Acupuncture for hot flashes in patients with prostate cancer.
To determine the effect of acupuncture on hot flash frequency and intensity, quality of life, and sleep quality in patients undergoing hormonal therapy for prostate cancer. Hot flashes are a common adverse effect of hormonal therapy for prostate cancer. Men who had a hot flash score > 4 who were receiving androgen deprivation therapy for prostate cancer underwent acupuncture with electrostimulation biweekly for 4 weeks, then weekly for 6 weeks, using a predefined treatment plan. The primary endpoint was a 50% reduction in the hot flash score after 4 weeks of therapy, calculated from the patients' daily hot flash diaries. The hot flash-related quality of life and sleep quality and biomarkers potentially related to hot flashes, including serotonin, calcitonin gene-related peptide, and urinary 5-hydroxyindoleacetic acid, were examined. A total of 25 men were enrolled from September 2003 to April 2007. Of these, 22 were eligible and evaluable. After 4 weeks, 9 (41%, 95% confidence interval 21%-64%) of 22 patients had had a > 50% reduction in the hot flash score. Of the 22 patients, 12 (55%, 95% confidence interval 32%-76%) met this response definition at any point during the therapy course. No patient had a significant increase in hot flash score during therapy. A reduced hot flash score was associated with improvement in the hot flash-related quality of life and sleep quality. Multiple placebo-controlled trials have demonstrated a 25% response rate to placebo treatment for hot flashes. Of the 22 patients, 41% had responded by week 4 and 55% overall in the present pilot study, providing evidence of a potentially meaningful benefit. Additional studies of acupuncture for hot flashes in this population are warranted.


Solution structure by NMR and molecular dynamics of a duplex containing a guanine opposite a N-(2-deoxy-beta-D-erythro-pentofuranosyl)formamide lesion.
One- and two-dimensional NMR spectroscopy has been used combined with molecular dynamics to determine the fine structure of the DNA duplex 5'-d(AGGAGCCACG).d(CGTGGFTCCT) where F is the N-(2-deoxy-beta-D-erythro-pentofuranosyl)formamide residue which is a ring fragmentation product of thymine. The formamide deoxyribose exists as two isomers with respect to the orientation about the peptide bond. The two isomers (trans and cis) are observed in a ratio 3:2 in solution. For both species, the oligonucleotide adopts a globally B form structure although conformational changes are observed around the mismatch site. The formamide residue, whatever the isomer, is intrahelical and can pair with the guanine on the opposite strand with one hydrogen bond. For the cis isomer, the residue adopts a syn orientation and is able to form a second hydrogen bond with the guanine on the 5' side on the same strand. Off-resonance ROESY experiments have been used to investigate the chemical exchange observed at low temperature of the duplex. Conformational exchange has only been found for the oligonucleotide with the formamide residue in the trans conformation.


Three-dimensional deconvolution microfluidic microscopy using a tilted channel.
We have developed a microfluidic device that enables the computation of three-dimensional (3-D) images of flowing samples. Using a microfluidic channel that is tilted along the optical axis, we record several progressively defocused images of the flowing sample as it passes across the focal plane. The resulting focal stack is then deconvolved to generate 3-D images. Experimental results on flowing yeast cells reveal both volume and surface profile information. The microfluidic channel eliminates the need for a precise translation stage to control defocusing and enables high sample throughput in an insulated, nontoxic, liquid environment. The experimental device can be implemented in all existing microscopes as a modified slide stage and is ideally suited for 3-D profiling in flow cytometers.


A practical model of diabetes management and education.
This article discusses an evolving conceptual model of diabetes self-management and patient education. The model contains three primary levels or stages: 1) social environment and contextual factors, which have received little research attention; 2) patient-health care provider interactions, self-management behaviors, and short-term physiological outcomes, which constitute an ongoing cycle of care feedback system; and 3) longer term health and quality-of-life outcomes, which include the major societal costs of treating diabetes complications. The assessment and intervention implications of factors within each of these levels are discussed, with emphasis on both low-cost system-wide activities appropriate for all patients and higher cost activities and resources (e.g., intensive management à la the Diabetes Control and Complications Trial) for appropriately targeted or higher risk patients. I hope that such a systems approach to diabetes management can help reduce victim blaming (whether the victim is the noncompliant patient or the insensitive provider). Such conceptual models, if practically oriented, may help accelerate the development, evaluation, and dissemination of programs that facilitate both patient and health care team adherence to recommended guidelines for diabetes care.


Physical activity, opportunity for reinfection, and sibling history of heart disease as risk factors for Chagas' cardiopathy.
A case-control study was conducted to examine whether physical activity, sibling history of heart disease (HHD), and length of residence in an area endemic for Chagas' disease were associated with the risk of developing Chagas' cardiopathy. Two hundred forty-seven cases of Chagas' heart disease and 345 seropositive subjects with normal ECG (controls) were selected in a population survey in Goiânia, Brazil. Prevalence ratios for exposure variables were estimated for cases in relation to controls and for subgroups of seropositives with selected ECG abnormalities in relation to controls. Increasing age and male sex were consistently and significantly related to an increased risk of ECG abnormalities. HHD was significantly associated with ECG alterations in 3 of the 5 comparison subgroups (any ECG alteration, right bundle branch block, and left anterior hemiblock). No association was found between length of residence in an area endemic, physical activity, and ECG abnormalities. A sample of 529 seronegative subjects were also examined and the interaction between exposure variables and seropositivity was tested to assess whether the associations found were specific for seropositives. Males were at greater risk of any ECG alteration and left anterior hemiblock in relation to females if they were seropositive. An increasing risk of ventricular premature beats with age was clearer for seropositive than for seronegative subjects. Subjects with HHD were at an increased risk of ECG abnormalities and this was greater in those with a positive serological test (P less than 0.05). The findings suggest a possible geographical clustering or a familial aggregation of cases of Chagas' heart disease.


Recovery of a temperate reef assemblage in a marine protected area following the exclusion of towed demersal fishing.
Marine Protected Areas MPA have been widely used over the last 2 decades to address human impacts on marine habitats within an ecosystem management context. Few studies have quantified recovery of temperate rocky reef communities following the cessation of scallop dredging or demersal trawling. This is critical information for the future management of these habitats to contribute towards conservation and fisheries targets. The Lyme Bay MPA, in south west UK, has excluded towed demersal fishing gear from 206 km(2) of sensitive reef habitat using a Statutory Instrument since July 2008. To assess benthic recovery in this MPA we used a flying video array to survey macro epi-benthos annually from 2008 to 2011. 4 treatments (the New Closure, previously voluntarily Closed Controls and Near or Far Open to fishing Controls) were sampled to test a recovery hypothesis that was defined as 'the New Closure becoming more similar to the Closed Controls and less similar to the Open Controls'. Following the cessation of towed demersal fishing, within three years positive responses were observed for species richness, total abundance, assemblage composition and seven of 13 indicator taxa. Definitive evidence of recovery was noted for species richness and three of the indicator taxa (Pentapora fascialis, Phallusia mammillata and Pecten maximus). While it is hoped that MPAs, which exclude anthropogenic disturbance, will allow functional restoration of goods and services provided by benthic communities, it is an unknown for temperate reef systems. Establishing the likely timescales for restoration is key to future marine management. We demonstrate the early stages of successful recruitment and link these to the potential wider ecosystem benefits including those to commercial fisheries.


Actomyosin-generated tension on cadherin is similar between dividing and non-dividing epithelial cells in early Xenopus laevis embryos.
Epithelia represent a unique situation where polarized cells must maintain sufficiently strong cell-cell contacts to guarantee the epithelial integrity indispensable for barrier functions. Nevertheless, epithelia must also keep sufficient plasticity which is crucial during development and morphogenesis. Adherens junctions and mechanical forces produced by the actomyosin cytoskeleton are major players for epithelial integrity maintenance and plasticity regulations. To understand how the epithelium is able to meet such a challenge, it is indispensable to determine how cellular junctions and mechanical forces acting at adherens junctions are regulated. Here, we investigate the tensile forces acting on adherens junctions via cadherin during cell division in the Xenopus embryos epithelium. Using the recently developed E-cadherin FRET tension sensor and a fastFLIM prototype microscope, we were able to measure mechanical forces applied on cadherin at cell-cell junctions. We have shown that the Xenopus epithelium is under tension, approximately 3 pN which remains stable, indicating that tensile forces acting on cadherin at the adherens junction are at equilibrium. Unexpectedly, mechanical tension across cadherin was similar between dividing and non-dividing epithelial cells.


Impact of pharmacotherapy on the incidence of transurethral prostatectomy for benign prostatic hyperplasia and the implications for surgical training.
Medical therapy has become first line treatment for Benign Prostatic Hypertrophy (BPH) and in many cases TURP may no longer be required. Proof and quantification of this evolution in practice has been somewhat elusive and provided the principle impetus for this study. This is a retrospective study of BPH management in Republic of Ireland from 1995 to 2008. National treatment databases were sourced for numbers undergoing TURP and pharmacotherapy prescribing data was obtained from individual pharmaceutical companies. A total of 28,240 TURP's were performed nationally between 1995 and 2008. TURP's performed annually, decreased by 1,494 (51%), alpha-blocker prescriptions increased from 8,710 to 302,159 units and the number of urology trainees increased by 10 (60%). Clear association between decreases in TURP's and increases in pharmacotherapy for BPH is demonstrated. Implications on training likely exist and will require proper evaluation in order to maintain future standards in this surgical practice.


Key stages in mammary gland development. Secretory activation in the mammary gland: it's not just about milk protein synthesis!
The transition from pregnancy to lactation is a critical event in the survival of the newborn since all the nutrient requirements of the infant are provided by milk. While milk contains numerous components, including proteins, that aid in maintaining the health of the infant, lactose and milk fat represent the critical energy providing elements of milk. Much of the research to date on mammary epithelial differentiation has focused upon expression of milk protein genes, providing a somewhat distorted view of alveolar differentiation and secretory activation. While expression of milk protein genes increases during pregnancy and at secretory activation, the genes whose expression is more tightly regulated at this transition are those that regulate lipid biosynthesis. The sterol regulatory element binding protein (SREBP) family of transcription factors is recognized as regulating fatty acid and cholesterol biosynthesis. We propose that SREBP1 is a critical regulator of secretory activation with regard to lipid biosynthesis, in a manner that responds to diet, and that the serine/threonine protein kinase Akt influences this process, resulting in a highly efficient lipid synthetic organ that is able to support the nutritional needs of the newborn.


Low-Level Hierarchical Multiscale Segmentation Statistics of Natural Images.
This paper is aimed at obtaining the statistics as a probabilistic model pertaining to the geometric, topological and photometric structure of natural images. The image structure is represented by its segmentation graph derived from the low-level hierarchical multiscale image segmentation. We first estimate the statistics of a number of segmentation graph properties from a large number of images. Our estimates confirm some findings reported in the past work, as well as provide some new ones. We then obtain a Markov random field based model of the segmentation graph which subsumes the observed statistics. To demonstrate the value of the model and the statistics, we show how its use as a prior impacts three applications: image classification, semantic image segmentation and object detection.


Inferential ecosystem models, from network data to prediction.
Recent developments suggest that predictive modeling could begin to play a larger role not only for data analysis, but also for data collection. We address the example of efficient wireless sensor networks, where inferential ecosystem models can be used to weigh the value of an observation against the cost of data collection. Transmission costs make observations "expensive"; networks will typically be deployed in remote locations without access to infrastructure (e.g., power). The capacity to sample intensively makes sensor networks valuable, but high-frequency data are informative only at specific times and locations. Sampling intervals will range from meters and seconds to landscapes and years, depending on the process, the current states of the system, the uncertainty about those states, and the perceived potential for rapid change. Given that intensive sampling is sometimes critical, but more often wasteful, how do we develop tools to control the measurement and transmission processes? We address the potential of data collection controlled and/or supplemented by inferential ecosystem models. In a given model, the value of an observation can be evaluated in terms of its contribution to estimates of state variables and important parameters. There will be more than one model applied to network data that will include as state variables water, carbon, energy balance, biogeochemistry, tree ecophysiology, and forest demographic processes. The value of an observation will depend on the application. Inference is needed to weigh the contributions against transmission cost. Network control must be dynamic and driven by models capable of learning about both the environment and the network. We discuss application of Bayesian inference to model data from a developing sensor network as a basis for controlling the measurement and transmission processes. Our examples involve soil moisture and sap flux, but we discuss broader application of the approach, including its implications for network design.


Adult lactose digestion status and effects on disease.
Adult assimilation of lactose divides humans into dominant lactase-persistent and recessive nonpersistent phenotypes. To review three medical parameters of lactose digestion, namely: the changing concept of lactose intolerance; the possible impact on diseases of microbial adaptation in lactase-nonpersistent populations; and the possibility that the evolution of lactase has influenced some disease pattern distributions. A PubMed, Google Scholar and manual review of articles were used to provide a narrative review of the topic. The concept of lactose intolerance is changing and merging with food intolerances. Microbial adaptation to regular lactose consumption in lactase-nonpersistent individuals is supported by limited evidence. There is evidence suggestive of a relationship among geographical distributions of latitude, sunhine exposure and lactase proportional distributions worldwide. The definition of lactose intolerance has shifted away from association with lactose maldigestion. Lactose sensitivity is described equally in lactose digesters and maldigesters. The important medical consequence of withholding dairy foods could have a detrimental impact on several diseases; in addition, microbial adaptation in lactase-nonpersistent populations may alter risk for some diseases. There is suggestive evidence that the emergence of lactase persistence, together with human migrations before and after the emergence of lactase persistence, have impacted modern-day diseases. Lactose maldigestion and lactose intolerance are not synonymous. Withholding dairy foods is a poor method to treat lactose intolerance. Further epidemiological work could shed light on the possible effects of microbial adaptation in lactose maldigesters. The evolutionary impact of lactase may be still ongoing.


Pparg-P465L mutation worsens hyperglycemia in Ins2-Akita female mice via adipose-specific insulin resistance and storage dysfunction.
The dominant-negative P467L mutation in peroxisome proliferator activated receptor-γ (PPARγ) was identified in insulin-resistant patients with hyperglycemia and lipodystrophy. In contrast, mice carrying the corresponding Pparg-P465L mutation have normal insulin sensitivity, with mild hyperinsulinemia. We hypothesized that murine Pparg-P465L mutation leads to covert insulin resistance, which is masked by hyperinsulinemia and increased pancreatic islet mass, to retain normal plasma glucose. We introduced in Pparg(P465L/+) mice an Ins2-Akita mutation that causes improper protein folding and islet apoptosis to lower plasma insulin. Unlike Ins2(Akita/+) littermates, male Pparg(P465L/+)Ins2(Akita/+) mice have drastically reduced life span with enhanced type 1 diabetes. Hyperglycemia in Ins2(Akita/+) females is mild. However, Pparg(P465L/+)Ins2(Akita/+) females have aggravated hyperglycemia, smaller islets, and reduced plasma insulin. In an insulin tolerance test, they showed smaller reduction in plasma glucose, indicating impaired insulin sensitivity. Although gluconeogenesis is enhanced in Pparg(P465L/+)Ins2(Akita/+) mice compared with Ins2(Akita/+), exogenous insulin equally suppressed gluconeogenesis in hepatocytes, suggesting that Pparg(P465L/+)Ins2(Akita/+) livers are insulin sensitive. Expression of genes regulating insulin sensitivity and glycogen and triglyceride contents suggest that skeletal muscles are equally insulin sensitive. In contrast, adipose tissue and isolated adipocytes from Pparg(P465L/+)Ins2(Akita/+) mice have impaired glucose uptake in response to exogenous insulin. Pparg(P465L/+)Ins2(Akita/+) mice have smaller fat depots composed of larger adipocytes, suggesting impaired lipid storage with subsequent hepatomegaly and hypertriglyceridemia. PPARg-P465L mutation worsens hyperglycemia in Ins2(Akita/+) mice primarily because of adipose-specific insulin resistance and altered storage function. This underscores the important interplay between insulin and PPARγ in adipose tissues in diabetes.


Myofibroblasts in pulmonary and brain metastases of alveolar soft-part sarcoma: a novel target for treatment?
Alveolar soft-part sarcoma (ASPS) is a rare neoplasm with chromosomal translocation that results in ASPL-TFE3 fusion. It is a slow-growing lesion associated with a high incidence of pulmonary and brain metastases indicating poor survival. We demonstrated that the ASPS metastases include also stromal myofibroblasts. These cells proliferate, express smooth-muscle genes, and synthesize extracellular matrix proteins, all of which are characteristics of activated myofibroblasts. The tumor cells also exhibited stromal components such as transforming growth factor beta (TGFbeta)-dependent, hypoxia-regulated cytoglobin (stellate cell activation association protein, cytg/STAP) and prolyl 4-hydroxylase, a collagen cross-linking enzyme. The pulmonary ASPS myofibroblasts synthesize serum response factor (SRF), a repressor of Smad3-mediated TGFbeta signaling essential for myofibroblast differentiation and Smad3. The phosphorylated active Smad3 was found mostly in the tumor cells. The brain tumor cells express cytg/STAP, but in contrast to the lung metastases, they also express SRF, Smad3, and phospho-Smad3. Halofuginone, an inhibitor of myofibroblasts' activation and Smad3 phosphorylation, inhibited tumor development in xenografts derived from renal carcinoma cells harboring a reciprocal ASPL-TFE3 fusion transcript. This inhibition was associated with the inhibition of TGFbeta/SRF signaling, with the inhibition of myofibroblasts' activation, and with the complete loss in TFE3 synthesis by the tumor cells. These results suggest that the myofibroblasts may serve as a novel target for treatment of ASPS metastases.


Psychological therapies for the treatment of post-traumatic stress disorder in children and adolescents.
Post-traumatic stress disorder (PTSD) is highly prevalent in children and adolescents who have experienced trauma and has high personal and health costs. Although a wide range of psychological therapies have been used in the treatment of PTSD there are no systematic reviews of these therapies in children and adolescents. To examine the effectiveness of psychological therapies in treating children and adolescents who have been diagnosed with PTSD. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to December 2011. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 -), MEDLINE (1950 -) and PsycINFO (1967 -). We also checked reference lists of relevant studies and reviews. We applied no date or language restrictions. All randomised controlled trials of psychological therapies compared to a control, pharmacological therapy or other treatments in children or adolescents exposed to a traumatic event or diagnosed with PTSD. Two members of the review group independently extracted data. If differences were identified, they were resolved by consensus, or referral to the review team.We calculated the odds ratio (OR) for binary outcomes, the standardised mean difference (SMD) for continuous outcomes, and 95% confidence intervals (CI) for both, using a fixed-effect model. If heterogeneity was found we used a random-effects model. Fourteen studies including 758 participants were included in this review. The types of trauma participants had been exposed to included sexual abuse, civil violence, natural disaster, domestic violence and motor vehicle accidents. Most participants were clients of a trauma-related support service.The psychological therapies used in these studies were cognitive behavioural therapy (CBT), exposure-based, psychodynamic, narrative, supportive counselling, and eye movement desensitisation and reprocessing (EMDR). Most compared a psychological therapy to a control group. No study compared psychological therapies to pharmacological therapies alone or as an adjunct to a psychological therapy.Across all psychological therapies, improvement was significantly better (three studies, n = 80, OR 4.21, 95% CI 1.12 to 15.85) and symptoms of PTSD (seven studies, n = 271, SMD -0.90, 95% CI -1.24 to -0.42), anxiety (three studies, n = 91, SMD -0.57, 95% CI -1.00 to -0.13) and depression (five studies, n = 156, SMD -0.74, 95% CI -1.11 to -0.36) were significantly lower within a month of completing psychological therapy compared to a control group.The psychological therapy for which there was the best evidence of effectiveness was CBT. Improvement was significantly better for up to a year following treatment (up to one month: two studies, n = 49, OR 8.64, 95% CI 2.01 to 37.14; up to one year: one study, n = 25, OR 8.00, 95% CI 1.21 to 52.69). PTSD symptom scores were also significantly lower for up to one year (up to one month: three studies, n = 98, SMD -1.34, 95% CI -1.79 to -0.89; up to one year: one study, n = 36, SMD -0.73, 95% CI -1.44 to -0.01), and depression scores were lower for up to a month (three studies, n = 98, SMD -0.80, 95% CI -1.47 to -0.13) in the CBT group compared to a control. No adverse effects were identified.No study was rated as a high risk for selection or detection bias but a minority were rated as a high risk for attrition, reporting and other bias. Most included studies were rated as an unclear risk for selection, detection and attrition bias. There is evidence for the effectiveness of psychological therapies, particularly CBT, for treating PTSD in children and adolescents for up to a month following treatment. At this stage, there is no clear evidence for the effectiveness of one psychological therapy compared to others. There is also not enough evidence to conclude that children and adolescents with particular types of trauma are more or less likely to respond to psychological therapies than others.The findings of this review are limited by the potential for methodological biases, and the small number and generally small size of identified studies. In addition, there was evidence of substantial heterogeneity in some analyses which could not be explained by subgroup or sensitivity analyses.More evidence is required for the effectiveness of all psychological therapies more than one month after treatment. Much more evidence is needed to demonstrate the relative effectiveness of different psychological therapies or the effectiveness of psychological therapies compared to other treatments. More details are required in future trials in regards to the types of trauma that preceded the diagnosis of PTSD and whether the traumas are single event or ongoing. Future studies should also aim to identify the most valid and reliable measures of PTSD symptoms and ensure that all scores, total and sub-scores, are consistently reported.


Acute management of acquired brain injury part I: an evidence-based review of non-pharmacological interventions.
To review the literature on non-pharmacological interventions used in acute settings to manage elevated intracranial pressure (ICP) and minimize cerebral damage in patients with acquired brain injury (ABI). A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PSYCHINFO) and hand-searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations made. Five non-invasive interventions for acute ABI management were assessed: adjusting head posture, body rotation (continuous rotational therapy and prone positioning), hyperventilation, hypothermia and hyperbaric oxygen. Two invasive interventions were also reviewed: cerebrospinal fluid (CSF) drainage and decompressive craniectomy (DC). There is a paucity of information regarding non-pharmacological acute management of patients with ABI. Strong levels of evidence were found for only four of the seven interventions (decompressive craniectomy, cerebrospinal fluid drainage, hypothermia and hyperbaric oxygen) and only for specific components of their use. Further research into all interventions is warranted.


Factors influencing the dielectric properties of agricultural and food products.
Dielectric properties of materials are defined, and the major factors that influence these properties of agricultural and food materials, namely, frequency of the applied radiofrequency or microwave electric fields, and water content, temperature, and density of the materials, are discussed on the basis of fundamental concepts. The dependence of measured dielectric properties on these factors is illustrated graphically and discussed for a number of agricultural and food products, including examples of grain, peanuts, fruit, eggs, fresh chicken meat, whey protein gel, and a macaroni and cheese preparation. General observations are provided on the nature of the variation of the dielectric properties with the major variables.


Curvature dependence of the effect of ionic functionalization on the attraction among nanoparticles in dispersion.
Solubilization of nanoparticles facilitates nanomaterial processing and enables new applications. An effective method to improve dispersibility in water is provided by ionic functionalization. We explore how the necessary extent of functionalization depends on the particle geometry. Using molecular dynamics/umbrella sampling simulations, we determine the effect of the solute curvature on solvent-averaged interactions among ionizing graphitic nanoparticles in aqueous dispersion. We tune the hydrophilicity of molecular-brush coated fullerenes, carbon nanotubes, and graphane platelets by gradually replacing a fraction of the methyl end groups of the alkyl coating by the ionizing -COOK or -NH3Cl groups. To assess the change in nanoparticles' dispersibility in water, we determine the potential-of-mean-force profiles at varied degrees of ionization. When the coating comprises only propyl groups, the attraction between the hydrophobic particles intensifies from spherical to cylindrical to planar geometry. This is explained by the increasing fraction of surface groups that can be brought into contact and the reduced access to water molecules, both following the above sequence. When ionic groups are added, however, the dispersibility increases in the opposite order, with the biggest effect in the planar geometry and the smallest in the spherical geometry. These results highlight the important role of geometry in nanoparticle solubilization by ionic functionalities, with about twice higher threshold surface charge necessary to stabilize a dispersion of spherical than planar particles. At 25%-50% ionization, the potential of mean force reaches a plateau because of the counterion condensation and saturated brush hydration. Moreover, the increase in the fraction of ionic groups can weaken the repulsion through counterion correlations between adjacent nanoparticles. High degrees of ionization and concomitant ionic screening gradually reduce the differences among surface interactions in distinct geometries until an essentially curvature-independent dispersion environment is created. Insights into tuning nanoparticle interactions can guide the synthesis of a broad class of nonpolar nanoparticles, where solubility is achieved by ionic functionalization.


Faster and economical screening for vancomycin-resistant enterococci by sequential use of chromogenic agar and real-time polymerase chain reaction.
Screening for vancomycin-resistant enterococci (VRE) by culture takes days to generate results, while polymerase chain reaction (PCR) testing directly from clinical specimens lacks specificity. The aims of this study were to develop a real-time PCR to detect and identify Enterococcus faecium, Enterococcus faecalis, and vanA and vanB genes, and to evaluate the impact of this PCR on test-reporting times when performing it directly from suspect VRE isolates present on screening chromogenic media. The tetraplex PCR primers were designed to amplify E. faecium, E. faecalis, and vanA and vanB genes, with melt-curve analysis of PCR products. Following analytical and clinical validation of the molecular assay, PCR testing was performed for target colonies present on VRE chromogenic media. PCR results were evaluated against conventional phenotypic identification and susceptibility testing, with the time to result being monitored for both modalities. A total of 519 colonies from clinical specimens were tested concurrently by real-time PCR and phenotypic methods. In all, 223 isolates were identified with phenotypic vancomycin resistance (vanA, n = 108; vanB, n = 105; non-vanA/vanB = 10), with complete agreement between PCR and phenotypic testing for vancomycin-resistant E. faecium and E. faecalis. The majority (88.6%) of PCR results were reported, on average, 24.8 hours earlier than those of phenotypic testing, with 68% reduction in total costs. The use of culture on selective media, followed by direct colony PCR confirmation allows faster and economical VRE screening.


Health-related quality of life among Chinese primary care patients with different lower urinary tract symptoms: a latent class analysis.
No previous study has used a data-driven approach to explore symptom subclasses among patients with lower urinary tract symptoms (LUTS). The objectives of this study were to use latent class analysis (LCA) to identify distinct classes of LUTS among primary care patients and to assess the class differences in health-related quality of life (HRQOL). In this cross-sectional study, 500 patients were randomly recruited, and 18 symptoms according to the International Continence Society 2002 criteria were assessed. Classes were identified by LCA. Patient HRQOL was measured using the 12-item Short Form Health Survey (version 2), the modified Incontinence Impact Questionnaire-Short Form and the HRQOL item from the International Prostate Symptom Score. Six distinct LUTS classes were identified: "asymptomatic" (26.0%), "mild symptoms" (22.6%), "moderate multiple symptoms" (17.0%), "urgency symptoms" (13.8%), "urinary incontinence" (12.0%) and "severe multiple symptoms" (8.6%). Multinomial regression analysis found differences in the gender distribution and prevalence of heart diseases across classes, and multiple linear regression found that patients with "severe multiple symptoms" and "urinary incontinence" had the poorest HRQOL. Almost three quarters of the primary care patients in this study were suffering from varying degrees of LUTS. The poor HRQOL in "severe multiple symptoms" and "urinary incontinence" implies that patients in these classes require additional attention and treatments.


Storage of prescription veterinary medicines on UK dairy farms: a cross-sectional study.
Prescription veterinary medicine (PVM) use in the UK is an area of increasing focus for the veterinary profession. While many studies measure antimicrobial use on dairy farms, none report the quantity of antimicrobials stored on farms, nor the ways in which they are stored. The majority of PVM treatments occur in the absence of the prescribing veterinarian, yet there is an identifiable knowledge gap surrounding PVM use and farmer decision making. To provide an evidence base for future work on PVM use, data were collected from 27 dairy farms in England and Wales in Autumn 2016. The number of different PVMs stored on farms ranged from 9 to 35, with antimicrobials being the most common therapeutic group stored. Injectable antimicrobials comprised the greatest weight of active ingredient found, while intramammary antimicrobials were the most frequent unit of medicine stored. Antimicrobials classed by the European Medicines Agency as critically important to human health were present on most farms, and the presence of expired medicines and medicines not licensed for use in dairy cattle was also common. The medicine resources available to farmers are likely to influence their treatment decisions; therefore, evidence of the PVM stored on farms can help inform understanding of medicine use.


HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3' untranslated regions of cytokine and angiogenic factor mRNAs.
Tumors of the central nervous system (CNS) often have sustained expression of labile genes, including angiogenic growth factors and immunosuppressive cytokines, which promote tumor progression. Stabilization of the RNA transcripts for these genes, such as vascular endothelial growth factor (VEGF), is an important molecular pathway for this up-regulation. HuR, a member of the Elav family of RNA-binding proteins, has been implicated in this pathway through its binding to adenine and uridine (AU)-rich stability elements (ARE) located in the 3' untranslated regions (3'-UTRs) of the mRNA. Whereas three of the Elav family members (Hel-N1, HuC, and HuD) are restricted to young and mature neurons, HuR is more broadly expressed, including proliferating cells of the developing CNS. Because RNA stabilization of labile genes may promote tumor growth, we analyzed and compared the expression pattern of HuR in 35 freshly resected and cultured CNS tumors to determine whether there was any correlation with tumor grade or histological type. We found that HuR mRNA was consistently expressed in all of the tumors, regardless of cell origin or degree of malignancy. Using a novel HuR-specific polyclonal antibody, we found that strong HuR protein expression was limited to high-grade malignancies (glioblastoma multiforme and medulloblastoma). Within the glioblastoma multiforme, prominent HuR expression was also detected in perinecrotic areas in which angiogenic growth factors are up-regulated. To further define its role as a potential RNA stabilizer, we analyzed whether HuR could bind to the stability motifs within the 3'-UTRs of cytokines and growth factors linked to brain tumor progression. We used a novel ELISA-based RNA binding assay and focused on the 3'-UTRs of angiogenic factors VEGF, COX-2, and (interleukin) IL-8 as well as the immunomodulating factors IL-6, transforming growth factor (TGF)-beta and tumor necrosis factor (TNF)-alpha as potential RNA ligands. Our results indicated overall a very high binding affinity to these RNA targets. A comparison of these ligands revealed a hierarchy of binding affinities with the angiogenic factors, and TGF-beta showing the highest (Kd of 1.8-3.4 nM), and TNF-alpha the lowest (Kd of 18.3 nM). The expression pattern of HuR, coupled with the RNA binding data, strongly suggests a role for this protein in the posttranscriptional regulation of these genes in CNS tumors.


Ascending projections to the medial geniculate body of the cat: evidence for multiple, parallel auditory pathways through thalamus.
The sources of ascending input to the medial geniculate body (MGB) of the cat were studied using the retrograde transport of horseradish peroxidase (HRP). HRP injections were made iontophoretically through micropipettes which were also used to record physiological properties at the injection sites. This technique produced small injections which appeared to be restricted to single subnuclei. The tectothalamic projection of the auditory system was found to consist of at least four distinct and separate pathways. The ventral division of the MGB receives a topographical projection from the central nucleus of the inferior colliculus (ICC) which preserves tonotopicity and provides short latency, sharply frequency-tuned responses. The medial part of the ICC projects to the deep dorsal nucleus, which contains only units tuned to high frequencies. The major inputs to the caudodorsal nucleus (DC) stem from nucleus sagulum and the pericentral nucleus of the inferior colliculus (ICP). Units in DC and the ventrolateral nucleus, which also receive input from ICP, have very broad tuning properties and late, habituating responses. Injections of HRP into the medial division (MGM) produced labeled cells scattered throughout the external nucleus of the inferior colliculus and the ventral part of ICC. This widespread input is reflected in the wide range of auditory responses found in MGM. Auditory responses in the suprageniculate nucleus were poorly defined and many units did not respond to tonal stimuli; following HRP injections no filled cells were found in the inferior colliculus, but labeled cells were found in the deeper layers of the superior colliculus and in the interstitial nucleus of the brachium of the inferior colliculus. Together with recent findings on the auditory thalamocortical projection, these results provide evidence for multiple parallel auditory pathways through the thalamus.


Si Nanocrystal-Embedded SiO x nanofoils: Two-Dimensional Nanotechnology-Enabled High Performance Li Storage Materials.
Silicon (Si) based materials are highly desirable to replace currently used graphite anode for lithium ion batteries. Nevertheless, its usage is still a big challenge due to poor battery performance and scale-up issue. In addition, two-dimensional (2D) architectures, which remain unresolved so far, would give them more interesting and unexpected properties. Herein, we report a facile, cost-effective, and scalable approach to synthesize Si nanocrystals embedded 2D SiO x nanofoils for next-generation lithium ion batteries through a solution-evaporation-induced interfacial sol-gel reaction of hydrogen silsesquioxane (HSiO1.5, HSQ). The unique nature of the thus-prepared centimeter scale 2D nanofoil with a large surface area enables ultrafast Li+ insertion and extraction, with a reversible capacity of more than 650 mAh g-1, even at a high current density of 50 C (50 A g-1). Moreover, the 2D nanostructured Si/SiO x nanofoils show excellent cycling performance up to 200 cycles and maintain their initial dimensional stability. This superior performance stems from the peculiar nanoarchitecture of 2D Si/SiO x nanofoils, which provides short diffusion paths for lithium ions and abundant free space to effectively accommodate the huge volume changes of Si during cycling.


Implementation of principles of pharmacoeconomics and pharmacovigilance to achieve optimal financial and therapeutic benefits through WHO - Essential medicine policy and adoption of NLEM-Based hospital formulary policy.
WHO in its development of the roadmap on access to medicines and vaccines 2019-2023 has emphasized that the greatest challenge in achieving Universal Health Coverage (UHC) stem from persistent barriers to accessing health services and to accessing affordable and quality assured health products. In this context, WHO introduced the concept of essential medicines in 1977, and since then, this concept, has been revised every 2 years and is accepted by many countries as guideline to develop National Drug Policy. The concept emphasizes that all aspects of drug management, including procurement, storage, distribution, and use, are easier if fewer essential medicines/items must be dealt with. Essential Medicines are those that satisfy the priority healthcare needs of the population. During 2017-18, based on the principles of Essential Medicines Concept, we decided to develop and implement "Quality Procurement Management Policies'(QPMP) at Sir Sundar Lal Hospital, at Varanasi. The Pharmaco-econmics and Pharmacovigilance tools are also used to further maximize financial and therapeutic benefits. This is evidence based, an observational, and retrospective study. Initially, the analysis of current data on sales of antibiotics during November 2017, December 2017, and January 2018, the procurement practices, selection of medicines, and pattern of use was studied and based on these findings reforms were designed and implemented through the Hospital Formulary Committee. This study revealed that- By the application of QPMP, both the Cost and Quality factors of Medication Management can be dealt with very effectively. And it is possible to make available Quality Assured Medicines at most economic prices, resulting in substantial savings. This study has further, shown that the confidence of physicians also improved as quality assured medicines are provided. The study at Sir Sundar Lal Hospital is thus worth emulating and shown that a doable roadmap with signposts at each and every turn can be designed and can be effectively implemented so that the goal of UHC can be achieved.


Diapause in Drosophila melanogaster - Photoperiodicity, cold tolerance and metabolites.
Unlike many insects where photoperiod per se induces diapause, reproductive arrest in Drosophila melanogaster adult females is observed at colder temperatures and can be enhanced by shorter photoperiods. Traditional experimental protocols raise flies at 25 °C from the larval stage and then the adults are placed at 12 °C for between 12 and 28 days. After 12 days diapause levels are usually higher than at 28 days, suggesting that the flies are in a cold induced quiescence, rather than a true diapause. By raising flies at more realistic lower temperatures, we observe quite dramatic and counter-intuitive effects on diapause, whose levels nevertheless correlate with various indices of cryoprotectant metabolites as well as resistance to chill shock. We also observe that photoperiodic effects are minimised when very small temperature oscillations associated with the light-dark incubator cycles are neutralised. Our results suggest that the reported photoperiodic component of fly diapause, at least in these strains, is mostly due to thermoperiodic rather than photoperiodic stimuli. In addition, the metabolite and chill shock analyses reveal that even by 12 days, flies are entering a state that is resistant to environmental stresses.


CYP19A1 genetic variation in relation to prostate cancer risk and circulating sex hormone concentrations in men from the Breast and Prostate Cancer Cohort Consortium.
Sex hormones, particularly the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiologic evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterized variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNP) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5% to 10% difference in estradiol concentrations in men [association per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 1 x 10(-5)], and with inverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterized by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk of prostate cancer.


Drosophila Central Nervous System Glia.
Molecular genetic approaches in small model organisms like Drosophila have helped to elucidate fundamental principles of neuronal cell biology. Much less is understood about glial cells, although interest in using invertebrate preparations to define their in vivo functions has increased significantly in recent years. This review focuses on our current understanding of the three major neuron-associated glial cell types found in the Drosophila central nervous system (CNS)-astrocytes, cortex glia, and ensheathing glia. Together, these cells act like mammalian astrocytes: they surround neuronal cell bodies and proximal neurites, are coupled to the vasculature, and associate closely with synapses. Exciting recent work has shown essential roles for these CNS glial cells in neural circuit formation, function, plasticity, and pathology. As we gain a more firm molecular and cellular understanding of how Drosophila CNS glial cells interact with neurons, it is becoming clear they share significant molecular and functional attributes with mammalian astrocytes.


Efficient CO oxidation at low temperature on Au(111).
The rate of CO oxidation to CO2 depends strongly on the reaction temperature and characteristics of the oxygen overlayer on Au(111). The factors that contribute to the temperature dependence in the oxidation rate are (1) the residence time of CO on the surface, (2) the island size containing Au-O complexes, and (3) the local properties, including the degree of order of the oxygen layer. Three different types of oxygen--defined as chemisorbed oxygen, a surface oxide, and a bulk oxide--are identified and shown to have different reactivity. The relative populations of the various oxygen species depend on the preparation temperature and the oxygen coverage. The highest rate of CO oxidation was observed for an initial oxygen coverage of 0.5 monolayers that was deposited at 200 K where the density of chemisorbed oxygen is maximized. The rate decreases when two-dimensional islands of the surface oxide are populated and further decreases when three-dimensional bulk gold oxide forms. Our results are significant for designing catalytic processes that use Au for CO oxidation, because they suggest that the most efficient oxidation of CO occurs at low temperature--even below room temperature--as long as oxygen could be adsorbed on the surface.


Deep learning-based electroencephalography analysis: a systematic review.
Electroencephalography (EEG) is a complex signal and can require several years of training, as well as advanced signal processing and feature extraction methodologies to be correctly interpreted. Recently, deep learning (DL) has shown great promise in helping make sense of EEG signals due to its capacity to learn good feature representations from raw data. Whether DL truly presents advantages as compared to more traditional EEG processing approaches, however, remains an open question. In this work, we review 154 papers that apply DL to EEG, published between January 2010 and July 2018, and spanning different application domains such as epilepsy, sleep, brain-computer interfacing, and cognitive and affective monitoring. We extract trends and highlight interesting approaches from this large body of literature in order to inform future research and formulate recommendations. Major databases spanning the fields of science and engineering were queried to identify relevant studies published in scientific journals, conferences, and electronic preprint repositories. Various data items were extracted for each study pertaining to (1) the data, (2) the preprocessing methodology, (3) the DL design choices, (4) the results, and (5) the reproducibility of the experiments. These items were then analyzed one by one to uncover trends. Our analysis reveals that the amount of EEG data used across studies varies from less than ten minutes to thousands of hours, while the number of samples seen during training by a network varies from a few dozens to several millions, depending on how epochs are extracted. Interestingly, we saw that more than half the studies used publicly available data and that there has also been a clear shift from intra-subject to inter-subject approaches over the last few years. About [Formula: see text] of the studies used convolutional neural networks (CNNs), while [Formula: see text] used recurrent neural networks (RNNs), most often with a total of 3-10 layers. Moreover, almost one-half of the studies trained their models on raw or preprocessed EEG time series. Finally, the median gain in accuracy of DL approaches over traditional baselines was [Formula: see text] across all relevant studies. More importantly, however, we noticed studies often suffer from poor reproducibility: a majority of papers would be hard or impossible to reproduce given the unavailability of their data and code. To help the community progress and share work more effectively, we provide a list of recommendations for future studies and emphasize the need for more reproducible research. We also make our summary table of DL and EEG papers available and invite authors of published work to contribute to it directly. A planned follow-up to this work will be an online public benchmarking portal listing reproducible results.


Elevated carbon monoxide in the exhaled breath of mice during a systemic bacterial infection.
Blood is the specimen of choice for most laboratory tests for diagnosis and disease monitoring. Sampling exhaled breath is a noninvasive alternative to phlebotomy and has the potential for real-time monitoring at the bedside. Improved instrumentation has advanced breath analysis for several gaseous compounds from humans. However, application to small animal models of diseases and physiology has been limited. To extend breath analysis to mice, we crafted a means for collecting nose-only breath samples from groups and individual animals who were awake. Samples were subjected to gas chromatography and mass spectrometry procedures developed for highly sensitive analysis of trace volatile organic compounds (VOCs) in the atmosphere. We evaluated the system with experimental systemic infections of severe combined immunodeficiency Mus musculus with the bacterium Borrelia hermsii. Infected mice developed bacterial densities of ∼10(7) per ml of blood by day 4 or 5 and in comparison to uninfected controls had hepatosplenomegaly and elevations of both inflammatory and anti-inflammatory cytokines. While 12 samples from individual infected mice on days 4 and 5 and 6 samples from uninfected mice did not significantly differ for 72 different VOCs, carbon monoxide (CO) was elevated in samples from infected mice, with a mean (95% confidence limits) effect size of 4.2 (2.8-5.6), when differences in CO2 in the breath were taken into account. Normalized CO values declined to the uninfected range after one day of treatment with the antibiotic ceftriaxone. Strongly correlated with CO in the breath were levels of heme oxygenase-1 protein in serum and HMOX1 transcripts in whole blood. These results (i) provide further evidence of the informativeness of CO concentration in the exhaled breath during systemic infection and inflammation, and (ii) encourage evaluation of this noninvasive analytic approach in other various other rodent models of infection and for utility in clinical management.


The role of structural flexibility and stability in the interaction of serine proteases with their inhibitors.
Serine proteases and their natural inhibitors have long been served as excellent models for studying (primary, secondary and tertiary) structure - activity relationships of biologically interacting proteins. As protein flexibility has been accepted as a "fourth dimension" of the protein structure, its contribution to the binding process has gained much interest. In this article we review extreme cases of serine protease interactions with canonical serine protease inhibitors that provide unique insights into the dynamics of protein- protein interactions. The major conclusions of our review article are: a) taxon-specific inhibitory effects of two highly homologous protease inhibitors from Schistocerca gregaria (SGCI and SGTI), as investigated by H/D exchange experiments and NMR spectroscopy, are due to their differential flexibilities, b) stabilities of some protease and inhibitor complexes, the wide-spread and increased flexibility of some segments in the protein-protein complexes, as studied by X-ray crystallography and NMR-spectroscopy, appear to be proportional to the physical stability of the complex.


Emotional problems among recent immigrants and parenting status: Findings from a national longitudinal study of immigrants in Canada.
The present study examined predictors of emotional problems amongst a nationally representative cohort of recent immigrants in Canada. Specifically, the effects of parenting status were examined given the association between parenting stress and mental health. Data came from the Longitudinal Survey of Immigrants to Canada (N = 7055). Participants were recruited 6-months post landing (2001-2002) and followed up at 2 and 4 years. Self-reported emotional problems over time were considered as a function of parenting status (Two Parent, Lone Parent, Divorced Non-Parent, Non-Divorced Non-Parent) and sociodemographic characteristics. Odds of emotional problems were higher among Two Parent, OR = 1.12 (1.01, 1.24), Lone Parent, OR = 2.24 (1.75, 2.88), and Divorced Non-Parent, OR = 1.30 (1.01, 1.66) immigrants compared to Non-Divorced Non-Parents. Visible minority status, female gender, low income, and refugee status were associated with elevated risk. Findings reveal that immigrant parents are at risk for emotional health problems during the post-migration period. Such challenges may be compounded by other sociodemographic risk.


PRISM (Program of Resources, Information and Support for Mothers) Protocol for a community-randomised trial [ISRCTN03464021].
In the year after birth one in six women has a depressive illness, and 30% are still depressed, or depressed again, when their child is 2 years old, 94% experience at least one major health problem (e.g. back pain, perineal pain, mastitis, urinary or faecal incontinence), 26% experience sexual problems and almost 20% have relationship problems with partners. Women with depression report less practical and emotional support from partners, less social support overall, more negative life events, and poorer physical health. Their perceptions of factors contributing to depression are lack of support, isolation, exhaustion and physical health problems. Fewer than one in three affected women seek help in primary care despite frequent contacts. PRISM aims to reduce depression and physical health problems of recent mothers through primary care strategies to increase practitioners' response to these issues, and through community-based strategies to develop broader family and community supports for recent mothers. Eligible local governments will be recruited and randomised to intervention or comparison arms, after stratification (urban/rural, size, birth numbers, extent of community activity), avoiding contiguous boundaries. Maternal depression and physical health will be measured six months after birth, in a one year cohort of mothers, in intervention and comparison communities. The sample size to detect a 20% relative reduction in depression, adjusting for cluster sampling, and estimating a population response fraction of 67% is 5740 x 2. Analysis of the physical and mental health outcomes, by intention to treat, will adjust for the correlated structure of the data.


Lactobacillus wasatchensis sp. nov., a non-starter lactic acid bacteria isolated from aged Cheddar cheese.
A Gram-stain positive, rod-shaped, non-spore-forming strain (WDC04T), which may be associated with late gas production in cheese, was isolated from aged Cheddar cheese following incubation on MRS agar (pH 5.2) at 6 °C for 35 days. Strain WDC04T had 97 % 16S rRNA gene sequence similarity with Lactobacillus hokkaidonensis DSM 26202T, Lactobacillus oligofermentans 533, 'Lactobacillus danicus' 9M3, Lactobacillus suebicus CCUG 32233T and Lactobacillus vaccinostercus DSM 20634T. API 50 CH carbohydrate fermentation panels indicated strain WDC04T could only utilize one of the 50 substrates tested, ribose, although it does slowly utilize galactose. In the API ZYM system, strain WDC04T was positive for leucine arylamidase, valine arylamidase, cysteine arylamidase (weakly), naphthol-AS-BI-phosphohydrolase and β-galactosidase activities. Total genomic DNA was sequenced from strain WDC04T using a whole-genome shotgun strategy on a 454 GS Titanium pyrosequencer. The sequence was assembled into a 1.90 Mbp draft genome consisting of 105 contigs with preliminary genome annotation performed using the RAST algorithm (rast.nmpdr.org). Genome analysis confirmed the pentose phosphate pathway for ribose metabolism as well as galactose, N-acetylglucosamine, and glycerol fermentation pathways. Genomic analysis places strain WDC04T in the obligately heterofermentative group of lactobacilli and metabolic results confirm this conclusion. The result of genome sequencing, along with 16S rRNA gene sequence analysis, indicates WDC04T represents a novel species of the genus Lactobacillus, for which the name Lactobacillus wasatchensis sp. nov. is proposed. The type strain is WDC04T ( = DSM 29958T = LMG 28678T).


Exosome: a significant nano-scale drug delivery carrier.
In recent years, due to the limitations of the nature of therapeutic agents, many synthetic nano-delivery systems have emerged to enhance the efficacy of drugs. Extracellular vesicles are currently a class of natural nano-scale drug carriers released by cells. As a tiny vesicle with a lipid bilayer membrane that can be secreted by most cells in the body, exosomes carry and transmit important signal molecules, Therefore, they have been a research hotspot in biomedicine and biomaterials due to their size advantages and huge potential in drug therapy. Many people are optimistic about the clinical application prospects of exosomes and are actively exploring the broad functions of exosomes and developing exosome therapeutic agents to make positive contributions to human health. In this review, we provide basic knowledge and focus on summarizing the advantages of exosomes as drug carriers, methods of loading drugs, targeting strategies, in vivo and in vitro tracing methods, and some of the latest developments in exosomes as drug carriers. In particular, the review provides an outlook for this field.


Health care seeking among urban minority adolescent girls: the crisis at sexual debut.
We wanted to explore the context of help seeking for reproductive and nonreproductive health concerns by urban adolescent girls. We undertook a qualitative study using in-depth interviews of African American and Latina girls (n = 22) aged 13 to 19 years attending public high schools in the Bronx, NY. Before the onset of sexual activity, most girls meet health needs within the context of the family, relying heavily on mothers for health care and advice. Many new needs and concerns emerge at sexual debut. Key factors modulating girls' ability to address their health needs and concerns include (1) the strategy of selective disclosure of information perceived to be harmful to close family relationships or threaten privacy; (2) the desire for personalized care, modeled on the emotional and physical care received from mother; and (3) relationships with physicians that vary in quality, ranging from distant relationships focused on providing information to close continuity relationships. Core values shaping these processes include privacy, a close relationship with the mother, and a perception of sexual activity as dangerous. No girl was able to meet her specific reproductive health needs within the mother-daughter relationship. Some find nonmaternal sources of personalized health care and advice for reproductive health needs, but many do not. Adolescent girls attempt to meet reproductive health needs within a context shaped by values of privacy and close mother-daughter relationships. Difficulty balancing these values often results in inadequate support and care.


Information-Theoretic Measures Predict the Human Judgment of Rhythm Complexity.
To formalize the human judgment of rhythm complexity, we used five measures from information theory and algorithmic complexity to measure the complexity of 48 artificially generated rhythmic sequences. We compared these measurements to human prediction accuracy and easiness judgments obtained from a listening experiment, in which 32 participants guessed the last beat of each sequence. We also investigated the modulating effects of musical expertise and general pattern identification ability. Entropy rate and Kolmogorov complexity were correlated with prediction accuracy, and highly correlated with easiness judgments. A logistic regression showed main effects of musical training, entropy rate, and Kolmogorov complexity, and an interaction between musical training and both entropy rate and Kolmogorov complexity. These results indicate that information-theoretic concepts capture some salient features of the human judgment of rhythm complexity, and they confirm the influence of musical expertise on complexity judgments.


Rubidium-strontium, uranium, and thorium-lead dating of lunar material.
Rubidiuom and stronztiulm concentrations and strontium isotopic compositions have been measutred on whole rock samples and density fractions of microgabbro. Density fractionis on two rocks define isochrons of 3400 and 4500 million years with large uincertainties owing to low enrichment of radiogenic strontium. Lead from fine surface material is highly radiogenic. An age of 4750 million years has been calculated from the ratio of (207)Pb/(206)Pb. The concentrations of uiranium, thorium, and lead isotopes are consistent with the evolution of lead in a 4700-million-year-old closed system characterized by the ratios of uranium to lead and of thoriunm to lead in this sutrface material.


The origin of high electrolyte-electrode interfacial resistances in lithium cells containing garnet type solid electrolytes.
Dense LLZO (Al-substituted Li7La3Zr2O12) pellets were processed in controlled atmospheres to investigate the relationships between the surface chemistry and interfacial behavior in lithium cells. Laser induced breakdown spectroscopy (LIBS), scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectroscopy, synchrotron X-ray photoelectron spectroscopy (XPS) and soft X-ray absorption spectroscopy (XAS) studies revealed that Li2CO3 was formed on the surface when LLZO pellets were exposed to air. The distribution and thickness of the Li2CO3 layer were estimated by a combination of bulk and surface sensitive techniques with various probing depths. First-principles thermodynamic calculations confirmed that LLZO has an energetic preference to form Li2CO3 in air. Exposure to air and the subsequent formation of Li2CO3 at the LLZO surface is the source of the high interfacial impedances observed in cells with lithium electrodes. Surface polishing can effectively remove Li2CO3 and dramatically improve the interfacial properties. Polished samples in lithium cells had an area specific resistance (ASR) of only 109 Ω cm(2) for the LLZO/Li interface, the lowest reported value for Al-substituted LLZO. Galvanostatic cycling results obtained from lithium symmetrical cells also suggest that the quality of the LLZO/lithium interface has a significant impact on the device lifetime.


Psychometric evaluation of the Korean Version of the Self-Efficacy for Exercise Scale for older adults.
We evaluated the psychometric properties of the Korean version of the Self-Efficacy for Exercise Scale (SEE-K). The SEE-K consists of nine items and was translated into Korean using the forward-backward translation method. We administered it to 212 community-dwelling older adults along with measures of outcome expectation for exercise, quality of life, and physical activity. The validity was determined using confirmatory factor analysis and Rasch analysis with INFIT and OUTFIT statistics, which showed acceptable model fit. The concurrent validity was confirmed according to positive correlations between the SEE-K, outcome expectation for exercise, and quality of life. Furthermore, the high physical activity group had higher SEE-K scores. Finally, the reliability of the SEE-K was deemed acceptable based on Cronbach's alpha, coefficients of determination, and person and item separation indices with reliability. Thus, the SEE-K appears to have satisfactory validity and reliability among older adults in South Korea.


Incomplete glycosylation during prion infection unmasks a prion protein epitope that facilitates prion detection and strain discrimination.
The causative factors underlying conformational conversion of cellular prion protein (PrPC) into its infectious counterpart (PrPSc) during prion infection remain undetermined, in part because of a lack of monoclonal antibodies (mAbs) that can distinguish these conformational isoforms. Here we show that the anti-PrP mAb PRC7 recognizes an epitope that is shielded from detection when glycans are attached to Asn-196. We observed that whereas PrPC is predisposed to full glycosylation and is therefore refractory to PRC7 detection, prion infection leads to diminished PrPSc glycosylation at Asn-196, resulting in an unshielded PRC7 epitope that is amenable to mAb recognition upon renaturation. Detection of PRC7-reactive PrPSc in experimental and natural infections with various mouse-adapted scrapie strains and with prions causing deer and elk chronic wasting disease and transmissible mink encephalopathy uncovered that incomplete PrPSc glycosylation is a consistent feature of prion pathogenesis. We also show that interrogating the conformational properties of the PRC7 epitope affords a direct means of distinguishing different prion strains. Because the specificity of our approach for prion detection and strain discrimination relies on the extent to which N-linked glycosylation shields or unshields PrP epitopes from antibody recognition, it dispenses with the requirement for additional standard manipulations to distinguish PrPSc from PrPC, including evaluation of protease resistance. Our findings not only highlight an innovative and facile strategy for prion detection and strain differentiation, but are also consistent with a mechanism of prion replication in which structural instability of incompletely glycosylated PrP contributes to the conformational conversion of PrPC to PrPSc.


Heart Rate and its Variability Assessed by Spectral Analysis in Elderly Subjects with Orthostatic Hypotension: A Case-Control Study.
The prevalence of orthostatic hypotension (OH) increases with age and is associated with changes in autonomic regulation of blood pressure (BP) and heart rate (HR). to assess HR and HR variability (HRV) in elderly subjects with OH and determine OH predictors. a total of 105 patients aged ≥ 60 years, 39 with OH (case group) and 66 without OH (control group) (age-matched) were studied. Patients underwent clinical assessment, electrocardiogram, biochemistry tests and Holter monitoring for spectral analysis of HRV (Fourier transform) in the supine and orthostatism positions to identify low frequency (LF) and high frequency (HF) components, as well as the LF/HF ratio. median age was 73.0 years, 64 patients were women. In all participants, there was a reduction in HF (133.0 versus 76.0 ms2, p = 0.001) and increase in LF/HF (1.6 vs 2.1; p < 0.001) and no change in LF (233.0 versus 218.0 ms2, p = 0.080). Between-group comparisons revealed significant differences in the median values of HR in the supine position (62.0 vs. 69.0 bpm, p = 0.001) and LF in the supine position (157.0 in case group vs. 275.0 ms2 in the control group, p = 0.014). Spearman's correlation coefficient of 0.27 was found between the groups. Multivariate analysis revealed that HR in the supine position was an independent variable for OH (p = 0.001- 95%CI = -0.022 and -0.006). Using the operating characteristic curve, the best cutoff point was 61 bpm, with a sensitivity of 77.3% and specificity of 51.3%, positive predictive value of 61.3%, and negative predictive value 69.3%. Odds ratio was 3.23 for OH in patients with a HR lower than 61 bpm. lower LF and HR in the supine position were found in patients with OH, regardless of age and gender. The independent predictor for OH was HR in the supine position, with an odds ratio of 3.23 for values lower than 61 bpm.


Stress relaxation properties of four orthodontic aligner materials: A 24-hour in vitro study.
To investigate the stress release properties of four thermoplastic materials used to make orthodontic aligners when subjected to 24 consecutive hours of deflection. Four types of aligner materials (two single and two double layered) were selected. After initial yield strength testing to characterize the materials, each sample was subjected to a constant load for 24 hours in a moist, temperature-regulated environment, and the stress release over time was measured. The test was performed three times on each type of material. All polymers analyzed released a significant amount of stress during the 24-hour period. Stress release was greater during the first 8 hours, reaching a plateau that generally remained constant. The single-layer materials, F22 Aligner polyurethane (Sweden & Martina, Due Carrare, Padova, Italy) and Duran polyethylene terephthalate glycol-modified (SCHEU, Iserlohn, Germany), exhibited the greatest values for both absolute stress and stress decay speed. The double-layer materials, Erkoloc-Pro (Erkodent, Pfalzgrafenweiler, Germany) and Durasoft (SCHEU), exhibited very constant stress release, but at absolute values up to four times lower than the single-layer samples tested. Orthodontic aligner performance is strongly influenced by the material of their construction. Stress release, which may exceed 50% of the initial stress value in the early hours of wear, may cause significant changes in the behavior of the polymers at 24 hours from the application of orthodontic loads, which may influence programmed tooth movement.


Engineering principles of clinical cell-based tissue engineering.
Tissue engineering is a rapidly evolving discipline that seeks to repair, replace, or regenerate specific tissues or organs by translating fundamental knowledge in physics, chemistry, and biology into practical and effective materials, devices, systems, and clinical strategies. Stem cells and progenitors that are capable of forming new tissue with one or more connective tissue phenotypes are available from many adult tissues and are defined as connective tissue progenitors. There are four major cell-based tissue-engineering strategies: (1) targeting local connective tissue progenitors where new tissue is desired, (2) transplanting autogenous connective tissue progenitors, (3) transplanting culture-expanded or modified connective tissue progenitors, and (4) transplanting fully formed tissue generated in vitro or in vivo. Stem cell function is controlled by changes in stem cell activation and self-renewal or by changes in the proliferation, migration, differentiation, or survival of the progeny of stem cell activation, the downstream progenitor cells. Three-dimensional porous scaffolds promote new tissue formation by providing a surface and void volume that promotes the attachment, migration, proliferation, and desired differentiation of connective tissue progenitors throughout the region where new tissue is needed. Critical variables in scaffold design and function include the bulk material or materials from which it is made, the three-dimensional architecture, the surface chemistry, the mechanical properties, the initial environment in the area of the scaffold, and the late scaffold environment, which is often determined by degradation characteristics. Local presentation or delivery of bioactive molecules can change the function of connective tissue progenitors (activation, proliferation, migration, differentiation, or survival) in a manner that results in new or enhanced local tissue formation. All cells require access to substrate molecules (oxygen, glucose, and amino acids). A balance between consumption and local delivery of these substrates is needed if cells are to survive. Transplanted cells are particularly vulnerable. Theoretical calculations can be used to explore the relationships among cell density, diffusion distance, and cell viability within a graft and to design improved strategies for transplantation of connective tissue progenitors. Rational strategies for tissue engineering seek to optimize new tissue formation through the logical selection of conditions that modulate the performance of connective tissue progenitors in a graft site to produce a desired tissue. This increasingly involves strategies that combine cells, matrices, inductive stimuli, and techniques that enhance the survival and performance of local or transplanted connective tissue progenitors.


Optimal and variant metal-ion routes in DNA polymerase β's conformational pathways.
To interpret recent structures of the R283K mutant of human DNA repair enzyme DNA polymerase β (pol β) differing in the number of Mg(2+) ions, we apply transition path sampling (TPS) to assess the effect of differing ion placement on the transition from the open one-metal to the closed two-metal state. We find that the closing pathway depends on the initial ion position, both in terms of the individual transition states and associated energies. The energy barrier of the conformational pathway varies from 25 to 58 kJ/mol, compared to the conformational energy barrier of 42 kJ/mol for the wild-type pol β reported previously. Moreover, we find a preferred ion route located in the center of the enzyme, parallel to the DNA. Within this route, the conformational pathway is similar to that of the overall open to closed transition of pol β, but outside it, especially when the ion starts near active site residues Arg258 and Asp190, the conformational pathway diverges significantly. Our findings should apply generally to pol β, since R283K is relatively far from the active site; further experimental and computational work are required to confirm this. Our studies also underscore the common feature that less active mutants have less stable closed states than their open states, in marked contrast to the wild-type enzyme, where the closed state is significantly more stable than the open form.


A quantitative assessment of the parameters of the role of receptionists in modern primary care using the work design framework.
Amidst increased pressures on General Practice across England, the receptionist continues to fulfil key administrative and clinically related tasks. The need for more robust support for these key personnel to ensure they stay focussed and motivated is apparent, however, to be effective a more systematic understanding of the parameters of their work is required. Here we present a valuable insight into the tasks they fulfil, their relationship with colleagues and their organisation and their attitudes and behaviour at work collectively defined as their 'work design'. Our aim was to quantitatively assess the various characteristics of receptionists in primary care in England using the validated Work Design Questionnaire (WDQ) a 21 point validated questionnaire, divided into four categories: task, knowledge and social characteristics and work context with a series of sub-categories within each, disseminated online and as a postal questionnaire to 100 practices nationally. Seventy participants completed the WDQ, 54 online and 16 using the postal questionnaire with the response rate for the latter being 3.1%. The WDQ suggested receptionists experience high levels of task variety, task significance and of information processing and knowledge demands, confirming the high cognitive load placed on receptionists by performing numerous yet significant tasks. Perhaps in relation to these substantial responsibilities a reliance on colleagues for support and feedback to help negotiate this workload was reported. The evidence of our survey suggests that the role of modern GP receptionists requires an array of skills to accommodate various administrative, communicative, problem solving, and decision-making duties. There are ways in which the role might be better supported for example devising ways to separate complex tasks to avoid the errors involved with high cognitive load, providing informal feedback, and perhaps most importantly developing training programmes.


The ghrelin receptor agonist HM01 mimics the neuronal effects of ghrelin in the arcuate nucleus and attenuates anorexia-cachexia syndrome in tumor-bearing rats.
The gastric hormone ghrelin positively affects energy balance by increasing food intake and reducing energy expenditure. Ghrelin mimetics are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to characterize the action of the nonpeptidergic ghrelin receptor agonist HM01 on neuronal function, energy homeostasis and muscle mass in healthy rats and to evaluate its possible usefulness for the treatment of CACS in a rat tumor model. Using extracellular single-unit recordings, we tested whether HM01 mimics the effects of ghrelin on neuronal activity in the arcuate nucleus (Arc). Furthermore, we assessed the effect of chronic HM01 treatment on food intake (FI), body weight (BW), lean and fat volumes, and muscle mass in healthy rats. Using a hepatoma model, we investigated the possible beneficial effects of HM01 on tumor-induced anorexia, BW loss, muscle wasting, and metabolic rate. HM01 (10(-7)-10(-6) M) mimicked the effect of ghrelin (10(-8) M) by increasing the firing rate in 76% of Arc neurons. HM01 delivered chronically for 12 days via osmotic minipumps (50 μg/h) increased FI in healthy rats by 24%, paralleled by increased BW, higher fat and lean volumes, and higher muscle mass. Tumor-bearing rats treated with HM01 had 30% higher FI than tumor-bearing controls and were protected against BW loss. HM01 treatment resulted in higher muscle mass and fat mass. Moreover, tumor-bearing rats reduced their metabolic rate following HM01 treatment. Our studies substantiate the possible therapeutic usefulness of ghrelin receptor agonists like HM01 for the treatment of CACS and possibly other forms of disease-related anorexia and cachexia.


A neurostimulator system for real, sham, and multi-target transcranial magnetic stimulation.
Objective.Transcranial magnetic stimulation (TMS) is a clinically effective therapeutic instrument used to modulate neural activity. Despite three decades of research, two challenging issues remain, the possibility of changing the (a) stimulated spot and (b) stimulation type (real or sham) without physically moving the coil. In this study, a second-generation programmable TMS device with advanced stimulus shaping is introduced that uses a five-level cascaded H-bridge inverter and phase-shifted pulse-width modulation. The principal idea of this research is to obtain real, sham, and multi-locus stimulation using the same TMS system.Approach.We propose a two-channel modulation-based magnetic pulse generator and a novel coil arrangement, consisting of two circular coils with a physical distance of 20 mm between the coils and a control method for modifying the effective stimulus intensity, which leads to the live steerability of the target and type of stimulation.Main results.Based on the measured system performance, the stimulation profile can be steered ±20 mm along a line from the centroid of the coil locations by modifying the modulation index.Significance.The proposed system supports electronic control of the stimulation spot without physical coil movement, resulting in tunable modulation of targets, which is a crucial step towards automated TMS machines.


Nanomaterials in complex biological systems: insights from Raman spectroscopy.
The interaction of nanomaterials with biomolecules, cells, and organisms plays an important role in cell biology, toxicology, and nanotechnology. Spontaneous Raman scattering can be used to probe biomolecules, cells, whole animals, and nanomaterials alike, opening interesting avenues to study the interaction of nanoparticles with complex biological systems. In this review we discuss work in biomedical Raman spectroscopy that has either been concerned directly with nanostructures and biosystems, or that indicates important directions for successful future studies on processes associated with nano-bio-interactions.


Detection of visual-tactile contingency in the first year after birth.
It is well documented that in the first year after birth, infants are able to identify self-performed actions. This ability has been regarded as the basis of conscious self-perception. However, it is not yet known whether infants are also sensitive to aspects of the self when they cannot control the sensory feedback by means of self-performed actions. Therefore, we investigated the contribution of visual-tactile contingency to self-perception in infants. In Experiment 1, 7- and 10-month-olds were presented with two video displays of lifelike baby doll legs. The infant's left leg was stroked contingently with only one of the video displays. The results showed that 7- and 10-month-olds looked significantly longer at the contingent display than at the non-contingent display. Experiment 2 was conducted to investigate the role of morphological characteristics in contingency detection. Ten-month-olds were presented with video displays of two neutral objects (i.e., oblong wooden blocks of approximately the same size as the doll legs) being stroked in the same way as in Experiment 1. No preference was found for either the contingent or the non-contingent display but our results confirm a significant decrease in looking time to the contingent display compared to Experiment 1. These results indicate that detection of visual-tactile contingency as one important aspect of self-perception is present very early in ontogeny. Furthermore, this ability appears to be limited to the perception of objects that strongly resemble the infant's body, suggesting an early sensitivity to the morphology of one's own body.


Complex economic activities concentrate in large cities.
Human activities, such as research, innovation and industry, concentrate disproportionately in large cities. The ten most innovative cities in the United States account for 23% of the national population, but for 48% of its patents and 33% of its gross domestic product. But why has human activity become increasingly concentrated? Here we use data on scientific papers, patents, employment and gross domestic product, for 353 metropolitan areas in the United States, to show that the spatial concentration of productive activities increases with their complexity. Complex economic activities, such as biotechnology, neurobiology and semiconductors, concentrate disproportionately in a few large cities compared to less--complex activities, such as apparel or paper manufacturing. We use multiple proxies to measure the complexity of activities, finding that complexity explains from 40% to 80% of the variance in urban concentration of occupations, industries, scientific fields and technologies. Using historical patent data, we show that the spatial concentration of cutting-edge technologies has increased since 1850, suggesting a reinforcing cycle between the increase in the complexity of activities and urbanization. These findings suggest that the growth of spatial inequality may be connected to the increasing complexity of the economy.


Effects of probiotic Lactobacillus paracasei-enriched artichokes on constipated patients: a pilot study.
To determine whether the consumption of artichokes enriched with a probiotic Lactobacillus paracasei strain affects fecal microbiota composition, fecal enzyme activity, and short-chain fatty acids production and symptom profile in patients suffering from constipation. Constipation is a common gastrointestinal disorder often related to the food diet. The beneficial effects of probiotics and prebiotics on human health are under investigation. Moreover, recent studies assessed the suitability of some vegetables, particularly olives and artichokes, to vehicle probiotic strains into the gastrointestinal tract. For 15 days, 8 volunteers (3M/5F age 40+/-14 y) integrated their normal diet with artichokes (180 gr) enriched with 20 billions of L. paracasei LMGP22043. Faecal samples were subjected to microbiologic and biochemical analyses. Besides, investigations on symptom profile of the volunteers and stool consistency were carried out by using a validated questionnaire (Gastrointestinal Symptom Rating Scale) and the Bristol stool form chart. The gut of all volunteers resulted to be colonized by the probiotic strain after 15 days feeding. No significant differences in the microbiological counts throughout the experimental period were registered, whereas a significant increase of butyric and valeric acids with a concomitant decrease of lactic acid was registered. At the same time, the fecal beta-glucuronidase activity was significantly reduced. Finally, the analysis of symptom profile indicated a marked reduction in abdominal distension and feeling of incomplete evacuation. These preliminary data suggest that novel approaches for treating constipation can come through ingestion of probiotic vegetable products that, acting as symbiotics, can ameliorate this common disorder.


Polymorphisms within the Telomerase Reverse Transcriptase gene (TERT) in four breeds of dogs selected for difference in lifespan and cancer susceptibility.
Enzymatic activity of Telomerase Reverse Transcriptase (TERT) is important in maintaining the telomere length and has been implicated in cancer and aging related pathology. Since cancer susceptibility as well as longevity of dogs vary between breeds, this study involved sequencing the entire TERT gene of Canis familiaris from DNA samples obtained from forty dogs, with ten dogs each of four breeds: Shih Tzu, Dachshund, Irish Wolfhound, and Newfoundland, each with different life expectancies and susceptibility to cancer. We compared the sequences of all forty individuals amongst one another and with the published sequence of canine TERT, and analyzed relationships between members of the same or different breeds. Two separate phylogenetic trees were generated and analyzed from these individuals. Polymorphisms were found most frequently in intronic regions of the gene, although exonic polymorphisms also were observed. In many locations genotypes were observed that were either homozygous for the reference sequence or heterozygous, but the variant homozygous genotype was not observed. We propose that these homozygous variants are likely to have adverse effects in dogs. It was also found that the polymorphisms did not segregate by breed. Because the four breeds chosen come from geographically and physiologically distinct backgrounds, it can be inferred that the polymorphic diversification of TERT preceded breed derivation.


Efficacy of gastric aspiration in reducing posttonsillectomy vomiting.
To determine the effectiveness of postoperative gastric decompression in reducing the incidence and complications associated with vomiting following tonsillectomy. A prospective, randomized controlled study. Private office and clinic of a university teaching hospital and research center. Eighty pediatric patients ranging in age from 22 months to 11 years, American Society of Anesthesiologists class I or II, undergoing tonsillectomy with or without adenoidectomy were enrolled in the study. Six were excluded from the final analysis, 5 because of failure of the parents to complete and return the data forms and 1 because of postoperative bleeding. Of the 74 patients included in the study, 35 were in the control group and 39 were in the study group. The 39 patients in the study group underwent postoperative aspiration of gastric contents with an orogastric tube placed under direct visualization while the patient was still under general anesthesia. The 35 patients in the control group did not undergo gastric aspiration following surgery. The incidence of vomiting, the number of episodes of vomiting before and after hospital discharge, the total volume of emesis, the postoperative length of stay, the need for rescue antiemetic prophylaxis, and the number of readmissions to the hospital for persistent vomiting were noted. No statistically significant difference (P<.05) was noted between the control group and the study group for the percentage of patients experiencing vomiting (74% vs 85%), the mean number of episodes of vomiting before (2.6 vs 2.8) and after (0.8 vs 0.7) hospital discharge, the mean volume of emesis (157 mL vs 222 mL), the postoperative length of stay (394 minutes vs 334 minutes), the percentage of patients requiring rescue antiemetics (34% [12 patients] vs 33% [13 patients]), and the percentage of unplanned admissions because of vomiting (9% [3 patients] vs 15% [6 patients]). Our results indicate that gastric aspiration does not decrease the incidence of vomiting following tonsillectomy.


Molecular targets for altering radiosensitivity: lessons from Ras as a pre-clinical and clinical model.
Ras activation has been correlated with malignant and metastatic cancer phenotypes and poor prognosis for cancer patients. In the preclinical setting, Ras activation by mutation or EGFR amplification results in increased clonogenic cell survival and decreased tumor growth delay following irradiation. Activation of the Ras pathway has also been associated with increased risk of local failure and decreased overall survival in patients receiving radiotherapy. Prenyltransferase inhibitors target the post-translational processing of Ras and have been shown to increase the radiosensitivity of human cancer cell lines. In the clinical setting, these inhibitors have been used with concurrent radiotherapy in a small number of phase I clinical trials with acceptable toxicity. Therefore, inhibiting Ras activation represents a promising molecular approach for radiosensitization in cancer therapy.


Development of ultrafine multichannel microfluidic mixer for synthesis of bimetallic nanoclusters: catalytic application of highly monodisperse AuPd nanoclusters stabilized by poly(N-vinylpyrrolidone).
On account of their novel properties, bimetallic nanoparticles and nanoclusters (NCs) are strong potential candidates for optical, magnetic, and catalytic functional materials. These properties depend on the chemical composition and size (number of constituent atoms) of the NCs. Control of size, structure, and composition is particularly important for fabricating highly functional materials based on bimetallic NCs. Size- and structure-controlled synthesis of two-element alloys can reveal their intrinsic electronic synergistic effects. However, because synergistic enhancement of activity is strongly affected by composition as well as by size and structure, controlled synthesis is a challenging task, particularly in catalytic applications. To investigate catalytic synergistic effects, we have synthesized highly monodisperse, sub-2 nm, solid-solution AuPd NCs stabilized with poly(N-vinylpyrrolidone) (AuPd:PVP) using a newly developed ultrafine microfluidic mixing device with 15 μm wide multiple lamination channels. The synergistic enhancement for catalytic aerobic oxidation of benzyl alcohol exhibited a volcano-shaped trend, with a maximum at 20-65 at. % Pd. From X-ray photoelectron spectroscopic measurements, we confirmed that the enhanced activity originates from the enhanced electron density at the Au sites, donated by Pd sites.


Evaluation of the diffusive gradients in thin films technique using a mixed binding gel for measuring iron, phosphorus and arsenic in the environment.
Simultaneous measurements of dissolved iron (Fe), phosphorus (P), and arsenic (As) were made using the diffusive gradients in thin films technique equipped with a mixed binding gel impregnated with zirconium oxide and Chelex-100 (ZrO-Chelex DGT). The ZrO-Chelex binding gel exhibited rapid binding dynamics to Fe(II), P(PO4(3-)), and As(III)/As(V) in mixed solutions of the three elements. The bound Fe, P, and As could be quantitatively recovered using an established four-step elution procedure. Simultaneous measurements of the three elements with ZrO-Chelex DGT were validated through time-series experiments, and there was no influence of pH (4.1 to 7.1) and ionic strength (0.01 to 800 mM). The DGT capacities for As(III) and As(V) were 69.0 μg and 186 μg per device, respectively, which were much greater than those of the widely used ferrihydrite DGT. Applications in synthesized freshwaters and in sediments further confirmed its feasibility in simultaneous measurements in the environment. The present study offered that the ZrO-Chelex DGT will be a useful tool in in situ monitoring of Fe-P-As and assessment of their interactions in the biogeochemical processes.


Evaluation of a chemically inducible promoter for developing a within-plant refuge for resistance management.
Chemically inducible production of Bacillus thuringiensis (Bt) toxins in transgenic plants may provide considerable benefits in preventing or delaying the evolution of insect resistance to Bt crops by creating within-plant temporal refuges. We examined the effect of inducible cry1Ab expression on survival of different genotypes (RR, RS, and SS) of diamondback moth, Plutella xylostella (L.), in transgenic broccoli, Brassica oleracea L., plants transformed with a PR-1a/cry1Ab expression cassette. Spraying leaves of these plants with the inducer acibenzolar-s-methyl [= benzo (1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester] (ASM) resulted in high levels of Bt toxin, and detached leaves from fully induced plants caused 100% mortality to all instars of P. xylostella SS and RS genotypes. When plants infested with larvae were treated with ASM, only a few larvae that were nearing completion of their development were able to survive the induction process. Signal transduction from ASM-treated leaves to new plant tissue also was evaluated using a larval assay. New foliage that emerged after plants were induced remained toxic to > or = 80% of RS larvae up to the fourth new leaf. In whole plant tests, however, induced plants remained protected from larval damage for > or = 3 wk. Uninduced PR-1a/cry1Ab plants seemed to produce low levels of Bt that were undetected by an enzyme-linked immunosorbent assay but that resulted in significant fitness costs for susceptible insects. The suitability of PR-1a/cry1Ab broccoli plants for insect resistance management and the requirements of an appropriate inducible promoter are discussed.