[A case of intussusception caused by low-grade appendiceal mucinous neoplasm with high serum levels of carcinoembryonic antigen resected by laparoscopy-assisted colectomy].
The patient was a 43-year-old woman who visited our hospital with a primary complaint of intermittent abdominal pain. Upper gastrointestinal endoscopy revealed mild gastritis. The patient was treated with oral drugs, and the course was followed. Subsequently, the abdominal pain aggravated, and computed tomography (CT) was performed, in which right colic intussusception with a 4 cm cystic mass in the advanced portion was noted. Reduction by enema was attempted on the same day; however, a residual tumorous lesion was present in the ileocecal region. The patient was diagnosed with a cecal submucosal tumor with intussusception, and therefore, laparoscopic surgery was performed. Intussusception of the entire appendix in the ascending colon was noted, for which laparoscopic ileocecal resection was performed. In the excised specimen, a cystic lesion comprising the appendix filled with mucus was present. The postoperative recovery was favorable, and the patient was discharged on the seventh postoperative day. The lesion was histopathologically diagnosed as low-grade appendiceal mucinous neoplasm.


[Otto Hilgenfeldt (1900 to 1983)--an unusual approach for finger reconstruction].
Reconstructive surgery of detached extremities, especially fingers, has a long historical tradition. The first clinically correctly documented cases go back to the 19th century. During the first and second world wars numerous reports appeared about the surgical care of war victims. Pioneering innovative surgical methods were developed by especially motivated surgeons for the reconstruction of these disfiguring war injuries in Europe. Because of these particular circumstances and the prevailing revolutionary spirit, many innovations in surgery were developed. The report of Otto Hilgenfeldt (1950) described his unusual approach in reconstructing a finger by using the great toe.


Endometrial stem cell transplantation in MPTP- exposed primates: an alternative cell source for treatment of Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. Cell-replacement therapies have emerged as a promising strategy to slow down or replace neuronal loss. Compared to other stem cell types, endometrium-derived stem cells (EDSCs) are an attractive source of stem cells for cellular therapies because of their ease of collection and vast differentiation potential. Here we demonstrate that endometrium-derived stem cells may be transplanted into an MPTP exposed monkey model of PD. After injection into the striatum, endometrium-derived stem cells engrafted, exhibited neuron-like morphology, expressed tyrosine hydroxylase (TH) and increased the numbers of TH positive cells on the transplanted side and dopamine metabolite concentrations in vivo. Our results suggest that endometrium-derived stem cells may provide a therapeutic benefit in the primate model of PD and may be used in stem cell based therapies.


[Qualitative study of the differences between men and women's perception of obesity, its causes, tackling and repercussions on health].
although obesity is a multidimensional health problem, few qualitative research studies have analyzed the discourse of obese individuals from the gender perspective in order to better understand the hard come by information gathered from quantitative research. to analyze the discourse of obese individuals in focus groups concerning factors underlying obesity, pathology risk perception, weight loss and other relevant factors. two single-sex focus groups, with a total of 14 participants, were held in separate sessions. A moderator directed the session, addressing the different dimensions of the problem. The groups were recorded in audio and textually transcribed. The discourse was analyzed using qualitative methods. important differences were observed between male and female perspectives. The self-perceived causes of obesity for women were pregnancy and menopause. Men attributed obesity to eating habits and cultural customs. For men, the final aim of reducing weight was to improve their health, whereas women also included aesthetics. Both sexes believe that obesity can lead to greater problems. Women expressed their fear of putting on weight, but men did not. Differences were also observed in the strategies adopted for combating obesity. differences in the perception of the causes and how to tackle obesity between men and women show us the need to consider therapeutic and preventive measures that take gender into account, in addition to the environmental aspects surrounding the patient.


Chloroquine attenuates paraquat-induced lung injury in mice by altering inflammation, oxidative stress and fibrosis.
Paraquat is one of the most extensively used herbicides and has high toxicity for humans and animals. However, there is no effective treatment for paraquat poisoning. The aim of the present study was to evaluate the effects of chloroquine on paraquat-induced lung injury in mice. Mice received a single intraperitoneal injection of paraquat and a daily intraperitoneal injection of the indicated dosages of chloroquine or dexamethasone. The histological changes, inflammation and oxidative stress in the lungs were examined at day 3, and the degree of pulmonary fibrosis was examined at day 28. H&E staining showed that chloroquine markedly attenuated lung injury induced by paraquat. In addition, the inflammatory responses induced by paraquat were inhibited after treatment with chloroquine, as indicated by the decreased number of leukocytes, the reduced levels of TNF-α, IL-1β and IL-6 in the bronchoalveolar lavage fluid, the reduced NO content, and downregulation of iNOS expression in lung tissues. No different effect was found between high-dose chloroquine and dexamethasone. Additionally, the treatment with chloroquine increased the activity of SOD and decreased the level of MDA in the lung tissues. The expressions of the anti-oxidative proteins, Nrf2, HO-1 and NQO1, were also upregulated by chloroquine treatment. The high-dose chloroquine was more effective than dexamethasone in its anti-oxidation ability. Finally, the results of Masson's staining illustrated that chloroquine markedly attenuated fibrosis in the paraquat-exposed lungs. Immunohistochemistry staining showed that the expressions of the pro-fibrotic proteins TGF-β and α-SMA were downregulated after treatment with chloroquine. In conclusion, chloroquine effectively attenuated paraquat-induced lung injury in mice.


Immunopathology of BCG infection in genetically resistant and susceptible mouse strains.
Natural resistance to Mycobacterium bovis (BCG) is under the control of a single gene, designated Bcg. Resistant (Bcgr) mice prevent multiplication of an i.v. injected inoculum of congruent to 10(4) dispersed BCG cells, whereas progressive multiplication of this pathogen occurs in the first 3 wk of infection in spleens and livers of susceptible (Bcgs) mice. Striking differences in the development of cellular immunity, as measured by granuloma formation in the liver and spleen, delayed-typed hypersensitivity, and a resistance to the challenge with homologous (BCG) and heterologous (Listeria monocytogenes) pathogens, were detected between Bcgr (C3H/HeN and A/J) and Bcgs (C57BL/6J and B10.A) strains. Cellular immune reactions progressively developed in the Bcgs mice, as a response to the increasing bacterial load, whereas greatly inferior levels of acquired immunity were observed in Bcgr strains. These findings support the concept that mice genetically resistant to BCG infection are able to prevent bacterial multiplication without the need for a cellular immune response, whereas genetically susceptible mice will eventually control bacterial multiplication with the acquisition of cellular immunity.


Solvation of anthraquinone and TEMPO redox-active species in acetonitrile using a polarizable force field.
Redox-active molecules are of interest in many fields, such as medicine, catalysis, or energy storage. In particular, in supercapacitor applications, they can be grafted to ionic liquids to form so-called biredox ionic liquids. To completely understand the structural and transport properties of such systems, an insight at the molecular scale is often required, but few force fields are developed ad hoc for these molecules. Moreover, they do not include polarization effects, which can lead to inaccurate solvation and dynamical properties. In this work, we developed polarizable force fields for redox-active species anthraquinone (AQ) and 2,2,6,6-tetra-methylpiperidinyl-1-oxyl (TEMPO) in their oxidized and reduced states as well as for acetonitrile. We validate the structural properties of AQ, AQ•-, AQ2-, TEMPO•, and TEMPO+ in acetonitrile against density functional theory-based molecular dynamics simulations and we study the solvation of these redox molecules in acetonitrile. This work is a first step toward the characterization of the role played by AQ and TEMPO in electrochemical and catalytic devices.


Potent in vivo anti-tumor activity of isolated CD62L(low) lymph node cells sensitized in vivo with tumor lysate-pulsed DC-based vaccines.
DC are potent APC that can activate both CD4 and CD8 T cells in vitro and in vivo. Although the efficacy of DC-based cancer vaccines is currently being evaluated in clinical trials, the systemic immune suppression in cancer patients negatively impacts the clinical benefit of this therapeutic approach. Therefore, in this study we tested the feasibility and anti-tumor effect of adoptive immunotherapy using in vitro-activated CD62L(low) lymph node cells that were isolated from DC-vaccinated draining lymph nodes (VDLN). DC were prepared from BM cells and loaded with tumor lysate for inoculating into naive mice. Subsequently, the VDLN were removed and CD62L(low) cells in the VDLN population isolated, expanded in vitro by 5-day culture with IL-2 and immobilized anti-CD3 stimulation, then injected into mice with established pulmonary tumors. Eighteen days after treatment, mice were killed in order to enumerate pulmonary tumor nodes. DC phagocytosed the tumor lysate efficiently and induced detectable T-cell responses and significant cell expansion in the draining lymph nodes. After induction of maturation by LPS treatment, DC expressed higher levels of CD40, CD86 and MHC class II molecules. When CD62L(low) VDLN cells that had been isolated and expanded in vitro were transferred into tumor-bearing mice, as few as 3 x 10(6) cells were able to cure metastatic pulmonary tumors in vivo. DC-based VDLN T cells are an important source of anti-tumor effector for adoptive immunotherapy. This study provides a novel and an effective protocol using T-cell adoptive immunotherapy for application in cancer patients; therefore, clinical trials based on this protocol may be warranted.


The patient who transformed motor neurone disease care.
In March 2015, Nursing Standard published a feature about a remarkable young man called Gordon Aikman. He had been diagnosed with motor neurone disease (MND) the previous year, aged 29, while working as director of research for the Better Together campaign, ahead of the Scottish independence referendum. The Scot, pictured, knew the prognosis wasn't good, and was determined to make the most of the time he had left.


Immunoexpression of HBME-1, high molecular weight cytokeratin, cytokeratin 19, thyroid transcription factor-1, and E-cadherin in thyroid carcinomas.
To examine the immunohistochemical alterations associated with the histological dedifferentiation of thyroid carcinomas, we performed staining for HBME-1, high molecular weight cytokeratin (HCK), CK 19, thyroid transcription factor-1 (TTF-1) and E-cadherin (E-CD) on 125 various types of thyroid carcinomas. The HBME-1 staining was strong and diffuse in follicular carcinoma (FC), papillary carcinoma (PC), and poorly differentiated carcinoma (PDC), while it was rare in undifferentiated carcinoma (UC) as well as in benign lesions. Strong, diffuse staining for CK19 and HCK was predominantly found in PC, and these markers were not much found in other carcinomas. TTF-1 uniformly stained the tumor cells of all cases of PC, FC and Hurthle cell carcinoma (HC) and 42% of the PDC, while there was only focal staining in one case of the UC. Compared to the strong, diffuse reactivity in the benign lesions, E-CD staining was noted in 67% of PC, 80% of FC, 83% of HC, 58% of PDC and none of the UC. These results suggest that HBME-1 may be a marker for well-differentiated carcinomas while CK19 and HCK are phenotypic markers for papillary carcinoma. The loss or reduced expression of TTF-1 and E-CD may be markers for dedifferentiation.


LetsTalkShots: personalized vaccine risk communication.
Vaccine hesitancy is a global health threat undermining control of many vaccine-preventable diseases. Patient-level education has largely been ineffective in reducing vaccine concerns and increasing vaccine uptake. We built and evaluated a personalized vaccine risk communication website called LetsTalkShots in English, Spanish and French (Canadian) for vaccines across the lifespan. LetsTalkShots tailors lived experiences, credible sources and informational animations to disseminate the right message from the right messenger to the right person, applying a broad range of behavioral theories. We used mixed-methods research to test our animation and some aspects of credible sources and personal narratives. We conducted 67 discussion groups (n = 325 persons), stratified by race/ethnicity (African American, Hispanic, and White people) and population (e.g., parents, pregnant women, adolescents, younger adults, and older adults). Using a large Ipsos survey among English-speaking respondents (n = 2,272), we tested animations aligned with vaccine concerns and specific to population (e.g., parents of children, parents of adolescents, younger adults, older adults). Discussion groups provided robust feedback specific to each animation as well as areas for improvements across animations. Most respondents indicated that the information presented was interesting (85.5%), clear (96.0%), helpful (87.0%), and trustworthy (82.2%). Tailored vaccine risk communication can assist decision makers as they consider vaccination for themselves, their families, and their communities. LetsTalkShots presents a model for personalized communication in other areas of medicine and public health.


Activation of the EGF Receptor by Ligand Binding and Oncogenic Mutations: The "Rotation Model".
The epidermal growth factor receptor (EGFR) plays vital roles in cellular processes including cell proliferation, survival, motility, and differentiation. The dysregulated activation of the receptor is often implicated in human cancers. EGFR is synthesized as a single-pass transmembrane protein, which consists of an extracellular ligand-binding domain and an intracellular kinase domain separated by a single transmembrane domain. The receptor is activated by a variety of polypeptide ligands such as epidermal growth factor and transforming growth factor α. It has long been thought that EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity for trans-autophosphorylation. An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding. Furthermore, recent progress in structural studies has provided insight into conformational changes during the activation of a pre-formed EGFR dimer. Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in the reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form (the "rotation model"). This model is also able to explain how oncogenic mutations activate the receptor in the absence of the ligand, without assuming that the mutations induce receptor dimerization. In this review, we discuss the mechanisms underlying the ligand-induced activation of the preformed EGFR dimer, as well as how oncogenic mutations constitutively activate the receptor dimer, based on the rotation model.


Optimization of DNA extraction for RAPD and ISSR analysis of Arbutus unedo L. Leaves.
Genetic analysis of plants relies on high yields of pure DNA. For the strawberry tree (Arbutus unedo) this represents a great challenge since leaves can accumulate large amounts of polysaccharides, polyphenols and secondary metabolites, which co-purify with DNA. For this specie, standard protocols do not produce efficient yields of high-quality amplifiable DNA. Here, we present for the first time an improved leaf-tissue protocol, based on the standard cetyl trimethyl ammonium bromide protocol, which yields large amounts of high-quality amplifiable DNA. Key steps in the optimized protocol are the addition of antioxidant compounds-namely polyvinyl pyrrolidone (PVP), 1,4-dithiothreitol (DTT) and 2-mercaptoethanol, in the extraction buffer; the increasing of CTAB (3%, w/v) and sodium chloride (2M) concentration; and an extraction with organic solvents (phenol and chloroform) with the incubation of samples on ice. Increasing the temperature for cell lyses to 70 °C also improved both DNA quality and yield. The yield of DNA extracted was 200.0 ± 78.0 μg/μL and the purity, evaluated by the ratio A(260)/A(280), was 1.80 ± 0.021, indicative of minimal levels of contaminating metabolites. The quality of the DNA isolated was confirmed by random amplification polymorphism DNA and by inter-simple sequence repeat amplification, proving that the DNA can be amplified via PCR.


Impact of 99mTc-HMPAO brain perfusion scan in the diagnosis of hemiplegic migraine.
Hemiplegic migraine (HM) is an unusual type of migraine, with few cases reported in the literature. Unlike other types of migraine, aura HM presents accompanying motor deficit manifestations that do not last more than 24 hours. We report a 27-year-old man referred to us from the emergency department to carry out a cerebral perfusion SPECT with (99m)Tc-HMPAO. He presented with intense headache and motor weakness. The brain perfusion scan was performed before and after intravenous infusion with nimodipine and showed a significant change of cerebral blood flow, allowing early and correct diagnosis.


Biomarkers in pulmonary hypertension: what do we know?
Pulmonary hypertension (PH) is a hemodynamic condition that has a poor prognosis and can lead to right-sided heart failure. It may result from common diseases such as left-sided heart or lung disease or may present as the rare entity of idiopathic pulmonary arterial hypertension. Biomarkers that specifically indicate the pathologic mechanism, the severity of the disease, and the treatment response would be ideal tools for the management of PH. In this review, markers related to heart failure, inflammation, hemostasis, remodeling, and endothelial cell-smooth muscle cell interaction are discussed, and their limitations are emphasized. Anemia, hypocarbia, elevated uric acid, and C-reactive protein levels are unspecific markers of disease severity. Brain natriuretic peptide and N-terminal fragment of pro-brain natriuretic peptide have been recommended in current guidelines, whereas other prognostic markers, such as growth differentiation factor-15, osteopontin, and red cell distribution width, are emerging. Chemokines of the CC family and matrix metalloproteases have been linked to the vascular pathologic mechanisms, and new markers such as apelin have been described. Circulating endothelial and progenitor cells have received much attention as markers of disease activity, but with controversial findings. A lack of standards for cell isolation and characterization methods and differences in the pathologic mechanisms of the investigated patients may have contributed to the discrepancies. In conclusion, although several promising markers have been identified over the past few years, the development of more specific markers, standardization, and prospective validation are warranted.


HIF has Biff - Crosstalk between HIF1a and the family of bHLH/PAS proteins.
Two decades of research into functions of the ubiquitous transcription factor HIF have revealed pervasive roles in development, oxygen homeostasis, metabolism, cancer and responses to ischemia. Unsurprisingly, HIF activities impinge on many pathologies, for which underlying molecular mechanisms are actively sought. HIF is a member of the heterodimeric bHLH/PAS family of transcription factors, a set of proteins that commonly function in developmental pathways and adaptive responses to environmental or physiological stress. Similarities in the mechanisms that regulate gene targeting by these transcription factors create opportunities for extensive crosstalk between family members. Data supporting pathway interactions between HIF1a and other bHLH/PAS factors, both collaborative and antagonistic, is beginning to surface in the areas of cancer, circadian rhythm, and immune responses. This review summarises the status of HIF1a-bHLH/PAS protein crosstalk and is dedicated to the memory of Lorenz Poellinger, a pioneer investigator into the molecular mechanisms of HIF, AHR, and ARNT bHLH/PAS factors.


Atypical neuroleptics: autonomy and compliance?
Non-compliance is a major stumbling block to the effectiveness of drug therapy. The nurse, both in hospital and community, has a crucial role to play in overcoming this problem to the benefit of the patient. Recent treatment advances, 'new-generation' anti-depressants and atypical neuroleptics, make this issue highly topical in mental health nursing. The atypical neuroleptics are a pharmacological breakthrough in the treatment of schizophrenia, which could herald a new era in psychiatry. These medicines give the benefits of the older (typical) neuroleptics but with fewer side-effects. Neuroleptics are sometimes called antipsychotics, antischizophrenics or major tranquillisers. Currently the atypical neuroleptics are not available in depot form. This critical review considers literature on interventions to promote compliance with neuroleptics generally and reflects on nursing implications relevant to the atypical neuroleptics. Three main forms of interventions emerge from the review; these are labelled as: imposed compliance, chosen compliance and active compliance. Historically the literature shows a gradual trend towards a realization by professionals that increased patient autonomy and involvement relates to improved compliance. This change in thinking is reflected in the new name 'adherence', which has begun to replace the term 'compliance'. It is concluded that mental health nurses have a key role to play in enabling this reconceptualization to change practice.


[Research Status and Prospect of New Ultrasound Technology in Predicting Cervical Lymph Node Metastasis of Thyroid Papillary Carcinoma].
Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer,accounting for 90%.Most cases of PTC are inert tumors,while a few are invasive.Cervical lymph node metastasis is one of the major manifestations of invasive PTC.Preoperative accurate prediction of cervical lymph node metastasis is of great significance for the selection of therapeutic regimen and the evaluation of prognosis.New ultrasound technology is a non-invasive,convenient,and radiation-free examination method,playing a key role in predicting the cervical lymph node metastasis of PTC.This paper reviews the research status and makes an outlook on new ultrasound technology in predicting cervical lymph node metastasis of PTC.


Bis[N-(2-furylmeth-yl)ethane-1,2-di-amine]-bis-(perchlorato)copper(II).
In the title complex, [Cu(ClO(4))(2)(C(7)H(12)N(2)O)(2)], the Cu(II) ion lies on a crystallographic inversion centre. The coordination sphere around Cu(II) ion can be described as tetragonally distorted octa-hedral with two perchlorate O atoms occupying the apical positions and four N atoms from two N(1)-(2-furyl-methyl)ethane-1,2-diamine ligands in the basal plane.


Effects induced by mono- and divalent cations on protein regions responsible for thermal adaptation in beta-glycosidase from Sulfolobus solfataricus.
The perturbation induced by mono- and divalent cations on the thermophilicity and thermostability of Solfolobus solfataricus beta-glycosidase, a hyperthermophilic tetrameric enzyme, has been investigated by spectroscopic and computational simulation methods to ascertain the Hofmeister effects on two strategic protein regions identified previously. Specifically, (1). an extra segment (83-124), present only in the sequence of hyperthermophilic glycosidases and recognized as an important thermostability determinant for the enzyme structure; and (2). a restricted area of the subunit interface responsible for the quaternary structure maintenance. Mono- and divalent cations inhibit to a different extent the beta-glycosidase activity, whose kinetic constants show an apparent competitive inhibition of the catalytic process that reflects the Hofmeister order. The thermostability is also affected by the nature and charge of the cations, reaching maximal effects for the case of Mg(2+). Fourier transform infrared spectroscopy has revealed very small changes in the protein secondary structure in the presence of the investigated cations at 20 degrees C, while large effects on the protein melting temperatures are observed. Computational analysis of the enzyme structure has identified negative patches on the accessible surface of the two identified regions. Following the Hofmeister series, cations weaken the existing electrostatic network that links the extra segment to the remaining protein matrix. In particular, the perturbing action of cations could involve the ionic pair interactions E107-R245 and E109-R185, thus leading to a local destructuring of the extra segment as a possible starting event for thermal destabilization. A detailed investigation of the electrostatic network at the A-C intermolecular interface of Sbetagly after energy minimization suggests that cations could cause a strong attenuation of the ion pair interactions E474-K72 and D473-R402, with consequent partial dissociation of the tetrameric structure.


Polarized distribution of extracellular nucleotides promotes gravity-directed polarization of development in spores of Ceratopteris richardii.
Gravity directs the polarization of Ceratopteris fern spores. This process begins with the uptake of calcium through channels at the bottom of the spore, a step necessary for the gravity response. Data showing that extracellular ATP (eATP) regulates calcium channels led to the hypothesis that extracellular nucleotides could play a role in the gravity-directed polarization of Ceratopteris spores. In animal and plant cells ATP can be released from mechanosensitive channels. This report tests the hypothesis that the polarized release of ATP from spores could be activated by gravity, preferentially along the bottom of the spore, leading to an asymmetrical accumulation of eATP. In order to carry out this test, an ATP biosensor was used to measure the [eATP] at the bottom and top of germinating spores during gravity-directed polarization. The [eATP] along the bottom of the spore averaged 7-fold higher than the concentration at the top. All treatments that disrupted eATP signaling resulted in a statistically significant decrease in the gravity response. In order to investigate the source of ATP release, spores were treated with Brefeldin A (BFA) and gadolinium trichloride (GdCl3). These treatments resulted in a significant decrease in gravity-directed polarization. An ATP biosensor was also used to measure ATP release after treatment with both BFA and GdCl3. Both of these treatments caused a significant decrease in [ATP] measured around spores. These results support the hypothesis that ATP could be released from mechanosensitive channels and secretory vesicles during the gravity-directed polarization of Ceratopteris spores.


Hemi[hexaaquamagnesium(II)] (mu-2,6-bis[[bis(carboxylatomethyl)amino]methyl]-4-chlorophenolato)bis[diaquamagnesium(II)] decahydrate.
The crystal structure of the title compound, [Mg(H2O)6]0.5[Mg2(C16H14ClN2O9)(H2O)4].10H2O, shows that this binuclear complex consists of two Mg centres in distorted octahedral geometry, joined by an oxo bridge which is a derivative of the deprotoned hydroxy group of the phenolate in the ligand molecule. In the anion, the coordination sphere of each MgII ion is completed by two carboxylates, a tertiary N atom and two water molecules. The inner coordination spheres for the MgII ions are very similar, both in ligand sets and in geometry. Each unit of the binuclear complex has one negative charge neutralized by a neighbouring hydrated cation, [Mg(H2O)6]2+, in which the Mg atom lies on an inversion centre. In each cell, there are 34 water molecules and most of them participate in the formation of hydrogen bonds, which contribute greatly to the stability of the whole structure.


Tracheostomy tubes and related appliances.
Tracheostomy tubes are used to administer positive-pressure ventilation, to provide a patent airway, to provide protection from aspiration, and to provide access to the lower respiratory tract for airway clearance. They are available in a variety of sizes and styles, from several manufacturers. The dimensions of tracheostomy tubes are given by their inner diameter, outer diameter, length, and curvature. Differences in length between tubes of the same inner diameter, but from different manufacturers, are not commonly appreciated but may have important clinical implications. Tracheostomy tubes can be angled or curved, a feature that can be used to improve the fit of the tube in the trachea. Extra proximal length tubes facilitate placement in patients with large necks, and extra distal length tubes facilitate placement in patients with tracheal anomalies. Several tube designs have a spiral wire reinforced flexible design and have an adjustable flange design to allow bedside adjustments to meet extra-length tracheostomy tube needs. Tracheostomy tubes can be cuffed or uncuffed. Cuffs on tracheostomy tubes include high-volume low-pressure cuffs, tight-to-shaft cuffs, and foam cuffs. The fenestrated tracheostomy tube has an opening in the posterior portion of the tube, above the cuff, which allows the patient to breathe through the upper airway when the inner cannula is removed. Tracheostomy tubes with an inner cannula are called dual-cannula tracheostomy tubes. Several tracheostomy tubes are designed specifically for use with the percutaneous tracheostomy procedure. Others are designed with a port above the cuff that allows for subglottic aspiration of secretions. The tracheostomy button is used for stoma maintenance. It is important for clinicians caring for patients with a tracheostomy tube to understand the nuances of various tracheostomy tube designs and to select a tube that appropriately fits the patient.


Associations between serum 25-hydroxyvitamin D levels and allergic sensitization in early childhood.
Vitamin D status may be related to allergen sensitizations, but the evidence is inconsistent. The objective of this study was to assess whether serum 25-hydroxyvitamin D (25(OH)D) levels were associated with allergic sensitizations in early childhood. Data were collected from 2642 children who visited the Guangdong Women and Children's Hospital from January 2016 to May 2017 for routine health check-ups. Serum 25(OH)D levels were tested by electrochemiluminescence immunoassay. Allergic sensitizations including food and inhalant allergens were tested for specific IgE antibodies at one year (12 months 0 days through 12 months 30 days) and two years (24 months 0 days through 24 months 30 days) of age. The mean level of serum 25(OH)D was 86.47±27.55nmol/L, with a high prevalence of vitamin D insufficiency (<75nmol/L) in children aged 0-2 years (36.8%). Lower 25(OH)D levels with serum total IgE of more than 200IU/mL (81.54±25.53nmol/L) compared with less than 100IU/mL (87.92±28.05nmol/L). The common sensitization to allergens in children aged one and two years were milk (44.2%), cat epithelium (26.4%), egg (13.1%), dog epithelium (12.7%) and Dermatophagoides farinae (6.7%). After multivariate adjustment, data in 25(OH)D treated as a continuous variable or categories, no consistent associations were found between 25(OH)D levels and allergen-specific IgEs. Serum 25(OH)D level showed an inverse relationship with total IgE level in early childhood. However, there is lack of evidence to support associations between low 25(OH)D levels and allergic sensitization to various allergens.


Idiopathic pulmonary haemosiderosis: spectrum of thoracic imaging findings in the adult patient.
Idiopathic pulmonary haemosiderosis (IPH) is a rare disease characterized by alveolar capillary haemorrhage resulting in deposition and accumulation of haemosiderin in the lungs. Although its precise pathophysiology remains unclear, several hypotheses have been proposed to explain the aetiology of the disorder, including autoimmune, environmental, allergic, and genetic theories. IPH is typically diagnosed in childhood, usually before the age of 10 years; however, this entity may be encountered in older patients given the greater awareness of the diagnosis, availability and utilization of advanced imaging techniques, and improved treatment and survival. The classic presentation of IPH consists of the triad of haemoptysis, iron-deficiency anaemia, and pulmonary opacities on chest radiography. The diagnosis is usually confirmed via bronchoscopy with bronchoalveolar lavage (BAL), at which time haemosiderin-laden macrophages referred to as siderophages, considered pathognomonic for IPH, may be identified. However, lung biopsy may ultimately be necessary to exclude other disease processes. For children with IPH, the disease course is severe and the prognosis is poor. However, adults generally have a longer disease course with milder symptoms and the prognosis is more favourable. Specific imaging features, although non-specific in isolation, may be identified on thoracic imaging studies, principally chest radiography and CT, depending on the phase of disease (acute or chronic). Recognition of these findings is important to guide appropriate clinical management.


Growth progression and 24-hour hormone profile in an infant treated chronically with a long-acting somatostatin derivative.
The diagnosis of nesidioblastosis was established in a 9-month-old male child with a history of recurrent convulsive seizures and hypoglycemia. After unsuccessful subtotal pancreatectomy, treatment was started with the long-acting somatostatin derivative Sandostatin (Octreotide, Sandoz) at a dosage of 25 micrograms t.i.d. spaced between carbohydrate-enriched meals. With this regime, blood glucose was maintained at the low normal range and seizures ceased. During a 30-month observation period, growth velocity and weight progression were well within the predicted limits. A 24-hour hormone profile recorded at the end of the observation period revealed the following: (1) failure to improve blood glucose with carbohydrate-enriched food due to reactive hyperinsulinemia; (2) hyperglycemic reaction after administration of Sandostatin caused by a reduction of plasma insulin; this effect was particularly marked during sleep; (3) low mean GH, decreased spiking frequency and reduced area covered by the nocturnal peaks by recognized standards, and (4) normal somatomedin C levels for age. Interpretation of growth hormone (GH) data is hindered by the lack of pertinent information from the patient's age group. Recording of normal growth progression in the case illustrated here can only be explained by the capability of a reduced GH secretory rate to maintain full biological activity as shown by the normal plasma level of somatomedin C. Indeed, recent evidence has been provided elsewhere for normal growth progression in the presence of low GH secretion, although other factors unrelated to this hormone may also be operative at this early age. Further reports concerning the treatment of non-GH-dependent conditions with somatostatin derivatives will certainly contribute to the better understanding of the mechanisms governing growth in the postnatal period.


Burden of Respiratory Syncytial Virus Disease and Mortality Risk Factors in Argentina: 18 Years of Active Surveillance in a Children's Hospital.
Respiratory syncytial virus is the leading cause of acute lower respiratory infection in children. We aimed to describe the clinical-epidemiologic pattern and risk factors for mortality associated with RSV infection. This is a prospective, cross-sectional study of acute lower respiratory infection in children admitted to the Children's Hospital during 2000 to 2017. Viral diagnosis was made by fluorescent antibody techniques or real-time-polymerase chain reaction. We compared clinical-epidemiologic characteristics of RSV infection in nonfatal versus fatal cases. Multiple logistic regression was used to identify independent predictors of mortality. Of 15,451 patients with acute lower respiratory infection, 13,033 were tested for respiratory viruses and 5831 (45%) were positive: RSV 81.3% (4738), influenza 7.6% (440), parainfluenza 6.9% (402) and adenovirus 4.3% (251). RSV had a seasonal epidemic pattern coinciding with months of lowest average temperature. RSV cases show a case fatality rate of 1.7% (82/4687). Fatal cases had a higher proportion of prematurity (P < 0.01), perinatal respiratory history (P < 0.01), malnourishment (P < 0.01), congenital heart disease (P < 0.01), chronic neurologic disease (P < 0.01) and pneumonia at clinical presentation (P = 0.014). No significant difference between genders was observed. Most deaths occurred among children who had complications: respiratory distress (80.5%), nosocomial infections (45.7%), sepsis (31.7%) and atelectasis (13.4%). Independent predictors of RSV mortality were moderate-to-severe malnourishment, odds ratio (OR): 3.69 [95% confidence interval (CI): 1.98-6.87; P < 0.0001]; chronic neurologic disease, OR: 4.14 (95% CI: 2.12-8.08; P < 0.0001); congenital heart disease, OR: 4.18 (95% CI: 2.39-7.32; P< 0.0001); and the age less than 6 months, OR: 1.99 (95% CI: 1.24-3.18; P = 0.004). RSV showed an epidemic pattern affecting mostly young children. Malnourishment, chronic neurologic disease, congenital heart disease and the age less than 6 months were the independent risk factors for RSV mortality.


Exploring Adolescent Cyber Victimization in Mobile Games: Preliminary Evidence from a British Cohort.
Mobile games, those played on smartphones and tablets, are rapidly becoming a dominant form of entertainment for young people. Given most of these games provide opportunities for competitive and cooperative play, they have the potential to build and enhance existing social relationships and might also provide an avenue for negative social experiences such as bullying or trolling behaviors. Unfortunately, little is understood about the prevalence or effects of cyberbullying for young people in this new form of electronic play. The present research, conducted in March 2018, surveyed a large and representative cohort of British adolescents and their caregivers (n = 2,008) with the aim of building an empirical understanding of this phenomenon. Adolescents were asked about their play habits and experiences, and caregivers provided data on their children's socioeconomic and demographic background and psychosocial functioning. Of key interest was estimating how frequently adolescents encounter bullying in mobile games, the extent to which bullying impacts them, and the sources of support adolescents seek following these events. Results indicated that bullying in mobile games is relatively common (33.5%), although less than 1 in 10 experiences serious repeated bullying (9.3%). Analysis showed males, players from a minority ethnicity, and those whose caregivers identified as having conduct problems, were the most likely to report significant victimization. Furthermore, nearly 4 in 10 (39.4%) reported feeling fairly or very upset by the experience and parents (49.3%), not gaming platforms (4.2%), were most likely to be sought out for support after bullying was experienced. Results are discussed with respect to this soon-to-be expanding research area and recommendations for the use of open scientific methodologies are provided.


Paracetamol increases sensitivity to ultraviolet (UV) irradiation, delays repair of the UNG-gene and recovery of RNA synthesis in HaCaT cells.
We have studied the effect of low levels of paracetamol (0.3 and 1.0 mM) on gene-specific DNA repair, recovery of total RNA synthesis and cytotoxicity after exposure of human keratinocyte cells (HaCaT) to ultraviolet (UV) irradiation. Repair of cyclobutane pyrimidine dimers (CPDs) was measured in the transcriptionally active uracil-DNA glycosylase (UNG) and c-MYC loci. Repair of both strands in the UNG gene was consistently lower in the presence of paracetamol, but this reduction reached significance only at 8 h after irradiation and no dose-response was observed. For the c-MYC gene, we found no significant effect of paracetamol on the repair of CPDs, possibly because UV-irradiation is known to induce transcription of the c-MYC gene and enhanced transcription coupled repair might counteract a negative effect of paracetamol on global genome repair. A dose-dependent delay in the recovery of total RNA synthesis after UV exposure was observed in the presence of paracetamol, which also caused a 20% increase in UV-induced cytotoxicity after 24 h. Paracetamol had no significant effect on either RNA synthesis or cell survival in the absence of UV after 24 h, but reduced cell survival by approximately 10% (at 0.3 mM) and 50%, (at 1.0 mM) after 96 h exposure. Our results demonstrate that paracetamol may inhibit gene-specific repair of CPDs by affecting global genome repair and that different genes may be differentially affected.


Monocytes in the Characterization of Pain in Palliative Patients with Severe Dementia-A Pilot Study.
In assessing and managing pain, when obtaining a self-report is impossible, therapeutic decision-making becomes more challenging. This study aimed to investigate whether monocytes and some membrane monocyte proteins, identified as a cluster of differentiation (CD), could be potential non-invasive peripheral biomarkers in identifying and characterizing pain in patients with severe dementia. We used 53 blood samples from non-oncological palliative patients, 44 patients with pain (38 of whom had dementia) and 0 without pain or dementia (controls). We evaluated the levels of monocytes and their subtypes, including classic, intermediate, and non-classic, and characterized the levels of specific phenotypic markers, namely CD11c, CD86, CD163, and CD206. We found that the relative concentrations of monocytes, particularly the percentage of classic monocytes, may be a helpful pain biomarker. Furthermore, the CD11c expression levels were significantly higher in patients with mixed pain, while CD163 and CD206 expression levels were significantly higher in patients with nociceptive pain. These findings suggest that the levels of monocytes, particularly the classic subtype, and their phenotype markers CD11c, CD163, and CD206 could serve as pain biomarkers in patients with severe dementia.


High-throughput multiplex HLA genotyping by next-generation sequencing using multi-locus individual tagging.
Unambiguous human leukocyte antigen (HLA) typing is important in transplant matching and disease association studies. High-resolution HLA typing that is not restricted to the peptide-binding region can decrease HLA allele ambiguities. Cost and technology constraints have hampered high-throughput and efficient high resolution unambiguous HLA typing. We have developed a method for HLA genotyping that preserves the very high-resolution that can be obtained by next-generation sequencing (NGS) but also achieves substantially increased efficiency. Unambiguous HLA-A, B, C and DRB1 genotypes can be determined for 96 individuals in a single run of the Illumina MiSeq. Long-range amplification of full-length HLA genes from four loci was performed in separate polymerase chain reactions (PCR) using primers and PCR conditions that were optimized to reduce co-amplification of other HLA loci. Amplicons from the four HLA loci of each individual were then pooled and subjected to enzymatic library generation. All four loci of an individual were then tagged with one unique index combination. This multi-locus individual tagging (MIT) method combined with NGS enabled the four loci of 96 individuals to be analyzed in a single 500 cycle sequencing paired-end run of the Illumina-MiSeq. The MIT-NGS method generated sequence reads from the four loci were then discriminated using commercially available NGS HLA typing software. Comparison of the MIT-NGS with Sanger sequence-based HLA typing methods showed that all the ambiguities and discordances between the two methods were due to the accuracy of the MIT-NGS method. The MIT-NGS method enabled accurate, robust and cost effective simultaneous analyses of four HLA loci per sample and produced 6 or 8-digit high-resolution unambiguous phased HLA typing data from 96 individuals in a single NGS run.


[C-MOS flat-panel sensor for real time X-ray imaging].
Flat-panel, self-scanning, solid state diagnostic x-ray imaging devices using complementary metal-oxide-semiconductor (C-MOS) arrays are under investigation. A unit device with a 5 cm by 5 cm sensor area was developed and tested. The device consists of a CsI scintillator and C-MOS detector arrays. The detector arrays are composed of a regular arrangement of pixels (256 x 256), each of which is made of a C-MOS photodiode sensor coupled to a C-MOS FET (field effect transistor). A common FET gate line is connected to all the FET gates along each column. A common date line is connected to all the FET drains of each row. The source contact of each FET is connected to that of its corresponding photodiode. A positive gate pulse applied to a gate turns on all FETs connected to the date lines. The readout continues column by column. Correlated double sampling circuits and an offset variance compensation circuit were installed to reduce noise. A sampling speed of 15 frames per second and spatial resolution of 2.5 line per mm were achieved. Noise level and maximum signal were 1.5 mV rms and 1.8 V, respectively. Image quality was considered acceptable for clinical use. It is also discussed how to fabricate a large area sensor with the unit device.


Injectable long-acting human immunodeficiency virus antiretroviral prodrugs with improved pharmacokinetic profiles.
While highly active antiretroviral therapy (HAART) has significantly reduced mortality rates in patients with human immunodeficiency virus type 1 (HIV-1), its efficacy may be impeded by emergence of drug resistance caused by lack of patient adherence. A therapeutic strategy that requires infrequent drug administration as a result of sustained release of antiretroviral drugs would put less burden on the patient. Long-acting antiretroviral prodrugs for HIV therapy were synthesized through modification of the active drugs, emtricitabine (FTC) and elvitegravir (EVG), with docosahexaenoic acid (DHA) in one-step, one-pot, high-yielding reactions. The in vitro drug release profiles of these synthetic conjugates demonstrated sustained and controlled release of the active drug over a period of 3-4 weeks attributable to the hydrolysis of the chemical linker in conjunction with the hydrophilicity of the parent drug. Both conjugates exhibited superior antiviral activities in tissue culture models of HIV replication as compared to those of the free drugs, strengthening their role as potent prodrugs for HIV therapy. Pharmacokinetic analysis in CD1 mice further confirmed the long-acting aspect of these conjugates with released drug concentrations in plasma detected at their respective IC90/IC95 values over a period of 2 weeks and discernable amounts of active drug even at 6 weeks. Our findings suggest that the injectable small molecule conjugates could be used as long-acting controlled release of FTC and EVG in attempts to mitigate adherence-related HIV resistance.


Thomas j. Burrill, pioneer in plant pathology.
Perhaps no other American plant pathologist is so deserving of the title "Pioneer of Plant Pathology" as Thomas J. Burrill. A product of the American frontier and a researcher and teacher of plant pathology before the science even had a name, Burrill was a pioneer in every sense of the word. His original research on the cause of fire blight resulted in the first major conceptual advance in plant pathology made by an American. He also played an important role as an administrator and teacher at the University of Illinois. Many of the problems Burrill faced during his long and distinguished career will sound familiar to academic scientists of our own time. In particular, he and his contemporaries contended with student unrest, flagging public interest in higher education, heavy teaching loads, and insufficient support for research activities. By any measure, Burrill was unusually successful in coping with these problems and he fashioned a career remarkable in its contributions to his university, the public, and the scientific community.


Kilogram-Scale Synthesis and Functionalization of Carbon Dots for Superior Electrochemical Potassium Storage.
Carbon dot is a type of carbon material with an ultrasmall size of less than 10 nm for all three dimensions, which has attracted more and more attention due to its useful merits. Unfortunately, the complicated synthesis method and low yield largely limit its wide large-scale application. Herein, an inexpensive and high-efficiency aldol condensation method under ambient temperature and pressure was proposed for the large-scale synthesis of CDs, which can obtain products with 1.083 kg in 2 h and realize the functionalization of carbon dots doped with nitrogen (NCDs) and sulfur/nitrogen doubly (NSCDs), and then the mechanism and structure of CDs formation were explained. Moreover, utilizing the feature of controllable assembly of carbon dots, and combined with theoretical calculations, we have designed functionalized 1D carbon fibers (CF) to construct high-performance potassium storage anode materials through the assembly of carbon dots induced by a Zn compound. Benefitting from the microstructure and surface functional groups derived from CDs, the N-doped CF (NCF700) exhibits superior electrochemical energy storage performance for potassium ion batteries (PIBs). This study provides a low-cost and high-yield method to produce CDs and promotes the practical application of CDs in electrochemical energy storage.


Fine Mapping and Transcriptome Analysis Reveal Candidate Genes Associated with Hybrid Lethality in Cabbage (Brassica Oleracea).
Hybrid lethality is a deleterious phenotype that is vital to species evolution. We previously reported hybrid lethality in cabbage (Brassica oleracea) and performed preliminary mapping of related genes. In the present study, the fine mapping of hybrid lethal genes revealed that BoHL1 was located on chromosome C1 between BoHLTO124 and BoHLTO130, with an interval of 101 kb. BoHL2 was confirmed to be between insertion-deletion (InDels) markers HL234 and HL235 on C4, with a marker interval of 70 kb. Twenty-eight and nine annotated genes were found within the two intervals of BoHL1 and BoHL2, respectively. We also applied RNA-Seq to analyze hybrid lethality in cabbage. In the region of BoHL1, seven differentially expressed genes (DEGs) and five resistance (R)-related genes (two in common, i.e., Bo1g153320 and Bo1g153380) were found, whereas in the region of BoHL2, two DEGs and four R-related genes (two in common, i.e., Bo4g173780 and Bo4g173810) were found. Along with studies in which R genes were frequently involved in hybrid lethality in other plants, these interesting R-DEGs may be good candidates associated with hybrid lethality. We also used SNP/InDel analyses and quantitative real-time PCR to confirm the results. This work provides new insight into the mechanisms of hybrid lethality in cabbage.


Final report of the safety assessment of L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as used in cosmetics.
L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate function in cosmetic formulations primarily as antioxidants. Ascorbic Acid is commonly called Vitamin C. Ascorbic Acid is used as an antioxidant and pH adjuster in a large variety of cosmetic formulations, over 3/4 of which were hair dyes and colors at concentrations between 0.3% and 0.6%. For other uses, the reported concentrations were either very low (<0.01%) or in the 5% to 10% range. Calcium Ascorbate and Magnesium Ascorbate are described as antioxidants and skin conditioning agents--miscellaneous for use in cosmetics, but are not currently used. Sodium Ascorbyl Phosphate functions as an antioxidant in cosmetic products and is used at concentrations ranging from 0.01% to 3%. Magnesium Ascorbyl Phosphate functions as an antioxidant in cosmetics and was reported being used at concentrations from 0.001% to 3%. Sodium Ascorbate also functions as an antioxidant in cosmetics at concentrations from 0.0003% to 0.3%. Related ingredients (Ascorbyl Palmitate, Ascorbyl Dipalmitate, Ascorbyl Stearate, Erythorbic Acid, and Sodium Erythorbate) have been previously reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel and found "to be safe for use as cosmetic ingredients in the present practices of good use." Ascorbic Acid is a generally recognized as safe (GRAS) substance for use as a chemical preservative in foods and as a nutrient and/or dietary supplement. Calcium Ascorbate and Sodium Ascorbate are listed as GRAS substances for use as chemical preservatives. L-Ascorbic Acid is readily and reversibly oxidized to L-dehydroascorbic acid and both forms exist in equilibrium in the body. Permeation rates of Ascorbic Acid through whole and stripped mouse skin were 3.43 +/- 0.74 microg/cm(2)/h and 33.2 +/- 5.2 microg/cm(2)/h. Acute oral and parenteral studies in mice, rats, rabbits, guinea pigs, dogs, and cats demonstrated little toxicity. Ascorbic Acid and Sodium Ascorbate acted as a nitrosation inhibitor in several food and cosmetic product studies. No compound-related clinical signs or gross or microscopic pathological effects were observed in either mice, rats, or guinea pigs in short-term studies. Male guinea pigs fed a control basal diet and given up to 250 mg Ascorbic Acid orally for 20 weeks had similar hemoglobin, blood glucose, serum iron, liver iron, and liver glycogen levels compared to control values. Male and female F344/N rats and B6C3F(1) mice were fed diets containing up to 100,000 ppm Ascorbic Acid for 13 weeks with little toxicity. Chronic Ascorbic Acid feeding studies showed toxic effects at dosages above 25 mg/kg body weight (bw) in rats and guinea pigs. Groups of male and female rats given daily doses up to 2000 mg/kg bw Ascorbic Acid for 2 years had no macro- or microscopically detectable toxic lesions. Mice given Ascorbic Acid subcutaneous and intravenous daily doses (500 to 1000 mg/kg bw) for 7 days had no changes in appetite, weight gain, and general behavior; and histological examination of various organs showed no changes. Ascorbic Acid was a photoprotectant when applied to mice and pig skin before exposure to ultraviolet (UV) radiation. The inhibition of UV-induced suppression of contact hypersensitivity was also noted. Magnesium Ascorbyl Phosphate administration immediately after exposure in hairless mice significantly delayed skin tumor formation and hyperplasia induced by chronic exposure to UV radiation. Pregnant mice and rats were given daily oral doses of Ascorbic Acid up to 1000 mg/kg bw with no indications of adult-toxic, teratogenic, or fetotoxic effects. Ascorbic Acid and Sodium Ascorbate were not genotoxic in several bacterial and mammalian test systems, consistent with the antioxidant properties of these chemicals. In the presence of certain enzyme systems or metal ions, evidence of genotoxicity was seen. The National Toxicology Program (NTP) conducted a 2-year oral carcinogenesis bioassay of Ascorbic Acid (25,000 and 50,000 ppm) in F344/N rats and B6C3F(1) mice. Ascorbic Acid was not carcinogenic in either sex of both rats and mice. Inhibition of carcinogenesis and tumor growth related to Ascorbic Acid's antioxidant properties has been reported. Sodium Ascorbate has been shown to promote the development of urinary carcinomas in two-stage carcinogenesis studies. Dermal application of Ascorbic Acid to patients with radiation dermatitis and burn victims had no adverse effects. Ascorbic Acid was a photoprotectant in clinical human UV studies at doses well above the minimal erythema dose (MED). An opaque cream containing 5% Ascorbic Acid did not induce dermal sensitization in 103 human subjects. A product containing 10% Ascorbic Acid was nonirritant in a 4-day minicumulative patch assay on human skin and a facial treatment containing 10% Ascorbic Acid was not a contact sensitizer in a maximization assay on 26 humans. Because of the structural and functional similarities of these ingredients, the Panel believes that the data on one ingredient can be extrapolated to all of them. The Expert Panel attributed the finding that Ascorbic Acid was genotoxic in these few assay systems due to the presence of other chemicals, e.g., metals, or certain enzyme systems, which effectively convert Ascorbic Acid's antioxidant action to that of a pro-oxidant. When Ascorbic Acid acts as an antioxidant, the Panel concluded that Ascorbic Acid is not genotoxic. Supporting this view were the carcinogenicity studies conducted by the NTP, which demonstrated no evidence of carcinogenicity. Ascorbic Acid was found to effectively inhibit nitrosamine yield in several test systems. The Panel did review studies in which Sodium Ascorbate acted as a tumor promoter in animals. These results were considered to be related to the concentration of sodium ions and the pH of urine in the test animals. Similar effects were seen with sodium bicarbonate. Because of the concern that certain metal ions may combine with these ingredients to produce pro-oxidant activity, the Panel cautioned formulators to be certain that these ingredients are acting as antioxidants in cosmetic formulations. The Panel believed that the clinical experience in which Ascorbic Acid was used on damaged skin with no adverse effects and the repeat-insult patch test (RIPT) using 5% Ascorbic Acid with negative results supports the finding that this group of ingredients does not present a risk of skin sensitization. These data coupled with an absence of reports in the clinical literature of Ascorbic Acid sensitization strongly support the safety of these ingredients.


Sensory Features of Partially Hydrogenated Oil and Their Connection with Melting and Crystalline Characteristics.
Although partially hydrogenated oil (PHO) provides foods with outstanding thick tastes and pronounced "creamy" flavor, the high level of artificial trans-fatty acids (TFA; about 30%) limits its usages around the world in the near future. It is necessary to produce trans-free alternatives with similar tastes to PHO. The relationship between sensory attributes and physicochemical characteristics of PHO and four typical specialty fats were therefore analyzed in the present study. PHO exhibited the highest greasiness score (8.19), accompanying by mild creaminess and aftertaste as well as a weak coolness during swallow, which were resulted from the close-packed arrangements of TFA, its cis-counterparts and other long chain fatty acids. None of artificial trans-fats, mainly anhydrous milk fat, cocoa butter, and coconut oil and its fully hydrogenated counterpart, were similar to PHO in terms of these sensory attributes. The unique fatty acid species of PHO and their arrangements contributed to the relatively smooth solid fat content profile and melting-crystallization curve, as well as forming uniform and dense β' crystal-structures (Db=1.80). The Pearson correlation analyses relevelled that long chain fatty acids, e.g., t-C18:1 and C18:1, and melting final temperatures were generally positive correlated with greasiness, creaminess and aftertaste; whereas these indices were negatively correlated with coolness. The melting enthalpy was highly connected with coolness, which reflected the endothermic effectiveness during the melting process of fats in the mouth. These indices screened by correlation analyses that were strongly correlated with sensory attributes could provide references for producing trans-free alternatives.


Pharmacology and pharmacokinetics of minoxidil.
Minoxidil is a potent oral vasodilator acting on the arteriolar side of the circulation. Reflex tachycardia and sodium retention are consequences of increased sympathetic activity. Its biotransformation is 90% hepatic, with no evidence of accumulation of minoxidil when it is given chronically in patients with either normal renal function. The half-life is approximately 3 hr, regardless of whether the dose is given singly or on a multiple-dose basis. It is widely distributed throughout the body, and hence its volume of distribution is greater than 200 liters. There appears to be a dissociation between the peak plasma concentration and the antihypertensive response owing to the fact that minoxidil rapidly leaves the plasma on its way to the principal site of action, that is, the vascular smooth-muscle receptor site. No tolerance or refractoriness appears to develop with long-term minoxidil administration.


Defective thyroglobulin synthesis in an experimental rat thyroid tumor: iodination and thyroid hormone synthesis in isolated tumor thyroglobulin.
Purified rat tumor thyroglobulin from the experimental rat thyroid tumor, line 1-1C2, was studied for its thyroid hormone content after in vivo and in vitro iodination and compared with normal and desialylated normal rat thyroglobulin. Tumor thyroglobulin had a very low sialic acid and iodine content; after in vivo iodination it contained only small amounts of triiodothyronine (T3) and no detectable thyroxine (T4). After in vitro iodination with 125I it showed a distribution of T3 and T4 very similar to that of normal and desialylated normal thyroglobulin iodinated in vitro. In vitro iodination dissociated tumor and desialylated normal thyroglobulin to a greater extent than normal thyroglobulin. Tumor tissue, on the other hand, showed considerable iodinating activity in the 105,000 X g pellet when studied with exogenous acceptors. These results are compatible with a role for sialic acid in the maturation and migration of thyroglobulin to the iodination site, rpovided that the intracellular distribution of the iodinating enzymes are normal.


Improving the Patient Experience by Implementing an ICU Diary for Those at Risk of Post-intensive Care Syndrome.
The critical care literature in the US has recently brought attention to the impact an ICU experience can have long after the patient survives critical illness, particularly if delirium was present. Current recommendations to mitigate post-intensive care syndrome (PICS) are embedded in patient and family-centered care and aim to promote family presence in the ICU, provide support for decision-making, and enhance communication with the health-care team. Evidence-based interventions are few in number but include use of an ICU diary to minimize the psychological and emotional sequelae affecting patients and family members in the months following the ICU stay. In this paper we describe our efforts to implement an ICU diary and solicit feedback on its role in fostering teamwork and communication between patients, family members, and ICU staff. Next steps will involve a PICS follow-up clinic where trained staff will coordinate specialty referrals and perform long-term monitoring of mental health and other quality of life outcomes.


XT-considered multiple backup paths and resources shared protection scheme based on ring covers.
With the rapid development of space division multiplexing (SDM) and flexible grid technology, the problem of resource allocation in optical network becomes much more complicated. Although there emerge a substantial number of works about link protection or restoration in SDM-EONs mesh networks, the topic of survivability is dug deeper in this work. It is acknowledged that protection schemes based on ring covers bring the advantages of shorter restoration time and lower costs. However, the RSCA problem in SDM-EON for link protection based on ring covers has rarely been investigated. To enhance the survivability of SDM-EON and make the best use of ring covers, we initially select a set of rings for the protection of all the links in a network topology according to constrains, aiming at taking full advantages of network resources. After that, we propose an algorithm to recover the traffic which will break off under link failures, basing on the set of rings. At the end of this protection scheme, we arrange the resources fulfilling the constrains of spectrum contiguity and core continuity constrains by using several different algorithms considering physical impairment. Based on the allocation in both spacial and spectral dimensions, our algorithms achieve better results of survivability. According to the simulations conducted for the evaluation of the proposed algorithms, our algorithms manage to recover at least 72.8% of traffic when the traffic request number is set to be 1000.


Using MoBIoS' scalable genome join to find conserved primer pair candidates between two genomes.
For the purpose of identifying evolutionary reticulation events in flowering plants, we determine a large number of paired, conserved DNA oligomers that may be used as primers to amplify orthologous DNA regions using the polymerase chain reaction (PCR). We develop an initial candidate set by comparing the Arabidopsis and rice genomes using MoBIoS (Molecular Biological Information System). MoBIoS is a metric-space database management system targeting life science data. Through the use of metric-space indexing techniques, two genomes can be compared in O(mlog n), where m and n are the lengths of the genomes, versus O(mn) for BLAST-based analysis. The filtering of low-complexity regions may also be accomplished by directly assessing the uniqueness of the region. We describe mSQL, a SQL extension being developed for MoBIoS that encapsulates the algorithmic details in a common database programming language, shielding end-users from esoteric programming. Available upon request from authors.


Different types of Internet use, depression, and social anxiety: the role of perceived friendship quality.
The current study examined the longitudinal associations of time spent on Internet activities for communication purposes (i.e., IM-ing) versus time spent on Internet activities for non-communication purposes (i.e., surfing) with depression and social anxiety, as well as the moderating role of perceived friendship quality in these associations. Questionnaire data were gathered from 307 Dutch middle adolescents (average age 15 years) on two waves with a one-year interval. For adolescents who perceive low friendship quality, Internet use for communication purposes predicted less depression, whereas Internet use for non-communication purposes predicted more depression and more social anxiety. These results support social compensation effects of IM-ing on depression and poor-get-poorer effects of surfing on depression and social anxiety, respectively.


Extent of sample loss on the sampling device and the resulting experimental biases when collecting volatile fatty acids (VFAs) in air using sorbent tubes.
Not all volatile organic compounds (VOCs) are suitable for sampling from air onto sorbent tubes (ST) with subsequent analysis by thermal desorption (TD) with gas chromatography (GC). Some compounds (such as C2 hydrocarbons) are too volatile for quantitative retention by sorbents at ambient temperature, while others are too reactive - either for storage stability on the tubes (post-sampling) or for thermal desorption/GC analysis. Volatile fatty acids (VFAs) are one of the compound groups that present a challenge to sorbent tube sampling. In this study, we evaluated sample losses on the inner wall surface of the sorbent tube sampler. The sorptive losses of five VFA (acetic, propionic, n-butyric, i-valeric, and n-valeric acid) were tested using two types of tubes (stainless steel and quartz), each packed with three sorbent beds arranged in order of sorbent strength from the sampling end of the tube (Tenax TA, Carbopack B, and Carbopack X). It showed significantly higher losses of VFAs in both liquid phase and vapor phase when using stainless steel tube samplers. These losses were also seen if vapor-phase fatty acids were passed through empty stainless steel tubing and increased dramatically with increasing molecular weight, e.g., losses of 33.6% (acetic acid) to 97.5% (n-valeric acid). Similar losses of VFAs were also observed from headspace sampling of cheese products. Considering that stainless steel sampling tubes are still used extensively by many researchers, their replacement with quartz tubes is recommended to reduce systematic biases in collecting VFA samples or in their calibration.


The root herbivore history of the soil affects the productivity of a grassland plant community and determines plant response to new root herbivore attack.
Insect root herbivores can alter plant community structure by affecting the competitive ability of single plants. However, their effects can be modified by the soil environment. Root herbivory itself may induce changes in the soil biota community, and it has recently been shown that these changes can affect plant growth in a subsequent season or plant generation. However, so far it is not known whether these root herbivore history effects (i) are detectable at the plant community level and/or (ii) also determine plant species and plant community responses to new root herbivore attack. The present greenhouse study determined root herbivore history effects of click beetle larvae (Elateridae, Coleoptera, genus Agriotes) in a model grassland plant community consisting of six common species (Achillea millefolium, Plantago lanceolata, Taraxacum officinale, Holcus lanatus, Poa pratensis, Trifolium repens). Root herbivore history effects were generated in a first phase of the experiment by growing the plant community in soil with or without Agriotes larvae, and investigated in a second phase by growing it again in the soils that were either Agriotes trained or not. The root herbivore history of the soil affected plant community productivity (but not composition), with communities growing in root herbivore trained soil producing more biomass than those growing in untrained soil. Additionally, it influenced the response of certain plant species to new root herbivore attack. Effects may partly be explained by herbivore-induced shifts in the community of arbuscular mycorrhizal fungi. The root herbivore history of the soil proved to be a stronger driver of plant growth on the community level than an actual root herbivore attack which did not affect plant community parameters. History effects have to be taken into account when predicting the impact of root herbivores on grasslands.


A negative correlation between insulin-like peptide 3 and bisphenol A in human cord blood suggests an effect of endocrine disruptors on testicular descent during fetal development.
Does a relationship exist between insulin-like peptide 3 (INSL3) and selected environmental endocrine disruptors (EEDs) in human cord blood (cb)? In the whole population (cryptorchid and control boys) cbINSL3 correlated negatively with cb free bisphenol A (BPA) providing indirect evidence for an impact of EEDs on fetal Leydig cell INSL3 production. INSL3 is a major regulator of testicular descent. This hormone has been shown to be decreased in cord blood from boys with idiopathic cryptorchidism, the most frequent male malformation. Fetal exposure to several EEDs has been suspected to be involved in the occurrence of idiopathic cryptorchidism. Correlations between cb INSL3 or testosterone and cb free bioactive BPA and maternal milk polychlorinated biphenyls (PCB153), dichlorodiphenyldichloroethylene (DDE), and monobutyl phthalate (mBP) were assessed in newborn boys in a prospective case-control study. All boys (n = 6246) born after 34 weeks of gestation were systematically screened at birth for cryptorchidism over a 3-year period (2002-2005), and a diagnosis of cryptorchidism confirmed by a senior paediatrician. We studied 52 cryptorchid (26 transient, 26 persistent) and 128 control boys born at two hospitals in southern France. INSL3 was assayed in CB by a modified validated enzyme-linked immunosorbent assay. Testosterone was measured in CB after diethyl-ether extraction by means of ultra-pressure liquid chromatography-tandem mass spectrometry. Free cbBPA was measured after an extraction step with a radioimmunoassay validated after comparison of values obtained by high-pressure liquid chromatography-mass spectrometry. The xenobiotic analysis in mothers' milk was performed after fat extraction by gas chromatography-mass spectrometry. EED concentrations were not increased in the cryptorchid versus control group although a trend for increased mBP (P = 0.09) was observed. In the whole study population, cb levels of BPA correlated negatively with INSL3 (P = 0.01; R² = 0.05) but not with testosterone. No other EED correlated with INSL3 or with testosterone. The levels of BPA and INSL3 in cb may not reflect chronic fetal exposure to EEDs. The deleterious impact of EEDs on fetal testicular descent during specific windows of development has yet to be demonstrated. The negative correlation between cb free BPA and INSL3 provides indirect evidence for an impact of EEDs on human fetal Leydig cell INSL3 production and points to cbINSL3 as a possible target of EED action during fetal testis development.


Low-temperature roll-to-roll atmospheric atomic layer deposition of Al₂O₃ thin films.
The Al2O3 thin films deposition through conventional ALD systems is a well-established process. The process under low temperatures has been studied by few research groups. In this paper, we report on the detailed study of low-temperature Al2O3 thin films deposited via a unique in-house built system of roll-to-roll atmospheric atomic layer deposition (R2R-AALD) using a multiple-slit gas source head. Al2O3 thin films have been grown on polyethylene terephthalate substrates under a very low-temperature zone of room temperature to 50 °C and working pressure of 750 Torr, which is very near to atmospheric pressure (760 Torr). Al2O3 thin films with superior properties were achieved in the temperature range of the ALD window. An appreciable growth rate of 0.97 Å/cycle was observed for the films deposited at 40 °C. The films have good morphological features with a very low average arithmetic roughness (Ra) of 0.90 nm. The films also showed good chemical, electrical, and optical characteristics. It was observed that the film characteristics improve with the increase in deposition temperature to the range of the ALD window. The fabrication of Al2O3 films was confirmed by X-ray photoelectron spectroscopy (XPS) analysis with the appearance of Al 2p, Al 2s, and O 1s peaks at the binding energies of 74, 119, and 531 eV, respectively. The chemical composition was also supported by the Fourier transform infrared spectroscopy (FTIR). The fabricated Al2O3 films demonstrate good insulating properties and optical transmittance of more than 85% in the visible region. The results state that Al2O3 thin films can be effectively fabricated through the R2R-AALD system at temperatures as low as 40 °C.


[New features in the recommendations of the Second Hungarian Therapeutic Consensus Conference].
The First Hungarian Therapeutic Consensus Conference took place on 3rd Nov. 2003 with the participation of 9 medical societies. Over the past 2 years the results of new major studies have been published and the American ATP III has also updated its guidelines issued in 2004. Based on the above proposals, the Second Hungarian Therapeutic Consensus Conference held on 3rd Nov. 2005 partly confirmed its earlier suggestions, but made some changes as well. Within the high risk category the Conference optionally created a very high risk group from those patients who - in addition to their cardiovascular disease--have either diabetes or metabolic syndrome or acut coronaria syndrome or who are chain smokers. We have included - as a complement - into the asymptomatic high risk category such newly emerging risk factors, one of which already in itself means high risk: ankle/arm index < or = 0.9, GFR <60 ml/min, microalbuminuria (30-300 mg), preclinical atherosclerosis (plaque). Besides, 4 other risk factors were also categorised such as Lp/a (> or = 30 mg/dl), CRP (> or = 3mg/l), homocysteine (> or = 12 micromol), familiarity--atherogenic gene constellation, but only the presence of at least two of these verify high risk. In very high risk group the goals of 3.5 mmol/l and 1.8 mmol/l were determined as therapeutic option. The goal in obese patients--expressed earlier only in BMI--can now be equally determined by the abdominal circumference (94 cm for men, 80 cm for women respectively). ACE inhibitors were recommended earlier as a preventive therapy in case of dysfunction of the left ventricle, while at present they are suggested for all patients with cardiovascular disease. In the recent recommendations guidelines related to nutrition, smoking, exercise have also been included.


Synthetic Lethality with Trifluridine/Tipiracil and Checkpoint Kinase 1 Inhibitor for Esophageal Squamous Cell Carcinoma.
Esophageal squamous cell carcinoma (ESCC) is a disease characterized by a high mutation rate of the TP53 gene, which plays pivotal roles in the DNA damage response (DDR) and is regulated by checkpoint kinase (CHK) 2. CHK1 is another key DDR-related protein, and its selective inhibition is suggested to be particularly sensitive to TP53-mutated cancers, because a loss of both pathways (CHK1 and/or CHK2-p53) is lethal due to the serious impairment of DDR. Such a therapeutic strategy is termed synthetic lethality. Here, we propose a novel therapeutic strategy based on synthetic lethality combining trifluridine/tipiracil and prexasertib (CHK1 inhibitor) as a treatment for ESCC. Trifluridine is a key component of the antitumor drug combination with trifluridine/tipiracil (an inhibitor of trifluridine degradation), also known as TAS-102. In this study, we demonstrate that trifluridine increases CHK1 phosphorylation in ESCC cells combined with a reduction of the S-phase ratio as well as the induction of ssDNA damage. Because CHK1 phosphorylation is considered to be induced as DDR for trifluridine-mediated DNA damage, we examined the effects of CHK1 inhibition on trifluridine treatment. Consequently, CHK1 inhibition by short hairpin RNA or treatment with the CHK1 inhibitor, prexasertib, markedly enhanced trifluridine-mediated DNA damage, represented by an increase of γH2AX expression. Moreover, the combination of trifluridine/tipiracil and CHK1 inhibition significantly suppressed tumor growth of ESCC-derived xenograft tumors. Furthermore, the combination of trifluridine and prexasertib enhanced radiosensitivity both in vitro and in vivo Thus, the combination of trifluridine/tipiracil and a CHK1 inhibitor exhibits effective antitumor effects, suggesting a novel therapeutic strategy for ESCC.


Functional clustering: identifying strongly interactive brain regions in neuroimaging data.
Brain imaging data are generally used to determine which brain regions are most active in an experimental paradigm or in a group of subjects. Theoretical considerations suggest that it would also be of interest to know which set of brain regions are most interactive in a given task or group of subjects. A subset of regions that are much more strongly interactive among themselves than with the rest of the brain is called here a functional cluster. Functional clustering can be assessed by calculating for each subset of brain regions a measure, the cluster index, obtained by dividing the statistical dependence within the subset by that between the subset and rest of the brain. A cluster index value near 1 indicates a homogeneous system, while a high cluster index indicates that a subset of brain regions forms a distinct functional cluster. Within a functional cluster, individual brain regions are ranked at the center or at the periphery according to their statistical dependence with the rest of that cluster. The applicability of this approach has been tested on PET data obtained from normal and schizophrenic subjects performing a set of cognitive tasks. Analysis of the data reveals evidence of functional clustering. A comparative evaluation of which regions are more peripheral or more central suggests distinct differences between the two groups of subjects. We consider the applicability of this analysis to data obtained with imaging modalities offering higher temporal resolution than PET.


Problem-based learning in dental education: a systematic review of the literature.
The purpose of this systematic review was to compare the effectiveness of problem-based learning (PBL) with that of traditional (non-PBL) approaches in dental education. The search strategy included electronic and manual searches of studies published up to October 2012. The PICO (Population, Intervention, Comparator, and Outcome) framework was utilized to guide the inclusion or exclusion of studies. The search strategy identified 436 articles, seventeen of which met the inclusion criteria. No randomized controlled trial was found comparing the effectiveness of PBL with that of lecture-based approach at the level of an entire curriculum. Three randomized controlled trials had evaluated the effectiveness of PBL at a single course level. The quality assessment rated four studies as being of moderate quality, while the other studies were assessed as being of weak quality. This review concludes that there are a very limited number of well-designed controlled studies evaluating the effectiveness of PBL in dental education. The data in those studies reveal that PBL does not negatively influence the acquisition of factual knowledge in dental students and PBL enhances the ability of students in applying their knowledge to clinical situations. In addition, PBL positively affects students' perceived preparedness.


Prevention, identification and treatment of vulvar squamous (pre)malignancies: a review focusing on quality of care.
Vulvar squamous cell carcinoma, its precursor lesions (usual and differentiated vulvar intraepithelial neoplasia) and lichen sclerosus are rare diseases that may have a large impact on the lives of affected women and their partners. Proper identification is vital, but the lesions are sometimes difficult to diagnose because of their rarity and variety of symptoms. High quality of care and proper treatment is important in order to minimize the morbidity and mortality caused by these lesions. This review gives an outline of the latest insights regarding the current evidence in this area and unresolved issues. Additionally, it highlights the improvements that should be made in order to optimize prevention and identification of (pre-)malignant vulvar lesions and to increase the quality of care for these patients.


[Cloning and identification of cellulase genes from uncultured microorganisms in pulp sediments from paper mill effluent].
The metagenomic DNA of pulp sediments from paper mill effluent was extracted and purified. The 16S rDNA was amplified using the purified metagenomic DNA as template and a 16S rDNA library was prepared. Sequence analysis of 16S rDNA clones showed that diverse of uncultured bacteria inhabit in this environment, which can be classified into 4 clusters as Spirochaetes, Proteobacteria, Bacteroidetes and Firmicutes. A metagenomic library containing 10000 clones was constructed into cosmid vector, and the capacity of inserted DNA of which was 3.53 x 10(8) bp. Functional screening of the library resulted in isolation of two independent clones expressing endoglucanase activity, three independent clones expressing exoglucanase activity and two independent clones expressing beta-glucosidase activity. One clone expressing strongest enzyme activity from each activity category was chosen to be further analyzed. Three novel cellulase genes designated as umcel5L, umcel5M and umbgl3D were identified by subcloning, sequencing and expression. The umcel5L encodes an endoglucanase belonging to glycosyl hydrolase family 5, which is most related to an endoglucanase from Bradyrhizobium japonicum at 43% identity and 59% similarity. The umcel5M encodes a cellodextrinase belonging to glycosyl hydrolase family 5, which is most similar to a cellodextrinase from Fibrobacter succinogenes at 48% identity and 69% similarity. The umbgl3D encodes a putative beta-glucosidase belonging to glycosyl hydrolase family 3, which shares highest homology with a beta-glucosidase from Thermotoga maritima at 46% identity and 61% similarity. It is the first time to reveal the bacterial diversity of pulp sediments from paper mill effluent and clone novel cellulase genes from the bacteria by culture-independent method.


Homozygous MHC genotypes and longevity.
To investigate the relevance of the major histocompatibility complex (MHC) in longevity, we carried out a molecular analysis of the MHC in 432 unrelated healthy individuals. The comparison of individuals < or = 25 years and > 25 years showed that the 5.8-kb DQA1 allele, which corresponds to HLA-DR53, was negatively associated with longevity (p = 0.0035) resulting mainly from decreased homozygosity with age for that allele (p = 0.008), and restricted to males (p = 0.008). The difference was more striking for the 5.8 kb DQA1: 9.0 kb HSP70 haplotype again only in males (26.3 vs. 6.2%; p = 0.017, OR = 5.4, 95% CI = 1.5 - 19.5). The oldest male subject homozygous for this DQA1: HSP70 haplotype was 54 years (p = 0.005). Comparing leukemic patients and healthy individuals with the same ethnic and geographical origin, homozygosity for these genotypes was more frequent in the young leukemic group. The results suggested the existence of recessive deleterious genes in a segment of HLA-DR53 haplotypes.


Isolated intracranial hypertension without cerebral venous sinus thrombosis in APLA syndrome: an unique association.
Antiphospholipid antibody (APLA) syndrome is an autoimmune disorder predisposing to thrombotic complications affecting CNS either by arterial vaso occlusion or venous thrombosis. Cerebral venous sinus thrombosis (CVST) secondarily produces raised intracranial pressure (ICP). However intracranial hypertension without evidence of CVST is rare entity. We present two cases of elevated ICP with absence of identifiable CVST. Case 1, a 28-year-old female presented with a 2 months history of headache followed by bilateral vision loss. Cerebrospinal fluid (CSF) opening pressure and fundoscopy along with Contrast Magnetic resonance imaging (MRI) was suggestive of Idiopathic intracranial hypertension (IIH) and patient improved with acetazolamide. 5 months later she presented with acute onset right sided hemiparesis. MRI showed acute left Middle cerebral artery (MCA) territory infarct with normal contrast Magnetic resonance venography (MRV). Anti-cardiolipin and Beta 2 glycoprotein (both IgG and IgM) titres were elevated. Case 2, a 23-year-old female presented with headache and diplopia of 2 months duration. Based on CSF, fundoscopy and contrast MRI brain was diagnosed as IIH and she too responded to diuretics. 2 years later she presented with recurrence of headache and APLA profile showed elevated beta 2 glycoprotein IgG and IgA. This is an important non thrombotic complication of APLA syndrome and requires further large-scale study for insight into the pathogenesis and early recognition to avoid future complications.


Photoaffinity labeling of the allosteric AMP site of biodegradative threonine dehydratase of Escherichia coli with 8-azido-AMP.
The photoreactive AMP analog, 8-azido-AMP, stimulated the activity of biodegradative threonine dehydratase of Escherichia coli in a reversible manner and, like AMP, decreased the Km for threonine. The concentrations required for half-maximal stimulation by AMP and 8-azido-AMP were 40 microM and 1.5 microM, respectively, and the maximum stimulation by 8-azido-AMP was 25% of that seen with AMP. Gel-filtration experiments revealed that 8-azido-AMP stabilized a dimeric form of the enzyme, whereas AMP promoted a tetrameric species. When present together, AMP and 8-azido-AMP showed mutual competition in influencing catalytic activity as well as the conformational state of the protein. Photolabeling of AMP-free dehydratase with 8-azido-[2-3H]AMP resulted in a time and concentration-dependent enzyme inactivation and concomitant incorporation of 8-azido-AMP into protein. At low 8-azido-AMP concentrations, incorporation of about 1 mol 8-azido-AMP/mol dehydratase tetramer was correlated with almost complete inactivation of the enzyme. The presence of AMP in the photolabeling reaction greatly reduced the extent of enzyme inactivation and 8-azido-AMP binding. Ultraviolet irradiation with 20 microM 3H-labeled 8-azido-AMP revealed one tryptic peptide, Thr230-Thr-Gly-Thr-Leu-Ala-Asp-Gly-Cys-Asp-Val-Ser-Arg242, with bound radioactivity. This peptide, labeled at low concentration of 8-azido-AMP, most likely represents the AMP-binding region on the dehydratase molecule.


(Mal)nutrition and the new epidemiological trend in a context of development and inequalities.
The current context of intense social, economic and political transformations has contributed to changes in the health profile of the population and generated discussions about the impact of these changes on the reorganization of society. At the present moment, the increase in non-communicable illnesses and diseases raises major concerns about the paradox of malnutrition and obesity. Based on an in-depth reading and interpretation of texts, documents and databases, this article discusses issues related to nutrition, considering the dimensions of shortages and excesses, the evolution of nutrition over time, and the connection with the new epidemiological trend. We begin with a conceptual characterization, the historical background and the anthropological connections with the guiding theme of the article. We then describe the prevalence, distribution and secular trend of malnutrition and obesity, as well as the temporal relationship with the new epidemiological trend in Brazil within a context of development and inequalities. Finally, we reflect on the issue of (mal)nutrition in post-modernity, the new interests at stake in the health-disease process, as well as international experiences and strategies of partnerships designed to overcome these problems. We conclude by discussing some current advances and challenges in relation to the complexity and speed of contemporary changes.


Deep phenotyping of 14 new patients with IQSEC2 variants, including monozygotic twins of discordant phenotype.
Whole-exome sequencing has established IQSEC2 as a neurodevelopmental disability gene. The IQSEC2 variant phenotype includes developmental delay, intellectual disability, epilepsy, hypotonia, autism, developmental regression, microcephaly and stereotypies but is yet to be fully described. Presented here are 14 new patients with IQSEC2 variants. In addition to the established features, we observed: gait ataxia in 7 of 9 (77.8%), drooling in 9 of 14 (64.2%), early feeding difficulties in 7 of 14 (50%), structural brain abnormalities in 6 of 13 (46.2%), brachycephaly in 5 of 14 (35.7%), and scoliosis and paroxysms of laughter each in 4 of 14 (28.6%). We suggest that these are features of the IQSEC2-related disorder. Gastrostomy requirement, plagiocephaly, strabismus and cortical blindness, each seen in 2 of 14 (14.3%), may also be associated. Shared facial features were noted in 8 of 14 patients, and shared hair patterning was identified in 5 of 14 patients. This study further delineates the IQSEC2 phenotypic spectrum and supports the notion of an emerging IQSEC2 syndrome. We draw parallels between the IQSEC2-related disorder and the Angelman-/Rett-/Pitt-Hopkins syndrome group of conditions and recommend the addition of IQSEC2 to epilepsy and developmental delay gene panels. We observed discordant phenotypes in monozygotic twins and apparent gonadal mosaicism, which has implications for recurrence risk counselling in the IQSEC2-related disorder.


Response of stratospheric water vapour to warming constrained by satellite observations.
Future increases in stratospheric water vapour risk amplifying climate change and slowing down the recovery of the ozone layer. However, state-of-the-art climate models strongly disagree on the magnitude of these increases under global warming. Uncertainty primarily arises from the complex processes leading to dehydration of air during its tropical ascent into the stratosphere. Here we derive an observational constraint on this longstanding uncertainty. We use a statistical-learning approach to infer historical co-variations between the atmospheric temperature structure and tropical lower stratospheric water vapour concentrations. For climate models, we demonstrate that these historically constrained relationships are highly predictive of the water vapour response to increased atmospheric carbon dioxide. We obtain an observationally constrained range for stratospheric water vapour changes per degree of global warming of 0.31 ± 0.39 ppmv K-1. Across 61 climate models, we find that a large fraction of future model projections are inconsistent with observational evidence. In particular, frequently projected strong increases (>1 ppmv K-1) are highly unlikely. Our constraint represents a 50% decrease in the 95th percentile of the climate model uncertainty distribution, which has implications for surface warming, ozone recovery and the tropospheric circulation response under climate change.


Living Preference Modifies the Associations of Living Arrangements With Loneliness Among Community-Dwelling Older Adults.
Living arrangement has been reported to have a significant influence on feelings of loneliness in older adults, but their living preferences may confound the association. This study aimed to investigate whether the associations of living arrangements with loneliness differ in community-dwelling older adults according to different living preferences. In the 2008/2009 (baseline) and 2011/2012 (follow-up) waves of the Chinese Longitudinal Healthy Longevity Survey, living arrangements [living with children mainly (LWC), living with spouse only (LWS), and living alone (LA)], living preferences [preferring living with children (PreLWC) and preferring living alone/only with spouse (PreLA)], and feelings of loneliness were assessed. The effect modifications of living preferences in the associations of living arrangements with loneliness were estimated using logistic regression models, and corresponding odds ratios (ORs) were calculated. Living preferences significantly modified the associations of living arrangements with loneliness at baseline (p for interaction = 0.009 for LWS and = 0.015 for LA). Compared with LWC, LWS was protective for loneliness only in the PreLA older adults at baseline (OR = 0.53, 95% CI = 0.45-0.64, p < 0.001), and LA was significantly associated with loneliness especially in the PreLWC older adults, compared with their PreLA counterparts (at baseline, ORs = 2.89 vs. 2.15; at follow-up, ORs = 1.68 vs. 1.51). Living preference modifies the associations of living arrangements with loneliness, and those who prefer living with children but live alone are more likely to feel lonely. It is recommended that living preferences should be considered when managing loneliness in community-dwelling older adults.


Identification of N-glycosylated proteins from the central nervous system of Drosophila melanogaster.
Although the function of many glycoproteins in the nervous system of fruit flies is well understood, information about the glycosylation profile and glycan attachment sites for such proteins is scarce. In order to fill this gap and to facilitate the analysis of N-linked glycosylation in the nervous system, we have performed an extensive survey of membrane-associated glycoproteins and their N-glycosylation sites isolated from the adult Drosophila brain. Following subcellular fractionation and trypsin digestion, we used different lectin affinity chromatography steps to isolate N-glycosylated glycopeptides. We identified a total of 205 glycoproteins carrying N-linked glycans and revealed their 307 N-glycan attachment sites. The size of the resulting dataset furthermore allowed the statistical characterization of amino acid distribution around the N-linked glycosylation sites. Glycan profiles were analyzed separately for glycopeptides that were strongly and weakly bound to Concanavalin A (Con A), or that failed to bind Concanavalin A, but did bind to wheat germ agglutinin (WGA). High- or paucimannosidic glycans dominated each of the profiles, although the wheat germ agglutinin-bound glycan population was enriched in more extensively processed structures. A sialylated glycan structure was unambiguously detected in the wheat germ agglutinin-bound fraction. Despite the large amount of starting material, insufficient amount of glycopeptides was retained by the Wisteria floribunda (WFA) and Sambucus nigra columns to allow glycan or glycoprotein identification, providing further evidence that the vast majority of glycoproteins in the adult Drosophila brain carry primarily high-mannose, paucimannose, and hybrid glycans. The obtained results should facilitate future genetic and molecular approaches addressing the role of N-glycosylation in the central nervous system (CNS) of Drosophila.