Toward Hyperpolarization of Oil Molecules via Single Nitrogen Vacancy Centers in Diamond.

Efficient polarization of organic molecules is of extraordinary relevance when performing nuclear magnetic resonance (NMR) and imaging. Commercially available routes to dynamical nuclear polarization (DNP) work at extremely low temperatures, relying on the solidification of organic samples and thus bringing the molecules out of their ambient thermal conditions. In this work, we investigate polarization transfer from optically pumped nitrogen vacancy centers in diamond to external molecules at room temperature. This polarization transfer is described by both an extensive analytical analysis and numerical simulations based on spin bath bosonization and is supported by experimental data in excellent agreement. These results set the route to hyperpolarization of diffusive molecules in different scenarios and consequently, due to an increased signal, to high-resolution NMR.

Dissipatively Stabilized Quantum Sensor Based on Indirect Nuclear-Nuclear Interactions.

We propose to use a dissipatively stabilized nitrogen vacancy (NV) center as a mediator of interaction between two nuclear spins that are protected from decoherence and relaxation of the NV due to the periodical resets of the NV center. Under ambient conditions this scheme achieves highly selective high-fidelity quantum gates between nuclear spins in a quantum register even at large NV-nuclear distances. Importantly, this method allows for the use of nuclear spins as a sensor rather than a memory, while the NV spin acts as an ancillary system for the initialization and readout of the sensor. The immunity to the decoherence and relaxation of the NV center leads to a tunable sharp frequency filter while allowing at the same time the continuous collection of the signal to achieve simultaneously high spectral selectivity and high signal-to-noise ratio.

Questionable diagnostic benefit of the commercially available panel of bee venom components.

For many years, only the major allergen rApi m 1 has been available on the ImmunoCAP system for routine diagnosis of bee venom (BV) allergy. Now, there are five components available, and we aimed to detect the sensitivity and specificity of rApi m 1, 2, 3, 5, and 10 in BV-allergic patients. We further evaluated the sensitivity of rApi m 1 and 2 of an alternative platform and investigated possible differences in the sensitization profile between monosensitization and clinically relevant double sensitization. Analysis of the whole panel of BV allergens of the CAP system still resulted in a lower sensitivity than analysis of the combination of rApi m 1 and 2 of the Immulite (71.6% vs 85.8%). Sensitization rate of rApi m 5 was more than doubled in double-sensitized patients, while there was no difference for rApi m 2. The benefit of the commercially available panel of BV components is questionable, due to the insufficient sensitivity and still unavailable important cross-reacting allergens.

Robust temperature change rate actuated valving and switching for highly integrated centrifugal microfluidics.

We present new unit operations for valving and switching in centrifugal microfluidics that are actuated by a temperature change rate (TCR) and controlled by the rotational frequency. Implementation is realized simply by introducing a comparatively large fluidic resistance to an air vent of a fluidic structure downstream of a siphon channel. During temperature decrease at a given TCR, the air pressure inside the downstream structure decreases and the fluidic resistance of the air vent slows down air pressure compensation allowing a thermally induced underpressure to build up temporarily. Thereby the rate of temperature change determines the time course of the underpressure for a given geometry. The thermally induced underpressure pulls the liquid against a centrifugal counterpressure above a siphon crest, which triggers the valve or switch. The centrifugal counterpressure (adjusted by rotation) serves as an independent control parameter to allow or prevent valving or switching at any TCR. The unit operations are thus compatible with any temperature or centrifugation protocol prior to valving or switching. In contrast to existing methods, this compatibility is achieved at no additional costs: neither additional fabrication steps nor additional disk space or external means are required besides global temperature control, which is needed for the assay. For the layout, an analytical model is provided and verified. The TCR actuated unit operations are demonstrated, first, by a stand-alone switch that routes the liquid to either one of the two collection chambers (n = 6) and, second, by studying the robustness of TCR actuated valving within a microfluidic cartridge for highly integrated nucleic acid testing. Valving could safely be prevented during PCR by compensating the thermally induced underpressure of 3.52 kPa with a centrifugal counterpressure at a rotational frequency of 30 Hz with a minimum safety range to valving of 2.03 kPa. Subsequently, a thermally induced underpressure of 2.55 kPa was utilized for robust siphon valving at 3 Hz with a minimum safety range of 2.32 kPa.

[Mucosal diseases from an allergological perspective]. / Schleimhauterkrankungen aus allergologischer Sicht.

The oral allergy syndrome is one of the most common form of food allergy and manifests as contact urticaria of the oral mucosa after consumption of cross reacting foods. Whereas allergic contact stomatitis often occurs due to dental materials, allergic contact cheilitis is usually a reaction due to topical therapeutics like herpes ointments or lip care products. As late type reactions are more frequent than immediate type reactions in the anogenital mucosa, contact dermatitis in this area should be identified via epicutaneous testing. In case of contact urticaria at the genital mucosa, a semen allergy or a latex allergy should be given due consideration as a possible cause. Angioedemas, which are mostly common histamine mediated, usually prefer skin areas with loose connective tissue such as the oral or genital mucosa. Fixed drug eruption also occurs preferentially in these areas. Bullous drug-induced skin reactions (e.g., SJS and TEN) are characterized by severe hemorrhagic, erosive affections of mucous membranes.

Hymenoptera stings in the head region induce impressive, but not severe sting reactions.

Stings in the head region are considered to be a risk factor for severe systemic reactions to hymenoptera stings. We supposed that stings in skin areas, which are well supplied with blood, lead to more severe reactions and tested our hypothesis in 847 patients with confirmed hymenoptera venom allergy. However, symptom severity was independent from sting site: only 16.3% of patients with severe reactions were stung on the head (P = 0.017). But we confirmed age > 40 years (P < 0.001) as well as elevated basal tryptase levels (P = 0.001) as risk factors. Taking antihypertensive drugs seemed to have an influence: 41.7% of patients taking antihypertensive drugs experienced a severe reaction compared to 29.5% of patients, not taking such drugs (P = 0.019). However, considering patients' age in regression analysis, taking antihypertensive drugs had no effect on symptom severity (P = 0.342). Importantly, in most patients with severe reactions, cutaneous signs were absent (P < 0.001).

System-level network simulation for robust centrifugal-microfluidic lab-on-a-chip systems.

Centrifugal microfluidics shows a clear trend towards a higher degree of integration and parallelization. This trend leads to an increase in the number and density of integrated microfluidic unit operations. The fact that all unit operations are processed by the same common spin protocol turns higher integration into higher complexity. To allow for efficient development anyhow, we introduce advanced lumped models for network simulations in centrifugal microfluidics. These models consider the interplay of centrifugal and Euler pressures, viscous dissipation, capillary pressures and pneumatic pressures. The simulations are fast and simple to set up and allow for the precise prediction of flow rates as well as switching and valving events. During development, channel and chamber geometry variations due to manufacturing tolerances can be taken into account as well as pipetting errors, variations of contact angles, compliant chamber walls and temperature variations in the processing device. As an example of considering these parameters during development, we demonstrate simulation based robustness analysis for pneumatic siphon valving in centrifugal microfluidics. Subsequently, the influence of liquid properties on pumping and valving is studied for four liquids relevant for biochemical analysis, namely, water (large surface tension), blood plasma (large contact angle hysteresis), ethanol/water (highly wetting) and glycerine/water (highly viscous). In a second example, we derive a spin protocol to attain a constant flow rate under varying pressure conditions. Both examples show excellent agreement with experimental validations.

Microfluidic vapor-diffusion barrier for pressure reduction in fully closed PCR modules.

Microfluidic systems for polymerase chain reaction (PCR) should be fully closed to avoid vapor loss and to exclude the risk of contaminating the laboratory environment. In closed systems however, the high temperatures of up to 95 °C associated with PCR cause high overpressures up to 100 kPa, dominated by the increase of vapor partial pressure upon evaporation. Such high overpressures pose challenges to the mechanical stability of microfluidic chips as well as to the liquid handling in integrated sample-to-answer systems. In this work, we drastically reduce the pressure increase in fully closed PCR systems by integrating a microchannel that serves as a vapor-diffusion barrier (VDB), separating the liquid-filled PCR chamber from an auxiliary air chamber. In such configurations, propagation of vapor from the PCR chamber into the auxiliary air chamber and as a consequence the increase of pressure is limited by the slow diffusion process of vapor through the VDB. At temperature increase from 23 °C to 95 °C, we demonstrate the reduction of overpressure from more than 80 kPa without the VDB to only 35 kPa with the VDB. We further demonstrate proper function of VDB and its easy integration with downstream processes for PCR based nucleic acid amplification within centrifugal microfluidics. Without integration of the VDB, malfunction due to pressure-induced delamination of the microfluidic chip occurred.

Detecting and polarizing nuclear spins with double resonance on a single electron spin.

We report the detection and polarization of nuclear spins in diamond at room temperature by using a single nitrogen-vacancy (NV) center. We use Hartmann-Hahn double resonance to coherently enhance the signal from a single nuclear spin while decoupling from the noisy spin bath, which otherwise limits the detection sensitivity. As a proof of principle, we (i) observe coherent oscillations between the NV center and a weakly coupled nuclear spin and (ii) demonstrate nuclear-bath cooling, which prolongs the coherence time of the NV sensor by more than a factor of 5. Our results provide a route to nanometer scale magnetic resonance imaging and novel quantum information processing protocols.

Potential benefits of non-pharmacological therapies in fibromyalgia.

Fibromyalgia (FM) is an incurable common syndrome of non-articular origin, and with no effective treatment by now. A great deal of research has sought to assess the efficacy of different therapies, especially non-pharmacological and low-cost ones, in the reduction of the intensity of symptoms. Despite the availability of a wide range of alternative therapies nowadays, there is little scientific evidence of the potential benefits of most of them, with results being contradictories. The purpose of this paper is to review some of the less well known alternative therapies in FM treatment, to describe the more relevant clinical studies published in this matter, and to analyze the potential effects of the main alternative therapies, in order to verify their efficacy.

Solid-state characterization of non-stoichiometric hydrates of ester-type local anaesthetics. Part XI. Crystal polymorphism of local anaesthetic drugs.

Three structurally closely related local anaesthetic drugs, hydroxyprocaine hydrochloride (4-butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, HPCHC), tetracaine hydrochloride (4-butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, TCHC) and hydroxytetracaine hydrochloride (4-butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, SLCHC) are found to form hydrated crystals. Those were characterized by thermal analysis (hot stage microscopy, differential scanning calorimetry, thermogravimetry), vibrational spectroscopic methods (FTIR-, FT-Raman-spectroscopy), powder X-ray diffractometry, solid-state NMR and water sorption/desorption analysis. The formation and the stability of the hydrated solid phases are evaluated by sorption isotherms derived from different sorption/desorption analytic methods. The three substances investigated show conformational polymorphism with the anhydrated phases including a high temperature form mod. I, which is highly hygroscopic and isostructural with the hydrate. The hydrated form is present in commercial products at various contents. These hemihydrates crystallize from water, whereas the anhydrates crystallize from all other tested organic solvents. Different methods of water sorption/desorption analysis indicate the formation of non-stoichiometric hydrates. Different methods of drying lead to the same results. Solid-state NMR spectra were used to obtain both structural and molecular level mobility information.

Polymorphism and pseudopolymorphism of salicaine and salicaine hydrochloride crystal polymorphism of local anaesthetic drugs, part V.

The local anaesthetic drug salicaine hydrochloride (hydroxytetracaine hydrochloride, 4-butylamino-2-hydroxybenzoic acid 2-dimethylaminoethyl ester hydrochloride, SLCHC) and the free-base salicaine (SLC) were characterized by thermal analysis, vibrational and solid-state NMR-spectroscopy, X-ray powder diffraction, X-ray single crystal structure analysis, and water vapor sorption analysis. Additionally, the crystal structures of the anhydrate mod. II degrees (monoclinic, space group P2(1)/n), the hydrated mod. I (triclinic, space group P(bar)1), and of the free base (SLC) in the form of the hemihydrate (triclinic, space group P(bar)1 are discussed. Mod. II degrees of the polymorphic SLCHC is the thermodynamically stable form at room temperature and is present in commercial products mostly contaminated with a hydrated form that is isomorphic with mod. I. Mod. II degrees crystallizes from most organic solvents and from the melt below 110 degrees C. Mod. I crystallizes from the melt at temperatures above 110 degrees C, and additionally appears on dehydration of the hydrated mod. I. A third polymorph monotropically related to mod. II degrees was found by freeze-drying. The free-base SLC was found to crystallize from ethanol/water as a triclinic hemihydrate.

Freely accessible endoscope channels improve efficacy of cleaning.

BACKGROUND AND STUDY AIMS: Inadequate cleaning and disinfection of medical devices, including flexible endoscopes, can result in the transmission of micro-organisms to patients. The aim of this study was to investigate the influence of the design of medical devices on the efficacy of manual cleaning of endoscope channels. MATERIALS AND METHODS: The investigation was carried out using four endoscopes (two duodenoscopes and two gastroscopes). The air/water channels of one duodenoscope and one gastroscope were freely accessible and could be brushed. The instrumentation and the air/water channels were contaminated with blood containing Enterococcus faecium as a test organism. After manual cleaning of the channels by flushing and, where possible, brushing, the recovery rates for the test organism were studied. RESULTS: The comparable rates for recovery of the test organism after cleaning of the instrumentation channels proved that the method used was reproducible. With regard to the air/water channels, the rate of micro-organisms in the cleaning solution recovered after flushing alone was a maximum of 3 % relative to the rate detected after brushing and flushing. CONCLUSIONS: The data collected in the study show that only flushing channels that are not freely accessible resulted in significantly lower (P<0.001) recovery rates for the test organism. In practice, this means that contamination may remain in the channels, and it shows that the design of a medical device has an important influence on the reprocessing of reusable instruments such as flexible endoscopes.

Physiologic fluctuations of serum estradiol levels influence biochemical markers of bone resorption in young women.

We investigated the effect of physiologic variations in sex hormone levels during the menstrual cycle on biomarkers of bone turnover. Blood and 24-h and fasting urine samples were obtained in nine women (age, 25.1+/-3.0 yr) with regular menstrual cycles during the early follicular period (t1), 3 days before ovulation (t2), 3 days after ovulation (t3), at the midluteal period (t4) and again during the early follicular period of the next cycle (t5). All subjects had a calcium intake covering current dietary recommendations (above 1,000 mg/day, standardized food record). Serum calcium, phosphorus, calcitriol, 24-h and 2-h fasting urinary calcium, and phosphorus excretion remained constant during the menstrual cycle. Serum 25-hydroxyvitamin D3 levels decreased slightly from the beginning until the end of the study (P<0.05), indicating low cutaneous vitamin D synthesis during wintertime. The serum levels of sex hormones showed typical monthly variations, with the lowest estradiol (E2) levels at t1 and t5. Fasting 2-h pyridinoline (Pyd) concentrations (a marker of bone resorption) fell from t1 to t3 and rose again at t5 (P<0.01). Similar variations were observed for the resorption marker deoxypyridinoline (Dpd; P<0.05). The amplitude of the two biomarkers was 32% and 33%, respectively. The serum levels of the carboxyterminal propeptide of type I collagen (a marker of bone formation) showed an inverse cyclic pattern, as compared with the pyridinium cross-links. Low concentrations were observed at t1; a rise occurred until t3 and was followed by a decrease until t5 (P<0.05). A similar cyclic pattern was observed for serum PTH levels, with the highest concentrations at t3 (P<0.05). Dpd and Pyd values were significantly correlated with serum E2 levels (r = 0.52; P<0.0001 and r = 0.50; P<0.001, respectively). Neither progesterone nor LH nor FSH was correlated with Pyd or Dpd levels. The data suggest that normal menstrual cycling in young women is associated with monthly fluctuations in bone turnover. This physiological effect of the menstrual cycle is most probably related to variations in serum E2 concentrations.

Regulation of CD97 protein in thyroid carcinoma.

CD97 is a dimeric glycoprotein belonging to the secretin receptor superfamily and is abundantly expressed in cells of hematopoietic origin. The aim of this study was to analyze the expression of the CD97 protein in thyroid carcinomas and the role of all-trans-retinoic acid (RA) in the regulation of CD97 protein in monolayer culture of the human follicular thyroid carcinoma cell line FTC-133. In normal thyroid tissue, no immunoreactivity of CD97 could be found, whereas in differentiated thyroid carcinomas, CD97 expression was either lacking or low. Undifferentiated anaplastic thyroid carcinomas revealed high CD97 expression. The expression of CD97 protein seems to be correlated to the postoperative histopathological classification staging. Approximately 50% of FTC-133 cells expressed the CD97 protein under basal culture conditions. No differences were found in the number of CD97-positive cells after TSH, forskolin, and insulin treatment compared to control values. Epidermal growth factor treatment led to an increase in CD97 immunostaining (up to 90%), whereas phorbol 12-myristate 13-acetate slightly decreased the immunoreactivity of CD97 (from 50% to 30%). Under basal conditions, RA treatment for 72 h led to a decrease in total cell number by 33% and in CD97-positive cells from 50% to 30%. TSH, forskolin, phorbol 12-myristate 13-acetate, and insulin showed no effect after 72-h pretreatment with RA, whereas epidermal growth factor treatment led to a slight increase in the number of the CD97-positive cells (from 30% to 40%) compared to the control value. These data suggest that CD97 expression may play an important role in the dedifferentiation of thyroid tumors, and RA might interfere with this process in thyroid carcinoma by suppressing the dedifferentiation marker CD97.

Use of misoprostol during pregnancy and Möbius' syndrome in infants.

BACKGROUND: Patients with upper gastrointestinal ulceration may be treated with misoprostol, but it is not recommended for pregnant women because it may stimulate uterine contractions and cause vaginal bleeding and miscarriage. Recent data from Brazil, where misoprostol is used orally and vaginally as an abortifacient, have suggested a relation between the use of misoprostol by women in an unsuccessful attempt to terminate pregnancy and Möbius' syndrome (congenital facial paralysis) in their infants. METHODS: We compared the frequency of misoprostol use during the first trimester by mothers of infants in whom Möbius' syndrome was diagnosed and mothers of infants with neural-tube defects in Brazil. All diagnoses in infants were made between January 16, 1990, and May 31, 1996, by clinical geneticists at seven hospitals who also interviewed the mothers and recorded information about the administration of misoprostol, among other data. RESULTS: We identified 96 infants with Möbius' syndrome and matched them with 96 infants with neural-tube defects. The mean age at the time of the diagnosis of Möbius' syndrome was 16 months (range, 0.5 to 78), and the diagnosis of neural-tube defects was made within 1 week of birth in most cases. Among the mothers of the 96 infants with Möbius' syndrome, 47 (49 percent) had used misoprostol in the first trimester of pregnancy, as compared with 3 (3 percent) of the mothers of the 96 infants with neural-tube defects (odds ratio, 29.7; 95 percent confidence interval, 11.6 to 76.0). Twenty of the mothers of the infants with Möbius' syndrome had taken misoprostol only orally (odds ratio, 38.8; 95 percent confidence interval, 9.5 to 159.4), 20 had taken misoprostol both orally and vaginally, 3 had taken the drug vaginally, and 4 did not report how they took the drug. CONCLUSIONS: Attempted abortion with misoprostol is associated with an increased risk of Möbius' syndrome in infants.

Surface-active phospholipid as the lubricating component of lubricin.

To resolve the apparent conflict between a lubricating glycoprotein, 'lubricin', as the active ingredient in synovial fluid (SF) and surface-active phospholipid (SAPL) present in SF (and adsorbed to articular cartilage) as the boundary lubricant reducing friction to such low physiological levels, lubricin was isolated from bovine SF following the original procedure of Swann et al. (Arthritis Rheum 1981;24:22-30). Analysis of the lipid extract by thin-layer chromatography and phosphorus determination demonstrated a phospholipid component of 11.1 +/- 1.7% (N = 5) which corresponds very closely to the 9.2-13.0% of lubricin which had hitherto remained unidentified and which has previously been shown to be transferable to the articular surface to impart lubrication. These results would appear to resolve any theoretical conflict in that lubricin is, indeed, an active ingredient within SF. Yet, as a large water-soluble molecule, it really functions as a carrier for the highly insoluble SAPL which it deposits on the articular surface as the oligolamellar layer visualized in previous studies. However, it is this deposited SAPL, rather than lubricin, which actually lubricates.

Proverb explanation through the lifespan: a developmental study of adolescents and adults.

A proverb explanation task consisting of 24 low-familiarity expressions was administered to 353 individuals ranging in age from 13 through 79 years. Half the proverbs were composed of concrete nouns ("A caged bird longs for the clouds") and half were composed of abstract nouns ("Humility often gains more than pride"). The task was designed to examine how patterns of language growth in adults compare to those observed in adolescents. It also served as a tool for examining the "metasemantic hypothesis," the view that complex semantic units, such as proverbs, are learned through active analysis of the words they contain. Performance on the task improved markedly during adolescence and into early adulthood. It reached a plateau during the 20s, remained stable during the 30s, 40s, and 50s, and began a slight decline during the 60s that reached statistical significance during the 70s. Concrete proverbs were easier to explain than abstract proverbs for adolescents and for adults in their 20s, but the two proverb types did not differ for adults in their 30s and older. Thus, the metasemantic hypothesis was supported for adolescents and young adults. For the adults, performance on the proverb explanation task was related to the number of years of formal education they had completed.

Synovial surfactant: lamellar bodies in type B synoviocytes and proteolipid in synovial fluid and the articular lining.

Previous studies have shown that synovial surfactant could have beneficial roles in the joint, especially as a very effective boundary lubricant capable of high load bearing. This study is aimed at further characterization and identification of the source. Known to be an important minor component of pulmonary surfactant, proteolipid has now been detected in appreciable quantities in bovine synovial fluid and bound to the articular surface. Using standard procedures to separate it from the major component [surface-active phospholipid (SAPL)] by column chromatography, proteolipid: phospholipid ratios were found to be comparable to those in the lung or in lamellar bodies (LBs). LBs are the unequivocal source of surfactant in the lung and we have confirmed an earlier study demonstrating their presence in Type B synoviocytes. Using a fixation procedure specifically designed to preserve the graphite-like structure of SAPL deposited as oligolamellar layers, or coiled as lamellar bodies, we were able to demonstrate these structures in equine joints adjacent to the Golgi apparatus associated with the secretory mechanism of the cell. These results indicate that proteolipid could be facilitating the deposition of the graphite-like surface lining of SAPL providing efficient boundary lubrication just as it promotes surfactant adsorption in the lung and in the formation of myelin. Any deficiency in synovial surfactant, compromising its roles in the joint, is discussed in relation to osteoarthritis and the possible administration of exogenous SAPL to the degenerating joint.

Retrograde labelling of auditory brainstem neurons following tritiated glycine injection into the inferior colliculus of the chicken, Gallus domesticus.

We investigated retrograde labelling with tritiated glycine injected into the inferior colliculus of the chicken. Tracer deposits were placed in the central nucleus of the inferior colliculus at positions yielding unit activity with best frequencies between 0.4 and 4 kHz. Most neuron systems known to project to the inferior colliculus in birds were unlabelled, whereas strongly labelled cells were found in three nuclei, only on the ipsilateral side. The nucleus lemnisci lateralis pars ventralis contained numerous small glycine-transporting cells. The superior olivary nucleus contained few such cells of similar size in its peripheral region. The nucleus of the trapezoid body contained a group of larger labelled neurons. The observed specificity suggests that we labelled glycinergic neurons projecting to the inferior colliculus.