Molecular diagnosis of 5α-reductase deficiency in 4 elite young female athletes through hormonal screening for hyperandrogenism.
Although a rare occurrence, previously undiagnosed disorders of sex development (DSD) with hyperandrogenism are sometimes detected by hormonal screening during the international sports competitions. Identifying the cause of XY,DSD raises medical and ethical concerns, especially with regard to issues of the eligibility to compete. The aim of this study was to determine whether the detection of high plasma T in young elite female athletes during hormonal screening would reveal an unsuspected XY DSD. The study was performed in the Nice and Montpellier University Hospitals (France), which collaborate as reference centers for DSD in elite athletes on behalf of sports governing bodies. Four cases of elite young athletes with female phenotypes but high plasma T detected during hormonal screening were investigated for undiagnosed XY DSD. Evaluation of clinical, biological, radiological (magnetic resonance imaging and dual-energy x-ray absorptiometry) and genetic characteristics was conducted. The 4 athletes presented as tall, slim, muscular women with a male bone morphotype, no breast development, clitoromegaly, partial or complete labial fusion, and inguinal/intralabial testes. All reported primary amenorrhea. The hormonal analysis evidenced plasma T within the male range, the karyotype was 46, XY, and molecular analysis of the 5α-reductase type 2 (srd5A2) gene identified a homozygotic mutation in 2 cases, a heterozygotic compound in 1 case, and a deletion in 1 case. 5α-Reductase deficiency should be investigated in elite young female athletes with primary amenorrhea and high male T levels detected during antidoping programs to identify undiagnosed XY DSD.


Phenotypic and Functional Characterization of Mesenchymal Stem/Multipotent Stromal Cells from Decidua Basalis of Human Term Placenta.
Mesenchymal stem cell (MSC) therapies for the treatment of diseases associated with inflammation and oxidative stress employ primarily bone marrow MSCs (BMMSCs) and other MSC types such as MSC from the chorionic villi of human term placentae (pMSCs). These MSCs are not derived from microenvironments associated with inflammation and oxidative stress, unlike MSCs from the decidua basalis of the human term placenta (DBMSCs). DBMSCs were isolated and then extensively characterized. Differentiation of DBMSCs into three mesenchymal lineages (adipocytes, osteocytes, and chondrocytes) was performed. Real-time polymerase chain reaction (PCR) and flow cytometry techniques were also used to characterize the gene and protein expression profiles of DBMSCs, respectively. In addition, sandwich enzyme-linked immunosorbent assay (ELISA) was performed to detect proteins secreted by DBMSCs. Finally, the migration and proliferation abilities of DBMSCs were also determined. DBMSCs were positive for MSC markers and HLA-ABC. DBMSCs were negative for hematopoietic and endothelial markers, costimulatory molecules, and HLA-DR. Functionally, DBMSCs differentiated into three mesenchymal lineages, proliferated, and migrated in response to a number of stimuli. Most importantly, these cells express and secrete a distinct combination of cytokines, growth factors, and immune molecules that reflect their unique microenvironment. Therefore, DBMSCs could be attractive, alternative candidates for MSC-based therapies that treat diseases associated with inflammation and oxidative stress.


[Design and application of a cone-shaped warming-acupuncture-moxibustion apparatus].
To design a warming acupuncture-moxibustion apparatus suitable to warming acupuncture therapy and easily attaching to the filiform needle handle. The apparatus consists of a container for moxa, a tray and regulative clips. The container for moxa is for store of moxa-wool without bottom and it can prevent moxa fire and ash from dropping and burning the skin of the patient or the clothes; the tray with holes on it can serve as a support of the moxa in the container, and can control the moxa burning and heat radiation; the clips can adjust the distance between the cone and the skin. With the advantages of handy material, easy installation, lower cost, and convenient operation, the apparatus is worthy of clinical application and popularization.


Firearm use in intimate partner violence: a brief overview.
Readers of this volume are likely to have specific interests in domestic violence or in firearms policy. It is not assumed, however, that the typical reader will know about the interface of the two fields. Thus, the volume begins with a synopsis of the epidemiology of weapon use in intimate partner violence. The purpose of this article is to help readers better understand the nature of the problem, obtain knowledge that will provide a context for the policy, and understand practice implications of the articles that follow.


[Demineralising osteopathies: new aspects of diagnostic imaging].
The wide use of multimodal radiologic analysis of bone tissue has led to a new concept of the term osteopenia towards grouping the various osteopathies as demineralizing osteopathies. With bone densitometry measurements both high precision and accuracy can be achieved, whereas conventional radiographs provide insights into the architecture of the bone to better advantage. By using both modalities discrepancies of the radiological reports with the final diagnosis may be avoided. Despite ongoing success in techniques of semi-automated data analysis and reporting the radiological and the clinical assessment of bone diseases are still an indispensable part of establishing the diagnosis.


Porphyromonas gingivalis Administration Induces Gestational Obesity, Alters Gene Expression in the Liver and Brown Adipose Tissue in Pregnant Mice, and Causes Underweight in Fetuses.
Preventing adverse pregnancy outcomes is crucial for maternal and child health. Periodontal disease is a risk factor for many systemic diseases including adverse pregnancy outcomes, such as preterm birth and low birth weight. In addition, the administration of the periodontopathic bacterium Porphyromonas gingivalis exacerbates obesity, glucose tolerance, and hepatic steatosis and alters endocrine function in the brown adipose tissue (BAT). However, the effects of having periodontal disease during pregnancy remain unclear. Thus, this study investigates the effect of P. gingivalis administration on obesity, liver, and BAT during pregnancy. Sonicated P. gingivalis (Pg) or saline (Co) was injected intravenously and administered orally to pregnant C57BL/6J mice three times per week. Maternal body weight and fetal body weight on embryonic day (ED) 18 were evaluated. Microarray analysis and qPCR in the liver and BAT and hepatic and plasma triglyceride quantification were performed on dams at ED 18. The body weight of Pg dams was heavier than that of Co dams; however, the fetal body weight was decreased in the offspring of Pg dams. Microarray analysis revealed 254 and 53 differentially expressed genes in the liver and BAT, respectively. Gene set enrichment analysis exhibited the downregulation of fatty acid metabolism gene set in the liver and estrogen response early/late gene sets in the BAT, whereas inflammatory response and IL6/JAK/STAT3 signaling gene sets were upregulated both in the liver and BAT. The downregulation of expression levels of Lpin1, Lpin2, and Lxra in the liver, which are associated with triglyceride synthesis, and a decreasing trend in hepatic triglyceride of Pg dams were observed. P. gingivalis administration may alter lipid metabolism in the liver. Overall, the intravenous and oral administration of sonicated P. gingivalis-induced obesity and modified gene expression in the liver and BAT in pregnant mice and caused fetuses to be underweight.


Identification of two distinct populations of protein kinase C in rat brain membranes.
The regulatory enzyme protein kinase C (PKC) is proposed to be activated on its translocation from the cytosol to the membrane. However, a portion of the native activity is always associated with the membrane fraction. Using a noninvasive procedure to extract this endogenous activity from rat brain membranes, it has been possible to characterize the activity in a partially purified reconstituted system bearing resemblance to the in vivo system. Two subpopulations of membrane-associated PKC were identified and characterized at the level of activation, inhibition, and isozyme immunologic characteristics and chromatographic properties. One peak had properties similar to those of cytosolic PKC, whereas the second population, extracted as protein-lipid complexes, had considerable constitutive activity that could be stimulated further on addition of PKC activators. This latter activity was relatively resistant to staurosporine inhibition and phorbol ester treatment, but it phosphorylated the exogenous PKC substrates, histone 1 and the epidermal growth factor receptor peptide KTRLRR. The constitutive activity was totally dependent on its endogenous associated lipids coextracted by the solubilization procedure. The ratio between these two populations was ontogenetically regulated and modulated by phorbol ester treatment, suggesting that different PKC populations may serve unique functions in the rat brain regulated by the lipid environment. Analyses of the phospholipids extracted in these protein-lipid complexes showed differences in the major classes correlating to age. However, apart from a markedly lower cholesterol content in these complexes, no direct relationship between a specific lipid composition and the amount of constitutive PKC activity was evident.


Preoperative statins are associated with a reduced risk of postoperative delirium following vascular surgery.
Delirium is a common complication of vascular surgery. The protective effect of preoperative statins on delirium after vascular surgery is controversial. The authors hypothesized that preoperative statin administration would decrease the incidence of delirium after vascular surgery. From May 2010 to May 2015, 1,132 patients underwent vascular surgery. Postoperative delirium was diagnosed from patients' medical records. The incidence of delirium was 11.5%. The preoperative statin exposure was not associated with reduced delirium in the univariate analysis. After adjusting for covariates, preoperative statin exposure was associated with reduced delirium (OR, 0.54; 95% CI, 0.33-0.87; p = 0.011). This favor effect of statin for delirium was observed after propensity matching (OR, 0.59; 95% CI, 0.34-1.02; p = 0.060). However, the median hospital lengths of stay and in-hospital mortality were not statistically different between the two groups. CRP(C-reactive protein) levels in the unmatched population were lower in the preoperative statin group compared with the other group (p<0.001), however, there was only numerically different without statistical difference after matching (p = 0.083). Preoperative statin use was associated with a decreased incidence of postoperative delirium in patients who underwent vascular surgery. However, preoperative statin did not reduce mortality rate and hospital stay.


Knowledge about inhaler use among the chronic asthma patients in selected hospitals.
This cross sectional descriptive study was conducted among the chronic asthma patients attending three Institutes of Dhaka city namely National Asthma Center, The National Institute of Diseases of Chest and Hospital (NIDCH), Mohakhali, and Dhaka Medical College Hospital to assess the level of knowledge regarding inhaler use. Convenient sampling was adopted. Data were collected using one semi-structured questionnaire through face-to-face interview. The patients were aged from 18 to 75 years with mean age being 40.68 years and sd +/- 11.659 years. The mean monthly income of the respondents found was 8278.52 taka with standard deviation +/- 3523.315 taka. Mean duration of bronchial asthma was 9.44 years with sd +/- 4.862 years. Out of the total 298 respondents 103(35.8%) possessed "excellent knowledge" on inhalers. Ninety one (31.6%) had "adequate knowledge", sixty nine (24.0%) had "poor knowledge" and thirty five (8.7%) respondents were found having "no knowledge" about inhalers. Males were seen having better knowledge than the females (chi2 =66.582, df=3, p<0.001). The respondents receiving treatment from the indoor possessed better knowledge than those from the outdoors (p<0.001). Level of Knowledge was also found to be associated with the educational status of the respondents. Respondents with higher education possessed more than the respondents with lower education (p<0.001). Though most of the physicians now prescribe inhalers, but many of them do not explain the proper use of inhaler. This may be corrected through training and motivation of physicians at Medical Colleges and Hospitals and during various medical conferences and other programs. To reduce the extent of suffering and economic burden of asthma patients and their families, active education program for the patients and training program for the health care providers, regarding "inhaler use technique" demands early consideration.


Adiabatic quantum simulation of quantum chemistry.
We show how to apply the quantum adiabatic algorithm directly to the quantum computation of molecular properties. We describe a procedure to map electronic structure Hamiltonians to 2-body qubit Hamiltonians with a small set of physically realizable couplings. By combining the Bravyi-Kitaev construction to map fermions to qubits with perturbative gadgets to reduce the Hamiltonian to 2-body, we obtain precision requirements on the coupling strengths and a number of ancilla qubits that scale polynomially in the problem size. Hence our mapping is efficient. The required set of controllable interactions includes only two types of interaction beyond the Ising interactions required to apply the quantum adiabatic algorithm to combinatorial optimization problems. Our mapping may also be of interest to chemists directly as it defines a dictionary from electronic structure to spin Hamiltonians with physical interactions.


Exploring the capabilities of quantum optimal dynamic discrimination.
Optimal dynamic discrimination (ODD) uses closed-loop learning control techniques to discriminate between similar quantum systems. ODD achieves discrimination by employing a shaped control (laser) pulse to simultaneously exploit the unique quantum dynamics particular to each system, even when they are quite similar. In this work, ODD is viewed in the context of multiobjective optimization, where the competing objectives are the degree of similarity of the quantum systems and the level of controlled discrimination that can be achieved. To facilitate this study, the D-MORPH gradient algorithm is extended to handle multiple quantum systems and multiple objectives. This work explores the trade-off between laser resources (e.g., the length of the pulse, fluence, etc.) and ODD's ability to discriminate between similar systems. A mechanism analysis is performed to identify the dominant pathways utilized to achieve discrimination between similar systems.


Species variation in the predawn inhibition of ribulose-1,5-bisphosphate carboxylase/oxygenase.
The activity of ribulose-1,5-bisphosphate carboxylase/oxygenase was measured in extracts of leaves collected before dawn (predawn activity, pa) and at midday (midday activity, ma). Twenty-three of the 37 species examined showed a pa/ma ratio (</=0.75, while only Capsicum frutescens, Cucumis sativa, Glycine max, Nicotiana tabacum, Vigna unguiculata, and 3 Solanum species showed a pa/ma ratio </=0.5. Phaseolus vulgaris consistently showed a pa/ma ratio of </=0.1. Activities and pa/ma ratios of the same species grown in the United States and the United Kingdom were very similar. Gel filtration of extracts before assay had no effect on the observed activities and the pa/ma ratios. These data are consistent with the hypothesis that in a number of species the enzyme is partially inhibited following the night period by the presence of a tight-binding inhibitor.


GOLPH3 Promotes Cancer Growth by Interacting With STIP1 and Regulating Telomerase Activity in Pancreatic Ductal Adenocarcinoma.
Overexpression of Golgi phosphoprotein 3 (GOLPH3) predicts poor prognosis and is a potential therapeutic target in pancreatic ductal adenocarcinoma (PDAC). However, its role and underlying molecular mechanisms in the progression of PDAC remain unknown. In the present study, using high-throughput bimolecular fluorescence complementation (BiFC) analysis, we identified that stress-inducible protein-1 (STIP1) interacts with GOLPH3 and confirmed the interaction using co-localization and co-immunoprecipitation. The levels of GOLPH3 and STIP1 in PDAC tissues and adjacent non-cancerous pancreatic tissues were determined using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR. Real-time Quantitative-telomere repeat amplification (Q-TRAP) was applied to detect relative telomerase activity, and cell proliferation was measured when small interfering RNAs targeting GOLPH3 or STIP1 were transfected into PDAC cell lines. BALB/c nude mice were used to assess tumor growth inhibition of BXPC3 cells stably transfected with GOLPH3 short hairpin RNA. In summary, GOLPH3 was found to interact with STIP1 and both proteins were overexpressed and co-localized in PDAC tissues and cell lines. Moreover, suppression of GOLPH3 expression using shRNAs in PANC1 and BXPC3 cells inhibited tumor cell proliferation both in vitro and in vivo. Mechanistically, GOLPH3 interacts with STIP1 to activate telomerase reverse transcriptase (hTERT) and telomerase activity by c-Myc, and then upregulates cell cycle-related signaling proteins, including cyclin D1, to promote tumor cell growth, suggesting that disrupting the interaction between STIP1 and GOLPH3 would be a promising new strategy to treat PDAC.


Miniaturization and automation of an ubiquitin ligase cascade enzyme-linked immunosorbent assay in 1,536-well format.
Enzyme-linked immunosorbent assays (ELISAs) are a long established and widely used assay format for drug discovery and diagnostics. They offer many advantages over homogeneous assay formats, including high sensitivity and separation (wash) steps that remove detection-interfering compounds. Many high-throughput screening assays are now performed in miniaturized formats (1,536- and 3,456-well plates) for higher throughput and lower reagent consumption. With miniaturization, separation steps in assays such as ELISA can become difficult to implement. Here we report on the implementation of the Kalypsys, Inc. (San Diego, CA) 1,536-well plate washer to enable the successful miniaturization and full automation of an ELISA that monitors ubiquitin ligase activity. The 1,536-well plate ELISA was robust and used for the high-throughput screening of a large screening collection (>1 million compounds).


Direct estimation of the area under the receiver operating characteristic curve in the presence of verification bias.
The area under a receiver operating characteristic (ROC) curve (AUC) is a commonly used index for summarizing the ability of a continuous diagnostic test to discriminate between healthy and diseased subjects. If all subjects have their true disease status verified, one can directly estimate the AUC nonparametrically using the Wilcoxon statistic. In some studies, verification of the true disease status is performed only for a subset of subjects, possibly depending on the result of the diagnostic test and other characteristics of the subjects. Because estimators of the AUC based only on verified subjects are typically biased, it is common to estimate the AUC from a bias-corrected ROC curve. The variance of the estimator, however, does not have a closed-form expression and thus resampling techniques are used to obtain an estimate. In this paper, we develop a new method for directly estimating the AUC in the setting of verification bias based on U-statistics and inverse probability weighting (IPW). Closed-form expressions for the estimator and its variance are derived. We also show that the new estimator is equivalent to the empirical AUC derived from the bias-corrected ROC curve arising from the IPW approach.


Comparison of only T3 and T3-T4 sympathectomy for axillary hyperhidrosis regarding treatment effect and compensatory sweating.
Patients diagnosed with axillary hyperhidrosis can face psychosocial issues that can ultimately hinder their quality of life both privately and socially. The routine treatment for axillary hyperhidrosis is T3-T4 sympathectomy, but compensatory sweating is a serious side effect that is commonly seen with this approach. This study was designed to evaluate whether a T3 sympathectomy was effective for the treatment of axillary hyperhidrosis and whether this treatment led to less compensatory sweating than T3-T4 sympathectomies among our 60-patient population. One hundred and twenty endoscopic thoracic sympathectomies were performed on 60 patients who had axillary hyperhidrosis. The sympathectomies were accomplished by means of a single-lumen endotracheal tube and a single port. The axillary hyperhidrosis patients were randomly divided into two groups with 17 patients in Group 1 undergoing T3-T4 sympathectomies and 43 in Group 2 undergoing only T3 sympathectomies. We analysed the data associated with the resolution of axillary hyperhidrosis, the degree of patient satisfaction with the surgical outcome and the quality of life in parallel with compensatory sweating after the procedure as reported by the patient and confirmed by the examiner. Moreover, the results were compared statistically. No statistically significant difference was observed between the groups based on age (P=0.56), gender (P=0.81), duration of the surgery (P=0.35) or postoperative satisfaction levels (P=0.45). However, the incidence and degree of compensatory sweating were lower in the T3 group than the T3-T4 group at the 1-year follow-up (P=0.008). T3 sympathectomy was as effective as T3-T4 sympathectomy for the treatment of axillary hyperhidrosis based on the patients' reported postoperative satisfaction, and the T3 group demonstrated lower compensatory sweating at the 1-year follow-up.


Characteristics of acyrthosiphon pisum virus, a newly identified virus infecting the pea aphid.
A new virus was isolated from the pea aphid, Acyrthosiphon pisum, and tentatively named Acyrthosiphon pisum virus (APV). The isometric virus particles were approximately 31 nm in diameter and contained a single-stranded RNA molecule of approximately 10 kb. Four structural proteins were observed with molecular masses of approximately 23.3, 24.2, 34.5, and 66.2 kDa. The 34.5-kDa capsid protein was the most abundant product in purified virions. Computer-assisted analysis revealed no significant homology between an internal sequence of 37 amino acids of the 34.5-kDa protein of APV and other polypeptides of viral origin. APV was not immunologically related to other ssRNA viruses from hemipteroid insects, such as aphid lethal paralysis virus, Rhopalosiphum padi virus, and Nezara viridula virus type 1. Immunolocalization on ultrathin sections of 3-day-old nymphs of A. pisum showed that APV antigen was predominantly present in the epithelial cells of the digestive tract. Virus particles were also observed associated with the microvilli of the intestine. Occasionally, muscle cells and mycetocyte cells were found infected. Purified APV, fed to 1-day-old A. pisum nymphs, significantly reduced the growth of the aphid and increased the time needed to reach maturity.


Soluble and cell wall peroxidases in reed canarygrass in relation to disease resistance and localized lignin formation.
The relationship of peroxidases to an inducible disease-resistance mechanism involving lignification of leaf epidermal cell walls was studied. Reed canarygrass (Phalaris arundinacea L.) leaf discs were inoculated with Helminthosporium avenae Eidam and floated on water. In inoculated discs, the activity of soluble, ionic wall-bound and covalent wall-bound peroxidases was about twice the level of activity in noninoculated discs. The increase was attributable to increases in activity of three cathodic isoperoxidases and to the appearance of a new cathodic isoperoxidase. Peroxidase activity in cryostat microtome sections of inoculated discs was histochemically localized in the wall near the site of attempted penetration. When inoculated discs were floated on solutions of cycloheximide (25 mug/ml), increases in peroxidase activity were inhibited, and the fungus penetrated the tissue. The inhibition of peroxidase activity was related to inhibition of cathodic isoperoxidase activity. Anodic isoperoxidase activity did not show changes in response to inoculation or cycloheximide treatment.It was suggested that the resistance mechanism in P. arundinacea involves an induction of cathodic isoperoxidases in challenged tissue. These peroxidases may function in the biosynthesis of lignin at the site of attempted penetration.


Invasive Gastrointestinal Mucormycosis: A Master Masquerader.
We report 3 previously healthy children of postneonatal age who developed fatal form of gastrointestinal mucormycosis after systemic inflammatory response syndrome, shock and metabolic acidosis. Abdominal distension and peritonitis were secondary complications. The study highlights the importance of clinical suspicion of gastrointestinal mucormycosis when the triad of shock requiring vasoactive drugs, metabolic acidosis and abdominal distension is present.


Age trends in the sleep EEG of healthy older men and women.
The all-night sleep EEGs of 314 (191 women, 123 men) healthy older subjects between the ages of 45 and 90 were studied for age trends in the power spectra of the all-night NREM sleep EEG. Power spectra of the unnormalized EEG of the women show a power loss in the delta band and a power increase in the beta band with increasing age. For the men no significant trends in the power spectra of the unnormalized EEG were in evidence. A normalization of the power spectra was performed by referencing each logarithmically expressed spectra to its area between 2 Hz and 30 Hz. For both genders the normalized spectra show significant decreases in power at many frequencies below 16 Hz and significant increases in power at frequencies above 18 Hz with increasing age. The age trends observed in the spectra of this population (45-90 y age group) are about a third of the magnitude of those reported in the literature for subjects between the ages of 20 y and 40 y.


Fat-1 gene modulates the fatty acid composition of femoral and vertebral phospholipids.
Dietary polyunsaturated fatty acid (PUFA) incorporation into bone may alter its metabolism through changes in the fatty acid composition of membrane phospholipids. Alteration of the membrane phospholipid fatty acid composition may influence bone cell signalling and, potentially, bone mineralization. The objective of this study was to use the fat-1 mouse, a transgenic model that synthesizes n-3 from n-6 PUFA, to determine if the fat-1 gene modulates the fatty acid composition of femoral and vertebral phospholipids, and if so, whether the fatty acid levels would correlate with bone mineral density (BMD) at both skeletal sites. Male and female wild-type and fat-1 mice were fed an AIN93-G diet, containing 10% safflower oil, from weaning to 12 weeks of age. The fatty acid composition of femoral and vertebral phospholipids was measured by gas liquid chromatography. At 12 weeks of age, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine fractions in the vertebrae of fat-1 mice had a significantly lower n-6/n-3 ratio than wild-type mice (p<0.05). In fat-1 femurs, these fractions, along with phosphatidylinositol, had a lower n-6/n-3 ratio than wild-type mice (p<0.001). Docosahexaenoic acid (DHA) was positively correlated with BMD in all fractions in the vertebrae, and in phosphatidylinositol and phosphatidylserine in the femur (p<0.05). Overall, the fat-1 gene resulted in changes in the fatty acid composition of both femoral and vertebral phospholipids. Significant correlations between DHA and BMD may indicate a positive effect on bone mineralization.


Regioselective bromination tactics in the de novo synthesis of chlorophyll b analogues.
The ability to introduce substituents at designated sites about the perimeter of the chlorin or 13(1)-oxophorbine macrocycle is essential for fundamental studies related to chlorophylls. A chlorin is a dihydroporphyrin, whereas a 13(1)-oxophorbine is a chlorin containing an annulated oxopentano ring spanning positions 13 and 15. 13(1)-Oxophorbines bearing auxochromes at the 7-position of the macrocycle are valuable targets given their resemblance to chlorophyll a or b, which contains the 13(1)-oxophorbine skeleton and bears a 7-methyl or 7-formyl group, respectively. A rational route to 7-substituted 13(1)-oxophorbines was developed that relies on a new method for regioselective bromination. Under neutral conditions, a 13-acetyl-10-mesitylchlorin (FbC-M(10)A(13)) undergoes bromination (with 1 molar equiv of NBS in THF) both in ring B (7-position) and at the 15-position (42% versus 28% isolated yield), thereby thwarting installation of the isocyclic ring (ring E, spanning the 13-15 positions). Under acidic conditions (10% TFA in CH(2)Cl(2)), ring B is deactivated, and bromination occurs preferentially at the 15-position (87% yield). The capability for preferential 15-bromination is essential to install the isocyclic ring, after which bromination can be directed to the 7-position of ring B (neutral conditions, 86% yield). The ability to suppress bromination in ring B (under acidic media) has been exploited in syntheses of sparsely substituted analogues of chlorophyll b. The analogues contain a 7-substituent (acetyl, formyl, or TIPS-ethynyl), a 10-mesityl group, and the 18,18-dimethyl group as the only substituents in the 13(1)-oxophorbine skeleton. The three analogues exhibit absorption spectral features that closely resemble those of free base analogues of chlorophyll b. Taken together, the facile access to chlorins and 13(1)-oxophorbines bearing substituents at distinct sites should enable fundamental spectroscopic studies and diverse applications.


Performance analysis of data mining algorithms for diagnosing COVID-19.
An outbreak of atypical pneumonia termed COVID-19 has widely spread all over the world since the beginning of 2020. In this regard, designing a prediction system for the early detection of COVID-19 is a critical issue in mitigating virus spread. In this study, we have applied selected machine learning techniques to select the best predictive models based on their performance. The data of 435 suspicious cases with COVID-19 which were recorded from the Imam Khomeini Hospital database between May 9, 2020 and December 20, 2020, have been taken into consideration. The Chi-square method was used to determine the most important features in diagnosing the COVID-19; eight selected data mining algorithms including multilayer perceptron (MLP), J-48, Bayesian Net (Bayes Net), logistic regression, K-star, random forest, Ada-boost, and sequential minimal optimization (SMO) were applied in data mining. Finally, the most appropriate diagnostic model for COVID-19 was obtained based on comparing the performance of the selected algorithms. As the result of using the Chi-square method, 21 variables were identified as the most important diagnostic criteria in COVID-19. The results of evaluating the eight selected data mining algorithms showed that the J-48 with true-positive rate = 0.85, false-positive rate = 0.173, precision = 0.85, recall = 0.85, F-score = 0.85, Matthews Correlation Coefficient = 0.68, and area under the receiver operator characteristics = 0.68, respectively, had the higher performance than the other algorithms. The results of evaluating the performance criteria showed that the J-48 can be considered as a suitable computational prediction model for diagnosing COVID-19 disease.


Lithium-Based Upconversion Nanoparticles for High Performance Perovskite Solar Cells.
In this work, we report an easy, efficient method to synthesize high quality lithium-based upconversion nanoparticles (UCNPs) which combine two promising materials (UCNPs and lithium ions) known to enhance the photovoltaic performance of perovskite solar cells (PSCs). Incorporating the synthesized YLiF4:Yb,Er nanoparticles into the mesoporous layer of the PSCs cells, at a certain doping level, demonstrated a higher power conversion efficiency (PCE) of 19%, additional photocurrent, and a better fill factor (FF) of 82% in comparison to undoped PSCs (PCE = ~16.5%; FF = 71%). The reported results open a new avenue toward efficient PSCs for renewable energy applications.


Picric acid sensitive optode based on a fluorescence carrier covalently bound to membrane.
An acryloyl group was attached to fluorescein through the phenol hydroxyl group to make it photopolymerizable with 2-hydroxypropyl methacrylate and covalently immobilized on an optode glass surface modified with gamma-(methacryloxy)propyltrimethoxysilane. The optode system with a plastic-clad fused silica bifurcated fiber optic bundle shows satisfactory analytical performance characteristics for determining picric acid in terms of selectivity and reproducibility with a linear range from 8.0 x 10(-7) to 4.0 x 10(-3) mol L-1. The quenching mechanism was investigated. The optode membrane can be applied to the indirect determination of cinchonine drug and the results obtained were satisfactory.


Unmasking of a proliferation-restraining activity of the anti-apoptosis protein EBV BHRF1.
The BHRF1 protein of Epstein-Barr virus (EBV) is a structural and functional homolog of the Bcl-2 protein. Both BHRF1 and Bcl-2 proteins promote the survival of cells exposed to various apoptotic stimuli. This promotion of cell survival is associated with a block in proliferation. It is believed that the Bcl-2 family of anti-apoptosis proteins contribute to oncogenesis merely by promoting cell survival. We have discovered that mutations within a regulatory domain of the BHRF1 protein not only suppress apoptosis induced by the tumor suppressor protein p53, but also permit efficient proliferation of cells that would otherwise undergo total apoptosis. These gain-of-function mutants of BHRF1 cooperate more efficiently with the E1a oncogene in transformation of primary rat kidney cells where E1A expression results in apoptosis. Our results suggest that such mutational inactivation of a proliferation-restraining activity in the BHRF1 gene may play a direct role in oncogenesis.


Environmental exposure to lead and mercury in Mexican children: a real health problem.
Exposure to lead (Pb) and mercury (Hg) remains a world public health problem, particularly for young children in developing countries. In Mexico, the main sources of exposure to Pb and Hg are wastes from human activities that increase the natural sources of these metals. Pb and Hg are highly toxic during development and maturation periods of the central nervous system (CNS); these effects are associated with the risk for neurodegenerative diseases. Mexico has numerous exposure sources to Pb and Hg; nevertheless, information on exposure in children is limited, particularly for Hg. Therefore, we conducted a review of the studies performed in children exposed to Pb and Hg. Data presented support that an important proportion of Mexican children have Pb levels above values associated with dangerous effects. On the other hand, studies on Hg-exposure are scarce, so we need more studies to estimate the magnitude of the problem and to determine exposure levels in Mexican children. Available data support the urgent need for coordinated actions among researchers, and health and environmental government authorities to implement education and nutritional campaigns, as well as to decrease exposure and effects of Pb and Hg. In addition, there must be a priority for the implementation of educational campaigns directed to the general population, but with emphasis in parents, education staff and health care providers to decrease both the risk of exposure of children to Pb and Hg and the effects of the exposure to these metals.


Progress of a room temperature electron cyclotron resonance ion source using evaporative cooling technology at Institute of Modern Physics.
A new room temperature ECR ion source, Lanzhou Electron Cyclotron Resonance ion source No. 4 (LECR4, previously named DRAGON), is under intense construction at Institute of Modern Physics. LECR4 is designed to operate with 18 GHz microwave frequency. The maximum axial magnetic fields are 2.3 T at injection and 1.3 T at extraction, and the radial field at the plasma chamber wall of 76 mm inner diameter is 1.0-1.2 T. One of the unique features for LECR4 is that its axial solenoids are winded with solid square copper wires which are immersed in a kind of special evaporative cooling medium for cooling purpose. Till now, a prototype of the cooling system has been successfully constructed and tested, which has demonstrated that the cooling efficiency of the designed system could meet the requirements of LECR4 under the routine operation conditions. All the main components of the ion source have been completed. Assembly and commissioning is ongoing. The latest developments and test results will be presented in this paper.


Region-specific sex-dependent pattern of age-related changes of proximal femoral cancellous bone and its implications on differential bone fragility.
Despite evident interest in age-related bone changes, data on regional differences within the proximal femur are scarce. To date, there has been no comprehensive study on site-specific age-related changes in the trabecular architecture of three biomechanically important femoral subregions (medial neck, lateral neck, and intertrochanteric region) for both genders. In this study we investigated age-related deterioration in the trabecular architecture of those three subregions of the femoral neck for both genders. The research sample included 52 proximal femora (26 males, 26 females; age range, 26-96 years) from Forensic Department at University of Belgrade. Bone sections from the three regions of interest were scanned by micro-CT at University of Hamburg. The study revealed that proximal femoral microarchitecture cannot be perceived as homogeneous and, more importantly, that the aging process is not uniform. Besides the initial intersite differences, microarchitecture changed differently with increasing age, maintaining significant differences between the regions. In addition, we observed a different aging pattern between genders: deterioration was most significant in the intertrochanteric region in women, while the lateral neck was most affected in men. This finding supports epidemiological data about the differential occurrence of cervical vs. trochanteric fractures in aging males and females. In conclusion, the aging process in the proximal femur cannot be regarded as a simple function of quantitative bone loss but, rather, as an alteration of specific architecture that may degrade bone strength.


The effect of the menstrual cycle on exhaled nitric oxide and urinary nitrate concentration.
Exhaled nitric oxide (NO), early morning urinary nitrites/nitrates and urinary female sex steroid conjugates were measured daily to investigate whether there was a variation in NO generation during the menstrual cycle. Exhaled NO concentrations and early morning urine samples were taken for 30 consecutive days in five healthy normotensive women with proven ovulation. The urine samples were analysed for nitrite-nitrate creatinine ratios, oestrone-3-glucuronide (EG) and pregnanediol-3-alpha glucuronide (PG). The mean (95% CI) exhaled NO concentration was 52 ng g-1 in the 150 readings and the mean molar urinary nitrate-creatinine ratio was 0.18. There was no temporal relationship between the measurement of NO production and urinary sex steroid conjugates within the menstrual cycle. These findings suggest that oestrogens do not modulate exhaled NO concentration and appear not to increase the production of the early morning urinary nitrates in healthy premenopausal women. There was also no sex difference in exhaled NO generation.


Design and Synthesis of Hyperbranched Aromatic Polymers for Catalysis.
Aromatic polymers such as poly(ether sulfone), poly(ether ketone), and polyimide have been widely used in industry due to their thermal, mechanical, and chemical stabilities. Although their application to catalysis has been limited, the introduction of a hyperbranched architecture to such aromatic polymers is effective in developing catalytic materials that combine the advantages of homogenous and heterogeneous catalysts. This review article overviews the recent progress on the design and synthesis of hyperbranched aromatic polymers. Several acid catalyzed reactions and the aerobic oxidation of alcohols have been demonstrated using hyperbranched aromatic polymers as catalysts. The advantage of hyperbranched polymers against linear polymers is also discussed.


Preparation and Properties of a beta-d-Glucanase for the Specific Hydrolysis of beta-d-Glucans.
A beta-d-glucanase highly specific for glucans containing a linkage sequence ... Glc 1 --> 4 Glc 1 --> 3 Glc 1 --> 4 Glc ... has been isolated from several commercial preparations of Bacillus subtilis alpha-amylase including one purified by repeated crystallization. The beta-d-glucanase will not hydrolyze cellulose or laminarin. Gel filtration on a Bio-Gel P-200 column results in separation of the glucanase from the alpha-amylase. The enzyme is of the endo type as changes in the substrate viscosity appear long before the appearance of detectable reducing sugars. No evidence of product inhibition was revealed and appropriate substrates were converted to oligosaccharides, the quantity of which approaches theoretical yields. The products of the reaction were separated according to molecular size by use of Bio-Gel P-2 gel filtration and found to be consistent with the action pattern of the enzyme. Kinetic studies show that the enzyme has an optimum activity at pH 6.5, a V(max) of 13.9 mug glucose equivalent released/mug protein.hour, and an apparent Km of 3.4 mg of lichenan per ml. Potential application of this enzyme for the structural characterization of plant cell wall glucans is discussed.


Speed and direction of shift rotation.
This review paper deals with the issue of shift rotation, i.e. the number of consecutive shifts of the same type and the order of change between shifts. To minimize the disturbances of the circadian system and the accumulation of sleep deficits, rapidly and clockwise-rotating shift systems would seem to be preferable. Regarding consecutive night shifts, a week of night shifts seems to be the worst system with regard to performance and accidents. There is a lack of reliable data on the effects of permanent vs. rotating-shift systems on alertness, performance and accidents. This is also true for the comparison of forward (delaying) and backward (advancing) rotating-shift systems, although the former would seem to be associated with fewer problems. For both systems, controlled longitudinal studies are necessary.


[Multifocal nodular AL amyloidosis in primary Sjögren's syndrome].
Primary Sjögren's syndrome (primary SS) is characterized by lymphocytic and plasma cell infiltration of the lacrimal and salivary glands, sometimes extending to extraglandular sites. An increased incidence of B-cell lymphoproliferative disorders has been observed in patients with primary SS. We recently studied an unusual case of primary SS associated with multifocal nodular AL amyloidosis (amyloidomas), located in the lower respiratory tract and oral mucosa. A 66-year-old woman with primary Sjögren's syndrome since 1966 was hospitalized in 1996 because of multifocal nodular shadows on a chest radiograph. An open lung biopsy specimen was obtained, revealing a large mass of amorphous eosinophilic material with green birefringence when stained with Congo red. Numerous plasma cells surrounded the amyloid deposits, aggregated in nodules and around blood vessels. The cytoplasm of these cells stained monotypically with anti-lambda light chain, using a peroxidase technique. Amyloid material did not stain with antibodies directed against kappa and lambda light chains, or against IgG, IgA and IgM heavy chains. Immunofixation of the serum and concentrated urine did not demonstrate monoclonal immunoglobulins. AL-amyloidomas might be a manifestation of local immunoglobulin production and amyloid formation within extramedullary plasmacytoma. This plasmacytoma might be burned out, namely, overcome by the deposits and no longer recognizable.


Maximum Oxygen Uptake of Male Soccer Players According to their Competitive Level, Playing Position and Age Group: Implication from a Network Meta-Analysis.
The aim of the present meta-analysis was to compare the maximum oxygen uptake (VO2max) characteristics of male soccer players relative to their competitive level, playing position and age group and the interaction between them. The meta-analysis was based on 16 studies, employing 2385 soccer players aged 10-39 years. Higher-level soccer players showed greater (ES = 0.58 [95% CI 0.08-1.08], SE = 0.25, var = 0.06, z = 2.29, p = 0.022) VO2max performance with respect to their lower level counterparts. Furthermore, lower VO2max values in goalkeepers than defenders (ES = 1.31 (SE 0.46) [95% CI 0.41-2.21], var = 0.21, z = 2.84, p = 0.004) and midfielders (ES = 1.37 (SE 0.41) [95% CI 0.58 to 2.17], var = 0.16, z = 3.40, p = 0.001) were found. Thus, VO2max increased significantly with age (all, p < 0.01): Under 10 versus Under 11 years, Under 11 versus Under 12 years, Under 12 versus Under 13 years, Under 13 versus Under 14 years, Under 14 versus Under 15 years and Under 16-18 versus Under 20-23 years. VO2max performance is the most powerful discriminator between higher and lower-level soccer players. These findings indicate also the need for sports scientists and conditioning professionals to take the VO2max performance of soccer players into account when designing individualized position specific training programs.


Interaction of lipoamide dehydrogenase with the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii.
The interaction between lipoamide dehydrogenase (E3) and dihydrolipoyl transacetylase (E2p) from the pyruvate dehydrogenase complex was studied during the reconstitution of monomeric E3 apoenzymes from Azotobacter vinelandii and Pseudomonas fluorescens. The dimeric form of E3 is not only essential for catalysis but also for binding to the E2p core, because the apoenzymes as well as a monomeric holoenzyme from P. fluorescens, which can be stabilized as an intermediate at 0 degree C, do not bind to E2p. Lipoamide dehydrogenase from A. vinelandii contains a C-terminal extension of 15 amino acids with respect to glutathione reductase which is, in contrast to E3, presumably not part of a multienzyme complex. Furthermore, the last 10 amino acid residues of E3 are not visible in the electron density map of the crystal structure and are probably disordered. Therefore, the C-terminal tail of E3 might be an attractive candidate for a binding region. To probe this hypothesis, a set of deletions of this part was prepared by site-directed mutagenesis. Deletion of the last five amino acid residues did not result in significant changes. A further deletion of four amino acid residues resulted in a decrease of lipoamide activity to 5% of wild type, but the binding to E2p was unaffected. Therefore it is concluded that the C-terminus is not directly involved in binding to the E2p core. Deletion of the last 14 amino acids produced an enzyme with a high tendency to dissociate (Kd approximately 2.5 microM). This mutant binds only weakly to E2p. The diaphorase activity was still high. This indicates, together with the decreased Km for NADH, that the structure of the monomer is not appreciably changed by the mutation. Rather the orientation of the monomers with respect to each other is changed. It can be concluded that the binding region of E3 for E2p is constituted from structural parts of both monomers and binding occurs only when dimerization is complete.


Chyme reinfusion improved outcomes after definitive surgery for small-intestinal enteroatmospheric fistula in patients with enteral nutrition.
In patients suffering from small-intestinal enteroatmospheric fistula who are receiving enteral nutrition (EN), although the function of the small intestine is sufficient, without chyme reinfusion (CR), disuse of the distal intestine of enteroatmospheric fistula may occur. However, CR reverses such pathological changes and have an influence on improving outcomes following definitive surgery (DS) for small-intestinal enteroatmospheric fistula. This study attempted to investigate the effect of preoperative CR in patients with EN on the outcomes after DS for small-intestinal enteroatmospheric fistula. According to whether CR was performed between January 2012 and December 2019, patients receiving DS for small intestinal enteroatmospheric fistula were divided into the CR group and non-CR group. The effect of preoperative CR was then investigated. A total of 159 patients were finally enrolled, of which 72 patients were in the CR group and 87 patients were in the non-CR group. A total of 47 (29.56%) patients were found to have recurrent fistula after DS, the recurrent fistula rate in the CR group (multivariate odds ratio = 0.557; 95% CI, 0.351-0.842; P = 0.019) was lower. CR was also shown to promote postoperative recovery of bowel function (hazard ratio [HR] = 1.982; 95% CI, 1.199-3.275; P = 0.008), and shorten postoperative length of stay (LOS) (HR = 1.739; 95% CI, 1.233-2.453; P = 0.002). Preoperative CR may reduce the incidence of recurrent fistula, time to return of bowel function and postoperative LOS following DS for small-intestinal enteroatmospheric fistula.


AVGs: framework for ambulatory care payment.
In preparation for an ambulatory care prospective payment system, the Health Care Financing Administration (HCFA), Office of Research and Demonstration, supported a two-year grant project at Yale University for further development of an ambulatory patient classification system based on Ambulatory Visit Groups (AVGs). This article explains the premises of the study and gives us insight into what we may ultimately expect in an ambulatory care prospective payment system.


High prevalence of normal tests assessing hypercortisolism in subjects with mild and episodic Cushing's syndrome suggests that the paradigm for diagnosis and exclusion of Cushing's syndrome requires multiple testing.
Many Endocrinologists believe that a single determination of eucortisolism or a single demonstration of appropriate suppression to dexamethasone excluded Cushing's syndrome, except in what was previously thought to be the rare patient with episodic or periodic Cushing's syndrome. We hypothesize that episodic Cushing's syndrome is relatively common and a single test assessing hypercortisolism may not be sufficient to accurately rule out or diagnose Cushing's syndrome and retrospectively examined the number of normal and abnormal tests assessing hypercortisolism performed on multiple occasions in 66 patients found to have mild and/or episodic Cushing's syndrome compared to a similar group of 54 patients evaluated for, but determined not to have Cushing's syndrome. We found that 65 of the 66 patients with Cushing's syndrome had at least one normal test of cortisol status and most patients had several normal tests. The probability of having Cushing's syndrome when one test was negative was 92% for 23:00 h salivary cortisol, 88% for 24-h UFC, 86% for 24-h 17OHS, and 54% for nighttime plasma cortisol. These results demonstrated that episodic hypercortisolism is highly prevalent in subjects with mild Cushing's syndrome and no single test was effective in conclusively diagnosing or excluding the condition. Rather, the paradigm for the diagnosis should be a careful history and physical examination and in those patients in whom mild Cushing's syndrome/disease is strongly suspected, multiple tests assessing hypercortisolism should be performed on subsequent occasions, especially when the patient is experiencing signs and symptoms of short-term hypercortisolism.


Metabolic cost, mechanical work, and efficiency during normal walking in obese and normal-weight children.
This study aimed to investigate the influence of childhood obesity on energetic cost during normal walking and to determine if obese children choose a walking strategy optimizing their gait pattern. Sixteen obese children with no functional abnormalities were matched by age and gender with 16 normal-weight children. All participants were asked to walk along a nearly circular track 30 m in length at a self-selected speed. Spatiotemporal data, kinematics, and ground reaction force were collected during walking using a three-dimensional motion analysis system. Metabolic cost was collected by a portable gas analyzer simultaneously. The mechanical energy expenditure (MEE) was 72.7% higher in obese children than in normal-weight children. The net metabolic cost was 65.7% higher in obese children. No difference was found in the metabolic rate (J x kg(-1) x m(-1)), normalized MEE (J x kg(-1) x m(-1)) and mechanical efficiency between the obese and normal-weight groups. The obese children walked with a 0.15 m/s slower walking speed, 10.0% shorter cadence, and 30.9% longer double-support phase compared with normal-weight children. In addition, no differences were found in the mediolateral and vertical body center of mass displacement. Body mass played a dominant role in the total metabolic and mechanical cost per stride. Obese children may adopt a walking strategy to avoid an increase in the metabolic cost and the mechanical work required to move their excess body mass.


Malate Oxidation and Cyanide-Insensitive Respiration in Avocado Mitochondria during the Climacteric Cycle.
After preparation on self-generated Percoll gradients, avocado (Persea americana Mill, var. Fuerte and Hass) mitochondria retain a high proportion of cyanide-insensitive respiration, especially with alpha-ketoglutarate and malate as substrates. Whereas alpha-ketoglutarate oxidation remains unchanged, the rate of malate oxidation increases as ripening advances through the climacteric. An enhancement of mitochondrial malic enzyme activity, measured by the accumulation of pyruvate, closely parallels the increase of malate oxidation. The capacity for cyanide-insensitive respiration is also considerably enhanced while respiratory control decreases (from 3.3 to 1.7), leading to high state 4 rates.Both malate dehydrogenase and malic enzyme are functional in state 3, but malic enzyme appears to predominate before the addition of ADP and after its depletion. In the presence of cyanide, a membrane potential is generated when the alterntive pathway is operating. Cyanide-insensitive malate oxidation can be either coupled to the first phosphorylation site, sensitive to rotenone, or by-pass this site. In the absence of phosphate acceptor, malate oxidation is mainly carried out via malic enzyme and the alternative pathway. Experimental modification of the external mitochondrial environment in vitro (pH, NAD(+), glutamade) results in changes in malate dehydrogenase and malic enzyme activities, which also modify cyanide resistance. It appears that a functional connection exists between malic enzyme and the alternative pathway via a rotenone-insensitive NADH dehydrogenase and that this pathway is responsible, in part, for nonphosphorylating respiratory activity during the climacteric.


ssPNA templated assembly of oligo(p-phenylenevinylene)s.
A single-stranded oligothymine peptide nucleic acid (PNA) was used as a template for the assembly of a chiral oligo(p-phenylenevinylene) diaminotriazine derivative (OPV) in methylcyclohexane (MCH) revealing nanostructures in which the size is controlled by the template.


Regional labor markets and the household migration decision.
"The current work extends the modeling of the household migration decision to take into account location-specific influences and relates these to regional wage differentials. This allows for more complete analysis of real wage gains or losses associated with migration and inferences regarding the nature of equilibrium or disequilibrium wage differentials between regions." Data are from the Michigan Panel Study of Income Dynamics for the period 1976-1978. "The results indicate systematic and often substantial influences of household location on the nominal wage and on both job and residence mobility. Based on these findings, comparisons of wage growth patterns are made for those changing jobs and region of residence status. Although compared to other households the wage growth of these migrants is on average lower before migration and higher after migration, the analysis provides no support for arguments that nominal regional wage differentials reflect systematic ordering of real wage differentials. This finding suggests that real wage gains are closely tied to the interregional migration decision but are not related to regional nominal wage differentials in a simple fashion."


Effects of angiotensin metabolites in the coronary vascular bed of the spontaneously hypertensive rat: loss of angiotensin II type 2 receptor-mediated vasodilation.
Because angiotensin (Ang) metabolites mediate functions independent of Ang II, we investigated their effects on coronary flow in spontaneously hypertensive rats (SHRs). Results were compared with those in the iliac artery and abdominal aorta and the coronary circulation of the Wistar rat. Ang II, III, and IV decreased coronary flow in SHRs and Wistar rats, with Ang III and IV being approximately 10 and approximately 1000 times less potent than Ang II. Ang-(1-7) decreased coronary flow at concentrations >1 micromol/L in SHRs. The Ang II type 1 receptor antagonist irbesartan blocked the effects of Ang II, III, and IV, whereas the Ang II type 2 receptor antagonist PD123319 blocked the effects of Ang-(1-7). The maximal Ang II- and III-induced decreases in coronary flow in SHRs were twice as large as those in Wistar rats. PD123319 enhanced the constrictor effects of Ang II and III in Wistar rats so that, in the presence of this drug, their effects were comparable to those in SHRs. In contrast, PD123319 did not alter the Ang II- and III-induced responses in SHRs and blocked the constrictor effect of Ang II in iliac arteries. Ang II type 2 receptor-mediated relaxation did not occur in iliac arteries and abdominal aortas, and the constrictor effects of Ang metabolites in these vessels were identical in Wistar rats and SHRs. In conclusion, coronary constriction induced by Ang II, Ang III, and Ang-(1-7) is enhanced in SHRs as compared with Wistar rats. This is attributable to the absence of counterregulatory Ang II type 2 receptor-mediated relaxation and/or a change of the Ang II type 2 receptor phenotype from relaxant to constrictor.


Gene regulation systems for gene therapy applications in the central nervous system.
Substantial progress has been made in the development of novel gene therapy strategies for central nervous system (CNS) disorders in recent years. However, unregulated transgene expression is a significant issue limiting human applications due to the potential side effects from excessive levels of transgenic protein that indiscriminately affect both diseased and nondiseased cells. Gene regulation systems are a tool by which tight tissue-specific and temporal regulation of transgene expression may be achieved. This review covers the features of ideal regulatory systems and summarises the mechanics of current exogenous and endogenous gene regulation systems and their utility in the CNS.


Behavioral treatment of voice disorders in teachers.
The purpose of this paper is to review the literature on the behavioral treatment of voice disorders in teachers. The focus is on phonogenic disorders, that is voice disorders thought to be caused by voice use. Review of the literature and commentary. The review exposes distinct holes in the literature on the treatment of voice problems in teachers. However, emerging trends in treatment are noted. For example, most studies identified for review implemented a multiple-therapy approach in a group setting, in contrast to only a few studies that assessed a single-therapy approach with individual patients. Although the review reveals that the evidence around behavioral treatment of voice disorders in teachers is mixed, a growing body of data provides some indicators on how effectively rehabilitation of teachers with phonogenic voice problems might be approached. Specifically, voice amplification demonstrates promise as a beneficial type of indirect therapy and vocal function exercises as well as resonant voice therapy show possible benefits as direct therapies. Finally, only a few studies identified even remotely begin to meet guidelines of the Consolidated Standards of Reporting Trials statement, a finding that emphasizes the need to increase the number of investigations that adhere to strict research standards. Although data on the treatment of voice problems in teachers are still limited in the literature, emerging trends are noted. The accumulation of sufficient studies will ultimately provide useful evidence about this societally important issue.


N400 incongruity effect in an episodic memory task reveals different strategies for handling irrelevant contextual information for Japanese than European Canadians.
East Asians/Asian Americans show a greater N400 effect due to semantic incongruity between foreground objects and background contexts than European Americans (Goto, Ando, Huang, Yee, & Lewis, 2010). Using analytic attention instructions, we asked Japanese and European Canadians to judge, and later, remember, target animals that were paired with task-irrelevant original (congruent), or novel (incongruent) contexts. We asked: (1) whether the N400 also shows an episodic incongruity effect, due to retrieved contexts conflicting with later-shown novel contexts; and (2) whether the incongruity effect would be more related to performance for Japanese, who have been shown to have more difficulty ignoring such contextual information. Both groups exhibited episodic incongruity effects on the N400, with Japanese showing more typical N400 topographies. However, incongruent-trial accuracy was related to reduction of N400s only for the Japanese. Thus, we found that the N400 can reflect episodic incongruity which poses a greater challenge to Japanese than European Canadians.


Osthole shows the potential to overcome P-glycoprotein‑mediated multidrug resistance in human myelogenous leukemia K562/ADM cells by inhibiting the PI3K/Akt signaling pathway.
P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) has been reported to play a pivotal role in tumor chemotherapy failure. Study after study has illustrated that the phosphoinositide 3-kinase (PI3K)/Akt signaling cascade is involved in the MDR phenotype and is correlated with P-gp expression in many human malignancies. In the present study, osthole, an O-methylated coumarin, exhibited potent reversal capability of MDR in myelogenous leukemia K562/ADM cells. Simultaneously, the uptake and efflux of Rhodamine-123 (Rh-123) and the accumulation of doxorubicin assays combined with flow cytometric analysis suggested that osthole could increase intracellular drug accumulation. Furthermore, osthole decreased the expression of multidrug resistance gene 1 (MDR1) at both the mRNA and protein levels. Further experiments elucidated that osthole could suppress P-gp expression by inhibiting the PI3K/Akt signaling pathway which might be the main mechanism accounting for the reversal potential of osthole in the MDR in K562/ADM cells. In conclusion, osthole combats MDR and could be a promising candidate for the development of novel MDR reversal modulators.


Stimulation of rat granulosa cell progesterone production but not other differentiated functions by a splenocyte-derived factor.
Concanavalin A-stimulated splenocytes secrete a factor that stimulates progesterone production in cultured rat granulosa cells. The actions of this progesterone-stimulating factor (PSF) were characterized further by purifying it by sequential chromatographies on heparin-agarose, copper chelating-Sepharose and Mono S columns. Several of its effects on granulosa cells were then compared with those of FSH. Like FSH, PSF induced accumulation of progesterone and 20 alpha-dihydroprogesterone in granulosa cell culture media; however, the time course of progesterone accumulation in response to PSF was much slower than that in response to FSH. In contrast to FSH, PSF induced little accumulation of oestrogen. Induction of other differentiated responses was compared by pretreating cultured granulosa cells with either FSH or PSF, and then challenging with LH, prolactin, epidermal growth factor or the beta-adrenergic agonist, isoproterenol. Pretreatment with FSH induced subsequent responsiveness to all four agents, whereas pretreatment with PSF induced subsequent responsiveness only to isoproterenol. These results indicate that granulosa cell responses to PSF are much more limited than are those to FSH and that these responses are characterized by an increase in progestin production.


Patients' perceptions on shared decision making during prescription of subcutaneous biological drug treatments for inflammatory arthritis: The RHEU-LIFE survey.
The aim of this study was to explore the preferences of patients with rheumatic diseases and their perceived experience regarding participation in shared decision making (SDM) when they were prescribed a subcutaneous (SC) biological drug. A printed survey was handed to 1,000 patients with inflammatory rheumatic diseases treated with SC biological drug. The survey included closed questions about preferences regarding decision making and about patients' experience when they were prescribed an SC biological drug. Descriptive statistics were performed with stratification by patient profiles, using chi-square for comparisons between groups. A total of 592 surveys were received (response rate 59.2%, mean age 51.7 years, 57.6% women). Some 28.2% of patients reported preferring to take part in treatment selection, a percentage that was higher in younger patients, in those with higher academic degree and in those who search information in sources different to that of health care professionals. Over half of patients (56.3%) perceived that the rheumatologist considered their opinion when prescribing an SC biological drug, a percentage higher in younger people. Only in 40.8% of cases did the patients' preference match their perception of their participation in the process. No differences were observed by sex, disease or number of biologics. Patients with inflammatory rheumatic diseases want information about their treatments but mostly leave the prescription decision to the rheumatologist. Younger people, or those with higher academic degree, more often want to participate in the SDM. There are discrepancies between patient preferences and perceptions of this process.


Increased prevalence of luminal narrowing and stricturing identified by enterography in pediatric Crohn's disease patients with elevated granulocyte-macrophage colony stimulating factor autoantibodies.
Crohn's disease (CD) patients with elevated granulocyte-macrophage colony-stimulating factor autoantibodies (GM-CSF Ab) are more likely to develop stricturing behavior requiring surgery. Computed tomography or magnetic resonance enterography (CTE or MRE) may detect luminal narrowing (LN) before stricture development. The objective of this study was to determine whether CD patients with elevated GM-CSF Ab (≥1.6 μg/mL) have a higher prevalence of LN and stricturing on CTE or MRE. A single-center, cross-sectional study of 153 pediatric patients with CD and control subjects undergoing diagnostic CTE or MRE. Examinations were evaluated for disease activity using a novel scoring system and for the presence of LN, stricture, intra-abdominal abscess, or fistulae. Dichotomous outcomes were compared with respect to antibody status (high or low) using Fisher's exact test and logistic regression, whereas continuous outcomes were evaluated using unpaired t test. GM-CSF Ab were elevated in CD patients (n = 114) with a median (interquartile range) GM-CSF Ab level of 2.3 μg/mL (0.5-6.6 μg/mL) compared with 0.6 μg/mL (0.3-1.3 μg/mL) in healthy and disease control subjects (n = 39) (P = 0.001). Ileal disease location was more common in CD patients with high GM-CSF Ab (P < 0.001). LN increased from 39% in CD patients with low GM-CSF Ab to 71% in those with high levels (P = 0.004) and remained significantly associated with high GM-CSF Ab in a multivariate logistic model, which included age, gender, small bowel location, and duration of disease. Stricturing prevalence on CTE or MRE examination increased from 4% in CD patients with low GM-CSF Ab to 19% in those with high GM-CSF Ab (P = 0.03). Pediatric CD patients with high GM-CSF Ab levels have a higher prevalence of LN on CTE or MRE. Further study will be needed to determine whether medical therapy will reduce progression to stricturing behavior in these patients.


Chronic thrombotic microangiopathy secondary to antiphospholipid syndrome, presenting with severe hypertension and chronic renal impairment.
A 42-year-old woman was referred from a primary care centre for severe hypertension, stage 3A chronic kidney disease and proteinuria. This was associated with a significant obstetric history of pre-eclampsia during her previous two pregnancies. Secondary hypertension was suspected and autoimmune workup was positive for anticardiolipin IgG and lupus anticoagulant. A renal biopsy showed evidence of chronic thrombotic microangiopathy, with electron microscopy features suggestive of fibrillar glomerulonephritis. The diagnosis of antiphospholipid syndrome with antiphospholipid-associated nephropathy was made. She was started on anticoagulation with warfarin, and her hypertension was controlled with lisinopril and amlodipine with subsequent improvement in proteinuria. She remains on regular follow-up to monitor for possible development of malignancy or connective tissue disease.


[Cytomegaloviral inclusions detected in the seminal vesicle, ductus deferens and lungs in an autopsy case of lung cancer].
We report a case of cytomegalovirus infection of the seminal vesicle and ductus deferens in a 32-year-old Japanese man with papillary adenocarcinoma of the lung. Although the lungs are usually a target organ of cytomegalovirus infection, most organs can be involved. However, the male reproductive system has rarely been reported infected with the virus. H.E. sections of our case showed cytomegaloviral inclusions in many ductal epithelia of the seminal vesicle and ductus deferens as well as macrophages of the lungs. Immunohistochemistry using monoclonal antibody to cytomegalovirus disclosed viral antigenicity in these infected cells. Electron microscopy recovered enlarged infected cells packed with viral nucleocapsids approximately 100 nm in size. These nucleocapsids were enveloped in the cytoplasm and consistent with the Herpesviridae family. To our knowledge, our case is the first report of cytomegalovirus infection of the seminal vesicle and ductus deferens in the English and Japanese literature.


In vitro and in vivo evaluation of novel biodegradable Mg-Ag-Y alloys for use as resorbable bone fixation implant.
Magnesium (Mg) alloy is gaining more interest because of its degradability and osteogenic potential. Still, it has some deficiencies, such as its rapid degradation rate, insufficient mechanical property. This research aimed to design a novel biodegradable Mg-argentum (Ag)-yttrium (Y) alloy, and Y was added to improve degradable and mechanical property. Mg-Ag-Y alloys were characterized for mechanical features, practicabilities in vitro and in vivo. The mechanical features results shown that this novel component was similar to native bone tissue in elastic moduli, tensile, and compressive stress. Then mesenchymal stem cells (MSCs) were seeded in alloys to assess cell toxicity in vitro. The results showed that its aqueous extract was suitable for MSCs adhesion and proliferation. Then the alloy was evaluated for biomedical applications in nonfractured distal femora of Sprague Dawley rats for 6 weeks, compared with those of pure-Mg and stainless steel groups. All rats survived, and hematological and histological evaluation showed no abnormal physiology 6 weeks postimplantation, and measurements of serum Mg2+ concentration were within normal levels. X-ray scanning, microcomputed tomography, and histological examinations were performed to evaluate the degradability and osteogenic potential. The results indicated that the degradation rate of alloy was 0.91 mm per year, (range 0.77-1.22 mm), and pure-Mg 1.80 mm per year (1.43-2.26 mm). The new bone quantity was 3.18 mm3 (1.46-4.44 mm3 ) in Mg-Ag-Y alloys group, 1.39 mm3 (0.54-2.32 mm3 ) in pure-Mg group, and none in stainless steel group. These promising results suggest potential clinical application of Mg-Ag-Y alloys for use as resorbable bone fixation implant. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2059-2069, 2018.


DDQ-mediated direct intramolecular-dehydrogenative-coupling (IDC): expeditious approach to the tetracyclic core of ergot alkaloids.
An efficient route to 2-oxindoles bearing an all-carbon quaternary center at the pseudobenzylic position has been developed via a DDQ-mediated Intramolecular-Dehydrogenative-Coupling (IDC). The methodology involves a one-pot C-alkylation of β-N-arylamido esters (7) concomitant with dehydrogenative-coupling in the presence of stoichiometric amount of DDQ. A tentative mechanistic route has been proposed for the oxidative coupling. The methodology provides a two-step entry to the ergoline structure of ergot alkaloids.


Research on Quality Evaluation of Product Interactive Aging Design Based on Kano Model.
At present, China's population aging presents the characteristics of large base, fast aging process, and old age, but the research and development of product aging design in China is relatively late, which brings additional pressure to the daily life of the elderly. In such an environment, higher requirements are put forward for product aging design and service provision. Only products or services that timely meet the personalized and diversified needs of different customers can attract customers and improve customer satisfaction. How to design aging products with satisfactory appearance and humanized function is the focus of current research. Based on the product quality division of Kano model, this paper summarizes the domestic mainstream products and their functions. The designed questionnaire data are summarized; reliability and validity analysis, as well as descriptive statistical analysis, is performed on this basis for the constructed product service quality evaluation system. The service quality indicators are divided into three categories according to the Kano model: overall one-dimensional quality, charm quality, and necessary quality.


TCR vbeta usage of TSH receptor-specific CD4+ T cells in Graves' disease patients and healthy humans.
Healthy humans have CD4+ T cells specific for self-components. Since autoreactive T cells in autoimmune patients may use a limited number of TCR V-region genes, we investigated here whether this also occurs for the potentially autoreactive CD4+ cells present in healthy persons. We studied CD4+ cells specific for human TSH receptor (TSHr) sequences, that are present with high frequency in healthy subjects and, as expected, in Graves' disease (GD) patients. We used short-term CD4+ cell lines propagated from four GD patients and five healthy subjects by cycles of stimulation with a pool of overlapping synthetic peptides corresponding to the putative extracellular parts of the TSHr sequence. The lines recognized the pool of TSHr peptides specifically and vigorously. Their epitope repertoire had been characterized previously: each line recognized one or a few TSHr peptides, different for each subject. We determined their TCR Vbeta usage by a semi-quantitative reverse transcriptase PCR assay, using primers specific for each known human Vbeta region family, in conjunction with a constant region primer. Six lines preferentially used one Vbeta family (42-94%), different for each line. In all lines, three or less Vbeta families accounted for approximately 60% or more of the Vbeta usage. Different Vbeta regions were used by each subject. There was no obvious difference between the Vbeta usage of the lines from GD patients and healthy controls. These results suggest that a limited pool of potentially autoreactive T cells survives clonal deletion. The pathogenic CD4+ cells involved in autoimmune diseases are likely recruited from that pool, since they have similar characteristics of epitope and TCR repertoire as the CD4+ cells specific for the same autoantigen in healthy subjects.


Deletion of a malaria invasion gene reduces death and anemia, in model hosts.
Malaria parasites induce complex cellular and clinical phenotypes, including anemia, cerebral malaria and death in a wide range of mammalian hosts. Host genes and parasite 'toxins' have been implicated in malarial disease, but the contribution of parasite genes remains to be fully defined. Here we assess disease in BALB/c mice and Wistar rats infected by the rodent malaria parasite Plasmodium berghei with a gene knock out for merozoite surface protein (MSP) 7. MSP7 is not essential for infection but in P. falciparum, it enhances erythrocyte invasion by 20%. In vivo, as compared to wild type, the P. berghei Δmsp7 mutant is associated with an abrogation of death and a decrease from 3% to 2% in peak, circulating parasitemia. The Δmsp7 mutant is also associated with less anemia and modest increase in the size of follicles in the spleen. Together these data show that deletion of a single parasite invasion ligand modulates blood stage disease, as measured by death and anemia. This work is the first to assess the contribution of a gene present in all plasmodial species in severe disease.


Formation of thiosulfate from sulfite by Desulfovibrio vulgaris.
Crude extracts of Desulfovibrio vulgaris reduced sulfite to sulfide. Ammonium sulfate fractionation of crude extracts separated a thiosulfate-forming system from sulfite- and thiosulfate-reductase activities. Further purification by sucrose density centrifugation separated the thiosulfate-forming system into two components, both of which were required for the reaction. In addition to these two components, cytochrome c(3), ferredoxin, and hydrogenase were required to form thiosulfate from sulfite. By absorption spectra and from the effect of pH and substrate concentration, the ionic species acting as the substrate for thiosulfate-formation was concluded to be bisulfite.


Anti-termination by SIV Tat requires flexibility of the nascent TAR structure.
Substitution of the SIVmac239 promoter/enhancer by the strong EF1alpha promoter results in a severe replication defect due to a failure to respond to Tat. Revertant viruses with minimal promoter sequences (two Sp1 sites and a TATA box) were obtained that had fully restored their replicative potential. Comparison of the different LTRs indicated that structural alterations in the TAR stem due to a 31bp exon of the EF1alpha promoter rather than the mere presence of transcription factor binding sites within U3 were responsible for the attenuation. Structural models based on genuine RNA sequences combined with a refined algorithm to calculate the probability of the looping-mediated interaction between protein complexes bound to nucleic acid polymers indicated that the local concentration of TAR-bound Tat close to the RNA polymerase II complex was reduced more than 100-fold for the mutant as compared to SIVmac239. These results show that HIV/SIV replication requires only a minimal set of cis-acting elements in the promoter and suggest a hitherto unrecognised requirement of flexibility for the nascent TAR structure to allow anti-termination by Tat.


Differences in the nonverbal requests of great apes and human infants.
This study investigated how great apes and human infants use imperative pointing to request objects. In a series of three experiments (infants, N = 44; apes, N = 12), subjects were given the opportunity to either point to a desired object from a distance or else to approach closer and request it proximally. The apes always approached close to the object, signaling their request through instrumental actions. In contrast, the infants quite often stayed at a distance, directing the experimenters' attention to the desired object through index-finger pointing, even when the object was in the open and they could obtain it by themselves. Findings distinguish 12-month-olds' imperative pointing from ontogenetic and phylogenetic earlier forms of ritualized reaching.


Choroid plexus macrophages proliferate and release toxic factors in response to feline immunodeficiency virus.
Recent observations have suggested that lentiviruses stimulate the proliferation and activation of microglia. A similar effect within the dense macrophage population of the choroid plexus could have significant implications for trafficking of virus and inflammatory cells into the brain. To explore this possibility, we cultured fetal feline macrophages and examined their response to feline immunodeficiency virus (FIV) or the T-cell-derived protein, recombinant human CD40-ligand trimer (rhuCD40-L). The rhCD40-L was the most potent stimulus for macrophage proliferation, often inducing a dramatic increase in macrophage density. Exposure to FIV resulted in a small increase in the number of macrophages and macrophage nuclei labeled with bromodeoxyuridine. The increase in macrophage density after FIV infection also correlated with an increase in neurotoxic activity of the macrophage-conditioned medium. Starting at 16-18 weeks postinfection, well after the peak of viremia, a similar toxic activity was detected in cerebrospinal fluid (CSF) from FIV-infected cats. Toxicity in the CSF increased over time and was paralleled by strong CD18 staining of macrophages/microglia in the choroid plexus and adjacent parenchyma. These results suggest that lentiviral infection of the choroid plexus can induce a toxic inflammatory response that is fueled by local macrophage proliferation. Together with the observation of increasing toxic activity in the CSF and increased CD18 staining in vivo, these observations suggest that choroid plexus macrophages may contribute to an inflammatory cascade in the brain that progresses independently of systemic and CSF viral load.


Oropharyngeal stick injury in a Bengal cat.
A 16 month old cat presented with a history of acute onset oral pain and hypersalivation. Oral examination revealed a wooden stick that protruded from the right sublingual region. Lateral cervical radiography showed retro pharyngeal gas lucencies. An 11 cm wooden stick was removed per os and the resulting tract was endoscopically explored. There were no post-operative complications and the cat remains disease free four months after presentation. In contrast to dogs, where oropharyngeal stick injuries are an uncommon albeit well recognised condition, there have been no previous case reports of oropharyngeal stick injuries in the cat. This case report describes the presentation, diagnosis and treatment of an oropharyngeal stick injury in a cat.


Does the AAMC's Definition of "Underrepresented in Medicine" Promote Justice and Inclusivity?
In 2003, the Association of American Medical Colleges reframed the concept underrepresented minorities as underrepresented in medicine (URiM), which defines representation in medicine relative to representation in the US population. Schools are permitted to construct URiM definitions, suggesting the importance of regarding them as fluid works in progress as US demographics evolve. Where medical school admissions processes consider applicants' backgrounds and experiences of identity minoritization to be valuable, progress toward inclusive representation has been made. This article considers whether school-based URiM definitions are ethically sufficient and canvasses possible next steps in realizing equitable representation in medical education.


Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins.
A two-hybrid protein interaction screen was used to isolate cDNAs encoding human proteins that can interact with human CDK2 in yeast. A new member of the retinoblastoma susceptibility gene family, Rbr-2 (Rb-related), was obtained. The sequence of the Rbr-2 protein shares approximately 50% identify with p107 and homology to Rb within the pocket domain. Several lines of evidence indicate that Rbr-2 is the adenovirus E1A-associated p130. Like Rb and p107, p130Rbr-2 can bind to viral oncoproteins, SV40 large T antigen, and adenovirus E1A through its pocket domain. Although p130Rbr-2 does not bind to CDK2 in vitro, it can interact with cyclins, with a clear preference for D-type cyclins. Because both CDK2 and p130Rbr-2 show affinity for cyclins, we suggest that p130Rbr-2 and CDK2 interacted through a yeast-derived cyclin bridge in the two-hybrid screen. The gene encoding p130Rbr-2 mapped to 16q13, a region of frequent genomic alteration in human tumors.


Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols.
Master protocols, classified as basket trials, umbrella trials, and platform trials, are novel designs that investigate multiple hypotheses through concurrent sub-studies (e.g., multiple treatments or populations or that allow adding/removing arms during the trial), offering enhanced efficiency and a more ethical approach to trial evaluation. Despite the many advantages of these designs, they are infrequently used. We conducted a landscape analysis of master protocols using a systematic literature search to determine what trials have been conducted and proposed for an overall goal of improving the literacy in this emerging concept. On July 8, 2019, English-language studies were identified from MEDLINE, EMBASE, and CENTRAL databases and hand searches of published reviews and registries. We identified 83 master protocols (49 basket, 18 umbrella, and 16 platform trials). The number of master protocols has increased rapidly over the last five years. Most have been conducted in the US (n = 44/83) and investigated experimental drugs (n = 82/83) in the field of oncology (n = 76/83). The majority of basket trials were exploratory (i.e., phase I/II; n = 47/49) and not randomized (n = 44/49), and more than half (n = 28/48) investigated only a single intervention. The median sample size of basket trials was 205 participants (interquartile range, Q3-Q1 [IQR]: 500-90 = 410), and the median study duration was 22.3 (IQR: 74.1-42.9 = 31.1) months. Similar to basket trials, most umbrella trials were exploratory (n = 16/18), but the use of randomization was more common (n = 8/18). The median sample size of umbrella trials was 346 participants (IQR: 565-252 = 313), and the median study duration was 60.9 (IQR: 81.3-46.9 = 34.4) months. The median number of interventions investigated in umbrella trials was 5 (IQR: 6-4 = 2). The majority of platform trials were randomized (n = 15/16), and phase III investigation (n = 7/15; one did not report information on phase) was more common in platform trials with four of them using seamless II/III design. The median sample size was 892 (IQR: 1835-255 = 1580), and the median study duration was 58.9 (IQR: 101.3-36.9 = 64.4) months. We anticipate that the number of master protocols will continue to increase at a rapid pace over the upcoming decades. More efforts to improve awareness and training are needed to apply these innovative trial design methods to fields outside of oncology.


Animated video consultation for reducing pre-operative anxiety in dermatologic surgery.
Pre-operative anxiety is common in patients undergoing dermatologic surgery. This pilot study aimed to evaluate whether the addition of an animated educational video to conventional in-person surgery consultation helps to reduce pre-operative anxiety related to anesthesia, surgery, wound care, and post-operative pain in patients undergoing outpatient dermatologic surgery. Patients awaiting dermatologic surgery were randomized into groups with conventional consultation, or video with consultation prior to undergoing their procedure. The conventional consultation group received conventional consultation with the surgeon, whereas the video with consultation group received conventional consultation and a two-minute-long animated educational video. Intra- and inter-individual score differences were assessed based on baseline and subsequent surveys. Although not statistically significant, video with consultation group anxiety scores were lower than conventional consultation group across all categories. After crossing over, conventional consultation group patients reported statistically significant improvement in anxiety related to all areas except wound care, in which anxiety did not change significantly, although a trend toward reduced anxiety was seen. Animated educational videos during surgical consultation can reduce pre-operative anxiety related to anesthesia, surgery, and post-operative pain. Future studies should explore its benefit to clinical outcomes and overall surgical experience.


Modification of the existing maximum residue level for deltamethrin in carobs/Saint John's breads.
In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Bayer SAS - Crop Science Division submitted a request to the competent national authority in Spain to modify the existing maximum residue level (MRL) for the active substance deltamethrin in carobs/Saint John's breads. The data submitted in support of the request were found to suffice to derive an MRL proposal for carobs. An adequate analytical method for enforcement is available to control the residues of deltamethrin in the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results using the PRIMo rev. 3.1 model, EFSA concluded that the short-term consumer exposure for the intended post-harvest use on carobs did not exceed the toxicological reference value. The long-term intake of residues of deltamethrin indicated a consumer risk. Although residues in carobs are minor contributors to the overall chronic consumer exposure, a risk management consideration is required to decide whether the MRL proposal for carobs is acceptable. The risk assessment shall be regarded as indicative and affected by non-standard uncertainties.


Instrumentation and Motivations for Organised Cycling: The Development of the Cyclist Motivation Instrument (CMI).
'Serious leisure' cycling has developed as a reinterpretation of the traditional form of the sport. This short term, informal, unstructured and unconventional conceptualisation represents a challenge to participant numbers in the mainstream sport. The purpose of this study was twofold: (i) to ascertain the cultural, subcultural and ecological factors of participation in this new conceptualised form enabling clubs, associations and governments to a deeper understanding about participants practices and (ii) as an ongoing validation to previous qualitative work (see O'Connor and Brown, 2005). This study reports on the development and psychometric properties (principal components analysis, confirmatory factor analysis) of the Cyclists' Motivation Instrument. Four hundred and twenty two cyclists (371 males, 51 females) who were registered members of the state competitive cycling body completed a fifty-one item instrument. Five factors were identified: social, embodiment, self-presentation, exploring environments and physical health outcomes and these accounted for 47.2% of the variance. Factor alpha coefficients ranged from .63 to .88, overall scale reliability was .92, suggesting moderate to high reliability for each of the factors and the overall scale. Key pointsSerious leisure' cyclists' are fitness seeking enthusiasts that attach different meanings to the act of cycling and participate in different physical, social and natural environments in comparison to other cyclists.This study develops and validates a new tool, the Cyclists Motivation Instrument (CMI), and presents the initial psychometric properties (principal components analysis, confirmatory factor analysis).FIVE FACTORS WERE IDENTIFIED: social, embodiment, self-presentation, exploring environments and physical health outcomes.The scale demonstrates adequate reliability (total scale, α = 0.92) and validity.


A two-year longitudinal study of social support following amputation.
(1) To describe one aspect of social support, social integration, longitudinally for 2 years following lower limb amputation and (2) to explore the impact of social support on depression, pain interference, life satisfaction, mobility, and occupational functioning. Eighty-nine adults recruited from consecutive admissions to an orthopaedic surgery service completed telephone interviews 1, 6, 12 and 24 months following amputation surgery. Dependent variables included the Social Integration (SI) sub-scale of the Craig Handicap Assessment and Reporting Technique (CHART) and the Multidimensional Scale of Perceived Social Support (MSPSS). There was a high level of SI among most persons following lower limb amputations that was relatively unchanged in the 2 years following surgery. However, mean levels of SI were lower in this group compared to a sample without disabilities. MSPSS scores were highly variable, ranging from almost no support to the maximum amount of support. MSPSS was an important concurrent predictor of pain interference, life satisfaction, and mobility, controlling for demographic and amputation-related factors. Baseline MSPSS predicted mobility and occupational functioning 6 months post-amputation, controlling for demographic and amputation-related factors. Findings suggest that interventions aimed at improving the quality of social relationships after amputation may facilitate participation in activities.


Association between adjustment latitude and sickness presence - A panel study of Swedish employees.
This study is analyzing the unexpected reversed or lacking association between high adjustment latitude and sickness presence by examining whether it is due to confounding. Questionnaires were sent in 2004 and 2005 to a cohort of individuals aged 25-50 years, selected from the Statistics Sweden's register of the Swedish population. Information from 2397 individuals who answered both questionnaires was analyzed by the use of logistic regression analysis. The odds ratio for sickness presence among the individuals with a low adjustment latitude compared to those with high adjustment latitude was 1.7 (range: 1.4-2.2). This increased likelihood was almost entirely unaffected in the analysis of potential confounders. If the reversed association between adjustment latitude and sickness presence does not reflect confounding, it may be due to reporting bias, which may cause problems in research on sickness presence. We argue that more detailed studies are needed to explore the different sources of possible reporting problems.


Acidity and Acid-Sensing Ion Channels in the Normal and Alzheimer's Disease Brain.
Alzheimer's disease prevalence has reached epidemic proportion with very few treatment options, which are associated with a multitude of side effects. A potential avenue of research for new therapies are protons, and their associated receptor: acid-sensing ion channels (ASIC). Protons are often overlooked neurotransmitters, and proton-gated currents have been identified in the brain. Furthermore, ASICs have been determined to be crucial for proper brain function. While there is more work to be done, this review is intended to highlight protons as neurotransmitters and their role along with the role of ASICs within physiological functioning of the brain. We will also cover the pathophysiological associations between ASICs and modulators of ASICs. Finally, this review will sum up how the studies of protons, ASICs and their modulators may generate new therapeutic molecules for Alzheimer's disease and other neurodegenerative diseases.


Verbal communication of effect-sizes, possible comparators, and uncertainty of evidence in the Finnish clinical practice guidelines: Omitting effect-sizes and comparators without expressing much uncertainty.
Our aim was to investigate verbal representations of intervention effect-size, uncertainty of evidence, and possible intervention comparators in statements concerning effects of interventions in Finnish clinical practice guidelines. We selected 10 clinical practice guidelines on common diseases and risk factors published by The Finnish Medical Society Duodecim. All the statements that considered beneficial effects of interventions and that were graded with a level of evidence (levels A, high, to D, very low) were included in analyses. We assessed whether the statements verbally represented intervention effect-size, uncertainty of evidence or a possible comparator, and the reported outcome. Of 385 statements, verbal representation of beneficial effect-sizes occurred in 25 (6%) statements. Most (72%) statements indicated that intervention had a beneficial effect, but did not specify effect-size. Less than half (42%) of the statements represented uncertainty verbally. Comparisons to placebo or no-treatment were rare (3%) and 18% of the statements compared interventions to other treatments. Against instructions, a considerable part (35%) of statements with B-level evidence did not represent uncertainty. Communicating beneficial intervention effects, effect-sizes, possible comparators, and uncertainty of evidence require much broader attention in the clinical practice guideline context.