may be a complication of myopathy and needs to be delineated from stroke-like episodes, which are unique to mitochondrial disorders, particularly mitochondrial encephalopathy, lactacidosis and stroke- likeepisode syndrome. Ischemic stroke in myopathies is most frequently cardioembolic and treatment is not at variance from non-myopathic ischemic stroke. Treatment of stroke-like episodes is not standardized but seems to respond to L- arginine and adequate antiepileptic treatment.

The User Puzzle&#8212;Explaining the Interaction with Visual Analytics Systems

Abstract: Visual analytics emphasizes the interplay between visualization, analytical procedures performed by computers and human perceptual and cognitive activities. Human reasoning is an important element in this context. There are several theories in psychology and HCI explaining open-ended and exploratory reasoning. Five of these theories (sensemaking theories, gestalt theories, distributed cognition, graph comprehension theories and skill-rule-knowledge models) are described in this paper. We discuss their relevance for visual analytics. In order to do this more systematically, we developed a schema of categories relevant for visual analytics research and evaluation. All these theories have strengths but also weaknesses in explaining interaction with visual analytics systems. A possibility to overcome the weaknesses would be to combine two or more of these theories.

Inherited Mitochondrial Disorders

Abstract: Though inherited mitochondrial disorders (MIDs) are most well known for their syndromic forms, for which widely known acronyms (MELAS, MERRF, NARP, LHON etc.) have been coined, the vast majority of inherited MIDs presents in a non-syndromic form. Since MIDs are most frequently multisystem disorders already at onset or during the disease course, a MID should be suspected if there is a combination of neurological and non-neurological abnormalities. Neurological abnormalities occurring as a part of a MID include stroke-like episodes, epilepsy, migraine-like headache, movement disorders, cerebellar ataxia, visual impairment, encephalopathy, cognitive impairment, dementia, psychosis, hypopituitarism, aneurysms, or peripheral nervous system disease, such as myopathy, neuropathy, or neuronopathy. Non-neurological manifestations concern the ears, the endocrine organs, the heart, the gastrointestinal tract, the kidneys, the bone marrow, and the skin. Whenever there is an unexplained combination of neurological and non-neurological disease in a patient or kindred, a MID should be suspected and appropriate diagnostic measures initiated. Genetic testing should be guided by the phenotype, the biopsy findings, and the biochemical results.

How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study

Abstract: Diabet. Med. 29, e126–e132 (2012) Abstract Aims To assess the effect of lifestyle intervention on depressive symptoms during a 36-month randomized clinical trial designed to prevent Type 2 diabetes. Methods A total of 522 middle-aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants. Results On study entry, the mean Beck Depression Inventory scores ± sd were 6.8 ± 5.6 in the intervention group and 6.7 ± 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean ± sd (95% CI) reduction was 0.90 ± 4.54 (−1.99 to −0.19) scores in the intervention group and 0.75 ± 4.47 (−1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R2 = 0.209, P < 0.001). Conclusions Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one’s lifestyle and behaviour is associated with beneficial changes in mood.

Clinical heterogeneity in systematic reviews and health technology assessments: synthesis of guidance documents and the literature

Abstract: Objectives: The aim of this study was to synthesize best practices for addressing clinical heterogeneity in systematic reviews and health technology assessments (HTAs).Methods: We abstracted information from guidance documents and methods manuals made available by international organizations that develop systematic reviews and HTAs. We searched PubMed® to identify studies on clinical heterogeneity and subgroup analysis. Two authors independently abstracted and assessed relevant information.Results: Methods manuals offer various definitions of clinical heterogeneity. In essence, clinical heterogeneity is considered variability in study population characteristics, interventions, and outcomes across studies. It can lead to effect-measure modification or statistical heterogeneity, which is defined as variability in estimated treatment effects beyond what would be expected by random error alone. Clinical and statistical heterogeneity are closely intertwined but they do not have a one-to-one relationship. The presence of statistical heterogeneity does not necessarily indicate that clinical heterogeneity is the causal factor. Methodological heterogeneity, biases, and random error can also cause statistical heterogeneity, alone or in combination with clinical heterogeneity.Conclusions: Identifying potential modifiers of treatment effects (i.e., effect-measure modifiers) is important for researchers conducting systematic reviews and HTAs. Recognizing clinical heterogeneity and clarifying its implications helps decision makers to identify patients and patient populations who benefit the most, who benefit the least, and who are at greatest risk of experiencing adverse outcomes from a particular intervention.

MEMS Thermal Flow Sensor With Smart Electronic Interface Circuit

Abstract: A smart system for flow measurement is presented, consisting of a micromachined thermal flow sensor combined with a smart front-end electronic interface. The flow sensor is based on a novel thermal transduction method, which combines the hot-film and calorimetric sensing principles. The sensor consists of four germanium thermistors embedded in a thin membrane and connected to form a Wheatstone bridge supplied with a constant DC current. In this configuration, both the bridge unbalance voltage and the voltage at the bridge supply terminals are functions of the flow offering high initial sensitivity, i.e., near zero flow and wide measurement range, respectively. The front-end interface is based on a CMOS relaxation oscillator circuit where the frequency and the duty cycle of a rectangular-wave output signal are related to the bridge unbalance voltage and the voltage at the bridge supply terminals, respectively. Furthermore, the amplitude of the output signal is a linear function of the operating temperature. In this way, a single output signal advantageously carries two pieces of information related to the flow velocity and provides an additional measurement of the sensor operating temperature, which enables the correction of the temperature dependence of the sensor readouts. The system has been experimentally characterized for the measurement of nitrogen gas flow velocity at different sensor temperatures. The initial sensitivities at room temperature result 13.7 kHz/(m/s) and 23.5%/(m/s), in agreement with FEM simulations, for frequency and duty cycle readouts, respectively, with an equivalent velocity resolution of about 0.5 and 1.3 cm/s.

A Target-Orientated Algorithm for Regional Citrate-Calcium Anticoagulation in Extracorporeal Therapies

Abstract: Background: Citrate anticoagulation offers several advantages in comparison to conventional anticoagulation. Most algorithms for regional citrate-calcium anticoagulation are based on citrate and calcium chloride infusion coupled in a fixed proportion to the blood flow without considering the hematocrit (Hct)/plasma flow or the filter clearance of citrate and calcium. Methods: The aim of this study was to develop an algorithm for optimized citrate anticoagulation in extracorporeal therapies such as dialysis. A mathematical model was developed to calculate the volume of citrate infusion required to achieve a desired ionized calcium (iCa) target level in the extracorporeal circuit and to restore the total calcium level to a physiological value. Results: The model was validated by correlation analyses for different blood Hct values and shows an excellent fit to the laboratory measurements. Conclusion: The results for both iCa target concentrations, namely those after citrate and calcium infusion, proved that the software algorithm adapts well to variable treatment parameters.

Visual Analysis of Dynamic Networks Using Change Centrality

Abstract: The visualization and analysis of dynamic social networks are challenging problems, demanding the simultaneous consideration of relational and temporal aspects. In order to follow the evolution of a network over time, we need to detect not only which nodes and which links change and when these changes occur, but also the impact they have on their neighbourhood and on the overall relational structure. Aiming to enhance the perception of structural changes at both the micro and the macro level, we introduce the change centrality metric. This novel metric, as well as a set of further metrics we derive from it, enable the pair wise comparison of subsequent states of an evolving network in a discrete-time domain. Demonstrating their exploitation to enrich visualizations, we show how these change metrics support the visual analysis of network dynamics.

How should primary care doctors select which antidepressants to administer

Abstract: Clinicians can choose among various second-generation antidepressants for treating depressive disorders, such as major depressive disorder, subsyndromal depression, or dysthymia. Systematic reviews indicate that available drugs differ in frequency of administration, costs, and the risks of some adverse events but have similar efficacy for treating major depressive disorder. Furthermore, evidence does not support the choice of one antidepressant over another based on accompanying symptoms, such anxiety, insomnia, or pain. Available studies provide little guidance for clinicians about the benefits of second-generation antidepressants for treating dysthymia and subsyndromal depression. Evidence is also unclear about the comparative risks of serious adverse events, such as suicidality, seizures, fractures, increased bleeding, or serotonin syndrome. This article summarizes the best available evidence regarding comparative benefits and harms of second-generation antidepressants for treating depressive disorders.

Collaboration for Open Innovation Processes in Public Administrations

Abstract: In Government 2.0, public value no longer needs to be provided by government alone but can be provided by any combination of public agencies, the private sector, civil society organizations or citizens. The ubiquitous presence of ICT, citizens’ digital literacy, and their potential willingness to participate online can efficiently enable collaborative production. Models for the inclusion of external stakeholders in public value production can increase the degree of public sector innovation and improve the outcomes of such processes. Governments can use the most valuable resource they have, the citizens, by establishing opportunities for civil society and businesses to engage in an open government.

Reduction of collateral thermal impact of diode laser irradiation on soft tissue due to modified application parameters.

Abstract: The aim of this study was to investigate the effect of different working modes (pulsed and micropulsed) and power settings of a standardized 980-nm diode laser on collateral thermal soft-tissue damage. A total of 108 bovine liver samples were cut with a diode laser at various settings in pulsed and micropulsed mode and histologically assessed to determine the area and depth of carbonization, necrosis and reversible tissue damage, as well as incision depth and width. Incision depth and width and the area and depth of carbonization, necrosis and reversible damage were correlated strongly with cutting speed. The area and depth of reversible damage were correlated with average power. The micropulsed mode produced a smaller zone of carbonization and necrosis and a smaller incision width. Setting the laser parameters in accordance with the absorption characteristics of the tissue reduced collateral thermal tissue damage while maintaining an acceptable cutting ability. Reducing collateral thermal damage from diode laser incisions is clinically relevant for promoting wound healing.

Chondrogenic Differentiation of Amniotic Fluid Stem Cells and Their Potential for Regenerative Therapy

Abstract: Chronic articular cartilage defects are the most common disabling conditions of humans in the western world. The incidence for cartilage defects is increasing with age and the most prominent risk factors are overweight and sports associated overloading. Damage of articular cartilage frequently leads to osteoarthritis due to the aneural and avascular nature of articular cartilage, which impairs regeneration and repair. Hence, patients affected by cartilage defects will benefit from a cell-based transplantation strategy. Autologous chondrocytes, mesenchymal stem cells and embryonic stem cells are suitable donor cells for regeneration approaches and most recently the discovery of amniotic fluid stem cells has opened a plethora of new therapeutic options. It is the aim of this review to summarize recent advances in the use of amniotic fluid stem cells as novel cell sources for the treatment of articular cartilage defects. Molecular aspects of articular cartilage formation as well as degeneration are summarized and the role of growth factor triggered signaling pathways, scaffolds, hypoxia and autophagy during the process of chondrogenic differentiation are discussed.