CD28-mediated pro-survival signaling induces chemotherapeutic resistance in multiple myeloma.
Chemotherapeutic resistance remains a significant hurdle in the treatment of multiple myeloma (MM) and is significantly mediated by interactions between MM cells and stromal cells of the bone marrow microenvironment. Despite the importance of these interactions, the specific molecules and downstream signaling components involved remain incompletely understood. We have previously shown that the prototypic T-cell costimulatory receptor CD28, which is also expressed on MM cells, is a key mediator of MM survival and apoptotic resistance. Crosslinking CD28 by agonistic antibodies or myeloid dendritic cells (DC; these express the CD28 ligands CD80/CD86) prevents apoptosis caused by chemotherapy or serum withdrawal. We now report that CD28 pro-survival signaling is dependent upon downstream activation of phosphatidyl-inositol 3-kinase/Akt, inactivation of the transcription factor FoxO3a, and decreased expression of the pro-apoptotic molecule Bim. Conversely, blocking the CD28-CD80/CD86 interaction between MM cells and DC in vitro abrogates the DC's ability to protect MM cells against chemotherapy-induced death. Consistent with these observations, in vivo blockade of CD28-CD80/CD86 in the Vk*MYC murine myeloma model sensitizes MM cells to chemotherapy and significantly reduces tumor burden. Taken together, our findings suggest that CD28 is an important mediator of MM survival during stress and can be targeted to overcome chemotherapy resistance.


Novel Planar Strain Sensor Design for Capturing 3-Dimensional Fingertip Forces from Patients Affected by Hand Paralysis.
Assessment and therapy for individuals who have hand paresis requires force sensing approaches that can measure a wide range of finger forces in multiple dimensions. Here we present a novel strain-gauge force sensor with 3 degrees of freedom (DOF) designed for use in a hand assessment and rehabilitation device. The sensor features a fiberglass printed circuit board substrate to which eight strain gauges are bonded. All circuity for the sensor is routed directly through the board, which is secured to a larger rehabilitative device via an aluminum frame. After design, the sensing package was characterized for weight, capacity, and resolution requirements. Furthermore, a test sensor was calibrated in a three-axis configuration and validated in the larger spherical workspace to understand how accurate and precise the sensor is, while the sensor has slight shortcomings with validation error, it does satisfy the precision, calibration accuracy, and fine sensing requirements in orthogonal loading, and all structural specifications are met. The sensor is therefore a great candidate for sensing technology in rehabilitation devices that assess dexterity in patients with impaired hand function.


Airway Pathological Alterations Selectively Associated With Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage - Narrative Review.
Acute respiratory distress syndrome (ARDS) is a frequent and life-threatening entity. Recently, it has been demonstrated that diffuse alveolar damage (DAD), which is considered the histological hallmark in spite of presenting itself in only half of living patients with ARDS, exerts a relevant effect in the ARDS outcome. Despite the fact that the bronchial tree constitutes approximately 1% of the lung volume, discovering a relation between DAD and bronchial tree findings could be of paramount importance for a few reasons; (a) it could improve the description of ARDS with DAD as a clinical-pathological entity, (b) it could subrogate DAD findings with the advantage of their more accessible and safer analysis and (c) it could allow the discovery of new therapeutic targets. This narrative review is focused on pathological airway changes associated to Diffuse Alveolar Damage in the context of Acute Respiratory Distress Syndrome. It is organized into five sections: main anatomical and functional features of the human airway, why it is necessary to study airway features associated to DAD in patients with ARDS, pathological airway changes associated with DAD in animal models of ARDS, pathological airway changes associated with DAD in patients with ARDS, and the newest techniques for studying the histology of the bronchial tree and lung parenchyma.


[Biosynthesis of proteins in various organs of albino rats in experimental peritonitis].
Protein biosynthesis and the state of polysomes were studied in rat liver and spleen tissues under conditions of acute purulent peritonitis of abdominal cavity. In the both tissues studied synthesis of proteins was markedly inhibited at the initial period of the peritonitis development within 6 hrs, these patterns were further increased within 12-48 hrs but they remained lower the control values. The structure-functional impairments of polysomes were most distinct within 24-48 hrs after the disease beginning.


An application of polarized domains in ferroelectric thin films using scanning probe microscope.
The feasibility of utilizing PZT films as future data storage media was investigated using a modified AFM. Applying voltages between a conductive AFM tip and the PZT films causes the switching of ferroelectric domains. The domains are observed using an EFM imaging technique. The experimental results and calculations revealed that the electrostatic force generated between the polarized area and the tip is a main contributor for the imaging of the polarized domains. The written features on ferroelectric films were less than 100 nm in diameter, implying the possibility of realizing data storage devices with ultra-high area density. The disappearance of the polarized images without any applied voltage was observed, which is a drawback in this application of PZT thin films.


Potentiation of acetaminophen hepatotoxicity by acute physical exercise in rats.
Effects of acute physical exercise on the acetaminophen-induced hepatotoxicity were examined in adult female rats. Rats were forced to move at a speed of 10 m/min for 2 hr in a rotating cage. Immediately following the exercise bout rats were treated with acetaminophen (APAP; 700 mg/kg, i.p.). The physical exercise enhanced the hepatotoxicity of APAP as shown by increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities measured 24 hr following the treatment. A significant decrease in hepatic glutathione (GSH) was observed in the rats forced to exercise suggesting that the enhancement of APAP hepatotoxicity was associated with the depression of this endogenous tripeptide. The role of adrenergic stimulation in the exercise-induced hepatic GSH depression was examined by pretreating the animals with a receptor specific adrenergic antagonist, such as prazosin HCl (15 mg/kg, i.p.), propranolol HCl (15 mg/kg, i.p.), and yohimbine HCl (15 mg/kg, i.p.) 15 min prior to the exercise bout, but neither of the antagonists prevented the GSH depression. Administration of alpha-tocopherol acetate (450 mg/kg/day for 3 days and 150 mg/kg on day 4, i.p.) did not affect the exercise-induced GSH depression or lipid peroxidation in liver homogenates as determined by increases in malondialdehyde formation. These results suggest that neither adrenergic stimulation nor oxidative stress plays a significant role in the enhancement of APAP hepatotoxicity and hepatic GSH depression induced by acute physical exercise.


MU2A--reconciling the genome and transcriptome to determine the effects of base substitutions.
Next-generation sequencing technologies enable the identification of sequence variation in the genome and transcriptome. Differences between the reference genome and transcript libraries complicate the determination of the effect of genomic sequence variants on protein products; similarly, these differences complicate the mapping of sequence variants found in transcripts to their respective genomic position. We have developed MU2A, a publicly available web service for variant annotation that reconciles differences between the genome and transcriptome, enabling the rapid and accurate determination of the effects of genomic variants on protein products, and the mapping of variants detected in transcripts to genomic coordinates. The MU2A web service is available at http://krauthammerlab.med.yale.edu/mu2a. We have released MU2A as open source, available at http://code.google.com/p/mu2a/.


Exploration of trends in the incidence and prevalence of childhood maltreatment and domestic abuse recording in UK primary care: a retrospective cohort study using 'the health improvement network' database.
Describe the epidemiology of childhood maltreatment and domestic abuse (in women). Analysis of longitudinal records between 1 January 1995 to 31 December 2018. UK primary care database: 'The Health Improvement Network' (THIN). 11 831 850 eligible patients from 787 contributing practices. Childhood maltreatment and domestic abuse (women only) were defined as the presence of a recorded Read code. The incidence rate (IR) and prevalence of childhood maltreatment (in children aged 0-18 years) and domestic abuse (in women aged over 18) between 1996 and 2017. An adjusted incidence rate ratio (aIRR) is given to examine the differences in IRs based on sex, ethnicity and deprivation. The age and gender breakdown of THIN has been previously reported to be representative of the UK population, however, there is substantial missing information on deprivation quintiles (<20%) and ethnicity (approximately 50%). The IR (IR 60.1; 95% CI 54.3 to 66.0 per 100 000 child years) and prevalence (416.1; 95% CI 401.3 to 430.9 per 100 000 child population) of childhood maltreatment rose until 2017. The aIRR was greater in patients from the most deprived backgrounds (aIRR 5.14; 95% CI 4.57 to 5.77 compared with least deprived) and from an ethnic minority community (eg, black aIRR 1.25; 1.04 to 1.49 compared with white). When examining domestic abuse in women, in 2017, the IR was 34.5 (31.4 to 37.7) per 100 000 adult years and prevalence 368.7 (358.7 to 378.7) per 100 000 adult population. Similarly, the IR was highest in the lowest socioeconomic class (aIRR 2.30; 2.71 to 3.30) and in ethnic minorities (South Asian aIRR 2.14; 1.92 to 2.39 and black aIRR 1.64; 1.42 to 1.89). Despite recent improvements in recording, there is still a substantial under-recording of maltreatment and abuse within UK primary care records, compared with currently existing sources of childhood maltreatment and domestic abuse data. Approaches must be implemented to improve recording and detection of childhood maltreatment and domestic abuse within medical records.


Urinary bladder function and somatic sensitivity in vasoactive intestinal polypeptide (VIP)-/- mice.
Vasoactive intestinal polypeptide (VIP) is an immunomodulatory neuropeptide widely distributed in neural pathways that regulate micturition. VIP is also an endogenous anti-inflammatory agent that has been suggested for the development of therapies for inflammatory disorders. In the present study, we examined urinary bladder function and hindpaw and pelvic sensitivity in VIP(-/-) and littermate wildtype (WT) controls. We demonstrated increased bladder mass and fewer but larger urine spots on filter paper in VIP(-/-) mice. Using cystometry in conscious, unrestrained mice, VIP(-/-) mice exhibited increased void volumes and shorter intercontraction intervals with continuous intravesical infusion of saline. No differences in transepithelial resistance or water permeability were demonstrated between VIP(-/-) and WT mice; however, an increase in urea permeability was demonstrated in VIP(-/-) mice. With the induction of bladder inflammation by acute administration of cyclophosphamide, an exaggerated or prolonged bladder hyperreflexia and hindpaw and pelvic sensitivity were demonstrated in VIP(-/-) mice. The changes in bladder hyperreflexia and somatic sensitivity in VIP(-/-) mice may reflect increased expression of neurotrophins and/or proinflammatory cytokines in the urinary bladder. Thus, these changes may further regulate the neural control of micturition.


Habitat Utilization and Feeding Biology of Himalayan Grey Langur (Semnopithecus entellus ajex) in Machiara National Park, Azad Jammu and Kashmir, Pakistan.
Habitat utilization and feeding biology of Himalayan Grey Langur (Semnopithecus entellus ajex) were studied from April, 2006 to April, 2007 in Machiara National Park, Azad Jammu and Kashmir, Pakistan. The results showed that in the winter season the most preferred habitat of the langurs was the moist temperate coniferous forests interspersed with deciduous trees, while in the summer season they preferred to migrate into the subalpine scrub forests at higher altitudes. Langurs were folivorous in feeding habit, recorded as consuming more than 49 plant species (27 in summer and 22 in winter) in the study area. The mature leaves (36.12%) were preferred over the young leaves (27.27%) while other food components comprised of fruits (17.00%), roots (9.45%), barks (6.69%), flowers (2.19%) and stems (1.28%) of various plant species.


Family-centered theory: origins, development, barriers, and supports to implementation in rehabilitation medicine.
The concept of family-centered care was introduced to the public more than 4 decades ago, stressing the importance of the family in children's well being. Since then, family-centered values and practices have been widely implemented in child health. The purpose of this article is to offer an overview of the development and evolution of family-centered theory as an underlying conceptual foundation for contemporary health services. The focus includes key concepts, accepted definitions, barriers, and supports that can influence successful implementation, and discussion of the valid quantitative measures of family-centeredness currently available to evaluate service delivery. The article also provides the foundation, and proposes questions, for future research.


Hydrogen peroxide induces hyphal differentiation in Candida albicans.
In this study, we demonstrate that hyphal differentiation is induced by the subtoxic concentration of exogenous H(2)O(2) in Candida albicans. This finding is confirmed by the changing intracellular concentration of H(2)O(2). In order to induce the same level of differentiation, low concentrations of exogenous H(2)O(2) are required for the null mutants of the thiol-specific antioxidant and catalase, while higher concentrations are needed for cells treated with ascorbic acid, an antioxidant chemical.


An Overview of Literature Topics Related to Current Concepts, Methods, Tools, and Applications for Cumulative Risk Assessment (2007-2016).
Cumulative risk assessments (CRAs) address combined risks from exposures to multiple chemical and nonchemical stressors and may focus on vulnerable communities or populations. Significant contributions have been made to the development of concepts, methods, and applications for CRA over the past decade. Work in both human health and ecological cumulative risk has advanced in two different contexts. The first context is the effects of chemical mixtures that share common modes of action, or that cause common adverse outcomes. In this context two primary models are used for predicting mixture effects, dose addition or response addition. The second context is evaluating the combined effects of chemical and nonchemical (e.g., radiation, biological, nutritional, economic, psychological, habitat alteration, land-use change, global climate change, and natural disasters) stressors. CRA can be adapted to address risk in many contexts, and this adaptability is reflected in the range in disciplinary perspectives in the published literature. This article presents the results of a literature search and discusses a range of selected work with the intention to give a broad overview of relevant topics and provide a starting point for researchers interested in CRA applications.


Clinicopathologic profile of gastrointestinal stromal tumors (GISTs) with primary KIT exon 13 or exon 17 mutations: a multicenter study on 54 cases.
Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms driven by oncogenic, mutational activation of KIT or platelet-derived growth factor receptor alpha (PDGFRA). GIST-specific KIT or PDGFRA mutations have been linked to tumor location, tumor cell morphology and clinical behavior. The purpose of this study was to evaluate the clinicopathologic profile of GISTs that have KIT exon 13 or exon 17 mutations. Through the collaboration of several GIST research groups, we gathered 54 cases from the pre-imatinib era that had such primary mutations. From our observations and those in the literature, we estimate that the frequency of these mutations is no higher than 1-2%. Almost all (32 of 33, 97%) of the KIT exon 13 mutations were the 1945A>G substitution leading to Lys642Glu. A majority (15 of 21, 71.4%) of the KIT exon 17 mutations were the 2487T>A substitution leading to Asn822Lys. Demographic and clinicopathologic data were available for 26 and 14 KIT exon 13 and exon 17 mutant GISTs, respectively. Median age and male to female ratio were similar to ones reported in other GIST studies. Small intestinal tumors were two times more frequent than gastric ones among KIT exon 17 mutants. Also, intestinal tumors were slightly overrepresented among KIT exon 13 mutants when compared with population-based studies. The majority of KIT exon 13 or exon 17 mutants had a spindle-cell morphology and only a few had epithelioid features. Tumor size varied from 1.2 to 25 cm and average mitotic rates were 9.5 and 4.2 for KIT exon 13 and exon 17 mutants, respectively. Gastric KIT exon 13 mutant GISTs tend to be slightly larger and more aggressive than gastric GISTs in average, whereas the behavior of small intestinal GISTs with KIT exon 13 mutations does not differ from other small intestinal GISTs. The latter is also true for all KIT exon 17 mutant GISTs.


Enzyme characteristics of beta-D-galactosidase- and beta-D-glucuronidase-positive bacteria and their interference in rapid methods for detection of waterborne coliforms and Escherichia coli.
Bacteria which were beta-D-galactosidase and beta-D-glucuronidase positive or expressed only one of these enzymes were isolated from environmental water samples. The enzymatic activity of these bacteria was measured in 25-min assays by using the fluorogenic substrates 4-methylumbelliferyl-beta-D-galactoside and 4-methylumbelliferyl-beta-D-glucuronide. The enzyme activity, enzyme induction, and enzyme temperature characteristics of target and nontarget bacteria in assays aimed at detecting coliform bacteria and Escherichia coli were investigated. The potential interference of false-positive bacteria was evaluated. Several of the beta-D-galactosidase-positive nontarget bacteria but none of the beta-D-glucuronidase-positive nontarget bacteria contained unstable enzyme at 44.5 degrees C. The activity of target bacteria was highly inducible. Nontarget bacteria were induced much less or were not induced by the inducers used. The results revealed large variations in the enzyme levels of different beta-D-galactosidase- and beta-D-glucuronidase-positive bacteria. The induced and noninduced beta-D-glucuronidase activities of Bacillus spp. and Aerococcus viridans were approximately the same as the activities of induced E. coli. Except for some isolates identified as Aeromonas spp., all of the induced and noninduced beta-D-galactosidase-positive, noncoliform isolates exhibited at least 2 log units less mean beta-D-galactosidase activity than induced E. coli. The noncoliform bacteria must be present in correspondingly higher concentrations than those of target bacteria to interfere in the rapid assay for detection of coliform bacteria.


Becoming more egalitarian: A longitudinal examination of Mexican-origin adolescents' gender role attitudes.
The current study examined the trajectory of gender role attitudes of 471 Mexican-origin adolescents (236 girls, 235 boys) from 5th grade (Mage = 10.86 years) to 11th grade (Mage = 16.75 years), investigating how situating identities (i.e., gender, nativity, SES), ethnic identity (i.e., ethnic pride), and familial context (i.e., parents' attitudes) contributed to adolescents' gender role attitudes across time. Participant interviews were conducted every other year, resulting in 4 waves of data. Most parents (96%) were Mexico natives, with an average immigration age of 18.16 years for fathers and 14.01 years for mothers. Results revealed linear and quadratic trends in gender attitude traditionality for all adolescents, characterized by a linear decline through age 16 years that leveled off through age 18 years. Although both girls and boys trended toward egalitarian gender role attitudes across adolescence, girls endorsed more egalitarian attitudes than did boys. Adolescents from higher-SES backgrounds endorsed more egalitarian attitudes than those from lower-SES backgrounds. Significant within-person effects of ethnic pride surfaced, such that children with higher levels of ethnic pride at any given time also reported more traditional gender role attitudes. Significant between-person effects of mothers' and fathers' attitudes were found, such that parents with more traditional gender role attitudes tended to have children with relatively more traditional gender role attitudes. Overall, these findings highlight the importance of studying gender development in conjunction with situating identities, cultural identities, and the broader context, particularly when children are embedded in multiple cultures with contrasting gender role expectations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Is food availability a circannual zeitgeber in tropical birds? A field experiment on stonechats in tropical Africa.
Equatorial stonechats (Saxicola torquata axillaris) in Africa are seasonal breeders like their temperate-zone conspecifics (S.t. rubicola). Their annual cycle in gonadal size and function is controlled by an endogenous circannual rhythmicity that has been shown to run for up to 10 years in a constant equatorial photoperiod under laboratory conditions, with a period deviating from 12 months. In nature, however, this rhythm is synchronized with the actual year. Because photoperiod is essentially constant at the equator, it is likely that other environmental factors act as zeitgebers. The authors test whether food availability affects reproductive cycles of free-living East African stonechats. The authors offered supplemental food to the birds 2 months before the regular onset of the breeding season. Supplementally fed males started to sing and display earlier than males of control pairs that did not receive extra food. Although the supplemented food advanced the onset of the breeding season in the pairs that were fed, the onset of the postnuptial molt following the breeding season was not correspondingly shifted. Furthermore, in the year following the experiment, all pairs initiated breeding at the same time. The authors conclude that food availability does not act as a zeitgeber, but rather as a factor that modifies the timing of reproduction without affecting the underlying rhythmicity. The authors propose that this is adaptive under environmental conditions that are relatively constant within a given year but may vary considerably between years. The zeitgeber synchronizing the endogenous rhythmicity remains to be identified.


Making informed choices in social care: the importance of accessible information.
The current policy trend is to encourage greater choice in the use of welfare services. To make informed choices, people need information. The process of finding and using information has costs for individuals in terms of effort, time and material resources. These costs are different for different people and impact on their use of information in different ways. Thus, the accessibility of information is important in ensuring those people who need to make choices can do so in an informed way. This paper discusses the importance of information in making informed choices about social support by drawing on the findings of a scoping review of government research and development activity on the accessibility of information about adult social care services. The scoping review was carried out in spring 2006. Details of recent, current and planned projects were obtained through discussions with staff in government departments, government agencies and other related organisations identified using a snowballing technique. Forty-two contacts were made. Eleven research and 36 development projects were identified that aimed to investigate or improve the accessibility of information about social care services. A limited literature search was undertaken on information needs in areas not already under investigation by government. Eighteen articles were identified. Information and helpline staff from six voluntary organisations gave their views on the accessibility of information about social care services. Our findings show that there is no government-related or other recent research evidence on the specific information access needs for some user groups and services, for example, people from ethnic minority groups. For other user groups, such as people with chaotic lifestyles, there is evidence on information needs but no current or planned development projects to address these needs. The implications for the costs of finding and processing information to aid informed choices are discussed.


Memory shapes visual search strategies in large-scale environments.
Search is a central visual function. Most of what is known about search derives from experiments where subjects view 2D displays on computer monitors. In the natural world, however, search involves movement of the body in large-scale spatial contexts, and it is unclear how this might affect search strategies. In this experiment, we explore the nature of memory representations developed when searching in an immersive virtual environment. By manipulating target location, we demonstrate that search depends on episodic spatial memory as well as learnt spatial priors. Subjects rapidly learned the large-scale structure of the space, with shorter paths and less head rotation to find targets. These results suggest that spatial memory of the global structure allows a search strategy that involves efficient attention allocation based on the relevance of scene regions. Thus spatial memory may allow less energetically costly search strategies.


Image segmentation with directed trees.
This correspondence presents a simple algorithm to detect and label homogeneous areas in an image, using directed trees for region labeling. The scheme constructs directed trees with the image points as nodes, guided by an edge value computed at every point. These directed trees segment the image into disjoint regions. Because of a valley seeldng property of the tree construction procedure, the boundaries separating the resultant segments pass through the center of the edges. The algorithm thus performs wel1 with thick and wide edges of varying height, because no thresholding of the edge image is involved. The properties of the resultant segments are stated in terms of the edge image. The algorithm is shown to be simple, efficient, and effective for detecting homogeneous segments in the presence of noise. Results of application in the algorithm to segment a LANDSAT multispectral scene of an agricultural area are included.


Using the 'protective environment' framework to analyse children's protection needs in Darfur.
A major humanitarian concern during the continuing crisis in Darfur, Sudan, has been the protection of children, although there has been little in the way of comprehensive analysis to guide intervention. Founded on a situational analysis conducted between October 2005 and March 2006, this paper documents the significant threats to children's well-being directly linked to the political conflict. It demonstrates the role of non-conflict factors in exacerbating these dangers and in promoting additional protection violations, and it uses the 'protective environment' framework (UNICEF Sudan, 2006a) to identify systematic features of the current environment that put children at risk. This framework is shown to provide a coherent basis for assessment and planning, prompting broad, multidisciplinary analysis, concentrating on preventive and protective action, and fostering a systemic approach (rather than placing an undue focus on the discrete needs of 'vulnerable groups'). Constraints on its present utility in emergency settings are also noted.


Two variable active site residues modulate response regulator phosphoryl group stability.
Many signal transduction networks control their output by switching regulatory elements on or off. To synchronize biological response with environmental stimulus, switching kinetics must be faster than changes in input. Two-component regulatory systems (used for signal transduction by bacteria, archaea and eukaryotes) switch via phosphorylation or dephosphorylation of the receiver domain in response regulator proteins. Although receiver domains share conserved active site residues and similar three-dimensional structures, rates of self-catalysed dephosphorylation span a >or= 40,000-fold range in response regulators that control diverse biological processes. For example, autodephosphorylation of the chemotaxis response regulator CheY is 640-fold faster than Spo0F, which controls sporulation. Here we demonstrate that substitutions at two variable active site positions decreased CheY autodephosphorylation up to 40-fold and increased the Spo0F rate up to 110-fold. Particular amino acids had qualitatively similar effects in different response regulators. However, mutant proteins matched to other response regulators at the two key variable positions did not always exhibit similar autodephosphorylation kinetics. Therefore, unknown factors also influence absolute rates. Understanding the effects that particular active site amino acid compositions have on autodephosphorylation rate may allow manipulation of phosphoryl group stability for useful purposes, as well as prediction of signal transduction kinetics from amino acid sequence.


Copper-Catalyzed Regio- and Enantioselective Hydroboration of Difluoroalkyl-Substituted Internal Alkenes.
Catalytic asymmetric hydroboration of fluoroalkyl-substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl-substituted alkenes without fluorine elimination has been a long-standing challenge in this field. Herein, a copper-catalyzed hydroboration of difluoroalkyl-substituted internal alkenes with high levels of regio- and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom-economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated.


Placing marine protected areas onto the ecosystem-based management seascape.
The rapid increase in the science and implementation of marine protected areas (MPAs) around the world in the past 15 years is now being followed by similar increases in the science and application of marine ecosystem-based management (EBM). Despite important overlaps and some common goals, these two approaches have remained either separated in the literature and in conservation and management efforts or treated as if they are one and the same. In the cases when connections are acknowledged, there is often little assessment of if or how well MPAs can achieve specific EBM goals. Here we start by critically evaluating commonalities and differences between MPAs and EBM. Next, we use global analyses to show where and how much no-take marine reserves can be expected to contribute to EBM goals, specifically by reducing the cumulative impacts of stressors on ocean ecosystems. These analyses revealed large stretches of coastal oceans where reserves can play a major role in reducing cumulative impacts and thus improving overall ocean condition, at the same time highlighting the limitations of marine reserves as a single tool to achieve comprehensive EBM. Ultimately, better synergies between these two burgeoning approaches provide opportunities to greatly benefit ocean health.


Glioblastoma-derived cells in vitro unveil the spectrum of drug resistance capability - comparative study of tumour chemosensitivity in different culture systems.
Resistance to cancer drugs is a complex phenomenon which could be influenced by in vitro conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three in vitro models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture.The experimental models were evaluated according to 'stemness state' and epithelial-to-mesenchymal transition (EMT) status, invasion capability and their expression pattern of genes related to the phenomenon of tumour drug resistance. Additionally, the response to drug treatments of three different culture models was compared with regard to the type of cell death.Multi-gene expression profiling revealed differences between examined culture types with regard to the expression pattern of the selected genes. Functionally, the examined genes were related to drug resistance and metabolism, DNA damage and repair and cell cycle control, and included potential therapeutic targets.Cytotoxicity analyses confirmed that environmental factors can influence not only the molecular background of glioblastoma drug-resistance and efficiency of treatment, but also the mechanisms/pathways of cell death, which was reflected by a distinct intensification of apoptosis and autophagy observed in particular culture models. Our results suggest that parallel exploitation of different in vitro experimental models can be used to reveal the spectrum of cancer cell resistance capability, especially regarding intra-heterogeneous glioblastomas.


Mating system and intrapopulational genetic diversity of Copernicia prunifera (Arecaceae): a native palm from Brazilian semiarid.
The aim of this study was to investigate the mating system and genetic diversity of the palm Copernicia prunifera using inter-simple sequence repeat markers. We found that the C. prunifera has multiple inflorescences with hermaphroditic flowers and pollen viability of 62%. Outcrossing rates at the population level (N = 267) produced a multilocus outcrossing rate (tm) of 0.878 and a single-locus outcrossing rate (ts) of 0.738, indicating that C. prunifera has a mixed mating system that is preferentially allogamous. The rate of mating among relatives (tm - ts) was low, indicating limited outcrossing between closely related individuals. The fixation index between seed trees (F) was negative (0.200), suggesting an absence of inbreeding, while the correlation of selfing (rs) was high (0.914). The values of the diversity indices among adults and progenies did not differ statistically (HE = 0.319 and I = 0.470; HE = 0.337 and I = 0.505, respectively). In testing for the presence of genetic bottlenecks using the infinite allele model and the stepwise mutation model, we observed a reduction in the effective population, as well as a deficit in heterozygosity (P < 0.0001). The results of this study inform management strategies for the conservation and genetic improvement of the C. prunifera palm.


[Automated training system used for a course on eye diseases at a medical institute].
The authors have developed this system (AIS), realized via CM 1420 mini-computer for many-terminal regime. The program provides operation in both the instruction and control modes; the control is realized via a display, that permits individual dialogues of students with the computer. The dialogue involves 12-16 questions in the curriculum. The answers are estimated and remembered by the computer. When the operation in the control mode is over, a register with students' marks is printed out. Therefore, the suggested AIS promotes autotraining of the students in this course and rules out the subjective aspects in assessment of students' knowledge.


Extractable hydrocarbons and kin recognition in honeybee (Apis mellifera L.).
Hydrocarbons of worker honeybees of known pedigree were extracted and analyzed using gas chromatography and mass spectrometry. Variability in hydrocarbon extracts of individual workers is determined at least in part genetically. Correlations in hydrocarbon composition of extracts were highest among more closely related individuals. Individuals maintained in groups exchange hydrocarbons but still maintain enough self-produced compounds to retain genetically determined individual characteristics. These results demonstrate that extractable hydrocarbons of bees provide sufficiently reliable genetic information to function as labels for use during kin recognition.


A printer model using signal processing techniques.
An accurate printer model that is efficient enough to be used by halftoning algorithms is proposed. The proposed signal processing model (SPM) utilizes a physical model to train adaptive linear combiners (ALCs), after which the average exposure of each subpixel for any input pattern can be calculated using the optimized weight vector. The SPM can be used to model multi-level halftoning and resolution enhancement, as well as traditional halftoning. The SPM is comprised of a single ALC layer followed by a peak-to-average ratio (PAR) correction layer, which serves to produce a PAR of less than 1.5 in the modeled exposure. The PCN (PAR correction network) employs one ALC/pixel and exploits the physics governing the characteristics of exposure in small regions. A relatively small number of training patterns suffices to train the SPM.


Correlation between mutations in liaFSR of Enterococcus faecium and MIC of daptomycin: revisiting daptomycin breakpoints.
Mutations in liaFSR, a three-component regulatory system controlling cell-envelope stress response, were recently linked with the emergence of daptomycin (DAP) resistance in enterococci. Our previous work showed that a liaF mutation increased the DAP MIC of a vancomycin-resistant Enterococcus faecalis strain from 1 to 3 μg/ml (the DAP breakpoint is 4 μg/ml), suggesting that mutations in the liaFSR system could be a pivotal initial event in the development of DAP resistance. With the hypothesis that clinical enterococcal isolates with DAP MICs between 3 and 4 μg/ml might harbor mutations in liaFSR, we studied 38 Enterococcus faecium bloodstream isolates, of which 8 had DAP MICs between 3 and 4 μg/ml by Etest in Mueller-Hinton agar. Interestingly, 6 of these 8 isolates had predicted amino acid changes in the LiaFSR system. Moreover, we previously showed that among 6 DAP-resistant E. faecium isolates (MICs of >4 μg/ml), 5 had mutations in liaFSR. In contrast, none of 16 E. faecium isolates with a DAP MIC of ≤2 μg/ml harbored mutations in this system (P < 0.0001). All but one isolate with liaFSR changes exhibited DAP MICs of ≥16 μg/ml by Etest using brain heart infusion agar (BHIA), a medium that better supports enterococcal growth. Our findings provide a strong association between DAP MICs within the upper susceptibility range and mutations in the liaFSR system. Concomitant susceptibility testing on BHIA may be useful for identifying these E. faecium first-step mutants. Our results also suggest that the current DAP breakpoint for E. faecium may need to be reevaluated.


Metal Oxide Nanosheets as 2D Building Blocks for the Design of Novel Materials.
Research into 2-dimensional materials has soared during the last couple of years. Next to van der Waals type 2D materials such as graphene and h-BN, less well-known oxidic 2D equivalents also exist. Most 2D oxide nanosheets are derived from layered metal oxide phases, although few 2D oxide phases can be also made by bottom-up solution syntheses. Owing to the strong electrostatic interactions within layered metal oxide crystals, a chemical process is usually needed to delaminate them into their 2D constituents. This Review article provides an overview of the synthesis of oxide nanosheets, and methods to assemble them into nanocomposites, mono- or multilayer films. In particular, the use of Langmuir-Blodgett methods to form monolayer films over large surface areas, and the emerging use of ink jet printing to form patterned functional films is emphasized. The utilization of nanosheets in various areas of technology, for example, electronics, energy storage and tribology, is illustrated, with special focus on their use as seed layers for epitaxial growth of thin films, and as electrochemically active electrodes for supercapacitors and Li ion batteries.


Quantitative systems pharmacology model for Alzheimer's disease to predict the effect of aducanumab on brain amyloid.
Alzheimer's disease (AD) is an irreversible, progressive brain disorder that impairs memory and cognitive function. Dysregulation of the amyloid-β (Aβ) pathway and amyloid plaque accumulation in the brain are hallmarks of AD. Aducanumab is a human, immunoglobulin gamma 1 monoclonal antibody targeting aggregated forms of Aβ. In phase Ib and phase III studies, aducanumab reduced Aβ plaques in a dose dependent manner, as measured by standard uptake value ratio of amyloid positron emission tomography imaging. The goal of this work was to develop a quantitative systems pharmacology model describing the production, aggregation, clearance, and transport of Aβ as well as the mechanism of action for the drug to understand the relationship between aducanumab dosing regimens and changes of different Aβ species, particularly plaques in the brain. The model was used to better understand the pharmacodynamic effects observed in the clinical trials of aducanumab and assist in the clinical development of future Aβ therapies.


Dietary habits among snus users: a population-based cross-sectional study.
The dietary habits among snus users are largely unknown and have not been accounted for in observational studies on the health effects of snus use. To examine whether snus users eat unhealthier than never tobacco users. A total of 3,397 male participants, examined between 1994 and 2014 in the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, were included. Snus use and dietary habits were self-reported using questionnaires, from which intakes of different food groups, macronutrients, and a healthy diet score (HDS) were calculated (the latter as a proxy for overall diet quality). The association between snus use and dietary habits was examined by quantile regression models. In the multivariable-adjusted model, current snus users had a lower HDS (median difference: -0.86 [95% confidence interval: -1.32, -0.40]) than never tobacco users. Snus users also consumed fewer weekly servings of fruits and berries (median difference: -1.03 [-1.65, -0.40]), and their estimated percentage of energy intake consisted of less carbohydrates (median difference: -1.43 [-2.12, -0.74]) and of more total fat (median difference: 0.99 [0.30, 1.67]), saturated fat (median difference: 0.67 [0.29, 1.05]), monounsaturated fat (median difference: 0.44 [0.20, 0.68]), trans fat (median difference: 0.03 [0.01, 0.06]), and alcohol (median difference: 0.21 [0.02, 0.40]). We observed that snus users had an unhealthier diet than never tobacco users. Future studies on the association between snus use and health outcomes should, therefore, consider diet as a potential confounder.


The role of LEF/TCF factors in neoplastic transformation.
The T cell factor 4 (Tcf-4) interacts with beta-catenin in the Wnt signalling pathway and coactivates downstream target genes in diverse systems including the breast. This activity is important during normal development but its deregulation plays a pivotal role in cancer progression. In a rat model for breast cancer it has been shown that metastasis-inducing DNA (Met-DNA) sequesters the endogenous inhibitory Tcf-4 and thereby promotes transcription of the secreted extracellular matrix glycophosphoprotein, osteopontin, the direct effector of metastasis in this model system. Permanent transfection of the benign rat mammary cell line with a fragment from the Met-DNA containing the Tcf recognition sequence CAAAG induces the cells to metastasize in syngeneic rats in vivo. Tcf-4 expression in human breast carcinomas is inversely associated with osteopontin protein levels. High Tcf-4 expression impedes both OPN promoter activity and protein expression in rat mammary carcinoma cells. Understanding the role of Tcf-4 in cancer development and its transcription regulation should lay the foundation for novel therapeutic approaches in the future.


Principle or pathology? Adjudicating the right to conscience in the Israeli military.
The Israeli military's Conscience Committee evaluates and exempts pacifists from obligatory military service, based explicitly on concern for liberal tolerance. However, I found that liberal pacifist applicants' principled objections to violence challenged the state, and as such, applicants who articulated their refusal in such terms are rejected by the military review board. By contrast, pacifist conscientious objection based in embodied visceral revulsion to violence did not challenge the state and moral order, and such cases were granted exemption. Objections based in understanding pacifism as a physical incapacity depoliticizes it by making it incommensurable with public moral debate concerning military service. The pathologization of pacifism demonstrates a contradiction between liberalism's ideology and its practices, revealing that the limits of liberalism are not only exterior, in nonliberal alterity, but also on liberalism's own interior frontiers.


Association between coronary microvascular function and the vasa vasorum in patients with early coronary artery disease.
The vasa vasorum (VV) plays a role in the initial phase of atherosclerosis, and abnormalities in microvascular function may be sensitive measures of the early development of atherosclerosis. The current study was designed to access the association between coronary microvascular function and VV density in patients undergoing cardiac catheterization. Twenty-four patients with early coronary artery disease underwent endothelium-dependent (coronary blood flow, CBF) and endothelium-independent (coronary flow velocity reserve, CFVR) coronary microvascular function testing, and optical coherence tomography (OCT) imaging of the left anterior descending coronary artery (LAD). Using an intracoronary Doppler guidewire, CBF was examined by evaluating changes in blood flow in response to acetylcholine and CFVR in response to adenosine. VV density (VV volume/vessel volume × 100, %VV) of the proximal 10 mm of the LAD was quantified by OCT. The median values (Q1, Q3) of CFVR, % changes in CBF in response to acetylcholine, and the %VV were 2.70 (2.30, 2.90), -16.82 (-42.34, 54.52), and 2.62 (2.35, 3.35), respectively. %VV correlated inversely with CBF (r = -0.614, p = 0.001) and directly with CFVR (r = 0.423, p = 0.040). Multivariate analysis showed that only %VV was significantly correlated with CBF and the association was independent of other clinical variables, Framingham risk score, body mass index, and a family history of coronary heart disease. This study demonstrates that VV density has negative correlation with endothelium-dependent microvascular function in patients with early coronary atherosclerosis. These observations link adventitial VV structure and function to microvascular dysfunction in early coronary atherosclerosis.


[Structure-physiological activity correlation for picolinic acid derivatives based on quantum chemical data].
Correlation between structure and properties for picolinic acid derivatives with and without bimodal effect was evaluated by quantum chemical calculations. Comparative data obtained by SCF MO method in the 3-21G/6-31G* basis indicate lower ionization potential in picolinic acid derivatives with bimodal effect as compared to those lacking this effect. This validates our previous assumption that physiological bimodal effect is defined by the electron structure of the molecules. Quantum chemical calculations allowed us to predict bimodal physiological activity in amino-substituted derivatives of picolinic acid.


Sexually transmitted infections and sexual behaviour among commercial sex workers in a rural district of Malawi.
In Thyolo District, Malawi, a study was conducted among commercial sex workers (CSWs) attending mobile clinics in order to; determine the prevalence and pattern of sexually transmitted infections (STIs), describe sexual behaviour among those who have an STI and identify risk factors associated with 'no condom use'. There were 1817 CSWs, of whom 448 (25%) had an STI. Of these, the commonest infections included 237 (53%) cases of abnormal vaginal discharge, 109 (24%) cases of pelvic inflammatory disease and 95 (21%) cases of genital ulcer disease (GUD). Eighty-seven per cent had sex while symptomatic, 17% without condoms. Having unprotected sex was associated with being married, being involved with commercial sex outside a known rest-house or bar, having a GUD, having fewer than two clients/day, alcohol intake and having had no prior medication for STI. The high levels of STIs, particularly GUDs, and unprotected sex underlines the importance of developing targeted interventions for CSWs and their clients.


Protective and therapeutic effects of an extract mixture of alder tree, labiate herb, milk thistle green bean-rice bran fermentation, and turnip against ethanol-induced toxicity in the rat.
An herbal extract mixture and yogurt added to the herbal extract mixture were tested for their protective and therapeutic effects on ethanol-induced liver injury. The herbal extract mixture, yogurt and commercial drugs were used for treatment for two weeks prior to administering a single oral dose of ethanol (3 g/kg body weight). The herbal extract mixture and yogurt added to the herbal extract mixture were found to provide protection against ethanol-induced toxicity comparable to the commercial drug treatment, according to the serum and histopathological analysis. It was also shown that co-treatment with herbal extract mixture and yogurt against a triple oral dose of ethanol (2 g/kg body weight, over one week) provided protection against ethanol toxicity. After the initial set of experiments, the herbal extract mixture and yogurt treatments were extended for three more weeks. When compared to the positive control, further treatment with both the herbal extract and yogurt significantly reduced liver injury and resulted in a lower grade of lipid deposition.


Destabilization, Propagation, and Generation of Surfactant-Stabilized Foam during Crude Oil Displacement in Heterogeneous Model Porous Media.
Foam flooding in porous media is of increasing interest due to its numerous applications such as enhanced oil recovery, aquifer remediation, and hydraulic fracturing. However, the mechanisms of oil-foam interactions have yet to be fully understood at the pore level. Here, we present three characteristic zones identified in experiments involving the displacement of crude oil from model porous media via surfactant-stabilized foam, and we describe a series of pore-level dynamics in these zones which were not observed in experiments involving paraffin oil. In the displacement front zone, foam coalesces upon initial contact with crude oil, which is known to destabilize the liquid lamellae of the foam. Directly upstream, a transition zone occurs where surface wettability is altered from oil-wet to water-wet. After this transition takes place, a strong foam bank zone exists where foam is generated within the porous media. We visualized each zone using a microfluidic platform, and we discuss the unique physicochemical phenomena that define each zone. In our analysis, we also provide an updated mechanistic understanding of the "smart rheology" of foam which builds upon simple "phase separation" observations in the literature.


Topographical changes of biconvex objects during equatorial traction: an analogy for accommodation of the human lens.
To assess and compare the changes in shape of encapsulated biconvex structures undergoing equatorial traction with those changes reported in the human lens during accommodation. Equatorial traction was applied to several different biconvex structures: air, water, and gel filled mylar and rubber balloons and spherical vesicles. In the vesicles, traction was applied externally, using optical tweezers, or from within, by the assembly of encapsulated microtubules. The shape changes were recorded photographically and the change in central radius of curvature of water filled mylar balloons was quantified. Whenever an outward equatorial force was applied to the long axis of long oval biconvex objects, where the minor to major axis ratio was </=0.6, the central surfaces steepened and the peripheral surfaces flattened. Similar changes in the shape of the lens have been reported during human in vivo accommodation. All biconvex structures that have been studied demonstrate similar shape changes in response to equatorial traction. This effect is independent of capsular thickness. The consistent observation of this physical change in the configuration of biconvex structures in response to outward equatorial force suggests that this may be a universal response of biconvex structures, also applicable to the human lens undergoing accommodation.


Kinship promotes affiliative behaviors in a monkey.
In social mammals, kinship is an important factor that often affects the interactions among individuals within groups. In primates that live in a multilevel society, kinship may affect affiliative patterns between individuals at different scales within the larger group. For this study, we use field observations and molecular methods to reveal the profiles of how kinship affects affiliative behaviors between individuals in a breeding band of wild golden snub-nosed monkeys (Rhinopithecus roxellana). We use a novel nonparametric test, the partition Mantel test, to measure independently the correlation between kinship and each of three affiliative behaviors. Our results show that more closely related females are more likely to groom each other. Average relatedness between adult females within the same one-male unit (OMU) is higher than that between adult females from different OMUs. We suggest that closely related females may reside in the same OMU in order to attain inclusive fitness benefits, and that kinship plays an important role in maintaining the social structure of this species.


Detrimental effects of papaverine on the human internal thoracic artery.
We sought to determine the effects of papaverine on human and canine internal thoracic artery function and structure. Vascular function was assessed with wire myography, and apoptosis was examined with confocal microscopy in arteries stained with ApopTag. Acetylcholine-induced endothelium-dependent relaxation in phenylephrine-precontracted arteries was significantly impaired by papaverine treatment in both human and canine internal thoracic arteries (maximal relaxation: 68.35% +/- 7.13% vs 47.5% +/- 9.32% in human arteries and 74.8% +/- 5.5% vs 34.3% +/- 8.5% in canine arteries) but not by incubation with acidified saline solution (pH 3.9, which is equivalent to the pH of 10(-2) mol/L papaverine solution) in canine internal thoracic arteries. Contraction of human internal thoracic arteries to phenylephrine or to U46619 was not significantly affected by papaverine treatment and neither was the contraction of canine internal thoracic arteries to phenylephrine. Total apoptotic endothelial and smooth muscle cells were significantly greater in papaverine-treated human and canine internal thoracic arteries. Papaverine impairs endothelial function and triggers apoptosis of endothelial and smooth muscle cells of human and canine internal thoracic arteries. The long-term consequence of this impairment on vascular function is not known. Until this question is answered, it will be prudent to use other vasodilators that are less damaging to the internal thoracic artery for cardiac surgery.


Association of Glycemic Variability in Type 1 Diabetes With Progression of Microvascular Outcomes in the Diabetes Control and Complications Trial.
The Diabetes Control and Complications Trial (DCCT) demonstrated the beneficial effects of intensive versus conventional therapy on the development and progression of microvascular complications of type 1 diabetes. These beneficial effects were almost completely explained by the difference between groups in the levels of HbA1c, which in turn were associated with the risk of these complications. We assessed the association of glucose variability within and between quarterly 7-point glucose profiles with the development and progression of retinopathy, nephropathy, and cardiovascular autonomic neuropathy during the DCCT. Measures of variability included the within-day and updated mean (over time) of the SD, mean amplitude of glycemic excursions (MAGE), and M-value, and the longitudinal within-day, between-day, and total variances. Imputation methods filled in the 16.3% of expected glucose values that were missing. Cox proportional hazards models assessed the association of each measure of glycemic variation, as a time-dependent covariate, with the risk of retinopathy and nephropathy, and a longitudinal logistic regression model did likewise for cardiovascular autonomic neuropathy. Adjusted for mean blood glucose, no measure of within-day variability was associated with any outcome. Only the longitudinal mean M-value (over time) was significantly associated with microalbuminuria when adjusted for the longitudinal mean blood glucose and corrected for multiple tests using the Holm procedure. Overall, within-day glycemic variability, as determined from quarterly glucose profiles, does not play an apparent role in the development of microvascular complications beyond the influence of the mean glucose.


[Characterization and differentiation of fluorescent pseudemonads by substrate utilization studies].
A rapid procedure is described for detecting and differentiating pseudomonads by their ability to degrade substrates with diverse physico-chemical properties, including volatile and non-volatile water-insoluble compounds, strong organic acids and bases, surfactants, disinfectants, and other toxic substances. The bacteria are embedded in an agar medium containing mineral salts and exposed to about 5 mg amounts of six to eight different substrates placed on the surface of an agar plate. After incubation at 25 degrees C for 24 hrs, growth zones around utilizable substrates may be used to differentiate various Pseudomonas strains and species.


A large study on immunological response to a whole-cell killed oral cholera vaccine reveals that there are significant geographical differences in response and that O blood group individuals do not elicit a higher response.
The ABO blood group system has been implicated in susceptibility to cholera or in explaining variability in the immune response to a cholera vaccine. O blood group individuals were found to be more susceptible to cholera and elicited lower vibriocidal antibody response to cholera toxin B subunit-killed oral vaccine. Based on the observations that O blood group individuals were more susceptible to cholera and that high mortality was associated with cholera, an evolutionary explanation was provided for the extremely low prevalence of the O blood group in the Gangetic Delta (West Bengal, India, and Bangladesh). However, conflicting results were reported from a later study conducted in Indonesia using a live attenuated oral cholera vaccine; O blood group individuals showed a higher vibriocidal antibody response. In a study conducted in a region of India where cholera is endemic (Kolkata, West Bengal) that comprised 992 individuals vaccinated by a killed whole-cell oral cholera vaccine, we found no statistically significant difference between O and non-O individuals either in the frequency distributions of the fold increase or in the postvaccination increase in geometric mean titer compared to the baseline. Further, in contrast to the earlier observation that the O allele frequency is extremely low in the Gangetic Delta, we have noted that the O allele frequency exceeds 0.5 in the vast majority of ethnic groups of this region. In addition, we have found large differences in response to the vaccine among residents of an area where cholera is not endemic compared to an area where cholera is endemic to The percentages of vaccinees who seroconverted in an area where cholera is not endemic (Son La province of Vietnam) was >90% compared to approximately 50% in Kolkata, India, an area where cholera is endemic.


miR-34a regulates mouse neural stem cell differentiation.
MicroRNAs (miRNAs or miRs) participate in the regulation of several biological processes, including cell differentiation. Recently, miR-34a has been implicated in the differentiation of monocyte-derived dendritic cells, human erythroleukemia cells, and mouse embryonic stem cells. In addition, members of the miR-34 family have been identified as direct p53 targets. However, the function of miR-34a in the control of the differentiation program of specific neural cell types remains largely unknown. Here, we investigated the role of miR-34a in regulating mouse neural stem (NS) cell differentiation. miR-34a overexpression increased postmitotic neurons and neurite elongation of mouse NS cells, whereas anti-miR-34a had the opposite effect. SIRT1 was identified as a target of miR-34a, which may mediate the effect of miR-34a on neurite elongation. In addition, acetylation of p53 (Lys 379) and p53-DNA binding activity were increased and cell death unchanged after miR-34a overexpression, thus reinforcing the role of p53 during neural differentiation. Interestingly, in conditions where SIRT1 was activated by pharmacologic treatment with resveratrol, miR-34a promoted astrocytic differentiation, through a SIRT1-independent mechanism. Our results provide new insight into the molecular mechanisms by which miR-34a modulates neural differentiation, suggesting that miR-34a is required for proper neuronal differentiation, in part, by targeting SIRT1 and modulating p53 activity.


The ciliary membrane.
Cilia and flagella are important organizing centers for signaling in both development and disease. A key to their function is a poorly characterized barrier at their base that allows the protein and lipid composition of the ciliary membrane to be distinct from that of the plasma membrane. We review current models of ciliary membrane biogenesis, highlighting several structures, including the ciliary necklace and ciliary pocket, that appear during biogenesis and that likely contribute to the barrier. The regulated movement of membrane proteins and lipids across this barrier is central to the sensory function of these organelles.


Association of NPO Status and Type of Nutritional Support on Weight and Length of Stay in Infants Hospitalized With Bronchiolitis.
We investigated the association of nil per os (NPO) status and subsequent nutritional support with patient weight and length of stay (LOS) during admission for bronchiolitis in patients <2 years old. A retrospective chart review was performed of all patients <2 years old admitted to an academic pediatric hospital between November 2009 and June 2011 with a Current Procedural Terminology code of bronchiolitis. Data extracted from the medical record included respiratory rate, per os/NPO status, use of intravenous fluids, use of enteral tube feedings, weight, and LOS. Patients who did not have 2 weights recorded were excluded. The major outcome measures were weight change during admission and LOS. The study included 149 patients. The mean ± SD patient age was 3.7 ± 3.8 months, with a median age of 2 months. The median length of stay was 4 days (interquartile range: 3-6). Overall, 16% of patients were made NPO, 75% received intravenous fluids, and 9% received enteral tube feedings. The mean weight loss for all patients was 38 (289) g during the hospitalization, which was not statistically significant. No significant association was found between weight loss and LOS, per os/NPO status, or use of intravenous fluids. However, NPO status was associated with a significant increase in LOS. The infants admitted for bronchiolitis did not demonstrate weight loss in this study; however, an association was seen between NPO status and prolonged LOS.


Are online symptoms checkers useful for patients with inflammatory arthritis?
Online symptom checkers are increasingly used by patients however there is little published evidence of their effectiveness in real patients. The aim of this study was to evaluate how patients with inflammatory arthritis and inflammatory arthralgia use the internet to look for health information and to assess the advice given and diagnoses suggested by the NHS and WebMD symptom checkers in relation to the patients' actual diagnoses. Thirty-four patients with inflammatory arthritis (rheumatoid arthritis (n = 13), psoriatic arthritis (n = 4), unclassified arthritis (n = 4)) and inflammatory arthralgia (n = 13) newly presenting to a secondary care based clinic were identified using a consecutive sampling approach. Consenting patients were asked questions about their internet use in relation to their presenting symptoms. They then completed the NHS and the WebMD symptom checkers and their answers and the outcomes were recorded. Sixteen patients had previously consulted the internet regarding their symptoms. Neither age nor gender significantly influenced internet usage. Actions advised via the NHS symptom checker were: call an ambulance (n = 11), attend A&E (n = 4), contact your GP straight away (n = 2), see your GP today (n = 6), or see your GP within 36 h (n = 11). The 5 most common differential diagnoses given by Web MD were gout (n = 28), rheumatoid arthritis (n = 24), psoriatic arthritis (n = 22), osteoarthritis (n = 18) and finger dislocation (n = 10). The most common first differential diagnosis was osteoarthritis (n = 12). Only 4 out of 21 patients with inflammatory arthritis were given a first diagnosis of rheumatoid arthritis or psoriatic arthritis. Our data highlight that help seeking advice given online is often inappropriate and that the diagnoses suggested are frequently inaccurate. Recommendations to seek emergency advice may cause inappropriate healthcare utilization.


Transport modes and pathways of the strongly sorbing pesticides glyphosate and pendimethalin through structured drained soils.
Leaching of the strongly sorbing pesticides glyphosate and pendimethalin was evaluated in an 8-month field study focussing on preferential flow and particle-facilitated transport, both of which may enhance the leaching of such pesticides in structured soils. Glyphosate mainly sorbs to mineral sorption sites, while pendimethalin mainly sorbs to organic sorption sites. The two pesticides were applied in equal dosage to a structured, tile-drained soil, and the concentration of the pesticides was then measured in drainage water sampled flow-proportionally. The leaching pattern of glyphosate resembled that of pendimethalin, suggesting that the leaching potential of pesticides sorbed to either the inorganic or organic soil fractions is high in structured soils. Both glyphosate and pendimethalin leached from the root zone, with the average concentration in the drainage water being 3.5 and 2.7 μg L(-1), respectively. Particle-facilitated transport (particles >0.24 μm) accounted for only a small proportion of the observed leaching (13-16% for glyphosate and 16-31% for pendimethalin). Drain-connected macropores located above or in the vicinity of the drains facilitated very rapid transport of pesticide to the drains. That the concentration of glyphosate and pendimethalin in the drainage water remained high (>0.1 μg L(-1)) for up to 7d after a precipitation event indicates that macropores between the drains connected to underlying fractures were able to transport strongly sorbing pesticides in the dissolved phase. Lateral transport of dissolved pesticide via such discontinuities implies that strongly sorbing pesticides such as glyphosate and pendimethalin could potentially be present in high concentrations (>0.1 μg L(-1)) in both water originating from the drainage system and the shallow groundwater located at the depth of the drainage system.


Few-Shot Learning Enables Population-Scale Analysis of Leaf Traits in Populus trichocarpa.
Plant phenotyping is typically a time-consuming and expensive endeavor, requiring large groups of researchers to meticulously measure biologically relevant plant traits, and is the main bottleneck in understanding plant adaptation and the genetic architecture underlying complex traits at population scale. In this work, we address these challenges by leveraging few-shot learning with convolutional neural networks to segment the leaf body and visible venation of 2,906 Populus trichocarpa leaf images obtained in the field. In contrast to previous methods, our approach (a) does not require experimental or image preprocessing, (b) uses the raw RGB images at full resolution, and (c) requires very few samples for training (e.g., just 8 images for vein segmentation). Traits relating to leaf morphology and vein topology are extracted from the resulting segmentations using traditional open-source image-processing tools, validated using real-world physical measurements, and used to conduct a genome-wide association study to identify genes controlling the traits. In this way, the current work is designed to provide the plant phenotyping community with (a) methods for fast and accurate image-based feature extraction that require minimal training data and (b) a new population-scale dataset, including 68 different leaf phenotypes, for domain scientists and machine learning researchers. All of the few-shot learning code, data, and results are made publicly available.


A new technique for the treatment of comminuted, transverse fractures of the patella.
In an attempt to re-establish continuity of the quadriceps mechanism following partial patellectomy more securely in patients with comminuted, transverse fractures of the patella, a technique whereby the patellar ligament is inserted into a transverse groove created in the proximal patellar fragment and this anastomosis is then protected by a tension band wiring, is described and depicted. Using this method, it is possible to provide a larger surface area fro more satisfactory tendon to bone healing and to initiate relatively early motion of the knee, without compromising the site of reconstitution of the extensor mechanism.


Luteolin inhibits Porphyromonas gingivalis growth and alleviates alveolar bone destruction in experimental murine periodontitis.
Periodontal disease is a major oral infectious disease that destroys alveolar bones and causes tooth loss. Porphyromonas gingivalis is a key pathogen that plays a crucial role in periodontitis. In our previous study on the anti-P. gingivalis activity of flavonoid, luteolin, a major flavonoid in edible plants, inhibited the proteolytic activity of gingipains, the major virulence factor in P. gingivalis. This study demonstrated luteolin in vitro and in vivo anti-bacterial activities. Thus, luteolin inhibits planktonic growth and biofilm formation in P. gingivalis. Furthermore, oral administration of luteolin alleviated maxillary alveolar bone resorption in murine periodontitis induced by P. gingivalis infection. These results indicate that luteolin may be a potential therapeutic compound that targets P. gingivalis by hindering its growth, biofilm formation, and alveolar bone resorption in the oral cavity.


Electrophysiological Measure of Impaired Information Processing in Drivers with Hematological Malignancy.
The broad goal of this study is to measure remote effects of cancer on brain physiology and behaviors that underpin instrumental activities of daily living such as automobile driving. Studies of hematological malignancies (HM) have demonstrated impairments in multiple brain functions shown to be critical for safe automobile driving. In the current pilot study, brain physiology during driving simulation was examined in 14 HM patients and 13 healthy comparison drivers. Electroencephalography was used to measure the eye fixation-related potential (EFRP)-a positive amplitude deflection evoked approximately 100 milliseconds after eye movement termination. Previous studies have demonstrated sensitivity of EFRP activity to information-processing capacity. All drivers completed visual search tasks to evaluate the relationship between driving-related changes in performance and EFRP activity. Results showed smaller EFRP amplitudes in drivers who had: (1) greater driving-related changes in visual search performance (p = 0.03, Cohen's d = 0.91); and (2) HM diagnosis (p = 0.18, Cohen's d = 0.54). Extending previous studies, these results provide neural evidence of reduced information-processing capacity associated with cancer diagnosis. Future large-scale studies are needed to confirm these results, given the high level of uncertainty and small sample size. This study provides a novel platform for linking changes in brain physiology and safety-critical driving behaviors.


The extra-membranous domains of the competence protein HofQ show DNA binding, flexibility and a shared fold with type I KH domains.
Secretins form large oligomeric assemblies in the membrane that control both macromolecular secretion and uptake. Several Pasteurellaceae are naturally competent for transformation, but the mechanism for DNA assimilation is largely unknown. In Haemophilus influenzae, the secretin ComE has been demonstrated to be essential for DNA uptake. In closely related Aggregatibacter actinomycetemcomitans, an opportunistic pathogen in periodontitis, the ComE homolog HofQ is believed to be the outer membrane DNA translocase. Here, we report the structure of the extra-membranous domains of HofQ at 2.3 Å resolution by X-ray crystallography. We also show that the extra-membranous domains of HofQ are capable of DNA binding. The structure reveals two secretin-like folds, the first of which is formed by means of a domain swap. The second domain displays extensive structural similarity to K homology (KH) domains, including the presence of a GxxG motif, which is essential for the nucleotide-binding function of KH domains, suggesting a possible mechanism for DNA binding by HofQ. The data indicate a direct involvement in DNA acquisition and provide insight into the molecular basis for natural competence.


Chrysin Effect in Prevention of Acetaminophen-Induced Hepatotoxicity in Rat.
Acetaminophen is a commonly used analgesic drug that induces hepatotoxicity at high doses and produces the acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) through oxidase isoenzyme system. The antioxidant and anti-inflammatory activity of flavonoid chrysin has been reported in different studies. The present study was conducted to investigate the protective effect of chrysin on acute acetaminophen-induced hepatotoxicity. The cytotoxicity of chrysin on fibroblast cells was evaluated using MTT assay, and then, 54 rats were divided into nine groups of six, and acetaminophen (1500 mg/kg) was administered in all groups except for the control group, second and the seventh groups (40 mg/kg), and all groups were treated with chrysin for 14 days. Liver enzymes, inflammatory factors TNF-α and IL-2, and total antioxidant activity were measured in serum while liver tissue was histopathologically examined. Based on the MTT assay results, 31.25, 62.5, 125, 250, and 500 μg/mL chrysin had no adverse effects on healthy fibroblast cells (P < 0.05). Chrysin decreased the level of liver enzymes (ALT, AST, and ALP), which were previously increased after the use of acetaminophen (p < 0.05). The hepatoprotective effect and total antioxidant capacity increased in a dose-dependent manner and the effect of the highest concentration of chrysin was equal to the effect of silymarin (P < 0.05). TNF-α in groups 4 to 6 decreased in a dose-dependent manner (P = 0.04), and chrysin did not show any significant reducing effect on IL-2 compared to silymarin. Chrysin prevents the necrosis and injury of acute acetaminophen-induced hepatotoxicity by decreasing liver enzymes and TNF-α and increasing total antioxidant capacity and protecting the liver tissue.


Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition.
Identification of genomic alterations defining ovarian carcinoma subtypes may aid the stratification of patients to receive targeted therapies. We characterized high-grade serous ovarian carcinoma (HGSC) for the association of amplified and overexpressed genes with clinical outcome using gene expression data from 499 HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2, ZFP36, and URI. The Australian Ovarian Cancer Study and The Cancer Genome Atlas datasets were also used to assess the correlation between gene expression, patient survival, and tumor classification. In a multivariate analysis, high GAB2 expression was associated with improved overall and progression-free survival (P = 0.03 and 0.02), whereas high BMP8B and ATP13A4 were associated with improved progression-free survival (P = 0.004 and P = 0.02). GAB2 overexpression and copy number gain were enriched in the AOCS C4 subgroup. High GAB2 expression correlated with enhanced sensitivity in vitro to the dual PI3K/mTOR inhibitor PF-04691502 and could be used as a genomic marker for identifying patients who will respond to treatments inhibiting PI3K signaling.


Fungal endophyte diversity in Sarracenia.
Fungal endophytes were isolated from 4 species of the carnivorous pitcher plant genus Sarracenia: S. minor, S. oreophila, S. purpurea, and S. psittacina. Twelve taxa of fungi, 8 within the Ascomycota and 4 within the Basidiomycota, were identified based on PCR amplification and sequencing of the internal transcribed spacer sequences of nuclear ribosomal DNA (ITS rDNA) with taxonomic identity assigned using the NCBI nucleotide megablast search tool. Endophytes are known to produce a large number of metabolites, some of which may contribute to the protection and survival of the host. We speculate that endophyte-infected Sarracenia may benefit from their fungal associates by their influence on nutrient availability from within pitchers and, possibly, by directly influencing the biota within pitchers.


Programmed spatial organization of biomacromolecules into discrete, coacervate-based protocells.
The cell cytosol is crowded with high concentrations of many different biomacromolecules, which is difficult to mimic in bottom-up synthetic cell research and limits the functionality of existing protocellular platforms. There is thus a clear need for a general, biocompatible, and accessible tool to more accurately emulate this environment. Herein, we describe the development of a discrete, membrane-bound coacervate-based protocellular platform that utilizes the well-known binding motif between Ni2+-nitrilotriacetic acid and His-tagged proteins to exercise a high level of control over the loading of biologically relevant macromolecules. This platform can accrete proteins in a controlled, efficient, and benign manner, culminating in the enhancement of an encapsulated two-enzyme cascade and protease-mediated cargo secretion, highlighting the potency of this methodology. This versatile approach for programmed spatial organization of biologically relevant proteins expands the protocellular toolbox, and paves the way for the development of the next generation of complex yet well-regulated synthetic cells.


Predictors of narrative text quality in students with hearing loss.
Students with hearing loss (HL) often fall behind hearing peers in complex language tasks such as narrative writing. This study explored the effects of school grade, gender, cognitive and linguistic predisposition and audiological factors on narrative text quality in this target group. Eleven students with HL in Grades 5-6 and 7-8 (age 12-15) who took part in a writing intervention wrote four narrative texts over six months. A trained panel rated text quality. The effects of the students' working memory capacity, language comprehension, reading comprehension, school grade and gender and the intervention were analyzed as a mixed-effects regression model. Audiological factors were considered separately. The analysis showed that throughout the period, texts written by female students in Grade 7-8 received the highest text quality ratings, while those written by male students in Grade 7-8 received the lowest ratings. There was no effect of the intervention, or of the linguistic and cognitive measures. The students with the lowest text quality ratings received amplification later than those with high ratings, but HL severity was not associated with text quality. Hearing loss severity was not a decisive factor in narrative text quality. The intervention which the students took part in is potentially effective, with some adaptation to the special needs of students with HL. The strong gender effects are discussed.


Differences in denaturation of genetic variants of soy glycinin.
In heat denaturation studies conducted in the past the genetic variants of glycinin have been considered as a homogeneous group of proteins. In this work the validity of this assumption was tested. It was found by calorimetric studies that glycinin denatures heterogeneously at pH 7.6. When the temperature of isothermal treatment is increased from 70 to 82 degrees C the proportion of glycinin remaining native progressively decreases from 95% to 5% while the denaturation temperature of the glycinin remaining native increases from 88.5 to 95 degrees C. Similar trends were found for pH 3.8. Fractionation and subsequent analysis (MALDI-TOF and CE) of isothermally treated samples demonstrated that at pH 7.6 the heterogeneous denaturation is caused by differences in thermal stability of the genetic variants of glycinin. The stability increases in the order G2/G3/G1< A(4)< G5 < G4.


Expression of 5'-nucleotidase (CD73) related to other differentiation antigens in leukemias of B-cell lineage.
Ecto-5'nucleotidase (5'NT; CD73) expression was studied with a monoclonal antibody (7G2) and a radiochemical assay and compared with the expression of other antigens in B-cell-lineage leukemias on cells from 100 leukemic patients and two cell lines. A B-cell origin was confirmed by the expression of CD19 and HLA-DR. Four stages of B-cell leukemias were defined: stage I (pro-B) as CD10-, cytoplasmic mu- (c mu-), surface Ig- (sIg-); stage II (cALL) as CD10+/c mu-/sIg-; stage III (pre-B) as CD10+ or -/c mu+/sIg-; and stage IV (B) as CD10-/c mu-/sIg+. A linear correlation was found between immunohistochemical and radiochemical determination of 5'NT (r = .86). 5'NT expression was low in T-cell leukemias and stage I, high in stages II and III, and low again in stage IV of B-cell leukemias. 5'NT expression was not related to c mu, CD20, CD21, CD22, CD34, and terminal deoxynucleotidyl transferase (TdT) expression, but was significantly related to CD10 and inversely related to kappa/lambda expression. However, the 5'NT activity in CD10+ leukemias (stages II and III) shows a very wide range. Within the group of CD10+ leukemias no differences were detected between 5'NT+ and 5'NT- cells in their expression of other B-cell antigens. We conclude that the place of 5'NT in leukemias corresponding to early stages of B-cell development has been characterized. 5'NT is expressed in CD10+ stages and decreases before the expression of sIgs. Future studies should make clear whether a high expression of this enzyme in CD10+ stages is a normal maturation phenomenon or a malignant phenomenon.


Sleep functioning in relation to mood, function, and quality of life at entry to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).
Sleep disturbance in bipolar disorder can be both a risk factor and symptom of mood episodes. However, the associations among sleep and clinical characteristics, function, and quality of life in bipolar disorder have not been fully investigated. The prevalence of sleep disturbance, duration, and variability, as well as their associations with mood, function, and quality of life, was determined from 2024 bipolar patients enrolled in the National Institute of Mental Health Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Analyses indicated that 32% of patients were classified as short sleepers, 38% normal sleepers, and 23% long sleepers. Overall, short sleepers demonstrated greater mood elevation, earlier age at onset, and longer illness duration compared to both normal and long sleepers. Both short and long sleepers had greater depressive symptoms, poorer life functioning, and quality of life compared to normal sleepers. Short sleep duration in bipolar disorder was associated with a more severe symptom presentation, whereas both short and long sleep duration are associated with poorer function and quality of life compared to normal sleep duration. Sleep disturbance could be a trait marker of bipolar disorder, though longitudinal assessments are warranted to assess potential causal relations and the longer-term implications of sleep disturbance in bipolar disorder.


Functionally significant renal allograft rejection is defined by transcriptional criteria.
Renal allograft acute cellular rejection (ACR) is a T-cell mediated disease that is diagnosed histologically. However, many normally functioning allografts have T-cell infiltrates and histological ACR, and many nonimmune processes cause allograft dysfunction. Thus, neither histological nor functional criteria are sufficient to establish a significant rejection, and the fundamental features of clinical rejection remain undefined. To differentiate allograft lymphocyte infiltration from clinically significant ACR, we compared renal biopsies from patients with ACR to patients with: sub-clinical rejection (SCR, stable function with histological rejection); no rejection; and nontransplanted kidneys. Biopsies were compared histologically and transcriptionally by RT-PCR for 72 relevant immune function genes. Neither the degree nor the composition of the infiltrate defined ACR. However, transcripts up-regulated during effector T(H)1 T-cell activation, most significantly the transcription factor T-bet, the effector receptor Fas ligand and the costimulation molecule CD152 clearly (p = 0.001) distinguished the patient categories. Transcripts from other genes were equivalently elevated in SCR and ACR, indicating their association with infiltration, not dysfunction. Clinically significant ACR is not defined solely by the magnitude nor composition of the infiltrate, but rather by the transcriptional activity of the infiltrating cells. Quantitative analysis of selected gene transcripts may enhance the clinical assessment of allografts.


Tunable, omnidirectional, and nearly perfect resonant absorptions by a graphene-hBN-based hole array metamaterial.
In this paper, we propose an electrically tunable mid-infrared plasmonic-phononic absorber with omnidirectional and polarization insensitive nearly perfect resonant absorption characteristics. The absorber consists of a graphene/hexagonal boron nitride (hBN)/graphene multilayer on top of a gold bottom reflector separated by a dielectric spacer. The graphene/hBN/graphene multilayer is patterned as a hole array in square lattice. We analytically and numerically prove that, due to the support of hybrid plasmon-phonon-polaritons, nearly perfect multi-resonant absorption peaks with high quality factors are obtained both inside and outside of the Reststrahlen band of hBN. As a result of the hybridization of graphene plasmons with the hyperbolic phonon polaritons of hBN, the high quality resonant absorptions of the metamaterial are almost unaffected by decreasing the phenomenological electron relaxation time of graphene. Moreover, the obtained resonances can be effectively tuned in practice due to the continuity of the graphene layers in the hole array metamaterial. These features make the graphene-hBN metamaterial a skeptical design for practical purposes and mid-infrared multi-functional operations such as sensing.


Efficacy against lung metastasis with a tumor-targeting mutant of Salmonella typhimurium in immunocompetent mice.
Salmonella typhimurium double leu-arg auxotrophs have been shown to be highly effective as antitumor agents in nude mouse models of human metastatic cancer. In order to proceed to clinical development of the S. typhimurium double auxotroph, termed A1-R, it is necessary to evaluate antitumor efficacy in immunocompetent mice. In the present study, we have observed the efficacy of A1-R on the Lewis lung (LLC) carcinoma in vitro as well as in C57BL/6 (C57) immunocompetent mice. In vitro, A1-R treatment of LLC began to induce cell death within one hour. Various doses and schedules of A1-R were administered to C57 mice implanted with LLC, including bolus single intravenous injection; medium dose with weekly intravenous administration and metronomic treatment with small intravenous doses twice a week. Bolus treatment was toxic to the immunocompetent host, in contrast to nude mice. Lower-dose weekly doses and metronomic doses were well tolerated by the immunocompetent host. Weekly intravenous injection with 2 × 10(7) bacteria and twice a week intravenous injection with 10(7) bacteria significantly inhibited metastasis formation, while bolus injection was toxic. Intra-thoracic administration was carried out with 10(8) bacteria A1-R injected into Lewis lung-bearing C57 mice weekly for three weeks. Lung metastasis was significantly inhibited by intrathoracic bacterial administration, without toxicity. The results in this report, demonstrating the anti-metastatic efficacy of S. typhimurium A1-R in immunocompetent mice, indicate the clinical potential of bacterial therapy of cancer.


Forecasted Size of Measles Outbreaks Associated With Vaccination Exemptions for Schoolchildren.
Vaccine exemptions, which allow unvaccinated children to attend school, have increased by a factor of 28 since 2003 in Texas. Geographic clustering of unvaccinated children facilitates the spread of measles introductions, but the potential size of outbreaks is unclear. To forecast the range of measles outbreak sizes in each metropolitan area of Texas at 2018 and future reduced school vaccination rates. An agent-based decision analytical model using a synthetic population of Texas, derived from the 2010 US Census, was used to simulate measles transmission in the Texas population. Real schools were represented in the simulations, and the 2018 vaccination rate of each real school was applied to a simulated hypothetical equivalent. Single cases of measles were introduced, daily activities and interactions were modeled for each population member, and the number of infections over the course of 9 months was counted for 1000 simulated runs in each Texas metropolitan area. To determine the outcomes of further decreases in vaccination coverage, additional simulations were performed with vaccination rates reduced by 1% to 10% in schools with populations that are currently undervaccinated. Expected distributions of outbreak sizes in each metropolitan area of Texas at 2018 and reduced vaccination rates. At 2018 vaccination rates, the median number of cases in large metropolitan areas was typically small, ranging from 1 to 3 cases, which is consistent with outbreaks in Texas 2006 to 2017. However, the upper limit of the distribution of plausible outbreaks (the 95th percentile, associated with 1 in 20 measles introductions) exceeded 400 cases in both the Austin and Dallas metropolitan areas, similar to the largest US outbreaks since measles was eliminated in 2000. Decreases in vaccination rates in schools with undervaccinated populations in 2018 were associated with exponential increases in the potential size of outbreaks: a 5% decrease in vaccination rate was associated with a 40% to 4000% increase in potential outbreak size, depending on the metropolitan area. A mean (SD) of 64% (11%) of cases occurred in students for whom a vaccine had been refused, but a mean (SD) of 36% (11%) occurred in others (ie, bystanders). This study suggests that vaccination rates in some Texas schools are currently low enough to allow large measles outbreaks. Further decreases are associated with dramatic increases in the probability of large outbreaks. Limiting vaccine exemptions could be associated with a decrease in the risk of large measles outbreaks.


The effectiveness of dance movement interventions for older adults with mild cognitive impairment, Alzheimer's disease, and dementia: A systematic scoping review and meta-analysis.
To synthesize evidence and summarize research findings related to the effectiveness and feasibility of dance movement intervention (DMI) in older adults with mild cognitive impairment (MCI), Alzheimer's disease (AD), and dementia; to systemically map existing research gaps and research directions for future practice. A systematic search was conducted using six electronic databases: Web of Science, PubMed, PsycINFO, MEDLINE, ScienceDirect, and Cochrane Central Register of Controlled Trials. The methodological quality of included studies was assessed using the Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) and The Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). 29 dance intervention studies (13 RCT studies) were included in the scoping review: 62% of MCI, 10% of AD, and 28% of dementia; a total of 1708 participants (Female=1247; Male=461) aged from 63.8 ( ± 5.24) to 85.8 ( ± 5.27) years old. Eight RCT studies were included in the meta-analysis; results indicated that dance interventions had a significant effect on global cognition, memory, balance, and significantly decreased depression. No significant effects were found for executive function. Dance is a non-pharmacological, effective, affordable, and engaging intervention that can be used as a complementary treatment for older adults with MCI, AD, and dementia.


Is adolescence a period of identity formation for all youth? Insights from a four-wave longitudinal study of identity dynamics in Japan.
In the present study, we examined changes in identity dynamics during adolescence using the Dimensions of Identity Development Scale (DIDS), focusing on social and cultural factors possibly affecting identity formation. Identity formation among adolescents outside Western countries is largely unexplored; therefore, we focused on adolescents in Japan. We conducted a longitudinal study with 4 annual measurement points examining 968 Japanese adolescents (49.7% females). Two cohorts of participants were 13 and 16 years old at Time 1 and were followed until 16 and 19 years old, respectively. Latent class growth analysis extracted 3 identity trajectories corresponding to those found in previous research (i.e., achievement, troubled diffusion, and carefree diffusion) and 2 transitional trajectories newly identified in the present study (i.e., troubled diffusion-to-moratorium and moratorium-to-achievement). Adolescents following the achievement trajectory showed the best subjective well-being, whereas troubled diffused adolescents showed the worst. Furthermore, early-to-middle adolescents and urban adolescents tended to follow a low-commitment trajectory, whereas middle-to-late adolescents and rural adolescents tended to follow a high-commitment trajectory. These findings suggest that identity development proceeds toward integration during adolescence, but simultaneously, diverse developmental trajectories exist and incorporate contextual factors. Thus, in Japan, adolescence may be a period of identity formation for some adolescents, but not for others. (PsycINFO Database Record


[LH and triggered ovulation].
Actions of the LH peak Mechanisms of the LH-peak triggered ovulation Interest of reproducing the LH peak in stimulated cycles


Peanuts: allergic and other untoward reactions.
Serious sequalae to the ingestion of several foods such as egg, fish and milk--and the lack of profound reactions to chocolate--have been well documented. However, no comparable study exists in regard to peanut, which has long been known to be a patent antigen. This article explores the role of peanut with respect to its hazards as an antigen and as a foreign body in the upper respiratory tract, and documents a number of fatal and near-fatal reactions.