Delineating the practice profile of advanced practice nursing: a cross-sectional survey using the modified strong model of advanced practice.
To test a model that delineates advanced practice nursing from the practice profile of other nursing roles and titles. There is extensive literature on advanced practice reporting the importance of this level of nursing to contemporary health service and patient outcomes. Literature also reports confusion and ambiguity associated with advanced practice nursing. Several countries have regulation and delineation for the nurse practitioner, but there is less clarity in definition and service focus of other advanced practice nursing roles. A statewide survey. Using the modified Strong Model of Advanced Practice Role Delineation tool, a survey was conducted in 2009 with a random sample of registered nurses/midwives from government facilities in Queensland, Australia. Analysis of variance compared total and subscale scores across groups according to grade. Linear, stepwise multiple regression analysis examined factors influencing advanced practice nursing activities across all domains. There were important differences according to grade in mean scores for total activities in all domains of advanced practice nursing. Nurses working in advanced practice roles (excluding nurse practitioners) performed more activities across most advanced practice domains. Regression analysis indicated that working in clinical advanced practice nursing roles with higher levels of education were strong predictors of advanced practice activities overall. Essential and appropriate use of advanced practice nurses requires clarity in defining roles and practice levels. This research delineated nursing work according to grade and level of practice, further validating the tool for the Queensland context and providing operational information for assigning innovative nursing service.


Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial.
Capecitabine is an active agent in the treatment of breast cancer. It is not known whether integration of capecitabine into an adjuvant regimen that contains a taxane, an anthracycline, and cyclophosphamide improves outcome in early breast cancer. Women with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive either three cycles of docetaxel and capecitabine (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (CEX; n = 753) or three cycles of docetaxel (T) followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (CEF; n = 747). The primary end point was recurrence-free survival (RFS). During a median follow-up time of 59 months, 214 RFS events occurred (local or distant recurrences or deaths; TX/CEX, n = 96; T/CEF, n = 118). RFS was not significantly different between the groups (hazard ratio [HR], 0.79; 95% CI, 0.60 to 1.04; P = .087; 5-year RFS, 86.6% for TX/CEX v 84.1% for T/CEF). Fifty-six patients assigned to TX/CEX died during the follow-up compared with 75 of patients assigned to T/CEF (HR, 0.73; 95% CI, 0.52 to 1.04; P = .080). In exploratory analyses, TX/CEX improved breast cancer-specific survival (HR, 0.64; 95% CI, 0.44 to 0.95; P = .027) and RFS in women with triple-negative disease and in women who had more than three metastatic axillary lymph nodes at the time of diagnosis. We detected little severe late toxicity. Integration of capecitabine into a regimen that contains docetaxel, epirubicin, and cyclophosphamide did not improve RFS significantly compared with a similar regimen without capecitabine.


The carboxyl-terminal segment of the adaptor protein ALX directs its nuclear export during T cell activation.
The adaptor protein ALX acts downstream of CD28 to regulate the interleukin-2 (IL-2) promoter during T cell activation. Whereas ALX is predominantly localized to the cytoplasm, ALX partially resides in the nucleus, and the nuclear pool is rapidly depleted in response to T cell receptor (TCR)/CD28 signaling. Here it is shown that this depletion occurs via nuclear export of ALX, which depends on a leucine-rich nuclear export signal (NES) in its carboxyl segment and on the CRM-1 transport protein. Nuclear import of ALX also depends on its carboxyl-terminal segment. Blocking nuclear export of ALX, either pharmacologically, by leptomycin B, or by site-directed mutation of the ALX NES, impairs CD28-mediated phosphorylation of ALX. Additionally, upon overexpression, the ALX NES mutant was found to be impaired in inhibiting TCR/CD28-induced transcriptional up-regulation of the RE/AP composite element from the IL-2 promoter, whereas a truncated form of ALX that is a potent inhibitor of RE/AP activation was found to reside entirely in the cytoplasm. Together, these results show that ALX exerts its effect on IL-2 up-regulation in the cytoplasm and suggest an intricate relationship between the nuclear localization/export, phosphorylation, and activity of ALX in response to TCR and CD28 signaling.


Plant-based diets: Reducing cardiovascular risk by improving sleep quality?
The goal of this review is to evaluate recent research related to the effects of plant-based diets on sleep patterns. We discuss plausible mechanisms for the link between plant-based diets and sleep, and provide suggestions for future research in this area. Short sleep duration and poor sleep quality have been shown to negatively affect individual dietary habits, through enhanced appetite, increased overall caloric intake, as well as lower diet quality. Emerging data also indicate a novel bi-directional association by which dietary choices may also influence sleep duration and quality, but little is known about dietary patterns and their influence on sleep. Epidemiological studies report associations between Mediterranean diet eating patterns and sleep quality, suggesting a benefit of plant-rich diet consumption on sleep. The high isoflavone and tryptophan content of these diets may be a mechanism by which plant foods may enhance sleep quality. Plant-based diets may provide additional benefits to health via their potential effects on sleep quality. Research is needed to establish a causal relation between a plant-rich dietary pattern and sleep health.


QTc interval prolongation and severe apneas associated with a change in infant positioning.
For more than a decade there has been considerable interest in the role of QT interval prolongation in the pathogenesis of sudden infant death syndrome. It has been proposed that the QT interval is a surrogate marker for autonomic instability and can be used to identify infants at risk for significant morbidity and mortality, including sudden infant death syndrome. We present the case of an infant that experienced a significant increase in his QTc, as detected by continuous QTc monitoring in the NICU after repositioning from a supine to prone position. This increase from a 413 ± 6 millisecond baseline average to 500 milliseconds was sustained for 2 hours and associated with clinically relevant apnea that ultimately required repositioning of the infant back to the supine position. Repositioning resulted in an immediate decrease of the QTc back to the previous baseline and termination of the apneic events. This case demonstrates an example of how the use of continuous QTc monitoring in the NICU setting may be used to detect QTc-accentuating factors in real time and identify situations that cause perturbations in an infant's autonomic nervous system.


A protocol for developing reporting guidelines for laboratory studies in Endodontology.
Laboratory-based research studies are the most common form of research endeavour and make up the majority of manuscripts that are submitted for publication in the field of Endodontology. The scientific information derived from laboratory studies can be used to design a wide range of subsequent studies and clinical trials and may have translational potential to benefit clinical practice. Unfortunately, the majority of laboratory-based articles submitted for publication fail the peer-review step, because unacceptable flaws or substantial limitations are identified. Even when apparently well-conducted laboratory-based articles are peer-reviewed, they can often require substantial corrections prior to the publication. It is apparent that some authors and reviewers may lack the training and experience to have developed a systematic approach to evaluate the quality of laboratory studies. Occasionally, even accepted manuscripts contain limitations that may compromise interpretation of data. To help authors avoid manuscript rejection and correction pitfalls, and to aid editors/reviewers to evaluate manuscripts systematically, the purpose of this project is to establish and publish quality guidelines for authors to report laboratory studies in the field of Endodontology so that the highest standards are achieved. The new guidelines will be named-'Preferred Reporting Items for Laboratory studies in Endodontology' (PRILE). A steering committee was assembled by the project leads to develop the guidelines through a five-phase consensus process. The committee will identify new items as well as review and adapt items from existing guidelines. The items forming the draft guidelines will be reviewed and refined by a PRILE Delphi Group (PDG). The items will be evaluated by the PDG on a nine-point Likert scale for relevance and inclusion. The agreed items will then be discussed by a PRILE face-to-face consensus meeting group (PFCMG) formed by 20 individuals to further refine the guidelines. This will be subject to final approval by the steering committee. The approved PRILE guidelines will be disseminated through publication in relevant journals, presented at congresses/meetings, and be freely available on a dedicated website. Feedback and comments will be solicited from researchers, editors and peer reviewers, who are invited to contact the steering committee with comments to help them update the guidelines periodically.


Measuring community integration after spinal cord injury: validation of the Sydney psychosocial reintegration scale and community integration measure.
To evaluate the reliability, validity, sensitivity to change, and clinical usefulness of the Sydney Psychosocial Reintegration Scale (SPRS) and Community Integration Measure (CIM) for people with spinal cord injury (SCI). A sample of 58 people with recent traumatic SCI was followed up at 12 months post-discharge from inpatient rehabilitation. The SPRS, CIM, Craig Handicap Assessment and Reporting Technique (CHART) and SF-6D Health Utility Scale (SF-6D) were administered. The SPRS and CIM were internally consistent (α = .80 and .78, respectively). The SPRS showed greatest sensitivity to change as measured by percentage of participants meeting minimum difference in score change over time (21%). CIM and CHART had comparable sensitivity to change (14% minimum difference). SPRS correlated significantly with CHART (r = .72, P < .001), unlike CIM. Neither SPRS nor CIM discriminated between high and low impairment, unlike CHART. Correlations with CHART and SF-6D domains supported convergent and divergent validity of the SPRS domains. Research should continue to develop conceptually and psychometrically valid instruments to capture the multidimensionality of community integration. The SPRS and CIM show potential to extend measurement of community reintegration following SCI.


Mechanisms of hypnosis: toward the development of a biopsychosocial model.
Evidence supports the efficacy of hypnotic treatments, but there remain many unresolved questions regarding how hypnosis produces its beneficial effects. Most theoretical models focus more or less on biological, psychological, and social factors. This scoping review summarizes the empirical findings regarding the associations between specific factors in each of these domains and response to hypnosis. The findings indicate that (a) no single factor appears primary, (b) different factors may contribute more or less to outcomes in different subsets of individuals or for different conditions, and (c) comprehensive models of hypnosis that incorporate factors from all 3 domains may ultimately prove to be more useful than more restrictive models that focus on just 1 or a very few factors.


Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity.
Large doses of antiprogestin typically disrupt menstrual cyclicity. A chronic low-dose regimen of the potent new antiprogestin ZK 137 316, which permits continued menstrual cyclicity but alters gonadal-reproductive tract activity, was established. Rhesus monkeys received vehicle (n = 6) or 0.01 (n = 8), 0.03 (n = 8) or 0.1 (n = 5) mg ZK 137 316/kg body weight daily for five menstrual cycles (C-1 to C-5). Oestradiol, progesterone and gonadotrophin profiles were normal during cycles involving vehicle and 0.01 and 0.03 mg ZK 137 316/kg body weight. In the 0.1 mg/kg group, mid-cycle oestradiol and gonadotrophin surges, and subsequent progesterone production, were absent in C-3 and C-5. Ovarian cyclicity was accompanied by timely menstruation in the vehicle and 0.01 mg/kg groups. By C-3, half the animals in the 0.03 mg/kg group and all animals in the 0.1 mg/kg group were amenorrhoeic. A corpus luteum was noted during the mid-luteal phase of C-5 in the vehicle, 0.01 mg/kg and 0.03 mg/kg groups. Large antral and cystic follicles were evident in the 0.1 mg/kg group. Thus, a daily treatment with 0.01 mg/kg ZK 136317 permitted normal menstrual cyclicity in macaques. While the daily administration of 0.03 mg/kg ZK 136 317 allowed ovarian cyclicity, menstruation was disrupted in some animals. Increasing the dose to 0.1 mg/kg antagonized pituitary function and resulted in anovulation and amenorrhoea. A chronic low-dose regimen of the antiprogestin ZK 137 316, which permits normal ovarian/menstrual cyclicity, has potential as a contraceptive in women.


Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks.
Electronic cigarettes (e-cigarettes) are generally recognized as a safer alternative to combusted tobacco products, but there are conflicting claims about the degree to which these products warrant concern for the health of the vapers (e-cigarette users). This paper reviews available data on chemistry of aerosols and liquids of electronic cigarettes and compares modeled exposure of vapers with occupational safety standards. Both peer-reviewed and "grey" literature were accessed and more than 9,000 observations of highly variable quality were extracted. Comparisons to the most universally recognized workplace exposure standards, Threshold Limit Values (TLVs), were conducted under "worst case" assumptions about both chemical content of aerosol and liquids as well as behavior of vapers. There was no evidence of potential for exposures of e-cigarette users to contaminants that are associated with risk to health at a level that would warrant attention if it were an involuntary workplace exposures. The vast majority of predicted exposures are < <1% of TLV. Predicted exposures to acrolein and formaldehyde are typically <5% TLV. Considering exposure to the aerosol as a mixture of contaminants did not indicate that exceeding half of TLV for mixtures was plausible. Only exposures to the declared major ingredients--propylene glycol and glycerin--warrant attention because of precautionary nature of TLVs for exposures to hydrocarbons with no established toxicity. Current state of knowledge about chemistry of liquids and aerosols associated with electronic cigarettes indicates that there is no evidence that vaping produces inhalable exposures to contaminants of the aerosol that would warrant health concerns by the standards that are used to ensure safety of workplaces. However, the aerosol generated during vaping as a whole (contaminants plus declared ingredients) creates personal exposures that would justify surveillance of health among exposed persons in conjunction with investigation of means to keep any adverse health effects as low as reasonably achievable. Exposures of bystanders are likely to be orders of magnitude less, and thus pose no apparent concern.


Fragrance allergic contact dermatitis.
Fragrances are a common cause of allergic contact dermatitis in Europe and in North America. They can affect individuals at any age and elicit a spectrum of reactions from contact urticaria to systemic contact dermatitis. Growing recognition of the widespread use of fragrances in modern society has fueled attempts to prevent sensitization through improved allergen identification, labeling, and consumer education. This review provides an overview and update on fragrance allergy. Part 1 discusses the epidemiology and evaluation of suspected fragrance allergy. Part 2 reviews screening methods, emerging fragrance allergens, and management of patients with fragrance contact allergy. This review concludes by examining recent legislation on fragrances and suggesting potential additions to screening series to help prevent and detect fragrance allergy.


Analytical modeling, finite-difference simulation and experimental validation of air-coupled ultrasound beam refraction and damping through timber laminates, with application to non-destructive testing.
Reliable non-destructive testing (NDT) ultrasound systems for timber composite structures require quantitative understanding of the propagation of ultrasound beams in wood. A finite-difference time-domain (FDTD) model is described, which incorporates local anisotropy variations of stiffness, damping and density in timber elements. The propagation of pulsed air-coupled ultrasound (ACU) beams in normal and slanted incidence configurations is reproduced by direct definition of material properties (gas, solid) at each model pixel. First, the model was quantitatively validated against analytical derivations. Time-varying wavefronts in unbounded timber with curved growth rings were accurately reproduced, as well as the acoustic properties (velocity, attenuation, beam skewing) of ACU beams transmitted through timber lamellas. An experimental sound field imaging (SFI) setup was implemented at NDT frequencies (120 kHz), which for specific beam incidence positions allows spatially resolved ACU field characterization at the receiver side. The good agreement of experimental and modeled beam shifts across timber laminates allowed extrapolation of the inner propagation paths. The modeling base is an orthotropic stiffness dataset for the desired wood species. In cross-grain planes, beam skewing leads to position-dependent wave paths. They are well-described in terms of the growth ring curvature, which is obtained by visual observation of the laminate. Extraordinary refraction phenomena were observed, which lead to well-collimated quasi-shear wave coupling at grazing beam incidence angles. The anisotropic damping in cross-grain planes is satisfactorily explained in terms of the known anisotropic stiffness dataset and a constant loss tangent. The incorporation of high-resolution density maps (X-ray computed tomography) provided insight into ultrasound scattering effects in the layered growth ring structure. Finally, the combined potential of the FDTD model and the SFI setup for material property and defect inversion in anisotropic materials was demonstrated. A portable SFI demonstrator was implemented with a multi-sensor MEMs receiver array that captures and compensates for variable wave propagation paths in glued laminated timber, and improves the imaging of lamination defects.


Novel furano analogues of duocarmycin C1 and C2: design, synthesis, and biological evaluation of seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) analogues.
The design, synthesis and biological evaluation of novel seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and the seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) analogues of the duocarmycins are described. These novel analogues (4-7) were designed on the premise that the lone pair of electrons on the furano-oxygen atom could enter into conjugation with the isocyclopropylfurano[e]indolone (iso-CFI) alkylating moiety, formed from the loss of HCl in compounds 4-7. The seco-iso-CFI DNA alkylating pharmacophore was synthesized through a well precedented approach of 5-exo-trig aryl radical cyclization with a vinyl chloride. In our studies, in addition to the formation of the seco-iso-CFI product, an equal amount of an unexpected seco-CFQ product was also generated during the radical cyclization reaction. Like CC-1065 and adozelesin, using Taq DNA polymerase stop and thermal cleavage assays, the seco-iso-CFI compounds (4 and 6) and the seco-CFQ compounds (5 and 7) were shown to preferentially alkylate the adenine-N3 position within the minor groove of long stretches of A residues. A MM2 energy optimized molecular model of a 1:1 complex of compound 6 with DNA reveals that the iso-CFI compound fits snugly within the minor groove. Using a MTT based experiment, the cytotoxicity of compounds 4-7 were determined against the growth of murine leukemia (L1210), mastocytoma (P815) and melanoma (B16) cell lines. The concentrations of compounds required to inhibit the growth of these tumor cells by 50% is in the range of 10(-8)M. These compounds were also tested against a panel of human cancer cells by the National Cancer Institute, demonstrating that the compounds exhibited a high level of activity against selected solid tumors. At a concentration of 0.0084 microM (based on the IC(50) of compound 17 (seco-CBI-TMI) against the growth L1210 cells), while compounds 4 and 17 were toxic against murine bone marrow cells as judged by a colony forming study of freshly isolated murine progenitor hematopoeitic cells, compound 5, a seco-CFQ compound, was significantly less toxic. Flow cytometric analysis of P815 cells that had been incubated for 24h with compounds 4 and 5 at their cytotoxic IC(50) concentrations indicated the induction of apoptosis in a large percentage of cells, thereby suggesting that this might be the mechanism by which the iso-CFI compounds kill cells.


Human tumour clonality assessment--flawed but necessary.
One of the premises of the somatic mutation theory of carcinogenesis is that tumours are clonal lesions derived from a single mutated stem cell progenitor. This theory spawned a proliferation of clonality studies, using a variety of different molecular markers to try to determine tumour clonality in multiple organs. In order to establish true clonality, it is necessary to identify the original founding mutation that occurred at the initiation of the progenitor clone. Use of other lesions may only serve to identify sub-clones. As founding mutations have not been properly established in many organ systems, human clonality assessments carry this caveat. However it is only through clonality and mutation burden assessments that phylogenetic tress become established. Here, we review the advantages, disadvantages and use of different clonality markers.


Generalized Langevin dynamics: construction and numerical integration of non-Markovian particle-based models.
We propose a generalized Langevin dynamics (GLD) technique to construct non-Markovian particle-based coarse-grained models from fine-grained reference simulations and to efficiently integrate them. The proposed GLD model has the form of a discretized generalized Langevin equation with distance-dependent two-particle contributions to the self- and pair-memory kernels. The memory kernels are iteratively reconstructed from the dynamical correlation functions of an underlying fine-grained system. We develop a simulation algorithm for this class of non-Markovian models that scales linearly with the number of coarse-grained particles. Our GLD method is suitable for coarse-grained studies of systems with incomplete time scale separation, as is often encountered, e.g., in soft matter systems. We apply the method to a suspension of nanocolloids with frequency-dependent hydrodynamic interactions. We show that the results from GLD simulations perfectly reproduce the dynamics of the underlying fine-grained system. The effective speedup of these simulations amounts to a factor of about 104. Additionally, the transferability of the coarse-grained model with respect to changes of the nanocolloid density is investigated. The results indicate that the model is transferable to systems with nanocolloid densities that differ by up to one order of magnitude from the density of the reference system.


PSK protects macrophages from lipoperoxide accumulation and foam cell formation caused by oxidatively modified low-density lipoprotein.
In previous works, it has been evidenced that lipoperoxidative injury to macrophages caused by oxidatively modified low-density lipoprotein (O-LDL) plays an important role in foam cell formation, and that PSK, a protein bound polysaccharide extracted from the class Basidiomycetes Coriolus Versicolor, can protect macrophages from lipoperoxidative injury induced by tert-butyl hydroperoxide (tbOOH). In this paper PSK protection of macrophages from lipoperoxide (LPO) accumulation and foam cell formation caused by O-LDL and its action mechanism were further studied. The LPO accumulation was determined by using ACAS 570. Dynamic assay of the LPO level in eight single cells after adding O-LDL or determination of the average LPO content in a lot of cells incubated in advance with O-LDL for 12 h, both indicated that O-LDL might induce LPO accumulation in macrophages and the effects of O-LDL could be prevented by PSK. O-LDL might cause the changes of morphological structure in macrophages and the transformation of macrophages into foam cells, and the effects could also be prevented by PSK. The determination of selenium-dependent glutathione peroxidase (SeGSHPx) activities and mRNA contents of macrophages and changes of SeGSHPx activity and mRNA content after incubation with tbOOH showed that PSK might increase the SeGSHPx activity of macrophage and the enhanced SeGSHPx activity may occur at the level of gene transcription.


Buccal cell cytokeratin 14 identifies mild cognitive impairment and Alzheimer' s disease in the AIBL study of aging.
Previous studies have suggested that mild cognitive impairment (MCI) may be reflective of the early stages of neurodegenerative disorders such as Alzheimer's disease (AD). The hypothesis was that cytokeratin (CK) 14 expression can be used as a biomarker in isolated buccal mucosa to identify individuals with MCI or AD from the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging. Visual assessment of buccal cell CK14 expression was carried out using immunofluorescence techniques. The frequency of basal buccal cells expressing CK14 was significantly lower in the MCI (P=0.0002) and AD (P<0.05) groups compared with the control group. Receiver-operating characteristic (ROC) curves were carried out for CK14 expression and yielded an area under the curve (AUC) of 0.899 for the MCI (P<0.0001) group and 0.772 for the AD (P=0.004) group. When the CK14 expression data were combined with plasma homocysteine concentration, the AUC was further improved to 0.932 and 0.788 for the MCI (P=0.0001) and AD (P=0.004) groups, respectively. APOE ε4 carriers in the control group had 21% lower CK14 expression compared with control non APOE ε4 carriers, however this difference was not statistically significant. The changes in the buccal cell CK14 expression observed in this pilot study could prove useful as a potential biomarker in identifying individuals with an increased risk of developing MCI and eventually AD. These promising results need to be replicated in a larger subset of the AIBL cohort and in cohorts of other neurodegenerative disorders to determine changes specific to AD.


Overcompensatory population dynamic responses to environmental stochasticity.
1. To quantify the interactions between density-dependent, population regulation and density-independent limitation, we studied the time-series dynamics of an experimental laboratory insect microcosm system in which both environmental noise and resource limitation were manipulated. 2. A hierarchical Bayesian state-space approach is presented through which it is feasible to capture all sources of uncertainty, including observation error to accurately quantify the density dependence operating on the dynamics. 3. The regulatory processes underpinning the dynamics of two different bruchid beetles (Callosobruchus maculatus and Callosobruchus chinensis) are principally determined by environmental conditions, with fluctuations in abundance explained in terms of changes in overcompensatory dynamics and stochastic processes. 4. A general, stochastic population model is developed to explore the link between abundance fluctuations and the interaction between density dependence and noise. Taking account of time-lags in population regulation can substantially increase predicted population fluctuations resulting from underlying noise processes.


Search for supersymmetry with gauge-mediated breaking in diphoton events with missing transverse energy at CDF II.
We present the results of a search for supersymmetry with gauge-mediated breaking and chi(1)(0) --> gammaG in the gammagamma + missing transverse energy final state. In 2.6+/-0.2 fb(-1) of pp collisions at square root(s) = 1.96 TeV recorded by the CDF II detector we observe no candidate events, consistent with a standard model background expectation of 1.4+/-0.4 events. We set limits on the cross section at the 95% C.L. and place the world's best limit of 149 GeV/c2 on the chi(1)(0) mass at tau(chi(1)(0)) << 1 ns. We also exclude regions in the chi(1)(0) mass-lifetime plane for tau(chi(1)(0)) approximately < 2 ns.


Reliable PCR quantitation of estrogen, progesterone and ERBB2 receptor mRNA from formalin-fixed, paraffin-embedded tissue is independent of prior macro-dissection.
Gene expression analysis on messenger RNA (mRNA) purified from formalin-fixed, paraffin-embedded tissue is increasingly used for research purposes. Tissue heterogeneity may question specificity and interpretation of results from mRNA isolated from a whole slide section, and thresholds for minimal tumor content in the paraffin block or macrodissection are used to avoid contamination from non-neoplastic tissue. The aim was to test if mRNA from tissue surrounding breast cancer affected quantification of estrogen receptor α (ESR1), progesterone receptor (PGR) and human epidermal growth factor receptor 2 (ERBB2), by comparing gene expression from whole slide and tumor-enriched sections, and correlating gene expression from whole slide sections with corresponding immunohistochemistry. Gene expression, based on mRNA extracted from a training set (36 paraffin blocks) and two validation sets (133 + 1,083 blocks), were determined by quantitative reverse transcription polymerase chain reaction for all samples, as well as by microarray for 133 validation samples. In the training set, agreement between high vs. low mRNA expression from whole slide and tumor-enriched sections was absolute for ESR1 and ERBB2, and 83 % for PGR. Overall agreements, when comparing mRNA expression to immunohistochemistry, were 100 % (ERBB2), 89 % (ESR1) and 83 % (PGR), which was confirmed in the validation sets. Percentage of tumor in the sections did not influence the results. In conclusion, reliable quantification of ESR1, PGR and ERBB2 mRNA expression can be obtained from a whole slide section, and correlates well with immunohistochemistry. Prior removal of surrounding tissue was found to be unnecessary even with minimal tumor content in the section.


Sequentially shifted excitation Raman spectroscopy: novel algorithm and instrumentation for fluorescence-free Raman spectroscopy in spectral space.
A novel Raman spectrometer is presented in a handheld format. The spectrometer utilizes a temperature-controlled, distributed Bragg reflector diode laser, which allows the instrument to operate in a sequentially shifted excitation mode to eliminate fluorescence backgrounds, fixed pattern noise, and room lights, while keeping the Raman data in true spectral space. The cost-efficient design of the instrument allows rapid acquisition of shifted excitation data with a shift time penalty of less than 2 s. The Raman data are extracted from the shifted excitation spectra using a novel algorithm that is typically three orders of magnitude faster than conventional shifted-excitation algorithms operating in spectral space. The superiority of the instrument and algorithm in terms of background removal and signal-to-noise ratio is demonstrated by comparison to FT-Raman, standard deviation spectra, shifted excitation Raman difference spectroscopy (SERDS), and conventional multiple-shift excitation methods.


The transcription factor Lef1 switches partners from β-catenin to Smad3 during muscle stem cell quiescence.
Skeletal muscle stem cells (MuSCs), also known as satellite cells, persist in adult mammals by entering a state of quiescence (G0) during the early postnatal period. Quiescence is reversed during damage-induced regeneration and re-established after regeneration. Entry of cultured myoblasts into G0 is associated with a specific, reversible induction of Wnt target genes, thus implicating members of the Tcf and Lef1 (Tcf/Lef) transcription factor family, which mediate transcriptional responses to Wnt signaling, in the initiation of quiescence. We found that the canonical Wnt effector β-catenin, which cooperates with Tcf/Lef, was dispensable for myoblasts to enter quiescence. Using pharmacological and genetic approaches in cultured C2C12 myoblasts and in MuSCs, we demonstrated that Tcf/Lef activity during quiescence depended not on β-catenin but on the transforming growth factor-β (TGF-β) effector and transcriptional coactivator Smad3, which colocalized with Lef1 at canonical Wnt-responsive elements and directly interacted with Lef1 specifically in G0 Depletion of Smad3, but not β-catenin, reduced Lef1 occupancy at target promoters, Tcf/Lef target gene expression, and self-renewal of myoblasts. In vivo, MuSCs underwent a switch from β-catenin-Lef1 to Smad3-Lef1 interactions during the postnatal switch from proliferation to quiescence, with β-catenin-Lef1 interactions recurring during damage-induced reactivation. Our findings suggest that the interplay of Wnt-Tcf/Lef and TGF-β-Smad3 signaling activates canonical Wnt target promoters in a manner that depends on β-catenin during myoblast proliferation but is independent of β-catenin during MuSC quiescence.


An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice.
We describe a transgenic mouse line, Pax8-rtTA, which, under control of the mouse Pax8 promoter, directs high levels of expression of the reverse tetracycline-dependent transactivator (rtTA) to all proximal and distal tubules and the entire collecting duct system of both embryonic and adult kidneys. Using crosses of Pax8-rtTA mice with tetracycline-responsive c-MYC mice, we established a new, inducible model of polycystic kidney disease that can mimic adult onset and that shows progression to renal malignant disease. When targeting the expression of transforming growth factor beta-1 to the kidney, we avoided early lethality by discontinuous treatment and successfully established an inducible model of renal fibrosis. Finally, a conditional knockout of the gene encoding tuberous sclerosis complex-1 was achieved, which resulted in the early outgrowth of giant polycystic kidneys reminiscent of autosomal recessive polycystic kidney disease. These experiments establish Pax8-rtTA mice as a powerful tool for modeling renal diseases in transgenic mice.


First Report of Sphaeropsis Rot of Apple Caused by Sphaeropsis pyriputrescens in New York.
In March 2012, decayed 'Empire' apple fruit (Malus × domestica Borkh.) were sampled from apples grown in Albion (Orleans County) in New York State and stored in bins for 6 months under controlled atmosphere at a commercial packinghouse. At the packinghouse following storage prior to be packed, the fruit were completely rotten, spongy to firm, and light brown without pycnidia. All fruit rots originated from either stem-end or calyx-end infections but no wound infections were observed. The incidence of fruit with these symptoms in the total decay was relatively low (0.1%). To isolate the causal agent, small fragments of fruit flesh from 12 decayed fruit were cut and placed on potato dextrose agar (PDA) acidified with 0.1% lactic acid. The plates were incubated at 20°C for 4 days and sub-cultured on PDA to obtain a pure culture. The colonies initially appeared with dense hyaline mycelium and later turned light yellow to yellow, and black pycnidia formed after about 2 weeks of incubation under a 24-h fluorescent light at 20°C. Conidia were light brown to brown, clavate to subglobose to irregular, and 15 × 8 μm on average. The fungus was identified as Sphaeropsis pyriputrescens Xiao & J.D. Rogers based on the morphology of the fungus (3). The identity of a representative isolate was further confirmed by analysis of nucleotide sequences of the internal transcribed spacer (ITS) regions amplified using the primers ITS1/ITS4. A BLAST search in GenBank showed that the sequence had 99% homology to an S. pyriputrescens sequence (Accession No. GQ374241). One representative isolate was tested for pathogenicity on apple fruit. Organic 'Red Delicious' apple fruit were surface-disinfected in 0.6% sodium hypochlorite solution for 5 min, rinsed twice with deionized water, and air-dried. Each fruit was wounded with a sterilized finish-nail head (3 mm in depth and 4 mm in diameter) and inoculated by placing a 4-mm-diameter plug from the leading edge of a 4-day-old PDA culture on the wound. Control fruit were treated with sterile PDA plugs. The inoculation site was covered with two layers of moist cheesecloth to avoid dehydration. There were four 10-fruit replicates for each treatment, and fruit were placed in plastic crispers and stored at 4°C for 4 weeks. The experiments were conducted twice. Sphaeropsis rot developed on all inoculated fruit, while no decays appeared on the control fruit. Koch's postulates were fulfilled by reisolating the fungus from the decayed fruit. Sphaeropsis rot is a recently reported postharvest fruit rot disease of apple and pear (1,3). The disease was first observed on 'd'Anjou' pears, and later more serious economic losses were observed in apples in Washington State (1). The disease has also since been reported in British Columbia, Canada (2). To the best of our knowledge, this is the first report of the occurrence of Sphaeropsis rot caused by S. pyriputrescens on apple in New York or in any region outside of the Pacific Northwest in North America. References: (1) Y. K. Kim and C. L. Xiao. Plant Dis. 92:940, 2008. (2) P. L. Sholberg et al. Plant Dis. 93:843, 2009. (3) C. L. Xiao et al. Plant Dis. 88:223, 2004.


Antigen gene transfer to human plasmacytoid dendritic cells using recombinant adenovirus and vaccinia virus vectors.
Recombinant adenoviruses (RAd) and recombinant vaccinia viruses (RVV) expressing tumour-associated antigens (TAA) are used as anti-tumour vaccines. It is important that these vaccines deliver the TAA to dendritic cells (DC) for the induction of a strong immune response. Infection of myeloid DC (MDC) with RAd alone is relatively inefficient but CD40 retargeting significantly increases transduction efficiency and DC maturation. Infection with RVV is efficient without DC maturation. Plasmacytoid dendritic cells (PDC) play a role in the innate immune response to viral infections through the secretion of IFNalpha but may also play a role in specific T-cell induction. The aim of our study was to investigate whether PDC are better targets for RAd and RVV based vaccines. RAd alone hardly infected PDC (2%) while CD40 retargeting did not improve transduction efficiency, but it did increase PDC maturation (25% CD83 positive cells). Accordingly, specific CTL activation by RAd infected PDC was limited (the number of IFNgamma producing CTL was reduced by 75% compared to stimulation with peptide loaded PDC). RVV infected PDC specifically stimulated CTL but PDC were not activated. These results indicate that PDC are not ideal targets for RAd and RVV based vaccines. However, PDC induced specific CTL activation after pulsing with recombinant protein, indicating that PDC can also cross-present antigens released from surrounding infected cells.


Interleukin-12 regulation of host defenses against Coccidioides immitis.
We have previously reported on the alternate regulation of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) in inbred mouse strains which differ in their susceptibility to Coccidioides immitis. The genetically resistant DBA/2 mice manifest a predominant T-helper 1 (Th1) response, with early production of IFN-gamma, whereas susceptible BALB/c mice show an early production of the Th2 cytokine IL-4. Since IL-12 is one cytokine that can act early during host defenses to promote the differentiation of cytokine production towards IFN-gamma and thus may promote expression of a protective immune response, we investigated the role of IL-12 in resistance to C. immitis. Administration of recombinant IL-12 to the susceptible mouse strain before and after systemic (intraperitoneal) challenge with C. immitis significantly ameliorated the course of the disease, as measured by a reduction in the fungal load in the lungs, liver, and spleen. Analysis of the cytokine mRNA in lungs from infected BALB/c mice revealed that the protective effect of recombinant IL-12 was accompanied by a shift from a Th2 to a Th1 response. The importance of IL-12 in resistance to this fungus was further established by showing that neutralization of endogenous IL-12 in the resistant DBA/2 mouse strain led to a significant increase in the fungal burden in pulmonary and extrapulmonary tissues. These results establish that IL-12 plays a pivotal role in the host defense against systemic challenge with C. immitis.


Experimental detection of the actinospores of Myxobolus pseudodispar (Myxosporea: Myxobolidae) in oligochaete alternate hosts.
The development of Myxobolus pseudodispar Gorbunova, 1936, an intracellular myxosporean muscle parasite of the roach Rutilus rutilus L., was studied in experimentally infected oligochaetes. In one experiment, uninfected Tubifex tubifex Müller and Limnodrilus hoffmeisteri (Claparéde) were exposed to mature spores of M. pseudodispar. Triactinomyxon spores developed both in T. tubifex and L. hoffmeisteri specimens. Triactinospores were first released from the oligochaetes 76 d after initial exposure. At that time, pansporocysts containing 8 triactinospores were located in the gut epithelium of experimentally infected oligochaetes, but free actinosporean stages were also found in their gut lumen. Each triactinospore had 3 pyriform polar capsules and an elongated cylindrical sporoplasm with 8 secondary cells. The spore body joined the 3 caudal projections with a relatively long style. One of the 3 caudal projections was shorter than the other two. The total length of the triactinospore was on average 206.5 microns.


Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes.
We applied genome-wide allele-specific expression analysis of monocytes from 188 samples. Monocytes were purified from white blood cells of healthy blood donors to detect cis-acting genetic variation that regulates the expression of long non-coding RNAs. We analysed 8929 regions harboring genes for potential long non-coding RNA that were retrieved from data from the ENCODE project. Of these regions, 60% were annotated as intergenic, which implies that they do not overlap with protein-coding genes. Focusing on the intergenic regions, and using stringent analysis of the allele-specific expression data, we detected robust cis-regulatory SNPs in 258 out of 489 informative intergenic regions included in the analysis. The cis-regulatory SNPs that were significantly associated with allele-specific expression of long non-coding RNAs were enriched to enhancer regions marked for active or bivalent, poised chromatin by histone modifications. Out of the lncRNA regions regulated by cis-acting regulatory SNPs, 20% (n = 52) were co-regulated with the closest protein coding gene. We compared the identified cis-regulatory SNPs with those in the catalog of SNPs identified by genome-wide association studies of human diseases and traits. This comparison identified 32 SNPs in loci from genome-wide association studies that displayed a strong association signal with allele-specific expression of non-coding RNAs in monocytes, with p-values ranging from 6.7×10(-7) to 9.5×10(-89). The identified cis-regulatory SNPs are associated with diseases of the immune system, like multiple sclerosis and rheumatoid arthritis.


A Qualitative Systematic Review of Effects of Provider Characteristics and Nonverbal Behavior on Pain, and Placebo and Nocebo Effects.
Background: Previous research has indicated that the sex, status, and nonverbal behaviors of experimenters or clinicians can contribute to reported pain, and placebo and nocebo effects in patients or research participants. However, no systematic review has been published. Objective: The aim of this study was to investigate the effects of experimenter/clinician characteristics and nonverbal behavior on pain, placebo, and nocebo effects. Methods: Using EmBase, Web of Knowledge, and PubMed databases, several literature searches were conducted to find studies that investigated the effects of the experimenter's/clinician's sex, status, and nonverbal behaviors on pain, placebo, and nocebo effects. Results: Thirty-four studies were included, 20 on the effects of characteristics of the experimenter/clinician, 11 on the role of nonverbal behaviors, and 3 on the effects of both nonverbal behaviors and characteristics of experimenters/clinicians on pain and placebo/nocebo effects. There was a tendency for experimenters/clinicians to induce lower pain report in participants of the opposite sex. Furthermore, higher confidence, competence, and professionalism of experimenters/clinicians resulted in lower pain report and higher placebo effects, whereas lower status of experimenters/clinicians such as lower confidence, competence, and professionalism generated higher reported pain and lower placebo effects. Positive nonverbal behaviors (e.g., smiling, strong tone of voice, more eye contact, more leaning toward the patient/participant, and more body gestures) contributed to lower reported pain and higher placebo effects, whereas negative nonverbal behaviors (i.e., no smile, monotonous tone of voice, no eye contact, leaning backward from the participant/patient, and no body gestures) contributed to higher reported pain and nocebo effects. Conclusion: Characteristics and nonverbal behaviors of experimenters/clinicians contribute to the elicitation and modulation of pain, placebo, and nocebo effects.


Oxidative stress and antioxidant status in patients with erectile dysfunction.
Erectile dysfunction (ED) is increasingly recognized as a public health problem. The interaction between nitric oxide and reactive oxygen species is one of the important mechanisms implicated in the pathophysiological process of ED. Plasma contains various antioxidant components to prevent free-radical injury. The aim of this study was to determine and compare the oxidative and antioxidant status of peripheral venous blood in patients with ED of arteriogenic and non-arteriogenic origin. Oxidative stress and antioxidant status were assessed in 40 patients with ED and 20 healthy controls. Plasma reactive oxygen metabolite (ROM) concentrations were measured as an indicator of oxidative stress, and plasma total antioxidant status (TAS) to indicate antioxidant defense. Plasma ROM concentrations were higher (349.75 +/- 53.35 standard deviation [SD] U.Carr vs. 285.43 +/- 25.58 U.Carr, P < 0.001) and plasma TAS lower (0.54 +/- 0.16 SD mmol/L vs. 0.94 +/- 0.28 SD mmol/L, P < 0.0001) in patients with arteriogenic ED in comparison to those in patients with non-arteriogenic ED. Plasma ROM and TAS in controls were not significantly different from those in non-arteriogenic ED. Conclusions. This observation may be useful to better understand and distinguish arteriogenic from non-arteriogenic ED using laboratory tests. In addition, our findings provide important support for an antioxidant therapy to try to correct oxidative stress in arteriogenic ED patients.


A fall-off in cervical screening coverage of younger women in developed countries.
To analyse cervical screening coverage data by age over time in a number of developed countries throughout the world, with specific emphasis on trends for younger women and on age differentials between younger and older women. Routinely collected cervical screening statistics and survey data were collected on the proportion of women who have undergone cervical screening with cytology in seven countries in the period 1995 to 2005. Data for the 25-29 age group were examined. Coverage fell in most countries, in three by more than 5 percentage points. In two countries while overall coverage rose in the period, the rise was not as steep in the youngest group of women. Data for each available 5-year age group for the different countries shows a similar gradient in most, regardless of the absolute level of coverage. Although the trend is not uniform in every country, it appears that generally the gap between coverage of younger women and coverage of older women increased, sometimes dramatically, between the mid-1990s and the mid-2000s. There is a general trend in developed countries towards lower coverage in young women (25-29 years old). No common underlying cause has been clearly identified and there is a need for further studies to investigate the possible reasons for this phenomenon.


Reversible inhibition/activation of olefin metathesis: a kinetic investigation of ROMP and RCM reactions with Grubbs' catalyst.
The metathesis activity of Grubbs' catalyst 1 was investigated in the presence of N-donor ligands (1-methylimidazole [MIM], 4-(N,N-dimethylamino)pyridine [DMAP], pyridine, and 1-octylimidazole [OIM]). Ring opening metathesis polymerization (ROMP) reactions of cyclooctene (COE), bulk-ROMP reactions of COE and norbornadiene (NBD), and ring closing metathesis (RCM) reactions of diethyl diallylmalonate (DEDAM) were conducted containing various equivalents of N-donor with respect to catalyst. ROMP reactions could be stopped using MIM (1-5 equiv) and DMAP (2-5 equiv), and slowed with pyridine (1-5 equiv) by factors >100, in benzene solution for 24 h. The stopped reactions could be initiated with excess phosphoric acid (H3PO4), and the reactions proceeded faster than with uninhibited Grubbs' catalyst in the first 4 min after reactivation. Thereafter, the reaction proceeded at the same rate as the reaction with the uninhibited catalyst. ROMP reactions in neat COE and NBD could be inhibited for 72 h using 2 equiv of MIM, DMAP, or OIM and activated with H3PO4 to give polymer gels within minutes or less. RCM reactions could be completely inhibited with MIM (1-5 equiv), but upon treatment with H3PO4, the reaction would proceed at a fraction of the initial rate accomplished by uninhibited Grubbs' catalyst 1. A structural investigation of the inhibited species showed that MIM and DMAP completely or partially transform catalyst 1 into the hexacoordinate species 5a or 5b producing free PCy3, which additionally acts as an inhibitor for the ROMP reaction. Upon reactivation, the PCy3 is protonated along the N-donor ligand; however, over the period of 5 min, the phosphine has been found to coordinate back to the ruthenium catalyst. Therefore, the reaction slows to the same polymerization rate as the reaction using the uninhibited catalyst at this point. Complexes 5a and 5b were isolated, characterized, and employed in ROMP and RCM experiments where they exhibited very low catalytic activity.


Yersinia pestis evolution on a small timescale: comparison of whole genome sequences from North America.
Yersinia pestis, the etiologic agent of plague, was responsible for several devastating epidemics throughout history and is currently of global importance to current public heath and biodefense efforts. Y. pestis is widespread in the Western United States. Because Y. pestis was first introduced to this region just over 100 years ago, there has been little time for genetic diversity to accumulate. Recent studies based upon single nucleotide polymorphisms have begun to quantify the genetic diversity of Y. pestis in North America. To examine the evolution of Y. pestis in North America, a gapped genome sequence of CA88-4125 was generated. Sequence comparison with another North American Y. pestis strain, CO92, identified seven regions of difference (six inversions, one rearrangement), differing IS element copy numbers, and several SNPs. The relatively large number of inverted/rearranged segments suggests that North American Y. pestis strains may be undergoing inversion fixation at high rates over a short time span, contributing to higher-than-expected diversity in this region. These findings will hopefully encourage the scientific community to sequence additional Y. pestis strains from North America and abroad, leading to a greater understanding of the evolutionary history of this pathogen.


In vitro stimulation of metacyclogenesis in Leishmania braziliensis, L. donovani, L. major and L. mexicana.
Promastigotes of Leishmania braziliensis, L. donovani, L. major and L. mexicana recently derived from tissue amastigotes were cultured in Schneider's Drosophila medium supplemented with 20% (v/v) heat-inactivated foetal calf serum and 25 micrograms gentamicin sulfate/ml at pH 5.5. These cultures produced more metacyclic promastigotes in their stationary-phase populations than others cultured at pH 7.0. Metacyclic promastigotes possessed a short (< or = 8 microns) and narrow (< or = 1.5 microns) cell body with a flagellum twice or more the length of the cell body. Promastigotes from acidic cultures were more resistant to complement-mediated lysis and more infective in vivo than those grown at neutral pH. These results demonstrate that induction of metacyclogenesis by acidic pH is a response conserved across a variety of species of Leishmania.


Development and validation of a high-throughput calcium mobilization assay for the orphan receptor GPR88.
GPR88 is an orphan G protein-coupled receptor highly expressed in the striatum and is implicated in basal ganglia-associated disorders. However, the receptor functions of GPR88 are still largely unknown due to the lack of potent and selective ligands appropriate for central nervous system investigation. Development of a high-throughput screening assay for GPR88 should facilitate the discovery of novel ligands to probe GPR88 functions. In this paper, we describe the development of a CHO-Gαqi5-GPR88 cell-based calcium mobilization assay. The assay takes advantage of functional coupling of GPR88 with the promiscuous Gαqi5 protein and consequent mobilization of intracellular calcium, which can be measured in a 384-well format with a Fluorescent Imaging Plate Reader. The CHO-Gαqi5-GPR88 cell-based calcium mobilization assay was validated by the structure-activity relationship study of known GPR88 agonist (1R,2R)-2-PCCA analogues. The assay was automated and miniaturized to a 384-well format, and was deemed robust and reproducible with a Z'-factor of 0.72 and tolerated dimethyl sulfoxide to a final concentration of 2%. Screening a pilot neurotransmitter library consisting of 228 compounds yielded 10 hits, but none of the hits were confirmed as GPR88 agonists in follow-up assays. We have developed a high-throughput calcium mobilization assay for the orphan receptor GPR88. This calcium mobilization assay can be used to identify several different types of GPR88 ligands including agonists, competitive and noncompetitive antagonists, inverse agonists, and allosteric modulators. These ligands will serve as valuable tools to probe signaling mechanisms and in vivo functions of GPR88, and could expedite development of novel therapies for diseases potentially mediated by GPR88.


Consumption, drugs and style: Constructing intra-ethnic boundaries in Asian American youth cultures.
Based on 250 qualitative interviews with Asian American young men and women in the dance/club scenes in the San Francisco area, we examine the interplay between consumption, style and taste cultures with issues of ethnic identity, gender and acculturation. We explore the ways that consumption and taste markers (e.g. fashion, cars, music and drugs) are used to establish or negotiate symbolic boundaries between groups in this youth culture. The picture they paint of the dance scene is one less about cohesiveness and unity and more about divisions and boundaries, not only between but also significantly within ethnic groupings. The choice of drugs and ways of exhibiting intoxication are among the types of consumption that the young people drew upon to mark symbolic boundaries and establish identities. The young men and women in this study discuss a number of key boundaries in the scene, e.g. between FOBs and twinkies, between pretty boys and thugs, as they attempt to establish the cultural legitimacy of their own styles of Asian American identities.


Level of knowledge about anaphylaxis and its management among health care providers.
This study was conducted to assess the level of knowledge of health care providers regarding anaphylaxis and its management at a tertiary care teaching hospital. A pretested structured questionnaire was administered to interns, MBBS Phase II students, and nursing students. The subjects were asked to answer the questionnaire, which included questions regarding anaphylaxis and its management. Of 265 subjects, 151 (56.9%) of subjects answered correctly that adrenaline is the first line of drug for the treatment of anaphylaxis. Among 151 subjects, 40 (26.4%) answered the correct dose of adrenaline, of which 25 (16.5%) subjects selected intramuscular injection as the most appropriate route of administration. Medical students' performance was better than interns and nursing students on questions regarding dose, route, and site of adrenaline administration. Knowledge regarding the management of anaphylaxis was inadequate in almost all the health care providers who were included in the study. Improved education and training of health care providers are necessary for better management of anaphylaxis.


Identification of an inhibitory MHC receptor on alloreactive rat natural killer cells.
Studies of allogeneic lymphocyte cytotoxicity have shown that the rat NK allorecognition repertoire is controlled by genetic elements in both the MHC (RT1) and the NK gene complex (NKC). DA rats, possessing NK cells that are unable to lyse allogeneic lymphoblasts, were immunized with alloreactive NK cells from MHC-matched PVG.1AV1 rats, and two mAb, STOK1 and STOK2, were generated. STOK1 and STOK2 stained identical subsets of NKR-P1+ T and NK cells from certain strains of rats. Relative numbers varied markedly in a panel of MHC congenic strains, however, implicating a role for self MHC genes in their development. Both STOK1 and STOK2 immunoprecipitated a 110-kDa disulfide-linked homodimeric molecule, with extensive N-linked glycosylations, encoded by a gene that mapped to the NKC. NK cells expressing this glycoprotein displayed an increased ability to lyse allogeneic lymphoblasts, while syngeneic targets were spared. However, blockade of the STOK2 Ag with F(ab')2 of STOK2 permitted the NK lysis of syngeneic targets, but did not affect NK allorecognition. These results indicate that mAb STOK1 and STOK2 identify an NKC-encoded MHC receptor in the rat that acts as a negative regulator of cytotoxicity.


Economic costs associated with moderate and late preterm birth: a prospective population-based study.
We sought to determine the economic costs associated with moderate and late preterm birth. An economic study was nested within a prospective cohort study. Infants born between 32(+0) and 36(+6) weeks of gestation in the East Midlands of England. A sample of infants born at ≥37 weeks of gestation acted as controls. Data on resource use, estimated from a National Health Service (NHS) and personal social services perspective, and separately from a societal perspective, were collected between birth and 24 months corrected age (or death), and valued in pounds sterling, at 2010-11 prices. Descriptive statistics and multivariable analyses were used to estimate the relationship between gestational age at birth and economic costs. Cumulative resource use and economic costs over the first two years of life. Of all eligible births, 1146 (83%) preterm and 1258 (79%) term infants were recruited. Mean (standard error) total societal costs from birth to 24 months were £12 037 (£1114) and £5823 (£1232) for children born moderately preterm (32(+0) -33(+6) weeks of gestation) and late preterm (34(+0) -36(+6) weeks of gestation), respectively, compared with £2056 (£132) for children born at term. The mean societal cost difference between moderate and late preterm and term infants was £4657 (bootstrap 95% confidence interval, 95% CI £2513-6803; P < 0.001). Multivariable regressions revealed that, after controlling for clinical and sociodemographic characteristics, moderate and late preterm birth increased societal costs by £7583 (£874) and £1963 (£337), respectively, compared with birth at full term. Moderate and late preterm birth is associated with significantly increased economic costs over the first 2 years of life. Our economic estimates can be used to inform budgetary and service planning by clinical decision-makers, and economic evaluations of interventions aimed at preventing moderate and late preterm birth or alleviating its adverse consequences. Moderate and late preterm birth is associated with increased economic costs over the first 2 years of life.


Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.
Hodgkin's disease patients who never achieve complete remission with conventional chemotherapy (i.e., those with primary induction failure) have a poor prognosis. Some subjects who receive high-dose therapy with autologous hematopoietic progenitor-cell infusion experience prolonged progression-free survival. Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed to achieve complete remission after one or more conventional therapy regimens and subsequently received an autotransplant between 1989 and 1995 were reviewed. Median age was 27 years (range, 7 to 57 years). Median time from diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients received high-dose chemotherapy without radiation for pretransplantation conditioning (n = 107). The regimen most frequently used was cyclophosphamide, carmustine, and etoposide (n = 47). Fifteen patients received total-body irradiation (n = 15). The graft consisted of bone marrow (n = 86), blood stem cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence interval, 7% to 19%). Sixty patients (50%) were considered to have achieved complete remission after autotransplantation; 37 of these had negative imaging studies, whereas scan abnormalities of unknown significance persisted in 23 patients. Twenty-seven patients (22%) had no response or progressive disease after transplantation. Probabilities of progression-free and overall survival at 3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence interval, 39% to 60%), respectively. In multivariate analysis, "B" symptoms at diagnosis and poor performance score at transplantation were adverse prognostic factors for outcome. Autotransplants should be considered for patients with Hodgkin's disease who do not achieve complete remission with conventional therapy.


Connect MM Registry: The Importance of Establishing Baseline Disease Characteristics.
Connect MM is the first and largest observational, noninterventional, prospective registry of patients newly diagnosed with multiple myeloma (NDMM) in the United States. It collects longitudinal data on patients within clinical practice including patients in clinical trials. Of the 1513 patients enrolled, 1493 were protocol-eligible. Median age was 67 years, 81.9% (1223/1493) were Caucasian, and 57.2% (854/1493) were male. Of these patients, 26.5% (232/877) were International Staging System stage I, 34.9% (306/877) stage II, and 38.7% (339/877) stage III. Eastern Cooperative Oncology Group performance status of 0/1/2 were reported in 96.6% (1017/1053). Clonal plasma cells > 10% were found in 91.6% (1282/1399) of patients and M-component in 98.8% (1343/1359). Hypercalcemia was present in 7.3% (108/1481) of patients, serum creatinine > 2 mg/dL in 18.3% (271/1484), anemia in 45.1% (673/1493), and bone involvement in 76.7% (1143/1490). Of the 15 National Comprehensive Cancer Network (NCCN) recommended diagnostic tests, a median of 12 were performed. Lactate dehydrogenase assessment, serum free light chain ratio, and immunofixation were reported in 38.4% (574/1493), 62.1% (927/1493), and 66% (985/1493) of patients, respectively. Quantitative immunoglobulin, β-2 microglobulin, and protein electrophoresis (serum or urine) were reported in 72.3% (1080/1493), 74.1% (1107/1493), and 78.0% (1164/1493) of patients, respectively. Bone marrow biopsy was reported in 92.2% (1376/1493), but conventional cytogenetic and fluorescence in situ hybridization analysis were reported in only 63.2% (944/1493) and 59.8% (893/1493) of patients, respectively. A high-risk cytogenetic profile (according to International Myeloma Working Group [IMWG] criteria) was found in 16.9% (253/1493). This analysis provides insight into the demographic and disease characteristics of NDMM patients in a range of clinical practices. Creating solid records of baseline patient disease characteristics using suggested NCCN diagnostic work-up and IMWG criteria provides a foundation for monitoring disease progression and response to treatment.


Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial.
The generation of key uremic nephrovascular toxins, indoxyl sulfate (IS), and p-cresyl sulfate (PCS), is attributed to the dysbiotic gut microbiota in CKD. The aim of our study was to evaluate whether synbiotic (pre- and probiotic) therapy alters the gut microbiota and reduces serum concentrations of microbiome-generated uremic toxins, IS and PCS, in patients with CKD. Predialysis adult participants with CKD (eGFR=10-30 ml/min per 1.73 m(2)) were recruited between January 5, 2013 and November 12, 2013 to a randomized, double-blind, placebo-controlled, crossover trial of synbiotic therapy over 6 weeks (4-week washout). The primary outcome was serum IS. Secondary outcomes included serum PCS, stool microbiota profile, eGFR, proteinuria-albuminuria, urinary kidney injury molecule-1, serum inflammatory biomarkers (IL-1β, IL-6, IL-10, and TNF-α), serum oxidative stress biomarkers (F2-isoprostanes and glutathione peroxidase), serum LPS, patient-reported health, Gastrointestinal Symptom Score, and dietary intake. A prespecified subgroup analysis explored the effect of antibiotic use on treatment effect. Of 37 individuals randomized (age =69±10 years old; 57% men; eGFR=24±8 ml/min per 1.73 m(2)), 31 completed the study. Synbiotic therapy did not significantly reduce serum IS (-2 μmol/L; 95% confidence interval [95% CI], -5 to 1 μmol/L) but did significantly reduce serum PCS (-14 μmol/L; 95% CI, -27 to -2 μmol/L). Decreases in both PCS and IS concentrations were more pronounced in patients who did not receive antibiotics during the study (n=21; serum PCS, -25 μmol/L; 95% CI, -38 to -12 μmol/L; serum IS, -5 μmol/L; 95% CI, -8 to -1 μmol/L). Synbiotics also altered the stool microbiome, particularly with enrichment of Bifidobacterium and depletion of Ruminococcaceae. Except for an increase in albuminuria of 38 mg/24 h (P=0.03) in the synbiotic arm, no changes were observed in the other secondary outcomes. In patients with CKD, synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome. Large-scale clinical trials are justified.


Assessment of new sequencing information for genetically modified cotton DAS-24236-5 × DAS-21Ø23-5.
The GMO Panel has previously assessed genetically modified (GM) cotton DAS-24236-5 × DAS-21Ø23-5 and concluded that it is as safe as its conventional counterpart and other appropriate comparators with respect to potential effects on human and animal health and the environment in the context of its intended uses. On 17 November 2020, the European Commission requested EFSA to evaluate new DNA sequence information and updated bioinformatics data for cotton DAS-24236-5 × DAS-21Ø23-5 and to indicate whether the conclusions of the GMO Panel on the previously assessed cotton DAS-24236-5 × DAS-21Ø23-5 remain valid. The new sequence data of DAS-24236-5 showed the change of one nucleotide that results in one amino acid substitution, in the newly expressed Cry1F (synpro_L620Q) compared to the sequence originally reported. The GMO Panel concludes that this amino acid substitution in the protein is a mutation. Nonetheless with the exception of the bioinformatics analysis, the studies performed for the risk assessment of Cry1F in cotton DAS-24236-5 × DAS-21Ø23-5 remain valid. In addition, the new sequencing data showed a change in one nucleotide in the 5' flanking region of DAS-21Ø23-5 compared to the original sequence reported on the stack cotton DAS-24236-5 × DAS-21Ø23-5. The bioinformatic analyses of the newly sequenced DAS-21Ø23-5 event in the stack DAS-24236-5 × DAS-21Ø23-5 shows that the nucleotide difference is in the 5' flanking region outside the ORFs that span the 5' junction and is therefore not considered further in the safety assessment. Based on the information provided, the GMO Panel concludes that the corrected sequence does not give rise to any safety concerns, and therefore, the original risk assessment of cotton DAS-24236-5 × DAS-21Ø23-5 remains valid.


Control over the magnetism and transition between high- and low-spin states of an adatom on trilayer graphene.
Using density-functional theory, we investigate the electronic and magnetic properties of an adatom (Na, Cu and Fe) on ABA- and ABC-stacked (Bernal and rhombohedral) trilayer graphenes. In particular, we study the influence of an applied gate voltage on magnetism, as it modifies the electronic states of the trilayer graphene (TLG) as well as changes the adatom spin states. Our study performed for a choice of three different adatoms (Na, Cu, and Fe) shows that the nature of adatom-graphene bonding evolves from ionic to covalent in moving from an alkali metal (Na) to a transition metal (Cu or Fe). Applying an external electric field (EEF) to TLG systems with different stacking orders results in the transition between high- and low-spin states in the latter case (Cu, Fe) and induces a little of magnetism in the former (Na) without magnetism in the absence of an external electric field. Our study would be useful for controlled adatom magnetism and (organic) spintronic applications in nanotechnology.


Using multiple sources of data to assess the prevalence of diabetes at the subcounty level, Duval County, Florida, 2007.
Diabetes rates continue to grow in the United States. Effectively addressing the epidemic requires better understanding of the distribution of disease and the geographic clustering of factors that influence it. Variations in the prevalence of diabetes at the local level are largely unreported, making understanding the disparities associated with the disease more difficult. Diabetes death rates during the past 15 years in Duval County, Florida, have been disproportionately high compared with the rest of the state. We analyzed multiple sources of secondary data related to diabetes illness and death in Duval County, including data on hospital discharge, emergency department (ED) use, and vital statistics. We accessed diabetes and diabetes-related ED use and hospitalization and death data by using codes from the International Classification of Diseases versions 9 and 10. We analyzed data from the Behavioral Risk Factor Surveillance System survey for Duval County and adapted Centers for Disease Control and Prevention weighting formulas for subcounty analysis. We used relative risk-type disease ratios and geographic information systems mapping to analyze data. The urban, mostly minority, low-socioeconomic area of Duval County had twice the rate of diabetes-related illness and death as other areas of the county, and the inner-city, poor area of the county had almost 3 times the rate of hospitalization and ED use for diabetes and diabetes-related conditions compared with the other areas of the county. Our analyses show that diabetes-related disparities affect not only people and their families but also the community that absorbs the costs associated with the disproportionate health care use that results from these disparities. Analyzing data at the subcounty level has implications for health care planning and public health policy development at the local level.


A comparison of muscular activity during single and double mouse clicks.
Work-related musculoskeletal disorders (WMSDs) in the neck/shoulder region and the upper extremities are a common problem among computer workers. Occurrences of motor unit (MU) double discharges with very short inter-firing intervals (doublets) have been hypothesised as a potential additional risk for overuse of already exhausted fibres during long-term stereotyped activity. Doublets are reported to be present during double-click mouse work tasks. A few comparative studies have been carried out on overall muscle activities for short-term tasks with single types of actions, but none on occurrences of doublets during double versus single clicks. The main purpose of this study was to compare muscle activity levels of single and double mouse clicks during a long-term combined mouse/keyboard work task. Four muscles were studied: left and right upper trapezius, right extensor digitorum communis (EDC) and right flexor carpi ulnaris. Additionally, MU activity was analysed through intramuscular electromyography in the EDC muscle for a selection of subjects. The results indicate that double clicking produces neither higher median or 90th percentile levels in the trapezius and EDC muscles, nor a higher disposition for MU doublets, than does single clicking. Especially for the 90th percentile levels, the indications are rather the opposite (in the EDC significantly higher during single clicks in 8 of 11 subjects, P < 0.05). Although it cannot be concluded from the present study that double clicks are harmless, there were no signs that double clicks during computer work generally constitute a larger risk factor for WMSDs than do single clicks.


Genome-wide linkage scans for loci affecting total cholesterol, HDL-C, and triglycerides: the Family Blood Pressure Program.
Atherosclerosis accounts for 75% of all deaths from cardiovascular disease and includes coronary heart disease (CHD), stroke, and other diseases of the arteries. More than half of all CHD is attributable to abnormalities in levels and metabolism of lipids. To locate genes that affect total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglycerides, genome-wide linkage scans for quantitative trait loci were performed using variance components methods as implemented in SOLAR on a large diverse sample recruited as part of the Family Blood Pressure Program. Phenotype and genetic marker data were available for 9,299 subjects in 2,953 families for total cholesterol, 8,668 subjects in 2,736 families for HDL, and 7,760 subjects in 2,499 families for triglycerides. Mean lipid levels were adjusted for the effects of sex, age, age2, age-by-sex interaction, body mass index, smoking status, and field center. HDL-C and triglycerides were further adjusted for average total alcoholic drinks per week and estrogen use. Significant linkage was found for total cholesterol on chromosome 2 (LOD=3.1 at 43 cM) in Hispanics and for HDL-C on chromosome 3 (LOD=3.0 at 182 cM) and 12 (LOD=3.5 at 124 cM) in Asians. In addition, there were 13 regions that showed suggestive linkage (LOD >or= 2.0); 7 for total cholesterol, 4 for HDL, and 2 for triglycerides. The identification of these loci affecting lipid phenotypes and the apparent congruence with previous linkage results provides increased support that these regions contain genes influencing lipid levels.


Disability as a function of social networks and support in elderly African Americans and Whites: the Duke EPESE 1986--1992.
We examined the association of structural and functional aspects of social relationships with change in disability, and the degree to which race modifies these associations. Data are from a population-based sample of 4,136 African Americans and Whites aged > or = 65 living in North CAROLINA: Disability data were collected during seven consecutive yearly interviews and summarized in two outcome measures. Measures of social relationships included five measures representing network size, extent of social interaction, and specific type of relationships, as well as instrumental and emotional support. Weighted proportional odds models were fitted to model disability as a function of baseline social network and support variables, and the interaction of each variable with follow-up time. Network size and social interaction showed significant negative associations with disability risks, which did not vary by race, or as a function of time. Social interaction with friends was associated with a reduced risk for disability, but social interaction with children or relatives was not related to disability. Instrumental support was associated with a significantly increased disability risk, with a greater adverse effect among Whites than African AMERICANS: Emotional support was not associated with disability, but a protective effect for ADL disability was found after controlling for its intercorrelation with instrumental support. The findings provide further evidence for the role of social relationships in the disablement process, although not all types of social relationships may be equally beneficial. Furthermore, these associations may be more complex than simple causal effects. There were few racial differences in the association of social relationships with disability, with the possible exception of instrumental support, which may allude to possible sociocultural differences in the experience of instrumental support exchanges.


Lack of Knowledge Contrasts the Willingness to Counteract Sarcopenia Among Community-Dwelling Adults.
Objective: Sarcopenia is highly prevalent in older adults. Knowledge among community-dwelling adults is important for effective prevention and treatment of sarcopenia. This study aims to assess current knowledge about sarcopenia, investigate willingness for treatment and prevention, and awareness of muscle health. Method: Participants who attended health educational events completed a questionnaire on knowledge about sarcopenia. Self-perceived muscle health was assessed by visual analog scale. Objective muscle measures included muscle mass, handgrip strength, and gait speed. Results: Included participants were 197 (median aged 67.9 years [interquartile range = 57.0-75.1]). Eighteen participants (9%) reported to know what sarcopenia is. Participants' self-perceived muscle health showed a low correlation with all objective muscle measures. 76% were willing, in case of sarcopenia diagnosis, to start treatment and 71% were willing to prevent sarcopenia. Discussion: Knowledge about sarcopenia is limited while participants were willing to start treatment and prevention. Strategies to increase knowledge among community-dwelling adults are needed.


Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium.
While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient.


On multirate optimality of JPEG2000 code stream.
Arguably, the most important and defining feature of the JPEG2000 image compression standard is its R-D optimized code stream of multiple progressive layers. This code stream is an interleaving of many scalable code streams of different sample blocks. In this paper, we reexamine the R-D optimality of JPEG2000 scalable code streams under an expected multirate distortion measure (EMRD), which is defined to be the average distortion weighted by a probability distribution of operational rates in a given range, rather than for one or few fixed rates. We prove that the JPEG2000 code stream constructed by embedded block coding of optimal truncation is almost optimal in the EMRD sense for uniform rate distribution function, even if the individual scalable code streams have nonconvex operational R-D curves. We also develop algorithms to optimize the JPEG2000 code stream for exponential and Laplacian rate distribution functions while maintaining compatibility with the JPEG2000 standard. Both of our analytical and experimental results lend strong support to JPEG2000 as a near-optimal scalable image codec in a fairly general setting.


The use of complementary and integrative health approaches for chronic musculoskeletal pain in younger US Veterans: An economic evaluation.
To estimate the cost-effectiveness to the US Veterans Health Administration (VA) of the use of complementary and integrative health (CIH) approaches by younger Veterans with chronic musculoskeletal disorder (MSD) pain. VA healthcare system. We used a propensity score-adjusted hierarchical linear modeling (HLM), and 2010-2013 VA administrative data to estimate differences in VA healthcare costs, pain intensity (0-10 numerical rating scale), and opioid use between CIH users and nonusers. We identified CIH use in Veterans' medical records through Current Procedural Terminology, VA workload tracking, and provider-type codes. We identified 30,634 younger Veterans with chronic MSD pain as using CIH and 195,424 with no CIH use. CIH users differed from nonusers across all baseline covariates except the Charlson comorbidity index. They also differed on annual pre-CIH-start healthcare costs ($10,729 versus $5,818), pain (4.33 versus 3.76), and opioid use (66.6% versus 54.0%). The HLM results indicated lower annual healthcare costs (-$637; 95% CI: -$1,023, -$247), lower pain (-0.34; -0.40, -0.27), and slightly higher (less than a percentage point) opioid use (0.8; 0.6, 0.9) for CIH users in the year after CIH start. Sensitivity analyses indicated similar results for three most-used CIH approaches (acupuncture, chiropractic care, and massage), but higher costs for those with eight or more CIH visits. On average CIH use appears associated with lower healthcare costs and pain and slightly higher opioid use in this population of younger Veterans with chronic musculoskeletal pain. Given the VA's growing interest in the use of CIH, further, more detailed analyses of its impacts are warranted.


The effect of an ambulatory internal medicine rotation on students' career choices.
To assess the effect of an ambulatory care experience on medical students' perceptions of internal medicine and their choices of careers (as measured by residency selections). In 1990-91, the 196 third-year students enrolled in the 12-week internal medicine clerkship at the University of Texas Medical School at San Antonio were randomized to a curriculum that included a three-week ambulatory care component or to a traditional, exclusively inpatient curriculum. The ambulatory curriculum included the evaluation of walk-in-patients, exposure to community internists, and a lecture series. The students' perceptions of internal medicine were surveyed before and after the clerkship. Their career choices were determined by their residency selections at graduation. Data analysis employed chi-square tests, t-tests, and logistic regression. Of the 196 students, 184 (76 in the ambulatory and 108 in the traditional curricula) provided complete data. The ambulatory care students were somewhat more likely to enter an internal medicine residency (odds ratio = 1.49; 95% CI, 0.72 to 3.09) than were the traditional students. The ambulatory care students' perceptions of internal medicine did not change significantly from before to after the clerkship. The ambulatory curriculum had a modest but favorable effect on the students' selections of careers in internal medicine, but was not associated with changes in their perceptions of internal medicine.


[Photodynamic diagnostics in the urinary tract. Consensus paper of the Working Group for Oncology of the German Society for Urology].
Because of the frequency of occurrence and the long protracted course, bladder carcinoma is the most expensive solid tumor in terms of costs, from diagnosis to death of the patient. The most important cost factor within the total cost is the treatment of recurrent, non-muscle invasive bladder carcinoma. Photodynamic diagnosis (PDD) improves the early detection rate of non-muscle invasive bladder cancer, especially the detection of carcinoma in situ and severe dysplasia. PDD also reduces the number of residual tumors after TUR-B compared to white-light guided TUR-B and also the early recurrence rate although long-term outcome with hexylaminolaevulinic acid with regards to the general course of bladder cancer is still lacking. PDD has been used mainly for detection of bladder cancer and specifically carcinoma in situ in conjunction with diagnostic and therapeutic transurethral resection of the bladder. In 2006 hexylaminolaevulinic acid (HAL) was approved in the EU (EMEA) as a photosensitizer for the use in photodynamic diagnosis of the bladder. Several guidelines have incorporated PDD as optional form of diagnosis during endoscopy in proven or suspected bladder cancer, but no specific recommendations regarding indication and application of PDD exist. The German group of urologic oncology (AKO) invited urologists and biologists involved in the development of hexylaminolaevulinic acid as well its clinical use to participate in evaluating the data for HAL and its predecessor delta-aminolaevulinic acid (5-ALA). A consensus with regards to the indications, contraindications, technique, pre-clinical data, comparison of HAL and 5-ALA, current results, costs and follow-up was reached and are presented in this paper.


Association between Emotional Eating and Frequency of Unhealthy Food Consumption among Taiwanese Adolescents.
Emotional eating is one factor that increases the consumption of unhealthy food. This study aimed to investigate the association between emotional eating and frequencies of consuming fast food, high-fat snacks, processed meat products, dessert foods, and sugar-sweetened beverages (SSBs) in adolescents. The baseline survey data (2015) from the Taiwan Adolescent to Adult Longitudinal Study (TAALS) were fitted into multivariate logistic regression models adjusted for sex, school type, Body Mass Index (BMI), eating while doing something, nutrition label reading, skipping breakfast, smoking, binge drinking, sedentary lifestyle, physical activity, peer and school support, and parental education level. Among the 18,461 participants (48.5% male and 51.5% female), those exhibiting emotional eating were more likely to consume fast food (Odds ratio (OR) = 2.40, 95% Confidence interval (CI): 2.18-2.64), high-fat snacks (OR = 2.30, 95% CI: 2.12-2.49), processed meat products (OR = 1.92, 95% CI: 1.78-2.08), dessert foods (OR = 2.49, 95% CI: 2.31-2.69), and sugar-sweetened beverages (OR = 1.83, 95% CI: 1.70-1.98). Factors that were positively associated with unhealthy food consumption included eating while doing other activities, binge drinking, smoking, and sedentary lifestyle. Among all the covariates, nutrition label reading was the only factor that was inversely associated with frequent unhealthy food consumption. Sex and school type may moderate the effect of emotional eating on the frequent consumption of specific unhealthy food groups. In conclusion, adolescents with high emotional eating were more likely to report frequent consumption of unhealthy foods in Taiwan. Our findings showed that male participants appeared to consume fast foods, high-fat snacks, processed meat, and SSBs more often and dessert foods less often than females. Future longitudinal studies are recommended for understanding the causal relationship between emotional eating and unhealthy food consumption.


Efficacy and safety of AEZS-108 (LHRH agonist linked to doxorubicin) in women with advanced or recurrent endometrial cancer expressing LHRH receptors: a multicenter phase 2 trial (AGO-GYN5).
Advanced or recurrent endometrial cancer (EC) no longer amenable to surgery or radiotherapy is a life-threatening disease with limited therapeutic options left. Eighty percent of ECs express receptors for luteinizing hormone-releasing hormone (LHRH), which can be targeted by AEZS-108 (zoptarelin doxorubicin acetate). This phase 2 trial was performed to assess the efficacy and safety of AEZS-108 in this group of patients. Patients had FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) III or IV or recurrent EC, LHRH receptor-positive tumor status, and at least had 1 measurable lesion (Response Evaluation Criteria in Solid Tumors). Prior anthracycline therapy was not allowed. Patients received AEZS-108 as a 2-hour infusion on day 1 of a 21-day cycle. The treatment was continued for a maximum of 6 to 8 cycles. The primary end point was the response rate determined by the Response Evaluation Criteria in Solid Tumors. From April 2008 to November 2009, 44 patients were included in the study at 8 centers in Germany (AGO) and 3 centers in Bulgaria. Forty-three of these patients were eligible. Two (5%) patients had a complete remission, and 8 (18%) achieved a partial remission. Stable disease for at least 6 weeks was observed in 44%. The median time to progression was 7 months, and the median overall survival was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%). AEZS-108, an LHRH-agonist coupled to doxorubicin, has significant activity and low toxicity in women with advanced or recurrent LHRH receptor-positive EC, supporting the principle of receptor-mediated targeted chemotherapy.


CARMA1 is necessary for optimal T cell responses in a murine model of allergic asthma.
CARMA1 is a lymphocyte-specific scaffold protein necessary for T cell activation. Deletion of CARMA1 prevents the development of allergic airway inflammation in a mouse model of asthma due to a defect in naive T cell activation. However, it is unknown if CARMA1 is important for effector and memory T cell responses after the initial establishment of inflammation, findings that would be more relevant to asthma therapies targeted to CARMA1. In the current study, we sought to elucidate the role of CARMA1 in T cells that have been previously activated. Using mice in which floxed CARMA1 exons can be selectively deleted in T cells by OX40-driven Cre recombinase (OX40(+/Cre)CARMA1(F/F)), we report that CD4(+) T cells from these mice have impaired T cell reactivation responses and NF-κB signaling in vitro. Furthermore, in an in vivo recall model of allergic airway inflammation that is dependent on memory T cell function, OX40(+/Cre)CARMA1(F/F) mice have attenuated eosinophilic airway inflammation, T cell activation, and Th2 cytokine production. Using MHC class II tetramers, we demonstrate that the development and maintenance of Ag-specific memory T cells is not affected in OX40(+/Cre)CARMA1(F/F) mice. In addition, adoptive transfer of Th2-polarized OX40(+/Cre)CARMA1(F/F) Ag-specific CD4(+) T cells into wild-type mice induces markedly less airway inflammation in response to Ag challenge than transfer of wild-type Th2 cells. These data demonstrate a novel role for CARMA1 in effector and memory T cell responses and suggest that therapeutic strategies targeting CARMA1 could help treat chronic inflammatory disorders such as asthma.


Inequality in mortality decreased among the young while increasing for older adults, 1990-2010.
Many recent studies point to increasing inequality in mortality in the United States over the past 20 years. These studies often use mortality rates in middle and old age. We used poverty level rankings of groups of U.S. counties as a basis for analyzing inequality in mortality for all age groups in 1990, 2000, and 2010. Consistent with previous studies, we found increasing inequality in mortality at older ages. For children and young adults below age 20, however, we found strong mortality improvements that were most pronounced in poorer counties, implying a strong decrease in mortality inequality. These younger cohorts will form the future adult U.S. population, so this research suggests that inequality in old-age mortality is likely to decline.


Does hot pack application change the morphology of the median and ulnar nerves?
This study aims to investigate the effect of the hot pack application on the morphology of healthy median and ulnar nerves. Between August 2021 and September 2022, a total of 54 healthy volunteers (17 males, 37 females; mean age: 31.9±9.4 years; range, 21 to 63 years) were included in the study. The cross-sectional area (CSA) and depth of the right median and ulnar nerve were measured using ultrasonography before and after 20-min hot pack application. The right median nerve CSA and depth from the level of the scaphoid bone (at the level of the carpal tunnel) and from the mid-forearm were also measured. The right ulnar nerve CSA and depth from the level of the hook of hamate and the mid-forearm were evaluated. The depth measurements between the skin and the outer hyperechoic border of the nerve were performed. After the hot pack application, there was an increase in both the median nerve CSA at the carpal tunnel (from 0.06±0.01 to 0.09±0.02 cm2 ) and forearm (from 0.06±0.02 to 0.09±0.02 cm2 ) levels (p<0.001) and the ulnar nerve CSA at the hook of hamate (from 0.04±0.03 to 0.06±0.01 cm2 ) and forearm (0.05±0.01 to 0.08±0.02 cm2 ) levels (p<0.001). No statistically significant difference was observed between the pre- and post-application depth measurements (p>0.05). Our study results show that the hot pack application leads to acute swelling of the median and ulnar nerves. In future studies, the relationship between morphological changes in healthy and pathological nerves and electrodiagnostic findings should be investigated.


A decipherment of epi-olmec hieroglyphic writing.
The decipherment of part of the epi-Olmec script of ancient Mexico, which yields the earliest currently readable texts in Mesoamerica, has been achieved over the last 2 years. This was made possible by the discovery of a stela with a long inscription at La Mojarra, Veracruz, Mexico, in 1986. This decipherment is based on both a reconstruction of the early stages of languages spoken in the region and semantic clues provided by comparison with cultural practices and other script traditions of early southern Mesoamerica. Summarized here is the current state of the phonetic decipherment, the methods used for the decipherment, and results concerning the epi-Olmec language and script. The language identified in the inscriptions is pre-proto-Zoquean, the ancestor of four languages now spoken in the states of Veracruz, Tabasco, Chiapas, and Oaxaca. The decipherment contributes to knowledge of early Mixe-Zoquean language history. The script is more closely related to Mayan hieroglyphic writing than to other early Mesoamerican scripts, and this relation is closer than previously recognized.