[Determination of penicillins by means of an enzymatic electrode].
Penicillin sensitive enzyme electrodes were prepared on the basis of native penicillinase (EC 22.214.171.124) and penicillinamidase (CE 18.104.22.168), as well as penicillinase entrapped in a complex of polyethylenimine and polyacrylic acid or linked with albumin and lattice entrapped penicillinase. The time of the electrode response is 2-10 minutes. The electrode potential change within a minute is linear at 1-20 mM of benzylpenicillin and depends on the electrode type. The electrodes prepared on the basis of the native enzymes lost their sensitivity within the first 10 days. Sensitivity of immobilized penicillinase did not change for 15 days. The electrodes prepared on the basis of albumin-linked penicillinase preserved their high stability for 60 days. The sensitivity of these electrodes is slightly dependent on the phosphate buffer concentration (from 0.001 to 9 mM).


Sex-role orientation and attachment styles of sex offenders.
Given the increase of individuals who have a history of sexual offenses, there has been an increase in research on the etiology of sex-offending behavior. The present purpose was to evaluate the relationship between sex-role orientation and attachment styles of males who were sex offenders. Analysis yielded statistically significant differences between comparison (n = 22) and clinical groups (n = 21) in gender roles, with little sign of the androgynous gender type for sex offenders. The offender group showed significantly lower frequency of androgyny scores and significantly higher scores on feminine and undifferentiated orientations, supporting the theoretical view of sex offenders as being "cross-sex-typed." In addition, the sex offender group had a significantly higher mean score on anxious-avoidant relationship attachment. Based on the present findings, there appears to be a need to help sex offenders explore how their gender roles may relate to their sex-offending behavior and assist sex offenders in the development of adaptive relationships with reduced anxiety and ambivalence.


Giant cell arteritis mimicking idiopathic orbital inflammatory disease.
To report an unusual presentation of giant cell arteritis, referred from primary care, mimicking orbital apex syndrome. A 72 year old woman was referred with a two week history of pyrexia, dull right eye ache, 2mm of right proptosis, mild conjunctival chemosis and restriction of right eye movements. An erythrocyte sedimentation rate (ESR) was 90 and fluorescein angiography showed almost complete choroidal non-perfusion suggestive of giant cell arteritis. Temporal artery biopsy confirmed the diagnosis. Giant cell arteritis (GCA) typically presents with anterior ischemic optic neuropathy (AION), choroidal ischemia, central retinal artery occlusion, infrequently manifesting as an ocular motility problem, but has rarely been known to mimick idiopathic orbital inflammatory disease. Prompt recognition and therapy can minimize the chance of ipsilateral ocular involvement and protect the fellow eye.


[Cerebral oximetry in neurosurgical patients with cerebrovascular diseases. II. Comparison of electrophysiological methods of examination and cerebral oximetry].
Simultaneous monitoring by cerebral oximetry and electrophysiological methods (electroencephalography and electrocorticography) was performed in 21 patients with arterial cerebral aneurysms during direct intracranial interventions, endovascular interventions, and Matas' test. Electrophysiological methods are sufficiently accurate indicators of cerebral ischemia even at a functionally reversible level. The results of simultaneous monitoring were similar in 80% cases, indicating cerebral ischemia even at functionally reversible level, which was detected by both electrophysiological methods and cerebral oximetry. Variously directed shifts were detected in 4 cases; the causes are discussed. Cerebral oximetry detects cerebral ischemia with a sensitivity similar to that of electrophysiological methods. The method does not depend on temperature or anesthetics. Limitations of the method are due to its local application.


Inducible reporter/driver lines for the Arabidopsis root with intrinsic reporting of activity state.
Cell-, tissue- or organ-specific inducible expression systems are powerful tools for functional analysis of changes to the pattern, level or timing of gene expression. However, plant researchers lack standardised reagents that promote reproducibility across the community. Here, we report the development and functional testing of a Gateway-based system for quantitatively, spatially and temporally controlling inducible gene expression in Arabidopsis that overcomes several drawbacks of the legacy systems. We used this modular driver/effector system with intrinsic reporting of spatio-temporal promoter activity to generate 18 well-characterised homozygous transformed lines showing the expected expression patterns specific for the major cell types of the Arabidopsis root; seed and plasmid vectors are available through the Arabidopsis stock centre. The system's tight regulation was validated by assessing the effects of diphtheria toxin A chain expression. We assessed the utility of Production of Anthocyanin Pigment 1 (PAP1) as an encoded effector mediating cell-autonomous marks. With this shared resource of characterised reference driver lines, which can be expanded with additional promoters and the use of other fluorescent proteins, we aim to contribute towards enhancing reproducibility of qualitative and quantitative analyses.


Continuous Adaptive Evolution of a Fast-Growing Corynebacterium glutamicum Strain Independent of Protocatechuate.
Corynebacterium glutamicum is a commonly applied host for the industrial production of amino acids. While valued for its robustness, it is somewhat inferior to competing strains such as Escherichia coli because of the relatively low growth rate of 0.40 h-1 in synthetic, industrial media. Accordingly, adaptive laboratory evolution (ALE) experiments were performed in continuous cultivation mode to select for a growth-improved host. To ensure industrial attractiveness, this ALE study aimed at a reduction of dependency on costly growth-boosting additives such as protocatechuate (PCA) or complex media supplements. Consequently, double selection pressures were installed consisting of a steady increase in growth rate demands and a parallel reduction of complex medium fractions. Selection yielded C. glutamicum EVO5 achieving 0.54 h-1 and 1.03 gGlc gCDW -1 h-1 in minimal medium without abovementioned supplements. Sequencing revealed 10 prominent mutations, three of them in key regulator genes.


Conformational equilibria of alpha-L-iduronate residues in disaccharides derived from heparin.
The disaccharides IdoA(2SO3)-anManOH(6SO3) and IdoA-anManOH (where IdoA represents alpha-L-iduronate, anManOH represents 2,5-anhydro-D-mannitol and SO3 represents sulphate ester) were prepared from bovine lung heparin using HNO2 depolymerization, borohydride reduction and desulphation, and were examined by 400 MHz 1H-n.m.r. spectroscopy. Three-bond proton-proton coupling constants around the IdoA ring were determined under a range of experimental conditions. For unsulphated IdoA all four proton-proton coupling constants varied markedly as a function of temperature, pH and solvent, providing clear evidence for a rapid conformational equilibrium. These data were analysed in terms of the three most energetically stable IdoA conformers: 1C4, 4C1, and 2S0. Predicted coupling constants for these conformers were determined using a modified Karplus-type relationship. For unsulphated IdoA in dimethyl sulphoxide the equilibrium was provoked strongly in favour of a slightly distorted 4C1 'chair' IdoA conformer for which coupling constants have not previously been reported. For sulphated IdoA in aqueous conditions and at low pH the equilibrium is strongly in favour of the alternative 1C4 chair conformer. Under many conditions, however, significant contributions from all three conformers occur for the non-reducing terminal IdoA in these disaccharides.


Microglial NLRP3 inflammasome activation-mediated inflammation promotes prolactinoma development.
Prolactinomas have harmful effects on human health, and the pathogenesis is still unknown. Furthermore, 25% of prolactinoma patients do not respond to the therapy of dopamine receptor agonist in the clinic. Thus, it is important to reveal the pathogenesis and develop new therapeutic methods for prolactinomas. Herein, two animal models of prolactinomas, namely oestrogen-treated rats and transgenic D2 dopamine receptor-deficient mice, were used. PET/CT imaging detection showed that translocator protein-mediated microglia activation and inflammation significantly increased in the pituitary glands of prolactinomas rats. Messenger RNA microarrays were used to analyze and compare the differential gene and signal pathways of the pituitary glands between control and prolactinomas rats. Statistical results pertaining to gene enrichment showed that the innate immune response genes were upregulated in the pituitary glands of prolactinoma rats. This suggested that the innate immune response was activated. We analyzed the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome that is one of the most important members of the innate immune system in mammals and found that the expressions of NLRP3, Caspase-1, apoptosis-associated speck-like, interleukin 1B (IL1B) and IL18 proteins of pituitary glands in prolactinomas rats were increased considerably compared with those in control rats. This suggested the activation of the NLRP3 inflammasome during the emergence and evolution of prolactinomas. Immunohistochemistry results also confirmed that the NLRP3 expression was elevated in human prolactinoma tissues, and the microglia marker-ionised calcium binding adaptor molecule-1 was co-located with the NLRP3 protein in prolactinomas by immunofluorescence assay. Finally, compared with the WT mice, NLRP3-/- mice had smaller pituitary glands (weight/body weight) and diminished prolactin (PRL) expressions and secretions. These findings were associated with a reduction in the caspase-1 activation and maturation of IL1B. Furthermore, MCC950 decreased the PRL expression and secretion following the inhibition of NLRP3 inflammasome activation in GH3 cells stimulated with lipopolysaccharide and nigericin. And MCC950 inhibited the pituitary tumor overgrowth and PRL expression and secretion in prolactinoma rats. These data confirm that the microglial NLRP3 inflammasome activation upregulates the inflammatory cytokines IL1/IL18 in the pituitary glands and induces prolactinomas. Our findings showed that microglial NLRP3 inflammasome activation-mediated IL1B-related inflammation promoted the development of prolactinomas and identified the inflammasome as a new therapeutic target for prolactinomas.


Wood hydrolysate barriers: performance controlled via selective recovery.
Films and coatings were produced from a noncellulosic polysaccharide-rich wood hydrolysate (WH), and the resulting oxygen barrier performance was improved by a selective choice of upgrading conditions. The WH was obtained from process water in the hydrothermal treatment of hardwood and subjected to one of three alternative upgrading treatments, resulting in xylan-rich fractions with significant differences in structure, composition, and properties of the recovered WH fractions, which in turn had a major impact on their performance with respect to tensile and oxygen barrier properties. The WH in the least upgraded state, the crudest fraction, produced films with the best performance in terms of oxygen permeability and was superior to corresponding films based on highly purified hemicellulose.


Evidence for global electron transportation into the jovian inner magnetosphere.
Jupiter's magnetosphere is a strong particle accelerator that contains ultrarelativistic electrons in its inner part. They are thought to be accelerated by whistler-mode waves excited by anisotropic hot electrons (>10 kiloelectron volts) injected from the outer magnetosphere. However, electron transportation in the inner magnetosphere is not well understood. By analyzing the extreme ultraviolet line emission from the inner magnetosphere, we show evidence for global inward transport of flux tubes containing hot plasma. High-spectral-resolution scanning observations of the Io plasma torus in the inner magnetosphere enable us to generate radial profiles of the hot electron fraction. It gradually decreases with decreasing radial distance, despite the short collisional time scale that should thermalize them rapidly. This indicates a fast and continuous resupply of hot electrons responsible for exciting the whistler-mode waves.


Activating systemic T-cell immunity against self tumor antigens to support oncolytic virotherapy with vesicular stomatitis virus.
We have shown that the antitumor activity of vesicular stomatitis virus (VSV) against B16ova tumors in C57BL/6 mice is predominantly due to innate antiviral immune effectors. We have also shown that the innate immune-activating properties of VSV can be harnessed to prime adaptive T-cell responses against a tumor-associated antigen (TAA) if the virus is engineered to express the cDNA of the antigen. Here, we show that the combination of VSV expressing OVA as a model tumor antigen, along with adoptive T-cell therapy targeted against the same antigen, is superior to either treatment alone and induces systemic antitumor activity. In addition, we extend our findings with the OVA model to the therapeutic use of VSV expressing hgp100, a self TAA against which tolerance is well established in C57BL/6 mice. In contrast to VSV-ova, T-cell responses raised by VSV-hgp100 were insufficient to improve therapy against B16ova tumors compared with VSV-GFP alone. However, in combination with adoptive transfer of gp100-specific pmel T cells, intratumoral VSV-hgp100 cured significantly more mice than either virus or T cells alone. Even in an aggressive model of metastatic disease, antitumor therapy was generated at levels similar to those observed in the VSV-ova/OT-I model in which a potently immunogenic, nonself TAA was targeted. Therefore, individual poorly effective virotherapies and T-cell therapies that target self TAA of low immunogenicity, which reflects the situation in patients, can be combined to generate very effective antitumor therapy.


Complex Interplay between FleQ, Cyclic Diguanylate and Multiple σ Factors Coordinately Regulates Flagellar Motility and Biofilm Development in Pseudomonas putida.
Most bacteria alternate between a free living planktonic lifestyle and the formation of structured surface-associated communities named biofilms. The transition between these two lifestyles requires a precise and timely regulation of the factors involved in each of the stages that has been likened to a developmental process. Here we characterize the involvement of the transcriptional regulator FleQ and the second messenger cyclic diguanylate in the coordinate regulation of multiple functions related to motility and surface colonization in Pseudomonas putida. Disruption of fleQ caused strong defects in flagellar motility, biofilm formation and surface attachment, and the ability of this mutation to suppress multiple biofilm-related phenotypes associated to cyclic diguanylate overproduction suggests that FleQ mediates cyclic diguanylate signaling critical to biofilm growth. We have constructed a library containing 94 promoters potentially involved in motility and biofilm development fused to gfp and lacZ, screened this library for FleQ and cyclic diguanylate regulation, and assessed the involvement of alternative σ factors σN and FliA in the transcription of FleQ-regulated promoters. Our results suggest a dual mode of action for FleQ. Low cyclic diguanylate levels favor FleQ interaction with σN-dependent promoters to activate the flagellar cascade, encompassing the flagellar cluster and additional genes involved in cyclic diguanylate metabolism, signal transduction and gene regulation. On the other hand, characterization of the FleQ-regulated σN- and FliA-independent PlapA and PbcsD promoters revealed two disparate regulatory mechanisms leading to a similar outcome: the synthesis of biofilm matrix components in response to increased cyclic diguanylate levels.


The major immunogenic epitopes of Epstein-Barr virus (EBV) nuclear antigen 1 are encoded by sequence domains which vary among nasopharyngeal carcinoma biopsies and EBV-associated cell lines.
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is a protein expressed consistently in EBV-infected cells and EBV-associated malignant tissues. A panel of monoclonal antibodies (MAbs) was generated against the C terminus of EBNA-1 and evaluated for the detection of EBNA-1 in different cell lines. The epitopes recognized were mapped. Since sequence variations of EBNA-1 have been reported in nasopharyngeal carcinoma (NPC) tissues and in infected healthy individuals, the ability of these MAbs to recognize a recombinant protein derived from an NPC biopsy was also analysed. MAb 4H11 appeared to react with EBNA-1 sequences from different sources, whereas MAbs 5C11, 5F12 and 8F6 failed to recognize a recombinant EBNA-1 protein cloned from an NPC patient. Using different recombinant EBNA-1 fragments in an immunoblot format, this study demonstrates that the domain bounded by amino acids 408 and 498 is very immunogenic in mice in that epitopes in this region are recognized by various MAbs. Amino acid sequences of EBNA-1 were also deduced from nucleotide sequences amplified from three Burkitt's lymphoma cell lines, two spontaneous lymphoblastoid cell lines, two NPC biopsies and one NPC hybrid cell line, NPC-KT, and compared to the sequence from B95-8. The amino acid sequence of EBNA-1 in Akata is almost identical to that in an NPC biopsy, except for amino acid 585. The results of this study indicate that the immunogenic epitopes of EBNA-1 are highly variable.


Increased respiration in the sch9Delta mutant is required for increasing chronological life span but not replicative life span.
Loss of the protein kinase Sch9p increases both the chronological life span (CLS) and the replicative life span (RLS) of Saccharomyces cerevisiae by mimicking calorie restriction, but the physiological consequences of SCH9 deletion are poorly understood. By transcriptional profiling of an sch9Delta mutant, we show that mitochondrial electron transport chain genes are upregulated. Accordingly, protein levels of electron transport chain subunits are increased and the oxygen consumption rate is enhanced in the sch9Delta mutant. Deletion of HAP4 and CYT1, both of which are essential for respiration, revert the sch9Delta mutant respiratory rate back to a lower-than-wild-type level. These alterations of the electron transport chain almost completely blocked CLS extension by the sch9Delta mutation but had a minor impact on the RLS. SCH9 thus negatively regulates the CLS and RLS through inhibition of respiratory genes, but a large part of its action on life span seems to be respiration independent and might involve increased resistance to stress. Considering that TOR1 deletion also increases respiration and that Sch9p is a direct target of TOR signaling, we propose that SCH9 is one of the major effectors of TOR repression of respiratory activity in glucose grown cells.


Phenotypic diversity of starch granules in cassava germplasm.
Demand for the development of cassava varieties with different native starches has guided the search for these characteristics in the germplasm of Manihot esculenta Crantz. Therefore, the objective of this study was to estimate the genetic diversity of cassava accessions for root and starch granule characteristics to guide the future industrial application of this species. Starches from 56 accessions were evaluated for the number of granules in 1 g of starch (NTG), area (AG, μm2), length (LG, μm), width (WG, μm), starch granule roundness (Round), dry matter content in the roots (DMC, %), pulp color (PulCo), and cyanogenic compounds (HCN). Images captured by light microscopy were used to determine the average phenotypic values, and these were further analyzed by principal component analysis (PCA) considering mixed data (quantitative and qualitative). Significant differences between the cassava accessions for all traits measured revealed wide variability in starch granule characteristics. Four diversity groups with better fitness for the classification of cassava accessions based on PulCo were identified, in comparison with HCN. Accessions with differential starch characteristics were identified, and crossings for the generation of segregating populations in order to obtain table and industry varieties have been proposed.


Prevalence of Listeria monocytogenes in, and microbiological and sensory quality of, rainbow trout, whitefish, and vendace roes from Finnish retail markets.
The prevalence of Listeria monocytogenes in retail roe, as well as the microbiological and sensory qualities of the roe, were studied for three fish species under three different storage conditions. A total of 147 Finnish rainbow trout (Oncorhynchus mykiss), whitefish (Coregonus lavaretus), vendace (Coregonus albula), and burbot (Lota lota) roe samples were bought fresh, frozen, or frozen-thawed from Finnish retail markets. The overall prevalence of L. monocytogenes was 5%; however, the prevalence of the pathogen in fresh roe was 18%. Fresh-bought roe tested positive for Listeria spp. and for L. monocytogenes, respectively, 5 and 20 times as often as did frozen and frozen-thawed roe products combined. The microbiological quality (analyzed as total aerobic heterotrophic bacteria and coliform bacteria) of 78% of the roe samples was unacceptable. Frozen roe samples were found to have the best microbiological quality. According to the results of a sensory evaluation, at least one sensory attribute (appearance, odor freshness, texture, and freshness of taste) was unacceptable for 29% of the roe samples studied. The sensory quality of roe samples bought fresh was better than that of roe samples bought frozen or frozen-thawed. From the results of this study, it is concluded that both the microbiological and the sensory qualities of roe at the retail level need to be improved.


How Is Pain Influenced by Cognition? Neuroimaging Weighs In.
Neuroimaging can inform cognitive theories to the extent that particular patterns of brain activity are sensitively and specifically associated with particular types of cognitive processes. We illustrate the utility of neuroimaging data in one specific case: understanding cognitive influences on pain. We first argue that pain self-reports are often inadequate to fully characterize pain experience and the processes that underlie it. Then, we describe how neuroimaging measures have been used to corroborate the effects of psychological manipulations on pain by focusing on placebo treatments and demonstrating effects on the best available correlates of pain experience. In addition, using placebo analgesia as an example, we argue that brain evidence is useful for building psychological theories likely to yield valid and generalizable predictions, because biologically informed theories are grounded in the constraints inherent in the relevant physiological systems. Finally, we suggest that neuroimaging findings will become increasingly useful for constraining psychological inference as brain patterns diagnostic of particular types of mental events are identified and characterized. In our view, the relationships between biological findings and cognitive theory are empirically based and must develop through an iterative process of synthesis across studies, topics, and methods.


NaPO(4) cotransport type III (PiT1) expression in human embryonic kidney cells and regulation by PTH.
The aim of the present study was to characterize the type(s) of NaPO(4) cotransporter expressed in the human renal cell line HEK-293 and its regulation by parathyroid hormone (PTH) in wild-type cells and in cells transfected by the PTH/PTH-related protein (PTHrP) receptor. The results showed that human embryonic kidney HEK-293 cells expressed NaPO(4) cotransporter type III (PiT1) mRNA and protein. In contrast, type I (NPT1) or II (NPT2) cotransporter mRNA were not expressed. Na(+)-dependent phosphate uptake followed a Michaelis-Menten model (apparent maximal transport rate and affinity constant: 23.32 +/- 0.69 nmol PO(4). mg protein(-1). 10 min(-1) and 0.147 +/- 0.014 mM KH(2)PO(4), respectively), was stimulated by phosphate deprivation (maximal increase 24.5 +/- 0.8%, P < 0.001, after 15 h of phosphate deprivation), and was inhibited by increasing pH (3.6 +/- 0.2-fold decrease at pH 8.5, P < 0.0001). It was inhibited in a time- and concentration-dependent fashion by PTH in HEK-293 cells stably transfected by PTH/PTHrP receptors but not in parental HEK-293 cells. Maximal inhibition of Na(+)-dependent phosphate transport was observed at 30 min after the addition of 72 nM PTH-(1-34) (31.5 +/- 2.4% inhibition, P < 0.01). PTH inhibition of phosphate transport was maintained in phosphate-deprived cells and reversed by both GF109203X (10(-6) M) or staurosporine (5.5 nM), two protein kinase C inhibitors. Na(+)-dependent phosphate uptake was also significantly inhibited by phorbol 12-myristate 13-acetate (20.9 +/- 3.9% inhibition, P < 0.001) but not by dibutyril-cAMP (10(-4) M) or forskolin (50 microM). The physiological role played by type III NaPO(4) cotransport expression in the overall renal regulation of phosphate homeostasis remains to be established.


Ten good reasons to consider biological processes in prevention and intervention research.
Most contemporary accounts of psychopathology acknowledge the importance of both biological and environmental influences on behavior. In developmental psychopathology, multiple etiological mechanisms for psychiatric disturbance are well recognized, including those operating at genetic, neurobiological, and environmental levels of analysis. However, neuroscientific principles are rarely considered in current approaches to prevention or intervention. In this article, we explain why a deeper understanding of the genetic and neural substrates of behavior is essential for the next generation of preventive interventions, and we outline 10 specific reasons why considering biological processes can improve treatment efficacy. Among these, we discuss (a) the role of biomarkers and endophenotypes in identifying those most in need of prevention; (b) implications for treatment of genetic and neural mechanisms of homotypic comorbidity, heterotypic comorbidity, and heterotypic continuity; (c) ways in which biological vulnerabilities moderate the effects of environmental experience; (d) situations in which Biology x Environment interactions account for more variance in key outcomes than main effects; and (e) sensitivity of neural systems, via epigenesis, programming, and neural plasticity, to environmental moderation across the life span. For each of the 10 reasons outlined we present an example from current literature and discuss critical implications for prevention.


Increased Flexibility between Stems of Intramolecular Three-Way Junctions by the Insertion of Bulges.
Intramolecular junctions are a ubiquitous structure within DNA and RNA; three-way junctions in particular have high strain around the junction because of the lack of flexibility, preventing the junctions from adopting conformations that would allow for optimal folding. In this work, we used a combination of calorimetric and spectroscopic techniques to study the unfolding of four intramolecular three-way junctions. The control three-way junction, 3H, has the sequence d(GAAATTGCGCT5GCGCGTGCT5GCACAATTTC), which has three arms of different sequences. We studied three other three-way junctions in which one (2HS1H), two (HS12HS1), and three (HS1HS1HS1) cytosine bulges were placed at the junction to allow the arms to adopt a wider range of conformations that may potentially relieve strain. Through calorimetric studies, it was concluded that bulges produce only minor effects on the enthalpic and thermal stability at physiological salt concentrations for 2HS1H and HS1HS1HS1. HS12HS1 displays the strongest effect, with the GTGC stem lacking a defined transition. In addition to unfolding thermodynamics, the differential binding of counterions, water, and protons was determined. It was found that with each bulge, there was a large increase in the binding of counterions; this correlated with a decrease in the immobilization of structural water molecules. The increase in counterion uptake upon folding likely displaces binding of structural water, which is measured by the osmotic stress method, in favor of electrostricted waters. The cytosine bulges do not affect the binding of protons; this finding indicates that the bulges are not forming base-triplet stacks. These results indicate that bulges in junctions do not affect the unfolding profile or the enthalpy of oligonucleotides but do affect the number and amount of molecules immobilized by the junction.


COVID-19 myopericarditis with cardiac tamponade in the absence of respiratory symptoms: a case report.
Previous reports have shown various cardiac complications to be associated with COVID-19 including: myocardial infarction, microembolic complications, myocardial injury, arrythmia, heart failure, coronary vasospasm, non-ischemic cardiomyopathy, stress (Takotsubo) cardiomyopathy, pericarditis and myocarditis. These COVID-19 cardiac complications were associated with respiratory symptoms. However, our case illustrates that COVID-19 myopericarditis with cardiac tamponade can present without respiratory symptoms. A 58-year-old Caucasian British woman was admitted with fever, diarrhoea and vomiting. She developed cardiogenic shock and Transthoracic echocardiogram (TTE) found a pericardial effusion with evidence of cardiac tamponade. A nasopharyngeal swab showed a COVID-19 positive result, despite no respiratory symptoms on presentation. A pericardial drain was inserted and vasopressor support required on intensive treatment unit (ITU). The drain was removed as she improved, an antibiotic course was given and she was discharged on day 12. Our case demonstrates that patients without respiratory symptoms could have COVID-19 and develop cardiac complications. These findings can aid timely diagnosis of potentially life-threatening COVID-19 myopericarditis with cardiac tamponade.


Synthesis of N-arylsulfonamides via Fe-promoted reaction of sulfonyl halides with nitroarenes in an aqueous medium.
A fascinating Fe-promoted protocol for the synthesis of N-arylsulfonamides has been developed. Starting from commercially available nitroarenes and sulfonyl chlorides, moderate to excellent yields of the corresponding N-arylsulfonamides can be obtained. In particular, Fe dust serves as the sole reductant in the transformation and it can be easily performed on a large scale.


Multi-parametric radiomics of conventional T1 weighted and susceptibility-weighted imaging for differential diagnosis of idiopathic Parkinson's disease and multiple system atrophy.
This study aims to investigate the potential of radiomics with multiple parameters from conventional T1 weighted imaging (T1WI) and susceptibility weighted imaging (SWI) in distinguishing between idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA). A total of 201 participants, including 57 patients with PD, 74 with MSA, and 70 healthy control (HCs) individuals, underwent T1WI and SWI scans. From the 12 subcortical nuclei (e.g. red nucleus, substantia nigra, subthalamic nucleus, putamen, globus pallidus, and caudate nucleus), 2640 radiomic features were extracted from both T1WI and SWI scans. Three classification models - logistic regression (LR), support vector machine (SVM), and light gradient boosting machine (LGBM) - were used to distinguish between MSA and PD, as well as among MSA, PD, and HC. These classifications were based on features extracted from T1WI, SWI, and a combination of T1WI and SWI. Five-fold cross-validation was used to evaluate the performance of the models with metrics such as sensitivity, specificity, accuracy, and area under the receiver operating curve (AUC). During each fold, the ANOVA and least absolute shrinkage and selection operator (LASSO) methods were used to identify the most relevant subset of features for the model training process. The LGBM model trained by the features combination of T1WI and SWI exhibited the most outstanding differential performance in both the three-class classification task of MSA vs. PD vs. HC and the binary classification task of MSA vs. PD, with an accuracy of 0.814 and 0.854, and an AUC of 0.904 and 0.881, respectively. The texture-based differences (GLCM) of the SN and the shape-based differences of the GP were highly effective in discriminating between the three classes and two classes, respectively. Radiomic features combining T1WI and SWI can achieve a satisfactory differential diagnosis for PD, MSA, and HC groups, as well as for PD and MSA groups, thus providing a useful tool for clinical decision-making based on routine MRI sequences.


Incidence and Predictors of Thrombotic Complications in 4742 Patients with COVID-19 or Other Acute Infectious Respiratory Diseases: A Propensity Score-Matched Study.
A prothrombotic state, attributable to excessive inflammation, cytokine storm, hypoxia, and immobilization, is a feature of SARS-CoV-2 infection. Up to 30% of patients with severe COVID-19 remain at high risk of thromboembolic events despite anticoagulant administration, with adverse impact on in-hospital prognosis. We retrospectively studied 4742 patients with acute infectious respiratory disease (AIRD); 2579 were diagnosed to have COVID-19 and treated with heparin, whereas 2163 had other causes of AIRD. We compared the incidence and predictors of total, arterial, and venous thrombosis, both in the whole population and in a propensity score-matched subpopulation of 3036 patients (1518 in each group). 271 thrombotic events occurred in the whole population: 121 (4.7%) in the COVID-19 group and 150 (6.9%) in the no-COVID-19 group (p < 0.001). No differences in the incidence of total (p = 0.11), arterial (p = 0.26), and venous (p = 0.38) thrombosis were found between the two groups after adjustment for confounding clinical variables and in the propensity score-matched subpopulation. Likewise, there were no significant differences in bleeding rates between the two groups. Clinical predictors of arterial thrombosis included age (p = 0.006), diabetes mellitus (p = 0.034), peripheral artery disease (p < 0.001), and previous stroke (p < 0.001), whereas history of solid cancer (p < 0.001) and previous deep vein thrombosis (p = 0.007) were associated with higher incidence of venous thrombosis. Hospitalized patients with COVID-19 treated with heparin do not seem to show significant differences in the cumulative incidence of thromboembolic events as well as in the incidence of arterial and venous thrombosis separately, compared with AIRD patients with different etiological diagnosis.


[Influence of tetramethylthiuramide sulfide on the exocrine function of the pancreas].
The influence of different doses of tetramethylthiuramine sulphide (TMTDS) on the activity of the amylase, lipase and proteases in the pancreatic homogenate and the small intestine contents of albino rats was studied. Six hours after a single administration of the compound in a dose of 1/3 DL50 a 2--2.5-fold drop of the enzymatic activity in the chyme was observed and 24 hours thereafter it was inhibited in the glandular tissue as well. During the first months of a lenghty introduction of relatively small doses of TMTDS (1/20 and 1/50 DL50) a depression of the exosecretory function of the pancreas with its subsequent restoration at the 4--6th month was noted. Atropinization of the animals failed to prevent the inhibitory action of the compound on the secretion of pancreatic enzymes, this pointing to a direct effect of TMTDS on the acinal cells or to prevailing distrubances of humoral mechanisms regulating the activity of the glands.


Cranial muscles in amphibians: development, novelties and the role of cranial neural crest cells.
Our research on the evolution of the vertebrate head focuses on understanding the developmental origins of morphological novelties. Using a broad comparative approach in amphibians, and comparisons with the well-studied quail-chicken system, we investigate how evolutionarily conserved or variable different aspects of head development are. Here we review research on the often overlooked development of cranial muscles, and on its dependence on cranial cartilage development. In general, cranial muscle cell migration and the spatiotemporal pattern of cranial muscle formation appears to be very conserved among the few species of vertebrates that have been studied. However, fate-mapping of somites in the Mexican axolotl revealed differences in the specific formation of hypobranchial muscles (tongue muscles) in comparison to the chicken. The proper development of cranial muscles has been shown to be strongly dependent on the mostly neural crest-derived cartilage elements in the larval head of amphibians. For example, a morpholino-based knock-down of the transcription factor FoxN3 in Xenopus laevis has drastic indirect effects on cranial muscle patterning, although the direct function of the gene is mostly connected to neural crest development. Furthermore, extirpation of single migratory streams of cranial neural crest cells in combination with fate-mapping in a frog shows that individual cranial muscles and their neural crest-derived connective tissue attachments originate from the same visceral arch, even when the muscles attach to skeletal components that are derived from a different arch. The same pattern has also been found in the chicken embryo, the only other species that has been thoroughly investigated, and thus might be a conserved pattern in vertebrates that reflects the fundamental nature of a mechanism that keeps the segmental order of the head in place despite drastic changes in adult anatomy. There is a need for detailed comparative fate-mapping of pre-otic paraxial mesoderm in amphibians, to determine developmental causes underlying the complicated changes in cranial muscle development and architecture within amphibians, and in particular how the novel mouth apparatus in frog tadpoles evolved. This will also form a foundation for further research into the molecular mechanisms that regulate rostral head morphogenesis. Our empirical studies are discussed within a theoretical framework concerned with the evolutionary origin and developmental basis of novel anatomical structures in general. We argue that a common developmental origin is not a fool-proof guide to homology, and that a view that sees only structures without homologs as novel is too restricted, because novelties must be produced by changes in the same framework of developmental processes. At the level of developmental processes and mechanisms, novel structures are therefore likely to have homologs, and we need to develop a hierarchical concept of novelty that takes this into account.


Comparison of nevirapine plasma concentrations between lead-in and steady-state periods in Chinese HIV-infected patients.
To investigate the potential of nevirapine 200 mg once-daily regimen and evaluate the influence of patient characteristics on nevirapine concentrations. This was a prospective, multicentre cohort study with 532 HIV-infected patients receiving nevirapine as a part of their initial antiretroviral therapy. Plasma samples were collected at trough or peak time at the end of week 2 (lead-in period) and week 4, 12, 24, 36, and 48 (steady-state period), and nevirapine concentrations were determined using a validated HPLC method. Potential influencing factors associated with nevirapine concentrations were evaluated using univariate and multivariate logistic regression. A total of 2348 nevirapine plasma concentrations were collected, including 1510 trough and 838 peak values. The median nevirapine trough and peak concentration during the lead-in period were 4.26 µg/mL (IQR 3.05-5.61) and 5.07 µg/mL (IQR 3.92-6.44) respectively, which both exceeded the recommended thresholds of nevirapine plasma concentrations. Baseline hepatic function had a moderate effect on median nevirapine trough concentrations at week 2 (4.25 µg/mL v.s. 4.86 µg/mL, for ALT <1.5 × ULN and ≥ 1.5 × ULN, respectively, P = 0.045). No significant difference was observed in median nevirapine trough concentration between lead-in and steady-state periods in patients with baseline ALT and AST level ≥ 1.5 × ULN (P = 0.171, P = 0.769), which was different from the patients with ALT/AST level <1.5ULN. The median trough concentrations were significantly higher in HIV/HCV co-infected patients than those without HCV at week 48 (8.16 µg/mL v.s. 6.15 µg/mL, P = 0.004). The 200 mg once-daily regimen of nevirapine might be comparable to twice-daily in plasma pharmacokinetics in Chinese population. Hepatic function prior to nevirapine treatment and HIV/HCV coinfection were significantly associated with nevirapine concentrations.


Prophylactic implantable cardioverter defibrillator treatment in patients with end-stage heart failure awaiting heart transplantation.
This study was designed to delineate the role of implantable cardioverter defibrillator (ICD) therapy for the primary and secondary prevention of sudden cardiac death in patients listed for heart transplantation. Retrospective observational multicentre study. 1089 consecutive patients listed for heart transplantation in two tertiary heart transplant centres were enrolled. Of 550 patients (51%) on the transplant list with an ICD, 216 had received their ICD for the primary prevention of sudden cardiac death and 334 for secondary prevention. 539 patients did not receive an ICD. Treatment with or without an ICD was left to the discretion of the heart failure specialist. All-cause mortality. ICDs appear to be associated with a reduction in all-cause mortality in patients implanted with the device for primary and secondary prevention compared to those without an ICD despite a median time on the waiting list of only 8 months (estimated 1-year: 88±3% vs. 77±3% vs. 67±3%; p=0.0001). A Cox regressional hazard model (corrected for age, sex, underlying heart disease, atrial fibrillation, cardiac resynchronisation therapy, New York Heart Association (NYHA) class, ejection fraction, co-medication and year of listing) suggested an independent beneficial effect of ICDs that was most pronounced in patients who had received an ICD for primary prevention (HR 0.4, 95% CI 0.19 to 0.85; p=0.016). ICD implantation appears to be associated with an immediate and sustained survival benefit for patients awaiting heart transplantation.


Meningitis due to Moraxella nonliquefaciens in a paediatric patient: a case report and review of the literature.
Introduction.Moraxella nonliquefaciens is an unusual organism to be isolated from cerebral spinal fluid (CSF) and there exists only one case report of M. nonliquefaciens meningitis from a neonate. Moraxella species normally exist as part of the human upper respiratory tract flora and rarely cause invasive human disease. There are only a handful of case reports implicating the organism as a cause of endocarditis, bacteraemia, septic arthritis and endophthalmitis. Identification to the species level based on routine laboratory techniques has been challenging, with final identification often made through 16S rRNA sequencing. With the use of a newer diagnostic tool, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS, we were able to rapidly identify the organism and initiate appropriate treatment. Case presentation. We present a rare care of M. nonliquefaciens meningitis in a paediatric patient with an underlying cranial anatomical defect due to Crouzon syndrome. She had been admitted to hospital 3 months previously with Streptococcus pneumoniae meningitis and mastoiditis, and returned to the emergency department with meningismus. CSF culture grew M. nonliquefaciens. She was treated with ceftriaxone with rapid improvement and eventually was taken for endoscopic surgical repair of a right encephalocele defect. Conclusion. The use of MALDI-TOF MS allowed for the rapid identification of the organism. The patient recovered with appropriate antimicrobial therapy and eventual surgical correction. An underlying anatomical defect should be considered in all patients who present with meningitis due to this unusual organism.


Bacterial variability in the mammalian gut captured by a single-cell synthetic oscillator.
Synthetic gene oscillators have the potential to control timed functions and periodic gene expression in engineered cells. Such oscillators have been refined in bacteria in vitro, however, these systems have lacked the robustness and precision necessary for applications in complex in vivo environments, such as the mammalian gut. Here, we demonstrate the implementation of a synthetic oscillator capable of keeping robust time in the mouse gut over periods of days. The oscillations provide a marker of bacterial growth at a single-cell level enabling quantification of bacterial dynamics in response to inflammation and underlying variations in the gut microbiota. Our work directly detects increased bacterial growth heterogeneity during disease and differences between spatial niches in the gut, demonstrating the deployment of a precise engineered genetic oscillator in real-life settings.


Effect of radix Salviae miltiorrhizae on nitric oxide in cerebral ischemic-reperfusion injury.
It has been postulated that nitric oxide (NO) is produced in significant amount on reperfusion of ischemic brain and could cause brain edema and cell death. This study was undertaken in an attempt to determine whether Radix Salviae Miltiorrhizae (RSM) could reduce cerebral NO contents in 4-vessel occlusion rat model after 30 min of global ischemia and 15 min of reperfusion. There was a significant increase in cerebral NO level in untreated animals as compared with sham-operated ones. By pretreatment with RSM the cerebral NO concentration was reduced to normal level. The possibilities of neuroprotective role of RSM in cerebral ischemic-reperfusion injury were discussed.


Financial viability, medical technology, and hospital closures.
Informed investments in medical technology and information systems are associated with the financial viability of community hospitals. Financially distressed facilities are 3 to 4 years behind proactive hospitals in supporting high-speed data, voice, and image transmissions to physicians in various locations. Impact of the Balanced Budget Act of 1997, fraud and abuse activities, Y2K issues, and lack of information systems support for physicians will result in 800 hospital closures and mergers of distressed hospitals over the next 60 months. These findings are based on the application of an eight-step framework for classifying information systems in health care entities. This framework is validated by survey instruments, site visits, interviews with senior management in 44 health care entities containing 576 hospitals, and judgments on the financial status of the health care entities.


Orosomucoid-1 Arises as a Shared Altered Protein in Two Models of Multiple Sclerosis.
Multiple sclerosis (MS) is a complex autoimmune and neurodegenerative disorder that affects the central nervous system (CNS). It is characterized by a heterogeneous disease course involving demyelination and inflammation. In this study, we utilized two distinct animal models, cuprizone (CPZ)-induced demyelination and experimental autoimmune encephalomyelitis (EAE), to replicate various aspects of the disease. We aimed to investigate the differential CNS responses by examining the proteomic profiles of EAE mice during the peak disease (15 days post-induction) and cuprizone-fed mice during the acute phase (38 days). Specifically, we focused on two different regions of the CNS: the dorsal cortex (Cx) and the entire spinal cord (SC). Our findings revealed varied glial, synaptic, dendritic, mitochondrial, and inflammatory responses within these regions for each model. Notably, we identified a single protein, Orosomucoid-1 (Orm1), also known as Alpha-1-acid glycoprotein 1 (AGP1), that consistently exhibited alterations in both models and regions. This study provides insights into the similarities and differences in the responses of these regions in two distinct demyelinating models.


Conformity and change: community effects on female genital cutting in Kenya.
In this article, I analyze women's decisions to have their daughters circumcised based on data from 7,873 women in Kenya collected in the 1998 Kenya Demographic and Health Survey. I use multilevel models to assess the degree to which women s decisions are correlated with the decisions of other women in their community, in addition to studying the effects of socioeconomic characteristics measured at both the individual and community levels. I find some support for modernization theories, which argue that economic development leads to gradual erosion of the practice of female circumcision. However, more community-level variation is explained by the convention hypothesis, which proposes that the prevalence of female circumcision will decline rapidly once parents see that a critical mass of other parents have stopped circumcising their daughters. I also find substantial variation among different ethnic groups in the pace and onset of the decline of female genital cutting.


Isolation of cDNAs encoding the complete sequence of bovine type X collagen. Evidence for the condensed nature of mammalian type X collagen genes.
The complete primary structure of the bovine alpha 1(X) collagen chain was determined by nucleotide sequencing of cDNA clones. The overlapping cDNA clones encode 3144 bp with a 5'-terminal untranslated region of 148 bp, a 2025 bp reading frame and a 3'-terminal untranslated region of 971 bp. This represents the first complete sequence of a mammalian type X collagen cDNA and has allowed a number of informative comparisons to be made with the previously published chick alpha 1(X) sequence. The primary translation products of both bovine and chick type X collagen are 674 amino acid residues in length and there is a 73.3% identity at the amino acid level (67.8% at the base level). Sequence analyses reveal that the greatest degree of identity between the two species occurs within the triple-helical domain and the C-terminal non-collagenous domain, whereas the identity within the N-terminal non-collagenous domain is markedly lower. The interchain disulphide-bonding observed previously within the triple helix of bovine type X collagen is explained by the presence of two cysteine residues within an imperfection of the triple-helical domain encoded by -Gly-Xaa-Cys-Xaa-Yaa-Cys-Xaa-Yaa-Gly-. Southern blot analyses of bovine genomic DNA demonstrate that the bovine type X collagen gene is likely to have a condensed structure, similar to that of the chick, with at least 1.3 kb of the coding sequence being contained within one exon.


Detection and quantification of Geobacter lovleyi strain SZ: implications for bioremediation at tetrachloroethene- and uranium-impacted sites.
Geobacter lovleyi strain SZ reduces hexavalent uranium, U(VI), to U(IV) and is the first member of the metal-reducing Geobacter group capable of using tetrachloroethene (PCE) as a growth-supporting electron acceptor. Direct and nested PCR with specific 16S rRNA gene-targeted primer pairs distinguished strain SZ from other known chlorinated ethene-dechlorinating bacteria and closely related Geobacter isolates, including its closest cultured relative, G. thiogenes. Detection limits for direct and nested PCR were approximately 1 x 10(6) and 1 x 10(4) 16S rRNA gene copies per mul of template DNA, respectively. A quantitative real-time PCR (qPCR) approach increased the sensitivity to as few as 30 16S rRNA gene copies per mul of template DNA but was less specific. Melting curve analysis and comparison of the shapes of amplification plots identified false-positive signals and distinguished strain SZ from G. thiogenes when analyzed separately. These indicators were less reliable when target (strain SZ) DNA and nontarget (G. thiogenes) DNA with high sequence similarity were mixed, indicating that the development of qPCR protocols should not only evaluate specificity but also explore the effects of nontarget DNA on the accuracy of quantification. Application of specific tools detected strain SZ-like amplicons in PCE-dechlorinating consortia, including the bioaugmentation consortium KB-1, and two chlorinated ethene-impacted groundwater samples. Strain SZ-like amplicons were also detected in 13 of 22 groundwater samples following biostimulation at the uranium- and chlorinated solvent-contaminated Integrated Field-Scale Subsurface Research Challenge (IFC) site in Oak Ridge, TN. The numbers of strain SZ-like cells increased from below detection to 2.3 x 10(7) +/- 0.1 x 10(7) per liter groundwater, suggesting that strain SZ-like organisms contribute to contaminant transformation. The G. lovleyi strain SZ-specific tools will be useful for monitoring bioremediation efforts at uranium- and/or chlorinated solvent-impacted sites such as the Oak Ridge IFC site.


Well-controlled viremia reduces the progression of hepatocellular carcinoma in chronic viral hepatitis patients treated with lenvatinib.
Lenvatinib has been approved as one of the first-line treatments for advanced hepatocellular carcinoma (HCC) due to its high treatment efficacy being non-inferior to sorafenib. Previous studies have shown well-controlled viremia contributes to the prognosis of HCC patients receiving first-line sorafenib; hence, we postulated this association might also exist in HCC patients with lenvatinib treatment. From April 2018 to December 2021, 201 unresectable HCC patients with first-line lenvatinib treatment in our institute were assessed. High-effect nucleoside analogues were administered for hepatitis B virus (HBV) control, while direct-acting antivirals were used for hepatitis C virus (HCV) elimination. Based on our previous study, well-controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before lenvatinib. This study enrolled 129 patients, including 85 patients with HBV-related HCC (HBV-HCC) and 44 patients with HCV-related HCC (HCV-HCC), respectively. Progression-free survival (PFS) and overall survival (OS) rates between the two groups were not different. Before administration of lenvatinib, 57.1% of the HBV-HCC patients and 88.4% of the HCV-HCC patients had well-controlled viremia, and their PFS (8.8 vs. 3.1 months, p < 0.001) and OS (30.2 vs. 12.8 months, p = 0.041) were better than those who had uncontrolled viremia; moreover, well-controlled viremia reduced tumor progression in multivariate analysis (Hazard ratio: 0.41, 95% confidence interval: 0.25-0.68, p = 0.001) after adjusting for albumin-bilirubin grade and concurrent treatment. HBV or HCV infection was not associated with tumor progression of HCC patients receiving lenvatinib, but viremia, controlled or not, was.


Defence strategies and antibiotic resistance gene abundance in enterococci under stress by exposure to low doses of peracetic acid.
Peracetic acid (PAA) is an organic compound used efficiently as disinfectant in wastewater treatments. Yet, at low doses it may cause selection; thus, the effect of low doses of PAA on Enterococcus faecium as a proxy of human-related microbial waste was evaluated. Bacteria were treated with increasing doses of PAA (from 0 to 25 mg L-1 min) and incubated in regrowth experiments under non-growing, limiting conditions and under growing, favorable conditions. The changes in bacterial abundance, in bacterial phenotype (number and composition of small cell clusters), and in the abundance of an antibiotic resistance gene (ARG) was evaluated. The experiment demonstrated that the selected doses of PAA efficiently removed enterococci, and induced a long-lasting effect after PAA inactivation. The relative abundance of small clusters increased during the experiment when compared with that of the inoculum. Moreover, under growing favorable conditions the relative abundance of small clusters decreased and the number of cells per cluster increased with increasing PAA doses. A strong stability of the measured ARG was found, not showing any effect during the whole experiment. The results demonstrated the feasibility of low doses of PAA to inactivate bacteria. However, the stress induced by PAA disinfection promoted a bacterial adaptation, even if potentially without affecting the abundance of the ARG.


How Not to Argue for Selective Reproductive Procedures.
Many bioethicists try to secure a moral requirement to select against disability, while wishing to avoid denigrating disabled people. Dan Brock's arguments are representative of this attempt. Brock argues that the harm of giving birth to a disabled child when an able child could be had in its stead is a "nonperson-affecting harm." The harm is creating a world with less opportunity and more diminishment of opportunity. I argue that the presumptions that a life with disability is ceteris paribus a worse life, and that there is an inherent badness in living with a disability are contestable and fail to provide an argument that avoids the objections that disability scholars have voiced to reproductive selection against disability.


Statistical analysis of the overnight and daytime return.
We investigate the two components of the total daily return (close-to-close), the overnight return (close-to-open), and the daytime return (open-to-close), as well as the corresponding volatilities of the 2215 New York Stock Exchange stocks for the 20 year period from 1988 to 2007. The tail distribution of the volatility, the long-term memory in the sequence, and the cross correlation between different returns are analyzed. Our results suggest that (i) the two component returns and volatilities have features similar to that of the total return and volatility. The tail distribution follows a power law for all volatilities, and long-term correlations exist in the volatility sequences but not in the return sequences. (ii) The daytime return contributes more to the total return. Both the tail distribution and the long-term memory of the daytime volatility are more similar to that of the total volatility, compared to the overnight records. In addition, the cross correlation between the daytime return and the total return is also stronger. (iii) The two component returns tend to be anticorrelated. Moreover, we find that the cross correlations between the three different returns (total, overnight, and daytime) are quite stable over the entire 20 year period.


Outcomes of neonatal chylous effusions: A 20-year west-Australian tertiary center experience.
Neonatal chylous effusions are rare entity with limited evidence-based management. We conducted a retrospective review of neonates admitted to King Edward Memorial and Princess Margaret/Perth Children's Hospital over 20 years with laboratory-confirmed chylous effusions. A total of 51 infants with chylous effusion were identified. Median gestational age and birth weight were 35.5 weeks and 2620 grams respectively. Congenital [27/ 51] and acquired [24/51] cases were included. Antenatal interventions were performed in 17/22 with antenatal hydrops and 50/51 needed postnatal drains. Effusions were monitored with serial (≥2) chest ultrasounds in 29/51 infants and multiple (≥5) x-rays in 45/51 infants. Median duration of mechanical ventilation, oxygen requirement, and hospital stay was 294.5 hours, 400 hours, and 49 days respectively. 39/51 received medium chain triglyceride (MCT) diet while 8/51 received octreotide. Six infants died during hospital stay. 12/19 had normal developmental assessment at one-year. The acquired group had higher number of xrays done, need for MCT diet and inotropes, and hospital stay vs congenital group. Duration of drains, radiological investigations and immunoglobulin administration were higher in neonates who received octreotide. Syndromic association, duration of ventilation and oxygenation were risk factors for mortality. In our setting, neonatal chylous effusions are associated with significant morbidity and mortality.


Retrospective analysis of complications associated with dorsal root ganglion stimulation for pain relief in the FDA MAUDE database.
Dorsal root ganglion stimulation is an emerging therapy in the treatment of chronic pain. Compared with traditional spinal cord stimulation, it allows a discretely targeted stimulation profile and may act via differing mechanisms of action. Despite these advantages, little is known about the complications associated with this new modality. We queried the MAUDE (Manufacturer and User Facility Device Experience) database for all entries named 'Dorsal root ganglion stimulator for pain relief' reported between May 1, 2016 and December 31, 2017. We verified these data through the Office of the Freedom of Information Act at the US Food and Drug Administration. We then eliminated duplicate entries and categorized each complication based on the event description. A secondary analysis was performed to characterize the serious adverse events and the severity of new neurologic symptoms and infections. We identified 979 unique episodes following our process of deduplication. Almost half (47%) of entries were categorized as device-related complications, a quarter (28%) as procedural complications, with the remainder as patient complaints (12%), serious adverse events (2.4%), and 'other' complications (4.6%). The majority of complications were managed surgically with revision (n = 488; 49.8%) rather than explant (n = 161; 16.4%) events, respectively. The 'Dorsal root ganglion stimulator for pain relief' device has been publicized as a breakthrough in neuromodulation technologies. As with any new technology, we must proceed with caution and re-evaluate effectiveness as information becomes available. The MAUDE database has provided safety data unique for this device that will aid in informed consent and further refinement of this innovative therapy.


Active matter logic for autonomous microfluidics.
Chemically or optically powered active matter plays an increasingly important role in materials design, but its computational potential has yet to be explored systematically. The competition between energy consumption and dissipation imposes stringent physical constraints on the information transport in active flow networks, facilitating global optimization strategies that are not well understood. Here, we combine insights from recent microbial experiments with concepts from lattice-field theory and non-equilibrium statistical mechanics to introduce a generic theoretical framework for active matter logic. Highlighting conceptual differences with classical and quantum computation, we demonstrate how the inherent non-locality of incompressible active flow networks can be utilized to construct universal logical operations, Fredkin gates and memory storage in set-reset latches through the synchronized self-organization of many individual network components. Our work lays the conceptual foundation for developing autonomous microfluidic transport devices driven by bacterial fluids, active liquid crystals or chemically engineered motile colloids.


[Serodiagnosis of Lyme borreliosis].
There are various serodiagnostic tests available for the detection of antibodies against Borrelia burgdorferi. An indirect hemagglutination assay, which can detect both IgM and IgG antibodies, was developed for antibody screening. Regarding the confirmation and differentiation of IgM and IgG, we use the indirect immunofluorescence assay (most specific when performed with sera previously absorbed with Treponema phagedenis) as well as the ELISA test. The detection of significantly elevated antibody titers depends on the stage of the disease. In erythema migrans, only 20-50% of the patients are seropositive (with a prevalence of IgM); in neuroborreliosis, the figures amount to 70-90% of the patients (prevalence of IgM in early stages and IgG in advanced stages); and 90-100% of the cases with acrodermatitis and arthritis show elevated titers of IgG (IgM antibodies usually are not detectable in late manifestations). The clinical manifestations of the disease is serologically marked by IgM antibodies or--in neuroborreliosis--by intrathecal production or antibodies which can be detected on account of an increased CSF/serum index.


Four-Day Food Record Macronutrient Intake, With and Without Biomarker Calibration, and Chronic Disease Risk in Postmenopausal Women.
We recently evaluated associations of biomarker-calibrated protein intake, protein density, carbohydrate intake, and carbohydrate density with the incidence of cardiovascular disease, cancer, and diabetes among postmenopausal women in the Women's Health Initiative (1993-present, 40 US clinical centers). The biomarkers relied on serum and urine metabolomics profiles, and biomarker calibration used regression of biomarkers on food frequency questionnaires. Here we develop corresponding calibration equations using food records and dietary recalls. In addition, we use calibrated intakes based on food records in disease association estimation in a cohort subset (n = 29,294) having food records. In this analysis, more biomarker variation was explained by food records than by FFQs for absolute macronutrient intake, with 24-hour recalls being intermediate. However, the percentage of biomarker variation explained was similar for each assessment approach for macronutrient densities. Invasive breast cancer risk was related inversely to carbohydrate and protein densities using food records, in analyses that included (calibrated) total energy intake and body mass index. Corresponding analyses for absolute intakes did not differ from the null, nor did absolute or relative intakes associate significantly with colorectal cancer or coronary heart disease. These analyses do not suggest major advantages for food records or dietary recalls in comparison with less costly and logistically simpler food frequency questionnaires for these nutritional variables.


Alerts in mobile healthcare applications: requirements and pilot study.
Recent advances in mobile technologies have greatly extended traditional communication technologies to mobile devices. At the same time, healthcare environments are by nature "mobile" where doctors and nurses do not have fixed workspaces. Irregular and exceptional events are generated in daily hospital routines, such as operations rescheduling, laboratory/examination results, and adverse drug events. These events may create requests that should be delivered to the appropriate person at the appropriate time. Those requests that are classified as urgent are referred to as alerts. Efficient routing and monitoring of alerts are keys to quality and cost-effective healthcare services. Presently, these are generally handled in an ad hoc manner. In this paper, we propose the use of a healthcare alert management system to handle these alert messages systematically. We develop a model for specifying alerts that are associated with medical tasks and a set of parameters for their routing. We design an alert monitor that matches medical staff and their mobile devices to receive alerts, based on the requirements of these alerts. We also propose a mechanism to handle and reroute, if necessary, an alert message when it has not been acknowledged within a specific deadline.


Feasibility and success of HIV point-of-care testing in an emergency department in an urban Canadian setting.
Approximately 26% of Canadians living with HIV are unaware of their status. Point-of-care (POC) HIV tests have been introduced to simplify and expand HIV testing. To evaluate the feasibility and acceptability of POC testing in an emergency department (ED) setting in Winnipeg, Manitoba. A cross-sectional study of unselected adults presenting to the ED at the Health Sciences Centre Hospital (Winnipeg, Manitoba) was performed. Study procedures included pre- and post-test counselling, administration of the INSTI HIV-1/HIV-2 Antibody Test (bioLytical Laboratories, Canada) and a brief questionnaire. Venous blood samples were collected from participants for confirmatory testing on all reactive and indeterminate specimens. In total, 501 adults participated in the study. The majority of participants were younger than 40 years of age, approximately one-half (48.5%) were women and 53% self-identified as Aboriginal. Nearly one-half (49.1%) of the participants had undergone previous HIV testing, although 63% of these tests were performed more than a year earlier. A total of seven individuals tested reactive with the POC test, all of whom were confirmed positive using serological testing (1.4%) and were linked to an HIV specialist within 24 h. Nearly all of the participants (96%) reported satisfaction with the test and believed it belonged in the ED (93%). Of the participants tested, 1.4% tested reactive for HIV, which is significantly higher than the reported prevalence in Manitoba and in other similar studies conducted in North America. Furthermore, all individuals were linked to timely care. The present study demonstrated that this particular busy tertiary care ED is an important and feasible location for HIV POC testing.


[Antibiotic sensitivity of Vibrio cholerae 01 isolated from humans].
Antibiotic susceptibility of 1479 Vibrio cholerae 01 strains isolated from humans between 1991 and 1995 was studied. The antibiotics used belonged to different chemical groups. The assay method was that of serial dilutions in solid media. The isolates showed high susceptibility to tetracyclines, gentamicin, erythromycin, rifampicin, ampicillin, carbenicillin and cefazolin. The susceptibility to kanamycin and monomycin was moderate and that to chloramphenicol, streptomycin and polymixin B was low. The time and area peculiarities of the circulating cultures were observed. The susceptibility of the isolates was either changing or unchanging. The constant susceptibility levels were detected with respect to gentamicin, erythromycin, monomycin, kanamycin, streptomycin and polymyxin B. The susceptibility changing in time was shown with respect to tetracyclines, rifampicin and chloramphenicol. A gradual increase in the resistance to betalactams with greater numbers of the plasmid resistance pattern strains was recorded. Regular surveillance of the changes in the V.cholerae 01 antibiotic susceptibility is needed to timely correct the treatment and prophylaxis regimens.


[Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors].
To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma. Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR). Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05). Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.


Use of apple seed meal as a new source of beta-glucosidase for enzymatic glucosylation of 4-substituted benzyl alcohols and tyrosol in monophasic aqueous-dioxane medium.
A facile method for enzymatic glycosylation of 4-substituted benzyl alcohols and tyrosol with glucose in a monophasic aqueous-dioxane medium was reported, using a crude meal of apple seed as a new catalyst. The corresponding beta-d-glucosides were synthesized in moderate yields (13.1-23.1%), among which the salidroside was obtained in 15.8% yield.


Functional expression and biochemical characterization of an epitope-tagged connexin37.
To study the gap junction protein connexin37 (Cx37), we stably transfected cell lines with constructs of human Cx37 containing the epitope tag FLAG (DYKDDDDK). A Cx37 construct containing the FLAG moiety at the carboxyl terminus (Cx37F) was expressed in BWEM cells, and did not substantially alter the levels of endogenous Cx43 in these cells. Immunostaining showed that Cx37F colocalized with Cx43 at cell-cell contacts. Pulse-chase metabolic labeling and immunoprecipitation with anti-FLAG antibodies indicated that Cx37F was synthesized as a protein that ran at 35.9 +/- 0.9 kDa on reducing SDS-PAGE but chased into a slower migrating band at 38.0 +/- 1.0 kDa. This shift in mobility was due to phosphorylation on serine residues, based on [(32)P]-metabolic labeling, immunoprecipitation, and phosphoamino acid analyses. The transition to the phosphoCx37F correlated with a loss of solubility in 1% Triton X-100. Based on the [(35)S]-methionine pulse-chase experiments, the half-life of the labeled Cx37F was approximately 3 h, which is within the range reported for other connexins. Analysis of dye injection experiments indicated that dye transfer was reduced in Cx37-transfected cells in comparison to parental BWEM cells, suggesting that formation of heteromeric Cx37-Cx43 channels reduced the molecular permeability of communication between these cells. Moreover, the similarities of previously demonstrated kinetic details and modification of Cx43 to our new data regarding Cx37 provide evidence for a commonality in processing and assembly steps of these two connexins.


Biocompatible magnetite nanoparticles with varying silica-coating layer for use in biomedicine: physicochemical and magnetic properties, and cellular compatibility.
Magnetic nanoparticles (MNPs) are considered highly useful in therapeutic and diagnostic applications. However, MNPs require surface modification to promote dispersibility in aqueous solutions and thus biocompatibility. In this article, the authors modified MNPs with inorganic silica layer to create silica-coated magnetite nanoparticles (MNP@Si) via sol-gel process. Synthesis involves hydrolysis and condensation steps using tetraethylorthosilicate (TEOS) in methanol/ polyethylene glycol (PEG) solution and ammonia catalyst. Nanoparticles were characterized in terms of morphology, particle size, crystalline phase, chemical-bond structure, surface charge and magnetic properties: in particular, the MNP@Si size was easily tunable through alteration of the Fe(3) O(4) -to-TEOS ratio. As this ratio increased, the MNP@Si size decreased from 270 to 15 nm whilst maintaining core 12-nm MNP particle size, indicating decrease in thickness of the silica coating. All MNP@Si, in direct contrast to uncoated MNPs, showed excellent stability in aqueous solution. The particles' physicochemical and magnetic properties systematically varied with size (coating thickness), and the zeta potential diminished toward negative values, while magnetization increased as the coating thickness decreased. 15-nm MNP@Si showed excellent magnetization (about 64.1 emu/g), almost comparable to that of uncoated MNPs (70.8 emu/g). Preliminary in vitro assays confirmed that the silica layer significantly reduced cellular toxicity as assessed by increase in cell viability and reduction in reactive oxygen species production during 48 h of culture. Newly-developed MNP@Si, with a high capacity for magnetization, water-dispersibility, and diminished cell toxicity, may be potentially useful in diverse biomedical applications, including delivery of therapeutic and diagnostic biomolecules.


FGFR2 gene amplification in gastric cancer predicts sensitivity to the selective FGFR inhibitor AZD4547.
FGFR gene aberrations are associated with tumor growth and survival. We explored the role of FGFR2 amplification in gastric cancer and the therapeutic potential of AZD4547, a potent and selective ATP-competitive receptor tyrosine kinase inhibitor of fibroblast growth factor receptor (FGFR)1-3, in patients with FGFR2-amplified gastric cancer. Array-comparative genomic hybridization and FISH were used to identify FGFR2 amplification in gastric cancer patient tumor samples. The effects of FGFR2 modulation were investigated in gastric cancer cells with FGFR2 amplification and in patient-derived gastric cancer xenograft (PDGCX) models using two approaches: inhibition with AZD4547 and short hairpin RNA (shRNA) knockdown of FGFR2. Amplification of the FGFR2 gene was identified in a subset of Chinese and Caucasian patients with gastric cancer. Gastric cancer cell lines SNU-16 and KATOIII, carrying the amplified FGFR2 gene, were extremely sensitive to AZD4547 in vitro with GI50 values of 3 and 5 nmol/L, respectively. AZD4547 effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules and induced apoptosis in SNU-16 cells. Furthermore, inhibition of FGFR2 signaling by AZD4547 resulted in significant dose-dependent tumor growth inhibition in FGFR2-amplified xenograft (SNU-16) and PDGCX models (SGC083) but not in nonamplified models. shRNA knockdown of FGFR2 similarly inhibited tumor growth in vitro and in vivo. Finally, compared with monotherapy, we showed enhancement of in vivo antitumor efficacy using AZD4547 in combination with chemotherapeutic agents. FGFR2 pathway activation is required for driving growth and survival of gastric cancer carrying FGFR2 gene amplification both in vitro and in vivo. Our data support therapeutic intervention with FGFR inhibitors, such as AZD4547, in patients with gastric cancer carrying FGFR2 gene amplification.


AVP-induced increase in AQP2 and p-AQP2 is blunted in heart failure during cardiac remodeling and is associated with decreased AT1R abundance in rat kidney.
The objective was to examine the renal effects of long-term increased angiotensin II and vasopressin plasma levels in early-stage heart failure (HF). We investigated the regulations of the V2 vasopressin receptor, the type 1A angiotensin II receptor, the (pro)renin receptor, and the water channels AQP2, AQP1, AQP3, and AQP4 in the inner medulla of rat kidney. HF was induced by coronary artery ligation. Sixty-eight rats were allocated to six groups: Sham (N = 11), HF (N = 11), sodium restricted sham (N = 11), sodium restricted HF (N = 11), sodium restricted sham + DDAVP (N = 12), and sodium restricted HF + DDAVP (N = 12). 1-desamino-8-D-arginine vasopressin (0.5 ng h-1 for 7 days) or vehicle was administered. Pre- and post-treatment echocardiographic evaluation was performed. The rats were sacrificed at day 17 after surgery, before cardiac remodeling in rat is known to be completed. HF rats on standard sodium diet and sodium restriction displayed biochemical markers of HF. These rats developed hyponatremia, hypo-osmolality, and decreased fractional excretion of sodium. Increase of AQP2 and p(Ser256)-AQP2 abundance in all HF groups was blunted compared with control groups even when infused with DDAVP and despite increased vasopressin V2 receptor and Gsα abundance. This was associated with decreased protein abundance of the AT1A receptor in HF groups vs. controls. Early-stage HF is associated with blunted increase in AQP2 and p(Ser256)-AQP2 despite of hyponatremia, hypo-osmolality, and increased inner medullary vasopressin V2 receptor expression. Decreased type 1A angiotensin II receptor abundance likely plays a role in the transduction of these effects.


Quinidine effect on hydrosmotic response of collecting tubules to vasopressin and cAMP.
Quinidine, a compound thought to increase cytosolic calcium ion activity, has been found to inhibit the hydrosmotic response to vasopressin (VP) and adenosine 3',5'-cyclic monophosphate (cAMP) in the toad urinary bladder. To test whether this drug has a similar action in the mammalian nephron, the effect of quinidine on the hydraulic conductivity of the isolated perfused rabbit cortical collecting tubule (CCT) exposed to either 20 microU/ml VP or 10(-4) M 8-(p-chlorophenylthio) - adenosine 3',5' - cyclic monophosphate (8-CPT-cAMP) was studied. Quinidine had no effect on the basal water permeability of the CCT. Quinidine sulfate (10(-4) M) reduced the VP-stimulated water permeability from 280 +/- 50 X 10(-7) to 115 +/- 41 X 10(-7) cm X s-1 X atm-1 (P less than 0.05). The hydrosmotic response to 8-CPTcAMP was likewise reduced following exposure to quinidine. This effect was shown to be dose dependent. In paired experiments, inhibition of the response to 10(-4) M 8-CPTcAMP averaged 11% at 10(-6) M, 27% at 5 X 10(-6) M, 53% at 5 X 10(-5) M, and 50% at 10(-4) M quinidine. Inhibition of the response to 8-CPTcAMP was estimated to be half maximal at approximately 5 X 10(-6) M quinidine. Tubules were protected against the quinidine-induced inhibition by the addition of 6.5 X 10(-5) M quin 2-acetoxymethylester in the presence of low peritubular Ca concentration. These results are consistent with the view that elevated cytosolic Ca ion levels inhibit the increase in water permeability elicited by VP or exogenous cAMP in the mammalian CCT.


2009 H1N1 influenza A and pregnancy outcomes in Victoria, Australia.
Pregnant women have been identified as a group at risk of increased morbidity and mortality associated with the pandemic H1N1 influenza A 2009 (H1N1/09) outbreak. Six hospitals in the state of Victoria, Australia, contributed retrospective and prospective demographic and clinical data, reason for admission data, and maternal and fetal outcome data for women with laboratory-confirmed H1N1/09 admitted to the hospital from 20 May 2009 through 31 July 2009. Forty-three cases were reported during the study period, including 8 intensive care unit admissions, 1 maternal death, 2 fetal deaths, and 1 neonatal death. The most common reason for admission was uncomplicated influenza-like illness. Patients hospitalized for uncomplicated influenza-like illness had a length of stay significantly less than those with confirmed pneumonia. Thirty-six percent of women delivered during the hospitalization. Of the women delivering before 37 weeks' gestation, almost all had pneumonia. Almost half of our case series had no other comorbidity, a large proportion (77%) of women received antivirals, and 56% received antibiotics. The incidence of hospitalization was estimated at 0.46% (95% confidence interval, 0.31%-0.66%) of all 6094 pregnant women in the third trimester during the 3-month study period. The incidence of hospitalization in the second trimester was estimated at 0.21% (95% confidence interval, 0.11%-0.36%). This case series confirms a high number of complications in pregnant women due to pandemic H1N1/09. Many of these women had comorbidities, although almost 50% of the women in this case series who required hospitalization did not have an additional risk factor other than being pregnant.


Predictors of reduction in mitral regurgitation in patients undergoing cardiac resynchronisation treatment.
CRT causes reduction in MR due to left ventricular (LV) remodelling, but determinants of clinically meaningful MR reduction acutely after CRT have not been evaluated. We evaluated echocardiographic predictors of significant reduction in functional mitral regurgitation (MR) by cardiac resynchronisation treatment (CRT). 35 patients with >or= moderate to severe MR underwent CRT for presence of electrical and/or mechanical dyssynchrony. Significant reduction in MR post-CRT was defined as reduction to less than moderate MR (MR jet area/left atrial area <25%, group 1) on follow-up echocardiogram at 1.7 (SD 2.8) months post-CRT. Significant MR reduction of 62% (28%) from baseline MR occurred in 18 patients vs 22% (16%) in the remaining patients (group 2), p<0.01). Follow-up left ventricular ejection fraction (LVEF) was 0.43 (0.09) in group 1 patients vs 0.29% (0.1%) in group 2 patients (p<0.001). On multivariate analysis, time to peak strain in the mid inferior segment was the only significant predictor of MR reduction post-CRT (p = 0.008, OR = 1.023 (CI 1.006 to 1.041). The sensitivity and specificity of the combined variable of time to peak strain of >400 ms in the mid inferior segment and peak negative strain of >or=9% and 8% in the basal and mid posterior segments, respectively, to predict follow-up MR was 88% and 93% respectively and positive and negative predictive value was 94% and 87%. In patients with cardiomyopathy and significant MR, the presence of delayed longitudinal strain in the mid inferior LV segment along with preserved negative systolic strain in the basal and mid posterior segments predicts substantial reduction in MR post-CRT.


Positive Wigner functions render classical simulation of quantum computation efficient.
We show that quantum circuits where the initial state and all the following quantum operations can be represented by positive Wigner functions can be classically efficiently simulated. This is true both for continuous-variable as well as discrete variable systems in odd prime dimensions, two cases which will be treated on entirely the same footing. Noting the fact that Clifford and Gaussian operations preserve the positivity of the Wigner function, our result generalizes the Gottesman-Knill theorem. Our algorithm provides a way of sampling from the output distribution of a computation or a simulation, including the efficient sampling from an approximate output distribution in the case of sampling imperfections for initial states, gates, or measurements. In this sense, this work highlights the role of the positive Wigner function as separating classically efficiently simulable systems from those that are potentially universal for quantum computing and simulation, and it emphasizes the role of negativity of the Wigner function as a computational resource.


Understanding Pathways Between Agriculture, Food Systems, and Nutrition: An Evidence and Gap Map of Research Tools, Metrics, and Methods in the Last 10 Years.
New tools, metrics, and methods in agriculture, food systems, and nutrition (A&N) research proliferated in the decade following the 2007-2008 food price crisis. We map these developments across themes derived from conceptual A&N pathways and expert consultations. We created an interactive Evidence and Gap Map (EGM) from a systematic search of published and gray literature since 2008, following Campbell Collaboration guidelines. We retrieved over 30,000 reports from published literature databases, and individually searched 20 online repositories. We systematically screened 24,359 reports by title and/or abstract, 1577 by full report, and included 904 eligible reports. The EGM consists of rows of thematic domains and columns of types of tools, metrics, and methods, as well as extensive coding applied as filters. Each cell of the map represents research surrounding a type of tool, metric, or method within a given theme. Reports in each cell are grouped by stage of development, which expand to a corresponding bibliography. Users can filter EGM reports by various characteristics. The 4 most populated domains were: diets, nutrition, and health; primary food production; water, sanitation, and hygiene; and environment and sustainability. The 4 most common types of metrics, methods, and tools were: diet metrics; footprint analysis (especially water); technology applications; and network or Bayesian analysis. Gaps represent areas of few or no reports of innovation between 2008 and 2018. There were gaps in reports and innovations related to: power or conflicts of interest; food environments; markets; private sector engagement; food loss and waste; conflict; study design and system-level tools, metrics, and methods. The EGM is a comprehensive tool to navigate advances in measurement in A&N research: to highlight trends and gaps, conduct further synthesis and development, and prioritize the agenda for future work. This narrative synthesis accompanies the EGM, which can be found at https://www.anh-academy.org/evidence-and-gap-map.


Characteristics of personal health information management groups: findings from an online survey using Amazon's mTurk.
The study characterized three groups with different levels of familiarity with personal health information management (PHIM) in terms of their demographics, health knowledge, technological competency, and information sources and barriers. In addition, the authors examined differences among PHIM groups in subjective self-ratings and objective test scores for health literacy. A total of 202 survey participants were recruited using Amazon's Mechanical Turk (mTurk) service, a crowdsourcing Internet service. Using K-means clustering, three groups with differing levels of familiarity with PHIM were formed: Advanced, Intermediate, and Basic. The Advanced group was the youngest, and the Basic group contained the highest proportion of males, whereas the Intermediate group was the oldest and contained the fewest males. The Advanced group was significantly more likely to engage in provider- or hospital-initiated PHIM activities such as emailing with providers, viewing test results online, and receiving summaries of hospital visits via email or websites than the other groups. The Basic group had significantly lower information management skills and Internet use than the other groups. Advanced and Basic groups reported significant differences in several information barriers. While the Advanced group self-reported the highest general literacy, they scored lowest on an objective health literacy test. For effective personal health records management, it is critical to understand individual differences in PHIM using a comprehensive measure designed to assess personal health records-specific activities. Because they are trained to perform an array of information management activities, medical librarians or patient educators are well positioned to promote the effective use of personal health records by health consumers.


Review of the cardiovascular safety of zoledronic acid and other bisphosphonates for the treatment of osteoporosis.
In 2 large, randomized, placebocontrolled trials, yearly 5-mg infusions of the bisphosphonate zoledronic acid were associated with increased bone mineral density and reduced fracture incidence in patients with osteoporosis, previous fracture, or both. This review evaluated the cardiovascular risks of bisphosphonates (with a focus on zoledronic acid) for the treatment of osteoporosis and put these potential risks into perspective, summarizing available evidence from randomized clinical trials. A search of PubMed (1991-September 2009) for preclinical and clinical trials was conducted using the following search terms: arrhythmia, atrial fibrillation, bisphosphonate, osteoporosis, cardiovascular adverse events, bone mineral density, fracture incidence, stroke, alendronate, etidronate, ibandronate, risedronate, and zoledronic acid. New analyses using unpublished data from the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) and Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Recurrent Fracture Trial (HORIZON-RFT) were also performed to evaluate the cardiovascular risk of zoledronic acid using stepwise Cox proportional hazards regression and risk modeling. After selection of risk factors for the model, treatment-by-factor interactions were evaluated at the 0.10 level of significance. Atrial fibrillation (AF) serious adverse events (SAEs) were observed among more patients receiving zoledronic acid (1.3%) than placebo (0.5%) over 36 months in HORIZON-PFT (P < 0.001), but the overall incidence of AF events was not significantly different between groups. The timing of AF SAEs did not correspond with drug administration or the pharmacokinetic profile of the drug. Nearly all women with sick sinus syndrome had predisposing conditions. An electrocardiography study after the third yearly infusion found no differences between those who received zoledronic acid versus placebo. Cardiovascular deaths, stroke, and other nonarrhythmia cardiovascular adverse events (AEs) were not significantly different between groups, but arrhythmia was more common in the zoledronic acid group than in the placebo group (6.9% vs 5.3%; P = 0.003). In analyses of pooled data from HORIZON-PFT and HORIZON-RFT to determine risk factors associated with the likelihood of experiencing AF, atrial flutter, or stroke, the only treatment-by-factor interaction was age (hazard ratio = 0.963; P < 0.067), which may be attributable to the fact that, among those aged > or =85 years, AF AEs occurred in 5.9% of the placebo group and 5.3% of the zoledronic acid group. Preclinical and other clinical trials of zoledronic acid for the treatment of osteoporosis or other indications did not identify an effect on AF AEs. A reanalysis of risedronate controlled clinical trials found no difference in the incidence of AF among active-treatment or placebo groups. In alendronate trials, AF SAEs occurred in 1.5% of the alendronate group and 1.0% of the placebo group (P = 0.07); the overall incidence of AF AEs was similar. Despite the greater incidence of AF SAEs among zoledronic acid recipients versus placebo recipients in one study (not observed in other trials of this agent), clinical data for zoledronic acid, risedronate, and alendronate indicate no significant differences from placebo in overall incidence of AF AEs.


Nutraceutical effects of fucoxanthin for obesity and diabetes therapy: a review.
Obesity, which results from an imbalance between energy intake and energy expenditure, has become a major health risk factor worldwide, causing numerous and various diseases such as diabetes, hypertension, and cardiovascular diseases. Fucoxanthin, a specific carotenoid in brown algae, has garnered much attention for its anti-obesity and anti-diabetic effects attributable to a unique mechanism. Fucoxanthin induces uncoupling protein 1 (UCP1) expression in white adipose tissue (WAT). That inner membrane mitochondrial protein, UCP1, can dissipate energy through oxidation of fatty acids and heat production. Furthermore, fucoxanthin improves insulin resistance and ameliorates blood glucose levels through down-regulation of adipocytokines related to insulin resistance in WAT and up-regulation of glucose transporter 4 (GLUT4) in skeletal muscle. Algae fucoxanthin is a beneficial compound for the prevention of the metabolic syndrome.


Bronchial responsiveness to dry air hyperventilation in smokers may predict decline in airway status using indirect methods.
Disabling respiratory symptoms and rapid decline of lung function may occur in susceptible tobacco smokers. Bronchial hyperresponsiveness (BHR) elicited by direct challenge methods predicts worse lung function outcomes. The aim of this study was to evaluate whether BHR to isocapnic hyperventilation of dry air (IHDA) was associated with rapid deterioration in airway status and respiratory symptoms. One hundred twenty-eight smokers and 26 age- and sex-matched healthy individuals with no history of smoking were investigated. All subjects completed a questionnaire. Spirometry and impulse oscillometry (IOS) measurements were recorded before and after 4 min of IHDA. The tests were repeated after 3 years in 102 smokers and 11 controls. Eighty-five smokers (66 %) responded to the challenge with a ≥2.4-Hz increase in resonant frequency (F res), the cutoff limit defining BHR, as recorded by IOS. They had higher F res at baseline compared to nonresponding smokers [12.8 ± 3.2 vs. 11.5 ± 3.4 Hz (p < 0.05)] and lower FEV1 [83 ± 13 vs. 89 ± 13 % predicted (p < 0.05)]. Multivariable logistic regression analysis indicated that wheezing (odds ratio = 3.7, p < 0.01) and coughing (odds ratio = 8.1, p < 0.05) were significantly associated with hyperresponsiveness. An increase in F res was recorded after 3 years in responding smokers but not in nonresponders or controls. The difference remained when subjects with COPD were excluded. The proportion of hyperresponsive smokers was unexpectedly high and there was a close association between wheezing and coughing and BHR. Only BHR could discriminate smokers with rapid deterioration of airway status from others.