A canonical neural circuit for cortical nonlinear operations.
A few distinct cortical operations have been postulated over the past few years, suggested by experimental data on nonlinear neural response across different areas in the cortex. Among these, the energy model proposes the summation of quadrature pairs following a squaring nonlinearity in order to explain phase invariance of complex V1 cells. The divisive normalization model assumes a gain-controlling, divisive inhibition to explain sigmoid-like response profiles within a pool of neurons. A gaussian-like operation hypothesizes a bell-shaped response tuned to a specific, optimal pattern of activation of the presynaptic inputs. A max-like operation assumes the selection and transmission of the most active response among a set of neural inputs. We propose that these distinct neural operations can be computed by the same canonical circuitry, involving divisive normalization and polynomial nonlinearities, for different parameter values within the circuit. Hence, this canonical circuit may provide a unifying framework for several circuit models, such as the divisive normalization and the energy models. As a case in point, we consider a feedforward hierarchical model of the ventral pathway of the primate visual cortex, which is built on a combination of the gaussian-like and max-like operations. We show that when the two operations are approximated by the circuit proposed here, the model is capable of generating selective and invariant neural responses and performing object recognition, in good agreement with neurophysiological data.


Dutch teachers and parents about overweight prevention in pre-vocational schools.
Healthier lifestyles may contribute to prevent overweight in adolescents. Although school-based interventions show promising results, adoption and implementation by secondary schools and involvement of parents is difficult. Our study aims to gain a better understanding of the problem awareness and beliefs of school staff and parents regarding adolescents' overweight and energy balance-related behaviour, their motivation for health-promoting activities and suggested actions in the school environment. Focus group interviews were conducted with three groups of parents and three groups of school staff at three pre-vocational schools in the Netherlands. Comments concerning awareness, motivation to intervene and possible actions were analysed with the Atlas.ti program. Results showed that school staff and parents were aware of overweight as a health problem, but underestimated the prevalence and impact of overweight and unhealthy behaviour in their school. Health-related behaviour of adolescents was considered primarily the responsibility of parents, but the school staff also had a pedagogical responsibility. Parents and school staff agreed that health promotion efforts would have more impact on adolescents' behaviour, when school-based activities were supported by parents and parental efforts were supported by school health promotion. Therefore, parental efforts and school-based activities should be aligned by developing and expressing shared norms about healthy behaviour and parents should be taught how to discuss healthy dietary and physical activity behaviour with their children. To tackle peer group culture and the obese environment, parents' and school staff's efforts should be part of an integrated community approach.


Health and sleep problems in Cornelia de Lange Syndrome: a case control study.
Self-injury, sleep problems and health problems are commonly reported in Cornelia de Lange Syndrome (CdLS) but there are no comparisons with appropriately matched participants. The relationship between these areas and comparison to a control group is warranted. 54 individuals with CdLS were compared with 46 participants with intellectual disability (ID) of mixed aetiology who were similar in terms of degree of ID, mobility, age and gender using informant-based measures of health problems, sleep and self-injury. Participants with CdLS experienced significantly more current and lifetime health problems with eye problems and gastrointestinal disorders prominent. Although 55% of those with CdLS experienced sleep problems this prevalence was not different from the comparison group. Sleep disorder was not associated with self-injury in the CdLS group, skin problems were associated with severity of self-injury but not presence. People with CdLS experience a range of significant health problems and have more health concerns than others with the same degree of ID. Although this has been well documented in the past, the current high prevalence of health concerns indicates the need for regular health assessment and appropriate intervention.


Surface-enhanced terahertz spectroscopy using gold rod structures resonant with terahertz waves.
Terahertz (THz) spectroscopy is a promising method to measure the spectrum of low-frequency modes of molecules or ensembles, such as crystals and polymers, including proteins. However, the main drawback of THz spectroscopy is its extremely low sensitivity. In the present study, we report on signal enhancement in THz spectroscopy achieved by depositing amino acid molecules or their derivatives on a gold rod structured silicon substrate whose localized surface plasmon resonance is exhibited in the THz frequency region. The distinct peaks derived from the enhancement of the inherent spectrum based on a molecular crystal were clearly observed when a longitudinal plasmon resonance mode of the gold rod structure was excited and the plasmon resonance band overlapped the molecular/intermolecular vibrational mode. We discuss the mechanism by which surface-enhanced THz spectroscopy was induced from the viewpoint of the enhancement of light-matter coupling due to plasmon excitation and the modulation of the plasmon band by dipole coupling between the plasmon dipole and molecular/intermolecular vibrational modes.


Kinetic analysis of matrix metalloproteinase activity using fluorogenic triple-helical substrates.
Matrix metalloproteinase (MMP) family members are involved in the physiological remodeling of tissues and embryonic development as well as pathological destruction of extracellular matrix components. To study the mechanisms of MMP action on collagenous substrates, we have constructed homotrimeric, fluorogenic triple-helical peptide (THP) models of the MMP-1 cleavage site in type II collagen. The substrates were designed to incorporate the fluorophore/quencher pair of (7-methoxycoumarin-4-yl)acetyl (Mca) and N-2,4-dinitrophenyl (Dnp) in the P(5) and P(5)' positions, respectively. In addition, Arg was incorporated in the P(2)' and P(8)' positions to enhance enzyme activity and improve substrate solubility. The desired sequences were Gly-Pro-Lys(Mca)-Gly-Pro-Gln-Gly approximately Leu-Arg-Gly-Gln-Lys(Dnp)-Gly-Ile/Val-Arg. Two fluorogenic substrates were prepared, one using a covalent branching protocol (fTHP-1) and one using a peptide self-assembly approach (fTHP-3). An analogous single-stranded substrate (fSSP-3) was also synthesized. Both THPs were hydrolyzed by MMP-1 at the Gly approximately Leu bond, analogous to the bond cleaved in the native collagen. The individual kinetic parameters for MMP-1 hydrolysis of fTHP-3 were k(cat) = 0.080 s(-1) and K(M) = 61.2 microM. Subsequent investigations showed fTHP-3 hydrolysis by MMP-2, MMP-3, MMP-13, a C-terminal domain-deleted MMP-1 [MMP-1(Delta(243-450))], and a C-terminal domain-deleted MMP-3 [MMP-3(Delta(248-460))]. The order of k(cat)/K(M) values was MMP-13 > MMP-1 approximately MMP-1(Delta(243-450)) approximately MMP-2 >> MMP-3 approximately MMP-3(Delta(248-460)). Studies on the effect of temperature on fTHP-3 and fSSP-3 hydrolysis by MMP-1 showed that the activation energies between these two substrates differed by 3.4-fold, similar to the difference in activation energies for MMP-1 hydrolysis of type I collagen and gelatin. This indicates that fluorogenic triple-helical substrates mimic the behavior of the native collagen substrate and may be useful for the investigation of collagenase triple-helical activity.


Visual or visual-tactile examination to detect and inform the diagnosis of enamel caries.
The detection and diagnosis of caries at the initial (non-cavitated) and moderate (enamel) levels of severity is fundamental to achieving and maintaining good oral health and prevention of oral diseases. An increasing array of methods of early caries detection have been proposed that could potentially support traditional methods of detection and diagnosis. Earlier identification of disease could afford patients the opportunity of less invasive treatment with less destruction of tooth tissue, reduce the need for treatment with aerosol-generating procedures, and potentially result in a reduced cost of care to the patient and to healthcare services. To determine the diagnostic accuracy of different visual classification systems for the detection and diagnosis of non-cavitated coronal dental caries for different purposes (detection and diagnosis) and in different populations (children or adults). Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 30 April 2020); Embase Ovid (1980 to 30 April 2020); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 30 April 2020); and the World Health Organization International Clinical Trials Registry Platform (to 30 April 2020). We studied reference lists as well as published systematic review articles. We included diagnostic accuracy study designs that compared a visual classification system (index test) with a reference standard (histology, excavation, radiographs). This included cross-sectional studies that evaluated the diagnostic accuracy of single index tests and studies that directly compared two or more index tests. Studies reporting at both the patient or tooth surface level were included. In vitro and in vivo studies were considered. Studies that explicitly recruited participants with caries into dentine or frank cavitation were excluded. We also excluded studies that artificially created carious lesions and those that used an index test during the excavation of dental caries to ascertain the optimum depth of excavation. We extracted data independently and in duplicate using a standardised data extraction and quality assessment form based on QUADAS-2 specific to the review context. Estimates of diagnostic accuracy were determined using the bivariate hierarchical method to produce summary points of sensitivity and specificity with 95% confidence intervals (CIs) and regions, and 95% prediction regions. The comparative accuracy of different classification systems was conducted based on indirect comparisons. Potential sources of heterogeneity were pre-specified and explored visually and more formally through meta-regression. We included 71 datasets from 67 studies (48 completed in vitro) reporting a total of 19,590 tooth sites/surfaces. The most frequently reported classification systems were the International Caries Detection and Assessment System (ICDAS) (36 studies) and Ekstrand-Ricketts-Kidd (ERK) (15 studies). In reporting the results, no distinction was made between detection and diagnosis. Only two studies were at low risk of bias across all four domains, and 15 studies were at low concern for applicability across all three domains. The patient selection domain had the highest proportion of high risk of bias studies (49 studies). Four studies were assessed at high risk of bias for the index test domain, nine for the reference standard domain, and seven for the flow and timing domain. Due to the high number of studies on extracted teeth concerns regarding applicability were high for the patient selection and index test domains (49 and 46 studies respectively). Studies were synthesised using a hierarchical bivariate method for meta-analysis. There was substantial variability in the results of the individual studies: sensitivities ranged from 0.16 to 1.00 and specificities from 0 to 1.00. For all visual classification systems the estimated summary sensitivity and specificity point was 0.86 (95% CI 0.80 to 0.90) and 0.77 (95% CI 0.72 to 0.82) respectively, diagnostic odds ratio (DOR) 20.38 (95% CI 14.33 to 28.98). In a cohort of 1000 tooth surfaces with 28% prevalence of enamel caries, this would result in 40 being classified as disease free when enamel caries was truly present (false negatives), and 163 being classified as diseased in the absence of enamel caries (false positives). The addition of test type to the model did not result in any meaningful difference to the sensitivity or specificity estimates (Chi2(4) = 3.78, P = 0.44), nor did the addition of primary or permanent dentition (Chi2(2) = 0.90, P = 0.64). The variability of results could not be explained by tooth surface (occlusal or approximal), prevalence of dentinal caries in the sample, nor reference standard. Only one study intentionally included restored teeth in its sample and no studies reported the inclusion of sealants. We rated the certainty of the evidence as low, and downgraded two levels in total for risk of bias due to limitations in the design and conduct of the included studies, indirectness arising from the in vitro studies, and inconsistency of results. Whilst the confidence intervals for the summary points of the different visual classification systems indicated reasonable performance, they do not reflect the confidence that one can have in the accuracy of assessment using these systems due to the considerable unexplained heterogeneity evident across the studies. The prediction regions in which the sensitivity and specificity of a future study should lie are very broad, an important consideration when interpreting the results of this review. Should treatment be provided as a consequence of a false-positive result then this would be non-invasive, typically the application of fluoride varnish where it was not required, with low potential for an adverse event but healthcare resource and finance costs. Despite the robust methodology applied in this comprehensive review, the results should be interpreted with some caution due to shortcomings in the design and execution of many of the included studies. Studies to determine the diagnostic accuracy of methods to detect and diagnose caries in situ are particularly challenging. Wherever possible future studies should be carried out in a clinical setting, to provide a realistic assessment of performance within the oral cavity with the challenges of plaque, tooth staining, and restorations, and consider methods to minimise bias arising from the use of imperfect reference standards in clinical studies.


Barriers for pregnant women living in rural, agricultural villages to accessing antenatal care in Cambodia: A community-based cross-sectional study combined with a geographic information system.
Maternal morbidity and mortality is still a major public health issue in low- and middle-income countries such as Cambodia. Improving access to antenatal care (ANC) services for pregnant women has been widely recognized as one of the most effective means of reducing maternal mortality and morbidity. As such, this study examined the barriers for pregnant women living in rural, agricultural villages to accessing ANC based on data collected in the Ratanakiri province, one of the least developed provinces in Cambodia, using a combination of a community-based cross-sectional survey and a geographic information system (GIS). A community-based cross-sectional survey was conducted among 377 mothers with children under the age of two living in 62 villages in the Ratanakiri province, Cambodia, in December 2015. Face-to-face interviews were conducted to ask mothers about their ANC service use, knowledge of ANC, barriers to accessing health facilities, and complications they experienced during the most recent pregnancy. At the same time, GIS data were also collected using a Global Positioning System (GPS) to accurately measure actual travel distance of pregnant women to access health facilities and to examine geographical and environmental barriers in greater detail. Only a third of the mothers met the recommendations made by the World Health Organization (WHO) of receiving ANC four times or more (achieved ANC4+), and a quarter of the mothers had never received ANC during their most recent pregnancy. Factors positively associated with achieving ANC4+ were mother's secondary or higher education (adjusted odds ratio [AOR] = 5.50, 95% confidence interval [CI]: 1.74, 17.37), being aware that receiving ANC is recommended (AOR = 2.74, 95% CI: 1.25, 6.00), and knowledge about the recommended frequency for ANC (AOR = 2.26, 95% CI: 7.22). Actual travel distance was negatively associated with achieving ANC4+. Mothers who had to travel 10.0-14.9 km were 68% less likely (AOR = 0.32, 95% CI: 0.10, 0.99), and those who had to travel 15.0 km or longer were 79% less likely (AOR = 0.21, 95% CI: 0.07, 0.62) to have achieved ANC 4+, both compared to those who travelled 5.0 km or less. While most previous studies have used a straight-line to measure distance traveled, this study much more accurately measured the actual distance traveled by using a GIS. As a result, there was a statistically significant discrepancy between actual travel distance and straight-line distance. This study revealed promoting factors and barriers for ANC use among pregnant women living in remote, agricultural villages in Cambodia. Furthermore, this study highlights the importance of measuring travel distances accurately to ensure that targeted interventions for ANC are not misguided by straight-line distances. The methodology used in this study can be applied widely to other developing countries, especially in remote areas with limited road networks where there may be a large discrepancy between actual and straight-line distances.


Molecular and electronic structures of donor-functionalized dysprosium pentadienyl complexes.
Two dysprosium complexes, [(C5H4Me)2Dy(L(1))] (3) and [(L(1))Dy(μ-Cl)3{Li(tmeda)}]2 (4), with amino-functionalized pentadienyl ligands L(1) are described. Crystallographic studies of 3 and 4 show that the pendant amino group influences the pentadienyl conformation and the ligand hapticity. Electronic structure calculations reveal that L(1) has a strong influence on the orientation of the main magnetic axis of the ground Kramers doublets in 3 and 4.


Somatic tetraploidy in specific chick retinal ganglion cells induced by nerve growth factor.
A subset of neurons in the normal vertebrate nervous system contains double the normal amount of DNA in their nuclei. These neurons are all thought to derive from aberrant mitoses in neuronal precursor cells. Here we show that endogenous NGF induces DNA replication in a subpopulation of differentiating chick retinal ganglion cells that express both the neurotrophin receptor p75 and the E2F1 transcription factor, but that lack the retinoblastoma protein. Many of these neurons avoid G2/M transition and remain alive in the retina as tetraploid cells with large cell somas and extensive dendritic trees, and most of them express beta2 nicotinic acetylcholine receptor subunits, a specific marker of retinal ganglion cells innervating lamina F in the stratum-griseum-et-fibrosum-superficiale of the tectal cortex. Tetraploid neurons were also observed in the adult mouse retina. Thus, a developmental program leading to somatic tetraploidy in specific retinal neurons exists in vertebrates. This program might occur in other vertebrate neurons during normal or pathological situations.


Innovative Solutions for State Medicaid Programs to Leverage Their Data, Build Their Analytic Capacity, and Create Evidence-Based Policy.
As states have embraced additional flexibility to change coverage of and payment for Medicaid services, they have also faced heightened expectations for delivering high-value care. Efforts to meet these new expectations have increased the need for rigorous, evidence-based policy, but states may face challenges finding the resources, capacity, and expertise to meet this need. By describing state-university partnerships in more than 20 states, this commentary describes innovative solutions for states that want to leverage their own data, build their analytic capacity, and create evidence-based policy. From an integrated web-based system to improve long-term care to evaluating the impact of permanent supportive housing placements on Medicaid utilization and spending, these state partnerships provide significant support to their state Medicaid programs. In 2017, these partnerships came together to create a distributed research network that supports multi-state analyses. The Medicaid Outcomes Distributed Research Network (MODRN) uses a common data model to examine Medicaid data across states, thereby increasing the analytic rigor of policy evaluations in Medicaid, and contributing to the development of a fully functioning Medicaid innovation laboratory.


Drugging the Cancers Addicted to DNA Repair.
Defects in DNA repair can result in oncogenic genomic instability. Cancers occurring from DNA repair defects were once thought to be limited to rare inherited mutations (such as BRCA1 or 2). It now appears that a clinically significant fraction of cancers have acquired DNA repair defects. DNA repair pathways operate in related networks, and cancers arising from loss of one DNA repair component typically become addicted to other repair pathways to survive and proliferate. Drug inhibition of the rescue repair pathway prevents the repair-deficient cancer cell from replicating, causing apoptosis (termed synthetic lethality). However, the selective pressure of inhibiting the rescue repair pathway can generate further mutations that confer resistance to the synthetic lethal drugs. Many such drugs currently in clinical use inhibit PARP1, a repair component to which cancers arising from inherited BRCA1 or 2 mutations become addicted. It is now clear that drugs inducing synthetic lethality may also be therapeutic in cancers with acquired DNA repair defects, which would markedly broaden their applicability beyond treatment of cancers with inherited DNA repair defects. Here we review how each DNA repair pathway can be attacked therapeutically and evaluate DNA repair components as potential drug targets to induce synthetic lethality. Clinical use of drugs targeting DNA repair will markedly increase when functional and genetic loss of repair components are consistently identified. In addition, future therapies will exploit artificial synthetic lethality, where complementary DNA repair pathways are targeted simultaneously in cancers without DNA repair defects.


Nonphagocytic dendritic cells are effective accessory cells for anti-mycobacterial responses in vitro.
The accessory cell requirements for a given T cell response may be examined in vitro by using highly purified lymph node T cells. We have examined the capacity of different antigen-presenting cells to stimulate proliferation of Mycobacterium tuberculosis-primed T cells when the antigenic challenge is either soluble or particulate in nature. By titrations of cell number and antigen concentration, it was shown that dendritic cells are not only extremely efficient at presenting soluble mycobacterial antigen compared with various macrophage populations, but also that they are capable of presenting whole mycobacteria. Because phagocytosis of mycobacteria does not occur with these cells, we suggest that processing of antigen by dendritic cells may be initiated at the plasma membrane. Because macrophages are not essential for this in vitro response, a role for dendritic cells in antibacterial immunity in vivo is implicated.


CoCrFeNi High-Entropy Alloy as an Enhanced Hydrogen Evolution Catalyst in an Acidic Solution.
High-entropy alloys (HEAs) have intriguing material properties, but their potential as catalysts has not been widely explored. Based on a concise theoretical model, we predict that the surface of a quaternary HEA of base metals, CoCrFeNi, should go from being nearly fully oxidized except for pure Ni sites when exposed to O2 to being partially oxidized in an acidic solution under cathodic bias, and that such a partially oxidized surface should be more active for the electrochemical hydrogen evolution reaction (HER) in acidic solutions than all the component metals. These predictions are confirmed by electrochemical and surface science experiments: the Ni in the HEA is found to be most resistant to oxidation, and when deployed in 0.5 M H2SO4, the HEA exhibits an overpotential of only 60 mV relative to Pt for the HER at a current density of 1 mA/cm2.


Autonomic control of cardiovascular functions during neonatal development and in adult sheep.
We studied the autonomic control of resting heart rate of systemic and pulmonary vascular blood pressures (BP) in chronically instrumented neonatal lambs 1-8 weeks of age. The maximum response to ganglionic blockade and sympathetic and parasympathetic antagonists was taken as an index of the magnitude of the total neural, adrenergic, and cholinergic tones. The reactivity of the circulatory parameters to adrenergic and cholinergic agonists also was investigated. All findings were compared with those in adult nonpregnant sheep studied concomitantly and with data previously obtained from term fetal lambs. The results of our studies show: (1) resting heart rate declines spontaneously throughout the 8 weeks of neonatal life approaching that of adult sheep; (2) the progressive bradycardia is not related to changes in the parasympathetic or sympathetic tone; (3) resting systemic BP is under strong neurohumoral control during the first two to three weeks of neonatal life; the control decreases progressively, becoming similar to that of adult sheep; (4) resting pulmonary artery pressure of neonatal and adult sheep has no neurohumoral control; (5) the systemic BP response of the neonate to autonomic agonists is greater than that of the term fetus and is similar to that of the adult; (6) in neonatal and adult sheep, compared to the term fetus, the pressor response to norepinephrine is accompanied by a baroreceptor-mediated bradycardia, and acetylcholine-induced systemci hypotension is accompanied by a "paradoxical" tachycardia mediated through beta-adrenergic stimulation; (7) in contrast to our finding for the fetus, the pulmonary vascular pressure of neonatal and adult sheep is unresponsive to autonomic agonists.


Measurement of Gross Photosynthesis, Respiration in the Light, and Mesophyll Conductance Using H218O Labeling.
A fundamental challenge in plant physiology is independently determining the rates of gross O2 production by photosynthesis and O2 consumption by respiration, photorespiration, and other processes. Previous studies on isolated chloroplasts or leaves have separately constrained net and gross O2 production (NOP and GOP, respectively) by labeling ambient O2 with 18O while leaf water was unlabeled. Here, we describe a method to accurately measure GOP and NOP of whole detached leaves in a cuvette as a routine gas-exchange measurement. The petiole is immersed in water enriched to a δ18O of ∼9,000‰, and leaf water is labeled through the transpiration stream. Photosynthesis transfers 18O from H2O to O2 GOP is calculated from the increase in δ18O of O2 as air passes through the cuvette. NOP is determined from the increase in O2/N2 Both terms are measured by isotope ratio mass spectrometry. CO2 assimilation and other standard gas-exchange parameters also were measured. Reproducible measurements are made on a single leaf for more than 15 h. We used this method to measure the light response curve of NOP and GOP in French bean (Phaseolus vulgaris) at 21% and 2% O2 We then used these data to examine the O2/CO2 ratio of net photosynthesis, the light response curve of mesophyll conductance, and the apparent inhibition of respiration in the light (Kok effect) at both oxygen levels. The results are discussed in the context of evaluating the technique as a tool to study and understand leaf physiological traits.


Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies.
We conducted the first phase 0 clinical trial in oncology of a therapeutic agent under the Exploratory Investigational New Drug Guidance of the US Food and Drug Administration. It was a first-in-human study of the poly (ADP-ribose) polymerase (PARP) inhibitor ABT-888 in patients with advanced malignancies. ABT-888 was administered as a single oral dose of 10, 25, or 50 mg to determine the dose range and time course over which ABT-888 inhibits PARP activity in tumor samples and peripheral blood mononuclear cells, and to evaluate ABT-888 pharmacokinetics. Blood samples and tumor biopsies were obtained pre- and postdrug administration for evaluation of PARP activity and pharmacokinetics. A novel statistical approach was developed and utilized to study pharmacodynamic modulation as the primary end point for trials of limited sample size. Thirteen patients with advanced malignancies received the study drug; nine patients underwent paired tumor biopsies. ABT-888 demonstrated good oral bioavailability and was well tolerated. Statistically significant inhibition of poly (ADP-ribose) levels was observed in tumor biopsies and peripheral blood mononuclear cells at the 25-mg and 50-mg dose levels. Within 5 months of study activation, we obtained pivotal biochemical and pharmacokinetic data that have guided the design of subsequent phase I trials of ABT-888 in combination with DNA-damaging agents. In addition to accelerating the development of ABT-888, the rapid conclusion of this trial demonstrates the feasibility of conducting proof-of-principle phase 0 trials as part of an alternative paradigm for early drug development in oncology.


Study of the effect of formulation parameters/variables to control the nanoencapsulation of hydrophilic drug via double emulsion technique.
Preparation of biodegradable nanoparticles containing active molecule is now taking much attention of researchers. The aim of the present work is to achieve the nanosize particles for the first time by double emulsion (W1/O/W2,) evaporation method to encapsulate hydrophilic substance using high performance stirring apparatus. A fluorescent stable hydrophilic agent (Stilbene derivative) was used as a model drug to be encapsulated. For this purpose, PCL (polycaprolactone) was chosen as polymer in this study. Several kinds of stabilizers [triton-405, tween 80, poloxamer, PVP (polyvinylpyrrolidone), PEG (poly ethylene glycol) & PVA (poly vinyl alcohol)] were investigated and the results indicate that the PVA (0.5% concentration) leads to the most stable double emulsion with the particle size in nano range. Different parameters affecting the size of particles have been studied such as stirring time (for 1st and 2nd emulsion), stirring speed (for 1st and 2nd emulsion), polymer and stabilizer concentrations etc. After duration of one month, the encapsulation efficiency of obtained particles was estimated using U.V. analysis. Transmission Electron Microscopy (TEM) showed that the prepared particles were spherical in shape. The size and size distribution were found to be submicron and ranging from 150 to 400 nm.


Cigar and pipe smoking in the U.S. military: prevalence, trends, and correlates.
This article examines the prevalence, trends, and correlates in cigar/pipe smoking and their relation to cigarette smoking among active duty U.S. military personnel. An examination of the trends in cigar/pipe smoking was conducted with data from 1985 to 1998, and predictors of smoking were determined for 1998. Rates of cigar/pipe smoking declined from 1985 until about 1992 and then began to increase. From 1995 to 1998, there was a 75% increase in the prevalence of cigar/pipe smoking. Greater prevalence of cigar/pipe smoking was associated with male gender, younger age, relatively favorable beliefs and values toward smoking, and being a current cigarette smoker. Findings indicate a notable increase in past-year cigar/pipe smoking. These findings suggest that military tobacco prevention and early intervention programs would benefit from including components that deal specifically with cigar and pipe use in addition to cigarette smoking.


Cancer mortality surveillance--United States, 1990-2000.
Cancer is the second leading cause of death in the United States and is expected to become the leading cause of death within the next decade. Considerable variation exists in cancer mortality between the sexes and among different racial/ethnic populations and geographic locations. The description of mortality data by state, sex, and race/ethnicity is essential for cancer-control researchers to target areas of need and develop programs that reduce the burden of cancer. 1990-2000. Mortality data from CDC were used to calculate death rates and trends, categorized by state, sex, and race/ethnicity. Trend analyses for 1990-2000 are presented for all cancer sites combined and for the four leading cancers causing death (lung/bronchus, colorectal, prostate, and breast) categorized by state, sex, and race/ethnicity. Death rates per 100,000 population for the 10 primary cancer sites with the highest age-adjusted rates are also presented for each state and the District of Columbia by sex. For males, the 10 primary sites include lung/bronchus, prostate, colon/rectum, pancreas, leukemia, non-Hodgkin lymphoma, liver/intrahepatic bile duct, esophagus, stomach, and urinary bladder. For females, the 10 primary sites include lung/bronchus, breast, colon/rectum, pancreas, ovary, non-Hodgkin lymphoma, leukemia, brain/other nervous system, uterine corpus, and myeloma. For 1990-2000, cancer mortality decreased among the majority of racial/ethnic populations and geographic locations in the United States. Statistically significant decreases in mortality among all races combined occurred with lung and bronchus cancer among men (--1.7%/year); colorectal cancer among men and women (--2.0%/year and--1.7%/year, respectively); prostate cancer (--2.6%/year); and female breast cancer (--2.3%/year). For 1990-2000, cancer mortality remained stable among American Indian/Alaska Native populations. Statistically significant increases in lung and bronchus cancer mortality occurred among women of all racial/ethnic backgrounds, except among Asian/Pacific Islanders. Although cancer remains the second leading cause of death in the United States, the overall declining trend in cancer mortality demonstrates considerable progress in cancer prevention, early detection, and treatment. More effective tobacco-cessation programs are necessary to reduce lung and bronchus cancer mortality among women and sustain the decrease in lung and bronchus cancer mortality among men. Additional programs that deter smoking initiation among adolescents are essential to ensure future decreases in lung and bronchus cancer mortality. Continued research in primary prevention, screening methods, and therapeutics is needed to further reduce disparities and improve quality of life and survival among all populations.


Next-generation sequencing identified genomic region and diagnostic markers for resistance to bacterial wilt on chromosome B02 in peanut (Arachis hypogaea L.).
Bacterial wilt, caused by Ralstonia solanacearum, is a devastating disease affecting over 350 plant species. A few peanut cultivars were found to possess stable and durable bacterial wilt resistance (BWR). Genomics-assisted breeding can accelerate the process of developing resistant cultivars by using diagnostic markers. Here, we deployed sequencing-based trait mapping approach, QTL-seq, to discover genomic regions, candidate genes and diagnostic markers for BWR in a recombination inbred line population (195 progenies) of peanut. The QTL-seq analysis identified one candidate genomic region on chromosome B02 significantly associated with BWR. Mapping of newly developed single nucleotide polymorphism (SNP) markers narrowed down the region to 2.07 Mb and confirmed its major effects and stable expressions across three environments. This candidate genomic region had 49 nonsynonymous SNPs affecting 19 putative candidate genes including seven putative resistance genes (R-genes). Two diagnostic markers were successfully validated in diverse breeding lines and cultivars and could be deployed in genomics-assisted breeding of varieties with enhanced BWR.


Plasmablast, Memory B Cell, CD4+ T Cell, and Circulating Follicular Helper T Cell Responses to a Non-Replicating Modified Vaccinia Ankara Vaccine.
Background: Vaccinia is known to induce antibody and cellular responses. Plasmablast, circulating follicular helper T (cTFH) cells, cytokine-expressing CD4 T cells, and memory B cells were compared between subcutaneous (SC) and needle-free jet injection (JI) recipients of non-replicating modified vaccinia Ankara (MVA) vaccine. Methods: Vaccinia-naïve adults received MVA SC or by JI on Days 1 and 29. Vaccinia-specific antibodies were quantified by plaque reduction neutralization test (PRNT) and enzyme-linked immunosorbent assay. Plasmablast, cTFH, and cytokine-expressing CD4 T cells were assessed on Days 1, 8, 15, 29, 36, 43 (cTFH and CD4+ only) and 57. Memory B cells were measured on Days 1 and 57. Results: Of the 36 enrolled subjects, only 22 received both vaccinations and had evaluable specimens after the second vaccine. Plasmablasts peaked one week after each vaccine. Day 15 plasmablasts correlated with peak PRNT titers. cTFH peaked on Days 8 and 36 and correlated with Day 36 plasmablasts. CD4+ peaked at Day 29 and one-third produced ≥2 cytokines. Day 57 memory B cells ranged from 0.1% to 0.17% of IgG-secreting B cells. Conclusions: This study provides insights into the cellular responses to non-replicating MVA, currently used as a vector for a variety of novel vaccines.


Gold Humanism Honor Society Election and Academic Outcomes: A 10-Institution Study.
This study examines relationships among election to the Gold Humanism Honor Society (GHHS) and election to Alpha Omega Alpha (AOA), class rank, and residency selection to determine if GHHS members are more likely to select primary care residencies than students not elected to GHHS membership. We evaluated five graduating classes (2006--2010) at 10 medical schools (n=5,481 students). Residency selections were grouped into primary care (family medicine, internal medicine, pediatrics, OB-GYN), surgery (including surgical specialties), or E-ROAD and other (including lifestyle practices-emergency medicine, radiology, ophthalmology, anesthesiology, and dermatology plus all other specialties, eg, neurology, pathology). A higher proportion of GHHS members were attracted to primary care compared to non-GHHS members (54.3% versus 44.5%). Additional comparisons between GHHS and non-GHHS members demonstrated that 33.1% of GHHS members matched into E-ROAD and other residencies, while 40.9% of non-GHHS went into one of these specialties. Fewer GHHS members chose general surgery or a surgical sub-specialty (12.6% versus 14.6%). More GHHS members were elected into AOA (30.3% versus 14.0%). Further, a far greater proportion of dual AOA/GHHS members elect family medicine residency versus AOA members not elected to GHHS. In addition, GHHS members had slightly higher mean scores on USMLE Step 1 and 2 CK (Clinical Knowledge) and mean class rank. This study demonstrates that students elected into the GHHS as an aggregate group tend to be academically higher achieving when compared to their non-GHHS peers and gravitate to a higher degree toward primary care and specifically to family medicine.


Exercise treadmill testing is a poor predictor of anatomic restenosis after angioplasty for acute myocardial infarction.
This study evaluated whether an exercise treadmill test could predict restenosis in 289 patients 6 months after a successful emergency angioplasty of the infarct-related artery for acute myocardial infarction. After excluding those with interim interventions (64), medical events (36), or medical contraindications to follow-up testing (25), both a treadmill test and a cardiac catheterization were completed in 144 patients, 88% of those eligible for this assessment. Four patients with left bundle branch block or pacemaker rhythm at the time of treadmill testing were also excluded from analysis. Of six follow-up clinical and treadmill variables examined by multivariable logistic regression analysis, only exercise ST deviation was independently correlated with restenosis at follow-up (chi 2 = 5, p = 0.02). The clinical diagnosis of angina at follow-up, although marginally related to restenosis when considered by itself (p = 0.04), did not add significant information once ST deviation was known. The sensitivity of ST deviation of 0.10 mV or greater for detecting restenosis was only 24% (13 of 55 patients), and the specificity was 88% (75 of 85 patients). The sensitivity of exercise-induced ST deviation for detection of restenosis was not affected by extent or severity of wall motion abnormalities at follow-up, by the timing of thrombolytic therapy or of angioplasty, or by the presence of collateral blood flow at the time of acute angiography. A second multivariable analysis evaluating the association of the same variables with number of vessels with significant coronary disease at the 6-month catheterization found an association with both exercise ST deviation (p = 0.003) and exercise duration (p = 0.04). Angina symptoms and exercise treadmill test results in this population had limited value for predicting anatomic restenosis 6 months after emergency angioplasty for acute myocardial infarction.


Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up.
Further assessment of the long-term risk of breast cancer associated with diethylstilbestrol (DES) during pregnancy. Follow-up continuation through June 1, 1989, of a historical cohort of DES-exposed and unexposed mothers ascertained by review of obstetric records. Totals of 3029 each of DES-exposed and unexposed mothers who had delivered live babies at four centers in the United States during 1940 through 1960. Questionnaires were returned for 92.6% of the DES-exposed and 88.8% of the unexposed women. Breast cancer incidence and mortality assessed from returned questionnaires and review of medical records and death certificates. The relative rate of breast cancer associated with DES exposure, after adjustment for demographic and reproductive variables, was 1.35 (95% confidence interval, 1.05 to 1.74). For 30 years or more following exposure, the relative rate was not appreciably higher (relative rate, 1.33; 95% confidence interval, 0.95 to 1.87) than that in earlier periods. Surveillance and increased detection seemed unlikely explanations for the increased risk, since DES-exposed women had excesses of both large and small breast cancers and the two cohorts reported similar breast cancer detection practices. A history of miscarriage before first term delivery was not associated with breast cancer occurrence. Exposure to DES during pregnancy is associated with a modest but statistically significant increased risk of breast cancer. Contrary to prior indications, the risk does not appear to increase greatly over time. The findings are sufficient to exclude the possibility of a doubling of risk for the period of 30 or more years following exposure.


An attenuation of the 'normal' category effect in patients with Alzheimer's disease: a review and bootstrap analysis.
There is a consensus that Alzheimer's disease (AD) impairs semantic information, with one of the first markers being anomia i.e. an impaired ability to name items. Doubts remain, however, about whether this naming impairment differentially affects items from the living and nonliving knowledge domains. Most studies have reported an impairment for naming living things (e.g. animals or plants), a minority have found an impairment for nonliving things (e.g. tools or vehicles), and some have found no category-specific effect. A survey of the literature reveals that this lack of agreement may reflect a failure to control for intrinsic variables (such as familiarity) and the problems associated with ceiling effects in the control data. Investigating picture naming in 32 AD patients and 34 elderly controls, we used bootstrap techniques to deal with the abnormal distributions in both groups. Our analyses revealed the previously reported impairment for naming living things in AD patients and that this persisted even when intrinsic variables were covaried; however, covarying control performance eliminated the significant category effect. Indeed, the within-group comparison of living and nonliving naming revealed a larger effect size for controls than patients. We conclude that the category effect in Alzheimer's disease is no larger than is expected in the healthy brain and may even represent a small diminution of the normal profile.


What facilitates or impedes family communication following genetic testing for cancer risk? A systematic review and meta-synthesis of primary qualitative research.
To systematically review and meta-synthesise primary qualitative research findings regarding family communication following genetic testing of cancer risk, in order to inform development of effective interventions. Systematic searches of CINAHL, Embase, Medline, British Nursing Index and PsycINFO databases were undertaken and relevant studies identified using strict criteria. The selected primary qualitative studies were appraised for quality and relevance by three independent researchers and then synthesized using a "Framework" approach. Fourteen (4.3%) studies met the inclusion criteria. The following factors influenced family communication following genetic testing for late-onset hereditary cancer: the informant's feelings about informing relatives about genetic testing; the perceived relevance of the information to other family members and their anticipated reactions; the "closeness" of relationships within the family; family rules and patterns (e.g., who is best placed to share information with whom); finding the right time and level of disclosure; and the supportive role of heath care professionals. The themes identified in this review could provide practitioners with a useful framework for discussing family communication with those undergoing genetic testing. This framework focuses on helping health care professionals to facilitate family communication. The next step will be the development of an intervention to directly support people in talking to their relatives.


The half-life of endogenous insulin and C-peptide in man assessed by somatostatin suppression.
The in-vivo half-lives of insulin and C-peptide have been assessed in normal man by a method which examines the decline of endogenously produced insulin and C-peptide after somatostatin suppression of secretion. Venous blood samples were taken each minute from seven normal subjects: i.v. glucose (0.1 g/kg ideal body weight) was given over 1 min to stimulate secretion, followed by a bolus of 250 micrograms of somatostatin-14 and an infusion of a further 250 micrograms somatostatin-14 over the subsequent 30 min. Plasma samples were analysed for C-peptide, glucose and insulin. The initial mono-exponential half-lives over 8 min were 3.9 +/- 0.3 and 10.2 +/- 0.7 min respectively (mean +/- SEM), with subsequent slower declines. Log transformed insulin and C-peptide yielded biphasic declinations which were assessed by a two-pool model. The rate constant of clearance of insulin implied avid uptake, while the kinetics of C-peptide clearance were slower, and irreversible loss might be explained by glomerular filtration alone. The somatostatin suppression method of measuring hormone kinetics could be used for newly described hormones which are not available for in-vivo studies.


Is early passive motion exercise necessary after arthroscopic rotator cuff repair?
Early passive motion exercise has been the standard rehabilitation protocol after rotator cuff repair for preventing postoperative stiffness. However, recent approaches show that longer immobilization may enhance tendon healing and quality. To elucidate whether early passive motion exercise affects functional outcome and tendon healing after arthroscopic rotator cuff repair. Randomized controlled trial; Level of evidence, 1. One hundred five consecutive patients who underwent arthroscopic repair for small to medium-sized full-thickness rotator cuff tears were included. Patients with large to massive tears and concomitant stiffness or labral lesions were excluded. Patients were instructed to wear an abduction brace for 4 to 5 weeks after surgery and to start active-assisted shoulder exercise after brace weaning. Fifty-six patients were randomly allocated into group 1: early passive motion exercises were conducted 3 to 4 times per day during the abduction brace-wearing period. Forty-nine patients were allocated into group 2: no passive motion was allowed during the same period. Range of motion (ROM) and visual analog scale (VAS) for pain were measured preoperatively and 3, 6, and 12 months postoperatively. Functional evaluations, including Constant score, Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) score, were also evaluated at 6 and 12 months postoperatively. Ultrasonography, magnetic resonance imaging, or computed tomography arthrography was utilized to evaluate postoperative cuff healing. There were no statistical differences between the 2 groups in ROM or VAS for pain at each time point. Functional evaluations were not statistically different between the 2 groups either. The final functional scores assessed at 12 months for groups 1 and 2 were as follows: Constant score, 69.81 ± 3.43 versus 69.83 ± 6.24 (P = .854); SST, 9.00 ± 2.12 versus 9.00 ± 2.59 (P = .631); and ASES score, 73.29 ± 18.48 versus 82.90 ± 12.35 (P = .216). Detachment of the repaired cuff was identified in 12% of group 1 and 18% of group 2 (P = .429). Early passive motion exercise after arthroscopic cuff repair did not guarantee early gain of ROM or pain relief but also did not negatively affect cuff healing. We suggest that early passive motion exercise is not mandatory after arthroscopic repair of small to medium-sized full-thickness rotator cuff tears, and postoperative rehabilitation can be modified to ensure patient compliance.


Integrated hydraulic modelling of water supply and urban drainage networks for assessment of decentralized options.
The impact of climate change, water scarcity, land use change, population growth and also population shrinking can only be predicted with uncertainties. Especially for assets with a long planning horizon this is a critical part for planning and design. One solution is to make centralized organized water infrastructure with a long-planning horizon resilient and adaptive. For existing centralized infrastructure such a transition would be to increasingly implement decentralized measures. But such a transition can cause severe impacts on existing centralized infrastructure. Low flow conditions in urban drainage systems can cause sediment deposition, and for water supply systems water age problems may occur. This work focuses on city-scale analysis for assessing the impact of such measures. For that a coupled model for integrated city-scale analysis is applied and further developed. In addition, a geographic information system (GIS)-based approach for sensitivity analysis is enhanced and also implemented in that model. The developed approach is applied to assess the water infrastructure of an alpine case study. With the obtained results it is demonstrated how the planning process is enhanced by indicating where and where not to implement decentralized measures in an existing water infrastructure.


Procedures for location of non-palpable breast lesions: a systematic review for the radiologist.
Accurate location of small breast lesions is mandatory for proper surgical management. The purpose of this article is systematically review procedures used to locate non-palpable breast lesions, including a description of the current status, advantages, and disadvantages for each technique. A total of 47 articles were finally included: 7 articles for the wire location technique, 5 articles for the radioguided location technique, 13 articles that compare wire location with radioguided location, 3 articles for the carbon location technique, 2 articles that compare wire location with carbon location, and 17 articles for the clip location technique. The success of location and the clear margin are reported for each location technique and for the separate articles included; clip migration shift, also, is reported for the clip location technique. Odds ratio with related 95 % confidence intervals were also calculated for successful location. Comparative analysis or meta-analysis for all the different breast lesion location techniques is missing. Prospective investigations and randomized investigations for homogeneous populations are still needed to determine which is the most cost-effective modality among those used to date.


Receptor-mediated activation of heterotrimeric G-proteins: current structural insights.
G-protein-coupled receptors (GPCRs) serve as catalytic activators of heterotrimeric G-proteins (Galphabetagamma) by exchanging GTP for the bound GDP on the Galpha subunit. This guanine nucleotide exchange factor activity of GPCRs is the initial step in the G-protein cycle and determines the onset of various intracellular signaling pathways that govern critical physiological responses to extracellular cues. Although the structural basis for many steps in the G-protein nucleotide cycle have been made clear over the past decade, the precise mechanism for receptor-mediated G-protein activation remains incompletely defined. Given that these receptors have historically represented a set of rich drug targets, a more complete understanding of their mechanism of action should provide further avenues for drug discovery. Several models have been proposed to explain the communication between activated GPCRs and Galphabetagamma leading to the structural changes required for guanine nucleotide exchange. This review is focused on the structural biology of G-protein signal transduction with an emphasis on the current hypotheses regarding Galphabetagamma activation. We highlight several recent results shedding new light on the structural changes in Galpha that may underlie GDP release.


Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation.
A classical twin study was performed to assess the relative contribution of genetic and environmental factors to bone metabolism, calcium homeostasis, and the hormones regulating them. It was examined further whether the genetic effect is menopause dependent. The subjects were 2136 adult twins (98.3% female): 384 monozygotic (MZ) and 684 dizygotic (DZ) twin pairs. The intraclass correlations were calculated, and maximum likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in MZ twin pairs. The heritabilities (95% CIs) obtained from model fitting for hormones regulating bone metabolism and calcium homeostasis were parathyroid hormone (PTH), 60% (54-65%); 25-hydroxyvitamin D [25(OH)D]; 43% (28-57%), 1,25-hydroxyvitamin D [1,25(OH)], 65% (53-74%); and vitamin D binding protein 62% (56-66%). The heritabilities (95% CIs) for markers of bone formation also were assessed; bone-specific alkaline phosphatase (BSAP), 74% (67-80%), and osteocalcin, 29% (14-44%); marker of bone resorption deoxypyridinoline (DPD), 58% (52-64%); and measure of calcium homeostasis 24 h urine calcium, creatinine (Cr), 52% (41-61%). The magnitude of genetic influence differed with menopause for most variables. This study provides evidence for the importance of genetic factors in determining bone resorption and formation, calcium excretion, and the hormones regulating these processes. It shows for the first time a clear genetic effect on bone resorption in premenopausal women and the regulation of PTH, vitamin D metabolism, and calcium excretion. The genes controlling bone hormones and markers are likely to be useful therapeutic and diagnostic targets.


Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2.
Sphingolipid-metabolizing enzymes control the dynamic balance of the cellular levels of important bioactive lipids, including the apoptotic compound ceramide and the proliferative compound sphingosine 1-phosphate (S1P). Many growth factors and inflammatory cytokines promote the cleavage of sphingomyelin and ceramide leading to rapid elevation of S1P levels through the action of sphingosine kinases (SK1 and SK2). SK1 and SK2 are overexpressed in a variety of human cancers, making these enzymes potential molecular targets for cancer therapy. We have identified an aryladamantane compound, termed ABC294640 [3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide], that selectively inhibits SK2 activity in vitro, acting as a competitive inhibitor with respect to sphingosine with a K(i) of 9.8 muM, and attenuates S1P formation in intact cells. In tissue culture, ABC294640 suppresses the proliferation of a broad panel of tumor cell lines, and inhibits tumor cell migration concomitant with loss of microfilaments. In vivo, ABC294640 has excellent oral bioavailability, and demonstrates a plasma clearance half-time of 4.5 h in mice. Acute and chronic toxicology studies indicate that ABC294640 induces a transient minor decrease in the hematocrit of rats and mice; however, this normalizes by 28 days of treatment. No other changes in hematology parameters, or gross or microscopic tissue pathology, result from treatment with ABC294640. Oral administration of ABC294640 to mice bearing mammary adenocarcinoma xenografts results in dose-dependent antitumor activity associated with depletion of S1P levels in the tumors and progressive tumor cell apoptosis. Therefore, this newly developed SK2 inhibitor provides an orally available drug candidate for the treatment of cancer and other diseases.


[Amenable mortality in Germany: spatial distribution and regional concentrations].
The aim of this study is to identify small areas in Germany burdened by exceptionally high rates of amenable mortality using the 439 counties as unit of analysis. To overcome shortcomings of conventional mortality measures, we construct an indicator for amenable mortality (AM) which captures deaths that should not occur given current medical knowledge and technology. We age-standardize individual-level data on mortality for the years 2000-2004 and plot the distribution of disease-specific AM on country maps. We consider deaths following ischaemic heart disease, cerebrovascular diseases, hypertension, diseases of the liver, traffic accidents, several cancer types and 24 other diseases that are classified as amenable to health care. The data is taken from the causes-of-death statistics (provided by Destatis). AM significantly differs between small areas within and between German federal states (Bundeslaender). Breast cancer and lung cancer in men are the most common AM-causes in Germany. The often discussed mortality-gap between East and West Germany is predominantly driven by differences in amenable deaths following cardiovascular diseases. However, the maps of most carcinogenic deaths show a north-south gradient rather than an east-west difference.


Metabolic Tissue Swelling and Local Microcirculation in Splanchnic Artery Occlusion Shock: Implications for Critical Illness.
Trauma is a leading cause of death in the US. Advancements in shock resuscitation have been disappointing because the correct upstream mechanisms of injury are not being targeted. Recently, significant advancements have been shown using new cell impermeant molecules that work by transferring metabolic water from swollen ischemic cells to the capillary, which restores tissue perfusion by microcirculatory decompression. The rapid normalization of oxygen transfer improves resuscitation outcomes. Since poor resuscitation and perfusion of trauma patients also causes critical illness and sepsis, and can be mimicked by ischemia-reperfusion of splanchnic tissues, we hypothesized that inadequate oxygenation of the gut during trauma drives development of later shock and critical illness. We further hypothesized that this is caused by ischemia-induced water shifts causing compression no-reflow. To test this, the superior mesenteric artery (SMA) of juvenile anesthetized swine was occluded for 30 minutes followed by 8 hours of reperfusion to induce mild splanchnic artery occlusion (SAO) shock. One group received the impermeant polyethylene glycol 20,000 (PEG-20k) that prevents metabolic cell swelling, and the other a lactated Ringers vehicle. Survival doubled in PEG-20k treated swine along with improved macro-hemodynamics and intestinal mucosal perfusion. Villus morphometry and plasma inflammatory cytokines normalized with impermeants. Plasma endotoxin rose over time after reperfusion and impermeants abolished the rise. Inert osmotically active cell impermeants like PEG-20k improve intestinal reperfusion injury, SAO shock, and early signs of sepsis, which may be due to early restoration of mucosal perfusion and preservation of the septic barrier by reversal of ischemic compression no-reflow. Significance Statement Significant advancements in treating shock and ischemia have been disappointing because the correct upstream causes have not been targeted. This study supports that poor tissue perfusion after intestinal ischemia from shock is caused by capillary compression no-reflow secondary to metabolic cell and tissue swelling, since selectively targeting this issue with novel PEG-20k based cell impermeant IV solutions reduces splanchnic artery occlusion shock, doubles survival time, restores tissue micro-perfusion, and preserves gut barrier function.


Aspergillus spp. invasive external otitis: favourable outcome with a medical approach.
Aspergillus spp. invasive external otitis (IEO) is a rare infection. We performed a seven-year, single-centre retrospective study from 2007 to 2014 including all patients with proven Aspergillus spp. IEO. Twelve patients were identified. All patients had a poorly controlled diabetes mellitus and one underwent solid organ transplant. The most frequently isolated species was Aspergillus flavus (n = 10) and voriconazole was the first-line therapy in all cases, with a median length of treatment of 338.5 days (158-804 days). None of the patients underwent extensive surgery. The clinical outcome was excellent. However, otological sequelae were reported, including hearing impairment (n = 7) and facial palsy (n = 3).


Organization of multisynaptic inputs to the dorsal and ventral dentate gyrus: retrograde trans-synaptic tracing with rabies virus vector in the rat.
Behavioral, anatomical, and gene expression studies have shown functional dissociations between the dorsal and ventral hippocampus with regard to their involvement in spatial cognition, emotion, and stress. In this study we examined the difference of the multisynaptic inputs to the dorsal and ventral dentate gyrus (DG) in the rat by using retrograde trans-synaptic tracing of recombinant rabies virus vectors. Three days after the vectors were injected into the dorsal or ventral DG, monosynaptic neuronal labeling was present in the entorhinal cortex, medial septum, diagonal band, and supramammillary nucleus, each of which is known to project to the DG directly. As in previous tracing studies, topographical patterns related to the dorsal and ventral DG were seen in these regions. Five days after infection, more of the neurons in these regions were labeled and labeled neurons were also seen in cortical and subcortical regions, including the piriform and medial prefrontal cortices, the endopiriform nucleus, the claustrum, the cortical amygdala, the medial raphe nucleus, the medial habenular nucleus, the interpeduncular nucleus, and the lateral septum. As in the monosynaptically labeled regions, a topographical distribution of labeled neurons was evident in most of these disynaptically labeled regions. These data indicate that the cortical and subcortical inputs to the dorsal and ventral DG are conveyed through parallel disynaptic pathways. This second-order input difference in the dorsal and ventral DG is likely to contribute to the functional differentiation of the hippocampus along the dorsoventral axis.


Macaques vaccinated with simian immunodeficiency virus SIVmac239Delta nef delay acquisition and control replication after repeated low-dose heterologous SIV challenge.
An effective human immunodeficiency virus (HIV) vaccine will likely need to reduce mucosal transmission and, if infection occurs, control virus replication. To determine whether our best simian immunodeficiency virus (SIV) vaccine can achieve these lofty goals, we vaccinated eight Indian rhesus macaques with SIVmac239Delta nef and challenged them intrarectally (i.r.) with repeated low doses of the pathogenic heterologous swarm isolate SIVsmE660. We detected a significant reduction in acquisition of SIVsmE660 in comparison to that for naïve controls (log rank test; P = 0.023). After 10 mucosal challenges, we detected replication of the challenge strain in only five of the eight vaccinated animals. In contrast, seven of the eight control animals became infected with SIVsmE660 after these 10 challenges. Additionally, the SIVsmE660-infected vaccinated animals controlled peak acute virus replication significantly better than did the naïve controls (Mann-Whitney U test; P = 0.038). Four of the five SIVsmE660 vaccinees rapidly brought virus replication under control by week 4 postinfection. Unfortunately, two of these four vaccinated animals lost control of virus replication during the chronic phase of infection. Bulk sequence analysis of the circulating viruses in these animals indicated that recombination had occurred between the vaccine and challenge strains and likely contributed to the increased virus replication in these animals. Overall, our results suggest that a well-designed HIV vaccine might both reduce the rate of acquisition and control viral replication.


Investigating the Effects of Particulate Matter on House Dust Mite and Ovalbumin Allergic Airway Inflammation in Mice.
Particulate matter (PM), a component of air pollution, has been shown to enhance allergen-mediated airway hypersensitivity and inflammation. Surprisingly, exposure to PM during the sensitization to allergen is sufficient to produce immunological changes that result in heightened inflammatory effects upon future allergen exposures (challenge) in the absence of PM. This suggests that PM has the ability to modulate the allergic immune response, thereby acting as an adjuvant by enhancing the immunological memory formed during the adaptive immune response; however, the mechanisms through which this occurs remain elusive. Establishing a reproducible animal model to study the PM-mediated immunotoxicological effects that enhance allergy, may provide insights to understand how air pollution activates the immune system and thereby modulates the pathophysiology of asthma. The basic protocol can be used to study various characteristics of air pollution, such as PM size, source, or chemical composition, to help elucidate how such features may affect the allergic response in a mouse model of asthma. Using a BALB/c model of acute exposure (14 days), mice are first sensitized with allergen and PM, and then subsequently challenged with allergen only. The endpoints of this basic protocol include the assessment of inflammation via cells recovered from broncho-alveolar lavage (BAL), histopathological analysis, gene expression profiles, and protein quantification of inflammatory markers. © 2016 by John Wiley & Sons, Inc.


Daily high-frequency transcranial random noise stimulation of bilateral temporal cortex in chronic tinnitus - a pilot study.
Several studies emphasized the potential of single and multiple transcranial random noise stimulation (tRNS) sessions to interfere with auditory cortical activity and to reduce tinnitus loudness. It was the objective of the present study to evaluate the use of high-frequency (hf) tRNS in a one-arm pilot study in patients with chronic tinnitus. Therefore, 30 patients received 10 sessions of high frequency tRNS (100-640 Hz; 2 mA; 20 minutes) over the bilateral temporal cortex. All patients had received rTMS treatment for their tinnitus at least 3 months before tRNS. Primary outcome was treatment response (tinnitus questionnaire reduction of ≥5 points). The trial was registered at clinicaltrials.gov (NCT01965028). Eight patients (27%) responded to tRNS. Exactly the same number of patients had responded before to rTMS, but there were only two "double responders" for both treatments. None of the secondary outcomes (tinnitus numeric rating scales, depressivity, and quality of life) was significant when results were corrected for multiple comparisons. tRNS treatment was accompanied by tolerable side effects but resulted in temporal increases in tinnitus loudness in 20% of the cases (2 drop-outs). Our trial showed that hf-tRNS is feasible for daily treatment in chronic tinnitus. However, summarizing low treatment response, increase of tinnitus loudness in 20% of patients and missing of any significant secondary outcome, the use of hf-tRNS as a general treatment for chronic tinnitus cannot be recommended at this stage. Differences in treatment responders between tRNS and rTMS highlight the need for individualized treatment procedures.


Characterization of yeast protein Deg1 as pseudouridine synthase (Pus3) catalyzing the formation of psi 38 and psi 39 in tRNA anticodon loop.
The enzymatic activity of yeast gene product Deg1 was identified using both disrupted yeast strain and cloned recombinant protein expressed in yeast and in Escherichia coli. The results show that the DEG1-disrupted yeast strain lacks synthase activity for the formation of pseudouridines psi 38 and psi 39 in tRNA whereas the other activities, specific for psi formation at positions 13, 27, 28, 32, 34, 35, 36, and 55 in tRNA, remain unaffected. Also, the His6-tagged recombinant yeast Deg1p expressed in E. coli as well as a protein fusion with protein A in yeast display the enzymatic activity only toward psi 38 and psi 39 formation in different tRNA substrates. Therefore, Deg1p is the third tRNA:pseudouridine synthase (Pus3p) characterized so far in yeast. Disruption of the DEG1 gene is not lethal but reduces considerably the yeast growth rate, especially at an elevated temperature (37 degrees C). Deg1p localizes both in the nucleus and in the cytoplasm, as shown by immunofluorescence microscopy. Identification of the pseudouridine residues present (or absent) in selected naturally occurring cytoplasmic and mitochondrial tRNAs from DEG1-disrupted strain points out a common origin of psi 38- and psi 39-synthesizing activity in both of these two cellular compartments. The sensitivity of Pus3p (Deg1p) activity to overall three-dimensional tRNA architecture and to a few individual mutations in tRNA was also studied. The results indicate the existence of subtle differences in the tRNA recognition by yeast Pus3p and by its homologous tRNA:pseudouridine synthase truA from E. coli (initially called hisT or PSU-I gene product).


Carcass Characteristics and Meat Quality of Swamp Buffaloes (Bubalus bubalis) Fattened at Different Feeding Intensities.
Twenty-four male 1-year old swamp buffaloes (Bubalus bubalis) were randomly allocated to 4 groups. One group grazed on guinea grass (GG) and another on guinea grass and the legume Stylosanthes guianensis (GL). The other two groups were kept in pens and fed freshly cut guinea grass and concentrate at an amount of 1.5% (GC1.5) and 2.0% (GC2.0) of body weight, respectively. The effect of the different feeding intensities on carcass characteristics and meat quality were assessed. The mean body weight at slaughter was 398 (±16) kg. Average daily gain was higher in concentrate-supplemented groups (570 and 540 g/d in GC1.5 and GC2.0, respectively) when compared to GG (316 g/d) and GL (354 g/d) (p<0.01). Likewise, the warm carcass weight was higher in GC1.5 and GC2.0 compared to GG and GL. Dressing percentage was 48.1% and 49.5% in GC1.5 and GC2.0 in comparison to 42.9% and 44.8% observed in GG and GL, respectively. Meat of Longissimus throracis from GC1.5 and GC2.0 was redder in color (p<0.01), while water holding capacity (drip and thawing loss) was improved in pasture-fed groups (p<0.05). Protein and fat content of Longissimus thoracis was higher in animals supplemented with concentrate (p<0.01), as was cholesterol content (p<0.05), whereas PUFA:SFA ratio was higher and n-6/n-3 ratio lower (p<0.01) in pasture-fed buffaloes. Results of the present study showed that the supplementation of pasture with concentrate enhances the growth and carcass characteristics of swamp buffaloes expressed in superior dressing percentage, better muscling, and redder meat with a higher content of protein and fat, whereas animals grazing only on pasture had a more favorable fatty acid profile and water holding capacity. In conclusion, the supplementation of concentrate at a rate of about 1.5% of body weight is recommended to improve the performance and carcass quality of buffaloes.


Low-temperature chemistry using the R-matrix method.
Techniques for producing cold and ultracold molecules are enabling the study of chemical reactions and scattering at the quantum scattering limit, with only a few partial waves contributing to the incident channel, leading to the observation and even full control of state-to-state collisions in this regime. A new R-matrix formalism is presented for tackling problems involving low- and ultra-low energy collisions. This general formalism is particularly appropriate for slow collisions occurring on potential energy surfaces with deep wells. The many resonance states make such systems hard to treat theoretically but offer the best prospects for novel physics: resonances are already being widely used to control diatomic systems and should provide the route to steering ultracold reactions. Our R-matrix-based formalism builds on the progress made in variational calculations of molecular spectra by using these methods to provide wavefunctions for the whole system at short internuclear distances, (a regime known as the inner region). These wavefunctions are used to construct collision energy-dependent R-matrices which can then be propagated to give cross sections at each collision energy. The method is formulated for ultracold collision systems with differing numbers of atoms.


Primary structures and partial toxicological characterization of two phospholipases A2 from Micrurus mipartitus and Micrurus dumerilii coral snake venoms.
Snake venom phospholipases A2 (PLA2) share high sequence identities and a conserved structural scaffold, but show important functional differences. Only a few PLA2s have been purified and characterized from coral snake (Micrurus spp.) venoms, and their role in envenomation remains largely unknown. In this report, we describe the isolation, sequencing and partial functional characterization of two Micrurus PLA2s: MmipPLA2 from Micrurus mipartitus and MdumPLA2 from Micrurus dumerilii, two species of clinical importance in Colombia. MmipPLA2 consisted of 119 amino acid residues with a predicted pI of 8.4, whereas MdumPLA2 consisted of 117 residues with a pI of 5.6. Both PLA2s showed the conserved 'group I' cysteine pattern and were enzymatically active, although MdumPLA2 had higher activity. The two enzymes differed notably in their toxicity, with MmipPLA2 being highly lethal to mice and mildly myotoxic, whereas MdumPLA2 was not lethal (up to 3 μg/g body weight) but strongly myotoxic. MdumPLA2 displayed higher anticoagulant activity than MmipPLA2in vitro and caused more sustained edema in the mouse footpad assay. Neither of these enzymes was cytolytic to cultured skeletal muscle C2C12 myotubes. Based on their structural differences, the two enzymes were placed in separate lineages in a partial phylogeny of Micrurus venom PLA2s and this classification agreed with their divergent biological activities. Overall, these findings highlight the structural and functional diversity of Micrurus venom PLA2s.


Stand Out in Class: restructuring the classroom environment to reduce sedentary behaviour in 9-10-year-olds - study protocol for a pilot cluster randomised controlled trial.
Sedentary behaviour (sitting) is a highly prevalent negative health behaviour, with individuals of all ages exposed to environments that promote prolonged sitting. Excessive sedentary behaviour adversely affects health in children and adults. As sedentary behaviour tracks from childhood into adulthood, the reduction of sedentary time in young people is key for the prevention of chronic diseases that result from excessive sitting in later life. The sedentary school classroom represents an ideal setting for environmental change, through the provision of sit-stand desks. Whilst the use of sit-stand desks in classrooms demonstrates positive effects in some key outcomes, evidence is currently limited by small samples and/or short intervention durations, with few studies adopting randomised controlled trial (RCT) designs. This paper describes the protocol of a pilot cluster RCT of a sit-stand desk intervention in primary school classrooms. A two-arm pilot cluster RCT will be conducted in eight primary schools (four intervention, four control) with at least 120 year 5 children (aged 9-10 years). Sit-stand desks will replace six standard desks in the intervention classrooms. Teachers will be encouraged to ensure all pupils are exposed to the sit-stand desks for at least 1 h/day on average using a rotation system. Schools assigned to the control arm will continue with their usual practice, no environmental changes will be made to their classrooms. Measurements will be taken at baseline, before randomisation, and at the end of the schools' academic year. In this study, the primary outcomes of interest will be school and participant recruitment and attrition, acceptability of the intervention, and acceptability and compliance to the proposed outcome measures (including activPAL-measured school-time and school-day sitting, accelerometer-measured physical activity, adiposity, blood pressure, cognitive function, academic progress, engagement, and behaviour) for inclusion in a definitive trial. A full process evaluation and an exploratory economic evaluation will also be conducted to further inform a definitive trial. The primary output of this study will be acceptability data to inform the development of a definitive cluster RCT designed to examine the efficacy of this intervention on health- and education-related outcomes in UK primary school children. ISRCTN12915848 (retrospectively registered, date registered 9 November 2016).


Paraneoplastic Leukemoid Reaction in Gastroesophageal Junction Adenocarcinoma: A Case Report.
BACKGROUND The presence of leukocytosis associated with non-hematological malignancy after ruling out other causes is defined as paraneoplastic leukemoid reaction (PLR). PLR is a rare manifestation of various solid tumors. It is associated with poor prognosis unless receiving effective antineoplastic treatments. CASE REPORT A 72-year-old female was referred to a hematologist/oncologist for the evaluation of leukocytosis with neutrophilia. Initial workup was unremarkable; however, she had progressively worsening leukocytosis with neutrophilia, associated with severe anemia and dysphagia. Computed tomography (CT) scan revealed wall thickening at the gastroesophageal junction (GEJ) and multiple hypodensities of the liver. Esophagogastroduodenoscopy (EGD) confirmed the diagnosis of GEJ tumor and biopsy returned as adenocarcinoma with human epidermal growth factor receptor 2 (HER2) overexpression. Leukocytosis resolved after the first round of chemotherapy and the patient remains progression-free with the addition of trastuzumab to her chemotherapy regimen. CONCLUSIONS We report a rare case of PLR caused by GEJ adenocarcinoma. This is the first case of PLR in a patient with metastatic GEJ adenocarcinoma with HER2 overexpression in the Caucasian population. It is important to workup leukocytosis promptly, to keep malignancy in the differential diagnosis and to seek early hematology/oncology consultation.


Lineage-specific gene expansions in bacterial and archaeal genomes.
Gene duplication is an important mechanistic antecedent to the evolution of new genes and novel biochemical functions. In an attempt to assess the contribution of gene duplication to genome evolution in archaea and bacteria, clusters of related genes that appear to have expanded subsequent to the diversification of the major prokaryotic lineages (lineage-specific expansions) were analyzed. Analysis of 21 completely sequenced prokaryotic genomes shows that lineage-specific expansions comprise a substantial fraction (approximately 5%-33%) of their coding capacities. A positive correlation exists between the fraction of the genes taken up by lineage-specific expansions and the total number of genes in a genome. Consistent with the notion that lineage-specific expansions are made up of relatively recently duplicated genes, >90% of the detected clusters consists of only two to four genes. The more common smaller clusters tend to include genes with higher pairwise similarity (as reflected by average score density) than larger clusters. Regardless of size, cluster members tend to be located more closely on bacterial chromosomes than expected by chance, which could reflect a history of tandem gene duplication. In addition to the small clusters, almost all genomes also contain rare large clusters of size > or =20. Several examples of the potential adaptive significance of these large clusters are explored. The presence or absence of clusters and their related genes was used as the basis for the construction of a similarity graph for completely sequenced prokaryotic genomes. The topology of the resulting graph seems to reflect a combined effect of common ancestry, horizontal transfer, and lineage-specific gene loss.


Single nucleotide polymorphisms of the human cyp2a13 gene: evidence for a null allele.
Human CYP2A13 is believed to be important in the metabolic activation of tobacco-specific nitrosamines in the respiratory tract; therefore, genetic polymorphisms of the CYP2A13 gene may be associated with interindividual differences in the risks of tobacco-related tumorigenesis. Our earlier studies identified a frequent single nucleotide polymorphism in CYP2A13 exon 5, Arg257Cys, which led to an approximate 50% decrease in metabolic activities. In the present study, three additional coding region mutations (Arg25Gln, Arg101Stop, and Asp158Glu) and several mutations in the introns and flanking regions were identified in a Chinese patient population. Of particular interest is the Arg101Stop mutation, which was due to a C > T change in exon 2. Thus, individuals homozygous for this nonsense mutation would not have a functional CYP2A13 protein and, therefore, might have reduced sensitivity to xenobiotic toxicity resulting from CYP2A13-mediated metabolic activation in the respiratory tract. The frequencies of the coding region mutations were further examined using random samples of white, black, Hispanic, and Asian newborns from New York. The frequency of the Arg25Gln mutation in Asian newborns (9.6%) was very similar to that found in the Chinese population (10.9%). On the other hand, the Arg101Stop mutation was not detected in 136 newborn samples examined (23 white, 21 black, 19 Hispanic, and 73 Asian), suggesting that this mutation may be unique for the Chinese patient population. Haplotype analysis indicated that the Arg25Gln and Arg257Cys mutations are parts of a common haplotype. However, an additional haplotype that consists of the 25Gln but not the 257Cys allele was also identified.


Surviving a gender-variant childhood: the views of transgender adults on the needs of gender-variant children and their parents.
Adults with gender-variant childhoods have often lived traumatic lives because of the attitudes and limited understanding that people in their environment had of the concept of gender variance. This study explores the childhoods of transgender adults with the aim to understand their gender-related difficulties as children, in order to identify their needs and the needs of their parents at that time. The authors conducted a semi-structured survey with 110 transgender adults in order to explore their retrospective childhood experiences. Responses were analyzed through content and thematic coding. Their needs most commonly identified as children were for educated authority figures; acceptance and support to discuss their gender variance; freedom of identity expression; validation; and recognition. The needs most commonly allocated to their parents were access to information, education to increase other's awareness, peer support, and access to educated professionals.


Integrated molecular, physiological and in silico characterization of two Halomonas isolates from industrial brine.
Two haloalkaliphilic bacteria isolated from industrial brine solutions were characterized via molecular, physiological, and in silico metabolic pathway analyses. Genomes from the organisms, designated Halomonas BC1 and BC2, were sequenced; 16S ribosomal subunit-based phylogenetic analysis revealed a high level of similarity to each other and to Halomonas meridiana. Both strains were moderate halophiles with near optimal specific growth rates (≥60 % μ max) observed over <0.1-5 % (w/v) NaCl and pH ranging from 7.4 to 10.2. Isolate BC1 was further characterized by measuring uptake or synthesis of compatible solutes under different growth conditions; in complex medium, uptake and accumulation of external glycine betaine was observed while ectoine was synthesized de novo in salts medium. Transcriptome analysis of isolate BC1 grown on glucose or citrate medium measured differences in glycolysis- and gluconeogenesis-based metabolisms, respectively. The annotated BC1 genome was used to build an in silico, genome-scale stoichiometric metabolic model to study catabolic energy strategies and compatible solute synthesis under gradients of oxygen and nutrient availability. The theoretical analysis identified energy metabolism challenges associated with acclimation to high salinity and high pH. The study documents central metabolism data for the industrially and scientifically important haloalkaliphile genus Halomonas.


Tocilizumab in patients with adult-onset still's disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial.
To evaluate the efficacy and safety of tocilizumab, an interleukin-6 receptor antibody, in patients with adult-onset Still's disease. In this double-blind, randomised, placebo-controlled phase III trial, 27 patients with adult-onset Still's disease refractory to glucocorticoids were randomised to tocilizumab at a dose of 8 mg/kg or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients received open-label tocilizumab for 40 weeks subsequently. The primary outcome was American College of Rheumatology (ACR) 50 response at week 4. The secondary outcomes included ACR 20/50/70, systemic feature score, glucocorticoid dose and adverse events at each point. In the full analysis set, ACR50 response at week 4 was achieved in 61.5% (95% CI 31.6 to 86.1) in the tocilizumab group and 30.8% (95% CI 9.1 to 61.4) in the placebo group (p=0.24). The least squares means for change in systemic feature score at week 12 were -4.1 in the tocilizumab group and -2.3 in the placebo group (p=0.003). The dose of glucocorticoids at week 12 decreased by 46.2% in the tocilizumab group and 21.0% in the placebo group (p=0.017). At week 52, the rates of ACR20, ACR50 and ACR70 were 84.6%, 84.6% and 61.5%, respectively, in both groups. Serious adverse events in all participants who received one dose of tocilizumab were infections, aseptic necrosis in the hips, exacerbation of adult-onset Still's disease, drug eruption and anaphylactic shock. The study suggests that tocilizumab is effective in adult-onset Still's disease, although the primary endpoint was not met and solid conclusion was not drawn.


Temperature-sensitive hydrogels with SiO2-Au nanoshells for controlled drug delivery.
Silica-gold (SiO(2)-Au) nanoshells are a new class of nanoparticles that consist of a silica dielectric core that is surrounded by a gold shell. These nanoshells are unique because their peak extinctions are very easily tunable over a wide range of wavelengths particularly in the near infrared (IR) region of the spectrum. Light in this region is transmitted through tissue with relatively little attenuation due to absorption. In addition, irradiation of SiO(2)-Au nanoshells at their peak extinction coefficient results in the conversion of light to heat energy that produces a local rise in temperature. Thus, to develop a photothermal modulated drug delivery system, we have fabricated nanoshell-composite hydrogels in which SiO(2)-Au nanoshells of varying concentrations have been embedded within temperature-sensitive hydrogels, for the purpose of initiating a temperature change with light. N-isopropylacrylamide-co-acrylamide (NIPAAm-co-AAm) hydrogels are temperature-sensitive hydrogels that were fabricated to exhibit a lower critical solution temperature (LCST) slightly above body temperature. The resulting composite hydrogels had the extinction spectrum of the SiO(2)-Au nanoshells in which the hydrogels collapsed reversibly in response to temperature (50 degrees C) and laser irradiation. The degree of collapse of the hydrogels was controlled by the laser fluence as well as the concentration of SiO(2)-Au nanoshells. Modulated drug delivery profiles for methylene blue, insulin, and lysozyme were achieved by irradiation of the drug-loaded nanoshell-composite hydrogels, which showed that drug release was dependent upon the molecular weight of the therapeutic molecule.


Focal properties of a plane grating in a convergent beam.
Focusing from a plane grating can be accomplished by using convergent radiation incident on the grating in such a manner that any incident angle alpha(n), the resulting diffraction angle beta(n), will be on the same side of the grating normal. The theory for the focal properties is developed by applying Fermat's principle of least time to selected terms resulting from a finite series expansion of the system's distance function. Derivations are given for finding the focal curve equation, astigmatism, and coma, of the most usable configuration of the optical components. Discussions of the aberrations disclose methods for eliminating the astigmatism and reducing the coma.


Image quality of EOS low-dose radiography in comparison with conventional radiography for assessment of ventriculoperitoneal shunt integrity.
Patients with shunted hydrocephalus often accumulate high levels of radiation over their lifetimes during evaluation of hardware integrity. Current practice involves the use of a series of conventional radiographs for this purpose. Newer low-dose EOS radiography is currently used to evaluate scoliosis but has not been explored to evaluate shunt integrity on a large scale. The goal of this study was to compare the quality of imaging using EOS low-dose radiography to conventional radiography to evaluate shunt tubing. A retrospective chart review was performed on 57 patients who previously had both conventional radiographs and low-dose EOS images of their cerebral shunt tubing from 2000 to 2018. Patient demographics (age, sex, type of shunt tubing, primary diagnosis) were collected. Conventional radiographic images and low-dose EOS images were independently analyzed by a neurosurgeon and neuroradiologist in three categories: image quality, delineation of shunt, and distinction of shunt compared to adjacent anatomy. All patients had shunted hydrocephalus due to spina bifida and Chiari type II malformation. Ratings of EOS and conventional radiographic images by both raters did not differ significantly in terms of image quality (rater 1, p = 0.499; rater 2, p = 0.578) or delineation of shunt (p = 0.107 and p = 0.256). Conventional radiographic images received significantly higher ratings than EOS on the ability to distinguish the shunt versus adjacent anatomy by rater 1 (p = 0.039), but not by rater 2 (p = 0.149). The overall score of the three categories combined was not significantly different between EOS and conventional radiography (rater 1, p = 0.818; rater 2, p = 0.186). In terms of cost, an EOS image was less costly than a conventional radiography shunt series ($236-$366 and $1300-$1547, respectively). The radiation dose was also lower for EOS images, with an effective dose of 0.086-0.140 mSv compared to approximately 1.6 mSv for a similar field of view with conventional radiography. The image quality of low-dose EOS radiography does not significantly differ from conventional radiography for the evaluation of cerebral shunts. In addition, EOS affords a much lower radiation dose and a lower cost.


What's my line? A narrative review and synthesis of the literature on Registered Nurses' communication behaviours between shifts.
To describe, appraise and synthesize the seminal and empirical literature around Registered Nurses' communication behaviours between shifts in acute hospital settings. Effective communication between shifts (at nursing handover) is acknowledged as a prerequisite to safe and high-quality patient-centred care. However, gaps and inconsistencies continue to prevail. Narrative review and synthesis. The electronic databases PubMED, CINAHL and Scopus were used. English language, peer-reviewed papers published between 1970-April 2012 were considered for review. Criteria included Registered Nurses' communication during handovers in adult hospital settings. Twenty-nine papers were reviewed. The research lacks a clear conceptual framework to define the core purposes of Nurses' communication behaviours between shifts. Seven themes were identified: overall purpose; report givers and receivers; seeing the whole picture; teaching and education; language; patient-centred care; and social cohesion. Two main communication processes are required - one articulating the whole picture and the other detailing information about patients. This area of research is challenged by lack of consistency in terminology and methodological rigour. While recent research has confirmed the findings from the seminal work, it has not been able to elaborate on some of the key challenges to refine the knowledge base. A more integrated approach is required to understand the complex process of improving nursing communication behaviours, particularly around the nursing handover. A neglected area of study is the role of the unit lead in determining the communication standards of the whole nursing team.


Identification of a chemical probe for NAADP by virtual screening.
Research into the biological role of the Ca(2+)-releasing second messenger NAADP (nicotinic acid adenine dinucleotide phosphate) has been hampered by a lack of chemical probes. To find new chemical probes for exploring NAADP signaling, we turned to virtual screening, which can evaluate millions of molecules rapidly and inexpensively. We used NAADP as the query ligand to screen the chemical library ZINC for compounds with similar three-dimensional shape and electrostatic properties. We tested the top-ranking hits in a sea urchin egg bioassay and found that one hit, Ned-19, blocks NAADP signaling at nanomolar concentrations. In intact cells, Ned-19 blocked NAADP signaling and fluorescently labeled NAADP receptors. Moreover, we show the utility of Ned-19 as a chemical probe by using it to demonstrate that NAADP is a key causal link between glucose sensing and Ca(2+) increases in mouse pancreatic beta cells.


Neighborhood educational disparities in active commuting among women: the effect of distance between the place of residence and the place of work/study (an ACTI-Cités study).
Active transportation has been associated with favorable health outcomes. Previous research highlighted the influence of neighborhood educational level on active transportation. However, little is known regarding the effect of commuting distance on social disparities in active commuting. In this regard, women have been poorly studied. The objective of this paper was to evaluate the relationship between neighborhood educational level and active commuting, and to assess whether the commuting distance modifies this relationship in adult women. This cross-sectional study is based on a subsample of women from the Nutrinet-Santé web-cohort (N = 1169). Binomial, log-binomial and negative binomial regressions were used to assess the associations between neighborhood education level and (i) the likelihood of reporting any active commuting time, and (ii) the share of commuting time made by active transportation modes. Potential effect measure modification of distance to work on the previous associations was assessed both on the additive and the multiplicative scales. Neighborhood education level was positively associated with the probability of reporting any active commuting time (relative risk = 1.774; p < 0.05) and the share of commuting time spent active (relative risk = 1.423; p < 0.05). The impact of neighborhood education was greater at long distances to work for both outcomes. Our results suggest that neighborhood educational disparities in active commuting tend to increase with commuting distance among women. Further research is needed to provide geographically driven guidance for health promotion intervention aiming at reducing disparities in active transportation among socioeconomic groups.