Cachectin/TNF or IL-1 alpha induces cachexia with redistribution of body proteins.
Macrophage secretory products are suspected to participate in the severe lean tissue wasting related to chronic illness. The protein metabolic effects of chronic, 7-day cachectin/tumor necrosis factor (cachectin) or interleukin 1 alpha (IL-1 alpha) administration in vivo were studied in male Wistar rats that were 1) freely fed, 2) pair fed, 3) total protein and calorie starved, 4) twice daily lipopolysaccharide (LPS) administered, 5) twice daily cachectin administered, and 6) twice daily IL-1 alpha administered. LPS, cachectin, or IL-1 alpha administration produced anorexia; weight loss in these groups was comparable to respective pair-fed animals. However, LPS, cachectin, or IL-1 alpha accelerated peripheral protein wasting while preserving liver protein content, unlike the pattern in the pair-fed or starved animals in which loss of liver proteins and relative preservation of skeletal muscle protein were observed. The decrease in skeletal muscle protein content in LPS- or cytokine-treated animals was associated with coordinate decreases in muscle mRNA levels for the myofibrillar proteins myosin heavy chain, myosin light chain, actin, and in the 18S and 28S subunits of ribosomal RNA. We conclude that chronic exposure to the cytokines, IL-1 alpha or cachectin, can simulate those body and muscle protein changes seen in experimental LPS administration or chronic disease and markedly differ from the pattern of protein redistribution due to caloric restriction.


Toward a hierarchical goal theory model of school motivation.
Instead of concentrating on mastery and performance goal orientations, recent research on school motivation has suggested a multidimensional structure of achievement goal orientations. Students in Australian high schools (N =774) responded to 35 survey items on 10 goal orientation constructs (effort, task, sense of purpose, praise, competition, power, token, social concern, social dependence, and affiliation) and 14 items on general mastery, general performance, general social, and global motivation constructs. Confirmatory factor analysis results supported a hierarchical, multidimensional school motivation construct. The hierarchical, multidimensional model has provided a strong theoretical structure for further school motivation research.


Demonstration of bioequivalence between ventasol syrup and ventolin syrup in humans and in dogs.
Ventasol syrup, a new locally produced salbutamol formulation, was compared with the standard salbutamol formulation, ventolin syrup, for determination of oral bioequivalence in stable asthmatic human subjects and in dogs. On separate occasions, each subject received a single 10 ml oral dose of each formulation containing 4 mg salbutamol. In the human subjects, statistically similar peak plasma concentrations of salbutamol were obtained (196 +/- 7 ng/ml for ventasol syrup and 185 +/- 6 ng/ml for ventolin syrup) 3 hours after oral administration of the formulations. From the ratio of the AUCo-infinity for the formulations (1.04), a relative oral bioavailability of 104%, indicating equivalent total salbutamol output, was also obtained in the human subjects. Similarly, in the dogs, the formulations produced statistically equivalent peak plasma concentrations of salbutamol (259 +/- 24ng/ml for ventasol syrup and 285 +/- 29ng/ml for ventolin syrup) 3 hours after oral administration. Also, from the ratio of the AUCo-infinity for the formulations (1.02), a relative oral bioavailability of 102%, indicating similar total salbutamol output, was obtained in the dogs. From these results, it is concluded that oral bioequivalence between ventasol syrup and ventolin syrup was demonstrated in human subjects and in dogs.


The immune system: a look from a distance.
The self-nonself discrimination is germline encoded for defense mechanisms, but it is somatically learned for the immune system and this is the fundamental difference between the two. When referring to the defense mechanisms of vertebrates, immunologists like to use the term "innate immune systems" to describe the germline encoded class of defense mechanism. It was the acquisition of a somatically learned S-NS discrimination during vertebrate evolution that permitted the immune system to develop large recognitive repertoires compared to those of defense mechanisms. This seemingly boundless immune repertoire has fascinated immunologists for almost a century. Today we have a better understanding of the size and function of the antibody repertoire. Humoral antibody effector functions depend upon secreted immunoglobulin and the concentration of antibody must reach a minimum effective threshold in a short enough time to stop a growing pathogen before it becomes lethal. This requires that initially an equivalent number of B-cells per ml respond to the pathogen. This number of B-cells must respond for each and every milliliter of animal. Consequently, the humoral immune system must be iterated. This straightforward conclusion has far reaching implications, some of which are explored in this review.


Adaptive cluster expansion approach for predicting the structure evolution of graphene oxide.
An adaptive cluster expansion (CE) method is used to explore surface adsorption and growth processes. Unlike the traditional CE method, suitable effective cluster interaction (ECI) parameters are determined, and then the selected fixed number of ECIs is continually optimized to predict the stable configurations with gradual increase of adatom coverage. Comparing with traditional CE method, the efficiency of the adaptive CE method could be greatly enhanced. As an application, the adsorption and growth of oxygen atoms on one side of pristine graphene was carefully investigated using this method in combination with first-principles calculations. The calculated results successfully uncover the structural evolution of graphene oxide for the different numbers of oxygen adatoms on graphene. The aggregation behavior of the stable configurations for different oxygen adatom coverages is revealed for increasing coverages of oxygen atoms. As a targeted method, adaptive CE can also be applied to understand the evolution of other surface adsorption and growth processes.


Alteration in molecular structure of alkali activated slag with various water to binder ratios under accelerated carbonation.
Carbonation of alkali activated materials is one of the main deteriorations affecting their durability. However, current understanding of the structural alteration of these materials exposed to an environment inducing carbonation at the nano/micro scale remains limited. This study examined the evolution of phase assemblages of alkali activated slag mortars subjected to accelerated carbonation (1% CO2, 60% relative humidity, up to 28 day carbonation) using XRD, FTIR and 29Si, 27Al, and 23Na MAS NMR. Samples with three water to binder (w/b) ratios (0.35, 0.45, and 0.55) were investigated. The results show that the phase assemblages mainly consisted of C-A-S-H, a disordered remnant aluminosilicate binder, and a minor hydrotalcite as a secondary product. Upon carbonation, calcium carbonate is mainly formed as the vaterite polymorph, while no sodium carbonate is found after carbonation as commonly reported. Sodium acts primarily as a charge balancing ion without producing sodium carbonate as a final carbonation product in the 28-day carbonated materials. The C-A-S-H structure becomes more cross-linked due to the decalcification of this phase as evidenced by the appearance of Q4 groups, which replace the Q1 and Q2 groups as observed in the 29Si MAS NMR spectra, and the dominance of Al(IV) in 27Al MAS NMR. Especially, unlike cementitious materials, the influence of w/b ratio on the crystalline phase formation and structure of C-A-S-H in the alkali activated mortars before and after carbonation is limited.


Design and synthesis of heterostructured quantum dots with dual emission in the visible and infrared.
The unique optical properties exhibited by visible emitting core/shell quantum dots with especially thick shells are the focus of widespread study, but have yet to be realized in infrared (IR)-active nanostructures. We apply an effective-mass model to identify PbSe/CdSe core/shell quantum dots as a promising system for achieving this goal. We then synthesize colloidal PbSe/CdSe quantum dots with shell thicknesses of up to 4 nm that exhibit unusually slow hole intraband relaxation from shell to core states, as evidenced by the emergence of dual emission, i.e., IR photoluminescence from the PbSe core observed simultaneously with visible emission from the CdSe shell. In addition to the large shell thickness, the development of slowed intraband relaxation is facilitated by the existence of a sharp core-shell interface without discernible alloying. Growth of thick shells without interfacial alloying or incidental formation of homogeneous CdSe nanocrystals was accomplished using insights attained via a systematic study of the dynamics of the cation-exchange synthesis of both PbSe/CdSe and the related system PbS/CdS. Finally, we show that the efficiency of the visible photoluminescence can be greatly enhanced by inorganic passivation.


[Paroxysmal supraventricular tachycardia].
Paroxysmal supraventricular tachycardias are often encountered in young and otherwise healthy patients. They are rarely life threatening even though they may alter the quality of life. In this article, we review the acute treatment of an episod of tachycardia and the prevention of recurrences.


Ethanol toxicity in pancreatic acinar cells: mediation by nonoxidative fatty acid metabolites.
Ethanol causes pancreatic damage by an unknown mechanism. Previously, we demonstrated that a sustained rise of the cytosolic Ca(2+) concentration ([Ca(2+)](i)) causes pancreatic acinar cell injury. Here we have investigated the effects of ethanol and its metabolites on Ca(2+) signaling in pancreatic acinar cells. Most cells exposed to ethanol (up to 850 mM) showed little or no increase in [Ca(2+)](i) (and never at concentrations <50 mM). During sustained exposure to 850 mM ethanol, acetylcholine (ACh) evoked a normal [Ca(2+)](i) elevation and following ACh removal there was a normal and rapid recovery to a low resting level. The oxidative metabolite acetaldehyde (up to 5 mM) had no effect, whereas the nonoxidative unsaturated metabolite palmitoleic acid ethyl ester (10-100 microM, added on top of 850 mM ethanol) induced sustained, concentration-dependent increases in [Ca(2+)](i) that were acutely dependent on external Ca(2+) and caused cell death. These actions were shared by the unsaturated metabolite arachidonic acid ethyl ester, the saturated equivalents palmitic and arachidic acid ethyl esters, and the fatty acid palmitoleic acid. In the absence of external Ca(2+), releasing all Ca(2+) from the endoplasmic reticulum by ACh (10 microM) or the specific Ca(2+) pump inhibitor thapsigargin (2 microM) prevented such Ca(2+) signal generation. We conclude that nonoxidative fatty acid metabolites, rather than ethanol itself, are responsible for the marked elevations of [Ca(2+)](i) that mediate toxicity in the pancreatic acinar cell and that these compounds act primarily by releasing Ca(2+) from the endoplasmic reticulum.


Validation of the General Self-Efficacy Scale in psychiatric outpatient care.
Self-efficacy has been used to explain and predict human characteristics in different domains, including health behavior. The aim of this paper is to study the internal consistency, components, and convergent validity of the Spanish version of the General Self-Efficacy Scale (GSE) in psychiatric outpatients. A convenience sample of 966 consecutive psychiatric out patients completed in 2014 the Spanish versions of the General Self-Efficacy Scale (GSE), Form C of the Multidimensional Health Locus of Control Scale (MHLC-C), the Hong Psychological Reactance Scale (HPRS), the Drug Attitude Inventory (DAI-10), and a questionnaire including socio-demographic and clinical variables. The GSE scale attained high internal consistency. Principal component analysis produced a general one-component solution. This structure accounted for more than 50% of the common variance. Further analyses yielded significant results with health locus of control dimensions, attitudes toward psychiatric treatment, age, and affective psychological reactance, but not with other socio-demographic or clinical variables. The structure of the General Self-efficacy Scale is unidimensional, homogenous and positively related to the constructs examined. The scale is a reliable and valid measure of the perception of self-efficacy in psychiatric outpatient care.


Untargeted Metabolomic Analysis of the Effects and Mechanism of Nuciferine Treatment on Rats With Nonalcoholic Fatty Liver Disease.
Metabolomic analysis has been used to characterize the effects and mechanisms of drugs for nonalcoholic fatty liver disease (NAFLD) at the metabolic level. Nuciferine is an active component derived from folium nelumbinis and has been demonstrated to have beneficial effects on a high-fat diet (HFD) induced hepatic steatosis model. However, the effect of the altered metabolites of nuciferine on NAFLD has not yet been elucidated. In this study, we established a NAFLD rat model using HFD and treated with nuciferine. The lipid content levels, pro-inflammatory cytokines, and oxidative stress were investigated to access the therapeutic effects of nuciferine. Additionally, the metabolic regulatory mechanisms of nuciferine on NAFLD were analyzed using untargeted metabolomics. Gene expression of the key enzymes related to the changed metabolic pathways following nuciferine intervention was also investigated. The results showed that nuciferine treatment significantly reduced the body weight, levels of lipids, and liver enzymes in the blood and improved the hepatic steatosis in the NAFLD rat model. Nuciferine treatment also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the levels of methane dicarboxylic aldehyde (MDA) in the liver. Nuciferine treatment decreased the serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) and upregulated the gene expression of IL-6, IL-1β, and TNF-α in the liver. Metabolomic analysis indicated a metabolism disorder in the NAFLD rat model reflected in a dysfunction of the glycerophospholipid, linoleic acid, alpha-linolenic acid, arginine and proline metabolism. Conversely, treatment with nuciferine improved the metabolic disorder in the NAFLD rat model. Nuciferine treatment also regulated the gene expression of key enzymes related to the glycerophospholipid, linoleic acid, and alpha-linolenic acid metabolism pathways in the liver. In conclusion, our study demonstrated an amelioration of the metabolic disorders following nuciferine treatment in NAFLD rat model. Our study contributes to the understanding of the effects and mechanisms of drugs for complex diseases using metabolomic analysis and experimental approaches.


Robust order representation is required for backward recall in the Corsi blocks task.
The storage and processing of spatial information is done by spatial working memory. To measure spatial working memory, the Corsi blocks task, which separates the memory into two types, forward and backward, is often used. Although it had been thought that backward recall requires more of the executive function than forward recall, some studies have shown otherwise. Here, we focused on the spatial and sequential aspects of the Corsi blocks task to investigate cognitive processes by dissociating forward and backward recall. We used a dual task method (serial articulatory suppression or spatial tapping as the secondary task) and analyzed two kinds of errors (position error and order error) to investigate cognitive performance during the forward and backward recall. We ran two experiments: in experiment 1, we employed the standard Corsi blocks task, and in experiment 2, we employed the modified Corsi blocks task in order to prevent verbal strategies. We found that spatial tapping affected both forward and backward recall, while serial articulatory suppression increased the number of order errors in the backward condition. These results indicate that stronger order representation is required for backward recall in the Corsi blocks task.


Neurotensin phosphorylates GSK-3alpha/beta through the activation of PKC in human colon cancer cells.
Neurotensin (NT), a gastrointestinal hormone, binds its receptor [neurotensin receptor (NTR)] to regulate the growth of normal and neoplastic intestinal cells; molecular mechanisms remain largely undefined. Glycogen synthase kinase-3 (GSK-3) regulates diverse cellular processes, including cell growth and apoptosis. Here, we show that NT induces the phosphorylation of GSK-3alpha/beta in the human colon cancer cell line HT29, HCT116, or SW480, which possesses high-affinity NTR. The effect of NT was blocked by inhibitors of protein kinase C (PKC), but not by inhibitors of MEK1 or phosphatidylinositol-3 kinase, suggesting a predominant role for PKC in GSK-3beta phosphorylation by NT. Pretreatment with Gö6976 (which inhibits PKCalpha and PKCbeta1) or downregulation of endogenous PKCalpha or PKCbeta1 blocked NT-mediated GSK-3beta (but not GSK-3alpha) phosphorylation. Moreover, a selective PKCbeta inhibitor, LY379196, reduced NT-mediated GSK-3beta (but not GSK-3alpha) phosphorylation, suggesting a role for PKCbeta1 in the NT-mediated phosphorylation of GSK-3beta and an undefined kinase in the NT-mediated phosphorylation of GSK-3alpha. Treatment with NT or the GSK-3 inhibitor SB216763 increased the expression of cyclin D1, a downstream effector protein of GSK-3 and a critical protein for the proliferation of various cells. Our results indicate that NT uses PKC-dependent pathways to modulate GSK-3, which may play a role in the NT regulation of intestinal cell growth.


Synthesis of cytokeratin 13, a component characteristic of internal stratified epithelia, is not induced in human epidermal tumors.
Human cytokeratin 13 is one of the most abundant intermediate filament (IF) proteins of many internal stratified epithelia and occurs, at least in certain cell cultures, in an O-glycosylated form binding the lectin, wheat germ agglutinin (WGA). As other groups have reported that, in the mouse, the synthesis of mRNA encoding the 47-kDa cytokeratin corresponding to human cytokeratin 13 is induced in epidermal keratinocytes during malignant transformation, we have examined the synthesis of cytokeratin 13 mRNA and protein in human epidermis and epidermal tumors, using specific cDNA probes and cytokeratin 13 antibodies. We isolated two different cDNA clones from the vulvar carcinoma cell line A-431, in which this protein is abundant: One clone seems to represent the entire mRNA, whereas the other is only a minor component and encodes a truncated cytokeratin 13 lacking most of the carboxy-terminal tail domain, probably a product of alternative, "incorrect" splicing. Comparison of the amino acid sequences with those of other cytokeratins revealed a high degree of conservation with respect to several other human type I cytokeratins, notably cytokeratin 15, and to the murine 47-kDa cytokeratin. When human epidermis and a series of benign and malignant epidermal tumors were examined with these cDNA probes and cytokeratin-13-specific antibodies we did not find an induction of expression in keratinocytes, normal or malignantly transformed, except for some scattered, sparse cytokeratin-13-positive cells and very low levels of cytokeratin 13 mRNA, detectable only with the highly sensitive polymerase chain reaction (PCR). We conclude that the gene(s) encoding cytokeratin 13 are not induced in human keratinocytes during epidermal carcinogenesis, in apparent contrast to reports of murine epidermal tumors, and we discuss possible explanations for this interspecies difference.


OXYGEN UPTAKE FROM A RESERVOIR OF LIMITED VOLUME BY THE HUMAN CORNEA IN VIVO.
Oxygen flux across the anterior surface of the human cornea from a closed reservoir of air-saturated, physiological, isotonic saline was measured in vivo as a function of time. The rate of oxygen consumption calculated from this flux compares favorably with estimates given in the literalure, which were based on studies in which the microrespirometer technique of Warburg was used.


Delayed encephalopathy of acute carbon monoxide intoxication in rats: potential mechanism and intervention of dexamethasone.
We aimed to investigate the potential mechanism (s) of delayed encephalopathy after acute carbon monoxide (CO) poisoning in rats, and the effect of dexamethasone on this process. A delayed encephalopathy animal model was generated by intraperitoneal injection of CO into Wistar rats. Normal rats were sent as a control group, and poisoning rats were randomly separated into two groups treated with vehicle and dexamethasone respectively. The rat behavior was evaluated by Morris water maze. The level of myelin basic protein (MBP), myeloperoxidase (MPO) expression in the serum and hippocampus of experimental rats was measured using enzyme-linked immunosorbent assay (ELISA) and immunohisto chemistry. The latency to find the platform was significantly increased by dexamethasone treatment for rats after poisoning at day 7 and 14. MBP serum concentration in the vehicle treatment group was significantly higher than that in rats injected with dexamethasone following poisoning at 90 min, 7d, 14d, 21d. Moreover, MPO concentration was higher at day 14 after poisoning as well. In addition, MBP expression was down regulated in the poisoning group, which was nearly reversed at control level in the dexamethasone group. Inflammation plays a key role in delayed encephalopathy of rats induced by acute CO intoxication, which could be attenuated by dexamethasone via protecting myelin from damage of inflammation response.


Congenital adrenal hyperplasia - how to improve the transition from adolescence to adult life.
Congenital adrenal hyperplasia (CAH) is caused by a defect in the biosynthesis of cortisol that results in maximal activity of the hypothalamic-pituitary adrenal axis with hyperplasia of the adrenals and hyperandrogenism due to the accumulation of androgen precursors. In the salt-wasting subtype of the disorder, which accounts for appr. 75 % of patients with classical CAH, patients are unable to synthesise sufficient amounts of aldosterone and are prone to life-threatening salt-losing crises, whereas the simple virilising form is predominantly characterized by clitoris hypertrophy and posterior labial fusion. In addition, a non-classical variant can be discerned which in most cases is diagnosed at the time of puberty or early adolescence when hirsutism and menstrual irregularities may occur. The vast majority of CAH patients have 21-hydroxylase deficiency (90 - 95 %). Less common forms, such as 11beta-hydroxylase deficiency, will not be discussed in this review. Unfortunately, a considerable number of CAH patients is lost to regular and competent follow-up once they move out of paediatric care. This is most probably the result of insufficient co-operation between paediatric and adult endocrinologists at the time of transition from adolescence to adulthood. Furthermore, there is a lack of clinical guidance regarding psychosexual development in these patients. In this overview we will focus on special aspects of CAH treatment in adolescence and adulthood, and report on our 10-year experience with a transfer system for endocrine patients from paediatric to internal medical care, known as the "Kieler Modell". For practical purposes, we here provide charts for follow-up of CAH patients that can be adapted for use in any endocrine outpatient clinic.


The role of public relations for image creating in health services: a sample patient satisfaction survey.
This study discusses the role of public relations for image creating in health services. Hospitals require public relations activities to distinguish them from competitors, provide bidirectional communication between the society and the hospital, and assist to create of a strong hospital image and culture. A satisfaction survey was conducted on 264 patients who have received health services at Maltepe University Hospital. The research focused on how the Hospital's examination, care, catering and physical services; doctor and nurse politeness towards patients and patient relatives, their attitudes and behaviors; examination, check-in, bedding and discharge operations; public relations activities in and out of the hospital were perceived. Another subject of the study was the degree of recommendation of patients who have been served by the hospital's health services to prospective patients seeking treatment.


In vitro activity-guided identification of antioxidants in aged garlic extract.
Activity-guided fractionation was applied on an aged garlic extract (AGE), reported to show strong antioxidant activity, in order to locate the key in vitro antioxidant ingredients by means of the hydrogen peroxide scavenging (HPS) assay as well as the ORAC assay. Besides the previously reported four tetrahydro-β-carbolines, (1R,3S)- and (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid and (1R,3S)- and (1S,3S)-1-methyl-1,2,3,4-tetrahydro-β-carboline-1,3-dicarboxylic acid, LC-MS/MS, LC-TOF-MS, and 1D/2D-NMR experiments led to the identification of coniferyl alcohol and its dilignols (-)-(2R,3S)-dihydrodehydrodiconiferyl alcohol, (+)-(2S,3R)-dehydrodiconiferyl alcohol, erythro-guaiacylglycerol-β-O-4'-coniferyl ether, and threo-guaiacylglycerol-β-O-4'-coniferyl ether as the major antioxidants in AGE. The purified individual compounds showed high antioxidant activity, with EC50 values of 9.7-11.8 μM (HPS assay) and 2.60-3.65 μmol TE/μmol (ORAC assay), respectively.


Comparative phenology of dormant Japanese pear (Pyrus pyrifolia) flower buds: a possible cause of 'flowering disorder'.
Mild winters influenced by global warming have increased the incidence of erratic flowering ('flowering disorder') in Japanese pear (Pyrus pyrifolia Nakai) trees in Japan. To discover how, when and what kind of disorder/damage occur in pear flower buds, we observed axillary flower buds of two cultivars, 'Kosui' (a mid-chill cultivar) and 'Niitaka' (a high-chill cultivar), grown at five locations. We focused on the phenology from autumn 2015 to spring 2016, when temperatures were higher than for average years, especially from September to January, and large fluctuations occurred due to El Niño. During the blooming season in the spring of 2016, both the percentage of blooming flower buds and the number of florets per flower bud decreased in trees located at lower latitudes (with lower chilling accumulation) with a more severe problem in 'Niitaka' than in 'Kosui'. As shown by forcing excised shoots, the onset and release of endodormancy occurred earlier in 'Kosui' than 'Niitaka' and occurred earlier in trees growing at higher latitudes than at lower latitudes (warmer regions). The freezing tolerance of flower buds, measured as the lethal temperature for 50% survival (LT50), was similar for the cultivars beginning in autumn and reached maximum levels, LT50 values of less than -12 °C, between late-December and mid-January in both cultivars, except for those in Kagoshima (the lowest latitude), where the maximum LT50 was only -5 °C throughout the season. We propose that warmer autumn-winter temperatures may prevent the acquisition of freezing tolerance, disturb endodormancy progression and disrupt floral organ development, thereby causing flowering disorder in pear trees. The risk of occurrence of flowering disorder in pear may be higher in high-chill cultivars than in low- or mid-chill cultivars and at lower latitudes compared with higher latitudes.


Dual-Polarization Observations of Slowly Varying Solar Emissions from a Mobile X-Band Radar.
The radio noise that comes from the Sun has been reported in literature as a reference signal to check the quality of dual-polarization weather radar receivers for the S-band and C-band. In most cases, the focus was on relative calibration: horizontal and vertical polarizations were evaluated versus the reference signal mainly in terms of standard deviation of the difference. This means that the investigated radar receivers were able to reproduce the slowly varying component of the microwave signal emitted by the Sun. A novel method, aimed at the absolute calibration of dual-polarization receivers, has recently been presented and applied for the C-band. This method requires the antenna beam axis to be pointed towards the center of the Sun for less than a minute. Standard deviations of the difference as low as 0.1 dB have been found for the Swiss radars. As far as the absolute calibration is concerned, the average differences were of the order of -0.6 dB (after noise subtraction). The method has been implemented on a mobile, X-band radar, and this paper presents the successful results that were obtained during the 2016 field campaign in Payerne (Switzerland). Despite a relatively poor Sun-to-Noise ratio, the "small" (~0.4 dB) amplitude of the slowly varying emission was captured and reproduced; the standard deviation of the difference between the radar and the reference was ~0.2 dB. The absolute calibration of the vertical and horizontal receivers was satisfactory. After the noise subtraction and atmospheric correction a, the mean difference was close to 0 dB.


Discrimination of Chinese Liquors Based on Electronic Nose and Fuzzy Discriminant Principal Component Analysis.
The detection of liquor quality is an important process in the liquor industry, and the quality of Chinese liquors is partly determined by the aromas of the liquors. The electronic nose (e-nose) refers to an artificial olfactory technology. The e-nose system can quickly detect different types of Chinese liquors according to their aromas. In this study, an e-nose system was designed to identify six types of Chinese liquors, and a novel feature extraction algorithm, called fuzzy discriminant principal component analysis (FDPCA), was developed for feature extraction from e-nose signals by combining discriminant principal component analysis (DPCA) and fuzzy set theory. In addition, principal component analysis (PCA), DPCA, K-nearest neighbor (KNN) classifier, leave-one-out (LOO) strategy and k-fold cross-validation (k = 5, 10, 20, 25) were employed in the e-nose system. The maximum classification accuracy of feature extraction for Chinese liquors was 98.378% using FDPCA, showing this algorithm to be extremely effective. The experimental results indicate that an e-nose system coupled with FDPCA is a feasible method for classifying Chinese liquors.


Nutritional manipulation between early to mid-gestation: effects on uncoupling protein-2, glucocorticoid sensitivity, IGF-I receptor and cell proliferation but not apoptosis in the ovine placenta.
In sheep, modest maternal nutrient restriction (NR) over the period of rapid placental growth restricts placentome growth and results in offspring in which glucocorticoid action is enhanced. Therefore, this study investigated the placental effects of early to mid-gestational NR on glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), uncoupling protein-2 (UCP2), and IGF type-I receptor (IGF-IR) mRNA abundance together with cell proliferation and apoptosis as determined histologically, and the mitochondrial proteins voltage-dependent anion channel and cytochrome c that are involved in apoptosis. Placenta was sampled at 80 and 140 days gestation (dGA; term ~147 dGA). NR was imposed between 28 and 80 days gestation when control and nutrient-restricted groups consumed 150 or 60% respectively of their total metabolizable energy requirements. All mothers were then fed to requirements up to term. Total fetal placentome weights were decreased by NR at 80 dGA but were heavier at 140 dGA following 60 days of nutritional rehabilitation. GR and UCP2 mRNA abundance increased whilst 11betaHSD2 mRNA decreased with gestational age. NR persistently up-regulated GR and UCP2 mRNA abundance. 11betaHSD2 mRNA was reduced by NR at 80 dGA but increased near to term. IGF-IRmRNA abundance was only decreased at 80 dGA. Placental apoptosis and mitochondrial protein abundance were unaffected by NR, whereas cell proliferation was markedly reduced. In conclusion, placental UCP2 and local glucocorticoid action are affected by the gestational nutritional status and may result in the offspring showing enhanced glucocorticoid sensitivity, thereby predisposing them to disease in later life.


Detection of Diffuse Peritoneal and Omental Metastases From Prostate Cancer With 18F-PSMA-1007 PET/CT.
Diffuse peritoneal and omental infiltration of prostate cancer detected by 18F-PSMA-1007 PET/CT was rarely reported. We report a case of an 80-year-old man who was suspected of prostate carcinoma metastasis and underwent 18F-PSMA-1007 PET/CT for restaging the disease. PET/CT imaging presented intense tracer uptake in the prostate gland, multiple lymph nodes, and bones. Interestingly, we found extremely increased radioactive uptake of diffuse peritoneum and omentum on 18F-PSMA-1007 PET/CT images, which are very rare metastatic sites for prostate cancer.


Transdermal analgesia with local anesthetics in children: review, update and future directions.
Topical local anesthetics in one form or another have been used for the past 20 years to alleviate the skin pain associated with needle puncture and venous cannulation in children. Although the application of topical anesthetic creams is painless compared with traditional local anesthetic infiltration of the skin and subcutaneous tissues prior to venipuncture and minor skin procedures, they remain underutilized, primarily due to their slow analgesic onset and inconsistent effectiveness. For a topical local anesthetic to be of practical use in busy clinical settings, it must be easy to apply, have minimal side effects, not require cumbersome equipment and be reasonably cost effective. Until recently, limitations in one or all of these areas have dissuaded pediatric practitioners from their routine use. However, recent advances in transdermal delivery technologies, have led to the emergence of a number of new delivery approaches that accelerate the onset time to 20 min or less and provide more consistent and deeper sensory skin analgesia. Although still in the early stages of investigation, technologies that promote the flux of drugs of all sizes through the skin by creating transient microchannels show great promise in circumventing the skin barrier and promoting the transdermal delivery of not only local anesthetics but also other drugs. Ultimately, the rationale to change clinical practice and use a new transdermal delivery system will depend upon the cost, ease of use, frequency of adverse events and the benefits to the patient relative to an alternative method.


A study of comparative modelling, simulation and molecular dynamics of CXCR3 receptor with lipid bilayer.
The G-coupled receptors seen on the cell surface are composites with a lipid bilayer. The chemokines are kind of G-coupled receptor which majorly involved in the activation and downstream signalling of the cell. In general, many G-coupled receptors lack their 3D structures which become a hurdle in the drug designing process. In this study, comparative modelling of the CXCR3 receptor was carried out, structure evaluation was done using various tools and softwares. Additionally, molecular dynamics and docking were performed to prove the structural quality and architecture. Interestingly, the studies like toggle switch mechanism, lipid dynamics, virtual screening were carried out to find the potent antagonist for the CXCR3 receptor. During virtual screening 14,303 similar molecules were retrieved among them only four compounds have an ability to interact with a crucial amino acid residue of an antagonist. Hence, these screened compounds can serve as a drug candidate for a CXCR3 receptor, but further in vitro and in vivo studies are ought to do to prove its same efficacy.


Ion-Selective Scattering Studied Using the Variable-Energy Electron Irradiation in the Ba0.2K0.8Fe2As2 Superconductor.
Low-temperature variable-energy electron irradiation was used to induce non-magnetic disorder in a single crystal of a hole-doped iron-based superconductor, Ba1-xKxFe2As2, x = 0.80. To avoid systematic errors, the beam energy was adjusted non-consequently for five values between 1.0 and 2.5 MeV when sample resistance was measured in situ at 22 K. For all energies, the resistivity raises linearly with the irradiation fluence suggesting the creation of uncorrelated dilute point-like disorder (confirmed by simulations). The rate of the resistivity increase peaks at energies below 1.5 MeV. Comparison with calculated partial cross-sections points to the predominant creation of defects in the iron sublattice. Simultaneously, superconducting Tc, measured separately between the irradiation runs, is monotonically suppressed as expected, since it depends on the total scattering rate, hence on the total cross-section, which is a monotonically increasing function of the energy. Our work experimentally confirms an often-made assumption of the dominant role of the iron sub-lattice in iron-based superconductors.


Glia Maturation Factor and Mitochondrial Uncoupling Proteins 2 and 4 Expression in the Temporal Cortex of Alzheimer's Disease Brain.
Alzheimer's disease (AD) is characterized by the presence of neuropathological lesions containing amyloid plaques (APs) and neurofibrillary tangles (NFTs). AD is associated with mitochondrial dysfunctions, neuroinflammation and neurodegeneration in the brain. We have previously demonstrated enhanced expression of the proinflammatory protein glia maturation factor (GMF) in glial cells near APs and NFTs in the AD brains. Parahippocampal gyrus consisting of entorhinal and perirhinal subdivisions of temporal cortex is the first brain region affected during AD pathogenesis. Current paradigm implicates oxidative stress-mediated neuronal damage contributing to the early pathology in AD with mitochondrial membrane potential regulating reactive oxygen species (ROS) production. The inner mitochondrial membrane anion transporters called the uncoupling proteins (UCPs), function as regulators of cellular homeostasis by mitigating oxidative stress. In the present study, we have analyzed the expression of GMF and mitochondrial UCP2 and UCP4 in the parahippocampal gyrus of AD and non-AD brains by immunostaining techniques. APs were detected by thioflavin-S fluorescence staining or immunohistochemistry (IHC) with 6E10 antibody. Our current results suggest that upregulation of GMF expression is associated with down-regulation of UCP2 as well as UCP4 in the parahippocampal gyrus of AD brains as compared to non-AD brains. Further, GMF expression is associated with up-regulation of inducible nitric oxide synthase (iNOS), the enzyme that induces the production of nitric oxide (NO), as well as nuclear factor kB p65 (NF-κB p65) expression. Also, GMF appeared to localize to the mitochondria in AD brains. Based on our current observations, we propose that enhanced expression of GMF down-regulates mitochondrial UCP2 and UCP4 thereby exacerbating AD pathophysiology and this effect is potentially mediated by iNOS and NF-κB. Thus, GMF functions as an activator protein that interferes with the cytoprotective mechanisms in AD brains.


A rare case of an intercostal lung herniation with fractures of the fifth and sixth ribs after thoracic surgery.
Lung herniation is a rare condition defined as a protrusion of the pleural-covered lung parenchyma through an abnormal defect or weakness in the thoracic wall. Postoperative lung herniation is reported to result from a preceding operation with inadequate closure of the chest wall. A 77-year-old woman was admitted to our hospital for treatment of hemoptysis and nausea. One year previously, she had undergone wedge resection of the right lower lobe (S6) for treatment of primary lung adenocarcinoma. Upon admission, chest radiograph and chest computed tomography showed a right lung herniation through the fifth enlarged intercostal space with right fifth and sixth rib fractures. She underwent surgical closure of the intercostal hernia using synthetic materials with fixation of the fifth and sixth ribs. The patient had developed no recurrence 9 months after surgical repair. In the present case, adequate closure of the right pleural cavity was ensured by fixation of both fifth and sixth ribs during the preceding video-assisted thoracic surgery for the primary lung carcinoma. Our patient may have had some exacerbation factors for lung herniation, increased intrathoracic pressure, attenuation of chest wall by prolonged coughing and rib fracture, and high abdominal pressure due to her hunched-over posture. It is important to know some exacerbation factors for postoperative intercostal lung herniation. Addition of monofirament-suture fixation of the ribs to patch repair is very effective for lung herniation repair in patients with concurrent lung herniation and rib fractures.


Causal variants screened by whole exome sequencing in a patient with maternal uniparental isodisomy of chromosome 10 and a complicated phenotype.
Uniparental disomy (UPD), which is the abnormal situation in which both copies of a chromosomal pair have been inherited from one parent, may cause clinical abnormalities by affecting genomic imprinting or causing autosomal recessive variation. Whole Exome Sequencing (WES) and chromosomal microarray analysis (CMA) are powerful technologies used to search for underlying causal variants. In the present study, WES was used to screen for candidate causal variants in the genome of a Chinese pediatric patient, who had been shown by CMA to have maternal uniparental isodisomy of chromosome 10. This was associated with numerous severe medical problems, including bilateral deafness, binocular blindness, stunted growth and leukoderma. A total of 13 rare homozygous variants of these genes were identified on chromosome 10. These included a classical splice variant in the HPS1 gene (c.398+5G>A), which causes Hermansky-Pudlak syndrome type 1 and may explain the patient's ocular and dermal disorders. In addition, six likely pathogenic genes on other chromosomes were found to be associated with the subject's ocular and aural disorders by phenotypic analysis. The results of the present study demonstrated that WES and CMA may be successfully combined in order to identify candidate causal genes. Furthermore, a connection between phenotype and genotype was established in this patient.


[The medical school of Padua and its Jewish graduates].
During the period between the 12th and 16th century, most European universities were under Papal control and Jews were restricted. An exception to this was the University of Padua, established in 1222. As "Universa Universis Patavina Liberta", outside of papal control, Jewish students were permitted to study and qualify for academic degrees. The Medical School, opened in 1250, was generally regarded as the best medical school in Europe. The universities tolerant and liberal approach attracted students the world-over, particularly drawing European Jews to Padua to study medicine. However, these young Jews lacked the necessary prerequisites, including a basic knowledge of Latin, the official university language. They benefited from the generous support of the Jewish community of Padua and, in particular, that of the Paduan medical alumni, the best known of whom was Dr. Salomo Conigliano. Between the years 1409 and 1816, 325 Jewish physicians graduated from the University of Padua. Among them were many distinguished scholars including Joseph Del Medigo, Joseph Hamiz, Benjamin Mussafia and Tovia Cohen, and many families of physicians who returned to their home countries to practice medicine. In addition to their medical contribution, Jewish graduates served their communities as religious and social leaders. They shared a common university background and cultural heritage, common interests and values. They also maintained close contact among themselves and among non-Jewish colleagues and hence were influenced by new social and cultural movements in Europe. These Jewish graduates of Padua played a crucial role in the developments of the Jewish culture and society, including the "Haskala" movement.


Analysis of fibrinogen gamma-chain truncations shows the C-terminus, particularly gammaIle387, is essential for assembly and secretion of this multichain protein.
To examine the role of the fibrinogen gamma chain in the assembly and secretion of this multichain protein, we synthesized a series of fibrinogen variants with truncated gamma chains, terminating between residues gamma379 and the C-terminus, gamma411. The variant fibrinogens were synthesized from altered gamma-chain complementary DNAs in cultured Chinese hamster ovary cells. Immunoassays of the culture media demonstrated that only those variants with gamma chain longer than 386 residues were secreted and that the concentration of fibrinogen decreased with the length of the gamma chain, from 1.4 microg/mL for normal fibrinogen to 0.39 microg/mL for gamma 387 fibrinogen. Immunoassays of cell lysates showed that all variant gamma chains were synthesized, although the levels varied significantly. For variants longer than 386 residues, levels decreased with length but remained near normal. In contrast, expression of the 4 variants with 386 residues or less was about 20-fold reduced. Quantitative reverse transcription-polymerase chain reaction demonstrated that the gamma-chain messenger RNA level was independent from chain length. Western blot analyses showed that lysates expressing variants with 387 residues or more contained species comparable to the known intermediates in fibrinogen assembly, including half-molecules. For shorter variants, these intermediates were not evident. We conclude that residues near the C-terminus of the gamma chain are essential for fibrinogen assembly, and more specifically, that gamma387 is critical. We propose that the loss of residue gamma387 destabilized the structure of gamma chain, preventing assembly of alphagamma and betagamma dimers, essential intermediates in the assembly of normal fibrinogen.


Frontal Connectivity in EEG Gamma (30-45 Hz) Respond to Spinal Cord Stimulation in Minimally Conscious State Patients.
Spinal cord stimulation (SCS) has become a valuable brain-intervention technique used to rehabilitate patients with disorders of consciousness (DOC). To explore how the SCS affects the cerebral cortex and what possible electrophysiological mechanism of SCS effects on the cortex, the present study investigated the functional connectivity and network properties during SCS in minimally conscious state (MCS) patients. MCS patients received both SCS and sham sessions. Functional connectivity of the phase lock value (PLV) in the gamma band (30-45 Hz) was investigated at the pre-, on- and post-SCS stages. In addition, to evaluate global network properties, complex network parameters, including average path length, cluster coefficient and small-world, were measured. When SCS was turned on, significantly decreased connectivity was noted in the local scale of the frontal-frontal region and in the large scales of the frontal-parietal and frontal-occipital regions. The global network showed fewer small-world properties, average path lengths increased and cluster coefficients decreased. When SCS was turned off, the large-scale connectivity and global network returned to its pre-SCS level, but the local scale of frontal-frontal connectivity remained significantly lower than its pre-SCS level. Sham sessions produced no significant changes in either functional connectivity or network. The findings directly showed that SCS could effectively intervene cortical gamma activity, and the intervention included immediate global effects (large scale connectivity and network alteration only occurred in stimulation period) and long-lasting local effects (local scale connectivity alteration persist beyond stimulation period). Moreover, considering the mechanism and propagation of gamma activity, it indicates that the frontal cortex plays a crucial role in the SCS effects on the cerebral cortex.


Evaluation of the antimycobacterial activity of crude extracts and solvent fractions of selected Ethiopian medicinal plants.
Tuberculosis (TB) is a global health problem complicated by drug resistance and human immunodeficiency virus that has dramatically increased active TB. Several medicinal plants are used traditionally to treat TB in Ethiopia and investigating these plants is required as plants are an alternative source for development of new anti-TB drugs. The purpose of this study was to investigate antimycobacterial activity of crude extract of Carissa edulis, Otostegia integrifolia, Persea americana, Pterolobium stellatum and Vernonia amygdalina as well as fractions of the most active crude extract. The effect of various doses of the crude extracts as well as solvent fractions on M. tuberculosis H37Rv and/or MDR-TB clinical isolate was determined using broth microdilution and microtiter resazurin assay methods. Minimum inhibitory concentration was determined by CFU count and resazurin color change observation. Chloroform and 80% methanol extracts of P. stellatum and O. integrifolia as well as 80% methanol and acetone extracts of P. americana had significant antimycobacterial activity (p < 0.001) against M. tuberculosis H37Rv. Chloroform extract of V. amygdalina and C. edulis didn't, however, show any significant activity compared to negative controls. P. stellatum chloroform extract was the most active on M. tuberculosis H37Rv (MIC 0.039 mg/ml) and AOZ8W-4 (MDR-TB clinical isolate) (MIC = 0.078 mg/ml). Ethyl acetate fraction of P. stellatum chloroform extract was the most active fraction. P. stellatum, O. integrifolia and P. americana were found to be endowed with antimycobacterial activity. However, P. stellatum appears to be the most promising plant based on criteria set by different studies. Ethyl acetate fraction of P. stellatum was found to be the most active and future studies should involve this fraction.


2-(Anilinomethyl)imidazolines as alpha1 adrenergic receptor agonists: the discovery of alpha1a subtype selective 2'-alkylsulfonyl-substituted analogues.
A series of 2'-alkylthio-2-(anilinomethyl)imidazolines were prepared to examine the effect of the alkyl group size, sulfur oxidation state, and phenyl ring substitution on ligand binding and agonism of alpha-adrenergic receptor subtypes alpha1a, alpha1b, alpha1d, alpha2a, and alpha2c. Binding at all receptor subtypes decreased for compounds in the sulfone oxidation state as compared to their sulfide analogues. While sulfides were generally potent, nonselective agonists, sulfones exhibited alpha1a subtype selectivity in a cell-based functional assay. Sulfone (32) was 250-7000-fold selective for alpha1a vs all other subtypes.


The occipital transtentorial approach to the posterior fossa in the pediatric patient.
The occipital transtentorial approach to the high posterior fossa has been previously described for the adult neurosurgical patient. In this presentation 5 pediatric patients with differing pathology in the posterior fossa are reported following successful occipital transtentorial operations. The advantages of this approach over the suboccipital route for microneurosurgery are discussed.


Aqueous Humor Levels of Soluble Vascular Endothelial Growth Factor Receptor and Inflammatory Factors in Diabetic Macular Edema.
Aqueous levels of soluble vascular endothelial growth factor receptor (sVEGFR) and inflammatory factors were measured in 35 patients (37 eyes) with diabetic macular edema (DME) receiving anti-vascular endothelial growth factor (VEGF) therapy. Aqueous levels of growth factors (VEGF, placental growth factor [PlGF], and platelet-derived growth factor AA [PDGF-AA]), sVEGFR-1 and -2, soluble intercellular adhesion molecule 1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, -8, -12, and -13, and interferon-inducible 10-kDa protein (IP-10) were significantly higher in the DME group than in the nondiabetic control group. The sVEGFR-2 level was significantly correlated with the neurosensory retinal thickness, as well as with the levels of growth factors (VEGF and PDGF-AA) and inflammatory factors (MCP-1, IL-6, and IL-8). Three growth factors (VEGF, PlGF, and PDGF-AA) were also significantly correlated with each other, as were sVEGFR-1 or -2 and the inflammatory factors (MCP-1, IL-6, IL-8, and IP-10). These findings suggest that sVEGFRs and growth/inflammatory factors have an important role in DME.


Serum CETP and PLTP activity in middle-aged men living in urban or rural area of the Lower Silesia region. PURE Poland sub-study.
The dependence of lipid transfer proteins on significant pro-atherogenic factors is unclear. The aim of the study was to evaluate serum cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activity in relation to lipid disturbances in men living in an urban or rural area. A group of 427 men, volunteers for the Prospective Urban Rural Epidemiology (PURE) sub-study - 263 urban inhabitants (aged 51.9 ±6.0) and 164 residents of villages (aged 51.1 ±5.9) - were examined. In the multivariable linear regression model, the following factors were included as potential confounders: age, body mass index (BMI), smoking, alcohol consumption, hs-C-reactive protein reaction (hs-CRP) and co-existence of chronic diseases. In multiple linear regression models, site of residence (urban or rural area) was the most important independent and consistent predictor of CETP and PLTP activity; β coefficients (95% CI) for CETP (0.18) and PLTP (-0.29) were significant at levels of p < 0.001. Three-way analysis of variance showed no effect of smoking or moderate alcohol consumption on lipid transfer proteins; however, CETP activity showed an interaction effect between these risk factors. In the group of all men, CETP activity was significantly and positively correlated with total cholesterol (r = 0.24), low-density lipoprotein cholesterol (r = 0.18), and non-high density lipoprotein cholesterol (r = 0.21), whereas PLTP activity was correlated with BMI (r = 0.12). Body mass index in rural men was higher than in the urban male population. Increased PLTP activity, recognized as a pro-atherogenic factor, and decreased CETP activity, known as a protective factor, both observed in men living in rural areas, are probably conditioned by nutritional and/or genetic factors.


Morphological and functional studies of human fetal liver cells in primary monolayer culture.
Livers from human fetuses between the 16th and 24th weeks of gestation were dissociated by successive dispase and collagenase digestion followed by two cycles of low-speed differential centrifugation. This improved method recovered approximately 1 X 10(7) cells (90% hepatocytes and 90% viable cells) from 4 g of liver tissue. These hepatocytes were set into primary culture and monolayer granular hepatocytes were obtained within a week. Both albumin and alpha-fetoprotein production was demonstrated in these granular hepatocytes by the immunoperoxidase method for 2 weeks and alpha-fetoprotein production in the culture medium occurred for a week by the single radial immunodiffusion method. The morphological features of the granular hepatocytes could be distinguished from those of the other type of epithelial cells with clear cytoplasm. During the cultivation period, gradual changes from granular to clear hepatocytes with high mitotic activity were found.


B-thromboglobulin content of human blood platelets.
There was a reduction in the B-thromboglobulin content of human blood platelets in patients with leukaemia after chemotherapy which inhibited platelet production. Thus, in these patients, as the circulating platelet population ages, B-thromboglobulin leaks out of, or is actively secreted by, platelets which remain in the circulation.


Mutational analysis of the hexose transporter of Plasmodium falciparum and development of a three-dimensional model.
Plasmodium falciparum infection kills more than 1 million children annually. Novel drug targets are urgently being sought as multidrug resistance limits the range of treatment options for this protozoan pathogen. PfHT1, the major hexose transporter of P. falciparum is a promising new target. We report detailed structure-function studies on PfHT1 using site-directed mutagenesis approaches on residues located in helix V (Q169N) and helix VII ((302)SGL --> AGT). Studies with hexose analogues in these mutants have established that hexose recognition and permeation are intimately linked to these helices. A "fructose filter" effect results from the Q169N mutation (abolishing fructose uptake but preserving affinity and transport of glucose, as reported in Woodrow, C. J., Burchmore, R. J. S., and Krishna, S. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 9931-9936). Associated changes in competition for glucose uptake by C-2, C-3, and C-6 glucose analogues compared with native PfHT1 indicate subtle alterations in substrate interaction in this mutant. The K(m) values for glucose uptake in helix VII mutants are also similar to native PfHT1. Hydrogen bonding to positions C-5 and C-6 in glucose analogues becomes relatively more important in these mutants compared with native PfHT1. To increase understanding of hexose permeation pathways in PfHT1, we have developed the first three-dimensional model for PfHT1. As predicted for GLUT1, the principal mammalian glucose transporter, PfHT1 contains a main and an auxiliary channel. After modeling, the Q169N mutation leads predominantly to local structural changes, including displacement of neighboring helix IV. The (302)SGL position in helix VII lies in the same plane as Gln-169 in helix V but is also adjacent to the main hexose permeation pathway, consistent with results from experiments mutating this triplet motif. Furthermore, there are obvious structural and functional differences between GLUT1 and PfHT1 that can now be explored in detail using the approaches presented here. The development of specific inhibitors for PfHT1 will also be aided by these insights.


Cutaneous metastases from breast carcinoma.
We report the case of a rare presentation of cutaneous metastatic breast carcinoma. A 72-year-old lady who was previously fit and well presented with a 2-month history of a rash over the left breast. Clinically, in addition to the rash, she had a fixed tender mass of left supraclavicular fossa and left axillary lymph nodes. Punch biopsy of the skin demonstrated metastatic carcinoma and ultrasound of the left breast revealed a 9 mm irregular mass which was biopsied, demonstrating poorly differentiated grade III adenocarcinoma. She was oestrogen receptor negative but human epidermal growth factor receptor-2 positive on immunohistochemistry. She is currently undergoing chemotherapy with taxotere and herceptin.


Motivating the masses for family planning in the People's Republic of China.
China's family planning efforts give the appearance of being substantial and effective, though in terms of hard data the precise degree of success achieved is hard to gauge. The author's five-week tour of China, upon which this article is based, showed a country that seemed capable of controlling its rate of population growth, but it was unclear whether the desired level of growth had in fact been attained. What was clear is that several unusual ingredients are primarily responsible for the marked progress made to date. Foremost among them is a public attitude of strict adherence to a moral code which effectively limits sexual relations to married couples and which encourages delay of marriage well beyond the teenage years. Enhancing this, a wide-ranging State publicity campaign promotes birth control through public address systems, brochures given newlyweds, classes and information provided to expectant parents, discussion groups designed to elicit "voluntary" adoption of birth control methods, and other means. To complement this, the Government provides a nationwide network of free or nearly free family planning services organized down to the local level and fully equipped to assist with contraception, sterilization, or termination of pregnancy upon request. Although general statistics have not been made available, it seems obvious that a substantial reduction in China's potential rate of population growth has been achieved.


Age-related changes in the mitotic and metabolic characteristics of muscle-derived cells.
Age-related sarcopenia could partly result from cumulative repeated episodes of incomplete repair and regeneration. We hypothesized that mitotic and metabolic events associated with satellite cell activation and proliferation could be altered with aging. Muscle-derived cells (mdc) were isolated from gastrocnemius and quadriceps muscles of young (3 wk old), adult (9 mo old), and old (24 mo old) Sprague-Dawley male rats (n = 10/group). The mdc from young growing rats started to proliferate earlier compared with adult and old animals. Cell cycle duration was significantly reduced with aging from 36.5 +/- 3.2 to 28.0 +/- 2.2 h. However, the proportion of noncycling (G0 phase) and cycling (G1 + S + G2 + M phases) cultured mdc was statistically unchanged among the three age groups. Significantly lower increase in c-met and proliferating cell nuclear antigen expression were observed in cultured mdc of old rats upon serum stimulation. Major changes in the expression of citrate synthase, lactate dehydrogenase, proteasome, caspase 3, plasminogen activators (PAs), and matrix metalloproteinase 2-9 (MMP2-9) were observed upon serum stimulation, but no age-related difference was noted. However, when measured on crushed muscle extracts, PAs and MMP2-9 enzyme activities were significantly decreased with aging. Our results show that cellular and biochemical events associated with the control of mdc activation and proliferation occur with aging. These alterations may participate in the accumulation of repeated episodes of incomplete repair and regeneration throughout the life span, thus contributing to the loss of skeletal muscle mass and function with aging.


Phytochemical Screening, Free Radical Scavenging and α-Amylase Inhibitory Activities of Selected Medicinal Plants from Western Nepal.
Background: More than 700 plants are reported to be used for medicinal purposes in Nepal; however, many of them are not studied for their scientific evidences. The aims of the present study were the estimation of the total phenolic and flavonoid contents, and the evaluation of the free radical scavenging and α-amylase inhibitory activities of five selected medicinal plants from western Nepal: Aeschynanthus parviflorus Wall. (Gesneriaceae), Buddleja asiatica Lour. (Loganiaceae), Carica papaya L. (Caricaceae), Drepanostachyum falcatum (Nees) Keng f. (Gramineae) and Spondias pinnata (L. f.) Kurz (Anacardiaceae). Methods: The total phenolic content (TPC) and total flavonoid content (TFC) were measured using Folin-Ciocalteu's phenol reagent and aluminium chloride methods, respectively. A 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay was used to evaluate the free radical scavenging activity and an α-amylase inhibitory assay was carried out to determine the in vitro antidiabetic activity. Results: The phytochemical screening of five hydroalcoholic plant extracts revealed the presence of various secondary metabolites, including alkaloids, flavonoids, reducing sugars, saponins, terpenoids and tannins. The amounts of total phenolics and flavonoids were found to be the highest in B. asiatica leaf extract, which also showed the most potent free radical scavenging activity. Extract of C. papaya fruits showed the highest α-amylase inhibitory activity, whereas the extracts of B. asiatica leaves and S. pinnata leaves exhibited moderate activity. Conclusions: Some of the medicinal plants selected in this study showed high TPC and TFC values and potent bioactivities. These results may provide the scientific evidences of the traditional uses of these plants. However, further detailed studies on bioactive compounds isolation and identification and evaluation of in vivo pharmacological activities should be performed in future.


Amniotic fluid lecithin/sphingomyelin ratio changes related to centrifugal force.
Lecithin/sphingomyelin ratio (L/S ratio) in amniotic fluid has gained wide clinical acceptance as an index of fetal lung maturity. We determined L/S ratios of amniotic fluids centrifuged at various "g-forces." Our studies demonstrate that the L/S ratio value is highly dependent on the g-force used to prepare the fluid. We recommend standardization of the g-force, time, and temperature used in preparation of the amniotic fluid for L/S ratio determination.


Genetic amniocentesis at 14 weeks or less.
The recent clinical trials indicate that EA is feasible. The use of ancillary tools, such as ultrasound, requires only a slight modification of the previously established techniques for MA. The amniotic fluid can be obtained and cultured. Combining the reported populations sampled, the procedural and cytogenetic failure rate were 2.0% and 0.3% respectively. The necessary information for prenatal diagnosis in the situations listed previously can be obtained. The one exception to this would be the patient at increased risk for NTD. As noted above, diagnostic levels for AFAFP have been established beginning at 13 weeks gestation. Therefore, amniocentesis before 13 weeks gestation should not be considered an option for these patients. The majority of the findings in these "pilot" studies have been promising, but the issue regarding the safety of EA has not been answered. Harrison et al. theorized that the function of the physiology hydramnios was to "provide a distention growth stimulus to the uterus ... and conversely to share in the maintenance of uterine inhibition." The amniotic fluid is constantly being replaced, having a complete turnover approximately every 3 hours. Does the reduction in volume, for even a short period of time, change the "distensive forces" enough to increase the pregnancy loss rate? Later publications have associated MA with increased rates of congenital orthopedic anomalies and neonatal pulmonary compromise. The true existence of these complications continues to be debated in the literature. Two of the authors have indicated that none of the reported neonates exposed to EA have had such anomalies.(ABSTRACT TRUNCATED AT 250 WORDS)


Successful intravenous human immunoglobulin treatment of drug-induced Stevens-Johnson syndrome in a dog.
A two-year-old, male English springer spaniel developed severe mucocutaneous ulceration following treatment with trimethoprim-potentiated sulphadiazine. The clinical signs were consistent with Stevens-Johnson syndrome (SJS): there were no target or arciform lesions typical of erythema multiforme minor and major; more than one mucosal surface was affected; epidermal detachment affected less than 10 per cent of the body surface area; and there was a clear history of drug exposure. Systemic signs included a severe hepatopathy, dyspnoea, pyrexia and cachexia. Glucocorticoid therapy was associated with secondary infection by Pseudomonas aeruginosa. The clinical signs rapidly resolved following a single intravenous infusion of 0.51 g/kg human immunoglobulin (ivHIG) as a 5 per cent solution. By blocking FAS/FAS ligand (CD95/CD95L) interactions, ivHIG is thought to prevent keratinocyte apoptosis. It also binds to immunoglobulin G Fc receptors, inhibiting cell activation and cytokine synthesis, neutralises autoantibodies and immune complexes, blocks complement activity, is antimicrobial and increases colloid osmotic pressure. To the authors' knowledge, this is the first report of successful treatment of canine SJS using ivHIG, although it has been used to treat erythema multiforme in a cat and toxic epidermal necrolysis in a dog.


PDCD5 inhibits progression of renal cell carcinoma by promoting T cell immunity: with the involvement of the HDAC3/microRNA-195-5p/SGK1.
Epigenetics exerts a vital role in the onset and development of renal cell carcinoma (RCC). Mounting evidence has shed light on the significance of human immune system in response to tumor infiltrating T cells. Hereby, we sought to unmask the immunomodulatory role of histone deacetylase 3 (HDAC3) and its potential upstream molecule, programmed cell death 5 (PDCD5) in RCC. RCC and adjacent non-cancerous tissues were clinically resected from 58 patients, in which the expression profile of microRNA-195-5p (miR-195-5p), PDCD5, HDAC3, and serum glucocorticoid-inducible kinase 1 (SGK1) was determined by RT-qPCR and Western blot analysis. Their relations were investigated by a series of luciferase assays in combination with ChIP and co-IP. RCC cells (A498) were intervened using gain- and loss-of-function approaches, followed by cell proliferation evaluation. After co-culture with CD3+ T cells, flow cytometry and interferon-γ (IFN-γ) determination were performed. A xenograft tumor mouse model was developed for in vivo validation. PDCD5 was downregulated in RCC tissues and A498 cells. Upregulation of HDAC3, as well as of SGK1, resulted in suppression of A498 cell proliferation and promotion of T cell activation as evidenced by higher IFN-γ expression. Re-expression of PDCD5 downregulated HDAC3, causing a subsequent upregulation of miR-195-5p, while miR-195-5p could inversely modulate its target gene, SGK1. The regulatory mechanism appeared to be functional in vivo. Our results highlight the possible manipulation by PDCD5 on RCC cell proliferation and T cell activation, which provides new clues to better understand the immune balance in RCC progression.


Essential and expendable features of the circadian timekeeping mechanism.
Circadian clocks control behavioral, physiological and metabolic rhythms via one or more transcriptional feedback loops. In animals, two conserved feedback loops are thought to keep circadian time by mediating rhythmic transcription in opposite phases of the circadian cycle. Recent work in cyanobacteria nevertheless demonstrates that rhythmic transcription is dispensable for circadian timekeeping, raising the possibility that some features of the transcriptional feedback loops in animals are also expendable. Indeed, one of the two feedback loops is not necessary for circadian timekeeping in animals, but rhythmic transcription and post-translational modifications are both essential for keeping circadian time. These results not only confirm additional requirements within the animal circadian timekeeping mechanism, but also raise important questions about the function of conserved, yet expendable, features of the circadian timekeeping mechanism in animals.


Use of turbidimetric growth curves for early determination of antifungal drug resistance of filamentous fungi.
A previously described microbroth kinetic system (J. Meletiadis, J. F. Meis, J. W. Mouton, and P. E. Verweij, J. Clin. Microbiol. 39:478-484, 2001) based on continuous monitoring of changes in the optical density of fungal growth was used to describe turbidimetric growth curves of different filamentous fungi in the presence of increasing concentrations of antifungal drugs. Therefore, 24 clinical mold isolates, including Rhizopus oryzae, Aspergillus fumigatus, Aspergillus flavus, and Scedosporium prolificans, were tested against itraconazole, terbinafine, and amphotericin B according to NCCLS guidelines. Among various parameters of the growth curves, the duration of the lag phase was strongly affected by the presence of antifungal drugs. Exposure to increasing drug concentrations resulted in prolonged lag phases of the turbidimetric growth curves. The lag phases of the growth curves at drug concentrations which resulted in more than 50% growth (for itraconazole and terbinafine) and more than 75% growth (for amphotericin B) after 24 h of incubation for R. oryzae, 48 h for Aspergillus spp., and 72 h for S. prolificans were 4 h longer than the lag phases of the growth curves at the corresponding drug-free growth controls which varied from 4.4 h for R. oryzae, 6.5 h for A. flavus, 7.9 h for A. fumigatus, and 11.6 h for S. prolificans. The duration of the lag phases showed small experimental and interstrain variability, with differences of less than 2 h in most of the cases. Using this system, itraconazole and terbinafine resistance (presence of >50% growth) as well as amphotericin B resistance (presence of >75% growth) was determined within incubation periods of 5.0 to 7.7 h for R. oryzae (for amphotericin B resistance incubation for up to 12 h was required), 8.8 to 11.4 h for A. fumigatus, 6.7 to 8.5 h for A. flavus, and 13 to 15.6 h for S. prolificans while awaiting formal MIC determination by the NCCLS reference method.


Clinical characteristics and complications of rotavirus gastroenteritis in children in east London: A retrospective case-control study.
Rotavirus is the leading cause of acute gastroenteritis in children and is associated with neurological complications such as seizures and encephalopathy. The aim of this study was to investigate the presentation and complications of rotavirus compared to non-rotavirus gastroenteritis in UK children. This was a retrospective, case-control, hospital-based study conducted at three sites in east London, UK. Cases were children aged 1 month to 16 years diagnosed with acute gastroenteritis between 1 June 2011 and 31 December 2013, in whom stool virology investigations confirmed presence of rotavirus by PCR. They were matched by age, gender and month of presentation to controls with rotavirus-negative gastroenteritis. Data were collected from 116 children (50 cases and 66 controls). Children with rotavirus gastroenteritis tended to present more frequently with metabolic acidosis (pH 7.30 vs 7.37, P = 0.011) and fever (74% versus 46%; P = 0.005) and were more likely to require hospitalisation compared to children with non-rotavirus gastroenteritis (93% versus 73%; P = 0.019). Neurological complications were the most common extra-intestinal manifestations, but did not differ significantly between children with rotavirus-positive gastroenteritis (RPG) and rotavirus-negative gastroenteritis (RNG) (24% versus 15%, respectively; P = 0.24). Encephalopathy occurred only in children with rotavirus infection (n = 3, 6%). Rotavirus causes longer and more severe disease compared to other viral pathogens. Seizures and milder neurological signs were surprisingly common and associated with multiple pathogens, but encephalopathy occurred only in children with rotavirus gastroenteritis. Rotavirus vaccination may reduce seizures and presentation to hospital, but vaccines against other pathogens causing gastroenteritis are required.


Family medicine's identity: being generalists in a specialist culture?
Family medicine has been in conflict about whether it is a specialty or a generalist discipline. Although for a time the family was offered as a solution to family medicine being marginalized in biomedicine, a more biomedical focus prevailed. As a result, the practice of family medicine came more to resemble the world of biomedicine despite an insistence on the discipline's distinctiveness. Ways to avoid identity pitfalls in the future might be to seek solutions that do not promise to solve our identity problem once and for all, to refrain from adopting generalized slogans that do not encourage critical thinking, to practice what we preach, to accept that specialization is part of the American cultural ethos, and to embrace reflective practice.


Efficacy and safety of oral roflumilast for moderate-to-severe psoriasis-a randomized controlled trial (PSORRO).
Roflumilast is a targeted inhibitor of phosphodiesterase (PDE)-4 and has been approved for treatment of severe chronic obstructive pulmonary disease for more than a decade. Generic versions are available in the United States. PDE-4 is involved in the psoriasis pathogenesis, but the efficacy and safety of oral roflumilast in patients with psoriasis have not previously been studied. A company-independent, multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.govNCT04549870). Patients were randomized 1:1 to receive monotherapy with oral roflumilast 500 μg once daily or placebo. At week 12, placebo patients were switched to open-label roflumilast through week 24. The primary endpoint was a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI75) at week 12. In all, 46 patients were randomized (roflumilast, n = 23; placebo, n = 23). At week 12, significantly more patients in the active arm achieved PASI75 (8 of 23 patients [35%]) vs. placebo (0 of 23 patients [0%], with a difference vs. placebo of 8 [35%] patients, 95% CI: 3 [13%]-13 [57%] patients) (p = 0.014). At week 24, 15 (65%), 10 (44%), 5 (22%), and 2 (9%) of patients treated with roflumilast from week 0 had PASI50, PASI75, PASI90, and PASI100 responses (key secondary endpoints), respectively. The most prevalent, drug-related adverse events in both treatment groups were transient gastrointestinal symptoms, weight-loss, headache, and insomnia. A total of three patients (roflumilast n = 2; placebo, n = 1) discontinued therapy due to adverse events. Oral roflumilast was efficacious and safe in treating moderate-to-severe plaque psoriasis over 24 weeks. With generic versions available, this drug may represent an inexpensive and convenient alternative to established systemic psoriasis treatments. Financial support was received from Herlev and Gentofte Hospital, University of Copenhagen, and independent grants from private foundations in Denmark. No pharmaceutical company, including the market authorization holder of roflumilast, was involved in the study at any point.


Serum protein electrophoresis under effective control of HIV-1 disease progression.
In this report, we compared the serum protein electrophoresis (SPE) patterns in a subset of HIV-1-infected subjects who did not progress to AIDS without antiretroviral treatment with those in whose control of disease progression was achieved by highly active antiretroviral therapy (HAART). SPE and immunofixation electrophoresis were performed on Helena Electrophoresis System according to manufacturer's instructions. The percentage of SPE abnormalities, resembling chronic inflammation, was significantly higher in HIV-1-infected subject without HAART compared with those under HAART (p = 0.001). The majority of individuals under HAART showed evidence of oligoclonal bands on the γ-band against a polyclonal background compared with those without HAART but ß-γ-band bridging was more evident. Immunofixation pattern was consistent with oligoclonal hypergammaglobulinaemia of IgG kappa type, which was found to be more intense in group without HAART. HIV clinical status did not show appreciable effect on the SPE pattern in subjects without HAART. However, under effective HAART, subjects with better CD4 T-cell count were associated with higher γ-globulin band. In group without HAART, acute infection was found to be associated the higher γ-globulin fraction compared with chronic infection. The opposite was the case under effective HAART. HIV infected subjects that did not progress to AIDS were associated with markedly abnormal SPE pattern. Overall results reflect the host ability compensate defective cellular immunity in HIV-1 infection with humoral immune responses. These findings underscore the usefulness of SPE monitoring HIV disease management and identifying individuals that may not progress to full-blown AIDS in the absence of treatment.


Downregulation of clusterin expression in testicular germ cell tumours.
Clusterin is implicated in many biological processes including cell adhesion, apoptosis and transformation. Clusterin expression was demonstrated during sperm maturation and is overexpressed in different malignancies including breast and prostate carcinomas and anaplastic large-cell lymphomas. The aim of this study was to determine the expression of clusterin in a series of different germ cell tumours by immunohistochemistry. Twenty-two seminomas, 27 embryonal carcinomas, 22 mature and immature teratomas, 8 yolk sac tumours and 1 chorion carcinoma as well as 30 normal testes were analysed using a monoclonal antibody. In normal testes strong signals were seen in the maturing germ cells and in Leydig cells. In most tumours examined no clusterin expression was detected (84%). Only a focal weak expression was seen in some teratomas (32%), embryonal carcinomas (15%) and yolk sac tumours (25%). Our results suggest that clusterin is associated with normal germ cell development and that the loss of clusterin expression might play a role in the malignant transformation of germ cells.


[The insertion/deletion polymorphism (I/D) of the ACE gene in pregnant women with excessive weight gain].
The body mass gain is conditioned by lifestyle, as well as many environmental and genetic factors. Recent studies suggest that renin-angiotensin system (RAS) plays a fundamental role in process of growth and differentiation of adipocytes through the acting of angiotensin II and seems to be a significant factor in excessive weight gain development. The purpose of this study was to determine the frequency and significance of insertion/deletion polymorphism (I/D) of the ACE gene in pregnant women with excessive weight gain. The examined group consisted of 212 pregnant women, including 107 women with normal (DeltaBMI< or =5) and 105 women with excessive weight gain (DeltaBMI>5). Genomic DNA was extracted from venous blood. The I/D polymorphism of ACE gene was determined by polymerase chain reaction (PCR). During the course of the study we did not observe the statistically significant higher frequency of ACE genotypes in any of the two investigated groups of women with normal and excessive weight gain. Nevertheless, an overrepresentation of II genotype frequency in group with excessive weight gain has been observed (33.3 vs 21.5%, p=ns). The same findings were visible as far as the frequency of I allele in group with excessive weight gain was concerned (55.2 vs 45.8%, p=ns). The frequency of observed genotypes was in agreement with Hardy-Weinberg equilibrium. Although overrepresentation of II genotype and I allele in the group of pregnant women with excessive weight gain (DeltaBMI>5) has been observed, a close correlation between II genotype and higher risk of overweight could be not indicated (due to the lack of significant difference). The results should be confirmed in a more numerous group of pregnant women. At this stage the results of the study did not suggested the presence of association of I/D polymorphism of ACE gene with weight gain in investigated group of pregnant women.


Treatment of Decubitis Ulcer Stage IV in the Patient with Polytrauma and Vertical Share Pelvic Fracture, Diagnosed Entherocollitis and Deep Wound Infection with Clostridium Difficile with Combined Negative Pressure Wound Therapy (NPWT) and Faecal Management System: Case Report.
The aim of this paper was to present a case with the successful treatment of decubitis ulcer stage IV in the patient with polytrauma and vertical share pelvic fracture and diagnosed entherocollitis combined with deep wound infection with Clostridium difficile treated with combined Negative Pressure Wound Therapy (NPWT) and faecal management system. Patient D.S.1967 treated on Traumatology Clinic after tentamen suicide on 9.2.2015 with diagnosis: brain contusion; contusion of thoracal space; vertical share pelvic fracture; open fracture type II of the right calcaneus; fracture of the left calcaneus; fracture on the typical place of the left radius; fracture of the right radius with dislocation. As a first step during the treatment in Intensive care unit we perform transcondylar extension of the left leg, and in that time we cannot operate because of the brain contusion. Four weeks after this treatment we intent to perform stabilisation of the pelvic ring, fixation of both arms, and fixation of both calcanear bones. But at the time before performing the saurgery, the patient got an intensive enterocollitis from Escherichia colli and Clostridium difficile, and during the inadequate treatment of enterocollitis she got a big decubitus on both gluteal regia Grade IV and deep muscular necrosis. Several times we perform a necrectomy of necrotic tissue but the wound become bigger and the infection have a progressive intention. In that time we used VAK system for 6 weeks combined with faecal management system and with local necrectomy and system application of Antibiotics and Flagyl for enterocollitis in doses prescripted from specialists from Infective clinic. This new device to manage faecal deep decubital infection and enterocollitis with Clostridium difficile are considered as adequate. 8Flexi-Seal® FMS has been also used. After two months we succeed to minimize the gluteal wound on quoter from the situation from the beginning and we used for next two months wound treatment from Departement for Plastic and Reconstructive Surgery. When faecal incontinence as a result of enterocollitis with Clostridium difficile does occur, a limiting contact with the patient's skin is extremely important as breakdown can occur rapidly. In addition to tissue injury, faecal incontinence can have a major impact on the patient's dignity and result in prolonged hospital stay. The main outcomes assested in the case studies were resolution of of decubital ulcers as a result of faecal incontinence, patient comfort and ease of application of the FMS and NPWT. The soft flexible catheter was easily inserted without discomfort to the patients. It gently conformed to the rectal vault, reducing significantly the risk of necrosis, and the risk for prolonged necrosis in cases with previously developed necrosis. FMS was successful in diverting faecal fluid away from the perineal tissue and resolved any decubitus ulcer developed previously in combination with use of NPWT. So, we can recommend this combination in those cases especially with polytraumatismus, vertical share pelvis fracture combined with diarrhea and deep wound infection of decubital ulcers Grade IV infected with Cl. difficile.


Driving the Way to Tuberculosis Elimination: The Essential Role of Fundamental Research.
Tuberculosis has impacted human health for millennia. The World Health Organization estimated that, in 2014, 9.6 million people developed tuberculosis and 1.5 million people died from the disease. In May 2014, the World Health Assembly endorsed the new "End TB Strategy" that presents a pathway to tuberculosis elimination. The strategy outlines 3 areas of emphasis, one of which is intensified research and innovation. In this article we highlight the essential role for fundamental tuberculosis research in the future of tuberculosis diagnostics, treatment, and prevention. To maximize the impact of fundamental research, we must foster collaboration among all stakeholders engaged in tuberculosis research and control to facilitate open dialogue to assure that critical gaps in outcome-oriented science are identified and addressed. We present here a framework for future discussions among scientists, physicians, research and development specialists, and public health managers for the reinforcement of national and international strategies toward tuberculosis elimination.


[Early relapse of hemophagocytic syndrome after reduced-intensity cord blood transplantation for relapsed acute lymphoblastic leukemia].
We report a 4-year-old girl who presented with acute onset of hemophagocytic syndrome (HPS) after induction therapy and HPS relapsed immediately after reduced-intensity cord blood transplantation (RI-CBT) for relapse of acute lymphoblastic leukemia. The patient underwent CBT from 2 locus-mismatched donor, after reduced-intensity conditioning therapy consisting of fludarabine, melphalan, and total body irradiation 4Gy. Prednisolone and cyclosporine were administered for prophylaxis against graft-versus-host disease. Bone marrow examination on day 20 revealed activated macrophages displaying hemophagocytosis. The origin of macrophages was 2(nd) donor derived. After administration of steroids, intravenous immunoglobulin and VP-16, the patient exhibited complete chimerism and remained in complete remission for over one year.


Spectral analysis based on compressive sensing in nanophotonic structures.
A method of spectral sensing based on compressive sensing is shown to have the potential to achieve high resolution in a compact device size. The random bases used in compressive sensing are created by the optical response of a set of different nanophotonic structures, such as photonic crystal slabs. The complex interferences in these nanostructures offer diverse spectral features suitable for compressive sensing.


Characterization of Bifidobacterium strains for use in soymilk fermentation.
Soybean milk, which serves as a base for a variety of beverages, contains raffinose, stachyose, pentanal and n-hexanal; the former two may be responsible for flatulence after fermentation, whilst the latter two for a beany flavour. Twenty-seven strains of Bifidobacterium were analyzed for their alpha-galactosidase activity and the production of lactic and acetic acids to determine their potential for use in the production of fermented soymilk. The behaviour of three strains in soymilk was studied to determine their ability to reduce alpha-D-galactosyl oligosaccharides and produce lactic and acetic acids. They all were able to reduce stachyose and raffinose. Pentanal and n-hexanal were metabolized by Bifidobacterium breve MB233. These data indicate that bifidobacteria can be used for biotechnological processes that employ soymilk as the substrate. A product with low levels of alpha-D-galactosyl oligosaccharides and alkylic aldehydes may be obtained.


Acidic and basic fibroblast growth factors suppress transcriptional activation of tissue factor and other inflammatory genes in endothelial cells.
Tissue factor (TF) is a transmembrane receptor that serves as a cofactor for factor VIIa and initiates the extrinsic pathway of blood coagulation. Under normal physiological conditions, TF is expressed in extravascular and perivascular cells but not in vascular endothelial cells and monocytes. TF can be induced in these cells by inflammatory regulators and other stimulators, such as LPS, thrombin, oxidized lipoproteins, and certain growth factors. An earlier study showed that growing primary cultures of human umbilical vein endothelial cells (HUVECs) with endothelial cell growth supplement (ECGS) and heparin had impaired the ability of monolayers to express surface membrane TF activity after perturbation. The mechanism by which ECGS suppressed TF activity was not known. In the present study, we investigated the effect of recombinant acidic and basic fibroblast growth factors (aFGF and bFGF) on the induction of TF in a HUVEC cell line and a fibroblast cell line. Both aFGF and bFGF suppressed the phorbol myristate acetate-induced expression of TF in endothelial cells but not the serum-induced expression of TF in fibroblast cells. Diminished expression of the cell surface TF activity observed in endothelial cells grown with aFGF or bFGF was due to the accumulation of a lower number of TF mRNA transcripts. TF mRNA stability was not altered in HUVECs grown with aFGF or bFGF. Nuclear run-on experiments revealed that the transcription of TF and several other genes that play an important role in inflammation and angiogenesis was reduced in the endothelial cells that were cultured with aFGF or bFGF. The diminished expression of TF may be part of a generalized response of endothelial cells to FGF that facilitates migration of endothelial cells during angiogenesis.


Exploring Factors That Influence Student Engagement in Community-Engaged Learning Activities Within a Pharmacy Context.
Objective. To investigate and identify factors that enhance and restrict Doctor of Pharmacy student engagement in mandatory and voluntary community-engaged learning activities.Methods. A phenomenological study exploring the motivations and barriers faced by pharmacy students in a mandatory community-engaged learning course and voluntary community-engaged learning activities (eg, community outreach) was conducted using semi-structured interviews. Fifteen students were randomly selected to participate in the interviews. Student responses were analyzed using qualitative thematic analysis.Results. Primary factors motivating student engagement in mandatory community-engaged learning included having structured learning activities for students and incorporating reflective learning. Motivating factors for students participating in voluntary community-engaged learning included personal interest in the topic, convenient location and time of activity, opportunity for career development, and the chance to advocate for the pharmacy profession. Overlapping motivations for both mandatory and voluntary community-engaged learning included developing a better understanding of and broader perspective on the diverse populations in the community and having a positive impact. Common barriers identified included having limited information about student responsibilities, being given a limited student role, and feeling unconfident or unprepared.Conclusion. Students perceived benefits from both mandatory and voluntary participation in community-engaged learning activities. However, opportunities exist for identifying and managing barriers to enhancing student engagement in community-engaged learning within a pharmacy program. Additionally, learning tools such as critical reflection can be used to further enhance student engagement with community-engaged learning activities.


Fresnel laws at curved dielectric interfaces of microresonators.
We discuss curvature corrections to Fresnel's laws for the reflection and transmission of light at a nonplanar refractive-index boundary. The reflection coefficients are obtained from the resonances of a dielectric disk within a sequential-reflection model. The Goos-Hänchen effect for curved light fronts at a planar interface can be adapted to provide a qualitative and quantitative extension of the ray model which explains the observed deviations from Fresnel's laws.


Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis.
Tumors produce multiple growth factors, but little is known about the interplay between various angiogenic factors in promoting tumor angiogenesis, growth, and metastasis. Here we show that 2 angiogenic factors frequently upregulated in tumors, PDGF-BB and FGF2, synergistically promote tumor angiogenesis and pulmonary metastasis. Simultaneous overexpression of PDGF-BB and FGF2 in murine fibrosarcomas led to the formation of high-density primitive vascular plexuses, which were poorly coated with pericytes and VSMCs. Surprisingly, overexpression of PDGF-BB alone in tumor cells resulted in dissociation of VSMCs from tumor vessels and decreased recruitment of pericytes. In the absence of FGF2, capillary ECs lacked response to PDGF-BB. However, FGF2 triggers PDGFR-alpha and -beta expression at the transcriptional level in ECs, which acquire hyperresponsiveness to PDGF-BB. Similarly, PDGF-BB-treated VSMCs become responsive to FGF2 stimulation via upregulation of FGF receptor 1 (FGFR1) promoter activity. These findings demonstrate that PDGF-BB and FGF2 reciprocally increase their EC and mural cell responses, leading to disorganized neovascularization and metastasis. Our data suggest that intervention of this non-VEGF reciprocal interaction loop for the tumor vasculature could be an important therapeutic target for the treatment of cancer and metastasis.


Vital Signs: Zika-Associated Birth Defects and Neurodevelopmental Abnormalities Possibly Associated with Congenital Zika Virus Infection - U.S. Territories and Freely Associated States, 2018.
Zika virus infection during pregnancy causes serious birth defects and might be associated with neurodevelopmental abnormalities in children. Early identification of and intervention for neurodevelopmental problems can improve cognitive, social, and behavioral functioning. Pregnancies with laboratory evidence of confirmed or possible Zika virus infection and infants resulting from these pregnancies are included in the U.S. Zika Pregnancy and Infant Registry (USZPIR) and followed through active surveillance methods. This report includes data on children aged ≥1 year born in U.S. territories and freely associated states. Receipt of reported follow-up care was assessed, and data were reviewed to identify Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection. Among 1,450 children of mothers with laboratory evidence of confirmed or possible Zika virus infection during pregnancy and with reported follow-up care, 76% had developmental screening or evaluation, 60% had postnatal neuroimaging, 48% had automated auditory brainstem response-based hearing screen or evaluation, and 36% had an ophthalmologic evaluation. Among evaluated children, 6% had at least one Zika-associated birth defect identified, 9% had at least one neurodevelopmental abnormality possibly associated with congenital Zika virus infection identified, and 1% had both. One in seven evaluated children had a Zika-associated birth defect, a neurodevelopmental abnormality possibly associated with congenital Zika virus infection, or both reported to the USZPIR. Given that most children did not have evidence of all recommended evaluations, additional anomalies might not have been identified. Careful monitoring and evaluation of children born to mothers with evidence of Zika virus infection during pregnancy is essential for ensuring early detection of possible disabilities and early referral to intervention services.