Altered placental macrophage numbers and subsets in pregnancies complicated with intrahepatic cholestasis of pregnancy (ICP) compared to healthy pregnancies.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) can result in adverse outcomes for both mother and fetus. Inflammatory (M1 subset) or anti-inflammatory (M2 subset) macrophage polarisation is associated with various complications of pregnancy. However, the influence of ICP on macrophage numbers and polarisation remains unknown. This study analyses macrophage density and distribution in placentas of patients with ICP compared to controls. Clinical parameters were correlated to macrophage distribution and ursodeoxycholic acid use (UDCA). METHODS: This study included routinely collected placental tissue samples of 42 women diagnosed with ICP and of 50 control pregnancies. Immunohistochemical staining was performed on placental tissue using CD68 antibody as a pan-macrophage marker, CD206 antibody as an M2 and HLA-DR antibody as an M1 macrophage marker. Macrophage density (cells/mm2) and distribution (CD206+/CD68+ or CD206+/CD68+HLA-DR+) in both decidua (maternal tissue) and villous parenchyma (fetal tissue) were compared between groups. Macrophage density and distribution were correlated to clinical parameters for ICP patients. RESULTS: The density of CD68+ macrophages differed significantly between groups in villous parenchyma. In both decidua and villous parenchyma, CD206+/CD68+ ratio was significantly lower in ICP patients compared to controls (p = 0.003 and p=<0.001, respectively). No difference was found based on UDCA use or in CD68+HLA-DR+ cell density. Significant correlations were found between macrophage density and peak serum bile acids and liver enzymes. DISCUSSION: In ICP patients, an immune shift was observed in both decidual and villous tissue, indicated by a lower CD206+/CD68+ ratio. ICP seems to affect placental tissue, however more research is required to understand its consequences.

Differences in identification of patients' deterioration may hamper the success of clinical escalation protocols.

BACKGROUND: Timely and consistent recognition of a 'clinical crisis', a life threatening condition that demands immediate intervention, is essential to reduce 'failure to rescue' rates in general wards. AIM: To determine how different clinical caregivers define a 'clinical crisis' and how they respond to it. DESIGN: An international survey. METHODS: Clinicians working on general wards, intensive care units or emergency departments in the Netherlands, the United Kingdom and Denmark were asked to review ten scenarios based on common real-life cases. Then they were asked to grade the urgency and severity of the scenario, their degree of concern, their estimate for the risk for death and indicate their preferred action for escalation. The primary outcome was the scenarios with a National Early Warning Score (NEWS) ≥7 considered to be a 'clinical crisis'. Secondary outcomes included how often a rapid response system (RRS) was activated, and if this was influenced by the participant's professional role or experience. The data from all participants in all three countries was pooled for analysis. RESULTS: A total of 150 clinicians participated in the survey. The highest percentage of clinicians that considered one of the three scenarios with a NEWS ≥7 as a 'clinical crisis' was 52%, while a RRS was activated by <50% of participants. Professional roles and job experience only had a minor influence on the recognition of a 'clinical crisis' and how it should be responded to. CONCLUSION: This international survey indicates that clinicians differ on what they consider to be a 'clinical crisis' and on how it should be managed. Even in cases with a markedly abnormal physiology (i.e. NEWS ≥7) many clinicians do not consider immediate activation of a RRS is required.

Fatigue, not self-rated motor symptom severity, affects quality of life in functional motor disorders.

While fatigue is found to be an impairing symptom in functional motor disorders (FMD) in clinical practice, scientific evidence is lacking. We investigated fatigue severity and subtypes in FMD compared to organic neurological disease. Furthermore, the role of fatigue within FMD and its impact on quality of life and self-rated health were investigated. Data from 181 patients participating in the self-help on the internet for functional motor disorders, randomised Trial were included. Data from 217 neurological controls with neuromuscular disorders (NMD) originated from a historical cohort. Fatigue was measured using the checklist individual strength (CIS). Motor symptom severity, depression and anxiety were correlated to fatigue. For multivariable regression analyses, physical functioning and pain were additionally taken into account. Severe fatigue was, respectively, present in 78 and 53% of FMD and NMD patients (p < 0.001). FMD patients scored higher than NMD patients on all fatigue subdomains (p < 0.001). In the FMD group, fatigue subdomains were correlated to depression, anxiety and partly to motor symptom severity. Quality of life was negatively associated with fatigue [OR 0.93 (0.90-0.96), p < 0.001] and depression [OR 0.87 (0.81-0.93), p < 0.001], but not self-rated motor symptom severity. Self-rated health was negatively associated with fatigue [OR 0.92 (0.88-0.96), p < 0.001] and pain [OR 0.98 (0.97-0.99), p < 0.001]. Fatigue was found to be a prevalent problem in FMD, more so than in organic neurological disease. It significantly affected quality of life and self-rated health, while other factors such as motor symptom severity did not. Fatigue should be taken into account in clinical practice and treatment trials.

Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation.

Sidestream Dark Field (SDF) imaging, a stroboscopic LED ring-based imaging modality, is introduced for clinical observation of the microcirculation. SDF imaging is validated by comparison to Orthogonal Polarization Spectral imaging. Nailfold capillary diameters and red blood cell velocities were measured using both techniques and equal quantitative results were obtained. An image quality system was developed to quantitatively compare the quality of sublingually-acquired microcirculatory images using OPS and SDF imaging. Venular contrast, sharpness, and quality were shown to be comparable for OPS and SDF imaging. However, capillary contrast and quality were shown to be significantly higher using SDF imaging. Venular granularity, in addition, was more clearly observable using SDF imaging.

Laser-induced (endo)vascular photothermal effects studied by combined brightfield and fluorescence microscopy in hamster dorsal skin fold venules.

The putative features of the (endo)vascular photothermal response, characterized by laser-induced thermal denaturation of blood and vessel wall constituents, have been elucidated individually, but not simultaneously in dynamic, isolated in vivo systems. A hamster dorsal skin fold model in combination with brightfield/fluorescence intravital microscopy was used to examine the effect of laser pulse duration and blood flow velocity on the size of the thermal coagulum, its attachment behavior, and laser-mediated vasomotion. The size of the coagulum and the extent of vasoconstriction and latent vasodilation were proportional to the laser pulse duration, but pulse duration had no effect on coagulum attachment/dislodgement. Blood flow velocity exhibited no significant effect on the studied parameters. The (endo)vascular photothermal response is governed predominantly by laser energy deposition and to a marginal extent by blood flow velocity.

Systolic blood pressure estimation using PPG and ECG during physical exercise.

In this work, a model to estimate systolic blood pressure (SBP) using photoplethysmography (PPG) and electrocardiography (ECG) is proposed. Data from 19 subjects doing a 40 min exercise was analyzed. Reference SBP was measured at the finger based on the volume-clamp principle. PPG signals were measured at the finger and forehead. After an initialization process for each subject at rest, the model estimated SBP every 30 s for the whole period of exercise. In order to build this model, 18 features were extracted from PPG signals by means of its waveform, first derivative, second derivative, and frequency spectrum. In addition, pulse arrival time (PAT) was derived as a feature from the combination of PPG and ECG. After evaluating four regression models, we chose multiple linear regression (MLR) to combine all derived features to estimate SBP. The contribution of each feature was quantified using its normalized weight in the MLR. To evaluate the performance of the model, we used a leave-one-subject-out cross validation. With the aim of exploring the potential of the model, we investigated the influences of the inclusion of PAT, regression models, measurement sites (finger and forehead), and posture change (lying, sitting, and standing). The results show that the inclusion of PAT reduced the standard deviation (SD) of the difference from 14.07 to 13.52 mmHg. There was no significant difference in the estimation performance between the model using finger- and forehead-derived PPG signals. Separate models are necessary for different postures. The optimized model using finger-derived PPG signals during physical exercise had a performance with a mean difference of 0.43 mmHg, an SD of difference of 13.52 mmHg, and median correlation coefficients of 0.86. Furthermore, we identified two groups of features that contributed more to SBP estimation compared to other features. One group consists of our proposed features depicting beat morphology. The other comprises existing features depicting the dicrotic notch. The present work demonstrates promising results of the SBP estimation model during physical exercise.

Sucrose Represses the Developmentally Controlled Transient Activation of the Plastocyanin Gene in Arabidopsis thaliana Seedlings.

The plastocyanin (PC) gene of Arabidopsis thaliana is activated independently of light during early seedling development. In etiolated seedlings, PC mRNA levels increase transiently and a maximum dark level is reached after 2 d of growth in darkness. In etiolated transgenic seedlings carrying a chimeric PC-promoter: luciferase fusion gene, luciferase activity is similarly increased after 2 d of growth. The transient increase in PC mRNA and luciferase activity levels can be repressed by sucrose. Nonmetabolizable sugars and polyethylene glycol do not have a major effect on PC gene expression. Also, light-grown seedlings show a similar transient and sucrose-sensitive increase in PC mRNA levels and luciferase activity, as in dark-grown seedlings, but here expression levels are 15- fold higher. These findings suggest the presence of a sucrose-sensitive, developmentally controlled expression mechanism that operates independently of light.

Anatomically distinct output channels of the caudate nucleus and orofacial dyskinesia: critical role of the subcommissural part of the globus pallidus in oral dyskinesia.

The findings in this feline study indicate that the enkephalin-positive subcommissural part of the globus pallidus, which is known to contain GABA and cholinergic cells projecting to the cortex, is innervated by the anterodorsal region of the caudate nucleus, but not by the core. Like stimulation of a particular subclass of dopamine receptors in the anterodorsal region of the caudate nucleus, inhibition of the GABA receptors in the noted part of the globus pallidus resulted in orofacial dyskinesia, viz. tic-like contractions of the facial, eye and ear muscles, and tongue protrusions. This phenomenon was elicited by intrapallidal injections of the GABA antagonist picrotoxin in a dose-dependent manner and could be attenuated by the GABA agonist muscimol. Previous studies have already shown that neither stimulation of the dopamine receptors in the core of the caudate nucleus nor any manipulation with the first- and second-order output-stations of the latter brain region, viz. (a) those regions of the substantia nigra, pars reticulata which receive afferents from the caudate nucleus, and (b) those regions of the intermediate layers of the superior colliculus which receive afferents from the latter nigral region, ever resulted in orofacial dyskinesia. These findings support the hypothesis that the anatomically distinct input-output channels of the caudate nucleus are differentially involved in orofacial dyskinesia. The clinical impact of these findings is discussed in view of the L-3,4-dihydroxyphenylalanine-induced tardive dyskinesia in man. In addition, the relevance of the anatomical data is discussed in view of the co-occurrence of Parkinson's Disease and Dementia of Alzheimer-type in certain patients.

Validated ultrasonic power measurements up to 20 W.

A project has been completed to develop reference methods for the measurement of ultrasonic power with a validated measurement uncertainty of < 7% at power levels of 1 to 20 W over the frequency range 1 to 3 MHz of collimated beams. The project is the result of collaborative research between the Physikalisch-Technische Bundesanstalt, Germany (PTB, DE), the National Physical Laboratory, UK (NPL, UK) and the Netherlands Organisation for Applied Scientific Research, Prevention and Health (TNO-PG, NL). The work has been undertaken under the 4th Framework Programme of the European Community (EC). Primary standard designs of radiation force balances based on both absorbing and reflecting targets have been constructed. To avoid heating effects, the measurements should be done relatively quickly (10 to 20 s). The methods have been validated using ultrasound (US) transducers that demonstrated an adequate short and long-term stability; a method to detect cavitation based on monitoring the acoustic signals produced by bubble oscillation and collapse has been confirmed. It has been shown that only the detection of the subharmonic can be used in practice as cavitation detector. Different procedures for obtaining degassed water have been investigated. A method showing significant promise to be used in a clinical or manufacturer's environment involves the addition of sodium sulphite (Na2SO3). During the validation process, commercially available radiation force balances and ultrasonic physiotherapy devices have also been evaluated. Limitations of current measurement methods and practices, including power measurements made on transducers exhibiting a diverging beam, have been identified. It has been shown that a reflecting target is not appropriate to measure powers of transducers with a ka-value < 30. Based on beam shape and target distance, it has been shown also that proper power measurements using a 45 degrees convex-conical reflecting target can never be performed for transducers with a ka-value < 17.4.

Development of an example flow test object and comparison of five of these test objects, constructed in various laboratories.

Doppler test objects are used to characterise Doppler systems, both stand-alone systems and the Doppler part of so-called duplex scanners. The aim of the project partially presented here is the development and validation of an example of a Doppler test object fulfilling the requirements of the IEC 1685. The project has been carried out by nine partners of five European countries and has been funded by the European Commission. The flow Doppler test object is composed of: tissue mimicking material (TMM), blood mimicking fluid (BMF), tube (embedded in the TMM and carrying the BMF), tank flow system, including a pump and a flow meter. In the normative part of the IEC 1685, requirements are given for the values of acoustical parameters of TMM and BMF such as sound velocity, attenuation and backscattering. For BMF, requirements are given also for values of density and viscosity. In an informative (but not compulsory) annex, a description is given of a flow test object meeting these requirements as an example. 'example test object' developed during the project is composed of TMM based on agar and including SiC- and Al2O3-powders, BMF based on nylon particles suspended in water and glycerine, and a tube of c-flex, a silicon copolymer. Two tube sizes are used: 4.0 mm ID and 8.0 mm ID. During the project, very precise recipes have been developed for the composition and preparation of both TMM and BMF. Based on these recipes and a description of the construction in a design five flow test objects have been constructed in the laboratories of five participants. The test objects have been compared by measurements of the physical parameters and by Doppler measurements of the five test objects with the Doppler system. The measurements have been carried out by five observers. Inter-test object and inter-observer variabilities are determined, yielding information about usefulness of the parameters.

[A test object for quality control of the instrument for doppler (duplex) ultrasonography, based on the Draft IEC 61685 Standard]. / Ein Testobjekt für die apparative Qualitätssicherung bei Ultraschall-Doppler(Duplex)-Geräten, ausgehend vom Normenentwurf IEC 61685.

PURPOSE: The authors, forming part of a multicenter project funded by the European Community, summarize the validation of a tissue-mimicking flow Doppler test object and of procedures for testing medical diagnostic Doppler equipment. The results of the project are expected to contribute to a future international IEC Standard concerning flow Doppler test objects (Draft IEC 61685 Standard) and for the European Medical Device Directive (MD 93/42/EEC). METHODS: Within this project a test protocol was developed that includes a set of different procedures, suitable for checking Spectral and Colour Doppler systems. The performance parameters for describing the image quality as well as the accuracy and the correct functioning of a system are in accordance with the definitions made in the Draft IEC 61685 Standard. RESULTS: A survey of the design and materials used for this Doppler test object will be presented with a special emphasis on the suitability of the procedures for routine measurement of performance parameters in hospitals. CONCLUSION: The test object satisfies the requirements of the Draft IEC 61685 Standard. The test procedures in combination with this test object can be used for checking different transducer models with nominal frequencies between 2.5-10.0 MHz.

From amplified spontaneous emission to laser oscillation: dynamics in a short-cavity polymer laser.

We present an experimental study of the input-output characteristics of an ultrashort pumped pi -conjugated polymer in solution. By comparing the results for configurations with zero, one, and two mirrors around the polymer, we show that the physics is driven by amplified spontaneous emission and not by cooperative emission. This finding is substantiated by picosecond-time-scale measurements of the evolution of the emission of the polymer. For the two-mirror configuration a sharply defined threshold for laser oscillation is found; the output of the laser exhibits strong pulsations.