Bioengineered tissue solutions for repair, correction and reconstruction in cardiovascular surgery.
The treatment of cardiac alterations is still nowadays a dramatic issue in the cardiosurgical practice. Synthetic materials applied in this surgery have failed in their long-term therapeutic efficacy due to low biocompatibility and compliance, especially when used in contractile sites. In order to overcome these treatment pitfalls, novel solutions have been developed based on biological tissues. Patches in pericardium, small intestinal submucosa, as well as engineered tissues of myocardium, heart valves and blood vessels have undergone a large preclinical investigation in regenerative medicine studies. Clinical translation has been started or reached by several of these new bioengineered treatment alternatives. This review will describe the preclinical and clinical experiences realized so far with the application of biological tissues in cardiovascular surgery. It will depict the progressive steps realized in the evolution of this research, as well as it will point out the challenges yet to face in order to generate the ideal biomaterial for cardiovascular repair, corrective and reconstructive surgery.


A Deep Learning Approach to Non-linearity in Wearable Stretch Sensors.
There is a growing need for flexible stretch sensors to monitor real time stress and strain in wearable technology. However, developing stretch sensors with linear responses is difficult due to viscoelastic and strain rate dependent effects. Instead of trying to engineer the perfect linear sensor we take a deep learning approach which can cope with non-linearity and yet still deliver reliable results. We present a general method for calibrating highly hysteretic resistive stretch sensors. We show results for textile and elastomeric stretch sensors however we believe the method is directly applicable to any physical choice of sensor material and fabrication, and easily adaptable to other sensing methods, such as those based on capacitance. Our algorithm does not require any a priori knowledge of the physical attributes or geometry of the sensor to be calibrated, which is a key advantage as stretchable sensors are generally applicable to highly complex geometries with integrated electronics requiring bespoke manufacture. The method involves three-stages. The first stage requires a calibration step in which the strain of the sensor material is measured using a webcam while the electrical response is measured via a set of arduino-based electronics. During this data collection stage, the strain is applied manually by pulling the sensor over a range of strains and strain rates corresponding to the realistic in-use strain and strain rates. The correlated data between electrical resistance and measured strain and strain rate are stored. In the second stage the data is passed to a Long Short Term Memory Neural Network (LSTM) which is trained using part of the data set. The ability of the LSTM to predict the strain state given a stream of unseen electrical resistance data is then assessed and the maximum errors established. In the third stage the sensor is removed from the webcam calibration set-up and embedded in the wearable application where the live stream of electrical resistance is the only measure of strain-this corresponds to the proposed use case. Highly accurate stretch topology mapping is achieved for the three commercially available flexible sensor materials tested.


Effects of intrathecal L- and N-type calcium channel blockers on the antinociception evoked by opioid agonists in the rat tail flick test.
The effects of intrathecal administration of nimodipine or omega-conotoxin GVIA (L- and N-type calcium channel blockers, respectively) alone or followed by DAMGO, DADLE or bremazocine (mu-, delta- and kappa-opioid agonists, respectively) were studied on the rat tail flick test. The N- (16 to 64 pmoles), but not the L-type blocker (60 to 240 pmoles) produced a dose and time-dependent increase in the latency for the tail-flick reflex. DAMGO (30 to 120 pmoles) or bremazocine (190 to 560 pmoles), but not DADLE (50 to 200 pmoles), produced a dose-dependent increase in the latency for the tail-flick reflex. The effect of the highest dose of DAMGO was smaller, while the effects of DADLE and bremazocine were not changed after nimodipine (60 pmoles). The effects of DADLE were significantly potentiated, while the effects of DAMGO and bremazocine were not changed after omega-conotoxin GVIA (16 pmoles). The intrathecal administration of an N-type calcium channel blocker with a delta-opioid agonist seems to be the most effective combination to produce antinociception in the rat tail flick test.


Colour photographs for screening in neovascular age-related macular degeneration: are they necessary?
To investigate whether optical coherence tomography (OCT) with associated infra-red images provide enough information to determine treatment decisions in the management of neovascular age-related macular degeneration (nAMD), or whether retinal colour photography is also necessary. In all, 87 OCT scans of 82 eyes with nAMD undergoing monitoring post ranibizumab treatment were taken using the Zeiss Stratus (Carl Zeiss Meditec, Jena, Germany; n=87) together with their corresponding infra-red images. Fundus colour photographs were also taken. These images were reviewed by an experienced assessor, and a ranibizumab treatment decision was made during a multidisciplinary team retinal image review meeting. In all, 30 OCT scans (34.5%) showed intraretinal or subretinal oedema. A total of 24 colour photographs (19.5%) demonstrated retinal haemorrhage. Corresponding OCT infra-red images gave poor sensitivity in detecting haemorrhages (0.176). In 16.7% of decisions to treat, haemorrhage alone was the deciding factor. Signs of disease activity seen only on colour photography were the deciding factor in clinical decisions for 8% of scans assessed. The presence or increase of intra-retinal oedema is an important sign of activity triggering ranibizumab retreatment, but some eyes show signs of retinal haemorrhage without coexisting oedema. These haemorrhages are often only seen on either colour imaging or fundoscopy and are unclear or invisible on OCT scans and infra-red images. Therefore, although retinal colour photography creates additional expense, it is indispensable for making informed retreatment decisions, if patients are monitored using retinal imaging alone.


Missing the Forest for the Trees: Why Cognitive Science Circa 2019 Is Alive and Well.
Núñez and colleagues (2019) chronicle in extraordinary detail the "demise" of cognitive science, as it was first defined in the late 1970s. The problem is that their account, however accurate, misses the forest for the trees. Cognitive science circa 2019 is alive and well; it just has not followed the path anticipated by its founders over 40 years ago.


A validated classification for external immobilization of the cervical spine.
Study Design Interobserver and intraobserver reliability study. Objective The aim of this study is to validate a new classification system of external cervical spine immobilization devices by measuring the interobserver and intraobserver agreement. Methods A classification system, with five main categories, based on the anatomical regions on which the device supports, was created. A total of 28 independent observers classified 50 photographs of different devices, designed to immobilize the cervical spine according to the new proposed classification system. At least 2 weeks later, the same devices were classified again in a new random order. Before and after the classification, all the participants answered questions about the usefulness of the proposed classification. Results The mean interobserver and intraobserver agreement Fleiss' kappa was 0.88 and 0.91, respectively. Both are, according to the interpretation described by Landis and Koch, "almost perfect." A majority of the participators answered that they needed a classification (89%) and considered the classification to be clear (96%). All the participants considered the classification to be useful in clinical practice. Conclusion This study showed that the new classification of external cervical spine immobilizers, based on anatomical support areas, has an excellent interobserver and intraobserver agreement. Furthermore, the study participants considered the proposed classification to be clear and useful in clinical practice. As the majority of patients with cervical spine injuries are treated with external immobilization devices, this new classification system can improve the closed treatment of cervical spine injuries in daily clinical practice. Furthermore, it makes reproducible comparisons between groups possible, which are essential for further evolution of evidence-based spine care.


Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study.
Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer's Disease (EMIF-AD; n=883), Alzheimer's Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233). Inclusion criteria were a baseline diagnosis of MCI, at least 6 months of follow-up, and availability of a baseline Mini-Mental State Examination (MMSE) and MRI or CSF biomarker assessment. The primary endpoint was clinical progression to any type of dementia. We evaluated performance of previously developed risk prediction models-a demographics model, a hippocampal volume model, and a CSF biomarkers model-by evaluating them across cohorts, incorporating different biomarker measurement methods, and determining prognostic performance with Harrell's C statistic. We then updated the models by re-estimating parameters with and without centre-specific effects and evaluated model calibration by comparing observed and expected survival. Finally, we constructed a model combining markers for amyloid deposition, tauopathy, and neurodegeneration (ATN), in accordance with the National Institute on Aging and Alzheimer's Association research framework. We included all 2611 individuals with MCI in the four cohorts, 1007 (39%) of whom progressed to dementia. The validated demographics model (Harrell's C 0·62, 95% CI 0·59-0·65), validated hippocampal volume model (0·67, 0·62-0·72), and updated CSF biomarkers model (0·72, 0·68-0·74) had adequate prognostic performance across cohorts and were well calibrated. The newly constructed ATN model had the highest performance (0·74, 0·71-0·76). We generated risk models that are robust across cohorts, which adds to their potential clinical applicability. The models could aid clinicians in the interpretation of CSF biomarker and hippocampal volume results in individuals with MCI, and help research and clinical settings to prepare for a future of precision medicine in Alzheimer's disease. Future research should focus on the clinical utility of the models, particularly if their use affects participants' understanding, emotional wellbeing, and behaviour. ZonMW-Memorabel.


Effect of the physical activities in leisure time and commuting to work on mental health.
Although some evidence suggests that exercise may improve mental health status, information regarding the intensity and duration of exercise is incomplete. The purpose of this study was to elucidate the association between physical activities in both leisure time and commuting to work and mental health. A questionnaire survey was conducted at three municipal offices in Japan. A total of 670 men and women completed the questionnaire. Mental health status was assessed by the 28-item General Health Questionnaire (GHQ). Respondents were asked about weekly hours of leisure-time exercise for four levels of exercise, and the volume of exercise was assessed using a metabolic equivalent task index. Information about commuting to work on foot or by bicycle was also obtained. The mean GHQ scores were calculated according to physical activity levels using analysis of covariance with adjustment of potential confounders including job stress. In men, the GHQ score decreased steadily with increasing levels of leisure-time exercise, and an inverse association was evident even for mild intensity exercise. Moreover, the GHQ score decreased according to increasing duration of time on commuting to work by either walking or cycling in men, but not in women. These relations did not materially change after adjustment for potential confounding factors. In women, there was no significant association between any of the indices of physical activity. In conclusion, leisure-time exercise and walking or cycling during commuting to work may be associated with better mental health in men.


[Frequency ratio of two forms of amitotic division of trophoblast cell nuclei in the mink blastocysts during the period of delayed implantation].
A comparative study of amitotic division activity of trophoblast cells by constriction and by extrusion in blastocysts of American mink during the obligatory period of delayed implantation has been carried out. The frequency of occurrence of amitotic figures was found to be nearly 10% at the onset of renewal of blastocyst growth (the blastocyst size was 0.4 mm in diameter), and nearly 20% at the stage of active growth (0.9 mm), as well as at the stage of expansion prior to blastocyst attachment to the uterine wall (1.7 mm). The ratios between the frequencies of division by extrusion and by constriction were 2:1, 5:1, and 4:1 at the three stages, respectively. We suggest that the cells generated via different amitotic ways play different roles in trophoblast differentiation.


Unveiling current Guanaco distribution in chile based upon niche structure of phylogeographic lineages: Andean puna to subpolar forests.
Niche description and differentiation at broad geographic scales have been recent major topics in ecology and evolution. Describing the environmental niche structure of sister taxa with known evolutionary trajectories stands out as a useful exercise in understanding niche requirements. Here we model the environmental niche structure and distribution of the recently resolved phylogeography of guanaco (Lama guanicoe) lineages on the western slope of the southern Andes. Using a maximum entropy framework, field data, and information on climate, topography, human density, and vegetation cover, we identify differences between the two subspecies (L.g.cacsilensis, L.g.guanicoe) and their intermediate-hybrid lineage, that most likely determine the distribution of this species. While aridity seems to be a major factor influencing the distribution at the species-level (annual precipitation <900 mm), we also document important differences in niche specificity for each subspecies, where distribution of Northern lineage is explained mainly by elevation (mean = 3,413 m) and precipitation seasonality (mean = 161 mm), hybrid lineage by annual precipitation (mean = 139 mm), and Southern subspecies by annual precipitation (mean = 553 mm), precipitation seasonality (mean = 21 mm) and grass cover (mean = 8.2%). Among lineages, we detected low levels of niche overlap: I (Similarity Index) = 0.06 and D (Schoener's Similarity Index) = 0.01; and higher levels when comparing Northern and Southern subspecies with hybrids lineage ( I = 0.32-0.10 and D = 0.12-0.03, respectively). This suggests that important ecological and/or evolutionary processes are shaping the niche of guanacos in Chile, producing discrepancies when comparing range distribution at the species-level (81,756 km(2)) with lineages-level (65,321 km(2)). The subspecies-specific description of niche structure is provided here based upon detailed spatial distribution of the lineages of guanacos in Chile. Such description provides a scientific tool to further develop large scale plans for habitat conservation and preservation of intraspecific genetic variability for this far ranging South American camelid, which inhabits a diversity of ecoregion types from Andean puna to subpolar forests.


Risk of stroke in women exposed to low-dose oral contraceptives: a critical evaluation of the evidence.
Use of the oral contraceptive pill (OCP) has been reported to be associated with stroke. With current OCPs containing less than 50 micro g of ethinyl estradiol, and many earlier studies reporting the association between OCPs and stroke, subjected to biases, we determined whether such an association exists and, if so, the magnitude of the risk. Two independent searches were conducted to obtain relevant articles from MEDLINE, EMBASE, and Science Citation (1970 to June 2000). Eligible articles published in English describing OCP use and stroke outcomes were retrieved, and relevant data were abstracted. Pooling of results from these studies was performed using odds ratios (ORs) provided, and heterogeneity was calculated using chi(2) analysis. From 779 potential articles, 36 eligible studies describing 20 distinct populations were retrieved (4 cohort and 16 case-control studies). The pooled OR from the cohort studies demonstrated no increased stroke risk with OCP use (0.95; 95% confidence interval [CI], 0.51-1.78; P =.01); the pooled OR from the case-control studies showed a significant association (2.13; 95% CI, 1.59-2.86; P<.001). The risk of stroke with OCP use, however, was significant only with thrombotic stroke (2.74; 95% CI, 2.24-3.35; P =.009) and not with hemorrhagic stroke or stroke death. There was statistically significant heterogeneity among these studies, and potential biases and confounders were not adequately addressed. These results cast doubt on a true association between low-dose OCPs and stroke because of the low absolute magnitude of the ORs, the severe methodological limitations, and the ORs of less than 1.0 in the cohort studies. The association is tenuous at best and perhaps nonexistent.


Human metabolism and body composition: prospects for novel studies.
Most articles on gut microbiota argue the importance of body composition assessment in patients; however, body composition assessments are fragile (ie, with methodological limitations) in the most recent studies. To present two suggestions for further research using the human body composition assessment. The methods used in this study are based on a Pinto et al article published in Nutrition Reviews. On the basis of data. obtained from the PubMed, SCOPUS, LILACS, and Web of Science databases, Pinto et al provided a current survey of intermittent fasting protocols and an understanding of the outcomes to date in terms of the profile of the intestinal microbiota in obese organisms. Of the 82 original articles identified from the databases, 35 were eliminated because of duplication and 32 were excluded for not meeting the inclusion criteria. Two additional articles found in a new search were added, yielding a total of 17 studies to be included in this review. Among the protocols, alternate-day fasting and time-restricted feeding were the most common, and they were shown to have different mechanisms of metabolic signaling. Time-restricted feeding influences body mass control and biochemical parameters by regulating the circadian system and improving satiety control systems by acting on leptin secretion. In contrast, alternate-day fasting leads to a reduction of ±75% of all energy consumption regardless of dietary composition, in addition to promoting hormonal adjustments that promote body mass control. Furthermore, both protocols could remodel the intestinal microbiota by changing the Firmicutes to Bacteroidetes ratio and increasing the abundance of strains such as Lactobacillus spp. and Akkermansia that have a protective effect on metabolism against the effects of body mass gain. Changes in adipose tissue (eg, body mass loss, control, gain) should be interpreted via the sum of skinfolds in absolute values, waist perimeter, and patients' body proportionality, because fat is just a fraction of the adipocyte (lipid).


Solar activity as a possible cause of large forest fires--a case study: analysis of the Portuguese forest fires.
Fires of large dimension destroy forests, harvests and housing objects. Apart from that combustion products and burned surfaces become large ecological problems. Very often fires emerge simultaneously on different locations of a region so a question could be asked if they always have been a consequence of negligence, pyromania, high temperatures or maybe there has been some other cause. This paper is an attempt of establishing the possible connection between forest fires that numerous satellites registered and activities happening on the Sun immediately before fires ignite. Fires emerged on relatively large areas from Portugal and Spain on August 2005, as well as on other regions of Europe. The cases that have been analyzed show that, in every concrete situation, an emission of strong electromagnetic and thermal corpuscular energy from highly energetic regions that were in geo-effective position had preceded the fires. Such emissions have, usually, very high energy and high speeds of particles and come from coronary holes that also have been either in the very structure or in the immediate closeness of the geo-effective position. It should also be noted that the solar wind directed towards the Earth becomes weaker with deeper penetration towards the topographic surface. However, the results presented in this paper suggest that, there is a strong causality relationship between solar activity and the ignition of these forest fires taking place in South-western Europe.


Self-calibrated microscopic dual-view tomographic holography for 3D flow measurements.
This paper introduces the application of microscopic dual-view tomographic holography (M-DTH) to measure the 3D position and motion of micro-particles located in dense suspensions. Pairing of elongated traces of the same particle in the two inclined reconstructed fields requires precise matching of the entire sample volume that accounts for the inherent distortions in each view. It is achieved by an iterative volumetric self-calibration method, consisting of mapping one view onto the next, dividing the sample volume into slabs, and cross-correlating the two views. Testing of the procedures using synthetic particle fields with imposed distortion and realistic errors in particle locations shows that the self-calibration method achieves a 3D uncertainty of about 1µm, a third of the particle diameter. Multiplying the corrected intensity fields is used for truncating the elongated traces, whose centers are located within 1µm of the exact value. Without correction, only a small fraction of the traces even overlap. The distortion correction also increases the number of intersecting traces in experimental data along with their intensity. Application of this method for 3D velocity measurements is based on the centroids of the truncated/shortened particle traces. Matching of these traces in successive fields is guided by several criteria, including results of volumetric cross-correlation of the multiplied intensity fields. The resulting 3D velocity distribution is substantially more divergence-free, i.e., satisfies conservation of mass, compared to analysis performed using single-view data. Sample application of the new method shows the 3D flow structure around a pair of cubic roughness elements embedded in the inner part of a high Reynolds number turbulent boundary layer.


Phenotyping cardiac and structural birth defects in fetal and newborn mice.
Mouse models are invaluable for investigating the developmental etiology and molecular pathogenesis of structural birth defects. While this has been deployed for studying a wide spectrum of birth defects, mice are particularly valuable for modeling congenital heart disease, given they have the same four-chamber cardiac anatomy as in humans. We have developed the use of noninvasive fetal ultrasound together with micro-computed tomography (micro-CT) imaging for high throughput phenotyping of mice for congenital heart defects (CHD) and other developmental anomalies. We showed the efficacy of fetal ultrasound and micro-CT imaging for diagnosis of a wide spectrum of CHD. With fetal ultrasound, longitudinal scans can be conducted to track the developmental profile of disease pathogenesis, providing both structural information with two-dimensional (2D) imaging, as well as functional data from hemodynamic assessments with color flow and spectral Doppler imaging. In contrast, with micro-CT imaging, virtual necropsies can be conducted rapidly postmortem for diagnosis of not only CHD, but also other structural birth defects. To validate the CHD diagnosis, we further showed the use of a novel histological technique with episcopic confocal microscopy to obtain rapid 3D reconstructions for accurate diagnosis of even the most complex anatomical defect. The latter histological imaging technique when combined with the use of ultrasound and micro-CT imaging provides a powerful combination of imaging modalities that will be invaluable in meeting the accelerating demands for high throughput mouse phenotyping of genetically engineered mice in the coming age of functional genomics. Birth Defects Research 109:778-790, 2017. © 2017 Wiley Periodicals, Inc.


Effects of nisoldipine on the no-reflow phenomenon in globally ischemic rat hearts.
Isolated working rat hearts, receiving no drug treatment, recovered low values of contractile function after 33 min of zero-flow global ischemia and 30-min reperfusion, had lower ATP and creatine phosphate (CrP) values in the subendocardium than in the subepicardium after reperfusion (subendocardial/subepicardial ratio ATP = 0.44, CrP = 0.45), and had a subendocardial reperfusion defect including 15.9% of ventricular cross-sectional area. Contracture pressure increased during the later part of ischemia to 25.4 mm Hg. Addition of nisoldipine (1 nM) 10 min before ischemia did not depress preischemic contractile function and did not delay or reduce contracture or the breakdown of high-energy phosphate compounds during ischemia. On reperfusion, nisoldipine-treated hearts showed a dramatic improvement in recovery of contractile function, increased subendocardial energy levels yielding a more uniform transmural energy distribution (subendocardial/subepicardial ratio ATP = 0.79, CrP = 0.94), and enhanced reflow to the subendocardium (area of no reflow = 1.0%). In contrast, addition of vehicle or a low concentration of verapamil (1 nM) before ischemia or nisoldipine during reperfusion did not improve recovery of contractile function. The beneficial effects do not appear to be induced by direct myocardial actions of nisoldipine but may reflect improved vascular function which is associated with the vascular selectivity of this calcium antagonist.


A label-free and enzyme-free signal amplification strategy for a sensitive RNase H activity assay.
We herein describe a label-free and enzyme-free signal amplification strategy for the sensitive determination of ribonuclease H (RNase H) activity, which relies on the target-triggered catalytic hairpin assembly (CHA) in conjunction with a G-quadruplex specific fluorescent binder, N-methyl mesoporphyrin IX (NMM). In the absence of RNase H, the RNA/DNA duplex serving as a substrate for RNase H cannot initiate the execution of CHA that produces G-quadruplexes; so NMM shows a low fluorescence signal. In contrast, the presence of RNase H that degrades RNA in the RNA/DNA duplex releases DNA designed to function as the catalyst for CHA. This consequently promotes the efficient CHA and generates a large number of G-quadruplexes with a significantly enhanced fluorescence signal from NMM. Based on this label-free and enzyme-free signal amplification strategy, we successfully determined the RNase H activity with a detection limit of 0.037 U mL-1 and screened potential RNase H inhibitors. Our results suggest that the developed system is a promising platform for a cost-effective, sensitive enzyme activity assay and inhibitor screening.


Addition of catfish gonadotropin-releasing hormone (GnRH) receptor intracellular carboxyl-terminal tail to rat GnRH receptor alters receptor expression and regulation.
Mammalian GnRH receptor (GnRHR) is unique among G protein-coupled seven-transmembrane segment receptors due to the absence of an intracellular C-terminal tail frequently important for internalization and/or desensitization of other G protein-coupled receptors. The recent cloning of nonmammalian (i.e. catfish, goldfish, frog, and chicken) GnRHRs shows that these contain an intracellular C terminus. Addition of the 51-amino acid intracellular C terminus from catfish GnRHR (cfGnRHR) to rat GnRHR (rGnRHR) did not affect rGnRHR binding affinity but elevated receptor expression by about 5-fold. Truncation of the added C terminus impaired the elevated receptor-binding sites by 3- to 8-fold, depending on the truncation site. In addition, introducing the C terminus to rGnRHR altered the pattern of receptor regulation from biphasic down-regulation and recovery to monophasic down-regulation. The extent of down-regulation was also enhanced. The alteration in receptor regulation due to the addition of a C terminus was reversed by truncation of the added C terminus. Furthermore, addition of the cfGnRHR C terminus to rGnRHR significantly augmented the inositol phospholipid (IP) response of transfected cells to Buserelin, but this did not result from the elevation of receptor-binding sites. Addition of the C terminus did not affect Buserelin-stimulated cAMP and PRL release. GH3 cells transfected with wild-type cfGnRHR did not show measurable Buserelin binding or significant stimulation of IP, cAMP, or PRL in response to Buserelin (10[-13]-10[-9] M). GH3 cells transfected with C terminus-truncated cfGnRHR showed no IP response to Buserelin (10[-13]-10[-7] M). These results suggest that addition of the cfGnRHR intracellular C terminus to rGnRHR has a significant impact on rGnRHR expression and regulation and efficiency of differential receptor coupling to G proteins.


AUTOMATED COLITIS DETECTION FROM ENDOSCOPIC BIOPSIES AS A TISSUE SCREENING TOOL IN DIAGNOSTIC PATHOLOGY.
We present a method for identifying colitis in colon biopsies as an extension of our framework for the automated identification of tissues in histology images. Histology is a critical tool in both clinical and research applications, yet even mundane histological analysis, such as the screening of colon biopsies, must be carried out by highly-trained pathologists at a high cost per hour, indicating a niche for potential automation. To this end, we build upon our previous work by extending the histopathology vocabulary (a set of features based on visual cues used by pathologists) with new features driven by the colitis application. We use the multiple-instance learning framework to allow our pixel-level classifier to learn from image-level training labels. The new system achieves accuracy comparable to state-of-the-art biological image classifiers with fewer and more intuitive features.


The psychological basis of music appreciation: Structure, self, source.
Research has investigated psychological processes in an attempt to explain how and why people appreciate music. Three programs of research have shed light on these processes. The first focuses on the appreciation of musical structure. The second investigates self-oriented responses to music, including music-evoked autobiographical memories, the reinforcement of a sense of self, and benefits to individual health and wellbeing. The third seeks to explain how music listeners become sensitive to the causal and contextual sources of music making, including the biomechanics of performance, knowledge of musicians and their intentions, and the cultural and historical context of music making. To date, these programs of research have been carried out with little interaction, and the third program has been omitted from most psychological enquiries into music appreciation. In this paper, we review evidence for these three forms of appreciation. The evidence reviewed acknowledges the enormous diversity in antecedents and causes of music appreciation across contexts, individuals, cultures, and historical periods. We identify the inputs and outputs of appreciation, propose processes that influence the forms that appreciation can take, and make predictions for future research. Evidence for source sensitivity is emphasized because the topic has been largely unacknowledged in previous discussions. This evidence implicates a set of unexplored processes that bring to mind causal and contextual details associated with music, and that shape our appreciation of music in important ways. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


An in-depth statistical analysis of the COVID-19 pandemic's initial spread in the WHO African region.
During the first wave of the COVID-19 pandemic, sub-Saharan African countries experienced comparatively lower rates of SARS-CoV-2 infections and related deaths than in other parts of the world, the reasons for which remain unclear. Yet, there was also considerable variation between countries. Here, we explored potential drivers of this variation among 46 of the 47 WHO African region Member States in a cross-sectional study. We described five indicators of early COVID-19 spread and severity for each country as of 29 November 2020: delay in detection of the first case, length of the early epidemic growth period, cumulative and peak attack rates and crude case fatality ratio (CFR). We tested the influence of 13 pre-pandemic and pandemic response predictor variables on the country-level variation in the spread and severity indicators using multivariate statistics and regression analysis. We found that wealthier African countries, with larger tourism industries and older populations, had higher peak (p<0.001) and cumulative (p<0.001) attack rates, and lower CFRs (p=0.021). More urbanised countries also had higher attack rates (p<0.001 for both indicators). Countries applying more stringent early control policies experienced greater delay in detection of the first case (p<0.001), but the initial propagation of the virus was slower in relatively wealthy, touristic African countries (p=0.023). Careful and early implementation of strict government policies were likely pivotal to delaying the initial phase of the pandemic, but did not have much impact on other indicators of spread and severity. An over-reliance on disruptive containment measures in more resource-limited contexts is neither effective nor sustainable. We thus urge decision-makers to prioritise the reduction of resource-based health disparities, and surveillance and response capacities in particular, to ensure global resilience against future threats to public health and economic stability.


Radionuclides released to the environment following nuclear events.
The accident at the Fukushima Daiichi nuclear power plant, precipitated by the devastating earthquake and subsequent tsunami that struck the northeastern coast of Japan in March 2011, has raised concerns about the fate of radioactive particles released into the environment. Radioactive particles with different composition, size, shape, structures, and colors have been identified throughout the world in different biotic and abiotic media. This article briefly summarizes what is currently understood about the fate of, and risks posed by, these materials in the environment.


His166 is the Schiff base proton acceptor in attractant phototaxis receptor sensory rhodopsin I.
Photoactivation of attractant phototaxis receptor sensory rhodopsin I (SRI) in Halobacterium salinarum entails transfer of a proton from the retinylidene chromophore's Schiff base (SB) to an unidentified acceptor residue on the cytoplasmic half-channel, in sharp contrast to other microbial rhodopsins, including the closely related repellent phototaxis receptor SRII and the outward proton pump bacteriorhodopsin, in which the SB proton acceptor is an aspartate residue salt-bridged to the SB in the extracellular (EC) half-channel. His166 on the cytoplasmic side of the SB in SRI has been implicated in the SB proton transfer reaction by mutation studies, and mutants of His166 result in an inverted SB proton release to the EC as well as inversion of the protein's normally attractant phototaxis signal to repellent. Here we found by difference Fourier transform infrared spectroscopy the appearance of Fermi-resonant X-H stretch modes in light-minus-dark difference spectra; their assignment with (15)N labeling and site-directed mutagenesis demonstrates that His166 is the SB proton acceptor during the photochemical reaction cycle of the wild-type SRI-HtrI complex.


Slave mortality during the cholera epidemic in Rio de Janeiro (1855-1856): a preliminary analysis.
The article offers a preliminary analysis of the sociodemographic profile of deaths recorded during the first cholera epidemic in Rio de Janeiro, based on data gathered from death records at Santa Casa de Misericórdia Hospital. After cholera appeared in the country in 1855, Brazilian medical reports indicated a social bias, with slaves and the free poor suffering high mortality. From a historical perspective, however, little research has been done on the epidemic and its dynamics. The recovery of original data on cholera and the analysis of cholera mortality rates help us to better understand aspects of the slave universe in the urban zone of Rio de Janeiro in the period following the end of the slave trade.


Three-dimensional duck's feet collagen/PLGA scaffold for chondrification: role of pore size and porosity.
An ideal tissue-engineered scaffold must provide sufficient porosity to allow free movement of cells, nutrients, and oxygen for proper cell growth and further maintenance. Owing to variation in pore sizes and shapes of as-fabricated scaffold, the amount of oxygen available for the cells attached to the scaffold and transfer of by-products and excrement will be different, which ultimately results in cell activity. Thus, optimizing pore size and porosity of a scaffold for a specific tissue regeneration are one of the key highlights, which should be considered while designing a scaffold as well as choosing a specific cell type. In this study, three-dimensional (3D) scaffolds based on blends of duck's feet collagen (DC) and poly (lactic-co-glycolic acid) (PLGA) with different pore sizes i.e. 90-180, 180-250, 250-355 and 355-425 μm were prepared using solvent casting/salt leaching approach and examined its effects on chondrification. The morphological analysis of the as-fabricated scaffolds was performed using SEM for studying porosity and pore size. The cell proliferation and gene expression were investigated after culturing costal chondrocytes on each scaffolds using 3-(4, 5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and qRT-PCR. Histological staining of in vivo implants was performed in nude mice as models. The biological evaluation showed a pore-size dependent chondrification at different time points. Especially, the 355-425 μm DC/PLGA scaffold showed a highest positive impact on maintenance of cell proliferation, costal chondrocyte phenotype and increased glycosaminoglycan accumulation than the other groups. These results indicated that DC/PLGA scaffolds with pore size ranging from 250 to 425 μm can be considered as highly-suitable constructs for enhanced chondrification.


Occupational Vocal Health of Elite Sports Coaches: An Exploratory Pilot Study of Football Coaches.
To explore the occupational voice use and vocal health of elite football coaches. This pilot study explored coaches' voice use patterns and vocal demands across workplace environments. Each coach's experiences of voice symptoms and voice problems were also investigated. Twelve Australian professional football coaches participated in a mixed-methods data collection approach. Data were collected through acoustic voice measurement (Ambulatory Phonation Monitor), semistructured interviews, and a voice symptom questionnaire (Voice Capabilities Questionnaire). Acoustic measures suggested heavy vocal loads for coaches during player training. All participants reported experiencing voice symptoms. They also suggested that the structure of their working week, workplace tasks, and vocal demands impacted on their voices. Despite this, participants reported little previous reflection or awareness of what impacted on their voices. Coaches typically did not consider how to support their voices during daily work and discussed experiencing voice symptoms as an inevitable part of their jobs. This study demonstrates that occupational vocal demands may negatively impact on sports coaches' vocal health. This is particularly important, considering coaches' heavy vocal loads across coaching tasks and reported negative occupational vocal health experience. Furthermore, coaches' limited insight into voice use and vocal health management may impact on their vocal performance and health. Given the exploratory nature of this study, further research into coaches' occupational vocal health is warranted.


Oxyluciferin Derivatives: A Toolbox of Environment-Sensitive Fluorescence Probes for Molecular and Cellular Applications.
In this work, we used firefly oxyluciferin (OxyLH2) and its polarity-dependent fluorescence mechanism as a sensitive tool to monitor biomolecular interactions. The chromophores, OxyLH2, and its two analogues, 4-MeOxyLH and 4,6'-DMeOxyL, were modified trough carboxylic functionalization and then coupled to the N-terminus part of Tat and NCp7 peptides of human immunodeficiency virus type-1 (HIV-1). The photophysical properties of the labeled peptides were studied in live cells as well as in complex with different oligonucleotides in solution. By monitoring the emission properties of these derivatives we were able, for the first time, to study in vitro biomolecular interactions using oxyluciferin as a sensor. As an additional application, cyclopropyl-oxyluciferin (5,5-Cpr-OxyLH) was site-specifically conjugated to the thiol group (Cys-232) of the human protein α-1 antytripsin to investigate its interaction with porcine pancreatic elastase. Our data demonstrate that OxyLH2 and its derivatives can be used as fluorescence reporters for monitoring biomolecular interactions.


Parameterization-invariant shape comparisons of anatomical surfaces.
We consider 3-D brain structures as continuous parameterized surfaces and present a metric for their comparisons that is invariant to the way they are parameterized. Past comparisons of such surfaces involve either volume deformations or nonrigid matching under fixed parameterizations of surfaces. We propose a new mathematical representation of surfaces, called q-maps, such that L² distances between such maps are invariant to re-parameterizations. This property allows for removing the parameterization variability by optimizing over the re-parameterization group, resulting in a proper parameterization-invariant distance between shapes of surfaces. We demonstrate this method in shape analysis of multiple brain structures, for 34 subjects in the Detroit Fetal Alcohol and Drug Exposure Cohort study, which results in a 91% classification rate for attention deficit hyperactivity disorder cases and controls. This method outperforms some existing techniques such as spherical harmonic point distribution model (SPHARM-PDM) or iterative closest point (ICP).


Effects of shRNA-Mediated Silencing of PKM2 Gene on Aerobic Glycolysis, Cell Migration, Cell Invasion, and Apoptosis in Colorectal Cancer Cells.
This study aims to explore the effects of shRNA-mediated silencing on Pyruvate kinase type M2 (PKM2) gene during aerobic glycolysis in colorectal cancer (CRC) cells. CRC tissues and adjacent normal tissues were obtained from 136 patients diagnosed with qRT-PCR, Western blotting, and immunohistochemistry (IHC) were performed to detect mRNA and protein expressions of PKM2. CRC cells were divided into a blank, vector, and PKM2-shRNA groups. Hexokinase (HK) and PKM2 activity were both determined by glucose-6-phosphate dehydrogenase (G-6-PD) coupled colorimetric assay and enzyme coupling rate method. The extracellular lactate concentration was measured by ultraviolet spectrophotometer and caspase activity was measured using spectrophotometry. The proliferation, cell cycle, apoptosis, invasion, and migration of CRC cells were detected by cell counting kit-8 (CCK-8) assay, flow cytometry, transwell assay, and scratch test. Three groups of nude mice were injected with 0.2 mL single-cell suspension from the blank, vector, and PKM2-shRNA groups, respectively. PKM2 protein content in CRC tissues was higher than that in adjacent normal tissues. Results showed that the PKM2-shRNA group exhibited significantly lower mRNA and protein expressions of PKM2, decreased PKM2 activity, reduced lactate metabolism level, increased cell apoptosis rate, elevated caspase-3 and caspase-9 activity, weakened proliferation, and a reduction in cell invasion and migration ability compared to the vector and blank groups. The optical density (OD) value was lower in the PKM2-shRNA group than in the blank and vector groups. These findings indicate that shRNA-mediated silencing of PKM2 gene promotes apoptosis and inhibits aerobic glycolysis, proliferation, migration, and invasion in CRC cells. J. Cell. Biochem. 118: 4792-4803, 2017. © 2017 Wiley Periodicals, Inc.


Presentation, diagnosis, and medical management of heart failure in children: Canadian Cardiovascular Society guidelines.
Pediatric heart failure (HF) is an important cause of morbidity and mortality in childhood. This article presents guidelines for the recognition, diagnosis, and early medical management of HF in infancy, childhood, and adolescence. The guidelines are intended to assist practitioners in office-based or emergency room practice, who encounter children with undiagnosed heart disease and symptoms of possible HF, rather than those who have already received surgical palliation. The guidelines have been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and are accompanied by practical Recommendations for their application in the clinical setting, supplemented by online material. This work does not include Recommendations for advanced management involving ventricular assist devices, or other device therapies.


Continued growth of Escherichia coli after stopping medium addition to a K+-limited chemostat culture.
The steady-state bacterial dry wt of Escherichia coli, growing under K+-limited conditions in the chemostat, was inversely dependent on the growth rate. This phenomenon was more carefully investigated in medium-flow stop experiments. Growth did not stop immediately but continued for a time, initially at the same rate as before. The dry wt increased to a value corresponding to a steady-state growth rate near zero, independent of the initial specific growth rate. This was observed in both the wild-type strain and a mutant that lacked the high-affinity K+ uptake system. The wild-type strain maintained a low extracellular K+ concentration both in the chemostat under steady-state conditions and after stopping the medium flow. The mutant, on the other hand, maintained a much higher extracellular K+ concentration in the steady state, which decreased to much lower values after stopping the medium flow. From the increase in bacterial dry wt and the low external K+ concentration after stopping the medium flow it is concluded that the intracellular K+ is redistributed among the cells, including new cells. The growth yield on K+ was highest in the stationary growth phase of a batch culture and all steady-state cultures converged ultimately to this yield value after the medium flow had been stopped. It is proposed that the growth rate of E. coli under K+-limited conditions is determined by the intracellular K+ concentration.


Effect of Different Composite Restorations on the Cuspal Deflection of Premolars Restored with Different Insertion Techniques- An In vitro Study.
This study was conducted to assess the effect of different composite materials on the cuspal deflection of premolars restored with bulk placement of resin composite in comparison to horizontal incremental placement and modified tangential incremental placement. The aim of this study was to evaluate the cuspal deflection caused by different composite materials when different insertion techniques were used. Two different composite materials were used that is Tetric N Ceram (Ivoclar Vivadent marketing, India) and SonicFillTM (Kerr Sybron Dental). Forty standardized Mesio-Occluso-Distal (MOD) preparations were prepared on maxillary first premolars. Each group was divided according to composite insertion technique (n=10), as follows: Group I - bulk insertion using Tetric N Ceram, Group II - Horizontal incremental insertion technique using Tetric N Ceram, Group III- Modified tangential incremental technique using Tetric N Ceram, and Group IV- bulk insertion using SonicFillTM. Preparations were acid-etched, and bonded with adhesive resin to provide micro mechanical attachment before restoration using a uniform etching and bonding protocol in all the groups. All groups received the same total photo-polymerization time. Cuspal deflection was measured during the restorative procedure using customized digital micrometer assembly. One-way ANOVA test was applied for the analysis of significant difference between the groups, p-value less than 0.05 was considered statistically significant. The average cuspal deflections for the different groups were as follows: Group I 0.045±0.018, Group II 0.029±0.009, Group III 0.018±0.005 and Group IV 0.017±0.004. The intergroup comparison revealed statistically significant difference. A measurable amount of cuspal deflection was present in all the four studied groups. In general, bulkfill restoration technique with conventional composite showed significantly highest cusp deflection. There were no significant differences in cuspal deflection among sonicFillTM and modified tangential incremental insertion techniques.


Induction for senior house officers. Part II: The departmental programme.
This study was designed to examine the content and usefulness of departmental induction programmes to senior house officers (SHOs) and to explore perceptions of the usefulness of a range of topics to these trainees. A total of 64 SHOs, in five hospitals in the Anglia region, participated in semi-structured interviews up to 3 months after starting their post. The interviews investigated the content of any induction received and also examined what the trainees would have liked to have received. Almost half (29) of the SHOs also completed a questionnaire which examined the perceived usefulness of various induction topics for a trainee starting a new post. The results showed that, although a departmental induction programme is considered important and highly valued, a substantial minority of SHOs had not received one. Of this minority, 75% would have welcomed an induction. Where an induction had taken place, the focus was primarily upon timetables, tours and meeting people, however, a quarter of the questionnaire sample had not received a service timetable, a third had not met any consultants, two-thirds had received no introduction to clinical management, and two-thirds had received no information about how their consultants manage their patients. Thus, although many trainees receive an induction, important information may not be covered. A staged approach to departmental induction is recommended, using a short, high-quality, and comprehensive induction programme. Flexible and timely programmes, supported by comprehensive written information, will contribute to meeting the needs of trainees in an efficient and effective way.


Percutaneous transplantation of human umbilical cord blood-derived multipotent stem cells in a canine model of spinal cord injury.
The authors describe a method for percutaneous transplantation of human umbilical cord blood (hUCB)-derived multipotent stem cells (MSCs) under fluoroscopic guidance. The investigators then tested whether percutaneous transplantation of hUCB-derived MSCs improved neurological functional recovery after acute spinal cord injury (SCI). The authors induced SCI in 10 dogs by percutaneous balloon compression. The 10 injured dogs were assigned randomly to the following groups (2 dogs each): Group 1, evaluated 2 weeks after sham transplantation; Group 2, evaluated 2 weeks after transplantation; Group 3, evaluated 4 weeks after sham transplantation; Group 4, evaluated 4 weeks after transplantation; and Group 5, evaluated 4 weeks after multispot transplantations. The dogs with sham transplantation (Groups 1 and 3) received the same volume of saline, as a control. A spinal needle was advanced into the spinal canal, and the investigators confirmed that the end of the spinal needle was located in the ventral part of spinal cord parenchyma by using contrast medium under fluoroscopic guidance. The hUCB-derived MSCs were transplanted into the cranial end of the injured segment in 6 injured dogs at 7 days after SCI. Two dogs in Group 2 showed no improvement until 2 weeks after transplantation. Three of 4 dogs (Groups 4 and 5) that received cellular transplants exhibited gradual improvement in hindlimb locomotion from 3 weeks after cell transplantation. The CM-DiI-labeled hUCB-derived MSCs were observed in the spinal cord lesions at 4 weeks posttransplantation and exerted a significant beneficial effect by reducing cyst and injury size. The transplanted cells were positive for NeuN, glial fibrillary acidic protein, and von Willebrand factor. The percutaneous transplantation technique described here can be easily performed, and it differs from previous techniques by avoiding surgical exposure and allowing cells to be more precisely transplanted into the spinal cord. This technique has many potential applications in the treatment of human SCI by cell transplantation. The results also suggest that transplantation of hUCB-derived MSCs may have therapeutic effects that decrease cavitation for acute SCI.


Medical expenditures of terminal cancer patients during the last year of life.
To measure the patterns of medical expenditures under conventional modes of cancer care for the terminally ill, we examined Blue Cross and Blue Shield Plan claims records for care during the 12 months preceding the deaths of 1,054 nonelderly patients diagnosed as having breast, colon-rectal, or lung cancer. Expenditures averaged +21,219 for the terminal year and grew exponentially as death approached, with +6,161 (29%) being spent in the final month alone. We found very few significant differences in spending or utilization by diagnosis, age, or sex of the terminal patient, but sizable differences by state of residence and between nonmetropolitan and metropolitan area residents. Our findings represent a baseline against which experience under new hospital payment strategies and alternative delivery systems might be compared.


Topical Oxygen Therapy for Wound Healing: A Critical Evaluation.
Oxygen is an undisputed key factor in wound healing. Adequate oxygen pressure in tissues allows for cell growth and proliferation, necessary for wound healing. In the case of peripheral arterial disease leading to hypoxemia, oxygen supplementation is beneficial. The roles and validity of topical and systemic oxygen therapy in wound healing is debated. Topical oxygen therapy (TOT) is delivered at 100% oxygen saturation and has been demonstrated to increase the pO2 levels within the wound base center, decrease the size of the wound, and decrease the time to wound healing compared to patients that did not undergo topical oxygen therapy. Alternatives to topical oxygen therapy are systemic oxygen therapy including hyperbaric oxygen therapy and inspired oxygen therapy. Systemic oxygen therapy carries the risk of oxygen organ toxicity as the result of an oxidative stress and genotoxicity state. Topical O2 therapy is a viable option for chronic wounds, with its demonstrated effects on decrease in wound size and time to healing. Adjunctive clinical wound debridement's decrease the necrotic debris and therefore the topical oxygen diffusion distance optimizing the therapy effect.


Assessment of angiographic vascularity of meningiomas with dynamic susceptibility contrast-enhanced perfusion-weighted imaging and diffusion tensor imaging.
The roles of DTI and dynamic susceptibility contrast-enhanced-PWI in predicting the angiographic vascularity of meningiomas have not been studied. We aimed to investigate if these 2 techniques could reflect the angiographic vascularity of meningiomas. Thirty-two consecutive patients with meningiomas who had preoperative dynamic susceptibility contrast-enhanced-PWI, DTI, and conventional angiography were retrospectively included. The correlations between angiographic vascularity of meningiomas, classified with a 4-point grading scale, and the clinical or imaging variables-age and sex of patient, as well as size, CBV, fractional anisotropy, and ADC of meningiomas-were analyzed. The meningiomas were dichotomized into high-vascularity and low-vascularity groups. The differences in clinical and imaging variables between the 2 groups were compared. Receiver operating characteristic curve analysis was used to determine the diagnostic performance of these variables. In meningiomas, angiographic vascularity correlated positively with CBV but negatively with fractional anisotropy. High-vascularity meningiomas demonstrated significantly higher CBV but lower fractional anisotropy as compared with low-vascularity meningiomas. In differentiating between the 2 groups, the area under the curve values were 0.991 for CBV and 0.934 for fractional anisotropy on receiver operating characteristic curve analysis. CBV and fractional anisotropy correlate well with angiographic vascularity of meningiomas. They may differentiate between low-vascularity and high-vascularity meningiomas.


Independent living skills and posttraumatic stress disorder in women who are homeless: implications for future practice.
Service delivery through community-based programs is the future of occupational therapy. This study examined independent living skills, traumatic experiences, and symptoms of Posttraumatic Stress Disorder (PTSD) in a sample of women residing in a supportive housing program for women and families who are homeless in order to determine the needs of this population and the possible role of occupational therapy in such a community-based program. Twenty-four women residing in a supportive housing shelter in Kansas City, Missouri, volunteered to participate in this study. The participants were evaluated for independent living skills with the Kohlman Evaluation of Living Skills. A structured interview format was used to determine whether participants experienced a trauma and whether they met diagnostic criteria for PTSD. Results indicated that women who are homeless have deficits in independent living skills, especially in the area of money management. Results also indicated that traumatic experiences and PTSD are more prevalent among women who are homeless than among women in the general population. The relationship between independent living skills and PTSD among women who are homeless was not made clear by this study. The information gathered in this study underscores the importance of identifying and addressing occupational and mental health issues of women who are homeless. Results suggest that occupational therapists have a major role to play, evaluating and facilitating independent living skills, as members of multidisciplinary treatment teams in supportive housing programs for persons who are homeless.


Th17 cells contribute to nontypeable Haemophilus influenzae-specific protective immunity induced by nasal vaccination with P6 outer membrane protein and α-galactosylceramide.
Nasal vaccination is an effective therapeutic means of preventing upper respiratory infection. Recently, nasal vaccination with P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) and alpha-galactosylceramide (α-GalCer) was reported to induce NTHi-specific protective immunity. The present study investigated the role of the Th17 cells induced by nasal vaccination. Mice were immunized with P6 and α-GalCer, and their P6-specific immune responses were examined. Cytokine-producing cells were analyzed by flow cytometry, and expression of cytokines in P6-specific CD4+ T cells was determined by reverse transcription-polymerase chain reaction. Bacterial challenges were performed with live NTHi. To examine the role of Th17 cells, bacterial clearance was also evaluated after interleukin (IL)-17 neutralization. P6-specific nasal wash immunoglobulin (Ig) A and serum IgG were increased after immunization with P6 and α-GalCer. Specific IgA-producing cells increased markedly in the nasal passages (NPs) of the immunized mice. In addition to P6-specific Th1 and Th2 cells, IL-17-producing Th17 cells were induced in the NPs and spleen. Bacterial clearance was enhanced by nasal vaccination. Interestingly, impaired NTHi clearance was shown after IL-17 neutralization. These findings suggest that nasal vaccination with P6 and α-GalCer is an effective regimen for the induction of NTHi-specific protective immunity in the upper respiratory tract. In addition to antigen-specific secretory-IgA, specific Th17 cells induced by nasal vaccination contribute to protection against NTHi.


Postmenopausal estrogen therapy and depressive symptoms in older women.
Evidence regarding the effect of postmenopausal estrogen therapy on mood is limited. To determine whether postmenopausal estrogen therapy is associated with fewer depressive symptoms in elderly women, we conducted a cross-sectional study of 6, 602 white women ages 71 years or older who were recruited from population-based listings in Baltimore, Md; Minneapolis, Minn; Portland, Ore; and the Monongahela Valley, Pa. Use of estrogen and progestin was determined by interview. Participants completed the Geriatric Depression Scale short form (GDS) and were considered depressed if they reported 6 or more of 15 possible symptoms of depression. A total of 6.3% (72/1,150) of current estrogen users, 7.2% (142/1,964) of past estrogen users, and 9.0% (313/3,488) of never users reported 6 or more symptoms of depression (P =.004). Current estrogen users had a decreased risk of reporting 6 or more depressive symptoms, compared with not current (past or never) users of estrogen (odds ratio [OR], 0.7; 95% CI, 0.5 to 0.9; P =.01], adjusted for living alone, bilateral oophorectomy, current smoking, physical activity, social network, self-perceived health, cognitive function, functional status, and antidepressant use. However, excluding women who use estrogen or progestin alone, we were unable to find an association between current use of combined estrogen plus progestin therapy and depressive symptoms (adjusted OR, 0.8; 95% CI, 0.5 to 1.4; P =.5). This cross-sectional study found that current use of unopposed estrogen was associated with a decreased risk of depressive symptoms in older women. Additional studies are needed to understand the effect of combined estrogen and progestin therapy on the prevalence of depressive symptoms in older women.


Pelvic inflammatory disease: improving awareness, prevention, and treatment.
Pelvic inflammatory disease (PID) is a common disorder of the reproductive tract that is frequently misdiagnosed and inadequately treated. PID and its complications, such as infertility, ectopic pregnancy, and chronic pelvic pain, are preventable by screening asymptomatic patients for sexually transmitted infections (STIs) and promptly treating individuals with STIs and PID. The rates of adverse outcomes in women with PID are high and disproportionately affect young minority women. There are key opportunities for prevention including improving provider adherence with national screening guidelines for STIs and PID treatment recommendations and patient medication adherence. Nearly half of all eligible women are not screened for STIs according to national quality standards, which may increase the risk of both acute and subclinical PID. Moreover, in clinical practice, providers poorly adhere to the Centers for Disease Control and Prevention recommendations for treatment of PID. Additionally, patients with PID struggle to adhere to the current management strategies in the outpatient setting. Novel evidence-based clinical and public health interventions to further reduce the rates of PID and to improve outcomes for affected women are warranted. We propose potential cost-effective approaches that could be employed in real-world settings.


Controlling feature selection in random forests of decision trees using a genetic algorithm: classification of class I MHC peptides.
Feature selection is an important challenge in many classification problems, especially if the number of features greatly exceeds the number of examples available. We have developed a procedure--GenForest--which controls feature selection in random forests of decision trees by using a genetic algorithm. This approach was tested through our entry into the Comparative Evaluation of Prediction Algorithms 2006 (CoEPrA) competition (accessible online at: http://www.coepra.org). CoEPrA was a modeling competition organized to provide an objective testing for various classification and regression algorithms via the process of blind prediction. In the competition GenForest ranked 10/23, 5/16 and 9/16 on CoEPrA classification problems 1, 3 and 4, respectively, which involved the classification of type I MHC nonapeptides i.e. peptides containing nine amino acids. These problems each involved the classification of different sets of nonapeptides. Associated with each amino acid was a set of 643 features for a total of 5787 features per peptide. The method, its application to the CoEPrA datasets, and its performance in the competition are described.


Extremely sensitive and selective NO probe based on villi-like WO3 nanostructures for application to exhaled breath analyzers.
Self-assembled WO3 thin film nanostructures with 1-dimensional villi-like nanofingers (VLNF) have been synthesized on the SiO2/Si substrate with Pt interdigitated electrodes using glancing angle deposition (GAD). Room-temperature deposition of WO3 by GAD resulted in anisotropic nanostructures with large aspect ratio and porosity having a relative surface area, which is about 32 times larger than that of a plain WO3 film. A WO3 VLNF sensor shows extremely high response to nitric oxide (NO) at 200 °C in 80% of relative humidity atmosphere, while responses of the sensor to ethanol, acetone, ammonia, and carbon monoxide are negligible. Such high sensitivity and selectivity to NO are attributed to the highly efficient modualtion of potential barriers at narrow necks between individual WO3 VLNF and the intrinsically high sensitivity of WO3 to NO. The theoretical detection limit of the sensor for NO is expected to be as low as 88 parts per trillion (ppt). Since NO is an approved biomarker of chronic airway inflammation in asthma, unprecedentedly high response and selectivity, and ppt-level detection limit to NO under highly humid environment demonstrate the great potential of the WO3 VLNF for use in high performance breath analyzers.


Measurement of Neurophysiological Signals of Ignoring and Attending Processes in Attention Control.
Attention control is the ability to selectively attend to some sensory signals while ignoring others. This ability is thought to involve two processes: enhancement of sensory signals that are to be attended and the attenuation of sensory signals that are to be ignored. The overall strength of attentional modulation is often measured by comparing the amplitude of a sensory neural response to an external input when attended versus when ignored. This method is robust for detecting attentional modulation, but precludes the ability to assess the separate dynamics of attending and ignoring processes. Here, we describe methodology to measure independently the neurophysiological signals of attending and ignoring using the intermodal attention task (IMAT). This task, when combined with electroencephalography, isolates neurophysiological sensory responses in auditory and visual modalities, when either attending or ignoring, with respect to a passive control. As a result, independent dynamics of attending and of a ignoring can be assessed in either modality. Our results using this task indicate that the timing and cortical sources of attending and ignoring effects differ, as do their contributions to the attention modulation effect, pointing to unique neural trajectories and demonstrating sample utility of measuring them separately.


Conservative therapy for appendicitis in children.
Question A 10-year-old girl who was seen in my office last week with acute-onset abdominal pain and fever was referred to an emergency department, was diagnosed with appendicitis, and was treated conservatively with antibiotics, without surgery. Has the paradigm for treating appendicitis changed, and which is the preferred treatment of appendicitis in children: antibiotics or appendectomy?Answer For more than 100 years, surgical management was the principal treatment of acute appendicitis. Potential adverse events associated with appendectomy include bleeding, surgical site infection, and ileus, as well as stress for children and their parents. The option of treating appendicitis with antibiotics has been known for decades, which has led to consideration of antibiotics alone as a therapeutic alternative to surgery for uncomplicated appendicitis. While there is a reasonable body of evidence in support of this practice in adults, the accumulation of evidence of the safety and effectiveness of non-operative management in children is ongoing. Large studies are still needed, and those are being conducted at this time, with results expected in the next few years.


Rearing Pigs with Intact Tails-Experiences and Practical Solutions in Sweden.
Tail biting is a common issue within commercial pig production. It is mainly an indicator of inadequate housing environment and results in reduced health welfare and production. To reduce the impact of tail biting, pigs are commonly tail docked, without pain relief, within the first week of life. EU Council Directive 2008/120/EC prohibits routine tail docking, but the practice is still widely used in many Member States. Sweden has banned tail docking since 1988 and all pigs have intact tails, yet tail biting is a minor problem. This paper summarises and synthesises experimental findings and practical expertise in production of undocked pigs in Sweden and describes solutions to facilitate a transition to producing pigs with intact tails within intensive pig production in the EU. Swedish pig housing conditions and management differ in many aspects from those in other EU Member States. Swedish experiences show that lower stocking density, provision of sufficient feeding space, no fully slatted flooring, strict maximum levels for noxious gases and regular provision of litter material are crucial for success when rearing pigs with intact tails. To prevent tail biting and to eliminate the need for tail docking, we strongly recommend that EU legislation should more clearly match the biological needs of pigs, as is done in Swedish legislation.


Maximizing prosthetic valve size with the Top Hat supra-annular aortic valve.
The CarboMedics Top Hat supra-annular aortic valve allows a one-size (and often two-size) increase over the standard intra-annular valve. This advantage should minimize the risk of patient-prosthesis mismatch, where the effective prosthetic valve orifice area is less than that of a normal valve. It is suggested that the ability to implant Top Hat valves having greater size, relative to standard intra-annular valves, may currently be under-utilized. Further, there has been some concern that Top Hat implantation can cause obstruction of the coronary ostia. This study evaluates the authors' clinical experience with Top Hat supra-annular aortic valve size selection, and the technical aspects of implantation. Between January 1999 and October 2005, a total of 251 consecutive patients underwent 252 aortic valve replacements with Top Hat supra-annular mechanical prostheses (CarboMedics, Inc., Arvada, CO, USA) at two institutions. Size frequency distribution was compared to published series, and to the manufacturer's US registry. The ventriculoaortic junction (VAJ) size was available in 234 patients, and compared to the size of the Top Hat valve implanted. Valves implanted were 2 mm larger than the VAJ in 56% of patients (130/234), 3 mm larger in 1.7% (4/234), and 4 mm larger in 42% (98/234). Numbers of 19-mm and 21-mm valves were less (p <0.001) in the present series (22%) than in published series (52%) and the US registry (46%). No patient required unplanned coronary bypass, and 30-day mortality was 2.0% (5/251), indicating a good safety profile for the valves implanted in this series. The general distribution of implant sizes in the US indicates that cardiac surgeons may be under-sizing the Top Hat supra-annular aortic valve during aortic valve replacement, thereby missing the full advantage of its unique design for lowering the transvalvular gradient and, consequently, left ventricular workload, leading to a reversal of left ventricular hypertrophy.


Cost and Clinical Benefits Associated with Oncotype DX® Test in Patients with Early-Stage HR+/HER2- Node-Negative Breast Cancer in the Netherlands.
Patients with early-stage HR+/HER2- N0 breast cancer may receive adjuvant chemotherapy in combination with surgery. However, chemotherapy does not always lead to improved survival and incurs high healthcare costs and increased adverse events. To support decision-making regarding adjuvant chemotherapy, genomic profile testing performed with tests such as the Oncotype DX® test can help healthcare practitioners decide whether chemotherapy provides any benefit to these patients. As such, a cost-consequence model was developed with the aim to estimate the economic impact of using different gene expression tests or no testing, in patients with node-negative early-stage breast cancer. A cost-consequence model was developed to estimate the economic impact of three different scenarios in the Dutch setting: (1) Oncotype DX® test, (2) MammaPrint®, and (3) and no genomic profile testing. The model included chemotherapy costs, administration costs, short- and long-term adverse event costs, productivity loss, genomic profiling testing costs, cost of cancer recurrence, and hospitalization costs. A treatment paradigm with Oncotype DX resulted in average savings per patient of €6,768 vs. a paradigm with MammaPrint and €13,125 vs. a paradigm with no genomic testing. Furthermore, due to less patients receiving adjuvant chemotherapy through better targeting by the Oncotype DX test, fewer adverse events, sick days, practice visits, and hospitalizations were required compared to MammaPrint and no genomic profiling. Testing with Oncotype DX test in Dutch clinical practice in patients with early-stage breast cancer proved to be cost-saving versus MammaPrint and no genomic profiling tests. Introducing the Oncotype DX test to the Dutch setting will likely reduce the economic resources that are required.


Prevalence and Risk Factors of Hookworm-Related Cutaneous Larva Migrans (HrCLM) in a Resource-Poor Community in Manaus, Brazil.
Hookworm-related cutaneous larva migrans (HrCLM) is a neglected tropical skin disease associated with significant clinical pathology. Little knowledge exists about prevalence and risk factors of HrCLM in endemic regions. To understand the epidemiology of HrCLM in Amazonia, we conducted a cross-sectional study in a resource-poor township in Manaus, Brazil. HrCLM was diagnosed in 8.2% (95% CI, 6.3-10.1%) of the study population (N = 806) with a peak prevalence of 18.2% (95% CI, 9.3-27.1%) in children aged 10-14. Most of the tracks (62.4%) were located on the feet, and 10.6% were superinfected. HrCLM was associated independently with age under 15, male sex, presence of animal faeces on the compound, walking barefoot on sandy ground and poverty. HrCLM is common in resource-poor communities in Amazonia and is related to poverty. To reduce the disease burden caused by HrCLM, living conditions have to be improved.


Origin of biquadratic exchange in Fe/Si/Fe
The thickness and temperature dependences of the interlayer exchange coupling in well-defined molecular beam epitaxy-grown Fe/Si/Fe sandwich structures have been studied. The biquadratic coupling shows a strong temperature dependence in contrast to the bilinear coupling. Both depend exponentially on thickness. These observations can be well understood in the framework of Slonczewski's loose spins model [J. Appl. Phys. 73, 5957 (1993)]. No bilinear contribution of the loose spins to the coupling was observed.


Prolonged NMDA-mediated responses, altered ifenprodil sensitivity, and epileptiform-like events in the malformed hippocampus of methylazoxymethanol exposed rats.
Cortical malformations are often associated with refractory epilepsy and cognitive deficit. Clinical and experimental studies have demonstrated an important role for glutamate-mediated synaptic transmission in these conditions. Using whole cell voltage-clamp techniques, we examined evoked glutamate-mediated excitatory postsynaptic currents (eEPSCs) and responses to exogenously applied glutamate on hippocampal heterotopic cells in an animal model of malformation i.e., rats exposed to methylazoxymethanol (MAM) in utero. Analysis revealed that the late N-methyl-D-aspartate (NMDA) receptor-mediated eEPSC component was significantly increased on heterotopic cells compared with age-matched normotopic pyramidal cells. At a holding potential of +40 mV, heterotopic cells also exhibited eEPSCs with a slower decay-time constant. No differences in the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) component of eEPSCs were detected. In 23% of heterotopic pyramidal cells, electrical stimulation evoked prolonged burst-like responses. Focal application of glutamate (10 mM) targeted to different sites near the heterotopia also evoked epileptiform-like bursts on heterotopic cells. Ifenprodil (10 microM), an NR2B subunit antagonist, only slightly reduced the NMDA receptor (NMDAR)-mediated component and amplitude of eEPSCs on heterotopic cells (MAM) but significantly decreased the late component and peak amplitude of eEPSCs in normotopic cells (control). Our data demonstrate a functional alteration in the NMDA-mediated component of excitatory synaptic transmission in heterotopic cells and suggest that this alteration may be attributable, at least in part, to changes in composition and function of the NMDAR subunit. Changes in NMDAR function may directly contribute to the hyperexcitability and cognitive deficits reported in animal models and patients with brain malformations.


Hepatic prohibitin 1 and methionine adenosyltransferase α1 defend against primary and secondary liver cancer metastasis.
Liver is a common site of cancer metastasis (a.k.a. secondary liver cancer, most commonly from colorectal cancer (CRC)) and primary liver cancers that have metastasized have poor prognosis. The underlying mechanisms of how the liver defends against these processes are largely unknown. Prohibitin 1 (PHB1) and methionine adenosyltransferase 1A (MAT1A) are highly expressed in the liver. They positively regulate each other and their deletion results in primary liver cancer. Here we investigated their roles in primary and secondary liver cancer metastasis. We identified common target genes of PHB1 and MAT1A using metastasis array, used luciferase reporter assay and chromatin immunoprecipitation to measure promoter activity and transcription factors binding. We examined how PHB1 or MAT1A loss promotes liver cancer metastasis and whether their loss sensitizes to CRC liver metastasis (CRLM). Matrix metalloproteinase-7 (MMP-7) is a common target of MAT1A and PHB1 and its induction is responsible for increased migration and invasion when MAT1A or PHB1 is silenced. Mechanistically, PHB1 and MAT1A negatively regulate the MMP-7 promoter activity via an AP-1 site by repressing the MAFG-FOSB complex. Loss of MAT1A or PHB1 also increased MMP-7 in extracellular vesicles, which was internalized by colon and pancreatic cancer cells to enhance their oncogenicity. Low hepatic MAT1A or PHB1 expression sensitized to CRLM, but not if endogenous hepatic MMP-7 was knocked down first, which lowered CD4+ T cells while increasing CD8+ T cells in the tumor microenvironment. Hepatocytes co-cultured with CRC express less MAT1A/PHB1 but higher MMP-7. Consistently, CRLM raised distant hepatocytes' MMP-7 expression in mice and humans. We have identified an PHB1/MAT1A-MAFG/FOSB-MMP-7 axis that controls primary liver cancer metastasis and sensitization to CRLM.


The significance of endothelial heterogeneity in thrombosis and hemostasis.
The endothelium is recognized today as a functional and dynamic component of the body that plays an important part in health and disease. This article briefly reviews the role of endothelium in thrombosis and hemostasis. There is a paradigm shift from one that regards the endothelium as one single entity to the concept that the endothelium is heterogeneous. Thrombotic complications in many disorders show a predilection to specific locations, despite the fact that a hypercoagulable state affects the entire body. Likewise, bleeding is more commonly encountered in certain anatomical locations than in others. Recent observations of the heterogeneous distribution of coagulation and fibrinolytic factors in the endothelium and the adaptation of the endothelium to various stimuli may provide an explanation for the diverse phenotypes. Recognition of this changing paradigm is helpful to for the diagnosis and management of bleeding and thrombotic complications. It also helps in the understanding of the pathogenesis of many bleeding and thrombotic disorders, and in the development of new drug designs for site-specific therapy.


Effect of pentobarbital anesthesia on amikacin concentrations in plasma and perilymph and evaluation of multiple sampling in perilymph of guinea pigs.
The purpose of this study was to determine whether a multiple-sampling procedure could be used in guinea pigs to study the kinetics of amikacin in perilymph. Amikacin was infused intravenously for 6 h into conscious anesthetized guinea pigs, and the concentrations of the drug in plasma and perilymph were measured. From each anesthetized guinea pig, five to six perilymph samples were collected from one ear, and one sample was collected from the other ear at 6 h. The concentrations of amikacin in perilymph were dose proportional and increased slowly during the 6-h infusion. However, after 6 h of intravenous infusion, the concentrations of amikacin in perilymph of the multiply sampled ears were significantly higher than those of the singly sampled ears, indicating that the multiple-sampling procedure should not be used as is to study the kinetics of amikacin in perilymph. Amikacin concentrations in perilymph were linearly related to amikacin concentrations in plasma in pentobarbital-anesthetized animals, as had previously been observed for conscious guinea pigs. However, the slope of the regression line was only 0.09 for anesthetized animals compared with 0.24 for conscious animals. Drug concentrations in plasma were found to be threefold higher in anesthetized animals, whereas drug levels in perilymph were the same in both groups at similar dosing rates. These results indicate that the amikacin concentration in perilymph is not solely dependent upon its concentration in plasma and that other factor(s) can affect the entry of amikacin into the inner ear.


Short-term glucocorticoid-related side effects and adverse reactions: a narrative review and practical approach.
Glucocorticoids are the mainstay treatment of a variety of inflammatory and autoimmune disorders. Unfortunately, metabolic side effects, drug interactions and adverse reactions commonly lead to glucocorticoid-related side effects, thereby compromising their intended anti-inflammatory and immunosuppressive effects. The goal of this review is to help clinicians to monitor the broad spectrum of side effects of short-term systemic glucocorticoid administration, defined as glucocorticoid treatment shorter than 30 days. We review the various systems affected, with a focus on metabolic conditions and hyperglycaemia management.


Glass capillary tube feeding: a method for infecting nymphal Ixodes scapularis (Acari: Ixodidae) with the lyme disease spirochete Borrelia burgdorferi.
We evaluated an artificial capillary feeding method to infect nymphal Ixodes scapularis (Say) ticks with Borrelia burgdoeferi, the causative agent of Lyme disease. Thirty to 70% of the nymphs were infected after feeding for 2.5 h from glass capillary tubes filled with a solution of spirochetes. Capillary infection was stable and persisted in the nymphs for at least 10 d after feeding. Capillary feeding also maintained natural vector competence patterns because I. scapularis ticks acquired infection unlike Dermacentor variablis (Say), which did not become infected. Capillary infected I. scapularis nymphs were capable of transmitting the infection to naive mice although not as efficiently as naturally infected nymphs. The capillary infection method is convenient and is a better alternative to syringe inoculation as a means of infecting animals with B. burgdorferi.


Classification of the Excitation Location of Snore Sounds in the Upper Airway by Acoustic Multifeature Analysis.
Obstructive sleep apnea (OSA) is a serious chronic disease and a risk factor for cardiovascular diseases. Snoring is a typical symptom of OSA patients. Knowledge of the origin of obstruction and vibration within the upper airways is essential for a targeted surgical approach. Aim of this paper is to systematically compare different acoustic features, and classifiers for their performance in the classification of the excitation location of snore sounds. Snore sounds from 40 male patients have been recorded during drug-induced sleep endoscopy, and categorized by Ear, Nose & Throat (ENT) experts. Crest Factor, fundamental frequency, spectral frequency features, subband energy ratio, mel-scale frequency cepstral coefficients, empirical mode decomposition-based features, and wavelet energy features have been extracted and fed into several classifiers. Using the ReliefF algorithm, features have been ranked and the selected feature subsets have been tested with the same classifiers. A fusion of all features after a ReliefF feature selection step in combination with a random forests classifier showed the best classification results of 78% unweighted average recall by subject independent validation. Multifeature analysis is a promising means to help identify the anatomical mechanisms of snore sound generation in individual subjects. This paper describes a novel approach for the machine-based multifeature classification of the excitation location of snore sounds in the upper airway.


Fibrous matrices facilitate pleurocidin killing of wound associated bacterial pathogens.
Conventional wound infection treatments neither actively promote wound healing nor address the growing problem of antibacterial resistance. Antimicrobial peptides (AMPs) are natural defense molecules, released from host cells, which may be rapidly bactericidal, modulate host-immune responses, and/or act as endogenous mediators for wound healing. However, their routine clinical use has hitherto been hindered due to their instability in the wound environment. Here we describe an electrospun carrier system for topical application of pleurocidin, demonstrating sufficient AMP release from matrices to kill wound-associated pathogens including Acinetobacter baumannii and Pseudomonas aeruginosa. Pleurocidin can be incorporated into polyvinyl alcohol (PVA) fiber matrices, using coaxial electrospinning, without major drug loss with a peptide content of 0.7% w/w predicted sufficient to kill most wound associated species. Pleurocidin retains its activity on release from the electrospun fiber matrix and completely inhibits growth of two strains of A. baumannii (AYE; ATCC 17978) and other ESKAPE pathogens. Inhibition of P. aeruginosa strains (PAO1; NCTC 13437) is, however, matrix weight per volume dependent, with only larger/thicker matrices maintaining complete inhibition. The resulting estimation of pleurocidin release from the matrix reveals high efficiency, facilitating a greater AMP potency. Wound matrices are often applied in parallel or sequentially with the use of standard wound care with biocides, therefore the presence and effect of biocides on pleurocidin potency was tested. It was revealed that combinations displayed additive or modestly synergistic effects depending on the biocide and pathogens which should be considered during the therapy. Taken together, we show that electrospun, pleurocidin-loaded wound matrices have potential to be investigated for wound infection treatment.


In delicate balance: stem cells and spinal cord injury advocacy.
Spinal cord injury (SCI) is a major focus for stem cell therapy (SCT). However, the science of SCT has not been well matched with an understanding of perspectives of persons with SCI. The online advocacy community is a key source of health information for primary stakeholders and their caregivers. In this study, we sought to characterize the content of SCI advocacy websites with respect to their discussion of SCT and stem cell tourism. We performed a comprehensive analysis of SCI advocacy websites identified through a web search and verified by expert opinion. Two independent researchers coded the information for major themes (e.g., scientific & clinical facts, research & funding, policy, ethics) and valence (positive, negative, balanced, neutral). Of the 40 SCI advocacy websites that met inclusion criteria, 50% (N=20) contained information about SCT. Less than 18% (N=7) contained information on stem cell tourism. There were more than ten times as many statements about SCT with a positive valence (N=67) as with a negative valence (N=6). Ethics-related SCT information comprised 20% (N=37) of the total content; the largest proportion of ethics-related content was devoted to stem cell tourism (80%, N=30 statements). Of those, the majority focused on the risks of stem cell tourism (N=16). Given the still-developing science behind SCT, the presence of cautionary information about stem cell tourism at advocacy sites is ethically appropriate. The absence of stem cell tourism information at the majority of advocacy sites represents a lost educational opportunity.


Dural band pathology in syringomyelia with Chiari type I malformation.
Surgical material taken from the 'outer layer' of thickened dura mater (dural band) at the craniovertebral junction of eight cases of syringomyelia with Chiari type I malformation was histologically examined in comparison with four autopsy cases as controls. The dural band was thickened and there were increased numbers of collagen fibers which showed fiber splitting, hyalinous nodule, calcification and/or ossification. These changes were not observed in the four control cases. Thus, it is suggested that the thickening of the dura mater may be a causative factor of syringomyelia with Chiari type I malformation. In addition, the histology of the thickened dura mater suggests the condition may be a consequence of birth injury in these patients.


[New applications of erythropoietin in cardiovascular disease: from haematopoiesis to cardiac protection].
Anaemia is common in patients with heart failure and is associated with poorer prognosis. The aetiology of anaemia in heart failure is diverse and includes renal failure, iron and vitamin deficiency, the use of medication, and insensitivity of the bone marrow to erythropoietin. Recently, small-scale clinical trials investigating the effect of erythropoietin on anaemia showed an improvement in the surrogate cardiovascular endpoints exercise tolerance, haemodynamics and number of hospitalisations. Erythropoietin also has non-haematopoietic (pleiotropic) effects, such as inhibition of apoptosis and neovascularisation. In preclinical studies, erythropoietin had a beneficial effect on heart function following acute myocardial infarction and in heart failure. Currently, these pleiotropic effects are being studied in patients with acute myocardial infarction.


Staffing level: a determinant of late-onset ventilator-associated pneumonia.
The clinical and economic burden of ventilator-associated pneumonia (VAP) is uncontested. We conducted the present study to determine whether low nurse-to-patient ratio increases the risk for VAP and whether this effect is similar for early-onset and late-onset VAP. This prospective, observational, single-centre cohort study was conducted in the medical intensive care unit (ICU) of the University of Geneva Hospitals. All patients who were at risk for ICU-acquired infection admitted from January 1999 to December 2002 were followed from admission to discharge. Collected variables included patient characteristics, admission diagnosis, Acute Physiology and Chronic Health Evaluation II score, co-morbidities, exposure to invasive devices, daily number of patients and nurses on duty, nurse training level and all-site ICU-acquired infections. VAP was diagnosed using standard definitions. Among 2,470 patients followed during their ICU stay, 262 VAP episodes were diagnosed in 209/936 patients (22.3%) who underwent mechanical ventilation. Median duration of mechanical ventilation was 3 days (interquartile range 2 to 6 days) among patients without VAP and 11 days (6 to 19 days) among patients with VAP. Late-onset VAP accounted for 61% of all episodes. The VAP rate was 37.6 episodes per 1,000 days at risk (95% confidence interval 33.2 to 42.4). The median daily nurse-to-patient ratio over the study period was 1.9 (interquartile range 1.8 to 2.2). By multivariate Cox regression analysis, we found that a high nurse-to-patient ratio was associated with a decreased risk for late-onset VAP (hazard ratio 0.42, 95% confidence interval 0.18 to 0.99), but there was no association with early-onset VAP. Lower nurse-to-patient ratio is associated with increased risk for late-onset VAP.


Specific and effective gene knock-down in early chick embryos using morpholinos but not pRFPRNAi vectors.
In the chick embryo, two methods are now used for studying the developmental role of genes by loss-of-function approaches: vector-based shRNA and morpholino oligonucleotides. Both have the advantage that loss-of-function can be conducted in a spatially and temporally controlled way by focal electroporation. Here, we compare these two methods. We find that the shRNA expressing vectors pRFPRNAi, even when targeting a non-expressed protein like GFP, cause morphological phenotypes, mis-regulation of non-targeted genes and activation of the p53 pathway. These effects are highly reproducible, appear to be independent of the targeting sequence and are particularly severe at primitive streak and early somite stages. By contrast, morpholinos do not cause these effects. We propose that pRFPRNAi should only be used with considerable caution and that morpholinos are a preferable approach for gene knock-down during early chick development.


Self-rated mental health and socio-economic background: a study of adolescents in Sweden.
Adolescents' mental health is a major public health issue. Previous research has shown that socio-economic factors contribute to the health status of adolescents. The present study explores the association between socio-economic status and self-rated mental health among adolescents. Cross sectional data from the Halmstad Youth Quality of Life cohort was collected in a town in Sweden. In all, 948 adolescents (11-13 younger age group and 14-16 older age group) participated. Information on self-rated mental health was collected from the subscale Psychological functioning in the Minneapolis Manchester Quality of Life instrument. The items were summarized into a total score and dichotomized by the mean. Indicators measuring socio-economic status (SES) were collected in a questionnaire using the Family Affluence Scale (FAS) and additional factors regarding parents' marital status and migration were added. Logistic models were used to analyze the data. Girls were more likely to rate their mental health below the mean compared to boys. With regard to FAS (high, medium, low), there was a significantly increased risk of self-rated mental health below the mean among younger boys in the medium FAS score OR; 2.68 (95% CI 1.35;5.33) and among older boys in the low FAS score OR; 2.37 (1.02;5.52) compared to boys in the high FAS score. No such trend was seen among girls. For younger girls there was a significant protective association between having parents born abroad and self-rated mental health below mean OR: 0.47 (0.24;0.91). A complex pattern of associations between SES and self-rated mental health, divergent between age and gender groups, was shown. The total FAS score was only associated with boys' self-rated mental health in both age groups, whereas parents' migratory status influenced only the girls' self-rated mental health. Because of the different association for girls' and boys' self-rated mental health and SES, other factors than SES should also be considered when investigating and exploring the mental health of adolescents in affluent communities.