[Relationship between Hemoglobin Level Variability and Effect of Repeated Blood Transfusion Therapeutic in Patients with Renal Anemia].
To observe the variability of hemoglobin (HB) level in patients with renal anemia, and to analyze its relationship with effect of repeated blood transfusion therapeutic in patients. A retrospective cohort study and propensity score matching method were used, 60 patients with renal anemia who had effective treatment with repeated blood transfusion in Changzhou No.2 People's Hospital from May 2018 to May 2021 were retrospectively analyzed and set as the effective group; 153 patients with renal anemia who had ineffective treatment with repeated blood transfusion in the hospital in the same period were collected and set as the ineffective group, the propensity score matching method was used, the patients who were effective and ineffective in repeated blood transfusion were matched 1∶1 for analysis; the medical records and laboratory indexes of the two groups were checked; the Hb level of patients within 6 months (1/month) were recorded, the residual standard deviation (Res-SD) of Hb of patients was calculated according to the Hb level and evaluated the variability of Hb level; the relationship between HB variability level and therapeutic effect of repeated blood transfusion in patients with renal anemia was analyzed. After propensity score matching, there was no statistical significant difference between the two groups in terms of baseline data such as age, sex, dialysis age and BMI (P>0.05). The levels of serum albumin and transferrin of patients in the ineffective group were significantly lower than those of patients in the effective group (P<0.05); at 1 and 2 months of the observation period, there was no statistical significant difference in Hb levels of patients in both groups (P>0.05); the Hb level of patients in the ineffective group was significantly lower than that of patients in the effective group at 3, 5 and 6 months, and significantly higher than that of patients in the effective group at 4 months (P<0.05); the Res-SD of male patients and female patients in the ineffective group were respectively significantly higher than that of male patients and female patients in the effective group (P<0.05). Logistic regression analysis results showed that high variability of Hb level (Res-SD) was a risk factor for the ineffective treatment of repeated blood transfusion in patients with renal anemia (OR>1, P<0.05); the decision curve results showed that, when the high-risk threshold was 0.0-1.0, Res-SD predicted the net benefit rates of male and female patients with renal anemia were greater than 0, which was clinically significant, the smaller the high-risk threshold in the above range, the greater the net benefit rate. The therapeutic effect of repeated blood transfusion in patients with renal anemia may be related to the variability of Hb level.


Synthetic models related to furanocoumarin-CYP 3A4 interactions. comparison of furanocoumarin, coumarin, and benzofuran dimers as potent inhibitors of CYP3A4 activity.
Furanocoumarin derivatives (dimers and monomers) present in commercially available grapefruit juice have the capacity to inhibit the activity of human CYP3A4. Such interactions are believed to result from the mechanism-based inhibition of CYP3A4 activity in the intestine. The aim of this work was to synthesize and test a series of dimers with a view to determining the relationship between structure and inhibitory activity and determining whether they might make suitable probes of CYP3A4 activity. We prepared a series of furanocoumarin, coumarin, and benzofuran derivatives that have inhibitory effects on the activity of human CYP3A4. A synthetic benzofuran dimer, which is more accessible than furanocoumarin dimers, exhibited activity against CYP3A4 comparable to that of furanocoumarin dimers.


Y chromosome haplotype analysis in Portuguese cattle breeds using SNPs and STRs.
DNA samples from 307 males of 13 Portuguese native cattle breeds, 57 males of the 3 major exotic breeds in Portugal (Charolais, Friesian, and Limousin), and 5 Brahman (Bos indicus) were tested for 5 single nucleotide polymorphisms, 1 "indel," and 7 microsatellites specific to the Y chromosome. The 13 Y-haplotypes defined included 3 previously described patrilines (Y1, Y2, and Y3) and 10 new haplotypes within Bos taurus. Native cattle contained most of the diversity with 7 haplotypes (H2Y1, H3Y1, H5Y1, H7Y2, H8Y2, H10Y2, and H12Y2) found only in these breeds. H6Y2 and H11Y2 occurred in high frequency across breeds including the exotics. Introgression of Friesian cattle into Ramo Grande was inferred through their sharing of haplotype H4Y1. Among the native breeds, Mertolenga had the highest haplotype diversity (0.68 +/- 0.07), Brava de Lide was the least differentiated. The analyses of molecular variance showed significant (P < 0.0001) differences between breeds with more than 64% of the total genetic variation found among breeds within groups and 33-35% within breeds. The detection of INRA189-104 allele in 8 native breeds suggested influence of African cattle in breeds of the Iberian Peninsula. The presence in Portuguese breeds of Y1 patrilines, also found in aurochs, could represent more ancient local haplotypes.


A randomized and controlled trial of a participative ergonomics intervention to reduce injuries associated with manual tasks: physical risk and legislative compliance.
A participative ergonomics approach to reducing injuries associated with manual tasks is widely promoted; however only limited evidence from uncontrolled trials has been available to support the efficacy of such an approach. This paper reports on a randomized and controlled trial of PErforM, a participative ergonomics intervention designed to reduce the risks of injury associated with manual tasks. One hundred and seventeen small to medium sized food, construction, and health workplaces were audited by government inspectors using a manual tasks risk assessment tool (ManTRA). Forty-eight volunteer workplaces were then randomly assigned to Experimental and Control groups with the Experimental group receiving the PErforM program. Inspectors audited the workplaces again, 9 months following the intervention. The results showed a significant decrease in estimates of manual task risk and suggested better legal compliance in the Experimental group.


Saccharomyces cerevisiae phenotypes can be predicted by using constraint-based analysis of a genome-scale reconstructed metabolic network.
Full genome sequences of prokaryotic organisms have led to reconstruction of genome-scale metabolic networks and in silico computation of their integrated functions. The first genome-scale metabolic reconstruction for a eukaryotic cell, Saccharomyces cerevisiae, consisting of 1,175 metabolic reactions and 733 metabolites, has appeared. A constraint-based in silico analysis procedure was used to compute properties of the S. cerevisiae metabolic network. The computed number of ATP molecules produced per pair of electrons donated to the electron transport system (ETS) and energy-maintenance requirements were quantitatively in agreement with experimental results. Computed whole-cell functions of growth and metabolic by-product secretion in aerobic and anaerobic culture were consistent with experimental data, and thus mRNA expression profiles during metabolic shifts were computed. The computed consequences of gene knockouts on growth phenotypes were consistent with experimental observations. Thus, constraint-based analysis of a genome-scale metabolic network for the eukaryotic S. cerevisiae allows for computation of its integrated functions, producing in silico results that were consistent with observed phenotypic functions for approximately 70-80% of the conditions considered.


Multicompartment Artificial Organelles Conducting Enzymatic Cascade Reactions inside Cells.
Cell organelles are subcellular structures entrapping a set of enzymes to achieve a specific functionality. The incorporation of artificial organelles into cells is a novel medical paradigm which might contribute to the treatment of various cell disorders by replacing malfunctioning organelles. In particular, artificial organelles are expected to be a powerful solution in the context of enzyme replacement therapy since enzymatic malfunction is the primary cause of organelle dysfunction. Although several attempts have been made to encapsulate enzymes within a carrier vehicle, only few intracellularly active artificial organelles have been reported to date and they all consist of single-compartment carriers. However, it is noted that biological organelles consist of multicompartment architectures where enzymatic reactions are executed within distinct subcompartments. Compartmentalization allows for multiple processes to take place in close vicinity and in a parallel manner without the risk of interference or degradation. Here, we report on a subcompartmentalized and intracellularly active carrier, a crucial step for advancing artificial organelles. In particular, we develop and characterize a novel capsosome system, which consists of multiple liposomes and fluorescent gold nanoclusters embedded within a polymer carrier capsule. We subsequently demonstrate that encapsulated enzymes preserve their activity intracellularly, allowing for controlled enzymatic cascade reaction within a host cell.


Detection and Prediction of Incident Alzheimer Dementia over a 10-Year or Longer Medical History: A Population-Based Study in Primary Care.
Despite the crucial role played by general practitioners in the identification and care of people with cognitive impairment, few data are available on how they may improve the early recognition of patients with Alzheimer dementia (AD), especially those with long (i.e., 10 years and longer) medical history. To investigate the occurrence and the predictors of AD during a 10-year or longer period prior AD diagnosis in primary care patients aged 60 years or older. A cohort study with a nested case-control analysis has been conducted. Data were extracted from the Italian Health Search Database (HSD), an Italian database with primary care data. AD cases have been defined in accordance with the International Classification of Diseases, ninth edition (ICD-9-CM) codes and coupled with the use of anti-dementia drugs. Prevalence and incidence rates of AD have been calculated. To test the association between candidate predictors, being identified in a minimum period of 10 years, and incident cases of AD, we used a multivariate conditional logistic regression model. As recorded in the primary care database, AD prevalence among patients aged 60 years or older was 0.8% during 2016, reaching 2.4% among nonagenarians. Overall, 1,889 incident cases of AD have been identified, with an incidence rate as high as 0.09% person-year. Compared with 18,890 matched controls, history of hallucinations, agitation, anxiety, aberrant motor behavior, and memory deficits were positively associated with higher odds of AD (p < 0.001 for all) diagnosis. A previous diagnosis of depression and diabetes and the use of low-dose aspirin and non-steroidal anti-inflammatory drugs were associated with higher odds of AD (p < 0.05 for all). Our findings show that, in accordance with primary care records, 1% of patients aged 60 years and older have a diagnosis of AD, with an incident AD diagnosis of 0.1% per year. AD is often under-reported in primary care settings; yet, several predictors identified in this study may support general practitioners to early identify patients at risk of AD.


Conceptual and procedural considerations for developmental assessment of learning and memory (dys)function following neurotoxicant exposure.
Symptoms of memory impairment are often reported following neurotoxicant exposure. Untoward effects on the developing organism, potentially reflected as later learning disabilities and memory problems, deserve critical evaluation. Animal models providing rigorous experimental control are extremely important in this context. The psychological literature offers a variety of tasks and procedures for use across many developmental ages. Most recent progress has demonstrated evidence of associative capacity in infrahumans as early as birth, and under specific conditions even prenatally. Common to all assessments of learning and memory capabilities, however, is the requisite that these processes be inferred from overt behavior. This requirement confers the responsibility of differentiating alterations of an associative nature from those of a nonassociative nature (e.g., motivation, attention, perception, sensory adaptation, fatigue, activity, and reactivity, etc.). When across age comparisons are also of interest, additional attention must be paid to potential differences in available sensory processes, response repertoire, and ecologically relevant contextual determinants (e.g., ambient temperature, presence of familiar odors or conspecifics), particularly with preweanling and neonatal animals. Specific guidelines are offered for the criteria and implementation of controls typically necessary to provide a convincing demonstration of an associative impairment.


Amplification of 1q32.1 Refines the Molecular Classification of Endometrial Carcinoma.
Purpose: Molecular classification of endometrial cancer identified distinct molecular subgroups. However, the largest subset of endometrial cancers remains poorly characterized and is referred to as the "nonspecific molecular profile" (NSMP) subgroup. Here, we aimed at refining the classification of this subgroup by profiling somatic copy-number aberrations (SCNAs).Experimental Design: SCNAs were analyzed in 141 endometrial cancers using whole-genome SNP arrays and pooled with 361 endometrial cancers from The Cancer Genome Atlas. Genomic Identification of Significant Targets in Cancer (GISTIC) identified statistically enriched SCNAs and penalized Cox regression assessed survival effects. The prognostic significance of relevant SCNAs was validated using multiplex ligation-dependent probe amplification in 840 endometrial cancers from the PORTEC-1/2 trials. Copy-number status of genes was correlated with gene expression to identify potential cancer drivers. One plausible oncogene was validated in vitro using antisense oligonucleotide-based strategy.Results: SCNAs affecting chromosome 1q32.1 significantly correlated with worse relapse-free survival (RFS) in the NSMP subgroup (HR, 2.12; 95% CI, 1.26-3.59; P = 0.005). This effect was replicated in NSMP endometrial cancers from PORTEC-1/2 (HR, 2.34; 95% CI, 1.17-4.70; P = 0.017). A new molecular classification including the 1q32.1 amplification improved risk prediction of recurrence. MDM4 gene expression strongly correlated with 1q32.1 amplification. Silencing MDM4 inhibited cell growth in cell lines carrying 1q32.1 amplification, but not in those without MDM4 amplification. Vice versa, increasing MDM4 expression in nonamplified cell lines stimulated cell proliferation.Conclusions: 1q32.1 amplification was identified as a prognostic marker for poorly characterized NSMP endometrial cancers, refining the molecular classification of this subgroup. We functionally validated MDM4 as a potential oncogenic driver in the 1q32.1 region. Clin Cancer Res; 23(23); 7232-41. ©2017 AACR.


[Ploidy level and alpha-fetoprotein production in spontaneous murine hematomas in relation to the degree of histological differentiation].
Comparative morphological, cytospectrophotometric and immunochemical studies were carried out on 26 hepatocarcinomas of various malignancy excised from 21 F1 (CBA X C57B16) mice. It has been shown that in morphologically similar hepatomas the ploidy level and alpha-fetoprotein production intensity may vary markedly. Highly differentiated carcinomas usually of smaller sizes and homogeneous morphology have the modal class nuclei with tetraploid (6 cases) or octaploid (3 cases) DNA content. In moderately- and low-differentiated carcinomas the diploid class of nuclei significantly increased (in 4 out of 6 tumours). Large tumours morphologically heterogeneous according to the differentiation level had polymodal DNA distributions with predominating tetraploid nuclei (II cases).


Effects of individualized acupuncture on sleep quality in HIV disease.
Although it may begin at any point, sleep disturbance often appears early in HIV disease and contributes to decreased quality of life during the course of the illness. Relatively few studies have explored the complex nature of poor sleep quality in HIV disease or tested interventions to improve sleep quality. The purpose of this study was threefold: explore the nature of sleep quality in HIV disease, test the relationship between pain and sleep quality, and test the effectiveness of acupuncture delivered in a group setting for improving sleep quality in those who are HIV infected. A pretest, posttest, preexperimental design was used to test the effects of acupuncture on sleep quality. Participating in the study were 21 HIV-infected men and women between the ages of 29 and 50 years who reported sleep disturbance three or more times per week and who scored greater than 5 on the Pittsburgh Sleep Quality Index. The Wrist Actigraph was used to measure sleep activity, and the Current Sleep Quality Index was used to measure sleep quality for 2 nights before and after a 5-week acupuncture intervention (10 treatments). Acupuncture was individualized to address insomnia and other symptoms reported by the participants. Sleep activity and sleep quality significantly improved following 5 weeks of individualized acupuncture delivered in a group setting.


The itinerant health worker: an experiment in rural health care delivery.
A model of rural health-care delivery employing itinerant health workers has been presented. Itinerant workers, whose role is principally community organization and technical assistance to village health committees in matters of environment health and endemic disease control, are suggested as an interim measure for strengthening village social structures in preparation for the eventual emergence of village health workers. The effectiveness of the model is reflected in the multiplier effect on the number of organized villages, the diffusion of the model to other parts of the Cameroun, and the impact on policy-making. The efficiency of the model, however, may be limited by such questions as budget for transport and per diem expenses and more seriously the limitation on training facilities. A deliberate allocation of budget to overcoming these obstacles is suggested as important to bringing the advantages of the model to the entire rural population.


Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes.
Elexacaftor-tezacaftor-ivacaftor is a small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious in patients with at least one Phe508del allele, which indicates that this combination can modulate a single Phe508del allele. In patients whose other CFTR allele contains a gating or residual function mutation that is already effectively treated with previous CFTR modulators (ivacaftor or tezacaftor-ivacaftor), the potential for additional benefit from restoring Phe508del CFTR protein function is unclear. We conducted a phase 3, double-blind, randomized, active-controlled trial involving patients 12 years of age or older with cystic fibrosis and Phe508del-gating or Phe508del-residual function genotypes. After a 4-week run-in period with ivacaftor or tezacaftor-ivacaftor, patients were randomly assigned to receive elexacaftor-tezacaftor-ivacaftor or active control for 8 weeks. The primary end point was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline through week 8 in the elexacaftor-tezacaftor-ivacaftor group. After the run-in period, 132 patients received elexacaftor-tezacaftor-ivacaftor and 126 received active control. Elexacaftor-tezacaftor-ivacaftor resulted in a percentage of predicted FEV1 that was higher by 3.7 percentage points (95% confidence interval [CI], 2.8 to 4.6) relative to baseline and higher by 3.5 percentage points (95% CI, 2.2 to 4.7) relative to active control and a sweat chloride concentration that was lower by 22.3 mmol per liter (95% CI, 20.2 to 24.5) relative to baseline and lower by 23.1 mmol per liter (95% CI, 20.1 to 26.1) relative to active control (P<0.001 for all comparisons). The change from baseline in the Cystic Fibrosis Questionnaire-Revised respiratory domain score (range, 0 to 100, with higher scores indicating better quality of life) with elexacaftor-tezacaftor-ivacaftor was 10.3 points (95% CI, 8.0 to 12.7) and with active control was 1.6 points (95% CI, -0.8 to 4.1). The incidence of adverse events was similar in the two groups; adverse events led to treatment discontinuation in one patient (elevated aminotransferase level) in the elexacaftor-tezacaftor-ivacaftor group and in two patients (anxiety or depression and pulmonary exacerbation) in the active control group. Elexacaftor-tezacaftor-ivacaftor was efficacious and safe in patients with Phe508del-gating or Phe508del-residual function genotypes and conferred additional benefit relative to previous CFTR modulators. (Funded by Vertex Pharmaceuticals; VX18-445-104 ClinicalTrials.gov number, NCT04058353.).


Potential impact of maternal vitamin D status on peripheral blood and endometrium cellular immunity in women with recurrent implantation failure.
This study aims to evaluate the modulatory effects of vitamin D on peripheral blood and endometrial cellular immunity in women with recurrent implantation failure (RIF). One hundred and fifty-four women with RIF were identified at a fertility center from January 2018 and March 2019. Blood and endometrium samples were collected during the mid-luteal phase before IVF treatment or pregnancy. The serum vitamin D status, NK cell cytotoxicity, Th1 cytokine production, and endometrial immune cells were detected before and after vitamin D supplementation. The NK cell cytotoxicity at an effector:target (E:T) ratio of 50:1 or 25:1 was significantly higher in vitamin D insufficiency group (VDI) than those in vitamin D normal group (VDN) (P < .05 each). The percentage of IFN-γ- or TNF-α-producing Th cells was significantly increased in VDI or vitamin D deficiency group (VDD) when compared with VDN (P < .05 each). The percentage of CD68+ macrophages on all endometrial cells in VDI and VDD was significantly higher than in VDN (P < .05 each), while no significant differences in the percentage of other endometrial immune cells among the three groups were observed. This dysregulation was significantly reduced with vitamin D supplementation. Our findings highlighted that vitamin D may have an important role in the regulation of not only systemic but also local immune response for optimization of maternal tolerance for implantation in women with RIF. Pre-conception optimization of vitamin D status should be considered in women with RIF.


Day-night changes in leaf water relations associated with the rhythm of crassulacean acid metabolism in Kalanchoë daigremontiana.
A study was made of the day-night changes under controlled environmental conditions in the bulk-leaf water relations of Kalanchoë daigremontiana, a plant showing Crassulacean acid metabolism. In addition to nocturnal stomatal opening and net CO2 uptake, the leaves of well-watered plants showed high rates of gas exchange during the whole of the second part of the light period. Measurements with the pressure chamber showed that xylem tension increased during the night and then decreased towards a minimum at about midday; a significant increase in xylem tension was also seen in the late afternoon. Cell-sap osmotic pressure paralleled leaf malate content and was maximum at dawn and minimum at dusk. The relationship between these two variables indicated that the nocturnally synthesized malate was apparently behaving as an ideal osmoticum. To estimate bulk-leaf turgor pressure, values for water potential were derived by correcting the pressurechamber readings for the osmotic pressure of the xylem sap. This itself was found to depend on the malate content of the leaves. Bulk-leaf turgor pressure changed rhythmically during the day-night cycle; turgor was low during the late afternoon and for most of the night, but increased quickly to a maximum of 0.20 MPa around midday. In water-stressed plants, where net CO2 uptake was restricted to the dark period, there was also an increase in bulk-leaf turgor pressure at the start of the light period, but of reduced magnitude. Such changes in turgor pressure are likely to be of considerable ecological importance for the water economy of crassulacean-acid-metabolism plants growing in their natural habitats.


Credentialing for eating disorder clinicians: a pathway for implementation of clinical practice standards.
Advances are needed to ensure safe and effective treatment is available for people with eating disorders. Recently developed clinical practice and training standards for mental health professionals and dietitians represent a significant step in this direction by providing a consensus statement on eating disorder treatment as a foundation on which to build competent practice. This commentary argues that a credentialing system could promote implementation of these practice standards through formal recognition of qualifications, knowledge, training and professional activities to meet minimum standards for delivery of safe and effective eating disorder treatment. Drivers for credentialing include the imperative to provide safe and effective care, promotion of workforce development in eating disorder practice and, importantly, readily available and transparent information for referrers, consumers, and carers to identify health professionals credentialed to provide eating disorder treatment. However, a number of factors must be considered to ensure that credentialing does not restrict access to care, such as prohibitively narrow criteria to become credentialed, absence of pathways for education, training, or professional development opportunities, and lack of consultation with or endorsement by stakeholders of the credentialing criteria, application and approval processes, and ways of identifying credentialed practitioners. Further work, including development of credentialing criteria and aligned training opportunities, currently being undertaken by the Australia & New Zealand Academy for Eating Disorders and the National Eating Disorders Collaboration in consultation with stakeholders in the eating disorders sector and health professions will advance understanding of the feasibility of a system of credentialing for eating disorders within Australia and New Zealand. The availability of clinical practice and training standards, supported by implementation pathways, including credentialing of eating disorders practitioners, aim to improve quality of life, reduce financial burden, and close the treatment gap.


Comparison between frailty index of deficit accumulation and fracture risk assessment tool (FRAX) in prediction of risk of fractures.
A frailty index (FI) of deficit accumulation could quantify and predict the risk of fractures based on the degree of frailty in the elderly. We aimed to compare the predictive powers between the FI and the fracture risk assessment tool (FRAX) in predicting risk of major osteoporotic fracture (hip, upper arm or shoulder, spine, or wrist) and hip fracture, using the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort. There were 3985 women included in the study, with the mean age of 69.4 years (standard deviation [SD] = 8.89). During the follow-up, there were 149 (3.98%) incident major osteoporotic fractures and 18 (0.48%) hip fractures reported. The FRAX and FI were significantly related to each other. Both FRAX and FI significantly predicted risk of major osteoporotic fracture, with a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 1.02-1.05) and 1.02 (95% CI: 1.01-1.04) for per-0.01 increment for the FRAX and FI respectively. The HRs were 1.37 (95% CI: 1.19-1.58) and 1.26 (95% CI: 1.12-1.42) for an increase of per-0.10 (approximately one SD) in the FRAX and FI respectively. Similar discriminative ability of the models was found: c-index = 0.62 for the FRAX and c-index = 0.61 for the FI. When cut-points were chosen to trichotomize participants into low-risk, medium-risk and high-risk groups, a significant increase in fracture risk was found in the high-risk group (HR = 2.04, 95% CI: 1.36-3.07) but not in the medium-risk group (HR = 1.23, 95% CI: 0.82-1.84) compared with the low-risk women for the FI, while for FRAX the medium-risk (HR = 2.00, 95% CI: 1.09-3.68) and high-risk groups (HR = 2.61, 95% CI: 1.48-4.58) predicted risk of major osteoporotic fracture significantly only when survival time exceeded 18months (550 days). Similar findings were observed for hip fracture and in sensitivity analyses. In conclusion, the FI is comparable with FRAX in the prediction of risk of future fractures, indicating that measures of frailty status may aid in fracture risk assessment and fracture prevention in the elderly. Further evidence from randomized controlled trials of osteoporosis medication interventions is needed to support the FI and FRAX as validated measures of fracture risk.


Tuning molecular fluctuation to boost the conductance in DNA based molecular wires.
Inherent molecular fluctuations are known to have a significant influence on the charge transport properties of biomolecules like DNA, PNA and proteins. In this work, we show ways to control these fluctuations and further demonstrate their use to enhance the conductance of two widely studied molecular wires, namely dsDNA (DNA) and G4 Quadruplex (G4-Quad). We quantify the molecular fluctuation in terms of the root mean square deviation (RMSD) of the molecule. In the case of DNA, we use temperature to control the fluctuations, while in the case of G4-Quad the fluctuations are tuned by the ions inside the pore. The electronic coupling between the bases of dsDNA and G4-Quad, which measures the conductance of these molecular wires, shows a non-monotonic behaviour with the increase in fluctuation. We find values of fluctuation which give rise to maximum electronic coupling and hence high conductivity for both the cases. In the case of DNA, these optimal fluctuations (∼2.5 Å) are achieved at a temperature of 210 K, which gives rise to an electronic coupling of 0.135 eV between the DNA bases. The optimal fluctuations in G4-Quad are achieved (∼7 Å) in a 4 base pair long system with 2 Na+ ions inside the pore, giving rise to an electronic coupling of 0.09 eV.


Molecular Recognition of Tyrosine-Containing Polypeptides with Pseudopeptidic Cages Unraveled by Fluorescence and NMR Spectroscopies.
The molecular recognition of Tyr-containing peptide copolymers with pseudopeptidic cages has been studied using a combination of fluorescence and NMR spectroscopies. Fluorescence titrations rendered a reasonable estimation of the affinities, despite the presence of dynamic quenching masking the unambiguous detection of the supramolecular complexes. Regarding NMR, the effect of polypeptide (PP) binding on relaxation and diffusion parameters of the cages is much more reliable than the corresponding chemical shift perturbations. To that, purification of the commercial PPs is mandatory to obtain biopolymers with lower polydispersity. Thus, the relaxation/diffusion-filtered 1H spectra of the cages in the absence vs presence of the PPs represent a suitable setup for the fast detection of the noncovalent interactions. Additional key intermolecular NOE cross-peaks supported by molecular models allow the proposal of a structure of the supramolecular species, stabilized by the Tyr encapsulation within the cage cavity and additional attractive polar interactions between the side chains of cage and PP, thus defining a binding epitope with a potential for implementing sequence selectivity. Accordingly, the cages bearing positive/negative residues prefer to bind the peptides having complementary negative/positive side chains close to the target Tyr, suggesting an electrostatic contribution to the interaction. Overall, our results show that both techniques represent a powerful and complementary combination for studying cage-to-PP molecular recognition processes.


Total Protein Intake in Patients with PKU: Adequacy Evaluation According to the European PKU Guidelines from 2017.
In PKU, the protein requirements are contentious. In 2018, we evaluated the protein intake in patients with PKU. Ninety-nine early treated patients aged 19.3 ± 8.2 years (54% males) were studied. A total of 24 had hyperphenylalaninemia (HPA), 48 mild and 27 classical PKU. All had an annual nutritional status evaluation. A total of 83% were on diet therapy only, and 17% were on diet with tetrahydrobiopterin therapy. Anthropometry, metabolic control and nutritional intake [total protein (TP, g/kg), natural protein (NP, g/kg), protein equivalent from protein substitutes (PE, g/kg)] were collected. TP adequacy (TPA) was calculated as a % of WHO (2007) safe levels of protein intake. Results were compared with the European PKU Guidelines (EPG). The median % contribution NP of TP intake was 53% [31-100]. Most patients (78%) had a TP intake above the EPG recommendations. The median TPA was 171% [146-203], with 79% [51-165] from NP and 84% [0-109] from PE. A TPA of 100-140% was observed in 16 (16%) patients. Only n = 6 (6%) patients had a TPA < 100%. These results emphasize the heterogeneity of PKU. More research is needed to understand the necessity of a single protein recommendation for all, as a 'one-size-fits-all' solution might not be appropriate.


Thermobifida halotolerans sp. nov., isolated from a salt mine sample, and emended description of the genus Thermobifida.
The actinomycete strain YIM 90462T was isolated from a salt mine sample collected from Yunnan province, south-west China. Comparative 16S rRNA gene sequence analysis demonstrated that the isolate, which had sequence similarities of more than 97 % to Thermobifida alba, Thermobifida fusca and Thermobifida cellulosilytica, was a candidate member of the genus Thermobifida. Subsequently, a polyphasic approach was used to clarify the taxonomic position of strain YIM 90462T. Its diagnostic diamino acid was meso-diaminopimelic acid and whole-cell sugars contained galactose, xylose and glucose. The predominant menaquinones were MK-10(H6) and MK-10(H8). The major fatty acids were iso-C16:0 and anteiso-C17:0. Results of DNA-DNA hybridizations and physiological and biochemical tests enabled genotypic and phenotypic differentiation of strain YIM 90462T from the three Thermobifida species with validly published names. Consequently, it is proposed that strain YIM 90462T should be recognized as a representative of a novel species of Thermobifida, Thermobifida halotolerans sp. nov. The type strain is YIM 90462T (=KCTC 19123T =DSM 44931T). In addition, an emended description of the genus Thermobifida is presented.


Using instrumental leadership to manage change.
Effective leadership is the key factor in directing and influencing change in an organization. In today's healthcare environment, leaders have less time to make decisions that will ensure their organization's survival, a fact that has forced them to recreate the way they do business and be cognizant of ways to remain competitive. In the environment of change, a new type of leader is needed--the instrumental leader--one who combines the charismatic traits of envisioning, energizing and enabling with the three key facilitating behaviors of controlling, structuring and rewarding. To these attributes the instrumental leader adds critical thinking, problem solving and a feedback mechanism. Leaders who focus on employees as individuals and on the organization as a whole will achieve greater success. Today's leader must share a picture of the intended reality with the organization's staff, constituents and the community. Those most affected by oncoming change must be included in future planning. A shared vision is, however, an ongoing process, with communication crucial for its success. At some point in the change process, leaders must spend time building teams, clarifying behaviors and administering rewards and punishments. Part of this process involves energizing and aligning employees who will find ways to implement the shared new vision. The instrumental leader understands the need for teams that will form the backbone of the integrated system. Creating objective measures for performance, based on the new shared vision, demonstrates the organization's values better than communication or vision alone. Additional training or dialogue may better clarify the organization's expectations of employees.


Role of repeated endoscopic ultrasound-guided fine needle aspiration in small solid pancreatic masses with previous indeterminate and negative cytological findings.
Despite advances in imaging techniques, the differentiation between pancreatic cancer and benign lesions remains difficult. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an effective method for providing tissue diagnosis, but problems occur when lesions are small or the cytological diagnosis is indeterminate. To prospectively evaluate the utility of EUS-FNA in patients with small solid pancreatic lesions and those with initial indeterminate or negative cytological diagnosis. During the study period we performed a total of 119 EUS-FNA procedures on 46 patients (mean age 56.3 years) for 47 small solid pancreatic lesions (range 7-30 mm, mean 17.2 mm in diameter). FNAs were performed in the presence of a cytopathologist. If cytological diagnoses were indeterminate, EUS-FNA was repeated within 3 weeks. Diagnoses were confirmed histologically or by follow-up (clinical and imaging: EUS +/- FNA and CT). Localization of the lesions: head 28 (60%), uncinate process 4 (9%), body 11 (23%) and tail 4 (9%). On average, 3.7 passes were performed. We observed no complications. Initial cytological findings were: malignant 17 (36%), benign 21 (45%), and indeterminate 9 (19%). 8 (78%) of the indeterminate findings were confirmed to be malignant on repeated procedures. A diagnosis of pancreatic cancer was subsequently confirmed in 1 patient who had a benign cytological finding. 19 patients underwent surgery. Histology confirmed a neoplasm in all cases. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 68, 100, 100, 73 and 83%, respectively. After repeated EUS-FNAs of indeterminate findings sensitivity, negative predictive value and diagnostic accuracy rose to 92, 77 and 96%, respectively. EUS-FNA is a highly effective method for providing tissue diagnosis in patients with small solid pancreatic masses. Repeated procedures enhanced diagnostic accuracy in indeterminate findings, among which was high percentage of malignancies. EUS-FNA reduced the number of operations in patients with pancreatic solid masses.


Effects of fish oil on graft arteriosclerosis and MHC class II antigen expression in rat heterotopic cardiac allografts.
The effect of fish oil on accelerated graft coronary arteriosclerosis was assessed in Lewis to Brown-Norway rat heterotopic cardiac allografts. Twelve Brown-Norway rats were supplemented with 2 ml/kg/day of fish oil (68.3 mg eicosopentaenoic acid and 47.5 mg decosahexaenoic acid per milliliter). Eleven additional animals, receiving an isocaloric amount of safflower oil, served as control. All diets began 1 week before operation. Immunosuppression was obtained with low-dose cyclosporine (2 mg/kg/d). When killed (100 days), there were no significant differences in percentage weight gain, graft function, or histologic rejection score. Although lipid profiles were comparable, total cholesterol:high-density lipoprotein ratio was marginally higher in animals treated with fish oil (p = 0.069). Mean percentage luminal occlusion (before and after correcting for differences in size between coronary vessels analyzed) and average intimal thickness were similar between animals treated with fish oil and safflower oil as assessed by computer-assisted digitized, morphometric planimetry. In all allografts, donor interstitial dendritic cells were repopulated with recipient dendritic cells. The major histocompatibility complex class II cell density in the fish oil group did not differ significantly from rats supplemented with safflower oil (1.48 +/- 0.68 vs 1.48 +/- 0.65 cells per mm2, p = 0.995). In conclusion, fish oil did not exert any beneficial effect over safflower oil in terms of graft coronary arteriosclerosis, histologic rejection, or plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS)


[The construction and identification of siRNA expression vector against hypoxia inducible factor -1 alpha in vitro].
Previous studies have suggested that under hypoxic conditions hypoxia inducible factor-1 alpha (HIF-1 alpha) contributes to the progression of neonatal pulmonary hemorrhage (NPH) by increasing the expression of endothelin-1 (ET-1) gene. RNA interference (RNAi) refers to the process of sequence-specific post-transcriptional gene-silencing mediated by double-stranded RNA. This new gene-silencing technique has recently been shown to be a powerful approach for studying gene function. The aim of this study was to construct the small interfering RNA (siRNA) eukaryotic expression vectors specific to human HIF-1 alpha gene (pSIREN-Shuttle HIF-1 alpha siRNAin order to observe its silencing effect on HIF-1 alpha under hypoxic conditions. Six potential siRNA target sites (a-fspecific to human HIF-1 alpha gene were designed and synthesized to two complementary oligonucleotides (A-F) for each siRNA target site. Using a gene recombination technique, the recombinant expression vectors (A-F') were constructed by cloning the double strands oligonucleotide into RNAi-Ready pSIREN vector. The recombinant vectors were then transfected into the cultured human umbilical vein endothelial cells (HUVECs). After 48 hrs of culture, the cells were treated with CoCl2 (100 mu M) for 3 hrs. Expression of HIF-1 alpha mRNA and protein was detected using RT-PCR and Western blot. ET-1 level in cell culture supernates was detected using ELISA. The recombinant HIF-1 alpha siRNA eukaryotic expression vectors A'-F'respectively aiming at sites (a-f) were constructed successfully. Compared to the non-transfection group, liposome-mediated gene transfection of pSIREN-Shuttle HIF-1 alpha siRNA expression vectors into HUVECs obviously down-regulated the mRNA and protein levels of HIF-1 alpha, and partly decreased the ET-1 level in the B' and D' transfection groups. The specific pSIREN-Shuttle HIF-1 alpha siRNA expression vectors B' and D' aiming at b and d sites can inhibit the expression of HIF-1 alpha, thus decreasing the level of its target gene ET-1. This may be helpful to study the relationship between HIF-1 alpha and neonatal pulmonary hemorrhage in vivo in future.


The role of DNA methylation in directing the functional organization of the cancer epigenome.
The holistic role of DNA methylation in the organization of the cancer epigenome is not well understood. Here we perform a comprehensive, high-resolution analysis of chromatin structure to compare the landscapes of HCT116 colon cancer cells and a DNA methylation-deficient derivative. The NOMe-seq accessibility assay unexpectedly revealed symmetrical and transcription-independent nucleosomal phasing across active, poised, and inactive genomic elements. DNA methylation abolished this phasing primarily at enhancers and CpG island (CGI) promoters, with little effect on insulators and non-CGI promoters. Abolishment of DNA methylation led to the context-specific reestablishment of the poised and active states of normal colon cells, which were marked in methylation-deficient cells by distinct H3K27 modifications and the presence of either well-phased nucleosomes or nucleosome-depleted regions, respectively. At higher-order genomic scales, we found that long, H3K9me3-marked domains had lower accessibility, consistent with a more compact chromatin structure. Taken together, our results demonstrate the nuanced and context-dependent role of DNA methylation in the functional, multiscale organization of cancer epigenomes.


Mistakes encountered during automatic peak identification of minor and trace constituents in electron-excited energy dispersive X-ray microanalysis.
Automated peak identification in electron beam-excited X-ray microanalysis with energy dispersive X-ray spectrometry has been shown to be subject to occasional mistakes even on well-separated, high-intensity peaks arising from major constituents (arbitrarily defined as a concentration, C, which exceeds a mass fraction of 0.1). The peak identification problem becomes even more problematic for constituents present at minor (0.01< or =C< or =0.1) and trace (C<0.01) levels. "Problem elements" subject to misidentification as major constituents are even more vulnerable to misidentification when present at low concentrations in the minor and trace ranges. Additional misidentifications attributed to trace elements include minor X-ray family members associated with major constituents but not assigned properly, escape and coincidence peaks associated with major constituents, and false peaks owing to chance groupings of counts in spectra with poor counting statistics. A strategy for robust identification of minor and trace elements can be based on application of automatic peak identification with careful inspection of the results followed by multiple linear least-squares peak fitting with complete peak references to systematically remove each identified major element from the spectrum before attempting to assign remaining peaks to minor and trace constituents.


Sleeping Unsafely Tucked in to Conserve Energy in a Nocturnal Migratory Songbird.
Each spring and fall, millions of normally diurnal birds switch to migrating at night. Most of these are small songbirds (passerine) migrating long distances that need to alternate their migratory flights with refueling stopovers [1, 2], which can account for up to 80% of the total migratory period [3]. After a long nocturnal flight, these birds face the contrasting needs to recover sleep and refill depleted energy stores, all while vulnerable to predation [4, 5]. Here, we investigated how garden warblers at a Mediterranean stopover site modulate their sleep behavior in relation to their metabolic state. At night, garden warblers in poor metabolic condition sleep more and exhibit less migratory restlessness than birds in good condition do. In addition, rather than sleeping with their head facing forward, birds in poor condition prefer to sleep with their head turned and tucked in their feathers. We further show that sleep with the head tucked is associated with lower respiratory and metabolic rates and reduced heat loss mediated by hiding the head-the body part with the highest heat dissipation-under the feathers. However, the benefit of conserving energy while sleeping with the head tucked was countered by reduced anti-predator vigilance. Birds presented with a sound simulating the approach of a predator responded more slowly when the head was tucked than when it was untucked. Consequently, our study demonstrates that through changing their sleep position and intensity, migrating songbirds can negotiate a previously unknown trade-off between sleep-mediated energy conservation and anti-predatory vigilance.


Cardiovascular actions of angiotensin in the fowl (Gallus domesticus). I. Analysis.
Chicken aorta, unlike the aortae of any other species tested, did not respond to angiotensin II (AII) at concentrations up to 10(-4) M. The anesthetized chicken did, however, show a blood pressure increase in response to AII, but this was apparently dependent on the sympathetic nervous system. In the conscious chicken a biphasic response to AII was seen--an initial depressor response followed by a pressor response. The depressor response was not inhibited by standard blocking agents, but was blocked by prior induction of tachyphylaxis to vasopressin. It is concluded that the depressor response to AII in the conscious chicken is due to release of vasotocin, the avian equivalent to vasopressin, and the subsequent pressor response to AII is due to activation of the sympathetic nervous system.


Implementing a spinosad-based local bait station to control Bactrocera cucurbitae (Diptera: Tephritidae) in high rainfall areas of Reunion Island.
Three species of fruit flies cause serious damage to cucurbit crops on Reunion Island: Bactrocera cucurbitae (Diptera: Tephritidae) (Coquillett 1899), Dacus ciliatus (Loew 1901), and Dacus demmerezi (Bezzi 1917). To control them, a program of agroecological management of cucurbit flies has been implemented based on the application of Synéis-appât, especially spot sprays on corn borders. However, the high rainfall on Reunion Island limits the long-term efficiency of the bait; in addition, this method cannot be used for large chayote trellises, because corn borders cannot be planted around them. The aim of this study was to design a bait station adapted to prevailing conditions on Reunion Island. An 'umbrella trap' tested in Taiwan was used as a reference to compare its efficacy with our local bait station. Experiments were conducted in field cages on B. cucurbitae to test different characteristics of bait stations and to construct one using local materials. Results were validated in the field. The attractiveness of the bait station was related mainly to the color of the external surface, yellow being the most attractive color. The efficacy of the bait station with respect to fly mortality was found to be linked to the accessibility of the bait, and direct application of Synéis-appât on the bait station was found to be the most efficient. In the field, B. cucurbitae were more attracted to the local bait station than to the umbrella trap, while the two other fly species displayed equal attraction to both trap types. Our local bait station is a useful alternative to spot sprays of Synéis-appât and is now included in a local pest management program and is well accepted by farmers.


Influence of diminished respiratory surface area on survival of sea turtle embryos.
It has been suggested that fungal presence on sea turtle eggs may impede gas exchange. To investigate the influence of diminished gas exchange surface upon embryo survivorship, flatback (Natator depressus) and green (Chelonia mydas) eggs were painted with petroleum jelly. Variable proportions of the egg surface were covered, including both respiratory and nonrespiratory domains. Embryo survival varied with site inhibited, proportion of eggshell affected, and species of turtle. If fungi on the exterior of the eggshell are able to impede respiratory gas exchange, their presence on the upper hemisphere (primary gas exchange area in early incubation) will result in the highest embryo mortality. Large eggs are likely to demonstrate a higher survivorship than small eggs, due to their larger available respiratory area and/or to variation in weight or stage-specific embryonic metabolic demands. Interspecific differences in egg size may therefore be a contributory factor to observed mortality rate differences in the natural presence of fungi.


A role for E-cadherin in mouse primordial germ cell development.
In this study we show that mouse primordial germ cells and fetal germ cells at certain stages of differentiation express E-cadherin and alpha and beta catenins. Moreover, we demonstrate that the formation of germ cell aggregates that rapidly occurs when monodispersed germ cell populations are released from embryonic gonads in culture is E-cadherin mediated, developmentally regulated, and dependent on the sex of the germ cells. Immunoblotting analyses indicate that the lower ability to form aggregates of primordial germ cells in comparison to fetal germ cells is not due to gross changes in E-cadherin expression, altered association with beta catenin, or changes in beta catenin phosphorylation. Investigating possible functions of E-cadherin-mediated adhesion in primordial germ cell development, we found that E-cadherin-mediated adhesion may stimulate the motility of primordial germ cells. Moreover, treatment of primordial germ cells cultured on STO cell monolayers with an anti-E-cadherin antibody caused a significant decrease in their number and markedly reduced their ability to form colonies in vitro. The same in vitro treatment of explanted undifferentiated gonadal ridges cultured for 4 days results in decreased numbers and altered localization of the germ cell inside the gonads. Taken together these results suggest that E-cadherin plays an important role in primordial germ cell migration and homing and may act as a modulator of primordial germ cell development.


Modeling genomic diversity and tumor dependency in malignant melanoma.
The classification of human tumors based on molecular criteria offers tremendous clinical potential; however, discerning critical and "druggable" effectors on a large scale will also require robust experimental models reflective of tumor genomic diversity. Here, we describe a comprehensive genomic analysis of 101 melanoma short-term cultures and cell lines. Using an analytic approach designed to enrich for putative "driver" events, we show that cultured melanoma cells encompass the spectrum of significant genomic alterations present in primary tumors. When annotated according to these lesions, melanomas cluster into subgroups suggestive of distinct oncogenic mechanisms. Integrating gene expression data suggests novel candidate effector genes linked to recurrent copy gains and losses, including both phosphatase and tensin homologue (PTEN)-dependent and PTEN-independent tumor suppressor mechanisms associated with chromosome 10 deletions. Finally, sample-matched pharmacologic data show that FGFR1 mutations and extracellular signal-regulated kinase (ERK) activation may modulate sensitivity to mitogen-activated protein kinase/ERK kinase inhibitors. Genetically defined cell culture collections therefore offer a rich framework for systematic functional studies in melanoma and other tumors.


Red deer synchronise their activity with close neighbours.
Models of collective animal behaviour frequently make assumptions about the effects of neighbours on the behaviour of focal individuals, but these assumptions are rarely tested. One such set of assumptions is that the switch between active and inactive behaviour seen in herding animals is influenced by the activity of close neighbours, where neighbouring animals show a higher degree of behavioural synchrony than would be expected by chance. We tested this assumption by observing the simultaneous behaviour of paired individuals within a herd of red deer Cervus elaphus. Focal individuals were more synchronised with their two closest neighbours than with the third closest or randomly selected individuals from the herd. Our results suggest that the behaviour of individual deer is influenced by immediate neighbours. Even if we assume that there are no social relationships between individuals, this suggests that the assumptions made in models about the influence of neighbours may be appropriate.


Polybrominated diphenyl ethers, toxaphenes, and other halogenated organic pollutants in great blue heron eggs.
The great blue heron (Ardea herodias) has been used as a bioindicator of the state of the St. Lawrence River (Québec, Canada) since 1996. At 5-year intervals, selected breeding colonies along the River and its estuary are visited to estimate reproductive success and determine levels of contamination. Brominated flame retardants are found in many ecosystems and are increasing in concentration in the Great Lakes, which is the source of much of the water for the St. Lawrence River. In 2001 and 2002, in addition to polychlorinated biphenyls (PCBs) and chlorinated pesticides, the levels of polybrominated diphenyl ethers (PBDEs), polychlorinated bornanes (toxaphene) congeners and non-ortho-substituted PCBs were measured for the first time in pools of great blue heron eggs. The PBDE levels in great blue heron eggs (70-1,377 ng/g wet wt) were comparable to those measured in herring gull (Larus argentatus) eggs from the Great Lakes. Toxaphene was detected in great blue heron eggs at levels comparable to those of other major chlorinated pesticides. Major toxaphene congeners were octachlorobornane P44 and the nonachlorobornane P50. Environ.


Constructive approximation to multivariate function by decay RBF neural network.
It is well known that single hidden layer feedforward networks with radial basis function (RBF) kernels are universal approximators when all the parameters of the networks are obtained through all kinds of algorithms. However, as observed in most neural network implementations, tuning all the parameters of the network may cause learning complicated, poor generalization, overtraining and unstable. Unlike conventional neural network theories, this brief gives a constructive proof for the fact that a decay RBF neural network with n+1 hidden neurons can interpolate n+1 multivariate samples with zero error. Then we prove that the given decay RBFs can uniformly approximate any continuous multivariate functions with arbitrary precision without training. The faster convergence and better generalization performance than conventional RBF algorithm, BP algorithm, extreme learning machine and support vector machines are shown by means of two numerical experiments.


Glioma-associated antigen expression in oligodendroglial neoplasms. Tenascin and epidermal growth factor receptor.
Epidermal growth factor receptor (EGFR), its variant, EGFRvIII, and tenascin are glioma-associated antigens that are hyperexpressed by neoplastic glial cells relative to normal brain, making them attractive antigenic targets for immunotherapy. Preliminary surveys indicate that oligodendroglial tumors also produce these proteins, although the exact patterns and degrees of reactivity are not known. In this study we examined the immunoreactivity of tenascin among 50 oligodendroglial tumors, including 25 well-differentiated oligodendrogliomas (WDOs) and 12 glioblastomas (GBMs) exhibiting high proportions of oligodendroglia-like cells. We used well-characterized immunoreagents with defined specificities against the target antigens on formalin-fixed, paraffin-embedded archival tissue. The tumors were graded according to WHO guidelines. Immunoreactivity was reported on a 1-3 scale according to staining intensity multiplied by a 1-3 distribution scale distribution within tumor as focal (1), multifocal (2), and diffuse (3) for both the parenchymal and the perivascular components. Although there is considerable overlap in antigen production among the grades of tumor, this study establishes the production of tenascin and wild-type EGFR (but not EGFR vIII) in oligodendroglial neoplasms and supports the concept that antigen production increases with tumor grade.


[A Case of Bilateral Trigeminal Neuralgia and the Possible Onset Mechanisms Based on the Operative Findings].
Several cases of bilateral trigeminal neuralgia(TN)have been reported;however, the possible onset mechanism has rarely been discussed. We encountered a case of bilateral TN occurring in two stages. A 64-year-old woman presented with left TN. Magnetic resonance imaging showed the transverse pontine vein adhering to the left trigeminal root and superior cerebellar artery adhering to the right trigeminal root;however, no symptoms were noted. Immediately after microvascular decompression(MVD)on the left side, TN disappeared completely. However, 2 years postoperatively, the patient presented with right TN. The second MVD surgery revealed that the right cerebellar surface severely adhered to the dura mater, particularly under the surface of the tentorium. The arachnoid membrane at the cerebellopontine angle was slightly adhered. The patient was completely free from pain after the second MVD. The intraoperative findings suggested that the brain stem may have shifted and the cerebellopontine cistern may have narrowed because of cerebellar adhesion to the surrounding structures and arachnoid adhesion. We speculate that such structural changes in the posterior fossa after the first operation may have caused the asymptomatic vascular adhesion to change into the symptomatic offending adhesion over time.


Control of antibiotic therapy in pediatric patients. I. A computer system to collect and analyze antibiotic prescriptions in hospitals.
A computer system to record and analyze antibiotic prescriptions in hospitalized children is described. This system is especially organized in order to obtain simultaneously a quantitative evaluation of antibiotic use and a qualitative analysis of the process by which the physician makes his decision for therapy. The practical employment of this program has been demonstrated by analyzing 765 prescriptions given in nine different pediatric hospital wards. Many errors of prescription have been demonstrated: antibiotic therapy was based on the clinical impression alone in 31.5% of the prescriptions, antibiotic choice was rational in 20.1% and the posology prescribed complied with the usually applied schemes in 22.4%. Finally, the physician's attitude regarding laboratory monitoring of side effects was adequate in 52.8% before treatment and 33.4% during antibiotic treatment.


The position of the aorta relative to the spine: a comparison of patients with and without idiopathic scoliosis.
There is little information documenting the relationship of the aorta to the thoracic scoliotic spine. Recent studies have suggested that the ends of screws placed during an anterior spinal arthrodesis, and pedicle screws used for the treatment of right thoracic scoliosis, may be in proximity to the aorta. The purpose of this study was to analyze the anatomical relationship between the aorta and the spine in a comparison of patients with idiopathic right thoracic scoliosis and patients with a normal spine. Thirty-six patients with adolescent idiopathic scoliosis with a right thoracic curve and forty-three with a normal straight spine were studied. Radiographs were analyzed to determine the Cobb angle, the apex of the curve, and the apical vertebral rotation for the patients with scoliosis. Axial magnetic resonance images from the fourth thoracic vertebra to the third lumbar vertebra at the midvertebral body level were used to measure the distance from the aorta to the closest point of the vertebral body cortex, the distance from the posterior edge of the aorta to the spinal canal, and the aorta-vertebral angle. No differences were found between the groups with respect to age or sex distribution. For the scoliosis and normal groups, boys had greater average vertebral body width and depth for all levels than did girls (p < 0.05). For the scoliosis group, the most common apical vertebra was the eighth thoracic vertebra, the average coronal curve measurement was 55.2 degrees, and the average apical rotation was 17.3 degrees. The average distance from the aortic wall to the vertebral body cortex at the apex of the curve was greater in the patients with scoliosis (4.0 mm) than at similar levels in the normal group (2.5 mm) (p < 0.05). The distance from the posterior aspect of the aorta to the anterior aspect of the spinal canal was less in the scoliosis group (11.1 mm) than in the normal group (19.2 mm) for the fifth to the twelfth thoracic level (p < 0.05). The aorta was positioned more laterally and posteriorly adjacent to the vertebral body at the fifth to the twelfth thoracic level in patients with scoliosis compared with that in normal patients as reflected in a smaller aorta-vertebral angle (p < 0.05). With an increasing coronal Cobb angle in the thoracic curve and apical vertebral rotation, the aorta was positioned more laterally and posteriorly (p < 0.05). In patients with right thoracic idiopathic scoliosis, the aorta is positioned more laterally and posteriorly relative to the vertebral body compared with that in patients without spinal deformity.


Efficacy and safety of fluticasone propionate/salmeterol and fluticasone propionate monotherapy in step-up treatment of childhood asthma: A systematic review and meta-analysis.
Asthma is a chronic respiratory disease that affects millions of children worldwide and can impair their quality of life and development. Inhaled glucocorticoids are the mainstay of asthma treatment, but some children require step-up therapy with additional drugs to achieve symptom control. Fluticasone propionate and salmeterol (FSC) has been shown to reduce asthma exacerbations and improve lung function in adults. However, the evidence for its efficacy and safety in children is limited. This study aims to provide a comprehensive basis for treatment selection by summarizing existing clinical randomized controlled trials (RCTs) on the efficacy of FSC compared to fluticasone propionate (FP) monotherapy in children with asthma who require step-up treatment. Five online databases and three clinical trial registration platforms were systematically searched. The effect size and corresponding 95% confidence interval (CI) were calculated based on the heterogeneity among the included studies. Twelve RCTs were identified and a total of 9, 859 patients were involved. The results of the meta-analysis revealed that the use of FSC was associated with a greater reduction in the incidence of asthma exacerbations than FP alone when the dose of FP was the same or when the duration of treatment exceeded 12 weeks. In addition, FSC resulted in a greater proportion of time with asthma-free and without the use of albuterol compared to FP alone when the duration of treatment exceeded 12 weeks. No significant differences were observed between FSC and FP alone in the incidence of drug-related adverse events and other adverse events. Both FSC and FP alone are viable options for the initial selection of step-up treatment in asthmatic children. While, FSC treatment demonstrates a greater likelihood of reducing asthma exacerbations which is particularly important for reducing the personnel, social and economic burden in children requiring step-up asthma treatment.


No involvement of antidiuretic hormone in acute antidiuresis during PEEP ventilation in humans.
Decreased urinary output (Vu ml/min) after institution of PEEP is attributed to a variety of mechanisms including decreased cardiac output and renal blood flow (RBF), activation of neurohormonal reflexes, increased catecholamines, plasma renin activity (PRA), and antidiuretic hormone (ADH) release. To evaluate these factors, seven normovolemic patients (36 yr +/- 13 SD), free of preexisting lung, cardiac, or renal disease, requiring continuous mandatory ventilation for neurologic reasons were studied. The authors measured or calculated: total blood volume (TBV) (51Cr); right atrial, pulmonary arterial, pulmonary wedge, and systemic pressures, cardiac index (CI); renal plasma flow (RPF) (iodohippurate sodium 131I [131I PAH] clearance); glomerular filtration rate (GFR) (creatinine clearance), free water clearance (CH2O), osmolal clearance (Cosm), fractional excretion of sodium (FENa+) and potassium (FEK+); and plasma renin activity (PRA) (ng X ml-1 X h-1), plasma ADH (pg/ml; radioimmunoassay), epinephrine (E in pg/ml), and norepinephrine (NE in pg/ml) (double-isotope radioenzymatic assay). Two conditions were studied after 90-min steady state: 1) zero PEEP (ZEEP); and 2) 15 cmH2O PEEP. PEEP caused a significant decrease in CI (-21%; P less than 0.01) and RPF (-19%; P less than 0.05) without significant decrease in GFR. A significant decrease in Vu (-55%; P less than 0.05), FENa+ (-39%; P less than 0.05) and Cosm (-36%; P less than 0.25) occurred without modification in CH2O. Plasma ADH remained in the normal range and did not increase when PEEP was applied.(ABSTRACT TRUNCATED AT 250 WORDS)


Kinetics of the Strongly Correlated CH3O + O2 Reaction: The Importance of Quadruple Excitations in Atmospheric and Combustion Chemistry.
Kinetics measurements on radical-radical reactions are often unavailable experimentally, and obtaining quantitative rate constants for such reactions by theoretical methods is challenging because the transition states and the reactants are often strongly correlated. Treating strongly correlated systems by coupled cluster theory limited to single, double, and triple connected excitations is often inadequate. We therefore use a new method, called GMM(P), for extrapolation to the complete configuration interaction limit to go beyond triple excitations and in particular to approximate the CCSDTQ(P)/CBS limit. Here, we present this method and use it to investigate the CH3O + O2 reaction. The contribution of connected quadruple excitations to the barrier height energy is found to be -3.13 kcal/mol, and adding a quasiperturbative calculation of the effect of connected pentuple excitations brings the post-connected-triples contributions to -3.44 kcal/mol, which corresponds to Boltzmann factors that increase calculated rate constants by factors of 1.0 × 103, 3.3 × 102, and 18 at 250, 298, and 600 K, respectively. We present rate constants for temperatures from 250 to 2000 K, and we find that the Arrhenius activation energy increases from 0.58 to 9.68 kcal/mol over this range. We also find reasonably good accuracy for the barrier height with the MN15-L exchange-correlation functional, and we calculate rate constants by a combination of GMM(P) and MN15-L electronic structure calculations and conventional and variational transition state theory, in particular canonical variational theory with small-curvature tunneling. The present findings have broad implications for obtaining quantitative rate constants for complex reaction systems in atmospheric and combustion chemistry.


Detection of hantaviral antibodies among patients with hepatitis of unknown etiology in Japan.
Hantaviral antibodies were detected in the sera from patients with hepatic disease of unknown etiology in Japan by several different serological diagnostic methods. A total of 105 sera from diseased patients which were negative to A-G hepatitis virus infections in the Tokyo area were tested. Among them, 3 out of 73 sera from patients with chronic hepatic disease were positive to hantaviral antibody by enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescent antibody assay (IFA) and Western blot analysis (WB). Neutralizing antibody titers of the 3 sera to Seoul virus (SEO) were 4 to 8 times higher than those to Hantaan virus (HTN). However, all of the 32 sera from patients with acute hepatitis were negative for hantaviral antibody. Among the 60 patients with chronic hepatitis in Hokkaido which were serologically negative to B and C hepatitis virus infection, one was positive for hantaviral antibody by ELISA and WB. In contrast, the sera from healthy adults in Japan, 550 from the Honshu and Kyushu regions, and 1,000 from the Hokkaido region, were negative for hantavirus antibody. These results show that hantaviral antibodies are more frequently detected in patients with hepatic disease than in healthy adults. However, the observation that no positive sera were detected from patients with acute hepatitis implies that hantavirus might not be directly related to hepatitis.


The ASP3 locus in Saccharomyces cerevisiae originated by horizontal gene transfer from Wickerhamomyces.
The asparagine degradation pathway in the S288c laboratory strain of Saccharomyces cerevisiae is comprised of genes located at two separate loci. ASP1 is located on chromosome IV and encodes for cytosolic l-asparaginase I, whereas ASP3 contains a gene cluster located on chromosome XII comprised of four identical genes, ASP3-1, ASP3-2, ASP3-3, and ASP3-4, which encode for cell wall-associated l-asparaginase II. Interestingly, the ASP3 locus appears to be only present, in variable copy number, in S. cerevisiae strains isolated from laboratory or industrial environments and is completely absent from the genomes of 128 diverse fungal species. Investigation of the evolutionary history of ASP3 across these 128 genomes as well as across the genomes of 43 S. cerevisiae strains shows that ASP3 likely arose in a S. cerevisiae strain via horizontal gene transfer (HGT) from, or a close relative of, the wine yeast Wickerhamomyces anomalus, which co-occurs with S. cerevisiae in several biotechnological processes. Thus, because the ASP3 present in the S288c laboratory strain of S. cerevisiae is induced in response to nitrogen starvation, its acquisition may have aided yeast adaptation to artificial environments. Our finding that the ASP3 locus in S. cerevisiae originated via HGT further highlights the importance of gene sharing between yeasts in the evolution of their remarkable metabolic diversity.


[A comparative evaluation of "cerebral oximetry" during anesthesia with xenon and other anesthetics].
The oxygen status dynamics during the general anesthesia is one of the most important issues of anesthetic monitoring. The set target was to study the cerebral oximetry (rSO2) in anesthesia with xenon as compared with other anesthetics. A total of 80 patients (class ASA I-II) were examined in the venectomy surgery. According to an anaesthetic used in induction and anesthesia management, the patients were divided into 3 groups. Group 1--40 patients with xenon mono-anesthesia; group 2--20 patients with propofol + N2O + neurolpangesia; and group 3--20 patients with N2O + ftorotan. At xenon induction, rSO2 went up by 6.4%. At propofol induction, there were no changes in rSO2. A biggest increase in the cerebral blood circulation was noted, at the anesthesia management stage, in the patients' group, who received ftorotan; a lesser increase was registered in xenon anesthesia. An increased rSO2 level was higher, during the wakening stage, in case of ftorotan administration than in the group, which received xenon; the process of recovering the initial parameters was slower in the former group. Xenon and ftorotan were shown to contribute to a higher oxygen status and an increased volume of the cerebral blood circulation. In case of xenon mono-anesthesia, there was a smaller increase in the cerebral blood circulation as compared to N2O + ftoratan anesthesia. Further special investigations are needed to give a final answer to the question on whether it is possible to use xenon in neuroanesthesiology and in intensive care of patients with a neuroresuscitation-type pathology of the brain.


Designing games to teach ethics.
This paper describes a teaching methodology whereby students can gain practical experience of ethical decision-making in the engineering design process. We first argue for the necessity to teach a 'practical' understanding of ethical issues in engineering education along with the usual theoretical or hypothetical approaches. We then show how this practical understanding can be achieved by using a collaborative design game, describing how, for example, the concept of responsibility can be explored from this practical basis. We conclude that the use of games in design education can provide an excellent basis for discussing practical and ethical reasoning during the process of design.


Development of hemagglutinin subtype-specific reference antisera by DNA vaccination of chickens.
Previously, we have shown that intramuscular vaccination of chickens with the eukaryotic expression vector (EEV), expressing the influenza H5 hemagglutinin (H) protein, can stimulate a measurable and protective antibody response. Based on these results, we cloned other H genes from Eurasian H5, North American and Eurasian H7, and H15 influenza viruses into the EEV for use in vaccination of chickens to produce reference antibodies for diagnostic purposes, such as the hemagglutination inhibition (HI) test. Three-week-old specific pathogen free (SPF) chickens were vaccinated with 100 microg of EEV mixed with a cationic lipid by intramuscular injection. Then the birds were boostered twice at monthly intervals after the original vaccination. Measurable antibody titers were present for most birds after 1 month and generally increased after each boost. To examine the cross reactivity of the sera with other subtypes, HI test was conducted with antigens prepared from 15 subtypes of influenza virus. Subtype specificity of the antisera prepared by DNA vaccination were comparable or better than the antisera prepared by traditional method using whole virus vaccination. Preparation of reference antisera by DNA vaccination holds good promise because it is safe and allows for the production of H specific antibodies without producing antibodies specific to other influenza viral proteins.


Walking stability of Rhyzopertha dominica (Fabricius, 1792) (Coleoptera: Bostrichidae).
Results obtained in studies can contribute to the advancement of science and innovative methods and techniques for developing practical activities. Reporting conditions that may restrict the implementation of research is critical to ensure the optimal development of further technical studies. The objective of this study was to assess the walking stability of R. dominica on a flat and smooth surface. The study was based on the determination of mortality, morphology and walking stability of the insect outside the grain mass, on a flat and smooth surface. Mortality of adults of this Coleoptera in conditions with and without food was similar, which explains the difficulty that this insect had for accessing the food source on the flat and smooth surface. The measurements of body length (BOL), width (BOW) and height (BOH) of R. dominica were compared with those of Tribolium castaneum (Coleoptera: Tenebrionidae), which showed good ability to walk in these conditions. This study indicated that the former presents lower BOL and BOW, and greater BOH than the second, and all these variables showed differences when analyzed simultaneously by means of the construction of multivariate morphometric indices (Width × Height, Length × Height and Height × Length × Width). These morphometric variables, together with the definition of the geometry most similar to the body shape, resulted in determination of the center of gravity (CG) and static rollover threshold (SRTgeom) for both species. Rhyzopertha dominica and T. castaneum presented CGs considered high and low, respectively, and together with the values obtained for SRTgeom, may justify that R. dominica can be considered a less stable species during movement, and presents greater risk of rollover on flat and smooth surfaces.


Outpatient management of young febrile infants with urinary tract infections.
Controversy exists regarding the disposition of young febrile infants who present to emergency departments (EDs) with urinary tract infections (UTIs). In a large multicenter cohort of such patients, we aimed to determine the variation in patient disposition and clinical factors independently associated with outpatient management. Secondary analysis of a retrospective study of infants 29 to 60 days with fever (≥38.0°C), urinalysis finding, and culture-proven UTIs presenting to 20 North American EDs belonging to the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. We determined independent factors associated with outpatient management. Of 1764 infants with UTIs, 132 (7.5%) were discharged home from the ED. The proportion of infants managed as outpatients varied among sites (0%-20.0%). Of the 132 infants, 29 (22.0%) were subsequently hospitalized after culture results were known, including 5 patients with bacteremia. None of the 107 patients initially discharged from the ED for whom outcomes were known had adverse events (0%; 95% CI, 0%-2.7%). On multivariable regression and generalized estimated equations analyses, only clinical site, presence of upper respiratory tract infection symptoms, absence of vomiting, and having fewer than 10 white blood cells per microliter on cerebrospinal fluid examination were independently associated with discharge from the ED. Clinical site was the factor most highly associated with outpatient management (odds ratio, 8.8; 95% confidence interval, 5.2-15.0). There is substantial practice variation regarding the disposition of febrile infants 29 to 60 days of age with UTIs. Institutional practice is the strongest predictor of outpatient management. Further evidence is needed to guide the management of non-toxic-appearing young febrile infants with UTIs.


Identification of a pre-S2 mutant in hepatocytes expressing a novel marginal pattern of surface antigen in advanced diseases of chronic hepatitis B virus infection.
The expression of hepatitis B viral (HBV) antigens in liver tissue reflects the replicative status of chronic HBV infection. We have previously recognized a novel marginal pattern of hepatitis B surface antigen (HBsAg) in hepatocytes, which usually clusters in groups and emerges at the late non-replicative phase. This study was designed to investigate whether the marginal-type HBsAg represented the gene product of a specific HBV-surface mutant. Microdissection of cirrhotic nodules homogeneously expressing marginal HBsAg was performed on two of 12 resected livers from HBsAg-seropositive patients with hepatocellular carcinoma. The gene presumably encoding marginal HBsAg was polymerase chain reaction (PCR)-cloned, sequenced and analysed. In vitro transfection and expression of the cloned surface mutant plasmids were performed on the Huh7 cell line to illustrate intrahepatic HBsAg expression. Immunohistochemical staining revealed that the marginal HBsAg was positive for pre-S1 and thus contained large surface proteins. The PCR cloning and sequencing of the genes presumably encoding marginal-type HBsAg in both cases revealed the same deletion at the 5' terminus (nt 2-55) of pre-S2. A point mutation on the small-surface (S) antigen was also found in one case. The pre-S2 deletion sequence and the mutation sites of the S gene coincide with human lymphocyte antigen-restricted T- and/or B-cell epitopes. In vitro transfection of the mutant plasmid revealed a blot-like retention or accumulation of HBsAg in the cytoplasm or at the periphery of hepatocytes, accompanied by a decreased secretion of HBsAg in the culture supernatant, mimicking intrahepatic expression. A natural pre-S2 deletion mutant was identified in hepatocytes expressing a novel marginal pattern of HBsAg, which probably contains mutant, large, surface proteins. The biological significance of the pre-S2 deletion mutant should be interesting in view of the clustering proliferation of hepatocytes expressing marginal HBsAg.


[Cerebral metastasis in Hodgkin's disease].
The article describes the case history of a 31 year old woman with a solitary intracranial metastasis from Hodgkin's lymphoma, and reviews the relevant literature. Metastasis to the central nervous system from Hodgkin's disease is uncommon. This affection is usually a result of metastasis to the meninges or bone, or of direct extension from paracranial or paraspinal lymph node involvement. Hematogenous metastasis of Hodgkin's disease confined to the brain is rare. Affection of the central nervous system is most common in lymphocyte depletion Hodgkin's disease. A higher frequency is seen in advanced clinical stages. The prognosis is poor.


Delirium diagnostic and classification challenges in palliative care: subsyndromal delirium, comorbid delirium-dementia, and psychomotor subtypes.
Delirium often presents difficult diagnostic and classification challenges in palliative care settings. To review three major areas that create diagnostic and classification challenges in relation to delirium in palliative care: subsyndromal delirium (SSD), delirium in the context of comorbid dementia, and classification of psychomotor subtypes, and to identify knowledge gaps and research priorities in relation to these three areas of focus. We combined multidisciplinary input from delirium researchers and knowledge users at an international delirium study planning meeting and relevant PubMed literature searches as the knowledge synthesis strategy in this review. We identified six (SSD), 33 (dementia), and 44 (psychomotor subtypes) articles of relevance in relation to the focus of our review. Recent literature data highlight the frequency and impact of SSD, the relevance of comorbid dementia, and the propensity for a hypoactive presentation of delirium in the palliative population. The differential diagnoses to consider are wide and include pain, fatigue, mood disturbance, psychoactive medication effects, and other causes for altered consciousness. Challenges in the diagnosis and classification of delirium in people with advanced disease are compounded by the generalized disturbance of central nervous system function that occurs in the seriously ill, often with comorbid illness, including dementia. Further research is needed to delineate the pathophysiological and clinical associations of these presentations and thus inform therapeutic strategies. The expanding aged population and growing focus on dementia care in palliative care highlight the need to conduct this research.


The development of laser angioplasty.
Recent developments in technology have stimulated interest in the use of catheter-directed laser energy for removal of atherosclerotic plaques. Over the past three years, intensive research efforts by a number of investigators have defined the potential therapeutic benefit of laser angioplasty, as well as its limitations. Unlike balloon angioplasty, the laser has the capacity to remove totally atheromatous plaque or thrombus by photovaporization. Unique properties of the laser allow light energy to be concentrated for plaque removal. Arterial damage adjacent to the plaque is prevented by certain lasers, while others produce thermal injury to the arterial wall. Chemical pretreatment with vital dyes or drugs has been shown to enhance absorption of laser radiation by plaque and may enable selective destruction of the arterial plaque. Fiberoptic catheters have been designed to transmit laser energy to remote intravascular targets; however, precise guidance systems for catheter delivery have not been developed sufficiently for safe intracoronary application. Complete arterial healing by endothelial cell migration has been demonstrated after laser ablation of plaque in animal studies. Among the first four clinical trials of laser angioplasty, relief of atherosclerotic obstruction was successful using argon, neodymium-YAG, and carbon dioxide lasers. Despite the satisfactory initial appearance of laser-treated arteries, the long-term effects and risk of atherogenesis are undetermined. A potential risk of thrombosis has been identified after laser application, especially with the argon and NdYAG lasers. Further basic and clinical research are needed to establish the role of this promising new technology in the treatment of cardiovascular disease.


[Magnetic materials in dentistry].
In the last 40 years, magnets have been used in dentistry. Initially as anecdotic reports, but recently, after the development of powerful rare earth magnets, new applications of them have arised and offer a clinically proved alternative to mechanical systems. Many experimental and clinical trials have demonstrated their adequate use in prosthetic rehabilitations, partial removable or overdentures, tooth or implant beared, or in other like orthodontics. The authors describe the historical evolution of magnetic systems used in dentistry, their physical and mechanical principles, their attributes as biomaterials and their designs and way of use.


[Characteristics of changes in the kinin system of blood in hypertensive disease].
The state of the kinin system of blood was studied in terms of its content of kininogen, prekallikrein, kallikrein inhibitor and the spontaneous esterase activity. The examination was conducted in 10 normal individuals and in 81 hypertensive patients with labile and stable arterial pressure and an uncomplicated course. The studies were conducted at rest, during the transfer into an orthostatic position, and after 15 or 60 minutes of walking. The normals demonstrated an activation of the kinin system that ensued in orthostasis, but was more distinct at walking. A significant correlation was noted between the content of prekallikrein and kininogen in all the states under examination. In cases of labile arterial hypertension an increased activation of the blood kinin system was observed at rest, a lack of its activation at walking, and disorders in the correlation between the content of prekallikrein and kininogen. The observed changes in the kinin system may affect the central haemodynamics and the formation of the hyperkinetic type of circulation.


Treatment of school refusal: one-year follow-up.
To conduct a 1-year follow-up of anxious-depressed school-refusing adolescents who participated in an 8-week study of imipramine versus placebo, each in combination with cognitive-behavioral therapy. Sixty-five percent (41 of 63) of the randomly assigned subjects returned for follow-up evaluation, which consisted of diagnostic interviews, clinician rating scales for anxiety and depression, family functioning measure, and a questionnaire regarding interim treatments and school programs. From the adolescent and/or parent perspective, 64.1% met criteria for an anxiety disorder and 33.3% met criteria for a depressive disorder. Remission rates and acquisition rates for specific anxiety and depressive disorders were determined. In the follow-up period, 67.5% received at least one psychotropic medication trial and 77.5% had outpatient therapy. Higher level of somatic complaints on the Anxiety Rating for Children-Revised Physiological subscale at baseline predicted more severe depression on the Children's Depression Rating Scale-Revised at follow-up (p = .029). In this naturalistic follow-up study, there was high utilization of mental health interventions. In addition, a substantial number of subjects met criteria for anxiety and/or depressive disorders 1 year after treatment. Investigation of duration of acute treatments and evaluation of maintenance treatments for school refusal is needed.


A quick method for identifying radiolytic hydrocarbons in low-fat-containing food.
As radiation-induced alterations of the lipid fraction of foods are related to their initial fat content, concentrations of fat degradation products used as irradiation markers are expected to be lower when irradiating low-fat-containing foods. Thus the sensitivity required when applying analytical methods for identifying irradiation markers in foods eventually depends on their respective amounts of fat. The aim of this study was to perform the qualitative analysis of characteristic hydrocarbons resulting from irradiation of samples with a fat content as low as 25 g kg(-1). A rapid extraction using a small amount of ethyl acetate was the unique sample pretreatment required to accomplish the analysis of radiolytic markers by using on-line coupling of reverse phase liquid chromatography and gas chromatography with mass spectrometry detection (RPLC/GC/MS). Efficient elimination of the large volumes (up to 2170 µL) directly transferred from LC to GC was achieved by optimising the operation mode of the through-oven transfer adsorption/desorption system used as interface. The reported procedure allowed confirmation, in less than 65 min, of the occurrence of up to five irradiation markers, namely n-pentadecane, 1-hexadecene, 1,7-hexadecadiene, n-heptadecane and 8-heptadecene, in cooked ham irradiated at doses as low as 2 kGy.


Improving "medical necessity" acceptance by health care providers and consumers.
A major problem for patients and providers has existed since establishment of peer review and authorization agency medical necessity guide lines, because physicians and patients who receive denial of proposed procedures and tests on the basis of so called "medical necessity" presume that the authorization agency considers the proposed procedure or test to be medically unnecessary, meaning of no health value to the patient. This may well not be the case. Both providers and consumers can be expected to be more accepting of negative authorization decisions if the principles of continuous quality improvement are brought to bear on the authorization process.


Delivery of Virtual Care in Oncology: Province-Wide Interprofessional Consensus Statements Using a Modified Delphi Process.
Virtual cancer care (i.e., teleoncology) was rapidly adopted during the COVID-19 pandemic to meet the needs of patients with cancer. However, there is a paucity of guidance for clinicians regarding virtual cancer care. We sought to develop consensus-based statements to guide the optimal provision of virtual care for clinicians caring for patients with cancer, using a modified Delphi consensus process with a 29-member panel consisting of an interprofessional group of clinicians caring for patients with cancer and patient representatives. The consensus process consisted of two rounds and one synchronous final consensus meeting. At the end of the modified Delphi process, 62 of 62 statements achieved consensus. Fifty-seven statements reached consensus in the first round of the process. Concerns regarding the ability to convey difficult news virtually and maintaining similar standards as in-person care without disproportionate strain on clinicians and patients were addressed in the consensus process. We achieved interprofessional consensus on virtual cancer care practices. Further research examining the impact of virtual cancer care on person-centred and clinical outcomes are needed to inform practices during the COVID-19 pandemic and beyond.


The Association between Away Rotations and Rank Order in the Integrated Plastic Surgery Match.
Given the competition in the integrated plastic surgery Match, away rotations are ubiquitous among plastic surgery applicants to differentiate their applications. This study aimed to characterize how performing an away rotation affects rank order and Match outcomes for integrated plastic surgery programs. An online survey was designed and distributed to the top 25 integrated plastic surgery programs in the United States as determined by Doximity. Programs were polled about away rotation structure, position of rotators on their 2018 to 2019 rank list, and composition of current resident classes. Twenty-five programs completed the survey (response rate, 100 percent). On average, programs interviewed 34.9 applicants (range, 22 to 50 applicants) and ranked 32.8 applicants (range, 10 to 50 applicants). Most "ranked-to-match" positions were occupied by home students or away rotators (60.9 percent). Rank order of home students, away rotators, and nonrotators varied significantly (p < 0.001), with median rank order of home students [5 (interquartile range, 1 to 9)] and rotators [14 (interquartile range, 6 to 27)] higher than nonrotators [17 (interquartile range, 10 to 29)]. Rank orders of away rotators tended to follow a bimodal distribution. Furthermore, 64.4 percent of integrated residents were either a home student or away rotator at their matched integrated program, with 20 percent of residency programs composed of greater than 70 percent of away rotators/home students across postgraduate years 1 through 6 classes. For integrated plastic surgery programs, the majority of ranked-to-match students on rank lists and current residents were either home students or away rotators at their respective program. Performing well on an away rotation appears to confer significant benefit to the applicant applying in the integrated plastic surgery Match.


Effects of dietary organic minerals, fish oil, and hydrolyzed collagen on growth performance and tibia characteristics of broiler chickens.
Nutrition is a crucial factor for growth and bone development in broiler chickens. Adjustments in dietary ingredients might affect bone development and consequently locomotion related problems. This study was designed to evaluate effects of dietary organic minerals (ORM), fish oil (FISH), and hydrolyzed collagen (COL) on growth performance and tibia characteristics of broiler chickens. A total of three hundred eighty four 1-day-old Ross 308 male broiler chickens were used in a complete randomized block design with 4 diet groups and 8 replicates per diet group. In the ORM diet, the inorganic macro and trace minerals were replaced by their organic varieties. In the FISH diet, palm oil and soybean oil were partly replaced by FISH. In the COL diet, soybean meal was partly replaced by COL. Results showed that the ORM and COL diet groups reached a higher body weight (BW) at 42 D of age than the FISH diet group, whereas the control group was in between. The feed conversion ratio between day 1 and 42 was lower in the ORM and COL diet groups than in both other diet groups. On day 28, 35, and 42, gait score (GS), Varus Valgus deformity, tibia length (TL), thickness, femoral and metatarsal head thickness (THT), mineral content (TMC), mineral density (TMD), breaking strength (TBS), stiffness (TSF), and energy to fracture (TEF) were measured (n = 3/replicate). The ORM diet group had higher TL at day 42, higher THT at day 28, higher TMC at day 42, higher TMD at day 28, 35, and 42, higher TBS at day 42, higher TSF at day 35 and 42, and higher TEF at day 42 compared to the FISH diet group, with the COL and control diet groups in between. It can be concluded that replacing dietary inorganic macro and trace minerals by their organic varieties seems to stimulate tibia dimensions, strength, and mineral content of broiler chickens. On the contrary, FISH appears to negatively affect tibia characteristics.