Effect on the tensile strength of human acellular dermis (Epiflex®) of in-vitro incubation simulating an open abdomen setting.

BACKGROUND: The use of human acellular dermis (hAD) to close open abdomen in the treatment process of severe peritonitis might be an alternative to standard care. This paper describes an investigation of the effects of fluids simulating an open abdomen environment on the biomechanical properties of Epiflex® a cell-free human dermis transplant. METHODS: hAD was incubated in Ringers solution, blood, urine, upper gastrointestinal (upper GI) secretion and a peritonitis-like bacterial solution in-vitro for 3 weeks. At day 0, 7, 14 and 21 breaking strength was measured, tensile strength was calculated and standard fluorescence microscopy was performed. RESULTS: hAD incubated in all five of the five fluids showed a decrease in mean breaking strength at day 21 when compared to day 0. However, upper GI secretion was the only incubation fluid that significantly reduced the mechanical strength of Epiflex after 21 days of incubation when compared to incubation in Ringer's solution. CONCLUSION: hAD may be a suitable material for closure of the open abdomen in the absence of upper GI leakage and pancreatic fistulae.

Micro-Twinning in IN738LC Manufactured with Laser Powder Bed Fusion.

Components manufactured with Metal Laser Powder Bed Fusion (PBF-LB/M) are built in a layerwise fashion. The PBF-LB/M build orientation affects grain morphology and orientation. Depending on the build orientation, microstructures from equiaxed to textured grains can develop. In the case of a textured microstructure, a clear anisotropy of the mechanical properties affecting short- and long-term mechanical properties can be observed, which must be considered in the component design. Within the scope of this study, the IN738LC tensile and creep properties of PBF-LB/M samples manufactured in 0° (perpendicular to build direction), 45° and 90° (parallel to build direction) build orientations were investigated. While the hot tensile results (at 850 °C) are as expected, where the tensile properties of the 45° build orientation lay between those of 0° and 90°, the creep results (performed at 850 °C and 200 MPa) of the 45° build orientation show the least time to rupture. This study discusses the microstructural reasoning behind the peculiar creep behavior of 45° oriented IN738LC samples and correlates the results to heat-treated microstructures and the solidification conditions of the PBF-LB/M process itself.

A New Method for the Calculation of Characteristics of Disc Springs with Trapezoidal Cross-Sections and Rounded Edges.

In the European standards specifying disc spring manufacturing, geometry, shape and characteristic, an edge rounding is prescribed. Common methods for the calculation of disc spring characteristics, even in these standards, are based on a rectangular cross-section. This discrepancy can lead to a considerable divergence of the computed characteristic from the characteristic determined by testing. In literature, this divergence has not yet been examined with regard to rounded edges. In this paper, a new method addressing this problem is introduced. For this purpose, the geometry of idealized disc springs is parameterized. Based on four edge radii and two angles of the inner and outer faces, equations to compute the initial cone angle and the lever arm are introduced. These equations are used to formulate an algorithm to adapt other computation methods to non-rectangular cross-sections and rounded edges. The method is applied to the formulas by Almen-Laszlo, Curti-Orlando, Zheng and those by Kobelev. FE simulations of disc springs with rounded edges and a non-rectangular cross-section were used to verify the new formulas. The results show that the introduced method can be applied to known characteristic computation methods and result in a model expansion taking cross-section variations into account. The adjusted characteristics show more accurate alignment to the FE simulation for the cross-section variations investigated. These findings not only close the geometric gap between the manufacturing guidelines and the computation on an analytical basis, they also define a new parameter space for designs of disc springs and a corresponding force computation method to optimize spring characteristics.

Robust Determination of Fatigue Crack Propagation Thresholds from Crack Growth Data.

The robust determination of the threshold against fatigue crack propagation ΔKth is of paramount importance in fracture mechanics based fatigue assessment procedures. The standards ASTM E647 and ISO 12108 introduce operational definitions of ΔKth based on the crack propagation rate da/dN and suggest linear fits of logarithmic ΔK- da/dN test data to calculate ΔKth. Since these fits typically suffer from a poor representation of the actual curvature of the crack propagation curve, a method for evaluating ΔKth using a nonlinear function is proposed. It is shown that the proposed method reduces the artificial conservativeness induced by the evaluation method as well as the susceptibility to scatter in test data and the influence of test data density.

Face Perception and Pareidolia Production in Patients With Parkinson's Disease.

In Parkinson's disease (PD) patients, visual misperceptions are a major problem within the non-motor symptoms. Pareidolia, i.e., the tendency to perceive a specific, meaningful image in an ambiguous visual pattern, is a phenomenon that occurs also in healthy subjects. Literature suggests that the perception of face pareidolia may be increased in patients with neurodegenerative diseases. We aimed to examine, within the same experiment, face perception and the production of face pareidolia in PD patients and healthy controls (HC). Thirty participants (15 PD patients and 15 HC) were presented with 47 naturalistic photographs in which faces were embedded or not. The likelihood to perceive the embedded faces was modified by manipulating their transparency. Participants were asked to decide for each photograph whether a face was embedded or not. We found that PD patients were significantly less likely to recognize embedded faces than controls. However, PD patients also perceived faces significantly more often in locations where none were actually present than controls. Linear regression analyses showed that gender, age, hallucinations, and Multiple-Choice Vocabulary Intelligence Test (MWT) score were significant predictors of face pareidolia production in PD patients. Montreal Cognitive Assessment (MoCA) was a significant predictor for pareidolia production in PD patients in trials in which a face was embedded in another region [F (1, 13) = 24.4, p = <0.001]. We conclude that our new embedded faces paradigm is a useful tool to distinguish face perception performance between HC and PD patients. Furthermore, we speculate that our results observed in PD patients rely on disturbed interactions between the Dorsal (DAN) and Ventral Attention Networks (VAN). In photographs in which a face is present, the VAN may detect this as a behaviourally relevant stimulus. However, due to the deficient communication with the DAN in PD patients, the DAN would not direct attention to the correct location, identifying a face at a location where actually none is present.

The Parkinson disease pain classification system: results from an international mechanism-based classification approach.

ABSTRACT: Pain is a common nonmotor symptom in patients with Parkinson disease (PD) but the correct diagnosis of the respective cause remains difficult because suitable tools are lacking, so far. We developed a framework to differentiate PD- from non-PD-related pain and classify PD-related pain into 3 groups based on validated mechanistic pain descriptors (nociceptive, neuropathic, or nociplastic), which encompass all the previously described PD pain types. Severity of PD-related pain syndromes was scored by ratings of intensity, frequency, and interference with daily living activities. The PD-Pain Classification System (PD-PCS) was compared with classic pain measures (ie, brief pain inventory and McGill pain questionnaire [MPQ], PDQ-8 quality of life score, MDS-UPDRS scores, and nonmotor symptoms). 159 nondemented PD patients (disease duration 10.2 ± 7.6 years) and 37 healthy controls were recruited in 4 centers. PD-related pain was present in 122 patients (77%), with 24 (15%) suffering one or more syndromes at the same time. PD-related nociceptive, neuropathic, or nociplastic pain was diagnosed in 87 (55%), 25 (16%), or 35 (22%), respectively. Pain unrelated to PD was present in 35 (22%) patients. Overall, PD-PCS severity score significantly correlated with pain's Brief Pain Inventory and MPQ ratings, presence of dyskinesia and motor fluctuations, PDQ-8 scores, depression, and anxiety measures. Moderate intrarater and interrater reliability was observed. The PD-PCS is a valid and reliable tool for differentiating PD-related pain from PD-unrelated pain. It detects and scores mechanistic pain subtypes in a pragmatic and treatment-oriented approach, unifying previous classifications of PD-pain.

On the Influence of Ultimate Number of Cycles on Lifetime Prediction for Compression Springs Manufactured from VDSiCr Class Spring Wire.

For the generation of fatigue curves by means of fatigue tests, an ultimate number of cycles must be chosen. This ultimate number of cycles also limits the permissible range of the fatigue curve for the design of components. This introduces extremely high costs for testing components that are to be used in the Very High Cycle Fatigue regime. In this paper, we examine the influence of the ultimate number of cycles of fatigue tests on lifetime prediction for compression springs manufactured from VDSiCr class spring wire. For this purpose, we propose a new kind of experiment, the Artificial Censoring Experiment (ACE). We show that ACEs may be used to permissibly extrapolate the results of fatigue tests on compression springs by ensuring that a batch-specific minimum ultimate number of cycles has been exceeded in testing. If the minimum ultimate number of cycles has not been exceeded, extrapolation is inadmissible. Extrapolated results may be highly non-conservative, especially for models assuming a pronounced fatigue limit.

A Novel Algorithm for the Determination of Walker Damage in Loaded Disc Springs.

In this paper, a novel algorithm for the determination of Walker damage in loaded disc springs is presented. The algorithm takes a 3D-scan of a disc spring, measured residual stresses, material parameters, and spring loads as inputs. It outputs a distribution of Walker damage over the surface area of the input disc spring. As the algorithm allows a fully automated determination of the Walker damage, it can be used by disc spring manufacturers to reduce the working time spent on this task by specialized engineers significantly. Compared to spreadsheet applications using analytical formulas and finite element models using idealized geometry, this approach offers a superior description of the stress states in disc springs.

Lewy body dementia and Parkinson's disease with dementia.

Parkinson's disease (PD) is characterized by its motor impairment. However, non-motor symptoms such as psychiatric disorders, autonomic disturbances and sleep disorders frequently complicate the course of the disease. In particular, psychiatric disturbances including cognitive impairment, depression and psychosis impact these patients considerably. Approximately 31 % of PD patients suffer from cognitive impairment and dementia. Currently, two different clinical presentations are distinguished in PD patients, who present with dementia: Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB), which are two different presentations of a single underlying disease process leading to the deposition of alpha-synuclein. Clinically, PDD is distinguished from DLB alone by the different temporal manifestations of extrapyramidal motor symptoms. Dementia is characterized by a subtle onset and progressive cognitive decline with a predominant dysexecutive syndrome, which can be accompanied by different behavioral symptoms such as hallucinations, depression, anxiety and sleep disorders. Dysregulation of different neurotransmitters has been associated with cognitive decline, but reduced cholinergic transmission is currently thought to be the pivotal mechanism in the development of cognitive dysfunction. Therefore, cholinesterase inhibitors are used in the treatment of dementia and accompanying behavioral symptoms in PDD and DLB. The occurrence of dementia impacts not only the patients themselves but also their care-givers and family.This article focuses on the clinical issues related to both disorders and is based on a meeting of experts which took place in April 2008 in Dresden.

McLeod myopathy revisited: more neurogenic and less benign.

The X-linked McLeod neuroacanthocytosis syndrome (MLS) has originally been denoted as 'benign' McLeod myopathy. We assessed the clinical findings and the muscle pathology in the eponymous index patient, Hugh McLeod, and in nine additional MLS patients. Only one patient had manifested with neuromuscular symptoms. During a mean follow-up of 15 years, however, eight patients including the initial index patient showed elevated skeletal muscle creatine kinase levels ranging from 300 to 3000 U/L, and had developed muscle weakness and atrophy. Two patients had disabling leg weakness. Muscle histology was abnormal in all 10 patients. Clear but unspecific myopathic changes were found in only four patients. All patients, however, had neurogenic changes of variable degree. Post-mortem motor and sensory nerve examinations support the view that muscle atrophy and weakness are predominantly due to an axonal motor neuropathy rather than to a primary myopathy. Multisystem manifestations developed in eight patients at a mean age of 39 years. Three patients manifested with psychiatric features comprising schizophrenia-like psychosis and personality disorder, two presented with generalized seizures and one with chorea. During follow-up, seven patients developed chorea, six had psychiatric disorders, five had cognitive decline and three had generalized seizures. Five patients died because of MLS-related complications including sudden cardiac death, chronic heart failure and pneumonia between 55 and 69 years. In conclusion, our findings confirm that MLS is not a benign condition but rather a progressive multisystem disorder sharing many features with Huntington's disease.

[Neurorehabilitation in Parkinson's disease]. / Neurorehabilitation bei der Parkinson-Krankheit.

Parkinson's disease (PD) is a chronic neurodegenerative disease which is characterized by the cardinal symptoms akinesia, rigidity, rest tremor and postural instability. Besides PD features also a wide range of non-motor symptoms. Physical activity is recommended for all stages of PD and may hypothetically even have a positive influence on the course of the disease. Rehabilitative treatments become increasingly important in the advanced stage of the disease and include mainly physiotherapy, occupational therapy and speech therapy. Neurorehabilitation is arguably most important for the treatment of axial symptoms such as freezing, hypophonia, dysphagia, postural instability and postural disturbances that respond poorly to drug therapy. This article provides an overview of current developments in the field of neurorehabilitation in PD.

Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson disease.

OBJECTIVE: Biomarkers are required for the diagnosis and monitoring of disease progression in Parkinson disease (PD). To date, most studies have concentrated on α-synuclein (α-Syn), a protein involved in Parkinson disease pathogenesis, as a potential biomarker, with inconsistent outcomes. Recently, naturally occurring autoantibodies against α-Syn (α-Syn-nAbs) have been detected in the serum of patients with PD. They represent a putative diagnostic marker for PD. METHODS: We established and validated an ELISA to quantify α-Syn-nAbs in serum samples. We analyzed serum samples from 62 patients with PD, 46 healthy controls (HC), and 42 patients with Alzheimer disease (AD) using this newly established ELISA. Additionally, serum levels of endogenous α-Syn were measured. RESULTS: There was a significant difference in α-Syn-nAbs levels between the investigated groups (p = 0.005; Kruskal-Wallis test). Levels of α-Syn-nAbs were significantly lower in patients with PD compared to HC (p < 0.05; Dunn multiple comparison post hoc test) or patients with AD (p < 0.05). Furthermore, we detected no difference between patients with AD and HC. The sensitivity and specificity of the assay for patients with PD vs. HC were 85% and 25%, respectively. The α-Syn-nAbs levels did not correlate with age, Hoehn & Yahr status, or duration of disease. Endogenous α-Syn had no influence on α-Syn-nAbs levels in sera. CONCLUSIONS: Using a well-validated assay, we detected reduced α-Syn-nAbs levels in patients with PD compared to patients with AD and HC. The assay did not achieve criteria for use as a diagnostic tool to reliably distinguish PD from HC. Further studies are needed to assess α-Syn-nAbs as a biomarker in PD.

Neurovascular coupling in Parkinson's disease patients: effects of dementia and acetylcholinesterase inhibitor treatment.

Alzheimer's disease (AD) and Parkinson's disease (PD) lead to a cholinergic deficit in the brain which is not only related to dementia, but may also lead to a disturbed neurovascular coupling. We investigated the effect of cholinergic decline on neurovascular coupling in PD patients. Patients with idiopathic PD were divided in groups without (n=59; 65 ± 9 y) or with moderate dementia as specified by Mini-Mental State Examination. The demented patients were assigned to groups with (n=55; 73 ± 6 y) or without (n=61; 72 ± 8 y) acetylcholinesterase inhibitor treatment. Neurovascular coupling was assessed by a simultaneous electroencephalography-Doppler technique applying a contrast-based visual stimulation task. Visually evoked potential amplitudes (N75-P100) and parameters of the hemodynamic response in the posterior cerebral artery were obtained using a control system approach (resting flow velocity, gain, attenuation, rate time, and natural frequency). Data were compared to a healthy control group of a similar age range (n=20; 63 ± 8 yr). Compared to controls, patient groups presented no differences in evoked potential amplitudes or neurovascular coupling parameters. The reported 30% decline in acetylcholinesterase activity in PD patients did not lead to measurable changes in neurovascular coupling. In AD patients additional factors might explain the uncoupling and higher cerebrovascular risk detected in clinical studies.

Parenteral ziprasidone: a new atypical neuroleptic for emergency treatment of psychosis in Parkinson's disease?

This is a report on a case series of five patients with psychosis in Parkinson's disease who were treated successfully with an intramuscular injection of ziprasidone (10-20 mg) for acute agitation. No deterioration of motor function or other clinically relevant side effects were seen.

Dopaminergic response in Parkinsonian phenotype of Machado-Joseph disease.

We report on a patient with genetically proven Machado-Joseph Disease (MJD) presenting with signs indistinguishable from Parkinson's disease (PD), including levodopa response and typical levodopa-induced motor fluctuations. Only after 10 years of prolonged benefit from levodopa and different dopamine agonists (DA), the patient developed cerebellar ataxia and pyramidal signs. Preferential D3-receptor-stimulating dopamine agonists especially showed a benefit at the time, when D2 receptor binding was reduced in IBZM SPECT. This is the first report of a meaningful response to DA in MJD.

Plasma and CSF markers of oxidative stress are increased in Parkinson's disease and influenced by antiparkinsonian medication.

We determined systemic oxidative stress in Parkinson's disease (PD) patients, patients with other neurological diseases (OND) and healthy controls by measurement of in vitro lipoprotein oxidation and levels of hydro- and lipophilic antioxidants in plasma and cerebrospinal fluid (CSF). Additionally, we investigated the influence of levodopa (LD) and dopamine agonist therapy (DA) on the oxidative status in PD patients. We found increased oxidative stress, seen as higher levels of lipoprotein oxidation in plasma and CSF, decrease of plasma levels of protein sulfhydryl (SH) groups and lower CSF levels of alpha-tocopherol in PD patients compared to OND patients and controls. Levodopa treatment did not significantly change the plasma lipoprotein oxidation but LD monotherapy tended to result in an increase of autooxidation and in a decrease of plasma antioxidants with significance for ubiquinol-10. DA monotherapy was significantly associated with higher alpha-tocopherol levels. Patients with DA monotherapy or co-medication with DA showed a trend to lower lipoprotein oxidation. These data support the concept of oxidative stress as a factor in the pathogenesis of PD and might be an indicator of a potential prooxidative role of LD and a possible antioxidative effect of DA in PD treatment.