Design and performance of an X-ray scanning microscope at the Hard X-ray Nanoprobe beamline of NSLS-II.

A hard X-ray scanning microscope installed at the Hard X-ray Nanoprobe beamline of the National Synchrotron Light Source II has been designed, constructed and commissioned. The microscope relies on a compact, high stiffness, low heat dissipation approach and utilizes two types of nanofocusing optics. It is capable of imaging with ∼15 nm × 15 nm spatial resolution using multilayer Laue lenses and 25 nm × 26 nm resolution using zone plates. Fluorescence, diffraction, absorption, differential phase contrast, ptychography and tomography are available as experimental techniques. The microscope is also equipped with a temperature regulation system which allows the temperature of a sample to be varied in the range between 90 K and 1000 K. The constructed instrument is open for general users and offers its capabilities to the material science, battery research and bioscience communities.

Pushing the limits: an instrument for hard X-ray imaging below 20 nm.

Hard X-ray microscopy is a prominent tool suitable for nanoscale-resolution non-destructive imaging of various materials used in different areas of science and technology. With an ongoing effort to push the 2D/3D imaging resolution down to 10 nm in the hard X-ray regime, both the fabrication of nano-focusing optics and the stability of the microscope using those optics become extremely challenging. In this work a microscopy system designed and constructed to accommodate multilayer Laue lenses as nanofocusing optics is presented. The developed apparatus has been thoroughly characterized in terms of resolution and stability followed by imaging experiments at a synchrotron facility. Drift rates of ∼2 nm h(-1) accompanied by 13 nm × 33 nm imaging resolution at 11.8 keV are reported.

[Current aspects of ototoxicity : Local ototoxic effects, diagnosis, prevention, and treatment]. / Aktuelle Aspekte zur Ototoxizität : Lokale ototoxische Wirkungen, Diagnostik, Prävention und Therapie.

The otorhinolaryngologist is often involved in an interdisciplinary approach to diagnose ototoxic side effects. Under certain conditions, chemical agents-particularly drugs-can have ototoxic effects. This is not only true for systemic administration, but also for local application (e.g., transdermal and transtympanal). Identifying and avoiding ototoxicity is still a challenge in clinical practice. The audiological monitoring of patients receiving potentially cochleotoxic drugs is now standardized. For diagnosis of suspected vestibulotoxic effects, the video head impulse test and vestibular evoked myogenic potentials seem to be suitable procedures for objective assessment. The early detection of such ototoxic effects has important implications for the prevention of hearing and balance disorders. Recent studies show that intratympanic delivery of medications might play an important role in the limitation of ototoxically induced hearing loss. In peripheral vestibulopathies with episodic vertigo, which strongly affect quality of life, ototoxic effects can be used for therapeutic purposes.

[Current aspects of ototoxicity. Ototoxic substances and their effects]. / Aktuelle Aspekte zur Ototoxizität : Ototoxische Substanzen und deren Effekte.

Ototoxicity describes reversible or irreversible disorders of inner ear functions due to the influence of chemical, biological, or physical substances. Ototoxicity should be kept in mind during differential diagnosis of hearing loss, tinnitus, dizziness, and vertigo. In clinical practice, drug-induced ototoxic effects play a major role. The otorhinolaryngologist should also be involved in interdisciplinary cooperation, e.g., during treatment with antineoplastic chemotherapeutic agents with potential ototoxic side effects. In clinical practice, multimedication and interactions between different agents can complicate precise correlation in individual cases. Recent studies also show that noncellular components, such as otoconia, are extremely sensitive to chemical attacks.

Impact of a Transplantation Critical Care Model on Short-Term Outcomes Following Liver Transplantation in High Acuity Patients: A Single-Center Experience.

BACKGROUND: Orthotopic liver transplantation (OLT) is the definitive treatment for end-stage liver disease (ESLD). Patients with high acuity ESLD are frequently denied life-saving OLT by transplant centers due to reported inferior outcomes. We sought to analyze the impact of a specialized transplant critical care model (TCCM) on patient access to OLT and survival outcomes in high acuity patients. METHODS: From January 2009 to December 2016, 122 adults were wait-listed at our transplant center with laboratory Model for ESLD ≥35 or Status I. Outcomes in Era I (prior to TCCM) were compared to Era II (TCCM established October 1, 2012). RESULTS: Era II (TCCM) led to a significant increase in patients' access to OLT. Frequency and need to seek OLT at another center dropped 4-fold in Era II. Compared to Era I, the majority of patients in Era II required intensive care unit management (22% vs 83%, P < .01) and renal replacement therapy (11% vs 70%, P < .01) prior to OLT. Despite a higher acuity of illness in Era II, 1-year patient survival was comparable (89% Era I, 80% Era II, P = .35). CONCLUSION: Implementation of a specialized TCCM expanded OLT access to high acuity patients, reduced the need to seek higher level of care elsewhere, and achieved excellent short-term post-transplant survival outcomes.

Reversal of delayed vasospasm by TS-011 in the dual hemorrhage dog model of subarachnoid hemorrhage.

PURPOSE: Arachidonic acid is avidly metabolized to a potent vasoconstrictor, 20-hydroxyeicosatetraenoic acid (20-HETE), in the cerebral circulation. 20-HETE has been reported to contribute to the acute fall in cerebral blood flow following subarachnoid hemorrhage (SAH), but its role in the development of delayed vasospasm is unknown. The present study examined whether delayed vasospasm is associated with elevations in 20-HETE in CSF in the dual hemorrhage model of SAH in dogs and if blockade of the synthesis of 20-HETE with N-(3-chloro-4-morpholin-4-yl)phenyl-N'-hydroxyimido formamide (TS-011) can reverse delayed vasospasm in this model. MATERIALS AND METHODS: Delayed vasospasm was induced in 22 adult beagle dogs by dual injection of blood (0.5 mL/kg) into the cisterna magna on days 1 and 4. Sequential samples of CSF were collected before intracisternal injections of blood on days 1 and 4 and after the development of delayed vasospasm on day 7. Sequential angiograms were obtained before and after intracisternal injection of blood on days 1 and 4 and before and 1 hour after administration of TS-011 (1 mg/kg IV) on day 7. RESULTS: The dogs consistently developed delayed vasospasm, and the diameter of the basilar artery fell to 68 +/- 3% (n = 15), 3 days after the second intracisternal injection of blood. The levels of 20-HETE in CSF increased from 4 +/- 2 to 39 +/- 16 pg/mL. In 9 dogs with delayed vasospasm, acute blockade of the synthesis of 20-HETE with TS011 (1 mg/kg IV) significantly increased the diameter of the basilar artery by 39%. Chronic administration of TS-011 (1 mg/kg per day) attenuated the development of delayed vasospasm, and the diameter of the basilar artery fell by 17 +/- 1% versus the 33 +/- 3% decrease in diameter seen in control animals 3 days following the second injection of blood into the cisterna magna. CONCLUSIONS: These results indicate that the development of delayed vasospasm in dogs is associated with an increase in 20-HETE levels in CSF, and acute blockade of the synthesis of 20-HETE with TS-011 reverses delayed vasospasm in this model.

The history of nitrite in human nutrition: a contribution from German cookery books.

In order to settle the question of when saltpetre (nitrate) came in use as an additive to human food, a number of historic cookery books from Germany and Austria were reviewed. Obviously, the change from vegetable dyes to saltpetre for the coloring or color preservation, respectively, of meat occurred between 1600 and 1750, probably near 1700. The addition of sugar which favours the reduction of nitrate to the active agent nitrite became common practice during the 19th century. Thus some historic parallels to the appearance of colorectal cancer, multiple sclerosis and rheumatoid arthritis in the medical literature became apparent.

The risk of multiple sclerosis in the U.S.A. in relation to sociogeographic features: a factor-analytic study.

The multiple sclerosis (MS) case-control ratio by state originating from the U.S. veteran series from World War II (Kurtzke Neurology 1979; 29: 1228-1235) was geographically compared with 46 sociogeographic variables from the period 1935-1958. Latitude was, by far, the variable most closely associated with MS in univariate testing. Multivariate analysis by factor analysis revealed that the MS rate was associated with 2 independent settings ("factors"). The first one was defined mainly socioeconomically and was characterized by indicators of higher affluence; better nutrition with a higher meat consumption in particular, and a higher sanitary level were the prominent features. The second MS-related bundle comprised characteristics of a colder climate along with further dietary variables (i.e. a diet low in fish and high in dairy products). The findings suggest a possible interaction of both socioeconomic and geoclimatic features in the etiology of MS; sanitation, diet and climate being of particular interest.

Some comments on the occurrence of multiple sclerosis in the Faroe Islands.

Some factors which might be related to the marked increase in multiple sclerosis in the Faroe Islands in mid-century were studied. Of these, only the occupation by British troops in World War II was found to be significant. A vague relationship with industrial changes earlier in the century was also found. These findings are discussed with caution with respect to the close association between population on the one hand and all features tested as well as multiple sclerosis on the other.

On the diagnostic value of different CSF investigations in multiple sclerosis.

An assessment was made of the relative values of different methods of calculating intrathecal IgG synthesis in multiple sclerosis. In 60 patients with definite, probable or possible multiple sclerosis the IgG/protein and IgG/albumin ratios, the IgG index, the Tourtellotte formula and the graphic evaluation according to Reiber were applied. All the patients had oligoclonal IgG in the CSF. Reiber's method was the most sensitive, yielding 66% of abnormal findings. Only the cell count showed significant differences between active and inactive stages. There was a correlation between the cell count and the daily rate of intrathecal IgG synthesis and between the latter and the number of oligoclonal bands in CSF, but none of these parameters correlated with duration of disease or the number of previous bouts.

Prognostic criteria in an epidemiological group of patients with multiple sclerosis: an exploratory study.

Demographic and clinical features and data on medical history and prior environmental exposure collected during an epidemiological long-term study of multiple sclerosis (MS) were tested for their possible prognostic value. Fifty-two benign MS patients were compared with 29 patients having a malignant course. A primary or secondary progressive course and cerebellar/lower brain-stem symptoms at onset indicated an unfavourable course, whereas no predictive value of sex or of any other type of onset symptomatology was found. Age at onset per se had no influence on prognosis but was associated with more rapid progression only by its relationship with a chronic progressive type of course. Prior illness, surgery, trauma and childhood exposure to defined environmental factors could not be identified as relevant for prognosis.

A possible paradox in the immunology of multiple sclerosis: its apparent lack of 'specificity' might provide clues to the etiology.

As a further development from an earlier hypothesis, a pathogenic role of polyspecific natural, idiotypically connected antibodies is claimed, that recognize concomitantly a variety of CNS antigens and are matured to some degree to higher-affinity anti-CNS antibodies without ever losing their network association. On that basis, nitrophenol-carrier conjugates well-known to be foreign target antigens of natural antibodies and present in food commodities that have epidemiological links to MS, are considered as paradigmatic for agents of possible etiologic importance.

The intrathecal immune response in multiple sclerosis: a different concept of 'specificity'.

A hypothesis is presented in which the immune response in multiple sclerosis is conceived as a primary response to an auto-antigen located within the immune system (e.g. a certain allotype or HLA epitope) which shows subsequent or simultaneous specificity for a greater number of nominal antigens [corrected]. The increased tendency of [corrected] such antibodies to self-aggregation might play a critical role in the pathogenesis.

Spontaneous fluctuations in cerebral oxygen supply. An introduction.

Spontaneous, low frequency (4-12 cpm) fluctuations, independent of the cardiac and respiratory cycles, in human and animal brains were first recorded with the O2 polarographic technique in the late 1950s. They were seen in NADH and cytochrome oxidase and associated with spontaneous vasomotion pial and large cerebral arteries. Renewed interest in spontaneous fluctuations was generated by studies with laser-Doppler flowmetry (LDF), reflectance oximetry and functional MRI. Spontaneous fluctuations were consistently produced when cerebral perfusion was challenged by systemic or local manipulations; the fluctuation amplitude reached 30-40% of the mean. The most potent stimuli are hypotension, hyperventilation, cerebral artery occlusion and cerebral vasoconstriction elicited, for example, by a nitric oxide synthase inhibitor but not by indomethacin. The fluctuations are suspended by CO2 and halothane at concentrations that produce hyperemia. Recently, spontaneous fluctuations were recorded by LDF microprobes in areas as small as 130 microns and by video-microscopy in single capillaries. The fluctuations were absent in severe, focally ischemic brain territories. The dependence of spontaneous fluctuations on intravascular pressure argues for the importance of a myogenic mechanism, however, neuronal modulation may also play a role. Coherence of small vessel vasomotion may be required for the emergence of regional flow fluctuations. There is a need to elucidate the spatial and frequency domains in which fluctuations are present under normal physiological conditions and those in which they may reflect brain injury and pathologies of diagnostic or prognostic value.

Epidural blood patch as treatment for a surgical durocutaneous fistula.

We describe the first case report of an epidural autologous blood patch used for the treatment of a durocutaneous fistula caused by a surgical dural tear. The epidural blood patch cured the patient's headache and was followed by a sequelae of back pain that responded to conservative therapy.

[Epidemiologic aspects of multiple sclerosis]. / Epidemiologische Aspekte der multiplen Sklerose.

Epidemiology plays a prominent role in the search for environmental risk factors in multiple sclerosis (MS). The basic pattern with the predilection for temperate zones of the globe, whites, females and medium age groups was confirmed throughout. Whether or not MS is increasing in frequency is highly debated. Although no clear risk factors have been demonstrated so far, a certain association of the MS risk with the factors "low temperatures and precipitation", "consumption of animal proteins/fats or meat", "familiar occurrence of MS" and with a late occurrence of common childhood infections became obvious. Many other putative risk factors were not confirmed in most studies.

Design and performance of a scanning ptychography microscope.

We have designed and constructed a dedicated instrument to perform ptychography measurements and characterization of multilayer Laue lenses nanofocusing optics. The design of the scanning microscope provides stability of components and minimal thermal drifts, requirements for nanometer scale spatial resolution measurements. We performed thorough laboratory characterization of the instrument in terms of resolution and thermal drifts with subsequent measurements at a synchrotron. We have successfully acquired and reconstructed ptychography data yielding 11 nm line focus.

Compact prototype apparatus for reducing the circle of confusion down to 40 nm for x-ray nanotomography.

We have constructed a compact prototype apparatus for active correction of circle of confusion during rotational motion. Our system combines fiber optic interferometry as a sensing element, the reference cylinder along with the nanopositioning system, and a robust correction algorithm. We demonstrate dynamic correction of run-out errors down to 40 nm; the resolution is limited by ambient environment and accuracy of correcting nanopositioners. Our approach provides a compact solution for in-vacuum scanning nanotomography x-ray experiments with a potential to reach sub-nm level of correction.

Performance and characterization of the prototype nm-scale spatial resolution scanning multilayer Laue lenses microscope.

Synchrotron based x-ray microscopy established itself as a prominent tool for noninvasive investigations in many areas of science and technology. Many facilities around the world routinely achieve sub-micrometer resolution with a few instruments capable of imaging with the spatial resolution better than 100 nm. With an ongoing effort to push the 2D/3D resolution down to 10 nm in the hard x-ray regime both fabrication of the nano-focusing optics and stability of a microscope become extremely challenging. In this work we present our approach to overcome technical challenges on the path towards high spatial resolution hard x-ray microscopy and demonstrate the performance of a scanning fluorescence microscope equipped with the multilayer Laue lenses focusing optics.

A questionnaire for multinational case-control studies of environmental risk factors in multiple sclerosis (EnvIMS-Q).

OBJECTIVES: The increasing incidence of multiple sclerosis (MS) worldwide, especially in women, points to the crucial role of environmental and lifestyle risk factors in determining the disease occurrence. An international multicentre case-control study of Environmental Risk Factors In Multiple Sclerosis (EnvIMS) has been launched in Norway, Sweden, Italy, Serbia and Canada, aimed to examine MS environmental risk factors in a large study population and disclose reciprocal interactions. To ensure equivalent methodology in detecting age-related past exposures in individuals with and without MS across the study sites, a new questionnaire (EnvIMS-Q) is presented. MATERIALS AND METHODS: EnvIMS-Q builds on previously developed guidelines for epidemiological studies in MS and is a 6-page self-administered postal questionnaire. Participants are de-identified through the use of a numerical code. Its content is identical for cases and controls including 'core' and population-specific questions as proxies for vitamin D exposure (sun exposure, dietary habits and supplementation), childhood infections (including infectious mononucleosis) and cigarette smoking. Information on possible confounders or effect modifiers is also obtained. EnvIMS-Q was initially drafted in English and subsequently translated into Italian, Serbian, Norwegian, Swedish and French-Canadian. EnvIMS-Q has been tested for acceptability, feasibility and reliability. RESULTS AND CONCLUSIONS: EnvIMS-Q has shown cross-cultural feasibility, acceptability and reliability in both patients with MS and healthy subjects from all sites. EnvIMS-Q is an efficient tool to ensure proper assessment of age-specific exposure to environmental factors in large multinational population-based case-control studies of MS risk factors.