The antidiabetogenic effect of GLP-1 is maintained during a 7-day treatment period and improves diabetic dyslipoproteinemia in NIDDM patients.
To investigate the long-term antidiabetogenic effect of glucagon-like peptide 1 (GLP-1) and its influence on diabetic dyslipoproteinemia, patients with NIDDM were treated with GLP-1 subcutaneously for 1 week. Twelve patients participated in the study. The 1st week of the study, all of them were on intensive insulin treatment and from day 8, four were randomized to a control group continuing with insulin, and eight to a treatment group where GLP-1 was given at meals together with regular insulin from day 8 to 12. On days 13 and 14, they were only given GLP-1 at meals. NPH insulin at bedtime was given throughout the study. In the GLP-1-treated patients, the doses of regular insulin, given to keep a satisfactory blood glucose control, were reduced compared with treatment with insulin only. GLP-1 virtually inhibited the early increase in blood glucose after the meals, whereas an increase of approximately 2 mmol was seen during an optimized insulin treatment. In agreement with the short half-life of the peptide, 2-h postprandial plasma insulin levels were significantly decreased both at day 12 and 14, suggesting that there was not enough GLP-1 left to stimulate endogenous insulin release and compensate for the decrease in the dose of exogenous insulin. Therefore, the effect of GLP-1 was lost before the next meal, resulting in increased preprandial blood glucose values at lunch and dinner. The concentration of VLDL triglycerides decreased already during the 1st week. This decrease persisted during the 2nd week when GLP-1 was included in the treatment. No changes were observed in the levels of LDL and HDL cholesterol. The LDL particle diameter increased from a mean of 22.3 to 22.6 nm (P < 0.01) in response to insulin treatment. A further increment to 22.9 nm (P < 0.05) was seen after GLP-1 treatment. The LDL particle size did not change in the control group. Lipoprotein lipase activity was decreased by 27% and hepatic lipase was reduced by 13% in the GLP-1-treated group. We confirm the antidiabetogenic effect of GLP-1 in NIDDM patients. This effect was maintained during 7 days, which implies that the patients did not develop tolerance during this treatment period. Intensive insulin treatment, leading to normotriglyceridemia, increased the mean LDL particle diameter, which is likely to lower the risk of future coronary heart disease in patients with NIDDM. Furthermore, an additive effect of GLP-1 is indicated. Hence, this study gives additional evidence that GLP-1 may be useful as an agent for treating NIDDM.


Quantitative phosphoproteomics reveals the role of the AMPK plant ortholog SnRK1 as a metabolic master regulator under energy deprivation.
Since years, research on SnRK1, the major cellular energy sensor in plants, has tried to define its role in energy signalling. However, these attempts were notoriously hampered by the lethality of a complete knockout of SnRK1. Therefore, we generated an inducible amiRNA::SnRK1α2 in a snrk1α1 knock out background (snrk1α1/α2) to abolish SnRK1 activity to understand major systemic functions of SnRK1 signalling under energy deprivation triggered by extended night treatment. We analysed the in vivo phosphoproteome, proteome and metabolome and found that activation of SnRK1 is essential for repression of high energy demanding cell processes such as protein synthesis. The most abundant effect was the constitutively high phosphorylation of ribosomal protein S6 (RPS6) in the snrk1α1/α2 mutant. RPS6 is a major target of TOR signalling and its phosphorylation correlates with translation. Further evidence for an antagonistic SnRK1 and TOR crosstalk comparable to the animal system was demonstrated by the in vivo interaction of SnRK1α1 and RAPTOR1B in the cytosol and by phosphorylation of RAPTOR1B by SnRK1α1 in kinase assays. Moreover, changed levels of phosphorylation states of several chloroplastic proteins in the snrk1α1/α2 mutant indicated an unexpected link to regulation of photosynthesis, the main energy source in plants.


Assessing structure, function and druggability of major inhibitory neurotransmitter gamma-aminobutyrate symporter subtypes.
Ambient level of gamma -aminobutyric acid (GABA), the major inhibitory neurotransmitter of the brain is mediated by neuronal and glial GABA transporters (GATs), members of the sodium and chloride ion-dependent solute carrier family. The neuronal GABA transporter subtype (GAT-1) has already been proven to be the target for the antiepileptic drug Tiagabine. However, druggability of glial GAT-2 and GAT-3 is yet to be established. Recent advances in structure elucidation of a bacterial orthologue leucine transporter in complex with different substrates substantiate homology modeling of human GATs (hGATs). These modeling studies can provide mechanistic clues for structure-based prediction of the potential of medicinal chemistry campaigns. A recently identified characteristic structural feature of the occluded conformation of hGATs is that similar extra- and intracellular gates are formed by middle-broken transmembrane helices TM1 and TM6. Binding crevice formed by unwound segments of broken helices facilitates symport of GABA with Na+ ion via fitting of GABA to TM1-bound Na+ closely inside. Favored accommodation of substrate inhibitors with high docking score predicts efficient inhibition of the neuronal hGAT-1 if the TM1-TM8 binding prerequisite for GABA was used. Docking, molecular dynamics and transport data indicate, that amino acids participating in substrate binding of the neuronal hGAT-1 and the glial hGAT-2 and hGAT-3 subtypes are different. By contrast, substrate binding crevices of hGAT-2 and hGAT-3 cannot be distinguished, avoiding sensible prediction of efficient selective substrate inhibitors. Glial subtypes might be specifically distinguished by interfering Zn2+ binding in the second extracellular loop of hGAT-3. Formation of the unique ring-like Na+-GABA complex in the occluded binding crevices anticipates family member symporters exploring chemiosmotic energy via reversible chemical coupling of Na+ ion.


Helicobacter pylori, gastrin and cyclooxygenase-2 in lung cancer.
Tumors arising in the lungs are in over 90% bronchogenic carcinomas that have been attributed predominantly to tobacco smoking, asbestos or air pollution but little is known about endogenous factors that could facilitate their development and invasiveness. The lungs originate embryologically from the same endoderm cells which form the epithelia lining the digestive tract, where gastrin is the major proliferative stimulus. Since lung cancer patients were recruited mostly among smokers, who also have been found to exhibit significantly higher infection rate of Helicobacter pylori (HP) infection than non-smokers and, as since the HP-infected subjects show enhanced plasma levels of gastrin, we decided 1) to compare the seroprevalence of HP and the expression of its cytotoxin, CagA, in lung cancer patients with those in the age- and gender-matched controls without cancer: 2) to determine the gene expression for gastrin and its receptors (CCKB-R) in lung cancer, 3) to assess the gastrin levels in plasma bronchial lavage and in tumor tissue and 4) to examine the expression of cyclooxygenase (COX)-1 and COX-2 in cancer tissue resection margin and intact bronchial mucosa. The trial material included 50 patients with lung carcinoma and 100 age- and gender-matched controls. Anti-HP and anti-CagA IgG seroprevalence was estimated by specific antisera using ELISA tests. Gene expression of gastrin, CCKB-R, COX-1 and COX-2 was examined using RT-PCR, while gastrin was measured by specific RIA. The seroprevalence of HP, especially that expressing CagA, is significantly higher in lung cancers than in healthy controls. Both gastrin and CCKB-R mRNA were detected in the cancer tissue and at the resection margin and similarly COX-2 mRNA was expressed in most cancers and resection margin but not in bronchial mucosa where only COX-1 was found. The lung cancer tissue and resection margin contained many folds larger amounts of immunoreactive gastrin than intact bronchial mucosa.


Modeling erotomania delusion in the laboratory with hypnosis.
Erotomania is the delusional belief that one is loved from afar by another person (the target). This study used hypnosis as a novel cognitive neuropsychological research tool to model erotomania. The authors developed 2 versions of a hypnotic erotomania suggestion and tested their impact by asking subjects to recall and interpret a story featuring ambiguous scenarios. They also challenged the delusion by asking subjects to justify their beliefs. The hypnotic erotomania suggestions successfully recreated the features of the clinical delusion for many high hypnotizable subjects. They believed that the target loved them, interpreted ambiguous information consistent with this belief and confabulated evidence in service of their delusion. Some also resisted all challenges to their delusion. These features are strikingly similar to clinical cases and highlight the value of using hypnosis to model clinical delusions. The authors also discuss some limitations of this approach.


The visual identification of relational categories.
An experiment was performed to investigate the ability of human observers to identify configural relations among three dots. Four stimulus categories were defined on the basis of whether or not the dots were arranged collinearly and whether or not the central dot was equally spaced relative to the two flanking dots. Observers were initially trained with feedback to identify these categories at a single orientation with a fixed uniform background, and then they were tested with variable orientations and backgrounds without feedback. The results revealed almost perfect generalization. We also simulated the same task using a recent feature hierarchy model (J. Mutch & D. G. Lowe, 2008) that is among the most successful for object recognition. This model performed well for fixed orientations and backgrounds, but it could not accurately identify these categories with variable orientations and backgrounds even when given training with those conditions. These findings suggest that feature hierarchy models represent the spatial relations within an image quite differently than human observers.


Fructose, trehalose and sorbitol malabsorption.
Carbohydrate malabsorption is a frequent clinical condition, often associated with abdominal symptoms. Although lactose represents the most commonly malabsorbed sugar, also other carbohydrates, such as fructose, trehalose and sorbitol may be incorrectly absorbed in the small intestine. Fructose malabsorption seems more common in patients with functional bowel disease, even if randomized and controlled studies on these topic were few and on small samples. Interpretation of breath hydrogen testing is difficult. In particular, neither studies comparing this test with a gold standard, nor validated doses and concentrations to be used, are available. Trehalose malabsorption due to trehalase deficiency represents a very rare condition and available studies do not support its relevance in clinical practice. Sorbitol absorption is dose and concentration related, and depends on the entity of intestinal absorption surface. Nevertheless, the finding of its malabsorption is not expression of a specific cause of intestinal bowel damage. From available data, it is not possible to draw definite conclusions about clinical relevance of fructose, trehalose and sorbitol malabsorption, as well as, about diagnostic accuracy of commonly used tests to detect all these conditions. On the other hand, in patients who refer abdominal discomfort after ingestion of different carbohydrate-containing foods, a small intestinal bacterial overgrowth, should be promptly considered. This is because the large amount of intestinal bacteria may unspecifically ferment sugars, causing an abnormal H2 production and consequently a misleading diagnosis of sugar malabsorption.


Community participation in malaria surveillance and treatment. II. Evaluation of the volunteer collaborator Network of Guatemala.
To evaluate the effectiveness of the Volunteer Collaborator Network (VCN) of Latin America as a community-based malaria case detection and treatment system, we conducted a study of the VCN of Guatemala. Volunteer Collaborators took 72.6% of all blood smears and identified 81.3% of all malaria cases reported by the Guatemalan National Malaria Service. The average volunteer treated 5.8 patients per month (range 0-32.8). In contrast, passive case detection (PCD) posts in government hospitals and health centers treated an average of 12.5 patients per month (range 0.5-91.4). The slide positivity rate of blood smears taken by Volunteer Collaborators was 16.2% compared with 9.7% for PCD posts in health centers and 10.3% for malaria workers during active case detection. The average delay between the date a blood smear was taken and examined ranged from 18.1 days on the Pacific coastal plain to 26.3 days in the less accessible northern region of the country. An additional 14.5 to 47.6 days elapsed before the radical treatments were initiated in these two regions. Seventy percent of the patients completed their radical treatments. In a survey conducted on the Pacific coastal plain of Guatemala, of 1,021 patients with chills and/or fever who believed they had malaria, 20.0% had visited a Volunteer Collaborator and 4.9% were treated at a government health center. Thus, the PCD network detected only 25% of all patients with symptoms suggestive of malaria. Most of the remaining patients treated themselves with antimalarial medications purchased in stores and pharmacies, but less than 15% of these patients used adequate courses of therapy. Furthermore, the rate of detection of symptomatic patients with malaria varied considerably from one community to another. Thus, data from the VCN are probably most useful when groups of communities or geographic areas are stratified for malaria control activities because at this level, variations between individual Volunteer Collaborator posts will be minimized. In spite of these problems, the VCN remains an excellent source of epidemiologic data for malaria control programs and the most practical means available for providing timely, appropriate antimalarial therapy to febrile patients in rural areas.


Differences in pulmonary function before vs. 1 year after hypofractionated stereotactic radiotherapy for small peripheral lung tumors.
To evaluate long-term pulmonary toxicity of stereotactic radiotherapy (SRT) by pulmonary function tests (PFTs) performed before and after SRT for small peripheral lung tumors. A total of 17 lesions in 15 patients with small peripheral lung tumors, who underwent SRT between February 2000 and April 2003, were included in this study. Twelve patients had primary lung cancer, and 3 patients had metastatic lung cancer. Primary lung cancer was T1-2N0M0 in all cases. Smoking history was assessed by the Brinkman index (number of cigarettes smoked per day multiplied by number of years of smoking). Prescribed radiation doses at the 80% isodose line were 40-60 Gy in 5-8 fractions. PFTs were performed immediately before SRT and 1 year after SRT. Test parameters included total lung capacity (TLC), vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and diffusing capacity of lung for carbon monoxide (DLCO). PFT changes were evaluated in relation to patient- and treatment-related factors, including age, the Brinkman index, internal target volume, the percentages of lung volume irradiated with >15, 20, 25, and 30 Gy (V15, V20, V25, and V30, respectively), and mean lung dose. There were no significant changes in TLC, VC, or FEV1.0 before vs. after SRT. The mean percent change from baseline in DLCO was significantly increased by 128.2%. Univariate and multivariate analyses revealed a correlation between DLCO and the Brinkman index. One year after SRT as compared with before SRT, there were no declines in TLC, VC, and FEV1.0. DLCO improved in patients who had been heavy smokers before SRT, suggesting a correlation between DLCO and smoking cessation. SRT seems to be tolerable in view of long-term lung function.


Porphyria cutanea tarda and melioidosis.
Porphyria cutanea tarda is a metabolic disorder in the haem biosynthetic pathway. It includes a heterogeneous group of conditions, which may be inherited or, more commonly, acquired. Although porphyria cutanea tarda presents with cutaneous lesions only, it is often associated with systemic disease. A 64-year-old Chinese patient, who developed sporadic porphyria cutanea tarda 1 year after the diagnosis of pulmonary melioidosis, is discussed. The patient presented with a history of recurrent photosensitive vesicles, blisters, and skin fragility on the sun-exposed areas of both forearms and hands, 6 months after commencing doxycycline and amoxycillin. Both the histological and biochemical findings were characteristic of porphyria cutanea tarda. All the lesions subsided after cessation of these antibiotics. The patient was free of further lesions at follow-up 6 months later. The association seen in this case between porphyria cutanea tarda and melioidosis is unlikely to be coincidental, because these two diseases are both very rare in Hong Kong. In addition, the temporal relationship between the antibiotic therapy and the clinical course of skin lesions in this patient suggests that the drugs were a trigger factor, precipitating their appearance.


CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist.
CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid) was found to be a potent, stereospecific inhibitor of N-methyl-D-aspartate (NMDA)-evoked, but not KCl-evoked, [3H] acetylcholine release from slices of the rat striatum. The concentration-response curve to NMDA was shifted to the right by CGS 19755 (pA2 = 5.94), suggesting a competitive interaction with NMDA-type receptors. CGS 19755 inhibited the binding of [3H]-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid to NMDA-type receptors with an IC50 of 50 nM, making it the most potent NMDA-type receptor antagonist reported to date. CGS 19755 failed to interact with 23 other receptor types as assessed by receptor binding, including the quisqualate- and kainate-type excitatory amino acid receptors. In crude P2 fractions, no evidence was obtained to suggest that CGS 19755 is taken up by an active transport system. Furthermore, CGS 19755 failed to affect the uptake of L-[3H]glutamate, or to interact with aconitine-induced inhibition of L-[3H]glutamate uptake, the latter finding suggesting a lack of membrane-stabilizing or local anesthetic properties. CGS 19755 selectively antagonized the excitatory effect of iontophoretically applied NMDA in the red nucleus of the rat without affecting the excitatory effects of quisqualate. CGS 19755 blocked the harmaline-induced increase in cerebellar cyclic GMP levels at a dose of 4 mg/kg i.p. with a duration of action exceeding 2 hr. CGS 19755 inhibited convulsions elicited by maximal electroshock in rat (ED50 = 3.8 mg/kg i.p. 1 hr after administration) and in mouse (ED50 = 2.0 mg/kg i.p. 0.5 hr after administration). Likewise, convulsions elicited by picrotoxin were inhibited by CGS 19755, whereas the compound was relatively weak in protecting against convulsions elicited by pentylenetetrazole or strychnine. CGS 19755 produced retention performance deficits in a dark avoidance task. However, CGS 19755 did not show a unique propensity for learning and memory disruption compared to other anticonvulsants.


Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis.
Chronic kidney diseases generally lead to renal fibrosis. Despite great progress having been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear, and so far no effective therapeutic antifibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis. Both gene and protein assay showed that the expression of glycolysis enzymes was upregulated in mouse kidneys with unilateral ureter obstruction (UUO) surgery or in transforming growth factor-β1 (TGF-β1)-treated renal interstitial fibroblasts. Aerobic glycolysis flux, indicated by glucose uptake and lactate production, was increased in mouse kidney with UUO nephropathy or TGF-β1-treated renal interstitial fibroblasts and positively correlated with fibrosis process. In line with this, we found that increasing aerobic glycolysis can remarkably induce myofibroblast activation while aerobic glycolysis inhibitors shikonin and 2-deoxyglucose attenuate UUO-induced mouse renal fibrosis and TGF-β1-stimulated myofibroblast activation. Furthermore, mechanistic study indicated that shikonin inhibits renal aerobic glycolysis via reducing phosphorylation of pyruvate kinase type M2, a rate-limiting glycolytic enzyme associated with cell reliance on aerobic glycolysis. In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy.


Electrospun Nanodiamond-Silk Fibroin Membranes: A Multifunctional Platform for Biosensing and Wound-Healing Applications.
Next generation wound care technology capable of diagnosing wound parameters, promoting healthy cell growth, and reducing pathogenic infections noninvasively would provide patients with an improved standard of care and accelerated wound repair. Temperature is one of the indicating biomarkers specific to chronic wounds. This work reports a hybrid, multifunctional optical material platform-nanodiamond (ND)-silk membranes as biopolymer dressings capable of temperature sensing and promoting wound healing. The hybrid structure was fabricated through electrospinning, and 3D submicron fibrous membranes with high porosity were formed. Silk fibers are capable of compensating for the lack of an extracellular matrix at the wound site, supporting the wound-healing process. Negatively charged nitrogen vacancy (NV-) color centers in NDs exhibit optically detected magnetic resonance (ODMR) and act as nanoscale thermometers. This can be exploited to sense temperature variations associated with the presence of infection or inflammation in a wound, without physically removing the dressing. Our results show that the presence of NDs in the hybrid ND-silk membranes improves the thermal stability of silk fibers. NV- color centers in NDs embedded in silk fibers exhibit well-retained fluorescence and ODMR. Using the NV- centers as fluorescent nanoscale thermometers, we achieved temperature sensing in 25-50 °C, including the biologically relevant temperature window, for cell-grown ND-silk membranes. An enhancement (∼1.5× on average) in the temperature sensitivity of the NV- centers was observed for the hybrid materials. The hybrid membranes were further tested in vivo in a murine wound-healing model and demonstrated biocompatibility and equivalent wound closure rates as the control wounds. Additionally, the hybrid ND-silk membranes exhibited selective antifouling and biocidal propensity toward Gram-negative Pseudomonas aeruginosa and Escherichia coli, while no effect was observed on Gram-positive Staphylococcus aureus.


Optical interactions in a plasmonic particle coupled to a metallic film.
The interplay between localized surface plasmon (LSP) and surface plasmon-polariton (SPP) is studied in detail in a system composed of a three-dimensional gold particle located at a short distance from a gold thin film. Important frequency shifts of the LSP associated with the particle are observed for spacing distances between 0 and 50 nm. Beyond this distance the LSP and SPP resonances overlap, although some cavity effects between the particle and the film can still be observed. In particular, when the spacing increases the field in the cavity decreases more slowly than one would expect from a simple image dipole interpretation. For short separations the coupling between the particle and the film can produce a dramatic enhancement of the electromagnetic field in the space between them, where the electric field intensity can reach 5000 times that of the illumination field. Several movies show the spectral and time evolutions of the field distribution in the system both in and out of resonance. The character of the different modes excited in the system is studied. They include dipolar and quadrupolar modes, the latter exhibiting essentially a magnetic response.


Acute tubular necrosis (ATN) presenting with an unusually prolonged period of marked polyuria heralded by an abrupt oliguric phase.
A 50-year-old African-American man presented with acute tubular necrosis (ATN) secondary to hypotension from non-typhoid Salmonella gastroenteritis and bacteraemia. The oliguric phase lasted only 24 h followed by prolonged polyuria for 20 days, with urine output in excess of 16 L/day at maximum. As indexed in PubMed this is only the second published case of this nature since 1974, in which an abrupt oliguric phase of 24 h or less heralded prolonged polyuria in ATN. The diagnosis is challenging as fractional excretion of sodium early in the clinical course and rapid normalisation of serum creatinine with intravenous fluids (IVF) may point towards prerenal azotaemia resulting in a premature discharge from hospital. Patients with an abrupt oliguric phase may suffer a secondary renal insult from the profound fluid loss that is to follow and may need inpatient monitoring with supplemental IVF to prevent deleterious outcomes.


Stress analysis of two methods of ceramic inlay preparation by finite element.
Ceramic inlays are bonded to tooth structure with resin cements. During the resin cement setting, shrinkage stress develops at the interfaces. During tooth preparation, the undercut areas formed due to the different patterns of caries progression can either be blocked out before taking impression with suitable cement such as glass ionomer cement, or before making the final restoration in the laboratory. Then, the relieved space will be filled with luting cement in clinic. The aim of this study was to compare these two methods of undercut filling in term of stress distribution in the ceramic inlay. An axisymmetric finite element analysis was performed to study the stress distribution during inlay cementing. The solid model was generated from a longitudinal section of maxillary premolar in which a class I cavity with 60 degree undercut at the preparation wall and 20 degree divergence of the vertical walls was prepared. A thermal model was used to simulate the polymerization shrinkage of the resin cement. Finite element analysis was carried out in ANSYS environment. Filling the undercut by glass ionomer cement decreased the stress concentration at the ceramic/cement interface. The dominant normal stress at the tooth cement interface in absence of glass ionomer cement was tensile with maximum of 30 Mpa. Using glass ionomer, cement developed stresses with different compressive and tensile signs. With increasing the thickness of resin cement (100 µm, 150 µm, 200 µm), the stress increased. Cements with minimum shrinkage and as thin layer as possible should be used. Filling the undercut with glass ionomer cement decreases the stress. Other experimental and clinical studies must follow this research.


The fitness of human translocation carriers.
A simple method to estimate the mean fitness of human translocation carriers is described. The method is based on information about the inheritance pattern of the translocations. This kind of data can be obtained from the surveys of the chromosome constitutions of new-born babies. The following fitness estimates are obtained: D/D translocation carriers, 0-94; D/G translocation carriers, 0-83; and reciprocal translocation carriers, 0-67. The estimates are rather uncertain due to the scarcity of information, but they are consistent with the expected results. More accurate estimates will be obtained in the future when more data on translocation carriers are available and the cytological classification of the different translocations becomes more exact.


Resonance energy transfer microscopy: observations of membrane-bound fluorescent probes in model membranes and in living cells.
A conventional fluorescence microscope was modified to observe the sites of resonance energy transfer (RET) between fluorescent probes in model membranes and in living cells. These modifications, and the parameters necessary to observe RET between membrane-bound fluorochromes, are detailed for a system that uses N-4-nitrobenzo-2-oxa-1,3-diazole (NBD) or fluorescein as the energy donor and sulforhodamine as the energy acceptor. The necessary parameters for RET in this system were first optimized using liposomes. Both quenching of the energy donor and sensitized fluorescence of the energy acceptor could be directly observed in the microscope. RET microscopy was then used in cultured fibroblasts to identify those intracellular organelles labeled by the lipid probe, N-SRh-decylamine (N-SRh-C10). This was done by observing the sites of RET in cells doubly labeled with N-SRh-C10 and an NBD-labeled lipid previously shown to label the endoplasmic reticulum, mitochondria, and nuclear envelope. RET microscopy was also used in cells treated with fluorescein-labeled Lens culinaris agglutinin and a sulforhodamine derivative of phosphatidylcholine to examine the internalization of plasma membrane lipid and protein probes. After internalization, the fluorescent lectin resided in most, but not all of the intracellular compartments labeled by the fluorescent lipid, suggesting sorting of the membrane-bound lectin into a subset of internal compartments. We conclude that RET microscopy can co-localize different membrane-bound components at high resolution, and may be particularly useful in examining temporal and spatial changes in the distribution of fluorescent molecules in membranes of the living cell.


Association between Indoor Air Pollution and Cognitive Impairment among Adults in Rural Puducherry, South India.
Recent evidences showed that outdoor air pollution had significant influence on cognitive functioning of adults. However, little is known regarding the association of indoor air pollution with cognitive dysfunction. Hence, the current study was done to assess the association between indoor air pollution and cognitive impairment among adults in rural Puducherry. A community-based cross-sectional study was done among 295 adults residing in rural field practice area of tertiary care institute in Puducherry during February and March 2018. Information regarding sociodemographic profile and household was collected using pretested semi-structured questionnaire. Mini-Mental State Examination was done to assess cognitive function. We calculated adjusted prevalence ratios (aPR) to identify the factors associated with cognitive impairment. Among 295 participants, 173 (58.6) were in 30-59 years; 154 (52.2%) were female; and 59 (20.0%) were exposed to indoor air pollution. Prevalence of cognitive impairment in the general population was 11.9% (95% confidence interval [CI]: 8.7-16.1). Prevalence of cognitive impairment among those who were exposed to indoor air pollution was 27.1% (95% CI: 17.4-39.6). Individuals exposed to indoor air pollution (aPR = 2.18, P = 0.003) were found to have two times more chance of having cognitive impairment. About one-fourth of the participants were exposed to indoor air pollution, out of which more than one-fourth was found to have cognitive impairment which is twice that of the general population. Hence, prevention of exposure to indoor air pollution needs to be done through increased availability to cleaner fuels for household usage.


Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury.
Neuronal injuries have been a challenging problem for treatment, especially in the case of complete and chronic cervical spinal cord injury (SCI). Recently, particular attention is paid to the potential of stem cell in treating SCI, but there are only few clinical studies and insufficient data. This study explored the efficacy of autologous bone marrow mesenchymal stem cells (BMMSCs) transplantation in the treatment of SCI. Forty patients with complete and chronic cervical SCI were selected and randomly assigned to one of the two experimental groups, treatment group and control group. The treatment group received BMMSCs transplantation to the area surrounding injury, while the control group was not treated with any cell transplantation. Both the transplant recipients and the control group were followed up to 6 months, postoperatively. Preoperative and postoperative neurological functions were evaluated with AIS grading, ASIA score, residual urine volume and neurophysiological examination. Results showed that in the treatment group 10 patients had a significant clinical improvement in terms of motor, light touch, pin prick sensory and residual urine volume, while nine patients showed changes in AIS grade. Neurophysiological examination was consistent with clinical observations. No sign of tumor was evident until 6 months postoperatively. In the control group, no improvement was observed in any of the neurological functions specified above. BMMSCs transplantation improves neurological function in patients with complete and chronic cervical SCI, providing valuable information on applications of BMMSCs for the treatment of SCI.


Arctigenin protects against liver injury from acute hepatitis by suppressing immune cells in mice.
As a phenylpropanoid and dibenzylbutyrolactone lignan present in medical plants, such as those used in traditional Chinese herbal medicine, including Arctium lappa (Niubang), arctigenin exhibits antimicrobial, anti-inflammatory, and anticancer activities. In this study, we investigated the protective role of arctigenin in Concanavalin A (ConA)-induced acute hepatitis in mice. Arctigenin remarkably reduced the congestion and necroinflammation of livers, and improved hepatic function (ALT and AST) in ConA-induced acute hepatitis in vivo. The infiltration of CD4 T, NKT and macrophages into the livers was found to be reduced with arctigenin treatment. Arctigenin suppressed ConA-induced T lymphocyte proliferations that might have resulted from enhanced IL-10 production by macrophages and CD4 T cells. These results suggested that arctigenin could be a powerful drug candidate for acute hepatitis through immune suppression.


Ultracentrifugation enrichment protocol followed by total RNA sequencing allows assembly of the complete mitochondrial genome.
The mitochondrial genome is an independent genetic system in each eukaryotic cell outside the nuclear genome. Mitochondrial DNA (mtDNA) appears in high copy number within one cell, unlike nuclear DNA, which exists in two copies. But nevertheless, mtDNA represent only small part of total cellular DNA what causes problematic analysis and identification of relevant mutations. While most researchers tend to overlook it because of its small size, the mitochondrial genome contains genes that are essential for cellular energetics and survival. Because of the increased awareness on the importance of metabolism and bioenergetics in a wide variety of human diseases, more and more mtDNA studies were performed. Mitochondrial genome research has established the connection between mtDNA and a wide variety of diseases such as cancer or neurodegenerative disorders. At the present time, several methods are known, that allow sequencing of mtDNA. However, genomic analysis is often complicated due to the low content of mtDNA compared to nuclear DNA. For this reason, we have designed a new approach to obtaining the genomic mitochondrial sequence. We chose RNA based sequencing. Since human mtDNA does not contain introns, the reconstruction of whole mitochondrial genome through RNA sequencing seems to be effective. Our method is based on total RNA sequencing coupled with simple ultracentrifugation protocol and de novo assembly. Following our protocol, we were able to assemble a complete mammalian mitochondrial genome with a length of 16,505 bp and an average coverage of 156. The method is a relatively simple and inexpensive which could help in the further research or diagnostics of mtDNA-based diseases.


Drinking water from alternative water sources: differences in beliefs, social norms and factors of perceived behavioural control across eight Australian locations.
Australia is facing serious challenges in the management of water in various urban and regional locations. Two popular responses to these challenges are increasing supply through alternative water sources such as recycled and desalinated water. However, significant gaps exist in our knowledge of community attitudes to these alternative sources of water, particularly for potable use. This paper reports results from an Australian study of community attitudes to alternative water sources. Sixty six qualitative interviews were held at eight locations with distinctly different water situations. This paper explores all three antecedents to the behaviour of drinking recycled water and desalinated water as postulated by the Theory of Planned Behaviour: attitudes, social norms and factors of perceived behavioural control. Key results indicate that while people hold both positive and negative beliefs (mostly cost, health and environmental concerns) about water from alternative sources, nearly all of them are willing to drink it if the water crisis were to deteriorate further. People also feel they lack knowledge and state that information from scientists would influence their decision to drink recycled and desalinated water most. Friends and relatives are most influential in preventing people from drinking recycled water. The findings reported in this paper have major implications for water policy, and will be of particular interest to water engineers. The paper raises a provocative question: Is it better to avoid public consultation in introducing water from alternative sources?


Keeping Employees Safe During Health Crises: The Effects of Media Exposure, HR Practices, and Age.
Occupational health and safety are critical in promoting the wellness of organizations and employees. The COVID-19 pandemic is one of the most life-threatening viruses encountered in recent history, providing a unique opportunity for research to examine factors that drive employee safety behavior. Drawing from terror management theory, we propose and test a moderated mediation model using data collected from employees working during a peak of the pandemic. We identify two sources of influence - one external (i.e., media exposure), and one internal (i.e., HR practices) to the organization - that shape employees' mortality salience and safety behaviors. We find that COVID-19 HR practices significantly moderate the relationship between daily COVID-19 media exposure and mortality salience, with media exposure positively associated with mortality salience at lower levels of HR practices but its effects substituted by higher levels of HR practices. Moreover, our results also show that mortality salience spurs safety behaviors, with age moderating this relationship such that younger - but not older - employees are more likely to engage in safety behaviors due to mortality salience. Taken together, we offer theoretical implications for the safety behavior literature and practical implications for organizations faced with health crises or having employees who commonly work in hazardous conditions.


DIACYLGLYCEROL ACYLTRANSFERASE1 Contributes to Freezing Tolerance.
Freezing limits plant growth and crop productivity, and plant species in temperate zones have the capacity to develop freezing tolerance through complex modulation of gene expression affecting various aspects of metabolism and physiology. While many components of freezing tolerance have been identified in model species under controlled laboratory conditions, little is known about the mechanisms that impart freezing tolerance in natural populations of wild species. Here, we performed a quantitative trait locus (QTL) study of acclimated freezing tolerance in seedlings of Boechera stricta, a highly adapted relative of Arabidopsis (Arabidopsis thaliana) native to the Rocky Mountains. A single QTL was identified that contained the gene encoding ACYL-COENZYME A:DIACYLGLYCEROL ACYLTRANSFERASE1 (BstDGAT1), whose expression is highly cold responsive. The primary metabolic enzyme DGAT1 catalyzes the final step in assembly of triacylglycerol (TAG) by acyl transfer from acyl-CoA to diacylglycerol. Freezing tolerant plants showed higher DGAT1 expression during cold acclimation than more sensitive plants, and this resulted in increased accumulation of TAG in response to subsequent freezing. Levels of oligogalactolipids that are produced by SFR2 (SENSITIVE TO FREEZING2), an indispensable element of freezing tolerance in Arabidopsis, were also higher in freezing-tolerant plants. Furthermore, overexpression of AtDGAT1 led to increased freezing tolerance. We propose that DGAT1 confers freezing tolerance in plants by supporting SFR2-mediated remodeling of chloroplast membranes.


Fractionated radiotherapy is the main stimulus for the induction of cell death and of Hsp70 release of p53 mutated glioblastoma cell lines.
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Despite a multimodal therapy consisting of resection followed by fractionated radiotherapy (RT) combined with the chemotherapeutic agent (CT) temozolomide (TMZ), its recurrence is almost inevitable. Since the immune system is capable of eliminating small tumor masses, a therapy should also aim to stimulate anti-tumor immune responses by induction of immunogenic cell death forms. The histone deacetylase inhibitor valproic acid (VPA) might foster this. Reflecting therapy standards, we applied in our in vitro model fractionated RT with a single dose of 2Gy and clinically relevant concentrations of CT. Not only the impact of RT and/or CT with TMZ and/or VPA on the clonogenic potential and cell cycle of the glioblastoma cell lines T98G, U251MG, and U87MG was analyzed, but also the resulting cell death forms and release of danger signals such as heat-shock protein70 (Hsp70) and high-mobility group protein B1 (HMGB1). The clonogenic assays revealed that T98G and U251MG, having mutated tumor suppressor protein p53, are more resistant to RT and CT than U87MG with wild type (WT) p53. In all glioblastoma cells lines, fractionated RT induced a G2 cell cycle arrest, but only in the case of U87MG, TMZ and/or VPA alone resulted in this cell cycle block. Further, fractionated RT significantly increased the number of apoptotic and necrotic tumor cells in all three cell lines. However, only in U87MG, the treatment with TMZ and/or VPA alone, or in combination with fractionated RT, induced significantly more cell death compared to untreated or irradiated controls. While necrotic glioblastoma cells were present after VPA, TMZ especially led to significantly increased amounts of U87MG cells in the radiosensitive G2 cell cycle phase. While CT did not impact on the release of Hsp70, fractionated RT resulted in significantly increased extracellular concentrations of Hsp70 in p53 mutated and WT glioblastoma cells. Our results indicate that fractionated RT is the main stimulus for induction of glioblastoma cell death forms with immunogenic potential. The generated tumor cell microenvironment might be beneficial to include immune therapies for GBM in the future.


Cotton dust-mediated lung epithelial injury.
To determine if constituents of cotton plants might play a role in byssinosis by injuring pulmonary epithelium, we added extracts of cotton dust, green bract, and field-dried bract to human A549 and rat type II pneumocytes. Injury was measured as pneumocyte lysis and detachment, and inhibition of protein synthesis. Extracts of cotton dust and field-dried bract produced significant dose- and time-dependent lysis and detachment of both target cells, while green bract extract was less damaging. Extracts treated with polyvinylpolypyrrolidone to remove tannins produced significantly less injury. In contrast, purified 5,7,3',4'-tetrahydroxy-flavan 3,4-diol (THF), a tannin in cotton dust and bract, caused substantial cell damage. Field-dried bract extract and THF also produced dose-dependent inhibition of pneumocyte protein synthesis. Endotoxin levels did not correlate with observed injury. THF added to rat tracheal explants caused epithelial disruption and desquamation, whereas endotoxin did not. Instillation of cotton dust and field-dried bract extract in rat lungs produced disruption of bronchial epithelium and smooth muscle constriction, while polyvinylpolypyrrolidone-treated cotton dust extract produced no injury. These findings suggest that extracts of cotton plants are toxic to alveolar, tracheal, and bronchial epithelium and that THF or other tannins may be the responsible agents.


Scholarly tracks in emergency medicine.
Over the past decade, some residency programs in emergency medicine (EM) have implemented scholarly tracks into their curricula. The goal of the scholarly track is to identify a niche in which each trainee focuses his or her scholarly work during residency. The object of this paper is to discuss the current use, structure, and success of resident scholarly tracks. A working group of residency program leaders who had implemented scholarly tracks into their residency programs collated their approaches, implementation, and early outcomes through a survey disseminated through the Council of Emergency Medicine Residency Directors (CORD) list-serve. At the 2009 CORD Academic Assembly, a session was held and attended by approximately 80 CORD members where the results were disseminated and discussed. The group examined the literature, discussed the successes and challenges faced during implementation and maintenance of the tracks, and developed a list of recommendations for successful incorporation of the scholarly track structure into a residency program. Our information comes from the experience at eight training programs (five 3-year and three 4-year programs), ranging from 8 to 14 residents per year. Two programs have been working with academic tracks for 8 years. Recommendations included creating clear goals and objectives for each track, matching track topics with faculty expertise, protecting time for both faculty and residents, and providing adequate mentorship for the residents. In summary, scholarly tracks encourage the trainee to develop an academic or clinical niche within EM during residency training. The benefits include increased overall resident satisfaction, increased success at obtaining faculty and fellowship positions after residency, and increased production of scholarly work. We believe that this model will also encourage increased numbers of trainees to choose careers in academic medicine.


The health-systems response to violence against women.
Health systems have a crucial role in a multisector response to violence against women. Some countries have guidelines or protocols articulating this role and health-care workers are trained in some settings, but generally system development and implementation have been slow to progress. Substantial system and behavioural barriers exist, especially in low-income and middle-income countries. Violence against women was identified as a health priority in 2013 guidelines published by WHO and the 67th World Health Assembly resolution on strengthening the role of the health system in addressing violence, particularly against women and girls. In this Series paper, we review the evidence for clinical interventions and discuss components of a comprehensive health-system approach that helps health-care providers to identify and support women subjected to intimate partner or sexual violence. Five country case studies show the diversity of contexts and pathways for development of a health system response to violence against women. Although additional research is needed, strengthening of health systems can enable providers to address violence against women, including protocols, capacity building, effective coordination between agencies, and referral networks.


Lipoprotein risk factors for cardiovascular disease in patients with type 2 diabetes mellitus treated with oral antihyperglycaemic agents.
To compare lipoprotein risk factors for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) treated with a sulphonylurea (SU) compound only, metformin (MET) only, or combined SU + MET. The study population consisted of 62 patients with type 2 DM, whose antihyperglycaemic treatment program had been stable for at least 3 months, divided into three groups: 26 patients in the SU group, 17 patients in the MET group and 19 patients in the SU + MET group. None of the patients were taking lipid-lowering drugs. Fasting venous blood samples were taken to measure concentrations of glucose, total cholesterol, triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and remnant lipoprotein-cholesterol (RLP-C) as well as for determination of LDL particle diameter. The three groups were similar in terms of age, gender, body mass index and fasting plasma glucose concentrations. Total cholesterol concentrations were significantly lower (p < 0.05 for trend) in those treated with SU + MET as compared with the other two groups. However, there were no significant differences between the three groups in their plasma concentrations of TG, LDL-C, HDL-C or RLP-C; furthermore, the proportion of individuals within each treatment group with small LDL particle diameter was also not different. The lipoprotein profile of patients with type 2 DM, matched for level of fasting hyperglycaemia, was similar irrespective of treatment with SU alone, MET alone or SU + MET. Thus, we could not identify any changes in lipoprotein metabolism that could account for differences in risk of CVD as a function of treatment.


Adverse event management in patients with advanced cancer receiving oral everolimus: focus on breast cancer.
Everolimus, an orally administered rapamycin analogue, inhibits the mammalian target of rapamycin (mTOR), a highly conserved intracellular serine-threonine kinase that is a central node in a network of signaling pathways controlling cellular metabolism, growth, survival, proliferation, angiogenesis, and immune function. Everolimus has demonstrated substantial clinical benefit in randomized, controlled, phase III studies leading to approval for the treatment of advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic origin, renal angiomyolipoma and subependymal giant-cell astrocytoma associated with tuberous sclerosis complex, as well as advanced hormone-receptor-positive (HR(+)) and human epidermal growth factor receptor-2-negative advanced breast cancer. We discuss clinically relevant everolimus-related adverse events from the phase III studies, including stomatitis, noninfectious pneumonitis, rash, selected metabolic abnormalities, and infections, with focus on appropriate clinical management of these events and specific considerations in patients with breast cancer. The majority of adverse events experienced during everolimus therapy are of mild to moderate severity. The safety profile and protocols for toxicity management are well established. The class-effect adverse event profile observed with everolimus plus endocrine therapy in breast cancer is (as expected) distinct from that of endocrine therapy alone, but is similar to that observed with everolimus in other solid tumors. Information gained from the experience in other carcinomas on prompt diagnosis and treatments to optimize drug exposure, treatment outcomes, and patients' quality of life also applies to the patient population with advanced breast cancer. As with all orally administered agents, education of both physicians and patients in the management of adverse events for patients receiving everolimus is critical to achieving optimal exposure and clinical benefit. Active monitoring for early identification of everolimus-related adverse events combined with aggressive and appropriate intervention should lead to a reduction in the severity and duration of the event.


Divergent expression regulation of gonad development genes in medaka shows incomplete conservation of the downstream regulatory network of vertebrate sex determination.
Genetic control of male or female gonad development displays between different groups of organisms a remarkable diversity of "master sex-determining genes" at the top of the genetic hierarchies, whereas downstream components surprisingly appear to be evolutionarily more conserved. Without much further studies, conservation of sequence has been equalized to conservation of function. We have used the medaka fish to investigate the generality of this paradigm. In medaka, the master male sex-determining gene is dmrt1bY, a highly conserved downstream regulator of sex determination in vertebrates. To understand its function in orchestrating the complex gene regulatory network, we have identified targets genes and regulated pathways of Dmrt1bY. Monitoring gene expression and interactions by transgenic fluorescent reporter fish lines, in vivo tissue-chromatin immunoprecipitation and in vitro gene regulation assays revealed concordance but also major discrepancies between mammals and medaka, notably amongst spatial, temporal expression patterns and regulations of the canonical Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2 protein distribution in the medaka ovary defined a new subpopulation of theca cells, where ovarian-type aromatase transcriptional regulation appears to be independent of Foxl2. In summary, these data show that the regulation of the downstream regulatory network of sex determination is less conserved than previously thought.


Molecular imprinting method for fabricating novel glucose sensor: polyvinyl acetate electrode reinforced by MnO2/CuO loaded on graphene oxide nanoparticles.
An enzyme free glucose sensor was prepared by a molecular imprinting method (MIP). The procedure was developed by in situ preparation of a new polyvinyl acetate (PVA) electrode reinforced by MnO2/CuO loaded on graphene oxide (GO) nanoparticles (PVA/MnO2@GO/CuO). The nanocomposite was modified in the presence of glucose and then imprinted. A carbone paste method with voltammetry was used in the fabrication of the sensor from prepared MIP nanocomposite. PVA/MnO2@GO/CuO electrode was characterized by X-ray diffraction, FT-IR spectroscopy and scanning electron microscopy. Electrocatalytic activity of the electrode toward glucose oxidation was then investigated by cyclic voltammetry in alkaline medium. The results show that the response of PVA/MnO2@GO/CuO MIP is much higher than PVA/MnO2@GO/CuO non-imprinted electrode toward glucose oxidation. The detection limit was 53μM, and the sensor responses are linear for concentrations from 0.5 to 4.4mM. Relative standard deviations for intra- and inter-day determination were less than 6.0%. The relative recoveries for different samples were 96%.


Comparative transcriptional profiling analysis of the two daughter cells from tobacco zygote reveals the transcriptome differences in the apical and basal cells.
In angiosperm, after the first asymmetric zygotic cell division, the apical and basal daughter cells follow distinct development pathways. Global transcriptome analysis of these two cells is essential in understanding their developmental differences. However, because of the difficulty to isolate the in vivo apical and basal cells of two-celled proembryo from ovule and ovary in higher plants, the transcriptome analysis of them hasn't been reported. In this study, we developed a procedure for isolating the in vivo apical and basal cells of the two-celled proembryo from tobacco (Nicotiana tabacum), and then performed a comparative transcriptome analysis of the two cells by suppression subtractive hybridization (SSH) combined with macroarray screening. After sequencing, we identified 797 differentially expressed ESTs corresponding to 299 unigenes. Library sequence analysis successfully identified tobacco homologies of genes involved in embryogenesis and seed development. By quantitative real-time PCR, we validated the differential expression of 40 genes, with 6 transcripts of them specifically expressed in the apical or basal cell. Expression analysis also revealed some transcripts displayed cell specific activation in one of the daughter cells after zygote division. These differential expressions were further validated by in situ hybridization (ISH). Tissue expression pattern analysis also revealed some potential roles of these candidate genes in development. The results show that some differential or specific transcripts in the apical and basal cells of two-celled proembryo were successfully isolated, and the identification of these transcripts reveals that these two daughter cells possess distinct transcriptional profiles after zygote division. Further functional work on these differentially or specifically expressed genes will promote the elucidation of molecular mechanism controlling early embryogenesis.


Optimised radiological diagnosis of hepatic fungal infection during the treatment of leukemia.
Hepatic fungal infection is a frequent complication in patients receiving intensive chemotherapy for acute leukaemia. Hepatic lesions may be detected using computerised tomographic (CT) scans, but there is no standardised CT protocol for the diagnosis and follow-up of hepatic fungal infection. We therefore retrospectively analysed the number and the volume of hepatic fungal lesions in 24 CT of 20 consecutive patients treated for acute leukaemia during late-arterial and porto-venous phase. The mean number of lesions per patient was 31 (range: 3-105) in the late-arterial and 26 (3-81) in the porto-venous CT (P = 0.026). The mean total volume of all lesions was 6.45 ml in the late-arterial and 4.07 ml in the porto-venous CT representing a 1.6fold difference between the two CT scans (P = 0.008). The total volume of the lesions negatively correlated to the absolute contrast difference between liver parenchyma and liver vein (Pearson correlation, r = -0.62; P = 0.002). In conclusion, the late-arterial CT provides a superior distinction of hepatic lesions due to a delayed perfusion of the outer rim of the fungal lesions resulting in an extended visibility. The late-arterial CT is superior to the porto-venous CT for initial diagnosis and follow-up of hepatic fungal infection.


Nitratireductor indicus sp. nov., isolated from deep-sea water.
A taxonomic study was carried out on a novel bacterial strain, designated C115(T), isolated from a crude-oil-degrading consortium, enriched from deep-sea water of the Indian Ocean. Cells were Gram-negative short rods, mobile by means of a monopolar flagellum. Growth was observed at salinities of 0-7 % and at 10-43 °C. It was unable to degrade Tween 80 or gelatin. 16S rRNA gene sequence analysis showed that strain C115(T) was related most closely to Nitratireductor aquibiodomus NL21(T) (96.5 % similarity), Nitratireductor kimnyeongensis KY 101(T) (96.4 %) and Nitratireductor basaltis J3(T) (96.2 %). The predominant fatty acids were summed feature 8 (C(18 : 1)ω7c and/or C(18 : 1)ω6c, 81.8 %) and C(18 : 0) (7.0 %). The G+C content of the chromosomal DNA of strain C115(T) was 59 mol%. Based on its morphology, physiology and fatty acid composition together with 16S rRNA gene sequence comparisons, the novel strain most appropriately belongs to the genus Nitratireductor, but can be distinguished readily from recognized species of the genus. Strain C115(T) is therefore considered to represent a novel species of the genus Nitratireductor, for which the name Nitratireductor indicus sp. nov. is proposed. The type strain is C115(T) (=RC92-7(T) =CCTCC AB 209298(T) =LMG 25540(T) =MCCC 1A01260(T)).


Levels of fungi and mycotoxins in samples of grain and grain dust collected on farms in Eastern Poland.
Ten samples of stored wheat grain and 10 samples of settled grain dust released during machine threshing of wheat grain were collected on 10 farms located in Lublin province (eastern Poland). The samples were examined for the concentration of total microfungi, Fusarium species, fusariotoxins (moniliformin, deoxynivalenol, nivalenol), and ochratoxin. Microfungi able to grow on malt agar were present in 30% of grain samples (median for all examined samples = 0, range 0-227.5 x 10(3) cfu/g) and in all samples of grain dust (median = 977.5 x 10(3) cfu/g, range 115.0-16,700.0 x 10(3) cfu/g). Fusarium species (F. avenaceum) were found only in 10% of grain samples (median = 0, range 0-800.0 x 10(3) cfu/g), but in 90% of grain dust samples (median = 1,150 x 10(3) cfu/g, range 5.5-10,060.0 x 10(3) cfu/g). The species F. avenaceum, F. culmorum, F. graminearum, F. poae and F. sporotrichioides were isolated respectively from 50%, 10%, 20%, 40% and 20% of examined grain dust samples. The presence of the mycotoxins produced by Fusarium (moniliformin, deoxynivalenol, and nivalenol) was found altogether in 70% of wheat grain samples (median = 0.1275 microg/g, range 0-1.480 microg/g) and in 90% of grain dust samples (median = 0.350 microg/g, range 0-1.090 microg/g). Moniliformin (MON), deoxynivalenol (DON), and nivalenol (NIV) were each detected in 40% of grain samples, and respectively in 80%, 40%, and 40% of grain dust samples. Ochratoxin A (OTA) was detected in 60% of grain samples and in 60% of grain dust samples (median in both cases was 0.0005 microg/g). The concentrations of F. poae (p<0.05) and of total Fusarium species (p<0.01) in grain samples, and the concentrations of F. culmorum and F. graminearum (p<0.05) in grain dust samples were significantly correlated with the concentration of deoxynivalenol. The concentrations of F. poae (p<0.05) and of total Fusarium species (p<0.01) in grain dust samples were significantly correlated with the concentration of total fusariotoxins. Moreover, the concentration of total Fusarium species in grain dust samples was significantly correlated with the concentration of nivalenol (p<0.05). In conclusion, the majority of samples of wheat grain and grain threshing dust collected on farms in eastern Poland contained notable quantities of fusaria and/or fusariotoxins. This fact poses a potential risk of mycotoxicoses to agricultural workers exposed to grain dust when handling wheat during threshing, unloading, shuffling, and other farm occupations.


Neutrophil-to-lymphocyte ratio for early renal failure under extracorporeal membrane oxygenation support for postcardiotomy shock.
This study aims to investigate the relationship between the neutrophil-to-lymphocyte ratio and renal injury in patients under extracorporeal membrane oxygenation support for postcardiotomy shock. Between January 2007 and July 2018, a total of 119 patients (38 males, 81 females; mean age 54.4±13.0 years; range, 24 to 74 years) who received extracorporeal membrane oxygenation support for postcardiotomy shock and survived at least 48 hours in our center were retrospectively analyzed. Pre- and postoperative neutrophil-to-lymphocyte ratios, demographic characteristics, renal function parameters, and extracorporeal membrane oxygenationrelated data of the patients were recorded. Occurrence and stages of renal injury was determined using the revised Acute Kidney Injury Network and Kidney Disease Improving Global Outcomes criteria. No significant relationship was found between preoperative neutrophil-to-lymphocyte ratio and renal injury (p>0.05). Postoperative neutrophil-to-lymphocyte ratio was higher in patients who developed renal injury, compared to patients without renal injury (8.68 [0.84-42.00] vs. 4.02 [1.04-21.21], respectively, p=0.004). When patients were grouped for renal injury stage according to the revised Acute Kidney Injury Network (p=0.015) and Kidney Disease Improving Global Outcomes (p=0.006) criteria, the patients with more severe renal injury had higher neutrophil-to-lymphocyte ratio. The receiver operating characteristics analysis revealed a cut-off value of 6.71 for the neutrophil-to-lymphocyte ratio for the detection of renal injury. Patients with a value above 6.71 had an odds ratio of 5.941 for occurrence of renal injury. Postoperative, but not preoperative neutrophil-tolymphocyte ratio is associated with presence and severity of renal injury in patients under extracorporeal membrane oxygenation support for postcardiotomy shock. Neutrophil-to-lymphocyte ratio is a simple and inexpensive marker of inflammation in this patient population.


Regulation of gene expression in Sertoli cells by follicle-stimulating hormone (FSH): cloning and characterization of LRPR1, a primary response gene encoding a leucine-rich protein.
Searching for hormone-regulated genes in testicular Sertoli cells, we cloned and sequenced a cDNA of 3108 base pairs, named LRPR1 (signifying leucine-rich primary response gene 1). This cDNA sequence has an open reading frame of 2238 base pairs encoding a leucine-rich protein of 746 amino acid residues with a relative molecular mass of 85.6 kDa. As much as 16% of the amino acid residues is leucine. Database analysis revealed significant similarity of LRPR1 to the human brain cDNA sequence EST00443, but not to any other sequences present in databases. The expression of LRPR1 mRNA in Sertoli cells is strongly and rapidly up-regulated by follicle-stimulating hormone (FSH). The level of LRPR1 mRNA was very low in Sertoli cells isolated from 21-day-old rats and cultured for 3 days in the absence of FSH, but LRPR1 mRNA expression was markedly increased within 2 h after addition of FSH to these cultures. A maximal response was reached within 4 h. Dibutyryl-cyclic AMP [(Bu)2cAMP] and forskolin had similar effects compared to FSH, indicating that cAMP acts as a second messenger in the regulation of LRPR1 expression. The up-regulation of LRPR1 mRNA expression by FSH was also observed in the presence of the protein synthesis inhibitor cycloheximide, indicating that FSH regulates LRPR1 mRNA expression through a direct mechanism which does not require de novo protein synthesis. Thus, LRPR1 represents a primary response gene in FSH action on Sertoli cells. The presently available data indicate that LRPR1 mRNA expression is regulated specifically by FSH, since several other hormones and growth factors did not affect LRPR1 mRNA expression in the cultured Sertoli cells. LRPR1 mRNA expression is relatively high in testis, ovary and spleen. A much lower mRNA level was found in brain and lung, and no expression was detected in liver, kidney, heart, muscle, pituitary gland, prostate, epididymis and seminal vesicle. The basal level of testicular LRPR1 expression in intact 21-day-old rats was markedly increased within several hours after a single i.p. injection of FSH, indicating that in vivo LRPR1 mRNA expression may appear to be a useful parameter to evaluate testicular FSH action.


Evaluation of the desensitizing effect of Gluma Dentin Bond on teeth prepared for complete-coverage restorations.
This clinical trial assessed the ability of Gluma Dentin Bond to inhibit dentinal sensitivity in teeth prepared to receive complete cast restorations. Twenty patients provided 76 teeth for the study. Following tooth preparation, dentinal surfaces were coated with either sterile water (control) or two 30-second applications of Gluma Dentin Bond (test) on either intact or removed smear layers. Patients were recalled after 14 days for a test of sensitivity of the prepared dentin to compressed air, osmotic stimulus (saturated CaCl2 solution), and tactile stimulation via a scratch test under controlled loads. A significantly lower number of teeth responded to the test stimuli for both Gluma groups when compared to the controls (P less than .01). No difference was noted between teeth with smear layers intact or removed prior to treatment with Gluma.


Effects of the nicotine patch on performance during the first week of smoking cessation.
Complaints of feeling unfocused and being unable to concentrate are common during smoking cessation, and such feelings may contribute to a subtle erosion of the motivation to quit. A heterogeneous sample of 21 established smokers (10 women, 11 men) completed this double-blind, placebo-controlled study to test the hypothesis that nicotine replacement during cessation therapy (using a 21-mg nicotine patch) would improve performance on tasks sensitive to nicotine deprivation. Participants were trained to stable performance on simple reaction time, mathematical processing, Sternberg memory, rapid visual-information processing, grammatical reasoning, and the Stroop Color-Word (Stroop) tasks. They received smoking cessation counseling and were randomly assigned to nicotine patch and placebo patch groups. Performance was assessed prior to cessation, and early (days 2 and 3) and late (days 5 through 7) in the first cessation week. The hypothesis was not supported. Increased accuracy was associated with the patch only for grammatical reasoning. No reaction time differences were found in the simple reaction time, grammatical reasoning, and mathematical processing tasks. Reaction time was faster in the placebo group on the more difficult portions of those tasks requiring sustained attention (rapid visual-information processing, Stroop Color-Word, and Sternberg memory tasks). These results differ substantially from those obtained when young adults are allowed to smoke or chew nicotine gum after relatively brief periods of deprivation. Evidence that smoking may interfere with cognition is accumulating; these results support this view. The subjective performance decrements noted by many smokers during cessation may be related to overall negative affect, rather than to direct effects on cognition and attention.


Molecular dynamics simulations of oligoester brushes: the origin of unusual conformations.
We present results from all-atom molecular dynamics simulations for the structural properties of oligomeric lactic acid chains (OLA) grafted to the surface of cellulose nanocrystals (CNCs) and immersed in the melt of polylactic acid (PLA). Earlier, we have found that the distribution of free ends of OLA molecules is bimodal [Glova et al., Polym. Int., 2016, 65(8), 892]. The results cannot be explained within the standard picture of uncharged polymer brushes exposed to the melt of a chemically identical polymer. Although the oligomeric brushes of the OLA chains are uncharged, they have partial polarization charges producing a non-zero dipole moment of the monomeric chain unit. We study the influence of partial charges on the structure of the layer of OLA chains grafted to the CNC surface. A detailed analysis of the conformations of the grafted chains shows that interaction of partial charges in the models causes bending of the OLA molecules toward the cellulose surface, forming a hairpin structure. The observed separation of the grafted chains into two populations increases with grafting density. We demonstrate that hydrogen bonds can be formed between the free ends of the grafted chains and the CNC surface, but they do not affect the brush structure significantly. Thus, dipole-dipole interactions turn out to be the key factor governing the unusual conformations of grafts.


Catalytic alkylation reactions of weakly acidic carbonyl and related compounds using alkenes as electrophiles.
Catalytic alkylation reactions of weakly acidic carbonyl and related pronucleophiles such as amides, esters, and sulfonamides with substituted alkenes have been reported. In the presence of a strong Brønsted base catalyst system, potassium hexamethyldisilazide and 18-crown-6 ether, the desired reactions proceeded in high yields at ambient temperature with a wide substrate scope. These are atom-economical catalytic alkylation reactions of carbonyl and related compounds.


Effects of aromatherapy acupressure on hemiplegic shoulder pain and motor power in stroke patients: a pilot study.
The aim of this study was to determine if aromatherapy acupressure, compared to acupressure alone, was effective in reducing hemiplegic shoulder pain and improving motor power in stroke patients. This work was a randomized, controlled trial. Thirty (30) stroke patients with hemiplegic shoulder pain participated in this study. Subjects were randomly assigned to either an aromatherapy acupressure group (N = 15) or an acupressure group ( N = 15), with aromatherapy acupressure using lavender, rosemary, and peppermint given only to the former group. Each acupressure session lasted 20 minutes and was performed twice-daily for 2 weeks. Shoulder pain and motor power were the outcome measures used in this study. The pain scores were markedly reduced in both groups at post-treatment, compared to pretreatment (both aroma acupressure and acupressure group, p < 0.001). A nonparametric statistical analysis revealed that the pain score differed significantly between the 2 groups at post-treatment ( p < 0.01). The motor power significantly improved at post-treatment, compared to pretreatment, in both groups ( p < 0.005). However, there was no intergroup difference between two groups. These results suggest that aromatherapy acupressure exerts positive effects on hemiplegic shoulder pain, compared to acupressure alone, in stroke patients.


A longitudinal study of housing status and crime in a homeless population.
It is well established that homelessness is associated with crime. Previous research suggests that this association is at least partially secondary to homeless status offenses (eg, vagrancy and trespassing resulting from behaviors intrinsic to homelessness). To investigate this relationship, this study compared criminal behavior in a homeless population under housed and unhoused conditions. Reported criminal and housing histories of 255 homeless individuals were examined at 3 annual interviews. Lifetime criminal charges incurred while homeless vs housed were compared for types of offenses. Prospective longitudinal data from these interviews were used to examine housing status and recent crime. At baseline, homeless status offenses were the most frequently reported charges and were the only type of crime for which charges were incurred more frequently in the homeless condition. Over the 2-year followup period, recent crime was consistently higher in groups who had been homeless relative to groups who had been housed, and crime rates fell after obtaining housing. These findings suggest that homelessness itself is linked to criminal behavior through homeless status offenses. Negative effects of arrest and incarceration on housing acquisition warrant consideration of alternative legal system interventions to break the cycle of homelessness.


Morbidity associated with operative management of bladder stones in spinal cord-injured patients.
Retrospective cohort study of spinal cord-injured (SCI) patients undergoing bladder stone removal operations between 1999 and 2013. To determine the morbidity associated with different operative management of bladder stones in SCI patients. National Spinal Injuries Unit, Stoke Mandeville Hospital, UK. Data on age, sex, level and Frankel classification of spinal cord injury, method of bladder drainage, method of bladder stone removal, complications and length of stay were collected from patient records. Complication was defined as bladder perforation, sepsis or persistent haematuria. Predictors of complications and length of stay were determined using univariate and multivariate regression analyses. Overall, 112 consecutive bladder stone removal operations were performed, one open cystolithotomy and 111 transurethral procedures utilising simple washout, stone punch or electrohydraulic lithotripsy (EHL). Of these procedures, 17% (19/112) had complications; 0/11 (0%) following washout, 5/44 (11%) after stone punch, 3/12 (25%) following EHL and 10/26 (38%) after combined procedures using stone punch and EHL. In a multivariate model, patients with a cervical-level injury and those undergoing a combined procedure were significantly more likely to have a complication (P=0.032 and P=0.046). Length of stay was longer following a complication, the mean was 4.18 days compared with 1.37 days without a complication (P<0.001). Controlling complications and age, use of a combined procedure was associated with significantly longer stay than use of stone punch alone. This study provides important outcome data that should guide operative procedure choice and inform patients about possible risks during consent. It sets a benchmark that other centres can evaluate their outcomes against.


Optical absorption and photoconductivity in iodine-excess ionic liquids: the case of 1-alkyl-3-methyl imidazolium iodides.
We investigated the optical absorption and photoconductivity of iodine-excess ionic liquids (ILs) based on 1-alkyl-3-methyl imidazolium iodide ([Cnmim][I]; n = 3, 4, and 6). The iodide concentration m was 2 ≦ m ≦ 8, which was determined by the molar fraction [Cnmim]+ : [Im]- = 1 : m. By adding iodine, an absorption edge shifted from 282 nm in the UV region to around 600 nm in the visible-light region. The optical bandgaps Eo decreased gradually from 2.3 eV to 1.9 eV with increasing m from 2 to 8. The alkyl-side chain lengths of the cations have little effect on the Eo. This experimental result was confirmed by ab initio molecular orbital calculations. The effects were reflected in the photoconductivity of the ILs, as expected. [C4mim][Im] exhibited greater photo-induced electron generation compared with [C3mim][Im] and [C6mim][Im]. The photoconductivity in both [C3mim][Im] and [C6mim][Im] increased slightly with increasing m. The trend of photoconductivity in [C4mim][Im] exhibited an N-shaped form. The highest photoconductivity 1.6 was observed in [C4mim][I8].


Serous otitis media in the 20th and 21st centuries: evolving views and treatments.
The historical study of serous otitis media (SOM) demonstrates steps in recognition of the disease, shifts in prevalence, and relationships between the disease's affect and evolving economic bases of society. SOM, although noted in early Roman and Arabic medicine, was only identified as a distinct and significant pathology in the last half of the 20th century. This paper examines the development of understanding of SOM, and ways in which it has been cared for during the 20th and 21st centuries. The medical literature from antiquity to the present was reviewed for mention of otological conditions that related to SOM. For this report, the primary source of each notation was examined. The first part of the 20th century saw little change from earlier times in the recognition or treatment of SOM. Our current 21st century conceptualization and concern for SOM has come about from five advances: antibiotics, the rediscovery of the tympanostomy tube, the clinical use of middle ear impedance, the association of a history of otitis with linguistic deficiency, and recognition of the significance of transformation to a communication-based economy.


Impact of cancer on work and education among adolescent and young adult cancer survivors.
To examine the impact of cancer on work and education in a sample of adolescent and young adult (AYA) patients with cancer. By using the Adolescent and Young Adult Health Outcomes and Patient Experience Study (AYA HOPE)-a cohort of 463 recently diagnosed patients age 15 to 39 years with germ cell cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, sarcoma, and acute lymphocytic leukemia from participating Surveillance, Epidemiology, and End Results (SEER) cancer registries-we evaluated factors associated with return to work/school after cancer diagnosis, a belief that cancer had a negative impact on plans for work/school, and reported problems with work/school after diagnosis by using descriptive statistics, χ(2) tests, and multivariate logistic regression. More than 72% (282 of 388) of patients working or in school full-time before diagnosis had returned to full-time work or school 15 to 35 months postdiagnosis compared with 34% (14 of 41) of previously part-time workers/students, 7% (one of 14) of homemakers, and 25% (five of 20) of unemployed/disabled patients (P < .001). Among full-time workers/students before diagnosis, patients who were uninsured (odds ratio [OR], 0.21; 95% CI, 0.07 to 0.67; no insurance v employer-/school-sponsored insurance) or quit working directly after diagnosis (OR, 0.15; 95% CI, 0.06 to 0.37; quit v no change) were least likely to return. Very intensive cancer treatment and quitting work/school were associated with a belief that cancer negatively influenced plans for work/school. Finally, more than 50% of full-time workers/students reported problems with work/studies after diagnosis. Although most AYA patients with cancer return to work after cancer, treatment intensity, not having insurance, and quitting work/school directly after diagnosis can influence work/educational outcomes. Future research should investigate underlying causes for these differences and best practices for effective transition of these cancer survivors to the workplace/school after treatment.


Evolution of a TRIM5-CypA splice isoform in old world monkeys.
The TRIM family proteins share a conserved arrangement of three adjacent domains, an N-terminal RING domain, followed by one or two B-boxes and a coiled-coil, which constitutes the tripartite-motif for which the family is named. However, the C-termini of TRIM proteins vary, and include at least nine evolutionarily distinct, unrelated protein domains. Antiviral restriction factor TRIM5alpha has a C-terminal B30.2/SPRY domain, which is the major determinant of viral target specificity. Here, we describe the evolution of a cyclophilin-A encoding exon downstream of the TRIM5 locus of Asian macaques. Alternative splicing gives rise to chimeric transcripts encoding the TRIM motif fused to a C-terminal CypA domain (TRIM5-CypA). We detected TRIM5-CypA chimeric transcripts in primary lymphocytes from two macaque species. These were derived in part from a CypA pseudogene in the TRIM5 locus, which is distinct from the previously described CypA insertion in TRIM5 of owl monkeys. The CypA insertion is linked to a mutation in the 3' splice site upstream of exon 7, which may prevent or reduce expression of the alpha-isoform. All pig-tailed macaques (M. nemestrina) screened were homozygous for the CypA insertion. In contrast, the CypA-containing allele was present in 17% (17/101) of rhesus macaques (M. mulatta). The block to HIV-1 infection in lymphocytes from animals bearing the TRIM5-CypA allele was weaker than that in cells from wild type animals. HIV-1 infectivity remained significantly lower than SIV infectivity, but was not rescued by treatment with cyclosporine A. Thus, unlike owl monkey TRIMCyp, expression of the macaque TRIM5-CypA isoform does not result in increased restriction of HIV-1. Despite its distinct evolutionary origin, Macaca TRIM5-CypA has a similar domain arrangement and shares approximately 80% amino-acid identity with the TRIMCyp protein of owl monkeys. The independent appearance of TRIM5-CypA chimeras in two primate lineages constitutes a remarkable example of convergent evolution. Based on the presence of the CypA insertion in separate macaque lineages, and its absence from sooty mangabeys, we estimate that the Macaca TRIM5-CypA variant appeared 5-10 million years ago in a common ancestor of the Asian macaques. Whether the formation of novel genes through alternative splicing has played a wider role in the evolution of the TRIM family remains to be investigated.


A DFT study of EPR parameters in Cu(II) complexes of the octarepeat region of the prion protein.
The present paper shows how theoretically determined electron paramagnetic resonance (EPR) parameters can help in assigning the most favorable structure of Cu(ii) complexes in octarepeat (OR) regions (PHGGGWGQ) of the prion protein (PrP). This could contribute to a better understanding of the molecular structure of the Cu(OR) complexes, as some features of such species in solution are still unclear. The present theoretical investigation on [Cu(ii)(HGGG)] and [Cu(ii)(HGGGW)] complexes was carried out to confirm the stability of relevant isomers, and in particular, to evaluate the hyperfine coupling constants (hcc) with (63)Cu, (14)N and (17)O nuclei, as well as the g values. The hcc (and to a lesser extent the g components) are useful probes for checking whether the computed EPR parameters for specific isomers fit the experimental data, thus permitting the association of the observed spectra with a specific complex structure. The results obtained suggest that the Cu(ii) ion in the [Cu(HGGG)] isomers prefers a square pyramidal coordination with three nitrogen atoms of the peptide and one carbonyl oxygen atom in the basal plane. Also the Cu(ii) ion in the [Cu(HGGGW)] complex is penta-coordinated. The penta-coordination does not actually involve the tryptophan residue but an additional water molecule, forced to occupy the axial coordination position by a rather extended hydrogen-bond network, promoted by the tryptophan residue. The comparison between the calculated and experimental values of EPR parameters allows one to suggest the assignment of the coordination mode of the Cu(ii) ion in the considered peptide ligands. The computed values of the g components seem to be little affected by a particular coordination mode. In particular, the g( parallel) component is always underestimated by about 0.1 with respect to the experiment. The calculated values of the hcc, in contrast, are in acceptable agreement with the experimental values, in spite of the fact that the large size of the species under consideration forced us to accept a certain level of approximation in the computational procedure. Nevertheless, the present study must be considered as one of the first examples of truly ab initio calculations of EPR parameters for systems as large as the Cu(OR)-type complexes.


Nicotine metabolism, human drug metabolism polymorphisms, and smoking behaviour.
Large interindividual differences occur in human nicotine disposition, and it has been proposed that genetic polymorphisms in nicotine metabolism may be a major determinant of an individual's smoking behaviour. Hepatic cytochrome P4502A6 (CYP2A6) catalyses the major route of nicotine metabolism: C-oxidation to cotinine, followed by hydroxylation to trans-3'-hydroxycotinine. Nicotine and cotinine both undergo N-oxidation and pyridine N-glucuronidation. Nicotine N-1-oxide formation is catalysed by hepatic flavin-containing monooxygenase form 3 (FMO3), but the enzyme(s) required for cotinine N-1'-oxide formation has not been identified. trans-3'-Hydroxycotinine is conjugated by O-glucuronidation. The uridine diphosphate-glucuronosyltransferase (UGT) enzyme(s) required for N- and O-glucuronidation have not been identified. CYP2A6 is highly polymorphic resulting in functional differences in nicotine C-oxidation both in vitro and in vivo; however, population studies fail to consistently and conclusively demonstrate any associations between variant CYP2A6 alleles encoding for either reduced or enhanced enzyme activity with self-reported smoking behaviour. The functional consequences of FMO3 and UGT polymorphisms on nicotine disposition have not been investigated, but are unlikely to significantly affect smoking behaviour. Therefore, current evidence does not support the hypothesis that genetic polymorphisms associated with nicotine metabolism are a major determinant of an individual's smoking behaviour and exposure to tobacco smoke.


Readmission of known MRSA carriers and MRSA colonization pressure in hospital.
Readmission of asymptomatic methicillin-resistant Staphylococcus aureus (MRSA) carriers may contribute to the hospital reservoir. Using an electronic alert system, we assessed the weight of readmission of known MRSA carriers on MRSA colonization pressure in a hospital setting. During the 2004-2010 period, 2058 alerts were generated for 1060 inpatients. A total of 486/1060 patients (46%) were readmitted at least once, and 330/486 (64·4%) were readmitted <3 months after discharge. A mean of 20 MRSA patients were present on the same day (from 40 in 2004 to eight in 2010). The number of MRSA patient-days was 34 575, i.e. 2·5% of the 1 366 277 patient-days of the study period, and 17 737 (51·3%) MRSA patient-days were due to readmission of known MRSA carriers. The number of new MRSA cases was partly correlated with the number of MRSA patients hospitalized (R 2 = 0·49). Rapid electronic identification of these patients proved essential in decreasing the global burden of MRSA in our hospital.


Characteristics of Children Aged <18 Years with Zika Virus Disease Acquired Postnatally - U.S. States, January 2015-July 2016.
Zika virus is an emerging mosquito-borne flavivirus that typically causes an asymptomatic infection or mild illness, although infection during pregnancy is a cause of microcephaly and other serious brain abnormalities. Guillain-Barré syndrome and other neurologic complications can occur in adults after Zika virus infection. However, there are few published reports describing postnatally acquired Zika virus disease among children. During January 2015-July 2016, a total of 158 cases of confirmed or probable postnatally acquired Zika virus disease among children aged <18 years were reported to CDC from U.S. states. The median age was 14 years (range = 1 month-17 years), and 88 (56%) were female. Two (1%) patients were hospitalized; none developed Guillain-Barré syndrome, and none died. All reported cases were travel-associated. Overall, 129 (82%) children had rash, 87 (55%) had fever, 45 (29%) had conjunctivitis, and 44 (28%) had arthralgia. Health care providers should consider a diagnosis of Zika virus disease in children who have an epidemiologic risk factor and clinically compatible illness, and should report cases to their state or local health department.


Materials for suspension (semi-solid) electrodes for energy and water technologies.
Suspension or semi-solid electrodes have recently gained increased attention for large-scale applications such as grid energy storage, capacitive water deionization, and wastewater treatment. A suspension electrode is a multiphase material system comprised of an active (charge storing) material suspended in ionic solution (electrolyte). Gravimetrically, the electrolyte is the majority component and aids in physical transport of the active material. This principle enables, for the first time, scalability of electrochemical energy storage devices (supercapacitors and batteries) previously limited to small and medium scale applications. This critical review describes the ongoing material challenges encompassing suspension-based systems. The research described here combines classical aspects of electrochemistry, colloidal science, material science, fluid mechanics, and rheology to describe ion and charge percolation, adsorption of ions, and redox charge storage processes in suspension electrodes. This review summarizes the growing inventory of material systems, methods and practices used to characterize suspension electrodes, and describes universal material system properties (rheological, electrical, and electrochemical) that are pivotal in the design of high performing systems. A discussion of the primary challenges and future research directions is included.


Asbestos in toys: an exemplary case.
DAS was an artificial clay which, once molded, hardened at room temperature. It was largely used as a toy between 1963 and 1975 in Italy, Netherlands, Germany, UK and Norway. This case report describes and reports the presence of asbestos in DAS. We investigated the presence of asbestos in DAS using light and electron microscopy on samples of the original material. We searched administrative documents at the State Archive of Turin and conducted interviews with past employees on annual production, suppliers, and purchasers. The analytical tests confirmed the presence of asbestos fibers in DAS: about 30% of its composition. The documents found at the State Archive confirmed the annual purchase of hundreds tons of raw asbestos from the Amiantifera di Balangero, the Italian asbestos mine. DAS was found to be used also within craftsmanship. Asbestos fibers in DAS may have caused exposure to production workers and a variety of users, including artists, teachers, and children. Over 13 years, about 55 million packs of DAS were produced and sold. The number of users is difficult to estimate but may have been in the order of millions. In Italy, a specific question on the use of DAS has been included in a routinely used mesothelioma questionnaire. As DAS was exported to other countries, our findings suggest that mesothelioma patients should be asked about their past use of DAS, in particular individuals not reporting a clear past asbestos exposure. Additionally, this discovery shows the incompleteness of records on asbestos uses and suggests to test items, including toys, imported from countries where asbestos is not forbidden.


Developing a multi-component immune model for evaluating the risk of respiratory illness in athletes.
Clinical and laboratory identification of the underlying risk of respiratory illness in athletes has proved problematic. The aim of this study was to determine whether clinical data, combined with immune responses to standardised exercise protocols and genetic cytokine polymorphism status, could identify the risk of respiratory illness (symptoms) in a cohort of highly-trained athletes. Male endurance athletes (n=16; VO2max 66.5 ± 5.1 mL.kg-1.min-1) underwent a clinical evaluation of known risk factors by a physician and comprehensive laboratory analysis of immune responses both at rest and after two cycling ergometer tests: 60 min at 65% VO2max (LONG); and 6 x 3 min intervals at 90% VO2max (INTENSE). Blood tests were performed to determine Epstein Barr virus (EBV) status and DNA was genotyped for a panel of cytokine gene polymorphisms. Saliva was collected for measurement of IgA and detection of EBV DNA. Athletes were then followed for 9 months for self-reported episodes of respiratory illness, with confirmation of the underlying cause by a sports physician. There were no associations with risk of respiratory illness identified for any parameter assessed in the clinical evaluations. The laboratory parameters associated with an increased risk of respiratory illnesses in highly-trained athletes were cytokine gene polymorphisms for the high expression of IL-6 and IFN-ɣ; expression of EBV-DNA in saliva; and low levels of salivary IgA concentration. A genetic risk score was developed for the cumulative number of minor alleles for the cytokines evaluated. Athletes prone to recurrent respiratory illness were more likely to have immune disturbances that allow viral reactivation, and a genetic predisposition to pro-inflammatory cytokine responses to intense exercise.


The analysis and utilization of cycling training data.
Most mathematical models of athletic training require the quantification of training intensity and quantity or 'dose'. We aim to summarize both the methods available for such quantification, particularly in relation to cycle sport, and the mathematical techniques that may be used to model the relationship between training and performance. Endurance athletes have used training volume (kilometres per week and/or hours per week) as an index of training dose with some success. However, such methods usually fail to accommodate the potentially important influence of training intensity. The scientific literature has provided some support for alternative methods such as the session rating of perceived exertion, which provides a subjective quantification of the intensity of exercise; and the heart rate-derived training impulse (TRIMP) method, which quantifies the training stimulus as a composite of external loading and physiological response, multiplying the training load (stress) by the training intensity (strain). Other methods described in the scientific literature include 'ordinal categorization' and a heart rate-based excess post-exercise oxygen consumption method. In cycle sport, mobile cycle ergometers (e.g. SRM and PowerTap) are now widely available. These devices allow the continuous measurement of the cyclists' work rate (power output) when riding their own bicycles during training and competition. However, the inherent variability in power output when cycling poses several challenges in attempting to evaluate the exact nature of a session. Such variability means that average power output is incommensurate with the cyclist's physiological strain. A useful alternative may be the use of an exponentially weighted averaging process to represent the data as a 'normalized power'. Several research groups have applied systems theory to analyse the responses to physical training. Impulse-response models aim to relate training loads to performance, taking into account the dynamic and temporal characteristics of training and, therefore, the effects of load sequences over time. Despite the successes of this approach it has some significant limitations, e.g. an excessive number of performance tests to determine model parameters. Non-linear artificial neural networks may provide a more accurate description of the complex non-linear biological adaptation process. However, such models may also be constrained by the large number of datasets required to 'train' the model. A number of alternative mathematical approaches such as the Performance-Potential-Metamodel (PerPot), mixed linear modelling, cluster analysis and chaos theory display conceptual richness. However, much further research is required before such approaches can be considered as viable alternatives to traditional impulse-response models. Some of these methods may not provide useful information about the relationship between training and performance. However, they may help describe the complex physiological training response phenomenon.