An RNA-Binding Protein Secreted by a Bacterial Pathogen Modulates RIG-I Signaling.
RNA-binding proteins (RBPs) perform key cellular activities by controlling the function of bound RNAs. The widely held assumption that RBPs are strictly intracellular has been challenged by the discovery of secreted RBPs. However, extracellular RBPs have been described in eukaryotes, while secreted bacterial RBPs have not been reported. Here, we show that the bacterial pathogen Listeria monocytogenes secretes a small RBP that we named Zea. We show that Zea binds a subset of L. monocytogenes RNAs, causing their accumulation in the extracellular medium. Furthermore, during L. monocytogenes infection, Zea binds RIG-I, the non-self-RNA innate immunity sensor, potentiating interferon-β production. Mouse infection studies reveal that Zea affects L. monocytogenes virulence. Together, our results unveil that bacterial RNAs can be present extracellularly in association with RBPs, acting as "social RNAs" to trigger a host response during infection.


Comparative life cycle assessment (LCA) of construction and demolition (C&D) derived biomass and U.S. northeast forest residuals gasification for electricity production.
With the goal to move society toward less reliance on fossil fuels and the mitigation of climate change, there is increasing interest and investment in the bioenergy sector. However, current bioenergy growth patterns may, in the long term, only be met through an expansion of global arable land at the expense of natural ecosystems and in competition with the food sector. Increasing thermal energy recovery from solid waste reduces dependence on fossil- and biobased energy production while enhancing landfill diversion. Using inventory data from pilot processes, this work assesses the cradle-to-gate environmental burdens of plasma gasification as a route capable of transforming construction and demolition (C&D) derived biomass (CDDB) and forest residues into electricity. Results indicate that the environmental burdens associated with CDDB and forest residue gasification may be similar to conventional electricity generation. Land occupation is lowest when CDDB is used. Environmental impacts are to a large extent due to coal cogasified, coke used as gasifier bed material, and fuel oil cocombusted in the steam boiler. However, uncertainties associated with preliminary system designs may be large, particularly the heat loss associated with pilot scale data resulting in overall low efficiencies of energy conversion to electricity; a sensitivity analysis assesses these uncertainties in further detail.


Suitability of tandem-in-time mass spectrometry for polybrominated diphenylether measurement in fish and shellfish samples: comparison with high resolution mass spectrometry.
The first part of the present study focused on the development of an alternative automated sample preparation method for the measurement of selected polybrominated diphenyl ethers (PBDEs) in fish and shellfish. A previously developed automated method has been further optimized and simplified to decrease blank levels and cost. Sorbent and solvent quantities have been significantly reduced without altering extract quality. The second part of the study consisted of comparing tandem-in-time quadrupole ion storage mass spectrometry (QISTMS/MS) to high resolution mass spectrometry (HRMS) for the isotope dilution (ID) measurement step after gas chromatography (GC) separation. Both mass spectrometric methods performed similarly in terms of accuracy but better precision was observed for HRMS. Although better sensitivity can be attained with the high resolution sector instrument, method limits of quantification (mLOQs) were very similar for both approaches as they were dependent on the procedural blanks levels. The mLOQ values ranged between 0.04 and 3.56 ng/g fat, depending on the congener. They allowed the unambiguous identification and quantification of all target analytes, except for BDE-183, in most considered fish extracts. An analytical procedure based on rapid automated sample preparation and QISTMS/MS appeared to be suitable for the measurement of PBDEs in fish and shellfish speciment under quality assurance/quality control (QA/QC) criteria.


"The unpredictable death"-The last year of life for patients with advanced COPD: Relatives' stories.
The end stage of chronic obstructive pulmonary disease (COPD) is described as prolonged, and the symptom burden for patients with COPD is often high. It progresses slowly over several years and can be punctuated by abrupt exacerbations that sometimes end in sudden death or a recovery of longer or shorter duration. This makes it difficult to identify the critical junctures in order to prognosticate the progress and time of death. Patients with COPD often express a fear that the dying process is going to be difficult. There is a fear that the dyspnea will worsen and lead to death by suffocation. The present article aimed to retrospectively describe the final year of life for patients with advanced COPD with a focus on death and dying from the perspective of relatives. Interviews were conducted with the relatives of deceased family members who had advanced COPD. In total, 13 interviews were conducted and analyzed by means of content analysis. All relatives described the patients as having had a peaceful death that did not correspond with the worry expressed earlier by both the patients and themselves. During the final week of life, two different patterns in the progress of the illness trajectory emerged: a temporary improvement where death was unexpected and a continued deterioration where death was inevitable. The patients and their relatives lived with uncertainty up until the time of death. Little support for psychosocial and existential needs was available. It is essential for the nurse to create relationships with patients and relatives that enable them to talk about dying and death on their own terms.


Fluorescein-related extensive jaundice.
Fluorescein is a chemical dye frequently used in eye diseases to assess blood flow in the retina, choroid tissue, and iris. Although it has many known adverse effects, it has not previously been reported to lead to jaundice. The purpose of this case report was to emphasize that for patients presenting at the emergency department with jaundice symptoms, it should not be forgotten by emergency physicians that jaundice can develop after fluorescein angiography. Case: A 65-year-old woman presented at the emergency department with extensive jaundice that had developed on her entire body a few hours after fluorescein angiography applied because of vision impairment. The test results for all the diseases considered to cause jaundice were normal,and fluorescein-related jaundice was diagnosed. Conclusion: A detailed anamnesis should be taken when jaundice is seen in patients who have undergone fluorescein angiography, and it should not be forgotten that fluorescein dye is a rare cause of jaundice.


Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome.
Immunoglobulin (Ig) genes were isolated from unamplified conventional as well as polymerase chain reaction-generated cDNA libraries constructed from the peripheral blood cells of a patient with complete DiGeorge syndrome. Comparison of the sequences of 36 heavy chain clones to the recently expanded database of human VH genes permitted identification of the germline VH genes that are expressed in this patient as well as placement of 19 of these genes in a partially resolved 0.8-mb region of the human VH locus. The pattern of VH gene use does not resemble the fetal (early) repertoire. However, as in the fetal repertoire, there are a number of cDNAs derived from germline genes that previously have been identified as autoantibodies. Two D mu sequences also were identified, as was another sequence resulting from a unique recombination event linking JH to an unidentified sequence containing a recombination signal sequence-like heptamer. All of the DiGeorge cDNAs are closely related to germline VH genes, showing little or no evidence of somatic mutation. In contrast, comparably selected IgM VH sequences derived from normal adult and age-matched human libraries, and from a second DiGeorge syndrome patient in whom the degree of thymic dysfunction is much less severe, exhibit considerable evidence of somatic mutation. The absence of somatic mutation is consistent with the atypical development of functional antibody responses associated with complete DiGeorge syndrome and implicates a role for T cells in the generation of diversity within the B cell repertoire.


PrPSc formation and clearance as determinants of prion tropism.
Prion strains are characterized by strain-specific differences in neuropathology but can also differ in incubation period, clinical disease, host-range and tissue tropism. The hyper (HY) and drowsy (DY) strains of hamster-adapted transmissible mink encephalopathy (TME) differ in tissue tropism and susceptibility to infection by extraneural routes of infection. Notably, DY TME is not detected in the secondary lymphoreticular system (LRS) tissues of infected hosts regardless of the route of inoculation. We found that similar to the lymphotropic strain HY TME, DY TME crosses mucosal epithelia, enters draining lymphatic vessels in underlying laminae propriae, and is transported to LRS tissues. Since DY TME causes disease once it enters the peripheral nervous system, the restriction in DY TME pathogenesis is due to its inability to establish infection in LRS tissues, not a failure of transport. To determine if LRS tissues can support DY TME formation, we performed protein misfolding cyclic amplification using DY PrPSc as the seed and spleen homogenate as the source of PrPC. We found that the spleen environment can support DY PrPSc formation, although at lower rates compared to lymphotropic strains, suggesting that the failure of DY TME to establish infection in the spleen is not due to the absence of a strain-specific conversion cofactor. Finally, we provide evidence that DY PrPSc is more susceptible to degradation when compared to PrPSc from other lymphotrophic strains. We hypothesize that the relative rates of PrPSc formation and clearance can influence prion tropism.


Myeloid-derived suppressor cells: general characteristics and relevance to clinical management of pancreatic cancer.
Recent studies describe a heterogeneous population of cells of the myeloid lineage, termed myeloid derived suppressor cells (MDSC), which are observed with increased prevalence in the peripheral blood and tumor microenvironment of cancer patients, including pancreatic cancer. Accumulation of MDSC in the peripheral circulation has been related to extent of disease, and correlates with stage. MDSC have primarily been implicated in promoting tumor growth by suppressing antitumor immunity. There is also compelling evidence MDSC are also involved in angiogenesis and metastatic spread. Two main subsets of MDSC have been identified in cancer patients: a monocytic subset, characterized by expression of CD14, and a granulocytic subset characterized by expression of CD15. Both subsets of MDSC actively suppress host immunity through a variety of mechanisms including production of reactive oxygen species and arginase. Just as in humans, accumulation of monocytic and granulocytic MDSC has been noted in the bone marrow, spleen, peripheral circulation, and tumors of tumor bearing mice. Successful targeting of MDSC in mice is associated with improved immune responses, delayed tumor growth, improved survival, and increased efficacy of vaccine therapy. By further elucidating mechanisms of MDSC recruitment and maintenance in the tumor environment, strategies could be developed to reverse immune tolerance to tumor. We discuss here what is currently known about MDSC as well as some potential strategies targeting MDSC in the context of our work on pancreatic cancer and recent literature. Due to the number of new reports on MDSC, the most pertinent ones have been selected.


Diagnosis of pulmonary tuberculosis in young children.
The Stop TB Strategy encompasses promotion and support for childhood TB including diagnosis. The diagnosis of TB in low-income countries needs to be improved using existing technology. All hospitals involved in managing children with TB should have a regular stock of tuberculin. A chest radiograph (CXR) is an integral part of the diagnosis of pulmonary TB and hospitals should be able to take satisfactory CXRs of young children. If there is a reliable laboratory service, bacterial confirmation should be undertaken in selected cases. The laboratory should be able to deal satisfactorily with paediatric specimens. Gastric aspiration is the method of choice to obtain sputum from young children and generally produces higher yields than other methods, and, with good technique, results in outpatients may not be much lower than in inpatients. Nasopharyngeal aspiration is a simple alternative method requiring limited equipment. Sputum induction requires a special room, capital and recurrent equipment and a dedicated nurse. Laryngeal swabs are suitable for older outpatients unable to produce adequate sputum. Each hospital should have a clinician trained in the diagnosis and management of childhood TB, including the interpretation of CXRs and skill in fine-needle aspiration. Radiologists and clinicians should use a simple, clear, internationally accepted classification of paediatric CXRs. The clinician(s) in charge of TB services should oversee all inpatients with TB and be at the forefront in running the TB clinic. A TB nurse specialist(s) should be part of the team. There is now a will to improve the diagnosis and management of childhood TB but bringing it to fruition requires efforts by the local TB service, paediatricians, radiology departments and laboratory services.


Zebrafish embryos as a model host for the real time analysis of Salmonella typhimurium infections.
Bacterial virulence is best studied in animal models. However, the lack of possibilities for real time analysis and the need for laborious and invasive sample analysis limit the use of experimental animals. In the present study 28 h-old zebrafish embryos were infected with DsRed-labelled cells of Salmonella typhimurium. Using multidimensional digital imaging microscopy we were able to determine the exact location and fate of these bacterial pathogens in a living vertebrate host during three days. A low dose of wild-type S. typhimurium resulted in a lethal infection with bacteria residing and multiplying both in macrophage-like cells and at the epithelium of blood vessels. Lipopolysaccharide (LPS) mutants of S. typhimurium, known to be attenuated in the murine model, proved to be non-pathogenic in the zebrafish embryos and were partially lysed in the bloodstream or degraded in macrophage-like cells. However, injection of LPS mutants in the yolk of the embryo resulted in uncontrolled bacterial proliferation. Heat-killed, wild-type bacteria were completely lysed extracellularly within minutes after injection, which shows that the blood of these zebrafish embryos does already contain lytic activity. In conclusion, the zebrafish embryo model allows for rapid, non-invasive and real time analysis of bacterial infections in a vertebrate host.


Ambulatory monitoring of blood pressure disturbs sleep and raises systolic pressure at night in patients suspected of suffering from sleep-disordered breathing.
1. The aim of the study was to assess the effect of ambulatory monitoring of blood pressure on sleep and on blood pressure in middle-aged patients. 2. Nine consecutive patients (seven men, two women; mean age 57 years) complaining of snoring and various degrees of excessive daytime somnolence were studied. Five patients were normotensive and four were being treated for hypertension. During one night standard laboratory polysomnography was performed with monitoring of blood pressure by a silent ambulatory monitor and continuous infrared blood pressure by photoplethysmography. 3. Ambulatory blood pressure significantly disturbs sleep architecture, causing EEG arousals in 64% of measurements, and induces a significant rise in blood pressure during systolic pressure measurement by the ambulatory monitor (rise in systolic pressure, 13.7 +/- 15.9 mmHg, P < 0.001; rise in diastolic pressure, 3.7 +/- 8.2 mmHg, P < 0.01). At the time of diastolic measurement, blood pressure had returned to the preinflation value. The rise in systolic blood pressure was higher when an arousal was associated with cuff inflation (P < 0.001). This rise in blood pressure is probably the consequence of sympathetic nervous system activation. 4. We conclude that ambulatory blood pressure recordings of systolic blood pressure during sleep should be interpreted with caution as systolic blood pressure may be significantly increased in patients suspected of suffering from sleep-disordered breathing.


Effect of instructor feedback on skills retention after laparoscopic simulator training: follow-up of a randomized trial.
Instructor feedback reduces the number of repetitions and time to reach proficiency during laparoscopic simulator training. The objective of this study was to examine the effect of instructor feedback on long-term skill retention. A 6-month follow-up of a randomized trial. Participants were surgical novices (medical students). All participants (n = 99) initially practiced a laparoscopic salpingectomy on the LapSim virtual reality simulator to proficiency. The intervention group could request instructor feedback, whereas the control group could not. After 6 months, the participants (n = 65) practiced on the simulator until they reached proficiency again. The primary outcomes were the total time and the number of repetitions. Initially, the intervention group used significantly fewer repetitions (29 vs 65, p < 0.0005) and less total training time (162 vs 342 min, p < 0.0005) than the control group to reach the proficiency level. At follow-up, both the groups used an equal number of repetitions (21 vs 20, p = 0.72) and time (83 vs 73 min, p = 0.37) to reach the same proficiency level. Instructor feedback during proficiency-based laparoscopic simulator training does not affect the long-term retention of skills.


No increase in readmissions or adverse events after implementation of fast-track program in total hip and knee replacement at 8 Swedish hospitals: An observational before-and-after study of 14,148 total joint replacements 2011-2015.
Background and purpose - Fast-track care programs in elective total hip and knee replacement (THR/TKR) have been introduced in several countries during the last decade resulting in a significant reduction of hospital stay without any rise in readmissions or early adverse events (AE). We evaluated the risk of readmissions and AE within 30 and 90 days after surgery when a fast-track program was introduced in routine care of joint replacement at 8 Swedish hospitals. Patients and methods - Fast-track care programs were introduced at 8 public hospitals in Västra Götaland region from 2012 to 2014. We obtained data from the Swedish Hip and Knee Arthroplasty Registers for patients operated with THR and TKR in 2011-2015. All readmissions and new contacts with the health care system within 3 months with a possible connection to the surgical intervention were requested from the regional patient register. We compared patients operated before and after the introduction of the fast-track program. Results - Implementation of the fast-track program resulted in a decrease in median hospital length of stay (LOS) from 5 to 3 days in both THR and TKR. The total readmission rate <90 days for THR was 7.2% with fast-track compared with 6.7% in the previous program, and for TKR 8.4% in both groups. Almost half of the readmissions occurred without any AE identified. There was no statistically significant difference concerning readmissions or AE when comparing the programs. Interpretation - Implementation of a fast-track care program in routine care of elective hip and knee replacement is effective in reducing hospital stay without increasing the risk of readmissions or adverse events within 90 days after surgery.


Copper/zinc superoxide dismutase-like immunoreactivity in the metamorphosing brain of the sphinx moth Manduca sexta.
Cu/Zn superoxide dismutase (SOD) is part of the defense mechanism that protects cells from being damaged by reactive oxygen species. During metamorphosis of the nervous system, neurons undergo various fates, which are all coupled to high metabolic activities, such as proliferation, differentiation, pathfinding, and synaptogenesis. We describe the pattern of SOD immunoreactivity of identified neurons and neuron groups in the brain of Manduca sexta from the late larva through metamorphosis into adult. We focused on neurons of the developing antennal lobes, the optic lobes, and the central brain. Our results indicate the transient expression of SOD during phases in which the neurons develop their final adult identities. Our data also suggest that the SOD immunoreactivity may be used as an indicator for the period in which developing neurons form their synapses. We also observed SOD immunoreactivity within nitric oxide-sensitive cells as characterized by immunolabeling against 3'5'-cyclic guanosine monophosphate and soluble guanylyl cyclase, a novel finding in insects.


Probabilistic learning in immune network: weighted tree matching model.
Adaptive learning properties (of clonal selection and affinity maturation) in the immune network model are investigated in this paper under a nonlinear data structural representation of the involved molecules. Weighted trees are constructed to model the multiple paratopes/epitopes on the antibodies/antigens. Parallel computing experiments are carried out for the canonical coding of these trees and the corresponding multiple matching interactions. Our experiments on real data have shown significant results on the cognitive properties of the immune network. These and other computational results are presented along with a discussion of future applications.


Type 2 Diabetes Mellitus and Heart Failure, A Scientific Statement From the American Heart Association and Heart Failure Society of America.
Type 2 diabetes mellitus is a risk factor for incident heart failure and increases the risk of morbidity and mortality in patients with established disease. Secular trends in the prevalence of diabetes mellitus and heart failure forecast a growing burden of disease and underscore the need for effective therapeutic strategies. Recent clinical trials have demonstrated the shared pathophysiology between diabetes mellitus and heart failure, the synergistic effect of managing both conditions, and the potential for diabetes mellitus therapies to modulate the risk of heart failure outcomes. This scientific statement on diabetes mellitus and heart failure summarizes the epidemiology, pathophysiology, and impact of diabetes mellitus and its control on outcomes in heart failure; reviews the approach to pharmacological therapy and lifestyle modification in patients with diabetes mellitus and heart failure; highlights the value of multidisciplinary interventions to improve clinical outcomes in this population; and outlines priorities for future research.


Radiographic analysis of the sagittal alignment and balance of the spine in asymptomatic subjects.
There is an increasing recognition of the clinical importance of the sagittal plane alignment of the spine. A prospective study of several radiographic parameters of the sagittal profile of the spine was conducted to determine the physiological values of these parameters, to calculate the variations of these parameters according to epidemiological and morphological data, and to study the relationships among all of these parameters. Sagittal radiographs of the head, spine, and pelvis of 300 asymptomatic volunteers, made with the subject standing, were evaluated. The following parameters were measured: lumbar lordosis, thoracic kyphosis, T9 sagittal offset, sacral slope, pelvic incidence, pelvic tilt, intervertebral angulation, and vertebral wedging angle from T9 to S1. The radiographs were digitized, and all measurements were performed with use of a software program. Two different analyses, a descriptive analysis characterizing these parameters and a multivariate analysis, were performed in order to study the relationships among all of them. The mean values (and standard deviations) were 60 degrees 10 degrees for maximum lumbar lordosis, 41 degrees +/- 8.4 degrees for sacral slope, 13 degrees +/- 6 degrees for pelvic tilt, 55 degrees +/-10.6 degrees for pelvic incidence, and 10.3 degrees +/- 3.1 degrees for T9 sagittal offset. A strong correlation was found between the sacral slope and the pelvic incidence (r = 0.8); between maximum lumbar lordosis and sacral slope (r = 0.86); between pelvic incidence and pelvic tilt (r = 0.66); between maximum lumbar lordosis and pelvic incidence, pelvic tilt, and maximum thoracic kyphosis (r = 0.9); and, finally, between pelvic incidence and T9 sagittal offset, sacral slope, pelvic tilt, maximum lumbar lordosis, and thoracic kyphosis (r = 0.98). The T9 sagittal offset, reflecting the sagittal balance of the spine, was dependent on three separate factors: a linear combination of the pelvic incidence, maximum lumbar lordosis, and sacral slope; the pelvic tilt; and the thoracic kyphosis. This description of the physiological spinal sagittal balance should serve as a baseline in the evaluation of pathological conditions associated with abnormal angular parameter values. Before a patient with spinal sagittal imbalance is treated, the reciprocal balance between various spinal angular parameters needs to be taken into account. The correlations between angular parameters may also be useful in calculating the corrections to be obtained during treatment.


A series of Mg-Zn heterometallic coordination polymers: synthesis, characterization, and fluorescence sensing for Fe3+, CS2, and nitroaromatic compounds.
Herein, the solvothermal preparations, crystal structures, and fluorescence properties of three Mg-Zn heterometallic coordination polymers (CPs), i.e. [Mg2Zn2(OH)2(1,4-NDC)3(H2O)2]·6H2O (1), [Mg1.13Zn1.87(1,4-NDC)3(dppe)(CH3OH)] (2), and [Mg1.17Zn1.83(1,4-NDC)3(py)2]·1.5py (3), based on the mixed ligands of 1,4-naphthalene dicarboxylic acid (1,4-H2NDC) and N-containing ligands of 1,3-di(4-pyridyl)propane (dppe) or pyridine (py) are presented. In the title compounds, Zn and Mg are statistically distributed, as confirmed by single crystal analysis, and the ratios of Zn and Mg have been identified by inductively coupled plasma (ICP) measurements. In compound 1, the metal ions are tetra- or hexa-coordinated by the oxygen atoms of the carboxylate and μ3-OH group to form a one-dimensional (1D) ribbon, and these 1D ribbons are further bridged by 1,4-NDC linkers to grow into a 3D framework with 1D channels along the b axis. In compounds 2 and 3, the metal ions also adopt tetra- or hexa-coordination modes and are inter-bridged by carboxylate oxygen atoms to form a tri-nuclear secondary building unit (SBU). Due to the introduction of N-containing ligands acting as terminal molecules, these SBUs are linked by 1,4-NDC ligands to form a 2D network. Photoluminescence (PL) studies indicated that the title compounds showed strong blue emissions. Significantly, compound 1 demonstrated sensitive fluorescence sensing for Fe3+, carbon disulfide (CS2), and nitroaromatic compounds at low concentrations. The fluorescence sensing properties of compound 2 were also comparatively investigated in detail.


Norepinephrine release in the amygdala after systemic injection of epinephrine or escapable footshock: contribution of the nucleus of the solitary tract.
Several findings based largely on lesions and drug manipulations within the amygdala suggest that norepinephrine (NE) systems in the amygdala contribute to enhancement of memory processes by epinephrine (EPI). However, no studies to date have directly measured changes in the release of NE in the amygdala after EPI injection. In Experiment 1, in vivo microdialysis was used to assess amygdala NE release after systemic injection of saline, EPI (0.1 or 0.3 mg/kg), and administration of an escapable footshock (0.8 mA, 1 s). Both doses of EPI produced a significant elevation in NE release that persisted for up to 60 min. In Experiment 2, the local anesthetic lidocaine (2%) was infused (0.5 microl) into the nucleus of the solitary tract (NTS) immediately before injection of 0.3 mg/kg EPI. The EPI-induced elevation in amygdala NE release observed in Experiment I was attenuated by inactivation of the NTS. These findings indicate that systemic injection of EPI increases release of NE in the amygdala and suggest that the effects are mediated in part by activation of brainstem neurons in the NTS that project to the amygdala.


Revealing variations in perception of mental states from dynamic facial expressions: a cautionary note.
Although a great deal of research has been conducted on the recognition of basic facial emotions (e.g., anger, happiness, sadness), much less research has been carried out on the more subtle facial expressions of an individual's mental state (e.g., anxiety, disinterest, relief). Of particular concern is that these mental state expressions provide a crucial source of communication in everyday life but little is known about the accuracy with which natural dynamic facial expressions of mental states are identified and, in particular, the variability in mental state perception that is produced. Here we report the findings of two studies that investigated the accuracy and variability with which dynamic facial expressions of mental states were identified by participants. Both studies used stimuli carefully constructed using procedures adopted in previous research, and free-report (Study 1) and forced-choice (Study 2) measures of response accuracy and variability. The findings of both studies showed levels of response accuracy that were accompanied by substantial variation in the labels assigned by observers to each mental state. Thus, when mental states are identified from facial expressions in experiments, the identities attached to these expressions appear to vary considerably across individuals. This variability raises important issues for understanding the identification of mental states in everyday situations and for the use of responses in facial expression research.


[Validation of two brief scales for Internet addiction and mobile phone problem use].
This study describes the construction and validation process of two questionnaires designed to assess the addictive use of Internet and mobile phones. The scales were applied to a sample of 1,879 students. Results support a two-factor model, presenting an acceptable internal consistency and indices of convergent and discriminant validity. The Questionnaire of Experiences Related to Internet was found to assess intra- and interpersonal conflicts related to Internet use. The Questionnaire of Experiences Related to the Mobile Phone was found to assess conflicts related to mobile phone abuse and to maladaptive emotional and communicational patterns. Our results indicate that the mobile phone does not produce the same degree of addictive behavior as Internet; it could rather be interpreted as problematic use. Men displayed more addictive use of Internet, whilst women seemed to use the mobile phone as a means for emotional communication. It seems that the use of both technologies is more problematic during adolescence and normalizes with age toward a more professional and less playful use, and with fewer negative consequences.


Opposite metabolic responses of shoots and roots to drought.
Shoots and roots are autotrophic and heterotrophic organs of plants with different physiological functions. Do they have different metabolomes? Do their metabolisms respond differently to environmental changes such as drought? We used metabolomics and elemental analyses to answer these questions. First, we show that shoots and roots have different metabolomes and nutrient and elemental stoichiometries. Second, we show that the shoot metabolome is much more variable among species and seasons than is the root metabolome. Third, we show that the metabolic response of shoots to drought contrasts with that of roots; shoots decrease their growth metabolism (lower concentrations of sugars, amino acids, nucleosides, N, P, and K), and roots increase it in a mirrored response. Shoots are metabolically deactivated during drought to reduce the consumption of water and nutrients, whereas roots are metabolically activated to enhance the uptake of water and nutrients, together buffering the effects of drought, at least at the short term.


Six- and seven-dimensional experiments by combination of sparse random sampling and projection spectroscopy dedicated for backbone resonance assignment of intrinsically disordered proteins.
Two novel six- and seven-dimensional NMR experiments are proposed. The new experiments employ non-uniform sampling that enables achieving high resolution in four indirectly detected dimensions and synchronous sampling in the additional dimensions using projection spectroscopy principle. The resulted data sets could be processed as five-dimensional data using existing software. The experiments facilitate resonance assignment of intrinsically disordered proteins. The novel experiments were successfully tested using 1 mM sample of α-synuclein on 600 and 800 MHz NMR spectrometers equipped with standard room temperature probes. The experiments allowed backbone assignment from a 1-day acquisition.


Safety, tolerability and pharmacokinetic characterisation of DACRA KBP-042 in healthy male subjects.
There is a need for antidiabetic agents successfully targeting insulin sensitivity and treating obesity control at the same time. The aim of this first-in-human study was (a) to evaluate safety and tolerability, (b) to evaluate pharmacokinetics and (c) to assess indications of receptor engagement of single ascending doses of KBP-042, a dual amylin and calcitonin receptor agonist (DACRA) that has shown promising preclinical data, with superior activity in terms of typical amylin-induced responses including reduction of food intake, weight loss and gluco-regulatory capacities. A randomised double-blind placebo-controlled single ascending dose study was performed with six dose levels of KBP-042 (5, 7.5, 10, 20, 20 (evening), 40 ug) in healthy male adults. KBP-042 or placebo was administered as a single dose after an overnight fast, followed by a standardized lunch after 4 hours. KBP-042 was associated with dose-dependent complaints of nausea and vomiting, with a lack of tolerability at doses of 20 μg and above. Doses of 5-40 μg KBP-042 behaved according to a linear pharmacokinetic profile. Indications of target receptor engagement were observed at the level of glucose control and lowering of bone resorption, compared to placebo. The results of this study showed that doses up to 40 μg were safe, although tolerability was not present at the highest doses. The study confirmed target receptor engagement at the studied doses.


Discrepancies in the widely applied GAM42a fluorescence in situ hybridisation probe for Gammaproteobacteria.
A bacterial culture collection of 104 strains was obtained from an activated sludge wastewater treatment plant to pursue studies into microbial flocculation. Characterisation of the culture collection using a polyphasic approach indicated seven isolates, phylogenetically affiliated with the deep-branching Xanthomonas group of the class Gammaproteobacteria, were unable to hybridise the GAM42a fluorescence in situ hybridisation (FISH) probe for Gammaproteobacteria. The sequence of the GAM42a probe target region in the 23S rRNA gene of these isolates was determined to have mismatches to GAM42a. Probes perfectly targeting the mismatches (GAM42a_T1038_G1031, and GAM42a_T1038 and GAM42a_A1041_A1040) were synthesised, and used in conjunction with GAM42a in FISH to study the Gammaproteobacteria community structure in one full-scale activated sludge plant. Several bacteria in the activated sludge biomass bound the modified probes demonstrating their presence and the fact that these Gammaproteobacteria have been overlooked in community structure analyses of activated sludge.


Bis(ethyl-eneglycolato-κ(2) O,O')tellurium(IV).
The title compound, C4H8O4Te, crystallized from a solution of Te(4+) in ethyl-ene glycol. The Te(IV) atom is in a distorted seesaw coordination defined by four O atoms from two different ethyl-eneglycate ligands. The C atoms of the ethyl-eneglycate ligands are disorderd over two positions, with population parameters of 50.3 (6) and 49.7 (6)% indicating a statistical distribution. Due to the possibility to transform the primitive monoclinic unit cell into a metrically ortho-rhom-bic C unit cell, the data are twinned and were refined with the twin law -100/0-10/101 with the relative scale factor refining to 1.82 (4)% for the minor component.


Integrating Biodiversity Data into Botanic Collections.
Today's species names are entry points into a web of publicly available knowledge and are integral parts of legislation concerning biological conservation and consumer safety. Species information usually is fragmented, can be misleading due to the existence of different names and might even be biased because of an identical name that is used for a different species. Safely navigating through the name space is one of the most challenging tasks when associating names with data and when decisions are made which name to include in legislation. Integrating publicly available dynamic data to characterise plant genetic resources of botanic gardens and other facilities will significantly increase the efficiency of recovering relevant information for research projects, identifying potentially invasive taxa, constructing priority lists and developing DNA-based specimen authentication. To demonstrate information availability and discuss integration into botanic collections, scientific names derived from botanic gardens were evaluated using the Encyclopedia of Life, The Catalogue of Life and The Plant List. 98.5% of the names could be verified by the combined use of these providers. Comparing taxonomic status information 13 % of the cases were in disagreement. About 7 % of the verified names were found to be included in the International Union for Conservation of Nature Red List, including one extinct taxon and three taxa with the status "extinct in the wild". As second most important factor for biodiversity loss, potential invasiveness was determined. Approximately 4 % of the verified names were detected using the Global Invasive Species Information Network, including 208 invasive taxa. According to Delivering Alien Invasive Species Inventories for Europe around 20 % of the verified names are European alien taxa including 15 of the worst European invasive taxa. Considering alternative names in the data recovery process, success increased up to 18 %.


Optimization of the Aqueous Extraction of Phenolic Compounds from Olive Leaves.
Olive leaves are an agricultural waste of the olive-oil industry representing up to 10% of the dry weight arriving at olive mills. Disposal of this waste adds additional expense to farmers. Olive leaves have been shown to have a high concentration of phenolic compounds. In an attempt to utilize this waste product for phenolic compounds, we optimized their extraction using water-a "green" extraction solvent that has not yet been investigated for this purpose. Experiments were carried out according to a Box Behnken design, and the best possible combination of temperature, extraction time and sample-to-solvent ratio for the extraction of phenolic compounds with a high antioxidant activity was obtained using RSM; the optimal conditions for the highest yield of phenolic compounds was 90 °C for 70 min at a sample-to-solvent ratio of 1:100 g/mL; however, at 1:60 g/mL, we retained 80% of the total phenolic compounds and maximized antioxidant capacity. Therefore the sample-to-solvent ratio of 1:60 was chosen as optimal and used for further validation. The validation test fell inside the confidence range indicated by the RSM output; hence, the statistical model was trusted. The proposed method is inexpensive, easily up-scaled to industry and shows potential as an additional source of income for olive growers.


Cyclosporiasis Surveillance - United States, 2011-2015.
Cyclosporiasis is an intestinal illness caused by the parasite Cyclospora cayetanensis, which is transmissible by ingestion of fecally contaminated food or water. Cyclosporiasis is most common in tropical and subtropical regions of the world. In the United States, foodborne outbreaks of cyclosporiasis have been linked to various types of imported fresh produce (e.g., basil, raspberries, and snow peas). Validated molecular typing tools, which could facilitate detection and investigation of outbreaks, are not yet available for C. cayetanensis. 2011-2015. CDC has been conducting national surveillance for cyclosporiasis since it became a nationally notifiable disease in January 1999. As of 2015, cyclosporiasis was a reportable condition in 42 states, the District of Columbia, and New York City (NYC). Health departments voluntarily notify CDC of cases of cyclosporiasis through the National Notifiable Diseases Surveillance System and submit additional case information using the CDC cyclosporiasis case report form or the Cyclosporiasis National Hypothesis Generating Questionnaire (CNHGQ). For the 2011-2015 surveillance period, CDC was notified by 37 states and NYC of 2,207 cases of cyclosporiasis, including 1,988 confirmed cases (90.1%) and 219 probable cases (9.9%). The annual number of reported cases ranged from 130 in 2012 to 798 in 2013; the annual population-adjusted incidence rate ranged from 0.05 cases per 100,000 persons in 2012 to 0.29 in 2013. A total of 415 patients (18.8%) had a documented history of international travel during the 14 days before illness onset, 1,384 (62.7%) did not have a history of international travel, and 408 (18.5%) had an unknown travel history. Among the 1,359 domestically acquired cases with available information about illness onset, 1,263 (92.9%) occurred among persons who became ill during May-August. During 2011-2015, a total of 10 outbreaks of cyclosporiasis associated with 438 reported cases were investigated; a median of 21 cases were reported per outbreak (range: eight to 162). A food vehicle of infection (i.e., a food item or ingredient thereof) was identified (or suspected) for at least five of the 10 outbreaks; the food vehicles included a berry salad (one outbreak), cilantro imported from Mexico (at least three outbreaks), and a prepackaged salad mix from Mexico (one outbreak). Cyclosporiasis continues to be a U.S. public health concern, with seasonal increases in reported cases during spring and summer months. The majority of cases reported for this 5-year surveillance period occurred among persons without a history of international travel who became ill during May-August. Many of the seemingly sporadic domestically acquired cases might have been associated with identified or unidentified outbreaks; however, those potential associations were not detected using the available epidemiologic information. Prevention of cases and outbreaks of cyclosporiasis in the United States depends on outbreak detection and investigation, including identification of food vehicles of infection and their sources, which could be facilitated by the availability of validated molecular typing tools. Surveillance for cases of cyclosporiasis and efforts to develop and validate molecular typing tools should remain U.S. public health priorities. During periods and seasons when increased numbers of domestically acquired cases are reported, the CNHGQ should be used to facilitate outbreak detection and hypothesis generation. Travelers to areas of known endemicity (e.g., in the tropics and subtropics) should follow food and water precautions similar to those for other enteric pathogens but should be advised that use of routine chemical disinfection or sanitizing methods is unlikely to kill C. cayetanensis. Health care providers should consider the possibility of Cyclospora infection in persons with persistent or remitting-relapsing diarrheal illness, especially for persons with a history of travel to areas of known endemicity or with symptom onset during spring or summer. If indicated, laboratory testing for Cyclospora should be explicitly requested because such testing is not typically part of routine examinations for ova and parasites and is not included in all gastrointestinal polymerase chain reaction panels. Newly identified cases of cyclosporiasis should be promptly reported to state or local public health authorities, who are encouraged to notify CDC of the cases.


A comparison of disease burden and the government budget for mental health in Korea.
The lifetime prevalence of mental disorders in South Korea was 25.4% in 2016. The Act on Mental Health enabled the expansion of psychiatric facilities; however, resources were allocated without considering the population structure or the characteristics of mental health problems. This paper investigates the status and trends of disease burden and the government budget for Korean mental health. The burden of mental and behavioral disorders (MBDs) was measured using the incidence-based disability-adjusted life years (DALYs), and the mental health budget data was from the Ministry of Health and Welfare of South Korea. We estimated that the disease burden of MBDs accounted for 6.4% of the total disease burden, ranking as the seventh leading cause of Korean DALYs. The mental health budget in South Korea was USD 253.4 million in 2019 (USD 90.3 million from the general account, USD 65.8 million from the National Health Promotion Fund, and USD 97.3 million from the special account for the national mental hospitals). Challenges are created by the MBD burden on the Korean healthcare system, and the budget is insufficient to address this disease burden, suggesting that resource allocation systems should be improved.


PTEN loss mediated Akt activation promotes prostate tumor growth and metastasis via CXCL12/CXCR4 signaling.
The chemokine CXCL12, also known as SDF-1, and its receptor, CXCR4, are overexpressed in prostate cancers and in animal models of prostate-specific PTEN deletion, but their regulation is poorly understood. Loss of the tumor suppressor PTEN (phosphatase and tensin homolog) is frequently observed in cancer, resulting in the deregulation of cell survival, growth, and proliferation. We hypothesize that loss of PTEN and subsequent activation of Akt, frequent occurrences in prostate cancer, regulate the CXCL12/CXCR4 signaling axis in tumor growth and bone metastasis. Murine prostate epithelial cells from PTEN+/+, PTEN+/-, and PTEN-/- (prostate specific knockdown) mice as well as human prostate cancer cell lines C4-2B, PC3, and DU145 were used in gene expression and invasion studies with Akt inhibition. Additionally, HA-tagged Akt1 was overexpressed in DU145, and tumor growth in subcutaneous and intra-tibia bone metastasis models were analyzed. Loss of PTEN resulted in increased expression of CXCR4 and CXCL12 and Akt inhibition reversed expression and cellular invasion. These results suggest that loss of PTEN may play a key role in the regulation of this chemokine activity in prostate cancer. Overexpression of Akt1 in DU145 resulted in increased CXCR4 expression, as well as increased proliferation and cell cycle progression. Subcutaneous injection of these cells also resulted in increased tumor growth as compared to neo controls. Akt1 overexpression reversed the osteosclerotic phenotype associated with DU145 cells to an osteolytic phenotype and enhanced intra-osseous tumor growth. These results suggest the basis for activation of CXCL12 signaling through CXCR4 in prostate cancer driven by the loss of PTEN and subsequent activation of Akt. Akt1-associated CXCL12/CXCR4 signaling promotes tumor growth, suggesting that Akt inhibitors may potentially be employed as anticancer agents to target expansion of PC bone metastases.


Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius.
Sodalis glossinidius, a vertically transmitted microbial symbiont of the tsetse fly, is currently considered as a potential delivery system for anti-trypanosomal components that reduce or eliminate the capability of the tsetse fly host to transmit parasitic trypanosomes, an approach also known as paratransgenesis. An essential step in developing paratransgenic tsetse is the stable colonization of adult flies and their progeny with recombinant Sodalis bacteria, expressing trypanocidal effector molecules in tissues where the parasite resides. In this study, Sodalis was tested for its ability to deliver functional anti-trypanosome nanobodies (Nbs) in Glossina morsitans morsitans. We characterized the in vitro and in vivo stability of recombinant Sodalis (recSodalis) expressing a potent trypanolytic nanobody, i.e. Nb_An46. We show that recSodalis is competitive with WT Sodalis in in vivo conditions and that tsetse flies transiently cleared of their endogenous WT Sodalis population can be successfully repopulated with recSodalis at high densities. In addition, vertical transmission to the offspring was observed. Finally, we demonstrated that recSodalis expressed significant levels (ng range) of functional Nb_An46 in different tsetse fly tissues, including the midgut where an important developmental stage of the trypanosome parasite occurs. We demonstrated the proof-of-concept that the Sodalis symbiont can be genetically engineered to express and release significant amounts of functional anti-trypanosome Nbs in different tissues of the tsetse fly. The application of this innovative concept of using pathogen-targeting nanobodies delivered by insect symbiotic bacteria could be extended to other vector-pathogen systems.


Physiological characterization of formyl peptide receptor expressing cells in the mouse vomeronasal organ.
The mouse vomeronasal organ (VNO) is a chemosensory structure that detects both hetero- and conspecific social cues. Based on largely monogenic expression of either type 1 or 2 vomeronasal receptors (V1Rs/V2Rs) or members of the formyl peptide receptor (FPR) family, the vomeronasal sensory epithelium harbors at least three neuronal subpopulations. While various neurophysiological properties of both V1R- and V2R-expressing neurons have been described using genetically engineered mouse models, the basic biophysical characteristics of the more recently identified FPR-expressing vomeronasal neurons have not been studied. Here, we employ a transgenic mouse strain that coexpresses an enhanced variant of yellow fluorescent protein together with FPR-rs3 allowing to identify and analyze FPR-rs3-expressing neurons in acute VNO tissue slices. Single neuron electrophysiological recordings allow comparative characterization of the biophysical properties inherent to a prototypical member of the FPR-expressing subpopulation of VNO neurons. In this study, we provide an in-depth analysis of both passive and active membrane properties, including detailed characterization of several types of voltage-activated conductances and action potential discharge patterns, in fluorescently labeled vs. unmarked vomeronasal neurons. Our results reveal striking similarities in the basic (electro) physiological architecture of both transgene-expressing and non-expressing neurons, confirming the suitability of this genetically engineered mouse model for future studies addressing more specialized issues in vomeronasal FPR neurobiology.


Use of photographs for the identification of pressure ulcers in elderly hospitalized patients: validity and reliability.
To evaluate the ability of research nurses to identify pressure ulcers, the authors assembled digital photographs of the skin of 160 consenting elderly patients (80% African American, 63% women). The series included 39 photos of pressure ulcers, 109 of normal skin, and 12 of other skin conditions, determined by consensus by two experts (D.J.M. and S.H.K.). Photos were packaged electronically into eight blocks of 20, with pressure ulcer prevalence ranging from 20% to 30% per block. The eight blocks were duplicated to create two sets of 160 photos each. Each of six raters (experienced clinical research nurses), working independently, evaluated the 320 photos as if each photo depicted a different patient. For analysis, the ratings were collapsed into binary determinations (any pressure ulcer vs. none). The overall sensitivity and specificity of the ratings were 0.97 (95% confidence interval: 0.94, 0.98) and 0.81 (95% confidence interval: 0.77, 0.86), respectively. Rater-specific prevalence (range: 31.8-47.5%) exceeded the true prevalence (24.4%). Inter- and intrarater reliability coefficients were 0.69 and 0.84, respectively. Trained research nurses can accurately classify pressure ulcers from photographs, even when patients are largely non-White and the photographs depict pressure ulcers spanning all pressure ulcer stages.


An Exploratory Analysis of Fecal Immunochemical Test Performance for Colorectal Cancer Screening in Nigeria.
The fecal immunochemical test (FIT) for hemoglobin is recommended for colorectal cancer (CRC) screening in resource-limited environments. However, there are several unique variables that may alter FIT performance in this setting, including endemic intestinal parasites and high ambient temperature. This prospective study evaluated the performance of FIT in asymptomatic, average-risk individuals of screening age in rural Nigeria. Three hundred and twenty-four community volunteers completed a questionnaire and provided stool specimens for parasitology and microbiome analysis. Specimens were frozen and stored at -80 °C. Of 324 subjects, 139 met criteria for average-risk CRC screening and had a stool sample for analysis. These were thawed and tested with a qualitative FIT. Specimens positive for occult blood were retested every two days to evaluate the impact of time and temperature on test performance. Of 139 individuals, 69 (49.6%) were positive for intestinal parasites and 10 (7.2%) were positive for occult blood. The most common pathogen was Cryptosporidium (40.6%). Among patients with intestinal parasites, 10.1% (7/69) had a positive FIT. Only 4.3% (3/70) of patients without parasites had a positive FIT (p = 0.208). On bivariate analysis, sociodemographic variables were not associated with a positive FIT result. Thirty percent (3/10) of the FIT-positive specimens became FIT-negative with routine storage. Although a positive FIT result was more common in those with parasitic infection, the relationship was not significant in this small cohort. The impact of high ambient temperature on test positivity may necessitate shorter processing time guidelines for equatorial countries. Additional prospective studies are needed to validate FIT performance in Nigeria.


Genetics of rectal cancer.
Two operational subdivisions of hereditary colorectal cancer susceptibility are those with and those without premalignant adenomatous colonic polyp expression. In both of these subdivisions, reliable biomarkers of gene carriage would be of value in patient management as we have previously emphasized. Consideration must also be given to the familial (hereditary) occurrence of inflammatory bowel diseases associating with colorectal cancer susceptibility. The occurrence of rectal cancers should therefore alert the physician to investigate the possibility of a significant family medical history in order to fully elucidate the genetic heterogeneity of susceptibility to this disease. Clinicians should also be alert to the possibility of extracolonic malignancies where probable genetic colorectal cancer susceptibility is evident. Whenever possible, all potential biomarkers should be investigated to aid in definition of genetic heterogeneity.


Body representation difficulties in children and adolescents with autism may be due to delayed development of visuo-tactile temporal binding.
Recent research suggests visuo-tactile binding is temporally extended in autism spectrum disorders (ASD), although it is not clear whether this specifically underlies altered body representation in this population. In the current study children and adolescents with ASD, and typically developing controls, placed their hand into mediated reality system (MIRAGE) and saw two identical live video images of their own right hand. One image was in the proprioceptively correct location (veridical hand) and the other was displaced to either side. While visuo-tactile feedback was applied via brushstroke to the participant's (unseen) right finger, they viewed one hand image receiving synchronous brushstrokes and the other receiving brushstrokes with a temporal delay (60, 180 and 300ms). After brushing, both images disappeared from view and participants pointed to a target, with direction of movement indicating which hand was embodied. ASD participants, like younger mental aged-matched controls, showed reduced embodiment of the spatially incongruent, but temporally congruent, hand compared to chronologically age-matched controls at shorter temporal delays. This suggests development of visuo-tactile integration may be delayed in ASD. Findings are discussed in relation to atypical body representation in ASD and how this may contribute to social and sensory difficulties within this population.


Abdominal and hip flexor muscle activity during 2 minutes of sit-ups and curl-ups.
Previous studies have compared muscle activity between different types of sit-ups and curl-ups. However, few have examined the exercises used by the armed forces or investigated the influence of exercise duration on muscle activation. The aim of this study was to compare abdominal and hip flexor muscle activity between the style of sit-up used by the British Army and 4 variations of a curl-up, at the start, middle, and end of a 2-minute exercise period. Surface electromyograms (EMGs) were recorded from the upper and lower rectus abdominis, external oblique, transversus abdominis and internal oblique, and the rectus femoris (RF) of 23 British Army personnel. Isometric maximal voluntary contractions were used to normalize integrated EMGs to allow them to be compared between exercises. Curl-ups with arms crossed and feet restrained produced the highest integrated EMG in all the abdominal muscles (p < 0.05). Feet-restrained sit-ups and curl-ups also resulted in significantly higher activity in the RF than in nonrestrained versions of the curl-up (p < 0.001). The significant increase observed in muscle activity between the start and the end of the exercises (p < 0.001) was deemed to be in response to a reduction in force producing capacity of existing motor units. The RF experienced the greatest increase during exercises that activated the muscle the most, that is, sit-ups and curl-ups with feet restrained (p < 0.001). Previous research has indicated that such exercises produce high shear and compressive forces in the lower back, which can be injurious. Thus, if an organization wishes to assess the endurance of abdominal muscles, rather than hip flexors, then curl-ups without restraint of the feet should be performed instead of exercises in which the feet are restrained.


Charcot-Marie-Tooth 2B mutations in rab7 cause dosage-dependent neurodegeneration due to partial loss of function.
The small GTPase Rab7 is a key regulator of endosomal maturation in eukaryotic cells. Mutations in rab7 are thought to cause the dominant neuropathy Charcot-Marie-Tooth 2B (CMT2B) by a gain-of-function mechanism. Here we show that loss of rab7, but not overexpression of rab7 CMT2B mutants, causes adult-onset neurodegeneration in a Drosophila model. All CMT2B mutant proteins retain 10-50% function based on quantitative imaging, electrophysiology, and rescue experiments in sensory and motor neurons in vivo. Consequently, expression of CMT2B mutants at levels between 0.5 and 10-fold their endogenous levels fully rescues the neuropathy-like phenotypes of the rab7 mutant. Live imaging reveals that CMT2B proteins are inefficiently recruited to endosomes, but do not impair endosomal maturation. These findings are not consistent with a gain-of-function mechanism. Instead, they indicate a dosage-dependent sensitivity of neurons to rab7-dependent degradation. Our results suggest a therapeutic approach opposite to the currently proposed reduction of mutant protein function. DOI: http://dx.doi.org/10.7554/eLife.01064.001.


Large angular dispersion by a virtually imaged phased array and its application to a wavelength demultiplexer.
A new scheme that shows large angular dispersion is proposed and demonstrated. The key idea to this method is a virtually imaged phased array (VIPA). The angular dispersion of a VIPA is 10-20 times larger than those of common diffraction gratings, which have blaze angles of ~30 deg. With the VIPA, wavelength demultiplexing for 10 channels with 0.8-nm spacing is achieved. Low polarization-state dependence (~0.1 dB) is also confirmed.


Non-invasive diagnosis of cirrhosis and the natural history of its complications.
Several methods have been studied in the attempt to reach a diagnosis of cirrhosis by non-invasive means. Although abdominal ultrasound can detect the hepatic and extra-hepatic changes consistent with cirrhosis, its ability to distinguish chronic hepatitis from compensated cirrhosis is limited. Serum markers can rule in or rule out fibrosis in up to 35% of patients but, in individual patients, cannot differentiate the stages of fibrosis reliably. Transient elastography (Fibroscan) might be of value for the non-invasive diagnosis of cirrhosis; however, its reproducibility needs to be further validated. Cirrhosis can be divided into 4 stages: stage 1, no varices, no ascites; stage 2, varices without ascites and without bleeding; stage 3, ascites+/-varices; stage 4, bleeding+/-ascites. Yearly mortality ranges from 1% in stage 1 to 57% in stage 4. The yearly incidence of oesophageal varices is 5-7%; their rate of enlargement is 10-12% per year. The incidence of variceal bleeding is about 25% at 2 years. Bleeding stops spontaneously in about 50% of cases but early rebleeding occurs in 30-40% of patients. Bleeding-related mortality has declined over time and is now around 20% at 6 weeks.


Functional analysis of PA binding by influenza a virus PB1: effects on polymerase activity and viral infectivity.
Influenza A virus expresses three viral polymerase (P) subunits-PB1, PB2, and PA-all of which are essential for RNA and viral replication. The functions of P proteins in transcription and replication have been partially elucidated, yet some of these functions seem to be dependent on the formation of a heterotrimer for optimal viral RNA transcription and replication. Although it is conceivable that heterotrimer subunit interactions may allow a more efficient catalysis, direct evidence of their essentiality for viral replication is lacking. Biochemical studies addressing the molecular anatomy of the P complexes have revealed direct interactions between PB1 and PB2 as well as between PB1 and PA. Previous studies have shown that the N-terminal 48 amino acids of PB1, termed domain alpha, contain the residues required for binding PA. We report here the refined mapping of the amino acid sequences within this small region of PB1 that are indispensable for binding PA by deletion mutagenesis of PB1 in a two-hybrid assay. Subsequently, we used site-directed mutagenesis to identify the critical amino acid residues of PB1 for interaction with PA in vivo. The first 12 amino acids of PB1 were found to constitute the core of the interaction interface, thus narrowing the previous boundaries of domain alpha. The role of the minimal PB1 domain alpha in influenza virus gene expression and genome replication was subsequently analyzed by evaluating the activity of a set of PB1 mutants in a model reporter minigenome system. A strong correlation was observed between a functional PA binding site on PB1 and P activity. Influenza viruses bearing mutant PB1 genes were recovered using a plasmid-based influenza virus reverse genetics system. Interestingly, mutations that rendered PB1 unable to bind PA were either nonviable or severely growth impaired. These data are consistent with an essential role for the N terminus of PB1 in binding PA, P activity, and virus growth.


PRDM16 controls a brown fat/skeletal muscle switch.
Brown fat can increase energy expenditure and protect against obesity through a specialized program of uncoupled respiration. Here we show by in vivo fate mapping that brown, but not white, fat cells arise from precursors that express Myf5, a gene previously thought to be expressed only in the myogenic lineage. We also demonstrate that the transcriptional regulator PRDM16 (PRD1-BF1-RIZ1 homologous domain containing 16) controls a bidirectional cell fate switch between skeletal myoblasts and brown fat cells. Loss of PRDM16 from brown fat precursors causes a loss of brown fat characteristics and promotes muscle differentiation. Conversely, ectopic expression of PRDM16 in myoblasts induces their differentiation into brown fat cells. PRDM16 stimulates brown adipogenesis by binding to PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) and activating its transcriptional function. Finally, Prdm16-deficient brown fat displays an abnormal morphology, reduced thermogenic gene expression and elevated expression of muscle-specific genes. Taken together, these data indicate that PRDM16 specifies the brown fat lineage from a progenitor that expresses myoblast markers and is not involved in white adipogenesis.


Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial.
The aim of the study was to compare the safety and effectiveness of as-needed formoterol with salbutamol in a large international real-life asthma study. Children and adults (n=18,124) were randomised to 6 months as-needed treatment with open-label formoterol 4.5 microg Turbuhaler or salbutamol 200 microg pressurised metered dose inhaler or equivalent. Primary safety variables were asthma-related and nonasthma-related serious adverse events (SAE)s and adverse events (AE)s resulting in discontinuation (DAE)s. The primary efficacy variable was time to first asthma exacerbation. The incidences of AEs, SAEs and DAEs arising from SAEs were not significantly different between treatments. DAEs for nonserious AEs were higher with formoterol. Asthma-related AEs decreased with formoterol (1,098 (12.3%) versus 1,206 (13.5%)), asthma-related SAEs were similar (108 (1.2%) versus 121 (1.4%)) but more asthma-related DAEs occurred in the formoterol group (89 (1.0%) versus 48 (0.5%)). Time to first exacerbation was prolonged (hazard ratio 0.86) and less as-needed and maintenance medication was used with formoterol. Reductions of exacerbations with as-needed formoterol versus salbutamol increased with increasing age and asthma medication level. This real-life study demonstrates that formoterol as-needed has a similar safety profile to salbutamol, and its use as a reliever therapy is associated with fewer asthma symptoms and exacerbations.


[Psychological factors contributing to unsafe behavior in train drivers].
This research considered whether unsafe behaviors increase the likelihood of accident on the railway, and if so, what psychological factors contribute to unsafe behaviors? Study 1 investigated how frequently train drivers had committed errors and unsafe behaviors when train accidents occurred. Content analysis on 251 cases of railway accident reports revealed that intention errors (i.e., no intention or wrong one) and unsafe behaviors occurred simultaneously in most cases of accident. Furthermore, it was suggested that unsafe behaviors contribute to the occurrence of accidents. Study 2 examined the effect of psychological factors on unsafe behaviors. 148 train drivers completed questionnaires. We assumed the causal model that organizational factors affect unsafe behaviors indirectly through personal factors. Results of path analysis revealed as follows. (a) Concerning personal factors, evaluated cost (e.g., increased workload) and ineffectiveness of safety rules increased the frequency of unsafe behavior. (b) Concerning organizational factors, organizational management and norms increased the frequency of unsafe behavior indirectly through their effects on personal factors. Based on these findings, we discussed implications for more effective accident prevention.


Effect of actinomycin D and guanidine on the formation of a ribonucleic acid polymerase induced by foot-and mouth-disease virus and on the replication of virus and viral ribonucleic acid.
The RNA-dependent RNA polymerase induced in baby-hamster kidney cells by infection with foot-and-mouth-disease virus can be detected as early as 60min. after infection, which is 60min. before viral RNA synthesis commences. The time at which the polymerase can first be detected coincides with the latest time at which actinomycin D (50mug./10(7) cells) or guanidine (1mg./10(7) cells) inhibits virus replication. However, by increasing the concentration of guanidine, viral replication can be inhibited later in the growth cycle, casting doubt on the validity of the hypothesis that guanidine acts specifically on the formation of the viral RNA polymerase.


Comparative microarray analysis and pulmonary changes in Brown Norway rats exposed to ovalbumin and concentrated air particulates.
The interaction between air particulates and genetic susceptibility has been implicated in the pathogenesis of asthma. The overall objective of this study was to determine the effects of inhalation exposure to environmentally relevant concentrated air particulates (CAPs) on the lungs of ovalbumin (ova) sensitized and challenged Brown Norway rats. Changes in gene expression were compared with lung tissue histopathology, morphometry, and biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF). Ova challenge was responsible for the preponderance of gene expression changes, related largely to inflammation. CAPs exposure alone resulted in no significant gene expression changes, but CAPs and ova-exposed rodents exhibited an enhanced effect relative to ova alone with differentially expressed genes primarily related to inflammation and airway remodeling. Gene expression data was consistent with the biochemical and cellular analyses of the BALF, the pulmonary pathology, and morphometric changes when comparing the CAPs-ova group to the air-saline or CAPs-saline group. However, the gene expression data were more sensitive than the BALF cell type and number for assessing the effects of CAPs and ova versus the ova challenge alone. In addition, the gene expression results provided some additional insight into the TGF-beta-mediated molecular processes underlying these changes. The broad-based histopathology and functional genomic analyses demonstrate that exposure to CAPs exacerbates rodents with allergic inflammation induced by an allergen and suggests that asthmatics may be at increased risk for air pollution effects.


Community researchers conducting health disparities research: Ethical and other insights from fieldwork journaling.
Lay persons who are trained to conduct research in their own communities form an essential part of many research projects. However, the effects of conducting research in their own communities have not been adequately explored. This paper examines the experiences, perceptions, and challenges faced by a group of community researchers during their involvement in a research project that examined if, and how, the relationships between mothers and their adolescent daughters could be harnessed to develop a daughter-initiated cervical cancer intervention. Seven community researchers interviewed 157 mother-daughter pairs in Cape Town, South Africa. We examine the use of journaling as a tool to document the experiences of community researchers, and we consider how journaling may help the community-based researcher grapple with the research process, and, more broadly, what such journal content illustrates with respect to the nature and challenges of community-engaged health research. An analysis of the content of the journals provides a strong indication of how personal and intimate the research process can be for community researchers by virtue of the background that they bring into the process as well as the additional weight of the research process itself. The complexities of navigating dual and somewhat oppositional roles - the role of impartial scientist or researcher and the role of invested community person - has been both underestimated and insufficiently researched.


Weight Management Interventions in Adult and Pediatric Asthma Populations: A Systematic Review.
Ample evidence suggests a dose-response relationship between increasing weight and level of asthma risk or reduced asthma control. To establish reversibility, several randomized controlled trials (RCTs) have recently been published to investigate the impact of weight management on asthma. This systematic review synthesizes evidence from these RCTs on the effects of weight management (weight loss, weight maintenance, maintenance of lost weight, or weight gain prevention) interventions on asthma outcomes in both adult and pediatric populations. We searched Medline, CINAHL, PsychInfo, and Cochrane for studies published between 1950 and November 2014. Two researchers independently rated the included studies using the quality assessment tool for RCTs as outlined in the 2013 Obesity Treatment Guideline. Discrepancies were resolved by consensus after discussion between the raters and, if needed, with the senior author. Four RCTs in adults and 3 in children and adolescents were included. The adult studies seem to consistently support the benefit of substantial weight loss, but a threshold effect may exist such that only weight loss beyond a minimal amount will likely lead to clinically important improvement in asthma outcomes. Three of them suggest that the threshold may lie between 5-10% of weight loss. RCTs in youth suggest that modest calorie reductions alone or combined with increased physical activity, or even a healthy normocaloric diet, may lead to improved asthma outcomes. However, most RCTs reviewed were limited by small sample size, short intervention durations, and short follow-up periods. Trial evidence shows the promise of weight loss interventions for asthma control in adults and youth. More adequately-powered, long-term RCTs are needed to elucidate the role of weight loss and other weight management interventions in asthma control and prevention. Definitive data are needed to guide clinical and public health practice to effectively address the dual epidemic of obesity and asthma.


Physical activity and cancer-specific mortality in the NIH-AARP Diet and Health Study cohort.
Higher physical activity levels have been associated with a lower risk of developing various cancers and all-cancer mortality, but the impact of pre-diagnosis physical activity on cancer-specific death has not been fully characterized. In the prospective National Institutes of Health-AARP Diet and Health Study with 293,511 men and women, we studied prediagnosis moderate to vigorous intensity leisure time physical activity (MVPA) in the past 10 years and cancer-specific mortality. Over a median 12.1 years, we observed 15,001 cancer deaths. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for MVPA with cancer mortality overall and by 20 specific cancer sites, adjusting for relevant risk factors. Compared to participants reporting never/rare MVPA, those reporting >7 hr/week MVPA had a lower risk of total cancer mortality (HR = 0.89, 95% CI 0.84-0.94; p-trend <0.001). When analyzed by cancer site-specific deaths, comparing those reporting >7 hr/week of MVPA to those reporting never/rare MVPA, we observed a lower risk of death from colon (HR = 0.70; 95% CI 0.57-0.85; p-trend <0.001), liver (0.71; 0.52-0.98; p-trend = 0.012) and lung cancer (0.84; 0.77-0.92; p-trend <0.001) and a significant p-trend for non-Hodgkins lymphoma (0.80; 0.62-1.04; p-trend = 0.017). An unexpected increased mortality p-trend with increasing MVPA was observed for death from kidney cancer (1.42; 0.98-2.03; p-trend = 0.016). Our findings suggest that higher prediagnosis leisure time physical activity is associated with lower risk of overall cancer mortality and mortality from multiple cancer sites. Future studies should confirm observed associations and further explore timing of physical activity and underlying biological mechanisms.


Computational prediction of functional abortive RNA in E. coli.
Failure by RNA polymerase to break contacts with promoter DNA results in release of bound RNA and re-initiation of transcription. These abortive RNAs were assumed to be non-functional but have recently been shown to affect termination in bacteriophage T7. Little is known about the functional role of these RNA in other genetic models. Using a computational approach, we investigated whether abortive RNA could exert function in E. coli. Fragments generated from 3780 transcription units were used as query sequences within their respective transcription units to search for possible binding sites. Sites that fell within known regulatory features were then ranked based upon the free energy of hybridization to the abortive. We further hypothesize about mechanisms of regulatory action for a select number of likely matches. Future experimental validation of these putative abortive-mRNA pairs may confirm our findings and promote exploration of functional abortive RNAs (faRNAs) in natural and synthetic systems.


Role for migratory wild birds in the global spread of avian influenza H5N8.
Avian influenza viruses affect both poultry production and public health. A subtype H5N8 (clade 18.104.22.168) virus, following an outbreak in poultry in South Korea in January 2014, rapidly spread worldwide in 2014-2015. Our analysis of H5N8 viral sequences, epidemiological investigations, waterfowl migration, and poultry trade showed that long-distance migratory birds can play a major role in the global spread of avian influenza viruses. Further, we found that the hemagglutinin of clade 220.127.116.11 virus was remarkably promiscuous, creating reassortants with multiple neuraminidase subtypes. Improving our understanding of the circumpolar circulation of avian influenza viruses in migratory waterfowl will help to provide early warning of threats from avian influenza to poultry, and potentially human, health.


Influence of texture and grain misorientation on the ionic conduction in multilayered solid electrolytes - interface strain effects in competition with blocking grain boundaries.
Interface strain and its influence on the ionic transport along hetero-interfaces has gained a lot of attention over the last decade and is controversially discussed. We investigate the relaxation of mismatch induced interfacial strain as a function of the degree of orientation/texture of the columnar crystallites and assess the impact on the oxygen ion conductivity in Er2O3/YSZ multilayer systems. Results from X-ray diffraction clearly show, that the width of the strained hetero-interface region increases with an increasing degree of orientation of the crystallites. The combined impact of film texture and strain at the hetero-interfaces of the film on the ionic conductivity however is not easily deduced from these measurements. The samples with the highest degree of orientation, i.e. with only one azimuthal variant, show strong anisotropic electrical properties. In samples with a lower degree of orientation, i.e. samples with a fiber texture, anisotropic properties cannot be detected, possibly due to a geometrical averaging of the electrical properties. The expected strain induced monotonic increase of the ionic conductivity with decreasing layer thickness and thus increasing interfacial influence could only be detected for samples with a fiber texture and a considerable degree of crystallite misorientation. This leads to the important conclusion that the texture and therefore the nature of the grain boundaries and their network influence the ionic conductivity of the multilayer thin films in the same order of magnitude as the misfit induced interface strain. Thus, the potential design of strain-controlled ionic conductors requires additionally the control of the microstructure in terms of grain orientation.


Mastering the risk of HLA antibodies in kidney transplantation: an algorithm based on pretransplant single-antigen flow bead techniques.
The utilization of sensitive techniques of detection of HLA antibodies to define and measure sensitization has greatly evolved in recent years. We present here an approach to minimize the risk of HLA antibodies in kidney transplantation based on the evaluation of graft accessibility of sensitized patients by calculated PRA (cPRA) and estimation of potential matched donors (PMD) using a national simulation software program. This study included all registered patients on our waiting list (WL) for deceased donor (DD) kidney transplants. All patients were screened by single-antigen flow bead (SAFB) techniques. Of the 502 registered patients, 174 (34.7%) were sensitized. Among these, 48.3% (84 pts) had a cPRA>85%. For 75.3% of sensitized patients (90 pts with cPRA≤85% and 41 pts with cPRA>85%), the flow of PMD was considered sufficient to allow a transplant avoiding all unacceptable antigens. The 41 patients with a cPRA>85% (48.8%) had a satisfactory donor flow in the framework of the national prioritization program for highly sensitized patients. Finally, 43 sensitized patients (24.7%) were deemed eligible for a strategy of higher immunological risk through desensitization protocols or transplantation against HLA-DSAs. This approach provides a logical and systematic strategy to rationalize the access of sensitized patients to kidney transplantation minimizing the risk of HLA antibodies.


Nurse teacher models in clinical education from the perspective of student nurses--A mixed method study.
The aim was to describe and compare the clinical teacher's role in different models of clinical practice from the perspective of student nurses. The study took place in collaboration with two Swedish universities that applied different educational models in clinical practice. A mixed method approach was used. The quantitative part had a comparative design and the qualitative part had a descriptive design. The study group consisted of 114 student nurses (response rate 87%). Fifty-three of them had met clinical teachers employed at the university and not participating in the daily clinical work (University Nurse Teachers, UNTs), whilst 61 had met clinical teachers dividing their time between teaching and nursing (Clinical Nurse Teachers, CNTs). Eight students participated in the qualitative part of the study. A questionnaire including the CLES+T scale was used to ascertain the students' perception of the clinical teacher's role, complemented by interviews directed towards an enrichment of this perception. Students meeting CNTs agreed more strongly than those meeting UNTs that the teacher had the ability to help them integrate theory and practice. Whilst spontaneous meetings between students and CNTs occurred, students mostly met UNTs in seminars. Students meeting UNTs felt alone but did appreciate having someone outside the clinical environment to provide support if they did not get along with their preceptor. In the case of UNTs, it is important that they keep their knowledge of clinical issues updated and visit the clinical placement not only for seminars but also to give students emotional support. In the case of CNTs, it is important that they are members of the faculty at the university, take part in the planning of the clinical courses and are able to explain the learning goals to the students.


Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products.
Twelve monoclonal antibodies (HC-MoAb) were prepared against a mixture of denatured HLA-B7 and -B40 heavy chains and were characterized by biochemical methods. The patterns of reactivity of 11 out of 12 of these MoAb were very similar and showed marked preference for the HLA-B locus heavy chains. A single antibody, HC-3, reacted with a subset of the HLA class I heavy chains recognized by the other HC-MoAb, which react with all HLA-B locus heavy chains tested. In pulse-chase experiments, only biosynthetic intermediates consisting of free class I heavy chains were precipitated by the HC MoAb. In addition to free HLA-B and minor quantities of some HLA-A heavy chains, additional class I polypeptides were recognized by the HC-MoAb. A number of these additional class I polypeptides showed a striking correlation with HLA-C as determined serologically. None of these polypeptides could be clearly identified in immunoprecipitations prepared from continuously labeled cells with the MoAb W6/32, previously thought to recognize all HLA-A, B, and C specificities. These findings suggest that in human cells, HLA-C locus products may be associated only weakly with B2m, explaining some of the difficulties encountered in biochemical studies of HLA-C antigens.


Crossing the line: estimations of line length in the Oppel-Kundt illusion.
In the Oppel-Kundt illusion, one of the oldest and least understood geometrical visual illusions, a line subdivided by a series of short orthogonal ticks appears longer than an identical line without these. Paradoxically, bisecting a long line with a single tick leads to perceived shortening of the line. We have systematically investigated the effects of adding 1 to 12 ticks on perceived line length and results suggest that at least three mechanisms must be at work: (a) bisection, which reduces perceived length; (b) a filled extent effect, which is also apparent in the von Helmholtz illusion, though no satisfactory explanation for it exists; and (c) a local contour repulsion effect of the penultimate tick upon the perceived position of the end tick, but this effect, though significant, is too small to explain the Oppel-Kundt illusion in its entirety.


Breast-feeding and childhood hospitalizations for infections.
Infectious disease is a leading cause of morbidity and hospitalization for infants and children. During infancy, breast-feeding protects against infectious diseases, particularly respiratory infections, gastrointestinal infections, and otitis media. Little is known about the longer-term impact of breast-feeding on infectious disease in children. We investigated the relationship between infant feeding and childhood hospitalizations from respiratory and gastrointestinal infections in a population-based birth cohort of 8327 children born in 1997 and followed for 8 years. The main outcomes were public hospital admissions for respiratory infections, gastrointestinal infections, and all infectious diseases. Cox regression was used to assess time to first hospitalization. Breast-feeding only (no formula-feeding) for 3 or more months was associated with a lower risk of hospital admission in the first 6 months of life for respiratory infections (hazard ratio = 0.64 [95% confidence interval = 0.42-0.97]), gastrointestinal infections (0.51 [0.25-1.05]), and any infection (0.61 [0.44-0.85]), adjusted for sex, type of hospital at birth, and household income. Partial breast-feeding (both breast-feeding and formula-feeding) in the first 3 months also reduced hospitalizations from infections but with smaller effect sizes. Beyond 6 months of age, there was no association between breast-feeding status at 3 months and hospitalization for infectious disease. Giving breast milk and no formula for at least 3 months substantially reduced hospital admissions for many infectious diseases in the first 6 months of life, when children are most vulnerable.


Clostridium difficile has an original peptidoglycan structure with a high level of N-acetylglucosamine deacetylation and mainly 3-3 cross-links.
The structure of the vegetative cell wall peptidoglycan of Clostridium difficile was determined by analysis of its constituent muropeptides with a combination of reverse-phase high pressure liquid chromatography separation of muropeptides, amino acid analysis, mass spectrometry and tandem mass spectrometry. The structures assigned to 36 muropeptides evidenced several original features in C. difficile vegetative cell peptidoglycan. First, it is characterized by a strikingly high level of N-acetylglucosamine deacetylation. In addition, the majority of dimers (around 75%) contains A(2)pm(3) → A(2)pm(3) (A(2)pm, 2,6-diaminopimelic acid) cross-links and only a minority of the more classical Ala(4) → A(2)pm(3) cross-links. Moreover, a significant amount of muropeptides contains a modified tetrapeptide stem ending in Gly instead of D-Ala(4). Two L,D-transpeptidases homologues encoding genes present in the genome of C. difficile 630 and named ldt(cd1) and ldt(cd2), were inactivated. The inactivation of either ldt(cd1) or ldt(cd2) significantly decreased the abundance of 3-3 cross-links, leading to a marked decrease of peptidoglycan reticulation and demonstrating that both ldt(cd1)-and ldt(cd2)-encoded proteins have a redundant L,D-transpeptidase activity. The contribution of 3-3 cross-links to peptidoglycan synthesis increased in the presence of ampicillin, indicating that this drug does not inhibit the L,D-transpeptidation pathway in C. difficile.


Autonomic Modulation in Older Women: Using Resistance Exercise as a Countermeasure.
It is unclear if resistance training (RT) can be used to alter declines in autonomic modulation associated with aging. Young women (YW; range 18-25 yrs) and older women (OW; range 50-72 yrs) were compared at baseline. Only OW underwent supervised RT 2 days a week for 12-weeks. Baseline and post-training measurements included heart rate variability (HRV) and complexity (Sample Entropy) to assess autonomic modulation. The 12-weeks of RT consisted of 9 exercises performing 3 sets of 8-12 repetitions. At baseline, group differences in maximal strength, and autonomic modulation were evaluated with a one-way ANOVA with BMI as a covariate. In the OW, the effects of RT were evaluated with repeated-measures ANOVA in order to compare baseline to after RT. The YW had significantly (p≤0.05) lower diastolic, but not systolic blood pressure. The YW also had significantly (p≤0.05) greater absolute Ln (natural logarithm) high-frequency (HF) power and normalized HF power compared to the OW. In addition, there were significantly (p≤0.05) greater levels of normalized low-frequency power (LF) (and the LF/HF ratio) in the OW compared to the YW before RT. However, no difference was found for Sample Entropy. After RT, OW significantly (p≤0.05) increased the chest press (28%) and leg extension (33%). RT had no significant effect on any autonomic parameter suggesting that it may not be a sufficient stimulus to alter the effects of aging.


What influences social outcomes among offenders with personality disorder: A systematic review.
Personality disorder is highly prevalent in offender populations and is associated with poor health, criminal justice, and social outcomes. Research has been conducted into factors that influence offending and health, but, in order to improve (re)habilitation, service providers must also be able to identify the variables associated with social outcomes and the mechanisms by which they operate. To establish what is known about what influences social outcomes among offenders with personality disorder. A systematic review was completed using Cochrane methods, expanded to include nonrandomised trials. Anticipated high heterogeneity informed a narrative synthesis. Three studies met inclusion criteria. Two were qualitative studies including only 13 cases between them. All studies were low quality. There is insufficient evidence to determine what influences good social outcomes among offenders with personality disorder. Research is required to identify associated variables, to inform the development of effective interventions.


Speeding up nuclear magnetic resonance spectroscopy by the use of SMAll Recovery Times - SMART NMR.
A drastic reduction of the time required for two-dimensional NMR experiments can be achieved by reducing or skipping the recovery delay between successive experiments. Novel SMAll Recovery Times (SMART) methods use orthogonal pulsed field gradients in three spatial directions to select the desired pathways and suppress interference effects. Two-dimensional spectra of dilute amino acids with concentrations as low as 2 mM can be recorded in about 0.1 s per increment in the indirect domain.


The Value of Quick Sepsis-Related Organ Failure Assessment Scores in Patients With Acute Pancreatitis Who Present to Emergency Departments: A Three-Year Cohort Study.
Distinguishing sepsis from other inflammatory syndromes continues to be a clinical challenge. The goal of risk stratification tools is to differentiate sepsis from other conditions. We compare the ability of quick sepsis-related organ failure assessment (qSOFA) and systemic inflammatory responses syndrome (SIRS) scores to predict prolonged length of stay (LOS) among patients who presented to the emergency department and hospital ward with acute pancreatitis (AP). We compiled a retrospective database of all adult patients hospitalized for AP during 2015 - 2018 at a single tertiary care center. Independent t-tests, Pearson's correlation and multiple regressions were performed with hospital LOS as the dependent variable, versus demographic characteristics and etiology of the pancreatitis as independent variables. Prolonged LOS was defined as > 5 days. The sensitivity and specificity of an SIRS score of 2 or greater for the detection of patients with prolonged LOS were 61% and 80%, respectively. The qSOFA score of 2 or greater corresponded to a diagnosis of significant AP with a specificity of 99% and a sensitivity of 4%. Multiple regression analysis demonstrated that each point increase in an SIRS score is associated with 2.24 days in additional hospital LOS. Interestingly, SIRS scores were found to correlate with the LOS, but not qSOFA. The qSOFA is a tool designed to identify patients at high risk of mortality due to sepsis. The data suggest that as with sepsis, patients with AP who are triaged with only qSOFA could be underrecognized and subsequently undertreated. Secondarily, the data suggest that SIRS scoring has the potential to promptly predict how long patients with AP will stay in the hospital.


A focused microarray for screening rat embryonic stem cell lines.
Here, we describe a focused microarray for screening rat embryonic stem cells (ESCs) and provide validation data that this array can distinguish undifferentiated rat ESCs from rat trophoblast stem (TS) cells, rat extraembryonic endoderm cells, mouse embryonic fibroblast feeder cells, and differentiated rat ESCs. Using this tool, genuine rat ESC lines, which have been expanded in a conventional rat ESC medium containing two inhibitors (2i), for example, glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase (MEK) inhibitors, and leukemia inhibitory factor, and genuine rat ESCs, which have been expanded in rat ESC medium containing four inhibitors (4i), for example, GSK3, MEK, Alk5, and Rho-associated kinase inhibitors were compared; as were genuine rat ESCs from 4 different strains of rats. Expression of Cdx2, a gene associated with trophoblast determination, was observed in genuine, undifferentiated rat ESCs from 4 strains and from both 2i and 4i ESC derivation medium. This finding is in contrast to undifferentiated mouse ESCs that do not express Cdx2. The rat ESC focused microarray described in this report has utility for rapid screening of rat ESCs. This tool will enable optimization of culture conditions in the future.


Intrinsic dreams are not produced without REM sleep mechanisms: evidence through elicitation of sleep onset REM periods.
The hypothesis that there is a strict relationship between dreams and a specific rapid eye movement (REM) sleep mechanism is controversial. Many researchers have recently denied this relationship, yet none of their studies have simultaneously controlled both sleep length and depth prior to non-REM (NREM) and REM sleep awakenings, due to the natural rigid order of the NREM--REM sleep cycle. The failure to control sleep length and depth prior to arousal has confounded interpretations of the REM-dreams relationship. We have hypothesised that different physiological mechanisms underlie dreaming during REM and NREM sleep, based on recent findings concerning the specificity of REM sleep for cognitive function. Using the Sleep Interruption Technique, we elicited sleep onset REM periods (SOREMP) from 13 normal subjects to collect SOREMP and sleep onset NREM (NREMP) dreams without the confounds described above. Regression analyses showed that SOREMP dream occurrences were significantly related to the amount of REM sleep, while NREMP dream occurrences were related to arousals from NREM sleep. Dream properties evaluated using the Dream Property Scale showed qualitative differences between SOREMP and NREMP dream reports. These results support our hypothesis and we have concluded that although 'dreaming' may occur during both REM and NREM periods as previous researchers have suggested, the dreams obtained from these distinct periods differ significantly in their quantitative and qualitative aspects and are likely to be produced by different mechanisms.