A Quantitative Profiling Method of Phytohormones and Other Metabolites Applied to Barley Roots Subjected to Salinity Stress.
As integral parts of plant signaling networks, phytohormones are involved in the regulation of plant metabolism and growth under adverse environmental conditions, including salinity. Globally, salinity is one of the most severe abiotic stressors with an estimated 800 million hectares of arable land affected. Roots are the first plant organ to sense salinity in the soil, and are the initial site of sodium (Na+) exposure. However, the quantification of phytohormones in roots is challenging, as they are often present at extremely low levels compared to other plant tissues. To overcome this challenge, we developed a high-throughput LC-MS method to quantify ten endogenous phytohormones and their metabolites of diverse chemical classes in roots of barley. This method was validated in a salinity stress experiment with six barley varieties grown hydroponically with and without salinity. In addition to phytohormones, we quantified 52 polar primary metabolites, including some phytohormone precursors, using established GC-MS and LC-MS methods. Phytohormone and metabolite data were correlated with physiological measurements including biomass, plant size and chlorophyll content. Root and leaf elemental analysis was performed to determine Na+ exclusion and K+ retention ability in the studied barley varieties. We identified distinct phytohormone and metabolite signatures as a response to salinity stress in different barley varieties. Abscisic acid increased in the roots of all varieties under salinity stress, and elevated root salicylic acid levels were associated with an increase in leaf chlorophyll content. Furthermore, the landrace Sahara maintained better growth, had lower Na+ levels and maintained high levels of the salinity stress linked metabolite putrescine as well as the phytohormone metabolite cinnamic acid, which has been shown to increase putrescine concentrations in previous studies. This study highlights the importance of root phytohormones under salinity stress and the multi-variety analysis provides an important update to analytical methodology, and adds to the current knowledge of salinity stress responses in plants at the molecular level.


Incidence of serum creatine kinase elevation and its relation to medications used after heart transplantation.
Rhabdomyolysis after heart transplantation is well described as a drug-related phenomenon. The incidence of serum creatine kinase (CK) elevation after heart transplantation is not formally reported in previous clinical studies. This study sought to find the incidence of asymptomatic serum CK elevation after heart transplantation and assess its relation to medications that are commonly used after transplantation. Data were collected in outpatient basis between August 2002 and August 2003. Patients with acute rejection, infection or muscle pain were excluded. All patients were followed monthly at a special clinic. Physical examinations and routine blood tests including serum CK were performed monthly. We evaluated the results of 106 asymptomatic patients and 765 serial data to determine the incidence of serum CK elevation after transplantation. Logistic regression was used to identify its risk factors. The incidence of serum CK elevation in asymptomatic heart transplant recipients was 16.2%. Risk factors of its elevation were diabetes mellitus and use of medications including cyclosporine, drugs for hypertriglyceridemia, antihypertensives, and prednisolone. Among the antihypertensives commonly used, angiotensin converting enzyme inhibitors, angiotensin receptor blockers and calcium antagonists were associated with a higher incidence of serum CK elevation, but beta-blockers protected patients from serum CK elevation. The incidence of serum CK elevation in asymptomatic heart transplant recipients was not low. Serum CK measurements should be part of the routine follow-up in transplant recipients, especially when patients had diabetes mellitus. Medications commonly used after heart transplantation significantly affected the incidence of serum CK elevation.


Evidence of recent thrust faulting on the Moon revealed by the Lunar Reconnaissance Orbiter Camera.
Lunar Reconnaissance Orbiter Camera images reveal previously undetected lobate thrust-fault scarps and associated meter-scale secondary tectonic landforms that include narrow extensional troughs or graben, splay faults, and multiple low-relief terraces. Lobate scarps are among the youngest landforms on the Moon, based on their generally crisp appearance, lack of superposed large-diameter impact craters, and the existence of crosscut small-diameter impact craters. Identification of previously known scarps was limited to high-resolution Apollo Panoramic Camera images confined to the equatorial zone. Fourteen lobate scarps were identified, seven of which are at latitudes greater than +/-60 degrees, indicating that the thrust faults are globally distributed. This detection, coupled with the very young apparent age of the faults, suggests global late-stage contraction of the Moon.


Extrahepatic transcription of human C-reactive protein.
We synthesized and cloned cDNA from human peripheral blood mononuclear cell (PBMC) transcripts that were hybrid selected by pCRP5, a liver C-reactive protein (CRP)-specific cDNA (Woo, P.,J.R. Korenberg, and A.S. Whitehead. 1985. J.Biol. Chem. 260:13384). Three hybrid-selected cDNA clones, HScDNA1, HScDNA3, and HScDNA8, were isolated and characterized. Nucleotide sequence analysis of the 5' end of the smaller clones, HScDNA1 and HScDNA8, demonstrated that these two PBMC clones are homologous to the 3' and 5' ends, respectively, of pCRP5. Our largest clone, HScDNA3, is larger than pCRP5, extending beyond both the 5' and 3' limits of pCRP5. Therefore, HScDNA3 was coded by human PBMC and not by the hybrid selection vehicle, pCRP5. HScDNA3 lacks the intervening sequence verifying that this clone is DNA made from a PBMC mRNA and not genomic DNA. The complete nucleotide sequence revealed that HScDNA3 is greater than 99% homologous to the CRP gene. These results demonstrate that PBMC express the CRP gene. Based on our previous report, which shows that peripheral blood cells synthesize a peptide recognized by anti-CRP (Kuta, A.E., and L.L. Baum. 1986. J. Exp. Med. 164:321), in conjunction with the data presented here, we conclude that human PBMC can synthesize CRP.


The Vaginal Microbiome as a Tool to Predict rASRM Stage of Disease in Endometriosis: a Pilot Study.
Endometriosis remains a challenge to understand and to diagnose. This is an observational cross-sectional pilot study to characterize the gut and vaginal microbiome profiles among endometriosis patients and control subjects without the disease and to explore their potential use as a less-invasive diagnostic tool for endometriosis. Overall, 59 women were included, n = 35 with endometriosis and n = 24 controls. Rectal and vaginal samples were collected in two different periods of the menstrual cycle from all subjects. Gut and vaginal microbiomes from patients with different rASRM (revised American Society for Reproductive Medicine) endometriosis stages and controls were analyzed. Illumina sequencing libraries were constructed using a two-step 16S rRNA gene PCR amplicon approach. Correlations of 16S rRNA gene amplicon data with clinical metadata were conducted using a random forest-based machine-learning classification analysis. Distribution of vaginal CSTs (community state types) significantly differed between follicular and menstrual phases of the menstrual cycle (p = 0.021, Fisher's exact test). Vaginal and rectal microbiome profiles and their association to severity of endometriosis (according to rASRM stages) were evaluated. Classification models built with machine-learning methods on the microbiota composition during follicular and menstrual phases of the cycle were built, and it was possible to accurately predict rASRM stages 1-2 verses rASRM stages 3-4 endometriosis. The feature contributing the most to this prediction was an OTU (operational taxonomic unit) from the genus Anaerococcus. Gut and vaginal microbiomes of women with endometriosis have been investigated. Our findings suggest for the first time that vaginal microbiome may predict stage of disease when endometriosis is present.


Locality-sensitive hashing for the edit distance.
Sequence alignment is a central operation in bioinformatics pipeline and, despite many improvements, remains a computationally challenging problem. Locality-sensitive hashing (LSH) is one method used to estimate the likelihood of two sequences to have a proper alignment. Using an LSH, it is possible to separate, with high probability and relatively low computation, the pairs of sequences that do not have high-quality alignment from those that may. Therefore, an LSH reduces the overall computational requirement while not introducing many false negatives (i.e. omitting to report a valid alignment). However, current LSH methods treat sequences as a bag of k-mers and do not take into account the relative ordering of k-mers in sequences. In addition, due to the lack of a practical LSH method for edit distance, in practice, LSH methods for Jaccard similarity or Hamming similarity are used as a proxy. We present an LSH method, called Order Min Hash (OMH), for the edit distance. This method is a refinement of the minHash LSH used to approximate the Jaccard similarity, in that OMH is sensitive not only to the k-mer contents of the sequences but also to the relative order of the k-mers in the sequences. We present theoretical guarantees of the OMH as a gapped LSH. The code to generate the results is available at http://github.com/Kingsford-Group/omhismb2019. Supplementary data are available at Bioinformatics online.


Does it make sense that diabetes is reciprocally associated with periodontal disease?
Epidemiological studies indicated that more than 15% of the population in western countries suffer because of severe forms of periodontitis, In this respect, the recognition of the relationship between oral and systemic health is growing, thus receiving remarkable interest in scientific literature. In fact, periodontitis may increase the risk for a group of life-threatening conditions such as atherosclerosis, stroke or low birth weight. The American Diabetes Association has reported that individuals with uncontrolled diabetes (defined as 200mg/dL of glucose on three consecutive readings) undergo an increased risk of infections, abnormal wound healing and consequent increased recovery time. Moreover, diabetics may be more likely to develop periodontal and cardiovascular disease than non diabetics, if note. History of poorly controlled chronic periodontal disease can alter diabetic/glycemic control. This may originate from a likely continuous passege of bacterial toxins and/or bacteria into the bloodstream, and/or from an exaggerated release of inflammatory mediators. This review is aimed at elucidating the connections between the status of oral health and glycemic control in diabetes.


Muscular dystrophy in adult and aged anti-NGF transgenic mice resembles an inclusion body myopathy.
The role of nerve growth factor (NGF) and its receptors in the physiology of skeletal muscles has not been extensively studied in animal models. We describe the production of transgenic lines of mice expressing a neutralizing antibody against NGF (alphaD11) and the morphological and histochemical analysis of skeletal muscles from adult and aged anti-NGF mice. This study reveals that the chronic deprivation of NGF results in a decreased size of myofibers of dorsal and hindlimb muscles in adult but not in postnatal day (P)2 mice. In myofibers from adult anti-NGF mice, the presence of central nuclei, vacuolization of the cytoplasm, and inflammatory cell infiltration was observed. The immunohistochemical analysis of these muscular fibers revealed an upregulation of p75 expression, a decrease in adenosine triphosphatase (ATP)ase activity, and a subsarcolemmal Congo Red-positive staining. Immunostaining with an antibody against amyloid precursor protein showed an increased labeling of the cytoplasm of myofibers from adult and aged anti-NGF mice. These features are reminiscent of human myopathies, such as inclusion body myositis. We conclude that NGF deficits might be relevant for a class of human myopathies.


Clinical evidence for polyol efficacy.
Xylitol is a safe dental caries preventive when incorporated into chewing gum or confections used habitually. The goal of this paper is to identify and assess the work on xylitol and other polyols and dental caries since 2008. Xylitol is effective when used by the mother prenatally or after delivery to prevent mutans transmission and subsequent dental caries in the offspring. One new completed trial confirmed that children of mothers who used xylitol lozenges after delivery had less dental caries than a comparison group. A similar study confirmed that the use of xylitol gum by the mother either prevented or postponed MS transmission to the offspring. Xylitol use among schoolchildren delivered via a gummy bear confection reduced S. mutans levels, but a once per day use of xylitol-containing toothpaste did not. Randomized trials, with caries outcomes, assessing xylitol-containing lozenges in adults and xylitol-containing gummy bears in children will release results in the coming year. Other studies are ongoing but are not systematic and will fail to answer important questions about how xylitol, or other polyols, can address the global dental caries problem.


National Institutes of Health-sponsored workshop on inflammation and immunity in dilated cardiomyopathy.
Nonischemic dilated cardiomyopathy (DCM) is an uncommon cause of heart failure but has widespread importance because it is the cause of 45% of heart transplantations. Multiple experimental and clinical lines of evidence have implicated altered immunity in the pathogenesis of DCM. However, advances in the understanding of the mechanisms of altered immunity have not affected the diagnosis or treatment of DCM. In recognition of this problem, the National Institutes of Health sponsored an expert workshop with 2 aims: to review the current understanding of inflammation and immunity as they relate to DCM and to identify the most promising areas for future clinical research efforts in the field. This report summarizes the scientific opportunities, perceived needs and barriers, and workshop recommendations on research directions in DCM. The major recommendations from the members of the workshop are organized according to the following themes: cardiotropic viruses, innate and acquired immune responses, environmental factors, novel diagnostics, and novel therapeutics.


Administration timing and duration-dependent effects of sesamin isomers on lipid metabolism in rats.
Metabolism of lipids such as cholesterol and triglycerides has daily variations and is controlled by a circadian clock. Sesamin isomers, a mixture of sesamin and episesamin (SE), are types of lignans in sesame seed that have shown the improvement of lipid metabolism with various diseases in an animal model. We therefore tested whether the effects of SE on lipid metabolism are influenced by timing of administration. High-fat diet (HFD)-loaded rat was administered SE in the ZT13 or 14 (at the beginning of the active phase) or ZT23 or 22 (at the end of the active phase) every day for 7 or 28 days, and the effects on lipid metabolism were evaluated. The effects of SE were enhanced by duration-dependency: 28-day administration of SE strongly affected some parameters related to lipid metabolism, particularly cholesterol metabolism, as compared to 7-day administration. In particular, in 28-day administration, the analysis of serum and liver cholesterol levels revealed that SE administration decreases more effectively at the beginning of the active phase when compared to at the end of that. Furthermore, quantitative real-time polymerase chain reaction (QRT-PCR) and functional analysis indicated that suppression of cholesterol synthesis in the liver and promotion of cholesterol excretion from the liver, as well as inhibition of the functional activity and gene expression of sterol response element-binding protein 2 (Srebp2), which is a transcriptional factor and controls the gene expression involved in cholesterol-metabolism enzymes, contribute to enhancement of SE's effects at this administration timing. No significant differences were observed in triglyceride metabolism with regard to timing of SE administration. After 28-day administration of SE, administration at the beginning of the active phase only affected the expression of clock genes in the liver with phase-advance. In the pharmacokinetic study, administration time had no effect on the level of sesamin, episesamin or their metabolites in the liver after administration of SE for 28 days. The present results suggest that continuous long administration of SE at the beginning of the active phase is preferable for obtaining beneficial effects on lipid metabolism.


An Internet-based simulation model for nitrogen management in agricultural settings.
Complex chemical, physical, and biological processes mediate nitrogen (N) transformations and movement during agricultural production, making the optimization of fertilizer use and environmental protection exceedingly difficult. Various computer models have been developed to simulate the site-specific fate and transport of N resulting from different crop production scenarios, but these models are very complex and difficult to use for most farmers, consultants, and conservationists. In an effort to facilitate access and simplify the use of sophisticated models, the U.S. Department of Agriculture (USDA) has developed an Internet-based nitrogen analysis tool. Based on the Nitrate Leaching and Economic Analysis Package (NLEAP), the Web site allows a user to conduct multiyear N simulation modeling specific to a crop field. Servers handle much of the required data assembly and formatting, thus sparing the user"s resources. Model runs are executed on the servers and the results are transmitted to the user. This new tool is presented along with early implementation results.


Dynein-mediated cargo transport in vivo. A switch controls travel distance.
Cytoplasmic dynein is a microtubule-based motor with diverse cellular roles. Here, we use mutations in the dynein heavy chain gene to impair the motor's function, and employ biophysical measurements to demonstrate that cytoplasmic dynein is responsible for the minus end motion of bidirectionally moving lipid droplets in early Drosophila embryos. This analysis yields an estimate for the force that a single cytoplasmic dynein exerts in vivo (1.1 pN). It also allows us to quantitate dynein-mediated cargo motion in vivo, providing a framework for investigating how dynein's activity is controlled. We identify three distinct travel states whose general features also characterize plus end motion. These states are preserved in different developmental stages. We had previously provided evidence that for each travel direction, single droplets are moved by multiple motors of the same type (Welte et al. 1998). Droplet travel distances (runs) are much shorter than expected for multiple motors based on in vitro estimates of cytoplasmic dynein processivity. Therefore, we propose the existence of a process that ends runs before the motors fall off the microtubules. We find that this process acts with a constant probability per unit distance, and is typically coupled to a switch in travel direction. A process with similar properties governs plus end motion, and its regulation controls the net direction of transport.


Quality of and patient satisfaction with primary health care for anxiety disorders.
Most patients with anxiety disorders receive their care from primary care practitioners (PCPs). The purpose of this study was to evaluate quality of and patient satisfaction with primary health care for anxiety disorders. A survey was performed among 1,004 outpatients with anxiety disorders (diagnosed according to DSM-IV) referred by their PCPs from 17 primary care clinical settings (3 of which were university-affiliated) in 4 regions of the United States for participation in the Coordinated Anxiety Learning and Management (CALM) study, a therapeutic trial. Participating research institutions were the University of Washington at Seattle, the University of California at San Diego and Los Angeles, and the University of Arkansas for Medical Sciences at Little Rock. Enrollment took place between June 2006 and April 2008. Patients were contacted by telephone after enrollment to provide information about previous care received (during the 6 months prior to referral) and satisfaction with that care. Quality-of-care indicators were self-reported type, dose, and duration of antianxiety medication treatment and self-reported psychotherapy with cognitive-behavioral therapy (CBT) elements. A total of 576 patients (57.4%) had received an appropriate antianxiety medication in the previous 6 months, but only 289 patients (29.4% of 983 who answered this question) had received the medication at adequate dose for at least 2 months. A total of 465 patients (46.3%) had received some counseling with at least 1 element of CBT, but only 213 patients (21.2%) had received counseling with a strong (3+ elements) CBT focus. Overall, 416 patients (41.4%) had received quality pharmacotherapy or psychotherapy, and 81 patients (8.1%) had received both. Only 432 patients (44.8% of 964 who answered this question) were at least somewhat satisfied with their mental health care. Receipt of quality psychotherapy was the sole positive predictor (adjusted odds ratio = 2.71; 95% CI, 1.94-3.80; P < .0005) of satisfaction with mental health care for anxiety. Moreover, there was a dose-response relationship between the number of CBT elements consistently delivered and satisfaction with care (test for trend, z = 4.06, P < .0005). Despite recognition of these patients' anxiety disorders and referral by their PCPs to an anxiety treatment study, fewer than half of the patients had in the prior 6 months received quality pharmacologic and/or psychosocial mental health care. Receipt of CBT-oriented, quality psychosocial (but not pharmacologic) care showed a strong dose-response relationship with satisfaction with mental health care.


Preoperative duration of retinal detachment and subretinal immunoreactive endothelin-1: repercussion on logarithmic visual acuity.
To analyze whether preoperative duration of primary rhegmatogenous retinal detachment (RD) influences endothelin-1 (ET-1)--a vasoactive, mitogenic, and pro-apoptotic peptide- levels with repercussions on logarithmic (LogMAR) visual acuity (VA). Prospective clinical cohort study on 66 healthy patients [33 with proliferative vitreoretinopathy (PVR) and 33 with no PVR] with unilateral RD candidates for scleral buckling (SB) surgery. Using radioimmunoassay, immunoreactive ET-1 (IR-ET-1) was tested in both plasma and subretinal fluid (SRF) of these RD patients. Pearson's correlations were evaluated between preoperative RD duration and each IR-ET-1 level (plasma, SRF and the difference SRF minus plasma) and also between both variables and the LogMAR VAs (preoperative, postoperative 8 months, and the difference: postoperative 8 months minus preoperative). PVR was associated with higher preoperative RD duration, higher LogMAR VA values (pre- and postoperative 8 months) and higher IR-ET-1 values (plasma, SRF and the difference: SRF minus plasma) than no-PVR IR-ET-1 levels (plasma and SRF) were only correlated (r = 0.462, p = 0.007; r = 0.397, p = 0.022 respectively) with preoperative RD duration in the no-PVR group. IR-ET-1 values (plasma, SRF and the difference:SRF minus plasma) showed statistically significant correlations with pre- and with postoperative 8 months LogMAR VAs in no-PVR and with postoperative 8 months LogMAR VA and LogMAR VA difference in PVR The highest correlation between IR-ET-1 levels and LogMAR VAs was found between SRF IR-ET-1 and postoperative 8 months LogMAR VA in PVR (cases with macula-on) (r = 0.956, p < 0.0001). Preoperative RD duration showed statistically significant positive correlations with pre- and with postoperative 8 months LogMAR VAs in both the no-PVR and the PVR groups and with IR-ET-1 measurements (plasma and SRF: lower correlations) only in the no-PVR group. These findings support the idea of doing primary and prompt vitrectomy for RD and perhaps using coadjutant pharmacologic therapy in order to improve visual results.


[Insomnia: concept analysis].
Sleep performs an essential function in humans. Insomnia is one of the common phenomena in a poor sleep pattern. Long-term suffering can result in somatic symptoms and the development of diseases. It can even induce diseases with a mental dimension. Insomnia causes indications of poor health. No systematic analysis of insomnia has been performed, however. The purpose of this study, therefore, was to describe the concept of insomnia. In accordance with Walker and Avant's (2005) methodology of concept analysis, this paper presents a review of the conceptual definitions, characteristics, antecedents and consequences, constructing examples, and empirical references of insomnia. The results indicate that: (1) Insomnia's defining attributes are recognized as an insufficient of quality and quantity for sleep for more than one month. (2) Antecedents of insomnia include changes in life habits, physiological demands caused by sleep time changes, and the experience of uncomfortable sensations. (3) Consequences of insomnia include a poor condition, with physical, psychological, social, and global dimensions. (4) There are many instruments that can be used to inspect insomnia, including questionnaires and tools for physiological measurement. Insomnia is a serious problem with various facets. An understanding of the concept of insomnia will help nurses to perceive this problem in caring for subjects.


A method for attachment of peptides to a solid surface with enhanced immunoreactivity.
Another method has been developed to attach synthetic peptides to solid supports for use in enzyme immunoassays. The method is based on passively adsorbing a synthetic peptide to a solid-phase support, then further attaching more of the same peptide by means of cross-linking to the previously adsorbed peptide. This method results in highly enhanced peptide immunoreactivity compared with that obtained with standard methodologies.


Genetic analysis of regulatory mutants affecting synthesis of extracellular proteinases in the yeast Yarrowia lipolytica: identification of a RIM101/pacC homolog.
Depending on the pH of the growth medium, the yeast Yarrowia lipolytica secretes both an acidic proteinase and an alkaline proteinase, the synthesis of which is also controlled by carbon, nitrogen, and sulfur availability, as well as by the presence of extracellular proteins. Recessive mutations at four unlinked loci, named PAL1 to PAL4, were isolated which prevent alkaline proteinase derepression under conditions of carbon and nitrogen limitation at pH 6.8. These mutations markedly affect mating and sporulation. A dominant suppressor of all four PAL mutations was isolated from a wild-type genomic library, which turned out to be a C-terminally truncated form of a 585-residue transcriptional factor of the His2Cys2 zinc finger family, which we propose to call YlRim101p. Another C-terminally truncated version of YlRim101p (419 residues) is encoded by the dominant RPH2 mutation previously isolated as expressing alkaline protease independently of the pH. YlRim101p is homologous to the transcriptional activators Rim101p of Saccharomyces cerevisiae, required for entry into meiosis, and PacC of Aspergillus nidulans and Penicillium chrysogenum, which were recently shown to mediate regulation by ambient pH. YlRim101p appears essential for mating and sporulation and for alkaline proteinase derepression. YlRIM101 expression is autoregulated, maximal at alkaline pH, and strongly impaired by PAL mutations.


Sex, price and preferences: accounting for unsafe sexual practices in prostitution markets.
Unsafe sexual practices are persistent in prostitution interactions: one in four contacts can be called unsafe. The determinants of this are still matter for debate. We account for the roles played by clients' preferences and the hypothetical price premium of unsafe sexual practices with the help of a large dataset of clients' self-reported commercial sexual transactions in Belgium and The Netherlands. Almost 25,000 reports were collected, representing the whole gamut of prostitution market segments. The first set of explanations consists of an analysis of the price-fixing elements of paid sex. With the help of the so-called hedonic pricing method we test for the existence of a price incentive for unsafe sex. In accordance with the results from studies in some prostitution markets in the developing world, the study replicates a significant wage penalty for condom use of an estimated 7.2 per cent, confirmed in both multilevel and fixed-effects regressions. The second part of the analysis reconstructs the demand side basis of this wage penalty: the consistent preference of clients of prostitution for unsafe sex. This study is the first to document empirically clients' preference for intercourse without a condom, with the help of a multilevel ordinal regression.


Among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth dependent on the type of analogue used? A systematic review and meta-analysis.
This systematic review and meta-analysis aimed to answer the following clinical question: among patients treated for IVF with gonadotrophins and GnRH analogues, is the probability of live birth per randomized patient dependent on the type of analogue used? Eligible studies were randomized controlled trials (RCTs), published as a full manuscript in a peer-reviewed journal, that contained sufficient information to allow ascertainment of whether randomization was true and whether equality was present between the groups compared. A literature search identified 22 RCTs comparing GnRH antagonists and GnRH agonists that involved 3176 subjects. Where live birth was not reported in a study that fulfilled the inclusion criteria, an effort was made to contact the corresponding authors to retrieve the missing information. If this was not possible, the reported outcome measure, clinical pregnancy or ongoing pregnancy was converted to live birth in 12 studies using published data (Arce et al., 2005). No significant difference was present in the probability of live birth between the two GnRH analogues [odds ratio (OR), 0.86; 95% confidence intervals (CI), 0.72 to 1.02]. This result remains stable in subgroup analysis that ordered the studies by type of population studied, gonadotrophin type used for stimulation, type of agonist protocol used, type of agonist used, type of antagonist protocol used, type of antagonist used, presence of allocation concealment, presence of co-intervention and the way the information on live birth was retrieved. In conclusion, the probability of live birth after ovarian stimulation for IVF does not depend on the type of analogue used for pituitary suppression.


Synthesis of substituted piperidines by enantioselective desymmetrizing intramolecular aza-Michael reactions.
An organocatalytic enantioselective intramolecular aza-Michael reaction has been described for the first time in a desymmetrization process employing substrates different from cyclohexadienones. By using 9-amino-9-deoxy-epi-hydroquinine as the catalyst and trifluoroacetic acid as a co-catalyst, a series of enantiomerically enriched 2,5-and 2,6-disubstituted piperidines have been obtained in good yields and with moderate diastereoselectivity. Depending on the catalyst/co-catalyst loading ratio, either the major or the minor diastereoisomer of the final piperidine products was achieved with high levels of enantioselectivity. Finally, some mechanistic insights have been considered by means of theoretical calculations which were in agreement with the experimental results obtained in the desymmetrization reaction.


Escaping Atom Types in Force Fields Using Direct Chemical Perception.
Traditional approaches to specifying a molecular mechanics force field encode all the information needed to assign force field parameters to a given molecule into a discrete set of atom types. This is equivalent to a representation consisting of a molecular graph comprising a set of vertices, which represent atoms labeled by atom type, and unlabeled edges, which represent chemical bonds. Bond stretch, angle bend, and dihedral parameters are then assigned by looking up bonded pairs, triplets, and quartets of atom types in parameter tables to assign valence terms and using the atom types themselves to assign nonbonded parameters. This approach, which we call indirect chemical perception because it operates on the intermediate graph of atom-typed nodes, creates a number of technical problems. For example, atom types must be sufficiently complex to encode all necessary information about the molecular environment, making it difficult to extend force fields encoded this way. Atom typing also results in a proliferation of redundant parameters applied to chemically equivalent classes of valence terms, needlessly increasing force field complexity. Here, we describe a new approach to assigning force field parameters via direct chemical perception. Rather than working through the intermediary of the atom-typed graph, direct chemical perception operates directly on the unmodified chemical graph of the molecule to assign parameters. In particular, parameters are assigned to each type of force field term (e.g., bond stretch, angle bend, torsion, and Lennard-Jones) based on standard chemical substructure queries implemented via the industry-standard SMARTS chemical perception language, using SMIRKS extensions that permit labeling of specific atoms within a chemical pattern. We use this to implement a new force field format, called the SMIRKS Native Open Force Field (SMIRNOFF) format. We demonstrate the power and generality of this approach using examples of specific molecules that pose problems for indirect chemical perception and construct and validate a minimalist yet very general force field, SMIRNOFF99Frosst. We find that a parameter definition file only ∼300 lines long provides coverage of all but <0.02% of a 5 million molecule drug-like test set. Despite its simplicity, the accuracy of SMIRNOFF99Frosst for small molecule hydration free energies and selected properties of pure organic liquids is similar to that of the General Amber Force Field, whose specification requires thousands of parameters. This force field provides a starting point for further optimization and refitting work to follow.


Validity of accelerometry for measurement of activity in people with brain injury.
To evaluate the validity of a uniaxial accelerometer (MTI Actigraph) for measuring physical activity in people with acquired brain injury (ABI) using portable indirect calorimetry (Cosmed K4b(2)) as a criterion measure. Fourteen people with ABI and related gait pattern impairment (age 32 +/- 8 yr) wore an MTI Actigraph that measured activity (counts.min(-1)) and a Cosmed K4b(2) that measured oxygen consumption (mL.kg(-1).min(-1)) during four activities: quiet sitting (QS) and comfortable paced (CP), brisk paced (BP), and fast paced (FP) walking. MET levels were predicted from Actigraph counts using a published equation and compared with Cosmed measures. Predicted METs for each of the 56 activity bouts (14 participants x 4 bouts) were classified (light, moderate, vigorous, or very vigorous intensity) and compared with Cosmed-based classifications. Repeated-measures ANOVA indicated that walking condition intensities were significantly different (P < 0.05) and the Actigraph detected the differences. Overall correlation between measured and predicted METs was positive, moderate, and significant (r = 0.74). Mean predicted METs were not significantly different from measured for CP and BP, but for FP walking, predicted METs were significantly less than measured (P < 0.05). The Actigraph correctly classified intensity for 76.8% of all activity bouts and 91.5% of light- and moderate-intensity bouts. Actigraph counts provide a valid index of activity across the intensities investigated in this study. For light to moderate activity, Actigraph-based estimates of METs are acceptable for group-level analysis and are a valid means of classifying activity intensity. The Actigraph significantly underestimated higher intensity activity, although, in practice, this limitation will have minimal impact on activity measurement of most community-dwelling people with ABI.


Gibberellin reactivates and maintains ovary-wall cell division causing fruit set in parthenocarpic Citrus species.
Citrus is a wide genus in which most of the cultivated species and cultivars are natural parthenocarpic mutants or hybrids (i.e. orange, mandarin, tangerine, grapefruit). The autonomous increase in GA1 ovary concentration during anthesis was suggested as being the stimulus responsible for parthenocarpy in Citrus regardless of the species. To determine the exact GA-role in parthenocarpic fruit set, the following hypothesis was tested: GA triggers and maintains cell division in ovary walls causing fruit set. Obligate and facultative parthenocarpic Citrus species were used as a model system because obligate parthenocarpic Citrus sp (i.e. Citrus unshiu) have higher GA levels and better natural parthenocarpic fruit set compared to other facultative parthenocarpic Citrus (i.e. Citrus clementina). The autonomous activation of GA synthesis in C. unshiu ovary preceded cell division and CYCA1.1 up-regulation (a G2-stage cell cycle regulator) at anthesis setting a high proportion of fruits, whereas C. clementina lacked this GA-biosynthesis and CYCA1.1 up-regulation failing in fruit set. In situ hybridization experiments revealed a tissue-specific expression of GA20ox2 only in the dividing tissues of the pericarp. Furthermore, CYCA1.1 expression correlated endogenous GA1 content with GA3 treatment, which stimulated cell division and ovary growth, mostly in C. clementina. Instead, paclobutrazol (GA biosynthesis inhibitor) negated cell division and reduced fruit set. Results suggest that in parthenocarpic citrus the specific GA synthesis in the ovary walls at anthesis triggers cell division and, thus, the necessary ovary growth rate to set fruit.


First Report of Alternaria Species Groups Involved in Disease Complexes of Hazelnut and Walnut Fruit.
During the last 5 years, two new diseases, brown apical necrosis (BAN) and gray necrosis (GN), were observed on English walnut (Juglans regia) and hazelnut (Corylus avellana), respectively (2,3). Both diseases caused severe fruit drop resulting in yield loss often exceeding 30%. Previous work demonstrated that BAN and GN are disease complexes caused by several fungi (Alternaria spp., Fusarium spp., and a Phomopsis sp.) (2,3). In both diseases, preliminary identification of Alternaria spp. revealed they were a complex of small-spored catenulate taxa related to A. alternata. To further characterize these taxa, additional pathogenicity tests and morphological examinations were conducted with isolates obtained from each host. Single-spored isolates were prescreened for pathogenicity by inoculating detached, surface-disinfested hazelnut leaves or walnut leaflets (1). Only isolates that produced foliar lesions after 5 days were used in subsequent fruit inoculations. From this screening, 35 isolates were selected (19 from walnut and 16 from hazelnut). For each isolate, attached fruit of respective hosts were inoculated at bloom by placing 10 μl of a conidial suspension (1 × 106 conidia per ml of H2O + 0.26% agar) onto the stigmas (150 fruit per isolate). Controls (150 fruit) were treated with agar solution only. After 15 days, fruit were examined for development of disease symptoms, and examination continued until fruit maturation (late July). Approximately 20 to 50% of the inoculated fruit displayed discoloration or necrosis of internal tissue, particularly the pericarp and the embryo, although symptoms were more limited than those typically seen in fully expressed BAN and GN. No differences in symptoms were evident among the isolates tested. The controls showed no symptom development initially, although 5% began to develop discoloration at fruit maturity. Fungal isolates used as inoculum were reisolated from all symptomatic fruit by surface disinfesting tissue from the margins of necrotic lesions. For each isolate, the conidial characteristics were described from cultures grown under defined conditions (4). Three distinct groups of isolates were identified. Alternata sp. group isolates produced conidial chains (8 to 20 spores) with numerous secondary and occasionally tertiary chains branching from apical and median cells. Conidia were typically ovate and often possessed a one-celled apical extension. Tenuissima sp. group isolates developed conidial chains (10 to 22 spores) with occasional branching forming secondary chains from apical and median cells. Conidia were ovate to obclavate, often with long apical extensions (10 to 35 μm). Arborescens sp. group isolates developed conidial chains (5 to 12 spores) with numerous secondary, tertiary, and quaternary short chains branching from apical cells. Conidia were typically ovate with minimal apical extensions. Of the walnut isolates, 12, 4, and 3 were from the arborescens, alternata, and tenuissima sp. groups, respectively. Of the hazelnut isolates, 7, 6, and 3 were from the arborescens, alternata, and tenuissima sp. groups, respectively. The finding that Alternaria from several distinct sp. groups can cause similar disease on a single host is consistent with previous work on pistachio, almond, and pear (4). References: (1) A. Belisario et al. Plant Dis. 83:696, 1999. (2) A. Belisario et al. Plant Dis. 86:599, 2002. (3) A. Belisario et al. Inf. Agrario 59:71, 2003. (4) B. M. Pryor et al. Phytopathology 92:406, 2002.


Declining Dioxin Concentrations in the Rhone River Basin, France, Attest to the Effectiveness of Emissions Controls.
Emission-control policies have been implemented in Europe and North America since the 1990s for polychlorodibenzodioxins (PCDDs) and furans (PCDFs). To assess the effect of these policies on temporal trends and spatial patterns for these compounds in a large European river system, sediment cores were collected in seven depositional areas along the Rhone River in France, dated, and analyzed for PCDDs and PCDFs. Results show concentrations increase in the downstream direction and have decreased temporally at all sites during the last two decades, with an average decrease of 83% from 1992 to 2010. The time for a 50% decrease in concentrations (t1/2) averaged 6.9±2.6 and 9.1±2.9 years for the sum of measured PCDDs and PCDFs, respectively. Congener patterns are similar among cores and indicate dominance of regional atmospheric deposition and possibly weathered local sources. Local sources are clearly indicated at the most downstream site, where concentrations of the most toxic dioxin, TCDD, are about 2 orders of magnitude higher than at the other six sites. The relatively steep downward trends attest to the effects of the dioxin emissions reduction policy in Europe and suggest that risks posed to aquatic life in the Rhone River basin from dioxins and furans have been greatly reduced.


Increased oxidants and reduced antioxidants in irradiated parenteral nutrition solutions may contribute to the inflammatory response.
To measure reactive oxidant production and the decline in antioxidant potential in commercially available, irradiated parenteral nutrition (PN) solutions and the effect that these have on oxidant production in patients in the intensive care unit. Vitamin E and malondialdehyde in irradiated and nonirradiated commercially available, PN solutions were measured. The PBN (alpha-phenyl-n-test-butylnitrone (PBN) spin trap was used to measure free radicals and TEMPOL (2,2,6,6-tetramethyl-4-hydroxy-piperidine-oxyl) was used to assess antioxidant capacity. The irradiated PN was administered (as per unit protocol) to 10 patients with gut failure and plasma and urinary isoprostanes and interleukin-6 (IL-6) were measured 1 hour preadministration, at the time of, and 1 and 2 hours postadministration of PN. Irradiation reduced vitamin E significantly (P < .0025). Malondialdehyde products were present in both samples, but more so in irradiated samples (P < .0001), as were free radicals measured by PBN spin trapping. Irradiated samples had a higher scavenging capacity of TEMPOL free radical due to depletion of antioxidants in irradiated samples. Urinary isoprostanes increased at time 2 by 6.3 units relative to time 0 and by 5.23 units relative to time 1(Friedman ANOVA: P < .01413). Lipid hydroperoxides are formed in PN solutions and increase further following irradiation. This is associated with a significant reduction in vitamin E and antioxidant potential. The increase in urinary isoprostanes indicates a potentially proinflammatory effect of irradiated PN.


Can an elderly woman's heart be too strong? Increased mortality with high versus normal ejection fraction after an acute coronary syndrome. The Global Registry of Acute Coronary Events.
Coronary artery disease is the leading cause of death in women. We sought to validate previous clinical experience in which we have observed that elderly women with a very high left ventricular ejection fraction (LVEF) are at increased risk of death compared with elderly women with acute coronary syndromes with a normal LVEF. Data from 5,127 elderly female patients (age >65 years) enrolled in the Global Registry of Acute Coronary Events were collected. Patients were divided into 3 groups based on their LVEF: group I had a low ejection fraction (<55%), group II had a normal ejection fraction (55%-65%), and group III had a high ejection fraction (>65%). χ² test and multiple logistic regression analysis were performed. The main outcome measures were death in-hospital and death, stroke, rehospitalization, and myocardial infarction at 6-month follow-up. Hospital mortality was 12% in group I. Patients in group III were more likely to die in-hospital than those in group II (P = .003). Multivariable logistic regression showed that high ejection fraction was an independent predictor of hospital death (odds ratio [OR] 2.5, 95% CI [CI] 1.2-5.2, P = .01), 6-month death (OR 2.0, 95% CI 1.1-3.4, P = .01), and cardiac arrest/ventricular fibrillation (OR 2.5, 95% CI 1.2-5.0, P = .01) compared with the normal ejection fraction group. Having a very high LVEF (> 65%) is associated with worse survival and higher rates of sudden cardiac death than an LVEF considered to be in the reference range.


Exploration of Scaffolds from Natural Products with Antiplasmodial Activities, Currently Registered Antimalarial Drugs and Public Malarial Screen Data.
In light of current resistance to antimalarial drugs, there is a need to discover new classes of antimalarial agents with unique mechanisms of action. Identification of unique scaffolds from natural products with in vitro antiplasmodial activities may be the starting point for such new classes of antimalarial agents. We therefore conducted scaffold diversity and comparison analysis of natural products with in vitro antiplasmodial activities (NAA), currently registered antimalarial drugs (CRAD) and malaria screen data from Medicine for Malaria Ventures (MMV). The scaffold diversity analyses on the three datasets were performed using scaffold counts and cumulative scaffold frequency plots. Scaffolds from the NAA were compared to those from CRAD and MMV. A Scaffold Tree was also generated for each of the datasets and the scaffold diversity of NAA was found to be higher than that of MMV. Among the NAA compounds, we identified unique scaffolds that were not contained in any of the other compound datasets. These scaffolds from NAA also possess desirable drug-like properties making them ideal starting points for antimalarial drug design considerations. The Scaffold Tree showed the preponderance of ring systems in NAA and identified virtual scaffolds, which may be potential bioactive compounds.


Current role of retroperitoneal lymph node dissection in testicular cancer.
Carcinoma of the testis is the most common malignancy in males 15 to 35 years of age. Testicular cancer has become one of the most curable solid neoplasms and as such, serves a paradigm for the multimodality treatment of malignancies. The cure rate for patients with clinical stage I disease is nearly 100%, and patients with advanced disease now achieve complete remission rates of over 90%. The markedly improved outlook for patients with this cancer over the past 15 years has led to a reassessment of management options, especially in patients with clinical stage I disease. The realization that platinum-based chemotherapy could cure most patients with an advanced nonseminomatous germ cell tumor (NSGCT), especially those with minimal disease, led to the introduction of various strategies to decrease the morbidity associated with surgical management. These strategies include surveillance protocols, chemotherapy for clinical stage II disease, and observation protocols for a subset of patients with advanced disease who have had a partial response to chemotherapy. Retroperitoneal lymph node dissection (RPLND) has an important place in the management of both low- and high-stage testicular cancer. It offers the patient two basic benefits: accurate staging and the possibility of a surgical care, even in the presence of metastatic disease.


What Did Latino Family Caregivers Expect and Learn From Education Intervention "Caregivers Like Me"?
US Latinos historically have underutilized end-of-life (EOL) resources. This study reports the views of family caregivers before and after education intervention Caregivers Like Me geared to improve knowledge and attitudes regarding EOL resources among Latino caregivers. This is a qualitative substudy within a multicentered cross-sectional study design. Educational intervention was offered to family caregivers of Latino elders from 3 different communities, using an audiovisual presentation, including a case-based video telenovela and pre-posttest questionnaires with open-ended questions. This study pertains to the qualitative results for the open-ended questions before and after education intervention. Participants (N = 145) were mostly females (79%) with a mean age of 56 ± 15 years and reported (92%) active learning from intervention. The pretest open-ended question on expected learning identified 2 themes, care for the sick and self-care. It included 5 subthemes and the most common one was how to help the sick. The posttest question on actual learning identified the same 2 themes and 4 subthemes that were similar but different from the pretest. Accepting help and knowledge of services available were the most common. The education intervention Caregivers Like Me was able to improve attitudes toward EOL care because participants who wanted to help their loved ones realized that they need to accept professional help and were made aware of the services available.


Association between the Use of Biomass as Fuel for Cooking and Acute Respiratory Infections in Children under 5 Years of Age in Peru: An Analysis of a Population-Based Survey, 2019.
Acute respiratory infections (ARIs) are the most frequent respiratory diseases associated with the use of biomass as fuel within the home. ARIs are the main cause of mortality in children under 5 years of age. We aimed to evaluate the association between the use of biomass as cooking fuel and ARI in children under 5 years of age in Peru in 2019. A secondary data analysis of the 2019 Peru Demographic and Family Health Survey (ENDES) has been performed. The outcome variable was a history of ARI. The exposure variable was the use of biomass as fuel for cooking food. To evaluate the association of interest, generalized linear models from the Poisson family with logarithmic link function considering complex sampling to estimate crude prevalence ratio (cPR) and adjusted prevalence ratio (aPR) with their respective 95% confidence intervals have been performed. P values <0.05 were considered statistically significant. A total of 16,043 children were included in the analysis. Of the total, biomass was used as fuel to cook food in the homes of 3,479 (20.0%) children. Likewise, 2,185 (14.3%) of the children had a history of ARI. In the adjusted model, it was found that children living in homes in which biomass was used as cooking fuel had a greater probability of presenting ARI (aPR = 1.13; 95% CI: 1.01-1.28). It has been found that biomass was used to cook food in two of every 10 households. Likewise, almost one-seventh of children under 5 years old presented an ARI. The use of biomass as a source of energy for cooking in the home was associated with a higher probability of presenting ARIs.


A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the Drosophila embryo.
The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the Drosophila embryo, Toll is required to establish gene expression domains along the dorsal-ventral axis. Pathway activation induces degradation of the IκB inhibitor Cactus, resulting in a ventral-to-dorsal nuclear gradient of the NFκB effector Dorsal. Here, we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and on Dorsal target genes. Quantitative analysis using a series of loss- and gain-of-function conditions shows that the ventral and lateral aspects of the Dorsal gradient can behave differently with respect to Cactus fluctuations. In lateral and dorsal embryo domains, loss of Cactus allows more Dorsal to translocate to the nucleus. Unexpectedly, cactus loss-of-function alleles decrease Dorsal nuclear localization ventrally, where Toll signals are high. Overexpression analysis suggests that this ability of Cactus to enhance Toll stems from the mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that Cactus acts to bolster Dorsal activation, in addition to its role as a NFκB inhibitor, ensuring a correct response to Toll signals.


Ionic liquid-salt aqueous two-phase extraction based on salting-out coupled with high-performance liquid chromatography for the determination of sulfonamides in water and food.
Ionic liquid-salt aqueous two-phase extraction coupled with high-performance liquid chromatography with ultraviolet detection was developed for the determination of sulfonamides in water and food samples. In the procedure, the analytes were extracted from the aqueous samples into the ionic liquid top phase in one step. Three sulfonamides, sulfamerazine, sulfamethoxazole, and sulfamethizole were selected here as model compounds for developing and evaluating the method. The effects of various experimental parameters in extraction step were studied using two optimization methods, one variable at a time and Box-Behnken design. The results showed that the amount of sulfonamides did not have effect on the extraction efficiency. Therefore, a three-level Box-Behnken experimental design with three factors, which combined the response surface modeling, was used to optimize sulfonamides extraction. Under the most favorable extraction parameters, the detection limits (S/N = 3) and quantification limits (S/N = 10) of the proposed method for the target compounds were achieved within the range of 0.15-0.3 ng/mL and 0.5-1.0 ng/mL from spiked samples, respectively, which are lower than or comparable with other reported approaches applied to the determination of the same compounds. Finally, the proposed method was successfully applied to the determination of sulfonamide compounds in different water and food samples and satisfactory recoveries of spiked target compounds in real samples were obtained.


Epithelial ovarian cancer and the ability to conceive.
Relationships between ovarian cancer and ability to conceive were explored in a case-control study of 188 women with histologically confirmed epithelial ovarian cancer and 539 control women in the San Francisco Bay Area. Control women consisted of two groups: those hospitalized without cancer, matched to cases by age, race, and hospital of diagnosis (n = 280); and those selected from the general population by random digital dialing, matched to cases by age, race, and telephone prefix (n = 259). Ovarian cancer risk among nulliparous (but not parous) women was positively associated with a history of unsuccessful attempts to conceive, of physician-diagnosed infertility, and of doubts about ability to conceive. Among all women, risk increased with increasing years of unprotected intercourse (P value for trend = 0.02). Risk among women having 10 or more yr of unprotected intercourse was 1.8 relative to that among women having less than 2 such yr (P = 0.01). This association was independent of parity, oral contraceptive use, and estimated years of ovulation, each associated with ovarian cancer. Further, duration of unprotected intercourse combined multiplicatively with each of these latter characteristics in increasing ovarian cancer risk. For example, while cancer risk exhibited a 2-fold range from lowest to highest years of unprotected intercourse and a 4-fold range from lowest to highest years of ovulation, risk among women in the highest joint category of these characteristics was 8 times that of women in the lowest category. We believe that some abnormality of ovulation that reduces the likelihood of conception plays a role in epithelial ovarian cancer.


A physiological perspective on the response of body size and development time to simultaneous directional selection.
Natural selection typically acts on multiple traits simultaneously. Quantitative genetics provides the theory for predicting the response to selection of multiple traits and predicts symmetrical responses to selection (the response to upward selection on both traits is equal to their response to downward selection). In reality, however, the response to simultaneous selection on two traits is often asymmetrical. We provide a physiology-based framework to explain the asymmetrical response to simultaneous selection on two important life history traits: body size and development time. The tobacco hornworm, Manduca sexta, is particularly well suited for such a study, as the physiological control of body size and development time is well known in this species. Three physiological factors control both life history traits in M. sexta: growth rate, the critical weight that measures the timing of the onset of the cessation of juvenile hormone secretion (which initiates the processes leading to pupation) and the time interval between the critical weight and secretion of the molting hormone 20-hydroxyecdysteroid (the interval to cessation of growth, ICG). Asymmetry in the response to simultaneous selection on the two life history traits is due to the different types of selection acting on the three physiological factors. The critical weight and ICG are always under synergistic selection when both focal traits are selected in the same direction and under antagonistic selection when the focal traits are selected in opposite directions. Growth rate follows the opposite pattern. We propose a general model to explain the asymmetric response to simultaneous selection. This model emphasizes the importance of physiological processes in understanding evolutionary responses to selection and the control of complex traits.


Malaria diagnosis by dipstick assay in a Honduran population with coendemic Plasmodium falciparum and Plasmodium vivax.
A Plasmodium lactate dehydrogenase dipstick designed to separately detect P. falciparum and P. vivax malaria was evaluated in two Honduran populations where both species are endemic. The dipstick was compared to thick film microscopy; the polymerase chain reaction (PCR) was used to analyze discordant results. The dipstick had a sensitivity of 100% and a specificity of 95% compared with microscopy in the diagnosis of Plasmodium infections in a hospital population; the mean parasite density was approximately 590/mm3. In a field sample of mostly asymptomatic volunteers, the sensitivity of the dipstick for Plasmodium infection varied with parasite density. Additionally, the sensitivity and specificity of the dipstick was similar to thick film microscopy in the diagnosis of vivax malaria compared with the PCR. The dipstick was unable to detect P. vivax in the presence of P. falciparum because of cross-reactivity in the pan-specific band. Accurate species identification in mixed infections remains a problem in malaria diagnosis.


Survival of the Fittest: Essential Roles of Cell Competition in Development, Aging, and Cancer.
Multicellular organisms evolved to resolve conflicts between individual cells, protecting the internal organization of the individual. This is illustrated by cell competition, a process that eliminates suboptimal cells from growing tissues by apoptosis. Since its early characterization in Drosophila an increasing number of conditions have been associated with competition, and mounting evidence demonstrates conservation of this process. We describe here the broad range of contexts that utilize cell competition, including tissue health, aging, and tumor development. We then delineate different models for the processes underlying the recognition and elimination of outcompeted cells.


Atypical intradermal smooth muscle neoplasms (formerly cutaneous leiomyosarcomas): case series, immunohistochemical profile and review of the literature.
Atypical intradermal smooth muscle neoplasms (AISMN, formerly known as cutaneous leiomyosarcomas) are uncommon neoplasms, which seem to be remarkable for their excellent prognosis in contrast to their deeper counterparts. The rarity of AISMN has posed a challenge for characterizing the morphologic spectrum, immunohistochemical staining pattern, and behavior. In this study we evaluated the histologic and immunohistochemical features of 20 cases of AISMN. Clinical follow-up was available on 19 out of 20 patients and ranged from 1 to 124 months with an average of 35 months and a median of 20 months with a male predominance (male to female ratio was 2.3:1). Our data show a wide variation in differentiation and atypical features. Among these, the presence of mitotic figures is diagnostically valuable in rendering the final diagnosis. A broad panel of immunohistochemical stains revealed that smooth muscle actin and muscle specific actin, when used in combination, identified smooth muscle differentiation in 100% of the cases. With some caveats, CD34, S100, and CK 5/6 were helpful in ruling out other important cutaneous spindle cell neoplasms. Significantly, loss of phosphatase and tensin homolog (PTEN) staining was seen in the majority of our cases (80%), supporting a role for PTEN loss in the etiology of these lesions. Logistic regression analysis revealed that positive margin status was helpful for predicting recurrence (100% sensitivity and 94% specificity). We conclude that AISMN can have significant morphologic variation and overlap with other spindle cell neoplasms of the skin and that a limited panel of key immunohistochemical stains should be used to distinguish this lesion. The different surgical measures such as wide excision versus Mohs procedure showed a similar clinical outcome. Although the significance of frequent PTEN loss supports a molecular mechanism of tumor genesis, the diagnostic utility of the stain remains to be determined.


[German version of the math anxiety questionnaire (FRA) for 6- to 9-year-old children].
Is the FRA a reliable and valid instrument? Are there any gender differences concerning math anxiety? Are there any developmental changes in this regard in the course of the early grades? Together with the dyscalculia test TEDI-MATH, the FRA was presented to a total of 450 children from the first to the third grade of primary school (at least 40 girls and 40 boys per semester). The total scale has an internal consistency (Cronbach's alpha) between 0.83 and 0.91. Correlations between arithmetic skills and the FRA scales were mostly significant. The significantly higher negative scores for girls were taken into account by providing standard scores corrected for gender. No systematic developmental changes could be observed. The FRA is the first German math anxiety questionnaire for primary school children. High reliability, standard scores corrected for gender, and economic handling make it an instrument well suited for use in clinical settings (e.g., dyscalculia diagnostics and intervention).


[Score BISAP validation as a prognostic system in acute pancreatitis].
The BISAP score is a simple system, which englobes clinical features (laboratory and imagenology tests) allowing to predict the mortality in acute pancreatitis within the first 24 hours of hospitalization. To determine the validity of the BISAP score in the prediction of prognosis and severity of acute pancreatitis. In order to validate the BISAP score, a study was performed in 57 patients with a diagnosis of acute pancreatitis at the moment of admission. The reference test was the Atlanta criteria which confirmed severe clinical course beyond the fifth day, in many cases supported by CT. 71.9% were women. The mean age was 45.33 years. Biliary lithiasis was the most frequent cause (66.7%). According to the reference test 71.9% were mild and 28.1% severe. According to the BISAP score 77.2% mild and 22.8% severe. The sensitivity and specificity for the BISAP score was of 75% and 97.56% respectively. The predictive positive value was 92.31% and the predictive negative value was 90.91%. The BISAP score allows to predict the severity of the acute pancreatitis.


Role of Apo2L/TRAIL and Bcl-2-family proteins in apoptosis of multiple myeloma.
Apo2 Ligand or Tumour Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (Apo2L/TRAIL) is a member of the TNF gene superfamily that selectively induces apoptosis in tumor cells of diverse origins through engagement of death receptors. We have recently demonstrated that Type I interferons (IFN-alpha and beta) induce apoptosis in multiple myeloma (MM) cell lines and in plasma cells from MM patients. Moreover, Apo2L selectively induces apoptosis of patient MM tumor cells while sparing non-malignant cells. Apo2L induction is one of the earliest events following IFN administration in these cells. IFNs activate Caspases and the mitochondrial-dependent apoptotic pathway mediated by Apo2L production. Cell death induced by IFNs and Apo2L can be blocked by a dominant-negative Apo2L receptor, DRS, and is regulated by members of the Bcl-2 family of proteins. This review is focused on the apoptotic signaling pathways regulated by Apo2L and Bcl-2-family proteins and summarizes what is known about their clinical role.


Should the practice of medicine be a deontological or utilitarian enterprise?
There is currently an unrecognised conflict between the utilitarian nature of the overall NHS and the basic deontology of the doctor-patient interaction. This conflict leads to mistrust and misunderstanding between managers and clinicians. This misunderstanding is bad for both doctors and managers, and also leads to waste of time and resources, and poorer services to patients. The utilitarian thinkers (mainly managers and politicians) tend to value finite, short term, evidence based technical interventions, delivered according to specifications and contracts. They appear happy to break care up into smaller pieces, which can then be commissioned from multiple providers. The deontological thinkers (mainly doctors and other clinicians) tend to think about care delivered through a long term continuous relationship, and regard that relationship as therapeutic and salutogenic in itself. To them breaking care up into smaller fragments is a denial of what caring is really about. Very rarely are either or both sides of this debate fully aware of where their powerfully felt and often well argued positions start from. In this paper we offer an appraisal of the strengths and weaknesses of both moral viewpoints as applied in the UK NHS context and we suggest a way in which they can be reconciled, provided neither is pushed too far or too hard against the other. We believe this reconciliation would be good for patients, doctors, managers and improve the service as a whole.


Quantitative proteomics analysis of zebrafish exposed to sub-lethal dosages of β-methyl-amino-L-alanine (BMAA).
The non-protein amino acid β-methylamino-L-alanine (BMAA) is a neurotoxin present in microalgae and shown to accumulate in the food web. BMAA has been linked to the complex neurodegenerative disorder of Guam and to increased incidents sporadic ALS. Two main neurotoxic routes are suggested; an excitotoxic by acting as an agonist towards glutamate receptors and a metabolic by misincorporating into cellular proteins. We have used zebrafish, an increasingly used model for neurodegenerative diseases, to further identify signaling components involved in BMAA-induced toxicity. Zebrafish embryos were exposed to sub-lethal dosages of BMAA and a label-free proteomics analysis was conducted on larvae 4 days post fertilization. The exposed larvae showed no developmental abnormalities, but a reduced heart rate and increased expression of GSK3 isoforms. Search towards a reviewed database containing 2968 entries identified 480 proteins. Only 17 of these were regulated 2-fold or more in the exposed larvae. Seven of these proteins could be associated to glutamate receptor signaling and recycling. The remaining nine have all been linked to disturbance in protein homeostasis, reactive oxygen species (ROS) development or neuronal cell death. We also found that BMAA influenced the endocannabinoid system by up-regulation of fatty acid amide hydrolase (FAAH) and that FAAH inhibitor URB597 reduced the BMAA effect on heart rate and GSK3 expression.


The value of a new microculture method for diagnosis of visceral leishmaniasis by using bone marrow and peripheral blood.
We have demonstrated that the microculture method (MCM) enables the diagnosis of visceral leishmaniasis (VL) with samples from both the bone marrow (BM) and peripheral blood (PB). The MCM is superior to the traditional culture method (TCM) as determined by its higher sensitivity in the detection of promastigotes and the more rapid time for emergence of promastigotes. The sensitivity of MCM (100% in BMs and 77.8-100% in PB) was considerably higher than that of the TCM (37.5-100% in BMs and 0-100% in PB) according to decreasing parasite density (P < 0.05). The concentration of parasites in buffy coats has increased the sensitivity of both methods, especially that of the MCM. Detection of promastigotes by MCM requires lower amounts of culture media (25-50 microL) and shorter incubation periods (2-7 days) than TCM (2.5-3.5 mL and 15-35 days, respectively). MCM was found to be valuable with the advantages of simplicity and sensitivity, in addition to being cost-effective in the routine diagnosis for VL in Adana Turkey.


Presynaptic partners of dorsal raphe serotonergic and GABAergic neurons.
The serotonin system powerfully modulates physiology and behavior in health and disease, yet the circuit mechanisms underlying serotonin neuron activity are poorly understood. The major source of forebrain serotonergic innervation is from the dorsal raphe nucleus (DR), which contains both serotonin and GABA neurons. Using viral tracing combined with electrophysiology, we found that GABA and serotonin neurons in the DR receive excitatory, inhibitory, and peptidergic inputs from the same specific brain regions. Embedded in this overall similarity are important differences. Serotonin neurons are more likely to receive synaptic inputs from anterior neocortex while GABA neurons receive disproportionally higher input from the central amygdala. Local input mapping revealed extensive serotonin-serotonin as well as GABA-serotonin connectivity with a distinct spatial organization. Covariance analysis suggests heterogeneity of both serotonin and GABA neurons with respect to the inputs they receive. These analyses provide a foundation for further functional dissection of the serotonin system.


Drug interactions with paracetamol.
Paracetamol (acetaminophen) is one of the most commonly used analgesic antipyretic drugs worldwide, and it is widely available by prescription and over the counter (OTC). Fortunately, few clinically significant drug interactions have been documented. There is probable potentiation of hepatotoxicity following an overdose from the paracetamol metabolite NAPQI by enzyme-inducing drugs. There is considerable controversy regarding the possible interaction with warfarin in its potential to increase its anticoagulant effects because of discrepancies between observational studies and those in healthy volunteers. Otherwise, no serious adverse drug interactions with therapeutic doses of paracetamol have been confirmed in humans. Because the absorption of paracetamol is so dependent on gastric emptying, other drugs that alter gastric emptying can change its pharmacokinetics; but this would not cause serious adverse effects. Although animal experiments have demonstrated that many compounds can modify paracetamol hepatotoxicity, these are unlikely to be important at therapeutic doses.


Hashimoto encephalopathy presenting as schizophrenia-like disorder.
Hashimoto encephalopathy (HE) is associated with numerous neuropsychiatric symptoms and responds well to steroid therapy. In the past, only a few cases were reported to present with pure psychiatric syndromes. We describe a case of HE with presenting symptoms like that of schizophrenic patients. We describe a 73-year-old woman with a history of autoimmune thyroiditis. She had psychotic symptoms for 3 years that responded poorly to antipsychotic agents, and she was thus admitted in 2007. The diagnosis of HE was made, although the patient presented neurologic symptoms and signs including abnormal electroencephalography, recent memory impairment, and executive function declination. The psychotic symptoms subsided completely in a few days after high-dose intravenous steroid therapy. The neuropsychiatric manifestation of HE can be similar to typical schizophrenia. Considering the effectiveness of steroid therapy for HE, we suggested HE as an important differential diagnosis for psychotic disorders, particularly for those patients of late onset, with abnormal electroencephalography, history of autoimmune thyroiditis, or poor response to conventional psychiatric treatment, so as to provide prompt and effective treatment for these patients.


Retrieving clinical evidence: a comparison of PubMed and Google Scholar for quick clinical searches.
Physicians frequently search PubMed for information to guide patient care. More recently, Google Scholar has gained popularity as another freely accessible bibliographic database. To compare the performance of searches in PubMed and Google Scholar. We surveyed nephrologists (kidney specialists) and provided each with a unique clinical question derived from 100 renal therapy systematic reviews. Each physician provided the search terms they would type into a bibliographic database to locate evidence to answer the clinical question. We executed each of these searches in PubMed and Google Scholar and compared results for the first 40 records retrieved (equivalent to 2 default search pages in PubMed). We evaluated the recall (proportion of relevant articles found) and precision (ratio of relevant to nonrelevant articles) of the searches performed in PubMed and Google Scholar. Primary studies included in the systematic reviews served as the reference standard for relevant articles. We further documented whether relevant articles were available as free full-texts. Compared with PubMed, the average search in Google Scholar retrieved twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001). Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07). Google Scholar provided significantly greater access to free full-text publications (PubMed: 5%; Google Scholar: 14%; P<.001). For quick clinical searches, Google Scholar returns twice as many relevant articles as PubMed and provides greater access to free full-text articles.


Country-wide surveillance of norovirus outbreaks in the Portuguese Army, 2015-2017.
Gastrointestinal infections are among the most common foodborne and waterborne diseases in military populations, with direct implications in operational efficiency and force readiness. Through the surveillance system of reportable acute gastrointestinal illness in the Portuguese Army, four norovirus outbreaks were identified between October 2015 and October 2017 in mainland Portugal and the Azores archipelago. The present study documents the epidemiological, clinical and laboratory investigations of these norovirus outbreaks. Cases were investigated and epidemiological questionnaires were distributed to all soldiers in each military setting where the outbreaks occurred. Stool samples from soldiers with acute gastroenteritis illness were collected and screened for common enteropathogenic agents. Food and water samples served on the settings were also collected for microbiological investigation. Norovirus-positive samples were further characterised by sequence analysis using a public automated genotyping tool. The four outbreaks affected a total of 99 soldiers among the 618 stationed on base units and in a military exercise. A total of 27 soldiers provided a stool sample, of which 20 were positive for norovirus by real-time PCR. Phylogenetic analysis showed that the noroviruses involved were all genogroup II, namely GII.17, GII.Pe-GII.4 Sydney 2012, GII.P2-GII.2 and GII.P16-GII.2. Of note, 30 soldiers had to receive treatment at the military hospital due to severity of symptoms. In this short, two-year surveillance period, a total of four norovirus gastroenteritis outbreaks were detected in the Portuguese Army which caused a considerable morbidity, showing once again the impact of norovirus on Army effectiveness and force readiness.


Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole.
The immunity-related GTPases (IRGs) constitute an interferon-induced intracellular resistance mechanism in mice against Toxoplasma gondii. IRG proteins accumulate on the parasitophorous vacuole membrane (PVM), leading to its disruption and to death of the parasite. How IRGs target the PVM is unknown. We show that accumulation of IRGs on the PVM begins minutes after parasite invasion and increases for about 1 h. Targeting occurs independently of several signalling pathways and the microtubule network, suggesting that IRG transport is diffusion-driven. The intensity of IRG accumulation on the PVM, however, is reduced in absence of the autophagy regulator, Atg5. In wild-type cells IRG proteins accumulate cooperatively on PVMs in a definite order reflecting a temporal hierarchy, with Irgb6 and Irgb10 apparently acting as pioneers. Loading of IRG proteins onto the vacuoles of virulent Toxoplasma strains is attenuated and the two pioneer IRGs are the most affected. The polymorphic rhoptry kinases, ROP16, ROP18 and the catalytically inactive proteins, ROP5A-D, are not individually responsible for this effect. Thus IRG proteins protect mice against avirulent strains of Toxoplasma but fail against virulent strains. The complex cooperative behaviour of IRG proteins in resisting Toxoplasma may hint at undiscovered complexity also in virulence mechanisms.


The interaction of heparan sulfate proteoglycans with endothelial transglutaminase-2 limits VEGF165-induced angiogenesis.
Sprouting angiogenesis is stimulated by vascular endothelial growth factor (VEGF165) that is localized in the extracellular matrix (ECM) and binds to heparan sulfate (HS)-bearing proteins known as heparan sulfate proteoglycans (HSPGs). VEGF165 presentation by HSPGs enhances VEGF receptor-2 (VEGFR2) signaling. We investigated the effect of TG2, which binds to HSPGs, on the interaction between VEGF165 and HS and angiogenesis. Mice with tg2 deficiency showed transiently enhanced retina vessel formation and increased vascularization of VEGF165-containing Matrigel implants. In addition, endothelial cells in which TG2 was knocked down exhibited enhanced VEGF165-induced sprouting and migration, which was associated with increased phosphorylation of VEGFR2 at Tyr(951) and its targets Src and Akt. TG2 knockdown did not affect the phosphorylation of VEGFR2 at Tyr(1175) or cell proliferation in response to VEGF165 and sprouting or signaling in response to VEGF121. Decreased phosphorylation of VEGFR2 at Tyr(951) was due to ECM-localized TG2, which reduced the binding of VEGF165 to endothelial ECM in a manner that required its ability to bind to HS but not its catalytic activity. Surface plasmon resonance assays demonstrated that TG2 impeded the interaction between VEGF165 and HS. These results show that TG2 controls the formation of VEGF165-HSPG complexes and suggest that this regulation could be pharmacologically targeted to modulate developmental and therapeutic angiogenesis.


Relationship Between Sequence Homology, Genome Architecture, and Meiotic Behavior of the Sex Chromosomes in North American Voles.
In most mammals, the X and Y chromosomes synapse and recombine along a conserved region of homology known as the pseudoautosomal region (PAR). These homology-driven interactions are required for meiotic progression and are essential for male fertility. Although the PAR fulfills key meiotic functions in most mammals, several exceptional species lack PAR-mediated sex chromosome associations at meiosis. Here, we leveraged the natural variation in meiotic sex chromosome programs present in North American voles (Microtus) to investigate the relationship between meiotic sex chromosome dynamics and X/Y sequence homology. To this end, we developed a novel, reference-blind computational method to analyze sparse sequencing data from flow-sorted X and Y chromosomes isolated from vole species with sex chromosomes that always (Microtus montanus), never (Microtus mogollonensis), and occasionally synapse (Microtus ochrogaster) at meiosis. Unexpectedly, we find more shared X/Y homology in the two vole species with no and sporadic X/Y synapsis compared to the species with obligate synapsis. Sex chromosome homology in the asynaptic and occasionally synaptic species is interspersed along chromosomes and largely restricted to low-complexity sequences, including a striking enrichment for the telomeric repeat sequence, TTAGGG. In contrast, homology is concentrated in high complexity, and presumably euchromatic, sequence on the X and Y chromosomes of the synaptic vole species, M. montanus Taken together, our findings suggest key conditions required to sustain the standard program of X/Y synapsis at meiosis and reveal an intriguing connection between heterochromatic repeat architecture and noncanonical, asynaptic mechanisms of sex chromosome segregation in voles.


Recruitment potential of two perennial grasses with different growth forms at a semiarid-arid transition zone.
The objective of this study was to quantify differences in recruitment potential (seed production, seed presence in the soil) for two congeneric perennial grasses (Bouteloua gracilis, Bouteloua eriopoda [Poaceae]) that dominate adjacent arid and semiarid grassland biomes. It was hypothesized that these species have different recruitment strategies at the biome transition zone that are related to differences in their growth form and longevity. Recruitment potential for each Bouteloua species was compared in patches dominated by one or both species or codominated by the invasive shrub, Larrea tridentata (Zygophyllaceae). Regional variation in recruitment was examined for B. gracilis for cases in which comparable data were available in the literature for a site located within the semiarid grassland biome. The short-lived stoloniferous species B. eriopoda produced more seeds per plant than the long-lived bunchgrass B. gracilis, yet seed viability (<60%) and presence in the soil were lower. Mean viability of B. gracilis was higher (>90%) than that of B. eriopoda, and a greater percentage of seeds produced on a square meter basis was found in the soil (10-25%). Similar patterns were found for both species in all grass-dominated patches. Bouteloua eriopoda plants growing in patches codominated by L. tridentata produced fewer seeds per plant with lower viability, and fewer seeds were found in the soil compared to grass-dominated patches. Regional comparisons found greater seed production per square meter and more seeds in the soil for B. gracilis at the transitional site compared with a cooler, wetter site located within the semiarid grassland biome. These differences in recruitment potential along with published differences in rates of seedling establishment and vegetative spread may explain, at least in part, localized patterns in species dominance.


Phonological learning in semantic dementia.
Patients with semantic dementia (SD) have anterior temporal lobe (ATL) atrophy that gives rise to a highly selective deterioration of semantic knowledge. Despite pronounced anomia and poor comprehension of words and pictures, SD patients have well-formed, fluent speech and normal digit span. Given the intimate connection between phonological STM and word learning revealed by both neuropsychological and developmental studies, SD patients might be expected to show good acquisition of new phonological forms, even though their ability to map these onto meanings is impaired. In contradiction of these predictions, a limited amount of previous research has found poor learning of new phonological forms in SD. In a series of experiments, we examined whether SD patient, GE, could learn novel phonological sequences and, if so, under which circumstances. GE showed normal benefits of phonological knowledge in STM (i.e., normal phonotactic frequency and phonological similarity effects) but reduced support from semantic memory (i.e., poor immediate serial recall for semantically degraded words, characterised by frequent item errors). Next, we demonstrated normal learning of serial order information for repeated lists of single-digit number words using the Hebb paradigm: these items were well-understood allowing them to be repeated without frequent item errors. In contrast, patient GE showed little learning of nonsense syllable sequences using the same Hebb paradigm. Detailed analysis revealed that both GE and the controls showed a tendency to learn their own errors as opposed to the target items. Finally, we showed normal learning of phonological sequences for GE when he was prevented from repeating his errors. These findings confirm that the ATL atrophy in SD disrupts phonological processing for semantically degraded words but leaves the phonological architecture intact. Consequently, when item errors are minimised, phonological STM can support the acquisition of new phoneme sequences in patients with SD.


Inhibiting fibroblast aggregation in skin wounds unlocks developmental pathway to regeneration.
Salamanders are capable of full-thickness skin regeneration where removal of epidermis, dermis and hypodermis results in scar-free repair. What remains unclear is whether regeneration of these tissues recapitulates the cellular events of skin development or occurs through a process unique to regenerative healing. Unfortunately, information on the post-embryonic development of salamander skin is severely lacking, having focused on compartments or cell types, but never on the skin as a complete organ. By examining coordinated development of the epidermis and dermis in axolotls we establish six distinct stages of skin development (I-VI): I-V for normally paedomorphic adults and a sixth stage following metamorphosis. Raising animals either in isolation (zero density pressure) or in groups (density pressure) we find that skin development progresses as a function of animal size and that density directly effects developmental rate. Using keratins, p63, and proliferative markers, we show that when the dermis transforms into the stratum spongiosum and stratum compactum, keratinocytes differentiate into at least three distinct phenotypes that reveal a cryptic stratification program uncoupled from metamorphosis. Lastly, comparing skin regeneration to skin development, we find that dermal regeneration occurs through a unique process, relying heavily on remodeling of the wound extracellular matrix, rather than proceeding through direct development of a dermal lamella produced by the epidermis. By preventing fibroblast influx into the wound bed using beryllium nitrate, we show that in the absence of fibroblast generated ECM production skin regeneration occurs through an alternate route that recapitulates development.


Evaluation of thermal comfort and carbon dioxide levels during ventricular-assist-device implant.
Environmental measurements were performed in an operating theatre within a pediatric cardiac department, during a surgical operation involving the use of carbon dioxide for the implantation of a ventricular system (VAD). After some reports from the staff, who were complaining about low temperatures in the operating room, it was decided to check carbon dioxide levels, the conditions of thermal comfort and the presence of draughts. Microclimatic parameters and carbon dioxide concentration were performed with a microclimatic unit Delta OHM model HD 32.1. The carbon dioxide concentration values measured during the operation were below the levels at which the working environment was not comfortable, as expressed by both the ASHRAE (American Society of Heating, Refrigeration and Air Conditioning Engineers) and the ACGIH (American Conference of Government Industrial Hygienists) standards. PMV (Predicted Mean Vote) and PPD (Preticted Pencentage of Dissatisfied) values obtained indicate a thermal discomfort tendency to cold perception, perceived in particular by the anesthesiologist, circulating nurse and cardiovascular perfusionist. Airflow discomforts occurred at different stages of the operation. Acting on the air conditioning system, decreasing air velocity, while guaranteeing the minimum number of air recirculation prescribed by the regulations, appears to be the best prevention measure. Changing the mode of laminar air inlet above the cot may, however, affect the "wash" effect of the operating range. Otherwise, a "protective" measure could concern staff clothes, providing them with garments with better insulation, in order to protect the neck area, which is affected by the effects of draughts.


Employment, social capital, and community participation among Israelis with disabilities.
Employment, social capital, and community participation have emerged in recent years as significant concepts for realizing the human rights of individuals with disabilities. Yet the theoretical interrelationship of these concepts remains largely overlooked, as does the empirical basis for understanding the underlying connections. This study explores the relationship between employment status, social capital, community participation, and well-being among Israelis with disabilities. It also explores the unique contribution of social capital to the well-being and integration of individuals with disabilities. 274 participants with self-reported disabilities completed a questionnaire containing measures of individual social capital, community participation, well-being, and background data. Correlation and Univariate analysis were used to compare scores between employed (n=131) and non-employed (n=143) participants, and logistic regression analysis was conducted to test the unique contribution of employment to social inclusion and well-being. Employed participants reported significantly higher levels of social capital and were more integrated in leisure and civic activities than their non-employed counterparts. Moreover, employment status was found to have a significant contribution to the variance in the subjective well-being of participants. By more fully understanding the importance of social capital for community inclusion, practitioners can better address the importance of network-building during the rehabilitation process as a means of promoting social and vocational integration.


Quantified Morphology of the Cervical and Subdiaphragmatic Vagus Nerves of Human, Pig, and Rat.
It is necessary to understand the morphology of the vagus nerve (VN) to design and deliver effective and selective vagus nerve stimulation (VNS) because nerve morphology influences fiber responses to electrical stimulation. Specifically, nerve diameter (and thus, electrode-fiber distance), fascicle diameter, fascicular organization, and perineurium thickness all significantly affect the responses of nerve fibers to electrical signals delivered through a cuff electrode. We quantified the morphology of cervical and subdiaphragmatic VNs in humans, pigs, and rats: effective nerve diameter, number of fascicles, effective fascicle diameters, proportions of endoneurial, perineurial, and epineurial tissues, and perineurium thickness. The human and pig VNs were comparable sizes (∼2 mm cervically; ∼1.6 mm subdiaphragmatically), while the rat nerves were ten times smaller. The pig nerves had ten times more fascicles-and the fascicles were smaller-than in human nerves (47 vs. 7 fascicles cervically; 38 vs. 5 fascicles subdiaphragmatically). Comparing the cervical to the subdiaphragmatic VNs, the nerves and fascicles were larger at the cervical level for all species and there were more fascicles for pigs. Human morphology generally exhibited greater variability across samples than pigs and rats. A prior study of human somatic nerves indicated that the ratio of perineurium thickness to fascicle diameter was approximately constant across fascicle diameters. However, our data found thicker human and pig VN perineurium than those prior data: the VNs had thicker perineurium for larger fascicles and thicker perineurium normalized by fascicle diameter for smaller fascicles. Understanding these differences in VN morphology between preclinical models and the clinical target, as well as the variability across individuals of a species, is essential for designing suitable cuff electrodes and stimulation parameters and for informing translation of preclinical results to clinical application to advance the therapeutic efficacy of VNS.


Raman spectroscopy to distinguish grey matter, necrosis, and glioblastoma multiforme in frozen tissue sections.
The need exists for a highly accurate, efficient and inexpensive tool to distinguish normal brain tissue from glioblastoma multiforme (GBM) and necrosis boundaries rapidly, in real-time, in the operating room. Raman spectroscopy provides a unique biochemical signature of a tissue type, with the potential to provide intraoperative identification of tumor and necrosis boundaries. We aimed to develop a database of Raman spectra from normal brain, GBM, and necrosis, and a methodology for distinguishing these pathologies. Raman spectroscopy was used to measure 95 regions from 40 frozen tissue sections using 785 nm excitation wavelength. Review of adjacent hematoxylin and eosin sections confirmed histology of each region. Three regions each of normal grey matter, necrosis, and GBM were selected as a training set. Ten regions were selected as a validation set, with a secondary validation set of tissue regions containing freeze artifact. Grey matter contained higher lipid (1061, 1081 cm(-1)) content, whereas necrosis revealed increased protein and nucleic acid content (1003, 1206, 1239, 1255-1266, 1552 cm(-1)). GBM fell between these two extremes. Discriminant function analysis showed 99.6, 97.8, and 77.5% accuracy in distinguishing tissue types in the training, validation, and validation with freeze artifact datasets, respectively. Decreased classification in the freeze artifact group was due to tissue preparation damage. This study shows the potential of Raman spectroscopy to accurately identify normal brain, necrosis, and GBM as a tool to augment pathologic diagnosis. Future work will develop mapped images of diffuse glioma and neoplastic margins toward development of an intraoperative surgical tool.


The Macrophage Migration Inhibitory Factor (MIF) Promoter Polymorphisms (rs3063368, rs755622) Predict Acute Kidney Injury and Death after Cardiac Surgery.
Macrophage Migration Inhibitory Factor (MIF) is highly elevated after cardiac surgery and impacts the postoperative inflammation. The aim of this study was to analyze whether the polymorphisms CATT5-7 (rs5844572/rs3063368,"-794") and G>C single-nucleotide polymorphism (rs755622,-173) in the MIF gene promoter are related to postoperative outcome. In 1116 patients undergoing cardiac surgery, the MIF gene polymorphisms were analyzed and serum MIF was measured by ELISA in 100 patients. Patients with at least one extended repeat allele (CATT7) had a significantly higher risk of acute kidney injury (AKI) compared to others (23% vs. 13%; OR 2.01 (1.40-2.88), p = 0.0001). Carriers of CATT7 were also at higher risk of death (1.8% vs. 0.4%; OR 5.12 (0.99-33.14), p = 0.026). The GC genotype was associated with AKI (20% vs. GG/CC:13%, OR 1.71 (1.20-2.43), p = 0.003). Multivariate analyses identified CATT7 predictive for AKI (OR 2.13 (1.46-3.09), p < 0.001) and death (OR 5.58 (1.29-24.04), p = 0.021). CATT7 was associated with higher serum MIF before surgery (79.2 vs. 50.4 ng/mL, p = 0.008). The CATT7 allele associates with a higher risk of AKI and death after cardiac surgery, which might be related to chronically elevated serum MIF. Polymorphisms in the MIF gene may constitute a predisposition for postoperative complications and the assessment may improve risk stratification and therapeutic guidance.