Does urgent or emergent status influence choice in mitral valve operations? An analysis of outcomes from the Virginia Cardiac Surgery Quality Initiative.
Urgent or emergent status is often associated with increased risk among cardiac operations. The objective of this study was to analyze outcomes and cost differences in patients undergoing elective versus urgent or emergent mitral valve replacement (MVR) and repair operations. From 2003 to 2008, 1,477 patients underwent isolated, primary mitral valve (MV) operations at 11 different centers in the Commonwealth of Virginia. Patients were stratified into four groups: elective MVR (n = 419), elective MV repair (n = 674), urgent or emergent MVR (n = 261) and urgent or emergent MV repair (n = 123). Preoperative risk, operative features, outcomes, and total costs were evaluated. Mitral valve replacement patients had more risk factors, including advanced age. Female sex and severe mitral regurgitation were more common among MV repairs. Mitral valve replacement incurred higher operative mortality (5.2% versus 1.2%; p < 0.001), more major complications (20.6% versus 6.5%; p < 0.001), longer postoperative (10.8 days versus 6.2 days; p < 0.001) and intensive care unit (117.7 hours versus 51.4 hours; p < 0.001) duration, and greater total costs ($45,166 versus $26,229; p < 0.001) compared with MV repair operations. Postoperative length of stay was longer for elective MVR patients compared with elective MV repair patients (p < 0.001) as well as for urgent or emergent MVR patients compared with urgent or emergent MV repair patients (p = 0.001). Total hospital costs were also higher for both elective MVR (p < 0.001) and urgent or emergent MVR (p < 0.001) compared with elective MV repair and urgent or emergent MV repair. Risk-adjusted operative mortality (odds ratio, 11.4; p < 0.001) and major complication rates (odds ratio, 7.6; p < 0.001) were highest for urgent or emergent MVR. Mitral valve repair is associated with lower morbidity, mortality, and total costs compared with MVR. For urgent or emergent operations, the improved outcomes with mitral repair versus replacement are even more profound.


Human CRP defends against the toxicity of circulating histones.
C-reactive protein (CRP) is an acute-phase protein that plays an important defensive role in innate immunity against bacterial infection, but it is also upregulated in many noninfectious diseases. The generic function of this highly conserved molecule in diseases that range from infection, inflammation, trauma, and malignancy is not well understood. In this article, we demonstrate that CRP defends the human body against the toxicity of histones released into the circulation after extensive cell death. In vitro, CRP significantly alleviates histone-induced endothelial cell damage, permeability increase, and platelet aggregation. In vivo, CRP rescues mice challenged with lethal doses of histones by inhibiting endothelial damage, vascular permeability, and coagulation activation, as reflected by significant reductions in lung edema, hemorrhage, and thrombosis. In patients, elevation of CRP significantly increases the capacity to neutralize extracellular histones in the circulation. We have also confirmed that CRP interacts with individual histones in vitro and forms CRP-histone complexes in serum from patients with both elevated CRP and histones. CRP is able to compete with phospholipid-containing liposomes for the binding to histones. This explains how CRP prevents histones from integrating into cell membranes, which would otherwise induce calcium influx as the major mechanism of cytotoxicity caused by extracellular histones. Because histone elevation occurs in the acute phase of numerous critical illnesses associated with extensive cell death, CRP detoxification of circulating histones would be a generic host defense mechanism in humans.


Symbolic regression via neural networks.
Identifying governing equations for a dynamical system is a topic of critical interest across an array of disciplines, from mathematics to engineering to biology. Machine learning-specifically deep learning-techniques have shown their capabilities in approximating dynamics from data, but a shortcoming of traditional deep learning is that there is little insight into the underlying mapping beyond its numerical output for a given input. This limits their utility in analysis beyond simple prediction. Simultaneously, a number of strategies exist which identify models based on a fixed dictionary of basis functions, but most either require some intuition or insight about the system, or are susceptible to overfitting or a lack of parsimony. Here, we present a novel approach that combines the flexibility and accuracy of deep learning approaches with the utility of symbolic solutions: a deep neural network that generates a symbolic expression for the governing equations. We first describe the architecture for our model and then show the accuracy of our algorithm across a range of classical dynamical systems.


Multiple Drug Transporters Contribute to the Placental Transfer of Emtricitabine.
Emtricitabine (FTC) is a first-line antiviral drug recommended for the treatment of AIDS during pregnancy. We hypothesized that transporters located in the placenta contribute to FTC transfer across the blood-placenta barrier. BeWo cells, cell models with stable or transient expression of transporter genes, primary human trophoblast cells (PHTCs), and small interfering RNAs (siRNAs) were applied to demonstrate which transporters were involved. FTC accumulation in BeWo cells was reduced markedly by inhibitors of equilibrative nucleoside transporters (ENTs), concentrative nucleoside transporters (CNTs), organic cation transporters (OCTs), and organic cation/carnitine transporter 1 (OCTN1) and increased by inhibitors of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs). ENT1, CNT1, OCTN1, MRP1/2/3, and BCRP, but not ENT2, CNT3, OCTN2, or multidrug resistance protein 1 (MDR1), were found to transport FTC. FTC accumulation in PHTCs was decreased significantly by inhibitors of ENTs and OCTN1. These results suggest that ENT1, CNT1, and OCTN1 probably contribute to FTC uptake from maternal circulation to trophoblasts and that ENT1, CNT1, and MRP1 are likely involved in FTC transport between trophoblasts and fetal blood, whereas BCRP and MRP1/2/3 facilitate FTC transport from trophoblasts to maternal circulation. Coexistence of tenofovir or efavirenz with FTC in the cell medium did not influence FTC accumulation in BeWo cells or PHTCs.


Characterization of an isogenic mutant of Streptococcus pyogenes Manfredo lacking the ability to make streptococcal acid glycoprotein.
An isogenic mutant of Streptococcus pyogenes Manfredo that lacks the ability to make streptococcal acid glycoprotein (SAGP) has been constructed by inserting a deletion in the sagp gene using the method of allelic exchange. An assay of cell extracts (CE) prepared from the wild-type and mutant Manfredo strains for the enzyme arginine deiminase (AD) showed that significant activity was present in wild-type CE but none could be detected in mutant CE. These findings confirm our earlier conclusion that SAGP has AD activity (B. A. Degnan, J. M. Palmer, T. Robson, C. E. D. Jones, M. Fischer, M. Glanville, G. D. Mellor, A. G. Diamond, M. A. Kehoe, and J. A. Goodacre, Infect. Immun. 66:3050-3058, 1998). Wild-type CE but not mutant CE potently inhibited human peripheral blood mononuclear cell proliferation in response to phytohemagglutinin, and this inhibition was overcome by the addition of L-arginine to proliferation assay mixtures. Invasion assays showed that the isogenic mutant organisms lacking SAGP, and thus AD activity, were between three and five times less able to enter epithelial cells (Hep-2C and A549) than were the wild-type streptococci. Both wild-type and mutant S. pyogenes bacteria were extremely sensitive to low pH. However, L-arginine (1 mM or above) significantly increased the viability of the wild type but not the isogenic mutant organisms under acidic conditions. The difference in acid susceptibility between wild-type and mutant bacteria may explain the reduced capacity of the isogenic mutant bacteria to invade and survive intracellularly.


Anesthesiological considerations in shoulder surgery.
In 1970, Winnie proposed the brachial plexus block as an alternative and effective anaesthesia technique for shoulder surgery. From that date, several techniques have been developed to approach the brachial plexus: the use of a nerve stimulator and, more recently, the ultrasound guided nerve blockade have made the procedure easier and more effective; the availability of the new drugs demonstrates some major advantages due to the application of peripheral blocks. Nowadays the attention has been focused on postoperative pain control: although many techniques have been proposed, the application of a continuous infusion of local anaesthetics through an interscalene catheter seems the best available technique to achieve pain relief after shoulder surgery. Advantages ad disadvantages of regional anaesthesia and adverse events associated with interscalene brachial plexus blockade are reviewed.


Audiovestibular symptoms and facial nerve function comparing microsurgery versus SRS for vestibular schwannomas: a systematic review and meta-analysis.
Surgery and radiosurgery represent the most common treatment options for vestibular schwannoma. A systematic review and meta-analysis were conducted to compare the outcomes of surgery versus stereotactic radiosurgery (SRS). The Cochrane library, PubMed, Embase, and clinicaltrials.gov were searched through 01/2021 to find all studies on surgical and stereotactic procedures performed to treat vestibular schwannoma. Using a random-effects model, pooled odds ratios (OR) and their 95% confidence intervals (CI) comparing post- to pre-intervention were derived for pre-post studies, and pooled incidence of adverse events post-intervention were calculated for case series and stratified by intervention type. Twenty-one studies (18 pre-post design; three case series) with 987 patients were included in the final analysis. Comparing post- to pre-intervention, both surgery (OR: 3.52, 95%CI 2.13, 5.81) and SRS (OR: 3.30, 95%CI 1.39, 7.80) resulted in greater odds of hearing loss, lower odds of dizziness (surgery OR: 0.10; 95%CI 0.02, 0.47 vs. SRS OR: 0.22; 95%CI 0.05, 0.99), and tinnitus (surgery OR: 0.23; 95%CI 0.00, 37.9; two studies vs. SRS OR: 0.11; 95%CI 0.01, 1.07; one study). Pooled incidence of facial symmetry loss was larger post-surgery (14.3%, 95%CI 6.8%, 22.7%) than post-SRS (7%, 95%CI 1%, 36%). Tumor control was larger in the surgery (94%, 95%CI 83%, 98%) than the SRS group (80%, 95%CI 31%, 97%) for small-to-medium size tumors. Both surgery and SRS resulted in similar odds of hearing loss and similar improvements in dizziness and tinnitus among patients with vestibular schwannoma; however, facial symmetry loss appeared higher post-surgery.


Signal transduction in thymus development.
Reciprocal interaction between bone marrow derived lymphoid precursor cells and the thymic environment leads, through a series of developmental events, to the generation of a diverse repertoire of functional T-cells. During thymopoiesis fetal liver or bone marrow derived precursors enter the thymus and develop into mature T-cells in response to cues derived from the environment. The thymic micro-environment provides signals to the lymphoid cells as a result of cell-cell interactions, locally produced cytokines, chemokines and hormones. Developing thymocytes, in turn, influence the thymic stroma to form a supportive micro-environment. Stage-specific signals provide an exquisite balance between cellular proliferation, differentiation, cell survival and death. The result of this intricate signaling concert is the production of the requisite numbers of well educated self-restricted T-cells. Mature T-cells are exported to the peripheral lymphoid organs, where, upon encountering antigen, naive T-cells further mature into effector cells that provide cytolytic or T helper functions. While there are extra-thymic locations for T-cell development, majority of T-cells in peripheral lymphoid organs are thymus derived. In mice and humans, T-cells develop throughout life although the efficacy declines significantly with age. It is not clear if this is a direct consequence of deterioration of the thymic environment by involution, a paucity of bone marrow derived precursors, or both. However, new data clearly shows that the involuted adult thymus retains the ability to generate new T-cells. Recent advances have revealed many components of an exquisitely balanced signaling cascades that regulate cell fate, cellular proliferation and cell death in the thymus. This article describes fundamental features of developing thymocytes and the thymic micro-environment as they relate to the signaling pathways.


Human mitochondrial COX1 assembly into cytochrome c oxidase at a glance.
Mitochondria provide the main portion of cellular energy in form of ATP produced by the F1Fo ATP synthase, which uses the electrochemical gradient, generated by the mitochondrial respiratory chain (MRC). In human mitochondria, the MRC is composed of four multisubunit enzyme complexes, with the cytochrome c oxidase (COX, also known as complex IV) as the terminal enzyme. COX comprises 14 structural subunits, of nuclear or mitochondrial origin. Hence, mitochondria are faced with the predicament of organizing and controlling COX assembly with subunits that are synthesized by different translation machineries and that reach the inner membrane by alternative transport routes. An increasing number of COX assembly factors have been identified in recent years. Interestingly, mutations in several of these factors have been associated with human disorders leading to COX deficiency. Recently, studies have provided mechanistic insights into crosstalk between assembly intermediates, import processes and the synthesis of COX subunits in mitochondria, thus linking conceptually separated functions. This Cell Science at a Glance article and the accompanying poster will focus on COX assembly and discuss recent discoveries in the field, the molecular functions of known factors, as well as new players and control mechanisms. Furthermore, these findings will be discussed in the context of human COX-related disorders.


Calcite Kinks Grow via a Multistep Mechanism.
The classical model of crystal growth assumes that kinks grow via a sequence of independent adsorption events where each solute transitions from the solution directly to the crystal lattice site. Here, we challenge this view by showing that some calcite kinks grow via a multistep mechanism where the solute adsorbs to an intermediate site and only transitions to the lattice site upon the adsorption of a second solute. We compute the free energy curves for Ca and CO3 ions adsorbing to a large selection of kink types, and we identify kinks terminated both by Ca ions and by CO3 ions that grow in this multistep way.


[Diagnostic problems in fetal echocardiographic examination. Observations on a lot of study during 2005-2010].
Echocardiography is the key diagnostic method in the diagnostics of structural heart pathologies. To underline some possible situations that may cause errors in ultrasound examination of the fetal heart. We examined a number of 39,370 fetuses along a period of six years. The ultrasound scan was performed according with international standards of basic and extended cardiac scan. 442 of them (1.12%) were diagnosed with cardiac malformations. Ultrasound examination errors can cause false positive, false negative or incomplete diagnosis. Limitations in fetal echocardiography are related to the examiner experience to do an accurate diagnosis. The difficulty of assessing complex congenital heart lesion is increased. The unsatisfactory study should be repeated and sometimes the exact diagnosis requires sequential procedures. The aim is to define fetal heart anatomy and adise the family, in collaboration with neonatologist. The final results ia an optimal behavior for the fetus and newborn.


The development of Cushing's syndrome from a previously silent pituitary tumour.
A 60 year old woman originally presented with headache. Investigations revealed a pituitary tumour and endocrine investigations at that time showed normal plasma cortisol levels. Seven years after removal of this tumour, the patient developed the clinical and biochemical features of Cushing's disease. Immunoperoxidase staining of the original tumour was positive for adrenocorticotrophic hormone. This report suggests that immunocytochemistry may have an important role in the routine evaluation of pituitary tumours.


[Expression of retinoic acid-I nducible gene I in the muscle tissues of idiopathic inflammatory myopathies].
To investigate the expression of retinoic acid-I inducible gene I (RIG-I) in the muscle tissues from patients with idiopathic inflammatory myopathies (IIMs), and to speculate the possible role of RIG-I in the immunopathogenesis of IIMs. Muscle specimens were obtained from 20 dermatomyositis (DM) and 20 polymyositis (PM) patients who underwent muscle biopsies from February 2010 to April 2014 at Qilu hospital affiliated to Shandong University. Besides, 4 facioscapulohumeral muscular dystrophy (FSHD), and 4 non-myopathic patients were taken as control group. All the biopsy specimens were processed with hematoxylin-eosin and immunohistochemical (Mouse anti human RIG-I antibodies) staining. We also examined the co-localization of RIG-I and CD303, which is the specific surface marker of plasmacytoid dendridic cells (pDCs), by means of double immunofluorescence staining. Western blot was performed for quantitative analysis. There was strong expression of RIG-I protein in DM/PM muscle tissues while in normal controls was virtually absent. RIG-I was specifically expressed in inflammatory cells and vessel endothelium, and nonspecifically expressed in regenerating and necrotic fibers. Besides, strong positive expression was observed in the perimysial perifascicular fibers of DM. In FSHD muscle tissues, only a few regenerating and necrotic fibers was stained nonspecifically for RIG-I. However, co-expression of RIG-I and CD303 was not detected in DM/PM muscles. The mean grey value of RIG-I observed in DM (0.901 ± 0.470) and PM (0.630 ± 0.444) group was significantly higher than in control group including Normal (0.003 ± 0.003) and FSHD (0.019 ± 0.013) groups (P < 0.05). RIG-I may operate as a mediator in Th1 cytokine-I induced chemokine expression, so it is involved in the pathogenesis of IIMs. But RIG-I may not play a major role in innate immune reaction mediated by type I interferon.


Can occupancy-abundance models be used to monitor wolf abundance?
Estimating the abundance of wild carnivores is of foremost importance for conservation and management. However, given their elusive habits, direct observations of these animals are difficult to obtain, so abundance is more commonly estimated from sign surveys or radio-marked individuals. These methods can be costly and difficult, particularly in large areas with heavy forest cover. As an alternative, recent research has suggested that wolf abundance can be estimated from occupancy-abundance curves derived from "virtual" surveys of simulated wolf track networks. Although potentially more cost-effective, the utility of this approach hinges on its robustness to violations of its assumptions. We assessed the sensitivity of the occupancy-abundance approach to four assumptions: variation in wolf movement rates, changes in pack cohesion, presence of lone wolves, and size of survey units. Our simulations showed that occupancy rates and wolf pack abundances were biased high if track surveys were conducted when wolves made long compared to short movements, wolf packs were moving as multiple hunting units as opposed to a cohesive pack, and lone wolves were moving throughout the surveyed landscape. We also found that larger survey units (400 and 576 km2) were more robust to changes in these factors than smaller survey units (36 and 144 km2). However, occupancy rates derived from large survey units rapidly reached an asymptote at 100% occupancy, suggesting that these large units are inappropriate for areas with moderate to high wolf densities (>15 wolves/1,000 km2). Virtually-derived occupancy-abundance relationships can be a useful method for monitoring wolves and other elusive wildlife if applied within certain constraints, in particular biological knowledge of the surveyed species needs to be incorporated into the design of the occupancy surveys. Further, we suggest that the applicability of this method could be extended by directly incorporating some of its assumptions into the modelling framework.


Modulation of anger control in suicide attempters by TPH-1.
A genetic association between the tryptophan hydroxylase gene (TPH)-1 A218C polymorphism and suicidal behaviour is supported by numerous case-control studies as well as recent meta-analyses. Some data suggest that this polymorphism could also influence individual differences in anger-related personality traits, a phenotype partially under genetic control and known to increase the risk of suicide ideation and attempt. The aim of the present study was to investigate whether the TPH-1 A218C polymorphism affected anger-related personality traits in suicide attempters (n = 544). We hypothesized that suicide attempters carrying the AA genotype would display different scores on a scale measuring anger-related traits compared with suicide attempters carrying the CC genotype. Indeed, the dimension of Anger Control was significantly affected by the TPH-1 A218C polymorphism: suicide attempters carrying the AA genotype scored significantly lower on the Anger Control subscale than suicide attempters carrying the AC and CC genotypes. This polymorphism did not display any influence on the other State-Trait Anger Expression Inventory subscales. This result confirms our working hypothesis and suggests that the TPH-1 genotype could confer a vulnerability to suicidal behaviour through a reduced capacity to control anger, which in turn may represent a common psychopathological and behavioural pathway to suicidal behaviour in an important subgroup of clinical subjects.


Deletion of beta-fructofuranosidase (invertase) genes is associated with sucrose content in Date Palm fruit.
The fruit of date palm trees are an important part of the diet for a large portion of the Middle East and North Africa. The fruit is consumed both fresh and dry and can be stored dry for extended periods of time. Date fruits vary significantly across hundreds of cultivars identified in the main regions of cultivation. Most dried date fruit are low in sucrose but high in glucose and fructose. However, high sucrose content is a distinctive feature of some date fruit and affects flavor as well as texture and water retention. To identify the genes controlling high sucrose content, we analyzed date fruit metabolomics for association with genotype data from 120 date fruits. We found significant association of dried date sucrose content and a genomic region that contains 3 tandem copies of the beta-fructofuranosidase (invertase) gene in the reference Khalas genome, a low-sucrose fruit. High-sucrose cultivars including the popular Deglet Noor had a homozygous deletion of two of the 3 copies of the invertase gene. We show the deletion allele is derived when compared to the ancestral allele that retains all copies of the gene in 3 other species of Phoenix. The fact that 2 of the 3 tandem invertase copies are associated with dry fruit sucrose content will assist in better understanding the distinct roles of multiple date palm invertases in plant physiology. Identification of the recessive alleles associated with end-point sucrose content in date fruit may be used in selective breeding in the future.


The perception of farm safety and prevention issues among the Old Order Amish in Lancaster County, Pennsylvania.
The purpose of this study was to explore farm safety and prevention issues within an Old Order Amish community. A qualitative ethnographic approach was used to explore perceptions of Amish adults as to the issues related to farm safety and prevention for their children. Access to this community was facilitated through two contact people who were well known in the community. Data were collected using semistructured interviews and recorded as field notes. Data analysis was done by looking for themes based on the questions asked about safety and prevention. From this analysis, four themes were found related to safety and prevention. They included education of the parents, education of the children, home and farm preventive measures, and enforcement of established rules. In addition, childhood readiness was found to be another important issue related to farm safety. Childhood readiness was found to have three themes, developmental appropriateness, parental control and supervision, and birth order of the child. Data from this study suggested that farm safety is a concern of the Old Order Amish in Lancaster County. Their perceptions of safety and prevention issues centered on the incidents that have occurred and are considered dangerous. It is important to look at the identified safety and prevention and childhood readiness themes to identify the most beneficial approaches for the Amish to promote safety on their farms.


Applications and limitations of Centers for Disease Control and Prevention miniature light traps for measuring biting densities of African malaria vector populations: a pooled-analysis of 13 comparisons with human landing catches.
Measurement of densities of host-seeking malaria vectors is important for estimating levels of disease transmission, for appropriately allocating interventions, and for quantifying their impact. The gold standard for estimating mosquito-human contact rates is the human landing catch (HLC), where human volunteers catch mosquitoes that land on their exposed body parts. This approach necessitates exposure to potentially infectious mosquitoes, and is very labour intensive. There are several safer and less labour-intensive methods, with Centers for Disease Control light traps (LT) placed indoors near occupied bed nets being the most widely used. This paper presents analyses of 13 studies with paired mosquito collections of LT and HLC to evaluate these methods for their consistency in sampling indoor-feeding mosquitoes belonging to the two major taxa of malaria vectors across Africa, the Anopheles gambiae sensu lato complex and the Anopheles funestus s.l. group. Both overall and study-specific sampling efficiencies of LT compared with HLC were computed, and regression methods that allow for the substantial variations in mosquito counts made by either method were used to test whether the sampling efficacy varies with mosquito density. Generally, LT were able to collect similar numbers of mosquitoes to the HLC indoors, although the relative sampling efficacy, measured by the ratio of LT:HLC varied considerably between studies. The overall best estimate for An. gambiae s.l. was 1.06 (95% credible interval: 0.68-1.64) and for An. funestus s.l. was 1.37 (0.70-2.68). Local calibration exercises are not reproducible, since only in a few studies did LT sample proportionally to HLC, and there was no geographical pattern or consistent trend with average density in the tendency for LT to either under- or over-sample. LT are a crude tool at best, but are relatively easy to deploy on a large scale. Spatial and temporal variation in mosquito densities and human malaria transmission exposure span several orders of magnitude, compared to which the inconsistencies of LT are relatively small. LT, therefore, remain an invaluable and safe alternative to HLC for measuring indoor malaria transmission exposure in Africa.


Development of gut microbiota in infants not exposed to medical interventions.
Knowledge of the composition of a normal healthy gut microbiota during infancy is important for understanding the role of gut microbiota in disease. A limitation of previous studies is that they are based on infants who have been subject to factors, which can have a profound disruptive effect on the natural colonization process. We describe the colonization process, during the first 4 months after birth, in 85 infants who have experienced no major medical or dietary interventions. They were all vaginally delivered, healthy, term infants, who were not exposed to antibiotics, exclusively breastfed during their first month of life and at least partially breastfed up to 4 months. Selected microbial groups were identified by targeting small subunit microbial ribosomal RNA genes. In contrast to more recent studies, but in agreement with older studies, almost all our infants harbored γ-Proteobacteria and Bifidobacterium. Yet undefined non-cultivable species belonging to Bacteroides, as well as microbes identified as Lachnospiraceae 2, were common. Strong associations were observed between some specific constituents of microbiota at day 4 and the concentration of specific microbial groups at day 120, indicating that early gut microbiota may influence later microbiota. Novel information of the undisturbed composition of early gut microbiota in babies is presented.


Normative intercapillary distance and vessel density data in the temporal retina assessed by wide-field spectral-domain optical coherence tomography angiography.
A limitation of conventional optical coherence tomography angiography (OCTA) is the limited field of view normally used in data acquisition. As the technology improves, larger fields of view that capture information away from the macular are being explored in order to provide an enhanced ability to detect pathology. However, normative measurements for important OCTA metrics like vessel density and intercapillary distance are not currently well-characterized in the peripheral retina. In this prospective study, we measured vessel density and intercapillary distance of the superficial vascular complex, ganglion cell layer plexus, and deep capillary plexus in montaged macular/temporal scans from 53 (33 men) healthy volunteers. Vessel density and intercapillary distance were also compared across different regions of the retina, including along arcs at separate distance from the fovea. Compared to the central macular region, the temporal retina had significantly lower vessel density, decreased thickness, and greater intercapillary distance in the superficial vascular complex, GCLP ganglion cell layer plexus, and deep capillary plexus (Wilcoxon rank sum test P < 0.001), with each of the plexuses examined here showing a general decrease in vessel density and an increase in intercapillary distance towards the temporal region. No significant difference was noted comparing corresponding vessel density and intercapillary distance regions above and below the macula, and multiple linear regression showed that age and intraocular pressure were not associated with vessel density and intercapillary distance in most models. Repeatability analysis reported as intraclass correlation coefficients demonstrated moderate to excellent reliability of vessel density and intercapillary distance in all OCTA layers. These results should help provide an enhanced baseline to help identify vascular pathology in the peripheral retina.


Ultrasensitive Photonic Microsystem Enabling Sub-micrometric Monitoring of Arterial Oscillations for Advanced Cardiovascular Studies.
Cardiovascular diseases are the first cause of death globally. Their early diagnosis requires ultrasensitive tools enabling the detection of minor structural and functional alterations in small arteries. Such analyses have been traditionally performed with video imaging-based myographs, which helped to investigate the pathophysiology of the microvessels. Since new vascular questions have emerged, substantial modifications are necessary to improve the performance of imaging and tracking software, reducing the cost and minimizing the microvessel cleaning and manipulation. To address these limitations, we present a photonic microsystem fabricated in polydimethylsiloxane and integrating micro-optical elements and a lightguide-cantilever for sub-micrometric analysis of small arteries (between 125 and 400 μm of basal diameter). This technology enables simultaneous measurement of arterial distension, stiffness, vasomotion, and heartbeat and without the need for advanced imaging system. The microsystem has a limit of detection of 2 μm, five times lower than video imaging-based myographs, is two times more sensitive than them (0.5 μm/mmHg), reduces variability to half and doubles the linear range reported in these myographs. More importantly, it allows the analysis of intact arteries preserving the integrity and function of surrounding tissues. Assays can be conducted in three configurations according to the surrounding tissue: (i) isolated arteries (in vitro) where the surrounding tissue is partially removed, (ii) non-isolated arteries (in vivo) with surrounding tissue partially removed, and (iii) intact arteries in vivo preserving surrounding tissue as well as function and integrity. This technology represents a step forward in the prediction of cardiovascular risk.


Coronary computed tomography as a cost-effective test strategy for coronary artery disease assessment - a systematic review.
Cardiovascular imaging imparts a huge burden on healthcare spending. Coronary CT angiography (CCTA) may provide a cost effective means of diagnosing coronary artery disease (CAD) and reducing downstream cost of testing. We performed a systematic search of literature for randomized controlled trials or prospective or retrospective non-randomized comparative studies or case series, decision analytic models and technology reports in which some or all of the patients underwent CCTA and looking at the cost effectiveness, comparative effectiveness and downstream test utilization associated with the use of CCTA. We found 42 articles matching our criteria. CCTA either as first line or as a layering test may represent a cost effective strategy for initial evaluation of patients with CAD prevalence of 10%-50% in both near-term and long-term diagnostic periods. For CAD prevalence ≥70%, ICA as initial test may represent cost effective strategy for diagnosis of stable chest pain. CCTA may represent cost-effective strategy when performed as a layering test to equivocal initial stress imaging before performing ICA. Use of CCTA is cost- and time-effective strategy for evaluation of low risk (<30% CAD prevalence) acute chest pain patients in emergency department and can be used for safe exclusion of acute coronary syndrome (ACS). Use of coronary calcium score as an initial test may require further evidence to be deemed cost-effective strategy. CCTA may represent a cost effective and may be associated with less downstream testing for diagnosis of stable chest pain patients in low to intermediate risk patients whereas for low risk acute chest pain patients, use of CCTA is associated with expedited patient management, less cost and safe exclusion of ACS.


Mosaicism: Implications for Genetic Counseling and Medical Management.
Mosaicism describes the presence of two or more populations of cells with different genotypes in one individual that have developed from a single fertilized egg. This article reviews the various clinical presentations of mosaicism associated with hereditary cancer syndromes and the challenges in providing patients and their families with appropriate genetic testing, as well as provides recommendations for cancer presentation and early detection. Management of mosaicism is based on personal and family history, along with genetic testing results. .


Genetic disorders of surfactant dysfunction.
Mutations in the genes encoding the surfactant proteins B and C (SP-B and SP-C) and the phospholipid transporter, ABCA3, are associated with respiratory distress and interstitial lung disease in the pediatric population. Expression of these proteins is regulated developmentally, increasing with gestational age, and is critical for pulmonary surfactant function at birth. Pulmonary surfactant is a unique mixture of lipids and proteins that reduces surface tension at the air-liquid interface, preventing collapse of the lung at the end of expiration. SP-B and ABCA3 are required for the normal organization and packaging of surfactant phospholipids into specialized secretory organelles, known as lamellar bodies, while both SP-B and SP-C are important for adsorption of secreted surfactant phospholipids to the alveolar surface. In general, mutations in the SP-B gene SFTPB are associated with fatal respiratory distress in the neonatal period, and mutations in the SP-C gene SFTPC are more commonly associated with interstitial lung disease in older infants, children, and adults. Mutations in the ABCA3 gene are associated with both phenotypes. Despite this general classification, there is considerable overlap in the clinical and histologic characteristics of these genetic disorders. In this review, similarities and differences in the presentation of these disorders with an emphasis on their histochemical and ultrastructural features will be described, along with a brief discussion of surfactant metabolism. Mechanisms involved in the pathogenesis of lung disease caused by mutations in these genes will also be discussed.


Self-reported physical activity, subjective health, and cognitive performance in older adults.
The literature to date suggests a positive relationship between physiological indicators of physical fitness (such as aerobic capacity) and indices of cognitive performance. However, the complexity and cost of methods to measure physical fitness prohibit their use in large-population studies in cognitive aging research. In this study, a questionnaire measuring habitual physical activity was used as an indirect estimate of physical fitness, to predict performance in several cognitive domains in an age- and sex-stratified sample of 80 healthy older adults (55 years and older). Age effects were found on several measures of cognitive speed and fluency, but not on memory performance. Women were slower in sensorimotor speed than men but scored higher on memory tasks. No main effects of activity on cognitive measures were found, but two measures that assessed cognitive speed were sensitive to the age-by-activity interaction term. Subjective health also appeared to contribute to the explained variance in the same two indices of cognitive speed. Limitations of the use of activity questionnaires in cognitive aging research are discussed.


Prevalence of venous occlusion in patients referred for lead extraction: implications for tool selection.
Data concerning the incidence of venous obstruction in patients referred for lead extraction is limited. Thus, we aimed to assess the incidence of venous obstruction in patients referred for lead extraction and the implications for tool selection. Contrast venography of the access vein was obtained in 202 patients (147 men; mean age, 62.4 ± 14.5 years) scheduled for lead extraction. The indication for lead extraction included infection (n = 145, 72%) and other causes (n = 57, 28%). Two patients with device infection had superior vena caval occlusion. Access vein occlusion occurred in 6 (11%) patients without infection vs. 46 (32%) patients with infection [P = 0.002; odds ratio (OR) 3.94; 95% confidence interval (CI) 1.58-9.87]. No significant differences between occluded and non-occluded patients were seen for age, sex, device type, number of leads, time from implant of the initial lead, or anticoagulation therapy (all P>0.05). Procedural duration and fluoroscopy exposure time were significantly lower in the open group than in the occluded group (P < 0.05). Patients with venous occlusion required more advanced tools for lead extraction, such as dilator sheaths, evolution sheaths, and needle's eye snares (P = 0.019). Both systemic and local infections are associated with increased risk of access vein occlusion. We found no support for the hypothesis that venous occlusion increases with the number of leads present. Lead extraction was more difficult in patients with venous occlusion, requiring advanced tools and more time.


Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure.
Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 106 CD34+ cells/kg for a single or ≥5 × 106 CD34+ cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34+ cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34+ cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 106 CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19+ and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.


A Framework for Understanding the Emerging Role of Corticolimbic-Ventral Striatal Networks in OCD-Associated Repetitive Behaviors.
Significant interest in the mechanistic underpinnings of obsessive-compulsive disorder (OCD) has fueled research on the neural origins of compulsive behaviors. Converging clinical and preclinical evidence suggests that abnormal repetitive behaviors are driven by dysfunction in cortico-striatal-thalamic-cortical (CSTC) circuits. These findings suggest that compulsive behaviors arise, in part, from aberrant communication between lateral orbitofrontal cortex (OFC) and dorsal striatum. An important body of work focused on the role of this network in OCD has been instrumental to progress in the field. Disease models focused primarily on these regions, however, fail to capture an important aspect of the disorder: affective dysregulation. High levels of anxiety are extremely prevalent in OCD, as is comorbidity with major depressive disorder. Furthermore, deficits in processing rewards and abnormalities in processing emotional stimuli are suggestive of aberrant encoding of affective information. Accordingly, OCD can be partially characterized as a disease in which behavioral selection is corrupted by exaggerated or dysregulated emotional states. This suggests that the networks producing OCD symptoms likely expand beyond traditional lateral OFC and dorsal striatum circuit models, and highlights the need to cast a wider net in our investigation of the circuits involved in generating and sustaining OCD symptoms. Here, we address the emerging role of medial OFC, amygdala, and ventral tegmental area projections to the ventral striatum (VS) in OCD pathophysiology. The VS receives strong innervation from these affect and reward processing regions, and is therefore poised to integrate information crucial to the generation of compulsive behaviors. Though it complements functions of dorsal striatum and lateral OFC, this corticolimbic-VS network is less commonly explored as a potential source of the pathology underlying OCD. In this review, we discuss this network's potential role as a locus of OCD pathology and effective treatment.


[Mosquitoes of the subgenus Edwardsaedes of the fauna of the Palaeoarctic region with a description of the larva of Aedes (Edw.) bekkui].
Two species of the subgenus Edwardsaedes, Ae. (Edw.) pingpaensis Chang and Ae. (Edw.) bekkui Mogi, are spread in the Palaearctic region, the first one being known from China only and the second one from Japan and South Primorye, USSR. The name Ae. (Edw.) antuensis Su, Wang et Li, 1965 should be considered as a synonym of Ae. (Edw.) pingpaensis Chang, 1965; the larva of Ae. (Ochlerotatus) sticticus Mg. has been erroneously described by Su et al. (1978) as larva of Ae. antuensis. The differential diagnosis of the females, male genitalia, and larvae of mosquitoes Ae. pingpaensis and Ae. bekkui, is given. The description of the fourth stage larva of Ae. bekkui from the South Primorye is presented for the first time in the home literature.


Molecular characterization of Babesia and Theileria species in ticks collected in the outskirt of Monte Romano, Lazio Region, Central Italy.
In 2012-2013, an investigation was carried out in the Viterbo province, Lazio region, on ticks and tick-borne Apicomplexan protozoa of the Babesia and Theileria genera. This followed the reporting of high density of ticks by soldiers operating in a military shooting range, and the signaling by owners and local veterinary authorities of several cases of babesiosis among cattle. A total of 422 ticks were collected from 35 heads, whereas 96 ticks were collected by dragging. Ticks were identified as Rhipicephalus (Boophilus) annulatus Say (n = 373), Rhipicephalus bursa Canestrini & Fanzago (n = 63), Rhipicephalus sanguineus/turanicus (n = 32), Hyalomma marginatum Koch (n = 49) and Dermacentor marginatus Sulzer, 1776 (n = 1). A randomly selected sample of ticks (235 from animals and 36 by dragging) was analyzed using molecular methods to detect species of Babesia and Theileria. In total, 11 ticks collected from animals (4.7%) and two ticks (5.5%) collected by dragging were positive. Sequencing of PCR products of the small subunit ribosomal RNA gene revealed Babesia caballi (n = 2), Babesia bigemina (n = 3), Theileria sergenti/buffeli/orientalis (n = 7) and Theileria equi (n = 1). None of the detected species has been associated with human infection.


Magnesium-aspartate-hydrochloride reduces weight loss in heat-stressed laying hens.
Two separate experiments were conducted to determine the ability of magnesium aspartate hydrochloride (Mg-Asp-HCl) to antagonize the effects of thermal stress in laying hens. In both experiments, hens were exposed to either a cyclic ambient temperature of 27 C to 35 C (hyperthermic group) or 23 C (control group) for 7 days. In Experiment 1, hens were given a single injection of either saline, 40 mg, or 80 mg Mg-Asp-HCl. Experiment 2 hens received a single injection of saline, 40 mg Mg-Asp-HCl, or twice daily injection of 40 mg Mg-Asp-HCl. In both experiments, heat-stressed hens had elevated body temperature and reduced body weight, feed consumption, and circulating mean Mg concentrations. Hyperthermic hens also had reduced egg weights in Experiment 1. A single daily injection of 40 mg of Mg-Asp-HCl significantly reduced body weight loss in heat stressed hens by 41 and 51%, in Experiment 1 and 2, respectively, when compared with heat-stressed hens not receiving Mg-Asp-HCl (controls). The Mg-Asp-HCl treatment did not affect overall feed intake, egg production, or body temperature in either experiment. The highest dose of Mg-Asp-HCl (80 mg) elevated circulating magnesium concentrations. A single daily injection of 80 mg of Mg-Asp-HCl or twice daily injections of 40 mg Mg-Asp-HCl did not provide any additional benefit when compared with a single daily dose of 40 mg. The antistress effects of Mg-Asp-HCl are apparent in these experiments as evidenced by the increased body weight of heat-stressed hens. Use of this compound may prove to be beneficial in maintaining the performance characteristics of poultry exposed to elevated ambient temperature.


Distinctiveness of genotypes of Helicobacter pylori in Calcutta, India.
The genotypes of 78 strains of Helicobacter pylori from Calcutta, India (55 from ulcer patients and 23 from more-benign infections), were studied, with a focus on putative virulence genes and neutral DNA markers that were likely to be phylogenetically informative. PCR tests indicated that 80 to 90% of Calcutta strains carried the cag pathogenicity island (PAI) and potentially toxigenic vacAs1 alleles of the vacuolating cytotoxin gene (vacA), independent of disease status. This was higher than in the West (where cag PAI(+) vacAs1 genotypes are disease associated) but lower than in east Asia. The iceA2 gene was weakly disease associated in Calcutta, whereas in the West the alternative but unrelated iceA1 gene at the same locus is weakly disease associated. DNA sequence motifs of vacAm1 (middle region) alleles formed a cluster that was distinct from those of east Asia and the West, whereas the cagA sequences of Calcutta and Western strains were closely related. An internal deletion found in 20% of Calcutta iceA1 genes was not seen in any of approximately 200 strains studied from other geographic regions and thus seemed to be unique to this H. pylori population. Two mobile DNAs that were rare in east Asian strains were also common in Calcutta. About 90% of Calcutta strains were metronidazole resistant. These findings support the idea that H. pylori gene pools differ regionally and emphasize the potential importance of studies of Indian and other non-Western H. pylori populations in developing a global understanding of this gastric pathogen and associated disease.


CMBEAR: Python-Based Recharge Estimator Using the Chloride Mass Balance Method in Australia.
The chloride mass balance (CMB) method is widely used to estimate long-term rates of groundwater recharge. In regions where surface water runoff is negligible, recharge can be estimated using measurements of chloride concentrations of groundwater and precipitation, and an estimate of long-term average rainfall. This paper presents the Chloride Mass Balance Estimator of Australian Recharge (CMBEAR), a Jupyter (Python) Notebook that is set up to rapidly apply the CMB method using gridded maps of chloride deposition rates across the Australian continent. For an Australian context, the chloride deposition rate and rainfall maps have been provided. Thus, CMBEAR requires only a spreadsheet with the groundwater chloride concentration, the latitude and longitude of the sample location, and some simple user inputs. CMBEAR may be easily applied in other regions, providing that a gridded chloride deposition map is available. Recharge estimates from CMBEAR are compared against published applications of the CMB method. CMBEAR is also applied to a large dataset from the Northern Territory and is used to produce a gridded map of recharge for western Victoria. CMBEAR provides a reproducible and straightforward approach to apply the CMB method to estimate groundwater recharge.


Percutaneous lung abscess drainage: revisiting the old gold standard.
Lung abscess is defined as the necrosis of lung tissue with cavity formation due to varied etiology. The treatment of lung abscesses is medical involving antibiotics and chest physiotherapy. The failure of medical line of management requires an invasive surgical or percutaneous approach for drainage and control of infection. While the literature is ample regarding the surgical approach, it is rather scarce on the percutaneous approach. The percutaneous drainage has been most studied with computed tomography guidance. With our case series we describe to the treatment of lung abscesses non-responsive to medical management, by a bedside minimally invasive ultrasound or fluoroscopy guided percutaneous drainage approach.


Protocol for a study of nutritional factors and the low risk of colon cancer in Southern retirement areas.
Colon cancer shows a distinct geographic pattern in the United States, with mortality rates in the Northeast exceeding those in the South by about 50%. The North-South gradient remains even after adjustment for differences in urbanization and socioeconomic status. Those counties in the South that attract large numbers of retirees from the North retain the low colon mortality rates characteristic of the South, even at older ages. This observation implies either that certain life-style changes associated with migration at retirement rapidly reduce the risk of colon cancer or that individuals migrate selectively, based on some correlate of health. A specific hypothesis related to the former possibility is that consumption of fruits and vegetables, and the associated vitamin C, carotene, and fiber, is elevated in the South and related to the reduced risk of colon cancer. A protocol is presented for a case-control interview study in Southern retirement areas to assess these possible explanations. A detailed residential history, as well as information on frequency of consumption of specific foods, food groups, and micronutrients, will be collected by interview and will be complemented by selected serum micronutrient determinations and fecal mutagenicity assays.


The rate of blood loss from skin punctures during the Ivy bleeding time test.
The rate of blood loss from skin punctures during the performance of the Ivy bleeding time test has been measured by a simple technique in normal individuals, in patients without defects of the haemostatic or coagulation system, and in patients with known haemorrhagic disorders.A wide range was found in normal individuals, but repeated tests on a single individual showed a smaller variation. Nearly half of the tests on patients with von Willebrand's disease, thrombocytopenia, ;capillary type' of bleeding, or haemorrhagic renal failure gave abnormally high rates of blood loss. Haemophilic, Christmas disease, and Dinedevan-treated patients gave low volumes and rates of blood loss.A group of patients has been encountered in whom the bleeding time was normal but the rate of blood loss was increased. The majority of these had haemorrhagic symptoms and other evidence of a defective haemostatic or coagulation system. It is suggested that a consideration of the rate of blood loss in those patients with a normal bleeding time gives additional help in interpreting the Ivy test. A high rate may indicate the need for further investigation of the haemostatic and coagulation system.


A Life without Hunger: The Ups (and Downs) to Modulating Melanocortin-3 Receptor Signaling.
Melanocortin neurons conserve body mass in hyper- or hypo-caloric conditions by conveying signals from nutrient sensors into areas of the brain governing appetite and metabolism. In mice, melanocortin-3 receptor (MC3R) deletion alters nutrient partitioning independently of hyperphagia, promoting accumulation of fat over muscle mass. Enhanced rhythms in insulin and insulin-responsive metabolic genes during hypocaloric feeding suggest partial insulin resistance and enhanced lipogenesis. However, exactly where and how MC3Rs affect metabolic control to alter nutrient partitioning is not known. The behavioral phenotypes exhibited by MC3R-deficient mice suggest a contextual role in appetite control. The impact of MC3R-deficiency on feeding behavior when food is freely available is minor. However, homeostatic responses to hypocaloric conditioning involving increased expression of appetite-stimulating (orexigenic) neuropeptides, binge-feeding, food anticipatory activity (FAA), entrainment to nutrient availability and enhanced feeding-related motivational responses are compromised with MC3R-deficiency. Rescuing Mc3r transcription in hypothalamic and limbic neurons improves appetitive responses during hypocaloric conditioning while having minor effects on nutrient partitioning, suggesting orexigenic functions. Rescuing hypothalamic MC3Rs also restores responses of fasting-responsive hypothalamic orexigenic neurons in hypocaloric conditions, suggesting actions that sensitize fasting-responsive neurons to signals from nutrient sensors. MC3R signaling in ventromedial hypothalamic SF1(+ve) neurons improves metabolic control, but does not restore appetitive responses or nutrient partitioning. In summary, desensitization of fasting-responsive orexigenic neurons may underlie attenuated appetitive responses of MC3R-deficient mice in hypocaloric situations. Further studies are needed to identify the specific location(s) of MC3Rs controlling appetitive responses and partitioning of nutrients between fat and lean tissues.


Targeting the Gut Microbiota in Kidney Disease: The Future in Renal Nutrition and Metabolism.
There is increasing interest in the therapeutic potential of manipulating the gut microbiome of patients with chronic kidney disease (CKD). This is because there is a substantial deviation from a balanced gut microbiota profile in CKD, with many deleterious downstream effects. Nutritional interventions such as plant-based diets with reduced animal protein intake and the use of probiotics, prebiotics, and synbiotics may alter the microbiome. This article aims to briefly describe what is known about the gut microbiome in patients with CKD, factors contributing to gut dysbiosis, and outline important evidence gaps. Future potential therapies, including restoring the microbiota with food and microbiota-based and metabolomic-based therapies, are also discussed.


The psychosocial needs of gynaecological cancer survivors: A framework for the development of a complex intervention.
To develop and pilot test an intervention targeting the women's psychosocial needs during the follow-up period after surgical treatment for gynaecological cancer. The project consisted of four phases. Phase 1 involved development of an intervention on the basis of meetings with key healthcare professionals, a literature review and six semi-structured interviews with women who attended the existing follow-up program. The Guided Self-Determination (GSD) method developed in diabetes care was identified as an appropriate framework for the intervention. GSD consists of reflection sheets for patients and advanced professional communication skills. The GSD method was adapted to women in a follow-up program after gynaecologic cancer treatment (GSD-GYN-C). Phase 2 involved primary pilot testing of the intervention and the findings were used to modify the intervention in phase 3. This modification involved the development of additional reflection sheets and a fidelity assessment tool. A systematic training program was arranged for the GSD-GYN-C-nurses. Phase 4 involved secondary pilot testing where nurses and women confirmed the applicability of GSD-GYN-C and final adjustments were made. Selected measurements were tested for sensitivity during pilot testing. Data from phase 2 and 4 were also used to select the primary outcome and calculate power for a future randomized clinical trial (RCT). Pilot testing supported our hypothesis that GSD-GYN-C may be transferable and useful to survivors of gynaecological cancer. GSD-GYN-C was developed and validated and is now ready for evaluation in an RCT.


Baseline Concussion Clinical Measures Are Related to Sensory Organization and Balance.
This study aimed to examine relationships among baseline demographics, symptom severity, computerized neurocognitive outcomes, and balance performance in collegiate athletes. Collegiate varsity athletes (N = 207, age = 19.3 ± 1.0 yr) participating in an ongoing clinical research program who completed concussion baseline assessments including a demographic questionnaire, a graded symptom checklist, a neurocognitive assessment, and the Sensory Organization Test (SOT) were included in this study. The SOT composite equilibrium score (COMP) and three sensory ratio scores-vestibular (VEST), visual (VIS), and somatosensory (SOM)-were used to describe athletes' overall sensory organization and ability to use input from each sensory system to maintain balance. Separate stepwise multiple linear regression models were performed for each SOT outcome. Total symptom severity level and CNS Vital Signs domain scores served as predictor variables. Stepwise regression models for COMP (R = 0.18, F4,201 = 11.29, P < 0.001), VEST (R = 0.14, F4,201 = 8.16, P < 0.001), and VIS (R = 0.10, F4,201 = 5.52, P < 0.001) were all significant. Faster reaction times and higher executive function scores were associated with higher COMP and VEST scores in separate models. Those with faster reaction times also had significantly higher VIS scores. Reaction time and executive function demonstrated significant relationships with SOT balance performance. These cognitive processes may influence athletes' ability to organize and process higher-order information and generate appropriate responses to changes in their environment, with respect to balance and injury risk. Future investigations should consider these relationships after injury, and clinicians should be mindful of this relationship when considering concussion management strategies.


Inpatient warfarin: experience with a pharmacist-led anticoagulation management service in a tertiary care medical center.
The implementation of a pharmacist-led anticoagulation management service (AMS) and the clinical outcomes of inpatients receiving warfarin management are described. An AMS was established at St. Mary's Medical Center (SMMC) in Duluth, Minnesota, in November 2003 at the request of orthopedic surgeons to manage warfarin for their patients postoperatively. The AMS was also available to other inpatients by physician request. All AMS pharmacists received didactic and experiential training. Each day, the managing pharmacist, usually the decentralized pharmacist, was responsible for checking the patients' International Normalized Ratio (INR); reviewing other pertinent laboratory test values, any medication changes, and vital signs; monitoring changes in the patients' clinical status, and writing an order for a warfarin dose. A database was created to help monitor patients managed by the AMS and to analyze monthly outcomes data. Clinical outcomes data were evaluated to identify areas of improvement for the AMS. All hospitalizations for patients who received anticoagulation therapy with warfarin managed by the AMS from January 1, 2006, through August 31, 2007, were analyzed. Primary endpoints, including thrombosis and bleeding complications during hospitalization, were identified for inclusion in the final hospital discharge data. Of the 2794 hospitalizations for patients managed by the AMS evaluated, 59 complications were identified. Of these, 14 (0.5%) were thrombosis events and 45 (1.6%) were bleeding events. INR results were also analyzed as secondary endpoints. The evaluation of outcomes of the inpatient-based AMS at SMMC provided critical information to the anticoagulation subcommittee for consideration of quality-improvement efforts.


Policymakers' Research Capacities, Engagement, and Use of Research in Public Health Policymaking.
The use of research in public health policymaking is one of the prerequisites for successfully implemented health policies which have better population health as an outcome. This policy process is influenced by the actors involved under the policy umbrella, with inter-related contextual factors and specific structural and institutional circumstances. Our study investigates how policymakers' research capacities influence the use of research in the health policy process and identify areas where capacity-building interventions give the most meaning and impact. Furthermore, we investigate policymakers' research engagement and use this to inform public health policy in the public sector in Denmark. We collect and report data using Seeking, Engaging with, and Evaluation Research (SEER) methodology. Policymakers are reported to have research capacity, but it is questionable how those competences have actually been used in policymaking. Decision-makers were often not aware or did not know about the existing organizational tools and systems for research engagement and use and two third of respondents had not been part of any research activities or had any collaboration with researchers. Overall, research use in public health policymaking and evaluation was limited. As a conclusion, we propose that capacity-building interventions for increasing research use and collaboration in EIPM should be context-oriented, measurable, and sustainable in developing individual and organizational competences.


Preferential DNA-protein cross-linking by NiCl2 in magnesium-insoluble regions of fractionated Chinese hamster ovary cell chromatin.
Intracellular nickel ions (Ni2+) have been shown to cause single-strand breaks in DNA, that were rapidly repaired, and DNA-protein cross-links, that persisted for at least 24 h following removal of extracellular ionic nickel. In this study, we have used the techniques of alkaline elution, chromatin fractionation, and sodium dodecyl sulfate:polyacrylamide gel electrophoresis to examine the DNA-protein cross-linking induced by NiCl2 in Chinese hamster ovary cells. Continuous treatment of logarithmically growing Chinese hamster ovary cells with 2.5 mM NiCl2 in complete medium resulted in DNA single-strand breaks within 1 h, followed by a time-dependent increase in the induction of DNA-protein cross-links at 2, 3, and 6 h. Since the entry of nickel into cells was maximal within 2 h of exposure, the time delay for the formation of DNA-protein cross-links was not limited by metal uptake. The nickel-induced DNA-protein cross-linking appeared to require active cell cycling, since single-strand breaks but no cross-linking could be detected in confluent cells treated with 1, 2.5, or 5 mM NiCl2 for 3 h. DNA-protein cross-linking induced by nickel occurred in late S phase of the cell cycle. High-molecular-weight nonhistone chromatin proteins and possibly histone H1 migrating at the Mr 30,000 range became cross-linked to DNA after treatment of cells with NiCl2. All nickel-cross-linked proteins were concentrated in the magnesium-insoluble regions of fractionated chromatin and were stable to urea, 2-mercaptoethanol, and Nonidet P-40. Some proteins (Mr 48,000, 52,000, 55,000, 70,000, and 95,000), the association of which with DNA was also stable to Sarkosyl, salt, and EDTA, were detectable in DNA rigorously fractionated from untreated cells. Nickel therefore appeared to cause the cross-linking of proteins that normally reside in close association with DNA. Alterations of the normal association of these proteins with DNA by nickel may be an early event in the nickel transformation process.


Metallacyclic yttrium alkyl and hydrido complexes: synthesis, structures and catalytic activity in intermolecular olefin hydrophosphination and hydroamination.
Metallacyclic neutral and ionic yttrium alkyl complexes coordinated by a dianionic ene-diamido ligand ([2,6-iPr2C6H3NC(Me)=C(Me)NC6H3iPr2-2,6] = L(1)) [L(1)]Y(CH2SiMe3)(THF)2 (2), {[L(1)]Y(CH2SiMe3)2}(-){Li(THF)4}(+) (3), [L(1)]Y(OEt2)(μ-Me)2Li(TMEDA) (4) were synthesized using a salt-metathesis approach starting from the related chloro complex [L(1)]Y(THF)2(μ-Cl)2Li(THF)2 (1) in 70, 85 and 72% yields respectively. The reactions of 2 with H2 or PhSiH3 afford the dimeric hydride {[L(1)]Y(THF)(μ-H)}2(μ-THF) (5) containing two μ-bridging hydrido and one μ-bridging THF ligands (91 and 85% yields). The X-ray studies of complexes 2, 3 and 5 revealed η(2)-coordination of the C=C fragment of an ene-diamido ligand to a Y cation. DFT calculations were carried out to give an insight into the metal-ligand bonding and especially the interaction between the metal and the ene-diamido ligand. The observed bonding of the ene-diamido fragment is found to reflect the acidity of the metal center in the complex that is partially overcome by a better donation from the double bond (better overlap with an empty d orbital at the yttrium center). The treatment of complex 4 with DME resulted in the C-O bond cleavage of DME and afforded a three nuclear methoxide oxide complex [{[L(1)]Y}3(μ(2)-OMe)3(μ(3)-O)](2-)[Li(DME)3](+)2 (6). Complexes 2, 3, 5 and 7 proved to be efficient precatalysts for the intermolecular hydrophosphination of styrene, 4-vinylpyridine, and 1-nonene with PhPH2 and Ph2PH as well as hydroamination of styrene and pyrrolidine.


A feedback loop between BEX2 and ErbB2 mediated by c-Jun signaling in breast cancer.
BEX2 is a member of brain expressed X-linked gene family that is differentially expressed in primary breast tumors. We have previously demonstrated that BEX2 expression protects breast cancer cells against mitochondrial apoptosis and G1 cell cycle arrest. In addition, we have shown that BEX2 is a c-Jun target gene and, in turn, regulates the phosphorylation of c-Jun in breast cancer cells. In our study, we investigated BEX2 protein expression in a tissue microarray cohort of 225 breast tissue samples with known clinical, pathological and biomarker information. We observed that BEX2 protein was overexpressed in ∼50% of malignant breast tumors compared to only 7% of benign breast samples. Notably, BEX2 positive tumors identified a subset of breast cancers with the overexpression of ErbB2 and phosphorylated c-Jun proteins. Furthermore, using in vitro models, we demonstrated that the mechanism of this association is a functional feedback loop involving ErbB2, c-Jun and BEX2 in breast cancer cells. In this feedback loop, ErbB2 overexpression results in an induction of c-Jun and BEX2 expression. Importantly, ErbB2 induction of BEX2 expression was abrogated by a dominant-negative mutant of c-Jun, suggesting that this effect was mediated through the regulation of c-Jun signaling. In turn, the overexpression of BEX2 led to an increase in both c-Jun-mediated induction of ErbB2 and c-Jun binding to the ErbB2 promoter in MCF-7 cells. Our study suggests that BEX2 protein is overexpressed in approximately half of breast cancers and has a positive feedback loop with ErbB2 mediated by c-Jun signaling in breast cancer cells.


Food Insecurity, telomere length and the potential modifying effects of social support in National Health and Nutrition Examination Survey.
Telomere length (TL) is a posited pathway through which chronic stress results in biological dysregulation and subsequent adverse health outcomes. Food insecurity is associated with shorter TL. Social support, which is defined by the size and function of an individual's social network, is associated with better health outcomes. The present study assesses whether social support modifies the relationship between food security and TL. Cross-sectional study design. Linear regression was used to assess the association between food insecurity and TL, stratified by social support level. A multiplicative interacted model was used to formally test modification. Data come from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 waves. Adults aged 60 years and older who have measurements for TL. Our sample comprised 2674 participants, and 63·5 % of the total sample had low social support, with 13·3 % being food insecure. In fully adjusted models, food insecurity was negatively though modestly associated (P = 0·13) with TL. Associations between food insecurity and TL were significantly modified by social support (interaction P = 0·026), whereby food insecurity had a stronger effect among individuals with high social support (coefficient = -0·099 (95 % CI: -0·161, -0·038)) compared to low social support (coefficient = -0·001, (95 % CI: -0·033, 0·032)). Food insecurity is modestly associated with shorter TL. Contrary to our hypothesis, food insecurity had more deleterious effects on TL among participants with high social support than low social support. Results may indicate that the food insecure population is a higher needs population, and increased social support reflects these needs rather than providing protective effects.


Genome-wide perturbations by miRNAs map onto functional cellular pathways, identifying regulators of chromatin modifiers.
Regulation of gene expression by microRNAs (miRNAs) is critical for determining cellular fate and function. Dysregulation of miRNA expression contributes to the development and progression of multiple diseases. miRNA can target multiple mRNAs, making deconvolution of the effects of miRNA challenging and the complexity of regulation of cellular pathways by miRNAs at the functional protein level remains to be elucidated. Therefore, we sought to determine the effects of expression of miRNAs in breast and ovarian cancer cells on cellular pathways by measuring systems-wide miRNA perturbations to protein and phosphoproteins. We measure protein level changes by reverse-phase protein array (RPPA) in MDA-MB-231, SKOV3.ip1 and HEYA8 cancer cell lines transfected by a library of 879 human miRNA mimics. The effects of multiple miRNAs-protein networks converged in five broad functional clusters of miRNA, suggesting a broad overlap of miRNA action on cellular pathways. Detailed analysis of miRNA clusters revealed novel miRNA/cell cycle protein networks, which we functionally validated. De novo phosphoprotein network estimation using Gaussian graphical modeling, using no priors, revealed known and novel protein interplay, which we also observed in patient ovarian tumor proteomic data. We identified several miRNAs that have pluripotent activities across multiple cellular pathways. In particular we studied miR-365a whose expression is associated with poor survival across several cancer types and demonstrated that anti-miR-365 significantly reduced tumor formation in animal models. Mapping of miRNA-induced protein and phosphoprotein changes onto pathways revealed new miRNA-cellular pathway connectivity, paving the way for targeting of dysregulated pathways with potential miRNA-based therapeutics.


Co-Administration of Roxadustat and Zinc Stabilizes Both Serum Copper and Zinc Concentrations in Patients Undergoing Hemodialysis.
Patients undergoing hemodialysis often require zinc supplementation owing to hypozincemia, which may reduce serum copper concentrations. However, hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), which are used to treat renal anemia, have been reported to increase serum copper. Therefore, this study investigates the effectiveness of a combination of HIF-PHIs and zinc for the stabilization of serum copper and zinc concentrations during zinc supplementation for patients undergoing hemodialysis with renal anemia and hypozincemia. The serum zinc and copper concentrations were retrospectively compared over an 8-month period in 20 patients being administered roxadustat (an HIF-PHI) and 20 controls. The changes in concentrations were tracked in participants taking roxadustat who initiated or increased zinc supplementation. The serum zinc concentrations of the participants were significantly higher (p < 0.001) during zinc supplementation, regardless of roxadustat administration. Post-roxadustat, the serum copper concentrations were significantly higher than those pre-roxadustat or in non-roxadustat-treated participants, irrespective of zinc supplementation (p < 0.005). Even post-roxadustat, the serum copper concentrations were significantly lower, with no increase during zinc supplementation (p < 0.040). When zinc supplementation was initiated or increased in participants taking roxadustat, copper and zinc concentrations were normalized. Thus, combining zinc supplementation with roxadustat prevents both an excessive increase in serum copper and a decrease in serum zinc.


The efficacy of group cognitive-behavioural therapy plus duloxetine for generalised anxiety disorder versus duloxetine alone.
To explore whether and how group cognitive-behavioural therapy (GCBT) plus medication differs from medication alone for the treatment of generalised anxiety disorder (GAD). Hundred and seventy patients were randomly assigned to the GCBT plus duloxetine (n=89) or duloxetine group (n=81). The primary outcomes were Hamilton Anxiety Scale (HAMA) response and remission rates. The explorative secondary measures included score reductions from baseline in the HAMA total, psychic, and somatic anxiety subscales (HAMA-PA, HAMA-SA), the Hamilton Depression Scale, the Severity Subscale of Clinical Global Impression Scale, Global Assessment of Functioning, and the 12-item Short-Form Health Survey. Assessments were conducted at baseline, 4-week, 8-week, and 3-month follow-up. At 4 weeks, HAMA response (GCBT group 57.0% vs. control group 24.4%, p=0.000, Cohen's d=0.90) and remission rates (GCBT group 21.5% vs. control group 6.2%, p=0.004; d=0.51), and most secondary outcomes (all p<0.05, d=0.36-0.77) showed that the combined therapy was superior. At 8 weeks, all the primary and secondary significant differences found at 4 weeks were maintained with smaller effect sizes (p<0.05, d=0.32-0.48). At 3-month follow-up, the combined therapy was only significantly superior in the HAMA total (p<0.045, d=0.43) and HAMA-PA score reductions (p<0.001, d=0.77). Logistic regression showed superiority of the combined therapy for HAMA response rates [odds ratio (OR)=2.12, 95% confidence interval (CI) 1.02-4.42, p=0.04] and remission rates (OR=2.80, 95% CI 1.27-6.16, p=0.01). Compared with duloxetine alone, GCBT plus duloxetine showed significant treatment response for GAD over a shorter period of time, particularly for psychic anxiety symptoms, which may suggest that GCBT was effective in changing cognitive style.


Experimental cholesterol crystal arthropathy.
To understand the role of cholesterol crystals in the pathogenesis of synovial effusions, we studied the articular tissue reaction to an intraarticular injection of cholesterol crystals in rabbits' knees. With the right knee as control, the left knees of 14 adult male, white, New Zealand rabbits were injected with 11 mg of cholesterol crystals suspended in 0.5 ml of saline. At 4, 8, 24, 48 h and at 7, 14, 28 and 56 d postinjection, the animals were autopsied and these tissues, including synovial fluid (SF), examined by light and transmission electron microscopy. Crystal injection produced an acute synovitis which peaked at 24 h coincident with phagocytosis of crystals in SF. Cholesterol crystals persisted within the synovium throughout the experiment resulting in cholesterol granulomata, synovial lining cell hyperplasia and synovial fibrosis. Relative to urate and pyrophosphate crystals, cholesterol crystals appear to have weak phlogistic potential. Because of their insolubility and resistance to cellular degradation, crystals persist within the synovium for prolonged periods. This results in a chronic proliferative synovitis and fibrosis.


The golgi apparatus: two organelles in tandem.
The Golgi apparatus consists of distinct cis and trans compartments that may act sequentially to refine the protein export of the endoplasmic reticulum by removing escaped endoplasmic reticulum proteins. Refinement may be a multistage process akin to fractional distillation; the stack of cisternae comprising the cis Golgi may be the plates in this distillation tower. The trans Golgi, consisting of the last one or two cisternae, may be the receiver that collects from the cis Golgi only its most refined fraction for later distribution to specific locations throughout the cell.


Poly(ADP-ribose) polymerase inhibitors protect against MPTP-induced depletions of striatal dopamine and cortical noradrenaline in C57B1/6 mice.
Treatment of C57B1/6 mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reduced striatal dopamine and cortical noradrenaline levels by 77-83% and 43-46%, respectively, at 7 days post-treatment. Co-treatments with five different inhibitors of poly(ADP-ribose) polymerase (PARP), including benzamide, significantly prevented the MPTP-induced catecholamine depletions. Benzamide was present in the striatum, 30 min after single i.p. injection, at low millimolar concentrations known to selectively inhibit PARP in vitro. The protective activities of benzamide and its derivatives paralleled their in vitro efficacies and potencies both as neuroprotective agents and as inhibitors of PARP, while the activity of 1,5-dihydroxyisoquinoline, a structurally-unrelated compound, did not. In naive animals, the PARP inhibitors by themselves did not alter striatal dopamine levels at 7 days post-treatment. However, in acute studies, 1,5-dihydroxyisoquinoline and nicotinamide caused marked alterations in striatal dopamine metabolite levels; on the contrary, benzamide and its amino-derivatives showed little or no effect on dopamine metabolism. These results indicate that, although these compounds might act at other sites in addition to PARP, PARP inhibitors possess neuroprotective potential in vivo and suggest a role for PARP in MPTP neurotoxicity.


Standard examination and adjunctive techniques for detection of oral premalignant and malignant lesions.
This article outlines how to perform a standard comprehensive extraoral and intraoral examination and the existing commercially available adjunctive techniques for the early detection of oral cancer and premalignant lesions. Visualization-based techniques (e.g., autofluorescence and chemiluminescence), toluidine blue vital staining, cytopathologic tests and high-risk human papillomavirus testing are discussed in detail, including the indications and protocols for use, their advantages and disadvantages and clinical cases.


Induction of angiosarcomas by ring-necked pheasant virus.
Ring-necked pheasant virus, an avian leukosis virus, when injected into 10-day old chick embryos, caused angiosarcomas in the lungs of infected chickens within a short time. Angiosarcomas appeared as localized foci of proliferating cells in the lungs as early as 2 weeks posthatch, and by 6 weeks, the lungs of the infected chickens were frequently filled with tumor cells. Between 3 and 10 weeks of age, 80% of infected chickens died of the angiosarcomas; the 20% which lived 8 weeks or longer had small lung lesions and also developed fibrosarcomas, osteopetrosis, nephroblastoma, and lymphoid leukosis. Chickens with lung tumors were cyanotic, had breathing difficulty, and had packed cell volumes in excess of 50%. Other changes not necessarily correlated with lung tumor mass were stunting, lymphoid organ involution, and profuse diarrhea. Ring-necked pheasant virus has a genome RNA of 8.2 kb. This observation, together with its replication and disease induction after repeated plaque purification, suggests that ring-necked pheasant virus is a replication-competent avian retrovirus. Therefore, our results suggest that ring-necked pheasant virus is an avian leukosis virus which causes angiosarcomas rapidly at high incidence and which, therefore, may induce this type of tumor by a mechanism different from the induction of sarcomas by avian sarcoma viruses.


Functional reorganization in somatosensory cortical areas 3b and 1 of adult monkeys after median nerve repair: possible relationships to sensory recovery in humans.
Previous studies have shown that the primary somatosensory cortex of adult mammals undergoes somatotopic reorganization in response to peripheral nerve transection. The present study assesses how cortical organization is affected when a transected nerve subsequently regenerates. The median nerve to one hand of adult owl monkeys was transected and repaired. Following nerve regeneration, the representations of the hand in cortical areas 3b and 1 were studied with neurophysiological mapping methods. The major results were as follows: Peripherally, median nerve transection, repair, and regeneration resulted in reinnervation of the median nerve skin territory. Centrally, both the initial loss and subsequent regeneration of median nerve inputs caused reorganizational changes in cortex. Reorganizational changes were specifically restricted to regions of the hand cortex where inputs from the median nerve were normally represented. The functional features of cortical regions that recovered tactile responsiveness from reinnervated skin regions were abnormal in several respects. Most notably, these regions contained recording sites with abnormally located or multiple cutaneous receptive fields, and contained major topographical changes, such as reestablishment of palmar pad or digit representations in small, discontinuous patches of cortex. Normal organizational features were reestablished to a more limited extent. These features included recovery of delimited, discrete receptive fields and reestablishment of topographic representations for localized skin areas. Different transformations in topographical organization were seen in areas 3b and 1 of the same monkey. These results suggest that nerve regeneration reestablishes the cortical capacity to process tactile information from reinnervated skin via a prolonged reorganizational process that appears dependent on peripheral and central factors. Cortical recovery mechanisms clearly appear to have limitations, since preinjury patterns of cortical organization are not widely recovered even almost 1 year after repair. We suggest possible relationships between cortical reorganizational changes in these primates, and postrepair sensory changes in humans.


The privilege to be old.
Ample evidence has proven that the functional property of cells decreases over the years. Nevertheless, although it has taken decades to convince ourselves that elderly people belong to a specific age group both biologically and medicinally, and in whom special criteria have to be taken into consideration, it seems that even they themselves do not present an homogenous group. Today we often hear of authors of studies speaking of two subpopulation groups--one group that ages by all the laws of aging that we have encountered and accepted thus far, and the other group that seems to postpone aging due to 'programmed death', or more specifically due to low mastery/low emotional support or because of additional reasons; however, the existence of the two groups seems eminent. The identification of these two groups would allow us to find more realistic results in studies, and therefore a more efficient therapy for certain diseases. This hypothesis does not contradict the theories of aging that we have accepted (at least not the majority) and also does not contradict the fact that there is a large interindividual variability. This hypothesis doubts and claims there are exceptions to the initial assumption of geriatrists and gerontologists that 'parallel to the aging process, the functions of all organs and organ systems lessen.' The identification of these two groups would allow us to find more realistic results in studies, and therefore more efficient therapy for certain diseases.


Predicting early nonelective hospital readmission in nutritionally compromised older adults.
This study determined predictors of early nonelective hospital readmission in 92 (49 women and 43 men) nutritionally compromised Medicare patients. Subjects ranged in age from 65 to 92 y and represented patients hospitalized previously for medical or surgical services. The study used a repeated-measures design of multiple variables representing demographics, anthropometric and clinical values, and functional status. Data were collected during hospitalization and during home visits at 1 and 3 mo postdischarge. There were 26 readmissions, making the 4-mo nonelective readmission rate 26%. Subjects who were readmitted nonelectively were compared with those not readmitted. Univariate analyses suggested strong relations between readmission outcome and serum albumin, total lymphocyte count, change in weight, and change in white blood cell count. Sociodemographic variables were less useful in predicting readmission than were measurements of patients' clinical status. Measurements of change in clinical variables were generally more predictive of readmission than was any one single measurement. Multivariate-logistic-regression analyses suggested a model consisting of change in weight and change in serum albumin from hospitalization to 1 mo after discharge as being highly predictive of early nonelective readmission. Individuals with any amount of weight loss and no improvement in albumin concentrations during the first month after hospitalization were at a much higher risk of readmission than were those who maintained or increased their postdischarge weight and had repleted their serum albumin concentrations. More study is warranted to clarify whether routine monitoring of changes in weight and serum albumin after hospitalization is appropriate in older adults.


Proteome analysis of rat bone marrow mesenchymal stem cell differentiation.
Bone marrow multipotent stromal cells (or mesenchymal stem cells; MSCs) have the capacity for renewal and the potential to differentiate in culture into several cell types including osteoblasts, chondrocytes, adipocytes, cardiomyocytes, and neurons. This study was designed to investigate the protein expression profiles of rat bone marrow MSCs during differentiation into adipogenic (by dexamethasone, isobutylmethylxanthine, insulin, and indomethacin), cardiomyogenic (by 5-azacytidine), chondrogenic (by ascorbic acid, insulin-transferrin-selenous acid, and transforming growth factor-β1), and osteogenic (by dexamethasone, β-glycerophosphate, and ascorbic acid) lineages by well-known differentiation inducers. Proteins extracted from differentiated MSCs were separated using two-dimensional gel electrophoresis (2-DE) and protein spots were detected using Sypro Ruby dye. Protein spots that were determined to be up- or down-regulated when the expression of corresponding spots (between weeks 1 and 2, 1 and 3, 1 and 4) showed an increase (≥2-fold) or decrease (≤0.5-fold) were successfully identified by MALDI-TOF-MS. In summary, 23 new proteins were identified either up- or down-regulated during differentiation experiments.


Long-term effects of intracapsular partial tonsillectomy (tonsillotomy) compared with full tonsillectomy.
To compare the long-term effects (six years after surgery) of two techniques for pediatric tonsil surgery with respect to snoring, apneas, eating difficulties, infections and general health. The two methods were intracapsular partial tonsillectomy (tonsillotomy, "TT") using CO(2)-laser technique and traditional (total) blunt dissection tonsillectomy (TE). A questionnaire distributed by mail to the parents of children, who, in 1998, were included in a prospective clinical randomized study in one tertiary care ENT clinic. A 10 question survey follow-up of 41 children, between 9 and 15 years of age, who originally, six years earlier had been randomized to either TT with CO(2)-laser (n=21) or TE (n=20). The main indication for the surgery was a history of sleep related breathing distress (SRBD). Before the present study, all of the children had participated in earlier follow-ups at six months and one year after surgery. All the children in both groups answered the questionnaire. There were no significant differences between the answers from the two groups in any respects: the effect on snoring and apneas was equally stable for both groups. The number of children who remained free from snoring decreased from 40 after the first year to 25 after six years (11 TT, 14 TE). Snoring in the recurrent cases was not rated to be as frequent or as loud as before the surgery. Infections of the upper respiratory tract (URI) that had been treated with antibiotics occurred to the same extent in both groups. None had eating difficulties. The patients' satisfaction with the results of the surgery was high or very high in 18/21 TT and 20 TE cases, and the vast majority of the parents rated their children's present health status as improved compared with the preoperative condition. Tonsillotomy with CO(2)-laser seems to be a reliable method for tonsil surgery with substantially less primary morbidity than conventional tonsillectomy and with the same positive long-term effects after six years.


The impact of patient expectations on outcome following treatment for spinal trauma: Part 1: What are spine surgeons telling their patients?
Surgeon completed questionnaire. To determine information provided by spine surgeons to patients, part of a 4-part study determining the impact of patient expectations on outcome following spinal trauma. An important goal of treatment is patient satisfaction, which may be influenced by patient expectations. Impact of patient expectations on outcome has been demonstrated in various elective orthopedic populations. It is anticipated that there will be similar, if not greater, impact on outcome in a trauma setting. A questionnaire was developed, in a case-based format, to determine the information provided by spine surgeons to their patients. There were 3 questionnaires, each consisting of 5 cases and grouped by cervical spine trauma, thoracolumbar spine trauma, and spinal cord injury. These questionnaires were distributed to members of the Spine Trauma Study Group and our division. Statistical analysis consisted of a single-factor random effects model. In this analysis, the degree of variability was quantified as the ratio of surgeon induced variance over total variance for the questions. Questionnaires were distributed to 54 surgeons and 31 responses received (57%). There was substantial variability in responses ranging from a ratio of 9% [95% confidence interval (CI): 0-26] for the regaining range of motion 1 year following cervical spine trauma domain to a ratio of 84% (95% CI: 69-92) for the early postoperative spasticity following spinal cord injury domain. This study demonstrated substantial variability in the information provided by spine surgeons to spine trauma patients and the need to improve the quality of information provided, allowing patient expectations to be more appropriate, potentially maximizing their outcome. Further areas for study include, assessment of the best available evidence on which to base information provided to spinal trauma patients, determination of what information spinal trauma patients view as relevant and the effect appropriate expectations have on outcome.


Virological and immunological responses to porcine reproductive and respiratory syndrome virus in a large population of gilts.
Porcine reproductive and respiratory syndrome virus (PRRSV) causes a prolonged active infection followed by a persistent infection in lymphoid tissues lasting for several months. Pigs develop both an antibody and cell-mediated immune response following PRRSV infection, but the specific role of each type in the development of protective immunity and clearance of the virus is not yet known. The aims of this study were to characterize the dynamics of PRRSV persistence from 0 to 135 d post infection (pi), characterize the kinetics of the antibody mediated immune response following PRRSV infection, and characterize the cell mediated immune responses to PRRSV infection. Eighty, 4-month-old PRRSV-free gilts were obtained from a source known to be negative for PRRSV. On day 0, gilts were infected intranasally with 10(2.4) TCID/50 MN 30-100 PRRSV. Following infection, animals were bled between days 0 to 135 pi. Viremia was detected up to day 30. Serum antibody response (by enzyme-linked immunosorbent assay [ELISA] and virus neutralization antibody) was detected from day 14 to 120 pi. Cell-mediated immune response represented by interferon gamma (IFN-gamma) was detected from day 14 to 120 pi. Persistence of PRRSV in tissues was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) between days 30 to 135. These results indicate that serum neutralizing antibodies and IFN-gamma play an important role in the clearance of PRRSV. Nevertheless none of the parameters measured (virus neutralizing antibodies), either alone or in combination, are solely responsible for the clearance of the virus from the host and the development of sterilizing immunity.


Incidence of potential drug interactions in a transplant centre setting and relevance of electronic alerts for clinical practice support.
Adverse drug events may occur as a result of drug-drug interactions (DDIs). Information technology (IT) systems can be an important decision-making tool for healthcare workers to identify DDIs. The aim of the study is to analyse drug prescriptions in our main hospital units, in order to measure the incidence and severity of potential DDIs. The utility of clinical decision-support systems (CDSSs) and computerised physician order entry (CPOE) in term of alerts adherence was also assessed. DDIs were assessed using a Micromedex® healthcare series database. The system, adopted by the hospital, generates alerts for prescriptions with negative interactions and thanks to an 'acknowledgement function' it is possible to verify physician adherence to alerts. This function, although used previously, became mandatory from September 2010. Physician adherence to alerts and mean monthly incidence of potential DDIs in analysed units, before and after the mandatory 'acknowledgement function', were calculated. The intensive care unit (ICU) registered the greatest incidence of potential DDIs (49.0%), followed by the abdominal surgery unit and dialysis (43.4 and 42.0%, respectively). The cardiothoracic surgery unit (41.6%), step-down unit (38.3%) and post-anaesthesia care unit (30.0%) were comparable. The operating theatre and endoscopy registered the fewest potential DDIs (28.2 and 22.7%, respectively). Adherence to alerts after the 'acknowledgement function' increased by 25.0% in the ICU, 54.0% in the cardiothoracic surgery unit, 52.5% in the abdominal surgery unit, 58.0% in the stepdown unit, 67.0% in dialysis, 51.0% in endoscopy and 48.0% in the post-anaesthesia care unit. In the operating theatre, adherence to alerts decreased from 34.0 to 30.0%. The incidence of potential DDIs after mandatory use of the 'acknowledgement function' decreased slightly in endoscopy (-2.9%), the abdominal surgery unit (-2.7%), dialysis (-1.9%) and the step-down unit (-1.4%). Improving DDI alerts will improved patient safety by more appropriately alerting clinicians.