Stimulatory effect of glucose on macrophage lipoprotein lipase expression and production.
Cardiovascular diseases are the leading cause of morbidity and mortality in diabetes. Lipoprotein lipase (LPL), a major secretory product of macrophages, has been suggested to play a key role in the development of atherosclerosis. In the present study, we evaluated the effect of high glucose on macrophage LPL mRNA expression and secretion. Exposure of murine J774 macrophages to high D-glucose concentrations (20-30 mmol/l) resulted in a dramatic upregulation of LPL mRNA expression and immunoreactive mass. This effect was not observed when these cells were incubated in the presence of L-glucose or mannitol. High glucose concentrations were also found to enhance LPL gene expression and immunoreactive mass in human monocyte-derived macrophages. J774 cells cultured in a high glucose environment expressed increased c-fos mRNA levels. Treatment of these cells with c-fos antisense DNA or protein kinase C inhibitor inhibited the stimulatory effect of glucose on LPL mRNA expression. In J774 cells exposed to high glucose concentrations, enhanced nuclear protein binding to the AP-1-responsive region of the murine LPL promoter was observed, while LPL mRNA stability remained unchanged. Overall, these results demonstrate that high glucose upregulates macrophage LPL gene expression and immunoreactive mass and that this effect involves transcriptional events.


Exploiting nanoscale effects in phase change memories.
The market launch of Intel's 3D XPoint™ proves phase change technology has grown mature. Besides storing information in a fast and non-volatile way, phase change memories (PCMs) may facilitate neuromorphic and in-memory computing. In order to establish PCM as a lasting element of the electronics ecosystem, scalability to future technology nodes needs to be assured. Continued miniaturization of PCM devices is not only prescribed in order to achieve memories with higher data density and neuromorphic hardware capable of processing larger amounts of information. Smaller PCM elements are also incentivized by the prospect of increased power efficiency per operation as less material needs to be heated up for switching. For this reason, a good understanding of the effects of confinement on phase change materials is crucial. Here we describe how miniaturization increases the importance of interface effects and we show how in consequence the crystallization kinetics of phase change materials, when confined into nanometer sized structures, can change significantly. Based on this analysis, the implications of such nanoscale effects are discussed and possible ways of exploiting them proposed.


[Mothers' difficulty in childrearing classified in terms of their children's behavioral characteristics].
Mothers who experience difficulty in childrearing are becoming increasingly more prevalent in Japan. This study described and classified mothers' childrearing difficulty in terms of their children's behavioral characteristics and related factors. Self-administered questionnaires were distributed to 818 mothers at their children's 3-year-old health checkup in eight suburban cities in Japan. The questionnaire consisted of items assessing the mother's experience of difficulty in childrearing for the child undergoing the checkup. The subjects were classified into four groups according to their children's behavioral characteristics: "low needs," "internalizing behavior," "externalizing behavior," and "comorbid internalizing-externalizing behavior." Multiple regression analysis was performed to examine the relationships between mothers' difficulty in childrearing and related factors. A total of 775 respondents were divided as follows: 332 mothers had children with low needs, 104 had those with internalizing behavior, 230 had those with externalizing behavior, and 109 had those with comorbid internalizing-externalizing behavior. Mothers in the low needs group showed less childrearing difficulty than did mothers in the other groups. Childrearing difficulty increased by group in the following order: internalizing, externalizing, and comorbid internalizing-externalizing. In all four groups, mothers with low self-efficacy and less appraisal support from their family encountered greater childrearing difficulty. In the low needs group, experiencing childrearing difficulty with another child was related experiencing childrearing difficulty with the child undergoing the checkup. In the internalizing behavior group, mothers who had experienced greater difficulty in childrearing were more likely to be housewives and of younger age, and were more likely to have had boys as the child undergoing the checkup. In the externalizing behavior group, mothers with more difficulty in childrearing were more likely to be younger and less healthy, have less appraisal support from their friends, and live in apartments. In the comorbid internalizing-externalizing group, if the mothers were housewives, they were more likely to have difficulty in caring for their other children, receive less appraisal support from their friends, and experience more difficulty in childrearing. The results showed that mothers' difficulty in childrearing and the factors related to this difficulty differed according to their children's behavioral characteristics. Public health nurses could provide more effective care and support to mothers by considering children's behavioral characteristics.


A sex allocation theory for vertebrates: combining local resource competition and condition-dependent allocation.
Tests of sex allocation theory in vertebrates are usually based on verbal arguments. However, the operation of multiple selective forces can complicate verbal arguments, possibly making them misleading. We construct an inclusive fitness model for the evolution of condition-dependent brood sex ratio adjustment in response to two leading explanations for sex ratio evolution in vertebrates: the effect of maternal quality on the fitness of male and female offspring (the Trivers-Willard hypothesis [TWH]) and local resource competition (LRC) between females. We show (1) the population sex ratio can be either unbiased or biased in either direction (toward either males or females); (2) brood sex ratio adjustment can be biased in either direction, with high-quality females biasing reproductive investment toward production of sons (as predicted by the TWH) or production of daughters (opposite to predictions of the TWH); and (3) selection can favor gradual sex ratio adjustment, with both sons and daughters being produced by both high- and low-quality mothers. Despite these complications, clear a priori predictions can be made for how the population sex ratio and the conditional sex ratio adjustment of broods should vary across populations or species, and within populations, across individuals of different quality.


Thrombin-induced translocation of GLUT3 glucose transporters in human platelets.
Platelets derive most of their energy from anaerobic glycolysis; during activation this requirement rises approx. 3-fold. To accommodate the high glucose flux, platelets express extremely high concentrations (155+/-18 pmol/mg of membrane protein) of the most active glucose transporter isoform, GLUT3. Thrombin, a potent platelet activator, was found to stimulate 2-deoxyglucose transport activity 3-5-fold within 10 min at 25 degrees C, with a half-time of 1-2 min. To determine the mechanism underlying the increase in glucose transport activity, an impermeant photolabel, [2-3H]2N-4-(1-azi-2,2,2-trifluoethyl)benzoyl-1,3, -bis-(d-mannose-4-ylozy)-2-propylamine, was used to covalently bind glucose transporters accessible to the extracellular milieu. In response to thrombin, the level of transporter labelling increased 2.7-fold with a half-time of 1-2 min. This suggests a translocation of GLUT3 transporters from an intracellular site to the plasma membrane in a manner analogous to that seen for the translocation of GLUT4 in insulin-stimulated rat adipose cells. To investigate whether a similar signalling pathway was involved in both systems, platelets and adipose cells were exposed to staurosporin and wortmannin, two inhibitors of GLUT4 translocation in adipose cells. Thrombin stimulation of glucose transport activity in platelets was more sensitive to staurosporin inhibition than was insulin-stimulated transport activity in adipose cells, but it was totally insensitive to wortmannin. This indicates that the GLUT3 translocation in platelets is mediated by a protein kinase C not by a phosphatidylinositol 3-kinase mechanism. In support of this contention, the phorbol ester PMA, which specifically activates protein kinase C, fully stimulated glucose transport activity in platelets and was equally sensitive to inhibition by staurosporin. This study provides a cellular mechanism by which platelets enhance their capacity to import glucose to fulfil the increased energy demands associated with activation.


Direct Visualization of a Gold Nanoparticle Electron Trapping Effect.
A new atomic-scale anisotropy in the photoreaction of surface carboxylates on rutile TiO2(110) induced by gold clusters is found. STM and DFT+U are used to study this phenomenon by monitoring the photoreaction of a prototype hole-scavenger molecule, benzoic acid, over stoichiometric (s) s-TiO2, Au9/s-TiO2, and reduced (r) Au9/r-TiO2. STM results show that benzoic acid adsorption displaces a large fraction of Au clusters from the terraces toward their edges. DFT calculations explain that Au9 clusters on stoichiometric TiO2 are distorted by benzoic acid adsorption. The influence of sub-monolayers of Au on the UV/visible photoreaction of benzoic acid was explored at room temperature, with adsorbate depletion taken as a measure of activity. The empty sites, observed upon photoexcitation, occurred in elongated chains (2 to 6 molecules long) in the [11̅0] and [001] directions. A roughly 3-fold higher depletion rate is observed in the [001] direction. This is linked to the anisotropic conduction of excited electrons along [001], with subsequent trapping by Au clusters leaving a higher concentration of holes and thus an increased decomposition rate. To our knowledge this is the first time that atomic-scale directionality of a chemical reaction is reported upon photoexcitation of the semiconductor.


Impact of short-term exercise training intensity on β-cell function in older obese adults with prediabetes.
The effect of work-matched exercise intensity on β-cell function is unknown in people with prediabetes before clinical weight loss. We determined if short-term moderate continuous (CONT) vs. high-intensity interval (INT) exercise increased β-cell function. Thirty-one subjects (age: 61.4 ± 2.5 yr; body mass index: 32.1 ± 1.0 kg/m2) with prediabetes [American Diabetes Association criteria, 75-g oral glucose tolerance test (OGTT)] were randomized to work-matched CONT (70% HRpeak) or INT (3 min 90% HRpeak and 3 min 50% HRpeak) exercise for 60 min/day over 2 wk. A 75-g 2-h OGTT was conducted after an overnight fast, and plasma glucose, insulin, C-peptide, and free fatty acids were determined for calculations of skeletal muscle [oral minimal model (OMM)], hepatic (homeostatic model of insulin resistance), and adipose (Adipose-IR) insulin sensitivity. β-Cell function was defined from glucose-stimulated insulin secretion (GSIS, deconvolution modeling) and the disposition index (DI). Glucagon-like polypeptide-1 [GLP-1(active)] and glucose-dependent insulinotropic polypeptide (GIP) were also measured during the OGTT, along with peak oxygen consumption and body composition. CONT and INT increased skeletal muscle- but not hepatic- or adipose-derived DI ( P < 0.05). Although both treatments tended to reduce fasting GLP-1(active) ( P = 0.08), early phase GLP-1(active) increased post-CONT and INT training ( P < 0.001). Interestingly, CONT exercise increased fasting GIP compared with decreases in INT ( P = 0.02). Early and total-phase skeletal muscle DI correlated with decreased total glucose area under the curve ( r = -0.52, P = 0.002 and r = -0.50, P = 0.003, respectively). Independent of intensity, short-term training increased pancreatic function adjusted to skeletal muscle in relation to improved glucose tolerance in adults with prediabetes. Exercise also uniquely affected GIP and GLP-1(active). Further work is needed to elucidate the dose-dependent mechanism(s) by which exercise impacts glycemia. NEW & NOTEWORTHY Exercise is cornerstone for reducing blood glucose, but whether high-intensity interval training is better than moderate continuous exercise is unclear in people with prediabetes before weight loss. We show that 2 wk of exercise training, independent of intensity, increased pancreatic function in relation to elevated glucagon-like polypeptide-1 secretion. Furthermore, β-cell function, but not insulin sensitivity, was also correlated with improved glucose tolerance. These data suggest that β-cell function is a strong predictor of glycemia regardless of exercise intensity.


Improved performance and stability in quantum dot solar cells through band alignment engineering.
Solution processing is a promising route for the realization of low-cost, large-area, flexible and lightweight photovoltaic devices with short energy payback time and high specific power. However, solar cells based on solution-processed organic, inorganic and hybrid materials reported thus far generally suffer from poor air stability, require an inert-atmosphere processing environment or necessitate high-temperature processing, all of which increase manufacturing complexities and costs. Simultaneously fulfilling the goals of high efficiency, low-temperature fabrication conditions and good atmospheric stability remains a major technical challenge, which may be addressed, as we demonstrate here, with the development of room-temperature solution-processed ZnO/PbS quantum dot solar cells. By engineering the band alignment of the quantum dot layers through the use of different ligand treatments, a certified efficiency of 8.55% has been reached. Furthermore, the performance of unencapsulated devices remains unchanged for over 150 days of storage in air. This material system introduces a new approach towards the goal of high-performance air-stable solar cells compatible with simple solution processes and deposition on flexible substrates.


Newborn screening in North America.
Newborn screening in North America dates to the early work of Bob Guthrie in the USA. Screening programmes in both the USA and Canada began in the early 1960s, with documented programmes in both countries as early as 1962. Throughout the 1960s and 1970s, many of the screening tests that later became part of routine screening around the world were developed in US and Canadian laboratories, including tests for phenylketonuria, other inborn errors of metabolism, congenital hypothyroidism, congenital adrenal hyperplasia, and haemoglobinopathies. An automated punching machine developed in the USA facilitated screening expansion by significantly reducing sample preparation time and effort. US and Canadian programmes were leaders in applying computerized data management to newborn screening in the 1980s. In the 1990s, DNA and tandem mass spectrometry testing protocols were developed in the USA and applied to newborn screening. US programmes have continually expanded over time, while most Canadian programmes have not. With impetus from private laboratories and professional and consumer groups, many US programmes now screen for more than 50 conditions and there is increased expansion activity in Canada. NBS research in the USA is focused on improving system efficiency and translating other genetic testing to NBS, particularly where new technologies and treatment therapies exist. Although national newborn screening policies do not exist in either Canada or the USA, there are intense efforts to provide uniform access to screening nationwide in both countries. New partnerships between health professionals, consumers and politicians are benefiting the overall screening systems in both countries.


Mental health stigma and primary health care decisions.
People with serious mental illness have higher rates of mortality and morbidity due to physical illness. In part, this occurs because primary care and other health providers sometimes make decisions contrary to typical care standards. This might occur because providers endorse mental illness stigma, which seems inversely related to prior personal experience with mental illness and mental health care. In this study, 166 health care providers (42.2% primary care, 57.8% mental health practice) from the Veteran׳s Affairs (VA) medical system completed measures of stigma characteristics, expected adherence, and subsequent health decisions (referral to a specialist and refill pain prescription) about a male patient with schizophrenia who was seeking help for low back pain due to arthritis. Research participants reported comfort with previous mental health interventions. Path analyses showed participants who endorsed stigmatizing characteristics of the patient were more likely to believe he would not adhere to treatment and hence, less likely to refer to a specialist or refill his prescription. Endorsement of stigmatizing characteristics was inversely related to comfort with one׳s previous mental health care. Implications of these findings will inform a program meant to enhance VA provider attitudes about people with mental illness, as well as their health decisions.


Whole genome methylation analyses of schizophrenia patients before and after treatment.
The aetiology of schizophrenia is still unknown but it involves both heritable and non-heritable factors. DNA methylation is an inheritable epigenetic modification that stably alters gene expression. It takes part in the regulation of neurodevelopment and may be a contributing factor to the pathogenesis of brain diseases. It was found that many of the antipsychotic drugs may lead to epigenetic modifications. We have performed 42 high-resolution genome-wide methylation array analyses to determine the methylation status of 27,627 CpG islands. Differentially methylated regions were studied with samples from 20 Bulgarian individuals divided in four groups according to their gender (12 males/8 females) and their treatment response (6 in complete/14 in incomplete remission). They were compared to two age and sex matched control pools (110 females in female pool/110 males in male pool) before and after treatment. We found significant differences in the methylation profiles between male schizophrenia patients with complete remission and control male pool before treatment (C16orf70, CST3, DDRGK1, FA2H, FLJ30058, MFSD2B, RFX4, UBE2J1, ZNF311) and male schizophrenia patients with complete remission and control male pool after treatment (AP1S3, C16orf59, KCNK15, LOC146336, MGC16384, XRN2) that potentially could be used as target genes for new therapeutic strategies as well as markers for good treatment response. Our data revealed major differences in methylation profiles between male schizophrenia patients in complete remission before and after treatment and healthy controls which supports the hypothesis that antipsychotic drugs may play a role in epigenetic modifications.


Duration of Absence from Work Is Related to Psychopathology, Personality, and Sociodemographic Variables in a Longitudinal Cohort.
To examine, in a non-clinical sample, the association of psychopathology, personality, sociodemographic information, and psychosocial indicators of non-occupational functioning with the duration of absence from work in the past 12 months. A longitudinal community cohort of 591 adults from Switzerland was analyzed using multilevel ordered logistic regression, with several alternative models as robustness checks. Psychopathology was assessed using the total score (Global Severity Index) of the Symptom Check List-90 Revised. The highest psychopathology levels were associated with absences of 3 or more week duration, largely independently of age. Extraversion and being divorced, widowed or separated also corresponded with longer absences from work in some analyses. No effect of sex was found. Most effects tested were not statistically significant and estimates showed large uncertainty. Although tentative, our results suggest a possible influence of psychopathology on work participation. It may thus be desirable in insurance-medical appraisals of work ability to include instruments for measuring psychopathology.


Mechanism of production of intestinal secretion by elevated venous pressure.
A study was carried out to elucidate the physiological mechanisms responsible for the intestinal secretion produced by venous pressure elevation. In dogs, measurements were made of the rate and composition of small intestinal secretion, rate of flow and composition of intestinal lymph, plasma composition, and mucosal water content, all in response to elevations of intestinal venous pressure. Venous pressure elevations above a threshold value of 30-35 cm H2O produce secretion at a rate of approximately proportional to the value of the pressure minus the threshold value. Above the threshold value, there were large increases in the rates of lymph flow and net sustained transcapillary filtration. These rates were also roughly proportional to the incremental venous pressure. It is concluded that intestinal secretion produced by elevated venous pressure is almost surely secretory filtration, a passive process with the driving force for secretion an increase in mucosal tissue fluid pressures to values of only some 4-6 cm H2O. The increased tissue fluid pressure not only provides the driving force but also produces an increase in the hydraulic permeability of the epithelium without which the driving force would be ineffective. The transepithelial channels are large enough to permit insulin to pass freely and even plasma protein to pass in large amounts, and hence are most probably intercellular. Secretory filtration probably represents a general pathophysiological response of transporting epithelia to elevated tissue fluid pressure. It is proposed that the threshold value for secretion and associated changes is explained by dilution of the tissue fluid protein colloid osmotic pressure in a small subepithelial, juxtacapillary compartment.


Comparison of reporter gene and iron particle labeling for tracking fate of human embryonic stem cells and differentiated endothelial cells in living subjects.
Human embryonic stem (hES) cells are pluripotent stem cells capable of self-renewal and differentiation into virtually all cell types. Thus, they hold tremendous potential as cell sources for regenerative therapies. The concurrent development of accurate, sensitive, and noninvasive technologies capable of monitoring hES cells engraftment in vivo can greatly expedite basic research prior to future clinical translation. In this study, hES cells were stably transduced with a lentiviral vector carrying a novel double-fusion reporter gene that consists of firefly luciferase and enhanced green fluorescence protein. Reporter gene expression had no adverse effects on cell viability, proliferation, or differentiation to endothelial cells (human embryonic stem cell-derived endothelial cells [hESC-ECs]). To compare the two popular imaging modalities, hES cells and hESC-ECs were then colabeled with superparamagnetic iron oxide particles before transplantation into murine hind limbs. Longitudinal magnetic resonance (MR) imaging showed persistent MR signals in both cell populations that lasted up to 4 weeks. By contrast, bioluminescence imaging indicated divergent signal patterns for hES cells and hESC-ECs. In particular, hESC-ECs showed significant bioluminescence signals at day 2, which decreased progressively over the following 4 weeks, whereas bioluminescence signals from undifferentiated hES cells increased dramatically during the same period. Post-mortem histology and immunohistochemistry confirmed teratoma formation after injection of undifferentiated hES cells but not hESC-ECs. From these data taken together, we concluded that reporter gene is a better marker for monitoring cell viability, whereas iron particle labeling is a better marker for high-resolution detection of cell location by MR. Furthermore, transplantation of predifferentiated rather than undifferentiated hES cells would be more suited for avoiding teratoma formation.


Towards a new class of heavy ion doped magnetic semiconductors for room temperature applications.
The article presents, using Bi doped ZnO, an example of a heavy ion doped oxide semiconductor, highlighting a novel p-symmetry interaction of the electronic states to stabilize ferromagnetism. The study includes both ab initio theory and experiments, which yield clear evidence for above room temperature ferromagnetism. ZnBi(x)O(1-x) thin films are grown using the pulsed laser deposition technique. The room temperature ferromagnetism finds its origin in the holes introduced by the Bi doping and the p-p coupling between Bi and the host atoms. A sizeable magnetic moment is measured by means of x-ray magnetic circular dichroism at the O K-edge, probing directly the spin polarization of the O(2p) states. This result is in agreement with the theoretical predictions and inductive magnetometry measurements. Ab initio calculations of the electronic and magnetic structure of ZnBi(x)O(1-x) at various doping levels allow to trace the origin of the ferromagnetic character of this material. It appears, that the spin-orbit energy of the heavy ion Bi stabilizes the ferromagnetic phase. Thus, ZnBi(x)O(1-x) doped with a heavy non-ferromagnetic element, such as Bi, is a credible example of a candidate material for a new class of compounds for spintronics applications, based on the spin polarization of the p states.


Does size really matter? Effects of fish surface area on the settlement and initial survival of Lepeophtheirus salmonis, an ectoparasite of Atlantic salmon Salmo salar.
The effect of the size of the surface area of a fish host on settlement and initial survival of Lepeophtheirus salmonis (Krøyer, 1837) was determined. Atlantic salmon Salmo salar L. of various sizes-small (43 +/- 4 g), medium (173 +/- 32 g) and large (644 +/- 62 g)-were initially examined to ascertain their respective body surface area, excluding gill surface. The initial examination showed a size-dependent body to fin area ratio, with the fin area of small fish representing 34% of the total body area and the fin area of medium and large fish representing 26 and 23%, respectively. Regression analysis of the body weight and standard length against total body surface area gave a good correlation and high R2 values. Two simultaneous experimental infections with approximately 7,000 copepodids of L. salmonis were carried out on fish populations of mixed sizes consisting of 30 small fish, 10 medium-sized fish and 5 large fish, with an approximate total surface area per size group of 2700 cm2. Higher numbers of parasites were found on the small size group, which also had the highest parasite density, with 0.25 and 0.45 parasites cm(-2). Comparison of samples of 5 fish per experimental group revealed that the larger fish had the highest mean numbers of parasites, but the smaller fish still retained the highest density. There was a statistically significantly higher settlement on the fins than on the remainder of the body surface in all size groups. Highest numbers of parasites were particularly found on the dorsal and pectoral fins. Examination of the surface surface area revealed that the dorsal fin had the greater parasite density, with >2 parasites cm(-2) in all fish size groups. These data provide insight into the effects of the amount of host surface area available on parasite settlement and survival, and highlight the potentially increased susceptibility of farmed salmon smolts to infection of this ectoparasite.


Designing a Pragmatic Intervention to Help Improve the Bladder Cancer Patient Experience.
Bladder cancer (BC) is the 10th most common malignancy worldwide and the patient experience is found to be worse than that for patients diagnosed with other cancer types. We aimed to develop a wellbeing intervention to help improve the bladder cancer patient experience by ameliorating their health-related Quality of Life (HRQoL). We followed the 3 phases of the modified Medical Research Council (MRC) Framework for development of complex interventions. Following a systematic review of the literature on mental, sexual, and physical wellbeing, we conducted discussion groups with patients and healthcare professionals on these 3 themes. A consultation phase was then conducted with all relevant stakeholders to co-design a wellbeing intervention as part of a feasibility study. A pragmatic wellbeing feasibility trial was designed based on the hypothesis that a wellbeing program will increase patient awareness and attendance to services available to them and will better support their needs to improve HRQoL. The primary feasibility endpoints are patient attendance to the services offered and changes in HRQoL. The principle of patient centered care has strengthened the commitment to provide a holistic approach to support BC patients. In this study, we developed a wellbeing intervention in collaboration with patients and healthcare professionals to meet an unmet need in terms of the BC patient experience.


[Visceral leishmaniasis epidemic in the State of Piauí, Brazil, 1980-1986].
The kala-azar epidemic in the State of Piauí 1980-1986 is analyzed on the basis of the data collected by SUCAM Piauí. The outbreak began in towns of central and northern Piauí in 1980. In contrast what has happened in endemic periods in which the disease occurred in areas of higher altitude and semi-arid climate, the epidemic developed in humid tropical river valleys in rural zones. The epidemic was worst in the towns. The state capital, Teresina, hit in 1981, reached the epidemic peak in 1984 and accounted, for more than 60% of the 1,509 cases in the state. The epidemic was not substantial in those regions sprayed to combat malaria and Chagas' disease. While control in Teresina was attempted through intensive use of insecticides, the outbreak gave way spontaneously in rural areas. Neither the number of cases nor the phlebotomine population of Teresina presented significant seasonal variations but were moderately correlated. There was greater prevalence in children of 5 years of age or less, especially during the peak epidemic years, and much lesser prevalence in adults over 40 years of age. The geographical distribution of the epidemic process and its beginning, concomitant with a prolonged drought with its accompanying migration of people and domestic animals from endemic to epidemic regions, suggests that migration unleashed the epidemic. The fact that the epidemic process spontaneously relinquished its hold in areas where no control was attempted, indicates that the end of the epidemic cannot be attributed solely to measures of control. An analysis of the coefficients of specific incidence within age groups sparks the discussion about the possibility that progressive reduction of susceptibility (determined by the great number of asymptomatic infections as well as by long-lasting immunity) contributed to the extinction of the epidemic.


The nerve growth factor reduces APOBEC3G synthesis and enhances HIV-1 transcription and replication in human primary macrophages.
Macrophages infected with HIV-1 sustain viral replication for long periods of time, functioning as viral reservoirs. Therefore, recognition of factors that maintain macrophage survival and influence HIV-1 replication is critical to understanding the mechanisms that regulate the HIV-1-replicative cycle. Because HIV-1-infected macrophages release the nerve growth factor (NGF), and NGF neutralization reduces viral production, we further analyzed how this molecule affects HIV-1 replication. In the present study, we show that NGF stimulates HIV-1 replication in primary macrophages by signaling through its high-affinity receptor Tropomyosin-related Kinase A (TrKA), and with the involvement of reticular calcium, protein kinase C, extracellular signal-regulated kinase, p38 kinase, and nuclear factor-κB. NGF-induced enhancement of HIV-1 replication occurred during the late events of the HIV-1-replicative cycle, with a concomitant increase in viral transcription and production. In addition, NGF reduced the synthesis of the cellular HIV-1 restriction factor APOBEC3G and also overrode its interferon-γ-induced up-regulation, allowing the production of a well-fitted virus. Because NGF-TrKA signaling is a crucial event for macrophage survival, it is possible that NGF-induced HIV-1 replication plays a role in the maintenance of HIV-1 reservoirs. Our study may contribute to the understanding of the immunopathogenesis of HIV-1 infection and provide insights about approaches aimed at limiting viral replication in HIV-1 reservoirs.


Field, experimental, and modeling study of arsenic partitioning across a redox transition in a Bangladesh aquifer.
To understand redox-dependent arsenic partitioning, we performed batch sorption and desorption experiments using aquifer sands subjected to chemical and mineralogical characterization. Sands collected from the redox transition zone between reducing groundwater and oxic river water at the Meghna riverbank with HCl extractable Fe(III)/Fe ratio ranging from 0.32 to 0.74 are representative of the redox conditions of aquifers common in nature. One brown suboxic sediment displayed a partitioning coefficient (K(d)) of 7-8 L kg(-1) at equilibrium with 100 μg L(-1) As(III), while two gray reducing sediments showed K(d) of 1-2 L kg(-1). Lactate amendment to aquifer sands containing 91 mg kg(-1) P-extractable As resulted in the reduction of As and Fe with sediment Fe(III)/Fe decreasing from 0.54 to 0.44, and mobilized an equivalent of 64 mg kg(-1) As over a month. Desorption of As from nonlactate-amended sediment was negligible with little change in sediment Fe(III)/Fe. This release of As is consistent with microbial reduction of Fe(III) oxyhydroxides and the resulting decrease in the number of surface sites on Fe(III) oxyhydroxides. Arsenic partitioning (K(d)) in iron-rich, sulfur-poor aquifers with circumneutral pH is redox-dependent and can be estimated by HCl leachable sediment Fe(III)/Fe ratio with typical Fe concentrations.


Impact of HACA on Immunomodulation and Treatment Toxicity Following ch14.18/CHO Long-Term Infusion with Interleukin-2: Results from a SIOPEN Phase 2 Trial.
GD₂-directed immunotherapies improve survival of high-risk neuroblastoma (NB) patients (pts). Treatment with chimeric anti-GD₂ antibodies (Ab), such as ch14.18, can induce development of human anti-chimeric Ab (HACA). Here, we report HACA effects on ch14.18/CHO pharmacokinetics, pharmacodynamics and pain intensity in pts treated by long-term infusion (LTI) of ch14.18/CHO combined with IL-2. 124 pts received up to 5 cycles of ch14.18/CHO 10 days (d) infusion (10 mg/m²/d; d8⁻18) combined with s.c. IL-2 (6 × 10⁶ IU/m²/d; d1⁻5, d8⁻12). HACA, treatment toxicity, ch14.18/CHO levels, Ab-dependent cellular- (ADCC) and complement-dependent cytotoxicity (CDC) were assessed using respective validated assays. HACA-negative pts showed a steadily decreased pain in cycle 1 (74% pts without morphine by d5 of LTI) with further decrease in subsequent cycles. Ch14.18/CHO peak concentrations of 11.26 ± 0.50 µg/mL found in cycle 1 were further elevated in subsequent cycles and resulted in robust GD₂-specific CDC and ADCC. Development of HACA (21% of pts) resulted in strong reduction of ch14.18/CHO levels, abrogated CDC and ADCC. Surprisingly, no difference in pain toxicity between HACA-positive and -negative pts was found. In conclusion, ch14.18/CHO LTI combined with IL-2 results in strong activation of Ab effector functions. Importantly, HACA response abrogated CDC but did not affect pain intensity indicating CDC-independent pain induction.


Gene therapy for the treatment of musculoskeletal diseases.
Research into the orthopaedic applications of gene therapy has resulted in progress toward managing chronic and acute genetic and nongenetic disorders. Gene therapy for arthritis, the original focus of research, has progressed to the initiation of several phase I clinical trials. Preliminary findings support the application of gene therapy in the treatment of additional chronic conditions, including osteoporosis and aseptic loosening, as well as musculoskeletal tumors. The most rapid progress is likely to be in tissue repair because it requires neither long-term transgene expression nor closely regulated levels of transgene expression. Moreover, healing probably can be achieved with existing technology. In preclinical studies, genetically modulated stimulation of bone healing has shown impressive results in repairing segmental defects in the long bones and cranium and in improving the success of spinal fusions. An increasing amount of evidence indicates that gene transfer can aid the repair of articular cartilage, menisci, intervertebral disks, ligaments, and tendons. These developments have the potential to transform many areas of musculoskeletal care, leading to treatments that are less invasive, more effective, and less expensive than existing modalities.


Platelets in Multiple Sclerosis: Early and Central Mediators of Inflammation and Neurodegeneration and Attractive Targets for Molecular Imaging and Site-Directed Therapy.
Platelets are clearly central to thrombosis and hemostasis. In addition, more recently, evidence has emerged for non-hemostatic roles of platelets including inflammatory and immune reactions/responses. Platelets express immunologically relevant ligands and receptors, demonstrate adhesive interactions with endothelial cells, monocytes and neutrophils, and toll-like receptor (TLR) mediated responses. These properties make platelets central to innate and adaptive immunity and potential candidate key mediators of autoimmune disorders. Multiple sclerosis (MS) is the most common chronic autoimmune central nervous system (CNS) disease. An association between platelets and MS was first indicated by the increased adhesion of platelets to endothelial cells. This was followed by reports identifying structural and functional changes of platelets, their chronic activation in the peripheral blood of MS patients, platelet presence in MS lesions and the more recent revelation that these structural and functional abnormalities are associated with all MS forms and stages. Investigations based on the murine experimental autoimmune encephalomyelitis (EAE) MS model first revealed a contribution to EAE pathogenesis by exacerbation of CNS inflammation and an early role for platelets in EAE development via platelet-neuron and platelet-astrocyte associations, through sialated gangliosides in lipid rafts. Our own studies refined and extended these findings by identifying the critical timing of platelet accumulation in pre-clinical EAE and establishing an initiating and central rather than merely exacerbating role for platelets in disease development. Furthermore, we demonstrated platelet-neuron associations in EAE, coincident with behavioral changes, but preceding the earliest detectable autoreactive T cell accumulation. In combination, these findings establish a new paradigm by asserting that platelets play a neurodegenerative as well as a neuroinflammatory role in MS and therefore, that these two pathological processes are causally linked. This review will discuss the implications of these findings for our understanding of MS, for future applications for imaging toward early detection of MS, and for novel strategies for platelet-targeted treatment of MS.


NPAS2: an analog of clock operative in the mammalian forebrain.
Neuronal PAS domain protein 2 (NPAS2) is a transcription factor expressed primarily in the mammalian forebrain. NPAS2 is highly related in primary amino acid sequence to Clock, a transcription factor expressed in the suprachiasmatic nucleus that heterodimerizes with BMAL1 and regulates circadian rhythm. To investigate the biological role of NPAS2, we prepared a neuroblastoma cell line capable of conditional induction of the NPAS2:BMAL1 heterodimer and identified putative target genes by representational difference analysis, DNA microarrays, and Northern blotting. Coinduction of NPAS2 and BMAL1 activated transcription of the endogenous Per1, Per2, and Cry1 genes, which encode negatively activating components of the circadian regulatory apparatus, and repressed transcription of the endogenous BMAL1 gene. Analysis of the frontal cortex of wild-type mice kept in a 24-hour light-dark cycle revealed that Per1, Per2, and Cry1 mRNA levels were elevated during darkness and reduced during light, whereas BMAL1 mRNA displayed the opposite pattern. In situ hybridization assays of mice kept in constant darkness revealed that Per2 mRNA abundance did not oscillate as a function of the circadian cycle in NPAS2-deficient mice. Thus, NPAS2 likely functions as part of a molecular clock operative in the mammalian forebrain.


Greenhouse gas emissions from membrane bioreactors: analysis of a two-year survey on different MBR configurations.
This study aimed at evaluating the nitrous oxide (N2O) emissions from membrane bioreactors (MBRs) for wastewater treatment. The study investigated the N2O emissions considering multiple influential factors over a two-year period: (i) different MBR based process configurations; (ii) wastewater composition (municipal or industrial); (iii) operational conditions (i.e. sludge retention time, carbon-to-nitrogen ratio, C/N, hydraulic retention time); (iv) membrane modules. Among the overall analysed configurations, the highest N2O emission occurred from the aerated reactors. The treatment of industrial wastewater, contaminated with salt and hydrocarbons, provided the highest N2O emission factor (EF): 16% of the influent nitrogen for the denitrification/nitrification-MBR plant. The lowest N2O emission (EF = 0.5% of the influent nitrogen) was obtained in the biological phosphorus removal-moving bed-MBR plant likely due to an improvement in biological performances exerted by the co-presence of both suspended and attached biomass. The influent C/N ratio has been identified as a key factor affecting the N2O production. Indeed, a decrease of the C/N ratio (from 10 to 2) promoted the increase of N2O emissions in both gaseous and dissolved phases, mainly related to a decreased efficiency of the denitrification processes.


The influence of age on transfer factor treatment of cellular immunodeficiency, chronic fatigue syndrome and/or chronic viral infections.
A group of 222 patients suffering from cellular immunodeficiency (CID), frequently combined with chronic fatigue syndrome (CFS) and/or chronic viral infections by Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), were immunologically investigated and treated with transfer factor (TF). The age range was 17-77 years. In order to elucidate the influence of aging on the course of the disease and on treatment, 3 subgroups were formed: 17-43 years, 44-53 years, and 54-77 years. Six injections of Immodin (commercial preparation of TF by SEVAC, Prague) were given in the course of 8 weeks. When active viral infection was present, IgG injections and vitamins were added. Immunological investigation was performed before the start of therapy, and subsequently according to need, but not later than after 3 months. The percentages of failures to improve clinical status of patients were in the individual subgroups, respectively: 10.6%, 11.5% and 28.9%. The influence of increasing age on the percentage of failures to normalize low numbers of T cells was very evident: 10.6%, 21.2% and 59.6%. In individuals uneffected by therapy, persistent absolute lymphocyte numbers below 1,200 cells were found in 23.1%, 54.5% and 89.3% in the oldest group. Statistical analysis by Pearson's Chi-square test, and the test for linear trend proved that the differences among the individual age groups were significant. Neither sex, nor other factors seemed to influence the results. The results of this pilot study show that age substantially influences the failure rate of CID treatment using TF. In older people, it is easier to improve the clinical condition than CID: this may be related to the diminished number of lymphocytes, however, a placebo effect cannot be totally excluded.


Hypolipidemic activity of Anethum graveolens in rats.
The aerial parts of Anethum graveolens (dillweed) are used in Iran as a hypolipidemic agent. The scientific basis for its use has yet to be established. In this study the hypolipidemic activity of dill powder and its essential oil (its most important fraction) were evaluated in male Wistar rats (180 +/- 20 g) fed a high cholesterol diet. Anethum graveolens essential oil (AGEO) was prepared by hydrodistillation and analysed using GC/MS. AGEO had a yield of 2% and GC/MS analysis showed that alpha-phellandrene (32%), limonene (28%) and carvone (28%) were its major components. Daily oral administration of AGEO to rats at doses of 45, 90 and 180 mg/kg for 2 weeks significantly and in a dose-dependent manner reduced total cholesterol, triglyceride and low density lipoprotein cholesterol (LDL-C). AGEO also increased significantly high density lipoprotein cholesterol (HDL-C). Anethum graveolens powder when added to the diet of animals showed similar effects on serum lipids. It is concluded that Anethum graveolens has significant lipid lowering effects and is a promising cardioprotective agent.


Iodine Intake is Associated with Thyroid Function in Mild to Moderately Iodine Deficient Pregnant Women.
Studies indicate that mild to moderate iodine deficiency in pregnancy may have a long-term negative impact on child neurodevelopment. These effects are likely mediated via changes in maternal thyroid function, since iodine is essential for the production of thyroid hormones. However, the impact of iodine availability on thyroid function during pregnancy and on thyroid function reference ranges are understudied. The aim of this study was to investigate the association between iodine intake and thyroid function during pregnancy. In a population-based pregnancy cohort including 2910 pregnant women participating in The Norwegian Mother and Child Cohort Study, we explored cross sectional associations of maternal iodine intake measured (1) by a food frequency questionnaire and (2) as iodine concentration in a spot urine sample, with plasma thyroid hormones and antibodies. Biological samples were collected in mean gestational week 18.5 (standard deviation 1.3) and diet was assessed in gestational week 22. Median iodine intake from food was 121 μg/day (interquartile range 90, 160), and 40% reported use of iodine-containing supplements in pregnancy. Median urinary iodine concentration (UIC) was 59 μg/L among those who did not use supplements and 98 μg/L in the women reporting current use at the time of sampling, indicating mild to moderate iodine deficiency in both groups. Iodine intake as measured by the food frequency questionnaire was not associated with the outcome measures, while UIC was inversely associated with FT3 (p = 0.002) and FT4 (p < 0.001). Introduction of an iodine-containing supplement after gestational week 12 was associated with indications of lower thyroid hormone production (lower FT4, p = 0.027, and nonsignificantly lower FT3, p = 0.17). The 2.5th and 97.5th percentiles of TSH, FT4, and FT3 were not significantly different by groups defined by calculated iodine intake or by UIC. The results indicate that mild to moderate iodine deficiency affect thyroid function in pregnancy. However, the differences were small, suggesting that normal reference ranges can be determined based on data also from mildly iodine deficient populations, but this needs to be further studied. Introducing an iodine-containing supplement might temporarily inhibit thyroid hormone production and/or release.


The electronic and optical properties of the sulvanite compounds: a many-body perturbation and time-dependent density functional theory study.
We have studied, by means of first-principles calculations, the electronic and optical properties of the sulvanite family: Cu3MX4 (M = V, Nb, Ta and X = S, Se), which, due to its broad range of gaps and chemical stability, have emerged as promising materials for technological applications such as photovoltaics and transparent conductivity. To address the reliability of those properties we have used semi-local and hybrid functionals (PBEsol, HSE06), many-body perturbation theory (G0W0 approximation and Bethe-Salpeter equation), and time-dependent density functional theory (revised bootstrap kernel) to calculate the quasi-particle dispersion relation, band gaps, the imaginary part of the macroscopic dielectric function and the absorption coefficient. The calculated valence band maximum and the conduction band minimum are located at the R and X-points, respectively. The calculated gaps using PBEsol are between 0.81 and 1.88 eV, with HSE06 into 1.73 and 2.94 eV, whereas the G0W0 values fall into the 1.91-3.19 eV range. The calculated dielectric functions and absorption coefficients show that all these compounds present continuous excitonic features when the Bethe-Salpeter equation is used. Contrarily, the revised bootstrap kernel is incapable of describing the excitonic spectra. The calculated optical spectra show that Cu3VS4 and Cu3MSe4 have good absorption in the visible, whereas Cu3NbS4 and Cu3TaS4 have it on the near ultraviolet.


Lumbar discectomy: a national survey of neurosurgeons and literature review.
To ascertain neurosurgical practices in the surgical management of one-level lumbar discectomies in the Canadian adult population. One page questionnaire faxed to each Neurosurgeon in Canada with questions relating to their practice in the management of this common neurosurgical procedure. All data analyzed using Chi-square statistics. 112 completed surveys were returned hence, giving a 64% response rate with the respondents being predominantly adult neurosurgeons. Of the respondents, 88% perform lumbar discectomy in adults. Only 15% of respondents had a Spine Fellowship. For preoperative imaging, 44% use BOTH CT and MRI whereas 28% use only MRI and 15% use only CT. Prior to initial skin incision, 57% use a localization X-ray image. Preoperative antibiotics are prescribed by 92% of respondents. Majority of respondents (60%) use a pre-incision local anesthetic, whereas only a minority (44%) of respondents employ pre-closure intramuscular injection. With respect to magnification, 70% use microscope, 19% loupes, and 8% neither. Only 12% use minimally invasive tubular retractors. 68% remove "as much disc as possible", while 31% remove "ONLY herniated part". In the case of dural tears, 77% of respondents use fibrin glue (Tisseel). Prior to skin closure, majority of neurosurgeons do NOT use a fat graft (72%), whereas 61% of respondents use epidural steroids. With respect to discharge from the hospital, 58% are discharged on the next day, 18% on the same day, and 23% in two days. Return to work is not recommended until at least six weeks post-op (96%). Most neurosurgeons (93%) would not operate on an individual with a chief complaint of low back pain. Our survey has identified variations in practice patterns amongst Canadian Neurosurgeons with respect to performing one-level lumbar discectomies. This survey is expected to form a basis for the design of a randomized controlled trial in the evaluation of the best management approach for this common neurosurgical procedure.


Fixed Points of Competitive Threshold-Linear Networks.
Threshold-linear networks (TLNs) are models of neural networks that consist of simple, perceptron-like neurons and exhibit nonlinear dynamics determined by the network's connectivity. The fixed points of a TLN, including both stable and unstable equilibria, play a critical role in shaping its emergent dynamics. In this work, we provide two novel characterizations for the set of fixed points of a competitive TLN: the first is in terms of a simple sign condition, while the second relies on the concept of domination. We apply these results to a special family of TLNs, called combinatorial threshold-linear networks (CTLNs), whose connectivity matrices are defined from directed graphs. This leads us to prove a series of graph rules that enable one to determine fixed points of a CTLN by analyzing the underlying graph. In addition, we study larger networks composed of smaller building block subnetworks and prove several theorems relating the fixed points of the full network to those of its components. Our results provide the foundation for a kind of graphical calculus to infer features of the dynamics from a network's connectivity.


Neural processing of emotional faces requires attention.
Attention gates the processing of stimuli relatively early in visual cortex. Yet, existing data suggest that emotional stimuli activate brain regions automatically, largely immune from attentional control. To resolve this puzzle, we used functional magnetic resonance imaging to first measure activation in regions that responded differentially to faces with emotional expressions (fearful and happy) compared with neutral faces. We then measured the modulation of these responses by attention, using a competing task with a high attentional load. Contrary to the prevailing view, all brain regions responding differentially to emotional faces, including the amygdala, did so only when sufficient attentional resources were available to process the faces. Thus, the processing of facial expression appears to be under top-down control.


Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine.
Pain intensity, muscle strength, static muscle endurance, pressure pain threshold, and pain tolerance at tender points and control points were assessed in 31 patients with fibromyalgia (FM), before and after intravenous administration of morphine (9 patients), lidocaine (11 patients), and ketamine (11 patients). The three different studies were double-blind and placebo-controlled. The patients were classified as placebo-responders, responders (decrease in pain intensity by > 50%) and non-responders. The morphine test did not show any significant changes. The lidocaine test showed a pain decrease during and after the infusion. The ketamine test showed a significant reduction in pain intensity during and after the test period. Tenderness at tender points decreased and endurance increased significantly, while muscle strength remained unchanged. The present results support the hypothesis that the NMDA receptors are involved in pain mechanisms in fibromyalgia. These findings also suggest that central sensitization is present in FM and that tender points represent secondary hyperalgesia.


Up-regulated miR-133a orchestrates epithelial-mesenchymal transition of airway epithelial cells.
Dysregulation of microRNAs (miRNAs) contributes to epithelial-mesenchymal transition (EMT) of cancer, but the pathological roles of miRNAs in airway EMT of lung diseases remains largely unknown. We performed sequencing and real-time PCR analysis of the miRNA expression profile of human airway epithelial cells undergoing EMT, and revealed miR-133a to be one of the most common up-regulated miRNAs. MiR-133a was previously reported to be persistently up-regulated in airway epithelial cells of smokers. We found that mice exposed to cigarette smoke (CS) showed airway hyper-responsiveness, a typical symptom occurring in CS-related lung diseases, up-regulation of miR-133a and EMT marker protein N-cadherin in airway epithelium. Importantly, miR-133a overexpression induces airway epithelial cells to undergo spontaneous EMT via down-regulation of grainyhead-like 2 (GRHL2), an epithelial specific transcriptional factor. Loss of GRHL2 causes down-regulation of epithelial splicing regulatory protein 1 (ESRP1), a central coordinator of alternative splicing processes that are critical in the regulation of EMT. Down-regulation of ESRP1 induces isoform switching of adherens junction-associated protein p120-catenin, and leads to the loss of E-cadherin. Our study is the first to demonstrate that up-regulated miR-133a orchestrates airway EMT via alternative splicing processes, which points to novel therapeutic possibilities for the treatment of CS-related lung disease.


Augmented annotation and orthologue analysis for Oryctolagus cuniculus: Better Bunny.
The rabbit is an important model organism used in a wide range of biomedical research. However, the rabbit genome is still sparsely annotated, thus prohibiting extensive functional analysis of gene sets derived from whole-genome experiments. We developed a web-based application that provides augmented annotation and orthologue analysis for rabbit genes. Importantly, the application allows comprehensive functional analysis through the use of orthologous relationships. Using data extracted from several public bioinformatics repositories we created Better Bunny, a database and query tool that extensively augments the available functional annotation for rabbit genes. Using the complete set of target genes from a commercial rabbit gene expression microarray as our benchmark, we are able to obtain functional information for 88 % of the genes on the microarray. Previously, functional information was available for fewer than 10 % of the rabbit genes. We have developed a freely available, web-accessible bioinformatics tool that enables investigators to quickly and easily perform extensive functional analysis of rabbit genes (http://cptweb.cpt.wayne.edu). The software application fills a critical void for a wide range of biomedical research that relies on the rabbit model and requires characterization of biological function for large sets of genes.


Synthesis of compositionally tunable, hollow mixed metal sulphide CoxNiySz octahedral nanocages and their composition-dependent electrocatalytic activities for oxygen evolution reaction.
Hollow nanostructures such as nanocages and nanoframes can serve as advanced catalysts with their enlarged active surface areas, and hence they have been of widespread interest. Despite the recent progress in the synthesis of this class of nanomaterials, hollow nanostructures with tunable compositions and controlled morphologies have rarely been reported. Here, we report a facile synthetic route to a series of compositionally tunable, hollow mixed metal sulphide (CoxNiySz) octahedral nanocages. The sulfidation of CoO octahedral nanoparticles generates CoO@CoxSy core-shell octahedra, and the in situ etching of the CoO core and annealing yield Co9S8 (pentlandite) octahedral nanocages (ONC). The addition of a Ni precursor during the etching/annealing process of CoO@CoxSy core-shell octahedra progressively yields hollow ONC structures of Co9-xNixS8, Ni9S8, Ni9S8/β-NiS, and Ni3S2/β-NiS via cation exchange reactions. Mixed cobalt/nickel sulphide, Co9-xNixS8 ONC, shows superior oxygen evolution reaction activity to monometallic sulphide ONC structures, demonstrating the synergy between different metal species.


Biochemical and ribotypic comparison of Actinomyces pyogenes and A pyogenes-like organisms from liver abscesses, ruminal wall, and ruminal contents of cattle.
To isolate Actinomyces pyogenes and A pyogenes-like (APL) organisms from the ruminal wall and ruminal contents of cattle and compare them with isolates from liver abscesses from the same animals, using ribosomal DNA restriction fragment length polymorphism analysis or ribotyping. Specimens of liver abscesses, ruminal walls, and ruminal contents were collected from 59 cattle at slaughter. All beta-hemolytic, pinpoint colonies that were gram positive, pleomorphic rod-shaped, and catalase negative, and that hydrolyzed casein and gelatin were presumptively identified as A pyogenes and were characterized biochemically, using an identification kit. The isolates that resembled A pyogenes but fermented mannitol or raffinose, or both, were called APL organisms. Isolates from the ruminal wall and ruminal contents were compared with liver abscess isolates from the same animal by use of ribotyping. Actinomyces pyogenes and APL organisms were isolated more frequently from the ruminal wall than from ruminal contents. Ruminal isolates of A pyogenes and APL had biochemical characteristics similar to those of the isolates from liver abscesses. Among 6 sets of isolates (4 A pyogenes and 2 APL), 2 isolates from liver abscesses had ribopatterns identical to the corresponding ruminal wall isolates. Also, the APL organisms isolated from the ruminal content matched with the corresponding liver abscess isolates for both sets of specimens tested. The ruminal wall may be the niche for A pyogenes and APL organisms in the rumen. The genetic similarity, on the basis of ribotyping among isolates from liver abscesses, the ruminal wall, and ruminal contents of the same animal suggests that A pyogenes and APL organisms that cause liver abscesses originate from the rumen.


Multidisciplinary studies with mutated HIV-1 capsid proteins reveal structural mechanisms of lattice stabilization.
HIV-1 capsid (CA) stability is important for viral replication. E45A and P38A mutations enhance and reduce core stability, thus impairing infectivity. Second-site mutations R132T and T216I rescue infectivity. Capsid lattice stability was studied by solving seven crystal structures (in native background), including P38A, P38A/T216I, E45A, E45A/R132T CA, using molecular dynamics simulations of lattices, cryo-electron microscopy of assemblies, time-resolved imaging of uncoating, biophysical and biochemical characterization of assembly and stability. We report pronounced and subtle, short- and long-range rearrangements: (1) A38 destabilized hexamers by loosening interactions between flanking CA protomers in P38A but not P38A/T216I structures. (2) Two E45A structures showed unexpected stabilizing CANTD-CANTD inter-hexamer interactions, variable R18-ring pore sizes, and flipped N-terminal β-hairpin. (3) Altered conformations of E45Aa α9-helices compared to WT, E45A/R132T, WTPF74, WTNup153, and WTCPSF6 decreased PF74, CPSF6, and Nup153 binding, and was reversed in E45A/R132T. (4) An environmentally sensitive electrostatic repulsion between E45 and D51 affected lattice stability, flexibility, ion and water permeabilities, electrostatics, and recognition of host factors.


The Benefits and Pitfalls of the Use of Risk Stratification Tools in Cardiac Surgery.
Risk assessment tools are increasingly used in surgery. In cardiac surgery, risk models are used for patient counselling, surgical decision-making, performance benchmarking, clinical research, evaluation of new therapies and quality assurance, among others. However, they have numerous disadvantages which need to be considered. This article evaluates the utility of risk assessment tools in cardiac surgery including a discussion of their advantages and disadvantages.


Benefit-risk of Patients' Online Access to their Medical Records: Consensus Exercise of an International Expert Group.
Patients' access to their computerised medical records (CMRs) is a legal right in many countries. However, little is reported about the benefit-risk associated with patients' online access to their CMRs. To conduct a consensus exercise to assess the impact of patients' online access to their CMRs on the quality of care as defined in six domains by the Institute of Medicine (IoM), now the National Academy of Medicine (NAM). A five-round Delphi study was conducted. Round One explored experts' (n = 37) viewpoints on providing patients with access to their CMRs. Round Two rated the appropriateness of statements arising from Round One (n = 16). The third round was an online panel discussion of findings (n = 13) with the members of both the International Medical Informatics Association and the European Federation of Medical Informatics Primary Health Care Informatics Working Groups. Two additional rounds, a survey of the revised consensus statements and an online workshop, were carried out to further refine consensus statements. Thirty-seven responses from Round One were used as a basis to initially develop 15 statements which were categorised using IoM's domains of care quality. The experts agreed that providing patients online access to their CMRs for bookings, results, and prescriptions increased efficiency and improved the quality of medical records. Experts also anticipated that patients would proactively use their online access to share data with different health care providers, including emergencies. However, experts differed on whether access to limited or summary data was more useful to patients than accessing their complete records. They thought online access would change recording practice, but they were unclear about the benefit-risk of high and onerous levels of security. The 5-round process, finally, produced 16 consensus statements. Patients' online access to their CMRs should be part of all CMR systems. It improves the process of health care, but further evidence is required about outcomes. Online access improves efficiency of bookings and other services. However, there is scope to improve many of the processes of care it purports to support, particularly the provision of a more effective interface and the protection of the vulnerable.


Airy-like beam transverse acceleration control by rainbow effect.
We propose and numerically analyze the transverse acceleration control for the Airy-like beams from incomplete Airy waveguide and Airy waveguide by rainbow effect. We show that the Airy-like beams have an obvious change in transverse acceleration with a slight variation (10 nm) in incident wavelength. The rainbow phenomenon is introduced to study the Airy-like beam propagation with a different wavelength. The equivalent initial launch angle is also considered to explain transverse acceleration of the Airy-like beams.


Beneficial Effect of Cissus quadrangularis Linn. on Osteopenia Associated with Streptozotocin-Induced Type 1 Diabetes Mellitus in Male Wistar Rats.
Petroleum ether fraction of Cissus quadrangularis (PECQ) impact on the development of osteopenia in type 1 diabetic rat model has been evaluated. Diabetic rats were treated orally with two doses of PECQ. Another group of diabetic rats were treated with subcutaneous injection of synthetic human insulin. The cortical and trabecular bone thickness and bone strength were significantly decreased in diabetic rats. Treatment with two doses of PECQ significantly prevented these changes in diabetic rats. However, PECQ treatment (two doses) did not alter the glycemic levels in these diabetic rats. Increased levels of serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), and hydroxyproline were noted in diabetic rats when compared to normal control rats. The two doses of PECQ treatment further improved the serum ALP levels and significantly decreased the serum levels of TRAP and hydroxyproline. The effects of PECQ treatment on histological, biomechanical, and biochemical parameters are comparable to those of insulin. Since PECQ improves the bone health in hyperglycemic conditions by enhancing the cortical and trabecular bone growth and altering the circulating bone markers, it could be used as an effective therapy against diabetes-associated bone disorders.


Endometrial factors under treatment with oestrogen and oestrogen/progestogen combinations.
In a continuing prospective study, uterine curettage was undertaken on sixty-four patients attending a Menopause Clinic prior to consideration of gonadal hormone therapy. Two of these patients (3.1%) were found to have endometrial hyperplasia, and subsequently they were not given gonadal hormone therapy. Sixty-two patients with normal endometrium at pre-treatment curettage received cyclical oestrogen regimens or sequential oestrogen/progestogen treatments. Four (30.8%) of the thirteen patients in receipt of cyclical 'high-dose' oestrogens developed cystic glandular hyperplasia, whereas none of the patients taking either cyclical 'low-dose' oestrogens (thirty patients) or cyclical-sequential oestrogen/progestogen regimens (nineteen patients) developed endometrial hyperplasia. Among the patients with a normal endometrium, both before and during cyclical gonadal hormone therapy, regular withdrawal bleeding was experienced by thirty-two patients (51.6%). Breakthrough bleeding occurred in nine (14.5%), while twenty-one patients (33.9%) had no vaginal bleeding. Of the four patients with normal endometrium at pre-treatment curettage who subsequently developed endometrial hyperplasia during cyclical 'high-dose' oestrogen therapy, regular withdrawal bleeding was experienced by two patients, and in one of these breakthrough bleeding also occurred. Furthermore, in the four patients who developed endometrial hyperplasia, this condition occurred within six months in two patients and within 9 and 10 months respectively in the remaining two. In the nineteen patients receiving cyclical sequential oestrogen/progestogen regimens, all had regular withdrawal bleeding, while one patient had breakthrough bleeding during sequential therapy. It is concluded that in those climacteric patients who present with severe menopausal symptoms which necessitate the administration of high-dose oestrogen regimes it is necessary either to undertake both pretreatment uterine curettage or to add a progestogen to the oestrogen in a sequential regimen.


Psychiatric disorders in spouse caregivers of care recipients with Alzheimer's disease and matched controls: a diathesis-stress model of psychopathology.
To test a diathesis-stress model of psychopathology, the authors examined the rates of current and lifetime psychiatric disorders in 82 spouse caregivers of Alzheimer's disease (AD) patients and 86 demographically matched controls. Caregivers and controls did not differ in the prevalence of disorders before the onset of care recipients' AD (or during a similar time period for the controls); caregivers experienced more depressive-anxiety disorders after the onset of patient's AD than controls. This study strongly supported the 3 key components of a diathesis-stress interaction. First, caregivers with a psychiatric history prior to the onset of patient's AD were more likely than caregivers with no history to receive a diagnosis after the onset of AD. Second, a similar relationship existed for controls. Finally, caregivers with a psychiatric history were more likely to experience a recurrence after the onset of AD than controls with a psychiatric history. These findings indicate that the diathesis of psychiatric history and the stress of caregiving interact, resulting in the observed group differences in the prevalence of psychiatric disorders.


Effect of GBR 12909 and fluoxetine on the acute and long term changes induced by MDMA ('ecstasy') on the 5-HT and dopamine concentrations in mouse brain.
We examined the long term effect of 3,4 methylenedioxymethamphetamine (MDMA, 10, 20 and 30 mg/kg, i.p.) on the cerebral 5-hydroxytryptamine (5-HT) and dopamine content in Swiss Webster mice. Three injections of MDMA (20 or 30 mg/kg, i.p.) given 3 h apart produced a marked depletion in the striatal content of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) 7 days later. None of the doses administered altered the concentration of 5-HT or its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in several brain areas. Pre-treatment with the dopamine uptake inhibitor GBR 12909 (10 mg/kg, i.p.), 30 min before each of the three MDMA (30 mg/kg, i.p.) injections, completely prevented the long term loss in the striatal catechol concentrations. However, GBR 12909 (10 mg/kg, i.p.) not only failed to prevent the acute effects induced by MDMA (30 mg/kg x 3, i.p.) on dopamine metabolism 30 min later, but in fact potentiated them. The 5-HT uptake inhibitor, fluoxetine (10 mg/kg, i. p.) failed to prevent both the acute and long term dopaminergic deficits. MDMA (30 mg/kg x 3) altered the body temperature of the mice biphasically, producing a rapid hyperthermia followed by prolonged hypothermia. In contrast, MDMA (20 mg/kg x 3) produced an initial hypothermia followed by hyperthermia. The present experiments therefore appear to rule out any direct relationship between the neurotoxic effects of MDMA and its acute effects on body temperature in mice. Fluoxetine administered 30 min before each MDMA (30 mg/kg) injection prevented these temperature changes, while GBR 12909 was without effect. This suggests that the neuroprotective effect of GBR 12909 against MDMA-induced neurotoxicity is not directly related to its ability to inhibit the MDMA-induced acute effects on dopamine metabolism or alter the MDMA-induced temperature change. The data illustrate major differences in the neurotoxic profile of MDMA in mice and rats.


Role of the MEOX2 homeobox gene in neurovascular dysfunction in Alzheimer disease.
Neurovascular dysfunction substantially contributes to Alzheimer disease. Here, we show that transcriptional profiling of human brain endothelial cells (BECs) defines a subset of genes whose expression is age-independent but is considerably altered in Alzheimer disease, including the homeobox gene MEOX2 (also known as GAX), a regulator of vascular differentiation, whose expression is low in Alzheimer disease. By using viral-mediated MEOX2 gene silencing and transfer, we show that restoring expression of the protein it encodes, GAX, in BECs from individuals with Alzheimer disease stimulates angiogenesis, transcriptionally suppresses AFX1 forkhead transcription factor-mediated apoptosis and increases the levels of a major amyloid-beta peptide (Abeta) clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP), at the blood-brain barrier. In mice, deletion of Meox2 (also known as Gax) results in reductions in brain capillary density and resting cerebral blood flow, loss of the angiogenic response to hypoxia in the brain and an impaired Abeta efflux from brain caused by reduced LRP levels. The link of MEOX2 to neurovascular dysfunction in Alzheimer disease provides new mechanistic and therapeutic insights into this illness.


Public health information systems for primary health care in India: A situational analysis study.
Information communication technology (ICT) based health information systems (HISs) are expected to transform health system functionality. The present study was aimed to evaluate HISs in India with a focus on primary health care (PHC). The study used a qualitative method to evaluate and understand various ICT-based HIS implemented at the state/union territory (UT) level in India. After initial scoping research on HIS through literature search and observation, in-depth interviews of key informants at various levels (programme managers, analysts, co-ordinators, data entry operator and health care providers) was carried out to have an insight on the user experience of these systems. An inductive applied thematic coding of qualitative data was done for analysing the data. Multiple applications have been developed under national health programmes to meet the health information needs, but at present, there is a limited role of these HISs in enhancing the effectiveness of comprehensive PHC. Many of these systems are proprietary-based, and the long-term sustainability and integration of these systems remain a challenge. A change is required in the approach to design a HIS that will cater to the needs of PHC. Moreover, HIS should be people-centred rather than technology-centric with focus on integration and sustainability.


Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.
Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.


Suitability of Wild Host Plants and Firewood as Hosts of Prostephanus truncatus (Coleoptera: Bostrichidae) in Mozambique.
Prostephanus truncatus (Horn) (Coleoptera: Bostrichidae) populations are maintained in wild host plants such as trees that act as pest reservoirs from where beetle infestation of maize granaries take place. In this study, we assessed the suitability of plant species sold and transported as firewood as well as other plant species in Mozambique as hosts for P. truncatus. Prostephanus truncatus was only recorded from three tree species, which are sold as firewood, i.e., Brachystegia spiciformis, Strychnos spinosa, and Colophospermum mopane. The pest survived and bred in 13 tree and 7 grass species. Dry wood of several tree species and the grasses Acroceras macrum and Hyparrhenia hirta were suitable hosts for pest development. Sale and transport of certain firewood species may be an important driver of the spread of this pest. The importance of dry maize stalks and several grass species in sustaining pest populations is described for the first time. Several grass species are used as thatch or fencing material and, together with maize crop residues close to small-scale granaries, may provide significant sources of beetle infestation.


Evaluating the evidence base: policies and interventions to address socioeconomic status gradients in health.
This chapter discusses the current evidence base for policies that could address socioeconomic status (SES) health gradients in the United States. The present volume has documented an enormous amount of research on the linkages between SES and health, but there are still relatively few studies that rigorously establish the effectiveness of particular policies or interventions in reducing those gradients. Given the difficulty in developing randomized evidence for many types of interventions related to social determinants of health, we argue for conducting policy analysis from a Bayesian perspective. This Bayesian approach combines information on best available theory and evidence regarding probable health benefits and costs of an intervention, providing a framework that also incorporates the probable costs of inaction. The second half of the chapter adopts a ladder metaphor to classify policies and interventions that could reduce SES gradients in population health. Using this framework, we consider the evidence base for various types of policies, focusing primarily on the social determinants of health, under the rubric that "all policy is health policy." We conclude by discussing promising strategies for future strengthening of the evidence base for policy, including the role of health impact assessment.


Neural Correlates to the Increase in Maximal Force after Dexamethasone Administration.
This study investigated the effects of short-term glucocorticoid administration on voluntary activation and intracortical inhibitory and facilitatory circuits. Seventeen healthy men participated in a pseudorandomized double-blind study to receive either dexamethasone (8 mg·d, n = 9 subjects) or placebo (n = 8 subjects) for 7 d. The ankle dorsiflexion torque, corresponding EMG of the tibialis anterior, and voluntary activation assessed by the interpolated twitch method using transcranial magnetic stimulation (TMS) were measured during a maximal voluntary contraction (MVC). Short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) were assessed at rest and during submaximal contraction (50% MVC torque) by paired-pulse TMS with the conditioning stimulus set at 0.8× of motor threshold and delivered 2 ms (SICI) and 13 ms (ICF) before the test stimulus (1.2× motor threshold). The MVC torque (+14%), tibialis anterior EMG (+31%), and voluntary activation (+3%) increased after glucocorticoid treatment (P < 0.05). The increase in voluntary activation was associated with the gain in MVC torque (r = 0.56; P = 0.032). The level of SICI and the duration of the EMG silent period that followed the test TMS decreased (-18.6% and -13.5%, respectively) during the 50% MVC after treatment (P < 0.05), whereas no significant change was observed for ICF. Neither SICI nor ICF changed after treatment when assessed at rest. Short-term dexamethasone treatment induced specific decrease in the excitability of intracortical inhibitory circuits that likely contributed to the increase in the voluntary activation and associated MVC torque.


Development of an unambiguous and discriminatory multilocus sequence typing scheme for the Streptococcus zooepidemicus group.
The zoonotic pathogen Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is commonly found harmlessly colonizing the equine nasopharynx. Occasionally, strains can invade host tissues or cross species barriers, and S. zooepidemicus is associated with numerous different diseases in a variety of hosts, including inflammatory airway disease and abortion in horses, pneumonia in dogs and meningitis in humans. A biovar of S. zooepidemicus, Streptococcus equi subsp. equi, is the causative agent of strangles, one of the most important infections of horses worldwide. We report here the development of the first multilocus sequence typing (MLST) scheme for S. zooepidemicus and its exploitation to define the population genetic structure of these related pathogens. A total of 130 unique sequence types were identified from 277 isolates of diverse geographical and temporal origin. Isolates of S. equi shared a recent evolutionary ancestor with isolates of S. zooepidemicus that were significantly associated with cases of uterine infection or abortion in horses (P<0.001). Isolates of S. zooepidemicus from three UK outbreaks of acute fatal haemorrhagic pneumonia in dogs during 1999, 2001 and 2008 were found to be related to isolates from three outbreaks of this disease in the USA during 2005, 1993 and 2006, respectively. Our data provide strong evidence that S. equi evolved from an ancestral S. zooepidemicus strain and that certain related strains of S. zooepidemicus have a greater propensity to infect particular hosts and tissues.


Awareness survey about the effects of malocclusion among young adults.
Malocclusion has been a problem since ancient times. Diverse factors influence malocclusion such as oral habits, anomalies in the dentition like changes in shape, position and number of teeth. But awareness and attitude about the problem differs within the neighborhood, depending upon their understanding and education. Hence, observation is essential to diminish and avoid the deleterious effects of malocclusion. Hence the objective of this study is to perceive the knowledge of youngsters and enlighten their perception on misaligned teeth. A cross sectional study was conducted among 1000 young adults between ages 18-22 in Sathyabama University, Chennai, India. A questionnaire consisting of 24 multiple choice questions were given to the participants to assess their awareness, attitude towards malocclusion and orthodontic treatment. Descriptive statistics and chi square test was done using SPSS software version 20. The level of significance was set at 0.05. More than 70% of the participants show concern and interest on self-image, 39.9% of the total study population were unhappy with the arrangement of their teeth. There was an overall lack of knowledge about the etiology and the effects of malocclusion among the participants. 60.2% of the population have not visited a dentist in the past 3 years. Many had false impressions towards orthodontic treatment. Awareness about the effects of malocclusion among young adults seems to be lacking. Most of the time, the treatment is neglected until the need for it arises.


Priming of circulating human eosinophils following late response to allergen challenge.
The eosinophil is recognized as an important effector cell in asthma. To investigate the role of eosinophils in the aetiology of asthma, we have examined whether peripheral blood eosinophils are primed following whole-lung allergen challenge. Nineteen mild asthmatics, who each demonstrated a late asthmatic response (LAR), were studied. The priming of eosinophils following allergen challenge was assessed by measuring: 1) platelet-activating factor (PAF) and complement factor 5a (C5a) stimulated H2O2 release upon fibrinogen-coated tissue culture plates (n = 8); and 2) ex-vivo cell survival (n = 11). Subjects were venepunctured before and 24 h after allergen challenge and eosinophils were prepared by immunomagnetic separation. Basal H2O2 release was increased from eosinophils following allergen challenge. The response to PAF stimulation was significantly increased in terms of cell sensitivity (negative log of concentration producing half the maximal effect (pD2)) and responsiveness (maximum effect Emax). With C5a, although there was no change in sensitivity there was a significant increase in the maximal response. Ex-vivo eosinophil survival (at 3 days and cell half-life) was significantly prolonged following allergen challenge. In conclusion, we have demonstrated the priming of circulating eosinophils following allergen challenge.


Licensing of natural killer cells by host major histocompatibility complex class I molecules.
Self versus non-self discrimination is a central theme in biology from plants to vertebrates, and is particularly relevant for lymphocytes that express receptors capable of recognizing self-tissues and foreign invaders. Comprising the third largest lymphocyte population, natural killer (NK) cells recognize and kill cellular targets and produce pro-inflammatory cytokines. These potentially self-destructive effector functions can be controlled by inhibitory receptors for the polymorphic major histocompatibility complex (MHC) class I molecules that are ubiquitously expressed on target cells. However, inhibitory receptors are not uniformly expressed on NK cells, and are germline-encoded by a set of polymorphic genes that segregate independently from MHC genes. Therefore, how NK-cell self-tolerance arises in vivo is poorly understood. Here we demonstrate that NK cells acquire functional competence through 'licensing' by self-MHC molecules. Licensing involves a positive role for MHC-specific inhibitory receptors and requires the cytoplasmic inhibitory motif originally identified in effector responses. This process results in two types of self-tolerant NK cells--licensed or unlicensed--and may provide new insights for exploiting NK cells in immunotherapy. This self-tolerance mechanism may be more broadly applicable within the vertebrate immune system because related germline-encoded inhibitory receptors are widely expressed on other immune cells.


Active optics, adaptive optics, and laser guide stars.
Optical astronomy is crucial to our understanding of the universe, but the capabilities of ground-based telescopes are severely limited by the effects of telescope errors and of the atmosphere on the passage of light. Recently, it has become possible to construct inbuilt corrective devices that can compensate for both types of degradations as observations are conducted. For full use of the newly emerged class of 8-meter telescopes, such active corrective capabilities, known as active and adaptive optics, are essential. Some physical limitations in the adaptive optics field can be overcome by artificially created reference stars, called laser guide stars. These new technologies have lately been applied with success to some medium and very large telescopes.


Preferential exclusion chromatography as a capture step for extracellular AAV harvest from adherent and suspension productions.
Preferential exclusion chromatography (PXC) sometimes described as hydrophobic interaction chromatography is a well-known, but not widely used technique for purification of Adeno-associated viruses. It employs high molarity of preferentially excluded cosolvent (salt in our case). The downside of this method is that high molarity of salt can lead to aggregation and precipitation of different compounds from the sample. In the case of viruses that are excreted to medium, the concentration of impurities is much lower compared to cell lysates, and PXC can be used as a first chromatographic, serotype independent step to concentrate and purify adeno-associated virus (AAV). Here, we explored PXC for adherent and suspension harvests using monolithic chromatographic columns (CIMmultus). Suspension extracellular adeno-associated virus, serotype 9 (AAV9) harvest had more impurities compared to adherent harvest, therefore it required higher input regarding method development. Final conditions for suspension harvest included higher molarity of binding salt and using more open channel format of chromatographic column (6 µm channel size). Vector genome analysis with droplet digital polymerase chain reaction (ddPCR) revealed 84% and 97% recovery for suspension and adherent AAV9 harvest, respectively. After PXC capture step, adherent AAV9 was purified by already described ion exchange techniques. Overall process vector genome recovery, from clarified harvest to anion exchange elution fraction, was 54% measured by ddPCR. Residual host cell DNA was measured at 40 ng per 1E13 vector genome, and empty AAV was below 5% in final anion exchange chromatography fraction.


Statistics of the fractal structure and phase singularity of a plane light wave propagation in atmospheric turbulence.
Numerical experiments are carried out for a plane wave propagating in the atmospheric turbulence for a weak to strong fluctuation condition, i.e., the Rytov index being in a large range of 2x10(-3) to 20. Mainly two categories of propagation events are explored for the same range of Rytov index. In one category the propagation distance and also the Fresnel length are kept fixed with the turbulence strength changing. In the other the turbulence strength is kept fixed with the distance changing. The statistical characteristics of the scintillation index, the maximum and minimum of the intensity, the fractal dimension of the intensity image, and the number density of the phase singularity are analyzed. The behaviors of the fractal dimension and the density of the phase singularity present obvious differences for the two categories of propagation. The fractal dimension depends both on the Rytov index and the Fresnel length. In both weak and strong fluctuation conditions the dimension generally increases with the Rytov index, but is at minimum at the onset region. The phase singularity density is coincident with the theoretical results under a weak fluctuation condition, and has a slowly increasing manner with the Rytov index in the strong fluctuation condition. The dependence on the Fresnel size is confident and there is no saturation for the phase singularity.


Endemic Pseudomonas aeruginosa infection in a neonatal intensive care unit.
Nosocomial infections due to Pseudomonas aeruginosa have been well described, but the environmental reservoir of the organism varies. We conducted an epidemiologic and molecular investigation of endemic P. aeruginosa infection among infants in a neonatal intensive care unit that was associated with carriage of the organisms on the hands of health care workers. In August 1998, colonization or infection with P. aeruginosa was identified in six infants. Surveillance cultures for P. aeruginosa were obtained from the other 27 infants in the unit, and possible environmental reservoirs were also assessed. The hands of health care workers were inspected and cultured, and risk factors for P. aeruginosa colonization were evaluated. Isolates were analyzed for clonality by pulsed-field gel electrophoresis. Surveillance cultures showed that three additional infants were colonized with P. aeruginosa. Cultures of environmental specimens were negative, but cultures of the hands of 10 of 165 health care workers (6 percent) were positive for P. aeruginosa. Increasing age (P=0.05) and a history of the use of artificial fingernails or nail wraps (P=0.03) were both risk factors for colonization of the hands. From January 1997 to August 1998, 49 infants were infected or colonized with P. aeruginosa. Pulsed-field gel electrophoresis demonstrated that 17 of these infants and 1 health care worker who had onychomycosis had the same clone. Infants who were exposed to this health care worker in August 1998 were at greater risk of having this clone than infants who were not exposed to this health care worker (odds ratio, 41.2; 95 percent confidence interval, 1.8 to 940.0; P=0.006). An increased rate of infection and colonization with P. aeruginosa among infants in neonatal intensive care units should be investigated by assessing potential reservoirs, including environmental sources as well as patients and health care workers.


Profiling Movement and Gait Quality Characteristics in Pre-School Children.
There is a dearth of suitable metrics capable of objectively quantifying motor competence. Further, objective movement quality characteristics during free play have not been investigated in pre-school children. The aims of this study were to characterize children's free play physical activity and investigate how gait quality characteristics cluster with free play in pre-school children (3-5 years old). Sixty-one children (39 boys; 4.3 ± 0.7 years, 1.04 ± 0.05 m, 17.8 ± 3.2 kg) completed the movement assessment battery for children and took part in free play while wearing an ankle- and hip-mounted accelerometer. Characteristics of movement quality were profiled using a clustering algorithm. Spearman's rho and the Mann-Whitney U tests were used to assess relationships between movement quality characteristics and motor competence classification differences in integrated acceleration and spectral purity, respectively. Significant differences were found between motor competency classifications for spectral purity and integrated acceleration (p < .001). Spectral purity was hierarchically clustered with motor competence and integrated acceleration. Significant positive correlations were found between spectral purity, integrated acceleration and motor competence (p < .001). This is the first study to report spectral purity in pre-school children and the results suggest that the underlying frequency component of movement is clustered with motor competence.


[Evolution and spatial analysis of leishmaniasis cases in a rural area bordering a community outbreak in Madrid: 2001-2017].
Leishmaniasis is a zoonotic disease, widely spread all over the world, and an endemic disease in some Spanish regions. Within the Autonomous Region of Madrid, some south populations were affected by an outbreak from 2009. This outbreak had special features and implications related to epidemiology, reservoir and environment intervention. An increased rate in rural areas bordering the outbreak area was detected by epidemiological surveillance. This area has the same environment characteristics. The objective of this study was to research and analyze the evolution of leishmaniasis cases declared in a rural area and their comparison with the cases of the outbreak area. The cases declared to Epidemiology Surveillance Network have been used. Kulldorff´s tools were used for the cluster analysis. A hot spot analysis (Getis-Ord Gi*) was made. Leporidae and vector information of the area was related to the location of cases. The number of observed cases exceeded the number of expected cases in this area (epidemic index 7.8 in 2013), after the outbreak. This showed a relation between both incidence rates. It seemed to be spatial correlation when the number of cases was analyzed by census sections and grids (Moran´s I 0,208; z= 9,336). Using the hot-spot analysis, a higher incidence of the study area could be observed, and within Health Basic Area of Griñón after the outbreak years. A spatial relation between cases and a greater presence of vectors and leporidae was found. The distribution of leishmaniasis cases, in the period and study area suggests a link between the community outbreak and the increase of cases in the study area last years, overall in the rural area. It would be useful to strengthen surveillance and it should apply effective measures used in the bordering area if they were necessary. These measures can help to control the spread of the outbreak.


Rumen cellulosomics: divergent fiber-degrading strategies revealed by comparative genome-wide analysis of six ruminococcal strains.
A complex community of microorganisms is responsible for efficient plant cell wall digestion by many herbivores, notably the ruminants. Understanding the different fibrolytic mechanisms utilized by these bacteria has been of great interest in agricultural and technological fields, reinforced more recently by current efforts to convert cellulosic biomass to biofuels. Here, we have used a bioinformatics-based approach to explore the cellulosome-related components of six genomes from two of the primary fiber-degrading bacteria in the rumen: Ruminococcus flavefaciens (strains FD-1, 007c and 17) and Ruminococcus albus (strains 7, 8 and SY3). The genomes of two of these strains are reported for the first time herein. The data reveal that the three R. flavefaciens strains encode for an elaborate reservoir of cohesin- and dockerin-containing proteins, whereas the three R. albus strains are cohesin-deficient and encode mainly dockerins and a unique family of cell-anchoring carbohydrate-binding modules (family 37). Our comparative genome-wide analysis pinpoints rare and novel strain-specific protein architectures and provides an exhaustive profile of their numerous lignocellulose-degrading enzymes. This work provides blueprints of the divergent cellulolytic systems in these two prominent fibrolytic rumen bacterial species, each of which reflects a distinct mechanistic model for efficient degradation of cellulosic biomass.