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Rationale: Sphingomyelins (SMs) and resulting metabolic products serve important functional and cell signaling roles and can act as potential biomarkers and therapeutic targets in many pathological disorders. SMs each contain a sphingoid base, an amide‐linked fatty acyl chain, and a phosphocholine headgroup. Despite these simple building blocks, variations and modifications of both the sphingoid base and the fatty acyl chain result in a diverse array of structurally complicated SM compounds. Conventional tandem mass spectrometry (MS/MS) using the collision‐induced dissociation (CID) method only provides limited structural information, necessitating other tools to unravel the structural complexity of these lipids. Methods: We utilize electron‐induced dissociation (EID) and sequential CID/EID approaches to elucidate detailed structural features of SMs. Integrating the CID/EID method into an imaging MS workflow enables accurate identification of SMs directly from kidney tissue. Results: The application of EID enables identification of SMs at the molecular species level, identifying the sphingosine base and the amide‐linked fatty acyl chains. Furthermore, removal of the phosphocholine headgroup via CID followed by sequential EID in an MS3 analysis (CID/EID) enhances the structural information obtained. CID/EID provides diagnostic fragmentation patterns revealing the hydroxylation site and double bond position in both the sphingosine base and amide‐linked fatty acyl chains. Conclusions: Detailed structural information of SMs from synthetic standards and biological tissue samples is obtained using an alternative electron‐based dissociation method. Accurate characterization of SMs promises to better inform studies of tissue biochemistry, lipid metabolism, and molecular pathology. [ABSTRACT FROM AUTHOR]

Fatty acids (FAs) contain a vast amount of structural diversity, and differences in fatty acid structure have been associated with various disease states. Accurate identification and characterization of fatty acids is critical to fully understand the biochemical roles these compounds play in disease progression. Conventional tandem mass spectrometry (MS/MS) workflows do not provide sufficient structural information, necessitating alternative dissociation methods. Gas‐phase charge inversion ion/ion reactions can be used to alter the ion type subjected to activation to provide improved or complementary structural information. Herein, we have used an ion/ion reaction between fatty acid (FA) anions and magnesium tris‐phenanthroline [Mg(Phen)3] dications to promote charge remote fragmentation of carbon‐carbon bonds along the fatty acid chain, allowing for localization of carbon‐carbon double bond (C=C) positions to successfully differentiate monounsaturated fatty acid isomers. Relative quantification was also performed to obtain the relative abundance of fatty acid isomers in different biological tissues. For example, the relative abundance of FA 18 : 1 (9) was determined to vary across regions of rat brain, rat kidney, and mouse pancreas, and FA 16 : 1 (9) was found to have a higher relative abundance in the dermis layer compared to the sebaceous glands in human skin tissue. [ABSTRACT FROM AUTHOR]

The use of mass spectrometry (MS) to acquire molecular images of biological tissues and other substrates has developed into an indispensable analytical tool over the past 25 years. Imaging mass spectrometry technologies are widely used today to study the in situ spatial distributions for a variety of analytes. Early MS images were acquired using secondary ion mass spectrometry and matrix‐assisted laser desorption/ionization. Researchers have also designed and developed other ionization techniques in recent years to probe surfaces and generate MS images, including desorption electrospray ionization (DESI), nanoDESI, laser ablation electrospray ionization, and infrared matrix‐assisted laser desorption electrospray ionization. Investigators now have a plethora of ionization techniques to select from when performing imaging mass spectrometry experiments. This brief perspective will highlight the utility and relative figures of merit of these techniques within the context of their use in imaging mass spectrometry. [ABSTRACT FROM AUTHOR]

Quantification of pharmaceutical compounds using matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is an alternative to traditional liquid chromatography (LC)‐MS techniques. Benefits of MALDI‐based approaches include rapid analysis times for liquid samples and imaging mass spectrometry capabilities for tissue samples. As in most quantification experiments, the use of internal standards can compensate for spot‐to‐spot and shot‐to‐shot variability associated with MALDI sampling. However, the lack of chromatographic separation in traditional MALDI analyses results in diminished peak capacity due to the chemical noise background, which can be detrimental to the dynamic range and limit of detection of these approaches. These issues can be mitigated by using a hybrid mass spectrometer equipped with a quadrupole mass filter (QMF) that can be used to fractionate ions based on their mass‐to‐charge ratios. When the masses of the analytes and internal standards are sufficiently disparate in mass, it can be beneficial to effect multiple narrow mass isolation windows using the QMF, as opposed to a single wide mass isolation window, to minimize chemical noise while allowing for internal standard normalization. Herein, we demonstrate a MALDI MS quantification workflow incorporating multiple sequential mass isolation windows enabled on a QMF, which divides the total number of MALDI laser shots into multiple segments (i.e., one segment for each mass isolation window). This approach is illustrated through the quantitative analysis of the pharmaceutical compound enalapril in human plasma samples as well as the simultaneous quantification of three pharmaceutical compounds (enalapril, ramipril, and verapamil). Results show a decrease in the limit of detection, relative standard deviations below 10%, and accuracy above 85% for drug quantification using multiple mass isolation windows. This approach has also been applied to the quantification of enalapril in brain tissue from a rat dosed in vitro. The average concentration of enalapril determined by imaging mass spectrometry is in agreement with the concentration determined by LC–MS, giving an accuracy of 104%. [ABSTRACT FROM AUTHOR]

The Silver Carp Hypophthalmichthys molitrix and Bighead Carp H. nobilis are two species of invasive bigheaded carp currently invading North American rivers and watersheds. Bigheaded carp were accidentally introduced into the lower Mississippi River basin in the early 1970s and have since invaded many water bodies in the Midwestern United States. Evidence of bigheaded carp reproduction and recruitment in the upper Mississippi River upstream of Lock and Dam 19 (LD19) at Keokuk, Iowa, thought to be a critical constriction point to their upstream establishment, has been limited to a few isolated detections of eggs, larvae, and juvenile life stages since 2012. Therefore, a more comprehensive assessment of bigheaded carp reproduction in this critical management zone was needed. We used quadrafoil light traps (n = 1,387) deployed during May–September 2016–2018 in Pools 17–19 of the Mississippi River to monitor for advanced larval bigheaded carp in low‐velocity habitats. Throughout the sampling period, we captured 1,747 larval and 35 postlarval bigheaded carp (N = 1,782). Bigheaded carp were collected on 15 sampling events that spanned from May 31, 2016, to September 13, 2018, with associated hatch dates estimated to represent 10 unique reproductive events from May 2016 to September 2018. The individual captures and backdated hatch estimates revealed a protracted spawning period of up to seven events in 2016, one event in 2017, and two events in 2018. Bigheaded carp were only captured in Pool 19, possibly due to the drifting requirements for egg maturation and the low‐velocity downstream reach of Pool 19. This research provides confirmation that bigheaded carp spawned upstream of LD19 are capable of transitioning past the yolk sac stage upstream of this bottleneck to more advanced larval stages. Knowledge of reproduction and larval retention and the field‐based evidence of protracted spawning fill critical research gaps needed for the management of bigheaded carp. [ABSTRACT FROM AUTHOR]

Mass spectrometry imaging (MSI) is an important analytical technique that simultaneously reports the spatial location and abundance of detected ions in biological, chemical, clinical, and pharmaceutical studies. As MSI grows in popularity, it has become evident that data reporting varies among different research groups and between techniques. The lack of consistency in data reporting inherently creates additional challenges in comparing intra‐ and inter‐laboratory MSI data. In this tutorial, we propose a unified data reporting system, SMART, based on the common features shared between techniques. While there are limitations to any reporting system, SMART was decided upon after significant discussion to more easily understand and benchmark MSI data. SMART is not intended to be comprehensive but rather capture essential baseline information for a given MSI study; this could be within a study (e.g., effect of spot size on the measured ion signals) or between two studies (e.g., different MSI platform technologies applied to the same tissue type). This tutorial does not attempt to address the confidence with which annotations are made nor does it deny the importance of other parameters that are not included in the current SMART format. Ultimately, the goal of this tutorial is to discuss the necessity of establishing a uniform reporting system to communicate MSI data in publications and presentations in a simple format to readily interpret the parameters and baseline outcomes of the data. [ABSTRACT FROM AUTHOR]

Within the Big Bend region of the northeastern Gulf of Mexico, one of the least developed coastlines in the continental USA, intertidal and subtidal populations of eastern oyster Crassostrea virginica (hereafter referred to as "oyster") are a critical ecosystem and important economic constituent. We assessed trends in intertidal oyster populations, river discharge, and commercial fishing activity in the Suwannee River estuary within the Big Bend region using fisheries-independent data from irregular monitoring efforts and publicly available environmental data. We used generalized linear models to evaluate counts of oysters from line-transect surveys over time and space. We assessed model performance using simulation to understand potential bias and then evaluated whether these counts were related to freshwater inputs from the Suwannee River and commercial oyster fishing effort and landings at different time lags. We found that intertidal oyster counts have declined over time and that most of these declines are found in inshore intertidal oyster bars, which are becoming degraded. We also found a significant relationship between oyster counts and a 1-year lag on mean daily Suwannee River discharge, but including commercial fishery trips or landings did not improve model fit. It is unclear whether declines in intertidal oyster bars are offset by formation of new oyster reefs elsewhere. These results quantify rapid declines in intertidal oyster reefs in a region of coastline with high conservation value that can be used to inform ongoing and proposed restoration projects in the region. [ABSTRACT FROM AUTHOR]

The specific matrix used in matrix‐assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) can have an effect on the molecules ionized from a tissue sample. The sensitivity for distinct classes of biomolecules can vary when employing different MALDI matrices. Here, we compare the intensities of various lipid subclasses measured by Fourier transform ion cyclotron resonance (FT‐ICR) IMS of murine liver tissue when using 9‐aminoacridine (9AA), 5‐chloro‐2‐mercaptobenzothiazole (CMBT), 1,5‐diaminonaphthalene (DAN), 2,5‐Dihydroxyacetophenone (DHA), and 2,5‐dihydroxybenzoic acid (DHB). Principal component analysis and receiver operating characteristic curve analysis revealed significant matrix effects on the relative signal intensities observed for different lipid subclasses and adducts. Comparison of spectral profiles and quantitative assessment of the number and intensity of species from each lipid subclass showed that each matrix produces unique lipid signals. In positive ion mode, matrix application methods played a role in the MALDI analysis for different cationic species. Comparisons of different methods for the application of DHA showed a significant increase in the intensity of sodiated and potassiated analytes when using an aerosol sprayer. In negative ion mode, lipid profiles generated using DAN were significantly different than all other matrices tested. This difference was found to be driven by modification of phosphatidylcholines during ionization that enables them to be detected in negative ion mode. These modified phosphatidylcholines are isomeric with common phosphatidylethanolamines confounding MALDI IMS analysis when using DAN. These results show an experimental basis of MALDI analyses when analyzing lipids from tissue and allow for more informed selection of MALDI matrices when performing lipid IMS experiments. [ABSTRACT FROM AUTHOR]

Spontaneous imbibition is a process occurring in a porous medium which describes wetting phase replacing nonwetting phase spontaneously due to capillary forces. This process is conventionally investigated by standardized, well‐established spontaneous imbibition tests. In these tests, for instance, a rock sample is surrounded by wetting fluid. The following cumulative production of nonwetting phase versus time is used as a qualitative measure for wettability. However, these test results are difficult to interpret, because many rocks do not show a homogeneous but a mixed wettability in which the wetting preference of a rock varies from location to location. Moreover, during the test the flow regime typically changes from countercurrent to cocurrent flow and no phase pressure or pressure drop can be recorded. To help interpretation, we complement Darcy‐scale production curves with X‐ray imaging to describe the differences in imbibition processes between water‐wet and mixed‐wet systems. We found that the formation of a spontaneous imbibition front occurs only for water‐wet systems; mixed‐wet systems show localized imbibition events only. The asymmetry of the front depends on the occurrence of preferred production sites, which influences interpretation. Fluid layers on the outside of mixed‐wet samples increase connectivity of the drained phase and the effect of buoyancy on spontaneous imbibition. The wider implication of our study is the demonstration of the capability of benchtop laboratory equipment to image a full Darcy‐scale experiment while at the same time obtaining pore‐scale information, resolving the natural length and time scale of the underlying processes. Key Points: We demonstrate the capability of imaging full Darcy‐scale experiments while obtaining pore‐scale resolutionIn the mixed‐wet system there is a difference between pore scale and Darcy scale production due to oil layers on the sample perimeterWater‐wet systems show a clear imbibition front, whereas mixed‐wet systems show only localized imbibition sites [ABSTRACT FROM AUTHOR]

Rationale: Liquid extraction surface analysis (LESA) can be used to generate spatially directed protein identifications in an imaging mass spectrometry (IMS) workflow. This approach involves the use of robotic micro‐extractions coupled to online liquid chromatography (LC). We have characterized the extraction efficiency of this method as well as its ability to identify proteins from a matrix assisted laser/desorption ionization (MALDI) IMS experiment. Methods: Proteins and peptides were extracted from transverse sections of a rat brain and sagittal sections of a mouse pup using liquid surface extractions. Extracts were either analyzed by online LC coupled to a high mass resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrometer or collected offline and analyzed by traditional LC/MS methods. Identifications were made using both top‐down and bottom‐up methodologies. MALDI images were acquired on a 15T FTICR mass spectrometer at 125 μm spatial resolution. Results: Robotic liquid surface extractions are reproducible across various tissue types, providing significantly improved spatial resolution, with respect to extractions, while still allowing for a robust number of protein identifications. A single 2‐μL extract can provide identification of over 14,000 peptides with little sample preparation, increasing throughput for spatially targeted workflows. Surface extractions from tissue were coupled directly to LC to gather spatially relevant proteomics data. Conclusions: Robotic liquid surface extractions can be used to interrogate discrete regions of tissue to provide protein identifications with high throughput, accuracy, and robustness. The direct coupling of tissue surface extractions and LC offers a new and effective approach to provide spatial proteomics data in an imaging experiment. [ABSTRACT FROM AUTHOR]

A matrix-assisted laser desorption/ionization time of flight/time of flight tandem mass spectrometer (MALDI TOF/TOF) has been used for high-speed precursor/fragment ion transition image acquisition. High-throughput analysis is facilitated by an Nd:YLF solid state laser capable of pulse repetition rates up to 5 kHz, a high digitizer acquisition rate (up to 50 pixels/s), and continuous laser raster sampling. MS/MS experiments are enabled through the use of a precision timed ion selector, second source acceleration, and a dedicated collision cell. Continuous raster sampling is shown here to facilitate rapid MS/MS ion image acquisition from thin tissue sections for the drug rifampicin and for a common kidney lipid, SM4s(d18:1/24:1). The ability to confirm the structural identity of an analyte as part of the MS/MS imaging experiment is an essential part of the analysis. Additionally, the increase in sensitivity and specificity afforded by an MS/MS approach is highly advantageous, especially when interrogating complex chemical environments such as those in biological tissues. Herein, we report continuous laser raster sampling TOF/TOF imaging methodologies which demonstrate 8 to 14-fold increases in throughput compared with existing MS/MS instrumentation, an important advantage when imaging large areas on tissues. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Several approaches for the generation of peptide radical cations using ion/ion reactions coupled with either collision induced dissociation (CID) or ultraviolet photo dissociation (UVPD) are described here. Ion/ion reactions are used to generate electrostatic or covalent complexes comprised of a peptide and a radical reagent. The radical site of the reagent can be generated multiple ways. Reagents containing a carbon-iodine (C-I) bond are subjected to UVPD with 266-nm photons, which selectively cleaves the C-I bond homolytically. Alternatively, reagents containing azo functionalities are collisionally activated to yield radical sites on either side of the azo group. Both of these methods generate an initial radical site on the reagent, which then abstracts a hydrogen from the peptide while the peptide and reagent are held together by either electrostatic interactions or a covalent linkage. These methods are demonstrated via ion/ion reactions between the model peptide RARARAA (doubly protonated) and various distonic anionic radical reagents. The radical site abstracts a hydrogen atom from the peptide, while the charge site abstracts a proton. The net result is the conversion of a doubly protonated peptide to a peptide radical cation. The peptide radical cations have been fragmented via CID and the resulting product ion mass spectra are compared to the control CID spectrum of the singly protonated, even-electron species. This work is then extended to bradykinin, a more broadly studied peptide, for comparison with other radical peptide generation methods. The work presented here provides novel methods for generating peptide radical cations in the gas phase through ion/ion reaction complexes that do not require modification of the peptide in solution or generation of non-covalent complexes in the electrospray process. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Reported herein are the preparation and characterization of trans-[Cr(cyclam)(X- gem-DEE)2]OTf compounds ( gem-DEE = σ- geminal-diethynylethene, OTf = trifluoromethanesulfonate) 1 and 2, which are the first examples of 3d metal complexes containing gem-DEE ligands. All compounds reported herein were characterized by visible, emission, and infrared spectroscopy, electrochemistry (CV and DPV), and high-resolution mass spectrometry, and compound 2 was further studied by single-crystal X-ray diffraction. Both the photophyiscal data and the structural data indicate that the gem-DEE ligands are similar to simple linear alkynyls in their coordination to the CrIII core. DFT calculations revealed that π delocalization is the most extensive within the SOMO and SOMO-1, in which both the vinyl and free ethynyl groups of the gem-DEE ligand contribute significantly to the π⟂ orbital that mixes intimately with both the d yz and d xz orbitals of the Cr core. [ABSTRACT FROM AUTHOR]

Wood preserved in the corrosion layer of two early medieval iron objects was examined using X-ray tomography. A state-of-the art multi-resolution X-ray tomography set-up (http://www.ugct.ugent.be) provided virtual cross-sections of the archaeological wood samples at sub-micron resolution. These were compared with scans of samples of similar modern wood. These scans demonstrate the power of sub-micron X-ray tomography for wood identification, although the process of mineralization pushes this technique to its limits. Furthermore, this technique facilitated appraisal of the mineral content of the archaeological wood, which is useful in selecting the most appropriate strategy for the (preventative) conservation of the archaeological object. [ABSTRACT FROM AUTHOR]

A thorough morphological description of the feeding apparatus in Hippocampus reidi, a long-snouted seahorse, and Dunckerocampus dactyliophorus, an extremely long-snouted pipefish, revealed specialized features that might be associated with the fast and powerful suction feeding, like the two ligamentous connections between the lower jaw and the hyoid, the saddle joint of the latter with the suspensorium and the vertebro-pectoral fusion that articulates on three points with the cranium. Despite the conserved morphology of the feeding apparatus, it was found that in H. reidi the orientation of the occipital joint is ventrocaudal, the sternohyoideus and epaxial muscles are more bulky and both have a short tendon. In D. dactyliophorus, on the other hand, the protractor hyoidei muscle is enclosed by the mandibulo-hyoid ligament, the sternohyoideus and epaxial tendons are long and a sesamoid bone is present in the latter. These features were compared to other syngnathid species with different snout lengths to evaluate the implications of snout elongation on the musculoskeletal structure of the cranium. The arched path of the adductor mandibulae and the greater rigidity of the lower jaw might be related to elongation of the snout, as it yields an increased mechanical advantage of the lower jaw system and a reduced torque between the elements of the lower jaw during protractor hyoidei muscle contraction, respectively. Nevertheless, most observed features did not seem to be related to snout length, but might be associated with different force-generating strategies. [ABSTRACT FROM AUTHOR]

Abstract Background Experimental data suggest that there is an imbalance between Th1 and Th2 cells in atopic dermatitis (AD) skin compared to allergic contact dermatitis (ACD). This imbalance (Th2 and Th1 predominance, respectively) implies the production of different cytokines in these two conditions leading to different expression of adhesion molecules on skin endothelial cells. Objective The expression of VCAM-1 (IL-4/Th2-dependent) and ICAM-1 (INF-γ/IL-1) on dermal vessels was compared in six patients with AD and six patients with ACD. The effect of cetirizine, a highly selective H1-receptor antagonist on the expressions was studied. Methods Six patients with AD were challenged with Dermatophagoides pteronyssimus (DPT patch tests applied to clinically normal skin) and six patients with ACD challenged in the same way with allergens of the European standard series. Skin biopsies at challenged sites were performed before and 6, 24 and 48 h after challenge. The experiment was carried out under double-blind cross-over conditions during a 4-day treatment with a placebo and cetirizine. Results In AD patients, the scores for both VCAM-1 and ICAM-1 were high before and after challenge. In ACD patients, the ICAM-1 score was high at each experimental time, but the VCAM-1 score, which was significantly lower before challenge, increased at 6, 24 and 48 h after challenge. The administration of cetirizine significantly reduced the VCAM-1 expression in AD patients at each experimental time. Conclusion It is concluded that the increased VCAM-1 expression in AD patients compared to ACD may reflect greater IL-4 and/or IL-13 production in situ. The study also confirms the existence of a modulating effect of cetirizine in vivo on adhesion molecule expression. [ABSTRACT FROM AUTHOR]

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A letter to the editor related to an online survey conducted by royal Belgian society for dermatology & venereology (RBSDV) on the job satisfaction and attitude of dermatologist, is presented.

During the rearing process of gilthead sea bream ( Sparus aurata), abnormal development of the opercular bone is particularly common (Aquaculture 156, 1997, 165). In order to alleviate its occurrence in rearing facilities, it’s crucial to identify the very first physical signs of deviation in normal skeletal development. Nano-CT-scanning was tested for its applicability to quantify deviations in bone mineralization levels. Seven opercles were dissected from larvi of 65 days post hatching, randomly sampled at the commercial sea bream hatchery Maricoltura di Rosignano Solvay (Livorno, Italy). The samples were nano-CT-scanned and computationally reconstructed. Mineralization intensity was colorcoded using Amira software, resulting in a detailed visualization of opercular morphology and mineralization patterns. In conclusion, nano-CT-scanning promises to be a good tool to both describe morphology and detect mineralization levels in the early onset of deformities. [ABSTRACT FROM AUTHOR]

Review: 169 refs. [ABSTRACT FROM AUTHOR]

This study assessed the effect of temperature on the potency of carbaryl using tadpoles of Rana clamitans. Temperature, chemical concentration, and the interaction of temperature and chemical significantly affected survival. Generally, increased temperature resulted in lowersurvival. This study suggests a range of temperatures realistic for a species should be used in toxicity tests. [ABSTRACT FROM AUTHOR]

Objectives: The Krapina rock shelter has yielded a large assemblage of early Neandertals. Although endocranial volume (ECV) has been estimated for four individuals from the site, several published values that appear in the literature warrant revisiting., Materials and Methods: We used virtual methods, including high-resolution surface models of fossils and 3D geometric morphometrics, to reconstruct endocasts and estimate ECV for five Krapina crania. We generated 10 reconstructions of each endocast to quantify missing data uncertainty. To assess the method and our ECV estimates, we applied these techniques to the Spy II Neandertal, and estimated ECV of a human reference endocast simulating the missing data of the Krapina fossils., Results: We obtained an average ECV estimate of 1,526 cm 3 for Spy II, consistent with previous research. Estimated ECV of juveniles Krapina 1 and 2 average 1,419 and 1,286 cm 3 , respectively. Estimates for the relatively complete adults Krapina 3 and 6 range from 1,247 to 1,310 cm 3 and 1,135 to 1,207 cm 3 , respectively, while the more fragmentary Krapina 5 averaged 1,397 cm 3 . The missing data simulation suggests more fragmentary crania yield more uncertain and possibly overestimated ECVs., Conclusions: We have provided new estimates of brain size of the Krapina Neandertals, including the first estimates for Krapina 2. Brain size at Krapina was similar to other pre-Würm Neandertals, within the range of but lower than the average of later Neandertals. Although the virtual approach overcomes many challenges of fossil preservation, our results are nevertheless subject to future revision., (© 2020 Wiley Periodicals LLC.)

In patients with enhanced risk for bleeding, heparin-free hemodialysis (HD) with conventional dialyzers is routinely used. To explore the potential benefit of using heparin-coated dialyzers, we used a reference CT-scanning technique and registered different clotting parameters to quantify coagulation with heparin-coated versus non-coated dialyzers. Six HD patients with thrombocytopenia were dialyzed 240 min in a randomized crossover study with Evodial 1.3 or FX600 Cordiax, each without anticoagulation. Blood samples were taken from the vascular access predialysis, and from the dialyzer inlet and outlet at 5 and 240 min after dialysis start. Predialysis blood samples were analyzed for hemoglobin, hematocrit, thrombocytes, fibrinogen, and activated partial thromboplastin time. On dialyzer inlet and outlet blood samples, a viscoelastic measurement of blood coagulation was performed using a Sonoclot analyzer. After dialysis, dialyzers were visually scored, subsequently dried for 24 h, weighed, and scanned with micro-CT at a resolution of 25 µm. After image reconstruction, the open, non-coagulated fibers were counted in a representative cross-section at the dialyzer outlet. No sessions were terminated prematurely for circuit clotting. Heparin-coated dialyzers had more patent fibers on micro-CT versus non-coated dialyzers and also had a better score of subjective visual assessment of fiber clotting. There was no difference in subjective assessment of clotting at the venous drip chamber. With both dialyzers, all ACT values remained in the normal range, and were lower at the dialyzer outlet versus inlet. In conclusion, dialysis with a heparin-coated versus non heparin-coated membrane results in substantially less coagulated fibers during 4 h hemodialysis without systemic anticoagulation. Eventual leaching of heparin, immobilized on the fiber membrane, does not result in measurable systemic anticoagulation., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: High-definition optical coherence tomography (HD-OCT) features of actinic keratosis (AK) may aid in its diagnosis and therapeutic strategy. A diagnostic algorithm permitting discrimination of AK from squamous cell carcinoma (SCC) and normal skin has been proposed. However, diagnostic accuracy strongly depends on the experience of physicians. In two recent studies, it was demonstrated that HD-OCT permits to quantify in vivo optical properties such as light attenuation in intrinsic ageing skin, in melanocytic lesions and in basal cell carcinoma. This approach seems to permit a semiautomated classification of lesions easier to handle by non-experts., Objectives: The aim of this paper was to quantify in vivo optical properties of facial located AK/SCC lesions, such as light attenuation, by HD-OCT. Additional objectives were to determine the best critical value of these optical properties for discrimination of AK from SCC and from normal sun exposed skin and to subdifferentiate AKs., Methods: The technique of semi-log plot has been implemented on HD-OCT signals. This permitted the in vivo measurement of OCT signals coming from the skin entrance up to the superficial reticular dermis. Moreover, relative attenuation factor (μ raf ) at different skin layers (1-3) could be determined., Results: Optical properties with high diagnostic accuracy (DA) and high negative predictive values (NPV) could be defined permitting the differentiation between normal skin, non-Bowenoid AK without follicular involvement, non-Bowenoid AK with follicular involvement, Bowenoid AK, hypertrophic and lichenoid form of AK and squamous cell carcinoma., Conclusion: HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3D microarchitectural structures with in vivo analysis of optical properties of tissue scatterers in AK/SCC lesions and normal sun-exposed skin. In vivoHD-OCT analysis of optical properties permits AK discrimination from SCC and AK subdifferentiation with higher accuracy than in vivoHD-OCT analysis of morphology alone., (© 2016 European Academy of Dermatology and Venereology.)

Background: Preliminary studies have described morphological features of basal cell carcinoma (BCC) imaged by high-definition optical coherence tomography (HD-OCT) and suggested that this technique may aid in its diagnosis and management. However, systematic studies evaluating the accuracy of HD-OCT for the diagnosis of BCC are lacking., Objective: The aim of this study was to identify three-dimensional (3-D) HD-OCT features able i) to distinguish BCC from clinical BCC imitators and ii) to discriminate between the most common BCC subtypes. Based on these particular features, a diagnostic algorithm will be suggested., Method: A total of 50 histopathologically confirmed BCCs (18 superficial, 19 nodular, 13 infiltrative) were imaged by HD-OCT at the centre of the lesion prior to standard surgical excision and subsequent histopathological analysis. Fifty images of clinical BCC imitators were also retrieved as a 'pitfalls' group., Results: The simultaneous presence of grey/dark subepidermal (hemi-spherical) or intradermal lobulated structure(s) presenting a typical cockade feature in both HD-OCT modes was a significant feature for BCC diagnosis. Features discriminating between BCC subtypes were location of the roof of BCC lobules, vascular pattern of the papillary plexus and stretching effect on the stroma. Clinical BCC imitators such as actinic keratosis, compound and intradermal naevi, amelanotic melanoma, sebaceous hyperplasia and small haemangioma could be differentiated from BCC by means of HD-OCT., Conclusion: This study provides a thorough description of 3-D HD-OCT features that can permit discrimination of BCC from clinical BCC imitators and differentiation of BCC subtypes. Based on these features, a diagnostic algorithm is proposed which requires additional validation, but enhances current understanding of the morphological correlates of HD-OCT images in skin., (© 2015 European Academy of Dermatology and Venereology.)

Background: Preliminary studies described morphological features of actinic keratosis (AK) and squamous cell carcinoma (SCC) imaged by High-Definition Optical Coherence Tomography (HD-OCT) and suggested that this technique may aid in their diagnosis. However, systematic studies evaluating the accuracy of HD-OCT for the diagnosis of AK and SCC are lacking so far., Objective: In this study, we sought to design an algorithm for AK classification that could (i) distinguish SCC from AK and normal skin, (ii) differentiate AK from normal skin and (iii) discriminate AKs with adnexal involvement from those without., Methods: A total of 53 histopathologically confirmed lesions (37 AKs and 16 SCC) were imaged by HD-OCT. Fifty-three HD-OCT images of normal skin of healthy volunteers, with matched age, skin type and anatomic site, were taken as reference. By comparing these 106 en face and cross-sectional HD-OCT images, particular features were selected based on their potential to discriminate AK from normal skin and from SCC, and to assess adnexal involvement in AK. This study represents a training set not a testing set. Severe (>300 μm) hyperkeratotic AKs were not included in this study., Results: Particular features with high Phi coefficient could be identified. The absence of an outlined dermo-epidermal junction (DEJ) on cross-sectional images allowed discriminating SCC from AK and normal skin (Phi coefficient = 0.84). AK could be discriminated from normal skin in both imaging modes by the presence of alternating hyperkeratosis/parakeratosis in cross-sectional mode and/or variability in shape, size and reflectivity of cells (atypical honeycomb pattern) in en face mode. Adnexal involvement of AK could be assessed by the disappearance of the typical cocarde image of adnexal epithelium in en face mode., Conclusion: This study provides select 3-D HD-OCT features having a potential to discriminate SCC from AK and normal skin. Based on these particular features with high Phi coefficient, a diagnostic algorithm is designed which will be used later in validation studies to determine HD-OCT accuracy in AK/SCC classification., (© 2015 European Academy of Dermatology and Venereology.)

Analysis of calls made to a northern Canadian Inuit crisis line in the territory of Nunavut between 1991 and 2001 revealed that the majority of users were adult females who called to discuss problems primarily related to relationships and loneliness/boredom. Younger callers tended to make prank calls. The volunteer staff used mostly empathetic listening and suggestions. Referral recommendations made were primarily to social services. Although some callers experienced a language barrier, others found the service to be helpful. Results suggest that the crisis line was underused by young Inuit males who represent a group that are most in need of crisis intervention., (© 2012 The American Association of Suicidology.)

Aquaporins (AQPs) are central players in mammalian physiology, allowing efficient water transport through cellular membranes. To date, 13 different aquaporins have been identified in mammals (AQP0-AQP12). Knocking out genes in mice and identification of mutations in the human genes provided important information on the role of AQPs in normal physiology. While the physiological role of many AQPs only becomes clear when the putative function is challenged, the lack of AQP2 directly results in a disease phenotype. Aquaporin 2 is highly expressed in the principal cells of the renal collecting duct, where it shuttles between intracellular storage vesicles and the apical membrane. Upon hypernatraemia or hypovolaemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary into blood and binds to its type 2 receptor on renal principal cells. This initiates a cAMP signalling cascade resulting in the translocation of AQP2-bearing vesicles to the apical membrane. Subsequently, pro-urinary water reabsorption and urine concentration occurs. This process is reversed by a reduction in circulating AVP levels, which is obtained with the establishment of isotonicity. In humans, mutations in the AQP2 gene cause congenital nephrogenic diabetes insipidus (NDI), a disorder characterized by an inability to concentrate urine in response to vasopressin. Until the recent development of several congenital NDI mouse models, our knowledge on AQP2 regulation was primarily based on in vitro studies. This review focuses on the similarities between the in vitro and in vivo studies and discusses new insights into congenital NDI obtained from the mouse models.