Nursing-related determinants of 30-day mortality for hospitalized patients.
The purpose of this study was to further our understanding of the effects of nursing-related hospital variables on 30-day mortality rates for hospitalized patients. A retrospective design was used to test the proposed 30-Day Mortality Model. The sample consisted of 75 acute-care hospitals in the province of Ontario, Canada. To develop hospital mortality rates, 46,941 patients discharged from these hospitals who had a most responsible diagnosis of acute myocardial infarction, stroke, pneumonia, or septicemia were included. To develop hospital-level nursing predictor variables, 3,998 responses to the Ontario Registered Nurse Survey of Hospital Characteristics were also included. The findings support a relationship between lower 30-day mortality and 3 predictors: a richer registered nurse skill mix, more years of experience on the clinical unit, and reported larger number of shifts missed. These findings can be used to predict the effects of hospital changes in nursing skill mix and years of RN experience on patient mortality.


The use of consultation in psychological practice: ethical, legal, and clinical considerations.
The importance of consulting with other professionals to maintain acceptable standards of care is well documented in many health care professions. However, evidence indicates that many psychologists fail to utilize consultation when needed, and that consultation use varies along dimensions such as the education and training of the consultee, the type of setting, number of years in practice, and proximity to available consultants. In this article, we review the research on the use of consultation by psychologists as well as other health care professionals. We discuss the clinical, ethical, and legal implications of seeking consultation as a professional psychologist. Finally, a detailed and practical model for the regular use of consultation is given to improve the routine use of consultation in clinical practice.


Evaluation of Effect of Antiepileptic Drugs on Serum Lipid Profile among Young Adults with Epilepsy in a Tertiary Care Hospital in Pondicherry.
Several studies have reported that commonly used antiepileptic drugs like phenytoin, and carbamazepine increase serum High Density Lipoproteins Cholesterol (HDL-C) levels, while some others documented no such effect. Further, some researchers also observed that valproic acid and other newer antiepileptic drugs like lamotrigine and levetiracetam has no influence on serum lipid profile. The present study was planned to assess and compare serum lipid profile of young adult patients on commonly used antiepileptic drugs (phenytoin, oxcarbazepine and valproic acid) and newer antiepileptic drug (levetiracetam) attending Neurology OPD of a tertiary care hospital in Puducherry, India compared to normal subjects. A prospective hospital based cross-sectional study was conducted in Tertiary care hospital. Epileptic patients attending Department of Neurology and taking antiepileptic drugs for last six months or more and on regular follow up; approximately 60 patients on commonly used antiepileptic drugs (20 on phenytoin, 20 on oxcarbazepine, 20 on valproic Acid) and 20 patients on newer antiepileptic drug (levetiracetam) was included in the study. Age and sex matching 80 controls were taken. Descriptive statistics explained using mean ± SD. Inferential statistics was used depending on the nature of variables. We used one-way-ANOVA and followed by independent t-test for comparison with control group and statistically significant was considered at p-value <0.05. We observed statistically significant high mean TC, HDL-C, LDL-C and TG levels in the group receiving phenytoin for more than six months when compared with control group. We observed statistically significant high mean TC, HDL-C and TG levels in the group receiving oxcarbazepine for more than six months when compared with control. However, no significant difference was observed in mean LDL-C levels when compared to control. We did not observe any statistically significant difference among mean TC, HDL-C, LDL-C and TG levels in the group receiving valproate. We did not observe any statistically significant difference among mean TC, HDL-C, LDL-C and TG levels in the group receiving levetiracetam. From the present study we can conclude that CYP enzyme inducer anti epileptic medicines like phenytoin and oxcarbazepine is strongly associated with increased levels of TC, LDL-C, HDL-C and TG where as valproate and levetiracetam showed no significant change. Therefore, the serum cholesterol level should be regularly monitored in patients undergoing therapy with inducer anti epileptic medicines.


Determination of complex dielectric functions at HfO(2)/Si interface by using STEM-VEELS.
The complex dielectric functions and refractive index of atomic layer deposited HfO(2) were determined by the line scan method of the valence electron energy loss spectrum (VEELS) in a scanning transmission electron microscope (STEM). The complex dielectric functions and dielectric constant of monoclinic HfO(2) were calculated by the density functional theory (DFT) method. The resulting two dielectric functions were relatively well matched. On the other hand, the refractive index of HfO(2) was measured as 2.18 by VEELS analysis and 2.1 by DFT calculation. The electronic structure of HfO(2) was revealed by the comparison of the inter-band transition strength, obtained by STEM-VEELS, with the density of states (DOS) calculated by DFT calculation.


Gender and the nurse practitioner role.
Many nurse practitioners are recognizing that some role development problems arise because they are women seeking more power and responsibility in a traditionally male-dominated world. Specific keys to reduce these pressures are given for the nurse practitioner.


Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India.
Primary immunodeficiency diseases (PID) are a clinically and immunologically heterogeneous group of disorders of immune system. Diagnosis of these disorders is often challenging and requires identification of underlying genetic defects, complemented by a comprehensive evaluation of immune system. Flow cytometry, with its advances in the last few decades, has emerged as an indispensable tool for enumeration as well as characterization of immune cells. Flow cytometric evaluation of the immune system not only provides clues to underlying genetic defects in certain PIDs and helps in functional validation of novel genetic defects, but is also useful in monitoring immune responses following specific therapies. India has witnessed significant progress in the field of flow cytometry as well as PID over last one decade. Currently, there are seven Federation of Primary Immunodeficiency Diseases (FPID) recognized centers across India, including two Indian Council of Medical research (ICMR) funded centers of excellence for diagnosis, and management of PIDs. These centers offer comprehensive care for PIDs including flow cytometry based evaluation. The key question which always remains is how one selects from the wide array of flow cytometry based tests available, and whether all these tests should be performed before or after the identification of genetic defects. This becomes crucial, especially when resources are limited and patients have to pay for the investigations. In this review, we will share some of our experiences based on evaluation of a large cohort of hemophagocytic lymphohistiocytosis, severe combined immunodeficiency, and chronic granulomatous disease, and the lessons learned for optimum use of this powerful technology for diagnosis of these disorders.


The distribution of cytochrome P-450-mediated drug oxidation and glutathione in periportal and perivenous rat hepatocytes after phenobarbital treatment.
The effect of phenobarbital pretreatment on acinar distribution of microsomal drug metabolizing enzymes was investigated by analysis of periportal (pp) and perivenous (pv) enriched rat hepatocytes isolated by collagenase gradient perfusion. In untreated animals the activities of cytochrome P-450, NADPH-cytochrome c reductase and microsomal ethanol oxidation were significantly higher in pv cells. Phenobarbital produced a 45% increase of the yielded microsomes related to the hepatocytic protein but did not change their relative distribution. The content of reduced glutathione (GSH) was lower in hepatocytes from the pv area. The GSH content was more than 20% increased after phenobarbital treatment in both subclasses of cells, but the distribution pattern remained unchanged. The higher activity of drug metabolizing enzymes in the pv area of untreated animals may account for the higher cytotoxicity of numerous drugs to the perivenous hepatocytes. A 3-day treatment with phenobarbital equalized the pp-pv difference by producing more induction of the periportal cytochrome P-450-mediated drug and ethanol oxidation capacities in microsomes derived from periportally enriched hepatocytes.


Climate Change and Otolaryngology-Head and Neck Surgery.
The COVID-19 pandemic has illustrated that global events can have a profound impact on our health systems. While the pandemic is unprecedented, it does underscore the need to prepare for future global health concerns. Climate change is a looming threat with significant consequences for otolaryngologists and our patients. In this commentary, we discuss the need to assess our preparedness for climate change as well as the importance of reflecting on our responsibility to minimize our footprint.


Early Nitrogenase Ancestors Encompassed Novel Active Site Diversity.
Ancestral sequence reconstruction (ASR) infers predicted ancestral states for sites within sequences and can constrain the functions and properties of ancestors of extant protein families. Here, we compare the likely sequences of inferred nitrogenase ancestors to extant nitrogenase sequence diversity. We show that the most-likely combinations of ancestral states for key substrate channel residues are not represented in extant sequence space, and rarely found within a more broadly defined physiochemical space-supporting that the earliest ancestors of extant nitrogenases likely had alternative substrate channel composition. These differences may indicate differing environmental selection pressures acting on nitrogenase substrate specificity in ancient environments. These results highlight ASR's potential as an in silico tool for developing hypotheses about ancestral enzyme functions, as well as improving hypothesis testing through more targeted in vitro and in vivo experiments.


Evolving Interactions and Emergent Functions in Microbial Consortia.
Microbial communities are constantly challenged with environmental stressors, such as antimicrobials, pollutants, and global warming. How do they respond to these changes? Answering this question is crucial given that microbial communities perform essential functions for life on Earth. Our research aims to understand and predict communities' responses to change by addressing the following questions. (i) How do eco-evolutionary feedbacks influence microbial community dynamics? (ii) How do multiple interacting species in a microbial community alter evolutionary processes? (iii) To what extent do microbial communities respond to change by ecological versus evolutionary processes? To answer these questions, we use microbial communities of reduced complexity coupled with experimental evolution, genome sequencing, and mathematical modeling. The overall expectation from this integrative research approach is to generate general concepts that extend beyond specific bacterial species and provide fundamental insights into the consequences of evolution on the functioning of whole microbial communities.


Post-translational Modifications in Regulation of Chloroplast Function: Recent Advances.
Post-translational modifications (PTMs) of proteins enable fast modulation of protein function in response to metabolic and environmental changes. Phosphorylation is known to play a major role in regulating distribution of light energy between the Photosystems (PS) I and II (state transitions) and in PSII repair cycle. In addition, thioredoxin-mediated redox regulation of Calvin cycle enzymes has been shown to determine the efficiency of carbon assimilation. Besides these well characterized modifications, recent methodological progress has enabled identification of numerous other types of PTMs in various plant compartments, including chloroplasts. To date, at least N-terminal and Lys acetylation, Lys methylation, Tyr nitration and S-nitrosylation, glutathionylation, sumoylation and glycosylation of chloroplast proteins have been described. These modifications impact DNA replication, control transcriptional efficiency, regulate translational machinery and affect metabolic activities within the chloroplast. Moreover, light reactions of photosynthesis as well as carbon assimilation are regulated at multiple levels by a number of PTMs. It is likely that future studies will reveal new metabolic pathways to be regulated by PTMs as well as detailed molecular mechanisms of PTM-mediated regulation.


Clinical features and management of chronic thromboembolic pulmonary hypertension in Thai.
The incidence and clinical features of chronic thromboembolic pulmonary hypertension (CTEPH) in Thailand are unknown. This may be due to the difficulties in diagnosis, poor disease recognition and non-specific presenting symptoms and signs. With the new revolution of diagnostic tools and advanced knowledge about this condition, CTEPH is now discovered much more often. Retrospective cross-sectional study. To evaluate common risk factors, symptoms, signs, commonly used investigations, treatment and results of treatment in Thai patients with CTEPH. All patients with confirmed CTEPH diagnoses were selected for analysis in this study. We evaluated characteristics of patients with CTEPH at Siriraj hospital. All CTEPH patients' data included demographics, symptoms, signs, investigations, treatments, outcome and risk factors such as malignancy; previous deep vein thrombosis, immobilization, and congenital thrombophilia were recorded. The descriptive statistics were used in this study. Categorical data and continuous data presented in term of percent and mean with standard deviation respectively. fourteen patients had confirmed diagnoses of CTEPH, five patients were male and 9 were female. The age of patients varied from 28 to 79-years-old. Mean age was 55-years-old. The most common presenting symptoms and signs were dyspnea (100%), followed by leg edema (78.6%), tachypnea (71.4%) and accentuation of pulmonic component of second heart sound (loud P2) (57.1%). At the time of diagnosis, four out of 14 patients were in NYHA class II, ten were in NYHA class III, and none of them was in NYHA class IV. Idiopathic CTEPH was found in 54.1% of patients. Congenital and acquired thrombophilia were the frequent risk factors found in our series. The most frequent radiographic abnormalities included enlarged pulmonary trunk, right atrium/right ventricle (RA/RV) dilatation, and cardiomegaly followed by prominent pulmonary trunk. Echocardiography findings were elevated right ventricular systolic pressure (RVSP); ranges varied from 60 mmHg to 137 mmHg (mean was 107.48 mmHg). The most common finding of arterial blood gas in APE patients was respiratory alkalosis with hypoxemia. The most frequent diagnostic tool used was ventilation-perfusion lung scan. Treatment of CTEPH patients was by anticoagulant, pulmonary thromboendarterectomy and inferior vena cava filter insertion. The success rate of surgical thromboendarterectomy in our institute was about 80%. Characteristics of CTEPH patients are unique and different from acute pulmonary embolism in aspects of clinical presentations, risk factors, investigation, common findings, treatment and outcome.


Safety and tolerability of serelaxin, a recombinant human relaxin-2 in development for the treatment of acute heart failure, in healthy Japanese volunteers and a comparison of pharmacokinetics and pharmacodynamics in healthy Japanese and Caucasian populations.
Serelaxin, a recombinant form of the human relaxin-2 hormone, is currently under clinical investigation for treatment of acute heart failure. This double-blind, placebo-controlled, dose-ranging study investigated the effect of Japanese ethnicity on the pharmacokinetics (PK), pharmacodynamics (PD), and safety and tolerability of serelaxin. Japanese healthy subjects (n = 32) received 10, 30, or 100 µg/kg/day of serelaxin, or placebo, administered as a 48-hour intravenous infusion. A Caucasian cohort (n = 8) receiving 30 µg/kg/day open-label serelaxin was included for comparison. In all subjects, serum serelaxin concentrations increased rapidly after the start of infusion, approached steady state as early as 4 hours, and declined rapidly upon treatment cessation. Serum exposure to serelaxin increased with increasing doses. Statistical dose proportionality was shown for AUC(inf) over the entire dose range. A significant increase in estimated glomerular filtration rate from baseline to Day 2 (30 and 100 µg/kg/day) and to Day 3 (10 and 100 µg/kg/day) was observed compared with placebo. Serelaxin was well tolerated by all subjects. In conclusion, PK, PD, and safety profiles of serelaxin were generally comparable between Japanese and Caucasian subjects, suggesting that no dose adjustment will be required in Japanese subjects during routine clinical use of this agent.


Urban Area Detection in Very High Resolution Remote Sensing Images Using Deep Convolutional Neural Networks.
Detecting urban areas from very high resolution (VHR) remote sensing images plays an important role in the field of Earth observation. The recently-developed deep convolutional neural networks (DCNNs), which can extract rich features from training data automatically, have achieved outstanding performance on many image classification databases. Motivated by this fact, we propose a new urban area detection method based on DCNNs in this paper. The proposed method mainly includes three steps: (i) a visual dictionary is obtained based on the deep features extracted by pre-trained DCNNs; (ii) urban words are learned from labeled images; (iii) the urban regions are detected in a new image based on the nearest dictionary word criterion. The qualitative and quantitative experiments on different datasets demonstrate that the proposed method can obtain a remarkable overall accuracy (OA) and kappa coefficient. Moreover, it can also strike a good balance between the true positive rate (TPR) and false positive rate (FPR).


Guarana powder polysaccharides: characterisation and evaluation of the antioxidant activity of a pectic fraction.
Guarana is a fruit from the Amazon whose seeds are used to produce guarana powder. Guarana powder is consumed by the population mainly for its stimulant activity. It has been shown that guarana seeds contain low-molar-mass compounds; however, no data have been reported concerning the polysaccharides. In this work, the polysaccharides present in guarana powder were investigated. A pectic fraction and a xylan were isolated and characterised. Antioxidant activity tests were performed with a methanolic extract and the pectic fraction at concentrations of 0.1-10 mg/ml. The methanolic extract exhibited a strong capacity for scavenging DPPH radicals (90.9% at 10 mg/ml). At the same concentration, the polysaccharide showed a DPPH(·)-scavenging activity of 68.4%. At a higher concentration, the methanolic extract and the polysaccharide exhibited similar hydroxyl radical-scavenging effects (~70%). The results suggest that the polysaccharides present in guarana can contribute to the possible biological effects of guarana powder.


Dermal oncogenicity bioassays of acrylic acid, ethyl acrylate, and butyl acrylate.
Male C3H/HeJ mice (40 per group) were treated with 25-microliter applications of undiluted ethyl acrylate, 1% acrylic acid, or 1% butyl acrylate on the dorsal skin 3 times weekly for their lifetime. A negative control group received acetone (diluent) only, and a positive control group received 0.1% 3-methylcholanthrene (MC). No epidermal tumors were observed in the animals that received any of the three test substances. In the positive control group, 39 animals had skin tumors, including 33 with confirmed squamous-cell carcinomas. Nonneoplastic skin changes such as dermatitis, dermal fibrosis, epidermal necrosis, and hyperkeratosis were observed in several mice that received ethyl acrylate. No statistically significant effects on survival were seen. Therefore, there was no evidence for local carcinogenic activity of acrylic acid, ethyl acrylate, or butyl acrylate under the conditions of these studies.


Prevalence of Congenital Hypothyroidism in Northern Border Region of Kingdom of Saudi Arabia.
This retrospective study was done to assess the prevalence of congenital hypothyroidism among children born in Arar city, Kingdom of Saudi Arabia during years 2008 to 2014. Data were collected from newborns registry in Central hospital. The prevalence of congenital hypothyroidism was 2.6 per 10,000 live births with no gender difference.


Modulation of dendritic cell differentiation and maturation by decoy receptor 3.
Decoy receptor 3 (DcR3), a soluble receptor belonging to the TNFR superfamily, is a receptor for both Fas ligand (FasL) and LIGHT. It has been demonstrated that DcR3 is up-regulated in lung and colon cancers, thus promoting tumor growth by neutralizing the cytotoxic effects of FasL and LIGHT. In this study, we found that DcR3.Fc profoundly modulated dendritic cell differentiation and maturation from CD14(+) monocytes, including the up-regulation of CD86/B7.2, and the down-regulation of CD40, CD54/ICAM-1, CD80/B7.1, CD1a, and HLA-DR. Moreover, DcR3-treated dendritic cells suppressed CD4(+) T cell proliferation in an allogeneic MLR and up-regulated IL-4 secretion of CD4(+)CD45RA(+) T cells. This suggests that DcR3.Fc may act not only as a decoy receptor to FasL and LIGHT, but also as an effector molecule to skew T cell response to the Th2 phenotype.


Quantitative measurement of lipoprotein particles containing both apolipoprotein AIV and apolipoprotein B in human plasma by a noncompetitive ELISA.
A reliable method for plasma would be useful to investigate the role of apolipoprotein (apo) AIV when associated with apo B-containing or triglyceride-rich lipoproteins. We used a sandwich ELISA to quantify lipoprotein B:AIV particles (Lp B:AIVf; lipoproteins containing at least apo B and apo AIV) in plasma. The method used microtiter plates coated with purified anti-apo B immunoglobulins that selectively retained apo B-containing particles. Lipoproteins containing both apo B and apo AIV were distinguished from those containing only apo B by use of a peroxidase-labeled anti-apo AIV antibody. These subspecies were revealed by ABTS reagent and further quantified by spectrophotometry. Results were expressed in mg/L apo AIV associated with apo B. This method was applied to samples with different cholesterol and triglyceride concentrations. The developed sandwich ELISA method identified and quantified Lp B:AIVf in plasma samples. Within- and between-run CVs were approximately 10%, and analytical recoveries were 95-107%. Results were not significantly influenced by addition of triglycerides or by storage at -20 degrees C (up to 9 months). Under these conditions, plasma Lp B:AIVf concentrations were statistically higher in hypercholesterolemic and mixed hyperlipidemic individuals (53 +/- 13 mg/L; P <0.001 and 70 +/- 18 mg/L; P <0.001, respectively) than in normolipidemic individuals (43 +/- 12 mg/L). Lp B:AIVf concentration appeared to be well correlated with total cholesterol, triglycerides, LDL-cholesterol, and apo B. These results were in contrast to total apo AIV, which was not different between dyslipidemic and normolipidemic individuals. The developed ELISA method for Lp B:AIVf in plasma combines specificity, reliability, and speed. The increase in Lp B:AIVf concentrations in various dyslipidemic states, together with a lack of change in total apo AIV concentrations, suggests a redistribution of apo AIV toward apo B-containing lipoproteins when these lipoproteins accumulate.


Phorbol myristate acetate stimulated NBT test: a simple method suitable for antenatal diagnosis of chronic granulomatous disease.
When endotoxin was compared with phorbol myristate acetate (PMA) for stimulation of phagocytes in the nitroblue tetrazolium (NBT) test, both methods discriminated between affected patients with X-linked chronic granulomatous disease (CGD) and controls, but only the PMA NBT test distinguished female carriers of CGD. Endotoxin provided no stimulation of normal fetal blood whereas PMA was an effective stimulator. Our results indicate the superiority of the PMA NBT test for diagnosis of patients and carriers of CGD and should allow accurate antenatal diagnosis of the disease.


Olanzapine as an add-on, pre-operative anti-emetic drug for postoperative nausea or vomiting: a randomised controlled trial.
Postoperative nausea or vomiting occurs in up to 40% in patients with multiple risk factors, despite prophylaxis. Olanzapine is an antipsychotic drug that is used to prevent nausea and vomiting in palliative care and to treat chemotherapy-induced nausea and vomiting. This study aimed to examine whether pre-operative olanzapine, as a prophylactic anti-emetic added to intra-operative dexamethasone, ondansetron and total intravenous anaesthesia, reduced the incidence of postoperative nausea or vomiting. We performed a multiply-blinded randomised controlled trial in patients aged 18-60 years with cancer at high risk of postoperative nausea or vomiting (three or four risk factors according to the Apfel criteria) plus a previous history of chemotherapy-induced nausea and vomiting. Patients were allocated at random to receive 10 mg olanzapine or placebo orally 1 h before surgery in addition to a two-drug regimen (dexamethasone and ondansetron) and propofol anaesthesia to prevent postoperative nausea or vomiting. The primary outcome was the incidence of postoperative nausea or vomiting in the first 24 h after surgery. In total, 100 patients were enrolled; 47 in the olanzapine group and 49 in the control group completed the study. The baseline characteristics of the groups were similar. The incidence of postoperative nausea or vomiting in the first 24 h after surgery was lower in the olanzapine group (12/47, 26%) than in the control group (31/49, 63%) (p = 0.008, RR 0.40 (95%CI 0.21-0.79)). Adding pre-operative oral olanzapine to intra-operative dexamethasone and ondansetron was highly effective in reducing the risk of postoperative nausea or vomiting in the first 24 hours after surgery in patients with a previous history of chemotherapy-induced nausea and vomiting and at least three Apfel risk factors for postoperative nausea or vomiting.


Review article: platelets in inflammatory bowel disease--pathogenetic role and therapeutic implications.
An elevated platelet count is well recognized as a marker of inflammatory bowel disease activity. There is an increased incidence of systemic thromboembolism in this disease. Recent work indicates that platelets exhibit several proinflammatory properties including release of inflammatory mediators, and recruitment, chemotaxis and modulation of the activity of other inflammatory cells. Furthermore there is evidence that microvascular thrombosis and a procoagulant state may play a role in the pathogenesis of inflammatory bowel disease. These observations prompted recent studies of platelet activity in inflammatory bowel disease, which indicate enhanced platelet aggregation in vivo and in vitro, and increased platelet activation as measured by increased release of intracellular proteins into plasma and expression of platelet surface markers, including P-selectin and GP53. These abnormalities could contribute to the pathogenesis of inflammatory bowel disease by enhancing inflammation and promoting microinfarction. Aminosalicylates reduce platelet activity although they also have many other additional properties to explain their efficacy in inflammatory bowel disease. There are however several specific antiplatelet drugs now available which may provide new therapeutic possibilities in the management of this disease.


Quantitative studies on the reactions of psoriatic epidermis to treatment.
An image-analysing computer has been used to assess the changes in the length of the dermo-epidermal junction and in the epidermal area in histological sections from psoriatic plaques in groups of patients undergoing various treatment regimes. The changes in these two features closely parallel one another, and measurement of the length of the dermo-epidermal junction may be a relatively simple quantitative method of gauging the course of the disease. Topical fluocinolone acetonide produced a greater improvement than did dithranol or coal tar. Variation in the number of epidermal mitotic figures was not a reliable guide to improvement or otherwise in the psoriatic lesion and reappearance of the granular layer can occur independently of any decrease in mitosis.


In Vitro Anti-Malassezia Activity of Castanea crenata Shell and Oil-Soluble Glycyrrhiza Extracts.
A new shampoo with anti-Malassezia properties obtained from various plants is required to provide seborrheic dermatitis patients with a wider range of treatment options. The aim of this study was to obtain in vitro susceptibility profiles of Malassezia restricta and M. globosa, the most important pathogenic organisms in the development of seborrheic dermatitis, to the plant extracts used in commercial anti-dandruff shampoos. Minimal inhibitory concentrations (MICs) were determined for eight candidate plant extracts and two plant-derived natural products diluted with Leeming and Notman medium to final concentrations of 0.016 to 1 mg/ml. Castanea crenata shell, Camellia sinensis leaf, and oil-soluble Glycyrrhiza extracts presented relatively low MIC values (≤0.5 mg/ml) against both strains. The C. crenata shell and oil-soluble Glycyrrhiza extracts demonstrated especially high anti-Malassezia activity, suggesting their potential use in the treatment of seborrheic dermatitis. The extracts also showed fungistatic activity against other common facultative pathogenic yeasts, Cryptococcus and Candida. C. crenata shell and oil-soluble Glycyrrhiza extracts could potentially be used as active ingredients in anti-seborrheic and anti-dandruff shampoo formulations. They could be helpful for repeated treatments and regular prophylaxis of scalp seborrheic dermatitis.


Bioelectrical impedance measures in different position and vs dual-energy X-ray absorptiometry (DXA).
Bioelectrical impedance analysis (BIA) is a safe, low-cost, non-invasive, rapid method for the assessment of body composition. It has therefore a great potential to be employed for epidemiological and clinical studies. However, many devices are available to estimate total body water (TBW), fat-free mass (FFM) and fat mass (FM) by bioelectrical impedance measurements. Moreover, bipedal devices allowing measurements in the only standing position are recently developed. They are easy and practical to use without operator, so a large diffusion can be forecasted in fields as sport and diet programs. Comparison of body composition estimation by a bipedal device with bioimpedance devices currently used, using dual-energy X-ray absorptiometry (DXA) as reference method. The study was performed on 18 healthy women volunteers, age 32.0+/-10.7 years divided in two groups at different levels of body fatness. A Xitron 4000 impedance analyser, a BIA-101 RJL System, and the bipedal device Tanita were used for comparison. The measurements were performed in standing and supine position for Xitron and RJL devices. DXA measurements were performed with a total body scanner DPX, Lunar. FM and FFM were not statistically different when measured with Xitron and RJL in comparison with DXA, while these variables were significantly different between Tanita and DXA measurements. No significant difference were found between measurements in the supine and standing position with the Xitron and RJL system. Our results suggest that FM and FFM evaluated by bipedal device Tanita are significantly different from FM and FFM measured by DXA in both normal and obese population.


The value of early third-trimester maternal serum alpha-fetoprotein determination.
The value of determination of maternal serum of alpha-fetoprotein (MSAFP) concentration in the second trimester is well established. In addition to open neural tube defects, pregnancies associated with elevated second-trimester MSAFP have been shown to be at increased risk for a variety of problems, including low birth weight, preterm delivery, and pregnancy-induced hypertension (PIH). We evaluated the potential usefulness of MSAFP in the early third trimester. MSAFP concentration was determined in over 200 women at the time of glucose screening. Results were analysed with regard to gestational age at sampling, maternal weight, race, diabetes, and presence of twins. MSAFP was twice as high in twin gestation, but not affected by race or the presence of diabetes. In contrast to levels in early gestation, third-trimester MSAFP does not appear to be predictive of preterm delivery, low birth weight, or PIH.


Posttreatment complications in pediatric cervical neuroblastoma: A retrospective case series at a tertiary cancer center.
Neuroblastomas rarely occur as primary tumors in the cervical region. Therefore, very little has been reported regarding treatment strategies, complications, and outcomes of these cervical neuroblastomas. The goal of this study is to review the presentation, management, and outcomes of all primary cervical pediatric neuroblastoma cases at a single tertiary care center. A retrospective cohort review of all neuroblastoma patients treated at a single center were performed. All patients with primary cervical neuroblastoma were reviewed for demographic information, tumor characteristics, treatment, and outcomes. Thirty (1.8%) patients were found to have undergone treatment for cervical neuroblastoma tumors diagnosed on average at 2.1 years old. Most presented with a swollen neck/palpable mass ± Horner's syndrome. Based on features including tumor staging, N-myc proto-oncogene protein (MYCN) amplification status, histology, most were deemed intermediate or high risk. Treatment strategies centered around chemotherapeutic regimens with surgery when possible as well as various adjuvant treatments including radiation therapy, immunotherapy, bone marrow transplant, and a neuroblastoma vaccine. Ten (33.3%) of patients experienced treatment-related complications and four (13.3%) died as a result of their disease progression. All four patients were high-risk patients, two of which had MYCN amplification. Cervical neuroblastomas generally have favorable outcomes. These tumors can be treated effectively with chemotherapy and surgical intervention with various adjuvant therapies. MYCN amplification and higher stage disease presentation contribute to worse outcomes.


Determination of anabolic steroids in muscle tissue by liquid chromatography-tandem mass spectrometry.
A specific and sensitive method based on liquid chromatography-tandem mass spectrometry using atmospheric pressure chemical ionization (LC-APCI-MS/MS) has been developed for the determination of four anabolic steroids [trenbolone, methylboldenone, methyltestosterone, and norethandrolone] in bovine muscle. Methyltestosterone- d 3 was used as internal standard. The procedure involved enzymatic hydrolysis, extraction with tert-butyl methyl ether, defattening, and final cleanup with solid-phase extraction with Oasis HLB cartridges. The analytes were analyzed by reversed-phase LC-MS/MS, acquiring two diagnostic product ions from the chosen precursor [M + H] (+) for the unambiguous confirmation of hormones. The method was validated according to the European Commission Decision 2002/657/EC for the detection and confirmation of residues in products of animal origin. The limits of detection (LOD) and limits of quantitation (LOQ) were found to be 0.3 ng/g and 1.0 ng/g, respectively. The accuracy and precision have been determined, with recoveries ranging from 83% to 104% and the CV factor not exceeding the value of 7%. The decision limits CCalpha were calculated and ranged from 0.05 to 0.15 ng/g while the detection capabilities CCbeta ranged from 0.09 to 0.25 ng/g. The method proved to be sensitive and reliable and thus renders an appropriate means for residue analysis studies.


Excessive consumption of mucin by over-colonized Akkermansia muciniphila promotes intestinal barrier damage during malignant intestinal environment.
Gut microbiota disorders damage the intestinal barrier, which causes intestinal disease. Thus, we screened the microbiota with significant changes using an in situ malignant colorectal cancer (CRC) model. Among the colonies with increased abundance, Akkermansia muciniphila (A. muciniphila) is known for its characteristic of breaking down mucin, which is an essential component of the intestinal barrier. The role of A. muciniphila remains controversial. To investigate the effect of excess A. muciniphila on the intestinal barrier, we established an over-colonized A. muciniphila mouse model by administering a live bacterial suspension after disrupting the original gut microbiome with antibiotics. The results showed that over-colonization of A. muciniphila decreased intestinal mucin content. The mRNA and protein expression levels of tight junction proteins also decreased significantly in the over-colonized A. muciniphila mouse model. Our findings reveal that excess colonization by A. muciniphila breaks the dynamic balance between mucin secretion and degradation, reduces the thickness of the intestinal mucus layer, and damages the intestinal barrier, which would eventually aggravate the development of colitis and CRC. These results will raise awareness about the safety of A. muciniphila serving as a probiotic.


Effective palliation for advanced esophageal cancer using intralumenal irradiation.
Palliative treatment by intracavitary irradiation alone has been used in 15 patients with advanced carcinoma of the esophagus. Most of them had already failed other palliative modalities including external irradiation, chemoradiotherapy, laserotherapy and dilatation. Intracavitary irradiation was carried out with a microSelectron HDR afterloading device and usually 22.5 Gy was given in three fractions repeated weekly. Up to three month after treatment, complete endoscopic regression was seen in 1 patient, partial endoscopic regression in 8 patients, no response in one and progressive disease in 5 patients. The median survival time is 6.2 months. There were not severe complications. We conclude that high dose rate intracavitary irradiation is a useful palliative modality in patients with advanced or recurrent esophageal cancer.


Measuring Social Support in People with Mental Illness: A Quantitative Analysis of the Social Network Map.
An instrument is needed for quantitatively evaluating changes in social support in people with mental illness, but no gold standard is available. The Social Network Map is a structured interview for assessing social support that is used in individual care settings, yet provides overwhelming output (16-128 data points per assessment). A method comprising two factors (quality and quantity of the social network) was developed. The psychometric properties were judged to be sufficient. This study shows that data from the Social Network Map can be analysed at the group level, yet further research on the psychometric properties is needed.


Manipulator Design and Operation for a Six-Degree-of-Freedom Handheld Tremor-Canceling Microsurgical Instrument.
This paper presents the design and actuation of a six-degree-of-freedom (6-DOF) manipulator for a handheld instrument, known as "Micron," which performs active tremor compensation during microsurgery. The design incorporates a Gough-Stewart platform based on piezoelectric linear motor, with a specified minimum workspace of a cylinder 4 mm long and 4 mm in diameter at the end-effector. Given the stall force of the motors and the loading typically encountered in vitreoretinal microsurgery, the dimensions of the manipulator are optimized to tolerate a transverse load of 0.2 N on a remote center of motion near the midpoint of the tool shaft. The optimization yields a base diameter of 23 mm and a height of 37 mm. The fully handheld instrument includes a custom-built optical tracking system for control feedback, and an ergonomic housing to serve as a handle. The manipulation performance was investigated in both clamped and handheld conditions. In positioning experiments with varying side loads, the manipulator tolerates side load up to 0.25 N while tracking a sinusoidal target trajectory with less than 20 μm error. Physiological hand tremor is reduced by about 90% in a pointing task, and error less than 25 μm is achieved in handheld circle-tracing.


On the Use of Broadened Admission Criteria in Higher Education.
There is an increasing interest in the use of broadened criteria for admission to higher education, often assessed through noncognitive instruments. We argue that there are several reasons why, despite some significant progress, the use of noncognitive predictors to select students is problematic in high-stakes educational selection and why the incremental validity will often be modest, even when studied in low-stakes contexts. Furthermore, we comment on the use of broadened admission criteria in relation to reducing adverse impact of testing on some groups, and we extend the literature by discussing an approach based on behavioral sampling, which showed promising results in Europe. Finally, we provide some suggestions for future research.


Apparent insulin resistance due to abnormal enzymatic insulin degradation: a new mechanism for insulin resistance.
A 16-year-old girl presented with severe, prolonged insulin resistance. Insulin antibodies, initially thought to be responsible for the insulin resistance, were suppressed using monocomponent insulin and immunosuppressive therapy; however insulin resistance persisted. Insulin kinetic studies suggested abnormal metabolism of a bolus injection of 125I insulin and the reappearance in the circulation of radioactive products, demonstrated by chromatography to be of different molecular weight to insulin. These products were of similar molecular weight to material obtained by incubating 125I insulin with protease. Trasylol significantly reduced the patient's insulin requirements and normalised the disappearance of 125I insulin from the circulation. Prolonged treatment with Trasylol resulted in a fall in insulin requirement to non "insulin-resistance" levels. The insulin requirement remained static when Trasylol was ceased. We propose abnormally rapid insulin degradation to be a new mechanism of resistance to insulin therapy.


Modeling triblock surfactant-templated mesostructured cellular foams.
Lattice Monte Carlo simulations are used to understand the role of surfactant self-assembly in the synthesis of templated mesoporous materials with ultralarge pores. Our system consists of model triblock surfactants in the presence of oil, water, and inorganic oxide. Depending on the temperature and component concentrations, these systems phase separate, and the surfactant-rich phase forms structures such as cylinders, lamellae, and spheres ordered in repetitive arrangements. In the absence of oil, the structures are cylindrical with diameters of 100 A, but increasing oil concentration produces ultralarge spheres with diameters above 500 A. Our results closely resemble the cylinder to sphere transition associated with the synthesis of the mesostructured cellular foams (MCFs). Pore size distributions of our model structures are qualitatively comparable with the pore size distributions of MCFs obtained from adsorption experiments. We also observe an increase in average pore size with oil concentration, which is consistent with the experimental reportings.


A comparison between a Canadian regional trauma unit and an American level I trauma center.
Although there has been recent comparison of the Canadian and American health care systems, the issue of trauma has received little attention. Data were collected on all adult motor vehicle crash (MVC) victims admitted to the Sunnybrook Trauma Unit (CAN), Toronto, Canada, and the R Adams Cowley Shock Trauma Center (USA), Baltimore, Maryland from July 1986 through July 1990. Similar MVC victims at CAN and USA had equivalent mortality rates with similar discharge dispositions (p = NS), but patients at USA were twice as likely to be admitted to the ICU and had longer ICU stays (p < 0.01). The hospital-based cost for an average MVC patient at CAN was significantly less than for an average patient at USA and professional charges were at least five times greater at USA. This study provides some insight into the differences in trauma care between Canada and the United States.


Diagnosis and prognosis in malignant pleural mesothelioma: a prospective study.
In a prospective study of 336 consecutive patients with long-term pleural effusions, 32 cases of malignant mesothelioma were found. Microscopic examination of pleural tissue specimens, preferably selected at thoracoscopy, proved superior to pleural fluid analysis as an aid to correct diagnosis. The epithelial proved to be the most common type of malignant mesothelioma. As an example of the mesothelial cells' multipotent ability, malignant cells were seen transforming into fat-like cells with lipid-containing vacuoles. In the fibrous tumour type, cytological examination of pleural fluid revealed only normal cells. Cells with malignant features were seen in fluid samples from epithelial and biphasic tumour types. The malignant cells often formed tubuli-like aggregates which could be mistaken for adenocarcinoma. Hyaluronic acid was more frequently detected in tissue specimens than in the pleural fluid samples. The morphological type and the patient's age had an impact on the survival time, whereas sex and extensive surgical treatment seemed less important.


Genetic Architecture of Phenomic-Enabled Canopy Coverage in Glycine max.
Digital imagery can help to quantify seasonal changes in desirable crop phenotypes that can be treated as quantitative traits. Because limitations in precise and functional phenotyping restrain genetic improvement in the postgenomic era, imagery-based phenomics could become the next breakthrough to accelerate genetic gains in field crops. Whereas many phenomic studies focus on exploratory analysis of spectral data without obvious interpretative value, we used field images to directly measure soybean canopy development from phenological stage V2 to R5. Over 3 years, we collected imagery using ground and aerial platforms of a large and diverse nested association panel comprising 5555 lines. Genome-wide association analysis of canopy coverage across sampling dates detected a large quantitative trait locus (QTL) on soybean (Glycine max, L. Merr.) chromosome 19. This QTL provided an increase in yield of 47.3 kg ha-1 Variance component analysis indicated that a parameter, described as average canopy coverage, is a highly heritable trait (h2 = 0.77) with a promising genetic correlation with grain yield (0.87), enabling indirect selection of yield via canopy development parameters. Our findings indicate that fast canopy coverage is an early season trait that is inexpensive to measure and has great potential for application in breeding programs focused on yield improvement. We recommend using the average canopy coverage in multiple trait schemes, especially for the early stages of the breeding pipeline (including progeny rows and preliminary yield trials), in which the large number of field plots makes collection of grain yield data challenging.


Polyarteritis Nodosa with Marked Eosinophilia, Associated with Severe Gastrointestinal Tract Involvement and Recurrent Venous Thrombosis.
A 45-year-old man was admitted with acute abdominal pain and eosinophilia. Abdominal computed tomography revealed thickness of the ascending and transverse colon with decreased contrast enhancement and a small amount of ascites. In an emergency operation, the necrotic colon was resected. Histopathology showed subserous medium-sized arteritis with abundant eosinophil infiltrates and thrombosis in the portal vein branches. He was diagnosed with polyarteritis nodosa (PAN), and immunosuppressive therapy improved his condition. Two years later, the disease recurred with ischemic cutaneous lesions and marked eosinophilia. Our experience suggests that marked eosinophilia in PAN may imply severe organ involvement, including gastrointestinal necrosis, as well as the association of venous thrombosis.


Epidermal growth factor receptor signalling contributes to house dust mite-induced epithelial barrier dysfunction.
Impaired airway epithelial barrier function has emerged as a key factor in the pathogenesis of allergic asthma. We aimed to discern the involvement of the epidermal growth factor receptor (EGFR) in allergen-induced epithelial barrier impairment, as we previously observed that house dust mite (HDM) signals through EGFR. We investigated the junctional integrity of human bronchial epithelial cells using electric cell-substrate impedance sensing and immunofluorescent staining. HDM induced a rapid, transient fall in epithelial resistance, concomitant with delocalisation of E-cadherin and zona occludens (ZO)-1, and proteolytic cleavage of the latter. EGFR inhibition by AG1478 reduced the HDM-triggered decrease in epithelial resistance and improved restoration of epithelial junctions. Similarly, AG1478 increased epithelial barrier recovery upon electroporation-induced injury, although it delayed the migration phase of the wound healing response. HDM-promoted redistribution of E-cadherin was mediated via EGFR-dependent activation of protease-activated receptor (PAR)-2, while the concomitant ZO-1 degradation was PAR-2/EGFR-independent. Importantly, the fibrogenic cytokine transforming growth factor (TGF)-β prolonged HDM-induced EGFR phosphorylation and inhibited ligand-induced EGFR internalisation/degradation, which resulted in sustained E-cadherin and ZO-1 redistribution. Thus, allergen-induced, PAR-2/EGFR-mediated signalling decreases epithelial resistance and promotes junction disassembly. The TGF-β-enhanced EGFR signalling may be an important contributor to barrier dysfunction and increased epithelial vulnerability in response to HDM.


Seasonal and spatial occurrence of glycerol-3-phosphate dehydrogenase variability in Ixodes ricinus (Acari: Ixodidae) populations.
Previous results indicate that glycerol-3-phosphate dehydrogenase variability represents the adaptation of Ixodes ricinus L. (Acari: Ixodidae) to fluctuations of environmental conditions, particularly to temperature. Analysis of crucial polymorphisms in I. ricinus Gpdh gene was done by the restriction method, and three different haplotypes were obtained (GPDH441 1, GPDH441 2, and GPDH441 3), corresponding to GPDH alleles detected by allozyme electrophoresis. Differences in GPDH441 haplotype and genotype frequencies were found between samples from open and forest habitats. Significant seasonal variations of GPDH441 haplotype and genotype frequencies were detected in samples from the open habitats. No seasonal variations were observed at forest localities, probably because of the less pronounced amplitude of environmental factors. The possible role of host availability was discussed as an important factor that affects seasonal dynamics and genetic composition of tick populations.


Plasma C-Reactive Protein and Pentraxin-3 Reference Intervals During Normal Pregnancy.
Although several biomarkers are available to monitor the acute phase response, the short pentraxin C-reactive protein (CRP) is dominating in clinical practice. The long pentraxin 3 (PTX3) is structurally and functionally related to CRP, but not liver-derived. In addition, increased levels of PTX3 have been linked to preeclampsia. Reference intervals are usually based on healthy blood donors. Several physiological and immunological alterations occur during normal pregnancy with subsequent potential effects on blood analytes. Hence, this study aims to determine pregnancy-specific reference intervals for CRP and PTX3. Longitudinal clinical data and blood plasma samples from the 1st, 2nd and 3rd trimester of 100 healthy, non-medicating, females aged 18-40 at the time-point of conception were available to us. High-sensitivity CRP measurements were performed by turbidimetry and enzyme-linked immunosorbent assay (ELISA) was used to quantify PTX3. CRP and PTX3 levels followed each other during the first two trimesters and both increased during the third trimester. CRP showed a median of 4.12 mg/L in the third trimester, and were significantly higher compared to the first (median 2.39 mg/L, p<0.0001) and the second (median 2.44 mg/L, p=0.0006) trimesters. In the third trimester PTX3 levels reached a median of 7.70 µg/L, and were significantly higher compared to the first (median 3.33 µg/L, p<0.0001) and the second (median 3.70 µg/L, p<0.0001) trimesters. Plasma albumin was inversely correlated with CRP (rho=-0.27, p<0.0001), but not with PTX3. In conclusion, it is important to consider pregnancy-specific reference values as elevations of CRP and PTX3 during the later phase may occur in absence of infection.


Genome-Wide Development of Polymorphic Microsatellite Markers and Association Analysis of Major Agronomic Traits in Core Germplasm Resources of Tartary Buckwheat.
Tartary buckwheat (TB; Fagopyrum tataricum Gaertn.) is an important multigrain crop and medicinal plant, but functional genomics and molecular breeding research in this species have been lacking for quite some time. Here, genome-wide screening was performed to develop simple sequence repeat (SSR) markers associated with six major agronomic traits and the rutin contents of 97 core germplasm resources. A total of 40,901 SSR loci were identified; they were uniformly distributed throughout the TB genome, with a mean distance of 11 kb between loci. Based on these loci, 8,089 pairs of SSR primers were designed, and 101 primer pairs for polymorphic SSR loci were used to genotype the 97 core germplasm resources. The polymorphic SSR loci showed high genetic variation in these core germplasm resources, with an average polymorphic information content (PIC) value of 0.48. In addition, multiple SSR markers, such as SXAU8002 [100-grain weight (HGW)] and SXAU8006 [stem diameter (SD)], were found to be associated with agronomic traits in the two environments. Finally, based on gene functional annotation and homology analysis, a candidate gene, FtPinG0007685500, that may affect the node number and SD of the main stem by participating in lignin synthesis was identified. This study reports the mining of genome-wide SSR loci and the development of markers in TB, which can be used for molecular characterization of the germplasm in its gene pool. In addition, the detected markers and candidate genes could be used for marker-assisted breeding and functional gene cloning in TB.


Non-convulsive status epilepticus associated with Whipple's disease.
A 69-year-old woman developed non-convulsive status epilepticus during inpatient investigation for abdominal pain. Initial detailed investigations did not identify the cause of seizures, but a jejunal biopsy and PCR testing in various fluids led to the diagnosis of Whipple's disease with neurological involvement. The seizures were controlled but she subsequently had moderate cognitive impairment. Whipple's disease is an important diagnosis, being treatable with antibiotics. Testing for Whipple's disease is not part of the recommended workup in for status epilepticus, but this case highlights the importance of considering this condition.


Dissociated primary human prostate cancer cells coinjected with the immortalized Hs5 bone marrow stromal cells generate undifferentiated tumors in NOD/SCID-γ mice.
Reconstitution of tumor development in immunodeficient mice from disaggregated primary human tumor cells is always challenging. The main goal of the present study is to establish a reliable assay system that would allow us to reproducibly reconstitute human prostate tumor regeneration in mice using patient tumor-derived single cells. Using many of the 114 untreated primary human prostate cancer (HPCa) samples we have worked on, here we show that: 1) the subcutaneum represents the most sensitive site that allows the grafting of the implanted HPCa pieces; 2) primary HPCa cells by themselves fail to regenerate tumors in immunodeficient hosts; 3) when coinjected in Matrigel with rUGM (rat urogenital sinus mesenchyme), CAF (carcinoma-associated fibroblasts), or Hs5 (immortalized bone marrow derived stromal) cells, primary HPCa cells fail to initiate serially transplantable tumors in NOD/SCID mice; and 4) however, HPCa cells coinjected with the Hs5 cells into more immunodeficient NOD/SCID-IL2Rγ(-/-) (NSG) mice readily regenerate serially transplantable tumors. The HPCa/Hs5 reconstituted 'prostate' tumors present an overall epithelial morphology, are of the human origin, and contain cells positive for AR, CK8, and racemase. Cytogenetic analysis provides further evidence for the presence of karyotypically abnormal HPCa cells in the HPCa/Hs5 tumors. Of importance, HPCa/Hs5 xenograft tumors contain EpCAM(+) cells that are both clonogenic and tumorigenic. Surprisingly, all HPCa/Hs5 reconstituted tumors are undifferentiated, even for HPCa cells derived from Gleason 7 tumors. Our results indicate that primary HPCa cells coinjected with the immortalized Hs5 stromal cells generate undifferentiated tumors in NSG mice and we provide evidence that undifferentiated HPCa cells might be the cells that possessed tumorigenic potential and regenerated HPCa/Hs5 xenograft tumors.


Aspects of the neuroendocrine control of ovulation and broodiness in the domestic hen.
The neuroendocrine control of ovulation and broodiness in the domestic hen involves complex interactions between hypothalamic neuropeptides, neurotransmitters, and ovarian steroids which regulate the secretion of luteinizing hormone (LH) and prolactin. Nuclear progesterone receptor is localized in many neurons throughout the hypothalamus but is absent from LHRH neurons. Hence, the positive feedback action of progesterone on LH release is not mediated by a genomic mechanism within the LHRH neuron. Precursors of 5-hydroxytryptamine (5HT) and dopamine (DA) inhibit the preovulatory release of LH, while the turnover rates of these neurotransmitters in the anterior hypothalamus decrease when preovulatory levels of LH are at their highest. Further, a population of receptors for 5HT which occurs in the anterior hypothalamus in laying birds is absent in nonlaying, incubating hens. Taken together, these observations suggest that the preovulatory surge of LH is mediated by a transitory decrease in the inhibitory action of 5HT and possibly DA, on the secretion of LHRH. Neurons containing 5HT may play a role in the regulation of prolactin release and, more specifically, in the control of broodiness. Drugs which enhance the function of 5HT neurons stimulate prolactin release while increased prolactin secretion in incubating hens is associated with an increase in the turnover of 5HT in the anterior hypothalamus. No receptors for 5HT were demonstrable in the anterior pituitary gland, showing that the prolactin-releasing activity of 5HT must be mediated by a prolactin-releasing factor (PRF). A candidate for a physiological PRF is vasoactive intestinal polypeptide (VIP).(ABSTRACT TRUNCATED AT 250 WORDS)


Quantitative analysis of the choline acetyltransferase-immunoreactive axonal network in the cat primary visual cortex: I. Adult cats.
The laminar distribution of cholinergic axons was analyzed quantitatively in the visual cortex of adult cats by using immunocytochemistry with a monoclonal antibody against choline acetyltransferase (ChAT). ChAT(+) fibers and varicosities were counted at different locations within area 17 and the distribution patterns in various animals were compared. Choline acetyltransferase-immunoreactivity was localized in fine, varicose fibers, which were present in all layers of the visual cortex. The density of labeled fibers was highest in layer I, which contained 14% of all fibers and 19.5% of all varicosities, and decreased toward deeper layers. The number of varicosities decreased more markedly toward deeper layers than the frequency of fibers. These distribution patterns were very consistent, showing only slight intra- and interindividual variability.


Phosphorylation of p53 at threonine 155 is required for Jab1-mediated nuclear export of p53.
The Jun activation-domain binding protein 1 (Jab1) induces p53 nuclear export and cytoplasmic degradation, but the underlying mechanism is poorly understood. Here, we show that phosphorylation at the threonine 155 residue is essential for Jab1-mediated p53 nuclear export. Jab1 stimulated phosphorylation of p53 at T155 was inhibited by curcumin, an inhibitor of COP9 signalosome (CSN)-associated kinases. The T155E mutant, which mimics phosphorylated p53, exhibited spontaneous cytoplasmic localization in the absence of Jab1. This process was prevented by leptinomycin B (LMB), but not by curcumin. The substitution of threonine 155 for valine (T155V) abrogated Jab1-mediated p53 nuclear export, indicating that phosphorylation at this site is essential for Jab1-mediated regulation of p53. Although T155E can be localized in the cytoplasm in the absence of Mdm2, the translocation of T155E was significantly enhanced by ectopic Hdm2 expression. Our data suggests that Jab1-mediated phosphorylation of p53 at Thr155 residue mediates nuclear export of p53. [BMB Reports 2017; 50(7): 373-378].


¹⁸F-fluorodeoxyglucose PET/CT findings of a solitary primary hepatic lymphoma: a case report.
Primary hepatic lymphoma is extremely rare, and only a few cases have been described on positron emission tomography (PET) or PET/computed tomography (PET/CT) imaging in the English literature. We report a case of a 55-year-old woman who presented with low-grade fever and weight loss of three months. On CT scanning, a mass was identified which appeared to be a hypoattenuating lesion, on ultrasonographic imaging, the mass was hypoechoic, therefore, liver abscess or hepatic metastasis from a gastrointestinal primary was initially suspected. Tumor markers such as alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19-9 were within normal limits. PET/CT demonstrated a large abnormal ring-like hypermetabolic focus in the right liver lobe. The lesion was resected and the histopathological findings were consistent with lymphoma. The patient was discharged two weeks after surgery and did not receive any further treatment. After 25 mo follow-up, she is in good health. (18)F-fluorodeoxyglucose PET/CT is useful in confirming the diagnosis of primary hepatic lymphoma by demonstrating no other foci with high uptake in other parts of the body.


Methane Bubble Growth and Migration in Aquatic Sediments Observed by X-ray μCT.
Methane bubble formation and transport is an important component of biogeochemical carbon cycling in aquatic sediments. To improve understanding of how sediment mechanical properties influence bubble growth and transport in freshwater sediments, a 20-day laboratory incubation experiment using homogenized natural clay and sand was performed. Methane bubble development at high resolution was characterized by μCT. Initially, capillary invasion by microbubbles (<0.1 mm) dominated bubble formation, with continued gas production (4 days for clay; 8 days for sand), large bubbles formed by deforming the surrounding sediment, leading to enhanced of macropore connectivity in both sediments. Growth of large bubbles (>1 mm) was possible in low shear yield strength sediments (<100 Pa), where excess gas pressure was sufficient to displace the sediment. Lower within the sand, higher shear yield strength (>360 Pa) resulted in a predominance of microbubbles where the required capillary entry pressure was low. Enhanced bubble migration, triggered by a controlled reduction in hydrostatic head, was observed throughout the clay column, while in sand mobile bubbles were restricted to the upper 6 cm. The observed macropore network was the dominant path for bubble movement and release in both sediments.


Squamous carcinoma of the oropharynx.
One hundred and ten patients with an oropharyngeal carcinoma seen in the period 1961--1971 at the Antoni van Leeuwenhoek Hospital in Amsterdam are analysed. Approximately 75% of the patients were older than 60 years. About 60% of the patients had a cervical lymph node metastasis at the time of admission. Virtually all patients were treated exclusively by radiotherapy. Of the total group, the absolute survival was 26%, for tumours of the tonsil 35%, and for the base of the tongue 17%. There was no significant correlation between the histological degree of differentiation and the survival. The possibility of improving the results of selected patients is discussed.


Regulation of pyrimidine formation in Pseudomonas oryzihabitans.
The regulation of pyrimidine formation in the opportunistic human pathogen Pseudomonas oryzihabitans was investigated at the level of enzyme synthesis and at the level of activity for the pyrimidine biosynthetic pathway enzyme aspartate transcarbamoylase. Although pyrimidine supplementation of succinate-grown P. oryzihabitans cells produced little effect on the de novo pyrimidine biosynthetic pathway enzyme activities, pyrimidine limitation experiments undertaken using an orotidine 5'-monophosphate decarboxylase mutant strain isolated from P. oryzihabitans ATCC 43272 indicated that repression of enzyme synthesis by pyrimidines was occurring. Following pyrimidine limitation of the succinate-grown decarboxylase mutant strain cells, aspartate transcarbamoylase and dihydroorotase activities were found to increase by about 3-fold while dihydroorotate dehydrogenase and orotate phosphoribosyltransferase activities were also observed to increase relative to their activities in the mutant strain cells grown on excess uracil. At the level of enzyme activity, aspartate transcarbamoylase in P. oryzihabitans was strongly inhibited by pyrophosphate, ADP, ATP and GTP in the presence of saturating substrate concentrations.


Activating Molecular Room-Temperature Phosphorescence by Manipulating Excited-State Energy Levels in Poly(vinyl alcohol) Matrix.
Poly(vinyl alcohol) (PVA) has been found as a wonderful matrix for chromophores to boost their room-temperature phosphorescence (RTP) character by forming abundant hydrogen bonding. Despite the well-utilized protective effect, the constructive role in accelerating the intersystem crossing is less investigated. Here, we focus on its role in manipulating the excited-state energy level to facilitate multiple intersystem crossing channels. Six benzoyl carbazole derivatives do not emit RTP in their solutions, powders, or crystals but exhibit significantly persistent RTP signals when embedded into the PVA matrix. Charge-transfer excited states were trapped by cofacial stacking in crystal, which blocks the intersystem crossing channels. In the PVA matrix, the allowed broad distribution of charge-transfer states covers the locally excited states, offering multiple intersystem crossing pathways via spin-vibronic orbit coupling. Consequently, efficient and persistent heavy-atom-free phosphors have been developed with the highest quantum yields of 7.7% and the longest lifetime of 2.3 s.


Micronutrients deficiencies in patients with spondylarthritis: the potential immunometabolic crosstalk in disease phenotype.
Micronutrient deficiencies (MNDs) are common among patients with certain chronic inflammatory diseases. They are associated with a pro-inflammatory status and co-morbidities. However, no studies have specifically investigated MNDs in Spondyloarthritis (SpA). This paper aimed at analyzing the occurrence of anemia and deficiencies of ferritin (Fe), vitamin D [25(OH)D], vitamin B12 (B12), and folic acid (FA) in SpA patients. The interplay of MNDs with age, gender, and metabolic abnormalities was also explored. MNDs were evaluated in 220 SpA outpatients (137 females and 83 age-matched males) with psoriatic arthritis (PsA, n=110) and non-psoriatic SpA (n=110). Metabolic parameters were analyzed. Disease activity was assessed by either Disease Activity in PSoriatic Arthritis (DAPSA) or Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein (ASDAS-CRP) as appropriate, while the functional status was evaluated using Health Assessment Questionnaire modified for SpA (HAQ-S). Anemia occurred in 13.6% of subjects of the study cohort and almost wholly in females (p=0.004). Females showed higher Fe deficiency (p=0.04) and lower Fe levels (p=0.0003) than males. Hemoglobin (Hb) resulted inversely related to age and CRP (p=0.01 and p=0.008) in male group. The 25(OH)D deficiency (≤20 ng/ml) was present in 23.2% of the cohort with a higher prevalence in males than females (p=0.02): moreover, 25(OH)D inversely correlated with disease duration (p=0.02) in males. The B12 deficiency (≤200 pmol/l) was rare (13.2%), while FA ≤4 ng/ml was frequent (22%) and associated with B12 deficiency in 31% of cases. SpA patients in moderate/high disease activity had higher Body Mass Index (BMI) (p=0.04) and HAQ-S (p<0.0001), as well as lower Hb (p=0.02), and Fe (p=0.03) than patients in remission/low disease activity (LDA). In patients with extra-articular manifestations, female sex was prevalent (F:M=2) and B12 levels were lower than in patients without (p=0.005). Interestingly, 25(OH)D was lower (p=0.04) and both BMI and HAQ-S (p=0.036 and p=0.01) were higher in patients without extra-articular involvement than patients with. Our findings documented a relevant prevalence of MNDs in SpA patients, and its strict interplay with gender and metabolic abnormalities by highlighting the role of MNDs in inflammatory-dependent dysmetabolism in SpA.


Amphotericin B in lipid emulsion: stability, compatibility, and in vitro antifungal activity.
Newer formulations of amphotericin B (AmB) complexed with liposomes or lipid suspensions have been developed. Preliminary studies have suggested that AmB in Intralipid (IL) may be as effective as, but less toxic than, conventional formulations of AmB, but few data are available regarding its stability, compatibility, or in vitro antifungal activity. A compatibility study was done to evaluate the effects of AmB concentrations in IL containing either 10 or 20% soybean oil. The effects of temperature, shaking, and AmB and IL concentrations on the stability of AmB-IL suspensions were analyzed by visual inspection and liquid chromatography. The in vitro antifungal activity of AmB-IL, compared to that of AmB alone against reference strains of Candida species was determined by using a broth macrodilution method in accordance with National Committee for Clinical Laboratory Standards guidelines (M27-T). Samples of AmB-IL which were lightly shaken retained more than 90% of the AmB concentration over 21 days when stored at either 4 or 23 degrees C. Varying the AmB concentration did not appear to affect the stability of AmB-IL. However, a precipitate was formed when mixtures with more than 30% lipid as a proportion of the total volume were centrifuged. AmB-IL and AmB alone had similar in vitro antifungal activities against reference strains of yeasts. Further pharmacologic and clinical studies with AmB-IL are warranted, although AmB should not be combined with IL in concentrations capable of producing a precipitate.


Rapid enrollment design for finding the optimal dose in immunotherapy trials with ordered groups.
In immunotherapy dose-finding trials, the optimal dose is usually defined based on both toxicity and response because the relationship between toxicity and response is different than that seen with cytotoxic anti-neoplastic therapies. In immunotherapy trials, toxicity and response often require a longer follow-up time compared to trials with cytotoxic agents. The rapid enrollment design has been proposed for dose-finding trials to find the maximum-tolerated dose where the follow-up for toxicity is long and it is desirable to assign a patient to a dose of a new therapy as soon as the patient is enrolled. We extend the rapid enrollment design to immunotherapy trials to find the optimal dose. We further describe how to use the design in immunotherapy trials with ordered groups where efficacy and safety considerations dictate running dose-finding trials in each group separately as efficacy and toxicity at the same dose can vary across groups. The estimation of the optimal dose in each of the groups can be improved in many, but not all, cases by using the monotonicity of toxicity and response among groups.


Cardiometabolic abnormalities in the polycystic ovary syndrome: pharmacotherapeutic insights.
The polycystic ovary syndrome (PCOS) affects 5-10% of all premenopausal women. It is diagnosed by a combination of oligo-amenorrhea and hyperandrogenism (NIH criteria) or by the presence of two out of three of: oligo-amenorrhea, hyperandrogenism, polycystic ovaries on ultrasound (Rotterdam criteria). PCOS is associated with obesity, insulin resistance and dyslipidemia. Different patterns of dyslipidemia can be present, both in lean and obese PCOS. Low HDL-cholesterol, with or without elevated TG, is the most prominent lipid abnormality. In addition, smaller HDL and LDL particles and elevated postprandial TG responses are reported. Hyperandrogenism, anovulation and insulin resistance affect multiple steps in lipid metabolism in PCOS, as will be discussed. Surrogate markers for atherosclerosis are consistently abnormal in PCOS, while studies on clinical CVD endpoints are limited and non-conclusive. The (pharmaco-) therapy of dyslipidemia in PCOS will be discussed. In addition, the effects of other PCOS related (pharmaco-) therapies, primarily aimed at hyperandrogenism, anovulation or insulin resistance, on lipid metabolism will be addressed.


The Correlation between Hemoglobin A1c (HbA1c) and Hyperreflective Dots (HRD) in Diabetic Patients.
Hyperreflective dots (HRD) are activated retinal microglial cells induced by retinal inflammation in diabetic patients. This study was conducted to compare the HRD count of normal and diabetic subjects; to determine the correlation between hemoglobin A1c (HbA1c) levels and HRD count; to determine HbA1c cut-off levels for the appearance of HRD in diabetic patients. A cross-sectional study was conducted among normal and diabetic patients. Fundus photos, SD-OCT images and HbA1c levels were taken. A total of 25 normal subjects, 32 diabetics without retinopathy and 26 mild-to-moderate nonproliferative diabetic retinopathy (NPDR) diabetics were recruited. There was a statistically significant difference between the mean count of HRD among the normal group, the diabetic without retinopathy group and the mild-to-moderate NPRD group. The mean HRD count in the inner retina layer was significantly higher compared to the outer retina layer. There was a significant linear relationship between the HbA1c levels and HRD count. Using the receiver operating curve, the HbA1c level of 5.4% was chosen as the cut-off point for the appearance of HRD. The positive linear correlation between the HbA1c levels and the appearance of HRD may indicate that hyperglycemia could activate retina microglial cells in diabetic patients.


Aggregation enhancement of coronene molecules by seeding with alkali-metal ions.
Microsolvation constitutes the first step in the formation of cluster structures of molecules that surround a solute in the bulk and it allows for a deep insight into the relationship between the structure of the solvation shells and other physical properties. We propose semiempirical potential energy functions that are able to describe the interaction between K+ or Cs+ with coronene. Such functions were calibrated through the comparison with accurate estimations of the interaction between the cation and the planar hydrocarbon, obtained by means of ab initio electronic-structure calculations. By employing the potential energy functions and an evolutionary algorithm (EA), we have investigated the structure and energetics of the clusters resulting from the microsolvation of either K+ or Cs+ with coronene molecules. The reliability of the results for smaller clusters was checked by performing geometry re-optimization exploiting a suitable DFT level of theory. This has allowed for the characterization of the first solvation shells of planar molecules of coronene around an alkali-metal ion. It has also been found that the presence of metal ion impurities considerably enhances the formation of small coronene clusters leading to much stronger binding energies for heterogeneous with respect to homogeneous aggregates. These clusters could represent relevant species involved in the early stages of soot nucleation.


Five-year study of surgical rates in Ontario's counties.
The surgical rates for eight operations (hysterectomy, tonsillectomy/adenoidectomy, cholecystectomy, prostatectomy, appendectomy, mastectomy, colectomy and cesarean section) done in Ontario's 44 counties from 1973 to 1977 were examined. There was considerable variation among the counties for all the operations studied, although the degree of intercounty variation decreased over the 5 years. Differences in resources (hospital beds and surgeons) explained little of the variation in the rates, but this may be because people crossed county lines for certain operations. Although some counties had consistently high or low rates for individual operations during the 5-year period, only four had consistently high rates for four or more operations, and only five had consistently low rates for four or more. The five counties with teaching health science centres had the highest ratios of specialists and surgeons to population, and, with the exception of one county in 1973, had above-average numbers of hospital beds. Despite the greater resources in these counties, their residents had consistently low rates for cholecystectomy, appendectomy, mastectomy and tonsillectomy/adenoidectomy. However, three of these counties had the highest rates for cesarean section. The variation in the rates is likely due to lack of agreement about indications for surgery or to variation in the use of technology rather than to differences in the incidence or prevalence of disorders.


ABCA7 Mediates Phagocytic Clearance of Amyloid-β in the Brain.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia and abnormal deposits of aggregated amyloid-β in the brain. Recent genome-wide association studies have revealed that ABCA7 is strongly associated with AD. In vitro evidence suggests that the role of ABCA7 is related to phagocytic activity. Deletion of ABCA7 in a mouse model of AD exacerbates cerebral amyloid-β plaque load. However, the biological role of ABCA7 in AD brain pathogenesis is unknown. We show that ABCA7 is highly expressed in microglia and when monocytes are differentiated into macrophages. We hypothesized that ABCA7 plays a protective role in the brain that is related to phagocytic clearance of amyloid-β. We isolated microglia and macrophages from Abca7-/- and wild type mice and tested them for their capacity to phagocytose amyloid-β oligomers. We found that the phagocytic clearance of amyloid-β was substantially reduced in both microglia and macrophages from Abca7-/- mice compared to wild type mice. Consistent with these results, in vivo phagocytic clearance of amyloid-β oligomers in the hippocampus was reduced in Abca7-/- mice. Furthermore, ABCA7 transcription was upregulated in AD brains and in amyloidogenic mouse brains specifically in the hippocampus as a response to the amyloid-β pathogenic state. Together these results indicate that ABCA7 mediates phagocytic clearance of amyloid-β in the brain, and reveal a mechanism by which loss of function of ABCA7 increases the susceptibility to AD.


Crisscross multilayering of cell sheets.
Hydrostatic skeletons such as the Hydra's consist of two stacked layers of muscle cells perpendicularly oriented. In vivo, these bilayers first assemble, and then the muscle fibers of both layers develop and organize with this crisscross orientation. In the present work, we identify an alternative mechanism of crisscross bilayering of myoblasts in vitro, which results from the prior local organization of these active cells in the initial monolayer. The myoblast sheet can be described as a contractile active nematic in which, as expected, most of the +1/2 topological defects associated with this nematic order self-propel. However, as a result of the production of extracellular matrix (ECM) by the cells, a subpopulation of these comet-like defects does not show any self-propulsion. Perpendicular bilayering occurs at these stationary defects. Cells located at the head of these defects converge toward their core where they accumulate until they start migrating on top of the tail of the first layer, while the tail cells migrate in the opposite direction under the head. Since the cells keep their initial orientations, the two stacked layers end up perpendicularly oriented. This concerted process leading to a crisscross bilayering is mediated by the secretion of ECM.


[Access to health care for migrants].
Migrants include a broad category of individuals moving from one place to another, either forced or voluntarily. Ethnicity and migration are interacting concepts which may act as determinants for migrants' health and access to health care. This access to health care may be measured by studying utilisation patterns or clinical outcomes like morbidity and mortality. Migrants' access to health care may be affected by several factors relating to formal and informal barriers. Informal barriers include economic and legal restrictions. Formal barriers include language and psychological and sociocultural factors.


Small elevations of glucose concentration redirect and amplify the synthesis of guanosine 5'-triphosphate in rat islets.
Recent studies suggest a permissive requirement for guanosine 5'-triphosphate (GTP) in insulin release, based on the use of GTP synthesis inhibitors (such as myocophenolic acid) acting at inosine monophosphate (IMP) dehydrogenase; herein, we examine the glucose dependency of GTP synthesis. Mycophenolic acid inhibited insulin secretion equally well after islet culture at 7.8 or 11.1 mM glucose (51% inhibition) but its effect was dramatically attenuated when provided at < or = 6.4 mM glucose (13% inhibition; P < 0.001). These observations were explicable by a stimulation of islet GTP synthesis derived from IMP since, at high glucose: (a) total GTP content was augmented; (b) a greater decrement in GTP (1.75 vs. 1.05 pmol/islet) was induced by mycophenolic acid; and (c) a smaller "pool" of residual GTP persisted after drug treatment. Glucose also accelerated GTP synthesis from exogenous guanine ("salvage" pathway) and increased content of a pyrimidine, uridine 5'-triphosphate (UTP), suggesting that glucose augments production of a common regulatory intermediate (probably 5-phosphoribosyl-1-pyrophosphate). Pathway-specific radiolabeling studies confirmed that glucose tripled both salvage and de novo synthesis of nucleotides. We conclude that steep changes in the biosynthesis of cytosolic pools of GTP occur at modest changes in glucose concentrations, a finding which may have relevance to the adaptive (patho) physiologic responses of islets to changes in ambient glucose levels.


Two pedigrees segregating Duane's retraction syndrome as a dominant trait map to the DURS2 genetic locus.
The genetic bases of Duane's retraction syndrome (DRS) were investigated to determine its molecular etiologies. In prior studies, the transcription factors SALL4 and HOXA1 were identified as the genes mutated in DRS with radial anomalies, and in DRS with deafness, vascular anomalies, and cognitive deficits, respectively. Less is known, however, about the genetic etiology of DRS when it occurs in isolation, and only one genetic locus for isolated DRS, the DURS2 locus on chromosome 2, has been mapped to date. Toward the goal of identifying the DURS2 gene, two pedigrees have been ascertained that segregate DRS as a dominant trait. Members of two large dominant DRS pedigrees were enrolled in an ongoing study of the genetic basis of the congenital cranial dysinnervation disorders, and linkage analysis was conducted to determine whether their DRS phenotype maps to the DURS2 locus. By haplotype analysis, the DRS phenotype in each family cosegregates with markers spanning the DURS2 region. Linkage analysis reveals maximum lod scores >2, establishing that the DRS phenotype in these two pedigrees maps to the DURS2 locus. These two pedigrees double the published pedigrees known to map to the DURS2 locus and can thus contribute toward the search for the DURS2 gene. The affected members represent a genetically defined population of DURS2-linked DRS individuals, and hence studies of their clinical and structural features can enhance understanding of the DURS2 phenotype, as described in the companion paper.


Uterine contractility and induction of abortion in early pregnancy by misoprostol and mifepristone.
A combination of the antiprogestagen mifepristone and an exogenous prostaglandin given by intramuscular injection or intravaginal pessary is a highly effective means of inducing abortion in early pregnancy. However, the search for a stable oral prostaglandin preparation has been largely unsuccessful. The effect of misoprostol, an orally active prostaglandin used to treat peptic ulcer, on uterine contractility was investigated in 33 women in early pregnancy (under 56 days' amenorrhoea). After administration of misoprostol in doses ranging from 200 micrograms to 600 micrograms, there was a significant increase in uterine pressure. In a second group of women who were given 200-1000 micrograms misoprostol 48 h after the administration of 200 mg mifepristone, there was a significant increase in the amplitude and frequency of uterine contractions. Complete abortion took place in 18 of the 21 women who received misoprostol after mifepristone, but in only 2 of 40 women given misoprostol alone. Our findings show that misoprostol increases uterine activity in early pregnancy and suggest that, in combination with mifepristone, it may be a highly effective method of inducing therapeutic abortion.


Distribution of Clinical NDM-1-Producing Gram-Negative Bacteria in Brazil.
New Delhi metallo-β-lactamase (NDM)-producing bacteria have been identified at a worrying rate in Brazil since 2013. Owing to the need to understand the extent of their spread, this study reports the dissemination of blaNDM in different species of Gram-negative bacilli in different regions and states of Brazil. A total of 81 isolates from nine states were studied, including 11 species. All isolates carried blaNDM-1 variant and were considered multidrug resistant. Colistin and amikacin were the agents with higher activity compared with the other drugs tested. The findings indicate that the NDM-1 enzyme is already widespread in the country.


[Phylogenetic theory of general pathology. Pericytes, function of the distal arterial bed, metabolic arterial hypertension and hypovolemic shock.]
The in vivo roles of pericyte contractile sphincters, smooth muscle cells, endothelial monolayer, precapillary muscle arterioles, exchange and volume capillaries in the physiological balance between peripheral blood pool and the blood pool volume in the distal arterial bed are not fully understood. However, it is highly probable that: 1. There is no primary arterial hypertension. The compensatory biological reaction of arterial pressure (AP) is always secondary, thus indicating the presence of symptomatic or metabolic arterial hypertension (AH). 2. Elevation of AP in proximal arterial bed is a compensatory response to metabolic disorders and impaired microcirculation and metabolism↔microcirculation biological reaction. The response develops locally in the distal arterial bed (muscle arterioles, functional sphincters, pericytes). 3. Metabolic AH is a pathology of the phylogenetically early distal arterial bed , endothelial monolayer, smooth muscle cell and pericyte function. 4. We believe that formation of acute hypovolemic shock is the condition of sphincter (pericyte) atonia in precapillary muscle arterioles with formation of a nonphysiological blood volume in the distal arterial bed when physiological volume of peripheral blood is insufficient to fill the bed. 5. When local disorder in the biological reaction metabolism↔microcirculation is not compensated by endothelium-dependent vasodilation, an efferent innervation signal from the vasomotor center at the entire organism level is sent to the heart and systemic AP increases first in the proximal then in the distal arterial bed. 6. Systemic AP elevation impairs function of the target organs: kidneys, brain and lungs. Each of these organs regulates hydrodynamics in the local pool of extracellular medium, their dysfunction inducing a compensatory response. 7. Metabolic arterial hypertension results from discoordinated systemic compensation of local disorders in the following biological functions: homeostasis, endoecology, trophology and adaptation. This discoordination occurs at the level of paracrine regulated cell communities of functionally different cells which are structural units of each internal organ.


[Vitamin D deficiency and carotid artery intima-media thickness and coronary calcification in patients with diabetic nephropathy].
To investigate the deficiencey and insufficiency of 25-hydroxyvitamin D3 [25 (OH) D3], 1,25- dihydroxyvitamin D3 [1,25 (OH)2 D3] in patients with diabetic nephropathy (DN), an their association with carotid artery intima-media thickness (IMT) and coronary artery calicfication. The concentrations of 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone (iPTH) were determined by radioimmunoassay in 151 DN patients. Based on the level of 25-hydroxyvitamin D3, the patients were divided into Vitamin D deficiency group (Vit-D-D group, <15 ng/mL), insufficiency group (Vit-D-I group, 15-30 ng/mL), and normal group (Vit-D-N group, >30 ng/mL). The association of Vitamin D with IMT and coronary artery calcification was examined through group comparisons, logistic regression analysis and multiple linear regression analysis. The mean level of 25-hydroxyvitamin D3 was (28 +/- 18.1) ng/mL, with an interquartile range of 16.92 - 35.45 ng/mL. The incidence of 25-hydroxyvitamin D3 insufficiency and deficiency was 47.01% (71/151) and 18.574% (28/151) respectively. The mean level of 1,25-dihydroxyvitamin D3 was (28.93 +/- 33.13) pg/mL, with an interquartile rang of 10.36 - 31.08 pg/mL. The incidence of 1,25-dihydroxyvitamin D3 insufficiency was 77.5% (117/151). Compared with the normal controls, the BMI, 24 h urine protein, CHO and LDL of those with Vitamin D deficiency increased significantly (P < 0.05). IMT ws associated with age, sex, and serum phosphorous. Coronary clcification was negative correlated with 1,25-dihydroxyvitamin D3. The incidence of vitamin D deficiency and insufficiency in DN patients is high. The patients with vitamin D deficiency have higher urinary protein, CHO and LDL. Corornary artery calcification is reversely correlated with 1,25(OH)2D3.


Increasing efficiency and reducing bias when assessing HPV vaccination efficacy by using nontargeted HPV strains.
Studies of vaccine efficacy often record both the incidence of vaccine-targeted virus strains (primary outcome) and the incidence of nontargeted strains (secondary outcome). However, standard estimates of vaccine efficacy on targeted strains ignore the data on nontargeted strains. Assuming nontargeted strains are unaffected by vaccination, we regard the secondary outcome as a negative control outcome and show how using such data can (i) increase the precision of the estimated vaccine efficacy against targeted strains in randomized trials and (ii) reduce confounding bias of that same estimate in observational studies. For objective (i), we augment the primary outcome estimating equation with a function of the secondary outcome that is unbiased for zero. For objective (ii), we jointly estimate the treatment effects on the primary and secondary outcomes. If the bias induced by the unmeasured confounders is similar for both types of outcomes, as is plausible for factors that influence the general risk of infection, then we can use the estimated efficacy against the secondary outcomes to remove the bias from estimated efficacy against the primary outcome. We demonstrate the utility of these approaches in studies of HPV vaccines that only target a few highly carcinogenic strains. In this example, using nontargeted strains increased precision in randomized trials modestly but reduced bias in observational studies substantially.


Intraplacental Choriocarcinoma: Rare or Underdiagnosed? Report of 2 Cases Diagnosed after an Incomplete Miscarriage and a Preterm Spontaneous Vaginal Delivery.
Intraplacental choriocarcinoma is a rare malignant tumor diagnosed after an abortion, an ectopic pregnancy, or a term or preterm pregnancy or following the diagnosis of a hydatidiform mole. During pregnancy, it may be more common than reported, as most patients are asymptomatic and placental choriocarcinomas are usually inconspicuous macroscopically and are often mistaken for an infarct. Based upon a case study methodology, we describe 2 cases of intraplacental choriocarcinoma: the first case was identified in the product of a uterine curettage following an incomplete miscarriage and the second in one of the placentas of a bichorionic twin pregnancy. Maternal investigation did not reveal evidence of metastatic disease and neither did the infants' one in the second case. The two cases underwent maternal surveillance with serum hCG and remained disease-free until the present. In conclusion, intraplacental choriocarcinoma is easily underdiagnosed but with current treatment, even in the presence of metastasis, the prognosis is excellent. A routine microscopic examination of all the placentas and products of miscarriage can increase the real incidence of this entity and consequently improve its management.


[Demonstration and topographical distribution of LHRH receptors in the central nervous system in the normal and castrated male rat].
The topographical distribution of [125I]-LHRH binding sites was studied on brain sections of adult male rat by quantitative autoradiography. High density of sites was observed in the hippocampus, amygdala and entorhinal cortex (4-7 fmol of LHRH bound/mg protein). Lower density of sites was observed in the septum and frontal cortex. The receptor density was not significantly modified at day 5 following castration. Under the same conditions the pituitary receptors were significantly increased. The presence of specific LHRH binding sites in the limbic system may explain the behavioural effect observed following intracerebroventricular injection of LHRH. However, their functions under physiological conditions remain to be elucidated.


In Vivo Fate of Carbon Nanotubes with Different Physicochemical Properties for Gene Delivery Applications.
Gene therapy has arisen as a pioneering technique to treat diseases by direct employment of nucleic acids as medicine. The major historical problem is to develop efficient and safe systems for the delivery of therapeutic genes into the target cells. Carbon nanotubes (CNTs) have demonstrated considerable promise as delivery vectors due to their (i) high aspect ratio and (ii) capacity to translocate through plasma membranes, known as the nanoneedle effect. To leverage these advantages, close attention needs to be paid to the physicochemical characteristics of the CNTs used. CNTs with different diameters (thinner and thicker) were treated by chemical oxidation to produce shorter fragments. Rigid (thick) and flexible (thin) CNTs, and their shortened versions, were coated with polyallylamine (ppAA) by plasma-enhanced chemical vapor deposition. The ppAA coating leads to a positively charged CNT surface that is able to electrostatically bind the green fluorescent protein plasmid reporter. This study shows how rigidity and length can affect their (i) behavior in biological media, (ii) ability to transfect in vitro, and (iii) biodistribution in vivo. This study also generates a set of basic design rules for the development of more efficient CNT-based gene-delivery vectors.


Active-site architecture of endopolygalacturonase I from Stereum purpureum revealed by crystal structures in native and ligand-bound forms at atomic resolution.
Crystal structures of endopolygalacturonase from Stereum purpureum were solved in native and two galacturonic acid complex states at atomic resolution. Endopolygalacturonase catalyzes the hydrolysis of alpha-1,4-glycosidic linkage of polygalacturonate in pectin. The native structure was determined by the multiple wavelength anomalous dispersion method and was refined anisotropically with SHELXL-97, with an R factor of 11.4% and an R(free) factor of 14.0% at 0.96 A resolution. The enzyme folds into a right-handed parallel beta-helix with 10 complete turns. The crystal structures of its binary complex with one D-galacturonate and its ternary complex with two D-galacturonates were also determined to identify the substrate binding site at 1.0 and 1.15 A resolutions, respectively. In the binary complex, one beta-D-galactopyranuronate was found in the +1 subsite, thus proving the strong affinity of the +1 subsite expected from the bond cleavage frequency on oligogalacturonates. In the ternary complex, an additional beta-D-galactofuranuronate was found in the -1 subsite. In both subsites, the recognition of the galacturonate carboxy group is important in galacturonate binding. In the +1 subsite, the carboxy group interacts with three basic residues, His195, Arg226, and Lys228, which were conserved in all endopolygalacturonases. In the -1 subsite, the unique nonprolyl cis-peptide bond is believed to be involved in binding the carboxy group of the substrate. The active site architecture of the complexes provides insight into the mechanism of inverting glycosyl hydrolases and also sheds light on the basis of the differences between the family 28 and the other inverting glycosyl hydrolases.