Bisphosphonates as inhibitors of Trypanosoma cruzi hexokinase: kinetic and metabolic studies.
Trypanosoma cruzi, the etiologic agent of Chagas disease, has an unusual ATP-dependent hexokinase (TcHK) that is not affected by D-glucose 6-phosphate, but is non-competitively inhibited by inorganic pyrophosphate (PP(i)), suggesting a heterotropic modulator effect. In a previous study we identified a novel family of bisphosphonates, metabolically stable analogs of PP(i), which are potent and selective inhibitors of TcHK as well as the proliferation of the clinically relevant intracellular amastigote form of the parasite in vitro (Hudock, M. P., Sanz-Rodriguez, C. E., Song, Y., Chan, J. M., Zhang, Y., Odeh, S., Kosztowski, T., Leon-Rossell, A., Concepcion, J. L., Yardley, V., Croft, S. L., Urbina, J. A., and Oldfield, E. (2006) J. Med. Chem. 49, 215-223). In this work, we report a detailed kinetic analysis of the effects of three of these bisphosphonates on homogeneous TcHK, as well as on the enzyme in purified intact glycosomes, peroxisome-like organelles that contain most of the glycolytic pathway enzymes in this organism. We also investigated the effects of the same compounds on glucose consumption by intact and digitonin-permeabilized T. cruzi epimastigotes, and on the growth of such cells in liver-infusion tryptose medium. The bisphosphonates investigated were several orders of magnitude more active than PP(i) as non-competitive or mixed inhibitors of TcHK and blocked the use of glucose by the epimastigotes, inducing a metabolic shift toward the use of amino acids as carbon and energy sources. Furthermore, there was a significant correlation between the IC(50) values for TcHK inhibition and those for epimastigote growth inhibition for the 12 most potent compounds of this series. Finally, these bisphosphonates did not affect the sterol composition of the treated cells, indicating that they do not act as inhibitors of farnesyl diphosphate synthase. Taken together, our results suggest that these novel bisphosphonates act primarily as specific inhibitors of TcHK and may represent a novel class of selective anti-T. cruzi agents.


Rigidity transitions in zero-temperature polygons.
We study geometrical clues of a rigidity transition due to the emergence of a system-spanning state of self-stress in underconstrained systems of individual polygons and spring networks constructed from such polygons. When a polygon with harmonic bond edges and an area spring constraint is subject to an expansive strain, we observe that convexity of the polygon is a necessary condition for such a self-stress. We prove that the cyclic configuration of the polygon is a sufficient condition for the self-stress. This correspondence of geometry and rigidity is akin to the straightening of a one dimensional chain of springs to rigidify it. We predict the onset of the rigidity transition and estimate the transition strain using purely geometrical methods. These findings help determine the rigidity of an area-preserving polygon just by knowing its geometry. Since two-dimensional spring networks can be considered as a network of polygons, we look for similar geometric features in underconstrained spring networks under isotropic expansive strain. We observe that all polygons attain convexity at the rigidity transition such that the fraction of convex, but not cyclic, polygons predicts the onset of the rigidity transition. Acyclic polygons in the network correlate with larger tensions, forming effective force chains.


Transiently higher release probability during critical period at thalamocortical synapses in the mouse barrel cortex: relevance to differential short-term plasticity of AMPA and NMDA EPSCs and possible involvement of silent synapses.
Thalamocortical connections undergo remarkable plasticity during the critical period and mounting evidence serves to demonstrate that the activation of silent synapses at postsynaptic sites is an important underlying mechanism in this process. However, relatively little is known about the nature of the presynaptic properties. In the present study, we examined the release probability (Pr) of thalamocortical synaptic terminals on a layer IV neuron in the developing mouse barrel cortex. Using the conventional paired-pulse ratio (PPR) method, both AMPA and NMDA receptor-mediated PPR were observed during development. We found that the NMDA PPR increased gradually (thus, a reduction in Pr) from postnatal day (P)4 to P22 but, unexpectedly, the AMPA PPR exhibited a simultaneous decrease. We then used an additional method for assessing release probability, the observation of a progressive block of NMDA receptor-mediated EPSCs using MK-801. With this method, we were able to identify two classes of terminals with high or low probabilities of release. Interestingly, the higher release showed a reduction in probability during the critical period, consistent with the NMDA PPR results. We confirmed that the discrepancy between the NMDA and the AMPA PPR results was due to the existence of silent, or NMDA-only, synapses, as suggested in previous literature. By analysing the correlation between the NMDA or AMPA PPR and the PPR discrepancy, we discuss the hypothesis that the terminals with transiently higher probability of release were found preferentially on silent synapses. Our results suggest that these presynaptic sites may also have an active role in plasticity by working concomitantly with postsynaptic sites during the critical period.


Antiepileptics in brain metastases: safety, efficacy and impact on life expectancy.
The aim of the study was to evaluate efficacy, safety and impact on life expectancy of levetiracetam (LEV), oxcarbazepine (OXC) and topiramate (TPM) monotherapy in patients with seizures related to brain metastases. We conducted a prospective observational study on 70 patients with brain metastases. Thirteen patients were excluded because they were in prophylactic therapy with antiepileptics, nine patients did not return to our Center. A total of 48 patients with epilepsy related to brain metastases were enrolled. Patients were treated with LEV, OXC and TPM in monotherapy and followed until their death. Eighteen patients dropped out. Therefore, we followed 30 patients. Mean duration of follow-up was 6.1 months. Upon visiting the patients prior to their death (i.e. last visit preceding the death of the patients), we observed a significant reduction (P < 0.001) in the mean monthly seizure frequency; with 19 patients (63.3%) obtaining complete seizure control in the whole population. A significant improvement of seizure frequency was also observed considering each antiepileptic treatment group separately. Median survival time was similar among the three groups of patients and was similar to Class I of prognostic factors of Radiation Therapy Oncology Group. Logistic regression showed that systemic treatments did not influence the antiepileptics' efficacy on seizure control (P = 0.614). In conclusion, regarding the use of newer antiepileptics in patients with seizures related to brain metastases, our data indicate that LEV, OXC and TPM significantly reduce seizure frequency (independently of systemic treatment), produce few side effects and appear not to affect life expectancy.


Chromenoquinoline-based thiol probes: a study on the quencher position for controlling fluorescent Off-On characteristics.
The design, synthesis and thiol sensing ability of chromenoquinoline-based fluorescent probes 4, 5 and 6 and are reported here. The relative position of the maleimide moiety was varied along the chromenoquinoline fluorophore to decrease the background fluorescence. Lower background fluorescence in probes 4 and 6 was rationalized by the smaller k(r)/k(nr) values compared to that of probe 5. An intramolecular charge transfer (ICT) mechanism was proposed for quenching and the extent was dependent on the position of the maleimide quencher. Fluorescent Off-On characteristics were evaluated by theoretical calculations. All probes were selective only towards thiol containing amino acids. Thiol sensing by probes 4 and 6 were much better compared to 5. Probe 4 displayed a better fluorescence response for less hindered thiol (185-, 223- and 156-fold for Hcy, Cys and GSH, respectively), while for probe 6, a higher enhancement in fluorescence was observed with more hindered thiols (180-, 205- and 245-fold for Hcy, Cys and GSH, respectively). The better response to bulkier thiol, GSH by probe 6 was attributed to the steric crowding at the C-4 position and bulkiness of the GSH group which force the succinimide unit to be in a nearly orthogonal conformation. This spatial arrangement was important in reducing the fluorescence quenching ability of the succinimide moiety. The application of probes 4, 5 and 6 was demonstrated by naked eye detection thiols using a 96-well plate system as well as by live-cell imaging.


Inhibition of Shp2 suppresses mutant EGFR-induced lung tumors in transgenic mouse model of lung adenocarcinoma.
Epidermal growth factor receptor (EGFR) mutants drive lung tumorigenesis and are targeted for therapy. However, resistance to EGFR inhibitors has been observed, in which the mutant EGFR remains active. Thus, it is important to uncover mediators of EGFR mutant-driven lung tumors to develop new treatment strategies. The protein tyrosine phosphatase (PTP) Shp2 mediates EGF signaling. Nevertheless, it is unclear if Shp2 is activated by oncogenic EGFR mutants in lung carcinoma or if inhibiting the Shp2 PTP activity can suppress EGFR mutant-induced lung adenocarcinoma. Here, we generated transgenic mice containing a doxycycline (Dox)-inducible PTP-defective Shp2 mutant (tetO-Shp2CSDA). Using the rat Clara cell secretory protein (CCSP)-rtTA-directed transgene expression in the type II lung pneumocytes of transgenic mice, we found that the Gab1-Shp2 pathway was activated by EGFRL858R in the lungs of transgenic mice. Consistently, the Gab1-Shp2 pathway was activated in human lung adenocarcinoma cells containing mutant EGFR. Importantly, Shp2CSDA inhibited EGFRL858R-induced lung adenocarcinoma in transgenic animals. Analysis of lung tissues showed that Shp2CSDA suppressed Gab1 tyrosine phosphorylation and Gab1-Shp2 association, suggesting that Shp2 modulates a positive feedback loop to regulate its own activity. These results show that inhibition of the Shp2 PTP activity impairs mutant EGFR signaling and suppresses EGFRL858R-driven lung adenocarcinoma.


[Plastic correction of aortic stenosis in two- and three heart valve diseases].
Plastic correction of aortic stenosis with simultaneous intervention on the mitral and, in some cases, on the tricuspid valve was performed on 50 patients whose ages ranged from 25 to 53 years (average age 43.2 years); 15 were in NYHA functional class III and 35 in class IV. There were 38 females and 12 males. Correction of the aortic stenosis was achieved by open valvulotomy and additional plane resection of the cusps, suture plastic was conducted whenever necessary. In 6 cases calcinates were removed form the cusps simultaneously. Mitral valve prosthetics was undertaken in 42 patients, and open mitral commissurotomy in 8 patients. In 17 patients aortic and mitral stenoses were attended by defect of the tricuspid valve which called for plastic correction. Among the 50 patients who underwent operation 8 (16.0%) died. there were no fatal outcomes among patients related to the NYHA functional class III. In 41 cases the result of aortic stenosis correction was satisfactory, which was confirmed by clinical and echocardiographic data. After the operation, opening of the aortic valve cusps during echocardiography in the M-regimen increased, on average, from 12 +/- 2.0 to 18 +/- 2.6 mm. According to doppler-echocardiogram, the gradient on the aortic valve reduced, on average, from 45 +/- 5.0 to 26.5 +/- 4.0 mm. Only in one female patient aortic incompetence started progressing after the operation and called for prosthetics 6 months later.


[Semi-quantitative risk assessment of human infection with H7N9 avian influenza epidemic in Zhejiang province].
To assess the risk of local outbreaks of H7N9 avian influenza infection in Zhejiang province and to explore the semi-quantitative assessment method for public health risks in emergency. Risk index system of human infection with H7N9 avian influenza caused by local transmission were reviewed. The weights of indexes were calculated by analytic hierarchy process, which was combined with the TOPSIS method to calculate the risk comprehensive index. Four primary indexes and 23 secondary indexes were identified for risk assessment in local outbreaks of H7N9 avian influenza infection. The weights ranked on the top five were:morbidity (0.0972), closure measures (0.0718), sterilization measures (0.0673), fatality rate (0.0651), and epidemic spread (0.0616). The comprehensive index of the risk of local outbreaks of H7N9 avian influenza ranged from high to low were Hangzhou (0.5910), Shaoxing (0.5711), Jiaxing (0.5199), Taizhou (0.5198), Huzhou (0.4662), Ningbo (0.3828), Wenzhou (0.3719), Jinhua (0.3392), Lishui (0.2727), Quzhou (0.2001) and Zhoushan (0.0508). A semi-quantitative method has been established in this study, which provides scientific basis for prevention and control of H7N9 avian influenza epidemic in Zhejiang province.


Influence of ecdysterone on the growth of cells and synthesis of macromolecules in established cell lines of Drosophila melanogaster.
Ecdysterone (beta-ecdysone) and 2-deoxy-alpha-ecdysone specifically inhibit the growth of established embryonic cells of D. melanogaster. A preparation of alpha-ecdysone is 100 times less active than ecdysterone. The action of ecdysterone is eliminated when it is removed within 24 h, but after 48 h the inhibiting influence of the hormone becomes irreversible. The diploid line, triploid and tetraploid sublines are sensitive to ecdysterone. The diploid subline with a spontaneously arisen translocation of an X-chromosome to an autosome of the third pair is substantially more resistant to ecdysterone. At 24 h after the addition of ecdysterone, there is a 2-5-fold suppression of the synthesis of total RNA; DNA synthesis is lowered to the same degree only after 48 h. The gross synthesis of proteins, measured according to the incorporation of C 14-lysine, was not suppressed even after 48 h.


The cpcE and cpcF genes of Synechococcus sp. PCC 7002. Construction and phenotypic characterization of interposon mutants.
The 3' region of the cpc operon of Synechococcus sp. PCC 7002 has been sequenced, transcriptionally characterized, and analyzed by interposon mutagenesis. The cpc operon contains six genes, 5' cpcB-cpcA-cpcC-cpcD-cpcE-cpcF 3', and gives rise to at least eight (more likely ten) discrete mRNA transcripts. The steady-state levels of transcripts for the cpcE and cpcF genes are very low and are estimated to represent only about 1-2% of the total transcripts arising from the cpc locus. The cpcE gene predicts a protein of 268 amino acid residues, whereas the cpcF gene predicts a protein of 205 amino acid residues. The deduced amino acid sequences of these proteins are about 50% identical and 70% similar to the predicted products of homologous genes which have been identified in other cyanobacterial cpc operons. Interposon insertion mutations were constructed in the cpcE and cpcF genes, and an interposon deletion mutation affecting both genes was constructed. The phenotypes of all mutant strains were similar. These strains were yellow-green in color, had doubling times approximately twice that of the wild-type strain, and failed to accumulate normal levels of phycocyanin. Further analyses indicated that these strains contained substantial amounts of apparently normal phycocyanin beta subunits; however the majority of the phycocyanin alpha subunit (about 90%) did not carry a phycocyanobilin chromophore. During serial subculturing of the mutant strains, suppressor mutations, which allowed cells to regain the ability to synthesize phycocyanin, arose at significant frequency. Based upon the results reported here, as well as those presented in the accompanying paper (Swanson, R. V., Zhou, J., Leary, J. A., Williams, T., de Lorimier, R., Bryant, D. A., and Glazer, A. N. (1992) J. Biol. Chem. 267, 16146-16154), we propose that the CpcE and CpcF polypeptides are the two subunits of a phycocyanobilin lyase specifically required for chromophorylation of the phycocyanin alpha subunit.


A National Audit of Smoking Cessation Services in Irish Maternity Units.
There is international consensus that smoking cessation in the first half of pregnancy improves foetal outcomes. We surveyed all 19 maternity units nationally about their antenatal smoking cessation practices. All units recorded details on maternal smoking at the first antenatal visit. Only one unit validated the self-reported smoking status of pregnant women using a carbon monoxide breath test. Twelve units (63%) recorded timing of smoking cessation. In all units women who reported smoking were given verbal cessation advice. This was supported by written advice in 12 units (63%), but only six units (32%) had all midwives trained to provide this advice. Only five units (26%) reported routinely revisiting smoking status later in pregnancy. Although smoking is an important modifiable risk factor for adverse pregnancy outcomes, smoking cessation services are inadequate in the Irish maternity services and there are variations in practices between hospitals.


Ultraviolet-irradiated vesicular stomatitis virus and defective-interfering particles are similar non-specific inhibitors of virus infection.
The way in which ultraviolet-irradiated vesicular stomatitis virus (VSV) inhibits the early events in VSV infection has been further characterized. Comparison of several different u.v.-irradiated thermolabile, temperature-sensitive mutants before and after heat inactivation established a requirement for inhibitory activity of functional G, N and L proteins, but not M protein. Defective-interfering (DI) particles, whether irradiated or not, inhibited VSV primary transcription as efficiently as UV-VSV, suggesting that virus proteins rather than transcription products are responsible for inhibition. Addition of inhibitory UV-VSV at different times after infection established that inhibition results from an action at an intracellular site, rather than at the cell surface or in the process of internalization. A similar inhibition by UV-VSV of infection by Sendai virus, Semliki Forest virus, Sindbis virus and influenza virus suggests that UV-VSV is acting by inducing a general change in the intracellular environment.


Examining the Prevalence of Adverse Childhood Experiences and Associated Cardiovascular Disease Risk Factors Among Low-Income Uninsured Adults.
Adverse childhood experiences (ACEs) are linked to poor adult health outcomes, including cardiovascular disease. However, little is known about its prevalence, specifically in low-income populations. The objective of this study was to estimate the extent of ACEs in a low-income, nonclinical, uninsured adult population and assess the relationship between ACEs and cardiovascular disease risk factors. This study leverages the OHIE's (Oregon Health Insurance Experiment) study population, uninsured adults who were randomly selected to apply for Medicaid, and data collected through in-person health screenings. We objectively measured obesity, cholesterol, blood pressure, and blood sugar. Smoking, physical activity, and history of chronic disease were self-reported. Independent variables were the 10-item ACEs questions covering neglect, abuse, and household dysfunction. The sample consisted of 12 229 low-income, nonelderly uninsured adults who participated in the OHIE health screenings from 2009 to 2010. A total of 5929 (48%) returned a follow-up survey reporting ACEs in 2012. ACEs were more prevalent in low-income adults compared with previous estimates in a general clinical population, with notably high rates of emotional abuse, emotional neglect, and household dysfunction. ACEs were statistically associated with higher rates of obesity, smoking, and physical inactivity, but not high cholesterol or diabetes mellitus. We detected a strong relationship between ACEs and a self-reported history of a hypertension diagnosis but no statistically significant differences in being hypertensive. This study design allowed us to assess the prevalence of ACEs among uninsured low-income adults and the association between ACEs and clinical indicators of cardiovascular disease risk that are difficult to ordinarily observe. Low-income adults have high rates of ACEs than previous prevalence estimates and ACEs were associated with higher rates of multiple cardiovascular disease risk factors. As states continue to expand Medicaid to the previously uninsured, providers may want to consider incorporating trauma-based approaches to care delivery.


Arylsulfone-based HIV-1 non-nucleoside reverse transcriptase inhibitors.
HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent one of the most significant classes of drugs for the treatment of AIDS/HIV infection. Over the past two decades several potent arylsulfone-based HIV-1 NNRTIs and related analogs have been developed. This review provides an essential overview of the structure-activity relationships of the arylsulfone-based HIV-1 NNRTIs. Furthermore, structural information useful for the design and development of new sulfur containing NNRTIs with enhanced antiretroviral activity against HIV-1 wild type and clinically relevant drug resistant HIV-1 mutant strains will be discussed.


Enzyme-based logic: OR gate with double-sigmoid filter response.
The first realization of a biomolecular OR gate function with double-sigmoid response (sigmoid in both inputs) is reported. Two chemical inputs activate the enzymatic gate processes, resulting in the output signal: chromogen oxidation, which occurs when either one of the inputs or both are present (corresponding to the OR binary function), and can be optically detected. High-quality gate functioning in handling of sources of noise is enabled by "filtering" involving pH control with an added buffer. The resulting gate response is sigmoid in both inputs when proper system parameters are chosen, and the gate properties are theoretically analyzed within a model devised to evaluate its noise-handling properties.


[Effect of intraoperative infusion-transfusion therapy on mortality of patients with massive blood loss].
The aim of the research is to determine the influence of infusion-transfusion therapy of the volume and structure on intraoperation and hospital lethality in patients with injuries and diseases, complicated in blood loss, exceeding circulating blood volume (CBV). It was conducted a retrospective analysis of the anaesthesia flow, infusion-transfusion therapy and treatment results in 112 patients with injuries and diseases complicated in intra-abdominal bleeding, volume of more than 4 liters. It was found that the risk of death increases in low-volume infusion therapy (less than 1.5 volume of blood), use of the maximum permitted doses of colloids, high speed of infusion therapy. Adverse factors of intraoperative transfusion: the lack of intraoperative compensation erythrocytes(less than 50% of the lost), ones transfuse more than 2 standard doses of the donor's erythrocytes and large volumes of fresh frozen plasma (FFP).


Twist sense control in terminally functionalized ortho-phenylenes.
Many abiotic foldamers are based on achiral repeat units but adopt chiral geometries, especially helices. In these systems, there is no inherent preference for one handedness of the fold; however, it is well-established that the point chirality of substituents can be communicated to the helix. This capability represents a basic level of control over folding that is necessary for applications in molecular recognition and in the assembly of higher-order structures. The ortho-phenylenes are a structurally simple class of aromatic foldamers that fold into helices driven by arene-arene stacking interactions. Although their folding is now reasonably well-understood, access to o-phenylenes enriched in one twist sense has been limited to resolution, yielding conformationally dynamic samples that racemize over the course of minutes to hours. Here, we report a detailed structure-property study of chiral induction from o-phenylene termini using a combination of NMR spectroscopy, CD spectroscopy, and computational chemistry. We uncover mechanistic details of chiral induction and show that the same substituents can give effective twist sense control in opposite directions in mixtures of interconverting conformers; that is, they are "ambidextrous". This behavior should be general and can be rationalized using a simple model based on sterics, noting that arene-arene stacking is, to a first approximation, unaffected by flipping either partner. We demonstrate control over this mechanism by showing that chiral groups can be chosen such that they both favor one orientation and provide effective chiral induction.


Presence of two tumor necrosis factor (tnf)-α homologs on different chromosomes of zebrafish (Danio rerio) and medaka (Oryzias latipes).
Two or more isoforms of several cytokines including tumor necrosis factors (tnfs) have been reported from teleost fish. Although zebrafish (Danio rerio) and medaka (Oryzias latipes) possess two tnf-α genes, their genomic location and existence are yet to be described and confirmed. Therefore, we conducted in silico identification, synteny analysis of tnf-α and tnf-n from both the fish with that of human TNF/lymphotoxin loci and their expression analysis in zebrafish. We identified two homologs of tnf-α (named as tnf-α1 and tnf-α2) and a tnf-n gene from zebrafish and medaka. Genomic location of these genes was found to be as: tnf-α1, and tnf-n and tnf-α2 genes on zebrafish chromosome 19 and 15 and medaka chromosome 11 and 16, respectively. Several features such as existence of TNF family signature, conservation of genes in TNF loci with human chromosome, phylogenetic clustering and amino acid similarity with other teleost TNFs confirmed their identity as tnf-α and tnf-n. There were a constitutive expression of all three genes in different tissues, and an increased expression of tnf-α1 and -α2 and a varied expression of tnf-n ligand in zebrafish head kidney cells induced with 20 μg mL(-1) LPS in vitro. Our results suggest the presence of two tnf-α homologs on different chromosomes of zebrafish and medaka and correlate this incidence arising from the fish whole genome duplication event.


A framework for plasticity implementation on the SpiNNaker neural architecture.
Many of the precise biological mechanisms of synaptic plasticity remain elusive, but simulations of neural networks have greatly enhanced our understanding of how specific global functions arise from the massively parallel computation of neurons and local Hebbian or spike-timing dependent plasticity rules. For simulating large portions of neural tissue, this has created an increasingly strong need for large scale simulations of plastic neural networks on special purpose hardware platforms, because synaptic transmissions and updates are badly matched to computing style supported by current architectures. Because of the great diversity of biological plasticity phenomena and the corresponding diversity of models, there is a great need for testing various hypotheses about plasticity before committing to one hardware implementation. Here we present a novel framework for investigating different plasticity approaches on the SpiNNaker distributed digital neural simulation platform. The key innovation of the proposed architecture is to exploit the reconfigurability of the ARM processors inside SpiNNaker, dedicating a subset of them exclusively to process synaptic plasticity updates, while the rest perform the usual neural and synaptic simulations. We demonstrate the flexibility of the proposed approach by showing the implementation of a variety of spike- and rate-based learning rules, including standard Spike-Timing dependent plasticity (STDP), voltage-dependent STDP, and the rate-based BCM rule. We analyze their performance and validate them by running classical learning experiments in real time on a 4-chip SpiNNaker board. The result is an efficient, modular, flexible and scalable framework, which provides a valuable tool for the fast and easy exploration of learning models of very different kinds on the parallel and reconfigurable SpiNNaker system.


Tumor Subregion Evolution-Based Imaging Features to Assess Early Response and Predict Prognosis in Oropharyngeal Cancer.
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rapidly increasing. Disease stage and smoking history are often used in current clinical trials to select patients for deintensification therapy, but these features lack sufficient accuracy for predicting disease relapse. Our purpose was to develop an imaging signature to assess early response and predict outcomes of OPSCC. Methods: We retrospectively analyzed 162 OPSCC patients treated with concurrent chemoradiotherapy, equally divided into separate training and validation cohorts with similar clinical characteristics. A robust consensus clustering approach was used to spatially partition the primary tumor and involved lymph nodes into subregions (i.e., habitats) based on 18F-FDG PET and contrast CT imaging. We proposed quantitative image features to characterize the temporal volumetric change of the habitats and peritumoral/nodal tissue between baseline and midtreatment. The reproducibility of these features was evaluated. We developed an imaging signature to predict progression-free survival (PFS) by fitting an L1-regularized Cox regression model. Results: We identified 3 phenotypically distinct intratumoral habitats: metabolically active and heterogeneous, enhancing and heterogeneous, and metabolically inactive and homogeneous. The final Cox model consisted of 4 habitat evolution-based features. In both cohorts, this imaging signature significantly outperformed traditional imaging metrics, including midtreatment metabolic tumor volume for predicting PFS, with a C-index of 0.72 versus 0.67 (training) and 0.66 versus 0.56 (validation). The imaging signature stratified patients into high-risk versus low-risk groups with 2-y PFS rates of 59.1% versus 89.4% (hazard ratio, 4.4; 95% confidence interval, 1.4-13.4 [training]) and 61.4% versus 87.8% (hazard ratio, 4.6; 95% confidence interval, 1.7-12.1 [validation]). The imaging signature remained an independent predictor of PFS in multivariable analysis adjusting for stage, human papillomavirus status, and smoking history. Conclusion: The proposed imaging signature allows more accurate prediction of disease progression and, if prospectively validated, may refine OPSCC patient selection for risk-adaptive therapy.


The role of extracellular vesicles in cancer microenvironment and metastasis: myths and challenges.
The concept of vesicles or cell debris released by cancer cells to promote metastasis is not new, but the mechanisms used to currently ascribe their impact in metastasis are of intense debate. A significant increase in reports describing the role of cancer-derived EVs in cancer metastasis has been followed by a growing amount of uncertainty behind these claims. This review will delve into the role of EVs in promoting cancer metastasis by relying on a balanced perspective that looks at challenges faced previously by extracellular vesicle biologists, current technical limitations in the field, and overlooked physiologic mechanisms that may play a confounding role. This review will also discuss how certain experimental approaches are misleading which ultimately lead to overly optimistic mechanisms that have minimally contributed to the pathophysiology of metastasis.


Effectiveness of inpatient and outpatient strategies in increasing referral and utilization of cardiac rehabilitation: a prospective, multi-site study.
Despite the evidence of benefit, cardiac rehabilitation (CR) remains highly underutilized. The present study examined the effect of two inpatient and one outpatient strategy on CR utilization: allied healthcare provider completion of referral (a policy that had been endorsed and approved by the cardiac program leadership in advance; PRE-APPROVED); CR intake appointment booked before hospital discharge (PRE-BOOKED); and early outpatient education provided at the CR program shortly after inpatient discharge (EARLY ED).In this prospective observational study, 2,635 stable cardiac inpatients from 11 Ontario hospitals completed a sociodemographic survey, and clinical data were extracted from charts. One year later, participants were a mailed survey that assessed CR use. Participating inpatient units and CR programs to which patients were referred were coded to reflect whether each of the strategies was used (yes/no). The effect of each strategy on participants' CR referral and enrollment was examined using generalized estimating equations. A total of 1,809 participants completed the post-test survey. Adjusted analyses revealed that the implementation of one of the inpatient strategies was significantly related to greater referral and enrollment (PRE-APPROVED: OR = 1.96, 95%CI = 1.26 to 3.05, and OR = 2.91, 95%CI = 2.20 to 3.85, respectively). EARLY ED also resulted in significantly greater enrollment (OR = 4.85, 95%CI = 2.96 to 7.95). These readily-implementable strategies could significantly increase access to and enrollment in CR for the cardiac population. The impact of these strategies on wait times warrants exploration.


Spire contains actin binding domains and is related to ascidian posterior end mark-5.
Spire is a maternal effect locus that affects both the dorsal-ventral and anterior-posterior axes of the Drosophila egg and embryo. It is required for localization of determinants within the developing oocyte to the posterior pole and to the dorsal anterior corner. During mid-oogenesis, spire mutants display premature microtubule-dependent cytoplasmic streaming, a phenotype that can be mimicked by pharmacological disruption of the actin cytoskeleton with cytochalasin D. Spire has been cloned by transposon tagging and is related to posterior end mark-5, a gene from sea squirts that encodes a posteriorly localized mRNA. Spire mRNA is not, however, localized to the posterior pole. SPIRE also contains two domains with similarity to the actin monomer-binding WH2 domain, and we demonstrate that SPIRE binds to actin in the interaction trap system and in vitro. In addition, SPIRE interacts with the rho family GTPases RHOA, RAC1 and CDC42 in the interaction trap system. Thus, our evidence supports the model that SPIRE links rho family signaling to the actin cytoskeleton.


Balanced internal hydration discriminates substrate binding to respiratory complex I.
Molecular recognition of the amphiphilic electron carrier ubiquinone (Q) by respiratory complexes is a fundamental part of electron transfer chains in mitochondria and bacteria. The primary respiratory complex I binds Q in a long and narrow protein chamber to catalyse its reduction. But, the binding mechanism and the role of chamber hydration in substrate selectivity and stability are unclear. Here, large-scale atomistic molecular dynamics simulations and estimated free energy profiles are used to characterize in detail the binding mechanism to complex I of Q with short and with long isoprenoid tails. A highly stable binding site with two different poses near the chamber exit and a secondary reactive site near the N2 iron-sulfur cluster are found which may lead to an alternative Q redox chemistry and help to explain complex I reactivity. The binding energetics depends mainly on polar interactions of the Q-head and on the counterbalanced hydration of Q-tail isoprenoid units and hydrophobic residues inside the protein chamber. Selectivity upon variation of tail length arises by shifting the hydration balance. This internal hydration mechanism may have implications for binding of amphiphilic molecules to cavities in other membrane proteins.


Experiments in Text Recognition with Binary n-Gram and Viterbi Algorithms.
The binary n-gram and Viterbi algorithms have been suggested as alternative approaches to contextual postprocessing for text produced by a noisy channel such as an optical character recognizer. This correspondence describes the underlying theory of each approach in unified terminology, and presents new implementation algorithms for each approach. In particular, a storage efficient data structure is proposed for the binary n-gram algorithm and a recursive formulation is given for the Viterbi algorithm. Results of extensive experiments with each algorithm are described.


Correlation of computer-based test anxiety with medical students' performance before, during and after assessments.
To explore the correlation of anxiety levels of medical students measured before, during and after assessments with their performance in formative assessments. A repeated measures cross-sectional study was conducted at Shifa College of Medicine, Islamabad with data collection at three points in time, from April-May 2020. A validated test anxiety questionnaire was used to assess anxiety. Eighty-two medical students recorded their responses on the questionnaire before, during and after three consecutive formative assessments in an integrated module. Relevant statistical tests were applied to investigate the correlation of anxiety levels at different stages with assessment scores. The mean scores of anxiety measured before, during and after the three consecutive formative assessments were 29.78±7.77, 28.0±8.88 and 26.11±7.83, respectively. The difference of means of anxiety measured at different stages during assessments was statistically significant (p<0.001). The negative correlation between anxiety level and academic scores of female students was statistically significant (p=0.05). Fluctuation in anxiety scores at different stages of assessments affects academic performance. Identification of the effect of anxiety may help improve the academic performance of medical students.


Receptive fields and properties of a new cluster of mechanoreceptor neurons innervating the mantle region and the branchial cavity of the marine mollusk Aplysia californica.
The rostral LE cluster (rLE) is a new set of mechanoreceptor neurons of the abdominal ganglion innervating the mantle area, the branchial cavity, the gill and the siphon of the marine mollusk Aplysia californica Cooper. We have compared the organization of rLE cell receptive fields with that of three other clusters of sensory neurons in the abdominal ganglion (LE, RE and RF) that we have reanalysed. There is extensive overlap of receptive fields from the four populations of sensory cells, and the most exposed areas of the mantle are the most densely innervated. The sensory threshold is similar for all groups. The action potentials of the LE, rLE and RE neurons are broadened by serotonin and the peptide SCPB and narrowed by dopamine and FMRFamide. The RF group does not show the same kind of sensitivity to these neuromodulators. The synaptic outputs of the LE and rLE neurons undergo similar synaptic depression and homosynaptic and heterosynaptic facilitation. We estimate that 100 mechanoreceptor neurons innervate the entire mantle and siphon skin, gill and branchial cavity of Aplysia. The degree of their convergence onto various interneurons and motor neurons mediating the gill- and siphon-withdrawal reflex and other reflexes is under investigation.


Evaluating the Surface Chemistry of Black Phosphorus during Ambient Degradation.
Black phosphorus (BP) is emerging as a promising candidate for electronic, optical, and energy storage applications. However, its poor ambient stability remains a critical challenge. Evaluation of few-layer liquid-exfoliated BP during ambient exposure using X-ray photoelectron spectroscopy and attenuated total reflectance Fourier transform infrared spectroscopy allows its surface chemistry to be investigated. Oxidation of liquid-exfoliated few-layer BP initially occurs through nonbridging oxide species, which convert to bridging oxide species after ambient exposure. We demonstrate the instability of these bridging oxide species, which undergo hydrolysis to form volatile phosphorus oxides and evaporate from the BP surface. FTIR spectroscopy, scanning transmission electron microscopy, and atomic force microscopy were used to confirm the formation of liquid oxides through a continuous oxidation cycle that results in the decomposition of BP. Furthermore, we show that the instability of few-layer BP originates from the formation of bridging oxide species.


Post-translational modifications, subcellular relocation and release in apoptotic microparticles: apoptosis turns nuclear proteins into autoantigens.
Autoantibodies against particular nuclear components, such as chromatin and snRNPs, are a characteristic feature of the autoimmune disease systemic lupus erythematosus. The last decade, evidence has suggested that apoptotic cells are the main source of autoantigens in this disease. Therefore, it has been proposed that protein modifications occurring during apoptosis lead to the formation of neo-epitopes, which can break the tolerance when apoptotic cells are not properly cleared. Indeed, many lupus autoantigens are prone to apoptosis-associated post-translational modifications and/or cleavage by caspases. In addition, lupus autoantigens are relocated from the nucleus to apoptotic blebs on the cell surface of early apoptotic cells. Therefore, to understand why certain nuclear proteins become autoantigens during apoptosis, it is important to know the apoptotic processing of these proteins. This review summarizes the current knowledge of apoptotic processing of lupus autoantigens and the possible effects on their encounter with the immune system in normal and autoimmune situations.


Characterization of airborne particles at a high-btu coal-gasification pilot plant.
Airborne particles in fugitive emissions have been measured at a slagging fixed-bed coal-gasification pilot plant using lignite. Sampling was conducted during shutdown operations and opening of the gasifier following an aborted startup. Aerosol collected with a Sierra high-volume impactor was subjected to analysis by gas chromatography, mass spectrometry, and scanning electron microscopy; aerosol collected with an Andersen low-volume impactor was subjected to flameless atomic absorption analysis. The data show that the bulk of the trace organic material is associated with small particles: these data are similar to data on ambient air reported in the literature. Particle morphologies resemble those of fly ash from coal combustion, including smooth spheres, vesicular spheres, and crystalline material. Trace element size distributions are bimodal and resemble data for ambient air. Pb-containing particles are generally submicron, while particles containing Al, Fe, and other crustal species are mostly of supermicron size. Aluminum-based aerosol enrichment factors calculated from the lignite composition show that the composition of the aerosol resembles that of the coal, with the exception of modest enrichments of Mg, Na, As, and Pb in the submicron size range. Aerosol enrichment factors based on the earth's crustal composition are somewhat greater than those based on coal composition for several elements, suggesting potential errors in using crustal enrichment data to investigate chemical fractionation during aerosol formation.


Effect of Early Pelvic Binder Use in the Emergency Management of Suspected Pelvic Trauma: A Retrospective Cohort Study.
We aimed to evaluate the effect of early pelvic binder use in the emergency management of suspected pelvic trauma, compared with the conventional stepwise approach. We enrolled trauma patients with initial stabilization using a pelvic binder when suspecting pelvic injury. The inclusion criteria were traumatic injury requiring a trauma team and at least one of the following: a loss of consciousness or a Glasgow coma score (GCS) of <13; systolic blood pressure of <90 mmHg; falling from ≥6 m; injury to multiple vital organs; and suspected pelvic injury. Various parameters, including gender, age, mechanism of injury, GCS, mortality, hospital stay, initial vital signs, revised trauma score, injury severity score, and outcome, were assessed and compared with historical controls. A total of 204 patients with high-energy multiple-trauma from a single level I trauma center in North Taiwan were enrolled in the study from August 2013 to July 2014. The two group baseline patient characteristics were all collected and compared. The trauma patients with suspected pelvic fractures initially stabilized with a pelvic binder had shorter hospital and intensive care unit (ICU) stays. The study group achieved statistically significantly improved survival and lower mean blood transfusion volume and mortality rate, although they were more severe in the trauma score. We recommend prompt pelvic binder use for suspected pelvic injury before definitive imaging is available, as a cervical spine collar is used to protect the cervical spine from further injury prior to definitive identification and characterization of an injury.


Improved prognosis for recurrent epithelial ovarian cancer by early diagnosis and 125I seeds implantation during suboptimal secondary cytoreductive surgery: a case report and literature review.
Epithelial ovarian cancer (EOC) has the worst prognosis in all of gynecologic malignant tumors because of its high recurrence and eventually chemo-resistance. Early diagnosis of recurrence is crucial to avoid diffuse dissemination. Failure of traditional treatment in recurrent epithelial ovarian cancer remains a challenge for clinicians. On the other hand, 125I brachytherapy has been accepted as a useful and hopeful treatment for multiple advanced cancers in recent years. However, its success in advanced epithelial ovarian cancer is limited. Here we report a case of recurrent ovarian cancer who had been early diagnosis of isolated recurrence and successfully treated with 125I seeds implantation during suboptimal cytoreductive surgery. A 59-year-old woman presented with recurrent epithelial ovarian cancer who have had a history of ovarian cancer stage IIIB and an R0 resection had been achieved nearly 2 years before presented in our hospital. She underwent suboptimal secondary cytoreductive surgery after four cycles of chemotherapy with little effectiveness and severe chemotherapy-related side effects. Approximately 70% of the cancer-bulk was resected during surgery. For residual lesion which fixed around the right ureter and right external iliac vessel, 125I seeds implantation was performed. Postoperatively, the patient was treated with two cycles of combination chemotherapy with paclitaxel and carboplatin. The patient was free of disease at 26 months' follow-up period. In recurrent EOC patients with unresectable isolated lesion, salvage 125I seeds implantation are feasible and may contribute to survival.


Heterogeneous resource allocation can change social hierarchy in public goods games.
Public goods games (PGGs) represent one of the most useful tools to study group interactions. However, even if they could provide an explanation for the emergence and stability of cooperation in modern societies, they are not able to reproduce some key features observed in social and economical interactions. The typical shape of wealth distribution-known as Pareto Law-and the microscopic organization of wealth production are two of them. Here, we introduce a modification to the classical formulation of PGGs that allows for the emergence of both of these features from first principles. Unlike traditional PGGs, where players contribute equally to all the games in which they participate, we allow individuals to redistribute their contribution according to what they earned in previous rounds. Results from numerical simulations show that not only a Pareto distribution for the pay-offs naturally emerges but also that if players do not invest enough in one round they can act as defectors even if they are formally cooperators. Our results not only give an explanation for wealth heterogeneity observed in real data but also point to a conceptual change on cooperation in collective dilemmas.


Efficacy of ivermectin against experimental and natural infections of Gasterophilus spp in ponies.
Antiparasitic efficacy of ivermectin against migrating Gasterophilus intestinalis was evaluated in 36 treated and 24 nontreated (n = 12) or vehicle-treated (n = 12) ponies experimentally and naturally infected with G intestinalis and naturally infected with G nasalis. Each pony was experimentally infected with 500 G intestinalis 1st instars in 2 divided doses on days -14 and -7 before treatment. On day 0, ivermectin was administered at the rate of 200 micrograms/kg of body weight by IV (n = 12) or IM injection (n = 12) or given as an oral paste (n = 12). Ponies were euthanatized and necropsied 21 days after treatment. In each nontreated or vehicle-treated pony, late 1st-, 1st- to 2nd- instar molt, and early 2nd-instars of G intestinalis were found in the mouth, and 2nd- and 3rd instars of G intestinalis and 3rd instars of G nasalis were found in the stomach. Bots were not found in any ivermectin-treated pony and, thus, ivermectin was 100% effective against oral and gastric stages. Adverse reactions were not observed in ponies given ivermectin by IM injection or orally, but 1 pony given the vehicle IV and 1 pony given ivermectin (in the vehicle) IV had an anaphylactic reaction, resulting in death of the ivermectin-treated pony. It was speculated that the adverse reaction was caused by histamines released in response to vehicle components given by IV injection.


Granulocyte activity in patients with cancer and healthy subjects.
In our study, we investigated the intracellular killing ability of granulocytes for healthy and ill subjects by measuring NADH oxidase activity and release of hydrogen peroxide. The protocol methodology measured the hydrogen peroxide released after granulocytes activation by PMA (phorbol 12-myristate 13-acetate) by using the Amplex Red assay, which included counting granulocytes by flow cytometer and measurement of the kinetic curve of NADPH oxidase activity by fluorometer. Two parameters were used to describe the level of granulocyte activity: the initial rate of NADPH-oxidase enzyme activity and the level of hydrogen peroxide released after 20 min of granulocyte activation. The method was applied to measure granulocyte activity in 55 healthy subjects and 30 patients with cancer. It was demonstrated that applied procedure is sensitive for estimation of the disease activity. The granulocyte activity in patients with cancer was compared with the granulocyte activity of healthy subjects and demonstrated the downregulation of NADPH oxidase activity. We showed that granulocytes of cancer patients had inhibited oxidative burst and less NADPH oxidase activity.


The absent lumbosacral articular process. A report of three cases and review of the literature.
Three cases of absent lumbar articular processes are presented, with special attention to the symptoms of the lesion, previous literature on this anomaly, and some of the possible embryologic explanations for its occurrence. The symptoms were improved after lumbosacral fusion. The possible role of torsional loading in lumbar disc degeneration is noteworthy in patients with congenital absence of intervertebral joints.


Creatine kinase isoenzymes in serum from cord blood and the blood of healthy full-term infants during the first three postnatal days.
Isoenzymes of creatine kinase (ATP:creatine phosphotransferase; EC 22.214.171.124; CK) were measured by electrophoresis in serum from cord blood and skin-puncture blood taken from 45 healthy full-term infants during the first three postnatal days. Mean total CK activities (in U/L at 30 degrees C) were 185 in cord samples, 536 in samples taken between 5--8 h postnatally, 494 between 24--33 h, and 288 in the 72-100 h samples. Values for all three isoenzymes increased to a peak over this period, with the highest values generally being found in the samples taken 5--33 h after birth; the subsequent decline was most rapid for CK-BB. Serum CK isoenzymes in cord samples and those taken at 72--100 h in the 11 babies delivered by cesarian section did not differ significantly from those of babies delivered vaginally. However the postnatal increases in total CK, CK-MM, and CK-MB (but not in CK-BB) were significantly greater in those patients born by vaginal delivery. The reasons for the increases in CK isoenzymes after birth are not clear, but our results and reported studies on the ontogeny of CK suggest that CK-MB cannot be regarded as a "cardiac-specific" isoenzyme in the neonatal period.


[Obesity treatment in specialized rehabilitation centers - the "Reha-Team" and process quality].
Obesity is a chronic disease with high economic relevance in particular for mutual pension funds. Evidence based guidelines describe strategies for weight reduction and maintenance. Successfull therapy requires trained staff of various professions with special skills in patient education and behaviour therapy enabling patients to make informed decisions. Using methods of quality management the process of obesity management can be optimized by training programmes as well as in-house guidelines for new obesity team members and by continued medical education in metabolic diseases and in patient communication.


[Minimally invasive transforaminal lumbar interbody fusion for treatment of degenerative lumbar scoliosis stenosis].
To explore the effectiveness of minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) for degenerative lumbar scoliosis stenosis by expandable tubular retractor. Between April 2009 and October 2010, 39 patients with degenerative lumbar scoliosis stenosis were treated. Of 39 patients, 20 underwent MI-TLIF (group A) and 19 underwent open surgery (group B). There was no significant differences in gender, age, disease duration, range of lumbar degenerative scoliosis, Cobb angle, Oswestry disability index (ODI), and visual analogue scale (VAS) between 2 groups (P > 0.05). The operation time, intraoperative blood loss, postoperative independently turning over time, postoperative complication rate, Cobb angle, fusion rates, ODI score, and VAS score were compared between 2 groups. The operation time of group A was significantly longer than that of group B (P < 0.05), and the intraoperative blood loss of group A was significantly less than that of group B (P < 0.05); no significant difference was found in postoperative independently turning over time between 2 groups (t=1.869, P=0.069). The complication rate was 20.0% (4/20) in group A and 26.3% (5/19) in group B, showing no significant difference (Chi2=0.219, P=0.640). All patients were followed up 2 years to 3 years and 6 months (mean, 2.9 years). At last follow-up, the fusion rate of bone graft was 92.9% (78/84) in group A and 95.2% (80/84) in group B, showing no significant difference (Chi2=0.425, P=0.514). According to the Macnab standard for effectiveness evaluation, the results were excellent in 12 cases, good in 6 cases, fair in 1 case, and poor in 1 case, with an excellent and good rate of 90.0% in group A; the results were excellent in 12 cases, good in 5 cases, and fair in 2 cases, with an excellent and good rate of 89.5% in group B; there was no significant difference between 2 groups (Z= -0.258, P=0.835). The postoperative VAS score, ODI score, and Cobb angle were significantly improved when compared with preoperative ones in 2 groups (P < 0.05); and there was no significant differences between 2 groups at 2 weeks after operation and last follow-up (P > 0.05). MI-TLIF by expandable tubular retractor is an available clinical choice in treating degenerative lumbar scoliosis stenosis. It can obtain the same effectiveness as the open surgery.


Neuroprotective effect of chondroitin sulfate on SH‑SY5Y cells overexpressing wild‑type or A53T mutant α‑synuclein.
Accumulation of α‑synuclein (α‑SYN) is a common pathology for Parkinson's disease (PD). There is abundant evidence that the toxic‑gain‑of‑function of α‑SYN's is associated with aggregation and consequent effects. To assess the potential of chondroitin sulfate (CS) in this regard, the present study investigated its neuroprotective on SH‑SY5Y cells overexpressing wild‑type (WT) or A53T mutant α‑SYN. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential were detected by flow cytometry. The protein expression levels of total α‑SYN, phosphorylated Ser129 α‑SYN, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and cytochrome‑c (Cyt‑c ) were analyzed by western blotting. It was observed that CS reduced the expression levels of total α‑SYN and phosphorylated Ser129 α‑SYN, prevented cell loss and inhibited apoptosis. The subsequent mechanism study indicated that CS inhibited ROS overproduction. CS also significantly attenuated WT and A53T mutant α‑SYN‑induced dysfunction, including decrease of mitochondrial membrane potential, decrease of Bcl‑2 expression, and increase of Bax expression, release of Cyt‑c from the mitochondria and activation of caspase‑3 and caspase‑9, which demonstrated that CS suppressed α‑SYN‑induced apoptosis possibly through mitochondria protection. These results suggested that CS protects SH‑SY5Y cells overexpressing WT or A53T mutant α‑SYN by inhibiting the expression and phosphorylation of α‑SYN, and ROS overproduction and mitochondrial apoptosis. These results implicate CS as a potential therapeutic agent for the treatment of PD.


DRAIN AMYLASE ON THE FIRST POSTOPERATIVE DAY OF WHIPPLE SURGERY: WHAT VALUE IS THE BEST PREDICTOR FOR EARLY DRAIN REMOVAL?
The value of drain amylase on the first postoperative day after pancreatic resections has been described as an efficient predictor of pancreatic fistula. In spite of this, the cut-off point below which the drains can be removed early remains controversial. Validate the use of the amylase on the 1st postoperative day in the correlation with pancreatic fistula and define the value at which early drain removal is safe. Were included patients undergoing Whipple surgery in the period of 2007 to 2016. Group 1 enrolled the ones who did not develop fistula and those who developed biochemical fistula for less than seven days postoperatively and group 2 included patients who developed persistent biochemical fistula between seven and 21 days and those with grade B and C fistula. Sixty-one patients were included, 41 comprised group 1 and 20 group 2. The incidence of abdominal collections, need for reoperation and time of hospitalization were for group 1 and 2, respectively: 17.1%, 17.1% and 9.5 days, and 65%, 40% and 21.1 days. The median of the amylase from the drain at 1st postoperative day was in group 1 and 2, respectively: 175 U/l and 3172.5 U/l (p=0.001). Using a cut-off of 180 to predict the group to which the patient would belong there was obtained sensitivity, specificity, positive predictive value and negative predictive value of 100%, 48.8%, 50% and 100% respectively. It was validated the cut-off value of 180 U/l as appropriate to early drain removal.


Gas-Phase vs. Grain-Surface Formation of Interstellar Complex Organic Molecules: A Comprehensive Quantum-Chemical Study.
Several organic chemical compounds (the so-called interstellar complex organic molecules, iCOMs) have been identified in the interstellar medium (ISM). Examples of iCOMs are formamide (HCONH2), acetaldehyde (CH3CHO), methyl formate (CH3OCHO), or formic acid (HCOOH). iCOMs can serve as precursors of other organic molecules of enhanced complexity, and hence they are key species in chemical evolution in the ISM. The formation of iCOMs is still a subject of a vivid debate, in which gas-phase or grain-surface syntheses have been postulated. In this study, we investigate the grain-surface-formation pathways for the four above-mentioned iCOMs by transferring their primary gas-phase synthetic routes onto water ice surfaces. Our objective is twofold: (i) to identify potential grain-surface-reaction mechanisms leading to the formation of these iCOMs, and (ii) to decipher either parallelisms or disparities between the gas-phase and the grain-surface reactions. Results obtained indicate that the presence of the icy surface modifies the energetic features of the reactions compared to the gas-phase scenario, by increasing some of the energy barriers. Therefore, the investigated gas-phase mechanisms seem unlikely to occur on the icy grains, highlighting the distinctiveness between the gas-phase and the grain-surface chemistry.


Bright-Emitting Perovskite Films by Large-Scale Synthesis and Photoinduced Solid-State Transformation of CsPbBr3 Nanoplatelets.
Lead halide perovskite nanocrystals are an emerging class of materials that have gained wide interest due to their facile color tuning and high photoluminescence quantum yield. However, the lack of techniques to translate the high performance of nanocrystals into solid films restricts the successful exploitation of such materials in optoelectronics applications. Here, we report a heat-up and large-scale synthesis of quantum-confined, blue-emitting CsPbBr3 nanoplatelets (NPLs) that self-assemble into stacked lamellar structures. Spin-coated films fabricated from these NPLs show a stable blue emission with a photoluminescence quantum yield (PLQY) of 25%. The morphology and the optoelectronic properties of such films can be dramatically modified by UV-light irradiation under ambient conditions at a high power, which transforms the self-assembled stacks of NPLs into much larger structures, such as square-shaped disks and nanobelts. The emission from the transformed thin films falls within the green spectral region with a record PLQY of 65%, and they manifest an amplified spontaneous emission with a sharp line width of 4 nm at full-width at half-maximum under femtosecond-pulsed excitation. The transformed films show stable photocurrents with a responsivity of up to 15 mA/W and response times of tens of milliseconds and are robust under treatment with different solvents. We exploit their insolubility in ethanol to fabricate green-emitting, all-solution-processed light-emitting diodes with an external quantum efficiency of 1.1% and a luminance of 590 Cd/m2.


Superior approach from the pocket for atrioventricular junction ablation performed at the time of conduction system pacing implantation.
Conduction system pacing (CSP) and atrioventricular junction ablation (AVJA) improve outcomes in patients with symptomatic, refractory atrial fibrillation (AF). Superior approach (SA) from the pocket via axillary or subclavian vein has been proposed as an alternative to the conventional femoral venous access (FA) to perform AVJA. To assess the feasibility and safety of SA for AVJA performed simultaneously with CSP, and to compare this approach with FA. A prospective, observational study, enrolling consecutive patients with symptomatic, refractory AF undergoing simultaneous CSP and AVJA. A total of 107 patients were enrolled: in 50, AVJA was primarily attempted with SA, in 69 from FA. AVJA with SA was successful in 38 patients (76.0%), while in 12 patients, a subsequent FA was required. AVJA from FA was successful in 68 patients (98.5%), while in one patient, a left-sided approach via femoral artery was required. Compared with FA, SA was associated with a significantly longer duration of ablation (238.0 ± 218.2 vs. 161.9 ± 181.9 s; p = .035), a significantly shorter procedure time (28.1 ± 19.8 vs. 19.8 ± 16.8 min; p = .018), an earlier ambulation (2.7 ± 3.2 vs. 19.8 ± 0.1 h; p < .001), and an earlier discharge from procedure completion (24.0 ± 2.7 vs. 27.1 ± 5.1 h; p < .001). After a median follow-up of 12 months, the rate of complications was similar in the two groups (2.0% in SA, 4.3% in FA; p = .483). Simultaneous CSP and AVJA with SA is feasible, with a safety profile similar to FA. Compared to FA, this approach reduces the procedure times and allows earlier ambulation and discharge.


(4-Chloro-benzohydrazidato-κN',O)[2-(4-chloro-benzoyl-hydrazinyl-idene-κN,O)-3-phenyl-propionato(2-)-κO]oxidovanadium(V) methanol monosolvate.
The V(V) atom in the title compound, [V(C(7)H(6)ClN(2)O)(C(16)H(11)ClN(2)O(3))O]·CH(3)OH, is N,O-chelated by the benzoyl-hydrazidate anion and O,N,O'-chelated by the (benzoyl-hydrazinyl-idene)propionate dianion. The distorted octa-hedral trans-N(2)O(4) coordination geometry is completed by the vanadyl O atom. The mononuclear and solvent mol-ecules are linked by N-H⋯O and O-H⋯O hydrogen bonds about a center of inversion, generating a dimer.


Characterization of a diesel sludge microbial consortia for bioremediation.
The organisms found growing in a mixed diesel sludge-chromium metal waste were characterized directly using environmental scanning electron microscopy (ESEM) and traditional fixation techniques with scanning electron microscopy (SEM). An attempt to identify organisms genetically directly from the sludge failed because of interference from chemicals in the waste with polymerase chain reaction (PCR). The organisms were isolated using plate culture techniques and isolates were characterized by SEM and genetic sequencing. A variety of organisms were found with differing morphologies and growth habits. Sequencing identified an organism homologous to Bacillus mycoides and matched other organisms such as Paenibacillus lautus, Paenibacillus spp., Bacillus spp., and Rhodobacter spp.


Looking at food in sad mood: do attention biases lead emotional eaters into overeating after a negative mood induction?
Emotional eating is associated with overeating and the development of obesity. Yet, empirical evidence for individual (trait) differences in emotional eating and cognitive mechanisms that contribute to eating during sad mood remain equivocal. The aim of this study was to test if attention bias for food moderates the effect of self-reported emotional eating during sad mood (vs neutral mood) on actual food intake. It was expected that emotional eating is predictive of elevated attention for food and higher food intake after an experimentally induced sad mood and that attentional maintenance on food predicts food intake during a sad versus a neutral mood. Participants (N = 85) were randomly assigned to one of the two experimental mood induction conditions (sad/neutral). Attentional biases for high caloric foods were measured by eye tracking during a visual probe task with pictorial food and neutral stimuli. Self-reported emotional eating was assessed with the Dutch Eating Behavior Questionnaire (DEBQ) and ad libitum food intake was tested by a disguised food offer. Hierarchical multivariate regression modeling showed that self-reported emotional eating did not account for changes in attention allocation for food or food intake in either condition. Yet, attention maintenance on food cues was significantly related to increased intake specifically in the neutral condition, but not in the sad mood condition. The current findings show that self-reported emotional eating (based on the DEBQ) might not validly predict who overeats when sad, at least not in a laboratory setting with healthy women. Results further suggest that attention maintenance on food relates to eating motivation when in a neutral affective state, and might therefore be a cognitive mechanism contributing to increased food intake in general, but maybe not during sad mood.


Post-mating gene expression profiles of female Drosophila melanogaster in response to time and to four male accessory gland proteins.
In Drosophila melanogaster, the genetic and molecular bases of post-mating changes in the female's behavior and physiology are poorly understood. However, DNA microarray studies have demonstrated that, shortly after mating, transcript abundance of >1700 genes is altered in the female's reproductive tract as well as in other tissues. Many of these changes are elicited by sperm and seminal fluid proteins (Acps) that males transfer to females. To further dissect the transcript-level changes that occur following mating, we examined gene expression profiles of whole female flies at four time points following copulation. We found that, soon after copulation ends, a large number of small-magnitude transcriptional changes occurred in the mated female. At later time points, larger magnitude changes were seen, although these occurred in a smaller number of genes. We then explored how four individual Acps (ovulin, Acp36DE, Acp29AB, and Acp62F) with unique functions independently affected gene expression in females shortly after mating. Consistent with their early and possibly local action within the female, ovulin and Acp36DE caused relatively few gene expression changes in whole bodies of mated females. In contrast, Acp29AB and Acp62F modulated a large number of transcriptional changes shortly after mating.


Multiscale integration of -omic, imaging, and clinical data in biomedical informatics.
This paper reviews challenges and opportunities in multiscale data integration for biomedical informatics. Biomedical data can come from different biological origins, data acquisition technologies, and clinical applications. Integrating such data across multiple scales (e.g., molecular, cellular/tissue, and patient) can lead to more informed decisions for personalized, predictive, and preventive medicine. However, data heterogeneity, community standards in data acquisition, and computational complexity are big challenges for such decision making. This review describes genomic and proteomic (i.e., molecular), histopathological imaging (i.e., cellular/tissue), and clinical (i.e., patient) data; it includes case studies for single-scale (e.g., combining genomic or histopathological image data), multiscale (e.g., combining histopathological image and clinical data), and multiscale and multiplatform (e.g., the Human Protein Atlas and The Cancer Genome Atlas) data integration. Numerous opportunities exist in biomedical informatics research focusing on integration of multiscale and multiplatform data.


Identification of the promoter of the Bacillus subtilis sdh operon.
The Bacillus subtilis sdhCAB operon contains the structural genes for the three subunits of the membrane bound succinate dehydrogenase complex. An sdh-specific transcript of about 3,450 nucleotides was detected in vegetative bacteria. S1 nuclease mapping experiments showed that the sdh operon is transcribed from a sigma-43 promoter; the transcript starts at a guanosine residue 90 base pairs upstream from the first gene of the operon, sdhC. No sdh transcript was found in B. subtilis carrying the sdh-115 mutation, which decreases expression of the sdh operon by more than 99%. The sdh-115 mutation is a G-to-A transition in the -35 region of the sigma-43 promoter. The sdh operon is sensitive to glucose repression. When the sdh promoter region was used to drive transcription of the cat-86 gene this gene also became glucose repressed.


Clinicopathological heterogeneity in the classification of mild head injury.
Research examining the neurobehavioral outcome after mild head injury has yielded inconsistent and contradictory findings. Such findings have been attributed to a variety of methodological weaknesses, such as failure to consider the preinjury status of the patient, lack of control groups, and variability in outcome time points. However, few researchers have examined the adequacy of the current diagnostic criteria. A Glasgow Coma Scale (GCS) score of 13 to 15 is one of the primary criteria in the classification of mild head injury. We propose that the use of GCS Scores 13 to 15 permits excessive heterogeneity in injury severity and contributes to variability in neurobehavioral outcome. The purpose of this study is to examine the relationship of admission GCS scores to variables indicative of injury severity. The case records of 3370 patients consecutively admitted to a Level I trauma center with nonmissile head injuries, positive loss of consciousness, and admission GCS scores of 13 to 15 were reviewed. The frequency of positive computed tomographic scan findings and the need for neurosurgical intervention within the first 24 hours were recorded. A chi 2 analysis revealed statistically significant differences between the frequency of positive computed tomographic scans and the need for neurosurgical intervention in patients with GCS scores of 13 versus 14, 14 versus 15, and 13 versus 15. These results indicate significant differences in injury severity among patients with admission GCS scores of 13 to 15. The implicit assumption of clinicopathological homogeneity among patients with such scores is challenged by these data. This study demonstrates the need for more precise research diagnostic criteria in the study of neurobehavioral outcome after mild head injury. These findings also provide compelling evidence for the re-examination of the classification of mild head injury. Serious consideration must be given to the segregation of patients with GCS scores of 15 from those with scores of 14 and 13.


[Experience in organizing the operations of a large histopathology laboratory].
In connection with the organization of large centralized pathology departments serving up to 4-6 thousand beds or more in hospitals the use of routine methods of work of histological laboratories becomes unacceptable. The authors shares his experience in organization work of a large histopathological laboratories, suggesting available devices increasing the labour productivity and culture and requiring no scarce glassware.


Anthropomorphic Breast and Head Phantoms for Microwave Imaging.
This paper deals with breast and head phantoms fabricated from 3D-printed structures and liquid mixtures whose complex permittivities are close to that of the biological tissues within a large frequency band. The goal is to enable an easy and safe manufacturing of stable-in-time detailed anthropomorphic phantoms dedicated to the test of microwave imaging systems to assess the performances of the latter in realistic configurations before a possible clinical application to breast cancer imaging or brain stroke monitoring. The structure of the breast phantom has already been used by several laboratories to test their measurement systems in the framework of the COST (European Cooperation in Science and Technology) Action TD1301-MiMed. As for the tissue mimicking liquid mixtures, they are based upon Triton X-100 and salted water. It has been proven that such mixtures can dielectrically mimic the various breast tissues. It is shown herein that they can also accurately mimic most of the head tissues and that, given a binary fluid mixture model, the respective concentrations of the various constituents needed to mimic a particular tissue can be predetermined by means of a standard minimization method.


Are Immigrants Scapegoats? The Reciprocal Relationships Between Subjective Well-Being, Political Distrust, and Anti-immigrant Attitudes in Young Adulthood.
This study examined the impact of native youth's subjective well-being on exclusionary attitudes toward immigrants, seeking to understand the relationship between subjective well-being, political distrust, and anti-immigrant attitudes over time. Using longitudinal data, we followed three cohorts of native young adults (N = 1352; Mage = 22.72, SD = 3.1) in Sweden over a period of 2 years. The results showed that subjective well-being did not predict an increase in anti-immigrant attitudes among native youth, but anti-immigrant attitudes had a significant impact on subjective well-being. The data also found bidirectional and mutually reinforcing relationships between subjective well-being and political distrust, and between political distrust and anti-immigrant attitudes. These results highlight that improving young adults' subjective well-being represents an important basis for preventing the development of political distrust, which in turn could reduce native youth's susceptibility to adopt hostile attitudes toward immigrants.


[Changes in total hemodynamics of central genesis following removal of basal meningiomas].
The removal of basal intracranial meningiomas in 54 patients, even under general anesthesia with neuro-autonomous blocking, was accompanied by cardiovascular reactions caused by both reflex effects and direct excitation of brain stem structures. These reactions were always of a pressor nature only. Postoperatively, the vascular reactions were also of a pressor nature and presented themselves as components of either a non-specific stress response or a developing diencephalo-catabolic syndrome. Taking into account that the leading cause of the vascular disorders in stress responses and the diencephalo-catabolic syndrome is the irritative process in the brain stem structures, it is important for the prevention and management of these disorders to suppress by pharmacological means the irritation of the median formations with simultaneous blood replacement and conduction of maintenance cardiac therapy.


Microfluidic screening of electrophoretic mobility shifts elucidates riboswitch binding function.
Riboswitches are RNA sensors that change conformation upon binding small molecule metabolites, in turn modulating gene expression. Our understanding of riboswitch regulatory function would be accelerated by a high-throughput, quantitative screening tool capable of measuring riboswitch-ligand binding. We introduce a microfluidic mobility shift assay that enables precise and rapid quantitation of ligand binding and subsequent riboswitch conformational change. In 0.3% of the time required for benchtop assays (3.2 versus 1020 min), we screen and validate five candidate SAM-I riboswitches isolated from thermophilic and cryophilic bacteria. The format offers enhanced resolution of conformational change compared to slab gel formats, quantitation, and repeatability for statistical assessment of small mobility shifts, low reagent consumption, and riboswitch characterization without modification of the aptamer structure. Appreciable analytical sensitivity coupled with high-resolution separation performance allows quantitation of equilibrium dissociation constants (K(d)) for both rapidly and slowly interconverting riboswitch-ligand pairs as validated through experiments and modeling. Conformational change, triplicate mobility shift measurements, and K(d) are reported for both a known and a candidate SAM-I riboswitch with comparison to in-line probing assay results. The microfluidic mobility shift assay establishes a scalable format for the study of riboswitch-ligand binding that will advance the discovery and selection of novel riboswitches and the development of antibiotics to target bacterial riboswitches.


Keratinocyte differentiation in acquired cholesteatoma and perforated tympanic membranes.
To evaluate the type of differentiation of keratinocytes of acquired cholesteatoma and its significance for cholesteatoma invasiveness. Forty acquired cholesteatomas and 10 tympanic membranes with persisting perforations were snap frozen and processed for immunohistochemical studies. Cytokeratin antibodies that represented all subgroups and antibodies that were directed against collagen components of the basal lamina were applied. Expression of these constituents was scored by using light microscopy. The phenotype of the matrix was generally characterized by an extension of expression of basal cell cytokeratin 14 and hyperproliferation-associated cytokeratins 6, 16, and 17 into the suprabasal cell layers, while the expression of keratinization marker cytokeratin 10 was down-regulated. These features varied greatly at different sites of the matrix and were most marked at the advancing front of the cholesteatoma. A comparable expression pattern, but less pronounced, was observed at the epidermal front of the mucocutaneous junction of the tympanic membrane perforations. This phenomenon was invariably associated with a mononuclear cell infiltrate in the dermis at both junctions. The basal lamina was always intact. Acquired cholesteatomas show hyperproliferative features. There is a striking similarity between the pronounced expression of this phenotype and the associated inflammation at the mucocutaneous junctions of cholesteatomas and tympanic membrane perforations and those that are observed after epidermal injury. This indicates that epidermis and middle ear epithelium do not form stable junctions and the front can be considered to be a persisting epidermal defect. This involves the permanent presence of "activated keratinocytes" in the junction area that will lead to proliferation and migration, when additional triggers are present.


[Experimental ocular larva migrans infection in mice].
To characterize the histologic alterations in the ocular globe of mice infected with eggs of Toxocara canis, during both the acute and chronic stages of the infection. Performance of an experimental, prospective study in vivo, with right and left ocular globes [using 5 groups of 4 mice in each study; 2 white (A/J) and 2 black (C57/BL)], infected by the intravenous injection of 1000 embrionated Toxocara canis eggs. The mice were sacrificed sequentially post infection (3-180 days), the eyes evaluated by conventional microscopic techniques and the histopathology findings recorded. All the mice revealed some degree of ocular damage in one or both eyes. The retina was the most affected layer with edema, hemorrhage and severe degenerative changes seen. Other alterations included inflammation of the cornea, and obliteration of the anterior chamber with fibrinoid material. We also demonstrated changes in the normal histology of the uvea and lens. In only two eyes were segments of larvae found in the retina, and in each instance there was no evidence of an inflammatory reaction around them. Most of the changes seen were not related to the presence of larval forms, suggesting they were due to the effect of excretion-secretion products during the infective phase.


Lignocellulosic ethanol and butanol production by Saccharomyces cerevisiae and Clostridium beijerinckii co-culture using non-detoxified corn stover hydrolysate.
Considering global economic and environmental -benefits, green renewable biofuels such as ethanol and butanol are considered as sustainable alternatives to fossil fuels. Thus, developing a co-culture strategy for ethanol and butanol production by Saccharomyces cerevisiae and Clostridium beijerinckii has emerged as a promising approach for biofuel production from lignocellulosic biomass. This study developed a co-culture of S. cerevisiae and C. beijerinckii for ethanol and butanol production from non-detoxified corn stover hydrolysate. By firstly inoculating 3 % S. cerevisiae and then 7 % C. beijerinckii with 8-10 h time intervals, the optimized co-culture process gave 24.0 g/L ABE (20.8 g/L ethanol and 2.4 g/L butanol), obtaining ABE yield and productivity of 0.421 g/g and 0.55 g/L/h. The demonstrated co-culture strategy made full use of hexose and pentose in hydrolysate and contributed to total yield and efficiency compared to conventional ethanol or ABE fermentation, indicating its great potential for developing economically feasible and sustainable bioalcohols production.


Gamma-aminobutyric acid and benzodiazepine receptors in an animal model of fulminant hepatic failure.
Hepatic encephalopathy (HE) is a syndrome of generalized neural inhibition, which complicates both acute and chronic liver failure. Since gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter of the brain and HE is associated with increased responsiveness to certain drugs (benzodiazepines and barbiturates) that mediate neural inhibition by binding to the GABA receptor complex on postsynaptic neural membranes, the status of this receptor complex in HE was investigated. Fulminant hepatic failure was induced in rabbits by the intravenous injection of galactosamine hydrochloride. Neural membranes were isolated from the brains of normal rabbits, rabbits in hepatic coma, and rabbits with another type of metabolic encephalopathy, uremic coma. To characterize GABA and benzodiazine receptors, measurements were made of the specific binding to neural membranes of 3H-GABA and 3H-flunitrazepam, respectively. Computer-assisted Scatchard plot analysis of the binding data suggested the presence of two independent receptors for GABA and a single class of receptor for benzodiazepines. Hepatic coma was associated with no changes in the affinities of these receptors but with significant increases in their densities: 0.34 vs. 0.60; 1.1 vs. 2.2; and 4.6 vs. 7.3 pmol/mg of membrane protein for the high-affinity GABA, low-affinity GABA and benzodiazepine receptors, respectively. Uremic coma was associated with no changes in the affinities or densities of GABA receptors. On the basis of these findings, it is suggested that (1) increased numbers of GABA receptors in liver failure may potentiate neural inhibition by increasing the sensitivity of the brain to GABA and (2) increased responsiveness to the sedative-hypnotic effects of benzodiazepines in liver failure may be mediated by increased numbers of receptors for this class of drug, permitting increased drug effect.


Development and shelf-life evaluation of pearl millet based upma dry mix.
Upma, a popular breakfast of southern India, traditionally made from wheat, was prepared using pearl millet semolina (PMS). Prior to preparation of semolina, pearl millet grains were hydro-thermally treated to reduce anti-nutritional factors and inactivate lipase activity. Hydrothermal treatments (soaking up to moisture 30 ± 2%, steaming 1.05 kg cm(-2), 20 min) reduced the anti-nutritional factors significantly (p ≤ 0.05). No lipase activity was detected after steaming. Central composite rotatable design (CCRD) with three independent variables i.e. vanaspati (vegetable fat), citric acid and water for rehydration were used to design the experiments. Sensory responses and rehydration ratio were used to study the individual and interactive effects of variables. Sensory score for taste varied from 6.5 to 8.1, mouth feel 6.7-8.0, overall acceptability 6.7-8.1 and rehydration ratio from 2.4 to 3.3. Based upon the experiments, the optimized level of ingredients was: vanaspati 46.5 g 100 g(-1) PMS, citric acid 0.17 g 100 g(-1) PMS and water for rehydration 244.6 ml 100 g(-1) dry mix with 98.5% desirability. The prepared upma mix was monitored for peroxide value, free fatty acids and thiobarbituric acid value as well as sensory quality during storage and was found stable for 6 months at ambient conditions (20-35 °C) in poly ethylene pouches (75 μ).


A national survey of thromboprophylaxis in traumatic brain injury in the United Kingdom.
Patients with traumatic brain injury (TBI) are at increased risk of venous thromboembolic events (VTE). In this survey, we aimed to assess current practice in the United Kingdom and identify areas of variation for further investigation. We distributed a case-based survey to neurosurgical consultants and trainees via e-mail. The survey included four index TBI cases commonly seen: a surgically treated acute extradural haematoma, bilateral frontal contusions treated conservatively, diffuse axonal injury requiring critical care and a conservatively managed small acute subdural haematoma. Each case vignette included questions looking at a range of areas regarding thromboprophylaxis. Sixty-two responses were collected among UK neurosurgeons with a good geographic distribution. In each case, over 90% of respondents would initiate mechanical prophylaxis (MTP) at admission. There was greater variation on the decision to commence pharmacological prophylaxis (PTP). Consultants showed a higher willing to commence PTP across all cases (84%) compared to trainees (77.4%). Low molecular weight heparin (LMWH) was the favoured PTP agent in over 90% of respondents. There was significant variability in the timing of initiation of PTP within and between cases. The median times to commence PTP across all four cases ranged from 1 to 7 days. This survey highlighted broad consensus on the use of MTP and choice of PTP agent, when used. However, the survey also demonstrated wide intra-case variation on whether to start PTP and particularly the timing of initiation. This discordance in practice shines light on the lack of evidence guiding thromboprophyalxis in TBI and adds weight to the need for prospective randomised trials to guide clinical management.


Protection against apoptosis by the vaccinia virus SPI-2 (B13R) gene product.
Vaccinia virus contains a gene, termed SPI-2 or B13R, that is closely related in its sequence to a potent inhibitor of apoptosis from cowpox virus (crmA). Infection by vaccinia virus protects HeLa cells against apoptosis that is induced by an immunoglobulin M antibody against the fas receptor or by tumor necrosis factor alpha. This effect is profoundly reduced when the SPI-2 gene is deleted. The SPI-2 gene, when transiently expressed in these cells, can also protect against apoptosis mediated by these agents. Given the similarity to crmA, it seems likely that SPI-2 functions in an analogous fashion, inhibiting the activity of ICE protease family members and blocking the onset of apoptosis.


Perceived self-efficacy and specific self-reported outcomes in persons with lower-limb amputation using a non-microprocessor-controlled versus a microprocessor-controlled prosthetic knee.
To measure self-efficacy in a group of individuals who have undergone a lower-limb amputation and investigate the relationship between self-efficacy and prosthetic-specific outcomes including prosthetic use, mobility, amputation-related problems and global health. A second purpose was to examine if differences exist in outcomes based upon the type of prosthetic knee unit being used. Cross-sectional study using the General Self-Efficacy (GSE) Scale and the Questionnaire for Persons with a Transfemoral Amputation (Q-TFA). Forty-two individuals participated in the study. Twenty-three used a non-microprocessor-controlled prosthetic knee joint (non-MPK) and 19 used a microprocessor-controlled prosthetic knee joint (MPK). The study sample had quite high GSE scores (32/40). GSE scores were significantly correlated to the Q-TFA prosthetic use, mobility and problem scores. High GSE scores were related to higher levels of prosthetic use, mobility, global scores and negatively related to problem score. No significant difference was observed between individuals using a non-MPK versus MPK joints. Individuals with high self-efficacy used their prosthesis to a higher degree and high self-efficacy was related to higher level of mobility, global scores and fewer problems related to the amputation in individuals who have undergone a lower-limb amputation and were using a non-MPK or MPK knee. Implications for rehabilitation Perceived self-efficacy has has been shown to be related to quality of life, prosthetic mobility and capability as well as social activities in daily life. Prosthetic rehabilitation is primary focusing on physical improvement rather than psychological interventions. More attention should be directed towards the relationship between self-efficacy and prosthetic related outcomes during prosthetic rehabilitation after a lower-limb amputation.


Blockage pattern of longitudinal flow in Meniere's disease.
In the present study, classification of the patterns of 3D CT images of the ductus reuniens (reuniting duct) (RD), saccular duct (SD), and endolymphatic sinus (ES) gave more precise information for assessing the pathological condition of Meniere's disease (MD) than our previous study. This study attempted to provide more detailed information on MD by classifying the patterns of 3D CT images of the RD, SD, and ES in patients with MD. We examined the ears of 62 patients with definitely diagnosed unilateral MD based on the criteria of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) using 3D CT. The 3D CT images of bony grooves of RD, SD, and ES (BRD, BSD, and BES) were classified into patterns according to aspects of their patency. BRD could be classified into six types by assessing their patency defined using the criteria in this study. In the ears on the affected side of patients with MD, the BRD, BSD, and BES lost continuity in 3D CT images along their bony routes and were significantly different from normal healthy ears (p < 0.01). There were no significant differences among each stage of MD in the distributions of BRD and BES except for BSD.


Organic matter reduces the amount of detectable environmental DNA in freshwater.
Environmental DNA (eDNA) is used for monitoring the occurrence of freshwater organisms. Various studies show a relation between the amount of eDNA detected and target organism abundance, thus providing a potential proxy for reconstructing population densities. However, environmental factors such as water temperature and microbial activity are known to affect the amount of eDNA present as well. In this study, we use controlled aquarium experiments using Gammarus pulex L. (Amphipoda) to investigate the relationship between the amount of detectable eDNA through time, pH, and levels of organic material. We found eDNA to degrade faster when organic material was added to the aquarium water, but that pH had no significant effect. We infer that eDNA contained inside cells and mitochondria is extra resilient against degradation, though this may not reflect actual presence of target species. These results indicate that, although estimation of population density might be possible using eDNA, measured eDNA concentration could, in the future, be corrected for local environmental conditions in order to ensure accurate comparisons.


Analysis of Food Hub Commerce and Participation Using Agent-Based Modeling: Integrating Financial and Social Drivers.
Factors influencing long-term viability of an intermediated regional food supply network (food hub) were modeled using agent-based modeling techniques informed by interview data gathered from food hub participants. Previous analyses of food hub dynamics focused primarily on financial drivers rather than social factors and have not used mathematical models. Based on qualitative and quantitative data gathered from 22 customers and 11 vendors at a midwestern food hub, an agent-based model (ABM) was created with distinct consumer personas characterizing the range of consumer priorities. A comparison study determined if the ABM behaved differently than a model based on traditional economic assumptions. Further simulation studies assessed the effect of changes in parameters, such as producer reliability and the consumer profiles, on long-term food hub sustainability. The persona-based ABM model produced different and more resilient results than the more traditional way of modeling consumers. Reduced producer reliability significantly reduced trade; in some instances, a modest reduction in reliability threatened the sustainability of the system. Finally, a modest increase in price-driven consumers at the outset of the simulation quickly resulted in those consumers becoming a majority of the overall customer base. Results suggest that social factors, such as desire to support the community, can be more important than financial factors. An ABM of food hub dynamics, based on human factors data gathered from the field, can be a useful tool for policy decisions. Similar approaches can be used for modeling customer dynamics with other sustainable organizations.


[Carbon dioxide angiography. A new injection system].
To evaluate the usefulness of a new carbon dioxide (CO2) intravascular injection system in digital subtraction angiography. March 1998 to May 1999, thirty-nine patients were submitted to digital subtraction angiography with CO2 injection by a new delivery system, CO2-Angioset, OptiMed, Ettingen, Germany. The patients were 29 men and 10 women, whose age ranged 32 to 76 (mean: 47), eighteen of them with absolute or relative contraindications to iodinated contrast media and 6 with poor diagnostic findings at previous conventional angiography. CO2 was used for comparison with iodinated contrast agents in 4 patients. We studied the following vascular districts: renal arteries in 9 patients, portal vein in 18, lower limb arteries in 7, upper limb veins in 4. In 1 patient CO2 angiography was carried out for the diagnosis and interventional treatment, by transcatheter embolization, of a postbioptic arteriovenous renal fistula. During the procedure, arterial blood pressure, EKG status and oxygen stauration were monitored, and subjective sensations recorded in all patients. CO2 angiography provided adequate visualization of vascular districts and of abnormal findings in 32 cases (82%), while its results were considered insufficient for correct and complete assessment in 7 cases (18%). In detail, renal arteries studies were adequate in 9/9 cases, providing good depiction of the arterial trunk and main branches but poor demonstration of interlobar and arcuate arteries. The portal trunk was well depicted in 12/18 cases, but CO2 angiography results were insufficient in 3 cases because of poor catheter wedging in the hepatic vein and in 2 cases because of CO2 drainage by an accessory hepatic vein. Peripheral circulation was clearly depicted in 5/7 cases, while there was incomplete filling of the abdominal aorta and of iliac and femoral arteries in 2 cases. We had only one transient complication (2.57%) due to mesenteric ischemia during an aortic injection, with mild abdominal pain and diarrhea which subsided spontaneously in few minutes. In our experience the CO2-Angioset delivery system has proved to be a simple and safe tool, particularly suitable for use in patients at risk for allergic reactions to iodinated contrast agents and in those with renal function impairment. Also, the system can help carry out some interventional procedures such as arteriovenous fistula embolization and transjugular portosystemic shunting.