ROS regulation of axonal mitochondrial transport is mediated by Ca2+ and JNK in Drosophila.
Mitochondria perform critical functions including aerobic ATP production and calcium (Ca2+) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using the Drosophila third instar larval nervous system as the in vivo model, we found that ROS inhibited mitochondrial axonal transport more specifically, primarily due to reduced flux and velocity, but did not affect transport of other organelles. To understand the mechanisms underlying these effects, we examined Ca2+ levels and the JNK (c-Jun N-terminal Kinase) pathway, which have been shown to regulate mitochondrial transport and general fast axonal transport, respectively. We found that elevated ROS increased Ca2+ levels, and that experimental reduction of Ca2+ to physiological levels rescued ROS-induced defects in mitochondrial transport in primary neuron cell cultures. In addition, in vivo activation of the JNK pathway reduced mitochondrial flux and velocities, while JNK knockdown partially rescued ROS-induced defects in the anterograde direction. We conclude that ROS have the capacity to regulate mitochondrial traffic, and that Ca2+ and JNK signaling play roles in mediating these effects. In addition to transport defects, ROS produces imbalances in mitochondrial fission-fusion and metabolic state, indicating that mitochondrial transport, fission-fusion steady state, and metabolic state are closely interrelated in the response to ROS.


Structural elucidation of fucoidan from Cladosiphon okamuranus (Okinawa mozuku).
Fucoidan is a sulphated polysaccharide, made up mainly of l-fucose, which is found in brown seaweeds. Its chemical structure is diverse and depends on maturity, species and geographical location. The objective of this study was to elucidate the chemical structure of fucoidan from Cladosiphon okamuranus harvested in Japan. The fucoidan was subject to purification prior to monosaccharide profiling, sulphate content determination, and linkage analysis. Our results showed that Japanese Cladosiphon okamuranus fucoidan contained 70.13 ± 0.22 wt% fucose and 15.16 ± 1.17 wt% sulphate. Other minor monosaccharides found were d-xylose, d-galactose, d-mannose, d-glucose, d-arabinose, d-rhamnose and d-glucuronic acid. Linkage analysis revealed that fucopyranoside units along the backbone are linked, through α-1,3-glycosidic bonds, with fucose branching at C-2, and one sulphate group at C-4 per every three fucose units, i.e. the structure of fucoidan from Japanese Cladosiphon okamuranus is [→3)-α-fuc(1→]0.52[→3)-α-fuc-4-OSO3-(1→]0.33[→2)-α-fuc]0.14.


Turpinionosides A-E: megastigmane glucosides from leaves of Turpinia ternata Nakai.
From leaves of Turpenia ternata (Staphylaceae), one megastigmane and seven of its glucosides (1-8) were isolated. Megastigmane and two of the glucosides were found to be known compounds, namely, 3S,5R,6R,9S-tetrahydroxymegastigmane (1), corchoionoside C (2), and icariside B4 (3). The structures of compounds 4-8 (turpinionosides A-E, respectively) were elucidated by means of spectroscopic analyses, and then their absolute structures were determined by the modified Mosher's method to be (3S,5R,6S,9S)-3,6,9-trihydroxymegastigman-7-ene 3-O- and 9-O-beta-D-glucopyranosides (4, 5, respectively), (1S,3S,5R,6S,9R)-3,9,12-trihydroxymegastigmane 3-O-beta-D-glucopyranoside (6), (3S,4R,9R)-3,4,6-trihydroxymegastigman-5-ene 3-O-beta-D-glucopyranoside (7), and (2S,9R)-2,9-dihydroxymegastigman-5-en-4-one 2-O-beta-D-glucopyranoside (8).


Photodissociation dynamics in the first absorption band of pyrrole. II. Photofragment distributions for the 1A2(πσ*)←X̃1A1(ππ) transition.
The analysis of the total kinetic energy release (TKER) of the photofragments pyrrolyl + H-atom formed in the photodissociation of pyrrole in the low-lying state 1A2(πσ*) is presented. The TKER distributions contain complementary and often more precise information on the fragmentation process than the broad diffuse absorption spectra. The distributions are calculated quantum mechanically for the diabatic state 1A2(πσ*) either isolated or coupled to the ground electronic state at an exit channel conical intersection. The calculations use the novel ab initio quasi-diabatic potential energy matrix constructed in the work of Picconi and Grebenshchikov [J. Chem. Phys. 148, 104103 (2018)]. The approximate overlap integral-based adiabatic mapping approach is introduced with which the quantum mechanical TKER distributions can be efficiently and accurately reproduced. Finally, the calculated TKERs are compared with the experimental results. The main features of the measured vibrationally resolved distributions are reproduced, and the spectral peaks are assigned and interpreted in detail.


Specificity and origin of the Mod2- mutation which restores respiratory sufficient phenotype in some pet mutants in Saccharomyces cerevisiae.
It has been found that Mod2- mutation restores respiratory sufficient phenotype in cytochrome b less mutant MB127-20C. Mod2- gene when present in the same haploid cell with mutant gene pet25 causing deficiency in cytochromes a+a3 and b seems to be responsible for reappearance of cytochrome b in the cytochrome spectrum as well partial respiratory activity. However, the restored respiratory activity seems to be inefficient as growth on unfermentable carbon sources is still impossible. Evidences are presented that the Mod2- mutation originates from respiratory sufficient strain 18-27 in which op1 mutation has been induced.


Effect of isoprenaline on salivary gland lipids of rats fed a choline-deficient diet.
Male adult rats were fed choline deficient and a choline-supplemented diet for 3 weeks. Half the rats from each group were injected with isoprenaline (16 mg/kg body weight) and the remainder with saline. After 2 and 8 hours, rats were sacrificed, their submandibular salivary glands were disected out, and extracted for lipids. The fatty acid composition of total lipids and some neutral and phospholipid fractions were determined. Isoprenaline administration resulted in a slightly higher level of oleic acid in SMSG of rats fed choline-deficient but not the control diet. There was an increase in the free fatty acid (FFA) concentrations of the gland after 2 hours of isoprenaline treatment in rats fed the control diet; no such increase was observed in the choline-deficient group. The fatty acid composition of FFA fraction was also slightly changed as a result of isoprenaline treatment, but only in the choline-deficient group. The fatty acid composition of triglyceride (TG), phosphatidyl choline (PC), and phosphatidyl ethanolamine (PE) fractions was not changed.


Task-related "cortical" bursting depends critically on basal ganglia input and is linked to vocal plasticity.
Basal ganglia-thalamocortical circuits are critical for motor control and motor learning. Classically, basal ganglia nuclei are thought to regulate motor behavior by increasing or decreasing cortical firing rates, and basal ganglia diseases are assumed to reflect abnormal overall activity levels. More recent studies suggest instead that motor disorders derive from abnormal firing patterns, and have led to the hypothesis that surgical treatments, such as pallidotomy, act primarily by eliminating pathological firing patterns. Surprisingly little is known, however, about how the basal ganglia normally influence task-related cortical activity to regulate motor behavior, and how lesions of the basal ganglia influence cortical firing properties. Here, we investigated these questions in a songbird circuit that has striking homologies to mammalian basal ganglia-thalamocortical circuits but is specialized for singing. The "cortical" outflow nucleus of this circuit is required for song plasticity and normally exhibits increased firing during singing and song-locked burst firing. We found that lesions of the striato-pallidal nucleus in this circuit prevented hearing-dependent song changes. These basal ganglia lesions also stripped the cortical outflow neurons of their patterned burst firing during singing, without changing their spontaneous or singing-related firing rates. Taken together, these results suggest that the basal ganglia are essential not for normal cortical firing rates but for driving task-specific cortical firing patterns, including bursts. Moreover, such patterned bursting appears critical for motor plasticity. Our findings thus provide support for therapies that aim to treat basal ganglia movement disorders by normalizing firing patterns.


Paternal mitochondrial DNA transmission during nonhuman primate nuclear transfer.
Offspring produced by nuclear transfer (NT) have identical nuclear DNA (nDNA). However, mitochondrial DNA (mtDNA) inheritance could vary considerably. In sheep, homoplasmy is maintained since mtDNA is transmitted from the oocyte (recipient) only. In contrast, cattle are heteroplasmic, harboring a predominance of recipient mtDNA along with varying levels of donor mtDNA. We show that the two nonhuman primate Macaca mulatta offspring born by NT have mtDNA from three sources: (1) maternal mtDNA from the recipient egg, (2) maternal mtDNA from the egg contributing to the donor blastomere, and (3) paternal mtDNA from the sperm that fertilized the egg from which the donor blastomere was isolated. The introduction of foreign mtDNA into reconstructed recipient eggs has also been demonstrated in mice through pronuclear injection and in humans through cytoplasmic transfer. The mitochondrial triplasmy following M. mulatta NT reported here forces concerns regarding the parental origins of mtDNA in clinically reconstructed eggs. In addition, mtDNA heteroplasmy might result in the embryonic stem cell lines generated for experimental and therapeutic purposes ("therapeutic cloning").


Abuse and mental disorders among women at walk-in clinics in Trinidad: a cross-sectional study.
To determine the prevalence of abuse by their partners and its association with mental disorders among female patients at walk-in clinics in Trinidad. Female participants from 16 randomly selected walk-in clinics, previously stratified to represent all administrative regions and urban and rural settings, who were 18 years or older, were surveyed during May to August 2007 using the WAST-Short and PRIME-MD questionnaires. 432 women participated (a 92% response rate), Of these 16% were aged 20-29, 11.8% 30-39 and 19% 40-49; 37% were married, 25% single; 44.7% were Indo- and 35% Afro-Trinidadian; 67.8% had achieved education up to age 14 only. 30.3% were employed and 3.0% reported incomes more than $5,001 TTD (Trinidad and Tobago Dollars) per month. Forty percent (173) of all respondents were positive for abuse as scored by the WAST-Short scale. Chi-square analysis suggested associations (p < 0.05) between abuse and age, employment status, being in a current relationship, and having the desire to cut down on alcohol intake. Further there were associations between abuse and the presence of depression, suicidal ideation, post-traumatic stress disorder and somatization as determined by the PRIME-MD scale. Logistic regression showed that the statistically significant (p < 0.05) predictors of woman abuse were age less than 49, wanting to cut down on alcohol use and currently being in a relationship. Among women of primarily lower socioeconomic status who attend walk-in clinics in Trinidad abuse as measured by the WAST-Short scale is high and there are statistically significant associations with mental disorders as determined by the PRIME-MD scale.


Novel RNAi-mediated approach to G protein-coupled receptor deorphanization: proof of principle and characterization of a planarian 5-HT receptor.
G protein-coupled receptors (GPCRs) represent the largest known superfamily of membrane proteins extending throughout the Metazoa. There exists ample motivation to elucidate the functional properties of GPCRs given their role in signal transduction and their prominence as drug targets. In many target organisms, these efforts are hampered by the unreliable nature of heterologous receptor expression platforms. We validate and describe an alternative loss-of-function approach for ascertaining the ligand and G protein coupling properties of GPCRs in their native cell membrane environment. Our efforts are focused on the phylum Platyhelminthes, given the heavy health burden exacted by pathogenic flatworms, as well as the role of free-living flatworms as model organisms for the study of developmental biology. RNA interference (RNAi) was used in conjunction with a biochemical endpoint assay to monitor cAMP modulation in response to the translational suppression of individual receptors. As proof of principle, this approach was used to confirm the neuropeptide GYIRFamide as the cognate ligand for the planarian neuropeptide receptor GtNPR-1, while revealing its endogenous coupling to Gα(i/o). The method was then extended to deorphanize a novel Gα(s)-coupled planarian serotonin receptor, DtSER-1. A bioinformatics protocol guided the selection of receptor candidates mediating 5-HT-evoked responses. These results provide functional data on a neurotransmitter central to flatworm biology, while establishing the great potential of an RNAi-based deorphanization protocol. Future work can help optimize and adapt this protocol for higher-throughput platforms as well as other phyla.


Thyroid hormones effects on RNA synthesis in brain and liver of neonatal hypothyroid rats.
The effect of replacement therapy with thyroid hormones upon RNA transcription was studied in isolated nuclei of cerebrum and liver from hypothyroid rats. The chronic administration of T4 to hypothyroid rats, from the 5th day of life, during ten days, corrected the RNA synthesis in isolated nuclei from cerebrum and liver. The injection of a single dose of T3 to neonatally thyroidectomized rats, ten days after birth, enhanced the endogeneous activity of RNA polymerase I and II of cerebrum and liver. In cerebrum the transcription of ribosomal RNA increased 40 minutes after T3 injection, this activity being constant during the whole period studied. On the other hand, the synthesis of heterogeneous RNA showed an increase only 5 hrs. after the beginning of the treatment. In liver, the lag period is higher for both enzymes, being the maximal response achieved 5 hs. after the hormonal administration.


Congenital heart disease in adults: the frequency of medical, surgical & obstetrical care.
Congenital cardiovascular disease is common in adults. Any patient seen for medical or surgical care may have some form of underlying congenital cardiac defect. We reviewed Missouri Health Statistics for 2001 and found 28,300 medical, surgical, or obstetrical encounters for patients over the age of 15 with some form of congenital cardiac disease. A subset was studied in detail revealing 80% of encounters involved conditions other than the congenital defect. All ages were represented including the medicare population.


Effects of silicon on Oryza sativa L. seedling roots under simulated acid rain stress.
Silicon (Si) has an important function in reducing the damage of environmental stress on plants. Acid rain is a serious abiotic stress factor, and Si can alleviate the stress induced by acid rain on plants. Based on these assumptions, we investigated the effects of silicon on the growth, root phenotype, mineral element contents, hydrogen peroxide (H2O2) and antioxidative enzymes of rice (Oryza sativa L.) seedling roots under simulated acid rain (SAR) stress. The results showed that the combined or single effects of Si and/or SAR on rice roots depend on the concentration of Si and the pH of the SAR. The combined or single effects of a low or moderate concentration of Si (1.0 or 2.0 mM) and light SAR (pH 4.0) enhanced the growth of rice roots, and the combined effects were stronger than those of the single treatment. A high concentration of Si (4.0 mM) or severe SAR (pH 2.0) exerted deleterious effects. The incorporation of Si (1.0, 2.0 or 4.0 mM) into SAR with pH 3.0 or 2.0 promoted the rice root growth, decreased the H2O2 content, increased the Si concentration and the superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and ascorbate peroxidase (APX) activities, maintained the balance of mineral element (K, Ca, Mg, Fe, Zn, and Cu) concentrations in the roots of rice seedlings compared with SAR alone. The alleviatory effects observed with a moderate concentration of Si (2.0 mM) were better than the effects obtained with a low or high concentration of Si (1.0 or 4.0 mM). The observed effects were due to disruptions in the absorption and utilization of mineral nutrients and impacts on the activity of antioxidant enzymes in roots, and this conclusion suggests that the degree of rice root damage caused by acid rain might be attributed to not only acid rain but also the level of Si in the soil.


The varied clinical and laboratory manifestations of type II Gaucher's disease.
An infant of Arab extraction with the Type II form of Gaucher's disease is described. His clinical presentation was unusual because in addition to the extensive neurological involvement and marked hepatosplenomegaly a severe congestive cardiomyopathy and renal tubular dysfunction were present. In addition, marked hypergammaglobulinemia and raised serum angiotensin converting enzyme levels were found. It is suggested that these varied manifestations may be ascribed to the consequences of glucocerebroside deposition within the macrophages of the reticuloendothelial system.


Triclonal gammopathy in a patient with plasma cell dyscrasia.
A triclonal gammopathy is an immunoglobulin abnormality in which three discrete monoclonal subpopulations of immunoglobulin molecules are present in a patient's serum. Monoclonal and biclonal gammopathies have been studied extensively, but relatively little is known about the much rarer triclonal gammopathies. The case described below illustrates some of the difficulties that this condition can present to the clinician and the clinical laboratory.


Determination of total arsenic, inorganic and organic arsenic species in wine.
Forty-five wine samples from the south of Spain of different alcoholic strength were analysed for total arsenic and its inorganic [As(III), As(V)] and organic (monomethylarsonic acid [MMAA], dimethylarsinic acid [DMAA]) species. The As levels of the wine samples ranged from 2.1 to 14.6 microg l(-1). The possible effect of the alcoholic fermentation process on the levels of the total arsenic and arsenical species was studied. The average total arsenic levels for the different samples were very similar, without significant differences between all types of wines. In table wines and sherry, the percentages of total inorganic arsenic were 18.6 and 15.6%, with DMAA or MMAA being the predominant species, respectively. In most samples, DMAA was the most abundant species, but the total inorganic aresenic fraction was considerable, representing 25.4% of the total concentration of the element. The estimated daily intakes of total arsenic and total inorganic arsenic for average Spanish consumers were 0.78 and 0.15 microg/person day(-1), respectively. The results suggest that the consumption of these types of wines makes no significant contribution to the total and inorganic arsenic intake for normal drinkers. However, wine consumption contributes a higher arsenic intake than through consumption of beers and sherry brandies.


A simple method for the assessment of electrophoretic mobility in porous media.
Developing paper-based electrophoretic methods involve dealing with significant uncertainty levels when compared to their capillary counterparts. Critical information for developing these kinds of methods are the electrophoretic mobility of background electrolytes and samples. This work presents the design and characterization of a device for measuring the electrophoretic mobilities of dyes in porous media. The device was developed with the aim of validating a previously presented model and also proposing a protocol for the straightforward determination of electrophoretic mobilities in porous media when open-channel values are already known. Whatman #1 paper was used as a model substrate as far as it is the most common porous medium substrate for paper-based electrophoresis. The device was designed using a numerical simulation-assisted approach, utilizing OpenFOAM® and specific solvers for capillary transport and electromigration, namely porousMicroTransport and electroMicroTransport, respectively. The electrophoretic mobilities of five dyes were analyzed experimentally with the proposed device. To establish appropriate comparative values at different pHs, experiments in fused silica capillaries were also performed. An effective parameter model for describing the electrophoretic behavior of dyes in porous media, that is, the constriction factor, was found consistent with previous reports for the Whatman #1 paper. This consistency was found after considering (via direct measurements) the chromatographic effect of the medium over each dye. Consequently, the recorded values hold significant worth due to their potential for direct application in designing new experiments or devices in Whatman #1 paper. With the validation of the model through the experiments with the proposed device, those researchers interested on developing electrophoretic methods in porous substrates can make use of the open-channel electrophoretic mobilities reported in the literature, or in the well-known software databases, and correct them for the media of interest just by performing two simple characterization steps.


Noble-Metal Nanocrystals with Controlled Facets for Electrocatalysis.
Noble-metal nanocrystals (NCs) show excellent catalytic performance for many important electrocatalysis reactions. The crystallographic properties of the facets by which the NCs are bound, closely associated with the shape of the NCs, have a profound influence on the electrocatalytic function of the NCs. To develop an efficient strategy for the synthesis of NCs with controlled facets as well as compositions, understanding of the growth mechanism of the NCs and their interaction with the chemical species involved in NC synthesis is quite important. Furthermore, understanding the facet-dependent catalytic properties of noble-metal NCs and the corresponding mechanisms for various electrocatalysis reactions will allow for the rational design of robust electrocatalysts. In this review, we summarize recently developed synthesis strategies for the preparation of mono- and bimetallic noble-metal NCs by classifying them by the type of facets through which they are enclosed and discuss the electrocatalytic applications of noble-metal NCs with controlled facets, especially for reactions associated with fuel-cell applications, such as the oxygen reduction reaction and fuel (methanol, ethanol, and formic acid) oxidation reactions.


Beneficial Effects of Appropriate Sleep Duration on Depressive Symptoms and Perceived Stress Severity in a Healthy Population in Korea.
Recently, several institutions, including the American Academy of Sleep Medicine, the Sleep Research Society, and the National Sleep Foundation, have made consensus recommendations concerning appropriate sleep duration for adults. Although numerous studies conducted in Western populations have provided evidence of the harmful effects of short or long sleep duration on mental health, it is still unclear whether these consensus recommendations are appropriate in Korean culture. Data from 1,892 subjects with no history of medical or psychiatric diagnoses were selected from the Korea National Health and Nutrition Examination Survey of 2014. Subjects were divided into seven groups based on their sleep duration (≤4, 5, 6, 7, 8, 9, and ≥10 hours). Depressive symptoms were measured using the Patient Health Questionnaire-9 and perceived stress severity was evaluated using a Likert-type scale. Group differences in depressive symptoms and severity of stress were analyzed using an analysis of covariance. Depressive symptoms in subjects with sleep duration of ≤4 hours (5.7±5.9) or 5 hours (3.4±3.9) were higher than in subjects with a sleep duration of 7 (2.2±2.9) or 8 hours (2.2±2.9) (corrected P<0.05). Furthermore, subjects with a short sleep duration (5 hours or below) had greater perceived stress severity than subjects with a sleep duration of 7 or 8 hours (corrected P<0.05). Our results suggest that maintaining an appropriate sleep duration as found in the recent consensus recommendation is important for mental health, even in healthy subjects without any medical or psychiatric illnesses, in Korea.


Essential fatty acid status and characteristics associated with colostrum-deprived gnotobiotic and conventional lambs. Growth, organ development, cell membrane integrity and factors associated with lower bowel function.
A factorial experiment involving gnotobiotic (GN) and conventional (CV) colostrum-deprived lambs and diets formulated to be adequate or deficient in linoleic acid was conducted to determine the effect(s) of the intestinal microflora on the essential fatty acid (EFA) status of the host and subsequent physiological consequences, i.e., growth, organ development, cell membrane integrity and lower bowel function. Lambs were obtained by sterile surgical procedures and housed in sterile isolators or in conventional metabolism stalls for 60 d. Skimmed cow's milk with 6% hydrogenated coconut oil and vitamins A, D and E added with and without .32% of the total calories as linoleic acid was homogenized, bottled and autoclaved, then fed to appetite three to four times daily. The GN lambs supplemented with linoleic acid gained significantly faster between 13 and 41 d of age and more efficiently between 27 and 41 d than the other treatment groups. The absence of dietary linoleic acid decreased liver and spleen weights and, in general, suppressed development of organs except the brain. Red blood cell hemolysis was not affected by treatment. Although showing signs of chronic mild diarrhea, the GN neonatal ruminant differed in Cl- concentration and dry matter percentage of its lower bowel contents from the "classic rodent model." The results indicate that neonatal colostrum-deprived lambs have an EFA requirement, as evidenced by decreased growth and performance characteristics in the GN linoleic deficient vs GN supplemented group, and suggests that the required level is in excess of .32% of the total caloric intake as linoleic acid.(ABSTRACT TRUNCATED AT 250 WORDS)


Induced reversion of a spontaneous point mutation within the Chinese hamster HPRT gene to the wild-type sequence.
The Chinese hamster hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient cell line TG15 produces apparently normal HPRT mRNA by northern analysis and was therefore presumed to contain a point mutation within the coding region. Sequencing cDNA from the TG15 cell line revealed an A to G transition which results in the substitution of the amino acid glycine for aspartic acid at position 135. TG15 cells revert to wild-type HPRT activity upon exposure to monofunctional alkylating agents. A rapid test to assay the site of the TG15 point mutation has been developed, utilizing the polymerase chain reaction and allele-specific oligonucleotide screening. In all revertants studied, the original point mutation has been corrected to the wild-type sequence. The TG15 point mutation lies within a proposed catalytic domain of the HPRT protein in common with other phosphoribosyltransferases.


Spontaneous, L-arginine-induced and spironolactone-induced regression of protein remodeling of the left ventricle in L-NAME-induced hypertension.
N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NO-production L-arginine were able to reverse the protein rebuilding of the left ventricle. Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginine-regression (4 weeks L-NAME + 3 weeks arginine), control 7 (7 weeks placebo). L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic and contractile as well as soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison with the control group. The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone.


A check on hypothetical personality structures and their theoretical interpretation at 14-16 years in T-data.
Basing hypotheses on interpretations of 12 personality factors most replicated in 10 past researches with children, this experiment sets up about eight subtests as specific markers for each. Ninety-five tests, taking eight hours in all, were administered to 394 14-16-year olds. A majority of the personality pattern hypotheses were sustained factor analytically by evidence on number of factors, significance of unique simple structure reached, and goodness of identifying match (chi-square test). Concept validities can be obtained for some six of the factors rivalling those for intelligence tests. A brief discussion is given of the bearing of the present results upon theoretical explanations of the given source traits, including extraversion, and it is pointed out that the psychological meaning of most, for personality research, is as important, in variance terms, as for the one or two, such as anxiety and extraversion, which have tended to monopolize discussion.


GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections.
Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain; however, the roles of GABA in antimicrobial host defenses are largely unknown. Here we demonstrate that GABAergic activation enhances antimicrobial responses against intracellular bacterial infection. Intracellular bacterial infection decreases GABA levels in vitro in macrophages and in vivo in sera. Treatment of macrophages with GABA or GABAergic drugs promotes autophagy activation, enhances phagosomal maturation and antimicrobial responses against mycobacterial infection. In macrophages, the GABAergic defense is mediated via macrophage type A GABA receptor (GABAAR), intracellular calcium release, and the GABA type A receptor-associated protein-like 1 (GABARAPL1; an Atg8 homolog). Finally, GABAergic inhibition increases bacterial loads in mice and zebrafish in vivo, suggesting that the GABAergic defense plays an essential function in metazoan host defenses. Our study identified a previously unappreciated role for GABAergic signaling in linking antibacterial autophagy to enhance host innate defense against intracellular bacterial infection.


A two-neuron system for adaptive goal-directed decision-making in Lymnaea.
During goal-directed decision-making, animals must integrate information from the external environment and their internal state to maximize resource localization while minimizing energy expenditure. How this complex problem is solved by the nervous system remains poorly understood. Here, using a combined behavioural and neurophysiological approach, we demonstrate that the mollusc Lymnaea performs a sophisticated form of decision-making during food-searching behaviour, using a core system consisting of just two neuron types. The first reports the presence of food and the second encodes motivational state acting as a gain controller for adaptive behaviour in the absence of food. Using an in vitro analogue of the decision-making process, we show that the system employs an energy management strategy, switching between a low- and high-use mode depending on the outcome of the decision. Our study reveals a parsimonious mechanism that drives a complex decision-making process via regulation of levels of tonic inhibition and phasic excitation.


LOCOMOTOR MODULES AND THE EVOLUTION OF AVIAN FLIGHT.
The evolution of avian flight can be interpreted by analyzing the sequence of modifications of the primitive tetrapod locomotor system through time. Herein, we introduce the term "locomotor module" to identify anatomical subregions of the musculoskeletal system that are highly integrated and act as functional units during locomotion. The first tetrapods, which employed lateral undulations of the entire body and appendages, had one large locomotor module. Basal dinosaurs and theropods were bipedal and possessed a smaller locomotor module consisting of the hind limb and tail. Bird flight evolved as the superimposition of a second (aerial) locomotor capability onto the ancestral (terrestrial) theropod body plan. Although the origin of the wing module was the primary innovation, alterations in the terrestrial system were also significant. We propose that the primitive theropod locomotor module was functionally and anatomically subdivided into separate pelvic and caudal locomotor modules. This decoupling freed the tail to attain a new and intimate affiliation with the forelimb during flight, a configuration unique to birds. Thus, the evolution of flight can be viewed as the origin and novel association of locomotor modules. Differential elaboration of these modules in various lineages has produced the diverse locomotor abilities of modern birds.


Towards professional autonomy: a commentary on "Expectations and disappointments' in development of the Royal College of Nursing.
The Royal College of Nursing of the United Kingdom has been engaged over recent years in a unique process of organizational change. Since 1973 sustained efforts have been made to mobilise widespread membership participation in shaping a new college structure which enables the Rcn to function effectively in representing the profession and in developing expertise on all aspects of nursing. A critical element has been creation of a network of "Rcn Centres' to provide a professional forum in each locality. A recent study by Bridget Ramsay has followed up this process. Its title, Expectations and Disappointments, reflects the mixed views of those involved on the progress which has been made. This article provides a commentary on Ramsay's analysis against the background of the complex situation of the Rcn in the early 1970s and the considerations which led the College to adopt an innovative approach to change. Particular attention is given to the influences which have made the growth of an active and integrated "Rcn at local level' quite problematic. It is suggested that the course Rcn development has taken in part reflects important elements in the nursing culture which members learn from their work in hospitals. Accordingly the Rcn experience has wider implications for the profession, not least for contemporary efforts, to achieve the greater professional autonomy necessary for nurses to implement more individualized patient care.


The antigen-induced selective recruitment of specific T lymphocytes to the lung.
The purpose of the present studies was to investigate the mechanisms by which specific T lymphocytes accumulate in the lung. After the intratracheal (IT) inoculation of influenza virus into guinea pigs, the detection of specific T lymphocytes in the lung coincided with the development of immunity in both hilar nodes and systemic lymphoid tissue. Animals immunized in the footpads with virus failed to develop immune responses in the lung unless rechallenged IT with immunogen. In adoptive transfer experiments, IT inoculation of influenza into nonimmune guinea pigs, followed immediately by the i.v. injection of a mixture of 3H-thymidine-labeled syngeneic T lymphocytes specific for influenza virus and 14C-thymidine-labeled syngeneic T lymphocytes specific for an irrelevant antigen resulted in the selective accumulation of the virus-specific T lymphocytes in the lung. Taken together, these studies indicate that the selective recruitment by antigen of circulating immune cells is one of the mechanisms by which specific T cells accumulate in the lung.


[Abdominal tuberculosis].
Abdominal tuberculosis develops according to a non-specific clinical picture, with a difficult differential diagnosis with respect to other entities of similar semiology. We present the case of a male who was admitted because of abdominal pain, progressive and notable loss of body weight and a fever of two months evolution. The culture from the colon biopsy showed the presence of Koch bacilli.


Prevalence of hand eczema in an adult Swedish population and the relationship to risk occupation and smoking.
Using a postal questionnaire the prevalence of hand eczema was determined in a general population of 11,798 individuals aged 20-77 years who were randomly drawn from the population records. The response rate was 78.1%. One-year prevalence of hand eczema among women varied between 1.9% and 10.8%, with the highest figure among those aged 30-39 years. The corresponding figures for men were 2.3% and 5.6%, with the highest figure among those aged 20-29 years. Lifetime prevalence varied between 5.7% and 16.7% among women and between 5.2% and 9.5% among men. Using multiple logistic regression analysis female sex (OR=1.91, 95% CI 1.47-2.47) and smoking (OR=1.35, 95% CI 1.04-1.75) were independent risk factors for reporting 1-year prevalence of hand eczema, whereas age (OR=0.99, 95% CI 0.97-0.99) was inversely related to the 1-year prevalence of hand eczema. Aggregated risk occupation or categorized occupation such as medical and nursing work, production or service were not significantly associated with 1-year prevalence of hand eczema.


Origin of non-Gaussian statistics in hydrodynamic turbulence.
Turbulent flows are notoriously difficult to describe and understand based on first principles. One reason is that turbulence contains highly intermittent bursts of vorticity and strain rate with highly non-Gaussian statistics. Quantitatively, intermittency is manifested in highly elongated tails in the probability density functions of the velocity increments between pairs of points. A long-standing open issue has been to predict the origins of intermittency and non-Gaussian statistics from the Navier-Stokes equations. Here we derive, from the Navier-Stokes equations, a simple nonlinear dynamical system for the Lagrangian evolution of longitudinal and transverse velocity increments. From this system we are able to show that the ubiquitous non-Gaussian tails in turbulence have their origin in the inherent self-amplification of longitudinal velocity increments, and cross amplification of the transverse velocity increments.


"Brevity is the Soul of Wit": Use of a Stepwise Project to Teach Concise Scientific Writing.
Skillful writing is essential for professionals in science and medicine. Consequently, many undergraduate institutions have adjusted their curriculum to include in-depth instruction and practice in writing for students majoring in the sciences. In neuroscience, students are often asked to write a laboratory report in the style of a primary scientific article or a term paper structured like a review article. Typically, students write section by section and build up to the final draft of a complete paper. In this way, students learn how to write a scientific paper. While learning to write such a paper is important, this is not the only type of written communication relevant to scientific careers. Here, I describe a stepwise writing project aimed to improve editing, succinctness, and the ability to synthesize the literature. Furthermore, I provide feedback from the students, and discuss the advantages and challenges of this project.


Simultaneous aortic valve replacement in left ventricular assist device recipients: single-center experience.
Aortic valve regurgitation or the presence of a mechanical aortic valve prosthesis is a relative contraindication for implantation of left ventricular assist devices (LVAD). However, concomitant aortic valve replacement by a biological prosthesis is one of the options in this situation. We analyzed our recent experience with left ventricular assist device implantation and concomitant aortic valve replacement. Between January 1, 2008 and January 15, 2012, 318 adult patients (>18 years old) were supported with a long-term implantable LVAD in our institution. In 19, simultaneous aortic valve replacement (6 redo and 13 primary procedures) was performed. Patients were divided into 2 groups according to INTERMACS (IM) level: Group 1 (n = 7) consisted of patients with IM level 1-2 and Group 2 (n = 12) of IM level 3-4 patients. As a control cohort we analyzed all LVAD recipients during the study period (n = 299, study group excluded). The control cohort was similarly divided into two groups according to the IM level: Group 3 (n = 162) consisted of patients with IM level 1-2 and Group 4 (n = 137) of those with IM level 3-5. Perioperative data and outcomes in all groups were retrospectively analyzed and compared (Group 1 compared to Group 3; and Group 2 to Group 4). In study Groups 1 and 2 all patients were male; in Groups 3 and 4, 80% and 88% respectively were male. Median age distribution in Groups was 55, 61, 54, and 57 years respectively. Patients from Group 2 were significantly older than those from Group 4 (p = 0.039). Body mass index was significantly lower in Group 1 than in Group 3 (p = 0.033). Cardio-pulmonary bypass time was significantly longer in Groups 1 and 2 compared with Groups 3 and 4 respectively (p=0.001). Patients from Group 1 had a trend more often to develop right ventricular failure requiring a right ventricular assist device (RVAD) than those in Group 3 (p = 0.09). Intensive care unit stay duration of mechanical ventilation and in-hospital mortality in Group 1 were significantly higher than in Group 3 (p = 0.025, p = 0.005, p = 0.038). Patients from Group 2 had similar outcomes compared to those from Group 4. In stable patients, simultaneous aortic valve replacement and LVAD implantation are not associated with an impaired outcome. In patients with cardiogenic shock an additional aortic valve replacement may impair outcome; therefore alternative techniques should be considered.


Change of treatment guidelines and evolution of ART initiation in rural South Africa: data of a large HIV care and treatment programme.
While WHO recommendations are to treat people earlier and earlier, it will considerably increase the number of HIV infected people eligible for antiretroviral therapy (ART). In South Africa, a country which carries one of the highest HIV burden worldwide, very few studies are available on the impact of the ART guidelines on time to ART initiation in both individuals with low CD4 count and those newly eligible for ART. We thus aimed to describe ART initiation percentages in a large HIV programme in rural KwaZulu-Natal, South Africa, according to the temporal changes of national ART eligibility guidelines from 2007 to 2012. Adults who accessed the decentralized Hlabisa HIV treatment programme in 2007-2012 were included. Three periods following the temporal change of ART eligibility guidelines were defined (Period 1: until April 2010; Period 2: April 2010 - July 2011; Period 3: from August 2011). Percentages of ART initiation within three months of programme entry were estimated in men, in women of childbearing age (<40 years old) and in older women, and stratifying by CD4 count. Trend tests and logistic regression models were used to study the effects of change of guidelines on ART initiation percentages. In individuals with CD4 count ≤200 cells/μL (N = 5709 men, N = 6743 women <40 years old and N = 2017 older women), percentages of ART initiation did not differ over time (p trend = 0.25; 0.28; and 0.14, respectively). In individuals with CD4 count = 201-350 cells/μL (N = 2680 men, N = 6086 women <40 years old and N = 1415 older women), percentages of ART initiation significantly increased over time (p trend <0.01 for the three groups): from 6 % in Period 1 to 20 % in Period 2 to 40 % in Period 3 in women of childbearing age, and from 7 % to 8-10 % to 42 % in men and in older women. As temporal changes of guidelines, percentages of ART initiation significantly increased in newly ART eligible people and did not decrease in individuals with very low CD4 counts. It will be crucial to continue verifying the evolution of these percentages of ART initiation with future recommendations reaching near-to-universal access to ART, to ensure that individuals most in need of ART receive it.


Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration.
Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy.


Organisational development.
The aim of the NHS Improvement national leadership and improvement strategy is to encourage leaders at all levels to develop leadership skills in their staff and themselves. It focuses on fostering compassionate, collaborative and inclusive leadership.


In vitro and in vivo activities of recombinant anthrax protective antigen co-expressed with thioredoxin in Escherichia coli.
Because of the central role it plays in the formation of lethal toxin and edema toxin, protective antigen (PA) is the principal target for the development of vaccines against anthrax. In the present study, we explored and compared the in vitro and in vivo activities of recombinant anthrax protective antigen (rPA) and receptor binding domain of protective antigen (PA4). As a result, the fully soluble rPA and PA4 proteins were successfully expressed in Escherichia coli by co-expression with thioredoxin (Trx), and the rPA was active in forming cytotoxic lethal toxins, indicating that the rPA protein retains a functionally biological activity. Furthermore, immunization with rPA protein induced stronger PA-specific immune responses in mice than PA4 protein. The protection elicited by immunization with PA4 suggests the presence of common neutralizing epitopes between rPA and PA4, but the immunization with rPA protein induced stronger neutralizing antibodies and protective levels against challenge with the B. anthracis strain A16R than the PA4 protein. The sera neutralizing antibodies titers correlated well with anti-PA group ELISA antibodies titers and the in vivo protective potency. Based on the results of cell cytotoxicity assays and the observed immune responses and protective potency, we concluded that the soluble rPA protein retains the in vitro and in vivo functionally biological activity and can be developed into a highly effective human subunit vaccine candidate against anthrax.


Failure of a 21-aminosteroid antioxidant to ameliorate cisplatin-induced nephrotoxicity.
1 Lazaroid (U74500A), a 21-aminosteroid antioxidant, was administered to rats at a dose of 10 mg kg-1 in an attempt to reduce the toxicity of cisplatin (5 mg kg-1). 2 No protective effect was apparent under the schedule used and, in contrast to other antioxidants and free-radical scavengers, U74500A offers no potential benefit in cisplatin treatment.


Long -term results of transradial rotational atherectomy for heavily calcified coronary artery lesions.
Percutaneous coronary intervention (PCI) for the heavily calcified coronary lesions remains a challenge, and the periprocedural complication rates of the transfemoral approach are high. This study was conducted to investigate the feasibility and long-term results of the transradial approach for rotational atherectomy (RA) prior to stent implantation via the transradial approach in patients with heavily calcified coronary artery lesions. RA followed by stent implantation via the transradial approach was performed in 47 patients with severely calcified coronary artery lesions in this retrospectively case-control study. The success rate of the procedure and the 3-year follow-up (36±7.5 months) results were analyzed. RA with subsequent stent implantation or balloon angioplasty procedures were successfully performed in all cases. 6F guiding catheters were used in 45 cases, and 7F catheters were used in 2 patients. Rotablation was performed with a 1.25-mm burr in 29 cases, a 1.25-mm burr followed by a 1.5-mm burr in 17 patients, and a 1.75-mm burr in 1 patient. Percutaneous transluminal coronary angioplasty after RA was performed, followed by stent implantation in all 47 patients. Restenosis was found in 7 cases (7/38) at 13 months (13±3.6) and in 13 cases (13/28) at 36 months (36±7.5) after the procedure; 3 patients died during the 3-year follow-up. The post-procedure cumulative 3-year event-free survival rate was 78%. RA prior to stent implantation via the transradial approach is feasible and safe, the success rate is high, and long-term outcome is satisfactory in patients with heavily calcified lesions of the coronary artery.


Spin in the abstracts of randomized controlled trials in periodontology and oral implantology: A cross-sectional analysis.
To investigate the presence and characteristics of spin (a distorted interpretation to make research findings seem favorable) in abstracts of randomized controlled trials (RCTs) in periodontology and oral implantology, and to explore its associated factors and influence on the subsequent literature. PubMed was searched to identify recent RCTs in periodontology and oral implantology, whose primary outcome was non-significant. Spin in abstracts was assessed and categorized according to pre-determined spin strategies. The associations between study characteristics and the presence / severity of spin were analyzed using multivariable logistic regressions. 196 abstracts were included, 137 (69.9%) of which had spin. 57 (29.1%) abstracts had spin in the Results Section, 126 (64.3%) had spin in the Conclusion Section. The main spin strategies in the Results and Conclusion Sections were focusing on secondary outcomes (16.3%) and focusing on within-group comparisons (28.6%), respectively. The presence of spin was associated with number of centers (OR=0.28, 95% CI: 0.11-0.73; p=0.009) while its severity was associated with topic (OR=0.24, 95% CI: 0.08-0.70; p=0.009). The frequency of spin is relatively high among published RCT abstracts in periodontology and oral implantology. Findings reported in these abstracts need to be interpreted with caution.


Significance of early biopsy in pediatric kidney transplantation.
Long-term renal allograft survival is limited mainly by the progressive process termed chronic allograft nephropathy (CAN) or chronic rejection. A pathological feature of CAN is characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)-beta(1) plays an important role in fibrogenesis. We investigated whether the degree of TGF-beta(1) expression in early biopsy specimens routinely obtained from stable allografts at 100 days could predict fibrosis and graft dysfunction in the late phase by immunohistochemistry. Patients were children with a graft from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF-beta(1) in the graft at 100 days using LC antibody (LC) for intracellular TGF-beta(1) and CC antibody (CC) for extracellular TGF-beta(1). We used the change in creatinine clearance between 100 days and 3 years after transplantation (Delta Ccr) as an index of long-term graft function. Image analysis was used to calculate the relative area involved by interstitial fibrosis in trichrome-stained sections of graft biopsy specimens at 100 days and 3 years, designating the change as Delta FI. Delta Ccr was - 4.2 +/- 9.4 mL/min in subjects with minimal early immunoreactivity for CC and - 20.5 +/- 5.9 mL/min in subjects with strong reactivity (p < 0.05). Delta Ccr was - 14.5 +/- 18.6 mL/min in subjects with minimal early immunoreactivity for LC and - 11.7 +/- 12.8 mL/min in those with strong reactivity. Delta FI in subjects with minimal CC reactivity (1.28 +/- 4.11 %) tended to be lower than in subjects with strong reactivity (8.45 +/- 15.47 %). Neither fibrosis at 100 days nor Delta FI differed between subjects with minimal and strong LC reactivity. Thus, extracellular TGF-beta(1) expression in grafts at 100 days after transplantation has an influence on long-term graft function and tends to be associated with increased graft fibrosis at 3 years.


Developmental plasticity of central serotonin neurons after 5,7-dihydroxytryptamine treatment.
Systemic administration of 5,7-HT to newborn rats produces an altered development of the 5-HT neurons in the central nervous system, with marked regional differences. 5,7-Hydroxytryptamine can enter the brain and elicit its neurotoxic actions after systemic administration in the neonatal stage due to an incompletely developed blood-brain barrier, which for 5,7-HT is elaborated between postnatal Days 5 and 7. Treatment with 5,7-HT at birth produces marked and permanent 5-HT denervation in the cerebral cortex and spinal cord, whereas hyperinnervation occurs in the 5-HT cell body-near regions (mesencephalon-pons-medulla). The latter effect is seen within the first week postnatally. Treatment with 5,7-HT also affects NA neurons in a similar manner, although the action is exerted preferentially on 5-HT neurons. A selective effect on 5-HT neurons can be achieved by DMI pretreatment, after which both NA and DA neurons develop normally. No signs of any interaction among growing 5-HT, NA, and DA neurons can be observed. Studies of the postsynaptic 5-HT receptor in vitro with [3H]-5-HT and [3H]LSD binding indicate that this receptor develops independently of presynaptic 5-HT nerve terminals. Neither 5-HT denervation nor 5-HT hyperinnervation was accompanied by any change in receptor-binding characteristics or receptor density. The results available are compatible with the view that the consequences for 5-HT neurons that occur after neonatal 5,7-HT administration are mainly due to a "pruning effect." The developing 5-HT neurons seem to be programmed to produce a certain quantity of nerve terminal arborizations, which they try to conserve after 5-HT-induced injury, leading to the observed rearrangement of 5-HT nerve terminals.


Use of hippocampal slices to study mRNA changes in relation to synaptic plasticity.
We have developed a method allowing suitable morphological conservation combined with in situ hybridization, on hippocampal slices used in conventional electrophysiological studies. After a bath application of kainate (KA, 750 nM, 2 min 15 s), electrical stimulation of the mossy fibre zone evoked epileptiform activity for up to 2 h. In situ hybridization performed on these slices showed a marked increased in expression of the transcription factor Zif/268 over the pyramidal and the granule cells and the surrounding neuropils. Bath application of tetraethylammonium (TEA, 25 mM, 10 min) elicited long-term potentiation in CA1 lasting up to 4 h. This was associated with enhanced expression of Zif/268 which returned to control values after 2 h 30 min. These observations suggest that slice preparations are suitable for the study of the role of neuronal activity in the regulation of gene expression.


Insulin resistance and fat patterning with aging: relationship to metabolic risk factors for cardiovascular disease.
Both insulin resistance and abdominal fat patterning are related to aging, and have been related to cardiovascular disease (CVD) risk factors such as dyslipidemia and hypertension. However, previous studies have not used direct methods to quantify the independent strength of the association of each of these two putative primary factors with metabolic outcomes. We quantified overall obesity by the body mass index (BMI) and used a previously validated magnetic resonance imaging (MRI) method to quantify abdominal fat in 63 healthy nondiabetic individuals aged 22 to 83 years. We also measured the glucose and insulin response to an oral glucose tolerance test and the insulin sensitivity ([SI] by modified minimal model analysis). Body fat patterning was evaluated by the waist to hip ratio (WHR) and by MRI, which allowed direct measurement of subcutaneous (SCF) and intraabdominal (IAF) fat depots at the umbilicus in these subjects. These independent parameters were related to risk factors for CVD (blood pressure, lipids, and lipoproteins) and to plasma concentrations of free fatty acids (FFAs). Measures of overall obesity (BMI), total fat [TF], and/or SCF measured at the abdomen by MRI), glucose/insulin metabolism and SI, and central fat patterning (WHR or IAF measured by MRI) were correlated with mean arterial pressure (MAP), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels in univariate analysis and after controlling for age and gender. An index of central fat patterning (WHR) added to the informativeness of the insulin area under the curve (IAUC) in explaining 24% of the variability in plasma TG concentration, but measures of overall obesity were not independently related. Both the BMI and TF contributed to the IAUC in explaining 32% to 34% of the variability in MAP, but central fat patterning was not independently related. No index of overall obesity, fat patterning, glucose/insulin metabolism, and/or SI, was independently related to the plasma concentration of HDL-C after controlling for any one of the other two. Direct measurement of glucose/insulin metabolism and SI, as well as fat patterning, provides information on their relative associations with CVD risk factors. The measures of glucose/insulin metabolism and SI were more consistently related to dyslipidemia and hypertension than were the overall obesity and fat patterning in this healthy population.


[Antimicrobial susceptibility of Salmonella enterica isolated during the pre-harvest period in swine in Colombia].
To determine the antimicrobial susceptibility of isolates of Salmonella enterica isolated from animals and during the pre-slaughter period. Antimicrobial susceptibility tests were performed using the agar diffusion method on 333 isolates of Salmonella enterica obtained from the pre-harvest period represented by transport trucks and pens. From the animals, isolates were obtained from the animals' feces in transport trucks and pens, mesenteric lymph nodes, and cecal content. The specimens were obtained from four slaughtering facilities. The antimicrobial susceptibility tests were performed obtaining the following results: 99.6 % (n=332) of isolates showed resistance to at least one antimicrobial agent. The following resistance percentages were found: amoxicillin-clavulanic acid 15.9 % (n=53), ampicillin 33.9 % (n=113), ceftiofur 41.4 % (n=138), ciprofloxacin 9 % (n=30 ), chloramphenicol 19.2 % (n=64), florfenicol 33 % (n=110), gentamicin 22.8 % (n=76), sulfamethoxazole-trimethoprim 24.9 % (n=83), tetracycline 93.1 % (n=310) and tilmicosin 73.8 % (n=246). The results show that it is essential to reinforce containment measures to prevent the development of antimicrobial resistances and improve training of the operators, workers, and veterinarians in Colombia involved in the primary production, product processing, distribution, and sale to the consumer, thereby guaranteeing a safe food product and the effectiveness of antimicrobial agents in human and veterinary medicine.


Continuous dynamics in behavior reveal interactions between perceptual warping in categorization and speech-in-noise perception.
Spoken language comprehension requires listeners map continuous features of the speech signal to discrete category labels. Categories are however malleable to surrounding context and stimulus precedence; listeners' percept can dynamically shift depending on the sequencing of adjacent stimuli resulting in a warping of the heard phonetic category. Here, we investigated whether such perceptual warping-which amplify categorical hearing-might alter speech processing in noise-degraded listening scenarios. We measured continuous dynamics in perception and category judgments of an acoustic-phonetic vowel gradient via mouse tracking. Tokens were presented in serial vs. random orders to induce more/less perceptual warping while listeners categorized continua in clean and noise conditions. Listeners' responses were faster and their mouse trajectories closer to the ultimate behavioral selection (marked visually on the screen) in serial vs. random order, suggesting increased perceptual attraction to category exemplars. Interestingly, order effects emerged earlier and persisted later in the trial time course when categorizing speech in noise. These data describe interactions between perceptual warping in categorization and speech-in-noise perception: warping strengthens the behavioral attraction to relevant speech categories, making listeners more decisive (though not necessarily more accurate) in their decisions of both clean and noise-degraded speech.


Nanobody-photosensitizer conjugates for targeted photodynamic therapy.
Photodynamic therapy (PDT) induces cell death through light activation of a photosensitizer (PS). Targeted delivery of PS via monoclonal antibodies has improved tumor selectivity. However, these conjugates have long half-lives, leading to relatively long photosensitivity in patients. In an attempt to target PS specifically to tumors and to accelerate PS clearance, we have developed new conjugates consisting of nanobodies (NB) targeting the epidermal growth factor receptor (EGFR) and a traceable PS (IRDye700DX). These fluorescent conjugates allow the distinction of cell lines with different expression levels of EGFR. Results show that these conjugates specifically induce cell death of EGFR overexpressing cells in low nanomolar concentrations, while PS alone or the NB-PS conjugates in the absence of light induce no toxicity. Delivery of PS using internalizing biparatopic NB-PS conjugates results in even more pronounced phototoxicities. Altogether, EGFR-targeted NB-PS conjugates are specific and potent, enabling the combination of molecular imaging with cancer therapy. From the clinical editor: This study investigates the role of EGFR targeting nanobodies to deliver traceable photosensitizers to cancer molecules for therapeutic exploitation and concomitant imaging. Altogether, EGFR-targeted NB-PS conjugates combine molecular imaging with cancer therapy, the method is specific and potent, paving the way to clinical application of this technology.


Treatment of winged scapula by pectoralis major transfer.
We report the transfer of the sternal part of the pectoralis major to the lower pole of the scapula in 15 patients with winged scapula. At follow-up after 1 to 16 years nine had a satisfactory result and were gainfully employed, though in four of these re-operation had been necessary. Two patients had fair results; the transplant functioned, but they had limited voluntary control. Four were failures: two had had paralysis of other shoulder girdle muscles in addition to the serratus anterior. The indications for the operation are discussed.


Mechanisms of immune suppression in AIDS: possibilities of prevention.
AIDS is primarily a disease of the CD4-expressing helper-inducer T lymphocytes and is caused by human immunodeficiency virus (HIV), a retrovirus of the lentivirus subgroup. The interaction of HIV envelope glycoprotein (gp 110) with the CD4 molecule itself accounts for the virus selective tropism and for its pathogenicity, which result in the ultimate destruction of immunocompetent cells. Viral replication occurs preferentially in case of activation of the infected target cells, which explains why multiple infections, frequent in at-risk subjects, might play the role of cofactors and enhance HIV dissemination. There is yet no proof that an effective immune response might be mounted against this virus. Based on the pathophysiological model that can be drawn from HIV biological properties, many therapeutic schemes can be proposed to interfere with the complex pathway of interaction between host and virus. Nevertheless, the use of retroviral agents appears to be central to all these new strategies, since disease progression seems indeed directly related to the extent of viral replication.


Evaluation of the Abel inversion integral in O-mode plasma reflectometry using Chebyshev-Gauss quadrature.
The Abel transform is often used to reconstruct plasma density profiles from O-Mode polarized reflectometry diagnostics. However, standard numerical trapezoidal evaluation of the Abel inversion integral can be computationally expensive for a large number of evaluation points, and an endpoint singularity exists on the upper-bound of the integral, which can result in an increased error. In this work, Chebyshev-Gauss quadrature is introduced as a new method to evaluate the Abel inversion integral for the problem of O-Mode plasma reflectometry. The method does not require numerical evaluation of an integral singularity and is shown to have similar accuracy compared to existing methods while being computationally efficient.


Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies.
Bacterial metabolism plays a fundamental role in gut microbiota ecology and host-microbiome interactions. Yet the metabolic capabilities of most gut bacteria have remained unknown. Here we report growth characteristics of 96 phylogenetically diverse gut bacterial strains across 4 rich and 15 defined media. The vast majority of strains (76) grow in at least one defined medium, enabling accurate assessment of their biosynthetic capabilities. These do not necessarily match phylogenetic similarity, thus indicating a complex evolution of nutritional preferences. We identify mucin utilizers and species inhibited by amino acids and short-chain fatty acids. Our analysis also uncovers media for in vitro studies wherein growth capacity correlates well with in vivo abundance. Further value of the underlying resource is demonstrated by correcting pathway gaps in available genome-scale metabolic models of gut microorganisms. Together, the media resource and the extracted knowledge on growth abilities widen experimental and computational access to the gut microbiota.


Interplay of antibiotics and bacterial inoculum on suture-associated biofilms.
Biofilms are often antibiotic resistant, and it is unclear if prophylactic antibiotics can effectively prevent biofilm formation. Experiments were designed to test the ability of high (bactericidal) concentrations of ampicillin (AMP), vancomycin (VAN), and oxacillin (OXA) to prevent formation of suture-associated biofilms initiated with low (10(4)) and high (10(7)) numbers of Staphylococcus aureus. S. aureus biofilms were cultivated overnight on silk suture incubated in biofilm growth medium supplemented with bactericidal concentrations of AMP, VAN, or OXA. Standard microbiological methods were used to quantify total numbers of viable suture-associated S. aureus. Crystal violet staining followed by spectroscopy was used to quantify biofilm biomass, which includes bacterial cells plus matrix components. To observe the effects of antibiotics on the microscopic appearance of biofilm formation, biofilms were cultivated on glass slides, then stained with fluorescent dyes, and observed by confocal microscopy. In the presence of a relatively low inoculum (10(4)) of S. aureus cells, bactericidal concentrations of AMP, VAN, or OXA were effective in preventing development of suture-associated biofilms. However, similar concentrations of these antibiotics were typically ineffective in preventing biofilm development on sutures inoculated with 10(7)S. aureus, a concentration relevant to contaminated skin. Confocal microscopy confirmed that bactericidal concentrations of AMP, VAN, or OXA inhibited, but did not prevent, development of S. aureus biofilms. Bactericidal concentrations of AMP, VAN, or OXA inhibited formation of suture-associated biofilms initiated with low numbers (10(4)), but not high numbers (10(7)), of S. aureus cells.


[Laser and corneal surgery: patient selection].
The aim of refractive surgery is a good postoperative visual acuity and the satisfaction of the patient. To reach this, a good selection of the patient is important. Each patient has to be evaluated personally and individually at the hand of the next criteria: A complete preoperative examination The motivation and the expectations of each patient The possibilities and the complications of each operative technique. the contra-indications of the refractive surgery and each operative technique. In case of small and moderate myopia, the results of the radial keratotomy and the excimer-laser are similar and comparable with each other. In case of moderate and high myopia, the excimer-laser (PRK and LASIK) is the only valuable operative technique.


[Activation of bradykinin formation cascade on receiving autologous blood transfusion through a white cell-reduction filter in a patient treated with an ACE inhibitor].
We have experienced a case of anaphylactoid reaction on receiving autologous blood transfusion through a WBC filter for packed red blood cell (PRBC). The patient was a 71-year-old man with a history of hypertension treated with oral antihypertensive drug; enalapril, an angiotensin converting enzyme (ACE) inhibitor, who received anesthesia for Y-graft replacement. Autologous blood was obtained after the induction of general anesthesia in the operating room. Upon starting to return the stored blood with an unintentional use of a WBC filter, arterial blood pressure (ABP) fell within the first minute of the transfusion. We obtained three blood samples; pre-filtered blood (PRE), postfiltered blood (POST) and arterial blood (CIRC) after the event, and analyzed concentrations of bradykinin (BK), high molecular weight kininogen (HMWK) and high molecular weight kininogen-light chain (HMWK-LC). BK was higher in POST than in PRE. HMWK was lower in POST than in PRE, while HMWK-LC was higher in POST than in PRE. HMWK in CIRC was lower than in PRE, and HMWK-LC was higher in CIRC than in PRE. HMWK and HMWK-LC changes after the event suggest that BK formation cascade in the patient was activated on receiving the transfusion. ACE inhibitors were reported to augment such activation. The WBC filter has the negatively charged surface on filteration material and may activate the cascade. While WBC filters can avoid transfusion related reactions, hemodynamic responses should be watched closely in patients treated with ACE inhibitors.


Structural insights into regulation of CNNM-TRPM7 divalent cation uptake by the small GTPase ARL15.
Cystathionine-β-synthase (CBS)-pair domain divalent metal cation transport mediators (CNNMs) are an evolutionarily conserved family of magnesium transporters. They promote efflux of Mg2+ ions on their own and influx of divalent cations when expressed with the transient receptor potential ion channel subfamily M member 7 (TRPM7). Recently, ADP-ribosylation factor-like GTPase 15 (ARL15) has been identified as CNNM-binding partner and an inhibitor of divalent cation influx by TRPM7. Here, we characterize ARL15 as a GTP and CNNM-binding protein and demonstrate that ARL15 also inhibits CNNM2 Mg2+ efflux. The crystal structure of a complex between ARL15 and CNNM2 CBS-pair domain reveals the molecular basis for binding and allowed the identification of mutations that specifically block binding. A binding deficient ARL15 mutant, R95A, failed to inhibit CNNM and TRPM7 transport of Mg2+ and Zn2+ ions. Structural analysis and binding experiments with phosphatase of regenerating liver 2 (PRL2 or PTP4A2) showed that ARL15 and PRLs compete for binding CNNM to coordinate regulation of ion transport by CNNM and TRPM7.


Effect of neuromuscular blockade reversal by pyridostigmine on spectral entropy values during recovery from desflurane anesthesia: a prospective, randomized, double-blind, controlled trial.
According to several studies investigating the relationship between muscle activity and electroencephalogram results, reversal of neuromuscular blockade (NMB) may affect depth of anesthesia indices. Therefore, we investigated the effect of pyridostigmine on these indices via spectral entropy. Fifty-six patients scheduled for thyroidectomy or parotidectomy were included in this study and randomized into two groups. At the start of skin suturing, the desflurane concentration was adjusted to 4.2 vol% in both groups. Following this, the pyridostigmine group (group P, n = 28) was administered pyridostigmine 0.2 mg/kg mixed with glycopyrrolate 0.04 mg/kg, while the control group (group C, n = 28) received normal saline. Entropy values (response entropy [RE] and state entropy [SE]), train of four (TOF) ratio, and end-tidal desflurane concentration were recorded from point of drug administration to 15 minutes post-drug administration. Mean RE values at 15 minutes, when the maximum effect of pyridostigmine was anticipated, showed a statistically significant difference between groups (53.8 ± 10.5 in group P and 48.0 ± 8.8 in group C; P = 0.030). However, mean SE at 15 minutes showed no significant difference between the two groups (P = 0.066). At 15 minutes, there were significant differences in the TOF ratio between the two groups (P < 0.001). NMB reversal by pyridostigmine significantly increased RE values but not SE values. This finding suggests that spectral entropy may be a useful alternative tool for monitoring anesthetic depth during recovery from anesthesia in the presence of electromyogram activity.


Transfusion Camp Rwanda: A prospective feasibility study evaluating the delivery of Transfusion Camp to a multidisciplinary group of postgraduate medical trainees in Rwanda.
Safe blood transfusion is an increasing priority in global health equity. The Global Health 2030 commission lists access to a safe blood supply as essential for all surgical and nonoperative patients. The objective of this study was to determine if Transfusion Camp, when modified through a collaborative partnership between experts in Canada and Rwanda, results in improved knowledge and confidence among trainees in a resource-limited setting in sub-Saharan Africa. This prospective study took place at The University Teaching Hospital of Kigali in Rwanda. Participants were postgraduate medical trainees from departments where blood transfusion is frequent. Participants watched five prerecorded lectures and then attended a 5-hour team-based learning seminar to consolidate learning. Pre- and post-data were analyzed on transfusion knowledge and trainee confidence. A Rasch analysis investigated the performance of individual questions in assessing respondent knowledge. Of 31 trainees from surgery, anesthesia, internal medicine, and pediatrics invited to the course, 27 trainees attended the in-person team-based learning and 24 trainees completed the pre- and post-course analysis. Trainee knowledge assessment improved from (mean ± SD) 7.7/20 ± 1.95 to 10.4/20 ± 2.4 (p < .0001) and this knowledge was maintained by 12 trainees on a 3-month follow-up with a mean score of 9.3/20 ± 2.3. Trainees reported increased confidence in managing transfusion medicine-related patient issues. This pilot study demonstrated that Transfusion Camp education content modified to the local context can result in increased knowledge and confidence in managing transfusion-related issues. These results will inform future planning of Transfusion Camp in resource-limited settings.


The Influence of Heavier Football Helmet Faceguards on Head Impact Location and Severity.
To determine whether players with heavier faceguards have increased odds of sustaining top of the head impacts and head impacts of higher severity. Cohort study. On-field. Thirty-five division I collegiate football players. Faceguard mass was measured. Head impact location and severity (linear acceleration [gravity], rotational acceleration [radian per square second], and Head Impact Technology severity profile [unitless]) were captured for 19 379 total head impacts at practices using the Head Impact Telemetry System. Players' faceguards were categorized as either heavier (>480 g) or lighter (≤480 g) using a median split. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for sustaining top of the head impacts between faceguard groups using a random intercepts generalized logit model. We compared head impact severity between groups using random intercepts general linear models (α = 0.05). Player position was included in all models. Overall, the 4 head impact locations were equally distributed across faceguard groups (F(3,26) = 2.16, P = 0.117). Football players with heavier faceguards sustained a higher proportion impacts to the top of the head (24.7% vs 17.5%) and had slightly increased odds of sustaining top (OR, 1.72; 95% CI, 1.01-2.94) head impacts rather than front of the head impacts. Football players wearing heavier faceguards might be slightly more prone to sustaining a higher proportion of top of the head impacts, suggesting that greater faceguard mass may make players more likely to lower their head before collision. Individuals involved with equipment selection should consider the potential influence of faceguard design on head impact biomechanics when recommending the use of a heavier faceguard.


Selective depletion of fibroblasts preserves morphology and the functional integrity of peritoneum in transgenic mice with peritoneal fibrosing syndrome.
A peritoneal fibrosing syndrome (PFS) can progressively reduce peritoneal ultrafiltration during chronic peritoneal dialysis in patients with renal failure. The pathogenesis of PFS is unclear and the role of peritoneal fibroblasts has not been evaluated experimentally. We followed the fate of fibroblasts producing PFS in a mouse model using fibroblast-specific protein 1 (FSP1) as a marker. PFS was induced by daily peritoneal infusions of chlorhexidine gluconate (CHG) saline into transgenic mice expressing the thymidine kinase (Delta tk) gene under the control of the FSP1 promoter (FSP1.Delta tk mice). To demonstrate the role of fibroblasts in PFS, we treated these FSP1.Delta tk mice with a nucleoside analogue to induce DNA chain termination and fibroblast death. Mice receiving peritoneal infusions of CHG saline every other day for 2 weeks developed increasing numbers of FSP1+ fibroblasts in the subserosal layers of the visceral peritoneum. Mac-3+ monocytes (macrophages) subsequently accumulated over the next 2 weeks in association with increased deposition of type I collagen and increased endothelial vascularity (CD31+) in these subserosal tissues. Since these peritoneal fibroblasts expressed monocyte chemoattractant protein-1 (MCP-1), heat shock protein 47 (HSP47), and vascular endothelial growth factor (VEGF), we suspect they were partially responsible for macrophage recruitment, matrix production, and the neoangiogenesis in the subserosal tissue. Treatment of PFS in FSP1.Delta tk transgenic mice with a nucleoside analogue selectively reduced the numbers of peritoneal fibroblasts and attenuated the attendant changes in peritoneal histology. Rescuing the peritoneal membrane from chronic thickening and neoangiogenesis by reducing the number of fibroblasts also preserved ultrafiltration. Peritoneal fibroblasts play a pivotal role in PFS, and their deletion using a fibroblasts-specific transgene was effective in preventing peritoneal fibrogenesis.


Backreflection diagnostics for ultra-intense laser plasma experiments based on frequency resolved optical gating.
We report on the development and implementation of a time resolved backscatter diagnostics for high power laser plasma experiments at the petawatt-class laser facility PHELIX. Pulses that are backscattered or reflected from overcritical plasmas are characterized spectrally and temporally resolved using a specially designed second harmonic generation frequency resolved optical gating system. The diagnostics meets the requirements made by typical experiments, i.e., a spectral bandwidth of more than 30nm with sub-nanometer resolution and a temporal window of 10ps with 50fs temporal resolution. The diagnostics is permanently installed at the PHELIX target area and can be used to study effects such as laser-hole boring or relativistic self-phase-modulation which are important features of laser-driven particle acceleration experiments.


Palliative occipito-cervical stabilization in patients with malignant tumors of the occipito-cervical junction and the upper cervical spine.
Occipital-cervical stability may be impaired in patients with primary malignant or metastatic tumors of the cranio-cervical junction and the upper cervical spine. The purpose of this study was to evaluate occipital-cervical fixation with pre-bent titanium-loops and sublaminar wiring in order to achieve a rigid and safe stabilisation of the occipito-cervical region in this group of patients. 20 patients with severe impairment of occipito-cervical stability due to primary malignant or metastatic cervical bone involvement were included in this study. For palliation of symptoms, resulting from destructive instability, a stabilization procedure using Ransford Loops with sublaminar cable fixation was used in these patients as a palliative therapeutic concept. Pain which was the major symptom in all patients treated, showed good and immediate response to the stabilization procedures. All 20 patients were either pain free or had good improvement with less intake of analgesic drugs. Signs of spinal cord compression like spasticity and quadraparesis were less likely to improve after surgery. However in 3 of 5 patients neurological function improved after surgery whereas in 2 patients no improvement was achieved. In all patients with impaired occipito-cervical stability due to primary malignant or metastatic tumors of the occipito-cervical junction and the upper cervical spine, immediate stabilization resulting in an improvement of pain was achieved. Occipito-cervical stabilization using contoured Ransford loops is a promising palliative therapeutic concept in this group of patients.


CD14 is a key mediator of both lysophosphatidic acid and lipopolysaccharide induction of foam cell formation.
Macrophage uptake of oxidized low-density lipoprotein (oxLDL) plays an important role in foam cell formation and the pathogenesis of atherosclerosis. We report here that lysophosphatidic acid (LPA) enhances lipopolysaccharide (LPS)-induced oxLDL uptake in macrophages. Our data revealed that both LPA and LPS highly induce the CD14 expression at messenger RNA and protein levels in macrophages. The role of CD14, one component of the LPS receptor cluster, in LPA-induced biological functions has been unknown. We took several steps to examine the role of CD14 in LPA signaling pathways. Knockdown of CD14 expression nearly completely blocked LPA/LPS-induced oxLDL uptake in macrophages, demonstrating for the first time that CD14 is a key mediator responsible for both LPA- and LPS-induced oxLDL uptake/foam cell formation. To determine the molecular mechanism mediating CD14 function, we demonstrated that both LPA and LPS significantly induce the expression of scavenger receptor class A type I (SR-AI), which has been implicated in lipid uptake process, and depletion of CD14 levels blocked LPA/LPS-induced SR-AI expression. We further showed that the SR-AI-specific antibody, which quenches SR-AI function, blocked LPA- and LPS-induced foam cell formation. Thus, SR-AI is the downstream mediator of CD14 in regulating LPA-, LPS-, and LPA/LPS-induced foam cell formation. Taken together, our results provide the first experimental evidence that CD14 is a novel connecting molecule linking both LPA and LPS pathways and is a key mediator responsible for LPA/LPS-induced foam cell formation. The LPA/LPS-CD14-SR-AI nexus might be the new convergent pathway, contributing to the worsening of atherosclerosis.


Antifungal Treatment for Pityriasis Versicolor.
Pityriasis versicolor (PV), also known as tinea versicolor, is caused by Malassezia species. This condition is one of the most common superficial fungal infections worldwide, particularly in tropical climates. PV is difficult to cure and the chances for relapse or recurrent infections are high due to the presence of Malassezia in the normal skin flora. This review focuses on the clinical evidence supporting the efficacy of antifungal treatment for PV. A systematic review of literature from the PubMed database was conducted up to 30 September 2014. The search criteria were "(pityriasis versicolor OR tinea versicolor) AND treatment", with full text available and English language required. Topical antifungal medications are the first-line treatment for PV, including zinc pyrithione, ketoconazole, and terbinafine. In cases of severe or recalcitrant PV, the oral antifungal medications itraconazole and fluconazole may be more appropriate, with pramiconazole a possible future option. Oral terbinafine is not effective in treating PV and oral ketoconazole should no longer be prescribed. Maintenance, or prophylactic, therapy may be useful in preventing recurrent infection; however, at this time, there is limited research evaluating the efficacy of prophylactic antifungal treatment.


Anemia in HIV Patients Attending Highly Active Antiretroviral Therapy Clinic at Hoima Regional Referral Hospital: Prevalence, Morphological Classification, and Associated Factors.
To determine the prevalence of anemia, the morphological classification and to assess the factors associated with anemia among HIV patients attending Highly Active Antiretroviral Therapy (HAART) clinic at Hoima Regional Referral Hospital. This was a cross-sectional study among 340 participants attending the HAART clinic at Hoima Regional Referral Hospital. Participants were recruited using a simple random sampling technique. A complete blood count (CBC) was performed using the Sysmex XN-550 hematology analyzer. Thick films were made and examined for malaria parasites, while thin films were examined for the morphological classification of anemia. Bivariate and multivariate logistic analyses were conducted using SPSS (version 23). Out of the 340 study participants, 255 (75%) were females, and the median age was 39 years (range: 6-76 years). The overall prevalence of anemia among the study participants was 16.8% (95% CI 13.1-21.1). Normocytic normochromic anemia was the most prevalent form of anemia (47.4%). The logistic regression at multivariate analysis showed that age groups (18-27 years, p = 0.017; 28-37 years, p = 0.005; and ≥38 years, p = 0.009), divorced marital status (p = 0.024), the presence of chronic disease (p = 0.010), a family history of anemia (p = 0.007), and the presence of malaria in the past one month (p = 0.001), presence of opportunistic infection (OR = 58, p = 0.000), use of antihelminthic drug in the past 3 months (OR = 0.10, p = 0.003) and unsuppressed viral load (OR = 10.74, p = 0.000) had a significant association with anemia. Anemia is prevalent in HIV/AIDS patients who receive treatment at Hoima Regional Referral Hospital. Age, marital status, the presence of chronic illnesses, a family history of anemia, experiencing malaria in the past 3 months, the presence of opportunistic infections, the use of antihelminthic drugs in the past 3 months, and an unsuppressed viral load were significantly associated with anemia.


[Plasmid profile of mycobacteria spread on the territory of the Russian Federation].
The plasmid profile of different species of mycobacteria vegetating in the Russian Federation was first studied. All the drug-resistant mycobacterial strains of tuberculosis were found to be truly polyresistant. There was a certain association between the plasmid carriage and the high viability of the mycobacterial population in nontuberculous mycobacteria.


Atypical pituitary adenoma with MEN1 somatic mutation associated with abnormalities of DNA mismatch repair genes; MLH1 germline mutation and MSH6 somatic mutation.
The mechanism of pituitary tumorigenesis remains largely unknown. Lynch syndrome is an autosomal, dominantly inherited syndrome caused by a defective mismatch repair (MMR) mechanism involved in the development of various tumors at an early age. In this case study, we showed the occurrence of pituitary tumors associated with Lynch syndrome for the first time and performed genetic and immunohistochemical analysis to evaluate the genetic aberrations that might be related to the tumorigenesis and proliferation. A 68-year-old female patient with Lynch syndrome due to mutL homolog 1 (MLH1) gene mutation suffered from hypersecretion of adrenocorticotrophic hormone (ACTH), hypercortisolism and a rapidly progressive pituitary tumor. We performed genetic analysis by whole genome sequencing with genomic DNA of the pituitary tumor and peripheral blood leukocytes, as well as immunohistochemical analysis of MMR proteins. Genetic analysis revealed that the tumor had homozygous gene mutation of MEN1 associated with pituitary tumorigenesis and mutS homolog 6 (MSH6) gene. Furthermore, immunohistochemical analysis showed that MLH1 and MSH6 immunoexpression were negative. We reveal for the first time that MMR abnormality could cause somatic mutation of MEN1 and pituitary tumor occurrence is associated with Lynch syndrome. We suggest that the identified gene mutations, especially those of MSH6 and MLH1 genes, may be involved in the pathogenesis and proliferation of pituitary tumor. The knowledge obtained from our case study is important to elucidate the pathogenesis and proliferation mechanisms of pituitary tumors.


Ecofriendly microwave assisted synthesis of some new pyridine glycosides.
An efficient, mild and rapid procedure was employed to prepare a novel series of pyridine glycosides. The protocol allows the reaction of 2-pyridone with 1,2,3,4,6-penta-O-acetyl-α-D-glucopyranose under solvent-free microwave-assisted synthesis using different solid supports. Silica gel has been found to be an efficient and environmentally friendly promoter. Structures of the new products were confirmed based on their elemental analyses and spectral data (LC-MS/MS, IR, UV, 1D- and 2D-NMR).


Pain Assessment and Management in Neonatal Intensive Care Units in the Eastern Province of Saudi Arabia: A Survey of Doctors and Nurses.
Despite its importance, no study from the Middle East has assessed the neonatal pain knowledge of health-care providers in neonatal intensive care units (NICUs). To evaluate the knowledge and attitudes of pediatricians and nurses in Saudi Arabia toward procedural pain assessment and its management in neonates. This questionnaire-based, cross-sectional study was conducted between March and June 2015 at three NICUs in the Eastern Province of Saudi Arabia, namely, King Fahd Hospital of the University, Al Khobar; Security Forces Hospital, Dammam; and King Fahd Medical Military Complex, Dhahran. All pediatricians/neonatologists and nurses in these units were included, and a previously validated questionnaire was distributed and collected by an assigned clinician. The questionnaire elicited pain-related knowledge of seven procedures using a 10-point Likert scale. A total of 150 questionnaires were distributed, from which 107 complete responses were obtained (nurses: 81 [75.7%]; doctors: 26 [24.3%]). The overall knowledge scores were high (mean ± standard deviation = 77.3% ±11.6%). The mean pain rankings of doctors (7.2) were higher than those of nurses (6.5) for all procedures. Nurses reported more frequent use of analgesia than doctors (15.4% vs. 11.5%). Doctors often did not use comfort measures for any procedures, except during procedures on term to 28-day-old neonates. The use of pain tools was reported by only 12 (11%) clinicians. This study found that despite adequate knowledge about pain perception by neonates, the use of analgesia for procedural pain relief is low among doctors in the NICUs of the Eastern Province of Saudi Arabia. In addition, there is underutilization of pain assessment tools, thereby indicating the need to address this knowledge-practice gap.


Risk factors and molecular analysis of panton-valentine leukocidin-positive methicillin-resistant Staphylococcus aureus colonization in healthy children.
Nasal carriage of Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA) is associated with community associated disease. The risk factors for and characteristics of PVL-positive MRSA colonization in the healthy pediatric population are not well understood. Anterior nares cultures were obtained from healthy children < or =14 years of age presenting for health maintenance visits or attending 1 of 8 kindergartens during a 3-year period. A case-control study and molecular typing studies were performed. A total of 131 (8.1%) of 1615 children had nares cultures positive for MRSA, and 25 (1.5%) were colonized with PVL-positive MRSA. Nasal colonization of PVL-positive MRSA was significantly higher in 2006 than in 2004 (2.8% versus 0.7%; P = 0.006). By multivariate analysis, antibiotic use during the past 12 months (odds ratio, 29.37; 95% confidence interval, 10.72-80.50; P < 0.001) was the major risk factor associated with PVL-positive MRSA colonization in healthy children. Comparison of hospital MRSA strains with the community colonization strains by antimicrobial susceptibility testing, macrolide-lincosamide-streptogramin resistance gene testing, staphylococcal cassette chromosome mec typing, exotoxin profiling, and pulsed-field gel electrophoresis typing revealed that clonal spread of PVL-positive MRSA distinct from clinical hospital strains contributed to the high PVL-positive MRSA burden in the community. Nasal PVL-positive MRSA colonization in healthy children with no relationship to the hospital setting has increased significantly in the past 3 years, suggesting that it may be a major factor in the emergence of community-acquired MRSA disease in Taiwan. Previous antibiotic use was associated with PVL-positive MRSA colonization.


Experience of three years with intra-operative radiation therapy using the Lyon intra-operative device.
Since November 1985, we have performed 54 Intra-Operative Radiation Therapy (IORT) interventions, essentially in gastric cancer (20 patients) and in pancreatic cancer (22 patients). Mortality, morbidity, and average of survival rates were compared with a non-randomized control group: mortality and morbidity rates were similar in the two groups, with or without IORT. The follow-up period was too short for any valid conclusions about IORT in gastric cancer to be reached. However, in the case of unresectable pancreatic cancer, a significant difference was observed in survival rates when patients were treated by surgery alone or surgery and IORT (4.7 months), and when they were treated by surgery, IORT and external postoperative radiotherapy (8.9 months) (p less than 0.05). The study also examined the relief of abdominal and back pain in patients with unresectable pancreatic cancer: in our experience, survival was longer and more comfortable for patients treated with surgery and IORT. In conclusion, it appears that today IORT is without doubt a good palliative treatment for unresectable pancreatic cancer, but more experience is needed before a conclusion can be reached regarding resectable pancreatic cancer and gastric cancer.


Metal-Organic Framework Nanoparticle-Based Biomineralization: A New Strategy toward Cancer Treatment.
Cancer treatment using functional proteins, DNA/RNA, or complex bio-entities is important in both preclinical and clinical studies. With the help of nano-delivery systems, these biomacromolecules can enrich cancer tissues to match the clinical requirements. Biomineralization via a self-assembly process has been widely applied to provide biomacromolecules exoskeletal-like protection for immune shielding and preservation of bioactivity. Advanced metal-organic framework nanoparticles (MOFs) are excellent supporting matrices due to the low toxicity of polycarboxylic acids and metals, high encapsulation efficiency, and moderate synthetic conditions. In this review, we study MOFs-based biomineralization for cancer treatment and summarize the unique properties of MOF hybrids. We also evaluate the outlook of potential cancer treatment applications for MOFs-based biomineralization. This strategy likely opens new research orientations for cancer theranostics.