Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes.
Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6-9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores (β^ - 0.13, 95% CI - 0.26, 0.00) but positively associated with Executive Functioning factor scores (β^ 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index (β^ - 0.17, 95% CI - 0.33, - 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision.


Hierarchical regulation of odorant receptor gene choice and subsequent axonal projection of olfactory sensory neurons in zebrafish.
In both Drosophila and mice, olfactory sensory neurons (OSNs) expressing a given odorant receptor (OR) project axons to specific glomeruli in the antennal lobe or olfactory bulb (OB), developing a topographic odor map. To gain insights into the modes of OR expression and axonal projection in zebrafish, we generated a bacterial artificial chromosome transgenic line carrying an OR gene cluster in which two OR-coding sequences, OR111-7 and OR103-1, were replaced with yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP), respectively. In the transgenic embryos, YFP and CFP signals appear in small populations of OSNs at an early stage of development when OR expression is first observed. Time-lapse imaging of living embryos revealed that both YFP- and CFP-expressing OSNs project axons to the medial portion of the OB. This pattern of axonal projection is maintained in the adult transgenic fish, in which fluorescently labeled OSN axons target a topographically fixed cluster of glomeruli in the medial OB. Because the OR-coding sequences were replaced with fluorescent reporter genes, we examined which OR genes are expressed in YFP/CFP-expressing OSNs and found that the OR choice is mostly restricted to OR members within the same subfamily of the cluster. Furthermore, we found that the one receptor-one neuron rule is not always applicable to zebrafish OSNs and that multiple receptors-one neuron is true for a subpopulation of OSNs in both wild-type and transgenic fish. These data demonstrate two distinct modes of OR expression and suggest a model of the hierarchical regulation of OR gene choice and subsequent axonal projection in the zebrafish olfactory system.


Impact of professional interpreters on outcomes for hospitalized children from migrant and refugee families with limited English proficiency: a systematic review.
The objective of the review was to identify, critically appraise and synthesize evidence on the impact of professional interpreters on outcomes for hospitalized children from migrant and refugee families with limited English proficiency. A key strategy to facilitate effective communication between limited-English-proficient migrant and refugee families and healthcare providers is the use of professional interpreters. Despite awareness of the importance of professional interpreters, interpreters are underutilized. This results in suboptimal care, including poor access to health care, increased risk of serious medical events, increased admission to hospital and inadequate health literacy. Limited-English-proficient migrant, refugee or asylum-seeker families with a hospitalized child aged 0 to 18 years, who had used a professional interpreter, were considered for this review. Comparators included standard care or no interpreter, and reported results of comparisons of the duration, frequency or mode of interpreter delivery. Outcomes were length of stay in hospital, unplanned readmission rates to hospital, non-attendance at hospital clinic appointments and ambulatory care, child and/or parent satisfaction with care in hospital, adherence to treatment, medication errors, and other adverse events relating to patient safety. The review considered all studies conducted using a quantitative approach. A three-step search strategy was used. Databases were searched in December 2018 for published and unpublished articles. Studies published in English were considered for inclusion. The recommended JBI approach to critical appraisal, study selection, data extraction and data synthesis was used. Six articles reporting results from three randomized controlled trials and one observational study were included. Studies were undertaken in the United States involving Spanish-speaking participants. Three studies were in emergency departments. There was a total of 1813 families, of whom 1753 had limited English proficiency. Migrant and refugee families with limited English proficiency reported greater satisfaction with aspects of care when a professional interpreter service was used compared with using ad hoc interpreters. Using professional in-person interpreters resulted in a shorter total emergency department throughput time compared to using professional interpreters via telephone. There was no difference in concordance of child's discharge diagnoses between parents assigned professional interpreters and those assigned bilingual physicians. Video interpretation provided better understanding of diagnoses than phone interpretation. There is evidence that use of ad hoc interpreters or no interpreter is inferior to use of professional interpreters of any mode. Although video and in-person interpreters are more favorable for some outcomes, mode of delivery may not be as important as the fact that a professional interpreter is being used. The mode of professional interpreter delivery should be based on accessibility, availability, language requirements and patient preference. PROSPERO CRD42017058161.


[Inhibiting effects of three components of Astragalus membranaceus on oxidative stress in Chang Liver cells].
The main objective of this research is to investigate the effects of astragaloside IV, calycosin separately glucoside, formononetin on oxidative stress in Chang Liver cells induced by H2O2. In the experiments, Chang Liver cells (a kind of normal human hepatocytes) were used as the research object, bifendate which has a clear hepatoprotective effect was used as the positive control drug, then the oxidative damage model of Chang Liver cells were established by H2O2. Cells were divided into six groups: blank control group, oxidative stress group, astragaloside IV group, calycosin separately glucoside group, formononetin group and positive control group. Then endogenous antioxidant system related indexes were detected by micro plate and colorimetric method; intracellular reactive oxygen species (ROS) were detected by DCFH-DA fluorescent probe; and the expressions of CYP2E1 were evaluated by liver microsomes, mRNA, and protein, respectively with spectrophotometry, Real-time PCR method, and Western blot technique. Results showed that H2O2 decreased antioxidant activity, and increased ROS level and expression of CYP2E1. The above oxidative stress status had been changed with protections of the three components of Astragalus membranaceus (compared with oxidative stress group, P < 0.05, P < 0.01), which taken as a whole had equivalent effects as the drug of positive control group( bifendate). Taken together, three Astragalus membranaceus ingredients all had significant or extremely significant inhibiting effects on oxidative damaged Chang Liver cells which were induced by H2O2, and the oxidative damage of Chang Liver cells had been relieved.


Combined use of stereotaxic CT and angiography for brain biopsies and stereotaxic irradiation.
A Riechert Mundinger stereotaxic device was modified to enable artifact-free computed tomographic (CT) scanning with the stereotaxic frame attached to the patient's head. A localization system was developed allowing determination of the XYZ coordinates of the target point directly from the CT cut. Angiography was performed intraoperatively with the stereotaxic frame attached. Coronal and sagittal CT reconstructions were enlarged to the radiographic magnification to allow direct comparison with angiography. CT offered optimum localization of the target, whereas angiography determined the safest approach. Computer programs were developed to enable three-dimensional radiotherapy planning. 125I seeds were implanted for treatment of low-grade gliomas and solid craniopharyngiomas. Yttrium-90 was applied in cystic craniopharyngiomas. Intracavitary rhenium-186 application was abandoned because of frequent cyst recurrence and leakage from the cyst.


Suppression of gene silencing: a general strategy used by diverse DNA and RNA viruses of plants.
In transgenic and nontransgenic plants, viruses are both initiators and targets of a defense mechanism that is similar to posttranscriptional gene silencing (PTGS). Recently, it was found that potyviruses and cucumoviruses encode pathogenicity determinants that suppress this defense mechanism. Here, we test diverse virus types for the ability to suppress PTGS. Nicotiana benthamiana exhibiting PTGS of a green fluorescent protein transgene were infected with a range of unrelated viruses and various potato virus X vectors producing viral pathogenicity factors. Upon infection, suppression of PTGS was assessed in planta through reactivation of green fluorescence and confirmed by molecular analysis. These experiments led to the identification of three suppressors of PTGS and showed that suppression of PTGS is widely used as a counter-defense strategy by DNA and RNA viruses. However, the spatial pattern and degree of suppression varied extensively between viruses. At one extreme, there are viruses that suppress in all tissues of all infected leaves, whereas others are able to suppress only in the veins of new emerging leaves. This variation existed even between closely related members of the potexvirus group. Collectively, these results suggest that virus-encoded suppressors of gene silencing have distinct modes of action, are targeted against distinct components of the host gene-silencing machinery, and that there is dynamic evolution of the host and viral components associated with the gene-silencing mechanism.


The Interaction between the Ribosomal Stalk Proteins and Translation Initiation Factor 5B Promotes Translation Initiation.
Ribosomal stalk proteins recruit translation elongation GTPases to the factor-binding center of the ribosome. Initiation factor 5B (eIF5B in eukaryotes and aIF5B in archaea) is a universally conserved GTPase that promotes the joining of the large and small ribosomal subunits during translation initiation. Here we show that aIF5B binds to the C-terminal tail of the stalk protein. In the cocrystal structure, the interaction occurs between the hydrophobic amino acids of the stalk C-terminal tail and a small hydrophobic pocket on the surface of the GTP-binding domain (domain I) of aIF5B. A substitution mutation altering the hydrophobic pocket of yeast eIF5B resulted in a marked reduction in ribosome-dependent eIF5B GTPase activity in vitro In yeast cells, the eIF5B mutation affected growth and impaired GCN4 expression during amino acid starvation via a defect in start site selection for the first upstream open reading frame in GCN4 mRNA, as observed with the eIF5B deletion mutant. The deletion of two of the four stalk proteins diminished polyribosome levels (indicating defective translation initiation) and starvation-induced GCN4 expression, both of which were suppressible by eIF5B overexpression. Thus, the mutual interaction between a/eIF5B and the ribosomal stalk plays an important role in subunit joining during translation initiation in vivo.


Validation of the psychometrics properties of a French quality of life questionnaire among a cohort of renal transplant recipients less than one year.
Renal transplantation is considered as the treatment of choice for patients with end-stage renal disease. Health-related quality of life (HRQoL) of renal transplant recipients (RTR) is very important to assess, especially during the first year after transplantation. To provide new evidence about the suitability of HRQoL measures in RTR during the first post-transplant year, we explored the internal structure, reliability and external validity of a French specific HRQoL instrument, the Renal Transplant Quality of life Questionnaire Second Version (RTQ V2). The data were issued from the French multicenter cohort of renal transplant patients followed during 4 years (EPIGREN). The HRQoL of RTR was assessed five times (at 1, 3, 6, 9 and 12 months after transplantation) with the RTQ V2, a specific instrument consisting of 32 items describing five dimensions. Socio-demographic information, clinical characteristics and HRQoL (i.e., RTQ V2 and SF-36) were collected. For the five times, psychometric properties of the RTQ V2 were compared to those reported from the reference population assessed in the validation study. Three hundred and thirty-four patients were enrolled. The proportions of well-projected items, item-internal consistency, item-discriminant validity, floor and ceiling effects, Cronbach's alpha coefficients and item goodness-of-fit statistics were satisfactory for each dimension at the five times of the study. The suitability indices of construct validity were higher than 90 % for each time (minimum-maximum: 90.8-97.4 %). The external validity was less satisfactory, with a suitability indices ranged from 46.7 % at M1 to 66.7 % at M12. However, the discrepancies with the reference population (mainly for the gender) appeared logical considering the scientific literature on HRQoL of RTR during the first post-transplant year and may not compromise the external validity. These results support the validity and reliability of the RTQ V2 for evaluating HRQoL in RTR during the first post-transplant year, and confirm that the RTQ V2 is a useful tool to assess the HRQoL precociously after transplant.


p,p'-DDE depresses the immune competence of chinook salmon (Oncorhynchus tshawytscha) leukocytes.
p,p'-DDE, the main metabolite of DDT, is still detected in aquatic environments throughout the world. Here, the effects and mechanisms by which p,p'-DDE exposure might affect the immune system of chinook salmon (Oncorhynchus tshawytscha) was studied. Isolated salmon splenic and pronephric leukocytes were incubated with different concentrations of p,p'-DDE, and cell viability, induction of apoptosis, and mitogenic responses were measured by flow cytometry and Alamar Blue assay. p,p'-DDE significantly reduced cell viability and proliferation and increased apoptosis. The effect of p,p'-DDE on pronephric leukocytes was more severe than on splenic leukocytes, likely because pronephric leukocytes had a higher proportion of granulocytes, cells that appear more sensitive to p,p'-DDE. The effect of p,p'-DDE on leukocytes appeared to vary between developmental stages or seasonal differences. The mitogenic response of leukocytes of chinook salmon exposed to p,p'-DDE in vivo exhibited a biphasic dose-response relationship. Only leukocytes isolated from salmon treated with 59 ppm p,p'-DDE had a significantly lower percentage of Ig+ blasting cells than controls, although the response was biphasic. These results support the theory that exposure to chemical contaminants could lead to an increase in disease susceptibility and mortality of fish due to immune suppression.


Time-dependent physiological regulation of rodent and ovine placental glucose transporter (GLUT-1) protein.
To examine the in vivo and in vitro time-dependent effects of glucose on placental glucose transporter (GLUT-1) protein levels, we employed Western blot analysis using placenta from the short-term streptozotocin-induced diabetic pregnancy (STZ-D), uterine artery ligation-intrauterine growth restriction (IUGR) rat models, pregnant sheep exposed to chronic maternal glucose and insulin infusions, and the HRP.1 rat trophoblastic cell line exposed to differing concentrations of glucose. In the rat, 6 days of STZ-D with maternal and fetal hyperglycemia caused no substantive change, whereas 72 h of IUGR with fetal hypoglycemia and ischemic hypoxia resulted in a 50% decline in placental GLUT-1 levels (P < 0.05). In late-gestation ewes, maternal and fetal hyperglycemia caused an initial threefold increase at 48 h (P < 0.05), with a persistent decline between 10 to 21 days, whereas maternal and fetal hypoglycemia led to a 30-50% decline in placental GLUT-1 levels (P < 0.05). Studies in vitro demonstrated no effect of 0 mM, whereas 100 mM glucose caused a 60% decline (P < 0.05; 48 h) in HRP.1 GLUT-1 levels compared with 5 mM of glucose. The added effect of hypoxia on 0 and 100 mM glucose concentrations appeared to increase GLUT-1 concentrations compared with normoxic cells (P < 0.05; 100 mM at 18 h). We conclude that abnormal glucose concentrations alter rodent and ovine placental GLUT-1 levels in a time- and concentration-dependent manner; hypoxia may upregulate this effect. The changes in placental GLUT-1 concentrations may contribute toward the process of altered maternoplacentofetal transport of glucose, thereby regulating placental and fetal growth.


What are the current indications for use of radiofrequency devices in hip arthroscopy? A systematic review.
The role of radiofrequency energy (RFE) devices has been minimally studied in hip arthroscopy. The purpose of this study was to determine the role of RFE devices in hip arthroscopy through a systematic review of the literature. We searched the PubMed database using the following Medical Subject Heading terms: hip arthroscopy, hip radiofrequency, thermal capsulorrhaphy, thermal chondroplasty and radiofrequency debridement. Two authors independently reviewed the literature and included articles based on predetermined inclusion criteria. We excluded review, technique and experimental articles. After title and abstract review, we selected 293 articles for full-text review. Ten articles met the inclusion and exclusion criteria. For the included articles, a total of 305 hips underwent arthroscopy with concomitant RFE treatment at a mean age of 25.7 years. Eight articles presented patient-reported outcome (PRO) instruments, one study did not report an outcome instrument but utilized an evaluation of postoperative range of motion (ROM) and 1 year magnetic resonance image (MRI) and computed tomography (CT) imaging. The remaining article measured only the ROM pre- and postoperatively. Only one of the articles reviewed reported complications. Current evidence on the safety and indications for use of RFE devices in hip arthroscopy is insufficient. The literature shows mixed results regarding its use in hip arthroscopy. Although the use of thermal energy is not without risk, if used judiciously and appropriate precautions are taken to avoid damage to adjacent tissues, those devices can be useful for the treatment of certain intra-articular hip pathologies arthroscopically.


Microglia-neuron interactions in the models of neuropathic pain.
Chronic pain is a debilitating condition that often emerges as a clinical symptom of inflammatory diseases. It has therefore been widely accepted that the immune system critically contributes to the pathology of chronic pain. Microglia, a type of immune cell in the central nervous system, has attracted researchers' attention because in rodent models of neuropathic pain that develop strong mechanical and thermal hypersensitivity, histologically activated microglia are seen in the dorsal horn of spinal cord. Several kinds of cytokines are generated by damaged peripheral neurons and contribute to microglial activation at the distal site of the injury where damaged neurons send their projections. Microglia are known as key players in the surveillance of the local environment in the central nervous system and have a significant role of circuit remodeling by physical contact to synapses. Key molecules for the pathology of neuropathic pain exist in the activated microglia, but the factors driving pain-inducible microglial activation remain unclear. Therefore, to find the key molecules inducing activation of spinal microglia and to figure out the precise mechanism of how microglia modulate neuronal circuits in the spinal cord to form chronic pain state is a critical step for developing effective treatment of neuropathic pain.


Dimensions of sustainability for a health communication intervention in African American churches: a multi-methods study.
Sustainability of evidence-based health promotion interventions has received increased research attention in recent years. This paper reports sustainability data from Project HEAL (Health through Early Awareness and Learning) a cancer communication implementation trial about early detection, based in African American churches. In this paper, we used a framework by Scheirer and Dearing (Am J Publ Health 101:2059-2067, 2011) to evaluate multiple dimensions of sustainability from Project HEAL. We examined the following dimensions of sustainability: (a) continued benefits for intervention recipients, (b) continuation of intervention activities, c) maintaining community partnerships, (d) changes in organizational policies or structures, (e) sustained attention to the underlying issues, (f) diffusion to additional sites, or even (g) unplanned consequences of the intervention. Project HEAL provided a three-workshop cancer educational series delivered by trained lay peer community health advisors (CHAs) in their churches. Multiple sources of sustainability were collected at 12 and 24 months after the intervention that reflect several levels of analysis: participant surveys; interviews with CHAs; records from the project's management database; and open-ended comments from CHAs, staff, and community partners. Outcomes differ for each dimension of sustainability. For continued benefit, 39 and 37% of the initial 375 church members attended the 12- and 24-month follow-up workshops, respectively. Most participants reported sharing the information from Project HEAL with family or friends (92% at 12 months; 87% at 24 months). For continuation of intervention activities, some CHAs reported that the churches held at least one additional cancer educational workshop (33% at 12 months; 24% at 24 months), but many more CHAs reported subsequent health activities in their churches (71% at 12 months; 52% at 24 months). No church replicated the original series of three workshops. Additional data confirm the maintenance of community partnerships, some changes in church health policies, and continued attention to health issues by churches and CHAs. The multiple dimensions of sustainability require different data sources and levels of analysis and show varied sustainability outcomes in this project. The findings reinforce the dynamic nature of evidence-based health interventions in community contexts.


Maintaining mimicry diversity: optimal warning colour patterns differ among microhabitats in Amazonian clearwing butterflies.
Mimicry is one of the best-studied examples of adaptation, and recent studies have provided new insights into the role of mimicry in speciation and diversification. Classical Müllerian mimicry theory predicts convergence in warning signal among protected species, yet tropical butterflies are exuberantly diverse in warning colour patterns, even within communities. We tested the hypothesis that microhabitat partitioning in aposematic butterflies and insectivorous birds can lead to selection for different colour patterns in different microhabitats and thus help maintain mimicry diversity. We measured distribution across flight height and topography for 64 species of clearwing butterflies (Ithomiini) and their co-mimics, and 127 species of insectivorous birds, in an Amazon rainforest community. For the majority of bird species, estimated encounter rates were non-random for the two most abundant mimicry rings. Furthermore, most butterfly species in these two mimicry rings displayed the warning colour pattern predicted to be optimal for anti-predator defence in their preferred microhabitats. These conclusions were supported by a field trial using butterfly specimens, which showed significantly different predation rates on colour patterns in two microhabitats. We therefore provide the first direct evidence to support the hypothesis that different mimicry patterns can represent stable, community-level adaptations to differing biotic environments.


Regulation of the CD4+ T cell allo-immune response by endothelial cells.
Recent studies have revealed the presence of pro-inflammatory and/or regulatory CD4(+) T cells within allografts promoting either graft rejection or tolerance. Histological evidence has identified the microvascular endothelium as the primary site of allograft damage as it is the first site of encounter with the recipient's immune system. The initial view of the human endothelial cell inducing an effector Th1 response leading to graft rejection has been extended by recent results which demonstrate the endothelial cell ability to generate other CD4(+) T cell sub-populations including Th17 and Treg cells. In the transplantation setting, the allo-reactivity of the endothelium with the CD4(+) T cell populations is likely to depend upon multiple factors including the vascular origin of the endothelial cell, the cytokine environment, the presence or absence of pro-inflammatory stimuli including ligands of Toll like receptors and alloantibodies. This review provides an update on the characteristics of the endothelial cell activation of the CD4(+) T cell response and an analysis of the factors, which can modify this activity in favor of either graft rejection or tolerance.


Supercritical CO2 extraction of Marrubium vulgare: intensification of marrubiin.
Supercritical carbon dioxide and Soxhlet extraction were employed for delivering Marrubium vulgare extracts. By varying process temperature and pressure, the impact of different densities of carbon dioxide on the extraction yield and chemical profile of the extracts was investigated. The highest extraction yields of M. vulgare were obtained by supercritical carbon dioxide extraction (3.51%) at 300 bar and 60 °C, while the yield obtained with the Soxhlet extraction was 3.23%. The chemical profiles of these two extracts were significantly different and marrubiin, the most dominant component of supercritical extracts was not present in extracts obtained by this conventional method. This labdane diterpene was the most abundant in extracts obtained at 200 bar and temperatures of 40, 50, and 60 °C (62.60, 68.41, and 71.96%, respectively). For the intensification of marrubiin, supercritical fractions were collected in successive time intervals over the course of the extraction (300 bar/60 °C). It was determined that after 1 h of extraction the highest content of marrubiin (75.14%) can be achieved. The similarities between the obtained extracts were estimated and the correlations to the content of identified lipophilic compounds were established using multivariate data analysis tools.


Estrogen-dependent cyclin E-cdk2 activation through p21 redistribution.
In order to elucidate the mechanisms by which estrogens and antiestrogens modulate the growth of breast cancer cells, we have characterized the changes induced by estradiol that occur during the G1 phase of the cell cycle of MCF-7 human mammary carcinoma cells. Addition of estradiol relieves the cell cycle block created by tamoxifen treatment, leading to marked activation of cyclin E-cdk2 complexes and phosphorylation of the retinoblastoma protein within 6 h. Cyclin D1 levels increase significantly while the levels of cyclin E, cdk2, and the p21 and p27 cdk inhibitors are relatively constant. However, the p21 cdk inhibitor shifts from its association with cyclin E-cdk2 to cyclin D1-cdk4, providing an explanation for the observed activation of the cyclin E-cdk2 complexes. These results support the notion that cyclin D1 has an important role in steroid-dependent cell proliferation and that estrogen, by regulating the activities of G1 cyclin-dependent kinases, can control the proliferation of breast cancer cells.


PRAS40 promotes NF-κB transcriptional activity through association with p65.
PRAS40 has been shown to have a crucial role in the repression of mammalian target of rapamycin (mTOR). Nonetheless, PRAS40 appears to have an oncogenic function in cancer cells. Whether PRAS40 mediates signaling independent of mTOR inhibition in cancer cells remains elusive. Here PRAS40 overexpression in lung adenocarcinoma and cutaneous melanoma was significantly correlated to worse prognosis. And we identified an unexpected role for PRAS40 in the regulation of nuclear factor (NF)-κB signaling. P65, a subunit of the NF-κB transcription factor complex, was confirmed to associate with PRAS40 by glutathione S-transferase co-precipitation. Importantly, we found that PRAS40 can enhance NF-κB transcriptional activity in a manner dependent upon PRAS40-P65 association. Furthermore, we found that a small p65-derived peptide can disrupt the PRAS40-P65 association and significantly decrease NF-κB transcriptional activity. These findings may help elucidate the pleiotropic functions of PRAS40 in cells and suggest a novel therapeutic strategy in cancer patients with high expression of PRAS40 and NF-κB.


Excited-State Charge Distribution of a Donor-π-Acceptor Zn Porphyrin Probed by N K-Edge Transient Absorption Spectroscopy.
Zinc porphyrin solar cell dyes with donor-π-acceptor architectures combine light absorber (π), electron-donor, and electron-acceptor moieties inside a single molecule with atomic precision. The donor-π-acceptor design promotes the separation of charge carriers following optical excitation. Here, we probe the excited-state electronic structure within such molecules by combining time-resolved X-ray absorption spectroscopy at the N K-edge with first-principles time-dependent density functional theory (TD-DFT) calculations. Customized Zn porphyrins with strong-donor triphenylamine groups or weak-donor tri-tert-butylbenzene groups were synthesized. Energetically well-separated N K-edge absorption features simultaneously probe the excited-state electronic structure from the perspectives of the macrocycle and triphenylamine N atoms. New absorption transitions between the macrocycle N atoms and the excited-state HOMO vacancy are observed, and the triphenylamine associated absorption feature blue-shifts, consistent with partial oxidation of the donor groups in the excited state.


Severe Scapular Pain Following Unintentional Cervical Epidural Air Injection.
This a unique case of severe scapular pain following unintentional epidural space air injection during epidural steroid injection.A 70-year-old woman presented for a fluoroscopically guided C7-T1 interlaminar epidural steroid injection. Three injection attempts were made using the loss of resistance with air technique. On the first attempt the epidural space was entered, but contrast injection showed that the needle was intravenous. On the second attempt an equivocal loss of resistance with air was perceived and 5 mL of air was lost from the syringe. The needle was withdrawn and redirected, and upon the third needle passage the contrast injection showed appropriate epidural space filling up to the C4-5 level. Injection of betamethasone mixed in lidocaine was initially uneventful.However, 20 minutes post-injection the patient experienced sudden sharp and continuous pain along the medial edge of the scapula. After failing to respond to multiple intravascular analgesics, the patient was transferred to the emergency room. Her pain subsided completely following an intravenous diazepam injection. Cervical spine computerized tomography showed obvious air in the posterior epidural space from C4-5 to C6-7 as well as outside the spinal canal from (C4-T2). Having recovered fully, she was discharged the following morning. In reviewing the procedure, the equivocal loss of resistance on the second passage was actually a true loss of resistance to epidural space and air was unintentionally injected. Surprisingly, severe scapular pain resulted in a delayed manner after the steroid solution was injected. The authors theorize that unintentional prefilling of the epidural space with air prior to the injection of the subsequent steroid mixture added sufficient pressure to the epidural space to cause right-sided C4 nerve root stretching/entrapment and ensuing radicular pain to the right scapular border. The subsequent intravenous diazepam provided cervical muscle relaxation and facilitated foramina passage of air out of the spinal canal.This case demonstrates that under certain conditions entry of air into cervical epidural space can lead to unexpected, albeit temporary, neurological symptoms.


[Molecular-genetic analysis of the R2 plasmid (group IncP-9)].
The IncP-9 test plasmid R2 controlling resistance to streptomycin, carbenicillin, sulfanylamides and UV irradiation was studied. The plasmid (67.5 kb) was physically mapped for restriction endonucleases EcoRI, BamHI, BglII and SmaI. The aphC, sulI and bla genes were localized on the physical map of the plasmid. The resistance genes are supposed to be comprised within the ANT-R element. The regions participating in replication and mobilization of this plasmid were cloned. The cloned oriV region of the plasmid mediated synthesis of the protein with molecular weight of about 36 kD.


Polymorphism of leukocyte and erythrocyte antigens in chronic kidney disease patients in southern Brazil.
We investigated the polymorphism of human leukocyte antigens (HLA) and Duffy erythrocyte antigens in chronic kidney disease (CKD) patients in southern Brazil. One hundred and eighty-three CKD patients, over 18 years old, on hemodialysis, were included. HLA-A, -B and -DRB1 typing was performed using the LABType®SSO (One Lambda, Inc.). Duffy phenotypes were determined by gel column agglutination using anti-Fy(a) and anti-Fy(b) monoclonal anti-sera. The patients' predominant ages ranged between 51 and 70 years (43%) and the predominant gender, ethnic group and dialysis period were, respectively, male (62%), white (62%) and 1-3 years (40%). The highest and lowest frequencies of Duffy phenotypes were Fy(a+b+) and Fy(a-b-), respectively. Nineteen HLA-A, 30 HLA-B and 13 HLA-DRB1 allele groups were identified. The most frequent HLA allele groups were HLA-A*01, -A*02, -A*03, -A*11, -A*24; HLA-B*07, -B*15, -B*35, -B*44, -B*51; HLA-DRB1*03, -DRB1*04, -DRB1*07, -DRB1*11 and -DRB1*13. Statistically significant differences were observed in the Duffy and HLA polymorphisms compared between CKD patients and healthy subjects. The Fy(a+b-) phenotype (p<0.0001, OR = 2.56, 95% CI = 1.60-4.07) was the most frequent in the patients (p<0.05), and the Fy(a+b+) phenotype (p = 0.0039, OR = 1.71, 95% CI = 1.18-2.51) was the most frequent in the healthy subjects in the same region of Paraná state (p<0.05). Regarding HLA, the HLA-B*42, -B*45, -B*51 and -DRB1*03 allele groups were the most frequent in the patients (p<0.05), and the HLA-B*44 allele group was the most frequent in the healthy subjects in the same region of Brazil (p<0.05). The polymorphism of these two markers among CKD patients in southern Brazil and healthy subjects of other studies, suggests that these markers might be involved with CKD development. Further studies should be undertaken to analyze the markers' influence on CKD and the long-term results from kidney transplantation.


The use of reflectance confocal microscopy for monitoring response to therapy of skin malignancies.
Reflectance confocal microscopy (RCM) is a new non-invasive imaging technique that enables visualizing cells and structures in living skin in real-time with resolution close to that of histological analysis. RCM has been successfully implemented in the assessment of benign and malignant lesions. Most importantly, it also enables monitoring dynamic changes in the skin over time and in response to different therapies, e.g., imiquimod, photodynamic therapy, and others. Given the often traumatic nature of skin cancer that affects both the physiology and the psychology of the patients, it is crucial to have methods that enable monitoring the response to treatment but that minimize the distress and discomfort associated with such process. This article provides a very brief overview of the fundamentals of RCM and then focuses on its recent employment as a monitoring tool in skin cancer and other pathologies that may require frequent follow-up.


Number of Adenomas Removed and Colorectal Cancers Prevented in Randomized Trials of Flexible Sigmoidoscopy Screening.
Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly associated with adenoma removal. We propose the following 2 new metrics for quantifying the relationship between adenoma removal and CRC prevented: number of adenomas needed to remove (NNR) and adenoma dwell time avoided (DTA). We collected data from 4 randomized trials of sigmoidoscopy screening (1 in the United States and 3 in Europe) to assess NNR and DTA. For each trial, NNR was computed as the number of adenomas removed from subjects in the intervention group, divided by the number of CRCs prevented. DTA was computed similarly but taking into account the timing of adenoma removal. Combined results across trials were assessed using standard meta-analytic techniques. The estimated NNR for the PLCO (Prostate, Lung, Colorectal and Ovarian) trial was 74 (95% confidence interval [CI], 56-110), for the NORCCAP (Norwegian Colorectal Cancer Prevention) trial was 71 (95% CI, 44-174), for the SCORE (Screening for Colon Rectum) trial was 27 (95% CI, 14-135), and for the UKFSST (UK Flexible Sigmoidoscopy Screening Trial) was 36 (95% CI, 28-52). The combined estimate (meta-analysis) of NNR was 52 (95% CI, 36-93) assuming heterogeneity (P for heterogeneity = .014). DTA estimates among trials ranged from 278 to 730 years, with a combined estimate of 500 (95% CI, 344-833) years assuming heterogeneity (P for heterogeneity = .035), or 2 CRC cases prevented per 1000 adenoma dwell years avoided. The combined estimates of NNR and DTA restricted to advanced adenomas were 13 (95% CI, 9-22) and 122 (95% CI, 90-190) years, respectively. We collected data from 4 randomized trials of sigmoidoscopy screening for CRC to develop metrics of endoscopic efficiency, NNR and DTA, which are directly linked to adenoma detection and removal. They can be used to compare screening among endoscopic modalities and to more precisely measure adenoma to carcinoma transition rates.


Antibiotic Resistance in Salmonella enterica Serovar Typhimurium Associates with CRISPR Sequence Type.
Salmonella enterica subsp. enterica serovar Typhimurium is a leading cause of food-borne salmonellosis in the United States. The number of antibiotic-resistant isolates identified in humans is steadily increasing, suggesting that the spread of antibiotic-resistant strains is a major threat to public health. S Typhimurium is commonly identified in a wide range of animal hosts, food sources, and environments, but little is known about the factors mediating the spread of antibiotic resistance in this ecologically complex serovar. Previously, we developed a subtyping method, CRISPR-multi-virulence-locus sequence typing (MVLST), which discriminates among strains of several common S. enterica serovars. Here, CRISPR-MVLST identified 22 sequence types within a collection of 76 S Typhimurium isolates from a variety of animal sources throughout central Pennsylvania. Six of the sequence types were identified in more than one isolate, and we observed statistically significant differences in resistance among these sequence types to 7 antibiotics commonly used in veterinary and human medicine, such as ceftiofur and ampicillin (P < 0.05). Importantly, five of these sequence types were subsequently identified in human clinical isolates, and a subset of these isolates had identical antibiotic resistance patterns, suggesting that these subpopulations are being transmitted through the food system. Therefore, CRISPR-MVLST is a promising subtyping method for monitoring the farm-to-fork spread of antibiotic resistance in S Typhimurium.


Balloon Laryngoplasty for Pediatric Subglottic Stenosis: A 5-year Experience.
The objective of this study was to present our experience and evaluate our results of endoscopic balloon laryngoplasty (BL) in children with subglottic stenosis (SGS) at a pediatric tertiary center over a 5-year period. This study reviewed 41 pediatric patients diagnosed with acquired SGS who had undergone BL as the primary course of treatment. Cases were analyzed for details including patient demographics, SGS grade and length, timing and the type of surgery, presence of tracheostomy, comorbidities, postoperative management, complications and outcomes of balloon dilatation. Forty-one children (22 girls and 19 boys) who had undergone BL at a mean age of 26 months (range, 1 month to 14 years) were included in the study. Nineteen (46.3%) were diagnosed with acute SGS (12 thin stenosis, 7 thick stenosis) and 22 (53.7%) with chronic SGS (9 thin stenosis, 13 thick stenosis). The success rate of BL was 100% in patients with acute and chronic thin membranous stenosis. The effectiveness of BL was significantly higher in patients with acute thick stenosis than in patients with chronic thick stenosis (p=0.016). This study confirms that BL in patients presenting with acquired SGS with thin membranous stenosis, regardless of whether acute or chronic, can have a good prognosis. However, the results are less promising in cases of chronic thick stenosis.


[Peculiarities of treating endocrine ophthalmopathy in patients with toxic goiter combined with diabetes mellitus].
Thyroid pathology is among autoimmune diseases the incidence of which is now on the increase. Endocrine ophthalmology (EO) often accompanying thyroid disorders may cause deterioration or loss of vision. EO can be corrected by several methods. The most pronounced effect is achieved by x-ray therapy on the orbit and intermittent glucocorticosteroid (GCS) large-dose therapy. GCS, however, affect carbohydrate metabolism. In physiological levels, GCS effects on regulation of carbohydrate metabolism are not significant, but high GCS concentrations may provoke hyperglycemia and even steroid diabetes.


Deacetylasperulosidic Acid Ameliorates Pruritus, Immune Imbalance, and Skin Barrier Dysfunction in 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis NC/Nga Mice.
The prevalence of atopic dermatitis (AD), a disease characterized by severe pruritus, immune imbalance, and skin barrier dysfunction, is rapidly increasing worldwide. Deacetylasperulosidic acid (DAA) has anti-atopic activity in the three main cell types associated with AD: keratinocytes, mast cells, and eosinophils. Our study investigated the anti-atopic activity of DAA in 2,4-dinitrochlorobenzene-induced NC/Nga mice. DAA alleviated the symptoms of AD, including infiltration of inflammatory cells (mast cells and eosinophils), epidermal thickness, ear thickness, and scratching behavior. Furthermore, DAA reduced serum IgE, histamine, and IgG1/IgG2a ratio and modulated the levels of AD-related cytokines and chemokines, namely interleukin (IL)-1β, IL-4, IL-6, IL-9, IL-10, IL-12, tumor necrosis factor-α, interferon-γ, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation the normal T cell expressed and secreted in the serum. DAA restored immune balance by regulating gene expression and secretion of Th1-, Th2-, Th9-, Th17-, and Th22-mediated inflammatory factors in the dorsal skin and splenocytes and restored skin barrier function by increasing the expression of the pro-filaggrin gene and barrier-related proteins filaggrin, involucrin, and loricrin. These results suggest DAA as a potential therapeutic agent that can alleviate the symptoms of AD by reducing pruritus, modulating immune imbalance, and restoring skin barrier function.


The influence of age and sex on the prevalence of depressive conditions: report from the National Survey of Psychiatric Morbidity .
Women are consistently reported to have a greater prevalence of depressive disorders than men. The reason for this is unclear, and is as likely to be social as biological. There is some evidence that the excess of depression is greater during women's reproductive lives. Data from the National Survey of Psychiatric Morbidity were used to test the hypothesis that the excess disappeared in the post-menopausal years and that obvious social explanations for this were inadequate. Subjects (N = 9792) from a random sample of the British population provided data for the analysis. Psychiatric assessment was carried out by lay interviewers using the CIS-R. Subjects with ICD-10 depressive episode or mixed anxiety/depression were compared with the remainder. Social variables that were likely to contribute to a post-menopausal decline in depressive disorders were controlled in logistic regression analyses. There was a clear reversal of the sex difference in prevalence of depression in those over age 55. This could not be explained in terms of differential effects of marital status, child care, or employment status. This large and representative survey adds considerably to the increasingly held view that the sex difference in prevalence of depression is less apparent in later middle age. This may be linked to the menopause, and our attempts to explain it in terms of obvious conditions among social variables were not successful. More specific studies are required to clarify the finding.


Quantitative T2 changes and susceptibility-weighted magnetic resonance imaging in murine pregnancy.
To evaluate gestational age-dependent changes in the T2 relaxation time in normal murine placentas in vivo. The role of susceptibility-weighted imaging (SWI) in visualization of the murine fetal anatomy was also elucidated. Timed-pregnant CD-1 mice at gestational day (GD) 12 and GD17 underwent magnetic resonance imaging. Multi-echo spin echo and SWI data were acquired. The placental T2 values on GD12 and GD17 were quantified. To account for the influence of systemic maternal physiological factors on placental perfusion, maternal muscle was used as a reference for T2 normalization. A linear mixed-effects model was used to fit the normalized T2 values, and the significance of the coefficients was tested. Fetal SWI images were processed and reviewed for venous vasculature and skeletal structures. The average placental T2 value decreased significantly on GD17 (40.17 ± 4.10 ms) compared to the value on GD12 (55.78 ± 8.13 ms). The difference in normalized T2 values also remained significant (p = 0.001). Using SWI, major fetal venous structures like the cardinal vein, the subcardinal vein, and the portal vein were visualized on GD12. In addition, fetal skeletal structures could also be discerned on GD17. The T2 value of a normal murine placenta decreases with advancing gestation. SWI provided clear visualization of the fetal venous vasculature and bony structures. © 2014 S. Karger AG, Basel.


Responding to unexpected infant deaths: experience in one English region.
New national procedures for responding to the unexpected death of a child in England require a joint agency approach to investigate each death and support the bereaved family. As part of a wider population-based study of sudden unexpected deaths in infancy (SUDI) we evaluated the implementation of this approach. A process evaluation was carried out using a population-based study of all unexpected deaths from birth to 2 years in the South West of England between January 2003 and December 2006. Local police and health professionals followed a standardised approach to the investigation of each death, supported by the research team set up to facilitate this joint approach as well as collect data for a wider research project. We were notified of 155/157 SUDI, with a median time to notification of 2 h. Initial multi-agency discussions took place in 93.5% of cases. A joint home visit by police officers with health professionals was carried out in 117 cases, 75% within 24 h of the death. Time to notification and interview reduced during the 4 years of the study. Autopsies were conducted on all cases, the median time to autopsy being 3 days. At the conclusion of the investigation, a local multi-agency case discussion was held in 88% of cases. The median time for the whole process (including family support) was 5 months. This study has demonstrated that with appropriate protocols and support, the joint agency approach to the investigation of unexpected infant deaths can be successfully implemented.


Assessment of prognostic aspects of cancer by Taila Bindu Pariksha.
For the diagnosis of various aspects of disease and diseased person, several methods have been described in the Ayurvedic texts. These can be broadly classified into Roga and Rogi Pariksha. Several methods of Roga-Rogi Pariksha such as Ashtasthana, Dashavidha, Dvadashavidha Pariksha are described. Mutra Pariksha was the main laboratory investigative tools in the past and it is included under Ashtasthana, Pariksha. There is no direct description of methodology to ascertain the prognosis of cancer in the Ayurvedic classics. Taila Bindu Pariksha, which is a part of Mutra Pariksha helps in assessing the prognosis of a disease. Eastern Cooperative Oncology Group (ECOG) had developed the scale to ascertain prognosis of cancer in 1955. These ECOG performance scale gives doctors and research scholars a scale with which they can quickly assess the functional capacity of a patient and the progress of disease. To evaluate the prognosis of cancer by Taila Bindu Pariksha and compare the results with ECOG scale. A pilot study was undertaken on a single group of 20 cancer patients which are advised radio or chemotherapy for further management. The urine samples collected from the patients were subjected to Taila Bindu Pariksha. The ECOG scale was also assessed and compared with shape and direction of spread. In majority of the patients, the correlation was found statistically highly significant. Taila Bindu Pariksha may be used as an alternative method to ascertain the prognosis of the cancer patients.


Comparison of the Masaoka-Koga staging and the International Association for the Study of Lung Cancer/the International Thymic Malignancies Interest Group proposal for the TNM staging systems based on the Chinese Alliance for Research in Thymomas retrospective database.
To compare the predictive effect of the Masaoka-Koga staging system and the International Association for the Study of Lung Cancer (IASLC)/the International Thymic Malignancies Interest Group (ITMIG) proposal for the new TNM staging on prognosis of thymic malignancies using the Chinese Alliance for Research in Thymomas (ChART) retrospective database. From 1992 to 2012, 2,370 patients in ChART database were retrospectively reviewed. Of these, 1,198 patients with complete information on TNM stage, Masaoka-Koga stage, and survival were used for analysis. Cumulative incidence of recurrence (CIR) was assessed in R0 patients. Overall survival (OS) was evaluated both in an R0 resected cohort, as well as in all patients (any R status). CIR and OS were first analyzed according to the Masaoka-Koga staging system. Then, they were compared using the new TNM staging proposal. Based on Masaoka-Koga staging system, significant difference was detected in CIR among all stages. However, no survival difference was revealed between stage I and II, or between stage II and III. Stage IV carried the highest risk of recurrence and worst survival. According to the new TNM staging proposal, CIR in T1a was significantly lower comparing to all other T categories (P<0.05) and there is a significant difference in OS between T1a and T1b (P=0.004). T4 had the worst OS comparing to all other T categories. CIR and OS were significantly worse in N (+) than in N0 patients. Significant difference in CIR and OS was detected between M0 and M1b, but not between M0 and M1a. OS was almost always statistically different when comparison was made between stages I-IIIa and stages IIIb-IVb. However, no statistical difference could be detected among stages IIIb to IVb. Compared with Masaoka-Koga staging, the IASLC/ITMIG TNM staging proposal not only describes the extent of tumor invasion but also provides information on lymphatic involvement and tumor dissemination. Further study using prospectively recorded information on the proposed TNM categories would be helpful to better grouping thymic tumors for predicting prognosis and guiding clinical management.


Humoral beta-cell autoimmunity is rare in patients with the congenital rubella syndrome.
The congenital rubella syndrome (CRS) is associated with increased risk for diabetes and thyroid disease. However, the mechanisms by which the rubella virus may cause these diseases are poorly characterized. Previous studies were carried out before modern immunological methods were available. The present study aimed at evaluating whether autoimmune mechanisms are involved in the pathogenesis by analysing antibodies to biochemically characterized autoantigens. The incidence of clinical diabetes, thyroid disease, coeliac disease and related antibodies (islet cell antibodies, ICA; insulin autoantibodies, IAA; antibodies to the tyrosine phosphatase related IA-2 molecule, IA-2 A and glutamic acid decarboxylase, GADA; thyroid peroxidase, TPO; tissue transglutaminase, TTGA; and gliadin, AGA) and HLA risk genotypes were analysed in 37 subjects affected by or exposed to rubella during fetal life (mean age 22.5 years). One patient had diabetes and four patients had clinical hypothyroidism at the time of the examination. ICA, IAA, GADA or IA-2 A were not detected in any of the patients, while five patients tested positive for TPO antibodies. Coeliac disease or TTGA were not observed. Eight patients carried the HLA-DR3-associated HLA-DQB1*02-DQA1*05 haplotype. These results provide no evidence of an increased frequency of markers for humoral beta-cell autoimmunity in patients with CRS suggesting that diabetes in CRS may be caused by other than autoimmune mechanisms.


Study of the interaction between cisplatin and the Au18(SR)14 cluster: in search of an appropriate cisplatin carrier.
Cisplatin is a well known anti-cancer drug and considered as essential by the World Health Organization. However, cisplatin features side effects during medical treatments due to its lack of selectivity resulting in the indiscriminate death of cells including healthy cells. To solve this issue, it is mandatory to improve its delivery towards affected organs or tissues. The well known bio-compatibility of gold clusters encouraged us to study the interaction between cisplatin molecules and the Au18(SR)14 cluster (named Au18) and our DFT calculations have provided insight into this aspect. Calculated adsorption energy values of the cisplatinn/Au18 complexes are within the 0.5-3.6 eV range, which attests to their unique interaction. In addition, their calculated optical absorption (UV-vis) and circular dichroism (CD) spectra display distinct peaks in such a manner that UV/CD spectra can be used as fingerprints by experimentalists.


Development of the Association of Pediatric Program Directors Global Educator Scholarship-Expanding Bidirectional Efforts in Global Health Education.
The Board of the Association of Pediatric Program Directors (APPD) partnered with the APPD Global Health Learning Community (GHLC) to establish the APPD Global Pediatric Educator Scholarship. This award seeks to recognize pediatric educators who demonstrate leadership in improving pediatric education in low- and middle-income countries, and provide them with career development opportunities by attending the APPD Spring meeting. Two educators per year have been awarded the scholarship since 2017. The authors sent survey questions via email and obtained responses from 6 (100%) of the scholarship awardees, 8 (75%) APPD GHLC leadership individuals, and 4 (67%) APPD Board members. Three authors analyzed the responses with consensus achieved on themes. Awardees noted learning about educational strategies, academic opportunities through networking, and context for stronger bilateral exchange with partners. APPD leaders noted an expansion of the organization's mission to include global presence. Challenges included program visibility, sustainable funding, and logistics. Suggestions included better incorporation of awardees into APPD membership, longitudinal mentorship, targeted conference navigation, and visits to local academic institutions. The APPD Global Educator Scholarship is a replicable model of organizational global outreach that expands the concept of bidirectional exchange to include career sponsorship for global partners.


Effects of extrusion variables on the properties of waxy hulless barley extrudates.
The objective of this research was to investigate the extrudability of waxy hulless barley flour under various extrusion conditions. Waxy hulless barley flour was processed in a laboratory-scale corotating twin-screw extruder with different levels of feed moisture content (22.3, 26.8, and 30.7%) and die temperature (130, 150, and 170 degrees C) to develop a snack food with high beta-glucan content. The effects of extrusion condition variables (screw configuration, moisture, and temperature) on the system variables (pressure and specific mechanical energy), the extrudate physical properties (sectional expansion index, bulk density), starch gelatinization, pasting properties (cold peak viscosity, trough viscosity, and final viscosity), and beta-glucan contents were determined. Results were evaluated by using response surface methodology. Increased extrusion temperature and feed moisture content resulted in decreases in exit die pressure and specific mechanical energy values. For extrudates extruded under low shear screw configuration (LS), increased barrel temperature decreased sectional expansion index (SEI) values at both low and high moisture contents. The feed moisture seems to have an inverse relationship with SEI over the range studied. Bulk density was higher at higher moisture contents, for both low and high barrel temperatures, for samples extruded under high shear screw configuration (HS) and LS. Cold peak viscosities (CV) were observed in all samples. The CV increased with the increase in extrusion temperature and feed moisture content. Although beta-glucan contents of the LS extrudates were comparable to that of barley flour sample, HS samples had generally lower beta-glucan contents. The extrusion cooking technique seems to be promising for the production of snack foods with high beta-glucan content, especially using LS conditions.


Biomarkers of maternal and fetal exposure to organochlorine pesticides measured in pregnant Hispanic women from Brownsville, Texas.
Biomarkers of organochlorine pesticides were measured in both venous and umbilical cord blood from 35 pregnant Hispanic women living in Brownsville, Texas, USA. Gas chromatography with an electron capture detector was used to analyze specimens for 30 individual pesticides or their metabolites. Results indicate that blood concentrations were relatively low for most individual compounds, but that high-end (upper 10th percentile) values for total DDT were comparatively high. Although health effects associated with measured blood concentrations are uncertain, there is concern that fetal exposure to low levels of these OC compounds, either individually or in combination, might contribute to subsequent health problems, including neurodevelopmental effects, cancer, endocrine disruption, obesity and diabetes.


Genetic mutations in thyroid carcinoma.
Thyroid carcinoma is the most common endocrine neoplasm and the seventh most frequent human malignancy. It can be distinguished into differentiated and undifferentiated. Differentiated tumors include those arising from thyrocytes, i.e. papillary and follicular carcinoma, while medullary carcinoma originates from parafollicular or C cells. Anaplastic carcinoma comprises undifferentiated tumors. The factors inducing thyroid carcinoma development are not fully understood despite some well-established associations, such as the one between ionizing radiation and papillary carcinoma and that between iodine deficiency and follicular carcinoma. Genetic investigations of differentiated thyroid tumors have documented mutation of genes involved in the regulation of MAP kinase pathway activation in papillary carcinoma, and of genes involved in the regulation of the PI3 kinase pathway in follicular carcinoma. Analysis of their clinical course and of positivity for mutations has demonstrated that prognosis is greatly affected by the type of mutated gene. Genetic investigations therefore have the potential to direct diagnosis, but especially to tailor therapy and follow-up to the individual patient and even the individual gene. Anaplastic carcinoma, a highly aggressive, undifferentiated form, can arise as such or else be the de-differentiated progression of a papillary or a follicular carcinoma. It displays a mutated tumor suppressor gene (p53), which is crucial in the regulation of cell apoptosis, in addition to the mutations found in papillary and follicular forms. Medullary carcinoma is a malignant neoplasm with an intermediate clinical course between differentiated and undifferentiated forms. It manifests more frequently as a sporadic neoplasm or as a familial MEN. The latter is a high-penetrance, autosomal dominant hereditary disorder. Identification of the gene responsible for medullary carcinoma has radically changed the diagnostic approach to the familial forms, enabling early neonatal diagnosis of mutation carriers and of the disease, and early surgical approach by prophylactic thyroidectomy. Genetic studies have significantly affected the endocrinologist's diagnostic approach, as in the case of medullary carcinoma; over the next few years they are expected to provide further information to tackle papillary and follicular thyroid carcinoma. This review addresses the main genetic mutations responsible for neoplastic transformation in thyroid disorders.


Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure.
Gitelmańs syndrome (GS) is an inherited recessive disorder caused by homozygous or compound heterozygous loss of function mutations of the NaCl cotransporter (NCCT) gene encoding the kidney-expressed NCCT, the pharmacological target of thiazide diuretics. An observational study estimated the prevalence of GS to 19/1,000,000, in Sweden, suggesting that approximately 1% of the population carries one mutant NCCT allele. As the phenotype of GS patients, who always carry two mutant alleles, is indistinguishable from that seen in patients treated with high-dose thiazide diuretics, we aimed at investigating whether subjects carrying one mutated NCCT allele have a phenotype resembling that of treatment with low-dose thiazide diuretics. We screened first-degree relatives of 18 of our patients with an established clinical end genetic diagnosis of GS for NCCT loss of function mutations and identified 35 healthy subjects carrying one mutant allele (GS-heterozygotes). Each GS-heterozygote was assigned a healthy control subject matched for age, BMI and sex. GS-heterozygotes had markedly lower blood pressure (systolic 103.3 +/- 16.4 versus 123.2 +/- 19.4 mmHg; diastolic 62.5 +/- 10.5 versus 73.1 +/- 9.4 mmHg; P < 0.001) than controls. There was no significant difference between the groups either in plasma concentration or urinary excretion rate of electrolytes, however, GS-heterozygotes had higher fasting plasma glucose concentration. Similar to patients being treated with low-dose thiazide diuretics, GS-heterozygotes have markedly lower blood pressure and slightly higher fasting plasma glucose compared with control subjects. Our findings suggest that GS-heterozygotes, the prevalence of which can be estimated to 1%, are partially protected from hypertension through partial genetic loss of function of the NCCT. However, as our study had a case-control design, it is important to underline that any potential effects on population blood pressure and risk of future cardiovascular disease need to be examined in prospective and population-based studies.


[The comparative sensitivity of isolated arteries and atrium from the cat to m-cholinoreceptor agonists].
A comparative assessment of the activities of some agonists of M-cholinoreceptors was made on the isolated mesatone-treated segments of arteries of various localization and the isolated left atrium of the cat. It was found that by the sensitivity to cholinomimetics the cat arteries may be divided in 2 groups: high- and low-sensitive (the latter include the aorta and renal artery). The left cat atrium is less sensitive to the agonists than the high-sensitive arteries and possesses approximately the same sensitivity to M-cholinomimetics as the aorta and renal artery.


Hypoxia shifts activity of neuropeptide Y in Ewing sarcoma from growth-inhibitory to growth-promoting effects.
Ewing sarcoma (ES) is an aggressive malignancy driven by an oncogenic fusion protein, EWS-FLI1. Neuropeptide Y (NPY), and two of its receptors, Y1R and Y5R are up-regulated by EWS-FLI1 and abundantly expressed in ES cells. Paradoxically, NPY acting via Y1R and Y5R stimulates ES cell death. Here, we demonstrate that these growth-inhibitory actions of NPY are counteracted by hypoxia, which converts the peptide to a growth-promoting factor. In ES cells, hypoxia induces another NPY receptor, Y2R, and increases expression of dipeptidyl peptidase IV (DPPIV), an enzyme that cleaves NPY to a shorter form, NPY3-36. This truncated peptide no longer binds to Y1R and, therefore, does not stimulate ES cell death. Instead, NPY3-36 acts as a selective Y2R/Y5R agonist. The hypoxia-induced increase in DPPIV activity is most evident in a population of ES cells with high aldehyde dehydrogenase (ALDH) activity, rich in cancer stem cells (CSCs). Consequently, NPY, acting via Y2R/Y5Rs, preferentially stimulates proliferation and migration of hypoxic ALDHhigh cells. Hypoxia also enhances the angiogenic potential of ES by inducing Y2Rs in endothelial cells and increasing the release of its ligand, NPY3-36, from ES cells. In summary, hypoxia acts as a molecular switch shifting NPY activity away from Y1R/Y5R-mediated cell death and activating the Y2R/Y5R/DPPIV/NPY3-36 axis, which stimulates ES CSCs and promotes angiogenesis. Hypoxia-driven actions of the peptide such as these may contribute to ES progression. Due to the receptor-specific and multifaceted nature of NPY actions, these findings may inform novel therapeutic approaches to ES.


The DEVA trial: protocol for a randomised controlled trial of dequalinium chloride versus usual care antibiotics for the treatment of bacterial vaginosis.
Bacterial vaginosis (BV) is the most common cause of vaginal discharge in women of reproductive age, and it is estimated that up to a third of women will experience it at some point in their lives. BV produces an offensive vaginal odour and it is associated with serious sequelae. The most frequently prescribed treatment for BV in the UK is 7-day oral metronidazole but recurrences are common following it. Dequalinium chloride (Fluomizin©) is an anti-infective, antiseptic agent administered as a vaginal tablet. Small studies have shown this to be an effective alternative to antibiotics as a BV treatment. This trial aims to investigate whether dequalinium is as effective as current antibiotic treatments for the treatment of BV 1 month after treatment start. DEVA is a multi-centre, randomised, open-label, parallel group, non-inferiority trial of dequalinium chloride versus usual care antibiotics for the treatment of BV. Recruitment will take place in 15 GUM clinics in the UK with Leeds Sexual Health also managing remote recruitment via the trial website. Women will be randomised 1:1 to receive dequalinium or usual care antibiotics. The primary outcome is to determine if the proportion of women reporting resolution of BV symptoms 4 weeks after treatment (without the need for additional treatment) is not worse in women treated with dequalinium chloride compared to usual care antibiotics. Questionnaire follow-up will take place 4 and 12 weeks after starting treatment, and remotely recruited patients will also provide a week 4 BV vaginal smear. The sample size is 904. This trial will provide high-quality evidence on the use of dequalinium chloride as a BV treatment, which could result in patients reducing the number of antibiotics they take. ISRCTN ISRCTN91800263. Prospectively registered on 20 January 2020.


[Capgras delusion: a review of aetiological theories].
Features of the Capgras delusion, the most common among the delusional misidentification syndromes, are reviewed. We describe its phenomenology in psychiatric and organic diseases, its prevalence and comorbidity with other reduplicative disorders and review aetiological models in order to elucidate the origins of the delusion from both the cognitive psychology and psychodynamics precepts, as the neuropsychiatry and anatomical basis. According to cognitive models, Capgras syndrome cannot be exclusively conceived as a dysfunction in facial recognition but in recognizing a person globally considered. Feeling of familiarity is absent due to the inability to integrate successive memories about a person along episodic experiences, thus generating delusional doubles in accordance to the patient's needs or drives. From the neuropsychiatry point of view Capgras delusion arises from the failure in reconciling information about identification of the person and its associated emotions by the disconnection between frontal lobes and right temporo-limbic regions (hippocampus), in addition to bilateral frontal damage. Delusions are more commonly associated with right hemisphere lesions because of the impairment of several functions such as self monitoring, reality monitoring, memory and feelings of familiarity as well as the necessary preservation of the left hemisphere. Aetiology of Capgras delusion should include the conjoint involvement of clinical, neuropsychiatric and neuropsychological data with different theoretical models.


A population-based study of the prevalence and sociodemographic risk factors of self-reported epilepsy among adults in the United Kingdom.
Few studies have investigated the prevalence of self-reported epilepsy among adults in the United Kingdom and none has focused on identifying risk factors associated with epilepsy. Data were obtained from the 2009 British Household Panel Survey, a population-based cohort study of adults ≥ 16 years of age residing in the United Kingdom (n=14,419). Cases were ascertained by identifying individuals who responded "yes" to having epilepsy. Prevalence rates were age- and sex-adjusted using mid-2009 population data and 95% confidence intervals (CI) were calculated. Logistic regression identified risk factors for self-reported epilepsy. A total of 112 individuals reported having epilepsy, resulting in a point prevalence of 8.6 per 1000 (95% CI: 6.6, 10.5). There were no differences in prevalence rates across strata of age, sex, marital status, employment status, employment satisfaction, academic or vocational qualifications, and socioeconomic status. Among males, the prevalence rate for the >75 age group was significantly lower compared to the 30-44 (p=0.0243) and 45-59 age groups (p=0.0099). Individuals who were younger OR=0.91 (0.85, 0.98), not married OR=0.80 (0.67, 0.95), had less education OR=0.84 (0.74, 0.95), were less satisfied with their employment OR=0.66 (0.57, 0.77), and had lower income OR=0.87 (0.78, 0.98) were more likely to have epilepsy. The prevalence rates reported are similar to those described previously. The rationale for observing these specific risk factors for self-reported epilepsy are discussed in terms of public attitudes and stigma associated with epilepsy.


How Coca-Cola Shaped the International Congress on Physical Activity and Public Health: An Analysis of Email Exchanges between 2012 and 2014.
There is currently limited direct evidence of how sponsorship of scientific conferences fits within the food industry's strategy to shape public policy and opinion in its favour. This paper provides an analysis of emails between a vice-president of The Coca-Cola Company (Coke) and prominent public health figures in relation to the 2012 and 2014 International Congresses of Physical Activity and Public Health (ICPAPH). Contrary to Coke's prepared public statements, the findings show that Coke deliberated with its sponsored researchers on topics to present at ICPAPH in an effort to shift blame for the rising incidence of obesity and diet-related diseases away from its products onto physical activity and individual choice. The emails also show how Coke used ICPAPH to promote its front groups and sponsored research networks and foster relationships with public health leaders in order to use their authority to deliver Coke's message. The study questions whether current protocols about food industry sponsorship of scientific conferences are adequate to safeguard public health interests from corporate influence. A safer approach could be to apply the same provisions that are stipulated in the Framework Convention on Tobacco Control on eliminating all tobacco industry sponsorship to the food industry.


Associations between Serum 25-hydroxyvitamin D and Lipids, Lipoprotein Cholesterols, and Homocysteine.
Serum 25(OH) vitamin D levels are inversely associated with cardiovascular disease (CVD) mortality, mediated in part by independent positive relationships with high-density lipoprotein cholesterol (HDLC) and inverse relationships with low-density lipoprotein cholesterol (LDLC), triglyceride, and homocysteine. In this study, we assessed relationships between fasting serum vitamin D and lipids, lipoprotein cholesterols, and homocysteine. We studied 1534 patients sequentially referred to our center from 2007 to 2016. Fasting serum total 25(OH) vitamin D, plasma cholesterol, triglyceride, HDLC, LDLC, and homocysteine were measured. Stepwise regression models were used with total cholesterol, triglyceride, HDLC, LDLC, and homocysteine as dependent variables and explanatory variables age, race, gender, body mass index (BMI), and serum vitamin D levels. Relationships between quintiles of serum vitamin D and triglycerides, HDLC, LDLC, and homocysteine were assessed after covariance adjusting for age, race, gender, and BMI. Fasting serum vitamin D was positively correlated with age, HDLC, and White race, and was inversely correlated with BMI, total and LDL cholesterol, triglyceride, and fasting serum homocysteine (P ≤ 0.0001 for all). Serum vitamin D was a significant independent inverse explanatory variable for total cholesterol, triglyceride, and LDL cholesterol, and accounted for the largest amount of variance in serum total cholesterol (partial R (2) =3.6%), triglyceride (partial R (2) =3.1%), and LDLC (partial R (2) =2.9%) (P < 0.0001 for all). Serum vitamin D was a significant positive explanatory variable for HDLC (partial R (2) = 1.4%, P < 0.0001), and a significant inverse explanatory variable for homocysteine (partial R (2) = 6.0-12.6%). In hyperlipidemic patients, serum vitamin D was a significant independent inverse determinant of total cholesterol, LDLC, triglyceride, and homocysteine, and a significant independent positive determinant of HDLC. Thus, serum vitamin D might be protective against CVD.


Bromido(quinolin-8-ol-κN,O)(quinolin-8-olato-κN,O)zinc(II) methanol monosolvate.
The title compound, [ZnBr(C(9)H(6)NO)(C(9)H(7)NO)]·CH(3)OH, has its metal atom N,O-chelated by a neutral and a deproton-ated 8-hy-droxy-quinoline ligand. The hy-droxy unit of the neutral ligand is a hydrogen-bond donor to the methanol O atom and the alk-oxy O atom of the monoanionic ligand is a hydrogen-bond acceptor to the methanol O atom. In the crystal, adjacent mol-ecules are linked by these two hydrogen bonds, generating a chain running along the a axis.


[Analysis of High-Risk Clinical Factors of Early Death in Secondary Hemophagocytic Lymphohistiocytosis].
To explore the high-risk clinical factors of early death in patients with secondary hemophagocytic lymphohistiocytosis (sHLH), and further identify the clinical factors related to the rapid progression of sHLH in the short term. The clinical manifestations, laboratory examination and prognosis of sHLH patients were retrospectively analyzed. Continuous variables were grouped by median, univariate and multivariate Cox regression analysis and Kaplan-Meier survival curve were used to explore the risk factors affecting early death of sHLH. Then, a nomogram model was established with independent risk factors, Bootstrap resampling method was used for verification, and consistency index (C-index) and calibration curve were used to detect the prediction accuracy. A total of 126 sHLH patients were enrolled, with a median age of 48.5(16-88) years, including 74 males and 52 females. Fifty-five patients (43.6%) died within 30 days, including 39 males and 16 females. Univariate regression analysis showed that lymphocyte count <0.45×109/L, platelet count (PLT) <39.5×109/L, prothrombin time (PT)≥13.3 s, activated partial thromboplastin time (APTT)≥39.7 s, albumin (ALB) <25.9 g/L, lactate dehydrogenase (LDH)≥811 U/L, creatinine (Cr) ≥67 μmol/L and procalcitonin (PCT)≥0.61 ng/ml were risk factors for death within 30 days in sHLH patients. Multivariate regression analysis showed that lymphocyte count <0.45×109/L, APTT≥39.7 s and ALB <25.9 g/L were independent risk factors for death within 30 days in sHLH patients. A nomogram model was established based on the above three risk factors, its C-index was 0.683, and the calibration chart showed good agreement between the observed and predicted values of sHLH. Lymphopenia, prolonged APTT, and hypoalbuminemia are risk factors for early death of sHLH patients. Early identification and positive intervention are expected to reduce early mortality in sHLH patients. The nomogram model based on the above risk factors provides a method for clinicians to evaluate sHLH.


[Adolescents and violence. Impact of African traditions and customs on the signification of the law to children in familial, social, educative and judicial practices].
Youth-related violence is a frequent topic of press reports and editorial comment. The most disturbing aspects of the phenomenon are the younger and younger age of delinquents and the greater and greater availability of firearms. While the advocates of an American-style approach of absolute repression clash with those of the educative approach to change aggressive attitudes and young people benefit from their "minor" status, the compelling reality is that all preventive programs have failed flatly. This purpose of this study was twofold. The first aim was to highlight the important contribution of tradition and custom to channeling youthful behavior in African society today and yesterday through signification and transmission of law in familial, social, educative and juridical practices. The second goal was to identify and define the psycho-relational elements that can be considered as factors promoting violent and self-destructive tendencies in minors of African origin tempted by migration in a society in which social representations inhibit parents and prevent them from conveying the limits of the law in their children.


Understanding why the thoracic region is the 'Cinderella' region of the spine.
The thoracic spine has for a long time been the 'Cinderella' region of the spine. There has been a lesser research focus to the thoracic region compared with the cervical and lumbar spine, and there continues to be a limited understanding of the aetiology and epidemiology of a range of neuromusculoskeletal presentations which have an anatomical connection to the thoracic spine. This paper firstly, provides a critical evaluation of the available evidence to provide some understanding for this under-exploration of the thoracic spine. Secondly the paper provides an evaluation of an emerging interest in this spinal region, with a body of evidence supporting the use of thoracic spine manipulation in the management of upper quadrant presentations. This has been linked to the theory of regional interdependence with the thoracic spine being viewed as a silent contributor to clinical presentations where a pain source lies elsewhere. Finally, a case for further research is made. Identified gaps in the current evidence base include, aetiology and epidemiology of thoracic spine pain and thoracic spine dysfunction, and to investigate mechanisms of action of currently used interventions.


Regulation of polyp-to-jellyfish transition in Aurelia aurita.
The life cycle of scyphozoan cnidarians alternates between sessile asexual polyps and pelagic medusa. Transition from one life form to another is triggered by environmental signals, but the molecular cascades involved in the drastic morphological and physiological changes remain unknown. We show in the moon jelly Aurelia aurita that the molecular machinery controlling transition of the sessile polyp into a free-swimming jellyfish consists of two parts. One is conserved and relies on retinoic acid signaling. The second, novel part is based on secreted proteins that are strongly upregulated prior to metamorphosis in response to the seasonal temperature changes. One of these proteins functions as a temperature-sensitive "timer" and encodes the precursor of the strobilation hormone of Aurelia. Our findings uncover the molecule framework controlling the polyp-to-jellyfish transition in a basal metazoan and provide insights into the evolution of complex life cycles in the animal kingdom.


Promoting safe use of isotretinoin by increasing contraceptive knowledge.
Isotretinoin, a known teratogen, is strictly regulated through the iPLEDGE program. However, isotretinoin-exposed pregnancies continue to occur. To evaluate an information sheet's effect on women's contraceptive knowledge. Women aged 18 to 45 years visiting a dermatology practice completed anonymous surveys assessing their knowledge of the typical effectiveness of 8 contraceptive methods before and after reviewing an educational information sheet. Participants categorized each contraceptive as "most effective, >99% effective," "medium effective, 92%-97% effective," or "least effective, <89% effective" or indicated that they had "never heard of" it. All participants were recruited from a single dermatology clinic between April and May 2014. A total of 118 women were approached by consecutive sampling, and surveys were completed by 100 women. Preintervention contraceptive effectiveness knowledge and change in contraceptive effectiveness knowledge after viewing the educational tool. Prior to viewing the contraceptive information sheet, more than half of women overestimated the typical effectiveness of condoms (75%), contraceptive injections (57%), and oral contraceptives (51%). Thirty-four percent had never heard of contraceptive implants, whereas 16% had never heard of an intrauterine contraceptive device (IUD). Participants correctly identified the typical effectiveness of only a mean (SD) of 3.8 (1.9) of the 8 contraceptives that they were asked about. Only 3% of participating women were able to correctly identify the typical effectiveness of all available contraceptives. On average, women spent less than 1 minute reviewing the contraceptive information sheet (mean [SD], 31 [27] seconds). After viewing the educational handout, the proportions of participants able to correctly identify the typical effectiveness of contraceptives increased for almost all methods (subdermal implant, 45% to 78% [P < .001]; IUD, 61% to 83% [P < .001]; injection, 28% to 44% [P = .02]; ring, 60% to 69% [P = .18]; patch, 50% to 71% [P = .002]; pills, 41% to 65% [P < .001]; condoms, 25% to 45% [P = .003]; withdrawal, 74% to 90% [P = .003]). A contraceptive information sheet can significantly improve patients' contraceptive knowledge and may be a useful addition to efforts to prevent isotretinoin-induced birth defects.


Gangliosides and Nogo receptors independently mediate myelin-associated glycoprotein inhibition of neurite outgrowth in different nerve cells.
In the injured nervous system, myelin-associated glycoprotein (MAG) on residual myelin binds to receptors on axons, inhibits axon outgrowth, and limits functional recovery. Conflicting reports identify gangliosides (GD1a and GT1b) and glycosylphosphatidylinositol-anchored Nogo receptors (NgRs) as exclusive axonal receptors for MAG. We used enzymes and pharmacological agents to distinguish the relative roles of gangliosides and NgRs in MAG-mediated inhibition of neurite outgrowth from three nerve cell types, dorsal root ganglion neurons (DRGNs), cerebellar granule neurons (CGNs), and hippocampal neurons. Primary rat neurons were cultured on control substrata and substrata adsorbed with full-length native MAG extracted from purified myelin. The receptors responsible for MAG inhibition of neurite outgrowth varied with nerve cell type. In DRGNs, most of the MAG inhibition was via NgRs, evidenced by reversal of inhibition by phosphatidylinositol-specific phospholipase C (PI-PLC), which cleaves glycosylphosphatidylinositol anchors, or by NEP1-40, a peptide inhibitor of NgR. A smaller percentage of MAG inhibition of DRGN outgrowth was via gangliosides, evidenced by partial reversal by addition of sialidase to cleave GD1a and GT1b or by P4, an inhibitor of ganglioside biosynthesis. Combining either PI-PLC and sialidase or NEP1-40 and P4 was additive. In contrast to DRGNs, in CGNs MAG inhibition was exclusively via gangliosides, whereas inhibition of hippocampal neuron outgrowth was mostly reversed by sialidase or P4 and only modestly reversed by PI-PLC or NEP1-40 in a non-additive fashion. A soluble proteolytic fragment of native MAG, dMAG, also inhibited neurite outgrowth. In DRGNs, dMAG inhibition was exclusively NgR-dependent, whereas in CGNs it was exclusively ganglioside-dependent. An inhibitor of Rho kinase reversed MAG-mediated inhibition in all nerve cells, whereas a peptide inhibitor of the transducer p75(NTR) had cell-specific effects quantitatively similar to NgR blockers. Our data indicate that MAG inhibits axon outgrowth via two independent receptors, gangliosides and NgRs.


A numerical model for magnetic induction tomographic measurements in biological tissues.
A finite-difference model has been developed for simulating measurements in magnetic induction tomography (MIT) for biological tissues. The model has three stages: (1) computation of the distribution of current induced in a volume of dielectric due to the magnetic field from an excitation coil; both the electrical conductivity and permittivity of the dielectric are taken into account: (2) computation of the e.m.f. induced in the sensing coil directly from the excitation coil; (3) computation of the e.m.f. induced in a sensing coil due to the current distribution in the dielectric. From the results of stages (2) and (3), the change in signal in the sensing coil due to the dielectric can be obtained, in magnitude and phase, as a fraction of the signal received in the absence of the dielectric. The peak values in the modelled curves agreed to within 14% of practical measurements at 10 MHz on volumes of saline solution with conductivities in the range 0.7 to 6 S m(-1).


Factors Associated With Opioid Prescribing for Distal Upper Extremity Fractures at a Pediatric Emergency Department.
The aims of this study were to describe the prescribing patterns of oxycodone for patients with distal upper extremity fractures and to evaluate factors that influence the quantity of oxycodone prescribed at discharge. We retrospectively studied oxycodone prescriptions for patients with upper extremity fractures presenting to a single center tertiary pediatric emergency department (ED) from June 1, 2014, to May 31, 2016. We used logistic regression models to evaluate the association of opioid administration in the ED, fracture reduction under ketamine sedation, initial pain scores (low, medium, and high), patient demographics, and type of prescriber (residents, attendings, fellows, and advanced registered nurse practitioners) with oxycodone prescription at discharge and the number of doses prescribed (≤12 or >12 doses). A total of 1185 patients met the inclusion criteria. Of these, 669 (56%) were prescribed oxycodone at discharge. Children with fractures requiring reduction had 13 times higher odds [95% confidence interval (CI), 9.45-20.12] of receiving an oxycodone prescription compared with children with fractures not requiring reduction. Opioid administration in the ED was associated with 7.5 times higher odds (95% CI, 5.41-10.51) of receiving an outpatient prescription. Children were more likely to have a higher quantity of oxycodone prescribed if they had a fracture reduction in the ED [odds ratio (OR), 1.73; 95% CI, 1.20-2.50], received an opioid in the ED (OR, 2.13; 95% CI, 1.43-3.20), or received their prescription from an emergency medicine resident (OR, 2.8; 95% CI, 1.44-5.74). Opioid prescribing differs based on patient- and provider-related factors. Given the variability in prescribing patterns, changing suggested opioid prescriptions in the electronic medical record may lead to more consistent practice and therefore decrease unnecessary prescribing while still ensuring adequate outpatient analgesia.


DNA nanostructures as models for evaluating the role of enthalpy and entropy in polyvalent binding.
DNA nanotechnology allows the design and construction of nanoscale objects that have finely tuned dimensions, orientation, and structure with remarkable ease and convenience. Synthetic DNA nanostructures can be precisely engineered to model a variety of molecules and systems, providing the opportunity to probe very subtle biophysical phenomena. In this study, several such synthetic DNA nanostructures were designed to serve as models to study the binding behavior of polyvalent molecules and gain insight into how small changes to the ligand/receptor scaffolds, intended to vary their conformational flexibility, will affect their association equilibrium. This approach has yielded a quantitative identification of the roles of enthalpy and entropy in the affinity of polyvalent DNA nanostructure interactions, which exhibit an intriguing compensating effect.


Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo.
Oleanolic acid (OA), a plant-derived pentacyclic terpenoid, is known to have hepatoprotective effects. In this study, we found that OA induced autophagic cell death in multiple human gastric cancer cell lines. Moreover, OA-induced autophagy was shown for the first time in human gastric cancer cells, evidenced by the formation of GFP-RFP-LC3 puncta and autophagosomes. OA suppressed phospho-mTOR through inhibition of the PI3 K/AKT and ERK/p38 MAPK signalling pathways and through activation of the AMPK signalling pathway. Furthermore, we found that OA-induced cytotoxicity and autophagy could be blocked by the autophagy inhibitor 3-methyladenine or via siRNA targeting Beclin-1. Our in vivo research showed that OA delayed the formation of MGC-803 tumours in an autophagy-dependent manner. These results reveal a novel mechanism for OA in gastric cancer cells and suggest that OA could be a novel agent in the treatment of gastric cancer.


Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell-lymphotoxin-dependent pathway.
Adaptive immune responses are characterized by substantial restructuring of secondary lymphoid organs. The molecular and cellular factors responsible for virus-induced lymphoid remodeling are not well known to date. Here we applied optical projection tomography, a mesoscopic imaging technique, for a global analysis of the entire 3-dimensional structure of mouse peripheral lymph nodes (PLNs), focusing on B-cell areas and high endothelial venule (HEV) networks. Structural homeostasis of PLNs was characterized by a strict correlation between total PLN volume, B-cell volume, B-cell follicle number, and HEV length. After infection with lymphocytic choriomeningitis virus, we observed a substantial, lymphotoxin (LT) beta-receptor-dependent reorganization of the PLN microarchitecture, in which an initial B-cell influx was followed by 3-fold increases in PLN volume and HEV network length on day 8 after infection. Adoptive transfer experiments revealed that virus-induced PLN and HEV network remodeling required LTalpha(1)beta(2)-expressing B cells, whereas the inhibition of vascular endothelial growth factor-A signaling pathways had no significant effect on PLN expansion. In summary, lymphocytic choriomeningitis virus-induced PLN growth depends on a vascular endothelial growth factor-A-independent, LT- and B cell-dependent morphogenic pathway, as revealed by an in-depth mesoscopic analysis of the global PLN structure.


2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially induce cytochrome P450 1A1, 1B1, and 19 in H295R human adrenocortical carcinoma cells.
Diindolylmethane (DIM) is an acid-catalyzed condensation product of indole-3-carbinol, a constituent of cruciferous vegetables, and is formed in the stomach. DIM alters estrogen metabolism and inhibits carcinogen-induced mammary tumor growth in rodents. DIM is a weak agonist for the aryl hydrocarbon (Ah) receptor and blocks the effects of estrogens via inhibitory Ah receptor-estrogen receptor cross-talk. DIM and various structural analogs were examined in H295R cells for effects on 3 cytochrome P450 (CYP) enzymes involved in estrogen synthesis and/or metabolism: CYP1A1, CYP1B1, and CYP19 (aromatase). Aromatase activity was measured by conversion of 1 beta-(3)H-androstenedione to estrone and (3)H(2)O. H295R cells were exposed to the test chemicals dissolved in dimethyl sulfoxide for 24 h prior to analyses. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) (0--30 nM) and DIM (0--10 microM) induced ethoxyresorufin-O-deethylase (EROD) activity, as a measure of CYP1A1 and possibly 1B1 activity, with EC(50) values of about 0.3 nM and 3 microM, respectively. DIM, but not TCDD, induced aromatase activity with an apparently maximal 2-fold increase at 10 microM; higher concentrations of DIM and many of its analogs were cytotoxic. TCDD (30 nM) significantly increased CYP1A1 and 1B1 mRNA levels, but had no effect on mRNA for CYP19. DIM (3 microM) significantly increased mRNA levels for all three CYPS: DIM analogs with substitutions on the 5 and 5' position (3 microM) induced aromatase and EROD activity, together with mRNA levels of CYP1A1, 1B1, and 19; analogs that were substituted on the central carbon of the methane group showed little or no inductive activity toward the CYPS: In conclusion, DIM and several of its analogs appear to induce CYPs via multiple yet distinct pathways in H295R human adrenocortical carcinoma cells.


Informational masking caused by contralateral stimulation.
Although informational masking is thought to reflect central mechanisms, the effects are generally much stronger when the target and masker are presented to the same ear than when they are presented to different ears. However, the results of a recent study by Brungart and Simpson [J. Acoust. Soc. Am. 112, 2985-2995 (2002)] indicated that a speech masker that is presented contralateral to a speech signal can produce substantial amounts of informational masking when a second speech masker is played simultaneously in the same ear as the signal. In this study, we conducted a series of experiments that paralleled those of Brungart and Simpson but used a pure-tone signal and multitone informational maskers in a detection task. Both the signal and the maskers were played as sequences of short bursts in each observation interval. The maskers were arranged in two types of spectrotemporal patterns. One type of pattern, called "multiple-bursts same" (MBS), has previously been shown to produce very large amounts of informational masking while the other type of pattern, called "multiple-bursts different" (MBD), has been shown to produce very small amounts of informational masking. Several conditions of ipsilateral, contralateral, and combined presentation of these maskers were tested. The results showed that presentation of the MBS masker in the contralateral ear produced a substantial amount of informational masking when the MBD masker was simultaneously presented to the ipsilateral ear. The results supported the earlier findings of Brungart and Simpson indicating that listeners are unable to selectively focus their attention on a single ear in some complex dichotic listening conditions. These results suggest that this contralateral masking effect is not restricted to speech and may reflect more general limitations on processing capacity. Further, it was concluded that the magnitude of the contralateral masking effect was related both to the informational masking value of the contralateral masker and the complexity of the stimulus and/or task in the ear in which the signal was presented.