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Retinal Vessel Analysis (RVA) in the context of subarachnoid hemorrhage: A proof of concept study
(2016)
Background
Timely detection of impending delayed cerebral ischemia after subarachnoid hemorrhage (SAH) is essential to improve outcome, but poses a diagnostic challenge. Retinal vessels as an embryological part of the intracranial vasculature are easily accessible for analysis and may hold the key to a new and non-invasive monitoring technique. This investigation aims to determine the feasibility of standardized retinal vessel analysis (RVA) in the context of SAH.
Methods
In a prospective pilot study, we performed RVA in six patients awake and cooperative with SAH in the acute phase (day 2–14) and eight patients at the time of follow-up (mean 4.6±1.7months after SAH), and included 33 age-matched healthy controls. Data was acquired using a manoeuvrable Dynamic Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and neurovascular coupling.
Results
Image quality was satisfactory in the majority of cases (93.3%). In the acute phase after SAH, retinal arteries were significantly dilated when compared to the control group (124.2±4.3MU vs 110.9±11.4MU, p<0.01), a difference that persisted to a lesser extent in the later stage of the disease (122.7±17.2MU, p<0.05). Testing for neurovascular coupling showed a trend towards impaired primary vasodilation and secondary vasoconstriction (p = 0.08, p = 0.09 resp.) initially and partial recovery at the time of follow-up, indicating a relative improvement in a time-dependent fashion.
Conclusion
RVA is technically feasible in patients with SAH and can detect fluctuations in vessel diameter and autoregulation even in less severely affected patients. Preliminary data suggests potential for RVA as a new and non-invasive tool for advanced SAH monitoring, but clinical relevance and prognostic value will have to be determined in a larger cohort.
The conjunction of (bio-)chemical recognition elements with nanoscale biological building blocks such as virus particles is considered as a very promising strategy for the creation of biohybrids opening novel opportunities for label-free biosensing. This work presents a new approach for the development of biosensors using tobacco mosaic virus (TMV) nanotubes or coat proteins (CPs) as enzyme nanocarriers. Sensor chips combining an array of Pt electrodes loaded with glucose oxidase (GOD)-modified TMV nanotubes or CP aggregates were used for amperometric detection of glucose as a model system for the first time. The presence of TMV nanotubes or CPs on the sensor surface allows binding of a high amount of precisely positioned enzymes without substantial loss of their activity, and may also ensure accessibility of their active centers for analyte molecules. Specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CPs was achieved via bioaffinity binding. These layouts were tested in parallel with glucose sensors with adsorptively immobilized [SA]-GOD, as well as [SA]-GOD crosslinked with glutardialdehyde, and came out to exhibit superior sensor performance. The achieved results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for future applications in biosensorics and biochips.
Hintergrund
Die Anwendung und das Verständnis von Statistik sind sehr wichtig für die biomedizinische Forschung und für die klinische Praxis. Dies gilt insbesondere auch zur Abschätzung der Möglichkeiten unterschiedlichster Diagnostik- und Therapieoptionen beim Glaukom. Die scheinbare Komplexität der Statistik, die zum Teil dem „gesunden Menschenverstand“ zu widersprechen scheint, zusammen mit der nur vorsichtigen Akzeptanz der Statistik bei vielen Medizinern können zu bewussten und unbewussten Manipulationen bei der Datendarstellung und -interpretation führen.
Ziel der Arbeit
Ziel ist die verständliche Darstellung einiger typischer Fehler in der medizinisch-statistischen Datenbehandlung.
Material und Methoden
Anhand hypothetischer Beispiele aus der Glaukomdiagnostik erfolgen die Darstellung der Wirkung eines hypotensiven Medikamentes sowie die Beurteilung der Ergebnisse eines diagnostischen Tests. Es werden die typischsten statistischen Einsatzbereiche und Irrtumsquellen ausführlich und verständlich analysiert
Ergebnisse
Mechanismen von Datenmanipulation und falscher Dateninterpretation werden aufgeklärt. Typische Irrtumsquellen bei der statistischen Auswertung und Datendarstellung werden dabei erläutert.
Schlussfolgerungen
Die erläuterten praktischen Beispiele zeigen die Notwendigkeit, die Grundlagen der Statistik zu verstehen und korrekt anwenden zu können. Fehlendes Grundlagenwissen und Halbwissen der medizinischen Statistik können zu folgenschweren Missverständnissen und falschen Entscheidungen in der medizinischen Forschung, aber auch in der klinischen Praxis führen.
An amperometric biosensor using a substrate recycling principle was realized for the detection of low adrenaline concentrations (1 nM) by measurements in phosphate buffer and Ringer’s solution at pH 6.5 and pH 7.4, respectively. In proof-of-concept experiments, a Boolean logic-gate principle has been applied to develop a digital adrenaline biosensor based on an enzyme AND logic gate. The obtained results demonstrate that the developed digital biosensor is capable for a rapid qualitative determination of the presence/absence of adrenaline in a YES/NO statement. Such digital biosensor could be used in clinical diagnostics for the control of a correct insertion of a catheter in the adrenal veins during adrenal venous-sampling procedure.
Purpose
The most commonly used mobility assessments for screening risk of falls among older adults are rating scales such as the Tinetti performance oriented mobility assessment (POMA). However, its correlation with falls is not always predictable and disadvantages of the scale include difficulty to assess many of the items on a 3-point scale and poor specificity. The purpose of this study was to describe the ability of the new Aachen Mobility and Balance Index (AMBI) to discriminate between subjects with a fall history and subjects without such events in comparison to the Tinetti POMA Scale.
Methods
For this prospective cohort study, 24 participants in the study group and 10 in the control group were selected from a population of patients in our hospital who had met the stringent inclusion criteria. Both groups completed the Tinetti POMA Scale (gait and balance component) and the AMBI (tandem stance, tandem walk, ten-meter-walk-test, sit-to-stand with five repetitions, 360° turns, timed-up-and-go-test and measurement of the dominant hand grip strength). A history of falls and hospitalization in the past year were evaluated retrospectively. The relationships among the mobility tests were examined with Bland–Altmananalysis. Receiver-operated characteristics curves, sensitivity and specificity were calculated.
Results
The study showed a strong negative correlation between the AMBI (17 points max., highest fall risk) and Tinetti POMA Scale (28 points max., lowest fall risk; r = −0.78, p < 0.001) with an excellent discrimination between community-dwelling older people and a younger control group. However, there were no differences in any of the mobility and balance measurements between participants with and without a fall history with equal characteristics in test comparison (AMBI vs. Tinetti POMA Scale: AUC 0.570 vs. 0.598; p = 0.762). The Tinetti POMA Scale (cut-off <20 points) showed a sensitivity of 0.45 and a specificity of 0.69, the AMBI a sensitivity of 0.64 and a specificity of 0.46 (cut-off >5 points).
Conclusion
The AMBI comprises mobility and balance tasks with increasing difficulty as well as a measurement of the dominant hand-grip strength. Its ability to identify fallers was comparable to the Tinetti POMA Scale. However, both measurement sets showed shortcomings in discrimination between fallers and non-fallers based on a self-reported retrospective falls-status.
The light-addressable potentiometric sensor (LAPS) has the unique feature to address different regions of a sensor surface without the need of complex structures. Measurements at different locations on the sensor surface can be performed in a common analyte solution, which distinctly simplifies the fluidic set-up. However, the measurement in a single analyte chamber prevents the application of different drugs or different concentrations of a drug to each measurement spot at the same time as in the case of multi-reservoir-based set-ups. In this work, the authors designed a LAPS-based set-up for cell culture screening that utilises magnetic beads loaded with the endotoxin (lipopolysaccharides, LPS), to generate a spatially distributed gradient of analyte concentration. Different external magnetic fields can be adjusted to move the magnetic beads loaded with a specific drug within the measurement cell. By recording the metabolic activities of a cell layer cultured on top of the LAPS surface, this work shows the possibility to apply different concentrations of a sample along the LAPS measurement spots within a common analyte solution.
Light-addressable potentiometric sensor as a sensing element in plug-based microfluidic devices
(2016)
A plug-based microfluidic system based on the principle of the light-addressable potentiometric sensor (LAPS) is proposed. The LAPS is a semiconductor-based chemical sensor, which has a free addressability of the measurement point on the sensing surface. By combining a microfluidic device and LAPS, ion sensing can be performed anywhere inside the microfluidic channel. In this study, the sample solution to be measured was introduced into the channel in a form of a plug with a volume in the range of microliters. Taking advantage of the light-addressability, the position of the plug could be monitored and pneumatically controlled. With the developed system, the pH value of a plug with a volume down to 400 nL could be measured. As an example of plug-based operation, two plugs were merged in the channel, and the pH change was detected by differential measurement.
While plate fixation of proximal ulna fractures might lead to superior clinical results compared to tension band wiring, regular plates represent an established risk factor for wound complications. The olecranon double plates (Medartis, Basel, CH) might decrease complications related to the osteosynthesis because of their low profile and better anatomical fit. This study aimed to evaluate the biomechanical performance and clinical results of the olecranon double plates.
Surgical reconstruction of the interosseous membrane (IOM) could restore longitudinal forearm stability to avoid persisting disability due to capituloradial and ulnocarpal impingement in Essex Lopresti lesions. This biomechanical study aimed to assess longitudinal forearm stability of intact specimens, after sectioning of the IOM and after reconstruction with a TightRope construct using either a single or double bundle technique.
Treatment of posttraumatic osteoarthritis of the radial column of the elbow joint remains a challenging yet common issue.
While partial joint replacement leads to high revision rates, radial head excision has shown to severely increase joint instability. Shortening osteotomy of the radius could be an option to decrease the contact pressure of the radiohumeral joint and thereby pain levels without causing valgus instability. Hence, the aim of this biomechanical study was to evaluate the effects of radial shortening on axial load distribution and valgus stability of the elbow joint.
Plate osteosynthesis of displaced proximal phalangeal neck fractures of the hand allows early mobilization due to a stable internal fixation. Nevertheless, joint stiffness—because of soft tissue irritation—represents a common complication leading to high complication rates. Del Pinal et al. recently reported promising clinical results for a new, minimally invasive fixation technique with a cannulated headless intramedullary compression screw. Hence, the aim of this study was to compare plate fixation of proximal phalangeal neck fractures to less two less invasive techniques: Crossed k-wire fixation and intramedullary screw fixation. We hypothesized that these fixation techniques provide inferior stability when compared to plate osteosynthesis.
The human arm consists of the humerus (upper arm), the medial ulna and the lateral radius (forearm). The joint between the humerus and the ulna is called humeroulnar joint and the joint between the humerus and the radius is called humeroradial joint. Lateral and medial collateral ligaments stabilize the elbow. Statistically, 2.5 out of 10,000 people suffer from radial head fractures [1]. In these fractures the cartilage is often affected. Caused by the injured cartilage, degenerative diseases like posttraumatic arthrosis may occur. The resulting pain and reduced range of motion have an impact on the patient’s quality of life. Until now, there has not been a treatment which allows typical loads in daily life activities and offers good long-term results. A new surgical approach was developed with the motivation to reduce the progress of the posttraumatic arthrosis. Here, the radius is shortened by 3 mm in the proximal part [2]. By this means, the load of the radius is intended to be reduced due to a load shift to the ulna. Since the radius is the most important stabilizer of the elbow it has to be confirmed that the stability is not affected. In the first test (Fig. 1 left), pressure distributions within the humeroulnar and humeroradial joints a native and a shortened radius were measured using resistive pressure sensors (I5076 and I5027, Tekscan, USA). The humerus was loaded axially in a tension testing machine (Z010, Zwick Roell, Germany) in 50 N steps up to 400 N. From the humerus the load is transmitted through both the radius and the ulna into the hand which is fixed on the ground. In the second test (Fig. 1 right), the joint stability was investigated using a digital image correlation system to measure the displacement of the ulna. Here, the humerus is fixed with a desired flexion angle and the unconstrained forearm lies on the ground. A rope connects the load actuator with a hook fixed in the ulna. A guide roller is used so that the rope pulls the ulna horizontally when a tensile load is applied. This creates a moment about the elbow joint with a maximum value of 7.5 Nm. Measurements were performed with varying flexion angles (0°, 30°, 60°, 90°, 120°). For both tests and each measurement, seven specimens were used. Student ́s t-test was employed to determine whether the mean values of the measurements in native specimen and operated specimens differ significantly.
The structure of the female pelvic floor (PF) is an inter-related system of bony pelvis,muscles, pelvic organs, fascias, ligaments, and nerves with multiple functions. Mechanically, thepelvic organ support system are of two types: (I) supporting system of the levator ani (LA) muscle,and (II) the suspension system of the endopelvic fascia condensation [1], [2]. Significantdenervation injury to the pelvic musculature, depolimerization of the collagen fibrils of the softvaginal hammock, cervical ring and ligaments during pregnancy and vaginal delivery weakens thenormal functions of the pelvic floor. Pelvic organ prolapse, incontinence, sexual dysfunction aresome of the dysfunctions which increases progressively with age and menopause due toweakened support system according to the Integral theory [3]. An improved 3D finite elementmodel of the female pelvic floor as shown in Fig. 1 is constructed that: (I) considers the realisticsupport of the organs to the pelvic side walls, (II) employs the improvement of our previous FEmodel [4], [5] along with the patient based geometries, (III) incorporates the realistic anatomy andboundary conditions of the endopelvic (pubocervical and rectovaginal) fascia, and (IV) considersvarying stiffness of the endopelvic fascia in the craniocaudal direction [3]. Several computationsare carried out on the presented computational model with healthy and damaged supportingtissues, and comparisons are made to understand the physiopathology of the female PF disorders.
Purpose
Two semi-empirical models were recently published, both making use of existing literature data, but each taking into account different physical phenomena that trigger hemolysis. In the first model, hemoglobin (Hb) release is described as a permeation procedure across the membrane, assuming a shear stress-dependent process (sublethal model). The second model only accounts for hemoglobin release that is caused by cell membrane breakdown, which occurs when red blood cells (RBC) undergo mechanically induced shearing for a period longer than the threshold time (nonuniform threshold model). In this paper, we introduce a model that considers the hemolysis generated by both these possible phenomena.
Methods
Since hemolysis can possibly be caused by permeation of hemoglobin through the RBC functional membrane as well as by release of hemoglobin from RBC membrane breakdown, our proposed model combines both these models. An experimental setup consisting of a Couette device was utilized for validation of our proposed model.
Results
A comparison is presented between the damage index (DI) predicted by the proposed model vs. the sublethal model vs. the nonthreshold model and experimental datasets. This comparison covers a wide range of shear stress for both human and porcine blood. An appropriate agreement between the measured DI and the DI predicted by the present model was obtained.
Conclusions
The semiempirical hemolysis model introduced in this paper aims for significantly enhanced conformity with experimental data. Two phenomenological outcomes become possible with the proposed approach: an estimation of the average time after which cell membrane breakdown occurs under the applied conditions, and a prediction of the ratio between the phenomena involved in hemolysis.