Neonatal Brain Temperature Monitoring Based on Broadband Near-Infrared Spectroscopy.

We present here the initial development of a novel algorithm based on broadband near-infrared spectroscopy (bNIRS) data to estimate the changes in brain temperature (BT) in neonates. We first explored the validity of the methodology on a simple numerical phantom and reported good agreements between the theoretical and retrieved values of BT and hemodynamic parameters changes, which are the parameters usually targeted by bNIRS. However, we noted an underestimation of the absolute values of temperature and haemoglobins' concentration changes when large variations of tissue saturation were induced, probably due to a crosstalk between the species in this specific case. We then tested this methodology on data acquired on 2 piglets during a protocol that induces seizures. We showed that despite a decrease in rectal temperature (RT) over time (-0.1048 °C 1.5 h after seizure induction, 95% CI: -0.1035 to -0.1061 °C), BT was raising (0.3122 °C 1.5 h after seizure induction, 95% CI: 0.3207 to 0.3237 °C). We also noted that the piglet displaying the largest decrease in RT also displays the highest increase in BT, which could be a marker of the severity of the seizure induced brain injury. These initial results are encouraging and show that having access to the changes in BT non-invasively could help to better understand the impact of BT on injury severity and to improve the current cooling methodologies in the neonatal neurocritical care following neonatal encephalopathy.

Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

AI-support for the detection of intracranial large vessel occlusions: One-year prospective evaluation.

Purpose: Few studies have evaluated real-world performance of radiological AI-tools in clinical practice. Over one-year, we prospectively evaluated the use of AI software to support the detection of intracranial large vessel occlusions (LVO) on CT angiography (CTA). Method: Quantitative measures (user log-in attempts, AI standalone performance) and qualitative data (user surveys) were reviewed by a key-user group at three timepoints. A total of 491 CTA studies of 460 patients were included for analysis. Results: The overall accuracy of the AI-tool for LVO detection and localization was 87.6%, sensitivity 69.1% and specificity 91.2%. Out of 81 LVOs, 31 of 34 (91%) M1 occlusions were detected correctly, 19 of 38 (50%) M2 occlusions, and 6 of 9 (67%) ICA occlusions. The product was considered user-friendly. The diagnostic confidence of the users for LVO detection remained the same over the year. The last measured net promotor score was -56%. The use of the AI-tool fluctuated over the year with a declining trend. Conclusions: Our pragmatic approach of evaluating the AI-tool used in clinical practice, helped us to monitor the usage, to estimate the perceived added value by the users of the AI-tool, and to make an informed decision about the continuation of the use of the AI-tool.

Stimulation parameters for motor evoked potentials during intraoperative spinal cord monitoring. A systematic review.

OBJECTIVE: The aim of this systematic review was to find the optimal stimulation parameters for muscle recorded transcranial electrical stimulation motor evoked potential (mTc-MEP) and D-wave monitoring during spinal cord monitoring. METHODS: A PRISMA systematic search in Medline and EMBASE and a QUADAS-2 quality evaluation was performed to identify studies that compared stimulation parameters consisting of stimulation location, number of pulses, pulse duration, interstimulus interval, double train (DTS) or recurrent train stimulation (RTS) and intertrain interval (ITI) for performing mTc-MEP and D-wave monitoring. Only studies that used total intravenous anaesthesia (TIVA) were included. RESULTS: Ten studies that compared stimulation parameters for performing mTc-MEP monitoring (stimulation location n = 4, number of pulses n = 2, pulse duration n = 1, interstimulus interval n = 4, DTS n = 1, RTS n = 2, ITI n = 2) were included. No studies compared stimulation parameters (stimulation location and pulse duration) for performing D-wave monitoring. CONCLUSIONS: Few studies examined the optimal stimulation parameters for monitoring mTc-MEPs and no studies were included for D-wave monitoring. There is a need for prospective research to investigate the optimal stimulation parameters for mTc-MEP with the use of TIVA and D-wave monitoring. SIGNIFICANCE: For mTc-MEP monitoring, a table is provided in which the recommended stimulation parameters are stated.

Feasibility and optimal choice of stimulation parameters for supramaximal stimulation of motor evoked potentials.

PURPOSE: The aim was to investigate the feasibility and optimal stimulation parameters for supramaximal stimulation of muscle recorded transcranial electrical stimulation motor evoked potentials (mTc-MEP). METHODS: Forty-seven consecutive patients that underwent scoliosis surgery were included. First, the feasibility of supramaximal stimulation was assessed for two settings (setting 1: pulse duration 0.075ms, interstimulus interval (ISI) 1.5ms; setting 2: pulse duration 0.300ms, ISI 3ms). Thereafter, three mTc-MEP parameters were considered for both settings; (1) elicitability, (2) amplitude, and (3) if supramaximal stimulation was achieved with ≥ 20 V below maximum output. Finally, ISIs (1ms-4ms) were optimized for setting 1. RESULTS: Nine patients (19.15%) were excluded. Of the remaining patients, supramaximal stimulation was achieved in all patients for setting 1, and in 26 (68.42%) for setting 2. In one patient, mTc-MEPs were elicitable in more muscles for setting (1) Amplitudes were not significantly different. Stimulation voltage could be increased ≥ 20 V in all 38 patients for setting 1 and in 10 (38.46%) for setting (2) Optimal ISI's differed widely. CONCLUSION: We recommend using setting 1 when monitoring mTc-MEPs with supramaximal stimulation, after which an individualized ISI optimization can be performed. Moreover, when using supramaximal stimulation, short ISI's (i.e. 1ms or 1.5ms) can be the optimal ISI for obtaining the highest mTc-MEP amplitude.

Systematic assessment of coronary calcium detectability and quantification on four generations of CT reconstruction techniques: a patient and phantom study.

In computed tomography, coronary artery calcium (CAC) scores are influenced by image reconstruction. The effect of a newly introduced deep learning-based reconstruction (DLR) on CAC scoring in relation to other algorithms is unknown. The aim of this study was to evaluate the effect of four generations of image reconstruction techniques (filtered back projection (FBP), hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), and DLR) on CAC detectability, quantification, and risk classification. First, CAC detectability was assessed with a dedicated static phantom containing 100 small calcifications varying in size and density. Second, CAC quantification was assessed with a dynamic coronary phantom with velocities equivalent to heart rates of 60-75 bpm. Both phantoms were scanned and reconstructed with four techniques. Last, scans of fifty patients were included and the Agatston calcium score was calculated for all four reconstruction techniques. FBP was used as a reference. In the phantom studies, all reconstruction techniques resulted in less detected small calcifications, up to 22%. No clinically relevant quantification changes occurred with different reconstruction techniques (less than 10%). In the patient study, the cardiovascular risk classification resulted, for all reconstruction techniques, in excellent agreement with the reference (κ = 0.96-0.97). However, MBIR resulted in significantly higher Agatston scores (61 (5.5-435.0) vs. 81.5 (9.25-435.0); p < 0.001) and 6% reclassification rate. In conclusion, HIR and DLR reconstructed scans resulted in similar Agatston scores with excellent agreement and low-risk reclassification rate compared with routine reconstructed scans (FBP). However, caution should be taken with low Agatston scores, as based on phantom study, detectability of small calcifications varies with the used reconstruction algorithm, especially with MBIR and DLR.

Upper Trapezius Muscle Tonicity, Assessed by Palpation, Relates to Change in Tissue Oxygenation and Structure as Measured by Time-Domain Near Infrared Spectroscopy.

Palpation is a diagnostic tool widely used by manual therapists despite its disputed reliability and validity. Previous studies have usually focused on the detection of myofascial trigger points (MTrPs), i.e., the points within muscles thought to have undergone molecular composition, oxygenation and structural changes, altering their tonicity. Time-domain near-infrared spectroscopy (TD-NIRS) could provide new insights into soft tissue oxygenation and structure, in order to objectively assess the validity and reliability of palpation. This pilot study aims at (1) assessing the ability of TD-NIRS to detect a difference between palpably normal and hypertonic upper trapezius (UT) muscles, and (2) to estimate the reproducibility of the TD-NIRS measurement on UT muscles. TD-NIRS measurements were performed on 4 points of the UT muscles in 18 healthy participants (10F, mean age: 27.6 years), after a physical examination by a student osteopath to locate these points and identify the most and least hypertonic. From TD-NIRS, the most hypertonic points had a higher concentration in deoxy- ([HHb]) (0.887 ± 0.253 µM, p < 0.001) and total haemoglobin ([HbT]) (1.447 ± 0.772 µM, p < 0.001), a lower tissue oxygen saturation (StO2) (-0.575 ± 0.286%, p < 0.001), and a greater scattering amplitude factor (AF) (0.2238 ± 0.1343 cm-1, p = 0.001) than the least hypertonic points. Moreover, the intraclass correlation coefficient one-way random-effects model (ICC (1,1)) calculated for each TD-NIRS parameter and for each point revealed an excellent reliability of the measurement (Mean ± SD, 0.9253 ± 0.0678). These initial results, showing that changes in TD-NIRS parameters correlate with changes in muscle tonicity as assessed by palpation, are encouraging and show that TD-NIRS could help to further assess the validity of palpation as a diagnostic tool in manual therapy.

Measuring saccades in patients with Niemann-Pick type C: A comparison between video-oculography and a novel eye tracking test based on continuous psychophysics.

Introduction: Vertical supranuclear gaze palsy is a key feature of Niemann-Pick type C (NP-C) and is commonly quantified using video-oculography (VOG). VOG requires sitting still for long times and performing specific tasks, thus it can be challenging or impossible for patients severely affected by movement disorders or cognitive impairment. To overcome this limitation, we measure saccades of NP-C patients using a fast eye tracking test based on continuous psychophysics and compare it to VOG. Methods: Saccades of six NP-C patients and six age-matched controls were assessed using VOG and Standardized Oculomotor and Neuro-ophthalmic Disorders Assessment (SONDA). In SONDA, participants continuously track a semi-randomly moving dot on a computer screen while their gaze is being tracked. For both assessments, saccades were quantified using four conventional measures: amplitude, gain, latency, and peak velocity. Furthermore, SONDA's continuous measures were quantified with several novel spatio-temporal properties. Results: In the NP-C patients, both methods revealed reduced amplitude, gain, peak velocity, and increased latency of vertical saccades compared to horizontal saccades and compared to healthy controls. Effect sizes obtained with SONDA were overall larger than those for VOG. SONDA's spatio-temporal properties showed similar trends. Conclusion: SONDA reveals a deterioration of vertical saccades in NP-C patients that is consistent with VOG. SONDA's measures based on continuous psychophysics are consistent with traditional saccadic parameters and can potentially provide complementary information. SONDA shows larger effect sizes than VOG, suggesting that it provides robust and clinically relevant outcomes with a more intuitive task and shorter testing time.

The contemporary pulmonary artery catheter. Part 2: measurements, limitations, and clinical applications.

Nowadays, the classical pulmonary artery catheter (PAC) has an almost 50-year-old history of its clinical use for hemodynamic monitoring. In recent years, the PAC evolved from a device that enabled intermittent cardiac output measurements in combination with static pressures to a monitoring tool that provides continuous data on cardiac output, oxygen supply and-demand balance, as well as right ventricular performance. In this review, which consists of two parts, we will introduce the difference between intermittent pulmonary artery thermodilution using bolus injections, and the contemporary PAC enabling continuous measurements by using a thermal filament which heats up the blood. In this second part, we will discuss in detail the measurements of the contemporary PAC, including continuous cardiac output measurement, right ventricular ejection fraction, end-diastolic volume index, and mixed venous oxygen saturation. Limitations of all of these measurements are highlighted as well. We conclude that thorough understanding of measurements obtained from the PAC is the first step in successful application of the PAC in daily clinical practice.

The contemporary pulmonary artery catheter. Part 1: placement and waveform analysis.

Nowadays, the classical pulmonary artery catheter (PAC) has an almost 50-year-old history of its clinical use for hemodynamic monitoring. In recent years, the PAC evolved from a device that enabled intermittent cardiac output measurements in combination with static pressures to a monitoring tool that provides continuous data on cardiac output, oxygen supply and-demand balance, as well as right ventricular (RV) performance. In this review, which consists of two parts, we will introduce the difference between intermittent pulmonary artery thermodilution using cold bolus injections, and the contemporary PAC enabling continuous measurements by using a thermal filament which at random heats up the blood. In this first part, the insertion techniques, interpretation of waveforms of the PAC, the interaction of waveforms with the respiratory cycle and airway pressure as well as pitfalls in waveform analysis are discussed. The second part will cover the measurements of the contemporary PAC including measurement of continuous cardiac output, RV ejection fraction, end-diastolic volume index, and mixed venous oxygen saturation. Limitations of all of these measurements will be highlighted there as well. We conclude that thorough understanding of measurements obtained from the PAC are the first step in successful application of the PAC in daily clinical practice.

Factors facilitating and hindering the implementation of the European Society of Cardiology Syncope Guidelines at the Emergency Department: A nationwide qualitative study.

AIMS: Syncope care is often fragmented and inefficient. Structuring syncope care through implementation of guidelines and Syncope Units has been shown to improve diagnostic yield, reduce costs and improve quality of life. We implemented the European Society of Cardiology (ESC) 2018 syncope guidelines at the Emergency Departments (ED) and established Syncope Units in five Dutch hospitals. We evaluated the implementation process by identifying factors that hinder ('barriers') and facilitate ('facilitators') the implementation. METHODS AND RESULTS: We conducted, recorded and transcribed semi-structured interviews with 19 specialists and residents involved in syncope care from neurology, cardiology, internal medicine and emergency medicine. Two researchers independently classified the reported barriers and facilitators, according to the framework of qualitative research (Flottorp), which distinguished several separate fields ('levels'). Software package Atlas.ti was used for analysis. We identified 31 barriers and 22 facilitators. Most barriers occurred on the level of the individual health care professional (e.g. inexperienced residents having to work with the guideline at the ED) and the organizational context (e.g. specialists not relinquishing preceding procedures). Participants reported most facilitators at the level of innovation (e.g. structured work-flow at the ED). The multidisciplinary Syncope Unit was welcomed as useful solution to a perceived need in clinical practice. CONCLUSION: Implementing ESC syncope guidelines at the ED and establishing Syncope Units facilitated a structured multidisciplinary work-up for syncope patients. Most identified barriers related to the individual health care professional and the organizational context. Future implementation of the multidisciplinary guideline should be tailored to address these barriers.

The influence of depth of anesthesia and blood pressure on muscle recorded motor evoked potentials in spinal surgery. A prospective observational study protocol.

For high-risk spinal surgeries, intraoperative neurophysiological monitoring (IONM) is used to detect and prevent intraoperative neurological injury. The motor tracts are monitored by recording and analyzing muscle transcranial electrical stimulation motor evoked potentials (mTc-MEPs). A mTc-MEP amplitude decrease of 50-80% is the most common warning criterion for possible neurological injury. However, these warning criteria often result in false positive warnings. False positives may be caused by inadequate depth of anesthesia and blood pressure on mTc-MEP amplitudes. The aim of this paper is to validate the study protocol in which the goal is to investigate the effects of depth of anesthesia (part 1) and blood pressure (part 2) on mTc-MEPs. Per part, 25 patients will be included. In order to investigate the effects of depth of anesthesia, a processed electroencephalogram (pEEG) monitor will be used. At pEEG values of 30, 40 and 50, mTc-MEP measurements will be performed. To examine the effect of blood pressure on mTc-MEPs the mean arterial pressure will be elevated from 60 to 100 mmHg during which mTc-MEP measurements will be performed. We hypothesize that by understanding the effects of depth of anesthesia and blood pressure on mTc-MEPs, the mTc-MEP monitoring can be interpreted more reliably. This may contribute to fewer false positive warnings. By performing this study after induction and prior to incision, this protocol provides a unique opportunity to study the effects of depths of anesthesia and blood pressure on mTc-MEPs alone with as little confounders as possible. Trial registration number NL7772.

Intraoperative neurophysiological monitoring during scoliosis surgery in patients with Duchenne muscular dystrophy.

PURPOSE: Little is known about the reliability and value of intraoperative neurophysiological monitoring (IONM) in patients with Duchenne muscular dystrophy (DMD) undergoing scoliosis correction surgery. The aim of this study was to investigate the feasibility of IONM and the cortical excitability in these patients. METHODS: Fifteen patients with DMD and scoliosis and 15 patients with adolescent idiopathic scoliosis (AIS) underwent scoliosis correction surgery with the use of IONM. IONM consisted of transcranial electrical stimulation motor evoked potential (Tc-MEP) and somatosensory evoked potential (SSEP) monitoring. The highest Tc-MEP amplitudes were collected to test the feasibility. Preoperative compound muscle action potentials (CMAPs) and transcranial magnetic stimulation (TMS)-MEPs were recorded to test the cortical excitability. SSEPs were scored as elicitable or not elicitable. RESULTS: Tc-MEP amplitudes were significantly lower in the DMD group for both the gastrocnemius and tibialis anterior muscles. However, the abductor hallucis muscle had similar amplitudes in both the DMD as the AIS group. TMS/CMAP and Tc-MEP/CMAP ratios were similar in the DMD and AIS group (P = 0.126 and P = 0.792 respectively). CONCLUSIONS: Tc-MEP and SSEP monitoring is feasible, particularly when Tc-MEPs are recorded from the abductor hallucis muscle in patients with DMD. Similar TMS/CMAP and Tc-MEP/CMAP ratios show that there were no differences observed in cortical excitability between the groups. IONM seems a feasible and valuable neurophysiological tool to signal possible surgically induced damage to the spinal cord during scoliosis correction surgery in patients with DMD.

Association of Motor and Cognitive Symptoms with Health-Related Quality of Life and Caregiver Burden in a German Cohort of Advanced Parkinson's Disease Patients.

Parkinson's disease (PD) is a chronic progressive movement disorder with severe reduction in patients' health-related quality of life (HR-QoL). Motor and cognitive symptoms are especially linked with decreased PD patients' HR-QoL. However, the relationship of these symptoms to caregiver burden is relatively unclear. Influence of the Montreal Cognitive Assessment scale (MoCA) as a cognitive screening tool and Movement Disorders Society Unified Parkinson's disease Rating Scale MDS-UPDRS symptoms in relation to patients' HR-QoL and caregivers` burden was analyzed. PD patients (n = 124) completed MDS-UPDRS, MoCA, and the PD questionnaire 8 (PDQ-8) as a measure of quality of life. Caregivers (n = 78) were assessed by the PD caregiver burden inventory (PDCB). PDQ-8 and PDCB scores were regressed on MDS-UPDRS subscales and MoCA subscores. PDQ-8 correlated with attention (R 2 0.1282; p < 0.001) and executive (R 2 0.0882; p 0.001) MoCA subscores and all parts of the MDS-UPDRS. PDCB correlated most strongly with MDS-UPDRS part III motor symptoms (R 2 0.2070; p < 0.001) and the MoCA attention subscore (R 2 0.1815; p < 0.001). While all facets of PD symptoms assessed by the MDS-UPDRS relate to PD patients' quality of life, motor symptoms are the most relevant factor for the prediction of caregiver burden. In addition, patients' attentional symptoms seem to affect not only them, but also their caregivers. These findings show the potential of a detailed analysis of MDS-UPDRS and MoCA performance in PD patients.

Broadband NIRS Cerebral Evaluation of the Hemodynamic and Oxidative State of Cytochrome-c-Oxidase Responses to +Gz Acceleration in Healthy Volunteers.

We used a miniature broadband NIRS system to monitor concentration changes in brain oxygenation (oxy- and deoxy- haemoglobin [HbO2], [HHb]) and oxidised cytochrome-c-oxidase ([oxCCO]) during a high +Gz acceleration, induced by a human centrifuge, on two healthy experienced volunteers (2 male, 34 and 37 years). We performed a sequence of several +Gz exposures that were terminated at the onset of visual symptoms (loss of peripheral vision). Systemic parameters were recorded (i.e. heart rate, blood pressure and arterial saturation), and brain tissue blood volume changes ([HbT] = [HbO2] + [HHb]) and oxygen delivery ([HbDiff] = [HbO2] - [HHb]) were calculated. Volunteer 1 demonstrated a decrease in [HbT] of -3.49 ± 0.02 µMol and [HbDiff] of -3.23 ± 0.44 µMol, and an increase of [oxCCO] of 0.42 ± 0.01µMol. Volunteer 2 demonstrated a decrease in [HbDiff] of -4.37 ± 0.23 µMol, and no significant change in [HbT] (0.53 ± 0.06 µMol) and [oxCCO] (0.09 ± 0.06 µMol). The variability of the brain metabolic response was related to the level of ischaemia, suggesting that suppression of metabolism was due to lack of glucose substrate delivery rather than oxygen availability.

Caregiver burden and health-related quality of life in idiopathic dystonia patients under botulinum toxin treatment: a cross-sectional study.

Dystonia is a chronic movement disorder that is associated with a reduction in health-related quality of life (HR-QoL) and restriction of activities of daily living. Botulinum neurotoxin (BT) improves disease-specific HR-QoL by reducing abnormal movements, postures, and pain. We examined the burden of the corresponding primary caregiver as a potential important factor for disease management and HR-QoL of dystonia patients under treatment with BT. 114 patients with focal, segmental, or generalized dystonia were recruited, together with 93 corresponding caregivers, whose burden was investigated using the Caregiver Burden Inventory. In addition, all participants were assessed for cognitive impairment, depression, anxiety, alexithymia, and HR-QoL. Only a small proportion of caregivers suffered from caregiver burden. Despite BT therapy, patients' HR-QoL was decreased compared to the age-matched general German population. Psychological symptoms, notably anxiety, and depression correlated significantly with reduced HR-QoL. Our data imply that caregiver burden emerged to be an issue in subgroups of dystonia patients. Furthermore, HR-QoL of dystonia patients is reduced even under optimized BT treatment in a specialized center.

Validating the Parkinson's disease caregiver burden questionnaire (PDCB) in German caregivers of advanced Parkinson's disease patients.

BACKGROUND: Advanced Parkinson's disease (PD) may place a high burden on patients and their caregivers. Understanding the determinants of caregiver burden is of critical importance. This understanding requires the availability of adequate assessment tools. Recently, the Parkinson's disease caregiver burden questionnaire (PDCB) has been developed as a PD-specific measure of caregiver burden. However, the PDCB has only been evaluated in a sample of Australian caregivers of patients at a less advanced stage of the disease. OBJECTIVE: We tested whether a German translation of the PDCB qualifies as an adequate measure of caregiver burden in a German sample of caregivers of advanced patients with PD. METHODS: We collected PDCB data from 65 caregivers of advanced patients with PD. Reliability of the scale was assessed and compared against the original version. To validate the German version of the PDCB, we examined the correlations with the caregiver burden inventory (CBI), the short form 36 health survey (SF-36), the Parkinson's disease quality of life questionnaire 39 (PDQ-39), disease duration, and the amount of caregiving time. RESULTS: The total PDCB score proved to be reliable and to be significantly related to CBI and SF-36 scores. PDCB scores also increased with increasing amounts of caregiving time. CONCLUSIONS: The German version of the PDCB appears to be an adequate measure of caregiver burden in caregivers of advanced PD patients.

Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass during cardiac surgery leads to impaired microcirculatory perfusion. We hypothesized that vascular leakage is an important contributor to microcirculatory dysfunction. Imatinib, a tyrosine kinase inhibitor, has been shown to reduce vascular leakage in septic mice. We investigated whether prevention of vascular leakage using imatinib preserves microcirculatory perfusion and reduces organ injury markers in a rat model of cardiopulmonary bypass. METHODS: Male Wistar rats underwent cardiopulmonary bypass after treatment with imatinib or vehicle (n=8 per group). Cremaster muscle microcirculatory perfusion and quadriceps microvascular oxygen saturation were measured using intravital microscopy and reflectance spectroscopy. Evans Blue extravasation was determined in separate experiments. Organ injury markers were determined in plasma, intestine, kidney, and lungs. RESULTS: The onset of cardiopulmonary bypass decreased the number of perfused microvessels by 40% in the control group [9.4 (8.6-10.6) to 5.7 (4.8-6.2) per microscope field; P<0.001 vs baseline], whereas this reduction was not seen in the imatinib group. In the control group, the number of perfused capillaries remained low throughout the experiment, whilst perfusion remained normal after imatinib administration. Microvascular oxygen saturation was less impaired after imatinib treatment compared with controls. Imatinib reduced vascular leakage and decreased fluid resuscitation compared with control [3 (3-6) vs 12 ml (7-16); P=0.024]. Plasma neutrophil-gelatinase-associated-lipocalin concentrations were reduced by imatinib. CONCLUSIONS: Prevention of endothelial barrier dysfunction using imatinib preserved microcirculatory perfusion and oxygenation during and after cardiopulmonary bypass. Moreover, imatinib-induced protection of endothelial barrier integrity reduced fluid-resuscitation requirements and attenuated renal and pulmonary injury markers.

Estimating the effective number of breeders from single parr samples for conservation monitoring of wild populations of Atlantic salmon Salmo salar.

This study assesses whether the effective number of breeders (Nb ) can be estimated using a time and cost-effective protocol using genetic sibship reconstruction from a single sample of young-of-the-year (YOY) for the purposes of Atlantic salmon Salmo salar population monitoring. Nb was estimated for 10 consecutive reproductive seasons for S. salar in the River Nivelle, a small population located at the rear-edge of the species distribution area in France, chronically under its conservation limit and subjected to anthropogenic and environmental changes. Subsampling of real and simulated data showed that accurate estimates of Nb can be obtained from YOY genotypes, collected at moderate random sampling intensity, achievable using routine juvenile electrofishing protocols. Spatial bias and time elapsed since spawning were found to affect estimates, which must be accounted for in sampling designs. Nb estimated in autumn for S. salar in the River Nivelle was low and variable across years from 23 (95% C.I. 14-41) to 75 (53-101) and was not statistically correlated with the estimated number of returning adults, but it was positively correlated with the estimated number of YOY at age 9 months. Nb was found to be lower for intermediate levels of redd aggregation, suggesting that the strength of the competition between males to access females affects reproductive success variance depending on redd spatial configuration. Thus, environmental factors such as habitat availability and quality for spawning and YOY development predominate over demographic ones (number of returning adults) in driving long-term population viability for S. salar in the River Nivelle. This study showcases Nb as an integrated parameter, encompassing demographic and ecological information about a reproductive event, relevant to the assessment of both short-term effects of management practices and long-term population conservation status.