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.

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.

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.

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.

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.

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.

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.

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.

Effect of diet and training on muscle glycogen storage and utilization in sled dogs.

Two groups of eight Alaskan huskies fed either a high-fat (HFD; 60% kcal from fat and 15% kcal from carbohydrate) or a high-carbohydrate diet (HCD; 60% kcal from carbohydrate and 15% kcal from fat) performed standard aerobic (1 h at 4 m/s on a 0% slope) and anaerobic (3 min at 6.7 m/s on a 10% slope) tests before and after training. Before and immediately after each exercise test, venous blood samples were collected and analyzed for lactate and pyruvate, and muscle biopsies were obtained under local anesthesia from the semitendinosus muscle and analyzed for total muscle glycogen (TMG) concentration. Training was associated with a significant increase in preexercise TMG in both diet groups; this effect was most marked in the HCD. There was no effect of diet or training on TMG utilization during the aerobic tests. The rate of TMG utilization during the anaerobic tests was between 20 and 40 times greater than that measured during the aerobic tests. The pre- to postexercise change in TMG was dependent on preexercise TMG in the HCD and HFD for both anaerobic tests (HCD: P < 0.01, r = 0.81; HFD: P < or = 0.03, r = 0.66). It is concluded that the increased glycogen storage associated with the HCD was more than offset by the more rapid rate of glycogen utilization in this group. HFD facilitated carbohydrate sparing during intense exercise and should thus be a better dietary strategy for endurance in sled dogs.

Delayed behavioral effects following intrahippocampal injection of aggregated A beta (1-42).

Beta amyloid protein (A beta) is the major extracellular component of Alzheimer's disease (AD) plaques. In the current study, A beta (1-42) was aggregated in vitro using a method which produces A beta aggregates similar to those found in the AD brain. Twelve male Sprague-Dawley rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio (ALCR) schedule. When performance was stable on the ALCR schedule, six subjects were injected (bilaterally into the CA3 area of the dorsal hippocampus) with 5.0 microliters aggregated A beta in suspension, and the remaining six subjects were injected with 5.0 microliters sterile water. Behavioral testing resumed 5 days after surgery and continued for 90 days post-injection. Aggregated A beta injection did not affect the number of lever switching errors made in a daily session but did affect the number of incorrect lever response perseverations. After approximately 30 days post-injection, aggregated A beta injection detrimentally affected ability to track the changing parameters of the schedule, and decreased the efficiency by which subjects obtained reinforcers. From approximately day 50 post-injection onward, A beta-injected subjects demonstrated significantly higher numbers of incorrect lever response perseverations than did sterile water-injected subjects. These effects appeared to be central rather than peripheral, as A beta injection did not decrease running response rates under the ALCR schedule. The delayed onset of behavioral effects seen in this and other behavioral studies may be a result of a cascade of potentially harmful responses induced through glial activation following aggregated A beta injection.

The contributions of larval growth and pupal duration to protandry in the black swallowtail butterfly, Papilio polyxenes.

Shorter male larval and pupal durations were sufficient to produce the protandrous emergence pattern of the black swallowtail butterfly. In 9 broods observed under natural conditions, the first male was seen 7.1±6.5 days before the first female, although the peak of captures relative to the first capture was similar in both sexes. The field data supported only weakly the predictions of the Wiklund-Fagerstrom model for protandry. Some prereproductive period was necessary for males, and they were limited in how frequently they could mate. A third of the females mated more than once.Males were significantly smaller in size and weight than females in both diapausing and non-diapausing broods. Feeding experiments indicated that male larvae ate less and converted their food into biomass more efficiently than females. Female pupae contained higher proportions of fat and protein than male pupae. Differential body composition may be involved in sexual dimorphism differences in both larval and pual developmental rates. Thus, in addition to size, chemical differences in composition or metabolism may contribute to the observed natural protandry.

Assessment of female reproductive status in captive-housed Hanuman langurs (Presbytis entellus) by measurement of urinary and fecal steroid excretion patterns.

The study reports on the use of urinary and fecal hormone measurements for monitoring female reproductive status in captive-housed Hanuman langurs (Presbytis entellus). Matched urine and fecal samples collected throughout 7 complete menstrual cycles of two females, and during part of one pregnancy in a third female were analyzed. Estrone conjugates (E1C) and immunoreactive pregnanediol glucuronide (PdG) in urine and immunoreactive estradiol (E2), progesterone (P4), pregnanediol (Pd) and 20α-hydroxyprogesterone (20αOHP) in feces were measured by enzymeimmunoassay. E1C and PdG in urine were excreted in a cyclic pattern with E1C levels increasing 3- to 4-fold during the follicular phase to reach preovulatory peak values 2 days before a defined rise in PdG concentrations. Cycle lengths ranged between 20 and 34 days comprising a variable follicular phase of 7-21 days and a more consistent luteal phase of 12-14 days. High pressure liquid chromatography (HPLC) analysis of fecal extracts confirmed the presence of all fecal hormones measured, but indicated large amounts of additional immunoreactivity in the three progestin assays. The patterns of excretion of fecal E2 and all three fecal progestins corresponded well with those of steroid metabolites in urine in showing a clear and well defined follicular phase E2 rise followed by a luteal phase progestin increase. Measurement of 20αOHP immunoreactivity revealed the most stable baseline and the highest follicular/luteal phase differential. Levels of all hormones were clearly elevated during pregnancy although urinary E1C and PdG showed a more pronounced increase compared to fecal metabolites. The results indicate that urinary and fecal hormone analysis can be applied to noninvasive monitoring of reproductive status in the Hanuman langur. © 1995 Wiley-Liss, Inc.

Asymptotic statistical theory of overtraining and cross-validation.

A statistical theory for overtraining is proposed. The analysis treats general realizable stochastic neural networks, trained with Kullback-Leibler divergence in the asymptotic case of a large number of training examples. It is shown that the asymptotic gain in the generalization error is small if we perform early stopping, even if we have access to the optimal stopping time. Based on the cross-validation stopping we consider the ratio the examples should be divided into training and cross-validation sets in order to obtain the optimum performance. Although cross-validated early stopping is useless in the asymptotic region, it surely decreases the generalization error in the nonasymptotic region. Our large scale simulations done on a CM5 are in good agreement with our analytical findings.

Enteroclysis: double contrast examination of the small bowel.

Enteroclysis is a double contrast study of the small bowel. This procedure allows the radiologist to evaluate the small bowel for disease processes including Crohn's disease, Meckel's diverticulum, and malabsorption diseases--all disease processes sometimes missed through single contrast SBFT. Through the use of enteroclysis, the radiologist can detect mucosal fold pattern changes, ulceration of the lumen, dilation of the loops, and intussusception, which can cause an obstruction. Even though the procedure is costly and time consuming, it provides a more accurate evaluation of the small bowel.

Dynamic imaging of the wrist.

Dynamic imaging of the wrist can be performed through the use of fluoroscopy, arthrography, and arthrotomography. These methods of imaging have proved valuable in the diagnosis of many pathologic conditions of the wrist. Fluoroscopy has proved valuable as it captures the kinematics of the wrist. Arthrography utilizes contrast media to demonstrate anatomic structures not normally visualized on plain radiographs. Last, the technique of arthrotomography improves evaluation by helping to eliminate the problem of superimposition of structures within the wrist. Dynamic imaging of the wrist has proved to be a valuable tool in the diagnosis of chronic conditions of the wrist.

Free clinics.

The simplicity and joy of practicing medicine in free clinics has been discovered by numerous Iowa physicians. They tell of the need to practice pure medicine for Iowans who truly need free medical care. They also share how to start a free clinic, step by step. It's simple, they say, with a little help from colleagues and the community.

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.