Vascular tissues are a primary source of BMP2 expression during bone formation induced by distraction osteogenesis.
Prior studies showed that bone regeneration during distraction osteogenesis (DO) was dependent on vascular tissue development and that inhibition of VEGFR signaling diminished the expression of BMP2. A combination of micro-computed tomography (μCT) analysis of vascular and skeletal tissues, immunohistological and histological analysis of transgenic mice containing a BAC transgene in which β-galactosidase had been inserted into the coding region of BMP2 and qRT-PCR analysis, was used to examine how the spatial temporal expression of the morphogenetic signals that drive skeletal and vascular tissue development is coordinated during DO. These results showed that BMP2 expression was induced in smooth muscle and vascular endothelial cells of arteries and veins, capillary endothelial cells, hypertrophic chondrocytes and osteocytes. BMP2 was not expressed by lymphatic vessels or macrophages. Separate peaks of BMP2 mRNA expression were induced in the surrounding muscular tissues and the distraction gap and corresponded first with large vessel collateralization and arteriole remodeling followed by periods of angiogenesis in the gap region. Immunohistological and qRT-PCR analysis of VEGF receptors and ligands showed that mesenchymal cells, lining cells and chondrocytes, expressed VEGFA, although PlGF expression was only seen in mesenchymal cells within the gap region. On the other hand VEGFR2 appeared to be predominantly expressed by vascular endothelial and hematopoietic cells. These results suggest that bone and vascular tissue formation is coordinated via a mutually supporting set of paracrine loops in which blood vessels primarily synthesize the morphogens that promote bone formation while mesenchymal cells primarily synthesize the morphogens that promote vascular tissue formation.


A study of changes in everyday mobility during the Covid-19 pandemic: As perceived by people living in Malmö, Sweden.
Sweden's strategy to manage the spread of Covid-19 has not included any form of lockdown, in contrast to the approaches adopted by most other countries. Instead, the strategy has been largely based on strong recommendations for society. Even though Sweden has not had any form of lockdown, the Covid-19 pandemic has during a relatively short period of time brought changes for society, significantly disrupting everyday life. The pandemic poses both challenges and opportunities for sustainable future transport, not least public transport provision, supply and use. The purpose of this study is to investigate how changes for society have translated into changes for mobility as an element of everyday life during the early stages of a pandemic. This study draws on a map-based online survey (public participatory GIS) which was purposefully designed to allow people to contribute with their experiences in order to capture how the current situation has affected several different facets of people's everyday life. Results suggest that effects on mobility, such as the possibility to telework, affect different groups differently and may exacerbate existing differences in terms of gender, geography and mobility. In order to mitigate negative effects, transport policy needs to be tailored in order to take these heterogeneities into account. Both spatio-temporal adjustment and modal adjustment were dominant themes for most activities, although the dominance of these themes varied among the activities. Our findings give an indication of both the short and long-term impacts on everyday mobility in the Swedish context, for groups of inhabitants in the city of Malmö. Through deepening our understanding of the processes at play, we suggest eight possible policy responses that can be carefully tailored, both in the interim and into the future.


The relationship between fMRI activation and cerebral atrophy: comparison of normal aging and alzheimer disease.
Functional MRI has recently been used to examine activation associated with aging and dementia, yet little is known regarding the effect of cerebral atrophy on fMRI signal. The purpose of this study was to examine the relationship between measures of global and regionally specific atrophy and fMRI activation in normal aging and in Alzheimer disease (AD). Two groups of subjects were studied with echoplanar imaging and quantitative structural volumetry: healthy controls spanning a broad age and atrophy range (n = 16) and patients with mild AD (n = 8). Results from a semantic task previously found to activate left inferior frontal (LIFG) and left superior temporal (LSTG) gyri were analyzed. The correlations between clusters of activation in the LIFG and LSTG and measures of local atrophy in the LIFG and LSTG regions were evaluated. For control subjects, there was no significant correlation between activation and regional or total brain atrophy (for LIFG r = -0.03, NS; for LSTG r = 0.20, NS). In contrast, for AD patients, there was a significant positive correlation between atrophy and activation in LIFG (r = 0.70, P = 0.05) but not LSTG (r = 0.00, NS). These results suggest that activation of language regions and atrophy within those regions may be independent among healthy adults spanning a broad age and atrophy range. However, in AD, a relationship exists in the LIFG that may reflect compensatory recruitment of cortical units or disease-specific changes in the hemodynamic response.


From 'omics to otoliths: responses of an estuarine fish to endocrine disrupting compounds across biological scales.
Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and population decline in fishes. However, few studies have linked environmental EDC exposures with responses at multiple tiers of the biological hierarchy, including population-level effects. To this end, we undertook a four-tiered investigation in the impacted San Francisco Bay estuary with the Mississippi silverside (Menidia audens), a small pelagic fish. This approach demonstrated links between different EDC sources and fish responses at different levels of biological organization. First we determined that water from a study site primarily impacted by ranch run-off had only estrogenic activity in vitro, while water sampled from a site receiving a combination of urban, limited ranch run-off, and treated wastewater effluent had both estrogenic and androgenic activity. Secondly, at the molecular level we found that fish had higher mRNA levels for estrogen-responsive genes at the site where only estrogenic activity was detected but relatively lower expression levels where both estrogenic and androgenic EDCs were detected. Thirdly, at the organism level, males at the site exposed to both estrogens and androgens had significantly lower mean gonadal somatic indices, significantly higher incidence of severe testicular necrosis and altered somatic growth relative to the site where only estrogens were detected. Finally, at the population level, the sex ratio was significantly skewed towards males at the site with measured androgenic and estrogenic activity. Our results suggest that mixtures of androgenic and estrogenic EDCs have antagonistic and potentially additive effects depending on the biological scale being assessed, and that mixtures containing androgens and estrogens may produce unexpected effects. In summary, evaluating EDC response at multiple tiers is necessary to determine the source of disruption (lowest scale, i.e. cell line) and what the ecological impact will be (largest scale, i.e. sex ratio).


Genetic analysis of membrane protein topology by a sandwich gene fusion approach.
We describe a cloning vector that allows the construction of phoA sandwich fusions in which mature alkaline phosphatase is inserted into target proteins. In contrast to previous fusions obtained using the TnphoA transposon, the entire amino acid sequence of the target protein is present in the fusion product. We have constructed a series of sandwich fusions of alkaline phosphatase to the multispanning cytoplasmic membrane protein MalF. Despite the fact that the alkaline phosphatase was tethered to MalF at both its N and its C terminus, the enzyme exhibited high activity when it was fused to a periplasmic domain of the membrane protein. Cells harboring an alkaline phosphatase sandwich fusion to the end of the first membrane-spanning segment of MalF exhibited both MalF and alkaline phosphatase activity. When alkaline phosphatase was inserted into a cytoplasmic domain of MalF, its specific activity was very low. Our results suggest that the alkaline phosphatase activity of phoA sandwich fusions provides a more sensitive monitor than previous methods of the cellular localization of the domain of the target protein to which the enzyme is fused. Thus, the sandwich fusion approach can give a more accurate picture of membrane protein topology.


Liver perfusion imaging in patients with primary and metastatic liver malignancy: prospective comparison between 99mTc-MAA spect and dynamic CT perfusion.
To prospectively analyze the correlation between parameters of liver perfusion from technetium99m-macroaggregates of albumin (99mTc-MAA) single photon emission computed tomography (SPECT) with those obtained from dynamic CT perfusion in patients with primary or metastatic liver malignancy. Twenty-five consecutive patients (11 women, 14 men; mean age 60.9 ± 10.8; range: 32-78 years) with primary (n = 5) or metastatic (n = 20) liver malignancy planned to undergo selective internal radiotherapy underwent dynamic contrast-enhanced CT liver perfusion imaging (four-dimensional spiral mode, scan range 14.8 cm, 15 scans, cycle time 3 seconds) and 99m)Tc-MAA SPECT after intraarterial injection of 180 MBq 99mTc-MAA on the same day. Data were evaluated by two blinded and independent readers for the parameters arterial liver perfusion (ALP), portal venous perfusion (PVP), and total liver perfusion (TLP) from CT, and the 99mTc-MAA uptake-ratio of tumors in relation to normal liver parenchyma from SPECT. Interreader agreements for quantitative perfusion parameters were high for dynamic CT (r = 0.90-0.98, each P < .01) and 99mTc -MAA SPECT (r = 0.91, P < .01). Significant correlation was found between 99mTc-MAA uptake ratio and ALP (r = 0.7, P < .01) in liver tumors. No significant correlation was found between 99mTc-MAA uptake ratio, PVP (r = -0.381, P = .081), and TLP (r = 0.039, P = .862). This study indicates that in patients with primary and metastatic liver malignancy, ALP obtained by dynamic CT liver perfusion significantly correlates with the 99mTc-MAA uptake ratio obtained by SPECT.


Efficacy of an early intervention program for at-risk preschool boys: a two-group control study.
We report the results of a preschool-based multidisciplinary intervention program. This study took place in two educational settings and included 81 preschool boys from unique cultural backgrounds and of low social economic status (SES). The settings were randomly assigned to an intervention or control group. In the intervention group, boys identified as at risk for or with developmental delays received 8 mo. of intervention through a monitoring model. Additionally, a collaborative consultation model was used with all participants. Performance skills (visual-motor integration, motor, and cognitive) and performance and participation in preschool activities were evaluated at pretest and posttest. At termination of intervention, all children in the intervention group scored significantly better than control children on most performance skills and more fully participated in preschool activities. A multidisciplinary preschool early intervention program appears to assist children of low SES with improving their performance skills, and participation in preschool activities.


The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.
It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.


Precision Medicine and Artificial Intelligence: A Pilot Study on Deep Learning for Hypoglycemic Events Detection based on ECG.
Tracking the fluctuations in blood glucose levels is important for healthy subjects and crucial diabetic patients. Tight glucose monitoring reduces the risk of hypoglycemia, which can result in a series of complications, especially in diabetic patients, such as confusion, irritability, seizure and can even be fatal in specific conditions. Hypoglycemia affects the electrophysiology of the heart. However, due to strong inter-subject heterogeneity, previous studies based on a cohort of subjects failed to deploy electrocardiogram (ECG)-based hypoglycemic detection systems reliably. The current study used personalised medicine approach and Artificial Intelligence (AI) to automatically detect nocturnal hypoglycemia using a few heartbeats of raw ECG signal recorded with non-invasive, wearable devices, in healthy individuals, monitored 24 hours for 14 consecutive days. Additionally, we present a visualisation method enabling clinicians to visualise which part of the ECG signal (e.g., T-wave, ST-interval) is significantly associated with the hypoglycemic event in each subject, overcoming the intelligibility problem of deep-learning methods. These results advance the feasibility of a real-time, non-invasive hypoglycemia alarming system using short excerpts of ECG signal.


Polar-solvent-free colloidal synthesis of highly luminescent alkylammonium lead halide perovskite nanocrystals.
A novel synthesis of hybrid organic-inorganic lead halide perovskite nanocrystals (CH3NH3PbX3, X = Br or I) that does not involve the use of dimethylformamide or other polar solvents is presented. The reaction between methylamine and PbX2 salts is conducted in a high-boiling nonpolar solvent (1-octadecene) in the presence of oleylamine and oleic acid as coordinating ligands. The resulting nanocrystals are characterized by high photoluminescence quantum efficiencies of 15-50%, outstanding phase purity and tunable shapes (nanocubes, nanowires, and nanoplatelets). Nanoplatelets spontaneously assemble into micrometer-length wires by face-to-face stacking. In addition, we demonstrate amplified spontaneous emission from thin films of green-emitting CH3NH3PbBr3 nanowires with low pumping thresholds of 3 μJ cm(-2).


Action of adenosine on cyclic 3',5'-nucleotides in glomeruli.
Recent in vivo studies indicated that adenosine has a profound effect on glomerular dynamics and renal circulation. Because its effect in nonrenal tissues is frequently mediated by adenosine 3',5'-cyclic monophosphate (cAMP), we examined adenosine's effect on cyclic nucleotides in rat kidney. Incubation of tissue slices from renal cortex or medulla with 0.1 mM adenosine resulted in marginal or no increase in cAMP. In isolated glomeruli, adenosine caused a marked and dose-dependent (10(-6) to 10(-4) M) increase in cAMP accumulation. Inosine, a deaminated metabolite of adenosine, had no effect on cAMP levels in glomeruli. No distinct effect of adenosine on cAMP was observed in cortical tubules under the same testing conditions. An increase in cAMP levels in glomeruli elicited by adenosine was blocked by theophylline, a known inhibitor of adenosine receptors. In contrast, theophylline enhanced rather than decreased the stimulation of cAMP accumulation in glomeruli by serotonin. Dipyridamole, a proposed inhibitor of cellular uptake of adenosine, did not inhibit but rather enhanced cAMP accumulation in glomeruli in response to adenosine. In the present experiments adenosine did not influence guanosine 3',5'-cyclic monophosphate levels in either glomeruli or other tested preparations of renal tissue. These results provide the first experimental evidence that adenosine stimulates cAMP accumulation in glomeruli and suggest that this effect is probably due to action on the adenosine receptor on the cell surface. Our observations raise the possibility that some of the effects of adenosine in glomerular cells may be mediated via cAMP accumulation.


PIK3CA mutations may be discordant between primary and corresponding metastatic disease in breast cancer.
PIK3CA mutations are frequent in breast cancer and activate the PI3K/Akt pathway. Unexpectedly, PIK3CA mutation appears in general to be associated with better outcome. In a cohort of patients where both primary and metastatic lesions were available, the objective was to assess changes in PIK3CA mutations. We wished to discern whether selective pressures occur and the influence of PIK3CA mutation on time to recurrence. Formalin-fixed paraffin-embedded tumor blocks were obtained from 104 patients with paired samples from primary tumors and corresponding asynchronous metastatic breast tumors. Samples were analyzed for PIK3CA mutations (exons 9 and 20) as well as immunohistochemical evaluation for PTEN, pAKT, Ki67, ER, and HER2. PIK3CA mutation was detected in 45% of the primary tumors. Overall, there was a net gain in mutation in metastatic disease, to 53%; nonetheless, there were instances where metastases were wild type in patients with PIK3CA mutant primary tumors. Laser capture microdissection on a subset of cases revealed microheterogeneity for PIK3CA mutational status in the primary tumor. PIK3CA mutants overall showed a significantly longer time to first recurrence than wild type cases (P = 0.03). PIK3CA mutations occur at high frequency in primary and metastatic breast cancer; these may not necessarily confer increased aggressiveness as mutants had a longer time to recurrence. Because PIK3CA status quite frequently changes between primary and metastatic disease, it emphasizes the necessity of assessing the PIK3CA status in the metastatic lesion for selection of PIK3CA inhibitor therapy.


School readiness and self-regulation: a developmental psychobiological approach.
Research on the development of self-regulation in young children provides a unifying framework for the study of school readiness. Self-regulation abilities allow for engagement in learning activities and provide the foundation for adjustment to school. A focus on readiness as self-regulation does not supplant interest in the development of acquired ability, such as early knowledge of letters and numbers; it sets the stage for it. In this article, we review research and theory indicating that self-regulation and consequently school readiness are the product of integrated developmental processes at the biological and behavioral levels that are shaped by the contexts in which development is occurring. In doing so, we illustrate the idea that research on self-regulation powerfully highlights ways in which gaps in school readiness and later achievement are linked to poverty and social and economic inequality and points the way to effective approaches to counteract these conditions.


Do inhalation general anesthetic drugs induce the neuronal release of endogenous opioid peptides?
The antagonism of some effects of inhalation general anesthetic agents by naloxone suggests that there may be an opioid component to anesthetic action. There is evidence that this opioid action component is due to neuronal release of endogenous opioid peptides. The strongest evidence is provided by studies that monitor changes in the concentration of opioid peptides in the perfused brain following inhalation of the anesthetic. Indirect or circumstantial evidence also comes from studies of anesthetic effects on regional brain levels of opioid peptides, antagonism of selected anesthetic effects by antisera to opioid peptides and anesthetic-induced changes radioligand binding to opioid receptors. It is likely that some inhalation general anesthetics (e.g., nitrous oxide) can induce neuronal release of opioid peptides and that this may contribute to certain components of general anesthesia (e.g., analgesia). More definitive studies utilizing in vivo microdialysis or autoradiography in selected areas of the brain during induction and successive states of general anesthesia have yet to be conducted.


An analysis of malaria in the Brazilian Legal Amazon using divergent association rules.
In data analysis, the mining of frequent patterns plays an important role in the discovery of associations and correlations between data. During this process, it is common to produce thousands of association rules (ARs), making the study of each one arduous. This problem weakens the process of finding useful information. There is a scientific effort to develop approaches capable of filtering interesting patterns, balancing the number of ARs produced with the goal of not being trivial and known by specialists. However, even when such approaches are adopted, the number of produced ARs can still be high. This work contributes by presenting Divergent Association Rules Approach (DARA), a novel approach for obtaining ARs that presents themselves in divergence with the data distribution. DARA is applied right after traditional approaches to filtering interesting patterns. To validate our approach, we studied the dataset related to the occurrence of malaria in the Brazilian Legal Amazon. The discovered patterns highlight that ARs brought relevant insights from the data. This article contributes both in the medical and computer science fields since this novel computational approach enabled new findings regarding malaria in Brazil.


Efficient sequential correspondence selection by cosegmentation.
In many retrieval, object recognition, and wide-baseline stereo methods, correspondences of interest points (distinguished regions) are commonly established by matching compact descriptors such as SIFTs. We show that a subsequent cosegmentation process coupled with a quasi-optimal sequential decision process leads to a correspondence verification procedure that 1) has high precision (is highly discriminative), 2) has good recall, and 3) is fast. The sequential decision on the correctness of a correspondence is based on simple statistics of a modified dense stereo matching algorithm. The statistics are projected on a prominent discriminative direction by SVM. Wald's sequential probability ratio test is performed on the SVM projection computed on progressively larger cosegmented regions. We show experimentally that the proposed sequential correspondence verification (SCV) algorithm significantly outperforms the standard correspondence selection method based on SIFT distance ratios on challenging matching problems.


The basic principles of chimeric antigen receptor design.
Chimeric antigen receptors (CAR) are recombinant receptors that provide both antigen-binding and T-cell-activating functions. A multitude of CARs has been reported over the past decade, targeting an array of cell surface tumor antigens. Their biologic functions have dramatically changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. These have recently shown clinical benefit in patients treated with CD19-targeted autologous T cells. CARs may be combined with costimulatory ligands, chimeric costimulatory receptors, or cytokines to further enhance T-cell potency, specificity, and safety. CARs represent a new class of drugs with exciting potential for cancer immunotherapy. CARs are a new class of drugs with great potential for cancer immunotherapy. Upon their expression in T lymphocytes, CARs direct potent, targeted immune responses that have recently shown encouraging clinical outcomes in a subset of patients with B-cell malignancies. This review focuses on the design of CARs, including the requirements for optimal antigen recognition and different modalities to provide costimulatory support to targeted T cells, which include the use of second- and third generation CARs, costimulatory ligands, chimeric costimulatory receptors, and cytokines.


Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats.
The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5mg/kg, i.v.) was given 1h following the procedure and every 24h thereafter for 2 days. Ischemia/reperfusion caused significant elevations of serum alanine aminotransferase and hepatic malondialdehyde, tumor necrosis factor-α and nitric oxide levels, associated with significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters mediated by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced liver damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin protein in ischemic/reperfused liver tissue. These results emphasize that cannabidiol represents a potential therapeutic option to protect the liver against hypoxia-reoxygenation injury.


Calcium transport in the nephron.
Ionized and complexed calcium are filtered at the glomerulus and more than 95% of the filtered load is reabsorbed along the length of the nephron. In the proximal convoluted tubule calcium is absorbed in proportion to sodium and water, suggesting a passive mechanism. The high permeability of this segment is compatible with passive transport, but evidence for active transport has been advanced. A role for Ca2+-ATPase and/or for a Ca2+/Na+ antiport has also been proposed. The straight portion of the proximal tubule appears to transport calcium actively but little is known about the mechanism and regulation of calcium absorption in this segment. Both passive and active transport of calcium in the thick ascending limb have been demonstrated, and heterogeneity in the function of medullary and cortical segments has been proposed. Definite evidence has been advanced for avid active calcium absorption in the distal convoluted tubule. Both chlorothiazide and parathyroid hormone enhance the transport of calcium in this segment. The granular portion of the collecting tubule resembles in its properties and function the distal convoluted tubule. The light portion, however, is incapable of transporting calcium. The distal tubule and collecting tubule may be the final regulators of urinary excretion of calcium but much more data are required before this view can be adopted.


Rapid initiation of intravenous epoprostenol infusion is the favored option in patients with advanced pulmonary arterial hypertension.
Intravenous infusion (IVI) of epoprostenol is an effective treatment for patients with advanced pulmonary arterial hypertension (PAH). However, there is no widely accepted standard method for initiating the IVI therapy. This study evaluated the hemodynamic improvements achieved with IVI epoprostenol to determine the optimal protocol for treatment initiation. We retrospectively analyzed 42 consecutive PAH patients who underwent IVI epoprostenol in Keio University Hospital from 2001 to 2013. The study group comprised 30 women with a mean age of 34.3 ± 1.9 years. The etiology of PAH was idiopathic or heritable PAH (I/HPAH) in 38 cases, PAH associated with connective tissue disease in 3, and Eissenmenger's syndrome in the remaining case. We divided the patients into rapid- and slow-initiation therapy groups according to the cumulative epoprostenol dose administered during the first 180 days, and compared the hemodynamic changes between the groups. The median cumulative doses were 6142 ± 165 μg/kg and 3998 ± 132 μg/kg epoprostenol, respectively. While there were no significant differences in mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), or cardiac index (CI) between the groups before the IVI epoprostenol therapy, the rapid-initiation therapy group achieved significant improvements in these hemodynamic data compared with the slow-initiation therapy group (P < 0.005) at the follow-up right-heart catheterization (RHC). Rapid initiation of IVI epoprostenol therapy achieved the optimal hemodynamic improvements in patients with severe PAH.


Evaluation of the contribution of gyrA mutation and efflux pumps to fluoroquinolone and multidrug resistance in pathogenic Escherichia coli isolates from dogs and cats.
To investigate the contribution of gyrA mutation and efflux pumps to fluoroquinolone resistance and multidrug resistance among Escherichia coli isolates from dogs and cats. 536 clinical isolates of E coli. Minimum inhibitory concentrations (MICs) were determined for enrofloxacin and 6 other drug classes by use of broth microdilution techniques. Real-time PCR assay was used to determine the mutation in gyrA; Phe-Arg-β-naphthylamide, an efflux pump inhibitor, was used to examine the contribution of efflux pump overexpression. The MIC for fluoroquinolones increased in a stepwise fashion and was lowest in the absence of mutations, higher with a single point mutation, and highest with 2 point mutations. Level of resistance in the latter category was high (8 times the breakpoint), but this was associated with expression of the AcrAB efflux pump. Inhibition of the efflux pump resulted in a reduction in the MIC to less than the susceptible breakpoint for isolates with an MIC ≤ 4 mg/L, regardless of the presence of a mutation. The greatest magnitude in MIC decrease (MIC was decreased by a factor of > 67 fold) was for isolates with a single mutation but the greatest absolute decrease in MIC (124 mg/L) was for isolates with 2 mutations. Inhibition of the AcrAB efflux pump in isolates characterized by multidrug resistance decreased the MIC of drugs structurally unrelated to fluoroquinolone. Fluoroquinolone resistance in E coli appeared to be a stepwise phenomenon, with MIC increasing as the number of point mutations in gyrA increased, but high-level resistance and multidrug resistance associated with fluoroquinolone resistance reflected overexpression of the AcrAB efflux pump.


GeneWaltz--A new method for reducing the false positives of gene finding.
Identifying protein-coding regions in genomic sequences is an essential step in genome analysis. It is well known that the proportion of false positives among genes predicted by current methods is high, especially when the exons are short. These false positives are problematic because they waste time and resources of experimental studies. We developed GeneWaltz, a new filtering method that reduces the risk of false positives in gene finding. GeneWaltz utilizes a codon-to-codon substitution matrix that was constructed by comparing protein-coding regions from orthologous gene pairs between mouse and human genomes. Using this matrix, a scoring scheme was developed; it assigned higher scores to coding regions and lower scores to non-coding regions. The regions with high scores were considered candidate coding regions. One-dimensional Karlin-Altschul statistics was used to test the significance of the coding regions identified by GeneWaltz. The proportion of false positives among genes predicted by GENSCAN and Twinscan were high, especially when the exons were short. GeneWaltz significantly reduced the ratio of false positives to all positives predicted by GENSCAN and Twinscan, especially when the exons were short. GeneWaltz will be helpful in experimental genomic studies. GeneWaltz binaries and the matrix are available online at http://en.sourceforge.jp/projects/genewaltz/.


Resource competition as a mechanism for B cell homeostasis.
Cellular competition for survival signals offers a cogent and appealing mechanism for the maintenance of cellular homeostasis [Raff, M. C. (1992) Nature (London) 356, 397-400]. We present a theoretical and experimental investigation of the role of competition for resources in the regulation of peripheral B cell numbers. We use formal ecological competition theory, mathematical models of interspecific competition, and competitive repopulation experiments to show that B cells must compete to persist in the periphery and that antigen forms a part of the resources over which B cells compete.


Effects of docosahexaenoic acid on learning and memory impairment induced by repeated propofol anesthesia in young rats.
The aim of the present study was to investigate the effects of docosahexaenoic acid (DHA) on the learning and memory ability of young rats exposed to propofol, and its underlying mechanisms. Sprague Dawley rats (n=60) were randomly divided into six groups: Control group (group A); solvent control group (group B); propofol group (group C); low-dose DHA + propofol group (group D); medium dose DHA + propofol group (group E); and high-dose DHA + propofol group (group F). The Morris water maze (MWM) test was performed to evaluate the rats' learning and memory ability, and tissue samples from the hippocampi of the rats were obtained for biochemical analysis. The results of the MWM test revealed that DHA supplementation administered to young rats led to an evident decrease in the latency to find the maze platform, and a significant increase in the number of platform crossings in groups E and F compared with group C (P<0.05). High-performance liquid chromatography indicated that glutamate concentration levels were significantly lower and γ-aminobutyric acid concentration levels were significantly higher in the hippocampi of group E and F rats treated with DHA compared with group C rats (P<0.05). Furthermore, DHA treatment alleviated the decrease in brain-derived neurotrophic factor levels (P<0.05), and superoxide dismutase (P<0.05) and glutathione peroxidase (P<0.05) activities induced by the administration of propofol. Additionally, DHA treatment decreased malondialdehyde levels in the hippocampi of rats (P<0.05). The aforementioned findings demonstrate that DHA was able to effectively improve learning and memory dysfunction induced by repeated propofol-induced anesthesia in young rats. This data suggests that DHA may be a potential candidate for further preclinical studies aimed at treating postoperative cognitive dysfunction.


Systems thinking in COVID-19 recovery is urgently needed to deliver sustainable development for women and girls.
In low-income and middle-income countries, such as those in sub-Saharan Africa and Latin America, the COVID-19 pandemic has had substantial implications for women's wellbeing. Policy responses to the COVID-19 pandemic have highlighted the gendered aspect of pandemics; however, addressing the gendered implications of the COVID-19 pandemic comprehensively and effectively requires a planetary health perspective that embraces systems thinking to inequalities. This Viewpoint is based on collective reflections from research done by the authors on COVID-19 responses by international and regional organisations, and national governments, in Latin America and sub-Saharan Africa between June, 2020, and June, 2021. A range of international and regional actors have made important policy recommendations to address the gendered implications of the COVID-19 pandemic on women's health and wellbeing since the start of the pandemic. However, national-level policy responses to the COVID-19 pandemic have been partial and inconsistent with regards to gender in both sub-Saharan Africa and Latin America, largely failing to recognise the multiple drivers of gendered health inequalities. This Viewpoint proposes that addressing the effects of the COVID-19 pandemic on women in low-income and middle-income countries should adopt a systems thinking approach and be informed by the question of who is affected as opposed to who is infected. In adopting the systems thinking approach, responses will be more able to recognise and address the direct gendered effects of the pandemic and those that emerge indirectly through a combination of long-standing structural inequalities and gendered responses to the pandemic.


Intralipid infusion ameliorates propranolol-induced hypotension in rabbits.
Recent case reports of successful amelioration of lipid-soluble drug toxidromes with Intralipid infusion have prompted interest in the scope of lipid emulsions as antidotal therapy. Propranolol is a highly lipid-soluble, nonselective beta-blocker with additional local-anaesthetic properties. We explored the hypothesis that propranolol toxicity may be similarly attenuated by Intralipid infusion in a rabbit model. Twenty sedated, invasively monitored, and mechanically ventilated New Zealand White rabbits underwent propranolol infusion at 4.2 mg/min to a target mean arterial pressure (MAP) of 60% baseline MAP. Animals subsequently received 6 ml/kg 20% Intralipid, or 6 ml/kg 0.9% saline solution over a 4-minute period. Pulse rate and MAP were recorded at 2.5-minute intervals to 15 minutes. MAP was greatest in the Intralipid group (median 69 mmHg, interquartile range [IQR] 17.5 mmHg Intralipid vs. median 53 mmHg, IQR 12.75 mmHg saline; p=0.029) at 15 minutes. No difference was observed in first derivative of MAP, or pulse rate between groups. Propranolol-induced hypotension is ameliorated by Intralipid infusion in this intact rabbit model. The mechanism of action remains to be elucidated.


Fibromyalgia and myofascial pain syndrome-a dilemma.
Pain and fatigue associated to the musculoskeletal system are among the leading causes of patients to visit their physicians and nearly one-third of such patients suffer from fibromyalgia. Fibromyalgia syndrome (FMS) is a chronic debilitating disorder characterized by widespread pain with tenderness in specific areas, leading to fatigue, headache and sleep disorder. Myofascial Pain Syndrome (MPS), is also a localized musculoskeletal pain producing condition whose diagnostic and management criteria differ from FMS but still considered by many only a subtype of FMS. Till date no exact cause has been held responsible for these painful conditions, therefore treatment of these disorders is always a challenge. The therapies are not precise but multimodal including pharmacological and alternative approaches. This article describes the existing knowledge pertaining to these conditions in regard of causative factors diagnosis and management.


Oral contraceptive pill use and the susceptibility to markers of exercise-induced muscle damage.
Firstly, to establish whether oral contraceptive pill (OCP) users are more susceptible to muscle damage compared to non-users, and secondly, to establish whether differences can be attributed to differences in patella tendon properties. Nine female OCP users and 9 female non-users participated in the investigation. Combining dynamometry, electromyography and ultrasonography, patella tendon properties and vastus lateralis architectural properties were measured pre and during the first of 6 sets of 12 maximal voluntary eccentric knee extensions. Serum oestrogen levels were measured on the 7th day of the pill cycle and the 14th day of menstrual cycle in OCP users and non-users, respectively. Maximal voluntary isometric knee extension torque loss, creatine kinase and muscle soreness were measured 48 h pre-damage, post-damage, and 48, 96 and 168 h post-damage. Oestrogen levels were significantly lower in OCP users compared to non-users (209 ± 115 and 433 ± 147 pg/ml, respectively, p = 0.004). Proposed determinants of muscle damage, patella tendon stiffness and maximal eccentric torque did not differ between OCP users and non-users. The change in creatine kinase from pre to peak was significantly higher in OCP users compared to non-users (962 ± 968 and 386 ± 474 Ul, respectively, p = 0.016). There were no other differences in markers of muscle damage. Although our findings suggest that, when compared to non-users, the OCP may augment the creatine kinase response following eccentric exercise, it does not increase the susceptibility to any other markers of muscle damage.


Focus group findings on the migraine patient experience during research studies and ideas for future investigations.
We conducted focus groups in people who had participated in mobile health (mHealth) studies of behavioral interventions for migraine to better understand: (a) Participant experience in the recruitment/enrollment process; (b) participant experience during the studies themselves; (c) ideas for improving participant experience for future studies. We conducted four focus groups in people who had agreed to participate in one of three studies involving mHealth and behavioral therapy for migraine. Inclusion criteria were being age 18-80, owning a smartphone, and having four or more headache days per month. All participants met the International Classification of Headache Disorders third edition beta version criteria for migraine. Exclusion criteria were not speaking English and having had behavioral therapy for migraine in the past year. Focus groups were audio recorded, fully transcribed and coded using general thematic analysis. The 12 focus group participants had a mean age of 45 ± 15, a mean age of headache onset of 21 ± 13 and mean MIDAS disability score was 39 ± 56. Participants were women (100%), white (50%), Asian (33.3%) or members of other racial groups (16.7%). Certain themes emerged from each topic area. With regard to recruitment/enrollment (a), key themes were: (i) Participants joined their study out of an interest in research and/or a desire to try a new migraine treatment modality (behavioral therapy). (ii) Enrollment should be simple and study requirements should be carefully explained prior to enrollment. When asked about their experiences during the studies (b), the following themes emerged: (i) It is difficult to participate in study follow-up and compliance phone calls; (ii) participants prefer to choose from among various options for contact with the study team; (iii) there are barriers that limit app use related to migraine itself, as well as other barriers; (iv) completing diaries on a daily basis is challenging; (v) technical difficulties and uncertainties about app features limit use; (vi) being part of a research study promoted daily behavioral therapy use; (vii) progressive muscle relaxation (PMR) is enjoyable, and has a positive impact on life; (viii) behavioral therapy was a preferred treatment to reduce migraine pain. Ideas for improving study design or patient experience (c) included: (i) Increased opportunity to interact with other people with migraine would be beneficial; (ii) navigating the app and data entry should be easier; (iii) more varied methods for viewing the data and measures of adherence are needed; (iv) more information on and more varied behavioral treatment modalities would be preferred. Though people with migraine are motivated to participate in mHealth and behavioral treatment studies, better communication up front about interventions as well as greater flexibility in interventions and follow-up methods are desired.


Genomic Approaches to Posttraumatic Stress Disorder: The Psychiatric Genomic Consortium Initiative.
Posttraumatic stress disorder (PTSD) after exposure to a traumatic event is a highly prevalent psychiatric disorder. Heritability estimates from twin studies as well as from recent molecular data (single nucleotide polymorphism-based heritability) indicate moderate to high heritability, yet robust genetic variants for PTSD have not yet been identified and the genetic architecture of this polygenic disorder remains largely unknown. To date, fewer than 10 large-scale genome-wide association studies of PTSD have been published, with findings that highlight the unique challenges for PTSD genomics, including a complex diagnostic entity with contingency of PTSD diagnosis on trauma exposure and the large genetic diversity of the study populations. The Psychiatric Genomics Consortium PTSD group has brought together more than 200 scientists with the goal to increase sample size for genome-wide association studies and other genomic analyses to sufficient numbers where robust discoveries of molecular signatures can be achieved. The sample currently includes more than 32,000 PTSD cases and 100,000 trauma-exposed control subjects, and collection is ongoing. The first results found a significant shared genetic risk of PTSD with other psychiatric disorders and sex-biased heritability estimates with higher heritability in female individuals compared with male individuals. This review describes the scope and current focus of the Psychiatric Genomics Consortium PTSD group and its expansion from the initial genome-wide association study group to nine working groups, including epigenetics, gene expression, imaging, and integrative systems biology. We further briefly outline recent findings and future directions of "omics"-based studies of PTSD, with the ultimate goal of elucidating the molecular architecture of this complex disorder to improve prevention and intervention strategies.


Anatomy of the abdomen, back, and pelvis as displayed by magnetic resonance imaging: Part Two.
In April 1986, magnetic resonance imaging (MRI) of the thorax and shoulder girdle was presented at the 99th Annual Meeting of the American Association of Anatomists. These images were the authors' first attempt to correlate the magnetic resonance display of the muscles and soft tissues of the chest in the coronal plane with surface gross anatomy. The original purpose of this study was to introduce the role of magnetic resonance imaging to anatomists, medical students, and the specialty of radiology. However, this approach has been expanded by imaging other sections of the body and applying the display of surface anatomy to augment the teaching of anatomy to surgical oncology, pathology, and kinesiology. This three-part article will display magnetic resonance images and will explain how magnetic imaging of the soft tissues can visually augment the teaching of gross anatomy without dissecting surface tissues.


Is race medically relevant? A qualitative study of physicians' attitudes about the role of race in treatment decision-making.
The role of patient race in medical decision-making is heavily debated. While some evidence suggests that patient race can be used by physicians to predict disease risk and determine drug therapy, other studies document bias and stereotyping by physicians based on patient race. It is critical, then, to explore physicians' attitudes regarding the medical relevance of patient race. We conducted a qualitative study in the United States using ten focus groups of physicians stratified by self-identified race (black or white) and led by race-concordant moderators. Physicians were presented with a medical vignette about a patient (whose race was unknown) with Type 2 diabetes and untreated hypertension, who was also a current smoker. Participants were first asked to discuss what medical information they would need to treat the patient. Then physicians were asked to explicitly discuss the importance of race to the hypothetical patient's treatment. To identify common themes, codes, key words and physician demographics were compiled into a comprehensive table that allowed for examination of similarities and differences by physician race. Common themes were identified using the software package NVivo (QSR International, v7). Forty self-identified black and 50 self-identified white physicians participated in the study. All physicians - regardless of their own race - believed that medical history, family history, and weight were important for making treatment decisions for the patient. However, black and white physicians reported differences in their views about the relevance of race. Several black physicians indicated that patient race is a central factor for choosing treatment options such as aggressive therapies, patient medication and understanding disease risk. Moreover, many black physicians considered patient race important to understand the patient's views, such as alternative medicine preferences and cultural beliefs about illness. However, few white physicians explicitly indicated that the patient's race was important over-and-above medical history. Instead, white physicians reported that the patient should be treated aggressively regardless of race. This investigation adds to our understanding about how physicians in the United States consider race when treating patients, and sheds light on issues physicians face when deciding the importance of race in medical decision-making.


Age-dependence of sensorimotor and cerebral electroencephalographic asymmetry in rats subjected to unilateral cerebrovascular stroke.
The human population mostly affected by stroke is more than 65 years old. This study was designed to meet the recommendation that models of cerebral ischemia in aged animals are more relevant to the clinical setting than young animal models. Until now the majority of the pre-clinical studies examining age effects on stroke outcomes have used rats of old age. Considering the increasing incidence of stroke among younger than old human population, new translational approaches in animal models are needed to match the rejuvenation of stroke. A better knowledge of alterations in stroke outcomes in middle-aged rats has important preventive and management implications providing clues for future investigations on effects of various neuroprotective and neurorestorative drugs against cerebrovascular accidents that may occur before late senescence. We evaluated the impact of transient focal ischemia, induced by intracerebral unilateral infusion of endothelin-1 (Et-1) near the middle cerebral artery of conscious rats, on volume of brain damage and asymmetry in behavioral and electroencephalographic (EEG) output measures in middle-aged (11-12 month-old) rats. We did not find any age-dependent difference in the volume of ischemic brain damage three days after Et-1 infusion. However, age was an important determinant of neurological and EEG outcomes after stroke. Middle-aged ischemic rats had more impaired somatosensory functions of the contralateral part of the body than young ischemic rats and thus, had greater left-right reflex/sensorimotor asymmetry. Interhemispheric EEG asymmetry was more evident in middle-aged than in young ischemic rats, and this could tentatively explain the behavioral asymmetry. With a multiparametric approach, we have validated the endothelin model of ischemia in middle-aged rats. The results provide clues for future studies on mechanisms underlying plasticity after brain damage and motivate investigations of novel neuroprotective strategies against cerebrovascular accidents that may occur before late senescence.


Integration of human pancreatic islet genomic data refines regulatory mechanisms at Type 2 Diabetes susceptibility loci.
Human genetic studies have emphasised the dominant contribution of pancreatic islet dysfunction to development of Type 2 Diabetes (T2D). However, limited annotation of the islet epigenome has constrained efforts to define the molecular mechanisms mediating the, largely regulatory, signals revealed by Genome-Wide Association Studies (GWAS). We characterised patterns of chromatin accessibility (ATAC-seq, n = 17) and DNA methylation (whole-genome bisulphite sequencing, n = 10) in human islets, generating high-resolution chromatin state maps through integration with established ChIP-seq marks. We found enrichment of GWAS signals for T2D and fasting glucose was concentrated in subsets of islet enhancers characterised by open chromatin and hypomethylation, with the former annotation predominant. At several loci (including CDC123, ADCY5, KLHDC5) the combination of fine-mapping genetic data and chromatin state enrichment maps, supplemented by allelic imbalance in chromatin accessibility pinpointed likely causal variants. The combination of increasingly-precise genetic and islet epigenomic information accelerates definition of causal mechanisms implicated in T2D pathogenesis.


Comparison of Electroacupuncture and Moxibustion for Relieving Visceral Hypersensitivity in Rats with Constipation-Predominant Irritable Bowel Syndrome.
Aim. To compare whether there is different effect between electroacupuncture (EA) and moxibustion (Mox) on visceral hypersensitivity (their analgesic effects) in constipation-predominant irritable bowel syndrome (C-IBS). Methods. EA at 1 mA and 3 mA and Mox at 43°C and 46°C were applied to the Shangjuxu (ST37, bilateral) acupoint in rats with C-IBS and normal rats. An abdominal withdrawal reflex (AWR) score was used to assess visceral hypersensitivity. Toluidine blue staining was used to assess mast cell (MC) activity in colon of rats. Immunochemistry was used to measure 5-HT and 5-HT4 receptor expression in the colon. Results. AWR scores in all EA (1 mA and 3 mA) and Mox (43°C and 46°C) treatment groups after colorectal distention (CRD) stimulation pressure of 20, 40, 60, and 80 mmHg were significantly lower than those of the model (MC) group (P all < 0.01). The MC counts and degranulation rates in the colon of all EA and Mox treatment groups and the MC group were significantly higher than those of the NC group (P all < 0.01). MC degranulation rates in the colon of all EA and Mox treatment groups were lower than those of the MC group (P all < 0.05). 5-HT expression in colon of all EA and Mox treatment groups was significantly lower than that of the MC group (P all < 0.01), and 5-HT4R expression in colon of both EA groups was significantly higher than that of the MC group (P both < 0.01). Conclusion. EA and Mox treatments may both ameliorate visceral hypersensitivity at different degree in rats with C-IBS, and EA treatment was better than Mox.


Distribution and molecular investigation of highly thermophilic bacteria associated with cool soil environments.
In this study, both molecular and culture-based methods were used to characterize thermophilic bacteria associated with the subsurface soil environment in Northern Ireland. A total of 53 thermophilic, aerobic, sporulating and non-sporulating bacteria were isolated from subsurface soil samples obtained from two sites. They were screened by amplified ribosomal DNA restriction analysis prior to 16 S rRNA gene sequencing. The majority of the sequences were associated with Geobacillus thermoleovorans (50%) and Geobacillus caldoxylosilyticus (34.6%). Isolates F10, F20 and Tf exhibited only 93% similarity with Geobacillus toebii strain F70. Hence they may represent a new species of the genus Geobacillus.


Composition differences between organic and conventional meat: a systematic literature review and meta-analysis.
Demand for organic meat is partially driven by consumer perceptions that organic foods are more nutritious than non-organic foods. However, there have been no systematic reviews comparing specifically the nutrient content of organic and conventionally produced meat. In this study, we report results of a meta-analysis based on sixty-seven published studies comparing the composition of organic and non-organic meat products. For many nutritionally relevant compounds (e.g. minerals, antioxidants and most individual fatty acids (FA)), the evidence base was too weak for meaningful meta-analyses. However, significant differences in FA profiles were detected when data from all livestock species were pooled. Concentrations of SFA and MUFA were similar or slightly lower, respectively, in organic compared with conventional meat. Larger differences were detected for total PUFA and n-3 PUFA, which were an estimated 23 (95 % CI 11, 35) % and 47 (95 % CI 10, 84) % higher in organic meat, respectively. However, for these and many other composition parameters, for which meta-analyses found significant differences, heterogeneity was high, and this could be explained by differences between animal species/meat types. Evidence from controlled experimental studies indicates that the high grazing/forage-based diets prescribed under organic farming standards may be the main reason for differences in FA profiles. Further studies are required to enable meta-analyses for a wider range of parameters (e.g. antioxidant, vitamin and mineral concentrations) and to improve both precision and consistency of results for FA profiles for all species. Potential impacts of composition differences on human health are discussed.


Coronary and aortic calcifications inter-relationship in stable angina pectoris: A Coronary Disease Trial Investigating Outcome with Nifedipine GITS (ACTION)--Israeli spiral computed tomography substudy.
Coronary heart disease and ischemic stroke are among the leading causes of morbidity and mortality in adults, and cerebrovascular disease is associated with the presence of symptomatic and asymptomatic CHD. Several studies noted an association between coronary calcification and thoracic aorta calcification by several imaging techniques, but this association has not yet been examined in stable angina pectoris patients with the use of spiral computed tomography. To examine by spiral CT the association between the presence and severity of CC and thoracic aorta calcification in patients with stable angina pectoris. The patients were enrolled in ACTION (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS) in Israel. The 432 patients (371 men and 61 women aged 40-89 years) underwent chest CT and were evaluated for CC and aortic calcification. CC was documented in 90% of the patients (n = 392) and aortic calcification in 70% (n = 303). A significant association (P < 0.05) was found between severity of CC and severity of aortic calcification (as measured by area, volume and slices of calcification). We also found an association between the number of coronary vessels calcified and the presence of aortic calcification: 90% of patients with triple-vessel disease (n = 157) were also positive for aortic calcification (P < 0.05). Age also had an effect: 87% of patients > 65 years (n=219) were positive for both coronary and aortic calcification (P = 0.005) while only 57% < or = 65 (n = 209) were positive for both (P = 0.081). Our study demonstrates a strong association between the presence and severity of CC and the presence and severity of calcification of thoracic aorta in patients with stable angina pectoris as detected by spiral CT.


First Report of Anthracnose Caused by Colletotrichum navitas on Switchgrass in New York.
Switchgrass (Panicum virgatum L.) is a perennial grass with significant potential as a biofuel crop. From 2007 to 2010, foliar lesions were observed in new and mature stands of switchgrass in various locations in New York. Lesions were elliptical with purple margins and white necrotic centers, generally <3 cm long, ~1 mm wide, often coalesced, and containing black setae. Upon incubation, symptomatic leaf tissue developed acervuli with masses of salmon-colored spores. The fungus was identified as Colletotrichum nativas Crouch on the basis of typical cultural characteristics and conidial morphology (1). Conidia were one-celled, hyaline, fusiform, and generally falcate. Conidial length averaged 40 μm (22 to 47 μm) and width averaged 5 μm (4 to 7 μm). Compared with other graminicolous species of Colletotrichum, the conidia were larger and varied from straight to irregularly bent. Sequences of the rDNA internal transcribed spacer (ITS) regions of three isolates (Cornell accession and corresponding GenBank Nos.: Cn071NY08 (from a >20-year-old naturalized stand of switchgrass in Steuben County), JF437053; Cn080NY08 (from 'Pathfinder' in Chemung County), JF437054; and Cn101NY09 (from 'Blackwell' in Chemung County), JF437055) exhibited 100% nucleotide identity to the type isolate of C. nativas (GenBank No. GQ919068) collected from switchgrass selection 'Brooklyn' in New Jersey (1). Pathogenicity of the sequenced isolates along with seven other isolates (Cn105NY09 from 'Sunburst' in Tompkins County; Cn107NY09 from 'Trailblazer' in Tompkins County; Cn109NY09 from 'Forestburg' in Tompkins County; Cn111NY09 and Cn112NY09 from 'Shelter' in Tompkins County; and Cn122NY09 and Cn123NY09 from 'Cave-in-Rock' in Genesee County) was evaluated in greenhouse experiments. Seven- to eight-week-old switchgrass plants were inoculated with conidial suspensions (1 × 106 conidia/ml) of C. nativas. Inoculum or sterilized water was sprayed until runoff. Three plants of each of 'Cave-in-Rock' and 'Kanlow' were sprayed per treatment and the experiment was repeated for 3 of the 10 isolates. Inoculated plants were placed in a mist chamber for 48 h before they were returned to the greenhouse and observed for disease development, which occurred within 1 week of inoculation for both cultivars. No symptoms developed on the control plants. Foliar lesions closely resembled those observed in the field. C. nativas was consistently reisolated from symptomatic tissue collected from greenhouse experiments. Switchgrass anthracnose associated with C. graminicola sensu lata has been reported in many U.S. states (2). On the basis of molecular phylogenetics and distinguishing morphological characters, Crouch et al. erected C. navitas as a novel species distinct from C. graminicola sensu stricto, a taxon restricted to the corn anthracnose pathogen (1). C. nativas was first documented on switchgrass in New Jersey (1) and appears to be the same pathogen causing anthracnose of switchgrass in the adjoining state of Pennsylvania (1,3). To our knowledge, this is the first report of C. nativas causing anthracnose of switchgrass in New York. References: (1) J. A. Crouch et al. Mycol. Res. 113:1411, 2009. (2) D. F. Farr and A. Y. Rossman. Fungal Databases, Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ , May 5, 2011. (3) M. A. Sanderson et al. Agron. J. 100:510, 2008.


Identifying Recommendations for Stopping or Scaling Back Unnecessary Routine Services in Primary Care.
Much of health care involves established, routine use of medical services for chronic conditions or prevention. Stopping these services when the evidence changes or if the benefits no longer outweigh the risks is essential. Yet, most guidelines focus on escalating care and provide few explicit recommendations to stop or scale back (ie, deintensify) treatment and testing. To develop a systematic, transparent, and reproducible approach for identifying, specifying, and validating deintensification recommendations associated with routine adult primary care. A focused review of existing guidelines and recommendations was completed to identify and prioritize potential deintensification indications. Then, 2 modified virtual Delphi expert panels examined the synthesized evidence, suggested ways that the candidate recommendations could be improved, and assessed the validity of the recommendations using the RAND/UCLA Appropriateness Method. Twenty-five physicians from Veterans Affairs and US academic institutions with knowledge in relevant clinical areas (eg, geriatrics, primary care, women's health, cardiology, and endocrinology) served as panel members. Validity of the recommendations, defined as high-quality evidence that deintensification is likely to improve patient outcomes, evidence that intense testing and/or treatment could cause harm in some patients, absence of evidence on the benefit of continued or repeated intense treatment or testing, and evidence that deintensification is consistent with high-quality care. A total of 409 individual recommendations were identified representing 178 unique opportunities to stop or scale back routine services (eg, stopping population-based screening for vitamin D deficiency and decreasing concurrent use of opioids and benzodiazepines). Thirty-seven recommendations were prioritized and forwarded to the expert panels. Panelists reviewed the evidence and suggested modifications, resulting in 44 recommendations being rated. Overall, 37 recommendations (84%) were considered to be valid, as assessed by the RAND/UCLA Appropriateness Method. In this study, a total of 178 unique opportunities to deintensify routine primary care services were identified, and 37 of these were validated as high-priority deintensification recommendations. To date, this is the first study to develop a model for identifying, specifying, and validating deintensification recommendations that can be implemented and tracked in clinical practice.


Supporting patients and their caregivers after-hours at the end of life: the role of telephone support.
Twenty-four hour access is accepted as a gold standard for palliative care service delivery, yet minimal data exist to justify the cost of this initiative to health care planners and policy makers. Further, there is scant information concerning optimal and efficient methods for delivering after-hours palliative care advice and support, particularly in regional and rural settings. This article reports on an evaluation of a local after-hours telephone support service in regional Australia. A centralized after-hours telephone support service was provided by generalist nurses at a Multipurpose Service in a rural community. A mixed-method evaluation, including semistructured interviews, was undertaken after 20 months of operation. During the period March 31, 2005 until November 15, 2006, 357 patients were registered as part of the Mid North Coast Rural Palliative Care Program. Ten percent of patients or their caregivers accessed the After-Hours Telephone Support Service, representing 55 occasions of service. The most common reason for contacting the service was for reassurance surrounding medication usage, symptom management, and anxiety. This experience demonstrates proof of concept that acceptable palliative care advice can be provided by generalist nurses in a cost-efficient manner. Common patterns emerged in utilization that can assist in service planning and staffing formulae. There is also a need to investigate mechanisms of interfacing with larger scale call centers, to explore the differences within generic and disease-specific approaches, and assess the appropriateness of after-hours telephone support with different cultural groups.


High-order adaptive optics requirements for direct detection of extrasolar planets: Application to the SPHERE instrument.
The detection of extrasolar planets implies an extremely high-contrast, long-exposure imaging capability at near infrared and probably visible wavelengths. We present here the core of any Planet Finder instrument, that is, the extreme adaptive optics (XAO) subsystem. The level of AO correction directly impacts the exposure time required for planet detection. In addition, the capacity of the AO system to calibrate all the instrument static defects ultimately limits detectivity. Hence, the extreme AO system has to adjust for the perturbations induced by the atmospheric turbulence, as well as for the internal aberrations of the instrument itself. We propose a feasibility study for an extreme AO system in the frame of the SPHERE (Spectro-Polarimetry High-contrast Exoplanet Research) instrument, which is currently under design and should equip one of the four VLT 8-m telescopes in 2010.


The spectral quality of light is a key driver of photosynthesis and photoadaptation in Stylophora pistillata colonies from different depths in the Red Sea.
Depth zonation on coral reefs is largely driven by the amount of downwelling, photosynthetically active radiation (PAR) that is absorbed by the symbiotic algae (zooxanthellae) of corals. The minimum light requirements of zooxanthellae are related to both the total intensity of downwelling PAR and the spectral quality of the light. Here we used Stylophora pistillata colonies collected from shallow (3 m) and deep (40 m) water; colonies were placed in a respirometer under both ambient PAR irradiance and a filter that only transmits blue light. We found that the colonies exhibited a clear difference in their photosynthetic rates when illuminated under PAR and filtered blue light, with higher photosynthetic performance when deep colonies were exposed to blue light compared with full-spectrum PAR for the same light intensity and duration. By contrast, colonies from shallow water showed the opposite trend, with higher photosynthetic performances under full-spectrum PAR than under filtered blue light. These findings are supported by the absorption spectra of corals, with deeper colonies absorbing higher energy wavelengths than the shallow colonies, with different spectral signatures. Our results indicate that S. pistillata colonies are chromatically adapted to their surrounding light environment, with photoacclimation probably occurring via an increase in photosynthetic pigments rather than algal density. The spectral properties of the downwelling light are clearly a crucial component of photoacclimation that should be considered in future transplantation and photoacclimation studies.


Insights Into Microbially Induced Salt Tolerance and Endurance Mechanisms (STEM) in Plants.
Salt stress threatens the achievement of sustainable global food security goals by inducing secondary stresses, such as osmotic, ionic, and oxidative stress, that are detrimental to plant growth and productivity. Various studies have reported the beneficial roles of microbes in ameliorating salt stress in plants. This review emphasizes salt tolerance and endurance mechanisms (STEM) in microbially inoculated (MI) plants that ensure plant growth and survival. Well-established STEM have been documented in MI plants and include conglomeration of osmolytes, antioxidant barricading, recuperating nutritional status, and ionic homeostasis. This is achieved via involvement of P solubilization, siderophore production, nitrogen fixation, selective ion absorption, volatile organic compound production, exopolysaccharide production, modifications to plant physiological processes (photosynthesis, transpiration, and stomatal conductance), and molecular alterations to alter various biochemical and physiological processes. Salt tolerance and endurance mechanism in MI plants ensures plant growth by improving nutrient uptake and maintaining ionic homeostasis, promoting superior water use efficiency and osmoprotection, enhancing photosynthetic efficiency, preserving cell ultrastructure, and reinforcing antioxidant metabolism. Molecular research in MI plants under salt stress conditions has found variations in the expression profiles of genes such as HKT1, NHX, and SOS1 (ion transporters), PIPs and TIPs (aquaporins), RBCS, RBCL (RuBisCo subunits), Lipoxygenase2 [jasmonic acid (JA) signaling], ABA (abscisic acid)-responsive gene, and APX, CAT, and POD (involved in antioxidant defense). Proteomic analysis in arbuscular mycorrhizal fungi-inoculated plants revealed upregulated expression of signal transduction proteins, including Ca2+ transporter ATPase, calcium-dependent protein kinase, calmodulin, and energy-related proteins (NADH dehydrogenase, iron-sulfur protein NADH dehydrogenase, cytochrome C oxidase, and ATP synthase). Future research should focus on the role of stress hormones, such as JA, salicylic acid, and brassinosteroids, in salt-stressed MI plants and how MI affects the cell wall, secondary metabolism, and signal transduction in host plants.


Bites by foreign venomous snakes in Britain.
In 1970-7 17 people in Britain were the victims of 32 bites by foreign venomous snakes. Crotalus atrox caused eight of these bites, Bitis arietans five, and the remaining 19 bites were caused by 12 different species. All the victims were bitten while handling the snake, and 24 bites were incurred by private individuals in their own homes. Poisoning was negligible in 17 of the 32 bites but life-threatening in at least two cases. Thus in the early stages snake bite may be unpredictable as a clinical problem. All victims of snake bite should be observed for at least 12 hours to assess the severity of poisoning and to ensure rational treatment. Local necrosis developed in six cases and resulted in prolonged illness in five of these cases; local incision was carried out and many have been a casual factor. Comprehensive stocks of antivenoms for treating bites by foreign venomous snakes are held by the National Health Services in Liverpool and London. Antivenom is indicated (a) for potentially serious systemic poisoning, as evidenced by hypotension, electrocardiographic changes, neurtrophilia, and acidosis (after viper or elapid bites), abnormal bleeding or non-clotting blood after viper bites; and ptosis or glossopharyngeal palsy after elapid bites; and (b) for bites from snakes whose venom causes local necrosis, to prevent or minimise this unpleasant complication. For effective antivenom treatment intravenous infusion is mandatory.


Psychological Interventions for Dementia Caregivers: What We Have Achieved, What We Have Learned.
With the rising dementia population, more and more programs have been developed to help caregivers deal with the care-recipient as well as their own frustrations. Many interventions aim to enhance caregiver's ability to manage behavior problems and other deteriorations in functioning, with less direct emphasis placed on caring for the caregivers. We argue that techniques based on psychotherapy are strategically important in assistance provided to caregivers because of their utility for promoting emotional health. This article provides a focused review of such methods used in evidence-based intervention programs, along with the mechanisms of change associated with these methods. While cognitive-behavioral therapy (CBT) has a strong evidence base, there is also a growing trend to package CBT techniques into various psychoeducational programs. These programs, which we call psychoeducation with psychotherapeutic programs, have been consistently found to be effective in reducing caregiver distress and are suited for delivery in group format, even by paraprofessionals, to lower the cost of intervention. A recent trend is the effective use of technological aids (e.g., the internet) to deliver CBT and psychoeducation, reaching more caregivers. As for therapeutic mechanisms, the use of coping skills, reduced dysfunctional thoughts, and increased self-efficacy in controlling upsetting thoughts has received support in studies. We conclude that psychotherapeutic techniques are increasingly being used effectively and efficiently to assist caregivers, aided by successful adaptation for educational or technologically advanced means of delivery. More research on therapeutic mechanisms is needed to understand how the techniques work and how they can be further refined.


The occupational sitting and physical activity questionnaire (OSPAQ): a validation study with accelerometer-assessed measures.
The Occupational Sitting and Physical Activity Questionnaire (OSPAQ) was developed as an easy-to-use instrument for self-reported assessment of percentage sitting, standing, walking, and performing heavy labour in a workplace setting. This study aimed to evaluate the concurrent validity of all dimensions of the OSPAQ compared to accelerometer-assessed measures of occupational physical activities in a mixed sample of sedentary and physically active professions. Data from the Flemish Employees' Physical Activity (FEPA) study were used, including employees from the service and production sector. All participants filled in a questionnaire, underwent clinical measurements, and wore two Axivity AX3 accelerometers for at least 2 consecutive working days. Intraclass (ICC) and Spearman rho correlations (r) were analyzed to assess concurrent validity. The sample included 401 workers (16% sedentary profession) with a mean age of 39.2 (± 11) years. Concurrent validity was good and moderate for assessing percentage of sitting (ICC = 0.84; r = 0.53), and standing (ICC = 0.64; r = 0.53), respectively. The concurrent validity for walking was weak to moderate (ICC = 0.50; r = 0.49), and weak for performing heavy labour (ICC = 0.28; r = 0.35). Stronger validity scores were found in sedentary professions for occupational sitting and standing. In physically active professions, an underestimation of self-reported sitting and standing was found, and an overestimation of self-reported walking and heavy labour. No significant self-reported over- or underestimation was found for sitting and heavy labour in sedentary professions, but an underestimation of self-reported standing and an overestimation of self-reported walking was observed. The OSPAQ has acceptable measurement properties for assessing occupational sitting and standing. Accelerometer-assessed measures of occupational walking and heavy labour are recommended, since a poor concurrent validity was found for both.


Visceral leishmaniasis and HIV coinfection in the Mediterranean region.
Visceral leishmaniasis is hypoendemic in Mediterranean countries, where it is caused by the flagellate protozoan Leishmania infantum. VL cases in this area account for 5%-6% of the global burden. Cases of Leishmania/HIV coinfection have been reported in the Mediterranean region, mainly in France, Italy, Portugal, and Spain. Since highly active antiretroviral therapy was introduced in 1997, a marked decrease in the number of coinfected cases in this region has been reported. The development of new diagnostic methods to accurately identify level of parasitemia and the risk of relapse is one of the main challenges in improving the treatment of coinfected patients. Clinical trials in the Mediterranean region are needed to determine the most adequate therapeutic options for Leishmania/HIV patients as well as the indications and regimes for secondary prophylaxis. This article reviews the epidemiological, diagnostic, clinical, and therapeutic aspects of Leishmania/HIV coinfection in the Mediterranean region.


Is overtriage associated with increased mortality? Insights from a simulation model of mass casualty trauma care.
To examine the relationship between overtriage and critical mortality after a mass casualty incident (MCI) using a simulation model of trauma system response. We created a discrete event simulation model of trauma system management of MCIs involving individual patient triage and treatment. Model variables include triage performance, treatment capability, treatment time, and time-dependent mortality of critically injured patients. We model triage as a variable selection process applied to a hypothetical population of critically and noncritically injured patients. Treatment capability is represented by staffed emergency department trauma bays with associated staffed operating rooms that are recycled after each use. We estimated critical and noncritical patient treatment times and time-dependent mortality rates from the trauma literature. In this simulation model, overtriage, the proportion of noncritical patients among all of those labeled as critical, has a positive, negative, or variable association with critical mortality depending on its etiology (ie, related to changes in triage sensitivity or to changes in the prevalence and total number of critical patients). In all of the modeled scenarios, the ratio of critical patients to treatment capability has a greater impact on critical mortality than overtriage level or time-dependent mortality assumption. Increasing overtriage may have positive, negative, or mixed effects on critical mortality in this trauma system simulation model. These results, which contrast with prior analyses describing a positive linear relationship between overtriage and mortality, highlight the need for alternative metrics to describe trauma system response after MCIs. We explore using the relative number of critical patients to available and staffed treatment units, or the critical surge to capability ratio, which exhibits a consistent and nonlinear association with critical mortality in this model.


Reducing central line-associated bloodstream infections in North Carolina NICUs.
Central lines in NICUs have long dwell times. Success in reducing central line-associated bloodstream infections (CLABSIs) requires a multidisciplinary team approach to line maintenance and insertion. The Perinatal Quality Collaborative of North Carolina (PQCNC) CLABSI project supported the development of NICU teams including parents, the implementation of an action plan with unique bundle elements and a rigorous reporting schedule. The goal was to reduce CLABSI rates by 75%. Thirteen NICUs participated in an initiative developed over 3 months and deployed over 9 months. Teams participated in monthly webinars and quarterly face-to-face learning sessions. NICUs reported on bundle compliance and National Health Surveillance Network infection rates at baseline, during the intervention, and 3 and 12 months after the intervention. Process and outcome indicators were analyzed using statistical process control methods (SPC). Near-daily maintenance observations were requested for all lines with a 68% response rate. SPC analysis revealed a trend to an increase in bundle compliance. We also report significant adoption of a new maintenance bundle element, central line removal when enteral feedings reached 120 ml/kg per day. The PQCNC CLABSI rate decreased 71%, from 3.94 infections per 1000 line days to 1.16 infections per 1000 line days with sustainment 1 year later (P = .01). A collaborative structure targeting team development, family partnership, unique bundle elements and strict reporting on line care produced the largest reduction in CLABSI rates for any multiinstitutional NICU collaborative.


Recombinant interleukin 2 regulates levels of c-myc mRNA in a cloned murine T lymphocyte.
The cellular oncogene c-myc has been implicated in the regulation of growth of normal and neoplastic cells. Recently, it was suggested that c-myc gene expression may control the G0----G1-phase transition in normal lymphocytes that were stimulated to enter the cell cycle by the lectin concanavalin A (ConA). Here we describe the effects of purified recombinant interleukin 2 (rIL2) and of ConA on levels of c-myc mRNA in the noncytolytic murine T-cell clone L2. In contrast to resting (G0) primary cultures of lymphocytes, quiescent L2 cells have a higher RNA content than resting splenocytes and express receptors for interleukin 2 (IL2). Resting L2 cells are therefore best regarded as early G1-phase cells. Purified rIL2 was found to stimulate the rapid accumulation of c-myc mRNA in L2 cells. Levels of c-myc mRNA became maximal within 1 h and declined gradually thereafter. In contrast, ConA induced slower accumulation of c-myc mRNA in L2 cells, with increased levels of c-myc mRNA becoming detectable 4 to 8 h after stimulation. Experiments with the protein synthesis inhibitor cycloheximide demonstrated that the increase in levels of c-myc mRNA that were induced by ConA was a direct effect of this lectin and not secondary to IL2 production. Cyclosporin A, an immunosuppressive agent, markedly reduced the accumulation of c-myc mRNA that was induced by ConA but only slightly diminished the accumulation of c-myc mRNA that was induced by rIL2. Taken together, these data provide evidence that (i) c-myc gene expression can be regulated by at least two distinct pathways in T lymphocytes, only one of which is sensitive to cyclosporine A, and (ii) the accumulation of c-myc mRNA can be induced in T cells by IL2 during the G1 phase of the cell cycle.


Dynamic electrophoretic mobility of concentrated dispersions of spherical colloidal particles. On the consistent use of the cell model.
This paper outlines a complete and self-consistent cell model theory of the electrokinetics of dense spherical colloidal suspensions for general electrolyte composition, frequency of applied field, zeta potential, and particle size. The standard electrokinetic equations, first introduced for any given particle configuration, are made tractable to computation by averaging over particle configurations. The focus of this paper is on the systematic development of suitable boundary conditions at the outer cell boundary obtained from global constraints on the suspension. The approach is discussed in relation to previously published boundary conditions that have often been introduced in an ad hoc manner. Results of a robust numerical calculation of high-frequency colloidal transport properties, such as dynamic mobility, using the present model are presented and compared with some existing dense suspension models.


Official Positions for FRAX(®) clinical regarding glucocorticoids: the impact of the use of glucocorticoids on the estimate by FRAX(®) of the 10 year risk of fracture from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®).
Given the significant impact the use of glucocorticoids can have on fracture risk independent of bone density, their use has been incorporated as one of the clinical risk factors for calculating the 10-year fracture risk in the World Health Organization's Fracture Risk Assessment Tool (FRAX(®)). Like the other clinical risk factors, the use of glucocorticoids is included as a dichotomous variable with use of steroids defined as past or present exposure of 3 months or more of use of a daily dose of 5 mg or more of prednisolone or equivalent. The purpose of this report is to give clinicians guidance on adjustments which should be made to the 10-year risk based on the dose, duration of use and mode of delivery of glucocorticoids preparations. A subcommittee of the International Society for Clinical Densitometry and International Osteoporosis Foundation joint Position Development Conference presented its findings to an expert panel and the following recommendations were selected. 1) There is a dose relationship between glucocorticoid use of greater than 3 months and fracture risk. The average dose exposure captured within FRAX(®) is likely to be a prednisone dose of 2.5-7.5 mg/day or its equivalent. Fracture probability is under-estimated when prednisone dose is greater than 7.5 mg/day and is over-estimated when the prednisone dose is less than 2.5 mg/day. 2) Frequent intermittent use of higher doses of glucocorticoids increases fracture risk. Because of the variability in dose and dosing schedule, quantification of this risk is not possible. 3) High dose inhaled glucocorticoids may be a risk factor for fracture. FRAX(®) may underestimate fracture probability in users of high dose inhaled glucocorticoids. 4) Appropriate glucocorticoid replacement in individuals with adrenal insufficiency has not been found to increase fracture risk. In such patients, use of glucocorticoids should not be included in FRAX(®) calculations.


Light Localization in Local Isomorphism Classes of Quasicrystals.
We study a continuum of photonic quasicrystal heterostructures derived from local isomorphism (LI) classes of pentagonal quasicrystal tilings. These tilings are obtained by direct projection from a five-dimensional hypercubic lattice. We demonstrate that, with the sole exception of the Penrose LI class, all other LI classes result in degenerate, effectively localized states, with precisely predictable and tunable properties (frequencies, frequency splittings, and densities). We show that localization and tunability are related to a mathematical property of the pattern known as "restorability," i.e., whether the tiling can be uniquely specified given only a set of rules that fix all allowed clusters smaller than some bound.


Origin and evolution of medium chain alcohol dehydrogenases.
Different lines of alcohol dehydrogenases (ADHs) have separate superfamily origins, already recognized but now extended and re-evaluated by re-screening of the latest databank update. The short-chain form (SDR) is still the superfamily with most abundant occurrence, most multiple divergence, most prokaryotic emphasis, and most non-complicated architecture. This pattern is compatible with an early appearance at the time of the emergence of prokaryotic cellular life. The medium-chain form (MDR) is also old but second in terms of all the parameters above, and therefore compatible with a second emergence. However, this step appears seemingly earlier than previously considered, and may indicate sub-stages of early emergences at the increased resolution available from the now greater number of data entries. The Zn-MDR origin constitutes a third stage, possibly compatible with the transition to oxidative conditions on earth. Within all these three lines, repeated enzymogeneses gave the present divergence. MDR-ADH origin(s), at a fourth stage, may also be further resolved in multiple or extended modes, but the classical liver MDR-ADH of the liver type can still be traced to a gene duplication ~550 MYA (million years ago), at the early vertebrate radiation, compatible with the post-eon-shift, "Cambrian explosion". Classes and isozymes correspond to subsequent and recent duplicatory events, respectively. They illustrate a peculiar pattern with functional and emerging evolutionary distinctions between parent and emerging lines, suggesting a parallelism between duplicatory and mutational events, now also visible at separate sub-stages. Combined, all forms show distinctive patterns at different levels and illustrate correlations with global events. They further show that simple molecular observations on patterns, multiplicities and occurrence give much information, suggesting common divergence rules not much disturbed by horizontal gene transfers after the initial origins.


Patient Perceptions of Telehealth Primary Care Video Visits.
Telehealth is a care delivery model that promises to increase the flexibility and reach of health services. Our objective is to describe patient experiences with video visits performed with their established primary care clinicians. We constructed semistructured, in-depth qualitative interviews with adult patients following video visits with their primary care clinicians at a single academic medical center. Data were analyzed with a content analysis approach. Of 32 eligible patients, 19 were successfully interviewed. All patients reported overall satisfaction with video visits, with the majority interested in continuing to use video visits as an alternative to in-person visits. The primary benefits cited were convenience and decreased costs. Some patients felt more comfortable with video visits than office visits and expressed a preference for receiving future serious news via video visit, because they could be in their own supportive environment. Primary concerns with video visits were privacy, including the potential for work colleagues to overhear conversations, and questions about the ability of the clinician to perform an adequate physical examination. Primary care video visits are acceptable in a variety of situations. Patients identified convenience, efficiency, communication, privacy, and comfort as domains that are potentially important to consider when assessing video visits vs in-person encounters. Future studies should explore which patients and conditions are best suited for video visits.


Readmission for infective endocarditis after ischemic stroke or transient ischemic attack.
Providers vary in their thresholds for obtaining blood cultures in patients with ischemic stroke or transient ischemic attack (TIA). We assessed the rate of missed diagnoses of infective endocarditis (IE) in patients discharged with stroke or TIA before blood culture results could have been available. Using administrative claims data, we performed a retrospective cohort study of all patients discharged from nonfederal California emergency departments or acute care hospitals from 2005 through 2011 with stroke (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 433.x1, 434.x1, or 436 in any position) or TIA (ICD-9-CM code 435 in the primary diagnosis position). We excluded patients with a length of stay >2 days to focus on those discharged before conclusive blood culture results could have been available. Our outcome was hospitalization within 14 days with a new diagnosis of IE (ICD-9-CM codes 391.1 or 421.x in any position). Among 173 966 eligible patients, 24 were subsequently hospitalized for IE-a readmission rate of 1.4 per 10 000 (95% confidence interval [CI], 0.8-1.9 per 10 000). Multiple logistic regression identified the following potential associations with readmission: prosthetic valve: odds ratio (OR), 15.8 (95% CI, 1.9-129.0); other valvular disease: OR, 1.5 (95% CI, 0.2-10.8); urinary tract infection: OR, 3.5 (95% CI, 1.0-12.3; P = .05). In patients with acute cerebral ischemia discharged before blood culture results could have been available, the rate of subsequent IE was negligible. These findings argue against the liberal use of blood cultures for the routine evaluation of stroke or TIA.


Prediction of bone marrow involvement in patients with malignant lymphoma by GM-CSF stimulation test.
Recently, a stimulation test with colony stimulation factors was found useful to predict bone marrow cellularity. We examined the usefulness of this test to predict the bone marrow involvement in patients with malignant lymphoma. A single dose of GM-CSF (5 micrograms/kg) was given subcutaneously to 12 patients with malignant lymphoma. Six patients had normocellular bone marrow. Five of these 6 patients showed an increase in neutrophils of more than 5 x 10(9)/l after GM-CSF administration. The remaining 6 patients who had bone marrow lymphoma involvement had a neutrophil count of less than 5 x 10(9)/l. Therefore, the change in neutrophil count with a cut-off value of 5 x 10(9)/l distinguished the marrow lymphoma involvement with a sensitivity and specificity of 83% and 100%, respectively. The nadir neutrophil count was significantly higher in patients with normal marrow than in patients with marrow involvement after chemotherapy (P < 0.02). In conclusion, the GM-CSF stimulation test is useful to predict the marrow involvement in patients with malignant lymphoma.


MIECT: How did it start?
Transiently assuming the functions of both heart and lungs as surgeons repair critical valves and vessel lesions can be achieved by mechanical circulatory support has its origins in cardiopulmonary bypass (CPB). However, CPB technologies induce also some unintended adverse effects. During the 90s, a mayor trend pushed many physicians to reconsider the place of coronary artery bypass grafting (CABG) and challenged the surgical reference treatment by less invasive catheter-based angioplasties. Nevertheless, best long-term patient outcomes were related to surgery. Therefore, a small number of multidisciplinary teams in Regensburg and Paris started to develop a minimally invasive CPB system. The basic concept relied on a closed-loop perfusion circuit with a non-occlusive pump. Moreover, the team in Paris pushed the concept further and developed a complete fully integrated CPB system allowed first closed-heart and later open-heart surgery with aortic cross-clamping and efficient cardioprotection. Those were the initial steps towards the future developments of minimally invasive extracorporeal circulation technologies. Initial clinical results were clearly positive in terms of overall morbimortality. Moreover, several preliminary results pointed out the biological benefits that decreased hemodilution, improved preservation of the immune reactions and more stable anticoagulation could bring to the field of ECT.


Water intake and hydration state in children.
Although low water intake has been associated with adverse health outcomes, available literature indicated that the majority of children do not meet the water intake guidelines and they are underhydrated based on elevated hydration biomarkers. This review examined the water intake habits and hydration status in children from 32 observational studies (n = 36813). PubMed, Web of Science, and CINAHL were used to identify relevant articles. Total water/fluid intake from 25 countries was compared with water intake recommendations and underhydration (urine osmolality greater than 800 mmol kg-1) was assessed. Risk of bias was assessed using customized categories following the review guideline for observational studies. From 32 studies, only 11 studies reported both water intake and hydration status. 12 out of 24 studies reported mean/median water/fluid intake below the guidelines, while 4 out of 13 studies that assessed hydration status indicated underhydration based on urine osmolality (greater than 800 mmol kg-1). Among the 19 countries that reported comparison of water/fluid intake with guidelines, 60 ± 24% of children (range 10-98%) failed to meet them. These findings suggest that children are not consuming enough water to be adequately hydrated.