The Revised Assessment of Sadistic Personality (ASP-8): Evidence for Validity across Four Countries.
Subclinical sadism, characterized by infliction of cruelty, aggression, or humiliation on another for subjugation or pleasure, provides important information in the prediction of aversive behaviors that have implications for individuals' and society's well-being worldwide. Given sadism's universal relevance, it is imperative that researchers ensure valid and reliable trait measurement not only among English-speaking individuals, but also cross-nationally among countries in which sadism remains relatively understudied. The objective of the current research was to validate the revised version of the Assessment of Sadistic Personality (ASP-8) (Plouffe et al., 2017) across samples of Russian (n = 1087, Mage = 37.36, SD = 10.36), Greek (n = 1195, Mage = 35.64, SDage = 13.08), Serbian (n = 443, Mage = 28.10, SDage = 6.60), and British (n = 511, Mage = 28.50, SDage = 11.62) adults. Overall, results supported the reliability, dimensionality, and scalar/partial scalar measurement invariance of the ASP-8 across cross-national samples. Convergent and discriminant validity were mostly supported through correlations with general personality traits, the Dark Triad, emotional intelligence, mental toughness, depression, anxiety, stress, satisfaction with life, aggression, and attitudes toward social groups. Based on our findings, we recommend the use of the ASP-8 in future investigations of aversive traits.


Links between the mechanics of ventilation and spine stability.
Spine stability is ensured through isometric coactivation of the torso muscles; however, these same muscles are used cyclically to assist ventilation. Our objective was to investigate this apparent paradoxical role (isometric contraction for stability or rhythmic contraction for ventilation) of some selected torso muscles that are involved in both ventilation and support of the spine. Eight, asymptomatic, male subjects provided data on low back moments, motion, muscle activation, and hand force. These data were input to an anatomically detailed, biologically driven model from which spine load and a lumbar spine stability index was obtained. Results revealed that subjects entrained their torso stabilization muscles to breathe during demanding ventilation tasks. Increases in lung volume and back extensor muscle activation coincided with increases in spine stability, whereas declines in spine stability were observed during periods of low lung inflation volume and simultaneously low levels of torso muscle activation. As a case study, aberrant ventilation motor patterns (poor muscle entrainment), seen in one subject, compromised spine stability. Those interested in rehabilitation of patients with lung compromise and concomitant back troubles would be assisted with knowledge of the mechanical links between ventilation during tasks that impose spine loading.


Celecoxib versus diclofenac in the management of osteoarthritis of the knee.
A clinical trial was conducted in 600 patients with OA of the knee to test the hypothesis that the specific COX-2 inhibitor, celecoxib, has equivalent efficacy and a superior tolerability/safety profile when compared to diclofenac, the current worldwide standard of care. Patients were administered celecoxib 100 mg BID, diclofenac 50 mg TID or placebo for 6 weeks in a multicentre, double-blind. placebo-controlled trial. Primary efficacy measures (index joint pain by VAS, WOMAC index) indicated statistically significant improvement versus placebo for both celecoxib and diclofenac and no statistically significant differences between celecoxib and diclofenac. American Pain Society (APS) measures to assess the rapidity of onset of action showed statistically significant and comparable pain relief versus placebo within 24 h for both celecoxib and diclofenac. More diclofenac patients reported GI side effects than patients treated with either placebo or celecoxib. Diclofenac-treated patients experienced statistically significant elevations in mean hepatic transaminases and serum creatinine and reductions in haemoglobin concentration when compared to placebo, events not observed with celecoxib. Celecoxib 200 mg daily is as effective as diclofenac 150 mg daily for relieving signs and symptoms of OA of the knee, including pain, and has a rapid onset of action. However, celecoxib appears to have a superior safety and tolerability profile.


[Magnetic resonance angiography in diagnosis of head and neck vessels diseases].
Aiming to study diagnostic potential of MRA 286 patients have bean observed with pathology of the brain vessels. High efficiency of MRA has been confirmed: sensitivity and specificity with vascular malformations were 98% and 96%, with arterial aneurysm it was 97% and 82%, with stenosis of more than 50% it was 98% and 46%, with stenosis of less than 50% it was 96% and 84%, with thrombosis--100% and 100%. It was noted that TOF method is the most informative nature to estimate the arterial bed. We have managed to study with the PC method venous component of malformation, residual flow in huge thrombosed aneurysm, condition of the external carotid arteries and their branches.


Unveiling surface redox charge storage of interacting two-dimensional heteronanosheets in hierarchical architectures.
Two-dimensional (2D) heteronanosheets are currently the focus of intense study due to the unique properties that emerge from the interplay between two low-dimensional nanomaterials with different properties. However, the properties and new phenomena based on the two 2D heteronanosheets interacting in a 3D hierarchical architecture have yet to be explored. Here, we unveil the surface redox charge storage mechanism of surface-exposed WS2 nanosheets assembled in a 3D hierarchical heterostructure using in situ synchrotron X-ray absorption and Raman spectroscopic methods. The surface dominating redox charge storage of WS2 is manifested in a highly reversible and ultrafast capacitive fashion due to the interaction of heteronanosheets and the 3D connectivity of the hierarchical structure. In contrast, compositionally identical 2D WS2 structures fail to provide a fast and high capacitance with different modes of lattice vibration. The distinctive surface capacitive behavior of 3D hierarchically structured heteronanosheets is associated with rapid proton accommodation into the in-plane W-S lattice (with the softening of the E2g bands), the reversible redox transition of the surface-exposed intralayers residing in the electrochemically active 1T phase of WS2 (with the reversible change in the interatomic distance and peak intensity of W-W bonds), and the change in the oxidation state during the proton insertion/deinsertion process. This proposed mechanism agrees with the dramatic improvement in the capacitive performance of the two heteronanosheets coupled in the hierarchical structure.


Ligamentum flavum hematoma in the rigid thoracic spinal segments: case report.
Ligamentum flavum hematoma, a rare cause of spinal nerve root and canal compression, typically occurs in the mobile lumbar spine segments. A thoracic ligamentum flavum hematoma is extremely rare--only one such case of a thoracolumbar (T11-12) lesion has been reported. The thoracolumbar region with its floating ribs, however, is structurally and biomechanically similar to the lumbar spine and its mobility is greater than the higher thoracic levels. To the best of their knowledge, the authors report the first case of a ligamentum flavum hematoma in the region of the rigid thoracic spinal segments with the contiguous rib cage. A symptomatic T9-10 ligamentum flavum hematoma is described in the case of a 66-year-old woman with compensatory thoracic lordosis secondary to the lumbar degenerative kyphosis. The hematoma was removed and the diagnosis was histologically confirmed. The authors speculate that thoracic lordosis might have contributed to the development of the hematoma because the ligamentum flavum and the facet joint were subjected to greater axial stress than in individuals with normal spinal alignment.


Instrument-free control of the standard potential of potentiometric solid-contact ion-selective electrodes by short-circuiting with a conventional reference electrode.
A simple, instrument-free method to control the standard potential (E°) of potentiometric solid-contact ion-selective electrodes (SC-ISE) is described. In this method, the electrode potential of a SC-ISE is reset by short-circuiting the electrode with a metallic wire to a conventional Ag/AgCl/3 M KCl reference electrode (RE) in a solution containing primary ions. The method is studied experimentally for SC-ISEs where the conducting polymer poly(3,4-ethylenedioxythiophene) doped with the bulky anion poly(sodium 4-styrenesulfonate), PEDOT(PSS), is used as the solid contact. Three different types of ion-selective membranes (ISMs) are studied: two potassium-selective membranes, with and without the lipohilic additive tetradodecylammonium tetrakis(4-chlorophenyl)borate (ETH-500) and a cation-sensitive membrane without an ionophore. When the SC-ISE is short-circuited with the RE, the PEDOT(PSS) layer is oxidized or reduced, thereby shifting the potential of the SC-ISE to the proximity of the potential of the RE so that the potential difference between these two electrodes becomes zero or close to zero. The slope of the calibration curve is preserved after the short-circuit treatment of the SC-ISEs. The short-circuiting method is an important step toward calibration-free potentiometric analysis.


Measuring psychological change during cognitive behaviour therapy in primary care: a Polish study using 'PSYCHLOPS' (Psychological Outcome Profiles).
Psychological outcome measures are evolving into measures that depict progress over time. Interval measurement during therapy has not previously been reported for a patient-generated measure in primary care. We aimed to determine the sensitivity to change throughout therapy, using 'PSYCHLOPS' (Psychological Outcome Profiles), and to determine if new problems appearing during therapy diminish overall improvement. Responses to PSYCHLOPS, pre-, during- and post-therapy were compared. patients offered brief cognitive behaviour therapy in primary care in Poland. 238 patients completed the pre-therapy questionnaire, 194 (81.5%) the during-therapy questionnaire and 142 the post-therapy questionnaire (59.7%). For those completing all three questionnaires (n = 135), improvement in total scores produced an overall Effect Size of 3.1 (2.7 to 3.4). We estimated change using three methods for dealing with missing values. Single and multiple imputation did not significantly change the Effect Size; 'Last Value Carried Forward', the most conservative method, produced an overall Effect Size of 2.3 (1.9 to 2.6). New problems during therapy were reported by 81 patients (60.0%): new problem and original problem scores were of similar magnitude and change scores were not significantly different when compared to patients who did not report new problems. A large proportion of outcome data is lost when outcome measures depend upon completed end of therapy questionnaires. The use of a during-therapy measure increases data capture. Missing data still produce difficulties in interpreting overall effect sizes for change. We found no evidence that new problems appearing during therapy hampered overall recovery.


The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance.
The Global Assessment Scale (GAS) is a rating scale for evaluating the overall functioning of a subject during a specified time period on a continuum from psychological or psychiatric sickness to health. In five studies encompassing the range of population to which measures of overall severity of illness are likely to be applied, the GAS was found to have good reliability. GAS ratings were found to have a greater sensitivity to change over time than did other ratings of overall severity or specific symptom dimensions. Former inpatients in the community with a GAS rating below 40 had a higher probability of readmission to the hospital than did patients with higher GAS scores. The relative simplicity, reliability, and validity of the GAS suggests that it would be useful in a wide variety of clinical and research settings.


Defining the mechanical border zone: a study in the pig heart.
Wall motion abnormalities can occur in nonischemic areas contiguous with ischemic myocardium. The extent of the mechanical border zone contiguous with an acute myocardial ischemic region was mapped in eight open-chest anesthetized pigs using sonomicrometer crystals implanted parallel with the visible ischemic border in the subepicardium of ischemic (IZ), proximal border (BZ1), distal border (BZ2), and remote normal (NZ) zones. Regional systolic shortening fraction was near 15%, and epicardial blood flow was approximately 1.5 ml X min-1 X g-1 in all locations before ischemia was induced. Blood flow fell to less than 0.05 ml X min-1 X g-1 and the left ventricular free wall supplied by the distal one-third of the left anterior descending artery exhibited holosystolic lengthening when the vessel was occluded. After occlusion, systolic shortening fraction was depressed by 45% in the BZ1 located 3.1 +/- 1.1 mm from the ischemic margin and by 25% in the BZ2, which was measured at 9.3 +/- 1.5 mm from the ischemic margin without significant flow reduction. The NZ, 22.3 +/- 4.6 mm from ischemic margin, was unaffected by occlusion. Computer analysis of the data shows that wall motion is depressed as far as 12 mm from the ischemic margin. This abnormal wall motion surrounding focal transmural myocardial ischemia is presumed to result from mechanical tethering.


Diruthenium complexes having a partially hydrogenated bipyridine ligand: plausible mechanism for the dehydrogenative coupling of pyridines at a diruthenium site.
The reactions of the diruthenium tetrahydrido complex, Cp*Ru(μ-H)4RuCp* (1) (Cp* = η5-C5Me5), with pyridines were investigated in relation to the dehydrogenative coupling of 4-substituted pyridines. Complex 1 reacted with γ-picoline to yield the bis(μ-pyridyl) complex, {Cp*Ru(μ-H)(μ-4-MeC5H3)}2 (2a), with the elimination of dihydrogen. Complex 2a immediately reacted with the liberated dihydrogen to yield μ-η2-dihydrobipyridine (dhbpy) complex 4avia C-C bond formation between the two pyridyl groups, in which one of the pyridine rings underwent partial hydrogenation. The X-ray structure of 4a shows that the dhbpy moiety adopts a μ-η2 coordination mode at the Ru2 site. Complex 4a was reversibly converted to 5avia the elimination of dihydrogen in which the dhbpy moiety adopts a μ-η2:η2 mode. Although 5a was coordinatively saturated, 5a readily reacted with tBuNC to yield 6a. This was owing to the ability of the dhbpy ligand changing its coordination mode between the μ-η2:η2 and μ-η2 modes. This also causes the dehydrogenation from the dhbpy ligand to yield μ-η2:η2-bipyridine complex 7a at 140 °C. However, 7a was not shown to be an intermediate of the catalysis. The reaction of 1 with 1,10-phenanthroline afforded μ-η2-phenanthroline complex 8 containing two hydrides, which can be a model compound for the bipyridine elimination from the Ru2 site. Dynamic NMR studies suggested that 8 was isomerised to an unsaturated μ-N-heterocyclic carbene (NHC) complex. The unsaturated nature of the μ-NHC complex is likely responsible for the uptake of the third pyridine molecule to turn over the catalytic cycle.


Spectral element boundary integral method with periodic layered medium dyadic Green's function for multiscale nano-optical scattering analysis.
In this work, we propose a numerical solver combining the spectral element - boundary integral (SEBI) method with the periodic layered medium dyadic Green's function. The periodic layered medium dyadic Green's function is formulated under matrix representation. The surface integral equations (SIEs) are then implemented as the radiation boundary condition to truncate the top and bottom computation domain. After describing the interior computation domain with the vector wave equations, and treating the lateral boundaries with Bloch periodic boundary conditions, the whole computation domains are discretized with mixed-order Gauss- Lobatto-Legendre basis functions in the SEBI method. This method avoids the discretization of the top and bottom layered media, so it can be much more efficient than conventional methods. Numerical results validate the proposed solver with fast convergence throughout the whole computation domain and good performance for typical multiscale nano-optical applications.


Loss-tolerant quantum dense metrology with SU(1,1) interferometer.
Heisenberg uncertainty relation in quantum mechanics sets the limit on the measurement precision of non-commuting observables in one system, which prevents us from measuring them accurately at the same time. However, quantum entanglement between two systems allows us to infer through Einstein-Podolsky-Rosen correlations two conjugate observables with precision better than what is allowed by Heisenberg uncertainty relation. With the help of the newly developed SU(1,) interferometer, we implement a scheme to jointly measure information encoded in multiple non-commuting observables of an optical field with a signal-to-noise ratio improvement of about 20% over the classical limit on all measured quantities simultaneously. This scheme can be generalized to the joint measurement of information in arbitrary number of non-commuting observables.


Minimal residual disease in acute myeloid leukaemia.
Relapse remains the main cause of treatment failure in acute myeloid leukaemia (AML). Studies to date suggest that monitoring of minimal residual disease (MRD) in AML is useful in identifying patients at high risk of relapse from those in durable remission. This chapter describes the methodological advances in the detection of MRD and, in particular, focuses on the development of highly sensitive RT-PCR techniques, including real-time, for quantifying MRD. Preliminary results on the clinical utility of MRD monitoring in AML with t(8;21) and inv(16) are promising and provide the basis for further evaluation by quantitative real-time analysis in prospective clinical trials. For AML without a specific fusion transcript, the WT1 gene is an alternative molecular target. The clinical value of quantitative MRD monitoring in AML, however, will need to be confirmed in future studies.


Natural transformation of Thermotoga sp. strain RQ7.
Thermotoga species are organisms of enormous interest from a biotechnological as well as evolutionary point of view. Genetic modifications of Thermotoga spp. are often desired in order to fully release their multifarious potentials. Effective transformation of recombinant DNA into these bacteria constitutes a critical step of such efforts. This study aims to establish natural competency in Thermotoga spp. and to provide a convenient method to transform these organisms. Foreign DNA was found to be relatively stable in the supernatant of a Thermotoga culture for up to 6 hours. Adding donor DNA to T. sp. strain RQ7 at its early exponential growth phase (OD600 0.18 ~ 0.20) resulted in direct acquisition of the DNA by the cells. Both T. neapolitana chromosomal DNA and Thermotoga-E. coli shuttle vectors effectively transformed T. sp. strain RQ7, rendering the cells resistance to kanamycin. The kan gene carried by the shuttle vector pDH10 was detected by PCR from the plasmid extract of the transformants, and the amplicons were verified by restriction digestions. A procedure for natural transformation of Thermotoga spp. was established and optimized. With the optimized method, T. sp. strain RQ7 sustained a transformation frequency in the order of 10⁻⁷ with both genomic and plasmid DNA. T. sp. strain RQ7 cells are naturally transformable during their early exponential phase. They acquire DNA from both closely and distantly related species. Both chromosomal DNA and plasmid DNA serve as suitable substrates for transformation. Our findings lend a convenient technical tool for the genetic engineering of Thermotoga spp.


Risk of Tendon Injury in Patients Treated With Fluoroquinolone (FQ) Versus Non-Fluoroquinolone Antibiotics for Community-Acquired Pneumonia (CAP).
Fluoroquinolones (FQs) are associated with increased risk of tendon injury but comparative risk versus other antibiotic options for the same indication has yet to be evaluated. Describe the incidence (relative risk) of any tendon injury in patients receiving FQ compared with other (non-FQs) antibiotics for treatment of community-acquired pneumonia (CAP). A retrospective propensity score weighted cohort study was performed to evaluate the association between FQ antibiotics and tendon injury risk at 2 time points (within 1 month and within 6 months of use) compared with non-FQ regimens for treatment of CAP. The evaluation was performed using the CCAE (MarketScan Commercial Claims and Encounters) and COB (Medicare Supplemental and Coordination of Benefits) databases from 2014 to 2020. Patients with ICD (International Classification of Diseases) 9/10 coding for outpatient pneumonia who were >18 years and without history of tendon injury were included. Patients with history of tendon injury, who received multiple antibiotic therapies for recurrent pneumonia, or who received both FQ and non-FQ regimens during the study period were excluded. Propensity score weighting was used to adjust for selection bias due to contributing risk factors, including demographics (age, sex), comorbidities (diabetes mellitus, chronic kidney disease), and concurrent medications (corticosteroids). At 1 month, the odds of tendon injury were estimated to be significantly higher (41.9%) in patients receiving FQs compared with those receiving a non-FQ-based regimen (odds ratio [OR] = 1.419, 95% confidence interval [CI] = [1.188-1.698]). The odds of tendon injury were also estimated to be higher (OR = 1.067, 95% CI = [0.975-1.173]) in the FQ population within 180 days, but this effect was not statistically significant. The most frequent sites of tendon injuries were rotator cuff, shoulder, and patellar tendon. Prescribers should recognize the risk of tendon injury within 1 month of FQ use when considering treatment regimens for CAP and use alternative options with lower risk whenever possible.


Cortisol stimulation of parathyroid hormone secretion by rat parathyroid glands in organ culture.
Addition of cortisol (10(-6) to 10(-8) M) and related glucocorticoid congeners to cultures of rat parathyroid glands stimulated dose-related increases in parathyroid hormone secretion; the addition of deoxycorticosterone or cortexolone was without effect. Cortexolone, however, inhibited the stimulatory activity of cortisol when both were added to the culture medium. This direct stimulatory effect of cortisol on parathyroid gland secretion may account in part for the increased concentration of parathyroid hormone in the serum of cortisol-treated animals.


Effect of exogenous interferon on rubella virus production in carrier cultures of cells defective in interferon production.
An established cell line (Vero) defective in interferon production was used to evaluate the role of interferon in chronic rubella virus infections of cell cultures. Inoculation of Vero cells with a low multiplicity of virus resulted in the development of carrier cultures which had the characteristics of a regulated infection. Although added interferon did not alter rubella virus production in carrier cultures of cells capable of producing interferon, such added interferon caused a dramatic reduction of virus production in the carrier cultures of Vero cells. There was a reduction of the fraction of cells producing virus in Vero carrier cultures, but not in carrier cultures of other cells upon incubation in the continual presence of rubella virus antibodies. In addition, the fraction of infected cells fluctuated in carrier cultures in Vero cells. The data indicate that interferon is not necessary for maintaining a chronic rubella virus infection in vitro and suggest an instability of the virus genome in Vero cells.


Research progress of metabolomics in cervical cancer.
Cervical cancer threatens women's health seriously. In recent years, the incidence of cervical cancer is on the rise, and the age of onset tends to be younger. Prevention, early diagnosis and specific treatment have become the main means to change the prognosis of cervical cancer patients. Metabolomics research can directly reflect the changes of biochemical processes and microenvironment in the body, which can provide a comprehensive understanding of the changes of metabolites in the process of disease occurrence and development, and provide new ways for the prevention and diagnosis of diseases. The aim of this study is to review the metabolic changes in cervical cancer and the application of metabolomics in the diagnosis and treatment. PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2022. With the emergence of metabolomics, metabolic regulation and cancer research are further becoming a focus of attention. By directly reflecting the changes in the microenvironment of the body, metabolomics research can provide a comprehensive understanding of the patterns of metabolites in the occurrence and development of diseases, thus providing new ideas for disease prevention and diagnosis. With the continuous, in-depth research on metabolomics research technology, it will bring more benefits in the screening, diagnosis and treatment of cervical cancer with its advantages of holistic and dynamic nature.


Increasing community integration and inclusion for people with intellectual disabilities.
Historically residential facilities for individuals with intellectual disabilities have served the role of segregation and congregation with no real focus on integration into the community. More recently the focus has been to get people out of residential institutions and into community-based living settings. This work examines an approach to changing the systems and culture at a large residential facility to create higher rates of transitions to community-based living settings. A multi-phased systematic implementation approach is discussed in which each successive phase builds upon the previous phase. This approach creates opportunities for community integrated activities and then utilizes these community contexts as functional learning opportunities. Results are evaluated in the areas of community presence, community participation, community integration and community inclusion. Data indicate significant increases in each of these areas based on changing the facility focus, simplifying the intrusive accountability systems, aligning resources and teaching staff how to utilize support plans more efficiently to teach skills in functionally appropriate community integrated activities.


Guided cobalamin biosynthesis supports Dehalococcoides mccartyi reductive dechlorination activity.
Dehalococcoides mccartyi strains are corrinoid-auxotrophic Bacteria and axenic cultures that require vitamin B12 (CN-Cbl) to conserve energy via organohalide respiration. Cultures of D. mccartyi strains BAV1, GT and FL2 grown with limiting amounts of 1 µg l(-1) CN-Cbl quickly depleted CN-Cbl, and reductive dechlorination of polychlorinated ethenes was incomplete leading to vinyl chloride (VC) accumulation. In contrast, the same cultures amended with 25 µg l(-1) CN-Cbl exhibited up to 2.3-fold higher dechlorination rates, 2.8-9.1-fold increased growth yields, and completely consumed growth-supporting chlorinated ethenes. To explore whether known cobamide-producing microbes supply Dehalococcoides with the required corrinoid cofactor, co-culture experiments were performed with the methanogen Methanosarcina barkeri strain Fusaro and two acetogens, Sporomusa ovata and Sporomusa sp. strain KB-1, as Dehalococcoides partner populations. During growth with H2/CO2, M. barkeri axenic cultures produced 4.2 ± 0.1 µg l(-1) extracellular cobamide (factor III), whereas the Sporomusa cultures produced phenolyl- and p-cresolyl-cobamides. Neither factor III nor the phenolic cobamides supported Dehalococcoides reductive dechlorination activity suggesting that M. barkeri and the Sporomusa sp. cannot fulfil Dehalococcoides' nutritional requirements. Dehalococcoides dechlorination activity and growth occurred in M. barkeri and Sporomusa sp. co-cultures amended with 10 µM 5',6'-dimethylbenzimidazole (DMB), indicating that a cobalamin is a preferred corrinoid cofactor of strains BAV1, GT and FL2 when grown with chlorinated ethenes as electron acceptors. Even though the methanogen and acetogen populations tested did not produce cobalamin, the addition of DMB enabled guided biosynthesis and generated a cobalamin that supported Dehalococcoides' activity and growth. Guided cobalamin biosynthesis may offer opportunities to sustain and enhance Dehalococcoides activity in contaminated subsurface environments.


Quantification of Multi-class Cyanopeptides in Swiss Lakes with Automated Extraction, Enrichment and Analysis by Online-SPE HPLC-HRMS/MS.
The frequency and intensity of cyanobacterial blooms continue to increase in freshwater systems across the globe. Cyanobacteria can release toxins and several bioactive secondary metabolites and analytical methods are needed to effectively assess their concentrations in surface waters. Since booms can evolve rapidly in parts of a lake, high resolution of spatial and temporal sampling increases the complexity of monitoring efforts. Here, we present the validation of an automated, online-solid phase extraction (SPE) high performance liquid chromatography (HPLC)-high resolution tandem mass spectrometry (HRMS/MS) method. This online-SPE HPLC-HRMS/MS methods enables quantitative monitoring of surface waters for 17 cyanobacterial peptides (cyanopeptides), spanning 5 distinct cyanopeptide classes, including: microcystins, anabaenopeptins, nodularins, cyclamides and cyanopeptolins. The method can quantify these cyanopeptides in the low ng/L-range with high accuracy (85-116%) and low relative matrix effects (<25%). We demonstrated its application to Swiss lake waters (Zürichsee, Hallwilersee, Greifensee), which also highlighted the value of adding cyanopeptides beyond common microcystins when monitoring surface waters for cyanobacteria.


Suspected antidepressant-induced switch to mania in unipolar depression: a first-person narrative.
Antidepressant-induced switch to mania has not been thoroughly characterized in bipolar disorder and is even less well understood in unipolar depression. I describe, as a first-person narrative, my own experience of psychotic mania, which was suspected to have been induced by the tricyclic antidepressant, dosulepin. I have had a 16-year history of depression and was receiving sertraline 50 mg od when I was prescribed, off licence, dosulepin 25 mg 1-2 nocte for insomnia. Within days, I developed mild hypomanic symptoms and returned to my GP, who discontinued dosulepin but continued treatment with sertraline. I was also referred for psychiatric assessment. Two months later, I was detained under Section II of the Mental Health Act 1983 and admitted to hospital with psychotic manic symptoms. More understanding of antidepressant-induced switch to mania is needed in unipolar depression. My case study highlights the need for prompt specialist care for patients with depression reporting even mild, sub-threshold symptoms of mania.


An Electron Paramagnetic Resonance (EPR) spectroscopy study on the γ-irradiation sterilization of the pharmaceutical excipient l-histidine: Regeneration of the radicals in solution.
The effects of γ-radiation sterilization on the parenteral excipient l-histidine were analysed by means of EPR spectroscopy. The irradiation process was found to induce the formation of a deamination radical which was persistent in the solid state. The nature and reactivity of the radicals following dissolution in water was evaluated using spin-trapping EPR experiments. The deamination radical was found to regenerate in solution in the presence of trace metals, potentially leading to radical induced degradation reactions occurring up to an hour after the dissolution process. Understanding this process is significant for the improved design of parental pharmaceutical formulations in which unwanted radical reactions after γ-radiation sterilization could lead to degradation of active ingredients.


Uptake and bio-reactivity of polystyrene nanoparticles is affected by surface modifications, ageing and LPS adsorption: in vitro studies on neural tissue cells.
Because of their capacity of crossing an intact blood-brain barrier and reaching the brain through an injured barrier or via the nasal epithelium, nanoparticles have been considered as vehicles to deliver drugs and as contrast materials for brain imaging. The potential neurotoxicity of nanoparticles, however, is not fully explored. Using particles with a biologically inert polystyrene core material, we investigated the role of the chemical composition of particle surfaces in the in vitro interaction with different neural cell types. PS NPs within a size-range of 45-70 nm influenced the metabolic activity of cells depending on the cell-type, but caused toxicity only at extremely high particle concentrations. Neurons did not internalize particles, while microglial cells ingested a large amount of carboxylated but almost no PEGylated NPs. PEGylation reduced the protein adsorption, toxicity and cellular uptake of NPs. After storage (shelf-life >6 months), the toxicity and cellular uptake of NPs increased. The altered biological activity of "aged" NPs was due to particle aggregation and due to the adsorption of bioactive compounds on NP surfaces. Aggregation by increasing the size and sedimentation velocity of NPs results in increased cell-targeted NP doses. The ready endotoxin adsorption which cannot be prevented by PEG coating, can render the particles toxic. The age-dependent changes in otherwise harmless NPs could be the important sources for variability in the effects of NPs, and could explain the contradictory data obtained with "identical" NPs.


Analysis of surgical margins with the molecular marker eIF4E: a prognostic factor in patients with head and neck cancer.
Complete excision of cancer is guided by histologic assessment of surgical margins. Molecular markers may be more sensitive in identifying malignant cells. eIF4E, a eukaryotic protein synthesis initiation factor, is found elevated in all head and neck squamous cell cancers (HNSCC). In a preliminary study using Western blots and a retrospective study using immunohistochemistry, eIF4E elevation in histologically tumor-free surgical margins correlated with a higher local-regional recurrence. We wanted to confirm this hypothesis in a prospective study. Immunohistochemical analysis of surgical margins and tumors with an antibody to eIF4E was performed on all newly diagnosed HNSCC patients who underwent surgical resection for their disease between January 1996 and December 1997. All 65 patients had elevated levels of eIF4E in the tumors. Thirty-six patients (55%) had elevated eIF4E in histologically tumor-free margins, and 20 of these patients (56%) have had local-regional recu rrences. Twenty-nine patients (45%) had no elevation of eIF4E in the margins, and only two of these patients (6.9%) have had recurrences. Cox regression analysis showed that elevated eIF4E in the margins was an independent prognostic factor (P =.009) for recurrence. The Kaplan-Meier curves for the probability of nonrecurrence were significantly different for positive and negative eIF4E margins (P =. 0001, log-rank test). In histologically tumor-free surgical margins, elevated levels of eIF4E predict a significantly increased risk of recurrence. Elevated levels of eIF4E in tumor margins may identify patients who could benefit from additional therapy.


Epidemiologic trends in penile anomalies and hypospadias in the state of California, 1985-2006.
Using statewide data, we evaluated whether the changing incidence of penile anomalies and hypospadias is reflected in the diverse California population of newborn males over the past 20 years. Discharge data from all California hospitals, prepared by the OSHPD (Sacramento, CA) was reviewed for the years 1985-2006 for male infant births with an ICD-9 code (752.6) for hypospadias, epispadias or other penile anomalies. Trends were examined by Generalized Estimation Equations for Poisson regression. From 1985 to 2006, the birth incidence of newborn penile anomalies increased in California from 47 to 57 cases per 10,000 newborn discharges, yet the trend for hypospadias alone appears stable from 1997. The rates for penile anomalies in newborns increased 1.4% annually (p < 0.001). All racial/ethnic groups analyzed showed this increase (p < 0.001 for each). During the study period there was a 2% increase per year in plural births (p < 0.001). Interestingly, the rate of change in penile anomaly incidence was greater in males of plural births compared to their singleton cohorts (2% vs 1% annually) (p < 0.001). The birth incidence of cleft palate, another congenital anomaly known to be stable over time, remained unchanged over this period. From 1985 to 2006 in California the incidence of penile anomalies increased in a statistically significant manner, but the incidence of hypospadias appears stable for the last decade. Our data support the notion that different racial/ethnic groups have distinct incidences of penile anomaly formation and that an association with plural births appears to be present.


Paeoniflorin inhibits inflammatory responses in mice with allergic contact dermatitis by regulating the balance between inflammatory and anti-inflammatory cytokines.
Paeoniflorin (Pae) was previously reported to inhibit inflammation in the skin of mice with allergic contact dermatitis (ACD); however, the mechanism remains unclear. The primary purpose of this study was to investigate the effect of Pae on the regulation of cytokine production in a murine model of ACD. ACD was induced in the mice by repeated application of dinitrochlorobenzene (DNCB) to their skin. Cutaneous inflammation was evaluated by measuring ear swelling and by histological examination. The cytokine levels were measured by enzyme-linked immunosorbent assays. The results showed that topical application of DNCB caused obvious swelling and inflammatory cell infiltration. Treatment with Pae (70 or 140 mg/kg/d) significantly inhibited the cutaneous inflammation and decreased thymocyte proliferation in the mice with ACD. Additional data indicated that Pae increased interleukin-4 (IL-4) and IL-10 production but reduced IL-2 and IL-17 levels in the serum as well as in thymocyte and splenocyte culture supernatants. As expected, IL-2 and IL-17 levels in the serum displayed a significant positive correlation with the severity of skin inflammation. In contrast, IL-4 and IL-10 levels were negatively correlated with the inflammation. The anti-inflammatory action of Pae in the murine model of ACD may be related to its regulation of an imbalanced cytokine production.


Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis.
Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function. A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. cortical bridging of three cortices or disappearance of fracture lines), or could be obtained at a single pre-determined timepoint, were patients are expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PRO's) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device. The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care.


Hyperlipidemia in Saudi Arabia.
To determine the prevalence of hyperlipidemia among Saudis of both genders in rural and urban communities. Selected Saudis in the age group of 30-70 years were studied over a 5-year period between 1995 and 2000 in Saudi Arabia. Data were obtained from history, physical examination, and analysis of fasting plasma lipids. The data were analyzed to classify individuals with hypercholesterolemia (HC) (total cholesterol > or =5.2 mmol/l), and hypertriglyceridemia (HT) (total triglycerides > or =1.69 mmol/l). Logistic regression analysis was performed to provide a risk assessment model and correlation with other coronary artery disease (CAD) risk factors. The number of study samples included in the final analysis was 16,819. The prevalence of HC was 54% with mean cholesterol level of 5.4+/-1.52 mmol/l. Prevalence of HC among males was 54.9% and 53.2% for females, while 53.4% among urban Saudis and 55.3% for rural Saudis. Hypertriglycemia prevalence was 40.3% with mean triglycerides level of 1.8+/-1.29 mmol/l. Males had statistically significant higher HT prevalence of 47.6% compared to 33.7% in females (p<0.0001). Hyperlipedimia is reaching higher prevalence rates in KSA. This finding may suggest that CAD will soon be a major health problem. Reduction in obesity by adopting healthier eating habits, and increasing physical activity are of considerable importance to our community.


Self-organized criticality and pattern emergence through the lens of tropical geometry.
Tropical geometry, an established field in pure mathematics, is a place where string theory, mirror symmetry, computational algebra, auction theory, and so forth meet and influence one another. In this paper, we report on our discovery of a tropical model with self-organized criticality (SOC) behavior. Our model is continuous, in contrast to all known models of SOC, and is a certain scaling limit of the sandpile model, the first and archetypical model of SOC. We describe how our model is related to pattern formation and proportional growth phenomena and discuss the dichotomy between continuous and discrete models in several contexts. Our aim in this context is to present an idealized tropical toy model (cf. Turing reaction-diffusion model), requiring further investigation.


Cervical screening at age 50-64 years and the risk of cervical cancer at age 65 years and older: population-based case control study.
There is little consensus, and minimal evidence, regarding the age at which to stop cervical screening. We studied the association between screening at age 50-64 y and cervical cancer at age 65-83 y. Cases were women (n = 1,341) diagnosed with cervical cancer at age 65-83 y between 1 April 2007 and 31 March 2012 in England and Wales; age-matched controls (n = 2,646) were randomly selected from population registers. Screening details from 1988 onwards were extracted from national databases. We calculated the odds ratios (OR) for different screening histories and subsequent cervical cancer. Women with adequate negative screening at age 65 y (288 cases, 1,395 controls) were at lowest risk of cervical cancer (20-y risk: 8 cancers per 10,000 women) compared with those (532 cases, 429 controls) not screened at age 50-64 y (20-y risk: 49 cancers per 10,000 women, with OR = 0.16, 95% CI 0.13-0.19). ORs depended on the age mix of women because of the weakening association with time since last screen: OR = 0.11, 95% CI 0.08-0.14 at 2.5 to 7.5 y since last screen; OR = 0.27, 95% CI 0.20-0.36 at 12.5 to 17.5 y since last screen. Screening at least every 5.5 y between the ages 50 and 64 y was associated with a 75% lower risk of cervical cancer between the ages 65 and 79 y (OR = 0.25, 95% CI 0.21-0.30), and the attributable risk was such that in the absence of screening, cervical cancer rates in women aged 65+ would have been 2.4 (95% CI 2.1-2.7) times higher. In women aged 80-83 y the association was weaker (OR = 0.49, 95% CI 0.28-0.83) than in those aged 65-69 y (OR = 0.12, 95% CI 0.09-0.17). This study was limited by an absence of data on confounding factors; additionally, findings based on cytology may not generalise to human papillomavirus testing. Women with adequate negative screening at age 50-64 y had one-sixth of the risk of cervical cancer at age 65-83 y compared with women who were not screened. Stopping screening between ages 60 and 69 y in women with adequate negative screening seems sensible, but further screening may be justifiable as life expectancy increases.


Measuring severe adverse events and medication selection using a "PEER Report" for nonpsychotic patients: a retrospective chart review.
We previously reported on an objective new tool that uses quantitative electroencephalography (QEEG) normative- and referenced-electroencephalography sampling databases (currently called Psychiatric EEG Evaluation Registry [PEER]), which may assist physicians in determining medication selection for optimal efficacy to overcome trial-and-error prescribing. The PEER test compares drug-free QEEG features for individual patients to a database of patients with similar EEG patterns and known outcomes after pharmacological interventions. Based on specific EEG data elements and historical outcomes, the PEER Report may also serve as a marker of future severe adverse events (eg, agitation, hostility, aggressiveness, suicidality, homicidality, mania, hypomania) with specific medications. We used a retrospective chart review to investigate the clinical utility of such a registry in a naturalistic environment. This chart review demonstrated significant improvement on the global assessment scales Clinical Global Impression - Improvement and Quality of Life Enjoyment and Satisfaction - Short Form as well as time to maximum medical improvement and decreased suicidality occurrences. The review also showed that 54.5% of previous medications causing a severe adverse event would have been raised as a caution had the PEER Report been available at the time the drug was prescribed. Finally, due to the significant amount of off-label prescribing of psychotropic medications, additional, objective, evidence-based data aided the prescriber toward better choices. The PEER Report may be useful, particularly in treatment-resistant patients, in helping to guide medication selection. Based on the preliminary data obtained from this chart review, additional studies are warranted to establish the safety and efficacy of adding PEER data when making medication decisions.


Frontal evaluation and posterior representation in target detection.
This study examined the topography of the event-related potential in visual-spatial compared to visual-object target detection. The initial index of target detection in the ERP was an inferior anterior P2a accompanied by a posterior N2b. Single unit studies in the monkey indicate that the detection of task-relevant stimuli requires interaction between prefrontal cortex and perceptual representation areas in the posterior brain. The posterior brain processes the physical features of stimuli while frontal cortex performs higher-order operations, such as evaluating the task-relevance of a stimulus. Target detection requires an interaction between feature representations and relevance representations. We hypothesize that the P2a and N2b ERP indices of target detection reflect this frontal/posterior interaction. Visual-spatial feature information is processed in the dorsal posterior brain (posterior parietal cortex) and visual-object information is processed in the ventral posterior brain (inferior occipito-temporal cortex). We observed that at the peak of the P2a the N2b was located over posterior dorsal leads in visual-spatial target detection and over posterior ventral leads in visual-object target detection. The P2a was largest over inferior prefrontal leads in both tasks. We suggest that this distribution is consistent with interaction between orbitofrontal cortical areas of salience representation and posterior cortical areas of stimulus feature representation.


Tubular urachal remnants in adult bladders.
We studied the structure and histologic appearance of intramural tubular urachal remnants in bladders from an unselected series of 122 autopsies, in which the patient age at death was 38 to 91 years. The bladders were fixed with formaldehyde introduced 10 minutes to 5 hours post mortem. Of the bladders 32 per cent showed tubular urachal remnants. The remnants were classified into 3 types on the basis of the epithelial extent and structure. Of the remnants 68.4 per cent had lumen covered with transitional epithelium, while the remainder had columnar epithelium. Bud-like epithelial proliferations were found in 43.6 per cent and mild dysplasia of the epithelium was found in 7.7 per cent of the urachal remnants, while mild inflammation in the loose peritubular tissue was demonstrated in 23.1 per cent.


T-Cell Specificity Influences Disease Heterogeneity in Multiple Sclerosis.
Encouraged by the enormous progress that the identification of specific autoantigens added to the understanding of neurologic autoimmune diseases, we undertook here an in-depth study of T-cell specificities in the autoimmune disease multiple sclerosis (MS), for which the spectrum of responsible autoantigens is not fully defined yet. The identification of target antigens in MS is crucial for therapeutic strategies aimed to induce antigen-specific tolerance. In addition, knowledge of relevant T-cell targets can improve our understanding of disease heterogeneity, a hallmark of MS that complicates clinical management. The proliferative response and interferon gamma (IFN-γ) release of CSF-infiltrating CD4+ T cells from patients with MS against several autoantigens was used to identify patients with different intrathecal T-cell specificities. Fresh CSF-infiltrating and paired circulating lymphocytes in these patients were characterized in depth by ex vivo immunophenotyping and transcriptome analysis of relevant T-cell subsets. Further examination of these patients included CSF markers of inflammation and neurodegeneration and a detailed characterization with respect to demographic, clinical, and MRI features. By testing CSF-infiltrating CD4+ T cells from 105 patients with MS against seven long-known myelin and five recently described GDP-l-fucose synthase peptides, we identified GDP-l-fucose synthase and myelin oligodendrocyte glycoprotein (35-55) responder patients. Immunophenotyping of CSF and paired blood samples in these patients revealed a significant expansion of an effector memory (CCR7- CD45RA-) CD27- Th1 CD4+ cell subset in GDP-l-fucose synthase responders. Subsequent transcriptome analysis of this subset demonstrated expression of Th1 and cytotoxicity-associated genes. Patients with different intrathecal T-cell specificities also differ regarding inflammation- and neurodegeneration-associated biomarkers, imaging findings, expression of HLA class II alleles, and seasonal distribution of the time of the lumbar puncture. Our observations reveal an association between autoantigen reactivity and features of disease heterogeneity that strongly supports an important role of T-cell specificity in MS pathogenesis. These data have the potential to improve patient classification in clinical practice and to guide the development of antigen-specific tolerization strategies.


TCEAL7, a putative tumor suppressor gene, negatively regulates NF-kappaB pathway.
We have previously shown that a frequently downregulated gene, transcription elongation factor A-like 7 (TCEAL7), promoted anchorage-independent growth and modulated Myc activity in ovarian surface epithelial cells immortalized with temperature-sensitive large T antigen and human telomerase reverse transcriptase (OSEtsT/hTERT). Analysis of protein/DNA array showed that TCEAL7 downregulation resulted in an approximately twofold increase in nuclear factor (NF)-kappaB binding to its target DNA sequence. In this study we showed that short hairpin RNA (shRNA)-mediated downregulation of TCEAL7 in two different immortalized OSE cells showed higher NF-kappaB activity, as determined using reporter and gel-shift assays. Transient transfection of TCEAL7 inhibited the activation of NF-kappaB in TCEAL7-downregulated clones, IOSE-523 and in other ovarian cancer cell lines (OVCAR8, SKOV3ip and DOV13), suggesting that TCEAL7 negatively regulates NF-kappaB pathway. Consistent with this observation, TCEAL7-downregulated clones showed higher levels of NF-kappaB targets, such as pro-proliferative (cyclin-D1 and cMyc), pro-angiogenic (interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF)), inflammatory (intercellular adhesion molecule 1 (ICAM-1) and cyclooxygenase-2 (Cox-2)) and anti-apoptotic (B-cell lymphoma-extra large (Bcl-xl)) genes when compared with vector controls. Inhibition of NF-kappaB by IkappaB kinase (IKK) inhibitor (BMS 345541) attenuated cell survival and proliferation of TCEAL-knockdown clones. Although TCEAL7 inhibited p65 transcriptional activity, it did not modulate the cytoplasmic signaling of the NF-kappaB pathway, by itself or by tumor necrosis factor-alpha (TNF-alpha). Chromatin immunoprecipitation (ChIP) assays revealed increased recruitment of p65 and p300 to the promoters of IL-8 and IL-6 in TCEAL7-downregulated clones. Collectively, these results indicate a novel role for TCEAL7 in the negative regulation of NF-kappaB signaling at the basal level by modulating transcriptional activity of NF-kappaB on its target gene promoters, potentially providing a novel mechanism by which NF-kappaB activity may be deregulated in ovarian cancer cells.


Contextually Mediated Spontaneous Retrieval Is Specific to the Hippocampus.
Although it is now well established that the hippocampus supports memory encoding [1, 2], little is known about hippocampal activity during spontaneous memory retrieval. Recent intracranial electroencephalographic (iEEG) work has shown that hippocampal activity during encoding predicts subsequent temporal organization of memories [3], supporting a role in contextual binding. It is an open question, however, whether the hippocampus similarly supports contextually mediated processes during retrieval. Here, we analyzed iEEG recordings obtained from 215 epilepsy patients as they performed a free recall task. To identify neural activity specifically associated with contextual retrieval, we compared correct recalls, intrusions (incorrect recall of either items from prior lists or items not previously studied), and deliberations (matched periods during recall when no items came to mind). Neural signals that differentiate correct recalls from both other retrieval classes reflect contextual retrieval, as correct recalls alone arise from the correct context. We found that in the hippocampus, high-frequency activity (HFA, 44-100 Hz), a proxy for neural activation [4], was greater prior to correct recalls relative to the other retrieval classes, with no differentiation between intrusions and deliberations. This pattern was not observed in other memory-related cortical regions, including DLPFC, thus supporting a specific hippocampal contribution to contextually mediated memory retrieval.


Principal component analysis of dynamic fluorescence diffuse optical tomography images.
Challenges remain in resolving drug distributions within small animals utilizing fluorescence diffuse optical tomography (FDOT). In this paper, we present a new method for detecting and visualizing organs with different kinetics utilizing principal component analysis (PCA). Indocynaine green (ICG) metabolic processes are simulated and imaged using FDOT. When applied to the time series of generated FDOT images, PCA provides a set of the principal components (PCs) which can represent spatial patterns associated with different kinetic behavior. Simulation and experiment studies are both performed to validate the performance of the proposed algorithm. The results suggest that we are able to extract and illustrate changes in ICG kinetic behavior between the heart and the lungs.


Rectal spirochaetosis--symptomatic response to metronidazole and mebendazole. A case report.
A white homosexual man presented with a 6-week history of intermittent diarrhoea, abdominal pain, nausea and malaise. Threadworm infestation was present, but other gastro-intestinal infection was excluded. Rectal spirochaetosis was found on examination of a rectal biopsy specimen. The patient's symptoms disappeared and the rectal tissue returned to normal on biopsy after treatment with metronidazole and mebendazole. It is suggested that the symptoms were directly related to the presence of rectal spirochaetosis, which responded to the antibiotic.


Structural evolution of reoviridae revealed by oryzavirus in acquiring the second capsid shell.
The conservation of the core structure and diversification of the external features among the turreted reoviruses appear to be relevant to structural evolution in facilitating the infection of diverse host species. The structure of Rice ragged stunt virus (RRSV), in the genus Oryzavirus of the family Reoviridae, is determined to show a core composed of capsid shell, clamps, and long turrets. The RRSV core structure is equivalent to the core structure of Orthoreovirus and the virion structure of Cytoplasmic polyhedrosis virus (CPV). In RRSV, five peripheral trimers surround each long turret and sit at the Q trimer position in the T=13l icosahedral symmetry, a structural feature unique to turreted reoviruses. That is, the core of RRSV is partially covered by 60 copies of the peripheral trimer. In contrast, the core of Orthoreovirus is covered by 200 copies of the trimer that sit at the Q, R, S, and T trimer positions. Our results suggest that among the three viruses, RRSV has a structure intermediate between that of Orthoreovirus and the CPV virion. This conclusion coincides with the results of the phylogenetic analysis of amino acid sequences of RNA-dependent RNA polymerases.


Characteristics of patients with atrial high rate episodes detected by implanted defibrillator and resynchronization devices.
Atrial high rate episodes (AHREs) are associated with increased risks of thromboembolism and cardiovascular mortality. However, the clinical characteristics of patients developing AHRE of various durations are not well studied. This was an ancillary analysis of the multicentre, randomized IMPACT trial. In the present analysis, we classified patients according to the duration of AHRE ≤6 min, >6 min to ≤6 h, >6 to ≤24 h and >24 h, and investigated the association between clinical factors and the development of each duration of AHRE. Of 2718 patients included in the trial, 945 (34.8%) developed AHRE. The incidence rates of each AHRE duration category were 5.4/100, 12.0/100, 6.8/100, and 3.3/100 patient-years, respectively. The incidence rates of AHRE >6 h were significantly higher in patients at high risk of thromboembolism (CHADS2 score ≥3) compared to those at low risk (CHADS2 score 1 or 2). Using Cox regression analysis, age ≥65 years and history of atrial fibrillation (AF) and/or atrial flutter (AFL) were risk factors for AHRE >6 min. In addition, hypertension was associated with AHRE >24 h (hazard ratio 2.13, 95% confidence interval 1.24-3.65, P = 0.006). Atrial high rate episode >6 min to ≤6 h were most prevalent among all AHRE duration categories. Longer AHREs were more common in patients at risk of thromboembolism. Age and history of AF/AFL were risk factors for AHRE >6 min. Furthermore, hypertension showed a strong impact on the development of AHRE >24 h rather than age.


[Development of index of social activities for the elderly].
In order to develop indices of social activities for the elderly, two surveys with 2 year intervals were conducted on the same 5,201 elderly subjects in four areas in Japan using a self-administered questionnaire. Social activities were defined as "activities which required contact with society" and were measured by 4 major facets of social activities, which were based on 21 questions relating to job activity, socially-plated activities, learning activities, and personal activities. The results were as follows; 1. The Wilcoxon scores in indices for 4 facets were given in sex and age groups. 2. Means of scores of indices increased with the degree of social activities from a subjective judgment. 3. Rank correlation coefficients between indices in two surveys were 0.60-0.71 for the persons whose answers were "no" to the question "did degrees of your activities change over the two years?" 4. Differences between indices in two surveys were higher in the persons with answers of "increase" to the above question than those with answers of "no", and were lower in those with answers of "decrease". These findings suggest that indices are available for assessing social activities as indicated by the reproducibility, validity and responsiveness found in this study.


Insight into the molecular interaction between the cyclic nucleotide-binding homology domain and the eag domain of the hERG channel.
The gating of the hERG channel is regulated by its eag domain through molecular interaction with either the cyclic nucleotide-binding homology domain (CNBHD) or the linker between transmembrane segments 4 and 5. Our NMR study on the purified CNBHD demonstrated that it contains nine β-strands and does not bind cAMP. We show that the eag domain binds to the CBND through an interface containing several disease-associated mutations. The N-terminal cap domain and R56 in the eag domain are important for the interaction with the CNBHD. Residues from the CNBHD that were affected by the interaction with the eag domain were also identified. A R56Q mutation does not cause major structural changes in the eag domain and showed reduced interaction with the CNBHD.


Gallic Acid Inhibits Bladder Cancer T24 Cell Progression Through Mitochondrial Dysfunction and PI3K/Akt/NF-κB Signaling Suppression.
Gallic acid (GA), a hydrolyzable tannin, has a wide range of pharmacological activities. This study revealed that, GA significantly inhibited T24 cells viability in a concentration- and time- dependent manner. The IC50 of GA stimulating T24 cells for 24, 48, and 72 h were 21.73, 18.62, and 11.59 µg/ml respectively, and the inhibition rate was significantly higher than the positive control drug selected for CCK-8 assay. Meanwhile, after GA treatment, the morphology of T24 cells were changed significantly. Moreover, GA significantly inhibited T24 cells proliferation and blocked T24 cells cycle in S phase (p < 0.001). GA induced T24 cells apoptosis (p < 0.001), accompanied by reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) depolarization. Western blotting analysis showed that GA significantly increased Cleaved caspase-3, Bax, P53, and Cytochrome C (Cyt-c) proteins expression, and decreased Bcl-2, P-PI3K, P-Akt, P-IκBα, P-IKKα, and P-NF-κB p65 proteins expression in T24 cells (p < 0.05). Real-Time PCR results verified that GA significantly promoted Caspase-3, Bax, P53, and Cyt-c genes expression, and inhibited Bcl-2, PI3K, Akt, and NF-κB p65 genes expression (p < 0.001). However, on the basis of GA (IC50) stimulation, NAC (an oxidative stress inhibitor) pretreatment reversed the apoptotic rate of T24 cells and the expression of Bax, Cleaved caspase-3, P53, Bcl-2 proteins, and the MMP level in T24 cells, as well as the expression of Cyt-c protein in T24 cells mitochondria and cytoplasm. In addition, GA significantly suppressed T24 cells migration and invasion ability with VEGF protein inhibition (p < 0.001). Briefly, GA can inhibit T24 cells proliferation, metastasis and promote apoptosis, and the pro-apoptotic activity is closely associated with mitochondrial dysfunction and PI3K/Akt/NF-κB signaling suppression. Our study will help in finding a safe and effective treatment for bladder cancer.


Relationship between sex roles and mental disorders.
The present study "Relationship between sex roles and mental disorders" analyses the various findings of research regarding the sex roles and mental problems. All these findings reveal that the women whether they work outside or not, face various mental problems especially functional psychosis and neurosis. This finding is also proved by the research of National Institute of Mental Health (NIMH) of U.S.A. They analysed the admissions and the treatment give for the psychologically affected persons in various hospitals and came across more women patients than the men. The research also formulates some possible suggestions to curb the mental disorders among the women.


Identification of Posttranslational Modifications in Peroxisome Proliferator-Activated Receptor γ Using Mass Spectrometry.
Posttranslational modification (PTM) of proteins is critical for various cellular processes. However, there are few studies examining PTMs in specific proteins using unbiased approaches. Here we report the attempt to identify the PTMs in peroxisome proliferator-activated receptor γ (PPARγ) proteins using our previously established PTM analysis system. In this study, we identified several PTMs in exogenously expressed PPARγ2 proteins from 293T cells as well as endogenous PPARγ1 proteins from a Caco-2 colon cancer cell line. The identified PTMs include phosphorylation of serine 112 and serine 81 in PPARγ2 and PPARγ1, respectively, both of which are well-known mitogen-activated protein kinase- (MAP kinase-) mediated PTMs in PPARγ proteins, thus confirming our experimental approach. Furthermore, previously unknown PTMs were also identified, demonstrating that this method can be applied to find previously unidentified PTMs in PPARγ proteins and other proteins including nuclear receptors.


Polonium-210 and lead-210 in the terrestrial environment: a historical review.
The radionuclides (210)Po and (210)Pb widely present in the terrestrial environment are the final long-lived radionuclides in the decay of (238)U in the earth's crust. Their presence in the atmosphere is due to the decay of (222)Rn diffusing from the ground. The range of activity concentrations in ground level air for (210)Po is 0.03-0.3 Bq m(-3) and for (210)Pb 0.2-1.5 Bq m(-3). In drinking water from private wells the activity concentration of (210)Po is in the order of 7-48 mBq l(-1) and for (210)Pb around 11-40 mBq l(-1). From water works, however, the activity concentration for both (210)Po and (210)Pb is only in the order of 3 mBq l(-1). Mosses, lichens and peat have a high efficiency in capturing (210)Po and (210)Pb from atmospheric fallout and exhibit an inventory of both (210)Po and (210)Pb in the order of 0.5-5 kBq m(-2) in mosses and in lichens around 0.6 kBq m(-2). The activity concentrations in lichens lies around 250 Bq kg(-1), dry mass. Reindeer and caribou graze lichen which results in an activity concentration of (210)Po and (210)Pb of about 1-15 Bq kg(-1) in meat from these animals. The food chain lichen-reindeer or caribou, and Man constitutes a unique model for studying the uptake and retention of (210)Po and (210)Pb in humans. The effective annual dose due to (210)Po and (210)Pb in people with high consumption of reindeer/caribou meat is estimated to be around 260 and 132 μSv a(-1) respectively. In soils, (210)Po is adsorbed to clay and organic colloids and the activity concentration varies with soil type and also correlates with the amount of atmospheric precipitation. The average activity concentration levels of (210)Po in various soils are in the range of 20-240 Bq kg(-1). Plants become contaminated with radioactive nuclides both by absorption from the soil (supported Po) and by deposition of radioactive fallout on the plants directly (unsupported Po). In fresh leafy plants the level of (210)Po is particularly high as the result of the direct deposition of (222)Rn daughters from atmospheric deposition. Tobacco is a terrestrial product with high activity concentrations of (210)Po and (210)Pb. The overall average activity concentration of (210)Po is 13 ± 2 Bq kg(-1). It is rather constant over time and by geographical origin. The average median daily dietary intakes of (210)Po and (210)Pb for the adult world population was estimated to 160 mBq day(-1) and 110 mBq day(-1), corresponding to annual effective doses of 70 μSv a(-1) and 28 μSv a(-1), respectively. The dietary intakes of (210)Po and (210)Pb from vegetarian food was estimated to only 70 mBq day(-1) and 40 mBq day(-1) corresponding to annual effective doses of 30.6 μSv a(-1) and 10 μSv a(-1), respectively. Since the activity concentration of (210)Po and (210)Pb in seafood is significantly higher than in vegetarian food the effective dose to populations consuming a lot of seafood might be 5-15 fold higher.


Prevalence of co-occurring mental health diagnoses in the autism population: a systematic review and meta-analysis.
Co-occurring mental health or psychiatric conditions are common in autism, impairing quality of life. Reported prevalences of co-occurring mental health or psychiatric conditions in people with autism range widely. Improved prevalence estimates and identification of moderators are needed to enhance recognition and care, and to guide future research. In this systematic review and meta-analysis, we searched MEDLINE, Embase, PsycINFO, Scopus, Web of Science, and grey literature for publications between Jan 1, 1993, and Feb 1, 2019, in English or French, that reported original research using an observational design on the prevalence of co-occurring mental health conditions in people with autism and reported confirmed clinical diagnoses of the co-occurring conditions and autism using DSM or ICD criteria. For co-occurring mental health conditions reported with at least 15 datapoints (studies), we assessed risk of bias and we determined pooled estimates of prevalence for different co-occurring conditions in autism using random-effects models, and descriptively compared these with prevalence estimates for the general population from the literature (post hoc). We investigated heterogeneity in prevalence estimates using random-effects meta-regression models. This systematic review is registered with PROSPERO, CRD42018103176. Of 9746 unique studies identified, 432 were selected for full-text review. 100 studies were eligible for inclusion in our qualitative synthesis, of which 96 were included in our meta-analyses. 11 categories of co-occurring conditions were investigated, of which eight conditions were included in the meta-analyses and three were descriptively synthesised (ie, trauma and stressor-related disorders, substance-related and addictive disorders, and gender dysphoria). From our meta-analyses, we found overall pooled prevalence estimates of 28% (95% CI 25-32) for attention-deficit hyperactivity disorder; 20% (17-23) for anxiety disorders; 13% (9-17) for sleep-wake disorders; 12% (10-15) for disruptive, impulse-control, and conduct disorders; 11% (9-13) for depressive disorders; 9% (7-10) for obsessive-compulsive disorder; 5% (3-6) for bipolar disorders; and 4% (3-5) for schizophrenia spectrum disorders. Estimates in clinical sample-based studies were higher than in population-based and registry-based studies, and these estimates were mostly higher than those in the general population (post hoc). Age, gender, intellectual functioning, and country of study were associated with heterogeneity in prevalence estimates, yet remaining heterogeneity not explained was still substantial (all I2 >95%). Co-occurring mental health conditions are more prevalent in the autism population than in the general population. Careful assessment of mental health is an essential component of care for all people on the autism spectrum and should be integrated into clinical practice. Academic Scholars Awards, Department of Psychiatry, University of Toronto; O'Brien Scholars Program, Slaight Family Child and Youth Mental Health Innovation Fund, and The Catherine and Maxwell Meighen Foundation via the Centre for Addiction and Mental Health Foundation.


Peripheral coding of tonic mechanical cutaneous pain: comparison of nociceptor activity in rat and human psychophysics.
These experiments investigated temporal summation mechanisms of tonic cutaneous mechanical pain. Human volunteers provided psychophysical estimates of pain intensity, which were compared with discharge patterns of rat cutaneous nociceptors tested with identical stimulus protocols. Human subjects made either intermittent or continuous ratings of pain intensity during stimulation of the skin between the thumb and first finger. Stimulus intensities of 25, 50, and 100 g were applied with a probe of contact area of 0.1 mm(2) for 2 min. Pain perception significantly increased during stimulation (temporal summation) for the 50- and 100-g stimulus intensities. Sequential conduction block of the myelinated fibers supplying the stimulated skin was used to investigate the role of A-fiber mechanoreceptors and nociceptors in this temporal summation. Conduction block of the Abeta fibers resulted in an increase in mechanically evoked pain estimates and an increase in temporal summation, consistent with loss of Abeta-mediated inhibition. When only conduction in the unmyelinated fibers remained, pain estimates were reduced to the preblock levels, but temporal summation was still present. Electrophysiological recordings were made from filaments of the sciatic nerve supplying receptors in the plantar skin of barbiturate-anesthetized rats. Forty units fulfilled the identification criteria for nociceptors: 20 A-fiber and 20 C-fiber nociceptors. Each unit was characterized by recording its responses to graded mechanical and heat stimuli. Nociceptors were also tested with stimuli identical to those applied to the human subjects. The responses of all units to sustained mechanical stimuli were adaptive-that is, they exhibited a gradual decline in response with time. However, the time course of adaptation varied among units. All the C-fiber nociceptors and one-half of the A-fiber nociceptors had rapidly adapting responses. The remainder of the A-fibers displayed slowly adapting responses. One-third of all units also showed short-duration increases in firing rate during stimulation. The latency after stimulus onset of this rate acceleration was inversely related to stimulus intensity. Despite the apparent disparity between perceptual temporal summation and nociceptor adaptation, central and peripheral mechanisms are proposed that can reconcile the relationship between nociceptor activity and pain perception.


Isolation and characterization of monoclonal antibodies to Shiga-like toxin II of enterohemorrhagic Escherichia coli and use of the monoclonal antibodies in a colony enzyme-linked immunosorbent assay.
The major obstacle in large-scale epidemiological investigations of the incidence of Shiga-like toxin (SLT)-producing Escherichia coli in diarrheal stools is the lack of a rapid, specific test to detect toxin. Enterohemorrhagic E. coli produces elevated levels of SLT-I, SLT-II, or both cytotoxins (also called Verotoxins). SLT-I but not SLT-II can be neutralized by antiserum to purified Shiga toxin and by monoclonal antibodies to the B subunit of SLT-I. In this study, monoclonal antibodies were generated against a crude preparation of SLT-II produced by an E. coli K-12 strain lysogenized with the 933W toxin-converting phage of enterohemorrhagic E. coli 933. Hybridoma culture supernatants were screened for anti-SLT-II antibodies by a cytotoxicity neutralization assay and by an enzyme-linked immunosorbent assay (ELISA). Of 53 ELISA-positive lines, 5 were capable of neutralizing the cytotoxicity of SLT-II but not of SLT-I, Shiga toxin, or a variant of SLT-II produced by E. coli that causes edema disease of swine. All five monoclonal antibodies immunoprecipitated the isolated A subunit of SLT-II but not the B subunit. Of these five neutralizing monoclonal antibodies, four were of the immunoglobulin M class and one belonged to the immunoglobulin G1 subclass. All five lines had kappa light chains. These neutralizing monoclonal antibodies have been used as probes in a colony ELISA to detect SLT-II-positive bacterial colonies. The colony ELISA with these monoclonal antibodies is a specific, sensitive test with potential diagnostic value.


Role of Aspergillus fumigatus DvrA in host cell interactions and virulence.
The transcription factors that regulate Aspergillus fumigatus interactions with host cells and virulence are incompletely defined. We investigated the role of the putative C2H2 transcription factor DvrA in governing these processes. Although DvrA was identified by its limited homology to Candida albicans Bcr1, a ΔdvrA mutant strain of A. fumigatus had wild-type adherence to host constituents in vitro. However, it had increased capacity to damage both endothelial cells and a pulmonary epithelial cell line compared to the ability of the wild-type strain and a ΔdvrA::dvrA-complemented strain. This increase in damage required direct contact between the mutant and host cells. The ΔdvrA mutant also stimulated greater CCL20, interleukin-8, and tumor necrosis factor mRNA expression in a pulmonary epithelial cell line compared to levels induced by the control strains. Also, it was resistant to nikkomycin Z, suggesting an altered cell wall composition. As predicted by these in vitro results, the ΔdvrA mutant had increased virulence and stimulated a greater pulmonary inflammatory response than the wild-type strain and ΔdvrA::dvrA-complemented strains in the nonneutropenic mouse model of invasive pulmonary aspergillosis. These results indicate that DvrA influences A. fumigatus virulence as well as its capacity to damage host cells and stimulate a proinflammatory response.


Influencing sexual practices among HIV-positive Zambian women.
This study assessed and compared the efficacy of culturally tailored behavioral interventions to increase use and acceptability of sexual barrier products among HIV-positive women in Zambia. It also sought to evaluate cultural preferences as facilitators or impediments to potential use of vaginal chemical barriers for sexual risk reduction within the Zambian context. Women (N=240), recruited from the University Teaching Hospital HIV Voluntary Counseling and Testing Center, were randomized into group or individual intervention arms. Participants attended a baseline assessment, three intervention sessions and follow up assessments at six and 12 months. All participants increased use and acceptability of female condoms and vaginal products and maintained male condom use at six and 12 months. Preliminary data indicated that group participants increased male condom use at six months and trial use and acceptability of female condoms and lubricants predicted their use in the group condition. Results support group interventions to increase sexual barrier use and acceptability in HIV-positive women within the Zambian context. From a public health standpoint, groups may represent a cost-effective and culturally congruent intervention.


Stress-induced changes in pathophysiology and interferon gene expression during primary HSV-1 infection.
Herpes simplex viruses (HSV) are the cause of the most common clinically recognized herpesvirus infections. The severity and duration of the primary HSV infection have been correlated with the frequency and severity of subsequent recurrences. Reactivation of latent HSV-1 can occur as a result of physical or emotional stress; however, the effects of stress on the modulation of the clinical pathophysiology of primary HSV-1 infections are not well understood. Although it is known that stress can be immunosuppresive, the immunological mechanisms by which stress modulates early immune responses, such as type I interferon gene expression during a primary HSV-1 infection are still not understood. It was hypothesized that due to suppressed early immune responses, stress would increase the severity of a cutaneous primary HSV-1 infection. In this investigation, a cutaneous HSV-1 model in the SKH-1 mouse was characterized and utilized to study the effect of restraint stress on the modulation of the clinical pathophysiology of primary HSV-1. Despite prolonged viral replication at the site of primary infection, restraint stress decreased the clinical severity of primary HSV-1 in the skin of SKH-1 mice. A decrease in type I and type II IFN expression was found in the skin of acutely infected restrained mice when compared to controls at day 3 post-infection using competitive RT-PCR. Using the glucocorticoid-receptor antagonist RU486, IFN-beta and INF-gamma expression were restored in restrained animals to control levels. Treatment with RU486 also increased the clinical severity of the cutaneous infection to control levels in restrained mice. Thus, RST masked the severity of an HSV-1 infection by decreasing its clinical signs while impairing the ability of the host to control viral replication prolonging the infectious period.


Gender disparities in pulmonary hypertension at a tertiary centre in Cameroon.
Pulmonary hypertension (PH) is a potent cause of heart failure and has been little investigated in the African setting. To investigate the effects of gender on the clinical presentation, echocardiographic features and outcomes of patients with PH in Douala, Cameroon. A prospective cohort study was conducted from March 2012 to December 2013 as part of the Pan African Pulmonary Hypertension Cohort study. PH was diagnosed by echocardiography and defined as a right ventricular systolic pressure >35 mmHg in the absence of acute right heart failure. Patients were followed up for a maximum of 12 months for primary endpoint mortality. In total, 130 patients with PH were recruited; 71 (54.6%) were women. The median age was 59.2 years for men and 58.3 years for women (p=0.76). Active smoking and alcohol use were more frequent in men than women (both p<0.001), but women had greater exposure to indoor cooking fumes than men (p<0.001). Previous tuberculosis infection (11.3% v. 1.7%) and S3 gallop rhythm (30.9% v. 11.9%) were more common in women (both p<0.03). Women had a significantly higher mean systolic blood pressure (134 mmHg v. 125 mmHg; p=0.04) and pulse pressure (53.8 mmHg v. 44.9 mmHg; p=0.01) and a lower mean haemoglobin concentration (10.4 g/dL v. 12.4 g/dL; p<0.05) compared with men. Echocardiographic left ventricular (LV) systolic dysfunction was more frequent in men: mean LV ejection fraction 42.6% v. 51.5% (p=0.01) and mean fractional shortening 21.4% v. 28.6% (p=0.01). The overall mortality rate was 20.3%, and rates were similar in the two groups (Kaplan-Meier log rank 1.1; p=0.30). Despite differences in baseline characteristics including cardiovascular risk factors, mortality rates on follow-up were similar in men and women in this study. However, these different baseline characteristics probably suggest differences in the pathogenesis of PH in men and women in our setting that need further investigation.


Rust Infection of Black Poplar Trees Reduces Photosynthesis but Does Not Affect Isoprene Biosynthesis or Emission.
Poplar (Populus spp.) trees are widely distributed and play an important role in ecological communities and in forestry. Moreover, by releasing high amounts of isoprene, these trees impact global atmospheric chemistry. One of the most devastating diseases for poplar is leaf rust, caused by fungi of the genus Melampsora. Despite the wide distribution of these biotrophic pathogens, very little is known about their effects on isoprene biosynthesis and emission. We therefore infected black poplar (P. nigra) trees with the rust fungus M. larici-populina and monitored isoprene emission and other physiological parameters over the course of infection to determine the underlying mechanisms. We found an immediate and persistent decrease in photosynthesis during infection, presumably caused by decreased stomatal conductance mediated by increased ABA levels. At the same time, isoprene emission remained stable during the time course of infection, consistent with the stability of its biosynthesis. There was no detectable change in the levels of intermediates or gene transcripts of the methylerythritol 4-phosphate (MEP) pathway in infected compared to control leaves. Rust infection thus does not affect isoprene emission, but may still influence the atmosphere via decreased fixation of CO2.


Space Radiation Protection Countermeasures in Microgravity and Planetary Exploration.
Space radiation is one of the principal environmental factors limiting the human tolerance for space travel, and therefore a primary risk in need of mitigation strategies to enable crewed exploration of the solar system. We summarize the current state of knowledge regarding potential means to reduce the biological effects of space radiation. New countermeasure strategies for exploration-class missions are proposed, based on recent advances in nutrition, pharmacologic, and immune science. Radiation protection can be categorized into (1) exposure-limiting: shielding and mission duration; (2) countermeasures: radioprotectors, radiomodulators, radiomitigators, and immune-modulation, and; (3) treatment and supportive care for the effects of radiation. Vehicle and mission design can augment the overall exposure. Testing in terrestrial laboratories and earth-based exposure facilities, as well as on the International Space Station (ISS), has demonstrated that dietary and pharmacologic countermeasures can be safe and effective. Immune system modulators are less robustly tested but show promise. Therapies for radiation prodromal syndrome may include pharmacologic agents; and autologous marrow for acute radiation syndrome (ARS). Current radiation protection technology is not yet optimized, but nevertheless offers substantial protection to crews based on Lunar or Mars design reference missions. With additional research and human testing, the space radiation risk can be further mitigated to allow for long-duration exploration of the solar system.


Subcellular fractions of vascular smooth muscle exhibiting calcium transport properties.
Vascular smooth muscle relies on two general sources of activator calcium, one the extracellular fluid and the other intracellular sites in the coupling between stimulation at the external membrane and tension development. Electron microscopic studies have demonstrated at least two subcellular elements, mitochondria and sarcoplasmic reticulum, that may participate in the release and/or sequestration of this activator calcium. In order to obtain quantitative answers to questions concerning the rates of calcium transport by these subcellular elements attempts to use differential centrifugation to obtain subcellular fractions from whole muscle homogenate have been reported. Mitochondrial enriched preparations have received little quantitative study as yet, although they possess active calcium uptake mechanisms. Nonmitochondrial preparations having active calcium uptake mechanisms have been found in a variety of smooth muscles. The method of preparation and properties of these nonmitochondrial preparations show a great deal of variation, indicating they are probably a heterogeneous mixture of sarcoplasmic reticulum and plasma membrane. Some preliminary experiments on the effects of vasoactive agents and cyclic AMP on the calcium transport by these nonmitochondrial preparations have yielded conflicting results. Resolution of these problems awaits clear identification of the calcium transport mechanisms with their appropriate subcellular structure.


Changes of Milk Metabolomic Profiles Resulting from a Mycotoxins-Contaminated Corn Silage Intake by Dairy Cows.
In this study, an untargeted metabolomics approach based on ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) was used for investigating changes in chemical profiles of cow milk considering diets based on mycotoxins-contaminated corn silages. For this purpose, 45 milk samples were classified into five clusters according to the corn silage contamination profile, namely (1) low levels of Aspergillus- and Penicillium-mycotoxins; (2) low levels of fumonisins and other Fusarium-mycotoxins; (3) high levels of Aspergillus-mycotoxins; (4) high levels of non-regulated Fusarium-mycotoxins; (5) high levels of fumonisins and their metabolites, and subsequently analyzed by UHPLC-HRMS followed by a multivariate statistical analysis (both unsupervised and supervised statistical approaches). Overall, the milk metabolomic profile highlighted potential correlations between the quality of contaminated corn silages (as part of the total mixed ration) and milk composition. Metabolomics allowed to identify 628 significant milk metabolites as affected by the five levels of corn silage contamination considered, with amino acids and peptides showing the highest metabolite set enrichment (134 compounds). Additionally, 78 metabolites were selected as the best discriminant of the prediction model built, possessing a variable importance in projection score >1.2. The average Log Fold-Change variations of the discriminant metabolites provided evidence that sphingolipids, together with purine and pyrimidine-derived metabolites were the most affected chemical classes. Also, metabolomics revealed a significant accumulation of oxidized glutathione in milk samples belonging to the silage cluster contaminated by emerging Aspergillus toxins, likely involved in the oxidative imbalance. These preliminary findings provide new insights into the potential role of milk metabolomics to provide chemical indicators of mycotoxins-contaminated corn silage feeding systems.


Detection of Pneumocystis jirovecii in oral wash from immunosuppressed patients as a diagnostic tool.
Diagnosis of Pneumocystis jirovecii (PJ) pneumonia ordinarily requires invasive procedures that could be avoided by PCR methodologies, if these could be designed with adequate cut-off values for confounding background carriage. We designed a novel quantitative real-time PCR assay to detect the mitochondrial large subunit rRNA gene of PJ in oral washes. To benchmark levels of PJ carriage versus infection, we tested asymptomatic immunosuppressed patients including Danish (n = 88) and West African HIV-infected (n = 142) patients, renal transplant recipients (n = 51), rheumatologic patients (n = 102), patients with inflammatory bowel diseases (n = 98), and healthy blood donors (controls, n = 50). The fungal burden in patients with PJ pneumonia (PCP, n = 7) was also investigated. Danish HIV-infected patients (with viremia/low CD4) and recent transplant recipients were at most risk of being carriers (prevalence of 23% and 16.7% respectively), whereas PJ was rarely detected among rheumatologic patients, patients with inflammatory bowel diseases, and untreated West African HIV patients. PJ was not detected among healthy controls. The fungal burden in patients with PCP fell rapidly on treatment. The quantitative PCR method described could conceivably discriminate between carriage and disease, given suitable threshold values for the former, and predict treatment efficacy by measures of the fungal burden in daily oral washes.


EDEN and EDEN-BP, a cis element and an associated factor that mediate sequence-specific mRNA deadenylation in Xenopus embryos.
During Xenopus early development, gene expression is regulated mainly at the translational level by the length of the poly(A) tail of mRNAs. The Eg family and c-mos maternal mRNAs are deadenylated rapidly and translationally repressed after fertilization. Here, we characterize a short sequence element (EDEN) responsible for the rapid deadenylation of Eg5 mRNA. Determining the core EDEN sequence permitted us to localize the c-mos EDEN sequence. The c-mos EDEN confered a rapid deadenylation to a reporter gene. The EDEN-specific RNA-binding protein (EDEN-BP) was purified and a cDNA obtained. EDEN-BP is highly homologous to a human protein possibly involved in myotonic dystrophy. Immunodepleting EDEN-BP from an egg extract totally abolished the EDEN-mediated deadenylation activity, but did not affect the default deadenylation activity. Therefore, EDEN-BP constitutes the first trans-acting factor for which an essential role in the specificity of mRNA deadenylation has been directly demonstrated.


[The elderly and driving in the canton of Vaud].
Which elderly person may drive and who should decide? These questions translate a frequent doctor's dilemma. Driving is a tremendously complex perceptive, motor, cognitive, and emotional activity. Assessing someone's ability to drive requires investigating these various components. However, a driving test is often needed. Driving limitations and a psychotherapeutic approach may help a patient give up driving, but occasionally forcing them to quit driving may prove unavoidable. Ideally, a preventive approach initiated long before old age might help decrease the frequency of the old driver's dilemma.


Limited benefit of repeating a sensitive question in a cross-sectional sexual health study.
Sexual health research relies heavily on self-reported data. We explored whether repeating a key measure - number of lifetime sexual partners - improved the validity of this self-reported response. Using data from a study of Tanzanian plantation residents, we examined which of 505 participants changed their responses when a question about sexual partners was repeated. We examined which variable (first, second, or maximum response) was more predictive of herpes simplex virus type 2 (HSV-2) seropositivity, a biomarker strongly associated with number of lifetime partners. HSV-2 status was assessed using the HerpeSelect 2 ELISA IgG test. When asked a second time, 10.7% of participants increased and 3.6% decreased their reported number of partners. Participants using audio computer-assisted self-interviews were more likely to change than those interviewed in person (p = 0.006). The increased odds of HSV-2 seropositivity with each additional partner ranged from 10% to 13% in men, and 33% to 37% in women, depending on which partner variable was used. Estimates had considerable confidence interval overlap and no substantial differences in precision. Some participants change their responses when asked a sensitive question a second time, but in this population, changes did not meaningfully affect associations between lifetime partners and HSV-2.


Effects of ambient temperature on the half-life and dosage regimen of amikacin in the gopher snake.
Eight gopher snakes were given amikacin (5 mg/kg of body weight IM) and were housed at ambient temperatures of 25 C or 37 C. Snakes housed at 37 C had a larger volume of distribution, and a more rapid body clearance of amikacin while the apparent half-life was not changed significantly. The minimum inhibitory concentrations of amikacin against isolated snake pathogens were determined at both temperatures. Bacteria were twice as sensitive at 37 C than at 25 C. The data indicated that amikacin should be given IM at a dose schedule of 5 mg/kg (loading dose) followed by 2.5 mg/kg every 72 hours, and that snakes should be housed near the high end of their preferred optimum ambient temperature during treatment.


Contemporary epidemiology and outcomes in recurrent infective endocarditis.
Recurrent infective endocarditis (IE) is a major complication of patients surviving a first episode of IE. This study sought to analyse the current state of recurrent IE in a large contemporary cohort. 1335 consecutive episodes of IE were recruited prospectively in three tertiary care centres in Spain between 1996 and 2015. Episodes were categorised into group I (n=1227), first-IE episode and group II (n=108), recurrent IE (8.1%). After excluding six patients, due to lack of relevant data, group II was subdivided into IIa (n=87), reinfection (different microorganism), and IIb (n=15), relapse (same microorganism within 6 months of the initial episode). The cumulative burden and incidence of recurrence was slightly lower in the second decade of the study (2006-2015) (7.17 vs 4.10 events/100 survivors and 7.51% vs 3.82, respectively). Patients with reinfections, compared with group I, were significantly younger, had a higher frequency of HIV infection, were more commonly intravenous drug users (IVDU) and prosthetic valve carriers, had less embolic complications and cardiac surgery, with similar in-hospital mortality. IVDU was found to be an independent predictor of reinfection (HR 3.92, 95% CI 1.86 to 8.28).In the relapse IE group, prosthetic valve endocarditis (PVE) and periannular complications were more common. Among patients treated medically, those with PVE had a higher relapse incidence (4.82% vs 0.43% in native valve IE, p=0.018). Staphylococcus aureus and PVE were independent predictors of relapse (HR 3.14, 95% CI 1.11 to 8.86 and 3.19, 95% CI 1.13 to 9.00, respectively) and in-hospital-mortality was similar to group I. Three-year all-cause mortality was similar in recurrent episodes compared with single episodes. Recurrent IE remains a frequent late complication. IVDU was associated with a fourfold increase in the risk of reinfection. PVE treated medically and infections caused by S. aureus increased the risk of relapse. In-hospital and long-term mortality was comparable among groups.