Ultrahigh resolution whole body photon counting computed tomography as a novel versatile tool for translational research from mouse to man.

X-ray computed tomography (CT) is a cardinal tool in clinical practice. It provides cross-sectional images within seconds. The recent introduction of clinical photon-counting CT allowed for an increase in spatial resolution by more than a factor of two resulting in a pixel size in the center of rotation of about 150 µm. This level of spatial resolution is in the order of dedicated preclinical micro-CT systems. However so far, the need for different dedicated clinical and preclinical systems often hinders the rapid translation of early research results to applications in men. This drawback might be overcome by ultra-high resolution (UHR) clinical photon-counting CT unifying preclinical and clinical research capabilities in a single machine. Herein, the prototype of a clinical UHR PCD CT (SOMATOM CounT, Siemens Healthineers, Forchheim, Germany) was used. The system comprises a conventional energy-integrating detector (EID) and a novel photon-counting detector (PCD). While the EID provides a pixel size of 0.6 mm in the centre of rotation, the PCD provides a pixel size of 0.25 mm. Additionally, it provides a quantification of photon energies by sorting them into up to four distinct energy bins. This acquisition of multi-energy data allows for a multitude of applications, e.g. pseudo-monochromatic imaging. In particular, we examine the relation between spatial resolution, image noise and administered radiation dose for a multitude of use-cases. These cases include ultra-high resolution and multi-energy acquisitions of mice administered with a prototype bismuth-based contrast agent (nanoPET Pharma, Berlin, Germany) as well as larger animals and actual patients. The clinical EID provides a spatial resolution of about 9 lp/cm (modulation transfer function at 10%, MTF10%) while UHR allows for the acquisition of images with up to 16 lp/cm allowing for the visualization of all relevant anatomical structures in preclinical and clinical specimen. The spectral capabilities of the system enable a variety of applications previously not available in preclinical research such as pseudo-monochromatic images. Clinical ultra-high resolution photon-counting CT has the potential to unify preclinical and clinical research on a single system enabling versatile imaging of specimens and individuals ranging from mice to man.

[Isolation precautions, diagnostics and organization in German emergency departments during the 2020 COVID-19 pandemic]. / Isolationsmaßnahmen, Diagnostik und Organisation in deutschen Notaufnahmen während der COVID-19-Pandemie 2020.

BACKGROUND: Since the beginning of the coronavirus disease 19 (COVID-19) pandemic, German emergency departments (ED) have been working in the area of conflict between high case load and demanding hygienic and organizational challenges. The aim of this study was to gain an overview of the current status of isolation measures, diagnostics and patient allocation of suspected COVID-19 cases. METHODS: Supported by the German Society for Interdisciplinary Emergency and Acute Medicine (DGINA) we invited leading ED physicians to answer an anonymous online survey regarding isolation measures, diagnostics and organization in emergency rooms during the COVID-19 pandemic. RESULTS: A total of 139 responders from all federal states and all levels of care took part in the survey. Standard operating procedures on COVID-19 exist in almost all participating EDs, although concrete measures to end isolation are often missing. Most EDs screen patients for the "classic" COVID-19 symptoms such as fever, respiratory symptoms or contact to positive subjects in a standardized fashion, although the threshold for prophylactic isolation varies greatly. The individual swab-testing and allocation strategies vary relatively strongly. Less than half of all EDs have a separate procedure for uninterrogatable patients (e.g. major trauma). In about 8% of suspected cases, COVID-19-specific thoracic computed tomography is performed in the ED. CONCLUSION: The current survey shows that the German EDs are well positioned for the moment, even though the isolation threshold is too high at some locations. In view of a possible increase in the number of cases during the winter season, a more precise differentiation of the previous recommendations of the Robert Koch Institute, especially for emergency admission patients, would be desirable. In this context, we propose a universal algorithm for the (de-)isolation of suspect cases in the ED.

Evidence of vitamin D synthesis in insects exposed to UVb light.

Vertebrates obtain the prohormone vitamin D primarily by endogenous cutaneous synthesis under ultraviolet b (UVb) exposure. To date, endogenous synthesis of vitamin D in insects has never been investigated. In an initial experiment, we exposed four insect species which differ in ecology and morphology (migratory locusts, house crickets, yellow mealworms and black soldier fly larvae (BSFL)) to a low irradiance UVb source. In a second experiment we exposed these species to a higher UV irradiance, and in a third we tested the effect of exposure duration on vitamin D concentrations in yellow mealworms. Low irradiance UVb tended to increase vitamin D3 levels in house crickets, vitamin D2 levels in BSFL and vitamin D2 and D3 in yellow mealworms. Higher UVb irradiance increased vitamin D3 levels in all species but BSFL. Both BSFL and migratory locusts had increased vitamin D2 levels. Longer UVb exposure of yellow mealworms increased vitamin D2 and increased vitamin D3 until a plateau was reached at 6400 IU/kg. This study shows that insects can synthesize vitamin D de novo and that the amounts depend on UVb irradiance and exposure duration.

Automatic scanning of large tissue areas in neurosurgery using optical coherence tomography.

BACKGROUND: With its high spatial and temporal resolution, optical coherence tomography (OCT) is an ideal modality for intra-operative imaging. One possible application is to detect tumour invaded tissue in neurosurgery, e.g. during complete resection of glioblastoma. Ideally, the whole resection cavity is scanned. However, OCT is limited to a small field of view (FOV) and scanning perpendicular to the tissue surface. METHODS: We present a new method to use OCT for scanning of the resection cavity during neurosurgical resection of brain tumours. The main challenges are creating a map of the cavity, scanning perpendicular to the surface and merging the three-dimensional (3D) data for intra-operative visualization and detection of residual tumour cells. RESULTS: Our results indicate that the proposed method enables creating high-resolution maps of the resection cavity. An overlay of these maps with the microscope images provides the surgeon with important information on the location of residual tumour tissue underneath the surface. CONCLUSION: We demonstrated that it is possible to automatically acquire an OCT image of the complete resection cavity. Overlaying microscopy images with depth information from OCT could lead to improved detection of residual tumour cells.

Motorization of a surgical microscope for intra-operative navigation and intuitive control.

BACKGROUND: During surgical procedures, various medical systems, e.g. microscope or C-arm, are used. Their precise and repeatable manual positioning can be very cumbersome and interrupts the surgeon's work flow. Robotized systems can assist the surgeon but they require suitable kinematics and control. However, positioning must be fast, flexible and intuitive. METHODS: We describe a fully motorized surgical microscope. Hardware components as well as implemented applications are specified. The kinematic equations are described and a novel control concept is proposed. RESULTS: Our microscope combines fast manual handling with accurate, automatic positioning. Intuitive control is provided by a small remote control mounted to one of the surgical instruments. Positioning accuracy and repeatability are < 1 mm and vibrations caused by automatic movements fade away in about 1 s. CONCLUSION: The robotic system assists the surgeon, so that he can position the microscope precisely and repeatedly without interrupting the clinical workflow. The combination of manual und automatic control guarantees fast and flexible positioning during surgical procedures.

Treatment of immune-mediated hemolytic anemia with individually adjusted heparin dosing in dogs.

BACKGROUND: A major cause of death in dogs with immune-mediated hemolytic anemia (IMHA) is thromboembolism. Previous studies suggest unfractionated heparin (UH) is not effective in preventing thromboembolism in IMHA; however, subtherapeutic dosing could explain the seeming lack of efficacy. HYPOTHESIS: Providing therapeutic plasma concentration of UH by individually adjusting doses based on antifactor Xa activity would improve survival in IMHA. ANIMALS: Fifteen dogs with primary IMHA. METHODS: Randomized, prospective, controlled clinical trial. Dogs received standardized therapy for IMHA and either constant dose (CD) (150 U/kg SC) (n = 7) or individually adjusted dose (IAD) (n = 8) UH, monitored via an anti-Xa chromogenic assay, adjusted according to a nomogram. UH was administered every 6 hours until day 7, and every 8 hours thereafter. UH dose was adjusted daily in IAD dogs until day 7, weekly until day 28, then tapered over 1 week. Dogs were monitored for 180 days. RESULTS: At day 180, 7 dogs in the IAD group and 1 in the CD group were alive (P= .01). Median survival time for the IAD group was >180 days, and 68 days for the CD group. Thromboembolic events occurred in 5 dogs in the CD group and 2 dogs in the IAD group. Doses of UH between 150 and 566 U/kg achieved therapeutic anti-Xa activity (0.35-0.7 U/mL). CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that IAD UH therapy using anti-Xa monitoring reduced case fatality rate in dogs with IMHA when compared with dogs receiving fixed low dose UH therapy.

The mitigating influence of time preference on the relation between smoking and BMI scores.

OBJECTIVE: Prior studies have found a strong negative relation between smoking and body mass index (BMI). Smoking and unhealthy eating both imply a preference for utility in the present at the expense of future consumption. This analysis seeks to proxy this preference through a composite index of equally weighted intertemporal behaviors to isolate the impact of smoking upon BMI independent of time discounting. DESIGN: Ordinary least squares regression is used to analyze BMI score based on a number of key independent variables. SUBJECTS: A total of 2970 individuals who provided data for the United States Department of Agriculture's (USDA) Continuing Survey of Food Intakes by Individuals (CSFII) 1994-1996, as well as the Diet and Health Knowledge Survey (DHKS). RESULTS: Adding time preference to a multivariate model inflates the magnitude of the smoking effect, consistent with discounted utility theory. CONCLUSIONS: Results suggest that full effect of the non-intertemporal aspects of smoking (e.g., the substitution of cigarettes for food) on BMI scores may be underestimated in previous studies that fail to account for the mitigating influence of time preference.

Brain mapping with transcranial magnetic stimulation using a refined correlation ratio and Kendall's tau.

Transcranial magnetic stimulation provides a mean to stimulate the brain non-invasively and painlessly. The effect of the stimulation hereby depends on the stimulation coil used and on its placement. This paper presents a mapping algorithm based on the assumption of a monotonous functional relationship between the applied electric field strength at the representation point of a muscle and the evoked motor potential. We combine data from coil characteristics, coil placement, and stimulation outcome to calculate a likelihood map for the representation of stimulated muscles in the brain. Hereby, correlation ratio (CR) and Kendall's rank coefficient tau are used to find areas in the brain where there is most likely a functional or monotonous relationship between electric field strength applied to this area and the muscle response. First results show a good accordance of our method with mapping from functional magnetic resonance imaging. In our case, classical evaluation of CR with binning is impossible, because sample data sets are too small and data are continuous. We therefore introduce a refined CR formula based on a Parzen windowing of the X-data to solve the problem. In contrast to usual windowing approaches, which require numeric integration, it can be evaluated directly in O(n2) time. Hence, its advantage lies in fast evaluation while maintaining robust applicability to small sample sets. We suggest that the presented formula can generally be used in CR-related problems where sample size is small and data range is continuous.

Brain-mapping using robotized TMS.

We present first results of brain-mapping using robotic Transcranial Magnetic Stimulation. This non-invasive procedure enables the reliable detection of the representation of individual muscles or muscle groups in the motor-cortex. The accuracy is only exceeded by direct electrical stimulation of the brain during surgery. Brain-mapping using robotic TMS can also be used to detect displacements of brain regions caused by tumors. The advantage of TMS is that it is non-invasive. In this study, we compare results from statistical mapping with robotic TMS to results achieved from direct stimulation done during tumor surgery. To our knowledge this is the first study of this type. We mapped the representation of three muscle groups (forearm, pinky and thumb) in tumor patients with the robot-aided TMS protocol and with direct stimulation. The resulting maps agree within 5mm.

A clinical study in situ to assess the effect of a food approved polymer on the erosion potential of drinks.

OBJECTIVES: The consumption of acidic soft drinks continues to rise as do concerns regarding effects of frequent intake. The aim of the study was to determine the effect of acidic soft drinks containing food approved polymers, on dental enamel. METHODS: The study design was a single blind, randomised, five-treatment crossover clinical trial involving 15 healthy dentate subjects. Subjects wore an upper removable acrylic appliance retaining two enamel specimens and consumed 250ml of beverage four times/day for 10 days. The following beverages were tested: (1) unmodified acidic soft drink, (2) experimental acidic soft drink with 0.02% polyphosphate, (3) experimental acidic soft drink with 0.02% polyphosphate and 0.01% calcium, (4) experimental acidic soft drink with 0.02% polyphosphate and 0.03% xanthan gum, and (5) mineral water. Tissue loss was measured at days 5 and 10 of each study leg using a profilometer. RESULTS: The order of erosion from most to least at day 10 was unmodified acidic soft drink>experimental acidic soft drink with polyphosphate>experimental acidic soft drink with polyphosphate+gum>experimental acidic soft drink with polyphosphate+calcium>mineral water. At day 10 the unmodified acidic soft drink was significantly (p=0.001) more erosive than all other drinks. CONCLUSIONS: Unmodified acidic soft drink with the addition of polyphosphate alone or combined with calcium or xanthan gum are all effective at reducing erosion of enamel compared with the unmodified soft acidic drink.

The relationship between enamel softening and erosion caused by soft drinks at a range of temperatures.

OBJECTIVES: Investigations of the erosive potential of soft drinks are usually performed at room or body temperature, but drinks are more frequently served chilled, with ice, or hot. Since the rate of chemical reactions usually increases with temperature, it is predicted that erosion is more severe at high temperatures and reduced at low temperatures. The aim of this study was to investigate the correlation between enamel softening, enamel erosion, and temperature. METHODS: Atomic force microscopy nanoindentation and non-contact optical profilometry were used to assess changes in enamel nanomechanical properties after 5 min and erosive material loss after 30 min exposure to two different non-carbonated soft drinks at 4, 25, 50 and 75 degrees C. RESULTS: For one drink (Robinson's Original Juice Drink), there was a statistically significant difference between nanomechanical properties and erosion depth at all temperatures, with softening and erosion increasing with temperature. For another drink (Ribena ToothKind Juice Drink), there was a slight softening and virtually no material loss, and temperature had no statistically significant impact on erosion. There was a good linear correlation (R2 = 0.94) between nanomechanical properties and material loss. CONCLUSIONS: The difference between the drinks can be explained by their composition. For the erosive drink, material loss increased, and nanohardness decreased, approximately linearly with temperature. The correlation between softening and erosion demonstrated that nanomechanical properties after very short erosion times can be considered a good predictor of bulk material loss after considerably longer erosion times.

Relationship between enamel erosion and liquid flow rate.

The association of severe erosion with certain habits of consuming soft drinks prompted a study of erosion in relation to fluid flow. In the main experiments, citric acid solution (pH 3.2) was directed at polished enamel surfaces at flow rates of 26, 67 or 126 ml min(-1) through outlets of diameters 1.0, 2.6 or 5.0 mm for up to 20 min. Erosion depth increased with time of exposure and total volume of solution, with increasing flow rate and with decreasing outlet diameter. Scanning electron microscopy of acid-treated surfaces and of the subsurface enamel indicated that the clearance of dissolution products, rather than the mechanical dislodgement of partly dissolved crystal bundles, was the main process involved. For an exposure time of 20 min, erosion increased with (liquid velocity)(1/4). In a secondary experiment, it was found that the erosive potential of a low-erosive drink did not increase with increasing liquid velocity. The rapid increase in the rate of erosion caused by citric acid at low liquid velocities shows that reproducible stirring is essential for precision and intercomparison of in vitro studies. It also accounts for the rapid erosion seen when erosive drinks are consumed from a straw placed labial to the anterior teeth, or are "swished" between the teeth.

Erosive effect of a new sports drink on dental enamel during exercise.

PURPOSE: To compare the potential erosive effect of a prototype carbohydrate-electrolyte drink (PCE) with a neutral control (water) and a commercially available carbohydrate-electrolyte drink (CCE) during exercise. METHODS: : Nineteen healthy adults (male, N = 16; female, N = 3) took part in this single blind, three-way crossover study. Subjects were given each of the three drinks according to a randomization schedule, approximately balanced for first-order carryover effects. At the beginning of each of the three study periods, the volunteers were fitted with an intraoral appliance containing two human enamel blocks. During each study period, volunteers exercised for 75 min.d(-1) (5 repetitions of 15 min of exercise, with 5-min rests between exercise repetitions), 5 d.wk(-1) for 3 wk. Each day, drink aliquots of 200 mL were consumed during a 5-min period before exercise and after every 15-min bout of exercise, followed by a final 400-mL aliquot ingested over a 10-min period: a total of 1400 mL per study day. Dental erosion was measured as tissue loss from the enamel blocks by profilometry at the end of each study period. RESULTS: Water, PCE, and CCE produced 0.138 microm (SD 0.090 microm), 0.138 microm (SD 0.038 microm), and 4.238 microm (SD 3.872 microm) of enamel loss, respectively. A Wilcoxon t statistic showed a significant statistical difference between the PCE and CCE drinks (P < 0.001), whereas no significant difference could be detected between the PCE drink and water (P = 0.740). CONCLUSION: The PCE solution showed minimal erosion compared with the commercially available drink, and was statistically indistinguishable from water under the conditions of this study. Use of CE solutions formulated to minimize erosion during exercise may provide significant dental benefits.

Rates and predictors for relapse in medication overuse headache: a 1-year prospective study.

The authors prospectively studied 98 patients with medication overuse headache. The 1-year relapse rate was 38% but was lower for patients with migraine compared with tension-type headache (22% vs 73%, p < or = 0.002) and combination of migraine and tension-type headache (22% vs 77%, p < or = 0.0001). The rate was also lower for patients overusing triptans than ergots (19% vs 20%, NS) and analgesics (19% vs 58%, p < or = 0.001). The long-term success of withdrawal depends on the type of primary headache and the type of overused medication.

Aspects of the physical chemistry of polymers, biomaterials and mineralised tissues investigated with atomic force microscopy (AFM).

Beyond being merely a tool for measuring surface topography, atomic force microscopy (AFM) has made significant contributions to various scientific areas dealing with physical chemistry processes. This paper presents aspects of the physical chemistry at surfaces and interfaces of polymers, biomaterials and tissues investigated with AFM. Selected examples presented include surface induced self-assembly of polymer blends, copolymer interfacial reinforcement of immiscible homopolymers, protein adsorption on biomaterials and erosion of mineralised human tissues. In these areas, AFM is a useful and versatile tool to study structural or dynamic sample properties including thermodynamically driven surface evolution of polymer surfaces, lateral surface composition of interfaces, adsorption processes, and the metrology of demineralisation phenomena.

The Early Stages of Native Enamel Dissolution Studied with Atomic Force Microscopy.

Food-induced demineralization (erosion) is one of the key factors in surface structural changes of tooth enamel, with soft drinks being a significant etiological agent. The objective of this study was to measure early stages of enamel loss with high accuracy on native enamel surfaces combined with qualitative observations of changes in the surface morphology using the atomic force microscope (AFM). Native unerupted third molar surfaces were partly covered with a gold reference layer. Samples were imaged with the AFM before dissolution (at baseline) and after exposure to three different drinks (mineral water, a "toothkind" blackcurrant drink, and a lemon and lime juice drink) at five different exposure times (15 min, 30 min, 1 h, 2 h, and 3 h). The changes in the surface morphology were investigated qualitatively as well as quantitatively. This study showed that the maximum material loss occurred at the aprismatic parts of the enamel close to the perikymata. The maximum enamel loss was greatest for the lemon and lime juice drink and lowest for water. A two-way ANOVA of the transformed data, employing the natural logarithm, showed a statistically significant difference between both the drinks and the exposure time at a 95% confidence level (P=0.000). This demonstrates that the AFM is a suitable tool for measuring early stages of enamel demineralization. Copyright 2000 Academic Press.

Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain.

The cancer-related event that is most disruptive to the cancer patient's quality of life is pain. To begin to define the mechanisms that give rise to cancer pain, we examined the neurochemical changes that occur in the spinal cord and associated dorsal root ganglia in a murine model of bone cancer. Twenty-one days after intramedullary injection of osteolytic sarcoma cells into the femur, there was extensive bone destruction and invasion of the tumor into the periosteum, similar to that found in patients with osteolytic bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there was a massive astrocyte hypertrophy without neuronal loss, an expression of dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal horn. Additionally, normally non-noxious palpation of the bone with cancer induced behaviors indicative of pain, the internalization of the substance P receptor, and c-Fos expression in lamina I neurons. The alterations in the neurochemistry of the spinal cord and the sensitization of primary afferents were positively correlated with the extent of bone destruction and the growth of the tumor. This "neurochemical signature" of bone cancer pain appears unique when compared to changes that occur in persistent inflammatory or neuropathic pain states. Understanding the mechanisms by which the cancer cells induce this neurochemical reorganization may provide insight into peripheral factors that drive spinal cord plasticity and in the development of more effective treatments for cancer pain.

Transmission of chronic nociception by spinal neurons expressing the substance P receptor.

Substance P receptor (SPR)-expressing spinal neurons were ablated with the selective cytotoxin substance P-saporin. Loss of these neurons resulted in a reduction of thermal hyperalgesia and mechanical allodynia associated with persistent neuropathic and inflammatory pain states. This loss appeared to be permanent. Responses to mildly painful stimuli and morphine analgesia were unaffected by this treatment. These results identify a target for treating persistent pain and suggest that the small population of SPR-expressing neurons in the dorsal horn of the spinal cord plays a pivotal role in the generation and maintenance of chronic neuropathic and inflammatory pain.

Molecular biological observations in some rare neoplasms: DNA ploidy and cell cycle data in liposarcoma and malignant fibrous histiocytoma.

INTRODUCTION: The prognostic significance of tumor DNA ploidy and cell cycle analysis for long-term survival has been examined in 19 patients with liposarcoma or malignant fibrous histiocytoma. In many cases, different tumor areas of primary tumors and local recurrences have been analyzed to reveal intratumoral heterogeneity. RESULTS: Among the primary tumors, there were eight aneuploid tumors, three of which showed diploid and aneuploid tumor regions. Correlations among DNA ploidy, grading, percentage of S-phase cells and infiltrative growth pattern of the tumors could be demonstrated. Poorly differentiated tumors (G3) showed aneuploidy in six of eight patients. Aneuploid tumors showed S-phase cells in 17.2% (range 3.2-38.1%), which was higher than the percentage of S-phase cells in diploid tumors (9.4%, range 2.1-27.4%). Aneuploid tumors showed a more infiltrative growth pattern (6 of 8 patients) than diploid tumors (6 of 11 patients). The median survival time of patients with diploid tumors was 86.5 months (8-144 months), compared with 40.9 months (11-54 months) for patients with aneuploid tumors. CONCLUSION: DNA ploidy and percentage of S-phase cells may be considered as prognostic factors.