Injuries to dancers: prevalence, treatment, and perceptions of causes.
A survey of injuries to dancers was commissioned by the National Organisation of Dance and Mime. Questionnaires asking about chronic and recent injuries were sent to 188 dancers and completed by 141 dancers from seven professional ballet and modern dance companies in the United Kingdom (75% response rate). It was found that of the 141 dancers, 67 (47%) had experienced a chronic injury and 59 (42%) an injury in the previous six months that had affected their dancing. A high proportion of injuries to the soft tissues had not responded to treatment. With correct treatment such injuries should usually heal completely. Dancers are aware of the high rate of injuries and also of procedures that might help to prevent injury--for example, dancing on floors that are sprung and in warmer studios; teachers' and choreographers' awareness of a dancer's limitations and the need for rest and adequate treatment when an injury occurs.


A United Kingdom survey of surgical technique and handling practice of inguinal canal structures during hernia surgery.
Recent trials have assessed the impact of elective nerve division on patient outcome after inguinal herniorrhaphy. The aim of this study was to establish UK surgical practice of handling of structures in the inguinal canal during herniorrhaphy. A cross-sectional survey of all Fellows (n = 1113) of the Association of Surgeons of Great Britain and Ireland (ASGBI) was performed. The main outcomes were to determine method of inguinal hernia repair and routine practice for intra-operative handling of structures in the inguinal canal. A total of 852 (77%) questionnaires were returned, of which 784 (92%) surgeons performed inguinal herniorrhaphy. Approximately two-thirds (63%) of responding surgeons performed less than 50 procedures per annum and 37% conducted more than 50 procedures annually. Mesh was the preferred method used by 90% of surgeons; 6% used non-mesh, and 4% used other (laparoscopic) methods. Routine practice in relation to the inguinal structures varied by volume of hernia surgery; surgeons who conducted more than 50 procedures annually were more likely to visualize and preserve inguinal nerve structures. However, inconsistency in the answers suggested confusion over anatomy. This is the first UK survey to investigate method of hernia repair and usual handling practice of inguinal canal structures. There was wide acceptance of the use of mesh in inguinal hernia repair, with the majority of UK surgeons favoring an open approach. Surgeons performing high volumes of herniorrhaphy were more likely to preserve, rather than transect, inguinal nerve structures. This variation in practice may confound assessment of long-term neuralgia and other post-herniorrhaphy pain syndromes.


Revisiting the density scaling of the non-interacting kinetic energy.
Scaling relations play an important role in the understanding and development of approximate functionals in density functional theory. Recently, a number of these relationships have been redefined in terms of the Kohn-Sham orbitals [Calderín, Phys. Rev. A: At., Mol., Opt. Phys., 2013, 86, 032510]. For density scaling the author proposed a procedure involving a multiplicative scaling of the Kohn-Sham orbitals whilst keeping their occupation numbers fixed. In the present work, the differences between this scaling with fixed occupation numbers and that of previous studies, where the particle number change implied by the scaling was accommodated through the use of the grand canonical ensemble, are examined. We introduce the terms orbital and ensemble density scaling for these approaches, respectively. The natural ambiguity of the density scaling of the non-interacting kinetic energy functional is examined and the ancillary definitions implicit in each approach are highlighted and compared. As a consequence of these differences, Calderín recovered a homogeneity of degree 1 for the non-interacting kinetic energy functional under orbital scaling, contrasting recent work by the present authors [J. Chem. Phys., 2012, 136, 034101] where the functional was found to be inhomogeneous under ensemble density scaling. Furthermore, we show that the orbital scaling result follows directly from the linearity and the single-particle nature of the kinetic energy operator. The inhomogeneity of the non-interacting kinetic energy functional under ensemble density scaling can be quantified by defining an effective homogeneity. This quantity is shown to recover the homogeneity values for important approximate forms that are exact for limiting cases such as the uniform electron gas and one-electron systems. We argue that the ensemble density scaling provides more insight into the development of new functional forms.


Using the Delphi and snow card techniques to build consensus among diverse community and academic stakeholders.
The New York University- New York City Health and Hospitals Corporation (NYU-HHC) Clinical and Translational Science Institute (CTSI) used a community-based participatory research (CBPR) and consensus-building approach among its community advisory board (CAB) and steering committee (SC) members to formulate research priorities to foster shared research collaborations. The Delphi technique is a methodology used to generate consensus from diverse perspectives and organizational agendas through a multi-method, iterative approach to collecting data. A series of on-line surveys was conducted with CAB members to identify health and research priorities from the community perspective. Subsequently, CAB and SC members were brought together and the snow card approach was utilized to narrow to two priority areas for shared research collaborations. Cardiovascular disease (CVD)/obesity and mental health were identified as health disparity areas for shared research collaborations within a social determinants framework. In response, two workgroups were formed with leadership provided by three co-chairs representing the three constituents of the NYU-HHC CTSI: NYU faculty, HHC providers, and community leaders The Delphi approach fostered ownership and engagement with community partners because it was an iterative process that required stakeholders' input into decision making. The snow card technique allowed for organizing of a large number of discrete ideas. Results have helped to inform the overall CTSI research agenda by defining action steps, and setting an organizing framework to tackle two health disparity areas. The process helped ensure that NYUHHC CTSI research and community engagement strategies are congruent with community priorities.


The Southern Ocean ecosystem under multiple climate change stresses--an integrated circumpolar assessment.
A quantitative assessment of observed and projected environmental changes in the Southern Ocean (SO) with a potential impact on the marine ecosystem shows: (i) large proportions of the SO are and will be affected by one or more climate change processes; areas projected to be affected in the future are larger than areas that are already under environmental stress, (ii) areas affected by changes in sea-ice in the past and likely in the future are much larger than areas affected by ocean warming. The smallest areas (<1% area of the SO) are affected by glacier retreat and warming in the deeper euphotic layer. In the future, decrease in the sea-ice is expected to be widespread. Changes in iceberg impact resulting from further collapse of ice-shelves can potentially affect large parts of shelf and ephemerally in the off-shore regions. However, aragonite undersaturation (acidification) might become one of the biggest problems for the Antarctic marine ecosystem by affecting almost the entire SO. Direct and indirect impacts of various environmental changes to the three major habitats, sea-ice, pelagic and benthos and their biota are complex. The areas affected by environmental stressors range from 33% of the SO for a single stressor, 11% for two and 2% for three, to <1% for four and five overlapping factors. In the future, areas expected to be affected by 2 and 3 overlapping factors are equally large, including potential iceberg changes, and together cover almost 86% of the SO ecosystem.


Viral targeting of TFIIB impairs de novo polymerase II recruitment and affects antiviral immunity.
Viruses have evolved a plethora of mechanisms to target host antiviral responses. Here, we propose a yet uncharacterized mechanism of immune regulation by the orthomyxovirus Thogoto virus (THOV) ML protein through engaging general transcription factor TFIIB. ML generates a TFIIB depleted nuclear environment by re-localizing it into the cytoplasm. Although a broad effect on gene expression would be anticipated, ML expression, delivery of an ML-derived functional domain or experimental depletion of TFIIB only leads to altered expression of a limited number of genes. Our data indicate that TFIIB is critically important for the de novo recruitment of Pol II to promoter start sites and that TFIIB may not be required for regulated gene expression from paused promoters. Since many immune genes require de novo recruitment of Pol II, targeting of TFIIB by THOV represents a neat mechanism to affect immune responses while keeping other cellular transcriptional activities intact. Thus, interference with TFIIB activity may be a favourable site for therapeutic intervention to control undesirable inflammation.


An instrument for measuring transfer functions and line spread functions of camera lenses.
A testing instrument for camera lenses is described which automatically measures transfer functions and line spread functions provided the focusing plane is maintained. The frequency covers a continuous range of 0 lines/mm to 150 lines/mm. The gauging to 1 with 0 lines/mm of the transfer function is automatic under all f stop, color, and defocusing conditions. The misalignment caused by instrumentation and the measuring principle is compensated by a function potentiometer. The instrument described allows focusing to infinity by collimators and focusing up to 6 m without collimators. Evaluated and measured curves are compared.


Ultrasonographic soft markers of aneuploidy in second trimester: are we lost?
Chromosomal abnormalities occur in 0.1% to 0.2% of live births, and the most common clinically significant aneuploidy among live-born infants is Down syndrome (trisomy 21). Other sonographically detectable aneuploidies include trisomy 13, 18, monosomy X, and triploidy. Second-trimester ultrasound scan detects 2 types of sonographic markers suggestive of aneuploidy. Markers for major fetal structural abnormalities comprise the first type; the second type of markers are known as "soft markers" of aneuploidy. These latter markers are nonspecific, often transient, and can be readily detected during the second-trimester ultrasound. The most commonly studied soft markers of aneuploidy include a thickened nuchal fold, rhizomelic limb shortening, mild fetal pyelectasis, echogenic bowel, and echogenic intracardiac focus and choroid plexus cyst. There is a great deal of interest in the ultrasound detection of aneuploidy, as evidenced by the large number of publications in the literature on this topic. Unfortunately, studies evaluating the significance of the soft markers of aneuploidy vary widely and show contradictory results. In this article, we review the most common ultrasonographic soft markers used to screen aneuploidy and discuss ultrasonographic technique and measurement criteria for the detection of soft markers. We also review the clinical relevance of soft markers to aneuploidy risk assessment and evidence-based strategies for the management of affected pregnancies with each of these markers in light of current literature.


Combination of computer extracted shape and texture features enables discrimination of granulomas from adenocarcinoma on chest computed tomography.
Differentiation between benign and malignant nodules is a problem encountered by radiologists when visualizing computed tomography (CT) scans. Adenocarcinomas and granulomas have a characteristic spiculated appearance and may be fluorodeoxyglucose avid, making them difficult to distinguish for human readers. In this retrospective study, we aimed to evaluate whether a combination of radiomic texture and shape features from noncontrast CT scans can enable discrimination between granulomas and adenocarcinomas. Our study is composed of CT scans of 195 patients from two institutions, one cohort for training ([Formula: see text]) and the other ([Formula: see text]) for independent validation. A set of 645 three-dimensional texture and 24 shape features were extracted from CT scans in the training cohort. Feature selection was employed to identify the most informative features using this set. The top ranked features were also assessed in terms of their stability and reproducibility across the training and testing cohorts and between scans of different slice thickness. Three different classifiers were constructed using the top ranked features identified from the training set. These classifiers were then validated on the test set and the best classifier (support vector machine) yielded an area under the receiver operating characteristic curve of 77.8%.


Rhodocetin-αβ selectively breaks the endothelial barrier of the tumor vasculature in HT1080 fibrosarcoma and A431 epidermoid carcinoma tumor models.
The tumor vasculature differs from normal blood vessels in morphology, composition and stability. Here, we describe a novel tumor vessel-disrupting mechanism. In an HT1080/mouse xenograft tumor model rhodocetin-αβ was highly effective in disrupting the tumor endothelial barrier. Mechanistically, rhodocetin-αβ triggered MET signaling via neuropilin-1. As both neuropilin-1 and MET were only lumen-exposed in a subset of abnormal tumor vessels, but not in normal vessels, the prime target of rhodocetin-αβ were these abnormal tumor vessels. Consequently, cells lining such tumor vessels became increasingly motile which compromised the vessel wall tightness. After this initial leakage, rhodocetin-αβ could leave the bloodstream and reach the as yet inaccessible neuropilin-1 on the basolateral side of endothelial cells and thus disrupt nearby vessels. Due to the specific neuropilin-1/MET co-distribution on cells lining such abnormal tumor vessels in contrast to normal endothelial cells, rhodocetin-αβ formed the necessary trimeric signaling complex of rhodocetin-αβ-MET-neuropilin-1 only in these abnormal tumor vessels. This selective attack of tumor vessels, sparing endothelial cell-lined vessels of normal tissues, suggests that the neuropilin-1-MET signaling axis may be a promising drugable target for anti-tumor therapy, and that rhodocetin-αβ may serve as a lead structure to develop novel anti-tumor drugs that target such vessels.


Gastric cancer, cytotoxin-associated gene A-positive Helicobacter pylori, and serum pepsinogens: an international study. The Eurogst Study Group.
CagA-positive Helicobacter pylori infection has been more closely associated with gastric disease than CagA-negative infection. This study evaluated whether geographic variation in the prevalence of CagA could explain variation in gastric cancer rates. The Eurogast study was conducted in 17 centers in 13 countries. Gastric cancer rates were calculated for each center, and serum samples from approximately 2850 subjects were assayed for immunoglobulin G antibodies to H. pylori and CagA and for pepsinogens A and C. The proportion of CagA-positive H. pylori infections varied across the centers, but this variation did not explain any more of the variation in gastric cancer rates than H. pylori alone. Subjects with CagA-positive infection had, however, significantly higher pepsinogen levels and a lower pepsinogen A/C ratio than subjects with CagA-negative infection; this pattern was observed consistently across the study centers. Variation in the seroprevalence of CagA did not explain geographic variation in gastric cancer rates any better than H. pylori alone. However, the consistent variation in pepsinogen levels with CagA status across the study centers supports the importance of the role of CagA in the development of gastric disease.


Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes.
Megakaryoblastic leukemia 1 (MKL1) is a myocardin-related transcription factor that we found strongly activated serum response element (SRE)-dependent reporter genes through its direct binding to serum response factor (SRF). The c-fos SRE is regulated by mitogen-activated protein kinase phosphorylation of ternary complex factor (TCF) but is also regulated by a RhoA-dependent pathway. The mechanism of this pathway is unclear. Since MKL1 (also known as MAL, BSAC, and MRTF-A) is broadly expressed, we assessed its role in serum induction of c-fos and other SRE-regulated genes with a dominant negative MKL1 mutant (DN-MKL1) and RNA interference (RNAi). We found that DN-MKL1 and RNAi specifically blocked SRE-dependent reporter gene activation by serum and RhoA. Complete inhibition by RNAi required the additional inhibition of the related factor MKL2 (MRTF-B), showing the redundancy of these factors. DN-MKL1 reduced the late stage of serum induction of endogenous c-fos expression, suggesting that the TCF- and RhoA-dependent pathways contribute to temporally distinct phases of c-fos expression. Furthermore, serum induction of two TCF-independent SRE target genes, SRF and vinculin, was nearly completely blocked by DN-MKL1. Finally, the RBM15-MKL1 fusion protein formed by the t(1;22) translocation of acute megakaryoblastic leukemia had a markedly increased ability to activate SRE reporter genes, suggesting that its activation of SRF target genes may contribute to leukemogenesis.


The Alström syndrome: ophthalmic histopathology and retinal ultrastructure.
A case of pigmentary retinal degeneration causing blindness in early childhood, progressive neurosensory hearing loss, diabetes mellitus, acanthosis nigricans, hypogonadism with normal secondary sex characteristics, and kyphoscoliosis without polydactyly and with no mental retardation is reported. The results of endocrinological studies, karyotype analysis, and digital dermatoglyphics supported the clinical diagnosis of the Alström syndrome. The patient had small globes, bilateral posterior subcapsular cataracts, lacy vacuolation of the iris, ciliary process hyalinisation, unilateral asteroid hyalosis, total absence of rods and cones, intraretinal melanin pigment, retinal pigment epithelium atrophy, focal chorioretinal fusion, preretinal fibrosis, bilateral giant optic disc drusen, and optic nerve atrophy. Electron microscopy of the retina demonstrated large numbers of melanolysosomes, numerous folds of basement membrane material, disruption of Bruch's membrane, and numerous bundles of extracellular collagen fibrils in the retinal pigment epithelium.


Identification, characterization, and ontogeny of a second cytochrome P450 3A gene from the fresh water teleost medaka (Oryzias latipes).
Multiple copies of cytochrome P450 gene family 3 have been identified from numerous mammalian species. Often these genes exhibit differential catalytic activities and gene regulation. To date however, little information is available regarding multiple forms of this gene family in teleost fishes. In this study, a second isozyme of cytochrome P450 3A has been cloned from the teleost fish Oryzias latipes and designated CYP3A40. Screening of a cDNA library to medaka liver resulted in the identification of a full length cDNA clone containing a 2316 base pair (bp) insert with an open reading frame encoding a single peptide of 502 amino acids. Comparisons of the deduced amino acid sequence to other known cytochrome P450 sequences indicate that this gene product is most similar to the CYP3A gene family and shares a 90% identity to CYP3A38 previously identified from medaka liver. Consistent with Northern blot and Western blot analysis, Southern blots of medaka genomic DNA demonstrated the presence of two CYP3A genes. Gene expression studies demonstrated that CYP3A38 and CYP3A40 are differentially regulated according to embryonic development. Northern blot analysis, using a probe to a conserved region of both CYP3A genes, demonstrated the presence of a single CYP3A transcript for early and late embryonic stages and two CYP3A transcripts in larvae and adult liver. Similarly, Western blots show a single faint immunoreactive cytochrome P450 3A protein in microsomes from early and late embryos and two abundant protein bands in microsomes from larval and adult liver. To further examine the transcriptional differences in CYP3A expression, RT-PCR analysis was performed on embryonic stages 11-35, 1- and 14-day-old larvae, and adult liver using primer sets specific for CYP3A38 and CYP3A40. These results demonstrate that CYP3A40 is expressed early in embryonic development and continues throughout adult stages. CYP3A38, however, is tightly regulated during embryonic development and is only expressed post-hatch.


Phase derivative estimation from a single interferogram using a Kalman smoothing algorithm.
We report a technique for direct phase derivative estimation from a single recording of a complex interferogram. In this technique, the interference field is represented as an autoregressive model with spatially varying coefficients. Estimates of these coefficients are obtained using the Kalman filter implementation. The Rauch-Tung-Striebel smoothing algorithm further improves the accuracy of the coefficient estimation. These estimated coefficients are utilized to compute the spatially varying phase derivative. Stochastic evolution of the coefficients is considered, which allows estimating the phase derivative with any type of spatial variation. The simulation and experimental results are provided to substantiate the noise robustness and applicability of the proposed method in phase derivative estimation.


Calcium-sensing receptor mutations in familial hypocalciuric hypercalcaemia with recurrent pancreatitis.
Pancreatitis is an unusual complication of the benign disorder familial hypocalciuric hypercalcaemia (FHH) such that it could represent a distinct subgroup of FHH. In order to study this, we investigated three FHH kindreds with recurrent pancreatitis for mutations of the extracellular calcium-sensing receptor (CaR) to identify a possible common genetic aetiology for typical FHH and that associated with pancreatitis. Three FHH kindreds (18 affected, 14 unaffected members) in which the proband had presented with recurrent pancreatitis were identified. The entire 3234bp coding region of the CaR gene was examined by direct DNA sequencing using fluorochrome labelled dideoxy-terminators. Mutations were confirmed and demonstrated to co-segregate with FHH by restriction enzyme analysis. Three novel heterozygous missense mutations (Asn178Asp, Arg220Gln and Pro221Ser) in the extracellular domain of the CaR were identified in each of the probands. These mutations, which co-segregated with the hypercalcaemia, were not detected as common polymorphisms in 55 unrelated normocalcaemic controls. Familial hypocalciuric hypercalcaemia with recurrent pancreatitis is associated with calcium-sensing receptor mutations, and thus this variant has the same genetic aetiology as typical familial hypocalciuric hypercalcaemia.


Human chromosomes 9, 12, and 15 contain the nucleation sites of stress-induced nuclear bodies.
We previously reported the identification of a novel nuclear compartment detectable in heat-shocked HeLa cells that we termed stress-induced Src-activated during mitosis nuclear body (SNB). This structure is the recruitment center for heat shock factor 1 and for a number of RNA processing factors, among a subset of Serine-Arginine splicing factors. In this article, we show that stress-induced SNBs are detectable in human but not in hamster cells. By means of hamster>human cell hybrids, we have identified three human chromosomes (9, 12, and 15) that are individually able to direct the formation of stress bodies in hamster cells. Similarly to stress-induced SNB, these bodies are sites of accumulation of hnRNP A1-interacting protein and heat shock factor 1, are usually associated to nucleoli, and consist of clusters of perichromatin granules. We show that the p13-q13 region of human chromosome 9 is sufficient to direct the formation of stress bodies in hamster>human cell hybrids. Fluorescence in situ hybridization experiments demonstrate that the pericentromeric heterochromatic q12 band of chromosome 9 and the centromeric regions of chromosomes 12 and 15 colocalize with stress-induced SNBs in human cells. Our data indicate that human chromosomes 9, 12, and 15 contain the nucleation sites of stress bodies in heat-shocked HeLa cells.


Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit.
Escobar syndrome is a form of arthrogryposis multiplex congenita and features joint contractures, pterygia, and respiratory distress. Similar findings occur in newborns exposed to nicotinergic acetylcholine receptor (AChR) antibodies from myasthenic mothers. We performed linkage studies in families with Escobar syndrome and identified eight mutations within the gamma -subunit gene (CHRNG) of the AChR. Our functional studies show that gamma -subunit mutations prevent the correct localization of the fetal AChR in human embryonic kidney-cell membranes and that the expression pattern in prenatal mice corresponds to the human clinical phenotype. AChRs have five subunits. Two alpha, one beta, and one delta subunit are always present. By switching gamma to epsilon subunits in late fetal development, fetal AChRs are gradually replaced by adult AChRs. Fetal and adult AChRs are essential for neuromuscular signal transduction. In addition, the fetal AChRs seem to be the guide for the primary encounter of axon and muscle. Because of this important function in organogenesis, human mutations in the gamma subunit were thought to be lethal, as they are in gamma -knockout mice. In contrast, many mutations in other subunits have been found to be viable but cause postnatally persisting or beginning myasthenic syndromes. We conclude that Escobar syndrome is an inherited fetal myasthenic disease that also affects neuromuscular organogenesis. Because gamma expression is restricted to early development, patients have no myasthenic symptoms later in life. This is the major difference from mutations in the other AChR subunits and the striking parallel to the symptoms found in neonates with arthrogryposis when maternal AChR auto-antibodies crossed the placenta and caused the transient inactivation of the AChR pathway.


MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells.
Mesenchymal stromal/stem cells (MSCs) are clinically useful for cell-based therapy, but concerns regarding their ability to replicate limit their human application. MSCs release extracellular vesicles (EVs) that mediate at least in part the paracrine effects of the parental cells. To understand the molecular basis of their biological properties, we characterized the RNA cargo of EVs from porcine adipose-tissue derived MSCs. Comprehensive characterization of mRNA and miRNA gene expression using high-throughput RNA sequencing (RNA-seq) revealed that EVs are selectively enriched for distinct classes of RNAs. For example, EVs preferentially express mRNA for transcription factors (e.g. MDFIC, POU3F1, NRIP1) and genes involved in angiogenesis (e.g. HGF, HES1, TCF4) and adipogenesis (e.g. CEBPA, KLF7). EVs also express Golgi apparatus genes (ARRB1, GOLGA4) and genes involved in TGF-β signaling. In contrast, mitochondrial, calcium signaling, and cytoskeleton genes are selectively excluded from EVs, possibly because these genes remain sequestered in organelles or intracellular compartments. RNA-seq generated reads for at least 386 annotated miRNAs, but only miR148a, miR532-5p, miR378, and let-7f were enriched in EVs compared to MSCs. Gene ontology analysis indicates that these miRNAs target transcription factors and genes that participate in several cellular pathways, including angiogenesis, cellular transport, apoptosis, and proteolysis. Our data suggest that EVs transport gene regulatory information to modulate angiogenesis, adipogenesis, and other cell pathways in recipient cells. These observations may contribute to development of regenerative strategies using EVs to overcome potential complications of cell-based therapy.


Prospective analysis of the effect of physician experience with the FAST examination in reducing the use of CT scans.
The objective of this study was to examine the effect of ultrasound experience level on emergency physicians' Focused Assessment with Sonography for Trauma (FAST) exam accuracy and emergency physicians' confidence in using FAST findings to assist in managing patients with blunt trauma. This prospective, consecutive enrolment study evaluated adult trauma team activation blunt trauma patients. Based on the number of post-training FAST exams carried out, 11 attending emergency physicians were grouped into A (<25 exams, n = 4), B (26-50 exams, n = 4) or C (>50 exams, n = 3). The FAST exam was carried out prior to other diagnostic studies. The emergency physicians were asked to prospectively judge their perception of the need for surgery, abdominal CT or no further tests. All study patients ultimately underwent CT, diagnostic peritoneal lavage or laparotomy. Among each physician group, the number of subsequent CT scans deemed necessary by the emergency physician after a 'normal' FAST was calculated and compared. Accuracy was greatest in group C. Sixty-nine of 80 patients in group A had a normal FAST exam; emergency physicians deemed CT necessary in 68/69 cases (99%; confidence interval [CI] 92-100%). Eighty-two of 98 patients in group C had a normal FAST exam; emergency physicians deemed CT necessary in 19/82 cases (23%; CI 15-34%). Physicians in groups B and C were less likely to order CT after a normal FAST than group A (P < 0.001). FAST accuracy was greatest among more experienced emergency physicians. A normal FAST exam assisted more experienced emergency physicians with the perceived need to order significantly fewer CT scans than less experienced emergency physicians.


Wild birds recognize individual humans: experiments on magpies, Pica pica.
The ability to distinguish among heterospecific individuals has been reported in only a few animal species. Humans can be viewed as a special type of heterospecifics because individuals differ widely in behavior, ranging from non-threatening to very threatening toward animals. In this study, we asked whether wild magpies can recognize individual humans who had accessed their nests. We compared the behavior of breeding pairs toward individual humans before and after the humans climbed up to the birds' nests, and also toward climbers and non-climbers. We have evidence for (i) aggressive responses of the magpie pairs toward humans who had repeatedly accessed their nests (climbers) and a lack of response to humans who had not accessed the nest (non-climbers); (ii) a total lack of scolding responses toward climbers by magpie pairs whose nests had not been accessed; (iii) a selective aggressive response to the climber when a climber and a non-climber were presented simultaneously. Taken together, these results suggest that wild magpies can distinguish individual humans that pose a threat to their nests from humans that have not behaved in a threatening way. The magpie is only the third avian species, along with crows and mockingbirds, in which recognition of individual humans has been documented in the wild. Here, we propose a new hypothesis (adopted from psychology) that frequent previous exposure to humans in urban habitats contributes to the ability of birds to discriminate among human individuals. This mechanism, along with high cognitive abilities, may predispose some species to learn to discriminate among human individuals. Experimental tests of these two mechanisms are proposed.


Disk evolution, element abundances and cloud properties of young gas giant planets.
We discuss the chemical pre-conditions for planet formation, in terms of gas and ice abundances in a protoplanetary disk, as function of time and position, and the resulting chemical composition and cloud properties in the atmosphere when young gas giant planets form, in particular discussing the effects of unusual, non-solar carbon and oxygen abundances. Large deviations between the abundances of the host star and its gas giants seem likely to occur if the planet formation follows the core-accretion scenario. These deviations stem from the separate evolution of gas and dust in the disk, where the dust forms the planet cores, followed by the final run-away accretion of the left-over gas. This gas will contain only traces of elements like C, N and O, because those elements have frozen out as ices. PRODIMO protoplanetary disk models are used to predict the chemical evolution of gas and ice in the midplane. We find that cosmic rays play a crucial role in slowly un-blocking the CO, where the liberated oxygen forms water, which then freezes out quickly. Therefore, the C/O ratio in the gas phase is found to gradually increase with time, in a region bracketed by the water and CO ice-lines. In this regions, C/O is found to approach unity after about 5 Myrs, scaling with the cosmic ray ionization rate assumed. We then explore how the atmospheric chemistry and cloud properties in young gas giants are affected when the non-solar C/O ratios predicted by the disk models are assumed. The DRIFT cloud formation model is applied to study the formation of atmospheric clouds under the influence of varying premordial element abundances and its feedback onto the local gas. We demonstrate that element depletion by cloud formation plays a crucial role in converting an oxygen-rich atmosphere gas into carbon-rich gas when non-solar, premordial element abundances are considered as suggested by disk models.


Cultural respect strategies in Australian Aboriginal primary health care services: beyond education and training of practitioners.
There is little literature on health-service-level strategies for culturally respectful care to Aboriginal and Torres Strait Islander Australians. We conducted two case studies, which involved one Aboriginal community controlled health care service and one state government-managed primary health care service, to examine cultural respect strategies, client experiences and barriers to cultural respect. Data were drawn from 22 interviews with staff from both services and four community assessment workshops, with a total of 21 clients. Staff and clients at both services reported positive appraisals of the achievement of cultural respects. Strategies included: being grounded in a social view of health, including advocacy and addressing social determinants; employing Aboriginal staff; creating a welcoming service; supporting access through transport, outreach, and walk-in centres; and integrating cultural protocol. Barriers included: communication difficulties; racism and discrimination; and externally developed programs. Service-level strategies were necessary to achieving cultural respect. These strategies have the potential to improve Aboriginal and Torres Strait Islander health and wellbeing. Primary health care's social determinants of health mandate, the community controlled model, and the development of the Aboriginal and Torres Strait Islander health workforce need to be supported to ensure a culturally respectful health system.


Monitoring Atrial Fibrillation After Catheter Ablation.
Although catheter ablation is an effective treatment for recurrent atrial fibrillation (AF), there is no consensus on the definition of success or follow-up strategies. Symptoms are the major motivation for undergoing catheter ablation in patients with AF, however it is well known that reliance on perception of AF by patients after AF ablation results in an underestimation of recurrence of the arrhythmia. Because symptoms of AF occurrence may be misleading, a reliable assessment of rhythm outcome is essential for the definition of success in both clinical care and research trials. Continuous rhythm monitoring over long periods of time is superior to intermittent recording using external monitors to detect the presence of AF episodes and to quantify the AF burden. Today, new devices implanted subcutaneously using a minimally invasive technique have been developed for continuous AF monitoring. Implantable devices keep detailed information about arrhythmia recurrences and might allow identification of very brief episodes of AF, the significance of which is still uncertain. In particular, it is not known whether there is any critical value of daily AF burden that has a prognostic significance. This issue remains an area of active discussion, debate and investigation. Further investigation is required to determine if continuous AF monitoring with implantable devices is effective in reducing stroke risk and facilitating maintenance of sinus rhythm after AF ablation.


A novel revision to the classical transnasal topical sphenopalatine ganglion block for the treatment of headache and facial pain.
The sphenopalatine ganglion (SPG) is located with some degree of variability near the tail or posterior aspect of the middle nasal turbinate. The SPG has been implicated as a strategic target in the treatment of various headache and facial pain conditions, some of which are featured in this manuscript. Interventions for blocking the SPG range from minimally to highly invasive procedures often associated with great cost and unfavorable risk profiles. The purpose of this pilot study was to present a novel, FDA-cleared medication delivery device, the Tx360® nasal applicator, incorporating a transnasal needleless topical approach for SPG blocks. This study features the technical aspects of this new device and presents some limited clinical experience observed in a small series of head and face pain cases. Case series. Pain management center, part of teaching-community hospital, major metropolitan city, United States. After Institutional Review Board (IRB) approval, the technical aspects of this technique were examined on 3 patients presenting with various head and face pain conditions including trigeminal neuralgia (TN), chronic migraine headache (CM), and post-herpetic neuralgia (PHN). The subsequent response to treatment and quality of life was quantified using the following tools: the 11-point Numeric Rating Scale (NRS), Modified Brief Pain Inventory - short form (MBPI-sf), Patient Global Impression of Change (PGIC), and patient satisfaction surveys. The Tx360® nasal applicator was used to deliver 0.5 mL of ropivacaine 0.5% and 2 mg of dexamethasone for SPG block. Post-procedural assessments were repeated at 15 and 30 minutes, and on days one, 7, 14, and 21 with a final assessment at 28 days post-treatment. All patients were followed for one year. Individual patients received up to 10 SPG blocks, as clinically indicated, after the initial 28 days. Three women, ages 43, 18, and 15, presented with a variety of headache and face pain disorders including TN, CM, and PHN. All patients reported significant pain relief within the first 15 minutes post-treatment. A high degree of pain relief was sustained throughout the 28 day follow-up period for 2 of the 3 study participants. All 3 patients reported a high degree of satisfaction with this procedure. One patient developed minimal bleeding from the nose immediately post-treatment which resolved spontaneously in less than 5 minutes. Longer term follow-up (up to one year) demonstrated that additional SPG blocks over time provided a higher degree and longer lasting pain relief. Controlled double blind studies with a higher number of patients are needed to prove efficacy of this minimally invasive technique for SPG block. SPG block with the Tx360® is a rapid, safe, easy, and reliable technique to accurately deliver topical transnasal analgesics to the area of mucosa associated with the SPG. This intervention can be delivered in as little as 10 seconds with the novice provider developing proficiency very quickly. Further investigation is certainly warranted related to technique efficacy, especially studies comparing efficacy of Tx360 and standard cotton swab techniques.


Extracorporeal glass-wool filtration of whole blood enhances post-ischemic recovery of the cortical sensory evoked response.
In twenty dogs, anticoagulated with heparin 300 units/kg, the right cortical sensory evoked response (CSER) to contralateral median nerve stimulation was suppressed during 60 min ischemia induced by periodic infusion of 50 to 100 microliter increments of air via the right internal carotid artery. The post-ischemic recovery of the CSER was followed an additional 60 min in 19 of these animals divided into 2 groups. Ten dogs were subjected to glass-wool filtration of their blood by extracorporeal shunting from femoral artery to femoral vein for one hr prior to infusing air. Nine dogs did not receive glass-wool filtration. Post-ischemic recovery of CSER amplitude, a quantifiable electrophysiologic index of neuronal function, was significantly greater in the filtered group than in the non-filtered group. 14C-antipyrine autoradiographic blood flow studies were performed in 3 dogs. One was studied at the end of a 60 min ischemic CSER suppression period and showed severe flow disruption by air embolism. Two dogs, one from each group, were studied at the conclusion of the 60 min recovery period. In the filtered animal, cortical blood flow exceeded the threshold for CSER maintenance while cortical flow rates in the unfiltered animal fell below this threshold. The enhanced postischemic neuronal recovery in the filtered group as indicated by the CSER in attributed to the preservation of injury zone nutrient blood flow that is supported by collateral circulation.


Characterizing Resistance to Phakopsora pachyrhizi in Soybean.
Resistance in soybean to Phakopsora pachyrhizi, the cause of soybean rust, is characterized by either reddish-brown (RB) lesions or an immune response. The RB type of resistance can be incomplete, as evidenced by the presence of sporulating uredinia within lesions. Susceptibility, on the other hand, is exemplified by tan-colored (TAN) lesions, and can be expressed in gradations of susceptibility or partial resistance that are less well defined. This study evaluated traits associated with incomplete or partial resistance to P. pachyrhizi in soybean by comparing 34 soybean accessions inoculated with four P. pachyrhizi isolates. Six accessions produced RB lesions to all four isolates, while 19 accessions produced TAN lesions, including plant introduction (PI) 200492 (Rpp1) and the susceptible check 'Williams'. Williams had among the largest area under the disease progress curve (AUDPC) values and area under the sporulating uredinia progress curve (AUSUPC) values, while eight accessions had lower AUSUPC values. Of the known sources of single-gene resistance, only PI 230970 (Rpp2), PI 459025B (Rpp4), and PI 594538A (Rpp1b) had lower AUDPC and AUSUPC values than Williams. PI 594538A and PI 561356 had RB lesions and had the lowest AUDPC and AUSUPC values. Of the known sources of single-gene resistance, only PI 230970 (Rpp2) and PI 594538A (Rpp1b) produced fewer and smaller-diameter uredinia than Williams. This study characterized reactions to P. pachyrhizi in 34 accessions based on lesion type and sporulation, and defined incomplete resistance and partial resistance in the soybean-P. pachyrhizi interaction.


A three-image algorithm for hard x-ray grating interferometry.
A three-image method to extract absorption, refraction and scattering information for hard x-ray grating interferometry is presented. The method comprises a post-processing approach alternative to the conventional phase stepping procedure and is inspired by a similar three-image technique developed for analyzer-based x-ray imaging. Results obtained with this algorithm are quantitatively comparable with phase-stepping. This method can be further extended to samples with negligible scattering, where only two images are needed to separate absorption and refraction signal. Thanks to the limited number of images required, this technique is a viable route to bio-compatible imaging with x-ray grating interferometer. In addition our method elucidates and strengthens the formal and practical analogies between grating interferometry and the (non-interferometric) diffraction enhanced imaging technique.


Novel orally swallowable IntelliCap(®) device to quantify regional drug absorption in human GI tract using diltiazem as model drug.
Typically, colonic absorption of a drug is mandatory for a sustained release formulation to hold the drug's plasma level for more than 12 or 24 h above the minimum therapeutic plasma concentration (efficacy). According to Drugs@FDA, only 7.4% of the oral drugs are extended release forms probably showing colonic absorption. Therefore an early determination of a drug's colonic absorption using the IntelliCap® in animals or humans will provide the mandatory information to initiate or stop a SR form development. Diltiazem (60 mg) is used in the oral swallowable IntelliCap® and the marketed SR form from Mylan (coated beads). A human study with 14 healthy volunteers compared the Mylan formulation with the IntelliCap® device that releases the drug identical to the in-vitro dissolution of the Mylan product. The plasma profiles of IntelliCap® and Mylan formulation are highly similar. The mean AUC (bioequivalence fulfilled) and mean Cmax of IntelliCap® shows only a difference of +15% and -12%, respectively. But the PK profile of the Mylan formulation shows a broader peak around Cmax. About 81.8% diltiazem was absorbed in the colon (IntelliCap®) comparable to former publications. The Mylan is a SR diffusion coated beads form whereas the IntelliCap® is a monolithic capsule. The beads are transported in the gut and spread which results in a longer Tmax and a broader Cmax peak. The IntelliCap® device can quantitatively measure the colonic absorption of a drug in excellent accordance to a standard oral SR dosage form.


Hormone Therapy and Breast Cancer: Emerging Steroid Receptor Mechanisms.
Although hormone therapy is widely used by millions of women to relieve symptoms of menopause, it has been associated with several side-effects such as coronary heart disease, stroke and increased invasive breast cancer risk. These side-effects have caused many women to seek alternatives to conventional hormone therapy, including the controversial custom-compounded bioidentical hormone therapy suggested to not increase breast cancer risk. Historically estrogens and the estrogen receptor were considered the principal factors promoting breast cancer development and progression, however, a role for other members of the steroid receptor family in breast cancer pathogenesis is now evident, with emerging studies revealing an interplay between some steroid receptors. In this review, we discuss examples of hormone therapy used for the relief of menopausal symptoms, highlighting the distinction between conventional hormone therapy and custom-compounded bioidentical hormone therapy. Moreover, we highlight the fact that not all hormones have been evaluated for an association with increased breast cancer risk. We also summarize the current knowledge regarding the role of steroid receptors in mediating the carcinogenic effects of hormones used in menopausal hormone therapy, with special emphasis on the influence of the interplay or crosstalk between steroid receptors. Unraveling the intertwined nature of steroid hormone receptor signaling pathways in breast cancer biology is of utmost importance, considering that breast cancer is the most prevalent cancer among women worldwide. Moreover, understanding these mechanisms may reveal novel prevention or treatment options, and lead to the development of new hormone therapies that does not cause increased breast cancer risk.


Oxygen distribution in the human eye: relevance to the etiology of open-angle glaucoma after vitrectomy.
Vitrectomy, when followed by cataract surgery, increases the risk of open-angle glaucoma. This study was conducted in patients to determine whether these procedures are associated with increased exposure of the trabecular meshwork to oxygen. Oxygen distribution was recorded with a fiberoptic probe in patients undergoing surgery for cataract, glaucoma, or retinal disease. pO(2) was measured beneath the central cornea, in the mid-anterior chamber, and in the anterior chamber angle. In patients who were pseudophakic or were scheduled for cataract extraction, pO(2) was also measured in the posterior chamber and near the lens. Eyes with no previous cataract or vitrectomy surgery had steep oxygen gradients in the aqueous humor between the cornea and lens. pO(2) was low in the posterior chamber and near the lens. Previous vitrectomy was associated with significantly increased pO(2) in the posterior chamber. Eyes with previous cataract surgery had significantly elevated pO(2) only in the posterior chamber and in front of the intraocular lens (IOL). Eyes that had both vitrectomy and previous cataract surgery had increased pO(2) in the posterior chamber, anterior to the IOL, and in the anterior chamber angle. pO(2) in the posterior chamber and the anterior chamber angle correlated strongly. Oxygen metabolism by the lens and cornea establishes oxygen gradients in the anterior segment. Vitrectomy and cataract surgery increase pO(2) in the anterior chamber angle, potentially damaging trabecular meshwork cells. We propose that oxygen levels in the anterior chamber angle are strongly influenced by oxygen derived from the ciliary body circulation.


The stretch-shortening cycle (SSC) revisited: residual force enhancement contributes to increased performance during fast SSCs of human m. adductor pollicis.
The stretch-shortening cycle (SSC) occurs in most everyday movements, and is thought to provoke a performance enhancement of the musculoskeletal system. However, mechanisms of this performance enhancement remain a matter of debate. One proposed mechanism is associated with a stretch-induced increase in steady-state force, referred to as residual force enhancement (RFE). As yet, direct evidence relating RFE to increased force/work during SSCs is missing. Therefore, forces of electrically stimulated m. adductor pollicis (n = 14 subjects) were measured during and after pure stretch, pure shortening, and stretch-shortening contractions with varying shortening amplitudes. Active stretch (30°, ω = 161 ± 6°s(-1)) caused significant RFE (16%, P < 0.01), whereas active shortening (10°, 20°, and 30°; ω = 103 ± 3°s(-1), 152 ± 5°s(-1), and 170 ± 5°s(-1)) resulted in significant force depression (9-15%, P < 0.01). In contrast, after SSCs (that is when active stretch preceded active shortening) no force depression was found. Indeed for our specific case in which the shortening amplitude was only 1/3 of the lengthening amplitude, there was a remnant RFE (10%, P < 0.01) following the active shortening. This result indicates that the RFE generated during lengthening affected force depression when active lengthening was followed by active shortening. As conventional explanations, such as the storage and release of elastic energy, cannot explain the enhanced steady-state force after SSCs, it appears that the stretch-induced RFE is not immediately abolished during shortening and contributes to the increased force and work during SSCs.


Are stress and coping associated with WISC-III performance among children?
This study examined the association between stress/coping variables and the newly developed Wechsler Intelligence Scale for Children--III (WISC-III) among children. Subjects included 98 children (72 males, 26 females), who ranged in age from 6 to 16 years and who were referred for multidisciplinary diagnostic testing during 1992-93. Demographic, DSM-III-R diagnostic, and testing data from the WISC-III were obtained from patient charts. Results suggest that stress and coping are associated with WISC-III performance among referred children in this archival and correlational study. Implications for future research are discussed.


Polysialic acid is required for optimal growth of axons on a neuronal substrate.
Formation of axonal pathways involves a variety of molecules that influence cell-cell interactions. The polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) is present on neuronal surfaces during process outgrowth. Our studies reveal that the removal of PSA causes a decrease in the rate of elongation of retinal cell processes on a substrate of neuronal membranes derived from chick tectum. This effect was partially reversed by antibodies against the L1 adhesion molecule, but not by antibodies against NCAM, N-cadherin, or beta 1-integrins. This predominant effect of PSA on L1 was also observed in short-term, cell-cell adhesion assays, suggesting that PSA promotes optimal outgrowth on neuronal substrates by limiting the consequences of L1-mediated adhesion.


Genomic haplotype blocks may not accurately reflect spatial variation in historic recombination intensity.
Recently, genomic data have revealed a "block-like" structure of haplotype diversity on human chromosomes. This structure is anticipated to facilitate gene mapping studies, because strong associations among loci within a block may allow haplotype variation to be tagged with a limited number of markers. But its usefulness to mapping efforts depends on the consistency of the block structure within and among populations, which in turn depends on how the block structure arises. Recombination hot spots are generally thought to underlie the block structure, but haplotype blocks can also develop stochastically under random recombination, in which case the block structure will show limited consistency among populations. Using coalescent models, which we upscaled to simulate the evolution of haplotypes with many markers at fixed distances, we show that the relationship between block boundaries and historic recombination intensity may be surprisingly weak. The majority of historic recombinations do not leave a footprint in present-day linkage disequilibrium patterns, and the block structure is sensitive to factors that affect the timing of recombination relative to marker mutation events in the genealogy, such as marker frequency bias and historic population size changes. Our results give insight into the potential of stochastic events to affect haplotype block structure, which can limit the usefulness of the block structure to mapping studies.


High-frequency stimulation of nucleus accumbens changes in dopaminergic reward circuit.
Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is a potential remedial therapy for drug craving and relapse, but the mechanism is poorly understood. We investigated changes in neurotransmitter levels during high frequency stimulation (HFS) of the unilateral NAc on morphine-induced rats. Sixty adult Wistar rats were randomized into five groups: the control group (administration of saline), the morphine-only group (systematic administration of morphine without electrode implantation), the morphine-sham-stimulation group (systematic administration of morphine with electrode implantation but not given stimulation), the morphine-stimulation group (systematic administration of morphine with electrode implantation and stimulation) and the saline-stimulation group (administration of saline with electrode implantation and stimulation). The stimulation electrode was stereotaxically implanted into the core of unilateral NAc and microdialysis probes were unilaterally lowered into the ipsilateral ventral tegmental area (VTA), NAc, and ventral pallidum (VP). Samples from microdialysis probes in the ipsilateral VTA, NAc, and VP were analyzed for glutamate (Glu) and γ-aminobutyric acid (GABA) by high-performance liquid chromatography (HPLC). The levels of Glu were increased in the ipsilateral NAc and VP of morphine-only group versus control group, whereas Glu levels were not significantly changed in the ipsilateral VTA. Furthermore, the levels of GABA decreased significantly in the ipsilateral NAc, VP, and VTA of morphine-only group when compared with control group. The profiles of increased Glu and reduced GABA in morphine-induced rats suggest that the presence of increased excitatory neurotransmission in these brain regions. The concentrations of the Glu significantly decreased while the levels of GABA increased in ipsilateral VTA, NAc, and VP in the morphine-stimulation group compared with the morphine-only group. No significant changes were seen in the morphine-sham stimulation group compared with the morphine-only group. These findings indicated that unilateral NAc stimulation inhibits the morphine-induced rats associated hyperactivation of excitatory neurotransmission in the mesocorticolimbic reward circuit.


Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial.
Postmenopausal women with elevated circulating androgen concentrations have an increased risk of developing breast cancer, yet interventions to reduce androgen levels have not been identified. We examined the effects of a 12-month moderate intensity exercise intervention on serum androgens. The study was a randomized clinical trial in 173 sedentary, overweight (body mass index > or = 24.0 kg/m(2), body fat > 33%), postmenopausal women, ages 50 to 75 years, not using hormone therapy and living in the Seattle, WA area. The exercise intervention included facility-based and home-based exercise (45 minutes, 5 days per week of moderate intensity sports/recreational exercise). A total of 170 (98.3%) women completed the study, with exercisers averaging 171 minutes per week of exercise. Women in the exercise and control groups experienced similar, nonsignificant declines in most androgens. Among women who lost >2% body fat, testosterone and free testosterone concentrations fell by 10.1% and 12.2% between baseline and 12 months in exercisers compared with a decrease of 1.6% and 8.0% in controls (P = 0.02 and 0.03 compared with exercisers, respectively). Concentrations of testosterone and free testosterone among exercisers who lost between 0.5% and 2% body fat declined by 4.7% and 10.4%. In controls who lost this amount of body fat, concentrations of testosterone and free testosterone declined by only 2.8% and 4.3% (P = 0.03 and 0.01 compared with exercisers, respectively). In summary, given similar levels of body fat loss, women randomized to a 12-month exercise intervention had greater declines in testosterone and free testosterone compared with controls. The association between exercise and breast cancer risk may be partly explained by the effects of exercise on these hormones.


Temperature-dependent shift of balance among the components of short-term plasticity in hippocampal synapses.
Studies of short-term plasticity (STP) in the hippocampus, performed mostly at room temperature, have shown that small central synapses rapidly depress in response to high-frequency stimulation. This decrease in synaptic strength with synapse use places constraints on the use of STP as a dynamic filter for processing of natural high-frequency input. Here we report that, because of a strong but differential temperature dependence of STP components, the properties of STP in excitatory hippocampal synapses change dramatically with temperature. By separating the contributions of various STP processes during spike trains at different temperatures, we found a shift from dominating depression at 23 degrees C to prevailing facilitation and augmentation at 33-38 degrees C. This shift of balance among STP components resulted from a large increase in amplitudes of facilitation and augmentation (Q10 approximately 2.6 and approximately 5.1, respectively) and little change in the amplitude of depression (Q10 approximately 1.1) with temperature. These changes were accompanied by the accelerated decay of all three processes (Q10 = 3.2, 6.6, and 2.1, respectively). The balance of STP components achieved at higher temperatures greatly improved the maintenance of synaptic strength during prolonged synaptic use and had a strong effect on the processing of natural spike trains: a variable mixture of facilitated and depressed responses at 23 degrees C changed into a significantly more reproducible and depression-free filtering pattern at 33-38 degrees C. This filtering pattern was highly conserved among cells, slices, and animals, and under various physiological conditions, arguing for its physiological significance. Therefore, the fine balance among STP components, achieved only at near body temperatures, is required for the robust function of STP as a dynamic filter during natural stimulation.


Analysis of resistance to Cry1Ac in field-collected pink bollworm, Pectinophora gossypiella (Lepidoptera:Gelechiidae), populations.
High survivorship of pink bollworrm, Pectinophora gossypiella in bolls of Bollgard® cotton hybrids and resistance to Cry1Ac protein, expressed in Bollgard cotton were reported in field-populations collected from the state of Gujarat (western India) in 2010. We have found Cry1Ac-resistance in pink bollworm populations sourced from Bollgard and non-Bt cotton fields in the adjoining states of Maharashtra and Madhya Pradesh in Central India. Further, we observed reduced binding of labeled Cry1Ac protein to receptors localized on the brush-border membrane of pink bollworm larval strains with high tolerance to Cry1Ac. These strains were sourced from Bollgard and conventional cotton fields. A pooled Cry1Ac-resistant strain, further selected on Cry1Ac diet also showed significantly reduced binding to Cry1Ac protein. The reduced binding of Cry1Ac to receptors could be an underlying mechanism for the observed resistance in pink bollworm populations feeding on Bollgard hybrids.


Body mass index measurement and obesity prevalence in ten U.S. health plans.
The objective of this study was to examine the frequency of body mass index (BMI) measurement before the implementation of two new Healthcare Effectiveness Data and Information Set (HEDIS) performance measures for obesity that require U.S. health plans to annually report the frequency of BMI and BMI percentile measurement among all adults and children who had at least one outpatient visit during the past two years. Cross-sectional study. A consortium of ten U.S. health plans and care delivery systems from the Health Maintenance Organization Research Network, which together provide care to more than 6.5 million adults and children. Children and adults, age 2 years and older, who were continuously enrolled in one of ten U.S. health plans for at least one full year from 2005 to 2006. We extracted available anthropometric data for 3.7 million adults and 1.2 million children with at least one visit captured from ten electronic medical record databases from 2005 to 2006. We found that the availability of BMI measurements for adults ranged widely across health plans from 28% to 88%, and availability of BMI percentiles for children ranged from 21% to 81%. Among adults and children with BMI measures in these ten health plans, the overall prevalence of overweight and obesity were very similar to those reported in the 2005 to 2006 U.S. national surveys that used measured heights and weights. The newly approved HEDIS performance measures likely represent an important step in addressing the quality of obesity care in the United States. The current study demonstrates that these HEDIS measures are achievable, especially among health plans that have implemented electronic medical records. Future research should assess the relationship between BMI assessment, provider counseling and treatment practices, and long-term changes in obesity rates among different population groups.


Microfluidic co-cultures with hydrogel-based ligand trap to study paracrine signals giving rise to cancer drug resistance.
Targeted cancer therapies are designed to deactivate signaling pathways used by cancer cells for survival. However, cancer cells are often able to adapt by activating alternative survival pathways, thereby acquiring drug resistance. An emerging theory is that autocrine or paracrine growth factor signaling in the cancer microenvironment represent an important mechanism of drug resistance. In the present study we wanted to examine whether paracrine interactions between groups of melanoma cells result in resistance to vemurafenib - an FDA approved drug targeting the BRAF mutation in metastatic melanoma. We used a vemurafenib-resistant melanoma model which secretes fibroblast growth factor (FGF)-2 to test our hypothesis that this is a key paracrine mediator of resistance to vemurafenib. Sensitive cells treated with media conditioned by resistant cells did not protect from the effects of vemurafenib. To query paracrine interactions further we fabricated a microfluidic co-culture device with two parallel compartments, separated by a 100 μm wide hydrogel barrier. The gel barrier prevented resorting/contact of cells while permitting paracrine cross-talk. In this microfluidic system, sensitive cells did become refractive to the effects of vemurafenib when cultured adjacent to resistant cells. Importantly, incorporation of FGF-2 capture probes into the gel barrier separating the two cell types prevented onset of resistance to vemurafenib. Microfluidic tools described here allow for more sensitive analysis of paracrine signals, may help better understand signaling in the cancer microenvironment and may enable development of more effective cancer therapies.


Echinacea-induced cytosolic Ca2+ elevation in HEK293.
With a traditional medical use for treatment of various ailments, herbal preparations of Echinacea are now popularly used to improve immune responses. One likely mode of action is that alkamides from Echinacea bind to cannabinoid type 2 (CB2) receptors and induce a transient increase in intracellular Ca2+. Here, we show that unidentified compounds from Echinacea purpurea induce cytosolic Ca2+ elevation in non-immune-related cells, which lack CB2 receptors and that the Ca2+ elevation is not influenced by alkamides. A non-immune human cell line, HEK293, was chosen to evaluate E. purpurea root extracts and constituents as potential regulators of intracellular Ca2+ levels. Changes in cytosolic Ca2+ levels were monitored and visualized by intracellular calcium imaging. U73122, a phospholipase C inhibitor, and 2-aminoethoxydiphenyl borate (2-APB), an antagonist of inositol-1,4,5-trisphosphate (IP3) receptor, were tested to determine the mechanism of this Ca2+ signaling pathway. E. purpurea root ethanol extracts were fractionated by preparative HPLC, screened for bioactivity on HEK293 cells and by GC-MS for potential constituent(s) responsible for this bioactivity. A rapid transient increase in cytosolic Ca2+ levels occurs when E. purpurea extracts are applied to HEK293 cells. These stimulatory effects are phospholipase C and IP3 receptor dependent. Echinacea-evoked responses could not be blocked by SR 144528, a specific CB2 receptor antagonist, indicating that CB2 is not involved. Ca2+ elevation is sustained after the Echinacea-induced Ca2+ release from intracellular Ca2+ stores; this longer-term effect is abolished by 2-APB, indicating a possible store operated calcium entry involvement. Of 28 HPLC fractions from E. purpurea root extracts, six induce cytosolic Ca2+ increase. Interestingly, GC-MS analysis of these fractions, as well as treatment of HEK293 cells with known individual and combined chemicals, indicates the components thought to be responsible for the major immunomodulatory bioactivity of Echinacea do not explain the observed Ca2+ response. Rather, lipophilic constituents of unknown structures are associated with this bioactivity. Our data indicate that as yet unidentified constituents from Echinacea stimulate an IP3 receptor and phospholipase C mediation of cytosolic Ca2+ levels in non-immune mammalian cells. This pathway is distinct from that induced in immune associated cells via the CB2 receptor.


Does This Patient Have Infectious Mononucleosis?: The Rational Clinical Examination Systematic Review.
Early, accurate diagnosis of infectious mononucleosis can help clinicians target treatment, avoid antibiotics, and provide an accurate prognosis. To systematically review the literature regarding the value of the clinical examination and white blood cell count for the diagnosis of mononucleosis. The databases of PubMed (from 1966-2016) and EMBASE (from 1947-2015) were searched and a total of 670 articles and abstracts were reviewed for eligibility. Eleven studies were included that reported data sufficient to calculate sensitivity, specificity, or both for clinical examination findings and white blood cell count parameters compared with a valid reference standard. Data were abstracted from each article by at least 2 reviewers, with discrepancies reconciled by consensus. Clinical findings evaluated in only 1 study are reported with sensitivity, specificity, likelihood ratio (LR), and 95% confidence interval, which were calculated from the available data. Findings evaluated in only 2 studies were summarized with their range, findings evaluated in 3 studies were summarized with a univariate random-effects summary, and findings evaluated in 4 or more studies were summarized with a bivariate random-effects meta-analysis. Sensitivity, specificity, and LRs for the diagnosis of mononucleosis. Mononucleosis is most commonly present among patients aged 5 to 25 years (especially those aged 16-20 years, among whom approximately 1 in 13 patients presenting with sore throat has mononucleosis). The likelihood of mononucleosis is reduced with the absence of any lymphadenopathy (summary sensitivity, 0.91; positive LR range, 0.23-0.44), whereas the likelihood increases with the presence of posterior cervical adenopathy (summary specificity, 0.87; positive LR, 3.1 [95% CI, 1.6-5.9]), inguinal or axillary adenopathy (specificity range, 0.82-0.91; positive LR range, 3.0-3.1), palatine petechiae (specificity, 0.95; positive LR, 5.3 [95% CI, 2.1-13]), and splenomegaly (specificity range, 0.71-0.99; positive LR range, 1.9-6.6). Symptoms are of limited value for the diagnosis of mononucleosis; sore throat and fatigue are sensitive (range, 0.81-0.83) but nonspecific. The presence of atypical lymphocytosis significantly increases the likelihood of mononucleosis (summary LR, 11.4 [95% CI, 2.7-35] for atypical lymphocytes ≥10%, 26 [95% CI, 9.6-68] for those with 20%, and 50 [95% CI, 38-64] for those with 40%). The combination of a patient having greater than 50% lymphocytes and greater than 10% atypical lymphocytes also is useful (specificity, 0.99; positive LR, 54 [95% CI, 8.4-189]). In adolescent and adult patients presenting with sore throat, the presence of posterior cervical, inguinal or axillary adenopathy, palatine petechiae, splenomegaly, or atypical lymphocytosis is associated with an increased likelihood of mononucleosis.


Near-field deformation from the El Mayor-Cucapah earthquake revealed by differential LIDAR.
Large [moment magnitude (M(w)) ≥ 7] continental earthquakes often generate complex, multifault ruptures linked by enigmatic zones of distributed deformation. Here, we report the collection and results of a high-resolution (≥nine returns per square meter) airborne light detection and ranging (LIDAR) topographic survey of the 2010 M(w) 7.2 El Mayor-Cucapah earthquake that produced a 120-kilometer-long multifault rupture through northernmost Baja California, Mexico. This differential LIDAR survey completely captures an earthquake surface rupture in a sparsely vegetated region with pre-earthquake lower-resolution (5-meter-pixel) LIDAR data. The postevent survey reveals numerous surface ruptures, including previously undocumented blind faults within thick sediments of the Colorado River delta. Differential elevation changes show distributed, kilometer-scale bending strains as large as ~10(3) microstrains in response to slip along discontinuous faults cutting crystalline bedrock of the Sierra Cucapah.


Association between severity of cardiac dysfunction caused by ventricular pre-excitation-led dyssynchrony and cardiac function recovery after ablation in children.
To investigate the association between the severity of cardiac dysfunction caused by ventricular pre-excitation-led dyssynchrony and cardiac function recovery time after catheter ablation and identify predictors of cardiac function recovery after ablation. A total of 49 children underwent successful ablation (median 2.92 years). This study included 23 patients with mild cardiac dysfunction (left ventricular ejection fraction [LVEF]: 45% ≤ LVEF ≤ 55%), 15 with moderate (30% ≤ LVEF < 45%), and 11 with severe (LVEF <30%). The time for mean LVEF reaching 55% was 0.75, 3, and more than 12 months, respectively. The mean LVEF of children with severe cardiac dysfunction aged ≤6 years normalized within 12 months of follow-up (63.00% ± 1.41%). Mean LVEF of those aged more than 6 years did not normalize at 12 months of follow-up (38.67% ± 10.97%). LVEF recovery time was significantly different between these two age groups (median 11 months vs >12 months, χ2 = 4.55; P = .04). Cox regression analysis showed that preablation smaller left ventricular diastolic diameter (LVDd) Z score and higher LVEF were predictors of cardiac dysfunction recovery time (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.82-0.99, P = .04; HR = 1.09, 95% CI = 1.03-1.15, P = .01). Patients with higher LVDd Z scores and lower LVEF tend to have slower improvement in cardiac function after ablation. Patients with LVEF less than 30% and aged more than 6 years need more than 12 months to fully recover, and some might not even completely recover. Early catheter ablation is suggested once ventricular pre-excitation-led cardiac dysfunction is suspected.


Transforming "apathy into movement": the role of prosocial emotions in motivating action for social change.
This article explores the synergies between recent developments in the social identity of helping, and advantaged groups' prosocial emotion. The authors review the literature on the potential of guilt, sympathy, and outrage to transform advantaged groups' apathy into positive action. They place this research into a novel framework by exploring the ways these emotions shape group processes to produce action strategies that emphasize either social cohesion or social change. These prosocial emotions have a critical but underrecognized role in creating contexts of in-group inclusion or exclusion, shaping normative content and meaning, and informing group interests. Furthermore, these distinctions provide a useful way of differentiating commonly discussed emotions. The authors conclude that the most "effective" emotion will depend on the context of the inequality but that outrage seems particularly likely to productively shape group processes and social change outcomes.


Basic body awareness therapy or exercise therapy for the treatment of chronic whiplash associated disorders: a randomized comparative clinical trial.
Chronic whiplash-associated disorders (WAD) incur both costs and suffering. Treatments that can relieve chronic WAD are therefore needed. Exercise therapy (ET) has been shown to provide pain relief. Another often used treatment for chronic pain in Scandinavia is basic body awareness therapy (BAT). We compared the effectiveness of 10 weeks of twice-weekly, 90-min sessions of either ET or BAT in a randomized comparative trial. We recruited 113 patients suffering from chronic WAD grades I-III and several years' duration of symptoms in a primary health care setting. 57 were allocated to ET and 56 to BAT. Primary outcome measures were Neck Disability Index and SF-36 v.2. From baseline to post-treatment, the BAT group increased their physical functioning (median 5, IQR = 15) more than the ET group (median = 0, IQR = 15), p = 0.032, effect size -0.54. Three months after the end of treatment, the BAT group had less bodily pain (m = 17.5, 95% CI 6.9-17.6) than the ET group (m = 4.9, 95% CI -0.1 to 9.8), p = 0.044, effect size -0.4. The BAT group had also increased their social functioning (m = 13.3, 95% CI 6.6-19.9) more than the ET group (m = 3.5, 95% CI -3 to 9.9), p = 0.037, effect size -0.41. No statistically significant differences between groups were found for the change of other outcomes. No serious adverse effects were found in either groups. The present trial indicates that BAT led to greater improvements than ET for the patients with chronic WAD. IMPLICATIONS FOR REHABILATION: Chronic whiplash-associated disorders are disabling and incur great costs to society often through inability to work. Exercise therapy (ET) may alleviate symptoms of chronic WAD. Basic body awareness therapy (BAT) is often a component of multimodal pain rehabilitation programs. In this randomized comparative trial, BAT increased physical functioning and led to greater pain reduction and social functioning 3 months after the end of treatment.


The effectiveness of treatments of diabetic autonomic neuropathy is not the same in autonomic nerves supplying different organs.
The aim of the study was to investigate antioxidant (alpha-lipoic acid [LA]) and gamma-linolenic acid treatments in the prevention of changes in autonomic nerves induced in streptozotocin-diabetic rats. Autonomic nerves supplying the heart, penis, and gut were examined using immunohistochemical and biochemical techniques. LA and gamma-linolenic acid (present in evening primrose oil [EPO]) were administered as dietary supplements ( approximately 80 and 200 mg. kg(-1). day(-1), respectively). LA treatment prevented the diabetes-induced decrease of norepinephrine (NA) in the heart and of type I nitric oxide synthase (NOS-I) expression in erectile tissue of the penis but failed to prevent diabetes-induced changes in NA-, vasoactive intestinal polypeptide-, or calcitonin gene-related peptide-containing nerves supplying the ileum. LA partially prevented and EPO totally prevented the increase in NOS-I activity induced by diabetes in the ileum. EPO treatment failed to prevent any other diabetes-induced changes in the heart, penis, or ileum. These results demonstrate that, whereas LA treatment is more effective than EPO in preventing diabetes-induced changes in autonomic nerves, the effectiveness of LA treatment varies with the target organ studied. Diabetes-induced changes in nerves supplying the ileum are more resistant to treatment than those of the heart and penis.


Fine-Mapping the Wheat Snn1 Locus Conferring Sensitivity to the Parastagonospora nodorum Necrotrophic Effector SnTox1 Using an Eight Founder Multiparent Advanced Generation Inter-Cross Population.
The necrotrophic fungus Parastagonospora nodorum is an important pathogen of one of the world's most economically important cereal crops, wheat (Triticum aestivum L.). P. nodorum produces necrotrophic protein effectors that mediate host cell death, providing nutrients for continuation of the infection process. The recent discovery of pathogen effectors has revolutionized disease resistance breeding for necrotrophic diseases in crop species, allowing often complex genetic resistance mechanisms to be broken down into constituent parts. To date, three effectors have been identified in P. nodorum. Here we use the effector, SnTox1, to screen 642 progeny from an eight-parent multiparent advanced generation inter-cross (i.e., MAGIC) population, genotyped with a 90,000-feature single-nucleotide polymorphism array. The MAGIC founders showed a range of sensitivity to SnTox1, with transgressive segregation evident in the progeny. SnTox1 sensitivity showed high heritability, with quantitative trait locus analyses fine-mapping the Snn1 locus to the short arm of chromosome 1B. In addition, a previously undescribed SnTox1 sensitivity locus was identified on the long arm of chromosome 5A, termed here QSnn.niab-5A.1. The peak single-nucleotide polymorphism for the Snn1 locus was converted to the KASP genotyping platform, providing breeders and researchers a simple and cheap diagnostic marker for allelic state at Snn1.


A multicenter, randomized, prospective study of 14-day ranitidine bismuth citrate- vs. lansoprazole-based triple therapy for the eradication of Helicobacter pylori in dyspeptic patients.
Proton-pump inhibitor and ranitidine bismuth citrate-based triple regimens are the two recommended first line treatments for the eradication of Helicobacter pylori. We aimed to compare the effectiveness and tolerability of these two treatments in a prospective, multicentric, randomized study. Patients with dyspeptic complaints were recruited from 15 study centers. Presence of Helicobacter pylori was investigated by both histology and rapid urease test. The patients were randomized to either ranitidine bismuth citrate 400 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=149) or lansoprazole 30 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=130) treatment arm for 14 days. Adverse events have been recorded during the treatment phase. A 13 C urea breath test was performed 6 weeks after termination of treatment to assess the efficacy of the therapy. Eradication rate was calculated by intention-to-treat and per-protocol analysis. Two hundred seventy-nine patients (123 male, 156 female) were eligible for randomization. In per-protocol analysis (n=247), Helicobacter pylori was eradicated with ranitidine bismuth citrate- and lansoprazole-based regimens in 74,6% and 69,2% of cases, respectively (p>0,05). Intention-to-treat analysis (n=279) revealed that eradication rates were 65,1% and 63,6% in ranitidine bismuth citrate and in lansoprazole-based regimens, respectively (p>0,05). Both regimes were well-tolerated, and no serious adverse event was observed during the study. Ranitidine bismuth citrate-based regimen is at least as effective and tolerable as the classical proton-pump inhibitor-based regimen, but none of the therapies could achieve the recommendable eradication rate.


Tetanus: 20 years of clinical experience.
Tetanus remains a life-threatening disorder and its fulminating course always presents a challenge to the clinician. We retrospectively evaluated 56 patients with tetanus admitted to VGH-Taipei between 1971 and 1990. All of these patients with tetanus on admission showed typical features, with the most common initial complaints being lockjaw and dysphagia (82.6%). They were diagnosed on clinical identification rather than isolation of the causative agent. The laboratory tests were usually nonspecific and of limited value for diagnosis. Overall, 38 patients were seized with tetanus after an identified wound infection. The most common routes were puncture wound (28.3%) and abrasion wound (19.6%). The majority of patients became symptomatic within 10 days (56.5%) and the shorter interval reflected a more overwhelming course (p less than 0.05). Intravenous drug abusers and larger wounds had a poorer prognosis. The average mortality was 39.1% (18 out of 46 patients; male/female 12/6), with lack of statistical difference between sex and mortality (p greater than 0.5). The course of tetanus in the newborn and elderly was also more deadly (mortality rates of 83.3% and 55.6% respectively). Aspiration pneumonia and subsequent respiratory failure accounted for the most common cause (11 cases, 61.1%) of death. The mortality was still high (28.6%) from 1980-90 even with better supportive care and modern therapeutic equipment.


Effects of polycythemia on systemic endothelial function in chronic hypoxic lung disease.
Chronic obstructive pulmonary disease (COPD) is a major risk factor for cardiovascular disease. Polycythemia, a common complication of hypoxic COPD, may affect systemic vascular function by altering blood viscosity, vessel wall shear stress (WSS), and endothelium-derived nitric oxide (NO) release. Here, we evaluated the effects of hypoxia-related polycythemia on systemic endothelial function in patients with COPD. We investigated blood viscosity, WSS, and endothelial function in 15 polycythemic and 13 normocythemic patients with COPD of equal severity, by recording brachial artery diameter variations in response to hyperemia and by using venous occlusion plethysmography (VOP) to measure forearm blood flow (FBF) responses to a brachial artery infusion of acetylcholine (ACh), bradykinin (BK), sodium nitroprusside (SNP), substance P (SP), isoptin, and N-monomethyl-L-arginine (L-NMMA). At baseline, polycythemic patients had higher blood viscosity and larger brachial artery diameter than normocythemic patients but similar calculated WSS. Flow-mediated brachial artery vasodilation was increased in the polycythemic patients, in proportion to the hemoglobin levels. ACh-induced vasodilation was markedly impaired in the polycythemic patients and negatively correlated with hemoglobin levels. FBF responses to endothelium- (BK, SP) and non-endothelium-dependent (SNP, isoptin) vasodilators were not significantly different between the two groups. L-NMMA infusion induced a similar vasoconstrictor response in both groups, in accordance with their similar baseline WSS. In conclusion, systemic arteries in polycythemic patients adjust appropriately to chronic or acute WSS elevations by appropriate basal and stimulated NO release. Overall, our results suggest that moderate polycythemia has no adverse effect on vascular function in COPD.


Hydrops associated with chondrodysplasia of the fetus in a miniature Scottish Highland cow.
CASE DESCRIPTION A 2-year-old primiparous miniature Scottish Highland cow with an unknown breeding date was evaluated for suspected hydrops. CLINICAL FINDINGS Transabdominal and transrectal ultrasonographic examination identified a large amount of hypoechoic fluid within an enlarged uterus; the fetus could not be identified. Presence of a severely distended uterus and concerns regarding associated health risks to the cow led to the decision to induce labor. Although fluids were expelled, parturition did not progress further over the following 48 hours. Vaginal examination revealed a partially dilated cervix and an abnormally shaped fetus that was too large to pass vaginally. TREATMENT AND OUTCOME Supportive care was provided to the cow, and a stillborn bull calf was delivered by cesarean section. Grossly evident chondrodystrophic dwarfism with hydrocephalus, compatible with so-called bulldog calf malformations, was confirmed by diagnostic imaging and histopathologic evaluation. The cow recovered from surgery uneventfully and was discharged from the hospital the following day. Genetic analysis of DNA from hair roots collected from the sire and dam confirmed both were carriers of an aggrecan-1 gene mutation (bulldog dwarfism1) previously associated with dwarfism and bulldog calf malformations in Dexter cattle. CLINICAL RELEVANCE To our knowledge, this is the first reported case of bulldog calf malformations associated with an aggrecan-1 gene mutation in miniature Scottish Highland cattle, confirming that at least 1 genetic mutation associated with this condition is found in cattle breeds other than Dexter. The findings highlighted the clinical importance of testing for known genetic diseases in breeding cattle, particularly among miniature breeds.


Behavioral and Structural Effects of Single and Repeat Closed-Head Injury.
The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure. We introduced a repetitive closed-head injury rodent model (n = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T2-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent t tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively. There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury (P < .05). Behavioral deficits (P < .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period. There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.


Polycystic Ovary Syndrome Presents Higher Sympathetic Cardiac Autonomic Modulation that is not altered by Strength Training.
Polycystic ovary syndrome (PCOS) may present important comorbidities, such as cardiovascular and metabolic diseases, which are often preceded by changes in cardiac autonomic modulation. Different types of physical exercises are frequently indicated for the prevention and treatment of PCOS. However, little is known about the effects of strength training on the metabolic, hormonal, and cardiac autonomic parameters. Therefore, our aim was to investigate the effects of strength training on the autonomic modulation of heart rate variability (HRV) and its relation to endocrine-metabolic parameters in women with PCOS. Fifty-three women were divided into two groups: CONTROL (n=26) and PCOS (n=27). The strength training lasted 4 months, which was divided into mesocycles of 4 weeks each. The training load started with 70% of one repetition maximum (1RM). Blood samples were collected before and after intervention for analysis of fasting insulin and glucose, HOMA-IR, testosterone, androstenedione and testosterone/androstenedione (T/A) ratio. Spectral analysis of HRV was performed to assess cardiac autonomic modulation indexes. The PCOS group presented higher insulin and testosterone levels, T/A ratio, along with increased sympathetic cardiac autonomic modulation before intervention. The training protocol used did not cause any change of endocrine-metabolic parameters in the CONTROL group. Interestingly, in the PCOS group, reduced testosterone levels and T/A ratio. Additionally, strength training did not have an effect on the spectral parameter values of HRV obtained in both groups. Strength training was not able to alter HRV autonomic modulation in women with PCOS, however may reduce testosterone levels and T/A ratio.


Comparing the Effectiveness of Dietary Vitamin C and Exercise Interventions on Fertility Parameters in Normal Obese Men.
Comparing the effectiveness of dietary vitamin C and weight loss exercises interventions for weight loss on semen characteristics in normal obese man. A total number of 200 men were randomly allocated into two groups based on body mass index, exercise and vitamin C groups. Also, 50 men with normal spermogram were placed in a control group. In exercise group, a 6 months intensive exercise program was designed under a coach's supervision to reduce the body weight. In vitamin C group, 1,000 mg of vitamin C were given every other day as supplement. Weight loss increased the volume of semen in participants with 25-30 (P = .02) and more than 30 body mass index (P = .001). The increased concentration of sperm per mL of semen in body mass index (BMI) 25-30 group (P = .01) and more than 30 (P = .003) BMI was significant. Improving sperm motility after two hours in participants with more than 30 (P = .01) BMI was significant. In vitamin C group, the improvement of sperm concentration in participants who had less than 25 (P = .01), between 25 and 30 (P = .01), more than 30 (P = .02) BMI was significant. Sperm motility improved in all three groups (P = .001, P = .02 and P = .003, respectively). Weight loss can significantly increase semen volume, its concentration, its mobility and percentage of normal morphology. Consuming vitamin C significantly improves sperm concentration and mobility, but the semen volume and the percentage of normal morphology will not change significantly.


Emerging or re-emerging bacterial zoonotic diseases: bartonellosis, leptospirosis, Lyme borreliosis, plague.
There are a whole series of emerging and re-emerging zoonotic diseases present in the Northern Hemisphere and the author describes four of them, namely, bartonellosis, leptospirosis, Lyme borreliosis and plague. Reasons for the emergence or re-emergence of such diseases are not clear, but factors such as human demographics, economic development and land use, international travel and commerce, and microbial adaptation, are thought to be involved. Control of emerging and re-emerging diseases has become a major challenge for the international community and it is important to disseminate information about diagnosis and control capabilities, particularly to people working in public health.


Negative pressure dressing combined with a traditional approach for the treatment of skull burn.
Deep burns of the calvarium due to high-voltage electrical current present serious therapeutic challenges in the healing. In this study, as an alternative approach to the treatment of burned skull, negative pressure dressing is used to facilitate separation of the necrotic bones from healthy margins of the cranium, and to encourage rapid granulation tissue formation after trephination of the bone. A 36-year-old male patient, who had been seriously injured on his head with high-voltage electrical current, is presented. On the fifth day after injury, necrosis of the scalp became clearly significant, thereby necessitating extensive debridement. Under general anesthesia, necrotic scalp was removed, leaving the calvarial bone exposed, and while devitalized calvaria was left in place, exposed bone was drilled. A vacuum-assisted dressing was then applied to the wound and set to 125 mmHg continuous pressure. Some granulation tissue developed in the holes and margins of the wound, but it was not sufficient to allow successful closure of the wound with skin grafting. Therefore, the patient underwent another operation in which devitalized outer table of the skull was easily removed from viable bone by using a little force. Elevation of the necrotic outer bony layer revealed profuse granulation tissue formation over the inner layer. When dealing with this experience, vacuum-assisted dressing seems to be a useful tool in acceleration of the separation of necrotic bones and stimulation of granulation tissue formation in burned calvarium.


America's Cup Sailing: Effect of Standing Arm-Cranking ("Grinding") Direction on Muscle Activity, Kinematics, and Torque Application.
Grinding is a key physical element in America's Cup sailing. This study aimed to describe kinematics and muscle activation patterns in relation to torque applied in forward and backward grinding. Ten male America's Cup sailors (33.6 ± 5.7 years, 97.9 ± 13.4 kg, 186.6 ± 7.4 cm) completed forward and backward grinding on a customised grinding ergometer. In forward grinding peak torque (77 Nm) occurred at 95° (0° = crank vertically up) on the downward section of the rotation at the end of shoulder flexion and elbow extension. Backward grinding torque peaked at 35° (69 Nm) following the pull action (shoulder extension, elbow flexion) across the top of the rotation. During forward grinding, relatively high levels of torque (>50 Nm) were maintained through the majority (72%) of the cycle, compared to 47% for backward grinding, with sections of low torque corresponding with low numbers of active muscles. Variation in torque was negatively associated with forward grinding performance (r = -0.60; 90% CI -0.88 to -0.02), but positively associated with backward performance (r = 0.48; CI = -0.15 to 0.83). Magnitude and distribution of torque generation differed according to grinding direction and presents an argument for divergent training methods to improve forward and backward grinding performance.