Morphological Diversity and Evolution of Jaw Morphologies in Zeiform Fishes (Teleostei, Paracanthopterygii).

Zeiformes (dories, tinselfishes, and oreos) are primarily benthopelagic acanthomorph fishes, distributed between 50 and 1000 m depth on continental slopes and on flanks of oceanic islands and seamounts. Among the interesting morphological adaptations of zeiform fishes are their unique and highly protrusible jaws involving premaxillae with long ascending processes and a four-bar linkage, including mobile palatines that pivot on their posterior articulation. This adaptation for increased jaw protrusion has enabled zeiform fishes to capture elusive prey more efficiently and is arguably a major factor in their morphological diversity and evolutionary success. This study examines the evolution of zeiform jaw morphologies using 3D landmark-based multivariate morphometrics as well as phylomorphospace analysis. Results show that the descendants of the zeiform ancestor branched rapidly early in their history, retaining conservative jaw morphologies during this early branching, but subsequently strongly diverged in many of the resulting lineages. Results from this study are compared with earlier research based on overall body form, demonstrating that morphological variation within Zeiformes arose along at least two distinct trajectories: body form and jaw morphology. Variation among genera in body form is not associated with variation among the same genera in jaw morphology, and vice versa. Hypotheses to explain the apparent decoupling of body shape and jaw morphology are addressed along with avenues for further study to better understand the morphological evolution of these iconic fishes.

Les Zéiformes (e.g., dorés, oréos et poissons scintillants) sont des poissons benthopélagiques du groupe des Acanthomorpha trouvés entre 50 et 1000m de profondeurs sur les talus continentaux, et sur les abords des iles océaniques et des monts sous-marins. Parmi les adaptations morphologiques des zéiformes figurent leur mâchoires protrusibles, composées de prémaxillaires avec de longs processus ascendants et un mécanisme à quatre barres qui implique des os palatins mobiles qui pivotent autour de leur articulation postérieure. Ces adaptations morphologiques conduisent à une protrusion buccale sur de plus grandes distances et plus efficace, permettant aux zéiformes de capturer des proies autrement insaisissables et sont des éléments majeurs de la diversité morphologique du groupe ainsi que de leur succès évolutif. Cette étude examine l'évolution de la morphologie des mâchoires des zéiformes via des mesures de morphométrie géométrique 3D par points d'intérêts et des analyses d'espace phylo-morphologique. Les résultats montrent que les Zéiformes se sont rapidement séparés du plus vieil ancêtre commun mais ont initialement conservés des morphologies de mâchoires similaires. Suite à cette séparation initiale, les morphologies ont rapidement divergé menant à la diversité courante du groupe. Une comparaison des résultats obtenus ici avec des études précédentes sur la forme du corps des Zéiformes soutient que l'évolution morphologique du groupe a suivi au moins deux axes distincts : la forme du corps et la morphologie des mâchoires. Les différences de formes du corps entre genres ne sont pas corrélées avec les différences de formes de mâchoires entre ces mêmes genres, ni réciproquement. Des hypothèses quant au découplage entre la forme du corps et la morphologie des mâchoires sont avancées et plusieurs pistes de recherche future pour nous permettre de mieux comprendre l'évolution morphologique de ce groupe de poissons fascinant sont proposées.

Los zeiformes (dorios, peces oropel y oreos) son peces acantomorfos principalmente bentopelágicos, los cuales se encuentran distribuidos entre 50 y 1000 m de profundidad en los taludes continentales, así como en los flancos de islas oceánicas y montes submarinos. Estos peces poseen adaptaciones morfológicas particulares, entre las cuales se incluye la presencia de una mandíbula altamente protusible incluyendo premaxilares con procesos ascendentes largos, y una articulación de 4-barras con palatinos móviles que pivotean sobre su articulación posterior. Esta adaptación en la protrusión mandibular ha permitido a los zeiformes capturar presas elusivas de manera más eficiente, y posiblemente ha sido un factor importante en su diversidad morfológica y éxito evolutivo. El presente estudio examina la evolución de la morfología de la mandíbula de los peces zeiformes utilizando un análisis morfométrico multivariado basado en puntos de referencia (3D landmark-based), así como un análisis de tipo filomorfoespacial. Los resultados de este trabajo muestran que los zeiformes se diversificaron rápidamente en su historia temprana, manteniendo la morfología de la mandíbula inicial durante esta etapa. No obstante, posteriormente este grupo de peces se diversificaron considerablemente en diferentes linajes. Asimismo, los resultados obtenidos se compararon con investigaciones anteriores basadas en la forma general del cuerpo, lo que demuestra que la variación morfológica de los zeiformes surgió a lo largo de al menos dos rasgos morfológicos distintos: la forma del cuerpo y la morfología de la mandíbula. Con relación a esto, se encontró que la variación de la forma del cuerpo no está asociada con la variación de la morfología de la mandíbula entre los mismos géneros de los peces zeifomes, y viceversa. Finalmente, este estudio aborda las hipótesis que explican la aparente disociación entre la forma del cuerpo y la morfología de la mandíbula de este grupo de peces, así como las rutas para estudios posteriores que ayude a comprender mejor la evolución morfológica de estos icónicos peces.

[Salivary gland ultrasound or biopsy? : Comparison of methods based on case examples]. / Speicheldrüsenultraschall oder Biopsie? : Methoden im Vergleich anhand von Fallbeispielen.

BACKGROUND: Ultrasound examination of the salivary glands (SG) is a quick and noninvasive method to detect and semiquantitatively estimate typical changes in the large SG in Sjögren's syndrome (SS). The differential diagnosis of SS is difficult because several diseases and adverse effects of treatment have a similar clinical picture as SS with sicca syndrome and can even induce alterations in the SG (mimic diseases). Hence, for a long time an SG biopsy was regarded as the diagnostic procedure of choice, especially in SS­A negative patients, whereas the significance of SD sonography is still controversially discussed. OBJECTIVE: Comparison of typical and atypical changes for SS in the salivary glands in ultrasound and associated histological sections. MATERIAL AND METHODS: This article describes six patient cases with antibody positive or negative SS with and without typical SS ultrasound patterns, SS-associated lymphoma, sarcoidosis and IgG4-associated disease. The findings of the sonographic examination of the parotid glands and the associated histology of the SD are explained and put into context. RESULTS: The SSA antibody positive patients with SS show a typical sonographic pattern with hypoechoic foci, especially if the disease has been present for a long time. This pattern can help support the diagnosis of SS. The ultrasound patterns of the mimic diseases sometimes differ significantly from the typical patterns of pSS. The histological examination of the SG helps to corroborate the diagnosis but low histological focus scores, in particular, require a critical synopsis of the clinical, serological and imaging findings. CONCLUSION: Both salivary gland ultrasound and the histological examination of SG biopsies are justified in the diagnostics and differential diagnosis of SS and sicca syndrome.

Nicotinamide riboside functions during development while beta-hydroxybutyrate functions during adulthood to extend C. elegans lifespan.

Nicotinamide riboside (NR), a form of vitamin B3 and a nicotinamide adenine dinucleotide (NAD + ) precursor, has been shown to activate the mitochondrial unfolded protein response (UPR mt ) and extend the lifespan when supplemented to C. elegans. The ketone body and histone deacetylase (HDAC) inhibitor beta-hydroxybutyrate (BHB) has also been shown to extend C. elegans lifespan. Experiments were performed that showed that NR extended lifespan by acting almost exclusively during larval development, while BHB extended lifespan by acting during adulthood, and the combination of NR during development and BHB during adulthood unexpectedly decreased lifespan. This suggests that hormesis is involved in the lifespan-altering effects of BHB and NR and that they are inducing parallel longevity pathways that converge on a common downstream target.

Fat causes necrosis and inflammation in parenchymal cells in human steatotic liver.

Adapted fixation methods for electron microscopy allowed us to study liver cell fine structure in 217 biopsies of intact human livers over the course of 10 years. The following novel observations and concepts arose: single fat droplets in parenchymal cells can grow to a volume four times larger than the original cell, thereby extremely marginalizing the cytoplasm with all organelles. Necrosis of single parenchymal cells, still containing one huge fat droplet, suggests death by fat in a process of single-cell steatonecrosis. In a later stage of single-cell steatonecrosis, neutrophils and erythrocytes surround the single fat droplet, forming an inflammatory fat follicle indicating the apparent onset of inflammation. Also, fat droplets frequently incorporate masses of filamentous fragments and other material, most probably representing Mallory substance. No other structure or material was found that could possibly represent Mallory bodies. We regularly observe the extrusion of huge fat droplets, traversing the peripheral cytoplasm of parenchymal cells, the Disse space and the endothelium. These fat droplets fill the sinusoid as a sinusoidal lipid embolus. In conclusion, adapted methods of fixation applied to human liver tissue revealed that single, huge fat droplets cause necrosis and inflammation in single parenchymal cells. Fat droplets also collect Mallory substance and give rise to sinusoidal fat emboli. Therefore, degreasing of the liver seems to be an essential therapeutic first step in the self-repairing of non-alcoholic fatty liver disease. This might directly reduce single-cell steatotic necrosis and inflammation as elements in non-alcoholic steatohepatitis progression.

The WHO 2016 diagnostic criteria for Acute Myeloid leukemia with myelodysplasia related changes (AML-MRC) produce a very heterogeneous entity: A retrospective analysis of the FAB subtype RAEB-T.

We studied 79 patients with AML-MRC or RAEB-T, who were later reclassified according to the WHO classification. Marrow slides were examined cytomorphologically with regard to dysplasia. Patients were followed up until March 2020. Thirty-one patients underwent allogeneic stem cell transplantation (median survival (ms) 16 months), 14 were treated with induction chemotherapy (ms 8.4 months), 18 received hypomethylating agents (ms 9.2 months), 16 received low dose chemotherapy or best supportive care (ms 2.4 months). Only 30.4 % fulfilled the morphologic WHO criteria. 46.8 % were classified as AML-MRC by an antecedent MDS, 54.4 % of the pts were classified by MDS-related chromosomal abnormalities. 5 % did not fulfill any of the criteria and were entered based on 20-29 % medullary blasts. There was no difference in ms between pts presenting with > 50 % dysplasia as compared to pts with dysplasia between 10 % and 50 % (ms 9.1 vs 9.9 months, p = n.s.) or for pts with antecedent MDS (ms 9.1 vs 8.9 months, p = n.s.). Myelodysplasia-related cytogenetic abnormalities were associated with a worse outcome (ms 8.1 vs 13.5 months, p = 0.026). AML-MRC in its current definition is a heterogenous entity. Dysplasia of ≥ 50 % in ≥ two lineages is not helpful for diagnostics and prognostication and therefore should be deleted in future classifications. We recommend utilizing the WHO guidelines for defining dysplasia (10 % or greater in ≥ 1 of the three myeloid cell lines) assisting in establishing the diagnosis of MDS.

Heterogeneous Microscopic Dynamics of Intruded Water in a Superhydrophobic Nanoconfinement: Neutron Scattering and Molecular Modeling.

With their strong confining porosity and versatile surface chemistry, zeolitic imidazolate frameworks-including the prototypical ZIF-8-display exceptional properties for various applications. In particular, the forced intrusion of water at high pressure (∼25 MPa) into ZIF-8 nanopores is of interest for energy storage. Such a system reveals also ideal to study experimentally water dynamics and thermodynamics in an ultrahydrophobic confinement. Here, we report on neutron scattering experiments to probe the molecular dynamics of water within ZIF-8 nanopores under high pressure up to 38 MPa. In addition to an overall confinement-induced slowing down, we provide evidence for strong dynamical heterogeneities with different underlying molecular dynamics. Using complementary molecular simulations, these heterogeneities are found to correspond to different microscopic mechanisms inherent to vicinal molecules located in strongly adsorbing sites (ligands) and other molecules nanoconfined in the cavity center. These findings unveil a complex microscopic dynamics, which results from the combination of surface residence times and exchanges between the cavity surface and center.

Excitons in CsPbBr3 Halide Perovskite.

Excitons in Bridgman grown halide perovskite CsPbBr3 single crystals were examined using photoluminescence (PL) spectroscopy to determine the nature of the electronic states. The photoluminescence intensity was strongly temperature-dependent and depended upon the specific exciton band. At low temperatures intrinsic disorder and its related shallow below bandgap tail states determine the emission properties. Photoluminescence at low temperature revealed the presence of several strong bands at the band edge that is attributed to free or trapped/bound excitons. This PL emission results from strong electron-phonon coupling with an average phonon energy Eph of 6.5 and 27.4 meV for the emissions, comparable to that observed in other perovskites. The Huang-Rhys parameter S was calculated to be 3.81 and 1.51, indicating strong electron-phonon coupling. The interactions between electrons and phonons produce small polarons that tend to bind charge carriers and result in trapped/bound excitons. The transient photoluminescence response of each specific band was studied, and the results indicated a multiphonon recombination process. Average PL lifetimes of ∼17 ns for free excitons and ∼38 ns for trapped/bound excitons were determined. The observed edge states could be associated with native defects such as vacancies and interstitials, as well as twinning due to the cubic-to-tetragonal phase transition in CsPbBr3. Elimination of the trapping sites for binding excitons could lead to improved charge transport mobilities, carrier lifetimes, and detector properties in this system.

Real-space observation of ferroelectrically induced magnetic spin crystal in SrRuO3.

Unusual features in the Hall Resistivity of thin film systems are frequently associated with whirling spin textures such as Skyrmions. A host of recent investigations of Hall Hysteresis loops in SrRuO3 heterostructures have provided conflicting evidence for different causes for such features. We have constructed an SrRuO3-PbTiO3 (Ferromagnetic - Ferroelectric) bilayer that exhibits features in the Hall Hysteresis previously attributed to a Topological Hall Effect, and Skyrmions. Here we show field dependent Magnetic Force Microscopy measurements throughout the key fields where the 'THE' presents, revealing the emergence to two periodic, chiral spin textures. The zero-field cycloidal phase, which then transforms into a 'double-q' incommensurate spin crystal appears over the appearance of the 'Topological-like' Hall effect region, and develop into a ferromagnetic switching regime as the sample reaches saturation, and the 'Topological-like' response diminishes. Scanning Tunnelling Electron Microscopy and Density Functional Theory is used to observe and analyse surface inversion symmetry breaking and confirm the role of an interfacial Dzyaloshinskii-Moriya interaction at the heart of the system.

Attenuated Directed Exploration during Reinforcement Learning in Gambling Disorder.

Gambling disorder (GD) is a behavioral addiction associated with impairments in value-based decision-making and behavioral flexibility and might be linked to changes in the dopamine system. Maximizing long-term rewards requires a flexible trade-off between the exploitation of known options and the exploration of novel options for information gain. This exploration-exploitation trade-off is thought to depend on dopamine neurotransmission. We hypothesized that human gamblers would show a reduction in directed (uncertainty-based) exploration, accompanied by changes in brain activity in a fronto-parietal exploration-related network. Twenty-three frequent, non-treatment seeking gamblers and twenty-three healthy matched controls (all male) performed a four-armed bandit task during functional magnetic resonance imaging (fMRI). Computational modeling using hierarchical Bayesian parameter estimation revealed signatures of directed exploration, random exploration, and perseveration in both groups. Gamblers showed a reduction in directed exploration, whereas random exploration and perseveration were similar between groups. Neuroimaging revealed no evidence for group differences in neural representations of basic task variables (expected value, prediction errors). Our hypothesis of reduced frontal pole (FP) recruitment in gamblers was not supported. Exploratory analyses showed that during directed exploration, gamblers showed reduced parietal cortex and substantia-nigra/ventral-tegmental-area activity. Cross-validated classification analyses revealed that connectivity in an exploration-related network was predictive of group status, suggesting that connectivity patterns might be more predictive of problem gambling than univariate effects. Findings reveal specific reductions of strategic exploration in gamblers that might be linked to altered processing in a fronto-parietal network and/or changes in dopamine neurotransmission implicated in GD.SIGNIFICANCE STATEMENT Wiehler et al. (2021) report that gamblers rely less on the strategic exploration of unknown, but potentially better rewards during reward learning. This is reflected in a related network of brain activity. Parameters of this network can be used to predict the presence of problem gambling behavior in participants.

Physician Assistants and Nurse Practitioners in Primary Care Plus: A Systematic Review.

INTRODUCTION: Shifting specialist care from the hospital to primary care/community care (also called primary care plus) is proposed as one option to reduce the increasing healthcare costs, improve quality of care and accessibility. The aim of this systematic review was to get insight in primary care plus provided by physician assistants or nurse practitioners. METHODS: Scientific databases and reference list were searched. Hits were screened on title/abstract and full text. Studies published between 1990-2018 with any study design were included. Risk of bias assessment was performed using QualSyst tool. RESULTS: Search resulted in 5.848 hits, 15 studies were included. Studies investigated nurse practitioners only. Primary care plus was at least equally effective as hospital care (patient-related outcomes). The number of admission/referral rates was significantly reduced in favor of primary care plus. Barriers to implement primary care plus included obtaining equipment, structural funding, direct access to patient-data. Facilitators included multidisciplinary collaboration, medical specialist support, protocols. CONCLUSIONS AND DISCUSSION: Quality of care within primary care plus delivered by nurse practitioners appears to be guaranteed, at patient-level and professional-level, with better access to healthcare and fewer referrals to hospital. Most studies were of restricted methodological quality. Findings should be interpreted with caution.

Universal free-energy landscape produces efficient and reversible electron bifurcation.

For decades, it was unknown how electron-bifurcating systems in nature prevented energy-wasting short-circuiting reactions that have large driving forces, so synthetic electron-bifurcating molecular machines could not be designed and built. The underpinning free-energy landscapes for electron bifurcation were also enigmatic. We predict that a simple and universal free-energy landscape enables electron bifurcation, and we show that it enables high-efficiency bifurcation with limited short-circuiting (the EB scheme). The landscape relies on steep free-energy slopes in the two redox branches to insulate against short-circuiting using an electron occupancy blockade effect, without relying on nuanced changes in the microscopic rate constants for the short-circuiting reactions. The EB scheme thus unifies a body of observations on biological catalysis and energy conversion, and the scheme provides a blueprint to guide future campaigns to establish synthetic electron bifurcation machines.

Longitudinal associations of light-intensity physical activity with quality of life, functioning and fatigue after colorectal cancer.

PURPOSE: Evidence from cross-sectional studies suggests that higher levels of light-intensity physical activity (LPA) are associated with better health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors. However, these associations have not been investigated in longitudinal studies that provide the opportunity to analyse how within-individual changes in LPA affect HRQoL. We investigated longitudinal associations of LPA with HRQoL outcomes in CRC survivors, from 6 weeks to 2 years post-treatment. METHODS: Data were used of a prospective cohort study among 325 stage I-III CRC survivors (67% men, mean age: 67 years), recruited between 2012 and 2016. Validated questionnaires were used to assess hours/week of LPA (SQUASH) and HRQoL outcomes (EORTC QLQ-C30, Checklist Individual Strength) at 6 weeks, and 6, 12 and 24 months post-treatment. We applied linear mixed regression to analyse longitudinal confounder-adjusted associations of LPA with HRQoL. RESULTS: We observed statistically significant longitudinal associations between more LPA and better global quality of life and physical, role and social functioning, and less fatigue over time. Intra-individual analysis showed that within-person increases in LPA (per 8 h/week) were related to improved HRQoL, including better global quality of life (ß = 1.67, 95% CI 0.71; 2.63; total range scale: 0-100) and less fatigue (ß = - 1.22, 95% CI - 2.37; - 0.07; scale: 20-140). Stratified analyses indicated stronger associations among participants below the median of moderate-to-vigorous physical activity (MVPA) at diagnosis. CONCLUSION: Higher levels of LPA were longitudinally associated with better HRQoL and less fatigue in CRC survivors up to two years post-treatment. Further prospective studies using accelerometer data are necessary to inform development of interventions targeting LPA.

Brain lateralization probed by water diffusion at the atomic to micrometric scale.

Combined neutron scattering and diffusion nuclear magnetic resonance experiments have been used to reveal significant interregional asymmetries (lateralization) in bovine brain hemispheres in terms of myelin arrangement and water dynamics at micron to atomic scales. Thicker myelin sheaths were found in the left hemisphere using neutron diffraction. 4.7 T dMRI and quasi-elastic neutron experiments highlighted significant differences in the properties of water dynamics in the two hemispheres. The results were interpreted in terms of hemisphere-dependent cellular composition (number of neurons, cell distribution, etc.) as well as specificity of neurological functions (such as preferential networking).

Incorporating non-stomatal limitation improves the performance of leaf and canopy models at high vapour pressure deficit.

Vapour pressure deficit (D) is projected to increase in the future as temperature rises. In response to increased D, stomatal conductance (gs) and photosynthesis (A) are reduced, which may result in significant reductions in terrestrial carbon, water and energy fluxes. It is thus important for gas exchange models to capture the observed responses of gs and A with increasing D. We tested a series of coupled A-gs models against leaf gas exchange measurements from the Cumberland Plain Woodland (Australia), where D regularly exceeds 2 kPa and can reach 8 kPa in summer. Two commonly used A-gs models were not able to capture the observed decrease in A and gs with increasing D at the leaf scale. To explain this decrease in A and gs, two alternative hypotheses were tested: hydraulic limitation (i.e., plants reduce gs and/or A due to insufficient water supply) and non-stomatal limitation (i.e., downregulation of photosynthetic capacity). We found that the model that incorporated a non-stomatal limitation captured the observations with high fidelity and required the fewest number of parameters. Whilst the model incorporating hydraulic limitation captured the observed A and gs, it did so via a physical mechanism that is incorrect. We then incorporated a non-stomatal limitation into the stand model, MAESPA, to examine its impact on canopy transpiration and gross primary production. Accounting for a non-stomatal limitation reduced the predicted transpiration by ~19%, improving the correspondence with sap flow measurements, and gross primary production by ~14%. Given the projected global increases in D associated with future warming, these findings suggest that models may need to incorporate non-stomatal limitation to accurately simulate A and gs in the future with high D. Further data on non-stomatal limitation at high D should be a priority, in order to determine the generality of our results and develop a widely applicable model.

Early suppression of peripheral mononuclear blood cells in sepsis in response to stimulation with cytomegalovirus, OKT3, and pokeweed mitogen.

Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is largely unknown. Therefore, we tested the hypotheses that reactivity of peripheral blood mononuclear cells (PBMCs) to secrete interferon-γ (IFNγ) following stimulation in vitro is decreased in patients with early sepsis compared with postoperative patients. IFNγ secretion [enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [days 1, 3, 5, and 7 after intensive care unit (ICU) admission] determined in patients with sepsis (n = 7) and patients undergoing major abdominal surgery (radical prostatectomy, cystectomy, n = 10). In a second cohort, HLA-DRA expression was assessed in 80 patients with sepsis, 30 postoperative patients, and 44 healthy volunteers (German clinical trials database no. 00007694). In patients with sepsis, IFNγ secretion (ELISpot) was decreased compared with controls after stimulation with CMV (P = 0.01), OKT3 (P = 0.02), and PWM (P = 0.02 on day 5), whereas unstimulated IFNγ secretion did not differ. HLA-DRA expression was also significantly decreased in patients with sepsis at all time points (P = 0.004) compared with postoperative surgical patients, a finding confirmed in the larger cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and OKT3 as well as HLA-DRA expression was already decreased upon ICU admission in patients with sepsis when compared with postoperative controls, suggesting early depression of acquired immunity. ELISpot assays may help to clinically characterize the time course of immunocompetence in patients with sepsis.NEW & NOTEWORTHY We observed suppression of reactivity to stimulation with cytomegalovirus, muromonab-anti-CD3, and pokeweed mitogen in mononuclear blood cells of patients with early sepsis when compared with postoperative controls. Thus, there is early depression of acquired immunity in sepsis. Enzyme-linked immunospot assays may help to characterize immunocompetence in patients with sepsis.

Alteration in propagating colonic contractions by dairy proteins in isolated rat large intestine.

Gastrointestinal conditions in which the transit of contents is altered may benefit from nutritional approaches to influencing health outcomes. Milk proteins modulate the transit of contents along different regions, suggesting that they have varying effects on neuromuscular function to alter gastrointestinal motility. We tested the hypothesis that bovine whey and casein milk protein hydrolysates could have direct modulatory effects on colonic motility patterns in isolated rat large intestine. Casein protein hydrolysate (CPH), whey protein concentrate (WPC), whey protein hydrolysate (WPH), and a milk protein hydrolysate (MPH; a hydrolyzed blend of 60% whey to 40% casein) were compared for their effects on spontaneous contractile waves. These contractions propagate along the length of the isolated intact large intestine (22 cm) between the proximal colon and rectum and were detected by measuring activity at 4 locations. Milk proteins were perfused through the tissue bath, and differences in contraction amplitude and frequency were quantified relative to pretreatment controls. Propagation frequency was decreased by CPH, increased by MPH, and unaffected by intact whey proteins. The reduced motility with CPH and increased motility with MPH indicate a direct action of these milk proteins on colon tissue and provide evidence for differential modulation by hydrolysate type. These findings mirror actions on lower gastrointestinal transit reported in vivo, with the exception of WPH, suggesting that other factors are required.

Use of test accuracy study design labels in NICE's diagnostic guidance.

BACKGROUND: A variety of study designs are available to evaluate the accuracy of tests, but the terms used to describe these designs seem to lack clarity and standardization. We investigated if this was the case in the diagnostic guidance of the National Institute of Care and Health Excellence (NICE), an influential source of advice on the value of tests. OBJECTIVES: To describe the range of study design terms and labels used to distinguish study designs in NICE Diagnostic Guidance and the underlying evidence reports. METHODS: We carefully examined all NICE Diagnostic Guidance that has been developed from inception in 2011 until 2018 and the corresponding diagnostic assessment reports that summarized the evidence, focusing on guidance where tests were considered for diagnosis. We abstracted labels used to describe study designs and investigated what labels were used when studies were weighted differently because of their design (in terms of validity of evidence), in relevant sections. We made a descriptive analysis to assess the range of labels and also categorized labels by design features. RESULTS: From a total of 36 pieces of guidance, 20 (56%) were eligible and 17 (47%) were included in our analysis. We identified 53 unique design labels, of which 19 (36%) were specific to diagnostic test accuracy designs. These referred to a total of 12 study design features. Labels were used in assigning different weights to studies in seven of the reports (41%) but never in the guidance documents. CONCLUSION: Our study confirms a lack of clarity and standardization of test accuracy study design terms. There seems to be scope to reduce and harmonize the number of terms and still capture the design features that were deemed influential by those compiling the evidence reports. This should help decision makers in quickly identifying subgroups of included studies that should be weighted differently because their designs are more susceptible to bias.

Anomalous water dynamics in brain: a combined diffusion magnetic resonance imaging and neutron scattering investigation.

Water diffusion is an optimal tool for investigating the architecture of brain tissue on which modern medical diagnostic imaging techniques rely. However, intrinsic tissue heterogeneity causes systematic deviations from pure free-water diffusion behaviour. To date, numerous theoretical and empirical approaches have been proposed to explain the non-Gaussian profile of this process. The aim of this work is to shed light on the physics piloting water diffusion in brain tissue at the micrometre-to-atomic scale. Combined diffusion magnetic resonance imaging and first pioneering neutron scattering experiments on bovine brain tissue have been performed in order to probe diffusion distances up to macromolecular separation. The coexistence of free-like and confined water populations in brain tissue extracted from a bovine right hemisphere has been revealed at the micrometre and atomic scale. The results are relevant for improving the modelling of the physics driving intra- and extracellular water diffusion in brain, with evident benefit for the diffusion magnetic resonance imaging technique, nowadays widely used to diagnose, at the micrometre scale, brain diseases such as ischemia and tumours.

Hybrid Oleate-Iodide Ligand Shell for Air-Stable PbSe Nanocrystals and Superstructures.

A postsynthetic treatment is presented to improve the air stability of PbSe nanocrystals (NCs) and PbSe square superstructures. The addition of z-type Pb(oleate)2 ligands together with x-type iodide ligands creates a hybrid ligand shell containing both ligands. The air stability of the PbSe NCs is checked by enduring absorption spectroscopy under ambient conditions. With a combined NaI + Pb(oleate)2 treatment, the absorption spectrum remains unchanged for several days under ambient conditions. Fourier transform infrared spectroscopy shows that the surface coordination of the oleate ligands changes by the chemical treatment: from mixed chelating bidentate + bridging to Pb for the pristine nanocrystals to almost exclusive chelating bidentate coordination after chemical passivation. The shift of the C-H stretching vibration shows that the oleate hydrocarbon layer is in a more liquidlike state after the chemical treatment, suggesting that oleate and iodide ligands are often present on adjacent surface positions.