EEG-Based Closed-Loop Neurofeedback for Attention Monitoring and Training in Young Adults.
Attention is an important mechanism for young adults, whose lives largely involve interacting with media and performing technology multitasking. Nevertheless, the existing studies related to attention are characterized by low accuracy and poor attention levels in terms of attention monitoring and inefficiency during attention training. In this paper, we propose an improved random forest- (IRF-) algorithm-based attention monitoring and training method with closed-loop neurofeedback. For attention monitoring, an IRF classifier that uses grid search optimization and multiple cross-validation to improve monitoring accuracy and performance is utilized, and five attention levels are proposed. For attention training, we develop three training modes with neurofeedback corresponding to sustained attention, selective attention, and focus attention and apply a self-control method with four indicators to validate the resulting training effect. An offline experiment based on the Personal EEG Concentration Tasks dataset and an online experiment involving 10 young adults are conducted. The results show that our proposed IRF-algorithm-based attention monitoring approach achieves an average accuracy of 79.34%, thereby outperforming the current state-of-the-art algorithms. Furthermore, when excluding familiarity with the game environment, statistically significant performance improvements (p < 0.05) are achieved by the 10 young adults after attention training, which demonstrates the effectiveness of the proposed serious games. Our work involving the proposed method of attention monitoring and training proves to be reliable and efficient.


Distinct emotion regulation skills explain psychopathology and problems in social relationships following childhood emotional abuse and neglect.
Efforts to differentiate between the developmental sequelae of childhood emotional abuse and childhood emotional neglect are critical to both research and practice efforts. As an oft-identified mechanism of the effects of child maltreatment on later adjustment, emotion dysregulation represents a key potential pathway. The present study explored a higher order factor model of specific emotion regulation skills, and the extent to which these skill sets would indicate distinct developmental pathways from unique emotional maltreatment experiences to multidomain adjustment. A sample of 500 ethnoracially diverse college students reported on their experiences. A two-factor model of emotion regulation skills based on subscales of the Difficulties in Emotion Regulation Scale was revealed. Significant indirect effects of childhood emotional abuse on psychopathology and problems in social relationships were found through response-focused difficulties in emotion regulation, whereas a significant indirect effect of childhood emotional neglect on problems in social relationships was found through antecedent-focused difficulties in emotion regulation. These results are consistent with theoretical models and empirical evidence suggesting differential effects of childhood emotional abuse and emotional neglect, and provide an important indication for developing targeted interventions focusing on specific higher order emotion dysregulation skill clusters.


Dynamic segmental kinematics of the lumbar spine during diagnostic movements.
Background: In vivo measurements of segmental-level kinematics are a promising avenue for better understanding the relationship between pain and its underlying, multi-factorial basis. To date, the bulk of the reported segmental-level motion has been restricted to single plane motions. Methods: The present work implemented a novel marker set used with an optical motion capture system to non-invasively measure dynamic, 3D in vivo segmental kinematics of the lower spine in a laboratory setting. Lumbar spinal kinematics were measured for 28 subjects during 17 diagnostic movements. Results: Overall regional range of motion data and lumbar angular velocity measurement were consistent with previously published studies. Key findings from the work included measurement of differences in ascending versus descending segmental velocities during functional movements and observations of motion coupling paradigms in the lumbar spinal segments. Conclusion: The work contributes to the task of establishing a baseline of segmental lumbar movement patterns in an asymptomatic cohort, which serves as a necessary pre-requisite for identifying pathological and symptomatic deviations from the baseline.


[Evaluation of the E-test and the ATB-PNEUMo battery for determining the beta-lactam MIC for Streptococcus pneumoniae in daily practice].
In 1999, during the survey of resistance of Streptococcus pneumoniae to antibiotics by 31 clinical laboratories of Rhône-Alpes area, MIC to penicillin (P), amoxicillin (AMX) and cefotaxime (CTX) of 877 PRP strains or with a diameter of inhibition to oxacillin inferior to 26 mm, were determined by each institution by E-test (n = 220 strains) or ATB-PNEUMO (n = 657 strains). MICs of these three antibiotics were determined by dilution in agar medium by the coordinating center. The essential agreement was respectively for ATB-PNEUMO and E-test 89% versus 84% for P (p > 0.05), of 86% vs 79% for AMX (p < 0.01), and of 91% vs 86% for CTX (p = 0.03). When the strains were classified in clinical category, the differences were significant (p < 0.001) for AMX (85% vs 71%) and for CTX (82% vs 75%) but not for P (73% vs 78%). ATB-PNEUMO method was more sensitive than E-test for the detection of strains susceptible to P (90 vs 73%), to AMX (83 vs 78%) and to CTX (80 vs 72%) and for the strains intermediate to AMX (90 vs 78%). On the contrary, E-test is more specific than ATB-PNEUMO for the detection of P-resistant strains (94 vs 86%). Finally, the specificity of both methods is the same for detection of P-S, AMX-R and CTX-I strains.


Changes of bacterial numbers and carbohydrate fermenting groups during in vitro rumen incubations with feedstuff materials.
Short in vitro incubations of mixed ruminal bacteria with feedstuff materials were conducted. In each series of experiments, the rumen bacterial population was divided into equal portions. One portion was washed anaerobically by centrifugation in a mineral buffer prior to initiation of incubation, whereas the other portion was not washed. Changes of carbohydrate group composition of the populations, of bacterial cell composition, and of incubation fluid characteristics were monitored over 24 h. Washing the bacterial inoculum did not affect adversely the ensuing feed fermentation and resulted in lower background carbohydrates and fermentation acids. Unwashed bacterial incubations had a greater tendency to produce more lactate. When the feedstuff substrate contained more soluble nutrients, the microbial population exhibited batch culture type growth, and bacteria fermenting soluble carbohydrate predominated. When alfalfa hay was the sole substrate, a more balanced fermentation resulted with respect to both carbohydrate group composition and fermentation acid production. Implications of these findings in relation to use of in vitro methods to estimate digestibility of feedstuff are addressed.


21st Century Neo-Androgyny: What Is Androgyny Anymore and Why We Should Still Care.
The notion of psychological androgyny as a research tool loiters on in an incapacitated state. The lack of a general theory and the belief that the biological gender differences are insignificant to non-existent has been the seeds for its de-construction. Over the decades, the testing of ideas associated with androgyny has declined. Indeed, the debates over its usefulness as a construct ended long ago. The judgment nowadays is that debating the constructs of masculinity, femininity, and androgyny as behavioral traits has been long settled, and a contemporary revisiting of androgyny is not warranted. However, from another contemporary viewpoint, if androgyny is to have any future, it needs a new theory devoid of masculinity and femininity. We present a novel theory with the potential to do just that. This article details a new de-gendered theory of psychological androgyny, neo-androgyny, as a candidate to replace traditional models that are now considered outdated and irrelevant. We present five potential factors for inclusion in a de-gendered model: social efficacy, creativity, capability, eminence, and determination. We review these factors concerning the future of androgyny theory.


Effect on transcription of low-molecular-weight RNA from calf thymus chromatin.
1. Two low-molecular-weight nuclear RNA fractions were isolated from the loosely-bound non-histone proteins of calf thymus chromatin: RNA I (of 4 - 5.5S, heterogeneous on polyacrylamide-gel electrohoresis), and RNA IV (of about 3S). 2. Under the reinitiation conditions, RNA I stimulates about 2.5-fold the template properties of homologous chromatin with bacterial RNA polymerase, while RNA IV inhibits these properties by about 50%. 3. When reinitiation is blocked, RNA I stimulates both the initiation and elongation steps (by 20 - 30% and 60%, respectively). 4. The two RNA fractions equally inhibit transcription (by 30 - 35%) with free homologous DNA as a template.


The department without walls. Acceptability, cost, and utilization of interactive video technology.
As groups of physicians continue to provide more of their activities in sites remote from the central office, communication among providers and staff and the provision of common educational activities are important priorities. An analysis of a 12-month period of the use of full-motion interactive video technology to accomplish these goals in a decentralized academic department shows this method to be acceptable and cost-effective. Careful attention to room environment and staff support were found to be important. Practical recommendations are provided for those considering the use of this technology.


A PP2C-1 Allele Underlying a Quantitative Trait Locus Enhances Soybean 100-Seed Weight.
Cultivated soybeans may lose some useful genetic loci during domestication. Introgression of genes from wild soybeans could broaden the genetic background and improve soybean agronomic traits. In this study, through whole-genome sequencing of a recombinant inbred line population derived from a cross between a wild soybean ZYD7 and a cultivated soybean HN44, and mapping of quantitative trait loci for seed weight, we discovered that a phosphatase 2C-1 (PP2C-1) allele from wild soybean ZYD7 contributes to the increase in seed weight/size. PP2C-1 may achieve this function by enhancing cell size of integument and activating a subset of seed trait-related genes. We found that PP2C-1 is associated with GmBZR1, a soybean ortholog of Arabidopsis BZR1, one of key transcription factors in brassinosteroid (BR) signaling, and facilitate accumulation of dephosphorylated GmBZR1. In contrast, the PP2C-2 allele with variations of a few amino acids at the N-terminus did not exhibit this function. Moreover, we showed that GmBZR1 could promote seed weight/size in transgenic plants. Through analysis of cultivated soybean accessions, we found that 40% of the examined accessions do not have the PP2C-1 allele, suggesting that these accessions can be improved by introduction of this allele. Taken together, our study identifies an elite allele PP2C-1, which can enhance seed weight and/or size in soybean, and pinpoints that manipulation of this allele by molecular-assisted breeding may increase production in soybean and other legumes/crops.


Attractiveness of vertebrate hosts to Culex pipiens (Diptera: Culicidae) and other mosquitoes in Israel.
Host preferences of mosquitoes, mainly Culex pipiens L. and Aedes caspius (Pallas), were studied in Israel using live baits, chemical attractants, light, and suction traps. The feeding habits of Cx. pipiens were opportunistic. This species used a wide range of mammalian and avian hosts; a calf, chickens, turkeys, and sheep were the most attractive baits. A. caspius fed mainly on large mammals and was most attracted to calf and sheep baits. Although sheep were attractive, few Cx. pipiens and no Ae. caspius engorged after entering the traps. In addition to defensive behavior and the mechanical protection afforded by the wool, sheep may possess a close-acting repellent that deters mosquitoes from biting. CO2 was the best attractant for host-seeking Cx. pipiens and Ae. caspius, Aedes detritus (Haliday), Culiseta annulata (Schrank), Culiseta longiareolata (Macquart), and Uranotaenia unguiculata Edwards were caught in small numbers, and their bloodmeal hosts were recorded.


Challenges in anaesthesia and pain management for burn injuries.
Burn-injured patients provide unique challenges to those providing anaesthesia and pain management. This review aims to update both the regular burn anaesthetist and the anaesthetist only occasionally involved with burn patients in emergency settings. It addresses some aspects of care that are perhaps contentious in terms of airway management, fluid resuscitation, transfusion practices and pharmacology. Recognition of pain management failures and the lack of mechanism-specific analgesics are discussed along with the opioid crisis as it relates to burns and nonpharmacological methods in the management of distressed patients.


Integrin αvβ6 promotes an osteolytic program in cancer cells by upregulating MMP2.
The molecular circuitries controlling osseous prostate metastasis are known to depend on the activity of multiple pathways, including integrin signaling. Here, we demonstrate that the αvβ6 integrin is upregulated in human prostate cancer bone metastasis. In prostate cancer cells, this integrin is a functionally active receptor for fibronectin and latency-associated peptide-TGF-β1; it mediates attachment and migration upon ligand binding and is localized in focal contacts. Given the propensity of prostate cancer cells to form bone metastatic lesions, we investigated whether the αvβ6 integrin promotes this type of metastasis. We show for the first time that αvβ6 selectively induces matrix metalloproteinase 2 (MMP2) in vitro in multiple prostate cancer cells and promotes osteolysis in vivo in an immunodeficient mouse model of bone metastasis through upregulation of MMP2, but not MMP9. The effect of αvβ6 on MMP2 expression and activity is independent of androgen receptor in the analyzed prostate cancer cells. Increased levels of parathyroid hormone-related protein (PTHrP), known to induce osteoclastogenesis, were also observed in αvβ6-expressing cells. However, by using MMP2 short hairpin RNA, we demonstrate that the αvβ6 effect on bone loss is due to upregulation of soluble MMP2 by the cancer cells, not due to changes in tumor growth rate. Another related αv-containing integrin, αvβ5, fails to show similar responses, underscoring the significance of αvβ6 activity. Overall, these mechanistic studies establish that expression of a single integrin, αvβ6, contributes to the cancer cell-mediated program of osteolysis by inducing matrix degradation through MMP2. Our results open new prospects for molecular therapy for metastatic bone disease.


[Learning dysfunction model in ddY mouse and IgG].
Mice of the ddy strain having once received an electric shock in the dark chamber of a passive avoidance response unit were divided into two groups according to their behavior pattern. It is suggested that learning function of the mice which did not avoid the dark chamber (negative-avoidance mice: N-mice) was disturbed. After an injection of IgG obtained from the positive-avoidance mice (P-mice) into the N-mice, these prior N-mice displayed the behavior pattern similar to that of P-mice following an application of electric shock. It was found that the sugar chain structure of N-mouse IgG was different from that of P-mouse IgG. This result indicates that the sugar chain structure is related to the learning ability of ddy mice.


Sexuality and sexual dysfunction in spinal cord-injured men in Turkey.
To provide a comprehensive evaluation of sexual function and dysfunction in spinal cord-injured men based on self-reports of patients. Forty-seven spinal cord-injured men who completed the spinal shock and rehabilitation period were included. Patients were asked to complete a questionnaire developed to assess social status, sexual activities, abilities, and sexuality education after injury. Neurologic levels of patients were classified according to American Spinal Cord Injury Association protocol. Erectile function was evaluated by International Index of Erectile Function-5 (IIEF-5) questionnaire. Patients were aged between 20 and 62 years (mean: 35.2). Twenty-eight patients had T10 and above, 15 between T11 and L2, and 4 cauda conus injury. While 61.7% of the patients declared sexual activity, 93.6% declared some degree of erection. Mean IIEF-5 score was 5.3 and 87.3% of the patients had moderate to severe erectile dysfunction. Continuation of sexual activity after injury is very important and has a great impact on quality of life and interpersonal relationships for spinal cord-injured men. More attention must be given to sexuality after spinal cord injury. A very high rate of sexual dysfunction in spinal cord-injured patients was found and the importance of sexual education was emphasized in this study.


Successful Control of Hypercalcemia with Sorafenib, Evocalcet, and Denosumab Combination Therapy for Recurrent Parathyroid Carcinoma.
Parathyroid carcinoma (PC) is a rare type of endocrine cancer. Recurrence and metastasis are common after surgery, and refractory hypercalcemia often leads to a poor prognosis. However, there are currently no specific strategies for PC recurrence. We herein report a 61-year-old Japanese man with metastatic PC who was treated with sorafenib, a multikinase inhibitor. In this case, the serum calcium level was under control for 10 months after the initiation of sorafenib. This case suggests that combination therapy with sorafenib, evocalcet, and denosumab may be an alternative, stronger management option for refractory hypercalcemia in recurrent PC.


Structure and function of YcnD from Bacillus subtilis, a flavin-containing oxidoreductase.
YcnD from the gram-positive bacterium Bacillus subtilis is a member of a family of bacterial proteins that act as NADH- and/or NADPH-dependent oxidoreductases. Here, we report for the first time on the biochemical characterization of the purified protein, demonstrating that YcnD is an FMN-containing enzyme that can be reduced by NADH or NADPH (Km = 6.4 and 4.4 microM, respectively). In the presence of free FMN as the electron-accepting substrate, the latter reductant showed a ping-pong Bi-Bi reaction mechanism, whereas utilization of NADH is competitively inhibited by this substrate. This finding suggests that NADPH is the physiological reductant of the enzyme. We also show that YcnD reduces nitro-organic compounds, chromate, and a series of azo dyes. The reduction of azo dyes appears to be mediated by free reduced FMN because the reaction is considerably slower in its absence. Structure determination by X-ray crystallography revealed that YcnD folds into a three layer alpha-beta-alpha sandwich strongly resembling the topology of the NADH oxidase superfamily. Similar to homologous bacterial oxidoreductase, YcnD forms homodimers with an extended dimer interface. The biochemical data and the structure are discussed in light of the putative physiological function of YcnD as an oxidoreductase delivering reduced FMN to enzymes that require the reduced cofactor for activity.


Entanglement prethermalization in an interaction quench between two harmonic oscillators.
Entanglement prethermalization (EP) refers to a quasi-stationary nonequilibrium state of a composite system in which each individual subsystem looks thermal but the entire system remains nonthermal due to quantum entanglement between subsystems. We theoretically study the dynamics of EP following a coherent split of a one-dimensional harmonic potential in which two interacting bosons are confined. This problem is equivalent to that of an interaction quench between two harmonic oscillators. We show that this simple model captures the bare essentials of EP; that is, each subsystem relaxes to an approximate thermal equilibrium, whereas the total system remains entangled. We find that a generalized Gibbs ensemble exactly describes the total system if we take into account nonlocal conserved quantities that act nontrivially on both subsystems. In the presence of a symmetry-breaking perturbation, the relaxation dynamics of the system exhibits a quasi-stationary EP plateau and eventually reaches thermal equilibrium. We analytically show that the lifetime of EP is inversely proportional to the magnitude of the perturbation.


Chronological distribution of readings in ambulatory blood pressure monitoring exams affects the nighttime average and the magnitude of blood pressure dipping.
Averaged nighttime blood pressure (BP) is superior to daytime BP for cardiovascular risk stratification, and the relative change between daytime/nighttime BP (dipping%) significantly predicts cardiovascular risk. Newer reports suggest that 4 measurements at night may be enough for cardiovascular risk stratification. Since BP oscillates across the night, the temporal distribution of measurements across the night may impact nighttime BP and dipping%. Therefore, we compared average nighttime BP and dipping% when using measurements in the first half (1st-half), second (2nd-half), and a combination of both (combined). Forty-three (17 females and twenty-six males) midlife adults aged 50±10 years old wore an ambulatory BP monitor for 24 hours at home, programmed to measure BP every 20 minutes when scheduled for daytime and every 30 minutes during a self-selected 8-hour nighttime for time-in-bed. We compared the nighttime BP averages and dipping% when using either the first four measurements from the 1st-half or 2nd-half of the nighttime and combined. Nighttime Systolic BP was significantly different across 1st-half, 2nd-half, and combined (111±9 vs.107±11 vs. 109±9 mmHg, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each). Systolic BP dipping% was significantly different across 1st-half, 2nd-half, and combined (9.9±5.5 vs.13.5±6.4 vs. 11.7±5.0 %, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each. Diastolic BP and diastolic dipping% were similar across the three different bins. In midlife adults, systolic nighttime BP and dipping% may depend upon when BP measurements are taken during the night.


In vivo administration of urolithin A and B prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats.
Emerging evidence suggests that specific (poly)phenols may constitute new preventative strategies to counteract cell oxidative stress and myocardial tissue inflammation, which have a key role in the patho-physiology of diabetic cardiomyopathy. In a rat model of early diabetes, we evaluated whether in vivo administration of urolithin A (UA) or urolithin B (UB), the main gut microbiota phenolic metabolites of ellagitannin-rich foods, can reduce diabetes-induced microenvironmental changes in myocardial tissue, preventing cardiac functional impairment. Adult Wistar rats with streptozotocin-induced type-1 diabetes (n = 29) were studied in comparison with 10 control animals. Diabetic rats were either untreated (n = 9) or subjected to daily i.p. injection of UA (n = 10) or UB (n = 10). After 3 weeks of hyperglycaemia, hemodynamics, cardiomyocyte contractile properties and calcium transients were measured to assess cardiac performance. The myocardial expression of the pro-inflammatory cytokine fractalkine and proteins involved in calcium dynamics (sarcoplasmic reticulum calcium ATPase, phospholamban and phosphorylated phospholamban) were evaluated by immunoblotting. Plasma, urine and tissue distribution of UA, UB and their phase II metabolites were determined. In vivo urolithin treatment reduced by approximately 30% the myocardial expression of the pro-inflammatory cytokine fractalkine, preventing the early inflammatory response of cardiac cells to hyperglycaemia. The improvement in myocardial microenvironment had a functional counterpart, as documented by the increase in the maximal rate of ventricular pressure rise compared to diabetic group (+18% and +31% in UA and UB treated rats, respectively), and the parallel reduction in the isovolumic contraction time (-12%). In line with hemodynamic data, both urolithins induced a recovery of cardiomyocyte contractility and calcium dynamics, leading to a higher re-lengthening rate (+21%, on average), lower re-lengthening times (-56%), and a more efficient cytosolic calcium clearing (-32% in tau values). UB treatment also increased the velocity of shortening (+27%). Urolithin metabolites accumulated in the myocardium, with a higher concentration of UB and UB-sulphate, potentially explaining the slightly higher efficacy of UB administration. In vivo urolithin administration may be able to prevent the initial inflammatory response of myocardial tissue to hyperglycaemia and the negative impact of the altered diabetic milieu on cardiac performance.


[Nursing audit: identifying notions and method].
The present study aimed at identifying and analyzing the opinions of auditing experts who work within the context of nursing and systematizing trends regarding the notion, methods and purposes of nursing audits at present and over the next five years. In terms of methodology, the study was structured using the Delphi technique, type of prospective and consensual evaluation of trends, performed by experts on the theme under investigation. Results demonstrated that the current notion of nursing audits focuses on the accounting and financial elements, the financial maintenance of the hospital being kept in mind as well as the controlling activity of trying to identify incorrect hospital bills. In the future, however, the notion of auditing is expected to become associated with evaluating the quality of care, with the involvement of other areas that have an impact on it.


Altered host range phenotype of the transformation-defective Ad12 mutant CS-1 is due to deletions in the E1 region.
Although it grows well in bulk infection, human adenovirus type 12 (Ad12) does not plaque efficiently in Vero cells of simian origin. After long-term passage of the virus or after transfection of Ad12 DNA into these cells, however, transformation-defective, host-range mutants giving high plaque yields in Vero cells were isolated. The original mutants have deletions in both E1a and E1b as well as additions of viral sequences at the right terminus of the genome. We have constructed a recombinant virus (Ad12d169) carrying both E1 alterations of the original mutant CS-1 on the Ad12 wild-type background. Another mutant (Ad12mut2) has additional sequences at the right terminus and an intact E1 region. In plaque assays mutant virus Ad12d169 carrying E1a deletions has an about thousandfold higher efficiency in Vero cells than Ad12wt and Ad12mut2, mapping the enhanced replication in Vero cells to the deletions in E1. Mechanical models for the influence of the E1 deletions, for example by up-regulation of the E2-encoded DNA-binding protein, are discussed to explain the efficient replication of mutant adenoviruses in Vero cells under plaque assay conditions.


Targeting the bone marrow microenvironment in multiple myeloma.
Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow (BM). Despite the significant advances in treatment, MM is still a fatal malignancy. This is mainly due to the supportive role of the BM microenvironment in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. The BM microenvironment is composed of a cellular compartment (stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells) and a non-cellular compartment. In this review, we discuss the interaction between the malignant plasma cell and the BM microenvironment and the strategy to target them.


Video Compression Artifact Reduction via Spatio-Temporal Multi-Hypothesis Prediction.
Annoying compression artifacts exist in most of lossy coded videos at low bit rates, which are caused by coarse quantization of transform coefficients or motion compensation from distorted frames. In this paper, we propose a compression artifact reduction approach that utilizes both the spatial and the temporal correlation to form multi-hypothesis predictions from spatio-temporal similar blocks. For each transform block, three predictions with their reliabilities are estimated, respectively. The first prediction is constructed by inversely quantizing transform coefficients directly, and its reliability is determined by the variance of quantization noise. The second prediction is derived by representing each transform block with a temporal auto-regressive (TAR) model along its motion trajectory, and its corresponding reliability is estimated from local prediction errors of the TAR model. The last prediction infers the original coefficients from similar blocks in non-local regions, and its reliability is estimated based on the distribution of coefficients in these similar blocks. Finally, all the predictions are adaptively fused according to their reliabilities to restore high-quality videos. The experimental results show that the proposed method can efficiently reduce most of the compression artifacts and improve both subjective and objective quality of block transform coded videos.


Prevalence and associated factors for self-reported asthma in a Canadian population: The Canadian Community Health Survey, 2014.
Asthma prevalence is increasing among adults, yet limited information regarding the association between adult asthma and environmental and personal exposures is available using large nationally representative population-based survey. To determine the prevalence of asthma and associated factors for self-reported asthma in a Canadian population aged 12 years and older by using the Canadian Community Health Survey (CCHS) 2014 cross-sectional cohort. We used data from the 2014 CCHS. Asthma was determined through self-reported health professional diagnosis. Information regarding covariates of importance, such as socio-economic status, life style variables, was obtained. A weighted logistic regression analysis was performed with appropriate technique for clustering effects. Estimated self-reported asthma prevalence of 8.1% in the greater than 12 years old Canadian population was observed. We found that a substantial proportion of Canadians (aged 12 and older) reported having asthma and geographical differences and differences between specific provinces in asthma prevalence. Women had higher prevalence of asthma than men, but the relationship depended on age and body mass index (BMI). Interactions between household income and smoking status were observed to predict the probability of asthma. Additional studies are needed to determine which factors influence the asthma prevalence between sex, BMI as well as smoking status and household income and its interactions with each other.


Library statistics of schools in the health sciences. II.
This report is a continuation of "Library Statistics of Health Science Libraries: Part I," published in the July 1966 issue of the Bulletin. Interlibrary loan transactions, space assigned to library functions, historical collections, pharmacy libraries, new library construction, and automation are covered in this paper. Questions are raised concerning the adaptation of a general university library questionnaire to the subset of health science libraries.


Cultural adaptation and content validation of the Single-Question for screening alcohol abuse.
Objective Describing the stages of translation, cultural adaptation and content validation of the Single-Question into Brazilian Portuguese, which will be named Questão Chave. Method This study is a cultural adaptation. The instrument was translated into Portuguese as two independent versions which led to a synthesis of translations (S1), and later to the synthesis S2, which was then submitted to evaluation by a Committee of Expert Judges in the area of alcohol use and instrument validation. The Content Validity Index and Kappa agreement coefficient were calculated from this evaluation. Results The judges evaluated the Questão Chave regarding the clarity of the sentence and aspects related to the quality of the translation (cultural adaptation, preservation of original meaning and correct use of technical terms). The Content Validity Index was 1 for clarity of sentence and correct use of technical terms, and 0.8 for adaptation and preservation of the original meaning. The Kappa index for concordance among the judges was 0.83. After an adjustment proposed by the judges, the S3 version was originated. Conclusion The Questão Chave had its content validity confirmed, which supports future studies that aim for its application in the target population to verify their psychometric properties.


Effects of serum complement levels on the mobilization of mature white blood cells in relation to mobilization of CFUS.
It was investigated whether the complement dependency of CFUS mobilization observed for certain mobilizing agents is unique for the CFUS compartment, or whether this mobilization reflects a more general mechanism, which involves also the mobilization of mature leukocytes. The number of all recognizable nucleated cell types in the blood was determined following the injection of the mobilizing agents, i.e. endotoxin, zymosan, cobra venom factor, proteinase, trypsin, dextran sulphate and the copolymer of polymethacrylic acid and styrene. The results indicate that if a mobilizing effect of a CFUS mobilizing agent on other nucleated cells occurs, this mobilization of nucleated cells is similarly inhibited or not by C3 to C9 depletion as is observed for the CFUS mobilization. The degree of inhibition is also comparable to the inhibition of CFUS mobilization. The significance of the complement system for the mobilization process is discussed.


White matter abnormalities associated with auditory hallucinations in schizophrenia: a combined study of voxel-based analyses of diffusion tensor imaging and structural magnetic resonance imaging.
White matter (WM) abnormalities in schizophrenia may offer important clues to a better understanding of the disconnectivity associated with the disorder. The aim of this study was to elucidate a WM basis of auditory hallucinations in schizophrenia through the simultaneous investigation of WM tract integrity and WM density. Diffusion tensor images (DTIs) and structural T1 magnetic resonance images (MRIs) were taken from 15 hallucinating schizophrenic patients, 15 non-hallucinating schizophrenic patients and 22 normal controls. Voxel-based analyses and post-hoc region of interest analyses were obtained to compare the three groups on fractional anisotropy (FA) derived from DTI as well as WM density derived from structural MRIs. In both the hallucinating and non-hallucinating groups, FA of the WM regions was significantly decreased in the left superior longitudinal fasciculus (SLF), whereas WM density was significantly increased in the left inferior longitudinal fasciculus (ILF). The mean FA value of the left frontal part of the SLF was positively correlated with the severity score of auditory hallucinations in the hallucinating patient group. Our findings show that WM changes were mainly observed in the frontal and temporal areas, suggesting that disconnectivity in the left fronto-temporal area may contribute to the pathophysiology of schizophrenia. In addition, pathologic WM changes in this region may be an important step in the development of auditory hallucinations in schizophrenia.


Purulent pericarditis with greenish pericardial effusion caused by Shewanella algae.
We report the first case of purulent pericarditis with greenish pericardial effusion caused by Shewanella algae in a patient with gastric and gallbladder cancer. This case expands the reported spectrum of infection caused by S. algae and raises the possibility that S. algae is a causative pathogen for purulent pericarditis.


Entropy and heat capacity calculations of simulated crystal-hexatic smectic-B-smectic-A liquid-crystal phase transitions.
Entropy and heat capacity are calculated in phase sequence of crystal, hexatic smectic- B , and smectic- A liquid crystals through constant pressure and temperature molecular-dynamics simulations of parallel soft spherocylinders. The transition from crystal to hexatic smectic- B phase is continuous while the transition to smectic- A phase is first order. The dependence of the phase sequence against the molecular shape anisotropy is investigated and there exists a triple point at a rather small anisotropy. Hopping diffusion of molecules is observed in the hexatic smectic- B phase.


Microbiological and Clinical Outcomes of Methicillin-Susceptible Staphylococcus aureus Isolated in Lung Transplant Perioperative Donor and Recipient Respiratory Cultures.
Staphylococcus aureus is one of the most common organisms isolated from respiratory secretions in lung transplant donors and recipients perioperatively. Within the first 90 days after lung transplantation, methicillin-susceptible Staphylococcus aureus (MSSA) infections have been associated with increased mortality and acute and chronic rejection. However, it is unclear whether respiratory cultures positive for MSSA at the time of transplantation can lead to clinically significant infection. The aim of this study was to assess the microbiological and clinical outcomes for lung transplant recipients (LTRs) with positive perioperative donor or/and recipient respiratory cultures for MSSA. A retrospective study was conducted evaluating MSSA-positive respiratory cultures at the time of lung transplantation from donors and/or recipients from January 1, 2008, to December 30, 2019. Patients who did not have a bronchoalveolar lavage at 2 weeks after the lung transplant or died within 2 weeks of lung transplant were excluded. The main outcome was MSSA eradication at 2-week bronchoscopy. Recipients were evaluated for MSSA infections at the 12-week period after the transplant. Of the 1,678 individuals who underwent lung transplantation, 218 LTRs had S. aureus isolated in perioperative donor or recipient respiratory cultures, and 29 were subsequently excluded. Of the remaining 189 LTRs, MSSA eradication at the 2-week bronchoscopy was achieved in 186 (98.4%) recipients. During the 12-week follow-up, 15 (7.9%) recipients were diagnosed with MSSA pneumonia; concurrent MSSA bacteremia was noted in one recipient. No anastomotic infection, empyema, or lung abscess related to MSSA was diagnosed during the follow-up period.In LTRs, the rate of MSSA eradication at 2-week post-transplant recipients is high, and it is associated with a low rate of infectious complication within the first 12 weeks after transplant. Most of the recipients received a combination therapy with at least one agent active against MSSA. More studies to evaluate the optimal antimicrobial stewardship policies regarding the regimen and duration of antibiotic therapy for these patients are needed.


Experiences with the Plasmacup--early stability, wear, remodelling, and outcome.
Whilst advances in cementing technique have led to improvement in the survival of cemented femoral stems in total hip arthroplasty (THA), cup failure due to aseptic loosening remains a major clinical problem. These observations have led to a move away from cemented cup designs, particularly in young patients, towards uncemented implants. The Plasmacup is a hemispherical, press-fit, cementless, titanium-shelled, acetabular component with a polyethylene liner. In this article we review our experience of its pattern of early migration, wear, bone remodelling, and mid-term survival. In 18 cups followed for 2 years in subjects with a mean age at operation of 58 years, the mean total vectorial cup migration was 0.75 mm, and cup orientation remained stable (EBRA method). The mean polyethylene linear wear rate over this period was 0.21 mm/year. In 27 cups followed for 6 months using dual-energy X-ray absorptiometry (DXA), average bone loss was -5%, and the pelvic bone-remodelling pattern was consistent with the rim-loading principle of the cup design. In a clinical review of the outcome of 128 cups in 104 patients with a mean age at operation of 51 years and follow-up of 59 months, we found that 82% of patients had a good or very good Merle D'Aubigne score, and cup survival rate was 98% (Kaplan-Meier). Four cups had small radiographic areas of focal osteolysis and three had been revised (two for recurrent dislocation and one for deep sepsis; none were revised for aseptic loosening). The mean linear wear rate in this series was 0.14 mm/year. In conclusion, the Plasmacup shows satisfactory early stability, a wear rate similar to other uncemented cups, and favourable mid-term clinical function and survival rates.


Mutagenesis and functional characterization of the four domains of GlnD, a bifunctional nitrogen sensor protein.
GlnD is a bifunctional uridylyltransferase/uridylyl-removing enzyme (UTase/UR) and is believed to be the primary sensor of nitrogen status in the cell by sensing the level of glutamine in enteric bacteria. It plays an important role in nitrogen assimilation and metabolism by reversibly regulating the modification of P(II) protein; P(II) in turn regulates a variety of other proteins. GlnD appears to have four distinct domains: an N-terminal nucleotidyltransferase (NT) domain; a central HD domain, named after conserved histidine and aspartate residues; and two C-terminal ACT domains, named after three of the allosterically regulated enzymes in which this domain is found. Here we report the functional analysis of these domains of GlnD from Escherichia coli and Rhodospirillum rubrum. We confirm the assignment of UTase activity to the NT domain and show that the UR activity is a property specifically of the HD domain: substitutions in this domain eliminated UR activity, and a truncated protein lacking the NT domain displayed UR activity. The deletion of C-terminal ACT domains had little effect on UR activity itself but eliminated the ability of glutamine to stimulate that activity, suggesting a role for glutamine sensing by these domains. The deletion of C-terminal ACT domains also dramatically decreased UTase activity under all conditions tested, but some of these effects are due to the competition of UTase activity with unregulated UR activity in these variants.


Reduced PCR sensitivity due to impaired DNA recovery with the MagNA Pure LC total nucleic acid isolation kit.
The increasing demand for molecular diagnostics in clinical microbiology laboratories necessitates automated sample processing. In the present study, we evaluated the performance of the MagNA Pure LC total nucleic acid isolation kit (M extraction) in comparison with the manual method (Si extraction) according to Boom et al. (R. Boom, C. J. A. Sol, M. M. M. Salimans, C. L. Jansen, P. M. Wertheim-van Dillen, and J. van der Noordaa, J. Clin. Microbiol. 28:495-503, 1990) for the detection of viral DNA by competitive quantitative PCR. Reconstruction experiments with HindIII-digested phage lambda DNA and HaeIII-digested phiX174 DNA showed that the recovery of DNA from phosphate-buffered saline, cerebrospinal fluid, EDTA-anticoagulated plasma, and EDTA-anticoagulated whole blood by M extraction is, on average, 6.6-fold lower compared to Si extraction. PCR signals of spiked PCR control DNAs for Epstein-Barr virus and varicella-zoster virus were also between 1.9- and 14.2-fold lower after M extraction compared to Si extraction, also suggesting impaired DNA recovery. M extraction of spiked cytomegalovirus strain AD 169 in whole blood showed a 5- to 10-fold reduction in PCR sensitivity compared to Si extraction. This reduction of PCR sensitivity was also observed when clinical whole blood samples were processed by M extraction. Before implementing M extraction, the clinical consequences of the reduced recovery should first be considered, especially when maximal sensitivity is required.


[The pathogenicity of amoebae-resisting chlamydiales].
During the last 15 years, several new bacterial species related to Chlamydia have been discovered within amoebae. Their ability to grow within these professionnal phagocytes suggests that they are also resistant to destruction by other phagocytic cells such as alveolar macrophages and that they may be excellent candidates as new agents of pneumonia. There are growing evidence that these Chlamydia-like organisms play a role as etiological agent of lower respiratory tract infections. Thus, Parachlamydia is apparently an agent of inhalation pneumonia and--at least in the immunocompromised host--of community-acquired pneumonia, whereas Simkania is considered as a common agent of bronchiolitis and an emerging agent of pneumonia. Nevertheless, their pathogenic potential remains underestimated since these obligate intracellular bacteria grow only poorly or not at all on the culture media generally used to detect pathogen in diagnostic laboratories.


Atypical Presentation of Hydatid Cyst in the Thigh.
To emphasise that hydatid cyst disease can present as a soft tissue mass even in an unusual site like the thigh, we report the case of a 21-year male patient who presented to Surgical Unit IV, Civil Hospital, Karachi, with a slow growing cystic swelling on the medial aspect of the left thigh. Based on serology and imaging, a diagnosis of solitary subcutaneous hydatid cyst thigh was made and cystopericystectomy was performed. Histopathology confirmed the diagnosis. Up to three months postoperatively, there was no recurrence. In the absence of visceral organ involvement, this is the first reported case of primary subcutaneous hydatid disease of the thigh in Pakistan.


Online continuing medical education (CME) for GPs: does it work? A systematic review.
Numerous studies have assessed the effectiveness of online continuing medical education (CME) designed to improve healthcare professionals' care of patients. The effects of online educational interventions targeted at general practitioners (GP), however, have not been systematically reviewed. A computer search was conducted through seven databases for studies assessing changes in GPs' knowledge and practice, or patient outcomes following an online educational intervention. Eleven studies met the eligibility criteria. Most studies (8/11, 72.7%) found a significant improvement in at least one of the following outcomes: satisfaction, knowledge or practice change. There was little evidence for the impact of online CME on patient outcomes. Variability in study design, characteristics of online and outcome measures limited conclusions on the effects of online CME. Online CME could improve GP satisfaction, knowledge and practices but there are very few well-designed studies that focus on this delivery method of GP education.


Renal tubular dysgenesis: report of two cases in a non-consanguineous couple and review of the literature.
Renal tubular dysgenesis is a rare congenital abnormality of renal development characterized by short and poorly developed proximal convoluted tubules. It is associated to late-appearing oligohydramnios, Potter's sequence, pulmonary hypoplasia and calvarial bone hypoplasia with enlarged fontanels. The onset of oligohydramnios is delayed and variable, normally later than 22 weeks of gestation, conditioning variation in the expression of the other deformities. We report 2 cases of renal tubular dysgenesis occurring in a non-consanguineous couple.


Tissue mRNA expression in rat of newly described matrix metalloproteinases.
Matrix metalloproteinases (MMPs) comprise a large group of endoproteinases that degrade all protein components of the extracellular matrix. Functionally, MMPs contribute to several different physiological as well as pathological conditions. The number of newly described MMPs has increased in recent years, although current knowledge about their expression pattern in various tissues remains incomplete. Here we analyzed the relative mRNA expression of the most recently described MMPs--MT5-MMP (MMP-24), MT6-MMP (MMP-25), MMP-27 and epilysin (MMP-28)--in a broad selection of rat tissues using real time-PCR. MMP-24 mRNA was found to be widely expressed with predominance in the central nervous system. MMP-25 mRNA, in contrast, exhibited peak expression levels in testis, kidney and skeletal muscle, differing from previously described distribution patterns in humans. mRNAs for MMP-27 and MMP-28 were generally expressed at a lower level. All four MMPs studied were detected at higher mRNA levels in bone and kidney, suggesting a possible role of these MMPs in physiological processes within these two organs. The present study highlights the differential distribution pattern of newly described MMPs among different tissues and underlines differences in the mRNA expression between different species.


Population size dependence of fitness effect distribution and substitution rate probed by biophysical model of protein thermostability.
The predicted effect of effective population size on the distribution of fitness effects and substitution rate is critically dependent on the relationship between sequence and fitness. This highlights the importance of using models that are informed by the molecular biology, biochemistry, and biophysics of the evolving systems. We describe a computational model based on fundamental aspects of biophysics, the requirement for (most) proteins to be thermodynamically stable. Using this model, we find that differences in population size have minimal impact on the distribution of population-scaled fitness effects, as well as on the rate of molecular evolution. This is because larger populations result in selection for more stable proteins that are less affected by mutations. This reduction in the magnitude of the fitness effects almost exactly cancels the greater selective pressure resulting from the larger population size. Conversely, changes in the population size in either direction cause transient increases in the substitution rate. As differences in population size often correspond to changes in population size, this makes comparisons of substitution rates in different lineages difficult to interpret.


Didymobotryum spirillum, a new synnematous hyphomycete from India.
A new synnematous hyphomycete, Didymobotryum spirillum D'Souza & Bhat, collected from decaying culms of bamboo, Dendrocalamus strictus, is described and illustrated from the forests of Western Ghats in Goa, India. The fungus produces monotretic, catenate didymoconidia on spirally twisted synnemata.


Influence of exogenous atrial natriuretic peptide on the pituitary-adrenal response to corticotropin-releasing hormone and vasopressin in healthy men.
Atrial natriuretic peptide (ANP) has been considered a potential candidate participating in the inhibitory control of pituitary-adrenal secretory activity. Here, we investigated the influence of ANP, infused at two different doses and over infusion intervals of two different durations, on the release of ACTH and cortisol after stimulation with CRH and with combined administration of CRH and vasopressin (VP). In young healthy men, three experiments were conducted. In Exp I, ACTH/cortisol secretory responses to CRH (50 microg) were examined during and after a 45-min period of ANP infusion at a rate of 4.4 microg/min (starting 15 min before CRH injection). In Exp II, ACTH/cortisol secretory responses to CRH (50 microg) were examined during and after a 90-min infusion period of ANP administered at rates of 4.4 and 8.8 microg/min. In Exp III, ANP was infused at a rate of 4.4 microg/min over 90 min, but instead of CRH, a combined administration of CRH (50 microg) and VP (0.5 IU infused within 5 min) was employed to stimulate ACTH/cortisol release. ANP diminished pituitary-adrenal secretory responses within the first hour after stimulation with exogenous secretagogues. Thereafter, the effect of ANP turned in the opposite direction, with distinctly enhanced concentrations of ACTH and cortisol during the third hour after stimulation. The inhibitory effect of ANP during the first hour of the pituitary-adrenal response was more pronounced on concentrations of cortisol than ACTH and was also more pronounced after combined administration of CRH/VP than after stimulation with CRH alone. Increasing the dose of ANP enhanced the late stimulatory effect on ACTH/cortisol release, thereby terminating the early period of inhibited ACTH/cortisol release more abruptly. The late stimulatory effect was enhanced with prolonged infusion of ANP. In addition, it was associated with reduced hematocrit, increased urine volumes collected, increased heart rate, and enhanced plasma VP concentrations. Together, these changes suggest that the late stimulatory effect of ANP on ACTH/cortisol release reflects an effect secondary to its hypovolemic actions. This stimulatory effect originating from peripheral systemic actions of ANP after exogenous administration appears to override a more direct inhibitory action of the peptide on pituitary-adrenal secretory activity. Therefore, we would expect that with localized release into portal hypophyseal blood the inhibitory component of the action of ANP on pituitary-adrenal secretory activity prevails.


Marginal zone B cells emerge as a critical component of pregnancy well-being.
The success of eutherian mammal evolution was certainly supported by the ability of the already existing immune system to adapt to the presence of the semi-allogeneic fetus without losing the capability to defend the mother against infections. This required the acquisition of highly regulated and coordinated immunological mechanisms. Failures in the development of these strategies not only lead to the interruption of pregnancy but also compromise maternal health. Alongside changes on the cytokine profile - expansion of tolerogenic dendritic and regulatory T cells - a profound adaptation of the B cell compartment during pregnancy was recently described. Among others, the suppression of B cell lymphopoiesis and B cell lymphopenia were proposed to be protective mechanisms tending to reduce the occurrence of autoreactive B cells that might recognize fetal structures and put pregnancy on risk. On the other hand, expansion of the pre-activated marginal zone (MZ) B cell phenotype was described as a compensatory strategy launched to overcome B cell lymphopenia thus ensuring a proper defense. In this work, using an animal model of pregnancy disturbances, we demonstrated that the suppression of B cell lymphopoiesis as well as splenic B cell lymphopenia occur independently of pregnancy outcome. However, only animals undergoing normal pregnancies, but not those suffering from pregnancy disturbances, could induce an expansion and activation of the MZ B cells. Hence, our results clearly show that MZ B cells, probably due to the production of natural protective antibodies, participate in the fine balance of immune activation required for pregnancy well-being.


Fit-to-Targets for the Desired Sensation Level Version 5.0a Hearing Aid Prescription Method for Children.
The purpose of this study was to measure the range of fit to Desired Sensation Level version 5.0 (DSL v5.0) targets in pediatric practice environments. Results will be used in the future to develop clinical-aided speech intelligibility index typical performance data. Clinical partners collected data from 161 final hearing aid settings for children aged ≤ 10 years. Measured data were obtained by performing 2-cm3 coupler-simulated real-ear measurements using the DSL v5.0 implementation on the Audioscan VF-1 (Etymonic Design Inc., Dorchester, ON, Canada) for soft, average, and loud speech inputs and maximum hearing aid output levels. Fittings were within ± 5-dB root-mean-square (RMS) error of target for 77%, 80%, and 82% of fittings for the soft, medium, and loud speech test levels, respectively. Aided maximum power output measures were within ± 5-dB RMS error in 72% of cases. Degree of hearing loss, test frequency, and frequency by test level were significant factors in deviation from target. The range of aided speech intelligibility index values exhibited a strong correlation with the hearing levels of the children tested. This study provides evidence that typical hearing aid fittings for children can be achieved within ± 5-dB RMS error of the DSL v5.0 target. Greater target deviations were observed at extreme frequencies and as the severity of hearing loss increased.


Hot-Carrier Dynamics and Chemistry in Dielectric Polymers.
Dielectric polymers are widely used in electronics and energy technologies, but their performance is severely limited by the electrical breakdown under a high electric field. Dielectric breakdown is commonly understood as an avalanche of processes such as carrier multiplication and defect generation that are triggered by field-accelerated hot electrons and holes. However, how these processes are initiated remains elusive. Here, nonadiabatic quantum molecular dynamics simulations reveal microscopic processes induced by hot electrons and holes in a slab of an archetypal dielectric polymer, polyethylene, under an electric field of 600 MV/m. We found that electronic-excitation energy is rapidly dissipated within tens of femtoseconds because of strong electron-phonon scattering, which is consistent with quantum-mechanical perturbation calculations. This in turn excites other electron-hole pairs to cause carrier multiplication. We also found that the key to chemical damage is localization of holes that travel to a slab surface and weaken carbon-carbon bonds on the surface. Such quantitative information can be incorporated into first-principles-informed, predictive modeling of dielectric breakdown.


Persistence and relapse of reinforced behavioral variability.
The present study examined persistence and relapse of reinforced behavioral variability in pigeons. Pigeons emitted four-response sequences across two keys. Sequences produced food according to a lag schedule, in which a response sequence was followed by food if it differed from a certain number of previous sequences. In Experiment 1, food was delivered for sequences that satisfied a lag schedule in both components of a multiple schedule. When reinforcement was removed for one component (i.e., extinction), levels of behavioral variability decreased for only that component. In Experiment 2, food was delivered for sequences satisfying a lag schedule in one component of a multiple schedule. In the other component, food was delivered at the same rate, but without the lag variability requirement (i.e., yoked). Following extinction, levels of behavioral variability returned to baseline for both components after response-independent food delivery (i.e., reinstatement). In Experiment 3, one group of pigeons responded on a lag variability schedule, and the other group responded on a lag repetition schedule. For both groups, levels of behavioral variability increased when alternative reinforcement was suspended (i.e., resurgence). In each experiment, we observed some evidence for extinction-induced response variability and for variability as an operant dimension of behavior.


Successful implementation of genomically based treatment of chemotherapy refractory peripheral T-cell lymphoma (PTCL).
The treatment of peripheral T-cell lymphoma (PTCL) after failure of standard therapy represents a significant clinical challenge as the best approach has not been defined. The outcomes of patients with peripheral T-cell lymphoma (PTCL) after relapse, in the absence of hematopoietic stem-cell transplantation, are poor with median overall survival is less than six months. Thus, relapsed/refractory PTCL presents an area of unmet medical need. Herein, we report an 84-year old woman with stage IV PTCL with extensive involvement of the bowel and abdominal pain. She was treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy which was complicated by prolonged pancytopenia, without response. Disease progression was manifested by small bowel obstruction, for which she received palliative radiation therapy, further complicated by cardiac arrhythmia and sepsis. In the meantime, clinical-grade next generation sequencing of a lymph node (406 gene panel) showed six genomic alterations: NRAS Q61R, PTEN Q17*, CREBBP R768*, EP300 R1529*, SETD2 loss exons 19-21, along with an intermediate tumor mutational burden. Tissue PD-L1 staining was low positive by immunohistochemistry. The patient was discussed in Molecular Tumor Board with consensus opinion favoring a combination of the MEK inhibitor trametinib (for the NRAS alteration) and the checkpoint inhibitor nivolumab for the elevated mutational burden and PD-L1 positivity. Her abdominal pain resolved and she achieved a complete remission ongoing at 5+ months. Side effects at five months included only low-grade rash and peripheral edema. Our observations suggest that matching patients with hematologic malignancies with customized combinations based on genomic sequencing warrants further study as a way to achieve and/or deepen responses, including in patients who are elderly and/or have refractory disease and significant disease-related complications.


[Involution-induced changes in arterial uterine blood flow].
The change of resistance in the uterine arteries was studied in 20 patients showing a normal involution on five consecutive days. A uterine artery was examined by Doppler sonography, the Doppler profile evaluated, and the quotient, Fmean, resistance index, and pulsatility index were calculated from the systole and diastole. These parameters, which provided information on vascular resistance independently of the angle between the Doppler beam and the vessel, indicated a continuous increase during the puerperium; the differences in values for different days were significant. The changes in the Doppler profiles in the puerperial period pointed to an increasing vascular resistance. In one-half of the patients this was shown only by an increasing slope to the systolic peak, a sharp drop to early diastole, and a clear distinction between systole and diastole. In the other half of the patients the Doppler curves were like those found in pregnant patients with EPH gestosis. This indicated that the pathologic mechanisms leading to increased resistance in the uterine vessels were the same in both groups. One cause of this may be contraction and compression of the blood vessels, the other, and probably principal, cause was reduction of the vascular system due to histolysis, as in the puerperium, or insufficient development of the vascular system, as in EPH gestosis. That is to say, functional and morphological changes occur in both cases. No decrease in resistance in the uterine vascular bed was detected in cases of puerperial subinvolution of the uterus.


The role of an iron-sulfur cluster in an enzymatic methylation reaction. Methylation of CO dehydrogenase/acetyl-CoA synthase by the methylated corrinoid iron-sulfur protein.
This paper focuses on how a methyl group is transferred from a methyl-cobalt(III) species on one protein (the corrinoid iron-sulfur protein (CFeSP)) to a nickel iron-sulfur cluster on another protein (carbon monoxide dehydrogenase/acetyl-CoA synthase). This is an essential step in the Wood-Ljungdahl pathway of anaerobic CO and CO2 fixation. The results described here strongly indicate that transfer of methyl group to carbon monoxide dehydrogenase/acetyl-CoA synthase occurs by an SN2 pathway. They also provide convincing evidence that oxidative inactivation of Co(I) competes with methylation. Under the conditions of our anaerobic assay, Co(I) escapes from the catalytic cycle one in every 100 turnover cycles. Reductive activation of the CFeSP is required to regenerate Co(I) and recruit the protein back into the catalytic cycle. Our results strongly indicate that the [4Fe-4S] cluster of the CFeSP is required for reductive activation. They support the hypothesis that the [4Fe-4S] cluster of the CFeSP does not participate directly in the methyl transfer step but provides a conduit for electron flow from physiological reductants to the cobalt center.


Synthesis and characterization of a Bi10O8(OAr)16 oxo-cluster supported by p-tert-butylcalix[5]arene ligands.
Reaction of a non-dried monobenzylated [(t)BuC5(OBn)(OH)4] ligand with excess of Bi[N(SiMe3)2]3 yields a mixture of the dimeric complex 1 [Bi{(t)BuC5(OBn)(OH)}]2 in 12% yield and complex 2 [Bi10O8{(t)BuC5(OBn)(OH)}4] in 48% yield. The highly symmetric complex 2 features a Bi10O8(OAr)16 central core with tetra-, hexa- and heptacoordinated bismuth(iii) centers, and (μ2)-(μ4) bridging oxygen atoms all arranged in a I4 symmetrical pattern. Cluster 2 represents the largest bismuth oxo-cluster supported by calix[n]arene ligands reported to date.


Accumulation of organochlorines and brominated flame retardants in the eggs and nestlings of great tits, Parus major.
Insectivorous birds may be very useful sentinels for local point-source contamination with persistent pollutants, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs). Eggs have been used extensively to monitor lipophilic contaminants, as females can pass contaminants stored in their body tissues into their eggs. Concentrations and profiles in eggs therefore relate to contamination in the female. Because nestlings are raised on food items collected locally, it is expected that the body burden in nestlings would reflect their diet and local pollution levels better than eggs. In this study we compared the accumulation and the profile of PCBs, PBDEs, and OCPs in great tit (Parus major) eggs, nestlings (5-, 10-, and 15-days old), and their food in two study sites. Our results showed that concentrations in great tit eggs were 4 to 6 times higher than those in nestlings. Concentrations in nestling great tits corresponded with concentrations predicted by a bioenergetics-based model. Most of the persistent organic pollutants in 15-day old nestlings were still from maternal origin. The profile of these persistent pollutants in eggs and nestlings also gradually changed during development. With increasing age, the proportion of the most persistent compounds decreased. This study shows that most of the persistent pollutants in fully grown nestlings may still be from maternal origin. For nestlings to be suitable as indicators of local contamination, most of the POPs they accumulate should originate from dietary sources rather than from maternal transfer via the egg. Nestling birds may therefore not be good sentinels for local contamination with persistent pollutants.


Interception of the enzymatic conversion of farnesyl diphosphate to 5-epi-aristolochene by using a fluoro substrate analogue: 1-fluorogermacrene A from (2E,6Z)-6-fluorofarnesyl diphosphate.
Tobacco 5-epi-aristolochene synthase (TEAS) catalyzes the Mg(II)-dependent cyclizations and rearrangements of (E,E)-farnesyl diphosphate (PP) to the bicyclic sesquiterpene hydrocarbon via a tightly bound (+)-germacrene A as a deprotonated intermediate. With the native enzyme, only a few percent of the putative germacrene A intermediate is released from the active site during the catalytic cycle. 6-Fluorofarnesyl PP was designed and synthesized with the aim of arresting the cyclization-rearrangement mechanism en route to 5-epi-aristolochene. Indeed, incubation of (2E,6Z)-6-fluorofarnesyl PP with recombinant TEAS afforded (-)-1-fluorogermacrene A as the sole product in 58% yield. Steady-state kinetic experiments with farnesyl PP and the 6-fluoro analogue showed that the overall catalytic efficiencies (k(cat)/K(m)) are essentially the same for both substrates. 1-Fluorogermacrene A was characterized by chromatographic properties (TLC, GC), MS, optical rotation, UV, IR and (1)H NMR data, and by heat-induced Cope rearrangement to (+)-1-fluoro-beta-elemene. (1)H NMR spectra at room temperature revealed that this (E,E)-configured fluorocyclodecadiene exists in solution as a 7:3 mixture of UU and UD conformers. 1-Fluorogermacrene A underwent trifluoroacetic acid-catalyzed cyclization to give three 1alpha-fluoroselinene isomers at a rate estimated to be about 1000 times slower than that of the similar cyclization of (+)-germacrene A to the parent selinenes.


Virus-induced gene silencing in soybean.
Understanding the biology of a system requires the association of gene functions to phenotypes and vice versa. Although a large number of resources and genomic tools are available for studies in the crop plant soybean, investigations related to gene function have been lacking. This is largely due to the fact that rapid functional genomics tools have been unavailable for application in soybean. This constraint was recently alleviated when a novel bean pod mottle virus (BPMV)-based system for virus-induced gene silencing in soybean was developed. This methodology exploits the plant's ability to silence virus-encoded sequences as a defense mechanism. Plants infected with recombinant viruses carrying sequences that are identical/near-identical to the plant's own genes suppress the expression of the target endogenous gene(s). Phenotypes associated with suppression of target sequence enable the assignment of functions to specific genes. The strategy involves inserting short sequences of target soybean genes into the viral genome to generate recombinant vectors. Soybean plants are then inoculated with the recombinant vectors, assessed for BPMV propagation and silencing of the target genes. Plants silenced for specific targets can then be analyzed for various different traits depending upon the known/predicted functions of the target genes. Using this strategy, we have identified genes participating in basal, resistance gene-mediated, and systemic immunity in soybean.


Genetic analysis of the O-antigen of Providencia alcalifaciens O30 and biochemical characterization of a formyltransferase involved in the synthesis of a Qui4N derivative.
O-Antigen is a component of the outer membrane of Gram-negative bacteria and one of the most variable cell surface constituents, giving rise to major antigenic variability. The diversity of O-antigen is almost entirely attributed to genetic variations in O-antigen gene clusters. Bacteria of the genus Providencia are facultative pathogens, which can cause urinary tract infections, wound infections and enteric diseases. Recently, the O-antigen gene cluster of Providencia was localized between the cpxA and yibK genes in the genome. However, few genes involved in the synthesis of Providencia O-antigens have been functionally identified. In this study, the putative O-antigen gene cluster of Providencia alcalifaciens O30 was sequenced and analyzed. Almost all putative genes for the O-antigen synthesis were found, including a novel formyltransferase gene vioF that was proposed to be responsible for the conversion of dTDP-4-amino-4,6- dideoxy-D-glucose (dTDP-D-Qui4N) to dTDP-4,6-dideoxy-4-formamido-D-glucose (dTDP-D-Qui4NFo). vioF was cloned, and the enzyme product was expressed as a His-tagged fusion protein, purified and assayed for its activity. High-performance liquid chromatography was used to monitor the enzyme-substrate reaction, and the structure of the product dTDP-D-Qui4NFo was established by electrospray ionization tandem mass spectrometry and nuclear magnetic resonance spectroscopy. Kinetic parameters of VioF were determined, and effects of temperature and cations on its activity were also examined. Together, the functional analyses support the identification of the O-antigen gene cluster of P. alcalifaciens O30.


Rapid and improved determination of furan in baby foods and infant formulas by headspace GC/MS.
Furan is a 5-membered ring compound with high volatility. The U.S. Food and Drug Administration (FDA) has recently published a report on the occurrence of furan in a large number of thermally processed foods. However, the FDA's analytical method, using standard curve addition, is not suitable for high-throughput routine laboratory operations. We developed a rapid and improved method for determination of furan in foods by headspace GC/MS. Quantification was achieved by using an internal standard of d4-furan and an external calibration curve of furan normalized against the internal standard. The incubation temperature for equilibration was set at 60 degrees C to avoid the formation of furan during analysis. The levels of furan in baby foods and infant formulas were determined with this method. Validation data showed good precision and accuracy. The LOD and LOQ were 0.2-0.5 ng/g and 0.5-2 ng/g for various food matrixes, respectively. The level of furan detected was in the range of 1.4 to 90 ng/g in baby foods and in the range of non-detectable to 36 ng/g in infant formulas.


Renal handling of uric acid in patients with recurrent calcium nephrolithiasis and hyperuricosuria.
Hyperuricosuria is a frequent finding in patients with recurrent calcium nephrolithiasis (RCN) that has been related to purine overingestion . The influence of diet and the renal handling of uric acid were investigated in patients with RCN to assess the pathogenic mechanism of excessive urate excretion. Among 50 patients with recurrent nephrolithiasis 42 formed renal stones containing calcium and 9 of these 42 patients demonstrated concomitant asymptomatic hyperuricosuria while on a self-selected diet. Ingestion of a purine-free diet normalized the uric acid excretion in 4 of these 9 patients. The other 5 patients showed persistent hyperuricosuria while on a purine-free diet. In order to assess a possible dysfunction in the renal handling of uric acid, pharmacological tests were undertaken in these 9 patients. Pyrazinamide administration almost completely suppressed urate excretion, excluding a presecretory reabsorption defect. Urate excretion in response to probenecid administration was decreased in 4 patients and increased in 1. This finding is in accordance with a postsecretory reabsorption defect in the former and an augmented tubular secretion of urate in the latter. This study proves that both dietary factors and tubular transport defects are involved in patients with recurrent calcium nephrolithiasis and hyperuricosuria.


Further observation on the lack of active uptake system for substance P in the central nervous system.
Crude mitochondrial P2 fractions from bovine hypothalamus and substantia nigra, slices from rabbit spinal cord and mesencephalon and glial fractions from rabbit brain were incubated with [3H]-substance P and the uptake was measured and compared with those for 5-HT and GABA. Substance P was to some extent taken up into the fractions but this uptake was neither temperature nor time dependent and the pellet/medium ratios were less than 1. Similar results were obtained in high potassium treated slices from rabbit mesencephalon. The rate of uptake for [3H]-substance P increased linearly in proportion to the medium concentration, suggesting a non-saturable binding. These results, together with our previous observations provide strong evidence that nerve terminals and glial cells lack a temperature sensitive, active uptake system capable of terminating transmitter action of substance P at the synapse.


Susceptibility of Ph-positive all to TKI therapy associated with Bcr-Abl rearrangement patterns: a retrospective analysis.
Tyrosine kinase inhibitors (TKIs) have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL) in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]). The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL. In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30) years. Overall survival (OS) and event-free survival (EFS) were analyzed. A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years) were enrolled, including those with BCR/ABL transcripts 190 (n = 52), 210 (n = 25), and 230 (n = 2); BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced by variable BCR/ABL transcripts and TKI administration, and BCR/ABL transcripts, hematopoietic stem cell transplantation (HSCT), and TKI administration were associated with the occurrence of events. The OS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKI administration (P = 0.008), the EFS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKIs (P = 0.012), and also higher than those with TKI salvage administration (P = 0.004). BCR/ABL transcripts 210 showed preferable OS and EFS compared with BCR/ABL transcripts 190 and 230 (P<0.05 for each). The susceptibility of Ph+-ALL to TKI associated with the patterns of BCR-ABL rearrangement is demonstrated for the first time, thus adding another risk-stratifying molecular prognostic tool for the management of patients with Ph+-ALL.


Abnormal frequency mismatch negativity in mentally retarded children and in children with developmental dysphasia.
The auditory event-related potential waveform termed "mismatch negativity" was examined in 12 mentally retarded children with delayed development of speech and language (aged 5-8 years) and in 13 children with developmental dysphasia (aged 5-9 years). The mismatch negativity waves were elicited with pure sine-wave tone stimuli using the oddball paradigm. We measured the peak latency and peak amplitude of mismatch negativity responses to frequency (500/553 Hz) difference. The mismatch negativity patterns were compared with those of 10 children with normal development of linguistic skills (aged 5-9 years). In both the mentally retarded and dysphasic groups, the peak amplitude of the frequency mismatch negativity was significantly attenuated when compared with the control group, but no significant difference was observed between the mentally retarded and dysphasic groups. Attenuated frequency mismatch negativity was related to impairment of linguistic skills irrespective of the child's cognitive skills. Because the mismatch negativity response reflects central auditory processing and is modal specific for auditory stimuli, this change-specific response can serve as an objective tool to elucidate central auditory deficits in children.


The Missing Link in Epstein-Barr Virus Immune Evasion: the BDLF3 Gene Induces Ubiquitination and Downregulation of Major Histocompatibility Complex Class I (MHC-I) and MHC-II.
The ability of Epstein-Barr virus (EBV) to spread and persist in human populations relies on a balance between host immune responses and EBV immune evasion. CD8(+) cells specific for EBV late lytic cycle antigens show poor recognition of target cells compared to immediate early and early antigen-specific CD8(+) cells. This phenomenon is due in part to the early EBV protein BILF1, whose immunosuppressive activity increases with lytic cycle progression. However, published data suggest the existence of a hitherto unidentified immune evasion protein further enhancing protection against late EBV antigen-specific CD8(+) cells. We have now identified the late lytic BDLF3 gene as the missing link accounting for efficient evasion during the late lytic cycle. Interestingly, BDLF3 also contributes to evasion of CD4(+) cell responses to EBV. We report that BDLF3 downregulates expression of surface major histocompatibility complex (MHC) class I and class II molecules in the absence of any effect upon other surface molecules screened, including CD54 (ICAM-1) and CD71 (transferrin receptor). BDLF3 both enhanced internalization of surface MHC molecules and reduced the rate of their appearance at the cell surface. The reduced expression of surface MHC molecules correlated with functional protection against CD8(+) and CD4(+) T cell recognition. The molecular mechanism was identified as BDLF3-induced ubiquitination of MHC molecules and their subsequent downregulation in a proteasome-dependent manner. Immune evasion is a necessary feature of viruses that establish lifelong persistent infections in the face of strong immune responses. EBV is an important human pathogen whose immune evasion mechanisms are only partly understood. Of the EBV immune evasion mechanisms identified to date, none could explain why CD8(+) T cell responses to late lytic cycle genes are so infrequent and, when present, recognize lytically infected target cells so poorly relative to CD8(+) T cells specific for early lytic cycle antigens. The present work identifies an additional immune evasion protein, BDLF3, that is expressed late in the lytic cycle and impairs CD8(+) T cell recognition by targeting cell surface MHC class I molecules for ubiquitination and proteasome-dependent downregulation. Interestingly, BDLF3 also targets MHC class II molecules to impair CD4(+) T cell recognition. BDLF3 is therefore a rare example of a viral protein that impairs both the MHC class I and class II antigen-presenting pathways.


Insights on adjuvant endocrine therapy for premenopausal and postmenopausal breast cancer.
In 2005, cancer accounted for 13% of all deaths worldwide. Breast cancer is the number-one cause of cancer-related death among women in the USA, affecting 178,480 of them in 2007. As 75% of tumors in postmenopausal women and half in premenopausal women express estrogen receptor, endocrine therapy plays a significant role as a systemic treatment. Robust datasets have demonstrated the impact of tamoxifen in reducing breast cancer recurrence and mortality, regardless of the age of the patient. Other estrogen-deprivation strategies, such as aromatase inhibitors in postmenopausal women and luteinizing hormone-releasing hormone agonists in premenopausal women, are being increasingly used for estrogen receptor-positive breast cancer. This review discusses basic principles regarding endocrine therapy, the need for accurate estrogen receptor testing and the role of menopause in therapy selection.


Molecular characterization of Orientia tsutsugamushi serotypes causing scrub typhus outbreak in southern region of Andhra Pradesh, India.
Scrub typhus is a vector-borne zoonotic infection caused by Orientiatsutsugamushi. Local epidemiology of the circulating serotypes of scrub typhus is not available from most parts of India. We conducted this study for the diagnosis of scrub typhus using IgM ELISA and to detect O. tsutsugamushi serotypes circulating in southern Andhra Pradesh, India. Samples were collected from patients clinically suspected to have scrub typhus and were subjected to IgM ELISA to measure IgM antibodies against O. tsutsugamushi. Nested polymerase chain reaction (PCR) was performed targeting strain-specific regions in ELISA-positive samples. Of a total of 663 samples, 258 (38.91%) were found to be positive by IgM ELISA. Serotypes could be detected in 230 (34.69%) samples only. Only two serotypes, Karp and Kawasaki, were found in the serum samples, with the former being predominant. The dual infection of Karp and Kawasaki serotypes was found in seven patients. Other serotypes such as Gilliam, Kuroki and Kato were not detected in the samples. The nested PCR products proved useful in presumptively identifying the endemic O. tsutsugamushi serotypes. The present study could be significant in understanding scrub typhus epidemiology in this region.


Early social communicative behaviours of preschoolers with autism spectrum disorder during interaction with their mothers.
The present study examined spontaneous symbolic play, declarative joint attention, social referencing and imitation of symbolic play in 3- to 6-year-old children with an autism spectrum disorder (ASD; n = 20) during interaction with their mothers. Compared to a control group (n = 20) matched on age and IQ, the children with ASD initiated less joint attention with their mothers when confronted with a pleasant event and they showed a tendency to play less symbolically and more non-functionally. Contrary to expectations, children with ASD showed no social referencing or imitation deficits. Interestingly, two clusters of intercorrelating behaviours were found in the ASD group: one suggesting symbolic or metarepresentational abilities, the other comprising interpersonal behaviours. The findings support the hypothesis that early social communicative abilities may follow a different developmental pathway in ASD, and stress the importance of a contextual factor, namely the presence of the mother.


Early aneurysm operation and outcome in two remote Scandinavian populations.
The Kuopio University Clinic is the neurosurgical referral center for a population of 930,000 inhabitants in central Finland while the Lund University Clinic is the neurosurgical referral center for a population of 1.46 million inhabitants in southern Sweden. The incidence of aneurysmal subarachnoid hemorrhage (SAH) is approximately 19/100,000/year in central Finland and approximately five/100,000/year in southern Sweden. During the calendar year 1982, 69 patients with a ruptured supratentorial aneurysm were admitted in Lund, and 71 such patients were admitted in Kuopio. Thirty-nine patients in neurological Grades I to III (according to Hunt and Hess) underwent early aneurysm operation in Lund, and 46 such patients were operated on within a week after SAH in Kuopio. In the combined series of 85 Grade I to III patients with aneurysm operation within a week after rupture, 78% made a good recovery; the morbidity rate was 14%, and the mortality rate was 8%.


Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene.
The adenomatous polyposis coli (APC) gene is a key tumor suppressor gene. Mutations in the gene have been found not only in most colon cancers but also in some other cancers, such as those of the liver. The APC gene product is a 312 kDa protein that has multiple domains, through which it binds to various proteins, including beta-catenin, axin, CtBP, Asefs, IQGAP1, EB1 and microtubules. Studies using mutant mice and cultured cells have demonstrated that APC suppresses canonical Wnt signalling, which is essential for tumorigenesis, development and homeostasis of a variety of cell types, such as epithelial and lymphoid cells. Further studies have suggested that APC plays roles in several other fundamental cellular processes. These include cell adhesion and migration, organization of the actin and microtubule networks, spindle formation and chromosome segregation. Deregulation of these processes caused by mutations in APC is implicated in the initiation and expansion of colon cancer.


Organophosphorus flame retardants and plasticizers: sources, occurrence, toxicity and human exposure.
Due to the restricted use and ban of brominated flame retardants, organophosphorus compounds (OPs), extensively used as flame retardants and plasticizers, are ubiquitous in various environmental compartments worldwide. The present study shows that the release of OPs from a wide variety of commercial products and wastewater discharge might be considered as primary emission sources and that high potential of long-range atmospheric transport and persistence of OPs would be responsible for their presence in various matrices on a global scale. The occurrence and environmental behaviors of OPs in diverse matrices (e.g., dust, air, water, sediment, soil and biota) are reviewed. Human exposures to OPs via dermal contact, dust ingestion, inhalation and dietary intake are comprehensively evaluated. Finally, this study identifies gaps in the existing issues and generates a future agenda for the emerging contaminants OPs.


Teachers' attitude is not an impediment to adolescent sexuality education in Enugu, Nigeria.
Studies have shown that adolescents in Nigeria have poor knowledge of reproductive health issues and that there was a need to provide them with correct broad-based information on reproductive health as part of a nationally-approved school curriculum. However, the non-application of the curriculum on sexuality education in many secondary schools in Nigeria has been blamed on a negative attitude of teachers. This study was undertaken to determine the attitude of secondary school teachers in Enugu, South-eastern Nigeria, to adolescent sexuality education and to determine whether this depends on their socio-demographic characteristics. A cross-sectional study of the attitude of teachers to adolescent sexuality education was done. A total of 249 teachers were studied. Their mean age was 38.7 years +/- 8.08 SD. Two hundred and ten teachers (84%) were females. Two hundred and twenty-four teachers (90%) were married and 168 (67.5%) were of Roman Catholic faith. The awareness of reproductive health activities was high. There was a high proportion of respondents who approved of sexuality education for adolescents (77.5%) and an equally high proportion who believed that it was important (89%). One hundred and ninety-eight (79%) of the respondents were willing to teach sexuality education. The attitude to sexuality education was independent of religion, sex or marital status (p>0.05). It was concluded that secondary school teachers in Enugu urban were willing to offer sexuality education to adolescents under their care irrespective of their religion, sex or marital status. It is, therefore, recommended that teachers in Enugu be given the necessary special training in the teaching of sexuality education now and that sexuality education be officially incorporated into the school curriculum in Enugu, preferably as part of moral studies.


Divergent selectivity in MgI(2)-mediated ring expansions of methylenecyclopropyl amides and imides.
We report a novel approach to prepare five- and six-membered heterocyclic compounds via a ring expansion of monoactivated methylenecyclopropanes (MCPs) with aldimines and aldehydes in the presence of MgI(2). Monoactivated MCPs behave as homo-Michael acceptors to afford bifunctional vinylogous enolates in the presence of MgI(2). The carbonyl moiety of the monoactivated MCP dramatically influences the reaction site in the dienolate with aryl aldimines and aldehydes as well as the size of the ring. Excellent divergent selectivity to five- vs. six-membered heterocycles is observed: alpha-alkylation/5-exo-tet cyclization (Z = NPh(2)) vs. gamma-alkylation/6-exo-trig cyclization (Z = 2-oxazolidone). Analogously, the reaction of the MCP imide with alkyl aldimines demonstrates the same selectivity by varying the size of electrophile or the reaction temperature. In addition, we observe the first example of the formation of the gamma-alkylation adduct in the reaction of a vinylogous imide enolate with a carbonyl compound.


Polymer Nanocoating of Amorphous Drugs for Improving Stability, Dissolution, Powder Flow, and Tabletability: The Case of Chitosan-Coated Indomethacin.
As a result of its higher molecular mobility, the surface of an amorphous drug can grow crystals much more rapidly than the bulk, causing poor stability and slow dissolution of drug products. We show that a nanocoating of chitosan (a pharmaceutically acceptable polymer) can be deposited on the surface of amorphous indomethacin by electrostatic deposition, leading to significant improvement of physical stability, wetting by aqueous media, dissolution rate, powder flow, and tabletability. The coating condition was chosen so that the positively charged polymer deposits on the negatively charged drug. Chitosan coating is superior to gelatin coating with respect to stability against crystallization and agglomeration of coated particles.


Synthesis and evaluation of gadolinium complexes based on PAMAM as MRI contrast agents.
Diethylenetriaminepentaacetic acid (DTPA) and pyridoxamine (PM) were incorporated into the amine groups on the surface of ammonia-core poly(amidoamine) dendrimers (PAMAM, Generation 2.0-5.0) to obtain dendritic ligands. These dendritic ligands were reacted with gadolinium chloride to yield the corresponding dendritic gadolinium (Gd) complexes. The dendritic ligands and their gadolinium complexes were characterized by(1)HNMR, IR, UV and elemental analysis. Relaxivity studies showed that the dendritic gadolinium complexes possessed higher relaxation effectiveness compared with the clinically used Gd-DTPA. After administration of the dendritic gadolinium complexes (0.09 mmol kg(-1) ) to rats, magnetic resonance imaging of the liver indicated that the dendritic gadolinium complexes containing pyridoxamine groups enhanced the contrast of the MR images of the liver, provided prolonged intravascular duration and produced highly contrasted visualization of blood vessels.


Personal construction of cough medicine among young substance abusers in Hong Kong.
Although cough medicine abuse is a growing problem in many places, there is no study examining the views of young substance abusers toward cough medicine. The objective of this study was to examine personal constructions of cough medicine abusers via the repertory grid tests (N = 11). Several observations are highlighted from the study. First, personal constructions of cough medicine were mixed, including the benefits and harmful effects of its abuse. Second, although the informants perceived cough medicine to be addictive and harmful, they perceived cough medicine to be less addictive and less harmful than did heroin. Third, while the informants construed cough medicine to be similar to ketamine and marijuana, they also perceived cough medicine to possess some characteristics of heroin. Fourth, relative to the construed similarity between heroin and the gateway drugs (cigarette, beer, and liquor), the informants construed cough medicine to be more similar to the gateway drugs. Finally, a higher level of perceived dissimilarity between cough medicine and gateway drugs was related to a higher level of perceived harm of cough medicine abuse.


Reducing Central Line-Associated Bloodstream Infection Rates in the Context of a Caring-Healing Environment: A Patient Safety Program Evaluation.
Central line-associated bloodstream infections (CLABSIs) prove to be detrimental to both the patient and the hospital. The present study was a quality improvement training project to affect CLABSI rates in the cardiac intensive care unit in the context of a caring-healing environment, and contributed to a culture of patient safety to empower staff to speak up if they see a breach in protocol at any time. A caring-healing environment encouraged staff to take the extra time and precautions to prevent infections for their patients and created a better quality of care for the patients.


[Determination of inorganic arsenic in food by hybrid generation-atomic fluorescence spectrometry (HG-AFS)].
A hybrid generation-atomic fluorescence spectrometry method (HG-AFS) was developed for determining total inorganic arsenic, As(III) and As(V). The inorganic arsenic in food extracted by 6 mol/L HCl and total inorganic arsenic could be determined in 2 mol/L HCl. As(III) was determined selectively in mixtures of As(III) with As(V) by the different acidities of As(III) and As(V) at hybrid generation. The linear correlation ranges of total inorganic arsenic and As(III) are 0-400 micrograms/ml and 0-300 micrograms/ml respectively. The RSD of inorganic arsenic is 1.93% and As(III) is 2.49%. The detection limits are 1.6 and 1.1 micrograms/ml for inorganic arsenic and As(III) respectively. There is no interference in the determination of general food samples.


Duodenal perforation: an unusual complication of sickle cell anemia.
Duodenal perforation in childhood is a rare condition with a high mortality rate if not treated surgically. Primary gastroduodenal perforation is frequently associated with peptic ulcer and exhibits a positive family history. Helicobacter pylorus is the most significant agent. Secondary gastroduodenal perforation may be a finding of specific diseases, such as Crohn disease, or more rarely may be associated with diseases such as cystic fibrosis or sickle cell anemia. A 14-year-old boy presented with abdominal and back pain. The patient was operated on for acute abdomen and diagnosed with duodenal perforation. Helicobacter pylorus was negative. There was no risk factor to account for duodenal perforation other than sickle cell anemia. Surgical intervention was successful and without significant sequelae. Duodenal perforation is a rare entity described in patients with sickle cell anemia. To our knowledge, this is the first report of duodenal perforation in a patient sickle cell anemia.