The Relationship Between Whole-Body External Loading and Body-Worn Accelerometry During Team-Sport Movements.
To investigate the relationship between whole-body accelerations and body-worn accelerometry during team-sport movements. Twenty male team-sport players performed forward running and anticipated 45° and 90° side-cuts at approach speeds of 2, 3, 4, and 5 m/s. Whole-body center-of-mass (CoM) accelerations were determined from ground-reaction forces collected from 1 foot-ground contact, and segmental accelerations were measured from a commercial GPS accelerometer unit on the upper trunk. Three higher-specification accelerometers were also positioned on the GPS unit, the dorsal aspect of the pelvis, and the shaft of the tibia. Associations between mechanical load variables (peak acceleration, loading rate, and impulse) calculated from both CoM accelerations and segmental accelerations were explored using regression analysis. In addition, 1-dimensional statistical parametric mapping (SPM) was used to explore the relationships between peak segmental accelerations and CoM-acceleration profiles during the whole foot-ground contact. A weak relationship was observed for the investigated mechanical load variables regardless of accelerometer location and task (R2 values across accelerometer locations and tasks: peak acceleration .08-.55, loading rate .27-.59, and impulse .02-.59). Segmental accelerations generally overestimated whole-body mechanical load. SPM analysis showed that peak segmental accelerations were mostly related to CoM accelerations during the first 40-50% of contact phase. While body-worn accelerometry correlates to whole-body loading in team-sport movements and can reveal useful estimates concerning loading, these correlations are not strong. Body-worn accelerometry should therefore be used with caution to monitor whole-body mechanical loading in the field.


Selective Immunomodulation of Inflammatory Pathways in Keratinocytes by the Janus Kinase (JAK) Inhibitor Tofacitinib: Implications for the Employment of JAK-Targeting Drugs in Psoriasis.
IFN-γ and IL-22 are deeply involved in the pathogenesis of psoriasis, as they boost the expression of inflammatory genes and alter proliferative and differentiative programs in keratinocytes. The JAK1/JAK2/STAT1 and JAK1/TYK2/STAT3 pathways triggered by IFN-γ and IL-22, respectively, are aberrantly activated in psoriasis, as highlighted by the peculiar STAT1 and STAT3 signatures in psoriatic skin lesions. To limit the detrimental consequences of IFN-γ and IL-22 excessive stimulation, psoriatic keratinocytes activate suppressor of cytokine signaling (SOCS)1 and SOCS3, which in turn dampen molecular signaling by inhibiting JAK1 and JAK2. Thus, JAK targeting appears to be a reasonable strategy to treat psoriasis. Tofacitinib is an inhibitor of JAK proteins, which, similarly to SOCS, impedes JAK phosphorylation. In this study, we evaluated the immunomodulatory effects of tofacitinib on epidermal keratinocytes in in vitro and in vivo models of psoriasis. We demonstrated the selectivity of tofacitinib inhibitory action on IFN-γ and IL-22, but not on TNF-γ or IL-17 proinflammatory signaling, with suppressed expression of IFN-γ-dependent inflammatory genes, and restoration of normal proliferative and differentiative programs altered by IL-22 in psoriatic keratinocyte cultures. Tofacitinib also potently reduced the psoriasiform phenotype in the imiquimod-induced murine model of psoriasis. Finally, we found that tofacitinib mimics SOCS1 or SOCS3 activities, as it impaired the same molecular pathways in IFN-γ or IL-22-activated keratinocytes.


Cost-effectiveness of cytochrome P450 2C19 *2 genotype-guided selection of clopidogrel or ticagrelor in Chinese patients with acute coronary syndrome.
The choice of antiplatelet therapy among Asian populations for the treatment of acute coronary syndrome (ACS) is complicated owing to the high prevalence of cytochrome P450 2C19 (CYP2C19) genetic polymorphism that has been associated with reduced efficacy of clopidogrel. Ticagrelor is a potent but more expensive alternative antiplatelet agent that is not affected by CYP2C19 polymorphism. This study aimed to evaluate the cost-effectiveness, from the Hong Kong health-care provider's perspective, of CYP2C19*2 genotype-guided selection of antiplatelet therapy compared with the universal use of clopidogrel or ticagrelor among ACS patients who undergo percutaneous coronary intervention (PCI). In the present study, a two-part model consisting of a 1-year decision tree and a lifetime Markov model was built to simulate the progress of a typical cohort of 60-year-old Chinese patients until age 85 years and compare three treatment strategies: (i) generic clopidogrel or ticagrelor based on CYP2C19*2 genotype, (ii) universal use of generic clopidogrel or (iii) universal use of ticagrelor for all patients. Incremental cost-effectiveness ratios (ICERs) of <1 gross domestic product per capita locally (US dollar (USD)42 423/quality-adjusted life year (QALY)) were considered cost-effective. Base-case results showed universal ticagrelor use was cost-effective compared with universal clopidogrel, but was dominated by genotype-guided treatment. Genotype-guided treatment was cost-effective compared with universal clopidogrel use (ICER of USD2560/QALY). Sensitivity analysis demonstrated that with the cost of genotype testing up to USD400, CYP2C19*2 genotype-guided antiplatelet treatment remained a cost-effective strategy compared with either universal use of generic clopidogrel or ticagrelor in post-PCI ACS patients in Hong Kong.


Granule cells and cerebellar boundaries: analysis of Unc5h3 mutant chimeras.
Mutations in the Unc5h3 gene, a receptor for the netrin 1 ligand, result in abnormal migrations of both Purkinje and granule cells to regions outside the cerebellum and of granule cells to regions within the cerebellum. Because both Purkinje and granule cells express this molecule, we sought to determine whether one or both of these cell types are the primary target of the mutation. Chimeric mice were made between wild-type ROSA26 transgenic mouse embryos (whose cells express beta-galactosidase) and Unc5h3 mutant embryos. The resulting chimeric brains exhibited a range of phenotypes. Chimeras that had a limited expression of the extracerebellar phenotype (movement of cerebellar cells into the colliculus and midbrain tegmentum) and the intracerebellar phenotype (migration of granule cells into white matter) had a normal-appearing cerebellum, whereas chimeras that had more ectopic cells had attenuated anterior cerebellar lobules. Furthermore, the colonization of colliculus and midbrain tegmentum by cerebellar cells was not equivalent in all chimeras, suggesting different origins for extracerebellar ectopias in these regions. The granule cells of the extracerebellar ectopias were almost entirely derived from Unc5h3/Unc5h3 mutant embryos, whereas the ectopic Purkinje cells were a mixture of both mutant and wild-type cells. Intracerebellar ectopias in the chimera were composed exclusively of mutant granule cells. These findings demonstrate that both inside and outside the cerebellum, the granule cell is the key cell type to demarcate the boundaries of the cerebellum.


Green Synthesis of New Category of Pyrano[3,2-c]Chromene-Diones Catalyzed by Nanocomposite as Fe3O4@SiO2-Propyl Covalented Dapsone-Copper Complex.
Nanomagnetic dapsone-Cu supported on the silica-coated Fe3O4 (Fe3O4@SiO2-pr@dapsone-Cu) nanocomposite was synthesized and characterized by Fourier transform infrared (FT-IR), energy-dispersive X-ray (EDX), X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), zeta potential, vibrating sample magnetometer (VSM), and thermogravimetric analysis (TGA). This newly synthesized nanocomposite was chosen to act as a green, efficient, and recyclable Lewis acid for the multicomponent synthesis of new derivatives of pyrano[3,2-c]chromene-diones through the reaction of aromatic aldehydes, indandione, and 4-hydroxycoumarin in water. All of the synthesized compounds are new and are recognized by FT-IR, NMR, and elemental analysis; this avenue is new and has advantages such as short reaction times, high productivity, economical synthesis, and use of green solvent, H2O, as a medium. The catalyst is magnetically recoverable and can be used after six runs without a decrease in the efficiency.


Nondiscrimination on the basis of disability in air travel. Final rule.
The Department of Transportation is amending its Air Carrier Access Act (ACAA) rules to apply to foreign carriers. The final rule also adds new provisions concerning passengers who use medical oxygen and passengers who are deaf or hard-of-hearing. The rule also reorganizes and updates the entire ACAA rule. The Department will respond to some matters raised in this rulemaking by issuing a subsequent supplemental notice of proposed rulemaking.


Oxidants increase intracellular free Zn2+ concentration in rabbit ventricular myocytes.
Oxidative stress may alter cardiac function by affecting intracellular free Zn2+ concentrations ([Zn2+]i). Rabbit ventricular myocytes loaded with fura 2 were used to fluorometrically measure resting [Zn2+]i (0.23 +/- 0.03 nM) and intracellular Ca2+ concentration ([Ca2+]i) (36 +/- 7 nM). Fluorescence quenching by the heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine was used to quantitate [Zn2+]i. The thiol-reactive oxidants hypochlorous acid (0.1 mM) and selenite (1 mM) increased [Zn2+]i to 7.7 +/- 1.7 and 6.1 +/- 1.7 nM, respectively, within 5 min. Dithiothreitol (0.5 mM), a disulfide-reducing agent, rapidly restored normal [Zn2+]i. The oxidants did not affect [Ca2+]i. However, depolarization-induced Ca2+ transients and Ca2+ currents were zinc dependent. [Zn2+]i-associated fluorescence was substantial and, if ignored, it led to overestimation of [Ca2+]i by approximately twofold before oxidant treatment and by approximately eightfold after oxidants. The results demonstrate that [Zn2+]i 1) can be greatly increased by thiol-reactive oxidants; 2) may contribute to oxidant-induced alterations of excitation-contraction coupling; and 3) has strong fura 2 fluorescence which, if overlooked, can lead to significant overestimation of [Ca2+]i.


Analysis of free amino acids in flue-cured tobacco leaves using ultra-high performance liquid chromatography with single quadrupole mass spectrometry.
Amino acids are one of the most important metabolites of organisms. They play an important role in plant growth, development, and product quality. A method based on RP ultra-performance LC with single quadrupole MS and 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate precolumn derivatization was developed for the analysis of free amino acids in flue-cured tobacco leaves. Unlike the corresponding UV detection method, this method avoids matrix interference of complicated tobacco components, and the quantitative accuracy and resolution were improved. Twenty free amino acids were detected in flue-cured tobacco leaves. The method showed a good linearity with correlation coefficients of 0.9966-0.9998. The LODs for derivatized amino acids were 0.2-9.7 fmol/μL. Good repeatability with an RSD of 2.5-8.6% and satisfactory intra- and interday precisions were obtained. The developed method was used to investigate free amino acids in flue-cured tobacco leaves in China. The effects of aroma type, variety, and growing regions on free amino acids were investigated. The results showed that free amino acids in tobacco were affected by growing regions and varieties.


O-GlcNAc transferase regulates mitotic chromatin dynamics.
Mitosis must faithfully divide the genome such that each progeny inherits the same genetic material. DNA condensation is crucial in ensuring that chromosomes are correctly attached to the mitotic spindle for segregation, preventing DNA breaks or constrictions from the contractile ring. Histones form an octameric complex of basic proteins important in regulating DNA organization and accessibility. Histone post-translational modifications are altered during mitosis, although the roles of these post-translational modifications remain poorly characterized. Here, we report that N-acetylglucosamine (O-GlcNAc) transferase (OGT), the enzyme catalyzing the addition of O-GlcNAc moieties to nuclear and cytoplasmic proteins at serine and threonine residues, regulates some aspects of mitotic chromatin dynamics. OGT protein amounts decrease during M phase. Modest overexpression of OGT alters mitotic histone post-translational modifications at Lys-9, Ser-10, Arg-17, and Lys-27 of histone H3. Overexpression of OGT also prevents mitotic phosphorylation of coactivator-associated arginine methyltransferase 1 (CARM1) and prevents its correct cellular localization during mitosis. Moreover, OGT overexpression results in an increase in abnormal chromosomal bridge formation. Together, these results show that regulating the amount of OGT during mitosis is important in ensuring correct chromosomal segregation during mitosis.


Glicentin inhibits internalization of enteric bacteria by cultured INT-407 enterocytes.
Glicentin, the main component of enteroglucagon, has trophic effects on intestinal mucosa. It may also have an inhibitory effect on extraintestinal invasion of enteric bacteria. We have established an in vitro bioassay system for determining the effects of recombinant human glicentin on bacterial internalization by confluent enterocytes. An INT-407 cell line was serum-deprived for 2 days and was then treated on transwell filters for 24 h with a medium containing one of the following: glicentin 100 ng-1 microg/ml, glucagons-like peptide-2 (GLP-2) 1 microg/ml, 10% fetal bovine serum (FCS), or without any growth factors. Pure cultures of Salmonella enteritidis, Escherichia coli, and Enterococcus faecalis were introduced to the upper chambers of the filter units. Following 2 h of incubation the numbers of bacteria in the lower chambers were measured. Pretreatment of enterocytes with glicentin inhibited bacterial internalization compared to untreated or GLP-2 enterocytes. Glicentin was associated with inhibition of enterocyte internalization of enteric bacteria by a mechanism that might be related to the integrity of the enterocyte adhesive junctions and tight junctions and to the production of sIgA. Glicentin seems to have a function as a barrier-sustaining agent that inhibits extraintestinal invasion of enteric bacteria.


Normalization of Flow-mediated Dilation to Brachial Artery Material Property: A Feasibility Study.
Endothelial reactivity (ER) is widely measured using flow-mediated dilation (FMD) of brachial artery. Conventional measurement of FMD is influenced by factors such as input shear stress, arterial transmural pressure, diameter and thereby arterial material properties (ε). Thus, for a reliable interpretation of FMD, it has to be normalized with respect to the above confounding factors. Normalization of FMD with shear stress at the time of measurement has been reported to reduce measurement variability. However, its widespread usage among the research community is limited. In this work, we examine the feasibility of normalizing the brachial FMD index (FMD%) to ε : extrema (εp), baseline (εb) and extrema change (∆ε) post-ischemia using its inter-day variability against FMD. In-vivo measurements were performed on 10 participants for 2 consecutive days and simultaneous pressure-diameter cycles were collected to estimate the material properties during reactive hyperemia (RH). The box-whisker plot reveals differences in the mean and deviation of FMD to FMD|εb. A significant value for repeatability (ICC ≥ 0.6) was obtained for normalized FMD (FMD|εb) for specific stiffness index (β), pressure-strain elastic modulus (Ep), and local pulse wave velocity (PWV) as compared to FMD. Hence, normalization of FMD% to arterial ε can potentially improve the measurement reliability of ER assessment.Clinical Relevance- This pilot study demonstrates the feasibility of brachial artery stiffness assessment during FMD and its potential use for normalizing the standard FMD measurement.


A Monte Carlo procedure for the construction of complementary cumulative distribution functions for comparison with the EPA release limits for radioactive waste disposal.
A Monte Carlo procedure for the construction of complementary cumulative distribution functions (CCDFs) for comparison with the U.S. Environmental Protection Agency (EPA) release limits for radioactive waste disposal (40 CFR 191, Subpart B) is described and illustrated with results from a recent performance assessment (PA) for the Waste Isolation Pilot Plant (WIPP). The Monte Carlo procedure produces CCDF estimates similar to those obtained with importance sampling in several recent PAs for the WIPP. The advantages of the Monte Carlo procedure over importance sampling include increased resolution in the calculation of probabilities for complex scenarios involving drilling intrusions and better use of the necessarily limited number of mechanistic calculations that underlie CCDF construction.


The pioneering use of ISSR (Inter Simple Sequence Repeat) in Neotropical anurans: preliminary assessment of genetic diversity in populations of Physalaemus cuvieri (Amphibia, Leiuperidae).
The greatest diversity of anurans in the world is in Brazil and one of the major challenges is to reconcile the accelerated economic development with strategies that aim to maintain this diversity in forest fragments, often representing ESUs of some biomes. This study aimed to obtain data that will support conservation projects through the pioneering use of ISSR analysis in Neotropical anurans, estimating the intra- and interpopulation genetic diversity of four populations of P. cuvieri (Paraná and São Paulo regions). Of the 65 loci scored 58 were polymorphic, with 0.797 intrapopulation variation and 0.203 interpopulation variation. The index of interpopulation genetic differentiation (FST) proved to be high among the population of Marmeleiro-PR and the three populations of SP (FST > 0.288); genetic dissimilarity was related to the geographical distance. The ISSR proved to be efficient and useful molecular markers in comparison with other markers most widely used for preliminary diagnosis of genetic diversity in populations of amphibians, and could be applied as a tool for future conservation projects, since they could identify potential ESUs and influence decisions on the preservation of fragments.


Virtual cavity in distributed Bragg reflectors.
We show theoretically and experimentally that distributed Bragg reflector (DBR) supports a surface electromagnetic wave exhibiting evanescent decay in the air and oscillatory decay in the DBR. The wave exists in TM polarization only. The field extension in the air may reach several wavelengths of light. Once gain medium is introduced into the DBR a novel class of diode lasers, semiconductor optical amplifiers, light-emitting diodes, etc. can be developed allowing a new type of in-plane or near-field light outcoupling. To improve the wavelength stability of the laser diode, a resonant cavity structure can be coupled to the DBR, allowing a coupled state of the cavity mode and the near-field mode. A GaAlAs-based epitaxial structure of a vertical-cavity surface-emitting laser (VCSEL) having an antiwaveguiding cavity and multiple GaInAs quantum wells as an active region was grown and processed as an in-plane Fabry-Pérot resonator with cleaved facets. Windows in the top stripe contact were made to facilitate monitoring of the optical modes. Three types of the optical modes were observed in electroluminescence (EL) studies under high current densities > 1 kA/cm2. Mode A with the longest wavelength is a VCSEL-like mode emitting normal to the surface. Mode B has a shorter wavelength, emitting light at two symmetric lobes tilted with respect to the normal to the surface in the direction parallel to the stripe. Mode C has the shortest wavelength and shifts with a temperature at a rate 0.06 nm/K. Polarization studies reveal predominantly TE emission for modes A and B and purely TM for mode C in agreement with the theory. Spectral position, thermal shift and polarization of mode C confirm it to be a coupled state of the cavity mode and near-field DBR surface-trapped mode.


Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests.
Bronchial provocation tests such as exercise, methacholine (MCH), and adenosine-5'-monophosphate (AMP) challenges are used extensively in the diagnosis of asthma. A study was undertaken to determine whether exhaled nitric oxide (eNO) can be used to diagnose asthma in patients with non-specific respiratory symptoms and to compare this test with conventional provocation tests. Patients with non-specific respiratory symptoms and normal spirometric parameters were included in the study. eNO was measured and exercise, MCH and AMP challenges performed in all subjects. Patients were defined as asthmatic based on clinical follow up 24 months after testing. Forty patients were considered asthmatic and 45 were not. The area under receiver operating characteristic curves gave values of 0.896 for eNO, 0.781 for exercise, 0.924 for MCH, and 0.939 for AMP (p = 0.033, 0.575 and 0.085 for eNO v exercise, MCH and AMP respectively). From our data, a cut off value of NO > 7 ppb at a flow rate of 250 ml/s best differentiates between asthmatics and non-asthmatics (sensitivity 82.5%, specificity 88.9%). Optimal cut off values for other tests were exercise: deltaFEV1 > or = 10% (sensitivity 57.9%, specificity 100%); PC20-MCH: < or = 3 mg/ml (sensitivity 87.5%, specificity 86.7%); and PC20-AMP: < or = 150 mg/ml (sensitivity 89.5%, specificity 95.6%). Measurement of eNO can be used as a safe, simple and rapid test for the diagnosis of asthma and is as good as bronchial provocation tests.


Characterization of the interaction between the baculovirus ssDNA-binding protein (LEF-3) and putative helicase (P143).
LEF-3 and P143 are two of six proteins encoded by the Autographa californica multinucleocapsid nucleopolyhedrovirus genome which are required for DNA replication in transient replication assays. LEF-3 has the properties of an ssDNA-binding protein and P143 exhibits amino acid sequence homology to helicases. In this report, the interaction of LEF-3 and P143 was studied by yeast two-hybrid and immunoaffinity analyses. Using the yeast two-hybrid system, the interaction domain of LEF-3 (385 aa) was mapped to amino acids between positions 1 and 165. Deletion analysis of P143 failed to reveal an interaction domain, suggesting that there were either multiple interaction domains or that the deletions disrupted the secondary structures required for the interaction between LEF-3 and P143.


The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1).
This multinational, Internet-based survey was designed to assess the prevalence, frequency, severity, and impact of opioid-induced bowel dysfunction (OBD) in patients receiving opioid therapy for chronic pain and taking laxatives. In total, 322 patients taking daily oral opioids and laxatives completed the 45-item questionnaire. At the time of the survey, 45% of patients reported <3 bowel movements per week. The most prevalent opioid-induced side effects were constipation (81%) and straining to pass a bowel movement (58%). Those side effects considered most bothersome by patients were (in order of rank) constipation, straining, fatigue, small or hard bowel movements, and insomnia. Most of the OBD symptoms specified in the questionnaire were experienced by the majority of patients >or=4 times a week. Constipation was the OBD symptom that was most often reported as severe. Most patients reported that their OBD symptoms had at least a moderate negative impact on their overall quality of life and activities of daily living. A third of patients had missed, decreased or stopped using opioids in order to make it easier to have a bowel movement. The survey findings confirm that OBD occurs frequently, despite the use of laxatives, in individuals taking daily oral opioids for chronic pain. These gastrointestinal symptoms add to the burden already experienced by chronic pain patients, negatively impacting quality of life and, in some cases, affecting opioid treatment itself.


Novel reassortant influenza A(H5N8) viruses in domestic ducks, eastern China.
Domestic ducks are natural reservoirs of avian influenza viruses and serve as reassortant hosts for new virus subtypes. We isolated 2 novel influenza A(H5N8) viruses from domestic ducks in eastern China, sequenced their genomes, and tested their pathogenicity in chickens and mice. Circulation of these viruses may pose health risks for humans.


Paramagnetic porous polymersomes.
The ability of chelated Gd to serve as an effective magnetic resonance (MR) contrast agent largely depends on fast exchange rates between the Gd-bound water molecules and the surrounding bulk water. Because water diffuses slowly across lipid bilayers, liposomes with encapsulated chelated Gd have not been widely adopted as MR contrast agents. To overcome this limitation, we have synthesized chemically stabilized, porous polymersomes with encapsulated gadolinium (Gd) chelates. The polymerosmes, 125 nm in diameter, were produced from the aqueous assembly of diblock copolymers, PEO(1300)- b-PBD(2500) (PBdEO), and phospholipids, 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine (POPC). The PBdEO was cross-linked using a chemical initiator and the POPC was extracted with surfactant, generating a highly porous outer membrane. The encapsulated Gd chelates were attached to dendrimers to prevent their leakage through the pores. It was estimated that, on average, nearly 44 000 Gd were encapsulated within each polymersome. As a result of the slower rotational correlation time of Gd-labeled dendrimers and the porous outer membrane, the paramagnetic porous polymersomes exhibited an R1 relaxivity of 7.2 mM (-1) s (1-) per Gd and 315 637 mM (-1) s (-1) per vesicle. This corresponds to a relaxivity that is amplified by a factor of approximately 10 (5) compared with Gd-DTPA.


Thermal control of SZ2080 photopolymerization in four-beam interference lithography.
Photopolymerization by four-beam interference lithography on a preheated SZ2080 sample was explored at different initial temperatures of the sample: 20 °C, 50 °C, 75 °C, 100 °C, 125 °C, and 150 °C, and at exposure times ranging from 0.5 s to 5 s. The average laser power selected was ∼100 mW for the 300 ps duration pulses at a 1 kHz repetition rate. The experimental results demonstrate that the higher initial temperature of the sample positively influences the crosslinking of the patterns. These findings will improve polymerization protocols for multi-beam interference lithography.


Short-term association between ambient air pollution and risk of hospitalization for acute myocardial infarction: results of the cardiovascular risk and air pollution in Tuscany (RISCAT) study.
Air pollutant levels have been widely associated with increased hospitalizations and mortality from cardiovascular disease. In this study, the authors focused on pollutant levels and triggering of acute myocardial infarction (AMI). Data on AMI hospitalizations, air quality, and meteorologic conditions were collected in 6 urban areas of Tuscany (central Italy) during 2002-2005. Levels of particulate matter with an aerodynamic diameter ≤10 μm (PM(10)) (range of 4-year mean values, 28.15-40.68 μg/m(3)), nitrogen dioxide (range, 28.52-39.72 μg/m(3)), and carbon monoxide (range, 0.86-1.28 mg/m(3)) were considered, and increases of 10 μg/m(3) (0.1 mg/m(3) for carbon monoxide) were analyzed. A time-stratified case-crossover approach was applied. Area-specific conditional regression models were fitted, adjusting for time-dependent variables. Stratified analyses and analyses in bipollutant models were performed. Pooled estimates were derived from random-effects meta-analyses. Among 11,450 AMI hospitalizations, the meta-analytical odds ratio at lag(2) (2-day lag) was 1.013 (95% confidence interval (CI): 1.000, 1.026) for PM(10), 1.022 (95% CI: 1.004, 1.041) for nitrogen dioxide, and 1.007 (95% CI: 1.002, 1.013) for carbon monoxide. More susceptible subgroups were elderly persons (age ≥75 years), females, and older patients with hypertension and chronic obstructive pulmonary disease. This study adds to evidence for a short-term association between air pollutants and AMI onset, also evident at low pollutant levels, suggesting a need to focus on more vulnerable subjects.


Fabrication and characterization of gold nanoparticle-loaded TiO2 nanotube arrays for medical implants.
Au nanoparticles (AuNPs) are successfully assembled on TiO2 nanotube (TN) arrays through electrochemical deposition technology to improve the surface characteristics of TN arrays as an implant material. The loading amount of AuNPs can be controlled by adjusting the deposition time of electrochemical deposition. The effect of the amount of the loaded AuNPs on surface roughness and surface energy is systematically investigated on the basis of various characterizations. Results show that the increase in the loading amount of AuNPs on the TN arrays can increase surface roughness and decrease surface energy. Potentiodynamic polarization tests indicate that AuNP-modified TNs possess a higher corrosion resistance than unmodified TNs. Corrosion resistance increases as the amount of the loaded AuNP increases. In vitro cell culture tests are performed on the basis of cell morphology observations and MTT assays. Osteoblast cell adhesion and proliferation ability on the AuNP-modified TN surface are greater than those on the unmodified TN surface. The sample fabricated at the deposition time of 90 s exhibits an optimum cell performance. This work can provide a new platform to develop the surface chemistry of TN arrays and to fabricate titanium-based implant materials to enhance bioactivity.


Delayed hypersensitivity in man: a correlate in vitro and transfer by an RNA extract.
The migration of sensitized human monocytic-phagocytic cells from lymph-node tissue-culture suspensions was regularly and specifically inhibited by purified protein derivative or histoplasmin. Moreover, when nonsensitive cells were incubated with an RNA extract from lymph nodes of donors sensitive to purified protein derivative, histoplasmin, or both, the migration of these cells was specifically inhibited by these antigens. Ribonuclease inactivated the RNA extract.


Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury.
Neuronal injury elicits potent cellular responses from glia, but molecular pathways modulating glial activation, phagocytic function and termination of reactive responses remain poorly defined. Here we show that positive or negative regulation of glial responses to axon injury is molecularly encoded by unique isoforms of the Drosophila melanogaster engulfment receptor Draper. Draper-I promotes engulfment of axonal debris through an immunoreceptor tyrosine-based activation motif (ITAM). In contrast, Draper-II, an alternative splice variant, potently inhibits glial engulfment function. Draper-II suppresses Draper-I signaling through a previously undescribed immunoreceptor tyrosine-based inhibitory motif (ITIM)-like domain and the tyrosine phosphatase Corkscrew (Csw). Intriguingly, loss of Draper-II-Csw signaling prolongs expression of glial engulfment genes after axotomy and reduces the ability of glia to respond to secondary axotomy. Our work highlights a novel role for Draper-II in inhibiting glial responses to neurodegeneration, and indicates that a balance of opposing Draper-I and Draper-II signaling events is essential to maintain glial sensitivity to brain injury.


Refining the priming principle for vecuronium during rapid-sequence induction of anesthesia.
Administration of a subparalyzing dose of a nondepolarizing muscle relaxant (priming dose) prior to its intubating dose hastens the onset time (time from muscle relaxant administration to 100% depression of twitch tension) of neuromuscular blockade. This study was undertaken to determine the optimal priming and intubating doses and time interval between these doses (priming interval) of vecuronium during rapid-sequence induction of anesthesia. The authors measured single-twitch tension in 79 healthy, awake, premedicated (fentanyl, 50-150 mu iv, and/or diazepam, 5-10 mg iv) patients. In Part A of the study, the priming dose was varied (0.0, 0.005, 0.01, 0.0015, or 0.02 mg/kg iv). Decrement of twitch tension and symptoms were recorded 3 min later. Four minutes after the priming dose, thiopental, 4-6 mg/kg iv, and vecuronium, 0.1 mg/kg iv, were given. Onset times for the 0.01, 0.015, and 0.02 mg/kg groups were significantly shorter than for 0.005 and 0.0 mg/kg groups. No breathing difficulties were encountered in any of the groups. Decrement of twitch tension greater than 25% of control only occurred in the 0.02 mg/kg group (4 of 11 patients). In Part B, the priming interval was varied (2, 4, or 6 min) after giving the optimal priming dose (0.01 mg/kg). Anesthesia was induced as in Part A. Onset times for the 4-min group were significantly faster than the 2- or 6-min groups. In Part C, the intubating dose was varied (0.07, 0.1, or 0.15 mg/kg iv) after the optimal priming dose and optimal priming interval (4 min). Onset times for the 0.1 mg/kg and 0.15 mg/kg groups were significantly faster than the 0.07 mg/kg group.(ABSTRACT TRUNCATED AT 250 WORDS)


Blood Pressure and Hypertension: Findings from 20 Years of the Tehran Lipid and Glucose Study (TLGS).
Hypertension (HTN) is a well-known modifiable risk factor for cardiovascular disease (CVD), chronic kidney disease and mortality. Positive effects of blood pressure (BP) lowering for prevention of CVD and death have been documented in several meta-analyses of randomized controlled trials. This review focuses on the key findings derived from the Tehran lipid and glucose study (TLGS) papers on different aspects of BP and HTN. A prevalence of 23% for HTN has been reported in the TLGS population, aged ≥ 20 years. Over a decade long follow-up, the crude incidence rate (95% CI) of new-onset HTN defined as systolic BP (SBP) ≥ 140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg, and not using antihypertensive medication was 33.63 (32.0 - 35.3) per 1000 person-years. Age, baseline SBP and body mass index were significant risk factors for development of isolated systolic HTN; regarding isolated diastolic HTN, baseline DBP and waist circumference were recognized as important risk factors whereas age, female gender and marriage were shown to be protective factors. SBP decreased significantly in both diabetic and non-diabetic participants; DBP showed a non-significant decrease in diabetic men and a statistically significant decrease in non-diabetic men. Among women, both those with and without diabetes (DM) generally experienced statistically significant decreases in DBP. Cox proportional hazard models showed that neither SBP nor DBP were associated with incident DM in the total population and in either gender, separately. All BP components were associated with CVD and all-cause mortality in the middle-aged population. Contribution of HTN to cerebrovascular events was also documented in the TLGS participants, aged ≥ 50 years. Several important findings regarding BP/HTN have been derived from the TLGS. According to data regarding the prevalence and incidence of preHTN and HTN and their contribution to cardiovascular morbidity and mortality in the TLGS population as a representative sample of Tehranian population, it is recommended that interventions be prioritized for lifestyle modifications for the prevention and appropriate management of preHTN/HTN.


The Effect of Sarcopenia and Metabolic PET-CT Parameters on Survival in Locally Advanced Non-Small Cell Lung Carcinoma.
The treatment of stage III non-small cell lung cancer (NSCLC) is complex. Here, we aimed to examine the prognostic utility of sarcopenia and metabolic muscle volumes and evaluate their relationship with oncological treatments in patients with locally advanced NSCLC. Patients with unresectable stage III NSCLC were evaluated retrospectively. Muscle fields were measured, and metabolic parameters of the psoas were obtained. The skeletal muscle index (SMI), sarcopenia, sarcopenic obesity, and body mass index (BMI)-associated sarcopenia were evaluated. Fifty-three (94.6%) patients were men, and three (5.4%) were women. Sarcopenia was identified in 36 (64.3%) patients. Pretreatment sarcopenia and BMI-associated sarcopenia negatively affected overall survival (p = 0.040 and 0.023, respectively). A high psoas SUVmean (Standardized Uptake Value mean) and low mean psoas HU (Hounsfield unit) were poor prognostic factors (p = 0.009 and 0.014, respectively). SMI and muscle mass decreased after oncological treatment. Advanced age, inability to complete treatment, administration of chemoradiotherapy after chemotherapy, presence of sarcopenia, and a low mean psoas HU decreased survival. In conclusion, sarcopenia and BMI-associated sarcopenia are poor prognostic factors in patients with lung cancer. Oncological treatments can adversely affect muscle mass. The metabolic parameters of the psoas muscle can predict patient prognosis.


Macronutrient intake influences the effect of 25-hydroxy-vitamin d status on metabolic syndrome outcomes in african american girls.
The objectives were to determine the effect of macronutrient modification on vitamin D status and if change in 25-hydroxy-vitamin D concentration influences components of metabolic syndrome in obese African American girls. Methods. Five-week intervention using reduced CHO (43% carbohydrate; 27% fat: SPEC) versus standard CHO (55% carbohydrate; 40% fat: STAN) eucaloric diet. Subjects were 28 obese African American females, aged 9-14 years. Dual energy X-ray absorptiometry and meal test were performed at baseline and five weeks. Results. Approximately 30% of girls had metabolic syndrome. Serum 25OHD increased in both groups at five weeks [STAN: 20.3 ± 1.1 to 22.4 ± 1.1 (P < 0.05) versus SPEC: 16.1 ± 1.0 to 16.8 ± 1.0 (P = 0.05)]. The STAN group, increased 25OHD concentration over five weeks (P < 0.05), which was positively related to triglycerides (P < 0.001) and inversely associated with total cholesterol (P < 0.001) and LDL (P < 0.001). The SPEC group, had increase in 25OHD (P = 0.05), which was positively related to fasting insulin (P < 0.001) and insulin sensitivity while inversely associated with fasting glucose (P < 0.05). The contribution of vitamin D status to metabolic syndrome parameters differs according to macronutrient intake. Improvement in 25OHD may improve fasting glucose, insulin sensitivity, and LDL; however, macronutrient intake warrants consideration.


Sensory Processing Sensitivity in the context of Environmental Sensitivity: A critical review and development of research agenda.
Sensory Processing Sensitivity (SPS) is a common, heritable and evolutionarily conserved trait describing inter-individual differences in sensitivity to both negative and positive environments. Despite societal interest in SPS, scientific knowledge is lagging behind. Here, we critically discuss how SPS relates to other theories, how to measure SPS, whether SPS is a continuous vs categorical trait, its relation to other temperament and personality traits, the underlying aetiology and neurobiological mechanisms, and relations to both typical and atypical development, including mental and sensory disorders. Drawing on the diverse expertise of the authors, we set an agenda for future research to stimulate the field. We conclude that SPS increases risk for stress-related problems in response to negative environments, but also provides greater benefit from positive and supportive experiences. The field requires more reliable and objective assessment of SPS, and deeper understanding of its mechanisms to differentiate it from other traits. Future research needs to target prevention of adverse effects associated with SPS, and exploitation of its positive potential to improve well-being and mental health.


Intraductal papillary tumors of the pancreas. Histopathologic correlation of MR cholangiopancreatography findings.
To evaluate MR cholangiopancreatography (MRCP) findings of intraductal papillary tumors of the pancreas and correlate them with histopathology. Seventeen patients with intraductal papillary tumor of the pancreas underwent MRCP before surgery. MRCP findings were correlated to histopathology with regard to the presence of septa and excrescent nodules in the cystic lesion, communication between the cystic lesion and the main pancreatic duct (MPD), degree of dilatation of MPD, and dilatation of the common bile duct (CBD). MRCP demonstrated septa in 17 cases (100%), excrescent nodules in 8 cases (47.1%), communication between the intraductal papillary tumor and the MPD in 14 cases (82.3%), dilatation of MPD over 50% in 6 cases (35.3%), and dilatation of CBD in 3 cases (17.6%). These findings showed excellent correlation with histopathology. The septum on MRCP corresponded with a layer of connective tissue with pancreatic duct epithelium. Excrescent nodules in the carcinomas consisted not only of malignant cells, but also of dysplasia and adenoma. Excrescent nodules in adenomas were consistent not only with minimal papillary growth of adenoma, but also with proliferation of fibrosis, and hematoma and organized fibrin with minimal fibrosis. Pancreatic tissue was affected by chronic pancreatitis in all cases. Cases with dilatation of CBD on MRCP were due to microscopic invasion by the carcinoma. MRCP appearances of intraductal papillary tumors are well correlated with the findings at histopathology.


State and Trait Anxiety Among University Students: A Moderated Mediation Model of Negative Affectivity, Alexithymia, and Housing Conditions.
Starting university education is a crucial period for the mental health of students, who report higher levels of distress compared to the general population. This study sought to better understand the distress experienced by students by considering contextual facets (e.g., housing conditions) as well as stable clinical variables (e.g., negative affectivity, emotion regulation, and anxiety). A total of 177 University students (71.2% females) aged 18-29 were administered the State-Trait Anxiety Inventory-Y, the Beck Depression Inventory-II, the Suicidal History Self-Rating Screening Scale, the Personality Inventory for DSM-5-Brief Form, and the Toronto Alexithymia Scale-20. University students showed concerning levels of distress, particularly concerning anxiety, and depression. We found that the relationship between negative affectivity and both state and trait anxiety was mediated by alexithymia but housing conditions did not act as a moderator for the indirect effect of negative affectivity on state or trait anxiety through alexithymia. Undoubtedly, university lifestyle can be demanding, but experiencing distress is not inevitable nor inexplicable. The present study sought to gain insight into the anxiety experienced by Italian University students while taking into account the importance of personality and clinical characteristics that have previously been widely underestimated. We found that these characteristics can be of extreme importance for developing preventative and therapeutic interventions tailored to the clinical characteristics of students, as well taking into account their living environment.


NCCP breast cancer referral guidelines--are breast cancer patients prioritised?
Following centralisation of breast cancer services, the National Cancer Control Programme (NCCP) introduced referral guidelines indicating which patients require urgent, early and routine review. This study prospectively analysed referrals to a symptomatic breast unit over 3 months to measure Primary Care Physician (GP) uptake of the NCCP referral guidelines, compare triage patterns of GP and consultant breast surgeon and evaluate the efficacy of the guidelines at identifying patients with breast cancer. 1044 consecutive referrals were categorised according to NCCP guidelines. 637 (61%) were referred using the NCCP form. GP referrals correlated well with consultant breast surgeon for patients requiring urgent review (r = 0.71, p < 0.001; Pearson). Patients categorised as "urgent" were more likely to have a breast biopsy compared to those categorised as "routine" (p < 0.0001; Chi2). The overall cancer incidence was 34 (3.3%) and significantly higher in the "urgent" group at 10.5%. NCCP guidelines were 91% sensitive for triaging breast cancer patients into the correct (urgent) category. The NCCP guidelines are accurate and should be considered the gold-standard for referral to the symptomatic breast service. Consideration should be given to a GP-delivered service to patients outside the "urgent" category.


[Establishment of human small cell lung carcinoma cell line (LTEP-sm 1) in nude mice and in vitro].
A serially transplatable tumor model was established by inoculating subcutaneously the surgical specimen of a patient with mixed type small cell lung carcinoma into nude mice (BALB/C nu/nu). A human small cell lung carcinoma cell line cultured in vitro was established from that tumor in nude mice. The cultured cell line gave a typical growth pattern with small round feature, cell clusters in suspension and float growth. Pathological sections of both the patient's tumor and transplantable tumor in nude mice showed the same morphological features. The typical APUD granules were observed in electron transmission microscopy. The transplantable tumor has been transferred for 9 passages in 14 months and the cell line in vitro for 71 passages in nearly one year.


Metabolic and ultrastructural aspects of the in vitro lysis of chronic lymphocytic leukemia cells by glucocorticoids.
Human chronic lymphocytic leukemia (CLL) cells like prothymocytes and immunoactivated T-lymphocytes are readily lysed in vitro by pharmacological concentrations of glucocorticoids such as cortisol, whereas peripheral blood lymphocytes and thymocytes are unaffected by the hormone. In this study, metabolic and ultrastructural aspects of the cortisol-induced killing process of CLL cells are recorded. In vitro lysis was found to be temperature dependent and was detected only after 6 to 8 hr incubation with cortisol by means of the trypan blue exclusion test. However, 30 min of incubation with cortisol at either 37 degrees or 4 degrees followed by the removal of the hormone was still sufficient to induce the lytic process. Ultrastructural studies demonstrated sequential changes in the cytoplasm, including swelling of mitochondria and cytoplasmic decompartmentalization, followed by loss of surface microvilli with the appearance of "holes" in the cell membrane, and subsequent condensation of nuclear chromatin. The large holes in the membrane appearing after 6 hr of incubation with the hormone may be the cause for the penetration of the viable stain into the dead cells, as seen by light microscopy. Addition of metabolic inhibitors including actinomycin D, puromycin, and cycloheximide following administration of cortisol resulted in inhibition of the cell lysis. An excess of an antagonist such as cortexolone was found to inhibit the cortisol-induced cytolysis of the CLL cells. It is suggested that the glucocorticoid-induced lysis of human CLL cells is similar to the phenomenon observed in rat or murine lymphocytes and is mediated by interaction of the steroid molecule with the cytoplasmic receptor. The resulting complex appears to activate specific gene(s) the products of which eventually cause cytolysis.


Bronchoscopic assessment of bronchial anastomosis by visualizing local circulation status-index of hemoglobin (IHb) imaging.
Healing of airway anastomosis is largely affected by local circulation. Index of hemoglobin (IHb) imaging is a color enhancement technique that clarifies local circulation in the gastrointestinal endoscopic field. In this study, we investigated the relationship between bronchoscopic assessment of bronchial anastomosis using IHb mode and occurrence of anastomosis-related complications. IHb was calculated by logarithmic transformation for each pixel of the electronic endoscopic images and expressed by colors of red, green, and blue. The distribution of each color area was automatically calculated by the summation of pixels. A preliminary experiment spraying vasodilator on swine was performed to confirm the relationship between bronchial mucosal circulation and the IHb image. Forty consecutive patients who underwent bronchoplasty were divided into retrospective training and prospective validation cohorts, and anastomosis-related complications and IHb images were analyzed. The IHb images immediately and accurately reflected the mucosal changes in the animal experiment. Among 25 cases in the retrospective training cohort, 6 cases experienced complications, with significantly lower red and higher blue values in IHb observed (P=0.03 and P=0.01, respectively). A receiver operating characteristic (ROC) curve for IHb red and blue distributions revealed the thresholds to differentiate cases with complications as 89.2 and 109.0, respectively. An analysis of the prospective validation cohort revealed that IHb blue on POD 7 was a potentially reliable predictor of complications, with 60.0% sensitivity and 90.0% specificity. IHb mode of bronchoscopy may be useful for assessing the local circulatory condition of bronchoplasty, which can predict anastomosis-related morbidity.


Parkinsonism and dystonia caused by the illicit use of ephedrone--a longitudinal study.
A neurological syndrome characterized by levodopa unresponsive bradykinesia, retropulsion with falls backwards, dysarthria, gait disturbance, dystonia, and emotional lability was identified in 13 male opiate addicts following the prolonged intravenous use of ephedrone (methcathinone), a central nervous stimulant prepared from pseudoephedrine, potassium permanganate, and vinegar. The natural history, response to treatment, and clinical features has been studied, and MR and dopamine transporter SPECT brain imaging were carried out. Pubic hair was sampled for manganese. The clinical and radiological picture closely resembled previous reports of chronic manganese poisoning and increased mean manganese level in pubic hair observed for at least 1 year after cessation of ephedrone. Odor identification was intact. Cognitive assessment showed a mild executive dysfunction and a mild depression. DaTSCANs were all normal. The neurological syndrome bears some similarities to PSP but differs from Parkinson's disease. Delayed neurological progression despite discontinuation of ephedrone occurred in one-third of cases. Ephedrone poisoning should be considered as a possible cause of secondary Parkinsonism in young adults, particularly from Eastern Europe.


Advanced Analytical Techniques for the Measurement of Nanomaterials in Food and Agricultural Samples: A Review.
Nanotechnology offers substantial prospects for the development of state-of-the-art products and applications for agriculture, water treatment, and food industry. Profuse use of nanoproducts will bring potential benefits to farmers, the food industry, and consumers, equally. However, after end-user applications, these products and residues will find their way into the environment. Therefore, discharged nanomaterials (NMs) need to be identified and quantified to determine their ecotoxicity and the levels of exposure. Detection and characterization of NMs and their residues in the environment, particularly in food and agricultural products, have been limited, as no single technique or method is suitable to identify and quantify NMs. In this review, we have discussed the available literature concerning detection, characterization, and measurement techniques for NMs in food and agricultural matrices, which include chromatography, flow field fractionation, electron microscopy, light scattering, and autofluorescence techniques, among others.


Vertical distributions of 239+240Pu activities and 240Pu/239Pu atom ratios in sediment cores: implications for the sources of Pu in the Japan Sea.
The vertical distributions of 239+240Pu-specific activities and 240Pu/239Pu atom ratios in sediment cores of the Japan Sea were investigated. For comparison, the 239+240Pu-specific activities and 240Pu/239Pu atom ratios in the surface layer of bottom sediments in the Sea of Okhotsk were also determined. The 239+240Pu-specific activities in the surface layer sediments varied from 0.43 to 2.65 mBq/g in the Japan Sea. The lowest value was seen in the eastern Japan Basin, while the highest value was found in a sample collected from a coastal area off Hokkaido in the northern Japan Sea. It was found that the 240Pu/239Pu atom ratios in the surface sediments for the Japanese side of the Japan Sea ranged from 0.15 to 0.22. The 240Pu/239Pu atom ratios in the surface sediments collected from the Yamato Basin and Japan Basin were typically close to the global fallout value of 0.18, but higher 240Pu/239Pu atom ratios (0.20-0.22) were seen in samples from the northern Japan Sea. Vertical profiles of 240Pu/239Pu atom ratios revealed that these atom ratios were higher than the global fallout value in the deeper layers in the sediment cores from the northern Japan Sea on the Hokkaido coast and the Yamato Basin. In addition, the sediment cores from the northern Japan Sea near the Soya Strait and in the Ishikari Estuary had a constant vertical distribution of 240Pu/239Pu atom ratios with a value around 0.20. The results obtained in this work support the hypothesis that the prevailing ocean currents transported Pu derived from the Pacific Proving Grounds to the Japan Sea, and this contributed to the general elevated Pu inventory in the Japan Sea.


Anticonvulsant drugs effective against human temporal lobe epilepsy prevent seizures but not neurotoxicity induced in rats by quinolinic acid: electroencephalographic, behavioral and histological assessments.
Intrahippocampal injection of quinolinic acid (QUIN) in rats caused an epileptic-like syndrome reminiscent of human temporal lobe epilepsy. By electroencephalographic (EEG) analysis, the authors assessed whether QUIN seizures were responsive to anticonvulsants effective in the treatment of the human disease. Anticonvulsants used in clinical practice to control partial seizures, such as carbamazepine, diphenylhydantoin, sodium phenobarbital, sodium valproate and diazepam, prevented QUIN-induced EEG seizures, whereas ethosuximide, which is specifically used to control absence attacks, and chlorpromazine, a sedative with no anticonvulsant properties, were ineffective. QUIN seizures showed particular sensitivity to carbamazepine (5 mg/kg) but were resistant to diphenylhydantoin unless a relatively high dose was used (100 mg/kg). None of the effective anticonvulsants completely suppressed EEG paroxysmal events like spikes and fast activity. Animals injected with QUIN displayed chewing, sniffing and rearing; no clear correlation was found between the ability of drugs to prevent QUIN-induced EEG seizures and effects on stereotypies, suggesting that these behavioral signs are not sensitive measures of anticonvulsant activity in this model. The anticonvulsants that protected animals from QUIN seizures did not prevent nerve cell degeneration induced by the excitotoxin, thus indicating that nerve cell death can occur even in the absence of sustained seizure activity. The data show that, in this animal model of epilepsy, the EEG seizure activity is specifically sensitive to anticonvulsants effective in partial epilepsy, thus suggesting that it could be used to test potential new drugs for this human disorder.


Is air pollution associated with increased risk of cognitive decline? A systematic review.
exposure to air pollution has been shown to increase risk of inflammatory processes and risk of cardiovascular mortality. Such exposure may therefore also be a risk factor for cognitive impairment/dementia. a systematic review of the literature was conducted with databases searched using keywords for air pollution, cognitive decline and dementia. All identified abstracts and potentially relevant articles were double read. For those papers meeting the inclusion criteria, summary tables were prepared and papers quality assessed. from 1,551 abstracts identified, 10 articles were retrieved of which two were rejected. Of the eight remaining six reported prevalent cognitive assessment with historical pollution exposure and two incident cognitive decline, also with historical pollution exposure. In general, an association was reported between exposure and poorer prevalent measures of cognitive function. Data were mixed for incident cognitive decline with one study finding an association and the other not. Reports were limited by a lack of detailed reporting, use of proxy measures of pollution exposure and a lack of clarity regarding cognitive testing methodology and analysis. this systematic review highlights that there is some evidence of a potential association between air pollution and subsequent cognitive decline. Further work is clearly required and longitudinal analysis of ongoing cohort studies or new research would add much needed clarity to this area.


Multifocal optical-resolution photoacoustic microscopy in vivo.
Although ultrasound arrays have been exploited in photoacoustic imaging to improve imaging speed, ultrasound-array-based optical-resolution photoacoustic microscopy (OR-PAM) has never been achieved previously to our knowledge. Here we present our development of multifocal OR-PAM using a microlens array for optical illumination and an ultrasound array for photoacoustic detection. Our system is capable of imaging hemoglobin concentration and oxygenation in individual microvessels in vivo at high speed. Compared with a single focus, multiple foci reduce the scanning load and increase the imaging speed significantly. The current multifocal system can acquire 1000 × 500 × 200 voxels at ~10 μm lateral resolution within 4 min.


Genotypic and phenotypic analysis of Streptococcus uberis isolated from bovine mammary secretions.
Genotypic and phenotypic analysis of 42 strains of Streptococcus uberis isolated from mammary secretions of 17 cows collected at different periods of the lactation cycle and from episodes of clinical mastitis were performed. Seventeen restriction endonuclease fingerprint (REF) patterns and 12 bacteriocin-like inhibitory substance (BLIS) fingerprints were observed. REF identified and differentiated closely related strains of S. uberis isolated from mammary secretions collected from the same cow at different periods of the lactation cycle and from episodes of clinical mastitis. BLIS fingerprinting of S. uberis complemented REF results. REF and BLIS fingerprinting provided evidence concerning persistence of infection in the same quarter or different quarters of the mammary gland over different periods of the lactation cycle, and occurrence of infection with similar and dissimilar strains of S. uberis. Biochemical profiles could not identify closely related strains nor did they complement REF results. Antibiotic resistance patterns alone were of little value in differentiating closely related strains, but were identical with isolates having same REF pattern. None of the S. uberis strains was found to carry plasmids. REF and BLIS fingerprinting can be utilized effectively to differentiate closely related and unrelated strains of S. uberis isolated from bovine mammary secretions.


The nutritional composition and cell size of microbial biomass for food applications are defined by the growth conditions.
It is increasingly recognized that conventional food production systems are not able to meet the globally increasing protein needs, resulting in overexploitation and depletion of resources, and environmental degradation. In this context, microbial biomass has emerged as a promising sustainable protein alternative. Nevertheless, often no consideration is given on the fact that the cultivation conditions affect the composition of microbial cells, and hence their quality and nutritional value. Apart from the properties and nutritional quality of the produced microbial food (ingredient), this can also impact its sustainability. To qualitatively assess these aspects, here, we investigated the link between substrate availability, growth rate, cell composition and size of Cupriavidus necator and Komagataella phaffii. Biomass with decreased nucleic acid and increased protein content was produced at low growth rates. Conversely, high rates resulted in larger cells, which could enable more efficient biomass harvesting. The proteome allocation varied across the different growth rates, with more ribosomal proteins at higher rates, which could potentially affect the techno-functional properties of the biomass. Considering the distinct amino acid profiles established for the different cellular components, variations in their abundance impacts the product quality leading to higher cysteine and phenylalanine content at low growth rates. Therefore, we hint that costly external amino acid supplementations that are often required to meet the nutritional needs could be avoided by carefully applying conditions that enable targeted growth rates. In summary, we demonstrate tradeoffs between nutritional quality and production rate, and we discuss the microbial biomass properties that vary according to the growth conditions.


Alkaloids from marine sponges as stimulators of initial stages of development of agricultural plants.
Damirone A (1), damirone B (2), makaluvamine G (3), debromohymenialdisine (4), and dibromoagelaspongin (5) were examined for their ability to stimulate growth of seedling roots of barley (Hordeum vulgare L.), buckwheat (Fagopyrum esculentum Moench), corn (Zea mays L.), soy (Glycine max (L.) Merr.}, and wheat (Triticum aestivum L.). It was shown that the stimulatory effects depend on the chemical structure of the alkaloids and on the plant species. Compounds 1, 3, and 4 are efficient for growth of seedling roots of barley, compounds 2-5, at different concentrations, stimulate growth of buckwheat roots, and compound 5 stimulates growth of wheat roots. These compounds can be recommended for field study as plant growth stimulators.


Calcium metabolism in embryos of the oviparous snake Coluber constrictor.
Total calcium in embryos of an oviparous, colubrid snake (Coluber constrictor L.) rises rapidly during the last half of incubation as the embryos increase in size. Although most of this calcium is drawn from stores in the yolk, hatchlings contain more calcium than was present in yolk of eggs at oviposition. Because shells from eggs incubated to hatching contain less calcium than do shells from freshly-laid eggs, the extra calcium appears to be drawn from the eggshell. Indeed, approximately 20% of the calcium required for development in this snake is obtained from the eggshell, with the remainder coming from the yolk. Thus, embryos of oviparous snakes, like embryonic chelonians, crocodilians and birds, withdraw calcium from their eggshells and do not rely exclusively on calcium supplied in their yolk for support of growth and development.


Ultranonlocality in time-dependent current-density-functional theory: application to conjugated polymers.
We solve the long-standing problem of the large overestimation of the static polarizability of conjugated polymers obtained using the local density approximation within density-functional theory. The local approximation is unable to describe the highly nonlocal exchange and correlation (xc) effects found in these quasi-one-dimensional systems. Time-dependent current-density-functional theory enables a local current description of ultranonlocal xc effects using the Vignale-Kohn functional [G. Vignale and W. Kohn, Phys. Rev. Lett. 77, 2037 (1996)]. Except for the model hydrogen chain, our results are in excellent agreement with the best available correlated methods.


RARγ promotes the invasion and metastasis of thyroid carcinoma by activating the JAK1-STAT3-CD24/MMPs axis.
The nuclear receptor superfamily RAR is generally considered to play a crucial role in the development of tumors by regulating the transcription of target genes. Nevertheless, whether RARγ performs tumor-promoting or tumor-suppressing functions and its specific mechanism in thyroid carcinoma (TC) remain unknown. Here, our study demonstrated that RARγ was abnormally overexpressed in TC tissues compared with normal thyroid tissues. Moreover, RARγ expression was remarkably correlated with cell phenotypes such as cell proliferation, migration and invasion. Mechanistically, RARγ knockdown effectively decreased the phosphorylation levels of JAK1 and STAT3, leading to decreased expression of the membrane protein CD24. In a coculture system, TC cells with high levels of CD24 in the membrane were more likely to escape phagocytosis by macrophages via the combination of CD24 with the inhibitory receptor Siglec-10 in the membrane of macrophages. In contrast, the ability of macrophages to engulf TC cells was notably elevated through exogenous addition of CD24 antibody. Collectively, our study revealed a previously undiscovered molecular mechanism of RARγ in promoting the development of TC, shedding light on RARγ as a promising therapeutic target for TC.


Repeated amphetamine pretreatment alters the responsiveness of striatal dopamine-stimulated adenylate cyclase to amphetamine-induced desensitization.
The repeated daily administration of moderate doses of amphetamine results in an augmentation of the behavioral response to subsequent amphetamine challenge. One feature of the augmentation is a shift in the type of perseverative behaviors to those generally associated with higher acute doses of the drug. Consistent with these observations, rats pretreated with six daily injections of amphetamine (3 mg/kg) exhibited primarily oral stereotypies to a challenge dose of 2.5 mg/kg of amphetamine, whereas control animals exhibited focused sniffing and repetitive head movements. Previously we found that the acute administration of amphetamine or methylphenidate only at doses which induce oral stereotypies promotes a rapid desensitization of striatal dopamine-stimulated adenylate cyclase. We therefore examined the effects of repeated amphetamine pretreatment on this index of D1 dopamine receptors. The administration of 2.5 mg/kg of amphetamine produced a 2-fold shift to the right in the concentration-response curve for dopamine-stimulated adenylate cyclase in animals pretreated with amphetamine, but not in saline pretreated controls. No effect of the chronic amphetamine pretreatment on dopamine stimulated cyclase in the absence of amphetamine challenge was observed. The binding of [3H]cis-flupenthixol to striatal D1 dopamine receptors was not affected by acute or chronic amphetamine. These results suggest a relationship between stimulant-induced desensitization of striatal D1 dopamine receptors and the induction of oral stereotypies.


Benzyl-substituted metallocarbene antibiotics and anticancer drugs.
Benzyl-substituted metallocarbene compounds synthesised by our group and others during the past 5 years give a new perspective on their activity as antibiotic and antitumoral drugs. N-heterocyclic carbenes containing an imidazole core were functionalised and their transition metal complexes (M = Ag, Au, Cu, Ru) have shown promising antibacterial as well as anticancer activity in vitro and in vivo. IC50 values in the nanomolar region or antibacterial activity comparable to conventional antibiotics lead the way towards novel drug candidates.


Fast and sensitive mapping of nanopore sequencing reads with GraphMap.
Realizing the democratic promise of nanopore sequencing requires the development of new bioinformatics approaches to deal with its specific error characteristics. Here we present GraphMap, a mapping algorithm designed to analyse nanopore sequencing reads, which progressively refines candidate alignments to robustly handle potentially high-error rates and a fast graph traversal to align long reads with speed and high precision (>95%). Evaluation on MinION sequencing data sets against short- and long-read mappers indicates that GraphMap increases mapping sensitivity by 10-80% and maps >95% of bases. GraphMap alignments enabled single-nucleotide variant calling on the human genome with increased sensitivity (15%) over the next best mapper, precise detection of structural variants from length 100 bp to 4 kbp, and species and strain-specific identification of pathogens using MinION reads. GraphMap is available open source under the MIT license at https://github.com/isovic/graphmap.


Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function.
Regulatory T cells (Treg cells), whose differentiation and function are controlled by transcription factor Foxp3, express the closely related family member Foxp1. Here we explored Foxp1 function in Treg cells. We found that a large number of Foxp3-bound genomic sites in Treg cells were occupied by Foxp1 in both Treg cells and conventional T cells (Tconv cells). In Treg cells, Foxp1 markedly increased Foxp3 binding to these sites. Foxp1 deficiency in Treg cells resulted in their impaired function and competitive fitness, associated with markedly reduced CD25 expression and interleukin-2 (IL-2) responsiveness, diminished CTLA-4 expression and increased SATB1 expression. The characteristic expression patterns of CD25, Foxp3 and CTLA-4 in Treg cells were fully or partially rescued by strong IL-2 signaling. Our studies suggest that Foxp1 serves an essential non-redundant function in Treg cells by enforcing Foxp3-mediated regulation of gene expression and enabling efficient IL-2 signaling in these cells.


Comparison of the Gross Motor Function Measure and Paediatric Evaluation of Disability Inventory in assessing motor function in children undergoing selective dorsal rhizotomy.
This study was designed to compare assessment with the functional outcome measures Gross Motor Function Measure (GMFM) and Pediatric Evaluation of Disability Inventory (PEDI) over time, in children with cerebral palsy (CP) undergoing selective dorsal rhizotomy combined with individualised physiotherapeutic interventions. Using the Gross Motor Function Classification System (GMFCS), 18 children with spastic diplegia were divided into two groups according to age-related severity of motor function impairment. Data were collected preoperatively, and at 6 and 12 months postoperatively. Both instruments were sensitive to changes in function over time in the series as a whole and in the group with milder impairment, although the PEDI detected significant changes earlier. In the group with more severe impairment, changes in function were detected only with the PEDI, not with the GMFM. Thus, the instruments are to be considered complementary tests, because they measure different aspects of function.


[Mitochondria and apoptosis].
It is now accepted that mitochondria are endosymbionts, originated in aerobic bacteria which were integrated by the ancestor of eukaryotic cells. A part of the apoptotic machinery could exist in unicellular eukaryotic and some controlling apoptosis components might be present in prokaryotes. It is therefore possible that the mechanism originally involved in the maintenance of the symbiosis between the bacterial ancestor of the mitochondria and the host cell precursor of eukaryotes, provided the basis for the actual mechanism controlling cell survival. Metazoans would have improved this possibility by connecting to the mitochondria as principal effector of cellular death to the pathways of signal transduction. A variety of events appoint to the mitochondria as principal effector of the apoptosis. This including the release caspase activators (cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro and antiapoptotic Bcl-2 proteins. The different signals that converge on mitochondria for activation or inhibition of these events, delineate several pathways in the physiology of the cellular death.


Synthesis and function of Actinomyces naeslundii T14V type 1 fimbriae require the expression of additional fimbria-associated genes.
The nucleotide sequence of the chromosomal DNA flanking the Actinomyces naeslundii (formerly A. viscosus) T14V type 1 fimbrial structural subunit gene (fimP) was determined. Six open reading frames (ORFs), in the order 5' ORF3, ORF2, ORF1,fimP, ORF4, ORF5, ORF6 3', were identified. ORF1 encoded a protein of 408 amino acid residues (Mr = 39,270) and had significant sequence homology with the A. naeslundii T14V type 1 and A. naeslundii WVU45 type 2 fimbrial structural subunits. An in-frame fusion of ORF1 to the malE gene of the expression vector, pMAL-c2, yielded a protein that was immunostained with antibodies raised against the maltose binding protein and A. naeslundii T14V whole bacteria. Digestion of the fusion protein with factor Xa released a protein (apparent molecular mass of 34 kDa) that was immunostained only with the antibody directed against A. naeslundii T14V whole bacterial cells. Integration plasmids carrying a kanamycin resistance gene (kan) that was used to substitute for ORF1 or for DNA fragments internal to the coding region of the other five ORFs were used to transform A. naeslundii T14V. Neither type 1 fimbriae nor the 65-kDa fimbrial structural subunit was detected in mutants obtained by allelic replacement of ORF1 or ORF2. Mutants obtained by allelic replacement of ORF3 or ORF4 expressed only the 65-kDa fimbrial structural subunit. These mutants did not bind, in vitro, to proline-rich proteins that serve as the receptors for Actinomyces type 1 fimbriae. In contrast, a mutant in which the integration plasmid DNA had been inserted at a site close to the carboxyl terminus of ORF6 expressed type 1 fimbriae and had adherence properties similar to those observed in the wild-type strain. These results demonstrate the existence of additional genes near fimP that are likely to be involved in the synthesis and function of cell surface fimbriae of A. naeslundii T14V.


Investigating the disagreement between clinicians' ratings of patients in ICUs.
We present a Bayesian analysis of ordinal annotations made by clinicians of patients in intensive care. In particular, we investigate the different ways in which clinicians can disagree and how their disagreement is reduced once they take part in a recently proposed procedure (INSIGHT) that aims at improving consistency. The model combines a nonparametric function (loosely interpretable as the health of the patient) with clinician-specific generative procedures for producing the observed ordinal values. Our analysis provides valuable details of the rating behavior of the individual clinicians and shows that the INSIGHT procedure is particularly effective at removing (some) clinician-specific inconsistencies and biases.


Identification and expression of a rat fatty acid elongase involved in the biosynthesis of C18 fatty acids.
A major part of the palmitic acid (C16:0) generated by fatty acid synthase is converted into stearic acid (C18:0) via carbon chain elongation. Here, we describe the cloning and expression of a rat hepatic enzyme, rELO2, responsible for the elongation of C16:0, presumably at the condensing reaction. Heterologous expression experiments in a yeast, Saccharomyces cerevisiae, demonstrated the elongation activity of rELO2 on C16:0 and to a lesser extent, C18:0 and fatty acids with low desaturation degree. This was distinct from that rELO1, a rat homolog of HELO1, which preferably catalyzed the elongation of mono- and polyunsaturated fatty acids of C16-C20. The Northern analysis showed that the expression of rELO2, but not rELO1, in hepatocytes was activated by the cycles of fasting and refeeding rats on a fat-free diet. Under these conditions, the rELO1 was expressed constitutively in various tissues but the rELO2 transcripts were detected predominantly in liver.


Tactile attention tasks enhance activation in somatosensory regions of parietal cortex: a positron emission tomography study.
We used positron emission tomography to study cortical regions mediating tactile attention. Cues selectively directed subjects to attend to the roughness or duration of contact with embossed gratings that rubbed against a single fingertip with controlled speed and force. The task required discriminating between paired gratings that differed in tactile features of roughness and/or length. For different blocks of trials, cues directed attention to one tactile feature or indicated a divided attention strategy to a change in either feature. All attention conditions unambiguously activated several somatosensory foci in the parietal cortex, including somatotopically appropriate portions of the primary somatosensory cortex in the postcentral gyrus (S1) and the secondary somatosensory region (S2) within parietal opercular regions. There was no evidence for separate processing foci for selective and divided attention strategies, or for selectively attending to roughness versus stimulus duration. We observed a greater magnitude blood flow change in S2 versus S1 during attention tasks, which suggests that S2 might actually influence S1 activity. Despite these differences, modulation of S1 and S2 supports concepts of early selection in tactile attention. There were also examples of non-sensory foci in frontal cortex, anterior cingulate gyrus and bilateral superior parietal regions at the fundus of the postcentral sulcus. Posterior parietal regions observed in this study did not overlap foci seen in studies of visual attention. Thus, the posterior parietal region may be subdivided into modality-specific subregions, each of which processes information needed to attend to a specific modality. These non-sensory areas may constitute a network that provides a source of modulating influences on the earlier stage, sensory areas.


Improved UV photoresponse of ZnO nanorod arrays by resonant coupling with surface plasmons of Al nanoparticles.
In this study, localized surface plasmon resonance mediated by aluminium nanoparticles (Al NPs) was employed to enhance the ultraviolet (UV) response of ZnO nanorod array (NRA) photodetectors grown vertically on a Quartz substrate using a simple vapor transport method. The responsivity of the ZnO NRA photodetector decorated with Al NPs was enhanced from 0.12 to 1.59 A W(-1) and the sensitivity and response rate have been improved greatly compared with those of the bare one. The measurement results in the transmittance spectra and time-resolved photoluminescence spectra suggest that the improved photoresponse and the enhanced spontaneous emission of the ZnO NRA photodetector with Al NP decoration are both attributed to resonant coupling between the excitons in ZnO and the localized surface plasmons (LSPs) in the Al NPs. Our results demonstrated that the plasmon-enhanced ZnO NRA photodetector has a great potential for application in building sensors with a fast response and reset time, high sensitivity, and good signal-to-noise ratio for photoelectric sensing.


[Geomicrobiological studies. XIV. Heavy metal tolerance of desulfurizing bacteria under various ecological conditions].
Tolerance and adaptation to heavy metals of Desulfovibrio- and Desulfotomaculum-strains of different origin have been investigated in enrichment cultures under different conditions of sulphate supply. Three groups of low, medium, and high toxicity were found with As, V, and Mo in the first, Ni, Sb, Co, and Hg in the second, and Cd, Zn, U, and Cu in the third group. If the SO"4-supply was restricted to heavy metal sulphates with a relation of 1:1 of heavy metal- and SO"4 -ions (2:3 with Sb2(SO4)3) the tolerance was somewhat lowered. Adaptation to higher concentrations of heavy metals was possible, if the strains had not yet been exposed and adapted to higher concentration levels at their natural habitats. The tolerance range of desulfurizers has been compared with the tolerance range of different biochemical types of microorganisms.


Changes in the amount of nonhaem iron in the plasma, whole body, and selected organs during the postlarval life of the lamprey Geotria australis.
The concentration of plasma nonhaem iron and the concentration and weight of all nonhaem iron in the whole body and selected organs, together with its partitioning into ferritin and haemosiderin iron, have been measured during the metamorphosis and upstream spawning migration of the Southern Hemisphere lamprey Geotria australis. Some nonhaem iron was lost from the animal during metamorphosis. However, the concentration and weight of nonhaem iron in the liver rose sharply at this time, following its release from important storage sites in adipose tissue and the degradation of larval haemoglobins. The nephric fold of larval and metamorphosing stages contained over 40% of all nonhaem iron in the body at the commencement of metamorphosis. This was predominantly in the form of haemosiderin. While the rise in liver iron during the transition from larva to adult primarily reflected an increase in the weight of ferritin iron, the amount of iron stored as haemosiderin rose conspicuously towards the end of metamorphosis. The rise in ferritin iron in the liver was accompanied by a decrease in ferritin iron in the plasma, which implies that changes in the liver during metamorphosis result in a greater filtering of circulating ferritin. Such a process would account for the very much lower plasma nonhaem iron concentrations which characterise later adult stages. The weight of nonhaem iron increased markedly in the liver and adult opisthonephros and in the whole animal during the nontrophic upstream spawning migration. This was primarily due to a marked rise in ferritin which in turn could be related to the degradation of adult haemoglobins.(ABSTRACT TRUNCATED AT 250 WORDS)


Improved wetland soil organic carbon stocks of the conterminous U.S. through data harmonization.
Wetland soil stocks are important global repositories of carbon (C) but are difficult to quantify and model due to varying sampling protocols, and geomorphic/spatio-temporal discontinuity. Merging scales of soil-survey spatial extents with wetland-specific point-based data offers an explicit, empirical and updatable improvement for regional and continental scale soil C stock assessments. Agency-collected and community-contributed soil datasets were compared for representativeness and bias, with the goal of producing a harmonized national map of wetland soil C stocks with error quantification for wetland areas of the conterminous United States (CONUS) identified by the USGS National Landcover Change Dataset. This allowed an empirical predictive model of SOC density to be applied across the entire CONUS using relational %OC distribution alone. A broken-stick quantile-regression model identified %OC with its relatively high analytical confidence as a key predictor of SOC density in soil segments; soils less than 6% OC (hereafter, mineral wetland soils, 85% of the dataset) had a strong linear relationship of %OC to SOC density (RMSE = 0.0059, ~4% mean RMSE) and soils greater than 6% OC (organic wetland soils, 15% of the dataset) had virtually no predictive relationship of %OC to SOC density (RMSE = 0.0348 g C cm-3, ~56% mean RMSE). Disaggregation by vegetation type, or region did not alter the breakpoint significantly (6% OC) nor improve model accuracies for inland and tidal wetlands. Similarly, SOC stocks in tidal wetlands were related to %OC, but without a mappable product for disaggregation to improve accuracy by soil class, region or depth. Our layered, harmonized CONUS wetland soil maps revised wetland SOC stock estimates downward by 24% (9.5 vs. 12.5Pg C) with the overestimation being entirely an issue of inland, organic wetland soils, (35% lower than SSURGO-derived SOC stocks). Further, SSURGO underestimated soil carbon stocks at depth, as modeled wetland SOC stocks for organic-rich soils showed significant preservation downcore in the NWCA dataset (<3% loss between 0-30 cm and 30-100 cm depths) in contrast to mineral-rich soils (37% downcore stock loss). Future CONUS wetland soil C assessments will benefit from focused attention on improved organic wetland soil measurements, land history, and spatial representativeness.


Structure-activity relationships of HIV-1 integrase inhibitors--enzyme-ligand interactions.
HIV-1 integrase is an essential enzyme for retroviral replication. It is involved in the integration of HIV DNA into host chromosomal DNA and appears to have no functional equivalent in human cells. Therefore it is an attractive and rational target for selective anti-AIDS therapy. A great number of HIV-1 integrase inhibitors have been described in the last decade and numerous reviews have been published. The biochemical mechanism of HIV-1 DNA integration, the enzyme structure and the possible targets for drug intervention have been thoroughly analyzed. Structure-based drug design including both ligand-based (pharmacophore) and target-based (docking) methods has also been discussed. The recent report of the crystal structure of HIV-1 integrase core domain with an inhibitor has given a new boost leading in the last two years to the emergence of diketoacids (DKAs). To date, with the dicaffeoyltartaric acids they are the only two classes of molecules that meet the criteria necessary to be considered lead molecules in the search for clinically useful inhibitors of HIV-1 integrase. After a survey of the function and the structure of this enzyme and the different available assays for the identification of new IN inhibitors, structure-activity relationships of HIV-1 integrase inhibitors that are expected to interact with the active site (or in its vicinity) will be discussed with emphasis on their different proposed mechanisms of action.


A randomized, double-blinded, placebo-controlled pilot study to investigate the effectiveness of a static magnet to relieve dysmenorrhea.
The aim of this study was to investigate the hypothesis that a specially designed, static magnet of 2700 gauss, attached over the pelvic area, could relieve menstrual pain. This was a randomized, double-blind, placebo-controlled, postal questionnaire study. The study was conducted in a primary care, single center. Sixty-five (65) women (mean age 29.1 +/- 1.52 years) were recruited from an advertisement in a London newspaper. The entry criterion was regular dysmenorrhea. The exclusion criterion was known secondary dysmenorrhea. Of the 65 women who were enrolled, 35 completed the study. A questionnaire-based assessment was completed by each subject and checked by telephone before and after random allocation to use of either the static magnet device (2700 gauss) or an identical, weaker magnetic placebo device (140 gauss). Assessment was made by telephone before and after a complete menstrual cycle. None of the participants was examined or seen face-to-face. The main outcome measures were level of pain, using the McGill Pain and Visual Analogue Scales, and ratings of associated symptoms such as irritability, restriction of usual activities, and painkiller consumption. There was a significant reduction (p < 0.02) in pain in the magnet group compared to the placebo group. Pain score differences (McGill pain score before-pain score after use of device) were -17 (-53, 13) (median and interquartile ranges) in the magnet group and -5.0 (-29, 27) in the placebo group. The 95% Mann-Whitney confidence intervals for the median difference between the magnet and placebo groups (magnet-placebo) were -53.0 to 23.38. A reduction in irritability symptoms in the magnet group approached statistical significance (p = 0.056). Despite the small number of participants, the level of significance reached in the reduction of pain merits reporting. This is a pilot study to a much larger study of the same device as an analgesic in women with primary dysmenorrhea.


Chemically Deposited CdS Buffer/Kesterite Cu2ZnSnS4 Solar Cells: Relationship between CdS Thickness and Device Performance.
Earth-abundant, copper-zinc-tin-sulfide (CZTS), kesterite, is an attractive absorber material for thin-film solar cells (TFSCs). However, the open-circuit voltage deficit (Voc-deficit) resulting from a high recombination rate at the buffer/absorber interface is one of the major challenges that must be overcome to improve the performance of kesterite-based TFSCs. In this paper, we demonstrate the relationship between device parameters and performances for chemically deposited CdS buffer/CZTS-based heterojunction TFSCs as a function of buffer layer thickness, which could change the CdS/CZTS interface conditions such as conduction band or valence band offsets, to gain deeper insight and understanding about the Voc-deficit behavior from a high recombination rate at the CdS buffer/kesterite interface. Experimental results show that device parameters and performances are strongly dependent on the CdS buffer thickness. We postulate two meaningful consequences: (i) Device parameters were improved up to a CdS buffer thickness of 70 nm, whereas they deteriorated at a thicker CdS buffer layer. The Voc-deficit in the solar cells improved up to a CdS buffer thickness of 92 nm and then deteriorated at a thicker CdS buffer layer. (ii) The minimum values of the device parameters were obtained at 70 nm CdS thickness in the CZTS TFSCs. Finally, the highest conversion efficiency of 8.77% (Voc: 494 mV, Jsc: 34.54 mA/cm2, and FF: 51%) is obtained by applying a 70 nm thick CdS buffer to the Cu2ZnSn(S,Se)4 absorber layer.


Testing the role of reward and punishment sensitivity in avoidance behavior: a computational modeling approach.
Exaggerated avoidance behavior is a predominant symptom in all anxiety disorders and its degree often parallels the development and persistence of these conditions. Both human and non-human animal studies suggest that individual differences as well as various contextual cues may impact avoidance behavior. Specifically, we have recently shown that female sex and inhibited temperament, two anxiety vulnerability factors, are associated with greater duration and rate of the avoidance behavior, as demonstrated on a computer-based task closely related to common rodent avoidance paradigms. We have also demonstrated that avoidance is attenuated by the administration of explicit visual signals during "non-threat" periods (i.e., safety signals). Here, we use a reinforcement-learning network model to investigate the underlying mechanisms of these empirical findings, with a special focus on distinct reward and punishment sensitivities. Model simulations suggest that sex and inhibited temperament are associated with specific aspects of these sensitivities. Specifically, differences in relative sensitivity to reward and punishment might underlie the longer avoidance duration demonstrated by females, whereas higher sensitivity to punishment might underlie the higher avoidance rate demonstrated by inhibited individuals. Simulations also suggest that safety signals attenuate avoidance behavior by strengthening the competing approach response. Lastly, several predictions generated by the model suggest that extinction-based cognitive-behavioral therapies might benefit from the use of safety signals, especially if given to individuals with high reward sensitivity and during longer safe periods. Overall, this study is the first to suggest cognitive mechanisms underlying the greater avoidance behavior observed in healthy individuals with different anxiety vulnerabilities.


Body weight-specific zinc compartmental masses in girls significantly exceed those reported in adults: a stable isotope study using a kinetic model.
Maintaining optimal zinc status is important for normal growth and development in children, but minimal data are available regarding zinc metabolism in this age group. Our objectives were to utilize stable isotope-based compartmental modeling techniques to investigate zinc metabolism in healthy children; to expand a current stable isotope-based model to include red blood cell data; and to compare kinetic parameters in children with those previously reported in adults. Seven healthy girls, age 9.94 +/- 0.79 y, received 1.1 mg of a (67)zinc-enriched tracer orally and 0.5 mg of a (70)zinc-enriched tracer intravenously. Blood, urine and fecal samples were collected for 6 d. Stable isotope enrichments were measured by thermal ionization magnetic sector mass spectrometry. A six-compartment model based on a model previously reported in adults was used; the model excluded red blood cell data. Body weight-corrected masses of the body zinc compartments derived using this model were significantly greater in children than those reported in adults. Modification of the model to include a red blood cell compartment increased the total identifiable zinc mass of the nongastrointestinal compartments by approximately 2.5%. We conclude that compartmental modeling can be used to describe zinc kinetics in children, and that the body weight-corrected zinc pool masses are significantly greater in children than in adults.


PREVALENCE AND FACTORS ASSOCIATED WITH ANEMIA IN CHILDREN ENROLLED IN DAYCARE CENTERS: A HIERARCHICAL ANALYSIS.
To determine the prevalence and factors associated with anemia in children younger than five years old enrolled in public daycare centers in a city in southwestern Bahia, in the northeast of Brazil. This was a cross-sectional study that included a sample of 677 children enrolled in public daycare centers in Vitória da Conquista, Bahia, Brazil. A portable hemoglobinometer was used to measure hemoglobin. The concentration of <11 g/dL was considered the cutoff point for a diagnosis of anemia. A questionnaire was applied to parents/guardians in order to collect socioeconomic data, maternal characteristics and information on the child's health and nutrition. Height and weight were measured to assess the child's nutritional status. Poisson regression with robust variance and hierarchical selection of variables was used to identify factors associated with anemia. The prevalence of anemia was 10.2% and was more frequent in children whose homes had no sanitary facilities (PR 3.36; 95%CI 1.40-8.03); in those who did not exclusively breastfeed (PR 1.80; 95%CI 1.12-2.91); in children aged less than 36 months (PR 1.85; 95%CI 1.19-2.89) and those who had low height for age (PR 2.06; 95%CI 1.10-3.85). The prevalence of anemia is considered to be a mild public health problem in the children, who are enrolled in daycare centers. Children with inadequate sanitary conditions, and that were not exclusively breastfed, as well as younger children and children with a nutritional deficit, were more likely to present the condition.


World Health Organization Grade II/III Glioma Molecular Status: Prediction by MRI Morphologic Features and Apparent Diffusion Coefficient.
Background A readily implemented MRI biomarker for glioma genotyping is currently lacking. Purpose To evaluate clinically available MRI parameters for predicting isocitrate dehydrogenase (IDH) status in patients with glioma. Materials and Methods In this retrospective study of patients studied from July 2008 to February 2019, untreated World Health Organization (WHO) grade II/III gliomas were analyzed by three neuroradiologists blinded to tissue results. Apparent diffusion coefficient (ADC) minimum (ADCmin) and mean (ADCmean) regions of interest were defined in tumor and normal appearing white matter (ADCNAWM). A visual rating of anatomic features (T1 weighted, T1 weighted with contrast enhancement, T2 weighted, and fluid-attenuated inversion recovery) was performed. Interobserver comparison (intraclass correlation coefficient and Cohen κ) was followed by nonparametric (Kruskal-Wallis analysis of variance) testing of associations between ADC metrics and glioma genotypes, including Bonferroni correction for multiple testing. Descriptors with sufficient concordance (intraclass correlation coefficient, >0.8; κ > 0.6) underwent univariable analysis. Predictive variables (P < .05) were entered into a multivariable logistic regression and tested in an additional test sample of patients with glioma. Results The study included 290 patients (median age, 40 years; interquartile range, 33-52 years; 169 male patients) with 82 IDH wild-type, 107 IDH mutant/1p19q intact, and 101 IDH mutant/1p19q codeleted gliomas. Two predictive models incorporating ADCmean-to-ADCNAWM ratio, age, and morphologic characteristics, with model A mandating calcification result and model B recording cyst formation, classified tumor type with areas under the receiver operating characteristic curve of 0.94 (95% confidence interval [CI]: 0.91, 0.97) and 0.96 (95% CI: 0.93, 0.98), respectively. In the test sample of 49 gliomas (nine IDH wild type, 21 IDH mutant/1p19q intact, and 19 IDH mutant/1p19q codeleted), the classification accuracy was 40 of 49 gliomas (82%; 95% CI: 71%, 92%) for model A and 42 of 49 gliomas (86%; 95% CI: 76%, 96%) for model B. Conclusion Two algorithms that incorporated apparent diffusion coefficient values, age, and tumor morphologic characteristics predicted isocitrate dehydrogenase status in World Health Organization grade II/III gliomas on the basis of standard clinical MRI sequences alone. © RSNA, 2020 Online supplemental material is available for this article.