Development of compact inductive energy storage pulsed-power generator driven by 13 kV SiC-MOSFET.
A compact inductive energy storage (IES) pulsed-power generator that is driven by a novel 13 kV silicon carbide (SiC)-MOSFET is developed and molded into a compact modified TO-268. In this article, the switching characteristics required for IES pulsed-power generator development are evaluated. The maximum slew rates at MOSFET turn-on and turn-off are 157 and 129 kV/μs, respectively, at an input voltage of 10 kV. The maximum current flow from the drain to the source terminal is limited to 128 A during short-circuit switching. The on-resistance between the drain and source terminals increases during the SiC-MOSFET's on state. It increases with the voltage and its minimum value is 1.07 Ω. These characteristics show that the device is suitable for use as an opening switch because of its low on-resistance and rapid large-current cutoff at high operating voltages. The characteristics of an IES pulsed-power generator composed of a SiC-MOSFET, a capacitor, and a pulsed transformer with a turn ratio of 5:15 are also evaluated. The output voltage peak and full width at half maximum reach 31.4 kV and 55 ns, respectively, at a charging voltage of 1100 V. The maximum energy transfer efficiency is 50.2% of the input energy with a load resistance of 2.5 kΩ. The results show that the MOSFET has excellent potential to support the development of a compact plasma generation system that offers better performance pulsed-power generators driven by semiconductor devices.


Sensing Properties of a Novel Temperature Sensor Based on Field Assisted Thermal Emission.
The existing temperature sensors using carbon nanotubes (CNTs) are limited by low sensitivity, complicated processes, or dependence on microscopy to observe the experimental results. Here we report the fabrication and successful testing of an ionization temperature sensor featuring non-self-sustaining discharge. The sharp tips of nanotubes generate high electric fields at relatively low voltages, lowering the work function of electrons emitted by CNTs, and thereby enabling the safe operation of such sensors. Due to the temperature effect on the electron emission of CNTs, the collecting current exhibited an exponential increase with temperature rising from 20 °C to 100 °C. Additionally, a higher temperature coefficient of 0.04 K-1 was obtained at 24 V voltage applied on the extracting electrode, higher than the values of other reported CNT-based temperature sensors. The triple-electrode ionization temperature sensor is easy to fabricate and converts the temperature change directly into an electrical signal. It shows a high temperature coefficient and good application potential.


New approach to the kinetics of heterogeneous unary nucleation on liquid aerosols of a binary solution.
The formation of a droplet on a hygroscopic center may occur either in a barrierless way via Kohler activation or via nucleation by overcoming a free energy barrier. Unlike the former, the latter mechanism of this process has been studied very little and only in the framework of the classical nucleation theory based on the capillarity approximation whereby a nucleating droplet behaves like a bulk liquid. In this paper the authors apply another approach to the kinetics of heterogeneous nucleation on liquid binary aerosols, based on a first passage time analysis which avoids the concept of surface tension for tiny droplets involved in nucleation. Liquid aerosols of a binary solution containing a nonvolatile solute are considered. In addition to modeling aerosols formed through the deliquescence of solid soluble particles, the considered aerosols constitute a rough model of "processed" marine aerosols. The theoretical results are illustrated by numerical calculations for the condensation of water vapor on binary aqueous aerosols with nonvolatile nondissociating solute molecules using Lennard-Jones potentials for the molecular interactions.


NADH-methemoglobin reductase (cytochrome b5 reductase) levels in two groups of American blacks and whites.
Sickle cell trait, glucose-6-phosphate dehydrogenase (G6PD) deficiency and alpha-thalassemia trait are common genetic abnormalities among the American Black population. Under oxidative stress, the presence of any of these conditions would predispose the hemoglobin (Hb) to oxidation resulting in accelerated methemoglobin (metHb) formation. It was hypothesized that red cells phenotypic for these genetic variants should have more or different levels of metHb reductase (cytochrome b5 reductase) activity. To test this hypothesis, we measured the red cell metHb reductase activity in 558 male subjects (316 Blacks and 242 Whites), by the procedure described by Beutler. All Black patients also had G6PD spot test and Hb electrophoresis. In addition, all patients had a complete blood count (CBC). If the hematocrit was < 35% a reticulocyte count was also done. Patients with corrected reticulocyte (retic count X hematocrit/45) index over 2% were excluded regardless of other findings. The results showed that Blacks had different metHb reductase activity levels than Whites (mean = 3.19 vs 2.89 IU/gHb, respectively with p = 0.03). However, the differences in metHb reductase activities in patients with sickle cell trait, G6PD deficiency, and low MCV < 80 micron3 (presumptively having alpha-thalassemia) in small subgroups did not reach statistical significance (p = 0.2), although, all 3 groups were comprised of small numbers. It is concluded that American Blacks have significantly different metHb reductase activity. The different metHb reductase activity in Blacks seems to be unrelated to the presence of G6PD deficiency, sickle cell trait, or alpha-thalassemia and it may be the result of genetic polymorphism. However, our study samples do not exactly represent the cross-sections of the Black and White populations. In addition, all patients were male in this study. Therefore, this study should be confirmed using larger and more population-representative samples. The clinical significance of this problem is not clear at this time.


Trace metals in postdate pregnancy.
Maternal and cord serum calcium, copper, iron and zinc concentrations were analyzed in 20 women with a postdate pregnancy. The control group consisted of 20 parturients with delivery at term and their newborns. Serum free estriol (E3) was also determined. Maternal serum copper, zinc and E3 were statistically significantly lower, while cord serum copper and fetomaternal ratio of zinc were significantly higher in the study group than in the control group. Further, a positive correlation between E3 and maternal serum copper level (r = 0.63) was found.


Cryptosporidiosis and isosporiasis in patients with AIDS.
Cryptosporidium and Isospora belli are coccidian protozoan parasites that were long recognized as pathogens of animals. They were brought to the attention of the medical community by the advent of AIDS. These parasites are associated with persistent, devastating enteritis in patients with AIDS and self-limited diarrheal illness in the immunocompetent host. Cryptosporidiosis appears to be more common than isosporiasis in both patients with AIDS and those who are not immunosuppressed. Clinically, cryptosporidiosis is indistinguishable from isosporiasis. Watery, noninflammatory diarrhea, abdominal cramping pain, and weight loss are the characteristic symptoms. Diagnosis is made by identification of the acid-fast organisms in stained fecal specimens. There is no known effective therapy for cryptosporidiosis, whereas patients with isosporiasis respond promptly to treatment with trimethoprim-sulfamethoxazole. Patients with AIDS and isosporiasis have a high frequency of recurrent infection and therefore should be maintained on suppressive therapy. Much more needs to be learned about these two fascinating and unique parasites to be able to intervene successfully in the management of infected patients with AIDS.


[Prehospital cricothyrotomy: a case report].
Case report of a patient with tonsillitis treated with anti-inflammatory. The patient presented a dyspnoea and finally a cardiac arrest. The oral intubation was impossible and cricothyrotomy had to be performed with a catheter over needle technique. We found a total airway obstruction due to an epiglottis abscess. The patient died few days later of sepsis. We recommend having wire-guided cricothyrotomy technique or catheter-over-needle technique in all prehospital emergency unit and having emergency physician trained to the cricothyrotomy technique.


A modified mallory-cason staining procedure for large cryosections.
The classic Mallory-Cason staining procedure has been modified for application to sections "on tape" obtained from large deep frozen tissue specimens. These 20 microns cryosections are collected on tape from a large heavy duty cryomicrotome. The stained sections provide anatomical details that are not revealed by other techniques. The merit of this procedure is found in the support of modern medical modalities, both for research and educational purposes.


The effects of short-term glyphosate-based herbicide exposure on insect gene expression profiles.
Glyphosate-based herbicides (GBHs) are the most frequently used herbicides worldwide. The use of GBHs is intended to tackle weeds, but GBHs have been shown to affect the life-history traits and antioxidant defense system of invertebrates found in agroecosystems. Thus far, the effects of GBHs on detoxification pathways among invertebrates have not been sufficiently investigated. We performed two different experiments-1) the direct pure glyphosate and GBH treatment, and 2) the indirect GBH experiment via food-to examine the possible effects of environmentally relevant GBH levels on the survival of the Colorado potato beetle (Leptinotarsa decemlineata) and the expression profiles of their detoxification genes. As candidate genes, we selected four cytochrome P450 (CYP), three glutathione-S-transferase (GST), and two acetylcholinesterase (AChE) genes that are known to be related to metabolic or target-site resistances in insects. We showed that environmentally relevant levels of pure glyphosate and GBH increased the probability for higher mortality in the Colorado potato beetle larvae in the direct experiment, but not in the indirect experiment. The GBHs or glyphosate did not affect the expression profiles of the studied CYP, GST, or AChE genes; however, we found a large family-level variation in expression profiles in both the direct and indirect treatment experiments. These results suggest that the genes selected for this study may not be the ones expressed in response to glyphosate or GBHs. It is also possible that the relatively short exposure time did not affect gene expression profiles, or the response may have already occurred at a shorter exposure time. Our results show that glyphosate products may affect the survival of the herbivorous insect already at lower levels, depending on their sensitivity to pesticides.


Characterization of the microbial composition and quality of lightly salted grass carp (Ctenopharyngodon idellus) fillets with vacuum or modified atmosphere packaging.
The effect of air packaging (AP), vacuum packaging (VP) and modified atmosphere packaging (MAP, 75% CO2/25% N2) on the composition of the microbial community of lightly salted grass carp (Ctenopharyngodon idellus) fillets stored at 4 °C was studied. Physicochemical characteristics (total volatile basic nitrogen (TVB-N) value, pH value and biogenic amines (BA)) were also monitored. Based on sensory evaluation, the shelf life of fillets under AP, VP, and MAP was 8, 16 and 24 days, respectively. High-throughput sequencing showed that Acinetobacter and Pseudomonas dominated the microflora of fresh grass carp. At the sensory rejection time, Pseudomonas and Psychrobacter dominated the AP products. Lactococcus became the predominant genus of both VP and MAP fillets, and there was no obvious difference in the composition of the dominant microbiota between these two treatments at the end of the shelf life.


In vivo administration of ethanol enhances the function of the gamma-aminobutyric acid-dependent chloride channel in the rat cerebral cortex.
The effect of in vivo administration of ethanol on the gamma-aminobutyric acidA (GABAA) receptor-coupled chloride channel was studied by measuring ex vivo t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding in the rat cerebral cortex. Intragastric administration of ethanol (0.5-1 g/kg) elicited in 40 min a significant decrease of [35S]TBPS binding to unwashed cortical membrane preparations, an effect mimicked by diazepam (0.5-1 mg/kg, i.p.). However, Scatchard plot analysis indicated that, unlike the case with diazepam, the decrease was entirely due to a reduction in the apparent affinity of [35S]TBPS receptors with no change in the total number of binding sites. Moreover, ethanol, like diazepam, reduced the increase of [35S]TBPS binding elicited by isoniazid (350 mg/kg, s.c.), an inhibitor of the GABAergic transmission. Finally, ethanol markedly potentiated the inhibitory action of diazepam on [35S]TBPS binding. The results suggest that ethanol, like benzodiazepines, enhances the function of the GABAA-coupled chloride channel.


[Pharmacogenetics in oncology: 5-fluorouracil and the dihydropyrimidine dehydrogenase].
5-fluorouracil (5-FU) forms the basis for the chemotherapy of advanced colorectal cancer and of other solid tumours. About 9% of patients suffer from serious, sometimes even life-threatening adverse effects of a 5-FU therapy, such as haemotoxicity, which cannot be reliably predicted by conventional clinical and pharmacokinetic criteria. The systemic exposure to 5-FU is fundamentally determined by the genetically polymorphic enzyme dihydropyrimidine dehydrogenase (DPD). This deficiency is closely related to 5-FU-induced toxicity and a variety of non-synonymous variants has been detected in affected patients. The exon14-skipping mutation is the gene defect most frequently associated with serious 5-FU-related adverse effects and it has been reported ten times more often in affected individuals than in the general population. The 2846A>T polymorphism, which leads to an amino acid substitution, appears to be of comparable importance. While the causative role of premature stop codons - presumably resulting from spontaneous mutations - is very likely, the pathophysiological relevance of various other amino acid changes is still unclear. Patients who harbour a high-risk genotype should not be treated with 5-FU if therapeutic alternatives are available. The present data indicate that complete genotyping of the encoding DPYD gene is desirable, in the interest of drug safety, before treatment is started, although only a small number of patients would actually benefit. A method for the quantification of the DPD activity in vivo would have the advantage of reflecting all genetic and non-genetic influences.' However, no such method is currently available for routine use. Prospective genotyping for the exon 14-skipping and the 2846A>T-polymorphisms may result in a reduction of serious, 5-FU-induced, toxic events of about 25%. Cost-effective screening methods should enable the future implementation of DPYD genotyping in clinical routine.


Sensor-based detection of gait speed in older adults: an integrative review.
Gait speed is an indicator of functional change in older adults. One approach to support older adults' preferences to "age in place" is through the use of technology to monitor gait speed in everyday life. The authors of the current article conducted an integrative review of the scientific literature to summarize the current state of gait speed detection technologies. A total of 539 articles were returned from searches, and 16 were included in the review. Technologies were categorized as body-worn or home-installed sensors. Evidence was classified as emerging (n = 8) or promising (n = 8). Gait speed technology research has advanced beyond the use of customized research hardware prototypes, and consumer technologies are now commonly used in gait speed research. However, a need exists for software systems that integrate data for analysis and presentation to stakeholders with different information needs. Future research should focus on approaches to integrate disparate data sources and visualizations of gait speed data.


Use of the anterolateral thigh flap for reconstruction of the head and neck.
The anterolateral thigh free flap has achieved recent popularity in North America for the reconstruction of head and neck defects after ablative surgery. The flap is most often based on either the septocutaneous or musculocutaneous perforators of the descending branch of the lateral circumflex femoral artery. Its versatility allows for a subcutaneous, fasciocutaneous, myocutaneous, or adipofascial flap to be obtained. Recent publications have described the utility of the anterolateral thigh flap for reconstruction of head and neck defects. It has been used successfully in the reconstruction of the laryngopharynx, oral cavity, oropharynx, external skin, and maxilla. Furthermore, when a thinner flap is needed, a suprafascial anterolateral thigh flap may be raised or the flap may be thinned after it is obtained. The anterolateral thigh flap is a highly versatile and reliable flap for use in the reconstruction of various soft tissue defects of the head and neck. This flap has gained great popularity in mainland China, Taiwan, and Japan given its versatility, ability for a two-team approach, and minimal donor site morbidity. However, it has not met the same enthusiasm in Europe and North America because of the relative difficulty in perforator dissection, reported variations of the vascular anatomy, and the presumed increased thickness of the anterolateral thigh tissue in the Western population in comparison with the patient population of the Far East. These obstacles may be overcome by increased surgical experience and by the ability to create a thinner suprafascial flap or thinning the flap after it has been obtained.


How Can Biological and Chemical Silver Nanoparticles Positively Impact Physio-Chemical and Chloroplast Ultrastructural Characteristics of Vicia faba Seedlings?
Through interactions with plant cells, silver nanoparticles (AgNPs) with both biological and chemical origins can stimulate physiological and metabolic processes in plants. To ensure their safe application in the food chain, it is necessary to investigate their effects on plant systems. Therefore, the effects of chemical AgNPs (chem-AgNPs) and biologically synthesized AgNPs (bio-AgNPs) at different levels (i.e., 0, 10, and 50 ppm) on physiological and biochemical traits {i.e., root and shoot growth traits, photosynthetic pigments (Chl a, Chl b, carotenoids, and total pigments), soluble sugars, total carbohydrates, starch, H2O2, and antioxidant enzyme activities} of Vicia faba L. seedlings were investigated. AgNPs were biosynthesized from silver nitrate (AgNO3) by a green synthesis approach using Jatropha curcas seed extract. The synthesized AgNPs were characterized by UV-vis spectroscopy, transmission electron microscopy (TEM), zeta potential, Fourier-transform infrared spectra (FT-IR), and X-ray diffraction (XRD). The results showed that bio-AgNPs at 10 ppm resulted in the highest growth, physiological, and biological traits of faba bean seedlings in comparison with those obtained from both AgNO3 and chem-AgNPs treatments. On the other hand, all AgNPs treatments adversely affected the chloroplast ultrastructure, however, fewer negative effects were obtained with the application of 10 ppm bio-AgNPs. In addition, the roots and shoots of seedlings contained the lowest Ag content under different treatments at 10 ppm AgNPs in comparison to the highest level of AgNPs (50 ppm), which indicates that additional studies should be incorporated to ensure safe use of lower concentrations of bio-AgNPs in seed priming. In conclusion, the application of biogenic nanoparticles at 10 ppm can be recommended to enhance plant growth and the productivity of strategic crops.


Tumor markers of pancreatic carcinoma.
There is no well-defined specific tumor marker for carcinoma of the pancreas. Carcinoembryonic antigen (CEA) and alphafetal protein (AFP) are produced by some pancreatic cancer cells. A pancreatic oncofetal antigen (POA) cross-reacts with other malignant neoplasms and is not produced by all pancreatic carcinomas. An ammonium sulfate fraction (0-25%) from an aqueous extract of pancreatic carcinoma tissues contains an antigen cross-reacting with extracts of other pancreatic carcinomas and various carcinomas representing all three germinal layers. A heterologous antiserum to this antigen cross-reacts with sera from patients with pancreatic carcinomas in a dilution of 1:16,000. At lower dilutions this antiserum reacts with sera from patients with other carcinomas and with sera from some apparently healthy individuals.


Why does atrial fibrillation occur?
Atrial fibrillation is often associated with atrial enlargement and stretch is known to cause electrophysiological alterations. Acute stretch may, depending on the moment at which it is applied, cause action potential shortening or induce both early and delayed afterdepolarizations which, when large enough, may initiate triggered premature action potentials. The effects of acute stretch may be very different from those of chronic stretch. In fact, in dogs with mitral valve disease in which progressive atrial enlargement, leading to atrial fibrillation, developed over a period of years, hardly any changes in transmembrane potential characteristics were found. In contrast, marked fibrosis developed which could favour re-entry because of slow fragmented conduction. A number of electrophysiological changes have been found in isolated preparations from human atria that had been fibrillating. Action potentials had a shorter duration and a triangular configuration in contrast to action potentials from normal atria that mostly showed a distinct plateau. Refractory periods were also shorter and the normal rate adaptation of the refractory period disappeared, so that, following a slowing of the heart rate, the refractory period did not prolong. These changes largely seem to be the result of prolonged episodes of rapid atrial activity and may be called electrophysiological remodelling. In addition, a marked dispersion refractoriness has been found which might be due to different factors, such as fibrosis and local denervation. It is likely that atrial dilatation and fibrosis are important factors in the occurrence and maintenance of atrial fibrillation. In an enlarged atrium, multiple re-entrant circuits can co-exist. Fibrosis leads to inhomogeneities in both conduction and refractoriness. Finally, the arrhythmia itself causes persistent shortening of refractoriness. All of these changes favour re-entry.


MEASURING SELECTION ON A POPULATION OF DAMSELFLIES WITH A MANIPULATED PHENOTYPE.
The estimation of the relationship between phenotype and fitness in natural populations is constrained by the distribution of phenotypes available for selection to act on. Because selection is blind to the underlying genotype, a more variable phenotypic distribution created by using environmental effects can be used to enhance the power of a selection study. I measured selection on a population of adult damselflies (Enallagma boreale) whose phenotype had been modified by raising the larvae under various levels of food availability and density. Selection on body size (combination of skeletal and mass at emergence) and date of emergence was estimated in two consecutive episodes. The first episode was survival from emergence to sexual maturity and the second was reproductive success after attaining sexual maturity. Female survival to sexual maturity was lower, and therefore opportunity for selection greater, than males in both years. Opportunity for selection due to reproductive success was greater for males. The total opportunity for selection was greater for males one year and for females the other. Survival to sexual maturity was related to mass gain between emergence and sexual maturity. Females gained more mass and survived less well than males in both years but there was no linear relationship between size at emergence and survival for females in either year. However, females in the tails of the phenotype distribution were less likely to survive than those near the mean. In contrast, small males consistently gained more mass than large males and survived less well in one year. There was significant selection on timing of emergence in both years, but the direction of selection changed due to differences in weather; early emerging females were more successful one year and late emerging males and females the other. The number of clutches laid by females was independent of body size. Because the resources used to produce eggs are acquired after emergence and this was independent of size at emergence, female fitness did not increase with size. Small males may have had lower survival to sexual maturity but they had higher mating success than large males. Resources acquired prior to sexual maturity are essential for reproductive success and may in some species alter their success in inter- and intrasexual competition. Therefore, ignoring the mortality associated with resource acquisition will give an incomplete and potentially misleading picture of selection on the phenotype.


Induction of a dose-related increase in sulfobromophthalein uptake velocity in freshly isolated rat hepatocytes by phenobarbital.
To determine whether phenobarbital affects hepatocellular bilirubin/sulfobromophthalein uptake mechanism, we administered it to male Sprague-Dawley rats, body weight 175 +/- 25 gm, at doses of 1 to 75 mg/kg body wt/day for 7 days. Control rats were given an equivalent volume of physiological saline solution. On day 8, hepatocytes were isolated by means of collagenase perfusion, suspended in Hanks' solution without albumin and incubated with high specific activity (3 Ci/mmol) [35S]sulfobromophthalein, which was synthesized in our laboratory and purified by means of a new reverse-phase high-pressure liquid chromatography procedure. The initial uptake rate of sulfobromophthalein was determined at sulfobromophthalein concentrations of 1 to 50 mumol/L with a rapid filtration technique. The maximum uptake velocity and Michaelis constant for sulfobromophthalein uptake at each phenobarbital dose were determined by means of a computer analysis. In control studies, maximum uptake and Michaelis constant were 48.0 +/- 16.7 (mean +/- S.D.) pmol/50,000 cells/min and 22 +/- 4 mumol/L, respectively. Maximum uptake velocity increased linearly with the log of the phenobarbital dose (r = 0.98, p < 0.01), the increase achieving statistical significance at a dose of 3 mg/kg/day. Michaelis constant, however, was essentially unchanged at phenobarbital doses of 50 mg/kg/day or less. The maximal observed increase in maximum uptake velocity of sulfobromophthalein (to 619% of control values) was appreciably greater than the maximal increase in UDP-glucuronyltransferase activity (200% of control) or immunoreactive ligandin concentrations (260% of control) seen in earlier studies, suggesting a direct effect on the plasma membrane transport mechanism.


Retinoic acid prevents synaptic deficiencies induced by alcohol exposure during gastrulation in zebrafish embryos.
In this study, we examined the effects of alcohol exposure during gastrulation on zebrafish embryos, specifically focusing on excitatory synaptic activity associated with neurons (Mauthner cells) that are born during gastrulation. Furthermore, we determined whether co-treatment of alcohol and retinoic acid (RA) could prevent the effects of alcohol exposure during gastrulation. We exposed zebrafish embryos to ethanol (150mM), RA (1nM), or a combination of RA (1nM) plus ethanol (150mM) for 5.5h from 5.25h post fertilization (hpf) to 10.75 hpf (gastrulation). Ethanol treatment resulted in altered hatching rates, survivability and body lengths. Immunohistochemical analysis of Mauthner cells (M-cells) suggested that ethanol treatment resulted in smaller M-cell bodies and thinner axons, while electrophysiological recordings of AMPA miniature excitatory postsynaptic currents (mEPSCs) associated with M-cells showed that ethanol treated animals had a significantly reduced mEPSC frequency. Other mEPSC parameters such as amplitude, rise times and decay kinetics were not altered by exposure to alcohol. Locomotor studies showed that ethanol treatment resulted in altered C-bend escape responses. For instance, the C-bends of alcohol-treated fish were larger than control embryos. Thus, ethanol treatment during gastrulation altered a range of features in embryonic zebrafish. Importantly, co-treatment with RA prevented all of the effects of ethanol including survivability, body length, M-cell morphology, AMPA mEPSC frequency and escape response movements. Together these findings show that ethanol exposure during the brief period of gastrulation has a significant effect on neuronal morphology and activity, and that this can be prevented with RA co-treatment.


Effect of Tb3+ doping in mixed-valence manganites and cobaltites.
The magnetic ordering of four Tb3+-doped manganites and cobaltites, La0.7Tb0.1Sr0.2MnO3, La0.7Tb0.1Ca0.2MnO3, La0.7Tb0.1Sr0.2CoO3 and La0.7Tb0.1Ca0.2CoO3, have been studied by means of neutron diffraction and SQUID magnetometry. All the samples were prepared by sintering of sol-gel precursors and their orthorhombic or rhombohedral perovskite structures at room and low temperatures were refined. A long-range ferromagnetic (FM) order was detected at the Mn and Co sites. In addition, a small but significant ordered moment was observed at A sites of studied cobaltites, which was attributed to local Tb3+ moments, aligned by exchange interactions due to FM ordered Co sublattice. No or minor Tb3+ contribution was detected in studied manganites.


Brief, weekly magnetic muscle therapy improves mobility and lean body mass in older adults: a Southeast Asia community case study.
Brief (10 min) weekly exposure to low energy pulsed electromagnetic fields (PEMFs) has been shown to improve human muscle mitochondrial bioenergetics and attenuate systemic lipotoxicity following anterior cruciate ligament surgical reconstruction. Here we present data generated from 101 participants, 62% female, aged 38-91 years, recruited from the QuantumTx Demo Centre in Singapore, wherein 87% of participants (n = 88) presented with pre-existing mobility dysfunction and 13% (n = 13) were healthy volunteers. Participants were recruited if: (i) not pregnant; (ii) above 35 years of age and; (iii) without surgical implants. All participants completed mobility testing, pre- and post- PEMF intervention for 12 weeks, whereas bioelectrical impedance analysis was conducted in a subgroup of 42 and 33 participants at weeks 4 and 8, respectively. Weekly PEMF exposure was associated with significant improvements in mobility (Timed Up and Go, 5 times Sit-to-Stand, and 4m Normal Gait Speed) and body composition (increased skeletal muscle mass and reduced total and visceral fat mass), particularly in the older participants. Perception of pain was also significantly reduced. PEMF therapy may provide a manner to counteract age-associated mobility and metabolic disruptions and merits future investigation in randomized controlled trials to elucidate its clinical benefits in the frail and older adult populations.


Cardiovascular and renal function during exercise-induced blood volume expansion in men.
To test the hypothesis that reduced baroreflex sensitivity is a direct result of exercise, we measured forearm vascular conductance (FVC) responses to graded lower body negative pressure (LBNP) 2, 20, and 44 h after intense exercise. Eight 4-min bouts of exercise at 85% of maximum oxygen uptake produced 3.5 +/- 0.7 and 3.9 +/- 1.0% blood volume (BV) expansions at 20 and 44 h of recovery, respectively. BV was unchanged from control values 2 h after exercise. The reduction in FVC was significantly less than control values during 30 and 40 mmHg of LBNP at 2 and 20 h of recovery, respectively, whereas heart rate and cardiac stroke volume responses were unchanged. Thus, a reduced FVC response to LBNP preceded BV expansion, demonstrating that exercise itself can elicit an attenuation of baroreflex function. To test the hypothesis that volume sensitivity of renal function is attenuated by intense exercise, we measured cardiovascular variables, plasma hormone concentrations, and renal output. At 20 h of recovery, resting mean arterial blood pressure and cardiac output were increased by 6 +/- 1 mmHg and 0.6 +/- 0.2 l/min, respectively, but resting plasma aldosterone and overnight Na+ excretion rate were unchanged. At 44 h of recovery, plasma aldosterone was decreased by 26 +/- 9% and overnight Na+ excretion rate was increased by 51 +/- 26%. Thus, appropriate endocrine and renal responses to increased BV were delayed until 44 h of recovery. Our findings suggest that a postexercise attenuation of baroreflex function participates in the induction of BV expansion by intense exercise.


[Preventive measures for improvement of suitability of water from individual water supply objects in the areas ravaged by war].
The aim of this article was to test the success of sanation of unsatisfactory individual water supply objects in the areas ravages of war. 198 individual water supply objects were consolidated in the area of Voćin, with hyperchlorination and pumping out of water, after which desinfection with chlorine preparation was carried out. Samples of drinking water taken for bacteriological analysis were analyzed on total coliform bacteria, fecal coliform bacteria and fecal streptococci by method of membranous filtration, while the number of colonies of aerobic bacteria at 22 degrees C and 37 degrees C were determined on triptosis-glucosis-yeast agar. Good samples, considering the Regulations on health suitability of drinking water, were 152, or 77%. In unfit samples, which were 46, or 23%, the most common isolates were fecal streptococci, with frequency of 30%. Although public waterworks represent the best way to supply people with good drinking water, it is possible to achieve a satisfactory degree of water quality from individual water supply objects with implementation of public health activities, if we execute them periodically and professionally.


Pharmacokinetics-directed Intravenous Busulfan Combined With High-dose Melphalan and Bortezomib as a Conditioning Regimen for Patients With Multiple Myeloma.
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m2 (Mel200) is the most commonly used preparative regimen. Several studies have provided evidence for potential synergism and safety when combining bortezomib (Btz) or busulfan (Bu) with melphalan (Mel). We conducted a prospective phase II study to investigate the safety and efficacy of conditioning with pharmacokinetics (PK)-directed intravenous (IV) Bu with Btz and Mel. Bu dosing was adjusted to target a total area under the curve (AUC) of 20,000 μM × min. Patients received Btz (1 mg/m2 × 4 doses) and Mel (140 mg/m2). A total of 19 subjects were enrolled. Their median age was 55 years, and the median follow-up period was 23.7 months. PK testing resulted in 86% of patients achieving an estimated total AUC of 20,000 ± 2500 μM × min. The overall response rate (ORR) at day +100 after ASCT was 100% in the evaluable patients, with 11% of patients achieving a complete response. The 2-year progression-free survival rate was 57.9% (95% confidence interval [CI], 38%-89%), and the 2-year overall survival rate was 88.5% (95% CI, 76%-100%). The most common grade 3 and 4 toxicities were febrile neutropenia, dysphagia/odynophagia, and oral mucositis. No case of hepatic sinusoidal obstruction syndrome developed. One treatment-related mortality occurred before day +100. A preparative regimen of PK-directed IV Bu with Btz and Mel led to an ORR of 100% with acceptable toxicity and should be considered for direct comparison with the Mel200 regimen in future trials.


A new methodology to structure a nutrition educational course: the results of a short-term educational-intervention pilot study.
The incidence of malnutrition in developing countries, such as Kenya, is still high. The most recent international reports outline an increase in the prevalence of overnutrition in Sub-Saharan Africa, where undernutrition and hidden hunger conditions still represent an emergency. Among the factors influencing malnutrition conditions connected to dietary intake and eating habits, evidence shows the importance of food knowledge. Traditionally, in developing countries, women represent the pillar of the food system and impact their children's nutrition: food-based, women-centred strategies are recommended to address nutrient gaps, educate and empower women, and counteract malnutrition. The short communication presents the results of the ACTION project: an educational-intervention pilot study targeting childbearing-age women living in rural areas of Southern Kenya. To evaluate the feasibility of the educational course built, the authors administered to the women a food knowledge questionnaire, before and after the intervention. Study results describe an increase in women's food knowledge after attending the food education course. This encourages to increase education courses which can represent a starting point in improving food habits with a positive effect on the health condition in developing counties too.


Approach for tuberculosis-associated immune reconstitution inflammatory syndrome in an HIV-negative patient.
A male refugee from the Middle East was diagnosed with pulmonary tuberculosis and Pott's disease with paravertebral abscess. After starting the standard regimen, the sputum culture converted to negative and the patient's general condition improved. Six weeks later, the patient presented with clinical worsening of known symptoms, new appearance of focal neurological deficits and progress of radiological features showing progression of the paravertebral abscess. Immune reconstitution inflammatory syndrome with Mycobacterium tuberculosis (TB-IRIS) was presumed, and treatment with high-dose steroids was started. Due to recurrent relapses while tapering, corticosteroids had to be given over a prolonged period. After treatment completion, the patient was in a good general condition, abscesses had decreased and neurological deficits were in complete remission. This case presents the rare manifestation of TB-IRIS in HIV-negative patients and its management in a high-income country.


Auditory observation of infant-directed speech by mothers: experience-dependent interaction between language and emotion in the basal ganglia.
Adults address infants with a special speech register known as infant-directed speech (IDS), which conveys both linguistic and emotional information through its characteristic lexicon and exaggerated prosody (e.g., higher pitched, slower, and hyperarticulated). Although caregivers are known to regulate the usage of IDS (linguistic and emotional components) depending on their child's development, the underlying neural substrates of this flexible modification are largely unknown. Here, using an auditory observation method and functional magnetic resonance imaging (fMRI) of four different groups of females, we revealed the experience-dependent influence of the emotional component on linguistic processing in the right caudate nucleus when mothers process IDS: (1) non-mothers, who do not use IDS regularly, showed no significant difference between IDS and adult-directed speech (ADS); (2) mothers with preverbal infants, who primarily use the emotional component of IDS, showed the main effect of the emotional component of IDS; (3) mothers with toddlers at the two-word stage, who use both linguistic and emotional components of IDS, showed an interaction between the linguistic and emotional components of IDS; and (4) mothers with school-age children, who use ADS rather than IDS toward their children, showed a tendency toward the main effect of ADS. The task that was most comparable to the naturalistic categories of IDS (i.e., explicit-language and implicit-emotion processing) recruited the right caudate nucleus, but it was not recruited in the control, less naturalistic condition (explicit-emotion and implicit-language processing). Our results indicate that the right caudate nucleus processes experience-and task-dependent interactions between language and emotion in mothers' IDS.


Insulin dose-response characteristics among individual muscle and adipose tissues measured in the rat in vivo with 3[H]2-deoxyglucose.
The dose-response characteristics of three skeletal muscles, three adipose tissue beds, and heart muscle to single i.v. injection of insulin were compared in vivo. Comparisons were made at 8 dose levels spanning the entire range for response by all tissues and for the integrated whole body response as reflected in the rate of disappearance of 3H-2-deoxyglucose from plasma. The insulin-sensitive tissues varied widely with respect to the magnitude of the maximal response and the sensitivity to insulin as judged by the effective dose 50% (ED 50). Among the muscles, a slow-twitch oxidative muscle, soleus, was more sensitive than the fast-twitch glycolytic muscle, extensor digitorum longus (EDL), while a mixed muscle, quadriceps femoris, displayed even lower sensitivity. Heart muscle sensitivity was comparable to EDL. Among the adipose sites, the rank order of sensitivity was subcutaneous greater than epididymal much greater than omental. The threshold for a detectable response to insulin was 0.013 U/kg rat.


Synthetic retinoid Am80 suppresses smooth muscle phenotypic modulation and in-stent neointima formation by inhibiting KLF5.
Modulation of smooth muscle cell (SMC) phenotype plays a central role in neointima formation. We recently demonstrated that Am80, a synthetic retinoic acid receptor alpha-specific agonist, inhibits the activity of the transcription factor KLF5, which is essential for neointima formation after vascular injury. In the present study, we aimed to further analyze the mechanism by which Am80 inhibits KLF5 and the effects of inhibiting KLF5 on SMCs and vascular lesion formation, as well as to evaluate potential of Am80 for use in the prevention of in-stent neointima formation. We found that Am80 inhibited both the expression and transcriptional function of KLF5. Of particular interest was our finding that KLF5 forms a transcriptionally active complex with unliganded RAR/RXR heterodimer on the PDGF-A promoter; Am80 disrupts this complex, thereby inhibiting KLF5-dependent transcriptional activation. Knocking down KLF5 using small interfering RNA suppressed serum-induced downregulation of SMC differentiation marker gene expression in cultured SMCs, and haploinsufficiency of KLF5 in mice attenuated phenotypic modulation of SMCs after vascular injury, indicating that KLF5 plays a key role in the control of SMC phenotype. Am80 augmented expression of the SMC differentiation marker genes in culture and within the vessel walls, and oral administration of Am80 significantly inhibited in-stent neointima formation in a rabbit stent-placement model. Taken together, these results demonstrate that KLF5 plays an important role in the control of SMC phenotype after vascular injury and suggest the feasibility of using Am80, delivered systemically and/or with a drug eluting stent, to prevent in-stent neointima formation.


Wall passivation for unstable angina.
The disruption of an atherosclerotic plaque in a coronary artery, appears to be fundamental for the development of arterial thrombosis and resultant ischaemia. Platelets play a central role in the pathogenesis of unstable angina; they can aggregate and cause mechanical obstruction if large enough. In addition, they can lead to fibrin deposition and extension of the thrombus. The fundamental goal in the treatment of unstable angina is to control the acute disease process that leads to vascular occlusion. In addition to the currently available pharmacological agents used to treat unstable angina, newer agents such as the direct thrombin inhibitors and the glycoprotein IIb/IIIa receptor antagonists may be more effective in achieving 'passivation'. This article summarizes the role of the vessel wall and its interaction with platelets in arterial thrombosis. The different pharmacological approaches used in achieving passivation of platelets in unstable angina are described.


The Mayo Clinic author catalog: a living repository of medical knowledge.
Since 1907 records have been kept of publications by staff members of the Mayo Clinic, and this information has been invaluable. The Author Catalog has proved itself such a useful tool for the Mayo Clinic that other libraries, large and small, may wish to consider adopting such a service. The Mayo medical complex is a large institution with more than 500 staff and faculty members engaged in the publication of clinical, educational, and research findings. The great amount of cross-disciplinary cooperation and interdepartmental research makes essential an up-to-date record of what is going on. The Mayo Clinic Library developed a comprehensive computerized method for identifying research and for identifying and indexing publications of Mayo staff members. At the end of 1971 more than 25,000 citations had been stored on computer tape.


Effect of ciclosporin on allogeneic hepatocyte transplantation: a morphological study.
Hepatocyte transplantation (HT) is among the most frequently employed approaches in the treatment of liver disease. This work deals with the occurrence of rejection when allogeneic hepatocytes are transplanted into the spleens of rats. Two strains of rats were used: Lewis and F344. The recipients were divided into two groups, one of which received ciclosporin (Cic), while the other received no treatment. After HT, the spleens were removed periodically. The animals that did not receive Cic suffered such intense rejection that 7 days after HT no hepatocytes could be identified in the splenic pulp. On the other hand, hepatocytes could be observed throughout the entire study in the spleens of rats treated with Cic. We conclude that HT is followed by intense rejection, which can be avoided by the administration of Cic.


Predictive Malaria Risk and Uncertainty Mapping in Nchelenge District, Zambia: Evidence of Widespread, Persistent Risk and Implications for Targeted Interventions.
Malaria risk maps may be used to guide policy decisions on whether vector control interventions should be targeted and, if so, where. Active surveillance for malaria was conducted through household surveys in Nchelenge District, Zambia from April 2012 through December 2014. Households were enumerated based on satellite imagery and randomly selected for study enrollment. At each visit, participants were administered a questionnaire and a malaria rapid diagnostic test (RDT). Logistic regression models were used to construct spatial prediction risk maps and maps of risk uncertainty. A total of 461 households were visited, comprising 1,725 participants, of whom 48% were RDT positive. Several environmental features were associated with increased household malaria risk in a multivariable logistic regression model adjusting for seasonal variation. The model was validated using both internal and external evaluation measures to generate and assess root mean square error, as well as sensitivity and specificity for predicted risk. The final, validated model was used to predict and map malaria risk including a measure of risk uncertainty. Malaria risk in a high, perennial transmission setting is widespread but heterogeneous at a local scale, with seasonal variation. Targeting malaria control interventions may not be appropriate in this epidemiological setting.


Efficacy and safety of oral granisetron versus oral prochlorperazine in preventing nausea and emesis in patients receiving moderately emetogenic chemotherapy.
To compare the efficacy and safety of oral granisetron hydrochloride tablets with that of oral prochlorperazine sustained-release capsules in preventing nausea and emesis induced by moderately emetogenic chemotherapeutic agents. In this multicenter, double-blind, randomized, parallel group study, oral granisetron and oral prochlorperazine were compared in 230 chemotherapy-naive, adult cancer patients who received moderately emetogenic chemotherapy. Patients were stratified by gender and randomized to receive either 1.0 mg oral granisetron HCI twice a day for 7 days, or 10 mg oral prochlorperazine sustained-release capsules twice a day for 7 days. The first dose was given 1 hour before initiation of chemotherapy and the second dose 12 hours after the first dose. Patients were evaluated for emetic episodes, extent of nausea, and adverse events for 7 days after the start of chemotherapy. Primary efficacy parameters were complete response (no emetic episodes, no greater than mild nausea, no antiemetic rescue) and total control (no emetic episodes, no nausea, no antiemetic rescue) in the 24 hours after the start of chemotherapy. Granisetron was significantly more effective than prochlorperazine in achieving a complete response (74% vs. 41%, respectively) and total control of nausea and vomiting (58% vs. 33%, respectively) at the 24-hour assessment. Complete response at 24 hours was significantly higher in the granisetron-treated patients than in prochlorperazine-treated patients. In women, granisetron showed a complete response rate of 69% versus 38% with prochlorperazine; in men, granisetron showed a complete response rate of 92% versus 61% with prochlorperazine. Both regimens were well tolerated, with headache (36% for granisetron, 29% for prochlorperazine) and constipation (31% for granisetron, 6% for prochlorperazine) the most common adverse events. : Oral granisetron 1 mg twice a day was significantly more effective than oral prochlorperazine sustained release capsules 10 mg twice a day in complete response and total control of nausea and vomiting at 24 hours after chemotherapy. Both agents were well tolerated.


The Competitiveness of Beef Exports From Burkina Faso to Ghana.
Despite large volumes of cattle stocks in the Sahel, most exports of cattle products remain as live animal sales rather than meat. However, there is increased interest amongst donors and governments to increase value-added exports of beef. In this paper, we provide results from a simulation analysis that explores the prospective competitiveness and benefits of exporting beef from Burkina Faso to Ghana rather than live animals. The paper reviews trading patterns in live animals along the corridor and meat imports from overseas destinations to Ghana. Model results highlight limited competitiveness of the main products demanded in destination markets (offals). Market segmentation strategies, infrastructure development, and animal productivity all generate marginal improvements in competitiveness, but not enough to compete with third-country supplies. Only specific, largely external macroeconomic conditions provide for significant improvements in competitiveness. The paper further reveals the relatively modest employment gains associated with increased exports of meat in lieu of live animals. The analysis suggests a re-think on large-scale investments in downstream functions in the value chain, instead illustrating the fundamental role of upstream investments in productivity, animal health, and collective action to promote greater market integration between pastoralists and formal sector buyers.


Explicit relations and optimal parameters for sidelobe suppression in optical vortices with a modified Bessel function.
This paper establishes explicit relations between the radial modulation and the optimal sidelobe expression effect in the Bessel-like modulation technique. It verifies that both central and outer ring areas of the phase plate result in sidelobes in the diffraction pattern, and the corresponding structural dimensions can be determined quantitatively. This approach gives rise to complete sidelobe suppression by taking optimal modulation parameters.


Net carbon exchange and evapotranspiration in postfire and intact sagebrush communities in the Great Basin.
Invasion of non-native annuals across the Intermountain West is causing a widespread transition from perennial sagebrush communities to fire-prone annual herbaceous communities and grasslands. To determine how this invasion affects ecosystem function, carbon and water fluxes were quantified in three, paired sagebrush and adjacent postfire communities in the northern Great Basin using a 1-m3 gas exchange chamber. Most of the plant cover in the postfire communities was invasive species including Bromus tectorum L., Agropyron cristatum (L.) Gaertn and Sisymbrium altissimum L. Instantaneous morning net carbon exchange (NCE) and evapotranspiration (ET) in native shrub plots were greater than either intershrub or postfire plots. Native sagebrush communities were net carbon sinks (mean NCE 0.2-4.3 micromol m-2 s-1) throughout the growing season. The magnitude and seasonal variation of NCE in the postfire communities were controlled by the dominant species and availability of soil moisture. Net C exchange in postfire communities dominated by perennial bunchgrasses was similar to sagebrush. However, communities dominated by annuals (cheatgrass and mustard) had significantly lower NCE than sagebrush and became net sources of carbon to the atmosphere (NCE declined to -0.5 micromol m-2 s-1) with increased severity of the summer drought. Differences in the patterns of ET led to lower surface soil moisture content and increased soil temperatures during summer in the cheatgrass-dominated community compared to the adjacent sagebrush community. Intensive measurements at one site revealed that temporal and spatial patterns of NCE and ET were correlated most closely with changes in leaf area in each community. By altering the patterns of carbon and water exchange, conversion of native sagebrush to postfire invasive communities may disrupt surface-atmosphere exchange and degrade the carbon storage capacity of these systems.


Chemosensitisation by manganese superoxide dismutase inhibition is caspase-9 dependent and involves extracellular signal-regulated kinase 1/2.
Chemoresistance and therapeutic selectivity are major obstacles to successful chemotherapy of ovarian cancer. Manganese superoxide disumutase (MnSOD) is an important antioxidant enzyme responsible for the elimination of superoxide radicals. We reported here that MnSOD was significantly elevated in ovarian cancer cells and its overexpression was one of the mechanisms that increased resistance to apoptosis in cancer cells. Knockdown of MnSOD by small-interfering RNA (siRNA) led to an increase in superoxide generation and sensitisation of ovarian cancer cells to the two front-line anti-cancer agents doxorubicin and paclitaxel whose action involved free-radical generation. This synergistic effect was not observed in non-transformed ovarian surface epithelial cells. Furthermore, our results revealed that this combination at the cellular level augmented activation of caspase-3 and caspase-9, but not caspase-8, suggesting involvement of an intrinsic apoptotic pathway. Evaluation of signalling pathways showed that MnSOD siRNA enhanced doxorubicin- and paclitaxel-induced phosphorylation of extracellular signal-regulated kinase 1/2. Akt activation was not affected. These results identify a novel chemoresistance mechanism in ovarian cancer, and show that combination of drugs capable of suppressing MnSOD with conventional chemotherapeutic agents may provide a novel strategy with a superior therapeutic index and advantage for the treatment of refractory ovarian cancer.


Anthracobic acids A and B, two polyketides, produced by an endophytic fungus Anthracobia sp.
Two new polyketides, anthracobic acids A and B (1 and 2, resp.), were isolated from a cultured endophytic fungus, Anthracobia sp. The NMR study revealed that both anthracobic acids contain a carboxylic acid conjugated tetraene attached to an octahydronaphthalene moiety. Both compounds showed antimicrobial activity.


Targeting the cannabinoid system to counteract the deleterious effects of stress in Alzheimer's disease.
Alzheimer's disease is a progressive neurodegenerative disorder characterized histologically in postmortem human brains by the presence of dense protein accumulations known as amyloid plaques and tau tangles. Plaques and tangles develop over decades of aberrant protein processing, post-translational modification, and misfolding throughout an individual's lifetime. We present a foundation of evidence from the literature that suggests chronic stress is associated with increased disease severity in Alzheimer's patient populations. Taken together with preclinical evidence that chronic stress signaling can precipitate cellular distress, we argue that chronic psychological stress renders select circuits more vulnerable to amyloid- and tau- related abnormalities. We discuss the ongoing investigation of systemic and cellular processes that maintain the integrity of protein homeostasis in health and in degenerative conditions such as Alzheimer's disease that have revealed multiple potential therapeutic avenues. For example, the endogenous cannabinoid system traverses the central and peripheral neural systems while simultaneously exerting anti-inflammatory influence over the immune response in the brain and throughout the body. Moreover, the cannabinoid system converges on several stress-integrative neuronal circuits and critical regions of the hypothalamic-pituitary-adrenal axis, with the capacity to dampen responses to psychological and cellular stress. Targeting the cannabinoid system by influencing endogenous processes or exogenously stimulating cannabinoid receptors with natural or synthetic cannabis compounds has been identified as a promising route for Alzheimer's Disease intervention. We build on our foundational framework focusing on the significance of chronic psychological and cellular stress on the development of Alzheimer's neuropathology by integrating literature on cannabinoid function and dysfunction within Alzheimer's Disease and conclude with remarks on optimal strategies for treatment potential.


Prevalent Transmission of 'Candidatus Liberibacter asiaticus' over 'Ca. Liberibacter americanus' in a Long-Term Controlled Environment.
In Brazil, citrus huanglongbing (HLB) is associated with 'Candidatus Liberibacter americanus' (CLam) and 'Ca. Liberibacter asiaticus' (CLas). However, there are few studies about HLB epidemiology when both Liberibacter spp. and its insect vector, the Asian citrus psyllid (ACP, Diaphorina citri), are present. The objective of this work was to compare the transmission of HLB by ACP when both CLam and CLas are present as primary inoculum. Two experiments were performed under screenhouse conditions from April 2008 to January 2012 (experiment 1) and from February 2011 to December 2015 (experiment 2). The experiments were carried out with sweet orange plants infected with CLam or CLas as inoculum source surrounded by sweet orange healthy plants. One hundred Liberibacter-free adult psyllids were monthly confined to the source of inoculum plants for 7 days with subsequent free movement inside the screenhouse. Fortnightly, nymphs and adults of psyllids were monitored. Psyllid and leaf samples were collected periodically for Liberibacter detection by PCR or quantitative PCR. CLas was detected more frequently than CLam in both psyllid and leaf samples. No mixed infections were detected in the psyllids. A clear prevalence of CLas over CLam was observed in both experiments. The final HLB incidences were 16.7 and 14.5% of Liberibacter-positive test plants, and CLas was detected in 92.3 and 93.1% of these infected plants. Mixed infection was observed only in 3.8% of infected test plants in experiment 1. These results endorse the shift in the prevalence of CLam to CLas observed in citrus orchards of São Paulo, Brazil.


[Computer-assisted test ring for cerebrospinal fluid drainage systems].
The present paper describes a computer-aided test rig for shunts used to treat hydrocephalus. The test rig permits the automatic testing of commercially available shunt systems at defined flow or pressure levels. A thin glass tube serves as a reference to ensure the proper functioning of the setup. Six brand-new shunt systems were tested. As an application example, the dependency of shunt function on angular orientation in space was investigated. It was found that such a dependency actually exists.


Sudden Cardiac Death in a Case of Non-Dominant Coronary Artery Obstruction Without Depressed Left Ventricular Function.
Acute myocardial infarction complicated with lethal cardiac arrhythmia remains the major cause of sudden death. The possible clinical presentation leading to lethal ventricular arrhythmia has been demonstrated but the data are limited. The previous study revealed no significant correlation between sudden cardiac death and the location of coronary obstruction site. And the possible mechanism of sudden cardiac death in non-dominant coronary artery obstruction is unclear. We presented a case of acute myocardial infarction with mid left circumflex artery occlusion complicated with new onset atrial fibrillation initially. The rhythm degenerated into ventricular fibrillation immediately and sudden cardiac death occurred. After resuscitation, he received coronary angioplasty, and the rhythm recovered to sinus after the occluded coronary artery reopened. We thick new onset atrial fibrillation could be a potential risk factor leading to sudden death in acute myocardial infarction with obstruction of non-dominant coronary artery. Control of ventricular rate and early restoration of sinus rhythm may be potential benefit.


Structural analysis of a novel anionic polysaccharide from Porphyromonas gingivalis strain W50 related to Arg-gingipain glycans.
The Arg-gingipains (RgpsA and B) of Porphyromonas gingivalis are a family of extracellular cysteine proteases and are important virulence determinants of this periodontal bacterium. A monoclonal antibody, MAb1B5, which recognizes an epitope on glycosylated monomeric RgpAs also cross-reacts with a cell-surface polysaccharide of P. gingivalis W50 suggesting that the maturation pathway of the Arg-gingipains may be linked to the biosynthesis of a surface carbohydrate. We report the purification and structural characterization of the cross-reacting anionic polysaccharide (APS), which is distinct from both the lipopolysaccharide and serotype capsule polysaccharide of P. gingivalis W50. The structure of APS was determined by 1D and 2D NMR spectroscopy and methylation analysis, which showed it to be a phosphorylated branched mannan. The backbone is built up of alpha-1,6-linked mannose residues and the side-chains contain alpha-1,2-linked mannose oligosaccharides of different lengths (one to two sugar residues) attached to the backbone via 1,2-linkage. One of the side-chains in the repeating unit contains Manalpha1-2Manalpha1-phosphate linked via phosphorus to a backbone mannose at position 2. De-O-phosphorylation of APS abolished cross-reactivity suggesting that Manalpha1-2Manalpha1-phosphate fragment forms part of the epitope recognized by MAb1B5. This phosphorylated branched mannan represents a novel polysaccharide that is immunologically related to the post-translational additions of Arg-gingipains.


Transmission of vibration from a vibrating plate to the head of standing people.
Little is known about the transmission of vibration to the head when using whole-body vibration (WBV) training machines. This paper investigates the effect of frequency and posture on the transmission of vibration from a vibrating plate to the head of standing people. Nine male participants were exposed to vertical vibration at nine frequencies in the range of 17-46 Hz and vibration acceleration in the range of 7.85-18.64 m/s2 (peak). The participants adopted four standing postures described as standing with locked knee (LK), bent knee (BK), one leg (OL), and one foot to the front and the other to the back (FB). The transmissibility to the head differed among postures (t-test, p < 0.05) and was greatest with the FB posture and smallest with the BK posture. The transmissibility to the head decreased with increasing the frequency (t-test, p < 0.05) but the extent of the decrease depended on the adopted posture. This frequency-posture interaction effect on the transmissibility should be considered when designing a training program. The data will be useful for developing standards/protocols that govern the use of WBV machines as well as for building human body models that can predict potential risks arising from using WBV machines.


Expression Profile of Long Noncoding RNAs, lnc-Cox2, and HOTAIR in Rheumatoid Arthritis Patients.
Despite the increased proof that long noncoding RNAs (lncRNAs) can control gene expression and broadly affect the normal physiological and disease conditions, the part of lncRNAs in rheumatoid arthritis (RA) is not well known. This study aimed to assess the serum expression levels of lnc-Cox2 and HOTAIR in RA and to investigate their role as novel noninvasive biomarkers in diagnosis of RA. Also, their relations with the levels of interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 and with other clinicolaboratory data in RA patients were analyzed. LncRNAs-Cox2 and HOTAIR expression levels were detected in serum by real-time quantitative polymerase chain reaction. Both IL-6 and MMP-9 levels in serum were measured by enzyme-linked immunosorbent assay. The mRNA expression of lncRNA-Cox2 and HOTAIR was significantly upregulated in RA patients compared with healthy controls. Serum levels of both IL-6 and MMP-9 were significantly higher in RA patients than in healthy subjects (P < 0.001 each). Receiver operating characteristic (ROC) curve demonstrated that lncRNA-Cox2 and HOTAIR could discriminate RA patients from healthy controls. HOTAIR (not lnc-Cox2) was observed to be an independent predictor for RA using multiple logistic regression analysis. We concluded that lnc-Cox2 and HOTAIR serum expression levels can be used as novel noninvasive biomarkers for the diagnosis of RA.


Paper-based electrochemiluminescent screening for genotoxic activity in the environment.
A low cost, microfluidic paper electrochemical device (μPED) was fabricated using screen printing of electrodes and heat transfer of patterned wax paper onto filter paper. The μPED features films of a light-emitting ruthenium metallopolymer, microsomal metabolic enzymes, and DNA to detect potential genotoxic pollutant activity in environmental samples. Unlike conventional analytical methods that detect specific pollutant compounds, the μPED was designed to rapidly measure the presence of genotoxic equivalents in environmental samples with the signal related to benzo[a]pyrene (B[a]P) as a reference standard. The analytical end point is the detection of DNA damage from metabolites produced in the device using an electrochemiluminescence output measured with a charge-coupled device (CCD) camera. Proof-of-concept of this measurement was established for smoke, water, and food samples. The μPED provides a rapid screening tool for on-site environmental monitoring that specifically monitors the genotoxic reactivity of metabolites of toxic compounds present in the samples.


Elucidation of interactions of Alzheimer amyloid beta peptides (Abeta40 and Abeta42) with insulin degrading enzyme: a molecular dynamics study.
In this study, interactions of the two full-length Alzheimer amyloid beta peptides (Abeta40 and Abeta42) with the fully active form of insulin degrading enzyme (IDE) through unrestrained, all-atom MD simulations have been investigated. This enzyme is a Zn-containing metallopeptidase that catalyzes the degradation of the monomeric forms of these peptides, and this process is critical for preventing the progression of Alzheimer's disease (AD). The available X-ray structures of the free and small fragment-bound (Asp1-Glu3 and Lys16-Asp23 of Abeta40 and Asp1-Glu3 and Lys16-Glu22 of Abeta42) mutated forms of IDE and NMR structures of the full-length Abeta40 and Abeta42 have been used to build the starting structures for these simulations. The most representative structures derived from the Abeta40-IDE and Abeta42-IDE simulations accurately reproduced the locations of the active site Zn(2+) metal and small fragments of the substrates and their interactions with the enzyme from the X-ray structures. The remaining fragments of both the substrates were found to interact with IDE through several hydrogen bonding, pi-pi, CH-pi, and NH-pi interactions. In comparison to Abeta40, Abeta42 is more flexible and interacts through a smaller number (17-22) of hydrogen bonds in the catalytic chamber of IDE. Both the substrates adopted more beta-sheet character in the IDE environment, an observation that is in line with experiments. Their structural characteristics inside IDE are significantly different than the ones observed in aqueous solution. The atomistic level details provided by these simulations can help in the elucidation of binding and degrading mechanisms of the Abeta peptides by IDE.


Prolonged fasting-induced hyperketosis, hypoglycaemia and impaired fat oxidation in child and adult patients with spinal muscular atrophy type II.
This study explored hypoglycaemia and metabolic crises, including hyperketosis, in patients with spinal muscular atrophy (SMA). The study comprised four adolescents aged 15-17 and six adults aged 19-37 with SMA type II and eight adult controls aged 21-41, who were recruited by the Rigshospitalet, Denmark, from May 1st to October 30th 2017. We used stable isotope technique and indirect calorimetry to investigate fat and glucose metabolism during a 24-h fast or until hypoglycaemia occurred. All patients with SMA II developed moderate to severe hyperketosis and 60% had symptoms of hypoglycaemia or blood glucose levels below 3 mmol/L. None of the controls developed hyperketosis or hypoglycaemia. Plasma bicarbonate decreased, in line with increased ketone bodies, indicating the start of metabolic acidosis in patients with SMA II. Increased fat production and utilisation were seen in healthy controls during the fasting period, but were absent in patients with SMA II, indicating blunted fat oxidation. Low skeletal muscle mass was the best explanation for why patients with SMA II had an increased risk of hypoglycaemia, hyperketosis, metabolic acidosis and disturbed fat and glucose metabolism during fasting. These risks have implications for children facing surgery and those with severe illnesses.


Acoustic particle motion detection in the snapping shrimp (Alpheus richardsoni).
Many crustaceans produce sounds that might be used in communication. However, little is known about sound detection in crustaceans, hindering our understanding of crustacean acoustic communication. Sound detection has been determined only for a few species, and for many species, it is unclear how sound is perceived: as particle motion or sound pressure. Snapping shrimp are amongst the loudest and most pervasive marine sound sources. They produce snaps during interactions with conspecifics, and they also interact with soniferous heterospecifics. If they can hear, then sound could facilitate key behavioral interactions. We measured the auditory sensitivity of the snapping shrimp, Alpheus richardsoni, using auditory evoked potentials in response to a shaker table that generated only particle motion and an underwater speaker that generated both particle motion and sound pressure. Auditory detection was most sensitive between 80 and 100 Hz, and auditory evoked potentials were detected up to 1500 Hz. Snapping shrimp responded to both the shaker table and the underwater speaker, demonstrating that they detect acoustic particle motion. Crushing the statocyst reduced or eliminated hearing sensitivity. We conclude that snapping shrimp detect acoustic particle motion using the statocyst, they might detect conspecifics and heterospecifics, and hearing could facilitate key behavioral interactions.


Event-Related Potentials Reflect Deficits in Lexical Access: The N200 in Prematurely Born School-Aged Children.
Children born preterm have a high prevalence of neurocognitive deficits early in life. We examined whether the neural correlates of lexical access are atypical in 9-year-old children born preterm, and whether the findings of acoustic mapping correlate with language- and attention-related skills. The subjects were fourteen 9-year-old children born preterm and 14 full-term, typically developing controls. Two auditory event-related potential (ERP) components, the N200 and the N400, were used to assess discrimination response and word recognition. A set of behavioral tests (naming ability, auditory attention, phonological processing, pseudoword repetition, and comprehension of instructions) was performed, and the results were compared with the amplitudes, latencies, and scalp distribution of the ERP results. In prematurely born children, neurophysiological deficits were associated with difficulties in auditory discrimination. The N200 amplitude correlated significantly with auditory attention and pseudoword repetition. The scalp distribution of both the N200 and the N400 was broader in children born preterm than in the controls. Low scores in the neuropsychological tasks referred to difficulties in auditory processing and memory. Children born preterm have difficulties in lexical access together with memory- and attention-related processes, which may have a longstanding impact on their school outcomes and academic skills.


A pragmatic randomized trial of cardiopulmonary resuscitation training for families of cardiac patients before hospital discharge using a mobile application.
Since over 80% of sudden cardiac arrests occur in the home, cardiopulmonary resuscitation (CPR) training for family members of high-risk cardiac patients represents a promising intervention. The use of mobile application-based (mApp) CPR training may facilitate this approach, but evidence regarding its efficacy is lacking. We conducted a multicenter, pragmatic, cluster-randomized trial assessing CPR training for family members of cardiac patients. The interventions were mApp (video, no manikin) and VSI (video + manikin). CPR skills were evaluated 6-months post-training. We hypothesized that chest compression (CC) rate from training with an mApp would be no worse than 5 compressions per minute (CPM) lower compared to VSI. From 01/2016 to 01/2018, we enrolled 1325 eligible participants (mean age 51.6 years, 68.2% female and 59.4% white). CPR skills were evaluated 6-months post-training in 541 participants (275 VSI, 266 mApp). Mean rate was 84.6 CPM (95% CI: 80.4, 88.6) in VSI, compared to 82.7 CPM (95% CI: 76.2, 89.1) in the mApp, and mean depth was 42.1 mm (95% CI: 40.3, 43.8) in VSI, compared to 38.9 mm (95% CI: 36.2, 41.6) in the mApp. After adjustment, the mean difference in CC rate was -2.3 CPM (95% CI -9.4, 4.8, p = 0.25, non-inferiority) and CC depth was -3.2 mm (95% CI -5.9, 0.1, p = 0.056). In this large prospective trial of CPR skill retention for family members of cardiac patients, mApp training was associated with lower CC quality. Future work is required to understand additional approaches to improve CPR skill retention. URL: ClinicalTrials.gov, Identifier: NCT02548793.


[Incidence and causes for fracture of removable plaque prostheses].
The great number of subjects in the former Mihajlovgrad district, asking for repair of removable dentures, provided grounds the author to study clinically that problem. A total of 324 subjects, aged from 16 to 90, with 320 prostheses were inquired according to various indices. Interstings facts and regularities were established necessitating an original prophylactic activity for reduction of the number of breakings and prolongation the functional fitness of the plaque partial prosthesis, in mass use in the practice. The upper prostheses are broken three times more often than the lower ones. The partial prostheses are broken 1.7 times more than the total. Almost half of all broken prostheses (47.38%) are upper partial. The most frequent defect is a broken prosthesis with complete separation of the fragments (56.20%). The cracked prostheses are 21%. Two thirds of all prostheses received (65%) are repaired more than once and 1/3 of all prostheses are repaired 3 and more than 3 times. Treatment with practically healed prostheitic field has been performed in only 20 per cent of the subjects. The author proposes a simultaneous laboratory lining in cases of broken old prostheses and the existence of great changes in the prosthetic field. Close attention is recommended in the clinical design and laboratory making of the upper partial prosthesis.


Microtubule inhibitor-based antibody-drug conjugates for cancer therapy.
The specificity of monoclonal antibodies represents a potential therapeutic advantage, but their use as single agents in oncology has proven limited to date. The development of antibody-drug conjugates (ADCs) takes advantage of the specificity of the monoclonal antibody and potent cytotoxic effect of chemotherapy, leading to enhanced cytotoxicity in target cells and limiting toxicity to normal tissue. Microtubules represent a validated oncologic target in a range of tumor types, with a number of anti-microtubule targeting cytotoxic drugs approved for cancer use. The systemic use of potent microtubule-binding agents is limited by their effects in normal cells, which leads to toxicity including myelosuppression and peripheral neuropathy. Linking these agents to monoclonal antibodies may limit toxicity to normal tissues and increase drug concentration in target tissues, also allowing the use of more potent agents which would be too toxic to administer in their unbound form. Two such ADCs have been approved for clinical use and many others are in development. Here we review the characteristics of each of the ADC components that have led to efficacious therapies and discuss some of the tubulin inhibitor-based ADCs in development for cancer therapy.


Midwife-led maternity care in Ireland - a retrospective cohort study.
Midwife-led maternity care is shown to be safe for women with low-risk during pregnancy. In Ireland, two midwife-led units (MLUs) were introduced in 2004 when a randomised controlled trial (the MidU study) was performed to compare MLU care with consultant-led care (CLU). Following study completion the two MLUs have remained as a maternity care option in Ireland. The aim of this study was to evaluate maternal and neonatal outcomes and transfer rates during six years in the larger of the MLU sites. MLU data for the six years 2008-2013 were retrospectively analysed, following ethical approval. Rates of transfer, reasons for transfer, mode of birth, and maternal and fetal outcomes were assessed. Linear-by-Linear Association trend analysis was used for categorical data to evaluate trends over the years and one-way ANOVA was used when comparing continuous variables. During the study period, 3,884 women were registered at the MLU. The antenatal transfer rate was 37.4% and 2,410 women came to labour in the MLU. Throughout labour and birth, 567 women (14.6%) transferred to the CLU, of which 23 were transferred after birth due to need for suturing or postpartum hemorrhage. The most common reasons for intrapartum transfer were meconium stained liquor/abnormal fetal heart rate (30.3%), delayed labour progress in first or second stage (24.9%) and woman's wish for epidural analgesia (15.1%). Of the 1,903 babies born in the MLU, 1,878 (98.7%) were spontaneous vaginal births and 25 (1.3%) were instrumental (ventouse/forceps). Only 25 babies (1.3%) were admitted to neonatal intensive care unit. All spontaneous vaginal births from the MLU registered population, occurring in the study period in both the MLU and CLU settings (n = 2,785), were compared. In the MLU more often 1-2 midwives (90.9% vs 69.7%) cared for the women during birth, more women had three vaginal examinations or fewer (93.6% vs 79.9%) and gave birth in an upright position (standing, squatting or kneeling) (52.0% vs 9.4%), fewer women had an amniotomy (5.9% vs 25.9%) or episiotomy (3.4% vs 9.7%) and more women had a physiological management of third stage of labour (50.9% vs 4.6%). Midwife-led care is a safe option that could be offered to a large proportion of healthy pregnant women. With strict transfer criteria there are very few complications during labour and birth. Maternity units without the option of MLU care should consider its introduction.


Development of the mouse inner ear and origin of its sensory organs.
The molecular mechanisms dictating the morphogenesis and differentiation of the mammalian inner ear are largely unknown. To better elucidate the normal development of this organ, two approaches were taken. First, the membranous labyrinths of mouse inner ears ranging from 10.25 to 17 d postcoitum (dpc) were filled with paint to reveal their gross development. Particular attention was focused on the developing utricle, saccule, and cochlea. Second, we used bone morphogenetic protein 4 (BMP4) and lunatic fringe (Fng) as molecular markers to identify the origin of the sensory structures. Our data showed that BMP4 was an early marker for the superior, lateral, and posterior cristae, whereas Fng served as an early marker for the macula utriculi, macula sacculi, and the sensory portion of the cochlea. The posterior crista was the first organ to appear at 11.5 dpc and was followed by the superior crista, the lateral crista, and the macula utriculi at 12 dpc. The macula sacculi and the cochlea were present at 12 dpc but became distinguishable from each other by 13 dpc. Based on the gene expression patterns, the anterior and lateral cristae may share a common origin. Similarly, three sensory organs, the macula utriculi, macula sacculi, and cochlea, seem to arise from a single region of the otocyst.


Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.
Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.


Integrated molecular pathway analysis informs a synergistic combination therapy targeting PTEN/PI3K and EGFR pathways for basal-like breast cancer.
The basal-like breast cancer (BLBC) subtype is characterized by positive staining for basal mammary epithelial cytokeratin markers, lack of hormone receptor and HER2 expression, and poor prognosis with currently no approved molecularly-targeted therapies. The oncogenic signaling pathways driving basal-like tumorigenesis are not fully elucidated. One hundred sixteen unselected breast tumors were subjected to integrated analysis of phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations by immunohistochemistry, mutation analysis, and gene expression profiling. Incidence and relationships between molecular biomarkers were characterized. Findings for select biomarkers were validated in an independent series. Synergistic cell killing in vitro and in vivo tumor therapy was investigated in breast cancer cell lines and mouse xenograft models, respectively. Sixty-four % of cases had an oncogenic alteration to PIK3CA, PTEN, or INPP4B; when including upstream kinases HER2 and EGFR, 75 % of cases had one or more aberration including 97 % of estrogen receptor (ER)-negative tumors. PTEN-loss was significantly associated to stathmin and EGFR overexpression, positivity for the BLBC markers cytokeratin 5/14, and the BLBC molecular subtype by gene expression profiling, informing a potential therapeutic combination targeting these pathways in BLBC. Combination treatment of BLBC cell lines with the EGFR-inhibitor gefitinib plus the PI3K pathway inhibitor LY294002 was synergistic, and correspondingly, in an in vivo BLBC xenograft mouse model, gefitinib plus PI3K-inhibitor PWT-458 was more effective than either monotherapy and caused tumor regression. Our study emphasizes the importance of PI3K/PTEN pathway activity in ER-negative and basal-like breast cancer and supports the future clinical evaluation of combining EGFR and PI3K pathway inhibitors for the treatment of BLBC.


Reaction-diffusion master equation, diffusion-limited reactions, and singular potentials.
To model biochemical systems in which both noise in the chemical reaction process and spatial movement of molecules is important, both the reaction-diffusion master equation (RDME) and Smoluchowski diffusion-limited reaction (SDLR) partial differential equation (PDE) models have been used. In previous work we showed that the solution to the RDME may be interpreted as an asymptotic approximation in the reaction radius to the solution of the SDLR PDE [S. A. Isaacson, SIAM J. Appl. Math. 70, 77 (2009)]. The approximation was shown to be divergent in the limit that the lattice spacing in the RDME approached zero. In this work we expand upon these results for the special case of the two-molecule annihilation reaction, A+B-->Ø. We first introduce a third stochastic reaction-diffusion PDE model that incorporates a pseudopotential based bimolecular reaction mechanism. The solution to the pseudopotential model is then shown to be an asymptotic approximation to the solution of the SDLR PDE for small reaction radii. We next illustrate how the RDME may be obtained by a formal discretization of the pseudopotential model, motivating why the RDME is itself an asymptotic approximation of the SDLR PDE. Finally, we give a more detailed numerical analysis of the difference between solutions to the RDME and SDLR PDE models as a function of both the reaction-radius and the lattice spacing (in the RDME).


Internal jugular vein thrombosis associated with acute mastoiditis in a pediatric age.
To discuss the clinical aspects and management of internal jugular vein thrombosis associated with acute otitis media. Case reports and review of the literature. University hospital, tertiary referral center. The authors describe two cases of internal jugular vein thrombosis, without sigmoid sinus thrombosis, secondary to acute otomastoiditis. Jugular vein thrombosis was diagnosed in both cases by observation of filling defects of the involved jugular bulb on contrast-enhanced computed tomography and confirmed by conventional magnetic resonance and magnetic resonance venography. Both patients recovered after recanalization of the vessel concomitant to anticoagulation and antibiotic treatment associated with a simple mastoidectomy. Internal jugular vein thrombosis may be a complication of acute otitis media, without involvement of the sigmoid sinus and with a starting point in the jugular bulb. Anticoagulation associated with antibiotic therapy can be considered a safe and effective treatment. Surgery should only be performed to eliminate the source of infection from the middle ear and mastoid.


Stability and morphology of Ag nanoplatelets probed by depolarized dynamic light scattering.
The stability of silver nanoplatelet (NP) suspensions prepared with different concentrations of trisodium citrate (TSC) was studied by depolarized dynamic light scattering (DDLS) and UV-vis spectrometry. The morphology of the nanoparticles, as well as the color and stability of the sols, are tuned by the concentration of the capping agent. The nanoparticles prepared with high TSC concentration (>10-4 M) are blue triangular NPs showing a slight truncation of the tips with aging. When low TSC concentrations are used, the color of the sols changes from blue to yellow with aging time and a strong modification of the morphology occurs: the nanoparticle shape changes from triangular to spherical. Remarkably, they show a high degree of anisotropy. The aging process was followed by the UV-vis spectra and by measuring the rotational diffusion coefficient by DDLS, providing information on the nanoparticle size and shape evolution. The high intensity of depolarized signal and the high value of rotational diffusion coefficient suggest that the aging process increases the thickness and the roughness of the nanoparticles.


Essential elements of and challenges to rapid ART implementation: a qualitative study of three programs in the United States.
Antiretroviral therapy (ART) initiation on the day of an HIV diagnosis or as soon as possible after diagnosis, known as rapid ART (henceforth "RAPID"), is considered to be a safe and effective intervention to quickly reduce viral load and potentially improve engagement in care over time. However, implementation of RAPID programming is not yet widespread. To facilitate broader dissemination of RAPID, we sought to understand health care worker experiences with RAPID implementation and to identify essential programmatic elements. We conducted 27 key informant interviews with medical providers and staff involved in RAPID service delivery in three distinct clinical settings: an HIV clinic, a Federally Qualified Health Center and a sexual health and wellness clinic. Interviews were structured around domains associated with the Consolidated Framework for Implementation Research and were audio-recorded, transcribed, and thematically analyzed. We identified seven (7) essential elements across settings associated with successful RAPID program implementation. These high-impact elements represent essential components without which a RAPID program could not function. There was no one requisite formation. Instead, we observed a constellation of essential elements that could be operationalized in various formations and by various people in various roles. The essential elements included: (1) presence of an implementation champion; (2) comfort and competence prescribing RAPID ART; (3) expedited access to ART medications; (4) expertise in benefits, linkage, and care navigation; (5) RAPID team member flexibility and organizations' adaptive capacity; (6) patient-centered approach; and (7) strong communication methods and culture. The RAPID model can be applied to a diverse range of clinical contexts. The operational structure of RAPID programs is shaped by the clinical setting in which they function, and therefore the essential elements identified may not apply equally to all programs. Based on the seven essential elements described above we recommend future implementers identify where these elements currently exist within a practice; leverage them when possible; strengthen them when necessary or develop them if they do not yet exist; and look to these elements when challenges arise for potential solutions.


Effect of losartan on exercise tolerance and echocardiographic parameters in patients with mitral regurgitation.
The aim of this study was to assess the effects of losartan treatment on exercise tolerance and echocardiographic parameters in patients with mitral regurgitation (MR) secondary to mitral valve prolapse or rheumatic heart disease. Twenty-seven patients (14 males, 13 females, mean age 51+/-11, range 21-76) with moderate MR due to mitral valve prolapse or rheumatic heart disease were examined by means of Doppler echocardiography. The subjects were submitted to treadmill exercise tests using the modified Bruce protocol at baseline, after six hours and after the six-week treatment period to be evaluated based on their exercise tolerance. Mitral Regurgitant Volume (MRV), effective regurgitant orifice diameter, left atrial volume, left ventricle (LV) end-diastolic volume index, LV end-systolic volume index, LV ejection fraction (LVEF), left ventricle mass index were calculated at baseline and after six weeks of treatment with single dose of losartan (50 mg/day). Total treadmill exercise time increased from 477.7+/-147.9 to 535.7+/-149.0 seconds after six hours (p<0.01) and to 559.6+/-142.8 seconds after six weeks of treatment. Also, metabolic equivalent values increased following six hours of first dose and six weeks of losartan treatment (from 10.9+/-2.9 to 11.8+/-3.1, p=0.006 and 12.4+/-3.1, p=0.002; respectively). However, peak exercise systolic blood pressure (BP) was reduced after six hours and six weeks of treatment, and resting diastolic BP did not change after six hours but reduced at the end of the treatment period. MR volume decreased significantly from 29.3+/-14.1 ml to 25.1+/-14.8 ml, (p=0.025) without significant change in regurgitant orifice diameter (0.72+/-0.37 cm vs. 0.66+/-0.37 cm, p=NS), left atrium diameter and area while LVEF increased from 51.70+/-13.37 to 54.11-11.75 (p=0.015) with losartan. We conclude that the angiotensin II receptor antagonist losartan improves exercise tolerance and echocardiographic parameters in patients with moderate MR.


Acute heart failure in elderly patients: a review of invasive and non-invasive management.
Acute heart failure (AHF) is a major cause of unplanned hospitalisations in the elderly and is associated with high mortality. Its prevalence has grown in the last years due to population aging and longer life expectancy of chronic heart failure patients. Although international societies have provided guidelines for the management of AHF in the general population, scientific evidence for geriatric patients is often lacking, as these are underrepresented in clinical trials. Elderly have a different risk profile with more comorbidities, disability, and frailty, leading to increased morbidity, longer recovery time, higher readmission rates, and higher mortality. Furthermore, therapeutic options are often limited, due to unfeasibility of invasive strategies, mechanical circulatory support and cardiac transplantation. Thus, the in-hospital management of AHF should be tailored to each patient's clinical situation, cardiopulmonary condition and geriatric assessment. Palliative care should be considered in some cases, in order to avoid unnecessary diagnostics and/or treatments. After discharge, a strict follow-up through outpatient clinic or telemedicine is can improve quality of life and reduce rehospitalisation rates. The aim of this review is to offer an insight on current literature and provide a clinically oriented, patient-tailored approach regarding assessment, treatment and follow-up of elderly patients admitted for AHF.


Elucidating the Beta-Diversity of the Microbiome: from Global Alignment to Local Alignment.
Quantitative comparison among microbiomes can link microbial beta-diversity to environmental features, thus enabling prediction of ecosystem properties or dissection of host-microbiome interaction. However, to compute beta-diversity, current methods mainly employ the entire community profiles of taxa or functions, which can miss the subtle differences caused by low-abundance community members that may play crucial roles in the properties of interest. In this work, I review the distance metrics and search engines that we developed to match microbiomes at a large scale based on whole-community-level similarities, as well as their limitations in tackling the microbiome changes caused by less abundant community features. Then I propose the concept of microbiome "local alignment," including an algorithm to measure microbiome similarity on specific fractions of biodiversity and an indexing strategy for rapidly fetching microbiome local-alignment matches from the data repository.