Graphene dispersions in alkanes: toward fast drying conducting inks.
Graphene inks are becoming widely popular. However the vast majority of these inks are formulated in polar solvents with high-boiling points. Their slow evaporation is a bottleneck factor in roll-to-roll printing processes. Here, we developed a highly-conductive fast-drying graphene ink in isooctane, a non-polar and low-boiling solvent. For this purpose, a diblock copolymer containing pendant cholesterol groups was used during the exfoliation of natural graphite in isooctane. The polymer develops non-covalent supramolecular interactions with the graphene conjugated system, resulting in the formation of stable graphene dispersions (up to c = 4 mg mL-1). These dispersions were used for direct writing on a variety of substrates, and were shown to dry instantly after application. The influence of polymer concentration on graphene characteristics, on colloidal stability and on electrochemical characteristics has been studied. The lowest sheet resistance (80 Ω □-1) was obtained when 23% of the graphene surface was covered by the polymer. In this case, the flakes were constituted of 2-5 graphene layers. More extensive exfoliation, down to single-layer graphene, was achieved at greater surface coverage, but led to inks with higher sheet resistance. Thus, by combining a tailored polymeric dispersant, a smooth exfoliation process and a low-boiling non-polar ink solvent, we were able to prepare highly-conductive fast-drying graphene inks which should have a high potentital for the development of roll-to-roll printed electronics.


Empowerment of promotoras as promotora-researchers in the Comidas Saludables & Gente Sana en las Colonias del Sur de Tejas (Healthy Food and Healthy People in South Texas Colonias) program.
Promotoras are trusted members of underserved, at-risk Hispanic communities experiencing social and health inequities. As promotora-researchers, promotoras have the unique ability and opportunity not only to provide outreach and education but also to be actively engaged in conducting research in their communities and serve as a cultural bridge between the community and researchers. In this article, we present a case study of personal and collective empowerment of six promotora-researchers who participated in seven community-based participatory research projects. Data sources included debriefing interviews with the promotora-researchers, milestone tracking and documentation completed during and after each study, and observations by the principal investigator and project managers regarding the role of the promotora-researchers in these studies. We qualitatively analyzed the data to identify the processes and decisions that were developed and implemented in a series of projects, which resulted in promotora-researcher empowerment. We found that active engagement empowered promotora-researchers personally and collectively in all phases of the research study. Common elements that contributed to the empowerment of promotora-researchers were valuing promotora-researchers' input, enabling promotora-researchers to acquire and utilize new skills, and allowing promotora-researchers to serve as both researchers and traditional promotoras. Together, these elements enabled them to more fully participate in research projects, while allowing them to identify and address needs within their own communities.


Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage.
Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development by signaling to both chondrocytes and perichondrial cells. Previous efforts to delineate direct effects of Ihh on chondrocytes by Col2-Cre-mediated ablation of Smoothened (Smo, encoding a transmembrane protein indispensable for Ihh signaling) has been only partially successful, due to the inability to discriminate between chondrocytes and perichondrial cells. Here we report a transgenic line (Col2-Cre) expressing under the control of the Colalpha1(II) promoter an inert form of Cre that is activatable by exogenous tamoxifen (TM); TM administration at proper times during embryogenesis induced Cre activity in chondrocytes but not in the perichondrium. By using this mouse line, we deleted Smo within subsets of chondrocytes without affecting the perichondrium and found that Smo removal led to localized disruption of the expression of parathyroid hormone-related protein (PTHrP) and the morphology of chondrocytes. Unexpectedly, TM invariably induced Cre activity in a subset of cells associated with the trabecular bone surface of long bones. These cells, when genetically marked and cultured in vitro, were capable of producing bone nodules. Expression of the Col2-Cre transgene in these cells likely reflected the endogenous Colalpha1(II) promoter activity as similar cells were found to express the IIA isoform of Colalpha1(II) mRNA endogenously. In summary, the present study has not only provided evidence that Ihh signaling directly controls PTHrP expression and chondrocyte morphology in the growth region cartilage, but has also uncovered a distinct cell type associated with the trabecular bone that appears to possess osteogenic potential.


Facial asymmetry assessment in skeletal Class III patients with spatially-dense geometric morphometrics.
Quantification and visualization of the location and magnitude of facial asymmetry is important for diagnosis and treatment planning. The objective of this study was to analyze the asymmetric features of the face for skeletal Class III patients using spatially-dense geometric morphometrics. Three-dimensional facial images were obtained for 86 skeletal Class III patients. About 7160 uniformly sampled quasi-landmarks were automatically identified on each face using template mapping technique. The pointwise surface-to-surface distance between original and mirror face was measured and visualized for the whole face after robust Procrustes superimposition. The degree of overall asymmetry in an individual was scored using a root-mean-squared-error. Automatic partitioning of the face was obtained, and the severity of the asymmetry compared among seven facial regions. Facial asymmetry was mainly located on, but not limited to, the lower two-thirds of the face in skeletal Class III patients. The lower cheek and nose asymmetry were detected to have more extensive and of a greater magnitude of asymmetry than other facial anatomical regions but with various individual variations. The overall facial asymmetry index and the regional facial asymmetry indices were higher in males and patients with chin deviation. Soft tissue asymmetry is predominately presented in the lower-third of the face in skeletal Class III patients and with various variations on other facial anatomical regions. Morphometric techniques and computer intensive analysis have allowed sophisticated quantification and visualization of the pointwise asymmetry on the full face.


Induction of human antigen-specific suppressor factors in vitro.
Based on methods used for the in vitro induction of antigen-specific suppressor cells in the mouse, we have cultured Ficoll-Isopaque-separated human blood cells with high dose of antigen (100 microgram/ml) in Marbrook culture vessels for 4 days. The resulting cells, when further recultured for 24 hr with a low dose of antigen (1 microgram/ml), released into the supernatant material, termed 'suppressor factor', which inhibited, in an antigen-specific manner, the antibody response of mouse spleen cells in culture. The suppressor factor was analysed using immunoabsorbents, and was bound to and eluted from specific antigen, concanavalin A and lentil lectin, anti-human Ia antibodies, and anti-mouse suppressor factor antibodies, but was not bound to antibodies against human IgG.


Transcranial Magnetic Mapping of the Short-Latency Modulations of Corticospinal Activity from the Ipsilateral Hemisphere during Rest.
Skilled hand function relies heavily on the integrity of the primary motor cortex (M1) and on a web of cortico-cortical connections projecting onto it. We used a novel explorative paradigm to map the origin of cortico-M1 pathways assessed by dual transcranial magnetic stimulation (TMS) in three healthy participants. Subthreshold conditioning TMS (cTMS) was delivered over a grid of ≈100 spots. Covering the left hemisphere, and was followed by suprathreshold test (tTMS) delivered over the ipsilateral M1. Grid points were tested eight times, with inter-stimulus intervals between cTMS and tTMS of 4 and 7 ms. Participants were asked to stay relaxed with no particular task. Motor evoked potentials (MEPs) from cTMS + tTMS were normalized to MEPs from tTMS alone and were compared to the value expected from tTMS alone using t-statistics. The t-values from each grid point were then used to plot statistical maps. Several foci of significant cortico-M1 interactions were found in the dorsal-medial frontal cortex, in the ventral frontal cortex, in the superior and inferior parietal lobules and in the parietal operculum. The majority of active foci had inhibitory effects on corticospinal excitability. The spatial location of the network of different subjects overlapped but with some anatomical variation of single foci. TMS statistical mapping during the resting state revealed a complex inhibitory cortical network. The explorative approach to TMS as a brain mapping tool produced results that are self-standing in single subjects overcoming inter-individual variability of cortical active sites.


Increased frequency of IL-6-producing non-classical monocytes in neuromyelitis optica spectrum disorder.
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system that preferentially affects the optic nerves, spinal cord, and area postrema. A series of evidence suggested that B cells play a fundamental role in the pathogenesis of NMOSD. However, there are still gaps left to be answered in NMOSD pathogenesis suggesting the roles of other immune cells. This study aimed to investigate the monocyte inflammatory characteristics, monocyte subset frequency and cytokine production, and cell-surface molecule expression in NMOSD, multiple sclerosis (MS), and healthy controls (HC). Peripheral blood mononuclear cells of 20 aquaporin 4IgG-positive NMOSD patients, 20 MS patients, and 20 healthy controls were collected to analyze the monocyte subsets and to purify monocytes. To mimic the adaptive immunity, we have activated the monocytes using CD40L and IFN-γ to observe the production of cytokines and expression of cell-surface molecules. NMOSD monocytes showed a remarkable increase in the production of pro-inflammatory cytokines (IL-6, IL-1β) and increased expression of cell-surface molecules (CD80, HLA, ICAM-1, CD16), as well as a decrease in the levels of anti-inflammatory cytokine IL-10, compared to healthy control (HC) monocytes. As expected, MS monocytes also exhibit increased inflammatory cytokine production and increased cell-surface molecule expression compared to HC monocytes. Further analysis of monocyte subsets revealed that NMOSD monocytes have an increased frequency of the non-classical monocyte subset (CD14+CD16++) and a decreased frequency of the classical monocyte subset (CD14++CD16+) compared to HC monocytes. This finding was distinctly different from that of MS monocytes, which had an increased intermediate monocyte (CD14+CD16+) subset. In addition, these NMOSD non-classical monocyte subsets were highly dedicated, IL-6-producing monocytes. Increased expression of cell-surface molecules and a reciprocal dysregulation of inflammatory and anti-inflammatory cytokines in NMOSD monocytes suggest an altered monocyte inflammatory response. CD14+CD16++ non-classical monocyte subset was more abundant in NMOSD monocytes than in HC or MS monocytes, and NMOSD non-classical monocyte subset had dysregulated IL-6 production, a phenotype which has been reported to be highly associated with NMOSD pathogenesis.


Voxel-based morphometry in opera singers: Increased gray-matter volume in right somatosensory and auditory cortices.
In contrast to instrumental musicians, professional singers do not train on a specific instrument but perfect a motor system that has already been extensively trained during speech motor development. Previous functional imaging studies suggest that experience with singing is associated with enhanced somatosensory-based vocal motor control. However, experience-dependent structural plasticity in vocal musicians has rarely been studied. We investigated voxel-based morphometry (VBM) in 27 professional classical singers and compared gray matter volume in regions of the "singing-network" to an age-matched group of 28 healthy volunteers with no special singing experience. We found right hemispheric volume increases in professional singers in ventral primary somatosensory cortex (larynx S1) and adjacent rostral supramarginal gyrus (BA40), as well as in secondary somatosensory (S2) and primary auditory cortices (A1). Moreover, we found that earlier commencement with vocal training correlated with increased gray-matter volume in S1. However, in contrast to studies with instrumental musicians, this correlation only emerged in singers who began their formal training after the age of 14years, when speech motor development has reached its first plateau. Structural data thus confirm and extend previous functional reports suggesting a pivotal role of somatosensation in vocal motor control with increased experience in singing. Results furthermore indicate a sensitive period for developing additional vocal skills after speech motor coordination has matured.


Hoverboard injuries in children and adolescents: results of a multicenter study.
With the increasing popularity of hoverboards in recent years, multiple centers have noted associated orthopaedic injuries of riders. We report the results of a multi-center study regarding hoverboard injuries in children and adolescents. who presented with extremity fractures while riding hoverboards to 12 paediatric orthopaedic centers during a 2-month period were included in the study. Circumstances of the injury, location, severity, associated injuries, and the required treatment were recorded and analysed using descriptive analysis to report the most common injuries. Between-group differences in injury location were examined using chi-squared statistics among (1) children versus adolescents and (2) males versus females. Seventy-eight patients (M/F ratio: 1.8) with average age of 11 ± 2.4 years were included in the study. Of the 78 documented injuries, upper extremity fractures were the most common (84.6%) and the most frequent fracture location overall was at the distal radius and ulna (52.6%), while ankle fractures comprised most of the lower extremity fractures (66.6%). Majority of the distal radius fractures (58.3%) and ankle fractures (62.5%) were treated with immobilization only. Seventeen displaced distal radius fractures and three displaced ankle fractures were treated with closed reduction in the majority of cases (94.1% versus 66.7%, respectively). The distal radius and ulna are the most common fracture location. Use of appropriate protective gear such as wrist guards, as well as adult supervision, may help mitigate the injuries associated with the use of this device; however, further studies are necessary to demonstrate the real effectiveness of these preventions.


The medium-/long-chain fatty acyl-CoA dehydrogenase (fadF) gene of Salmonella typhimurium is a phase 1 starvation-stress response (SSR) locus.
Salmonella enterica serovar Typhimurium (S. typhimurium) is an enteric pathogen that causes significant morbidity in humans and other mammals. During their life cycle, salmonellae must survive frequent exposures to a variety of environmental stresses, e.g. carbon-source (C) starvation. The starvation-stress response (SSR) of S. typhimurium encompasses the genetic and physiological realignments that occur when an essential nutrient becomes limiting for bacterial growth. The function of the SSR is to produce a cell capable of surviving long-term starvation. This paper reports that three C-starvation-inducible lac fusions from an S. typhimurium C-starvation-inducible lac fusion library are all within a gene identified as fadF, which encodes an acyl-CoA dehydrogenase (ACDH) specific for medium-/long-chain fatty acids. This identification is supported by several findings: (a) significant homology at the amino acid sequence level with the ACDH enzymes from other bacteria and eukaryotes, (b) undetectable beta-oxidation levels in fadF insertion mutants, (c) inability of fad insertion mutants to grow on oleate or decanoate as a sole C-source, and (d) inducibility of fadF::lac fusions by the long-chain fatty acid oleate. In addition, the results indicate that the C-starvation-induction of fadF is under negative control by the FadR global regulator and positive control by the cAMP:cAMP receptor protein complex and ppGpp. It is also shown that the fadF locus is important for C-starvation-survival in S. typhimurium. Furthermore, the results demonstrate that fadF is induced within cultured Madin-Darby canine kidney (MDCK) epithelial cells, suggesting that signals for its induction (C-starvation and/or long-chain fatty acids) may be present in the intracellular environment encountered by S. typhimurium. However, fadF insertion mutations did not have an overt effect on mouse virulence.


Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response.
Recent information has revealed the functional diversity and importance of mitochondria in many cellular processes including orchestrating the innate immune response. Intriguingly, several infectious agents, such as Toxoplasma, Legionella, and Chlamydia, have been reported to grow within vacuoles surrounded by host mitochondria. Although many hypotheses have been proposed for the existence of host mitochondrial association (HMA), the causes and biological consequences of HMA have remained unanswered. Here we show that HMA is present in type I and III strains of Toxoplasma but missing in type II strains, both in vitro and in vivo. Analysis of F1 progeny from a type II×III cross revealed that HMA is a Mendelian trait that we could map. We use bioinformatics to select potential candidates and experimentally identify the polymorphic parasite protein involved, mitochondrial association factor 1 (MAF1). We show that introducing the type I (HMA+) MAF1 allele into type II (HMA-) parasites results in conversion to HMA+ and deletion of MAF1 in type I parasites results in a loss of HMA. We observe that the loss and gain of HMA are associated with alterations in the transcription of host cell immune genes and the in vivo cytokine response during murine infection. Lastly, we use exogenous expression of MAF1 to show that it binds host mitochondria and thus MAF1 is the parasite protein directly responsible for HMA. Our findings suggest that association with host mitochondria may represent a novel means by which Toxoplasma tachyzoites manipulate the host. The existence of naturally occurring HMA+ and HMA- strains of Toxoplasma, Legionella, and Chlamydia indicates the existence of evolutionary niches where HMA is either advantageous or disadvantageous, likely reflecting tradeoffs in metabolism, immune regulation, and other functions of mitochondria.


Generalized Bienenstock-Cooper-Munro rule for spiking neurons that maximizes information transmission.
Maximization of information transmission by a spiking-neuron model predicts changes of synaptic connections that depend on timing of pre- and postsynaptic spikes and on the postsynaptic membrane potential. Under the assumption of Poisson firing statistics, the synaptic update rule exhibits all of the features of the Bienenstock-Cooper-Munro rule, in particular, regimes of synaptic potentiation and depression separated by a sliding threshold. Moreover, the learning rule is also applicable to the more realistic case of neuron models with refractoriness, and is sensitive to correlations between input spikes, even in the absence of presynaptic rate modulation. The learning rule is found by maximizing the mutual information between presynaptic and postsynaptic spike trains under the constraint that the postsynaptic firing rate stays close to some target firing rate. An interpretation of the synaptic update rule in terms of homeostatic synaptic processes and spike-timing-dependent plasticity is discussed.


Inadequate cervical cancer screening among mid-aged Australian women who have experienced partner violence.
Partner violence is linked to cervical cancer and other gynaecological conditions. However, results of current research into associations between partner violence and cervical cancer screening have been inconclusive. Therefore, the current research investigates the association between partner violence and inadequate cervical cancer screening. Participants were 7312 women aged 45-50 years who responded to the Australian Longitudinal Study on Women's Health population-based surveys in 1996 and 2004. The women self-reported frequency of Pap smears via mailed questionnaire. Women who had experienced partner violence at least eight years earlier, compared with those who had not, were more likely to report current inadequate screening (OR: 1.42, 95%CI: 1.21; 1.66). After adjusting for known barriers to preventive screening (education, income management, marital status, general practitioner visits, chronic conditions) and depression, partner violence was independently associated with inadequate Pap tests (OR: 1.20, 95%CI: 1.01; 1.42). This association was no longer significant once access to a GP of choice was added to the model (OR: 1.18, 95%CI: 0.99; 1.40). The significance of this study lies not just in confirming a negative relationship between cervical cancer screening and partner violence, but in suggesting that good access to a physician of choice appears to significantly decrease this negative relationship.


Effects of iodine status on thyroid volume and goiter in children living in an iodine-repleted area.
Adequate iodine intake is essential for growing children, and thyroid volume (Tvol) is considered as an indicator of iodine status. We investigated Tvol and goiter using ultrasonography (US) and their association with iodine status in 228 6-year-old children living in Korea. Iodine status was assessed using urine iodine concentration (UIC) and categorized as deficient (<100 μg/L), adequate (100-299 μg/L), mild excess (300-499 μg/L), moderate excess (500-999 μg/L), and severe excess (≥1000 μg/L). Tvol was measured using US, and a goiter on the US (goiter-US) was defined as Tvol > 97th percentile value by age- and body surface area (BSA)-specific international references. The median Tvol was 2.4 mL, larger than the international reference value (1.6 mL). The age- and BSA-specific goiter-US rates were 25.9% (n = 59) and 34.6% (n = 79), respectively. The prevalence of excess iodine was 73.7% (n = 168). As iodine status increased from adequate to severe excess, the goiter-US rate significantly increased (p for trend < 0.05). The moderate and severe iodine excess groups showed higher risk of goiter-US (aOR 3.1 [95% CI, 1.1-9.2] and aOR 3.1 [95% CI, 1.2-8.3], respectively; age-specific criteria) than the iodine-adequate group. Excess iodine was prevalent in Korean children, and their Tvol was higher than the international reference values. Goiter rate was associated with iodine excess, which significantly increased in the moderate and severe iodine excess groups. Further studies are warranted to define optimal iodine intake in children.


Liquid/gas and liquid/liquid phase equilibria of the system water/bovine serum albumin.
The thermodynamic behavior of the system H2O/BSA was studied at 25 °C within the entire composition range: vapor pressure measurements via head space sampling gas chromatography demonstrate that the attainment of equilibria takes more than one week. A miscibility gap was detected via turbidity and the coexisting phases were analyzed. At 6 °C the two phase region extends from ca. 34 to 40 wt % BSA; it shrinks upon heating. The polymer rich phase is locally ordered, as can be seen under the optical microscope using crossed polarizers. The Flory-Huggins theory turns out to be inappropriate for the modeling of experimental results. A phenomenological expression is employed which uses three adjustable parameters and describes the vapor pressures quantitatively; it also forecasts the existence of a miscibility gap.


Antibiotic control of antibiotic resistance in hospitals: a simulation study.
Using mathematical deterministic models of the epidemiology of hospital-acquired infections and antibiotic resistance, it has been shown that the rates of hospital-acquired bacterial infection and frequency of antibiotic infections can be reduced by (i) restricting the admission of patients colonized with resistant bacteria, (ii) increasing the rate of turnover of patients, (iii) reducing transmission by infection control measures, and (iv) the use of second-line drugs for which there is no resistance. In an effort to explore the generality and robustness of the predictions of these deterministic models to the real world of hospitals, where there is variation in all of the factors contributing to the incidence of infection, we developed and used a stochastic model of the epidemiology of hospital-acquired infections and resistance. In our analysis of the properties of this model we give particular consideration different regimes of using second-line drugs in this process. We developed a simple model that describes the transmission of drug-sensitive and drug-resistant bacteria in a small hospital. Colonized patients may be treated with a standard drug, for which there is some resistance, and with a second-line drug, for which there is no resistance. We then ran deterministic and stochastic simulation programs, based on this model, to predict the effectiveness of various treatment strategies. The results of the analysis using our stochastic model support the predictions of the deterministic models; not only will the implementation of any of the above listed measures substantially reduce the incidences of hospital-acquired infections and the frequency of resistance, the effects of their implementation should be seen in months rather than the years or decades anticipated to control resistance in open communities. How effectively and how rapidly the application of second-line drugs will contribute to the decline in the frequency of resistance to the first-line drugs depends on how these drugs are administered. The earlier the switch to second-line drugs, the more effective this protocol will be. Switching to second-line drugs at random is more effective than switching after a defined period or only after there is direct evidence that the patient is colonized with bacteria resistant to the first antibiotic. The incidence of hospital-acquired bacterial infections and frequencies of antibiotic resistant bacteria can be markedly and rapidly reduced by different readily implemented procedures. The efficacy using second line drugs to achieve these ends depends on the protocol used for their administration.


Clinical performance of complete dentures: a retrospective study.
Denture survival, or the time between the date of a denture's insertion and the date of its renewal for any clinical reason, was assessed in this retrospective study on 353 complete dentures. The procedures required to prolong the useful time of the study sample-relines, repair of denture base fractures, or replacement of lost artificial teeth-were also evaluated. All dentures were examined by the authors and were constructed according to a standardized protocol by full-time staff members of the Department of Prosthodontics, Regensburg University Medical Center, between 1984 and 2009. Two subgroups were assigned: 94 patients had one complete denture in each arch (group 1), while 165 patients had one complete denture in either the mandible or the maxilla (group 2). In group 1, the median (75th, 90th percentile) survival time of dentures was 15.8 years in the mandible (15.7, 7.0; 95% confidence interval [CI]: 15.5 to 16.1) and 19.4 years in the maxilla (15.8, 8.7; 95% CI: 14.0 to 24.7). Reline procedures were required most frequently in the maxilla, while 5-year event-free rates were 69.7% for the maxilla and 80.5% for the mandible. Denture base fractures were reported in 5.8% of patients in group 1 and tended to occur more frequently (median: 15.2%) if patients had only one denture (group 2, n = 25 [maxilla: n = 23, mandible: n = 2]). Loss of artificial teeth was a rare complication and found in only 5.8% of patients in group 1 and 10.9% of patients in group 2. During the first 5 years of service, more than 95% of patients in group 1 and 90% of patients in group 2 were "event free" with regard to loss of artificial teeth. Long-term functional service of complete dentures requires a high number of maintenance procedures, and there is a greater need for interventions in patients wearing only one complete denture (group 2).


A risk factor-based predictive model of outcomes in carotid endarterectomy: the National Surgical Quality Improvement Program 2005-2010.
Accurate knowledge of individualized risks and benefits is crucial to the surgical management of patients undergoing carotid endarterectomy (CEA). Although large randomized trials have determined specific cutoffs for the degree of stenosis, precise delineation of patient-level risks remains a topic of debate, especially in real world practice. We attempted to create a risk factor-based predictive model of outcomes in CEA. We performed a retrospective cohort study involving patients who underwent CEAs from 2005 to 2010 and were registered in the American College of Surgeons National Quality Improvement Project database. Of the 35 698 patients, 20 015 were asymptomatic (56.1%) and 15 683 were symptomatic (43.9%). These patients demonstrated a 1.64% risk of stroke, 0.69% risk of myocardial infarction, and 0.75% risk of death within 30 days after CEA. Multivariate analysis demonstrated that increasing age, male sex, history of chronic obstructive pulmonary disease, myocardial infarction, angina, congestive heart failure, peripheral vascular disease, previous stroke or transient ischemic attack, and dialysis were independent risk factors associated with an increased risk of the combined outcome of postoperative stroke, myocardial infarction, or death. A validated model for outcome prediction based on individual patient characteristics was developed. There was a steep effect of age on the risk of myocardial infarction and death. This national study confirms that that risks of CEA vary dramatically based on patient-level characteristics. Because of limited discrimination, it cannot be used for individual patient risk assessment. However, it can be used as a baseline for improvement and development of more accurate predictive models based on other databases or prospective studies.


Identification of risk factors for postoperative dysphagia after primary anti-reflux surgery.
Transient postoperative dysphagia is not uncommon after antireflux surgery and usually runs a self-limiting course. However, a subset of patients report long-term dysphagia. The purpose of this study was to determine the risk factors for persistent postoperative dysphagia at 1 year after surgery. All patients who underwent antireflux surgery were entered into a prospectively maintained database. After obtaining institutional review board approval, the database was queried to identify patients who underwent primary antireflux surgery and were at least 1 year from surgery. Postoperative severity of dysphagia was evaluated using a standardized questionnaire (scale 0-3). Patients with scores of 2 or 3 were defined as having significant dysphagia. A total of 316 consecutive patients underwent primary antireflux surgery by a single surgeon. Of these, 219 patients had 1 year postoperative symptom data. Significant postoperative dysphagia at 1 year was reported by 19 (9.1%) patients. Thirty-eight patients (18.3%) required postoperative dilation for dysphagia. Multivariate logistic regression analysis identified preoperative dysphagia (odds ratio (OR), 4.4; 95% confidence interval (CI), 1.2-15.5; p = 0.023) and preoperative delayed esophageal transit by barium swallow (OR, 8.2; 95% CI, 1.6-42.2; p = 0.012) as risk factors for postoperative dysphagia. Female gender was a risk factor for requiring dilation during the early postoperative period (OR, 3.6; 95% CI, 1.3-10.2; p = 0.016). No correlations were found with preoperative manometry. There also was no correlation between a need for early dilation and persistent dysphagia at 1 year of follow-up (p = 0.109). Patients with preoperative dysphagia and delayed esophageal transit on preoperative contrast study were significantly more likely to report moderate to severe postoperative dysphagia 1 year after antireflux surgery. This study confirms that the manometric criteria used to define esophageal dysmotility are not reliable to identify patients at risk for postfundoplication dysphagia, and that there is need for standardization of contrast swallow assessment of esophageal function.


Deep learning enables image-based tree counting, crown segmentation, and height prediction at national scale.
Sustainable tree resource management is the key to mitigating climate warming, fostering a green economy, and protecting valuable habitats. Detailed knowledge about tree resources is a prerequisite for such management but is conventionally based on plot-scale data, which often neglects trees outside forests. Here, we present a deep learning-based framework that provides location, crown area, and height for individual overstory trees from aerial images at country scale. We apply the framework on data covering Denmark and show that large trees (stem diameter >10 cm) can be identified with a low bias (12.5%) and that trees outside forests contribute to 30% of the total tree cover, which is typically unrecognized in national inventories. The bias is high (46.6%) when our results are evaluated against all trees taller than 1.3 m, which involve undetectable small or understory trees. Furthermore, we demonstrate that only marginal effort is needed to transfer our framework to data from Finland, despite markedly dissimilar data sources. Our work lays the foundation for digitalized national databases, where large trees are spatially traceable and manageable.


Src as a Therapeutic Target in Biliary Tract Cancer.
Src, a nonreceptor tyrosine kinase, is involved in a number of cancer-related signaling pathways and aberrantly activated in biliary tract cancer (BTC). This study aimed to elucidate the potential role of Src as a therapeutic target in BTC. We tested bosutinib, an orally active c-Src/Abl kinase inhibitor, alone or in combination with cytotoxic agents using 9 human BTC cell lines: SNU-245, SNU-308, SNU-478, SNU-869, SNU-1079, SNU-1196, HuCCT1, TFK-1, and EGI-1. Of these, SNU-308 and SNU-478 were relatively sensitive to bosutinib. Bosutinib abrogated phosphorylation of Src and its downstream molecules, and significantly increased G1 cell-cycle arrest and apoptosis. Bosutinib significantly inhibited cell migration and invasion and decreased epithelial-mesenchymal transition markers. Bosutinib combined with gemcitabine or cisplatin showed synergistic antiproliferative and antimigratory effects. In addition, this combination further inhibited phosphorylation of Src and its downstream molecules and decreased epithelial-mesenchymal transition marker expression compared with bosutinib alone. We established a SNU-478 xenograft model for in vivo experiments, because SNU-478 was more tumorigenic than SNU-308. Bosutinib combined with gemcitabine or cisplatin showed significantly more potent antitumor effects than bosutinib alone. Bosutinib combined with gemcitabine further decreased Ki-67 expression and Src phosphorylation, and further increased TUNEL expression. Our data suggest that Src might be a potential therapeutic target in BTC. Bosutinib demonstrated promising antitumor activity alone or in combination with gemcitabine or cisplatin in BTC cells, which supports further clinical development in patients with advanced BTC. Mol Cancer Ther; 15(7); 1515-24. ©2016 AACR.


Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial.
Early pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 μg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure. This study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss. We performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment. Overall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49). No baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors.


Bayesian estimation of partial population continuity using ancient DNA and spatially explicit simulations.
The retrieval of ancient DNA from osteological material provides direct evidence of human genetic diversity in the past. Ancient DNA samples are often used to investigate whether there was population continuity in the settlement history of an area. Methods based on the serial coalescent algorithm have been developed to test whether the population continuity hypothesis can be statistically rejected by analysing DNA samples from the same region but of different ages. Rejection of this hypothesis is indicative of a large genetic shift, possibly due to immigration occurring between two sampling times. However, this approach is only able to reject a model of full continuity model (a total absence of genetic input from outside), but admixture between local and immigrant populations may lead to partial continuity. We have recently developed a method to test for population continuity that explicitly considers the spatial and temporal dynamics of populations. Here, we extended this approach to estimate the proportion of genetic continuity between two populations, using ancient genetic samples. We applied our original approach to the question of the Neolithic transition in Central Europe. Our results confirmed the rejection of full continuity, but our approach represents an important step forward by estimating the relative contribution of immigrant farmers and of local hunter-gatherers to the final Central European Neolithic genetic pool. Furthermore, we show that a substantial proportion of genes brought by the farmers in this region were assimilated from other hunter-gatherer populations along the way from Anatolia, which was not detectable by previous continuity tests. Our approach is also able to jointly estimate demographic parameters, as we show here by finding both low density and low migration rate for pre-Neolithic hunter-gatherers. It provides a useful tool for the analysis of the numerous ancient DNA data sets that are currently being produced for many different species.


How many human proteoforms are there?
Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.


Maternal Immune Activation Delays Excitatory-to-Inhibitory Gamma-Aminobutyric Acid Switch in Offspring.
The association between maternal infection and neurodevelopmental defects in progeny is well established, although the biological mechanisms and the pathogenic trajectories involved have not been defined. Pregnant dams were injected intraperitoneally at gestational day 9 with polyinosinic:polycytidylic acid. Neuronal development was assessed by means of electrophysiological, optical, and biochemical analyses. Prenatal exposure to polyinosinic:polycytidylic acid causes an imbalanced expression of the Na+-K+-2Cl- cotransporter 1 and the K+-Cl- cotransporter 2 (KCC2). This results in delayed gamma-aminobutyric acid switch and higher susceptibility to seizures, which endures up to adulthood. Chromatin immunoprecipitation experiments reveal increased binding of the repressor factor RE1-silencing transcription (also known as neuron-restrictive silencer factor) to position 509 of the KCC2 promoter that leads to downregulation of KCC2 transcription in prenatally exposed offspring. Interleukin-1 receptor type I knockout mice, which display braked immune response and no brain cytokine elevation upon maternal immune activation, do not display KCC2/Na+-K+-2Cl- cotransporter 1 imbalance when implanted in a wild-type dam and prenatally exposed. Notably, pretreatment of pregnant dams with magnesium sulfate is sufficient to prevent the early inflammatory state and the delay in excitatory-to-inhibitory switch associated to maternal immune activation. We provide evidence that maternal immune activation hits a key neurodevelopmental process, the excitatory-to-inhibitory gamma-aminobutyric acid switch; defects in this switch have been unequivocally linked to diseases such as autism spectrum disorder or epilepsy. These data open the avenue for a safe pharmacological treatment that may prevent the neurodevelopmental defects caused by prenatal immune activation in a specific pregnancy time window.


ASID (HICSIG) position statement: infection control guidelines for patients with influenza-like illnesses, including pandemic (H1N1) influenza 2009, in Australian health care facilities.
Standard and Droplet Precautions are considered adequate to control the transmission of influenza in most health care situations. Vaccination of health care staff, carers and vulnerable patients against seasonal and, eventually, pandemic influenza strains is an essential protective strategy. Management principles include: performance of hand hygiene before and after every patient contact or contact with the patient environment, in accord with the national 5 Moments for Hand Hygiene Standard; disinfection of the patient environment; early identification and isolation of patients with suspected or proven influenza; adoption of a greater minimum distance of patient separation (2 metres) than previously recommended; use of a surgical mask and eye protection for personal protection on entry to infectious areas or within 2 metres of an infectious patient; contact tracing for patient and health care staff and restriction of prophylactic antivirals mainly to those at high risk of severe disease; in high aerosol-risk settings, use of particulate mask, eye protection, impervious long-sleeved gown, and gloves donned in that sequence and removed in reverse sequence, avoiding self-contamination; exclusion of symptomatic staff from the workplace until criteria for non-infectious status are met; reserving negative-pressure ventilation rooms (if available) for intensive care patients, especially those receiving non-invasive ventilation; ensuring that infectious postpartum women wear surgical masks when caring for their newborn infants and practise strict hand hygiene; and implementation of special arrangements for potentially infected newborns who require nursery or intensive care.


Molecular dynamics simulations of uniaxial deformation of thermoplastic polyimides.
The results of atomistic molecular-dynamics simulations of mechanical properties of heterocyclic polymer subjected to uniaxial deformation are reported. A new amorphous thermoplastic polyimide R-BAPO with a repeat unit consisting of dianhydride 1,3-bis-(3',4,-dicarboxyphenoxy)diphenyl (dianhydride R) and diamine 4,4'-bis-(4''-aminophenoxy)diphenyloxide (diamine BAPO) was chosen for the simulations. Our primary goal was to establish the impact of various factors (sample preparation method, molecular mass, and cooling and deformation rates) on the elasticity modulus. In particular, we found that the elasticity modulus was only slightly affected by the degree of equilibration, the molecular mass and the size of the simulation box. This is most likely due to the fact that the main contribution to the elasticity modulus is from processes on scales smaller than the entanglement length. Essentially, our simulations reproduce the logarithmic dependence of the elasticity modulus on cooling and deformation rates, which is normally observed in experiments. With the use of the temperature dependence analysis of the elasticity modulus we determined the flow temperature of R-BAPO to be 580 K in line with the experimental data available. Furthermore, we found that the application of high external pressure to the polymer sample during uniaxial deformation can improve the mechanical properties of the polyimide. Overall, the results of our simulations clearly demonstrate that atomistic molecular-dynamics simulations represent a powerful and accurate tool for studying the mechanical properties of heterocyclic polymers and can therefore be useful for the virtual design of new materials, thereby supporting cost-effective synthesis and experimental research.


Use of Edman degradation sequence analysis and matrix-assisted laser desorption/ionization mass spectrometry in designing substrates for matrix metalloproteinases.
The matrix metalloproteinase (MMP) family has been implicated in the process of a variety of diseases such as arthritis, atherosclerosis, and tumor cell metastasis. We have been designing single-stranded peptides (SSPs) and triple-helical peptides (THPs) as potential discriminatory MMP substrates. Edman degradation sequence and matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) analyses of proteolytic activity have been utilized to aid in further substrate design. THP models of the alpha1(I)772-786 sequence from type I collagen were synthesized to examine the triple-helical substrate specificity of MMP family members. Sequence and MALDI-MS analyses were used in conjunction with a fluorometric assay to determine the exact point of cleavage by each MMP. MMP-1 (interstitial collagenase) cleaved the substrates at a single Gly-Ile bond, analogous to the cleavage site in type I collagen. MMP-2 (Mr 72 000 type IV collagenase; gelatinase A) was found to cleave the substrates at two sites, a Gly-Ile bond and a Gly-Gln bond. MMP-3 (stromelysin 1) was found to cleave only one of the substrates after reaction for 48 h. Ultimately, sequence and MALDI-MS analyses allowed us to detect an additional cleavage site for MMP-2 in comparison to MMP-1, while MMP-3 was found to cleave a substrate after an extended time period. The second cleavage site would cause the kinetic parameters for MMP-2 to be overestimated by the fluorometric assay. Further design variations for these substrates need to consider the presence of more stable triple-helical conformation (to eliminate MMP-3 binding) and the removal of Gly-Gln bonds that may be susceptible to MMP-2.


Identification of Multiple Loci Associated with Social Parasitism in Honeybees.
In colonies of the honeybee Apis mellifera, the queen is usually the only reproductive female, which produces new females (queens and workers) by laying fertilized eggs. However, in one subspecies of A. mellifera, known as the Cape bee (A. m. capensis), worker bees reproduce asexually by thelytoky, an abnormal form of meiosis where two daughter nucleii fuse to form single diploid eggs, which develop into females without being fertilized. The Cape bee also exhibits a suite of phenotypes that facilitate social parasitism whereby workers lay such eggs in foreign colonies so their offspring can exploit their resources. The genetic basis of this switch to social parasitism in the Cape bee is unknown. To address this, we compared genome variation in a sample of Cape bees with other African populations. We find genetic divergence between these populations to be very low on average but identify several regions of the genome with extreme differentiation. The regions are strongly enriched for signals of selection in Cape bees, indicating that increased levels of positive selection have produced the unique set of derived phenotypic traits in this subspecies. Genetic variation within these regions allows unambiguous genetic identification of Cape bees and likely underlies the genetic basis of social parasitism. The candidate loci include genes involved in ecdysteroid signaling and juvenile hormone and dopamine biosynthesis, which may regulate worker ovary activation and others whose products localize at the centrosome and are implicated in chromosomal segregation during meiosis. Functional analysis of these loci will yield insights into the processes of reproduction and chemical signaling in both parasitic and non-parasitic populations and advance understanding of the process of normal and atypical meiosis.


Real-time feedback of air quality in children's bedrooms reduces exposure to secondhand smoke.
Secondhand smoke (SHS) exposure creates health risks for non-smokers and is especially detrimental to children. This study evaluated whether immediate feedback in response to poor indoor air quality in children's bedrooms can reduce the potential for SHS exposure, as measured by adherence to a World Health Organization (WHO) indoor air standard. Homes that contained children and an adult who regularly smoked inside (n=298) had an air particle monitor installed in the child's bedroom. These devices measured the concentration of particulate matter (PM2.5) for approximately three months and, for half of the participants, immediately provided aversive feedback in response to elevated PM2.5. Hierarchical linear models were fit to the data to assess whether the intervention increased the probability that: 1) a given day was below the WHO guideline for daily exposure, and 2) a household established and maintained a smoke-free home (SFH), operationalized as achieving 30 consecutive days below the WHO guideline. The intervention's impact was calculated as group-by-time effects. The likelihood that a child's bedroom met the WHO indoor air quality standard on a given day increased such that the baseline versus post-baseline odds ratio (OR) of maintaining indoor PM2.5 levels below the WHO guideline was 2.38 times larger for participants who received the intervention. Similarly, the baseline versus post-baseline OR associated with achieving an SFH was 3.49 times larger for participants in the intervention group. The real-time intervention successfully drove clinically meaningful changes in smoking behavior that mitigated indoor PM2.5 levels in children's bedrooms and thereby reduced SHS exposure. These results demonstrate the effectiveness of targeting sensitive microenvironments by giving caregivers actionable information about children's SHS risks. Future extensions should examine additional microenvironments and focus on identifying the potential for SHS exposure before it occurs.


Environmental impacts of eco-nutrition swine feeding programs in spatially explicit geographic regions of the United States.
This study was conducted to determine greenhouse gas (GHG) emissions, water consumption, land use, as well as nitrogen (N), phosphorus (P), and carbon (C) balance of five diet formulation strategies and feeding programs for growing-finishing pigs (25-130 kg body weight) in the three spatially explicit geographic regions where the majority of U.S. pork production occurs. Feeding programs evaluated consisted of 1) standard corn-soybean meal (CSBM) diets, 2) CSBM containing 15% corn distillers dried grains with solubles (DDGS), 3) CSBM with 8.6% thermally processed supermarket food waste (FW), 4) low crude protein CSBM diets supplemented with synthetic amino acids (SAA), and 5) CSBM with phytase enzyme (PHY) added at 600 FTU (phytase units)/kg of diet. An attributional Life Cycle Assessment approach using a highly specialized, spatially explicit Food System Supply-Chain Sustainability (FoodS3) model was used to quantify GHG emissions, water consumption, and land use of corn, soybean meal, and DDGS based on county level sourcing. The DDGS, FW, and SAA feeding programs had less estimated N and P intake and excretion than CSBM, and the PHY feeding program provided the greatest reduction in P excretion. The FW feeding program had the least overall GHG emissions (319.9 vs. 324.6 to 354.1 kg CO2 equiv./market hog), land use (331.5 vs. 346.5 to 385.2 m2/market hog), and water consumption (7.64 vs. 7.70 to 8.30 m3/market hog) among the alternatives. The DDGS feeding program had the greatest GHG emissions (354.1 kg CO2 equiv./market hog) among all programs but had less impacts on water consumption (7.70 m3) and land use (346.5 m2) per market hog than CSBM and PHY. The SAA feeding program provided a 6.5-7.4% reduction in land use impacts compared with CSBM and PHY, respectively. Regardless of feeding program, the Midwest had the least contributions to GHG emissions and land use attributed to feed and manure among regions. Water consumption per market hog associated with feeding programs was much greater in the Southwest (59.66-63.58 m3) than in the Midwest (4.45-4.88 m3) and Mid-Atlantic (1.85-2.14 m3) regions. Results show that diet composition and U.S. geographic region significantly affect GHG emissions, water consumption, and land use of pork production systems, and the potential use of thermally processed supermarket food waste at relatively low diet inclusion rates (<10%) can reduce environmental impacts compared with other common feeding strategies.


PROMIS® Parent Proxy Report Scales: an item response theory analysis of the parent proxy report item banks.
The objective of the present study is to describe the item response theory (IRT) analysis of the National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS(®)) pediatric parent proxy-report item banks and the measurement properties of the new PROMIS(®) Parent Proxy Report Scales for ages 8-17 years. Parent proxy-report items were written to parallel the pediatric self-report items. Test forms containing the items were completed by 1,548 parent-child pairs. CCFA and IRT analyses of scale dimensionality and item local dependence, and IRT analyses of differential item functioning were conducted. Parent proxy-report item banks were developed and IRT parameters are provided. The recommended unidimensional short forms for the PROMIS(®) Parent Proxy Report Scales are item sets that are subsets of the pediatric self-report short forms, setting aside items for which parent responses exhibit local dependence. Parent proxy-report demonstrated moderate to low agreement with pediatric self-report. The study provides initial calibrations of the PROMIS(®) parent proxy-report item banks and the creation of the PROMIS(®) Parent Proxy-Report Scales. It is anticipated that these new scales will have application for pediatric populations in which pediatric self-report is not feasible.


Self-assembled benzophenone bis-urea macrocycles facilitate selective oxidations by singlet oxygen.
This manuscript investigates how incorporation of benzophenone, a well-known triplet sensitizer, within a bis-urea macrocycle, which self-assembles into a columnar host, influences its photophysical properties and affects the reactivity of bound guest molecules. We further report the generation of a remarkably stable organic radical. As expected, UV irradiation of the host suspended in oxygenated solvents efficiently generates singlet oxygen similar to the parent benzophenone. In addition, this host can bind guests such as 2-methyl-2-butene and cumene to form stable solid host-guest complexes. Subsequent UV irradiation of these complexes facilitated the selective oxidation of 2-methyl-2-butene into the allylic alcohol, 3-methyl-2-buten-1-ol, at 90% selectivity as well as the selective reaction of cumene to the tertiary alcohol, α,α'-dimethyl benzyl alcohol, at 63% selectivity. However, these products usually arise through radical pathways and are not observed in the presence of benzophenone in solution. In contrast, typical reactions with benzophenone result in the formation of the reactive singlet oxygen that reacts with alkenes to form endoperoxides, diooxetanes, or hydroperoxides, which are not observed in our system. Our results suggest that the confinement, the formation of a stable radical species, and the singlet oxygen photoproduction are responsible for the selective oxidation processes. A greater understanding of the mechanism of this selective oxidation could lead to development of greener oxidants.


Pharmacological and phytochemical evaluation of Ocimum sanctum root extracts for its antiinflammatory, analgesic and antipyretic activities.
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases risk of having a range of gastrointestinal problems. Therefore, new anti-inflammatory, analgesic, antipyretic drugs having lesser side effects are being searched all overthe world as alternatives to NSAIDs. To evaluate the anti-inflammatory, analgesic and antipyretic profile of Ocimum sanctum root extracts. Anti-inflammatory profile of hexane (STH), chloroform (STC), ethyl acetate (STE), butanol (STB) and water (STW) extracts of OS was carried out by using carrageenan induced paw edema. STE a most active extract was further validated in dose dependent manner for anti-inflammatory, analgesic and antipyretic activity as well as oral toxicity profile in small laboratory animals. Identification of bioactives flux and chemical signature of most active fraction STE was developed by using the high-performance liquid chromatography fingerprinting. An ethyl acetate fraction (STE) exhibit most potent anti-inflammatory activity followed by STB, STW, STC and STH. Dose response study of STE showed anti-inflammatory, analgesic and anti-pyretic potential in dose-dependent manner without any toxic effect at dose 2000 mg/kg. Chemical fingerprint revealed the presence of flavanoids. The present research revealed that STE possess anti-inflammatory, analgesic and anti-pyretic properties. However, future research is advocated to evaluate the pharmacological properties of isolated bioactive compounds.


A framework for collaborative analysis of ENCODE data: making large-scale analyses biologist-friendly.
The standardization and sharing of data and tools are the biggest challenges of large collaborative projects such as the Encyclopedia of DNA Elements (ENCODE). Here we describe a compact Web application, Galaxy2(ENCODE), that effectively addresses these issues. It provides an intuitive interface for the deposition and access of data, and features a vast number of analysis tools including operations on genomic intervals, utilities for manipulation of multiple sequence alignments, and molecular evolution algorithms. By providing a direct link between data and analysis tools, Galaxy2(ENCODE) allows addressing biological questions that are beyond the reach of existing software. We use Galaxy2(ENCODE) to show that the ENCODE regions contain >2000 unannotated transcripts under strong purifying selection that are likely functional. We also show that the ENCODE regions are representative of the entire genome by estimating the rate of nucleotide substitution and comparing it to published data. Although each of these analyses is complex, none takes more than 15 min from beginning to end. Finally, we demonstrate how new tools can be added to Galaxy2(ENCODE) with almost no effort. Every section of the manuscript is supplemented with QuickTime screencasts. Galaxy2(ENCODE) and the screencasts can be accessed at http://g2.bx.psu.edu.


Hydrophobic gating in bundle-crossing ion channels: a case study of TRPV4.
Transmembrane ion channels frequently regulate ion permeation by forming bundle crossing of the pore-lining helices when deactivated. The resulting physical constriction is believed to serve as the de facto gate that imposes the major free energy barrier to ion permeation. Intriguingly, many ion channels also contain highly hydrophobic inner pores enclosed by bundle crossing, which can undergo spontaneous dewetting and give rise to a "vapor barrier" to block ion flow even in the absence of physical constriction. Using atomistic simulations, we show that hydrophobic gating and bundle-crossing mechanisms co-exist and complement one and another in the human TRPV4 channel. In particular, a single hydrophilic mutation in the lower pore can increase pore hydration and reduce the ion permeation free energy barrier by about half without affecting the bundle crossing. We believe that hydrophobic gating may play a key role in other bundle-crossing ion channels with hydrophobic inner pores.


Economic Impact of Aging on the Initial Spine Care of Patients With Acute Spine Trauma: From Bedside to Teller.
Aging of the population has prompted an escalation of service utilization and costs in many jurisdictions including North America. However, relatively little is known on the economic impact of old age on the management of acute spine trauma (AST). To examine the potential effects of age on the service utilization and costs of the management of patients with acute spine trauma. This retrospective cohort study included consecutive patients with AST admitted to an acute spine care unit of a Canadian quaternary university hospital between February, 2002 and September, 2007. The study population was grouped into elderly (≥65 yr) and younger individuals. All costing data were converted and updated to US dollars in June/2017. There were 55 women and 91 men with AST (age range: 16-92 yr, mean age of 49.9 yr) of whom 37 were elderly. The mean total hospital costs for initial admission after AST in the elderly (USD $19 338 ± $4892) were significantly greater than among younger individuals (USD $13 775 ± $1344). However, elderly people had significantly lower per diem total, fixed, direct, and indirect costs for AST than younger individuals. Both groups were comparable regarding the proportion of services utilized in the acute care hospital. Given the escalating demand for surgical and nonsurgical spine treatment in the age of aging population, the timely results of this study underline key aspects of the economic impact of the spine care of the elderly. Further investigations are needed to fulfill significant knowledge gaps on the economics of caring for elderly with AST.


A Multidimensional B-Spline Correction for Accurate Modeling Sugar Puckering in QM/MM Simulations.
The computational efficiency of approximate quantum mechanical methods allows their use for the construction of multidimensional reaction free energy profiles. It has recently been demonstrated that quantum models based on the neglect of diatomic differential overlap (NNDO) approximation have difficulty modeling deoxyribose and ribose sugar ring puckers and thus limit their predictive value in the study of RNA and DNA systems. A method has been introduced in our previous work to improve the description of the sugar puckering conformational landscape that uses a multidimensional B-spline correction map (BMAP correction) for systems involving intrinsically coupled torsion angles. This method greatly improved the adiabatic potential energy surface profiles of DNA and RNA sugar rings relative to high-level ab initio methods even for highly problematic NDDO-based models. In the present work, a BMAP correction is developed, implemented, and tested in molecular dynamics simulations using the AM1/d-PhoT semiempirical Hamiltonian for biological phosphoryl transfer reactions. Results are presented for gas-phase adiabatic potential energy surfaces of RNA transesterification model reactions and condensed-phase QM/MM free energy surfaces for nonenzymatic and RNase A-catalyzed transesterification reactions. The results show that the BMAP correction is stable, efficient, and leads to improvement in both the potential energy and free energy profiles for the reactions studied, as compared with ab initio and experimental reference data. Exploration of the effect of the size of the quantum mechanical region indicates the best agreement with experimental reaction barriers occurs when the full CpA dinucleotide substrate is treated quantum mechanically with the sugar pucker correction.


Relating cocaine blood concentrations to toxicity--an autopsy study of 99 cases.
We conducted a retrospective study of 48 men with cocaine-related deaths (CTOX), and a control group of 51 male cocaine users who died of lethal trauma (TRAU). Regression analysis and multiple t-tests were used to assess the relationship between cocaine and benzoylecgonire concentrations as well as autopsy measurements. Mean age was similar (35.9 vs 34.8 years, p = .549). Cocaine blood concentrations were not significantly different (1.12 vs .487 mg/L, p = .10), but mean BE concentrations were higher in CTOX (1.54 vs .946 mg/L, p = .018). CTOX decedents had a lower Body Mass Index (BMI) (24.6 vs 30.6, p = < .0001), larger hearts (426 vs 369, p = .009), and heavier lungs, livers, and spleens (1275 g vs 1007 g, p = .009, 1896 g vs 1628 g, p = .008, 193 g vs 146 g, p = .001). (1) Blood cocaine concentrations in cocaine-related deaths are indistinguishable from postmortem concentrations in recreational users, but BE is higher in cocaine-related deaths. (2) Increased lung, liver and spleen weights are consistent with cocaine induced heart failure, but (3) Decreased BMI and increased heart weights in CTOX must be a consequence of long term cocaine use. Cardiac alterations may explain why equal blood cocaine concentrations may be lethal in some cases and innocuous in others, (4) Isolated measurements of postmortem cocaine and BE blood concentrations cannot be used to assess, or predict toxicity.


Post-traumatic stress disorder associated with natural and human-made disasters in the World Mental Health Surveys.
Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20-40% range in disaster-focused studies but considerably lower (3-5%) in the few general population epidemiological surveys that evaluated disaster-related PTSD as part of a broader clinical assessment. The World Mental Health (WMH) Surveys provide an opportunity to examine disaster-related PTSD in representative general population surveys across a much wider range of sites than in previous studies. Although disaster-related PTSD was evaluated in 18 WMH surveys, only six in high-income countries had enough respondents for a risk factor analysis. Predictors considered were socio-demographics, disaster characteristics, and pre-disaster vulnerability factors (childhood family adversities, prior traumatic experiences, and prior mental disorders). Disaster-related PTSD prevalence was 0.0-3.8% among adult (ages 18+) WMH respondents and was significantly related to high education, serious injury or death of someone close, forced displacement from home, and pre-existing vulnerabilities (prior childhood family adversities, other traumas, and mental disorders). Of PTSD cases 44.5% were among the 5% of respondents classified by the model as having highest PTSD risk. Disaster-related PTSD is uncommon in high-income WMH countries. Risk factors are consistent with prior research: severity of exposure, history of prior stress exposure, and pre-existing mental disorders. The high concentration of PTSD among respondents with high predicted risk in our model supports the focus of screening assessments that identify disaster survivors most in need of preventive interventions.


In defense of the Halstead Reitan Battery: a critique of Lezak's review.
Since many neuropsychologists utilize the Halstead Reitan Battery (HRB), it is important to answer a critical review contained in Lezak's (1995) book. Lezak understands hypothesis testing but not HRB pattern analysis or the use of fixed batteries. A fixed battery provides a constant background, which reveals individual characteristics of the patient. Issues discussed include, types of batteries, legitimate review methods, and Reitan's method. This writing demonstrates that almost all of Lezak's criticisms of either the HRB or the Halstead Russell Neuropsychological Evaluation System (HRNES) are either incomplete, misleading or erroneous. Her critique of the Reitan method involved a confusion of terms. In spite of attempts to discredit the HRB not a single sound study questioning the validity of the HRB was presented, while many studies have demonstrated its validity. The fallacy of nonrefutation asserts that it is a fallacy to condemn methods that have been validated while recommending procedures that have not been validated. Lezak questions Reitan's method, the HRB and the HRNES, which have been thoroughly validated, while presenting no validating studies of her own recommended methods.


Molecular architectures of trimeric SIV and HIV-1 envelope glycoproteins on intact viruses: strain-dependent variation in quaternary structure.
The initial step in target cell infection by human, and the closely related simian immunodeficiency viruses (HIV and SIV, respectively) occurs with the binding of trimeric envelope glycoproteins (Env), composed of heterodimers of the viral transmembrane glycoprotein (gp41) and surface glycoprotein (gp120) to target T-cells. Knowledge of the molecular structure of trimeric Env on intact viruses is important both for understanding the molecular mechanisms underlying virus-cell interactions and for the design of effective immunogen-based vaccines to combat HIV/AIDS. Previous analyses of intact HIV-1 BaL virions have already resulted in structures of trimeric Env in unliganded and CD4-liganded states at ~20 Å resolution. Here, we show that the molecular architectures of trimeric Env from SIVmneE11S, SIVmac239 and HIV-1 R3A strains are closely comparable to that previously determined for HIV-1 BaL, with the V1 and V2 variable loops located at the apex of the spike, close to the contact zone between virus and cell. The location of the V1/V2 loops in trimeric Env was definitively confirmed by structural analysis of HIV-1 R3A virions engineered to express Env with deletion of these loops. Strikingly, in SIV CP-MAC, a CD4-independent strain, trimeric Env is in a constitutively "open" conformation with gp120 trimers splayed out in a conformation similar to that seen for HIV-1 BaL Env when it is complexed with sCD4 and the CD4i antibody 17b. Our findings suggest a structural explanation for the molecular mechanism of CD4-independent viral entry and further establish that cryo-electron tomography can be used to discover distinct, functionally relevant quaternary structures of Env displayed on intact viruses.


Syntheses and Structure Determinations of Calcium Thiolates.
The exploration of synthetic methodologies toward heavy alkaline-earth chalcogenolates resulted in the preparation and structural characterization of a family of calcium thiolates, including [Ca(SC(6)F(5))(2)(py)(4)], 1 (py = pyridine), the separated ion-triple [Ca(18-crown-6)(NH(3))(3))][SMes](2).2THF, 2 (Mes = 2,4,6-tBu(3)C(6)H(2)), and the contact triple [Ca(18-crown-6)(SMes)(2)].THF, 3. Compound 1 was prepared by treating [Ca(N(SiMe(3))(2))(2)](2) with 4 equiv of HSC(6)F(5) under addition of pyridine. The thiolates 2 and 3 were synthesized by treatment of calcium metal dissolved in dry, liquid NH(3) under addition of 2 equiv of HSMes and crown ether or, alternatively, by the reduction of MesSSMes with calcium metal in dry, liquid ammonia. We also report two reaction products isolated during attempted calcium thiolate syntheses: [CaBr(4)(THF)(2)(&mgr;(2)-Li)(2)(THF)(4)], 4, isolated as the product of a salt elimination reaction between CaBr(2) and 2 equiv of [Li(THF)(n)()S-2,4,6-(i)()Pr(3)C(6)H(2)](m)(). [(NH(4))(py)(SC(6)F(5))], 5, was obtained as the sole product in the reaction of metallic calcium with HSC(6)F(5) in liquid ammonia under addition of pyridine. All compounds were characterized by single-crystal X-ray crystallography in addition to IR and NMR spectroscopy.


Arterial stiffness and the development of hypertension. The ARIC study.
Decreased elasticity in large and medium-sized arteries has been postulated to be associated with cardiovascular diseases. We prospectively examined the relation between arterial elasticity and the development of hypertension over 6 years of follow-up in a cohort of 6992 normotensive men and women aged 45 to 64 years at baseline from the biracial, population-based Atherosclerosis Risk in Communities (ARIC) Study. Arterial elasticity was measured from high-resolution B-mode ultrasound examination of the left common carotid artery as adjusted arterial diameter change (in micrometers, simultaneously adjusted for diastolic blood pressure, pulse pressure, pulse pressure squared, diastolic arterial diameter, and height), Peterson's elastic modulus (in kilopascals), Young's elastic modulus (in kilopascals), and beta stiffness index. Incident hypertension (n=551) was defined as systolic blood pressure >/=160 mm Hg, diastolic blood pressure >/=95 mm Hg, or the use of antihypertensive medication at a follow-up examination conducted every 3 years. The age-, ethnicity-, center-, gender-, education-, smoking-, heart rate-, and obesity-adjusted means (SE) of baseline adjusted arterial diameter change, Peterson's elastic modulus, Young's elastic modulus, and beta stiffness index were 397 (5), 148 (2.0), 787 (12.7), and 11.43 (0.16), respectively, in persons who developed hypertension during follow-up, in contrast to 407 (1), 124 (0.6), 681 (3.7), and 10.34 (0.05), respectively, for persons who did not. The similarly adjusted cumulative incident rates of hypertension from the highest to the lowest quartiles of arterial elasticity were 6.7%, 8.0%, 7.3%, and 9.6%, respectively, when measured by adjusted arterial diameter change (P<0.01). One standard deviation decrease in arterial elasticity was associated with 15% greater risk of hypertension, independent of established risk factors for hypertension and the level of baseline blood pressure. These results suggest that lower arterial elasticity is related to the development of hypertension.


Small Amounts of Dietary Medium-Chain Fatty Acids Protect Against Insulin Resistance During Caloric Excess in Humans.
Medium-chain fatty acids (MCFAs) have in rodents been shown to have protective effects on glucose homeostasis during high-fat overfeeding. In this study, we investigated whether dietary MCFAs protect against insulin resistance induced by a hypercaloric high-fat diet in humans. Healthy, lean men ingested a eucaloric control diet and a 3-day hypercaloric high-fat diet (increase of 75% in energy, 81-83% energy [E%] from fat) in randomized order. For one group (n = 8), the high-fat diet was enriched with saturated long-chain FAs (LCSFA-HFD), while the other group (n = 9) ingested a matched diet, but with ∼30 g (5E%) saturated MCFAs (MCSFA-HFD) in substitution for a corresponding fraction of the saturated long-chain fatty acids (LCFAs). A hyperinsulinemic-euglycemic clamp with femoral arteriovenous balance and glucose tracer was applied after the control and hypercaloric diets. In LCSFA-HFD, whole-body insulin sensitivity and peripheral insulin-stimulated glucose disposal were reduced. These impairments were prevented in MCSFA-HFD, accompanied by increased basal fatty acid oxidation, maintained glucose metabolic flexibility, increased nonoxidative glucose disposal related to lower starting glycogen content, and increased glycogen synthase activity, together with increased muscle lactate production. In conclusion, substitution of a small amount of dietary LCFAs with MCFAs rescues insulin action in conditions of lipid-induced energy excess.


Cardiac and haemodynamic measurements in hypertensive pregnancy.
1. Haemodynamic and left ventricular variables were determined by M-mode echocardiography in 21 normotensive and 36 hypertensive patients during the last trimester of pregnancy. 2. Blood pressure of hypertensive patients was lowered by bed rest only, or by oxprenolol or methyldopa, but remained elevated. 3. Cardiac output was raised in the last trimester of pregnancy in both normotensive and hypertensive patients. 4. Left ventricular mass was increased in normal pregnancy, but displayed an exaggerated increase in hypertensive patients. 5. Total peripheral resistance was inappropriately elevated in hypertensive pregnancy, except in the oxprenolol-treated group. 6. There ws no reduction in heart rate or cardiac output in the group treated with beta-adrenoreceptor blocking agents. These factors, in combination with normal peripheral resistance, may contribute to the improvement in foetal outcome described in maternal hypertension of pregnancy treated with oxprenolol.


Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE): A multicentre observational study.
The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe. Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0-18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%-41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%-90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%-29.3%), and inconclusive in 22.5% (range across EDs: 0.4%-60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%-59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%-47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%-100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country. In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.


[A study of the progression of the incidental prostate cancer depending on the kind of treatment performed].
Prostate cancer is a common neoplasm, with a significant burden of mortality. Since it's diagnosed at old ages and usually growths slowly, agresive treatment of localised cancer of prostate could be of little benefit. The study of the evolution of incidental prostate cancer diagnosed 20 years ago could give directions for present decision-making. We performed a time survival analysis of patients diagnosed of incidental prostate cancer between 1980 and 2000, and followed them until april 2005. We analysed overall and disease-specific mortality, related to the kind of treatment and some anatomopathological characteristics. We included 80 cases. Treatment was hormonotherapy in 34 cases, surgery in 4, radiotherapy in 3 and watchful waiting in 39. Overall average survival was 8.87 years. Disease-specific survival in low risk group (Gleason lower than 6) was 16 years, and in high risk group (Gleason higher than 7) was 6 years. No differences were found between hormonotherapy and watchful waiting. While in low risk patients watchful waiting represents an acceptable aproaching, it could not be adequate in high risk cases. Hormonotherapy showed no benefit in incidental prostate cancer.


Management of Acute Isolated Soleal Vein Thrombosis in a Pregnant Patient With an Osteopathic Approach to Evaluation.
In pregnant women, the risk of venous thromboembolism increases 4 to 5 fold over that in nonpregnant women. Deep vein thromboses in the calf occur in approximately 6% of cases, with a 20% incidence of propagation, but new imaging methods suggest a higher rate. Nevertheless, the management of isolated soleal vein thrombosis is currently one of the most debated issues in the field of venous thromboembolism, and a clear set of principles for the management of this unique clinical problem remains undefined. The authors present the case of a 37-year-old woman with a history of recurrent spontaneous abortions and cervical insufficiency who presented with a short cervix and acute right isolated soleal vein thrombosis. Long-term anticoagulantion therapy was recommended. Future studies on the risk of isolated soleal vein thrombosis propagation in the setting of pregnancy are required to identify the most effective treatment options for this clinical problem.


Role of awake prone positioning in patients with moderate-to-severe COVID-19: an experience from a developing country.
There is limited evidence on the efficacy of awake prone positioning (PP) in non-ventilated patients with COVID-19 who have hypoxemia. We, therefore, aim to describe our experience with the use of early proning in awake, non-intubated patients with confirmed COVID-19. In our retrospective observational study, 23 patients with confirmed positive PCR test results for Severe Acute respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and hypoxemia that required oxygen therapy with or without non-invasive ventilation were treated with PP. Patients were classified into mild, moderate and severe COVID-19 disease. There were no targeted number of hours for proning per day and patients were kept in prone position according to their tolerance. The primary outcome measure was the avoidance of intubation and secondary outcomes were in-hospital mortality, length of hospital stays and complications related to PP. The mean (standard deviation) age of our cohort was 54.5 (11.7) years, and the majority were males (21/23, 91.3%). Sixty-one per cent (14/23) of the patients were suffering from severe disease and 82.6% (19/23) had bilateral lung involvement with interstitial infiltrates. Majority of the patients were prone positioned for a median of 6 days (IQR 4 - 8). Only one patient required transfer to ICU for mechanical ventilation and subsequently died due to severe ARDS. All 22 patients showed progressive improvement in oxygen requirement and PF ratio, mostly after 3-5 days of proning. The mean length of hospital stay was 12 days. All patients, except one, were discharged in stable conditions, on room air or on a minimal oxygen requirement of 1-2 liters. No major complication of PP was recorded. Awake prone positioning is a valuable and safe therapeutic adjunct that can be applied in patients with moderate-to-severe COVID-19. It can also be included in the home-based management protocols of COVID-19 to improve patient outcomes and mitigate the burden on health care facilities.


Clinical characteristics and prognostic factors analysis of core binding factor acute myeloid leukemia in real world.
Chromosomal translocations involving core binding factor (CBF) genes account for 15% of adult acute myeloid leukemia (AML) cases in China. Despite being classified as favorable-risk by European Leukemia Net (ELN), CBF-AML patients have a 40% relapse rate. This study aims to analyze clinical characteristics and prognosis of CBF-AML, compare its subtypes (inv(16) and t(8;21)), and validate prognostic factors. Retrospective analysis of 149 AML patients (75 CBF-AML, 74 non-CBF) at Peking University First Hospital (March 2012-March 2022). CBF-AML patients have significantly lower disease-free survival (DFS) (p = 0.005) and higher non-relapse mortality (NRM) (p = 0.028) compared to non-CBF AML. inv (16) and t(8;21) show distinct co-occurring gene mutation patterns, with inv(16) being prone to central nervous system (CNS) leukemia. Multivariate analysis identifies age as a risk factor for overall survival (OS) and disease free survival (DFS), kinase mutation as a risk factor for DFS and Recurrence, while WT1 mutation as a risk factor for OS and non relapse mortality (NRM) risk in t(8;21) AML. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves prognosis in low-risk t(8;21). Prognosis of CBF-AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo-HSCT may benefit low-risk t(8;21), but further research is needed for conclusive evidence.


Duodenal erosion with bleeding from a non-functioning islet cell tumour. A case report.
A patient with a clinically non-functioning pancreatic islet cell tumour in the medial wall of the duodenum with erosion of the overlying mucosa presented with gastro-intestinal bleeding. At gastroduodenoscopy, the tumour with its apical ulcer was thought to be a leiomyoma. The lesion was excised locally and two other non-functioning APUDomas were shelled out of the body and tail of the pancreas.


Association between Fibrinogen and Carotid Atherosclerosis According to Smoking Status in a Korean Male Population.
Although inconsistent, reports have shown fibrinogen levels to be associated with atherosclerosis. Accordingly, since cigarette smoking is associated with increased levels of fibrinogen and atherosclerosis, it may also affect the association between fibrinogen and atherosclerosis. We investigated the associations between fibrinogen and carotid intima-media thickness (IMT) according to smoking status in a Korean male population. Plasma fibrinogen levels were measured in 277 men aged 40-87 years without a history of myocardial infarction or stroke. High-resolution B-mode ultrasonography was used to examine the common carotid arteries. IMT level was analyzed both as a continuous (IMT-max, maximum value; IMT-tpm, 3-point mean value) and categorical variable (higher IMT; presence of plaque). Serial linear and logistic regression models were employed to examine the association between fibrinogen and IMT according to smoking status. Fibrinogen levels were positively associated with IMT-max (standardized β=0.25, p=0.021) and IMT-tpm (standardized β=0.21, p=0.038), even after adjusting for age, body mass index, systolic blood pressure, fasting glucose, and total cholesterol to high-density lipoprotein cholesterol ratio in current smokers (n=75). No significant association between fibrinogen and IMT, however, was noted in former smokers (n=80) or nonsmokers (n=122). Adjusted odds ratios (95% confidence interval) for having plaque per one standard deviation higher fibrinogen level were 2.06 (1.09-3.89) for current smokers, 0.68 (0.43-1.10) for former smokers, and 1.06 (0.60-1.87) for nonsmokers. Our findings suggest that cigarette smoking may modify the association between fibrinogen and carotid atherosclerosis. Further studies are required to confirm this finding in different populations.


An evaluation of student nurses experiences of being a researcher in a mental health research project.
Thirteen student nurses from the Mental Health and Learning Disability branches (Project 2000) of the School of Care Sciences at the University of Glamorgan volunteered to participate in a research study as research assistants. Participation of this kind represents a novel, practical way of learning about research. Following training and data collection within the research study we evaluated the student's experience of training and participation. Within the survey both quantitative and qualitative data were collected using a self-report questionnaire. Thirteen questionnaires were distributed and twelve completed questionnaires were returned to the School of Care Sciences. The overall results were extremely encouraging with regards to using this approach to increase research awareness. An evaluation of the student's experiences as a researcher confirmed that this was a successful strategy to learning, in particular increasing knowledge of the research process, ethical considerations and skills in interviewing. Involvement also increases the student's awareness of the topic area being studied. Limitations to the study were that this was a small sample.


The ontogeny of fairness in seven societies.
A sense of fairness plays a critical role in supporting human cooperation. Adult norms of fair resource sharing vary widely across societies, suggesting that culture shapes the acquisition of fairness behaviour during childhood. Here we examine how fairness behaviour develops in children from seven diverse societies, testing children from 4 to 15 years of age (n = 866 pairs) in a standardized resource decision task. We measured two key aspects of fairness decisions: disadvantageous inequity aversion (peer receives more than self) and advantageous inequity aversion (self receives more than a peer). We show that disadvantageous inequity aversion emerged across all populations by middle childhood. By contrast, advantageous inequity aversion was more variable, emerging in three populations and only later in development. We discuss these findings in relation to questions about the universality and cultural specificity of human fairness.


Sphingosine-1-phosphate facilitates trafficking of hematopoietic stem cells and their mobilization by CXCR4 antagonists in mice.
CXCL12 and VCAM1 retain hematopoietic stem cells (HSCs) in the BM, but the factors mediating HSC egress from the BM to the blood are not known. The sphingosine-1-phosphate receptor 1 (S1P(1)) is expressed on HSCs, and S1P facilitates the egress of committed hematopoietic progenitors from the BM into the blood. In the present study, we show that both the S1P gradient between the BM and the blood and the expression of S1P(1) are essential for optimal HSC mobilization by CXCR4 antagonists, including AMD3100, and for the trafficking of HSCs during steady-state hematopoiesis. We also demonstrate that the S1P(1) agonist SEW2871 increases AMD3100-induced HSC and progenitor cell mobilization. These results suggest that the combination of a CXCR4 antagonist and a S1P(1) agonist may prove to be sufficient for mobilizing HSCs in normal donors for transplantation purposes, potentially providing a single mobilization procedure and eliminating the need to expose normal donors to G-CSF with its associated side effects.


Inorganic oxide core, polymer shell nanocomposite as a high K gate dielectric for flexible electronics applications.
Organic/inorganic core shell nanoparticles have been synthesized using high K TiO(2) as the core nanoparticle, and polystyrene as the shell. This material is easy to process and forms transparent continuous thin films, which exhibit a dielectric constant enhancement of over 3 times that of bulk polystyrene. This new dielectric material has been incorporated into capacitors and thin film transistors (TFTs). Mobilities approaching 0.2 cm(2)/V.s have been measured for pentacene TFTs incorporating the new TiO(2) polystyrene nanostructured gate dielectric, indicating good surface properties for pentacene film growth. This novel strategy for generating high K flexible gate dielectrics will be of value in improving organic and flexible electronic device performance.