[Effect of emodin on pancreatic fibrosis: experiment with rats].
To study the effect of emodin on pancreatic fibrosis and potential mechanism thereof. Fifty SD rats were randomly divided into 5 equal groups: normal control group, model control group, low-dose emodin-treated group, mediate-dose emodin-treated group, and high-dose emodin-treated group. The rats of the latter 4 groups underwent infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duct so as to establish models of pancreatic fibrosis. The emodin-treated rats were fed with different doses of emodin (20, 40, and 80 mg/kg body weight), while the normal and model control groups received 0.9% sodium chloride solution instead. Twenty-eight days later the rats were killed, blood samples were collected, and their pancreases were taken out. The serum levels of hyaluronic acid (HA) and laminin (LN) were determined by radioimmunoassay. The histopathological alterations were studied by optical microscopy. The expression of collagen was examined by Van Gieson staining. Western blotting was used to detect the protein expression of transforming growth factor-beta(1) (TGF-beta(1)). (1) The serum level of HA of the low-dose, mediate-dose, and high-dose emodin-treated groups were 87 microg/L +/- 22 microg/L, 78 microg/L +/- 25 microg/L, and 62 microg/L +/- 19 microg/L respectively, all significantly lower than that of the model control group (113 microg/L +/- 27 microg/L, P < 0.05 or < 0.01). The serum levels of laminin in the low-dose, mediate-dose, and high-dose emodin-treated groups were 67 microg/L +/- 14 microg/L, 57 microg/L +/- 12 microg/L, and 44 microg/L +/- 10 microg/L respectively, all significantly lower than that of the model control group (86 microg/L +/- 17 microg/L, P < 0.05 or P < 0.01); (2) The degrees of fibrosis of the emodin-treated groups were obviously ameliorated in comparison with the model control group, the higher the dose of emodin the more improved the pathological changes, especially in the high-dose emodin-treated group (P < 0.05). (3) The percentages of collagen positive cells of the low-dose, mediate-dose, and high-dose emodin-treated groups were 39% +/- 7%, 38% +/- 4%, and 36% +/- 5% respectively, all lower than that of the model control group (42% +/- 6%), with a significant difference between the high-dose emodin-treated group and the model control group (P < 0.05). (4) The protein content of TGF-beta(1) of the low-dose, mediate-dose, and high-dose emodin-treated groups were 44.3% +/- 2.1%, 39.2% +/- 1.8%, and 28.8% +/- 1.6% respectively, all significantly lower than that of the model control group (60.7% +/- 1.7%, all P < 0.05), and the protein content of TGF-beta(1) of the high-dose emodin-treated group was significantly lower than those of the other 2 emodin-treated groups (both P < 0.05). Emoidn has an anti-fibrosis effect on pancreatic fibrosis, which maybe related to the content of TGF-beta(1) protein.


Equilibriumizing all food chain chaos through reproductive efficiency.
The intraspecific interference of a top-predator is incorporated into a classical mathematical model for three-trophic food chains. All chaos types known to the classical model are shown to exist for this comprehensive model. It is further demonstrated that if the top-predator reproduces at high efficiency, then all chaotic dynamics will change to a stable coexisting equilibrium, a novel property not found in the classical model. This finding gives a mechanistic explanation to the question of why food chain chaos is rare in the field. It also suggests that high reproductive efficiency of top-predators tends to stabilize food chains.


Vaginal Drug Delivery Systems to Control Microbe-Associated Infections.
The vagina has been regarded as a crucial route for drug delivery. Despite the wide range of available vaginal dosage forms for vaginal infection control, poor drug absorptivity remains a significant challenge due to various biological barriers in the vagina, such as mucus, epithelium, immune systems, and others. To overcome these barriers, different types of vaginal drug delivery systems (VDDSs), with outstanding mucoadhesive, mucus-penetrating properties, have been designed to enhance the absorptivity of vagina-administered agents in the past decades. In this Review, we introduce a general understanding of vaginal administration, its biological barriers, the commonly used VDDSs, such as nanoparticles and hydrogels, and their applications in controlling microbe-associated vaginal infections. Additionally, further challenges and concerns regarding the design of VDDSs will be discussed.


What can crystal structures of aminergic receptors tell us about designing subtype-selective ligands?
G protein-coupled receptors (GPCRs) are integral membrane proteins that represent an important class of drug targets. In particular, aminergic GPCRs interact with a significant portion of drugs currently on the market. However, most drugs that target these receptors are associated with undesirable side effects, which are due in part to promiscuous interactions with close homologs of the intended target receptors. Here, based on a systematic analysis of all 37 of the currently available high-resolution crystal structures of aminergic GPCRs, we review structural elements that contribute to and can be exploited for designing subtype-selective compounds. We describe the roles of secondary binding pockets (SBPs), as well as differences in ligand entry pathways to the orthosteric binding site, in determining selectivity. In addition, using the available crystal structures, we have identified conformational changes in the SBPs that are associated with receptor activation and explore the implications of these changes for the rational development of selective ligands with tailored efficacy.


Stem Cells, a New Generation Model for Predictive Nano Toxicological Assessment.
With the recent advancement in nanoscience and nanotechnology, there is a growing demand for assessment of the toxicological effects of nano materials to humans and other biological systems. And a predictive toxicology approach that uses in vitro screening assays in conjunction with in vivo study results are widely employed in nano safety evaluation. In recent years stem cells have gained wide attention in the scientific community owing to their potential benefits for various applications in health care systems. Stem cells are undifferentiated cells that have high replicative potential and multilineage differentiation capacity. And therefore, stem cells could be exploited for developing in vitro model systems to study nanomaterials interaction with the biological systems and a potential tool to predict toxicity in humans. The details provided in this article will give an overview of optimizing stem cell technology in predicting the toxicity of nano materials the essential features of the article.


Synthesis of Chiral γ-Lactams via in Situ Elimination/Iridium-Catalyzed Asymmetric Hydrogenation of Racemic γ-Hydroxy γ-Lactams.
Chiral γ-lactams have been synthesized in excellent yields and enantioselectivities (up to 99% yield and 96% ee) from easily accessible racemic γ-hydroxy γ-lactams via an iridium-phosphoramidite catalyzed asymmetric hydrogenation. The reaction was designed based on insight into the reaction mechanism demonstrated in previous work and can be carried out at a reduced catalyst loading of 0.1 mol % on a gram scale. Several potential bioactive compounds can be synthesized from the reduced products. Mechanistic studies indicated that the reduced products were obtained via the hydrogenation of the N-acyliminium cations, generated from γ-hydroxy γ-lactams.


Semantically enabling clinical decision support recommendations.
Clinical decision support systems have been widely deployed to guide healthcare decisions on patient diagnosis, treatment choices, and patient management through evidence-based recommendations. These recommendations are typically derived from clinical practice guidelines created by clinical specialties or healthcare organizations. Although there have been many different technical approaches to encoding guideline recommendations into decision support systems, much of the previous work has not focused on enabling system generated recommendations through the formalization of changes in a guideline, the provenance of a recommendation, and applicability of the evidence. Prior work indicates that healthcare providers may not find that guideline-derived recommendations always meet their needs for reasons such as lack of relevance, transparency, time pressure, and applicability to their clinical practice. We introduce several semantic techniques that model diseases based on clinical practice guidelines, provenance of the guidelines, and the study cohorts they are based on to enhance the capabilities of clinical decision support systems. We have explored ways to enable clinical decision support systems with semantic technologies that can represent and link to details in related items from the scientific literature and quickly adapt to changing information from the guidelines, identifying gaps, and supporting personalized explanations. Previous semantics-driven clinical decision systems have limited support in all these aspects, and we present the ontologies and semantic web based software tools in three distinct areas that are unified using a standard set of ontologies and a custom-built knowledge graph framework: (i) guideline modeling to characterize diseases, (ii) guideline provenance to attach evidence to treatment decisions from authoritative sources, and (iii) study cohort modeling to identify relevant research publications for complicated patients. We have enhanced existing, evidence-based knowledge by developing ontologies and software that enables clinicians to conveniently access updates to and provenance of guidelines, as well as gather additional information from research studies applicable to their patients' unique circumstances. Our software solutions leverage many well-used existing biomedical ontologies and build upon decades of knowledge representation and reasoning work, leading to explainable results.


Recommending blue ocean technologies for subcontractors: A framework based on business reports of prime contractors and patents.
Subcontractors depend heavily on their prime contractor and thus find it very risky to enter a new business on their own. This study proposes a framework for these subcontractors to develop blue ocean technologies related to their prime contractor. First, the primary technologies predicted to be promising are extracted from the business reports of the prime contractor. Sub-technologies are then selected through a patent-based search using keywords and International Patent Classification codes of the primary technologies. From them, blue ocean technologies are proposed by optimizing the weighted mean of the min-max normalized market value, degree of competition in the technology market, and subcontractors' potential technological capabilities for each sub-technology. This study shows that subcontractors can enhance their technology competitiveness by finding a low-risk blue ocean technology. Our empirical research on the subcontractors of a semiconductor firm identified technological patent fields for them to pursue. From our framework, subcontractors can identify blue ocean technologies by considering their prime contractor's future industrial areas and technologies of interest as well as their own technological capabilities. Furthermore, the prime contractors can gain the synergy effect of technology expansion through cooperation.


(E)-1-(4-Amino-phen-yl)-3-(naphthalen-2-yl)prop-2-en-1-one.
The mol-ecule of the title chalcone derivative, C(19)H(15)NO, exists in a trans configuration with respect to the C=C double bond. The mol-ecule is slightly twisted with a dihedral angle of 6.12 (12)° between the benzene ring and the naphthalene ring system. The prop-2-en-1-one bridge is nearly planar, with an r.m.s. deviation of 0.0194 (2), and makes dihedral angles of 8.05 (19) and 11.47 (18)° with the benzene ring and the naphthalene ring system, respectively. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds into chains along the b axis. Weak N-H⋯π and C-H⋯π inter-actions and a short N⋯O contact [2.974 (4) Å] are also observed.


Molecular cloning, gene expression in albino mutants and gene knockdown studies of tyrosinase mRNA in rainbow trout.
Tyrosinase has a role in melanin synthesis and several defects of the tyrosinase gene lead to albinism. Here, we cloned and characterized rainbow trout tyrosinase cDNAs and carried out the molecular and biochemical characterization of albino mutants. Two types of cDNA were cloned: tyrosinase-1 (Tyr-1) and tyrosinase-2 (Tyr-2). Both contained regions predicted to encode structural features of tyrosinase, and phylogenetic analysis confirmed that Tyr-1 and Tyr-2 were members of the tyrosinase family. Tyr-1 transcripts were first detected in embryos at 5 d post-fertilization (dpf) and Tyr-2 transcripts at 15 dpf. 3,4-dihydroxyphenylalanine assays revealed significantly reduced tyrosinase activities in dominant and recessive albino mutants compared with wild-type embryos. However, reverse-transcription PCR showed no differences in the amounts or lengths of the coding regions of Tyr-1 and Tyr-2 transcripts between wild-type embryos and albino mutants. Antisense morpholino oligonucleotides (AMOs) designed to knockdown tyrosinase gene expression in wild-type embryos led to reduced pigmentation in the retina and skin of embryos at 25 and 35 dpf, respectively. Furthermore, the tyrosinase activities of AMO-treated embryos were significantly reduced. We conclude that both Tyr-1 and Tyr-2 are crucial for melanin synthesis in rainbow trout embryos. Furthermore, we describe a potential application of AMOs in the treatment of hyperpigmentation.


[Psychoneurological and degenerative-dystrophic disorders in patients with pathology of the temporomandibular joint].
The aim of the study is to detail neuropsychiatric and degenerative-dystrophic disorders in patients with dysfunctional TMJ syndrome and develop principles for their correction. 84 patients with complaints of impaired TMJ function were examined: 14 men (16.67%) and 70 women (83.33%) aged 18 to 74 years. The average age of the patients was 63.22±18.82 years. The analysis of the dental status was carried out, the state of the musculoskeletal system and somatic status in patients with dysfunctional TMJ syndrome was studied. Methods of diagnosis of autonomic dysfunction syndrome were used to assess the state of neuropsychiatric status. Occlusive disorders were evaluated in relation to the peculiarities of maintaining posture and autonomic joint dysfunction. Occlusive disorders were assessed in relation to the peculiarities of posture maintenance and autonomic dysfunction of the joint. Pathology of the temporomandibular region was accompanied by psychovegetative disorders in 80% of patients. At the same time, autonomic dysfunction was diagnosed with pathological changes in the autonomic index, the formation of anxiety and depression. The adequacy of rehabilitation measures was associated with the preparation of rehabilitation programs, considering the severity of dental pathology, the state of the somatic and emotional-volitional spheres. Elimination of musculo-articular dysfunctions and pain syndrome was of leading importance in the rehabilitation of patients.


Advances in the management of leg ulcers--the potential role of growth factors.
Venous ulcers are a major health problem because of the increased costs of the treatment and the refractory nature of the ulcers. The treatment cost is estimated to be around 1 billion dollars per year in the United States (US), and the average cost for one patient over a lifetime exceeds dollars 400,000. There has been an increasing trend in the use of growth factors in their management. Genetic engineering has revolutionised the research of wound healing, as the majority of recombinant growth factors are now available for in vitro and in vivo studies. Online searches of Medline, Pub Medical and Embase were carried out using the terms venous ulcers, leg ulcers, growth factors and growth hormone. The literature regarding the potential role of growth factors in the management of leg ulcers is reviewed. The important clinical studies are critically analysed with a view to appreciate the emerging therapies and the further research possibilities in the management of venous leg ulcers. Clinical results with the use of growth factors in non-healing wounds are encouraging. However, small sample sizes and inconsistent end points in different clinical studies have been the main hurdle in reaching a definite conclusion. Further research is needed to provide the definite evidence. Future developments may include different delivery methods for the growth factors, use of different combinations of growth factors administered simultaneously or, sequentially, bioengineered skin grafts and chemical induction of angiogenesis with the use of gene transfer techniques.


Prognostic Significance of Nuclear β-Catenin Expression in Patients with Colorectal Cancer from Iran.
Beta catenin plays a key role in cancer tumorigenesis. However, its prognostic significance in patients with colorectal cancer (CRC) remains controversial. It has been demonstrated that 90% of all tumors have a mutation in individual components of multiple oncogenes in Wnt/β-catenin pathway. Accumulation of nuclear β-catenin in cytoplasm leads to uncontrolled cell proliferation. Thus, nuclear β-catenin accumulation may be a valuable biomarker associated with invasion, metastasis and poor prognosis of CRC. In this study the prognostic value of beta catenin expression in 165 Iranian CRC patients was evaluated. In this cross sectional retrospective study immunohistochemistry analyses of formalin-fixed paraffin-embedded (FFPE) tumor tissues were performed to characterize the expression of nuclear β-catenin in a series of 165 Iranian patients with colorectal carcinoma. Heat-induced antigen retrieval using the microwave method was applied for all staining procedures. Staining was scored independently by two observers, and a high level of concordance (90%) was achieved. Statistical analysis was done using the SPSS software for Windows, version 13.0.0 (SPSS Inc., Chicago, IL). Two-tailed P < 0.05 was considered statistically significant. The patients consisted of 85 males and 80 females. Eighty-eight patients had primary tumor of the rectum and sigmoid, while 77 patients had primary tumor of the colon. The mean period of follow-up was 47.2 ± 10 months and the median period of follow-up was 38 months (range 6 - 58) for each patient. Of 165 tumors, 32 tumors (19.39 %) showed expression of β-catenin and 133 (80.6 %) were negative for β-catenin expression. Based on our findings the distribution of Microsatellite Instability (MSI) status differed between patients with nuclear β-catenin positive and negative tumors and this difference was significant (P = 0.001). Patients with nuclear β-catenin positive expression profile were found to be younger than patients with negative nuclear β-catenin expression (P = 0.010). Univariate and multivariate analysis showed that tumors with β-catenin expression had a poorer prognosis compared to tumors without β-catenin expression. According to our findings, the distribution of nuclear b-catenin expression is a poor prognostic marker in patients with colon cancer.


[Carboxypeptidases from different microbiolorganisms].
Experiments were performed to detect "alkali" and "acid" carboxypeptidases in 39 enzymic preparations from fungi, yeast, actinomyces, bacteria and algae. Distribution of both types of carboxypeptidases is different: they are absent in the six of the studied sources, there are no "acid" carboxypeptidases in 11 sources and no "alkali" in nine ones. The largest amount of carboxypeptidases is in the objects from fungi and actinomycetes, the least, in those from bacteria and algae. There is no correlation between synthesis of these enzymes by one microorganism. Thus, fungi produce mainly "acid" enzymes, and actinomycetes only "alkali" ones. Asp. oryzae and Asp. flavus are powerful producers of the former, Streptomyces griseus of the latter. Specific activities 15-20 times as high as all the already studied ones are obtained for the preparations isolated from Str. griseus (protezym, proteinase-1, proteinase-3, crystal line complex of proteases). Carboxypeptidase of Str. griseus is relatively stable in comparison with "acid" ones in purification and concentration.


Stillborn Infants: Associated Malformations.
Stillbirth, defined as death of a fetus in utero after 20 weeks of gestation, occurs in 1 to 2% of pregnancies in the United States. Many of these stillborn infants have associated malformations, including chromosome abnormalities, neural tube defects, and malformation syndromes. Other causes are abnormalities of the placenta and maternal conditions, such as pre-eclampsia and obesity. A consecutive sample of malformed stillborn infants can establish the relative frequency and severity of the associated malformations. Stillbirths were identified in the Active Malformations Surveillance Program at Brigham and Women's Hospital (1972-2012). The findings at autopsy, including the findings in the placenta and the results of diagnostic studies, were compiled. One hundred twenty-seven stillborn infants with malformations were identified at autopsy among 289,365 pregnancies, including trisomies 21, 18, and 13; 45,X; triploidy; anencephaly; lower urinary tract obstruction; holoprosencephaly and severe heart defects, such as hypoplastic left heart syndrome and tetralogy of Fallot with pulmonary atresia. The severity of the abnormalities in stillborn infants was more severe than the spectrum of abnormalities identified in live-born infants. An autopsy of the stillborn fetus, including chromosome microarray and an examination of the placenta, can identify the underlying causes of the stillbirth. This review of stillborn fetuses with malformations showed that several different lethal malformations and heart defects are more common than among live-born infants. These postmortem examinations can improve the counseling of the parents about risks in future pregnancies. Birth Defects Research 110:114-121, 2018.© 2018 Wiley Periodicals, Inc.


Anomalous grazing incidence small-angle x-ray scattering studies of platinum nanoparticles formed by cluster deposition.
The size evolution of platinum nanoparticles formed on a SiO2/Si(111) substrate as a function of the level of surface coverage with deposited clusters has been investigated. The anisotropic shapes of sub-nanometer-size nanoparticles are changed to isotropic on the amorphous substrate as their sizes increased. Using anomalous grazing incidence small-angle x-ray scattering (AGISAXS), the scattering from nanoparticles on the surface of a substrate is well separated from that of surface roughness and fluorescence. We show that AGISAXS is a very effective method to subtract the background and can provide unbiased information about particle sizes of less than 1 nm.


Developing synthetic conical nanopores for biosensing applications.
In this review we bring together recent results from our group focused towards the development of biosensors from single conically-shaped artificial nanopores. The nanopores, used in the work presented here, were prepared using the track-etch process. The fabrication of track-etched conical nanopores has been optimized to allow for single nanopores with reproducible dimensions to be prepared. We have also demonstrated techniques that allow for easy and controllable manipulation of nanopore geometry (e.g., cone angle). We will consider the ion transport properties of the conical nanopores and factors that affect these properties. Methods for introducing functions that mimic biological ion channels, such as voltage-gating, into these nanopores will also be addressed. Three prototype sensors developed from single conical nanopores will be presented. In the first two sensors, the single conical nanopores function as resistive-pulse sensors and detect the presence of analytes as current-blockade events in the ion current. The third sensor functions in an on/off mode, much like a ligand-gated ion channel. In the presence of a target analyte, the ion current permanently shuts off.


Isolation and characterization of nanocrystalline cellulose from roselle-derived microcrystalline cellulose.
Roselle fiber is a renewable and sustainable agricultural waste enriched with cellulose polysaccharides. The isolation of Nanocrystalline cellulose (NCC) from roselle-derived microcrystalline cellulose (MCC) is an alternative approach to recover the agricultural roselle plant residue. In the present study, acid hydrolysis with different reaction time was carried out to degrade the roselle-derived MCC to form NCC. The characterizations of isolated NCC were conducted through Fourier Transform Infrared Ray (FTIR), Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FESEM), Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS), Energy Dispersive Spectroscopy (EDS), X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). As evaluated from the performed morphological investigations, the needle-like shape NCC nanostructures were observed under TEM and AFM microscopy studies, while irregular rod-like shape of NCC was observed under FESEM analysis. With 60min hydrolysis time, XRD analysis demonstrated the highest NCC crystallinity degree with 79.5%. In thermal analysis by TGA and DSC, the shorter hydrolysis time tended to produce NCC with higher thermal stability. Thus, the isolated NCC from roselle-derived MCC has high potential to be used in application of pharmaceutical and biomedical fields for nanocomposite fabrication.


Current readings: Redefining minimally invasive: uniportal video-assisted thoracic surgery.
Minimally invasive surgery is clearly dominating the modern surgical era across multiple surgical subspecialties and thoracic surgery is no exception. Video-assisted thoracic surgery (VATS) is a well-established method of performing various interventions, and it continues to gain momentum. Though small differences in VATS methods exist, it is commonly accepted as a non-rib-spreading approach into the thoracic cavity via 2-4 incisions and allows for a wide range of anatomical and nonanatomical pulmonary resections. As more experience is gained with VATS, more complex surgeries take place and greater refinement of the technique occurs. A newer single-incision or uniportal VATS has been described to minimize surgical trauma, to decrease the number and size of thoracic incisions, to reduce the number of complications, and to enable faster recovery. It allows performing a full spectrum of thoracic operations through a single incision adhering to surgical and oncological principles without compromise.


Predictors of prolonged mechanical ventilation after aortic arch surgery with deep hypothermic circulatory arrest plus antegrade selective cerebral perfusion.
The predictors of prolonged mechanical ventilation after aortic arch surgery with deep hypothermic circulatory arrest have not been comprehensively evaluated. The present study was designed to identify variables associated with prolonged ventilation in a group of aortic arch surgery patients from a single center. A retrospective study. Prolonged mechanical ventilation was defined as >72 hours. Cardiovascular operating rooms and the intensive care unit. Adults requiring aortic arch surgery with deep hypothermic circulatory arrest plus antegrade selective cerebral perfusion. None. After 7 patients who underwent 1-stage total or subtotal aortic replacement were excluded, 255 patients were enrolled in the study. The average age of the patients was 44.7 +/- 10.8 years with male predominance (74.1%). Two hundred twenty-nine patients were extubated within 72 hours postoperatively, and 26 patients needed prolonged mechanical ventilation. Patients with prolonged mechanical ventilation had higher incidences of in-hospital mortality, stroke, and renal failure requiring dialysis and reintubation and stayed longer in the intensive care unit and hospital than those without prolonged ventilation (p < 0.05). In multivariate analysis, predictors of prolonged ventilation were found to be prolonged cardiopulmonary bypass time, advanced age, emergency, and preoperative serum creatinine level (p < 0.05). The authors identified 4 preoperative and intraoperative predictors associated with increased risk of prolonged mechanical ventilation. This is helpful to identify patients with increased risk for prolonged ventilation, develop preemptive strategies, and allocate medical resources.


EXPERIENCE WITH A DIABETIC SERVICE IN AN "OPEN" HOSPITAL.
A survey of the management of diabetes mellitus in an "open" hospital, Calgary General Hospital, was conducted in 1954 by reviewing the records of 100 consecutive diabetic admissions and by interviewing medical, nursing and dietetic staff members. The diabetic state was controlled satisfactorily by diet and insulin, but early diabetic complications and patient education tended to be overlooked by physicians. Diabetic management from the nursing, administrative and dietetic standpoints was considered to be inefficient, unpredictable and incomplete.In 1955 a comprehensive diabetic service was instituted which co-ordinated the activities of medical, nursing and dietetic staffs and provided for patient education. A repeat survey conducted in 1961, in which the records of 87 consecutive diabetic admissions were reviewed, showed marked improvement in all areas of diabetic patient care.Objections to voluntary conformity by staff members were surprisingly absent. The institution of a diabetic service is recommended for all hospitals as a means of improving diabetic care.


Nutrient deficiency and obstetrical outcomes in pregnant women following Roux-en-Y gastric bypass: A retrospective Danish cohort study with a matched comparison group.
Roux-en-Y gastric bypass surgery and small-for-gestational-age births are known to be associated although the etiology is not fully understood. This study aimed to investigate pregnancy outcomes and maternal nutritional status among pregnant women with a history of Roux-en-Y gastric bypass using maternal anemia and gestational weight gain as indicators of micronutrient and macronutrient deficiency in pregnancy. The study was designed as a retrospective matched cohort study. All Roux-en-Y-gastric-bypass-operated pregnant women (n=151) who were followed in the outpatient obstetric clinic at Aalborg University Hospital in Denmark and gave birth between 1 January 2010 and 31 December 2013 were included. Each Roux-en-Y-gastric-bypass-operated woman was closely matched with a non-Roux-en-Y-gastric-bypass-operated woman. Primary outcomes were small-for-gestational-age birth, maternal anemia and gestational weight gain. The two groups (matched 1:1) were compared by paired tests on all measures, conditional logistic regression for paired binary data and the paired t-test or Wilcoxon signed-rank test for paired continuous data. The risk of small-for-gestational-age birth (odds ratio (OR)=2.67, 95% confidence interval (CI); 1.04-6.82) and maternal anemia (OR=3.0, 95% CI; 1.09-8.25) were significantly increased for the Roux-en-Y gastric bypass group compared to the non-Roux-en-Y gastric bypass group. No significant difference was found in gestational weight gain (p=0.169) between women with a history of Roux-en-Y gastric bypass (11.51kg±8.97 standard deviation (SD)) and non- Roux-en-Y-gastric-bypass-operated women (12.18kg±6.28 SD). A history of Roux-en-Y gastric bypass surgery increases the risk of small-for-gestational-age birth and anemia, while a finding of differences in gestational weight gain is uncorroborated. Our findings suggest a role of micronutrient deficiency rather than reduced gestational weight gain in the etiology of small-for-gestational-age birth among women with a history of Roux-en-Y gastric bypass surgery.


Biochemical studies in the evaluation and management of osteoporosis: current status and future prospects.
To examine the current status of biochemical markers of bone remodeling and to offer a perspective on their future clinical applications. We provide a comprehensive overview of the bone remodeling cycle, the hormonal control of bone remodeling, the specific biochemical markers of bone resorption and bone formation, and their current clinical applications. Bone remodeling occurs in discrete packets, known as bone modeling units, on the surfaces of the skeleton. Osteoclasts are responsible for bone resorption, and osteoblasts are responsible for bone formation. Bone resorption and formation are normally coupled, and an imbalance in these processes can lead to metabolic bone diseases such as osteoporosis. Investigators have attempted to measure various biochemical markers of bone resorption (such as urine calcium and hydroxyproline) and formation (such as bone-specific alkaline phosphatase and osteocalcin) as a reflection of response to therapy. Although several markers of bone resorption and formation can be assayed, an ideal marker has yet to be discovered or proved. Until a precise, inexpensive assay is developed, currently available biochemical markers, used in conjunction with measurements of bone density, are considered the most reasonable tools for classifying and directing the management of osteoporosis.


DABTZ as a new reagent for solid phase extraction and spectrophotometric determination of trace amount of Hg(II) in water sample.
A novel sensitive and simple method for rapid and selective extraction, preconcentration and determination of mercury as its 2,2' diamino-4,4' bithiazole (DABTZ) complex by using octadecylsilica cartridges and spectrophotometry is presented. Extraction efficiency and the influence of flow rates of sample solution and eluent, pH, amount of DABTZ, type and least amount of eluent for elution of mercury complex from cartridges, break through volume and limit of detection were evaluated. Also the effects of various cationic and anionic interferences on percent recovery of mercury were studied. Average extraction efficiency > 90% was obtained by elution of the cartridge with minimal amount of solvent in the presence of interferences. A preconcentration factor of 152 and a detection limit of 10.92 ng mL(-1) were obtained. The method was applied to the recovery and determination of mercury in different water samples.


Identification of non-heme diiron proteins that catalyze triple bond and epoxy group formation.
Acetylenic bonds are present in more than 600 naturally occurring compounds. Plant enzymes that catalyze the formation of the Delta12 acetylenic bond in 9-octadecen-12-ynoic acid and the Delta12 epoxy group in 12,13-epoxy-9-octadecenoic acid were characterized, and two genes, similar in sequence, were cloned. When these complementary DNAs were expressed in Arabidopsis thaliana, the content of acetylenic or epoxidated fatty acids in the seeds increased from 0 to 25 or 15 percent, respectively. Both enzymes have characteristics similar to the membrane proteins containing non-heme iron that have histidine-rich motifs.


Transcription of fractionated calf thymus chromatin by RNA polymerase of calf thymus and Escherichia coli.
Calf thymus chromatin has been sheared and fractionated on sucrose gradients. Approximately 5-10% of the chromatin is resolved from the bulk of the imput chromatin as a slowly sedimenting fraction. The protein/DNA ratio of the slowly sedimenting fraction is not greatly different from the protein/DNA ratio of the more rapidly sedimenting chromatin fraction. Analysis of DNA of the chromatin fractions by CsC1 equilibrium density gradient centrifugation indicates that DNA of the slowly sedimenting fraction is depleted in the satellite DNA banding at 1.716 g/cm3. The template properties of the chromatin fractions have been examined with Escherichia coli RNA polymerase and form II and form III RNA polymerases of calf thymus. At rate-limiting concentrations, the slowly sedimenting fraction is twofold more active than the rapidly sedimenting fraction as a template for E. coli RNA polymerase. Homologous form II and form III RNA polymerases are respectively 30-fold and 16-fold more active with the slowly sedimenting fraction than the rapidly sedimenting fraction. The activity of form II RNA polymerase in transcribing the slowly sedimenting fraction exceeds its activity in transcribing an equal concentration of native DNA. Kinetic studies, in which RNA polymerase activity is assayed at various concentrations of chromatin, indicate that the greater activity of E. coli RNA polymerase with the slowly sedimenting fraction is due to an increased rate of transcription at saturating concentrations of template (Vmax), and is not due to a lower concentration required for half-maximal rate of transcription (Km). In contrast, the increased rates of transcription of the slowly sedimenting chromatin faction by the homologous polymerases are due to a decrease in concentration required for half-maximal rate of transcription rather than an increased rate of transscription at saturation concentrations of template. The relative degrease of satellite DNA in the slowly sedimenting fraction of chromatin and the enhanced template activity of the slowly sedimenting fraction suggest that this fraction is equivalent to nuclear euchromatin while the more rapidly sedimenting chromatin is equivalent to nuclear heterochromatin.


Papular (erosive) herpes genitalis. A clinical variant in sarcoid and pregnancy.
A unique papular (erosive) variant of herpes genitalis is described in a patient with sarcoid and in 1 who was pregnant. The occurrence of this unique expression of herpes infection in two conditions associated with immunologic changes seems more than incidental. It is suggested that patients presenting with papular (erosive) herpes genitalis be studied for underlying immune deficiency.


Biomimetic Hybridization of Kevlar into Silk Fibroin: Nanofibrous Strategy for Improved Mechanic Properties of Flexible Composites and Filtration Membranes.
Silk, one of the strongest natural biopolymers, was hybridized with Kevlar, one of the strongest synthetic polymers, through a biomimetic nanofibrous strategy. Regenerated silk materials have outstanding properties in transparency, biocompatibility, biodegradability and sustainability, and promising applications as diverse as in pharmaceutics, electronics, photonic devices and membranes. To compete with super mechanic properties of their natural counterpart, regenerated silk materials have been hybridized with inorganic fillers such as graphene and carbon nanotubes, but frequently lose essential mechanic flexibility. Inspired by the nanofibrous strategy of natural biomaterials (e.g., silk fibers, hemp and byssal threads of mussels) for fantastic mechanic properties, Kevlar was integrated in regenerated silk materials by combining nanometric fibrillation with proper hydrothermal treatments. The resultant hybrid films showed an ultimate stress and Young's modulus two times as high as those of pure regenerated SF films. This is not only because of the reinforcing effect of Kevlar nanofibrils, but also because of the increasing content of silk β-sheets. When introducing Kevlar nanofibrils into the membranes of silk nanofibrils assembled by regenerated silk fibroin, the improved mechanic properties further enabled potential applications as pressure-driven nanofiltration membranes and flexible substrates of electronic devices.


[Preclinical AD and Biomarker; from J-ADNI to AMED Preclinical Study].
Alzheimer's disease (AD) is most prevalent cause of dementia and no cure has been discovered. Although the framework of AD clinical trials is being established utilizing results of large-scale observational studies such as the AD Neuroimaging Initiative (ADNI) and the Japanese-ADNI (J-ADNI), the development of disease-modifying therapy for Alzheimer's disease (AD) has not yet been achieved. Preclinical AD was recently defined as a new disease stage in which AD is asymptomatic but biomarkers suggest the presence of amyloid pathology. Preclinical AD has been focused as promising therapeutic time window and establishment of reliable biomarkers for preclinical AD is an urgent task. The Japanese Agency for Medical Research and Development (AMED) preclinical study is a nationwide multicenter observational study carried out by public research funding from AMED as a successor to the J-ADNI study. The goal of this study is to establish a biomarker that can quantitatively evaluate the disease progression of preclinical AD and mild cognitive impairment (MCI) or predict the progression to MCI and dementia in the future. To achieve this goal, the following assessments will be conducted over time for three years: clinical evaluations; cognitive tests; genetic testing; body fluid biomarker tests; and imaging biomarker studies such as MRI, FDG-PET, and amyloid PET. The obtained data will eventually be released to the public database.


[Radiotherapy in cancer of the rectum].
The response of adenocarcinoma of rectum to radiotherapy is dependent on the use of irradiation techniques that ensure a sufficient dose be applied to the tumor without exceeding tolerance limits of pelvic tissues. This has been clearly demonstrated by results of contact radiotherapy over the last 30 years or so. Doses of about 100 Gy provide local control in 90% of cases and a 5 year survival rate of 80% in patients with highly selected tumors. For several years now, contact radiotherapy has been associated with external irradiation and iridium therapy with resulting sterilization of T2 and even T3 or N1 tumors in inoperable cases. Endorectal ultrasound imaging is essential for selecting those patients requiring radiotherapy alone and for evaluating the results, but in more than 90% of patients, surgery remains basic treatment for cancer of rectum. The incidence of local recurrence, very difficult to treat, is non negligible, however, but combining radiotherapy with surgery has been shown to reduce the rate of by 50%. Opinions differ on the relative efficacy of pre- or post-operative radiotherapy, but tolerance to this treatment is good in both cases if the technique used limits radiation to the posterior pelvis. Results of a Swedish randomized trial demonstrated greater efficacy for pre-operative radiotherapy for controlling local spread. Meta analysis showed that irradiation produces a definite gain in local control with a resulting gain in survival of about 5 to 10%. In the USA, chemotherapy based on 5 FU combined with post-operative radiotherapy was equally favorable in terms of survival. Pre-operative radiotherapy may also increase the chance of conservation of the sphincter. Although numerous points concerning chronology and mode of treatment remain open to discussion, a combination of radiotherapy and surgery now appears as standard treatment for rectal cancer.


A subset of acute lymphoblastic leukemia with co-expression of myeloid antigens: prevalence and clinical significance.
In order to evaluate the biological features and clinical significance of myeloid antigen expression in acute lymphoblastic leukemia (ALL), immunophenotype analysis was performed on leukemic cells from 160 patients diagnosed as ALL by the French, American and British (FAB) criteria using a comprehensive panel of monoclonal antibodies to lymphoid and myeloid associated antigens. Expression of myeloid antigens was found in 32 cases (20%), including 11 out of 49 adults (22.4%) and 21 out of 111 children (18.9%). CD33 was positive in 18 patients (11.3% of the total cases), CD13 in 15 patients (9.4%), CD 11b in 12 patients (7.5%) and CD14 in 1 patient (0.6%). Nine patients expressed two or more myeloid antigens. There were no significant differences in clinical manifestations and hematological pictures between the ALL patients with myeloid antigen expression (My+ ALL) and those without (My- ALL). No consistent chromosomal abnormality was found in My+ ALL. Eighty percent of the childhood and 44.4% of the adult My+ ALL patients achieved complete remission, compared with 87% and 80%, respectively, for childhood and adult My- ALL, but the differences were not statistically significant. After a median follow-up of 2.1 years, there were also no statistically significant associations between myeloid antigen expression and shorter duration of remission or poorer survival rate for patients with both adult and childhood ALL.


First passage times of driven DNA hairpin unzipping.
We model the dynamics of voltage-driven transport of DNA hairpins through transmembrane channels. A two-dimensional stochastic model of the DNA translocation process is fit to the measurements of Mathé, who pulled self-hybridized DNA hairpins through lipid-embedded alpha-hemolysin channels. As the channel was too narrow to accommodate hybridized DNA, dehybridization of the hairpin became the rate-limiting step of the transport process. We show that the mean first passage time versus voltage curve for the escape of the DNA from the transmembrane channel can be divided into two regions: (1) a low-voltage region where the DNA slides out of the pore in reverse and without undergoing significant dehybridization, and (2) a region where the DNA dehybridizes under the influence of the applied voltage and translocates across the membrane.


Management of osteoporosis.
Osteoporosis or osteopenia occurs in about 44 million Americans, resulting in 1.5 million fragility fractures per year. The consequences of these fractures include pain, disability, depression, loss of independence, and increased mortality. The burden to the healthcare system, in terms of cost and resources, is tremendous, with an estimated direct annual USA healthcare expenditure of about $17 billion. With longer life expectancy and the aging of the baby-boomer generation, the number of men and women with osteoporosis or low bone density is expected to rise to over 61 million by 2020. Osteoporosis is a silent disease that causes no symptoms until a fracture occurs. Any fragility fracture greatly increases the risk of future fractures. Most patients with osteoporosis are not being diagnosed or treated. Even those with previous fractures, who are at extremely high risk of future fractures, are often not being treated. It is preferable to diagnose osteoporosis by bone density testing of high risk individuals before the first fracture occurs. If osteoporosis or low bone density is identified, evaluation for contributing factors should be considered. Patients on long-term glucocorticoid therapy are at especially high risk for developing osteoporosis, and may sustain fractures at a lower bone density than those not taking glucocorticoids. All patients should be counseled on the importance of regular weight-bearing exercise and adequate daily intake of calcium and vitamin D. Exposure to medications that cause drowsiness or hypotension should be minimized. Non-pharmacologic therapy to reduce the non-skeletal risk factors for fracture should be considered. These include fall prevention through balance training and muscle strengthening, removal of fall hazards at home, and wearing hip protectors if the risk of falling remains high. Pharmacologic therapy can stabilize or increase bone density in most patients, and reduce fracture risk by about 50%. By selecting high risk patients for bone density testing it is possible to diagnose this disease before the first fracture occurs, and initiate appropriate treatment to reduce the risk of future fractures.


[Evaluation of serum insulin levels after an oral glucose load for the diagnosis of insulin resistance].
In our country, the assessment of insulin resistance (IR) measuring serum insulin levels at 60 and 120 minutes after a 75 g oral glucose tolerance test (OGTT), is usual. However, there is no information about the distribution of serum insulin levels in the Chilean population. To assess the distribution of serum insulin levels at 60 and 120 minutes during OGTTs and suggest a statistical cut-off point to estimate the degree of IR. Retrospective analysis of 1815 OGTTs performed in non-diabetic subjects aged between 18 and 75 years, at a university medical center. HOMA-IR (Homeostasis Model Assessment), insulin sensitivity index of Matsuda (ISI-Composite), and their correlation with serum insulin levels at 60 and 120 minutes were calculated. The 75th percentiles for serum insulin levels at 60 and 120 minutes were 127 and 81 µU/mL, respectively. There was a high correlation between HOMA-IR and ISI-Composite (r = -089, p < 0.001). There was a weaker although significant correlation between HOMA-IR and ISI-Composite and insulin levels at 60 (r = 0.56 and -0.79 respectively, p < 0,001) and 120 minutes (r = 0.54 and -0.75 respectively, p < 0,001). We propose 60 and 120 min serum insulin levels of 130 and 80 µU/mL respectively, as cut-off values for normality during OGTT in Chilean normoglycemic individuals.


Possible ambiguities when testing viscosity in compendial monographs - characterisation of grades of cellulose ethers.
The European Pharmacopoeia (Ph. Eur.) monographs for the water-soluble cellulose ethers require viscosity determination, either in the "Tests" section or in the non-mandatory "Functionality-related characteristics" section. Although the derivatives are chemically closely related and used for similar applications, the viscosity tests strongly differ. Some monographs generically speak of the rotating viscometer method (2.2.10) and a fixed shear rate (e.g. 10 s-1), which would necessitate an absolute measuring system, while others recommend the capillary viscometer method for product grades of less than 600 mPa∙s and the rotating viscometer method and given operating conditions for grades of higher nominal viscosity. Viscometer methods also differ between the United States Pharmacopeia/National Formulary (USP/NF) and the Japanese Pharmacopoeia (JP) monographs. In addition, for some cellulose ethers the tests sometimes diverge from one pharmacopoeia to the other, although the three compendiums are in a harmonisation process. But the main issue is that the viscometer methods originally employed by the product manufacturers are often not those described in the corresponding monographs and generally vary from one manufacturer to the other. The aim of this study was therefore to investigate whether such a situation could invalidate the present pharmacopoeial requirements. 2 per cent solutions of several viscosity grades of hydroxyethylcellulose, hypromellose and methylcellulose were prepared and their (apparent) viscosity determined using both relative and absolute viscometer methods. The viscometer method used not only affects the measured viscosity but experimental values generally do not correspond to the product nominal viscosities. It emerges that, in contrast to Newtonian solutions (i.e. those of grades of up to ca. 50 mPa∙s nominal viscosity), some of the viscometer methods currently specified in the monographs are not able unambiguously to characterise the grades exhibiting non-Newtonian behaviour. It is also concluded that, unless the various manufacturers redefine their product viscosity grades using a single compendial test, two strategies could be adopted, both based on the operating conditions specified in the labeling (i.e those of the manufacturer), the test appearing either in the mandatory section if this is acceptable to the pharmacopoeia (like in some USP/NF monographs) or, for the Ph. Eur., in the "Functionality-related characteristics" section.


Dielectric breakdown model for composite materials.
This paper addresses the problem of dielectric breakdown in composite materials. The dielectric breakdown model was generalized to describe dielectric breakdown patterns in conductor-loaded composites. Conducting particles are distributed at random in the insulating matrix, and the dielectric breakdown propagates according to new rules to take into account electrical properties and particle size. Dielectric breakdown patterns are characterized by their fractal dimension D and the parameters of the Weibull distribution. Studies are carried out as a function of the fraction of conducting inhomogeneities, p. The fractal dimension D of electrical trees approaches the fractal dimension of a percolation cluster when the fraction of conducting particles approximates the percolation limit.


Renin inhibitors containing hydrophilic groups. Tetrapeptides with enhanced aqueous solubility and nanomolar potency.
Nineteen tetrapeptides containing statine (Sta) and 4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) were prepared. Solubility measurements of these compounds were carried out in H2O and in pH 7.4 phosphate buffer solution, and their partition coefficients were determined in a 1:1 1-octanol/sodium phosphate-citric acid buffer system. The tetrapeptides were tested in vitro for their ability to inhibit porcine, canine, and human plasma renins. Four compounds, 6, 12, 14, and 20, were potent inhibitors against all renins tested (IC50 = 10(-9) M). Compound 12 was administered orally to dogs and substantially inhibited plasma renin activity for up to 5 h. The addition of polar groups to the C-terminus of Sta- and ACHPA-containing tetrapeptides renders them soluble in aqueous milieu and provides a valuable tool with which to examine the role of the renin-angiotensin system in physiological and pathological circumstances.


Antibacterial activity of PD 131628 and proposed disc diffusion susceptibility test criteria.
The antibacterial activity of PD 131628 was compared with that of ciprofloxacin against 401 clinical isolates. The two drugs had comparable MICs for most Gram-negative species. PD 131628 was two to eight times more active against Gram-positive species and against Xanthomonas maltophilia. Both drugs were bactericidal, Among Gram-positive isolates, resistant mutants were not detected in vitro. Among Gram-negative bacilli, spontaneously occurring mutants resistant to PD 131628 were readily demonstrated more frequently than for ciprofloxacin. Resistance to PD 131628 was more readily induced by serially transferring the Gram-negative species, and resistant organisms emerged more rapidly on prolonged incubation in time-kill studies. Correlating the PD 131628 5 micrograms disc diffusion zone diameters with PD 131628 MICs, the following breakpoints are tentatively proposed: susceptible, MIC < or = 1 mg/L or zone > or = 19 mm; intermediate, MIC 2.0 mg/L or zones 16-18 mm; and resistant, MIC > or = 4.0 mg/L or zones < or = 15 mm.


Interprofessional Learning - Development and Implementation of Joint Medical Emergency Team Trainings for Medical and Nursing Students at Universitätsmedizin Greifswald.
Interprofessional collaboration is of great importance in clinical practice, particularly in the field of emergency medicine. The professions involved in providing emergency care must work hand in hand, and tasks and routines must be coordinated effectively. However, medical and nursing students have only few opportunities to experience interprofessional cooperation during their formal training. Addressing this situation, the Department of Anesthesiology and the Vocational School of Greifswald University Medical School initiated a project to increase patient safety by integrating interprofessional human factor training into the curriculum of both health professions. This manuscript addresses how an interprofessional course module focusing on clinical emergency medicine can be taught with an emphasis on competency and problem-solving. In addition, it was important to identify suitable instruments for systematic quality development and assurance of this teaching and learning format. The aim of the project, which took place from October 2013 to September 2015, was the development, implementation and evaluation of a simulation-based, interprofessional course module on clinical emergency medicine. Target groups were medical and nursing students. Modern pedagogical models and methods were applied to the design and teaching of the course content. The project was carried out in separate phases: definition, planning, practical implementation, evaluation and documentation. The project was accompanied by systematic quality development. Established guidelines for quality-centered school development were applied to quality development, assurance and evaluation. Over two years, a 16 credit-hour course module was developed and then taught and evaluated during the 2014 and 2015 summer semesters. A total of 120 medical students and 120 nursing students participated in the course module. Eighteen teachers from medicine and nursing were trained as instructors and assisted by 12 student tutors. Regular evaluations focused on different aspects of the project, using instruments for empirical educational research. Excellent ratings given to the course by the attendees indicate a high degree of satisfaction in both participating professions regarding course design and content, as well as the quality of teaching. In a position paper, the GMA committee on Interprofessional Education in Health Professions issued recommendations for interprofessional education. The recommendations given for teaching and quality assurance are drawn upon here, and relevant examples from the course concept presented. The design of the course corresponds to the recommendations of the GMA committee on Interprofessional Education in the Health Professions. Based on these, and considering the satisfactory evaluations, both continuation and further development of this interprofessional teaching format are justified.


Characteristics of grasping movements in a laboratory and in an everyday-like context.
To understand the principles of motor control, it is useful to know whether movements with the same physical constraints can be governed by different rules depending on the behavioral context. We therefore have recently introduced a paradigm in which subjects grasp from the same starting position to the same final object, once as a typical laboratory task and once as part of everyday-like behavior. In the laboratory context, grasping was repetitive, externally triggered and purposeless; in the everyday-like context, it was embedded in a complex activity, intentionally initiated, and served a purpose. Here we present a comprehensive analysis of data from that paradigm. Among 38 response parameters that reflected hand transport, grip shaping and object manipulation, 20 differed significantly between groups. Factor analysis further reduced them to four orthogonal factors: response speed, finger-object contact, response variability, and hand path curvature. This shows, for the first time, that behavioral context influences the execution of grasping movements in four independent ways, possibly reflecting four distinct functional modules in the motor system. This fits well with the view - derived from neurological data - that grasping is controlled by a set of interconnected brain areas which are differentially recruited to achieve different behavioral goals.


Bovine herpesvirus 1 glycoprotein B does not productively interact with cell surface heparan sulfate in a pseudorabies virion background.
Attachment to cell surface heparan sulfate proteoglycans is the first step in infection by several alphaherpesviruses. This interaction is primarily mediated by virion glycoprotein C (gC). In herpes simplex virus, in the absence of the nonessential gC, heparan sulfate binding is effected by glycoprotein B. In contrast, gC-negative pseudorabies virus (PrV) infects target cells via a heparan sulfate-independent mechanism, indicating that PrV virion gB does not productively interact with heparan sulfate. To assay whether a heterologous alphaherpesvirus gB protein will confer productive heparan sulfate binding on gC-negative PrV, gC was deleted from an infectious PrV recombinant, PrV-9112C2, which expresses bovine herpesvirus 1 (BHV-1) gB instead of PrV gB. Our data show that gC-negative PrV-BHV-1 gB recombinant 9112C2-delta gCbeta was not inhibited in infection by soluble heparin, in contrast to the gC-positive parental strain. Similar results were obtained when wild-type BHV-1 was compared with a gC-negative BHV-1 mutant. Moreover, infection of cells proficient or deficient in heparan sulfate biosynthesis occurred with equal efficiency by PrV-9112C2-delta gCbeta, whereas heparan sulfate-positive cells showed an approximately fivefold higher plating efficiency than heparan sulfate-negative cells with the parental gC-positive virus. In summary, our data show that in a PrV gC-negative virion background, BHV-1 gB is not able to mediate infection by productive interaction with heparan sulfate, and they indicate the same lack of heparin interaction for BHV-1 gB in gC-negative BHV-1.


Mapping the sex determination locus in the hāpuku (Polyprion oxygeneios) using ddRAD sequencing.
Hāpuku (Polyprion oxygeneios) is a member of the wreckfish family (Polyprionidae) and is highly regarded as a food fish. Although adults grow relatively slowly, juveniles exhibit low feed conversion ratios and can reach market size in 1-2 years, making P. oxygeneios a strong candidate for aquaculture. However, they can take over 5 years to reach sexual maturity in captivity and are not externally sexually dimorphic, complicating many aspects of broodstock management. Understanding the sex determination system of P. oxygeneios and developing accurate assays to assign genetic sex will contribute significantly towards its full-scale commercialisation. DNA from parents and sexed offspring (n = 57) from a single family of captive bred P. oxygeneios was used as a template for double digestion Restriction-site Associated DNA (ddRAD) sequencing. Two libraries were constructed using SbfI - SphI and SbfI - NcoI restriction enzyme combinations, respectively. Two runs on an Illumina MiSeq platform generated 70,266,464 raw reads, identifying 19,669 RAD loci. A combined sex linkage map (1367 cM) was constructed based on 1575 Single Nucleotide Polymorphism (SNP) markers that resolved into 35 linkage groups. Sex-specific linkage maps were of similar size (1132 and 1168 cM for male and female maps respectively). A single major sex-determining locus, found to be heterogametic in males, was mapped to linkage group 14. Several markers were found to be in strong linkage disequilibrium with the sex-determining locus. Allele-specific PCR assays were developed for two of these markers, SphI6331 and SphI8298, and demonstrated to accurately differentiate sex in progeny within the same pedigree. Comparative genomic analyses indicated that many of the linkage groups within the P. oxygeneios map share a relatively high degree of homology with those published for the European seabass (Dicentrarchus labrax). P. oxygeneios has an XX/XY sex determination system. Evaluation of allele-specific PCR assays, based on the two SNP markers most closely associated with phenotypic sex, indicates that a simple molecular assay for sexing P. oxygeneios should be readily attainable. The high degree of synteny observed with D. labrax should aid further molecular genetic study and exploitation of hāpuku as a food fish.


In vitro effects of some anesthetic drugs on enzymatic activity of human red blood cell glucose 6-phosphate dehydrogenase.
The study investigated in vitro effects of halothane, isoflurane, ketamine, sevoflurane, prilocaine, diazepam, and midazolam on enzymatic activity of human red blood cell glucose-6-phosphate dehydrogenase (G6PD; E.C. 220.127.116.11). G6PD was purified from human red blood cells by 2',5'-ADP-sepharose 4B affinity gel. Enzymatic activity was spectrophotometrically measured at 340 nm according to the method of Beutler. I50 values were determined from drug activity (%) - drug concentration curves. I50 values were as follows: 0.72 mM for isoflurane, 1.82 mM for sevoflurane, 0.38 mM for diazepam, and 0.0019 mM for midazolam. But halothane, ketamine and prilocaine had no inhibitory effect on the G6PD activity in in vitro.


Homocysteine-lowering interventions for preventing cardiovascular events.
Cardiovascular disease (including coronary artery disease, stroke and congestive heart failure), is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor is elevated circulating total homocysteine levels, which are associated with cardiovascular events. This is an update of a review previously published in 2009. To assess the clinical effectiveness of homocysteine-lowering interventions in people with or without pre-existing cardiovascular disease. We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 2), MEDLINE (1950 to Feb week 2 2012), EMBASE (1980 to 2012 week 07), and LILACS (1986 to February 2012). We also searched ISI Web of Science (1970 to February 2012). We handsearched the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. We included randomised controlled trials assessing the effects of homocysteine-lowering interventions for preventing cardiovascular events with a follow-up period of one year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. We performed study selection, 'Risk of bias' assessment and data extraction in duplicate. We estimated risk ratios (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model. In this updated systematic review, we identified four new randomised trials, resulting in a total of 12 randomised controlled trials involving 47,429 participants. In general terms, the trials had a low risk of bias. Homocysteine-lowering interventions compared with placebo did not significantly affect non-fatal or fatal myocardial infarction (pooled RR 1.02, 95% CI 0.95 to 1.10, I(2) = 0%), stroke (pooled RR 0.91, 95% CI 0.82 to 1.0, I(2) = 11%) or death by any cause (pooled RR 1.01 (95% CI 0.96 to 1.07, I(2): 6%)). Homocysteine-lowering interventions compared with placebo did not significantly affect serious adverse events (cancer) (1 RR 1.06, 95% CI 0.98 to 1.13; I(2) = 0%). This updated Cochrane review found no evidence to suggest that homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination should be used for preventing cardiovascular events. Furthermore, there is no evidence suggesting that homocysteine-lowering interventions are associated with an increased risk of cancer.


Ion selectivity of porcine skeletal muscle Ca2+ release channels is unaffected by the Arg615 to Cys615 mutation.
The Arg615 to Cys615 mutation of the sarcoplasmic reticulum (SR) Ca2+ release channel of malignant hyperthermia susceptible (MHS) pigs results in a decreased sensitivity of the channel to inhibitory Ca2+ concentrations. To investigate whether this mutation also affects the ion selectivity filter of the channel, the monovalent cation conductances and ion permeability ratios of single Ca2+ release channels incorporated into planar lipid bilayers were compared. Monovalent cation conductances in symmetrical solutions were: Li+, 183 pS +/- 3 (n = 21); Na+, 474 pS +/- 6 (n = 29); K+, 771 pS +/- 7 (n = 29); Rb+, 502 pS +/- 10 (n = 22); and Cs+, 527 pS +/- 5 (n = 16). The single-channel conductances of MHS and normal Ca2+ release channel were not significantly different for any of the monovalent cations tested. Permeability ratios measured under biionic conditions had the permeability sequence Ca2+ >> Li+ > Na+ > K+ > or Rb+ > Cs+, with no significant difference noted between MHS and normal channels. This systematic examination of the conduction properties of the pig skeletal muscle Ca2+ release channel indicated a higher Ca2+ selectivity (PCa2+:Pk+ approximately 15.5) than the sixfold Ca2+ selectivity previously reported for rabbit skeletal (Smith et al., 1988) or sheep cardiac muscle (Tinker et al., 1992) Ca2+ release channels. These results also indicate that although Ca2+ regulation of Ca2+ release channel activity is altered, the Arg615 to Cys615 mutation of the porcine Ca2+ release channel does not affect the conductance or ion selectivity properties of the channel.


Ultrastructural Alteration of Pulmonary Capillary Endothelial Glycocalyx During Endotoxemia.
The most recent diagnostic criteria for sepsis include organ failure. Microvascular endothelial injury is believed to lead to the multiple organ failure seen in sepsis, although the precise mechanism is still controversial. ARDS is the primary complication during the sequential development of multiple organ dysfunction in sepsis, and endothelial injury is deeply involved. Sugar-protein glycocalyx coats all healthy vascular endothelium, and its disruption is one factor believed to contribute to microvascular endothelial dysfunction during sepsis. The goal of this study was to observe the three-dimensional ultrastructural alterations in the pulmonary capillary endothelium, including the glycocalyx, during sepsis-induced pulmonary vasculitis. This study investigated the three-dimensional ultrastructure of pulmonary vascular endothelial glycocalyx in a mouse lipopolysaccharide-induced endotoxemia model. Lungs were fixed with lanthanum-containing alkaline fixative to preserve the glycocalyx. On both scanning and transmission electron microscopic imaging, the capillary endothelial glycocalyx appeared as a moss-like structure entirely covering the endothelial cell surface in normal mice. In the septic lung following liposaccharide injection, however, this structure was severely disrupted; it appeared to be peeling away and coagulated. In addition, syndecan-1 levels were significantly reduced in the septic lung, and numerous spherical structures containing glycocalyx were observed on the endothelial surface. It appears that endothelial glycocalyx in the lung is markedly disrupted under experimental endotoxemia conditions. This finding supports the notion that disruption of the glycocalyx is causally related to the microvascular endothelial dysfunction that is characteristic of sepsis-induced ARDS.


Understanding the diagnoses and medical care experience of patients with new daily persistent headache: a qualitative study in Spain.
To explore the experiences of patients suffering from new daily persistent headache (NDPH) regarding the diagnostic process, treatment and medical care. A qualitative phenomenological study was conducted. A specialised headache unit at two university hospitals in Spain between February 2017 and December 2018. Patients diagnosed with NDPH according to the International Classification of Headache disorders (third beta edition). Purposeful sampling was performed. Data were collected using unstructured and semistructured interviews, researchers' field notes and patients' drawings. An inductive thematic analysis was used to identify significant emerging themes from interviews, field notes and descriptions of patients' drawings. Also, Guillemin's proposal was used to analyse the contents of drawings. Nineteen patients with a mean age of 45.3 were recruited. Four main themes emerged: (1) Seeking a diagnosis, patients visit many doctors without receiving a clear answer and their diagnosis is delayed; (2) Self-medication-minimising pill intake, medication is ineffective, and therefore, some patients discontinue treatment, or are flexible with how they take medication; (3) Trying other non-pharmacological options, many patients turn to other therapies and complementary and/or alternative therapies as a second option, however these are ineffective and (4) Medical care, with two subthemes, referrals and lacking continuity of care, and building the doctor-patient relationship. Patients describe how the referral breaks the continuity of care, and how they identify the traits of a doctor who is approachable and which behaviours the doctor should avoid when caring for patients. An in-depth knowledge of the beliefs and expectations of patients with NDPH will allow the professional to establish a relationship of trust, which will improve the patients' knowledge of which therapies are the most appropriate, and to establish expectations based on the relationship with the doctor, and not only on patients' beliefs.


Separation of alpha 1 adrenergic and N-methyl-D-aspartate antagonist activity in a series of ifenprodil compounds.
Ifenprodil (1) represents a new class of N-methyl-D-aspartate (NMDA) antagonist. This drug also possesses potent activity at several other brain receptors (most notably alpha 1 adrenergic receptors). We have prepared the enantiomers and diastereomers of ifenprodil along with a series of partial structures in order to explore the basic structure activity relations within this class of compounds. From this study, it is clear that alpha 1 adrenergic and NMDA receptor activities may be separated by selection of the threo relative stereochemistry. Examination of the optical isomers of threo-ifenprodil (2) reveals that no further improvement in receptor selectivity is gained from either antipode. Individual removal of most of the structural fragments from the ifenprodil molecule generally results in less active compounds although fluorinated derivative 9 with threo relative stereochemistry is somewhat more potent and substantially more selective for the NMDA receptor. Finally a minimum structure for activity in this series (14) has been identified. This stripped-down version of ifenprodil possesses nearly equivalent affinity for the NMDA receptor with no selectivity over alpha 1 adrenergic receptors.


Surgical and medical measures in prevention of large bowel cancer.
Traditional methods for prevention of large bowel cancer rely on surveillance of patients with known precursors of bowel cancer, namely ulcerative colitis and those genetically linked polyposis syndromes that have malignant potential. Identification of heritable bowel cancer families and solitary polyp--cancer families provide additional populations that merit intensive scrutiny. Persuasive, if circumstantial, evidence suggests that maintaining patients free of large bowel polyps reduces the risk of developing large bowel cancer. Prospects for prevention of large bowel cancer are extended by recognition that a diet low in fat may reduce the risk of large bowel cancer. Furthermore, there is considerable evidence in animals that a variety of antioxidants limit large bowel carcinogenesis and preliminary evidence in man that these agents may control large bowel neoplasia.


Brief dialectical behavior therapy (DBT-B) for suicidal behavior and non-suicidal self injury.
The purpose of this study is to evaluate the effectiveness of a shorter course of Dialectical Behavior Therapy (DBT) in enhancing treatment retention and reducing: urges to engage in non-suicidal self injury (NSSI), NSSI, suicide ideation, and subjective distress in borderline personality disorder (BPD). Twenty patients with BPD received a six-month course of Dialectical Behavior Therapy (DBT-B). DBT-B was delivered in the standard manner except for the shortened duration from one-year minimum to six months. All variables were measured at baseline, and at six months. Data were analyzed using paired t-tests. Treatment retention rate was 95%. Significant reductions were found in NSSI urges, NSSI, suicide ideation, subjective distress, depression, and hopelessness between baseline and six months. These results support the use of DBT-B in a six-month format when NSSI and suicidal behavior and ideation are the targeted behaviors. Target behaviors were reduced significantly and retention was extremely high in comparison to other interventions for this population. A large scale randomized controlled trial investigating its efficacy is warranted to determine if the results can be replicated and if improvement can be sustained.


Flavonoids from the heartwood of Dalbergia odorifera and their protective effect on glutamate-induced oxidative injury in HT22 cells.
Two flavonoids, 4,2',5'-trihydroxy-4'-methoxychalcone (1) and (2S)-6,7,4'-trihydroxyflavan (2), along with fourteen known flavonoids and two other known arylbenzofurans were isolated from the heartwood of Dalbergia odorifera. The structure of compounds 1 and 2 were established by spectroscopic (NMR and MS) analyses. Of the isolates, eight compounds (1, 4, 7, 10, 12, 14, 15, 17) were found to have potent protective effect on glutamate-induced oxidative injury in HT22 cells.


Correlative histochemical study providing evidence for the dual nature of human colorectal cancer mucin.
Luminal secretions within colorectal cancers have been assumed to be the counterpart of normal goblet cell mucin. The aim of this study was to establish whether secretory material within colorectal cancers may in fact be traced to different lineages: goblet cells and columnar cells. The distribution of the apomucins MUC1 and MUC2, non-O-acetylated sialic acid and the carbohydrate structures sialosyl Tn, Tn, Lewis(x), sialosyl Lewis(x) and Lewis(y) was studied in normal colorectal mucosa and colorectal cancer specimens using standard histochemical techniques. Unmasking of MUC1 and MUC2 was achieved using periodic acid and saponification-neuraminidase-periodic acid pretreatment respectively. Within normal and malignant epithelium, correlations and/or co-localization could be demonstrated for goblet cells with MUC2, non-O-acetylated sialic acid, sialosyl Tn, Tn (Golgi region) and sialosyl Lewis(x), and for columnar cells with MUC1, Lewis(x), sialosyl Le(x), Tn (cytoplasm) and Lewis(y) (UEA-1). The goblet cell spectrum was associated with mucin-like (type I) luminal secretions within cancers, whereas the columnar cell spectrum characterized non-mucin-like (type II) secretions and intracytoplasmic lumina. These data indicate that colorectal cancer mucin can be broadly separated into two types: secretory mucin linked to cells of goblet lineage and up-regulated membrane-associated mucin of presumed columnar cell origin.


Treatment of laryngotracheobronchitis (croup). Use of intermittent positive-pressure breathing and racemic epinephrine.
Use of racemic epinephrine hydrochloride (Vaponefrin), delivered by intermittent positive-pressure breathing, in the treatment of laryngotracheobronchitis (croup) produced acute beneficial results in a controlled study. However, symptoms often recurred within two hours, suggesting that this form of treatment should not be used in the emergency room and the patient then sent home. This treatment had no effect on arterial oxygen gas pressure. The changes in clinical status 24 to 36 hours after admission into the study were similar for the patients in the treatment and control groups, suggesting that the natural history of the disease was not drastically altered by this form of treatment.


Liquid-to-solid transition of concentrated suspensions under complex transient shear histories.
Suspensions containing noncolloidal aluminum particles in a Newtonian carrier liquid and the effects of shear history on the rheological properties of suspensions are investigated showing a critical concentration phi(c), which is close to the "freezing" packing fraction of spherical particle suspensions. An apparent liquid-to-solid transition was clearly found for suspensions below phi(c) via transient step shear after long shear history as well as via the large amplitude oscillatory shear flow with controlled shear stress. The microstructures or the local flow characteristics of suspensions with phi<phi(c) and with phi>phi(c) are still different according to the Fourier Transform Rheological analysis. Although suspensions with phi<phi(c) show solidlike behaviors after long shear history, the flow behaviors keep unchanged as shear stress increases, and typically show solidlike, liquid-solid coexistence, liquidlike, and jamming behaviors, successively. However, liquidlike regime of concentrated suspensions with phi>phi(c) disappears after preshear.


Nutritional deficiencies and subsequent effects on mental and behavioral development in children.
Nutritional deficiencies at all stages of growth, both pre- and post-natal, can affect a child's physical, mental and behavioral development. In this paper, we review literature about how mental development is affected by the following nutritional conditions: low birth weight, mild, moderate, and severe protein-energy malnutrition, iodine deficiency, and iron deficiency.


Adult ADHD: Questioning Diagnosis and Treatment in a Patient with Multiple Psychiatric Comorbidities.
Adult Attention-Deficit/Hyperactivity Disorder (ADHD) is a contentious diagnostic issue, which has been increasing in prevalence in recent years, and is often comorbid with other psychiatric disorders. This report presents a detailed account of a clinical case involving a middle-aged man with a history of recurrent depressive episodes and an unsubstantiated diagnosis of ADHD, treated with stimulants. There is persistent debate around the use of psychostimulants both in adult ADHD and in the treatment of depression. Despite promising activating properties, psychostimulants carry significant risks of misuse and substance use disorder. In this report, we consider the potential benefits and adverse effects of stimulants in the treatment of adult ADHD and mood disorders and review the learning points of this complicated, but not uncommon, clinical case.


[Energy and nutritional intake in young weight lifters before and after nutritional counseling].
A well-balanced diet is an essential component for the development and maintenance of physical performance. Several studies on the dietary status of power athletes have shown, that there are still problems to realize the nutritional recommendations. The purpose of the present study was to analyse the energy- and nutrient intake of 11 young weight lifters aged 14 to 17 years before and after an intensive nutritional counselling (NC). Dietary status was evaluated by 7-day-protocols filled out by the young athletes 4 weeks before and 4 weeks after the NC. Before the NC the athletes (x: age 15, height 174 cm, weight 69.5 kg, BMI 22.2 kg/m2) had a mean energy intake of 179.7 kJ/kg body weight (11.2 MJ/day). The energy percentage of carbohydrate:fat:protein was 48:37:15. The protein consumption was 1.6 g/kg of body weight and the fluid intake was 1.7 l/day. The athletes did not meet the recommendation for niacin, folic acid, vitamin E, magnesium, calcium, iodine and zinc. After the NC the athletes had a significant higher energy percentage of carbohydrate and lower energy percentage of fat. In addition a significantly higher intake of fluid, dietary fiber, vitamins and minerals was observed. This study revealed that the young weight lifters without NC fall short of nutritional recommendations. With the intensive nutritional counselling an improvement of the nutrient intake could be reached. Additional nutritional counselling for the athletes and an intensive teamwork with the coach and parents of the athletes seem necessary to develop and stabilize a good nutritional behavior.


Multiple statistics for multiple events, with application to repeated infections in the growth factor studies.
Clinical studies that involve the recording of two or more distinct and well-defined events on each subject give rise to multiple event data. Treatment comparisons are usually reported in univariate analyses of time to first event or number of events observed. However, this approach may not uncover the 'full story' of the treatment effect; moreover, it may be inefficient because it does not make full use of the available data. There are a number of published statistical methods for analysing multiple event data. Using data from a real life example, this paper compares the results obtained using the 'older ad hoc' methods with those based on the more recent methods that utilize the multiplicity of the data.


[Skin and menopause].
Important changes related to declining level of several hormones occur during menopause: vasomotor instability, bone loss, anxiety, sexual dysfunction, skin aging... Our objective was a review of the literature concerning the histological and clinical changes seen in post menopausal skin, and also an analysis of the effect of hormonal replacement therapy in slowing down the aging process. Decline in progesterone increases the impact of androgen on the sebaceous glands and hair. Decreased estrogen slows down mitotic activity in the epidermal basal layer, reduces the synthesis of collagen and contributes to thickening of the dermo-epidermal junction. This hypoestrogenemia may be spontaneously attenuated by local synthesis of oestradiol in peripheral target tissues according to the intracrine process. This new hormonal pattern is associated with skin atrophy, hyperseborrhea, increased pilosity on the cheeks and upper lip, loss of scalp hair, increase in degeneration of elastic tissue, atrophy and dryness of the vaginal mucosa. Estrogen treatment in post menopausal women has been shown to increase collagen content, dermal thickness and elasticity. Biophysical properties are also significantly improved for the parameters reflecting hydration and sebum secretion. However, numerous side effects such as increased incidence of cancer and cardiovascular morbidity limit the use of this treatment. So non hormonal alternatives are proposed. Laser and lifting remain the most important options.


Optimization of cultural conditions for thermostable beta-1,3-1,4-glucanase production by Bacillus subtilis ZJF-1A5.
The optimization of cultural conditions for Beta-glucanase production by Bacillus subtilis ZJF-1A5 was investigated in flask trials. Temperature had great effect on Beta-glucanase production which maximized at optimal temperature of 37 degrees C and decreased significantly when temperature was over 37 degrees C. Charge quantity affected Beta-glucanase production significantly. Adding oxygen vector N-dodecane or acetic ether benefited Beta-glucanase production, but it depended on the concentration and charge quantity. The results of fractional factorial design showed that age and size of inoculum and shaking speed were the key factors affecting Beta-glucanase production and the cultivation time span to reach the highest Beta-glucanase activity. The optimal cultural conditions for Beta-glucanase production obtained with CCD were as follows: inoculum age and size (16 h, 3.82%(v/v)), shaking speed 210 r/min, charge quantity of 30 mL in 250 mL flask and initial pH 7.0, cultured at 37 degrees C for 50 h. Repeated experimental results accorded with those predicted by a second-order polynomial model. The amount of Beta-glucanase, Alpha-amylase and neutral protease produced by B subtilis ZJF-1A5 was associated partially with cell growth. Those three enzymes' activities increased following the cell growth and increased significantly when cells entered the stationary phase.


Chronic administration of verapamil, ketoconazole and carbamazepine: impact on immunological parameters.
Inhibitors of P-glycoprotein (P-gp) (verapamil) or cytochrome P-450 (ketoconazole) may reduce IL2 production and T lymphocyte proliferation in vitro. We have examined the effects of chronic oral administration of these drugs and of the cytochrome P450 inductor, carbamazepine, on the hematological and immunological parameters of mice. We found no changes after giving the mice 0.12 mg verapamil, 0.85 mg ketoconazole, or 0.514 mg carbamazepine per mouse for 4 weeks (5 days/week). But giving the drugs for an additional 7 weeks at 0.6 mg (verapamil), 4.25 mg (ketoconazole) or 2.57 mg/mouse (carbamazepine), resulted in significant decreases in monocytes in the verapamil treated group (-51%) and in CD4+ cells in the carbamazepine group (-35%). Chronic oral administration of these drugs reduced the lymphocyte counts of mice by 10-18% and their NK counts by 10-16%. These changes could be due to changes in P-gp function in the transport of IL2, with decreases caused by verapamil and ketoconazole.


Complete functional recovery after 24-hour heart preservation with University of Wisconsin solution and modified reperfusion.
Successful long-term myocardial preservation is dependent on optimizing conditions during arrest, storage, and reperfusion. Neonatal piglet hearts were arrested and stored in University of Wisconsin solution (UW) at 4 degrees C for 24 hours and reperfused on a blood-perfused, adult animal-supported isolated circuit. Results were compared with nonischemic continuously perfused control hearts (group 1, n = 5). The initial 10 minutes of reperfusion in groups 2-4 was modified by aspartate/glutamate-enriched leukocyte-depleted blood cardioplegia (group 2, n = 7), leukocyte depletion alone (group 3, n = 9), and aspartate/glutamate-enriched blood cardioplegia alone (group 4, n = 6). After 10 minutes, perfusion was continued with unmodified whole blood. In group 5 (n = 9), unmodified whole blood was used for initial reperfusion as well as subsequent perfusion. The stroke work index was determined 60 minutes after reperfusion. Biopsies for high-energy phosphates, myocardial water content, and electron microscopy were obtained after functional assessment. The stroke work index at left ventricular end-diastolic pressure of 9 mm Hg did not differ between groups 1 and 2 (19.0 +/- 1.4 x 10(3) and 19.0 +/- 1.5 x 10(3) [mean +/- SEM] erg/g, respectively). These were both different from group 5 (13.3 +/- 0.8 x 10(3) erg/g, p less than 0.05). Group 3 showed improved function (15.7 +/- 0.7 x 10(3) erg/g), but this did not reach statistical significance when compared with group 5. No difference was found between groups 4 and 5. Myocardial water content, high-energy phosphate levels, and ultrastructure were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)


α-amino trimethylation of CENP-A by NRMT is required for full recruitment of the centromere.
Centromeres are unique chromosomal domains that control chromosome segregation, and are epigenetically specified by the presence of the CENP-A containing nucleosomes. CENP-A governs centromere function by recruiting the constitutive centromere associated network (CCAN) complex. The features of the CENP-A nucleosome necessary to distinguish centromeric chromatin from general chromatin are not completely understood. Here we show that CENP-A undergoes α-amino trimethylation by the enzyme NRMT in vivo. We show that α-amino trimethylation of the CENP-A tail contributes to cell survival. Loss of α-amino trimethylation causes a reduction in the CENP-T and CENP-I CCAN components at the centromere and leads to lagging chromosomes and spindle pole defects. The function of p53 alters the response of cells to defects associated with decreased CENP-A methylation. Altogether we show an important functional role for α-amino trimethylation of the CENP-A nucleosome in maintaining centromere function and faithful chromosomes segregation.


Predictive factors for longer length of stay in an emergency department: a prospective multicentre study evaluating the impact of age, patient's clinical acuity and complexity, and care pathways.
It has been reported that emergency department length of stay (ED-LOS) for older patients is longer than average. Our objective was to determine the effect of age, patient's clinical acuity and complexity, and care pathways on ED-LOS and ED plus observation unit (EDOU) LOS (EDOU-LOS). This was a prospective, multicentre, observational study including all patients attending in 2011. Age groups were: I, <50; II, ≥50-64; III, ≥65-74; IV, ≥75-84; V, ≥85 years. Univariate and multivariate analyses were performed. Of 125 478 attendances, 20 845(16.6%) were of patients aged ≥65 years. Multivariate analysis found significant predictors for ED-LOS (C-statistics 0.79, p<0.0000001) to be: arrival mode (ambulance, OR 1.13 (95% CI 1.08 to 1.18)); acuity level (level 4, OR 1.24 (95% CI 1.21 to 1.28); level 1-3, OR 1.54 (95% CI 1.5 to 1.59)); haematological examinations (OR 3.34 (95% CI 3.15 to 3.56)); intravenous treatment (OR 1.58 (95% CI 1.47 to 1.69)); monitoring of vital signs (OR 1.89 (95% CI 1.69 to 2.10)); x-ray examinations (OR 1.53 (95% CI 1.45 to 1.61)); CT/MRI/ultrasound (OR 2.60 (95% CI 2.39 to 2.82)); and specialist advice (OR 1.39 (95% CI 1.30 to 1.48)). For EDOU-LOS (C-statistics 0.81, p<0.0000001) we found: age group (II, OR 1.19 (95% CI 1.16 to 1.22); III, OR 1.42 (95% CI 1.38 to 1.46); IV, OR 1.69 (95% CI 1.65 to 1.74); V, 2.01 (95% CI 1.96 to 2.07)); acuity level (level 4, OR 1.31 (95% CI 1.27 to 1.35); level 1-3, OR 1.71 (95% CI 1.66 to 1.77)); haematological examinations (OR 7.81 (95% CI 7.23 to 8.43)); intravenous treatment (OR 1.95 (95% CI 1.8 to 2.12)); x-ray examinations (OR 1.95 (95% CI 1.85 to 2.06)); CT/MRI/ultrasound (OR 6.74 (95% CI 5.98 to 7.6)); specialist advice (OR 2.24 (95% CI 2.07 to 2.42)); admission to a medical or surgical ward (OR 0.61 (95% CI 0.54 to 0.68)); and transfer (OR 1.79 (95% CI 1.54 to 2.07)). Whereas ED-LOS and EDOU-LOS seem to be directly related to patients' acuity and complexity, notably the need for diagnostic and therapeutic interventions, only EDOU-LOS was significantly associated with age and proposed care pathways. We propose that EDOU-LOS measurement should be made in EDs with an OU.


Controllable Photodynamic Therapy Implemented by Regulating Singlet Oxygen Efficiency.
With singlet oxygen (1O2) as the active agent, photodynamic therapy (PDT) is a promising technique for the treatment of various tumors and cancers. But it is hampered by the poor selectivity of most traditional photosensitizers (PS). In this review, we present a summary of controllable PDT implemented by regulating singlet oxygen efficiency. Herein, various controllable PDT strategies based on different initiating conditions (such as pH, light, H2O2 and so on) have been summarized and introduced. More importantly, the action mechanisms of controllable PDT strategies, such as photoinduced electron transfer (PET), fluorescence resonance energy transfer (FRET), intramolecular charge transfer (ICT) and some physical/chemical means (e.g. captivity and release), are described as a key point in the article. This review provide a general overview of designing novel PS or strategies for effective and controllable PDT.


A revision of the Afrotropical species of Pachylophus Loew (Diptera: Chloropidae) and some related Ovoviviparous genera.
In Pachylophus all described Afrotropical species are treated and P. aristalis, ismayi, nigeriensis, tschirnhausi, mirabilis, lacteibasis and stuckenbergi are described as new species. Pachylophus tellinii Bezzi is placed in synonymy. In Phyladelphus the type species thalhammeri and the single described Afrotropical species, P. geminus, are treated and P. woodi and P. maraisi are described as new species. The genus Sabeurina is erected to accommodate Eurina minuta Loew and a new Afrotropical species S. occidentalis. Some taxonomic notes are given on the Afrotropical species currently included in Platycephala. The immature stages and biological notes concerning the treated genera are described and discussed in the contexts of ovoviviparity and classification. Keys are provided for the identification of all the Afrotropical species known in each of the genera treated.


Overexpression of miR -155 promotes proliferation and invasion of human laryngeal squamous cell carcinoma via targeting SOCS1 and STAT3.
MicroRNA155 plays an important role in many solid malignancies. Expression and function of miR-155 in laryngeal carcinoma have not been fully understood. This study aims to investigate the expression and function of miR-155 in laryngeal squamous cell carcinoma (LSCC), the relationship between miR-155 and its downstream target suppressor of cytokine signaling 1 (SOCS1)-STAT3 pathway, and the related clinicopathological factors. Sixty-three samples of laryngeal squamous cell carcinoma and twenty-one samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and real-time PCR. Hep-2 cells were cultured and transfected with miR-155 mimic and ASO. Cell proliferation, migration and invasion assays were used to determine the role of miR-155 in regulation of LSCC growth, migration, and invasion, respectively. The expression levels of miR-155 in LSCC were significantly higher than those in the control mucosa tissues. Downregulation of SOCS1 expression and elevated expression of STAT3 were also observed in LSCC. The relevance of the three factors were statistically significant. Moreover, knockdown of miR-155 elevated SOCS1expression level, suppressed STAT3 expression, and inhibited hep-2 cells growth, migration and invasion. Whereas overexpression of miR-155 inhibited SOCS1expression, elevated STAT3 expression, and promoted hep-2 cells growth, migration and invasion. Furthermore, the miR-155 levels in T(3) T(4) stages, and poor/moderate cell differentiation were significantly higher than those in T(2) stage and higher degree of cell differentiation. The STAT3 protein in poor/moderate cell differentiation was significantly higher than those in higher degree of cell differentiation. We firstly demonstrated the aberrant expression and function of miR-155 and itsdownstream targets in LSCC. The current findings suggest that miR-155 play promotingrole during the development of LSCC, and miR-155 may be a useful marker for the prognosis and assessment of therapeutic effects.