Microstructure and Corrosion Behavior of (CoCrFeNi)95Nb₅ High-Entropy Alloy Coating Fabricated by Plasma Spraying.
In this paper, the (CoCrFeNi)95Nb₅ high-entropy alloy (HEA) coating with a thickness of 500 μm on Q235 steel substrate was fabricated by plasma spraying. The microscopic results showed that a new Laves phase is formed in the (CoCrFeNi)95Nb₅ HEA coating compared to the HEA powder, and elemental segregation occurs between the dendrites and the interdendrites of the coating, while the interdendritic phase enriches with the Cr and Nb. The phase composition change and elemental segregation behavior were mainly due to the faster cooling rate of the plasma spraying technique. At the junction of the coating and the substrate, the HEA coating bonded well to the substrate; in addition, the width of transition zone was merely 2 μm. The microhardness of the (CoCrFeNi)95Nb₅ HEA coating was 321 HV0.5, which is significantly higher than that of the substrate. In terms of corrosion resistance, the (CoCrFeNi)95Nb₅ HEA coating has good corrosion resistance in NaCl solution. Although the corrosion form was pitting corrosion, the pitting potential of the (CoCrFeNi)95Nb₅ HEA coating was significantly higher than that of other coatings, which was mainly because of the dense passivation film formed by Cr and Nb on the surface of the coating. Once the passivation film was destroyed by Cl-, the selective corrosion occurred on the surface of the (CoCrFeNi)95Nb₅ HEA coating. In summary, the (CoCrFeNi)95Nb₅ HEA coating prepared by plasma spraying technology can significantly improve the corrosion resistance and mechanical properties of the Q235 steel substrate.


Low level lead exposure and pregnancy outcomes in an observational birth cohort study: dose-response relationships.
National and international guidelines on safe levels for blood Pb in pregnancy focus on a threshold above which exposure is of concern. However, it has recently been suggested that the decrease in birth weight per unit increase in blood Pb is actually greater at lower than at higher concentrations of Pb without evidence of a lower threshold of effect. Our aim was to investigate whether there was evidence for a differential effect of maternal Pb levels on birth outcomes and/or a threshold value for effects. Blood samples from pregnant women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) were analysed. Data collected on the infants included anthropometric variables. We fitted adjusted multivariable fractional polynomial models for birth outcomes. Adjusted models that assumed a linear relationship between untransformed blood Pb and the outcomes provided the best fit: an increase of 1 µg/dl was associated with changes in birth weight of -9.93 (95 % CI -20.27, 0.41) g, head circumference -0.03 (95 % CI -0.06, 0.00) cm and crown-heel length -0.05 (95 % CI -0.10, 0.00) cm. There was no evidence in this study to suggest a supralinear dose-response relationship or a lower threshold for the effect of maternal blood Pb on birth outcomes. This has implications for consideration of national and international guidelines on levels of concern in pregnancy. Exposure to Pb should be kept as low as possible during pregnancy to minimise adverse outcomes.


Electrospun nanofiber-based drug delivery platform: advances in diabetic foot ulcer management.
Electrospinning is a facile and viable method for the fabrication of nanofibers. Electrospun nanofiber has a great potential in providing local drug or therapeutic molecule delivery to the wound site. The versatile nature of this technique ensures a broad scope of material used in the fabrication of nanofibers. A brief introduction to diabetic foot ulcer (DFU) is covered with its pathogenesis, followed by the role of electrospun nanofibers in DFU. This review covers the evolution of the electrospinning technique over the past few years, various types of electrospun nanofibers reported for DFU or chronic diabetic wounds, the challenges associated with the preparation of nanofibers, and various methods to evaluate their efficacy and performance in diabetic wound healing. Electrospinning-based nanofibers provide a safe, effective, and multifunctional system for effective management of DFU.


Quantitative electroencephalographic measures in homicidal men with antisocial personality disorder.
Many symptoms of antisocial personality disorder have been proposed to be related to decreased daytime vigilance. To explore this hypothesis, quantitative analyses were conducted of the electroencephalographic (EEG) activity of drug-free and detoxified homicidal male offenders with antisocial personality disorder as the primary diagnosis. Subjects comprised 16 men recruited from a forensic psychiatric examination in a special ward of a university psychiatric hospital. Fifteen healthy age- and gender-matched controls with no criminal record or history of physical violence consisted of hospital staff and students. An overall reduction of alpha power was observed in the waking EEG of offenders. A bilateral increase in occipital delta and theta power was also found in these individuals. This study provides further support to the growing evidence of brain dysfunction in severe aggressive behavior. Homicidal offenders with antisocial personality disorder seem to have difficulties in maintaining normal daytime arousal. Decreased vigilance, together with social and psychological variables, may explain their aberrant behavior in everyday life. New studies are, however, needed to specify the vigilance problems of this patient group.


Explicit estimation of visual uncertainty in human motion processing.
We examine whether human observers have explicit access to an estimate of their own uncertainty in extrapolating the motion trajectories of moving objects. Objects moved across a display area at constant speed changing direction at short time intervals. Each new direction was obtained by adding a random perturbation to the previous direction. The perturbation distribution was always symmetric with mean zero (no change in direction) but could differ in variability: objects with low directional variability tended to travel in straight lines while objects with high directional variability moved more erratically. Objects eventually disappeared behind the near edge of an occluder. Observers marked a 'capture region' along the far edge of the occluder that they estimated would contain the object when it re-emerged. We varied both occluder width and directional variability across trials and found that observers correctly compensated for these changes. We present a two-stage model of observer performance in which the visual system first estimates the directional variability of the object and then uses this estimate to set a capture region.


Interaction of an organic cation with Gibbs monolayers of n-hexadecyl phosphate.
Surface phase behavior of n-hexadecyl phosphate (n-HDP) and its mixture with L-arginine (L-arg), which behaves as L-argininium cation (L-arg(+)) in aqueous solution, at a molar ratio 2:3 in Gibbs adsorption layers has been studied by film balance, Brewster angle microscopy (BAM) and surface tensiometry at 20 degrees C. The monolayers of n-HDP show three phases that are gas (G), intermediate (I) and liquid condensed (LC), and two phase transitions. A first-order G-I phase transition that is followed by a second-order I-LC phase transition is found in these monolayers. Although the monolayers of the mixtures containing n-HDP and L-arg show three phases, the nature of the middle phase is different from that of the n-HDP monolayers. The three phases observed for the mixed systems are G, liquid expanded (LE) and LC phases. A first-order G-LE phase transition is found at a low surface pressure at > or =10 degrees C. This transition is followed by another first-order LE-LC phase transition at a certain higher surface pressure. The first-order nature of the phase transitions for both the systems is confirmed by the presence of plateaus in the pi-t curves, which are accompanied by two surface phases. A second-order phase transition in the monolayers of n-HDP is indicated by a gradual change in the surface morphology, from a uniformly bright isotropic to an anisotropic mosaic textured phase, which is accompanied by a continuous change in the surface pressure. The domains formed during the first-order phase transition in the adsorption layers of n-HDP are circular and remain unaffected by changing the temperature. Although the domains of an LE phase are circular, those of an LC phase at the latter transition are fractal in the mixed system. A further branching of the arms of the fractal domains is found to occur by an increase in the temperature. All the results are explained by considering salt formation between anion from n-HDP and L-arg(+).


Characterisation of Streptococcus suis isolates from wild boars (Sus scrofa).
Wild boar are widely distributed throughout the Iberian Peninsula and can carry potentially virulent strains of Streptococcus suis. The objective of this study was to determine the prevalence of S. suis in wild boars from two large geographical regions of Spain. Serotypes 1, 2, 7 and 9 identified were further genetically characterised by virulence-associated genotyping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to determine the population structure of S. suis carried by these animals. Streptococcus suis was isolated from 39.1% of the wild boars examined: serotype 9 was the most frequently isolated (12.5%), followed by serotype 1 (2.5%). Serotype 2 was rarely isolated (0.3%). Eighteen additional serotypes were identified indicating wide diversity of this pathogen within the wild boar population. This heterogeneity was confirmed by PFGE and MLST analyses and the majority of isolates exhibited the virulence-associated genotype mrp-/epf-/sly-. The results of this study highlight that the carriage of S. suis by wild boars is commonplace. However, MLST data indicate that these isolates are not related to prevalent clonal complexes ST1, ST16, ST61 and ST87 typically associated with infection of pigs or humans in Europe.


Involvement of opioid receptors in Met-enkephalin modulation of blast-transformation of mouse splenocytes.
The influence of Met-enkephalin on mitogenic stimulation of mouse splenocytes was investigated. Met-enkephalin (ME) was shown to suppress proliferation induced by Concanavalin A and activate proliferation induced by Staphylococcus enterotoxin A. Both effects were revealed at low (down to 10(-14) M) concentration of pentapeptide. Naloxone reversed ME influence on cell activation. The number of receptors for naloxone was shown to increase up to 2.5-fold during mitogenic activation. The difference in expression of various types of opioid receptors at mitogenic stimulation was demonstrated by ligand displacement experiments.


Effective and Safe Trajectory Planning for an Autonomous UAV Using a Decomposition-Coordination Method.
In this paper, we present a Decomposition Coordination (DC) method applied to solve the problem of safe trajectory planning for autonomous Unmanned Aerial Vehicle (UAV) in a dynamic environment. The purpose of this study is to make the UAV more reactive in the environment and ensure the safety and optimality of the computed trajectory. In this implementation, we begin by selecting a dynamic model of a fixed-arms quadrotor UAV. Then, we define our multi-objective optimization problem, which we convert afterward into a scalar optimization problem (SOP). The SOP is subdivided after that into smaller sub-problems, which will be treated in parallel and in a reasonable time. The DC principle employed in our method allows us to treat non-linearity at the local level. The coordination between the two levels is achieved after that through the Lagrange multipliers. Making use of the DC method, we can compute the optimal trajectory from the UAV's current position to a final target practically in real-time. In this approach, we suppose that the environment is totally supervised by a Ground Control Unit (GCU). To ensure the safety of the trajectory, we consider a wireless communication network over which the UAV may communicate with the GCU and get the necessary information about environmental changes, allowing for successful collision avoidance during the flight until the intended goal is safely attained. The analysis of the DC algorithm's stability and convergence, as well as the simulation results, are provided to demonstrate the advantages of our method and validate its potential.


Cholinergic urticaria: acetylcholine-receptor-dependent immediate-type hypersensitivity reaction to copper.
A patient with cholinergic urticaria syndrome was found to have an unusually large number of muscarinic cholinergic receptors in the urticarial sites. The amplification of these receptors may account for her heightened sensitivity to acetylcholine discharge following exercise, heat, and emotion. The acetylcholine presumably acts directly on the mast-cell membrane to initiate histamine release and thereby punctate urticaria. In addition, an otherwise occult sensitivity to copper was detected with a 48 h contact patch test to the metal followed by an exercise challenge. Under these conditions, the patch test site developed hives after the autonomic stress stimulus of exercise but showed nothing on conventional patch testing before exercise. Such "cholinergic patch testing" is recommended for the demonstration of other examples of antigen enhancement of acetylcholine-mediated reactions.


Current knowledge in cleft lip and palate treatment from an orthodontist's point of view.
The aim of this review was to put new clinical research findings into proper perspectives relative to previously accepted knowledge on treatment of patients with cleft lip and palate. The first part of the paper deals with various aspects of infant orthopedic treatment, such as its influence on primary surgery, maxillary arch form and dimensions, feeding, psychological situation of the parents and speech development. Following parts analyze general maxillofacial growth outcome after surgery and also maxillofacial growth in relation to particular surgical procedures (palatal repair, periosteoplasty/gingivoplasty, bone grafting). The last part of the review discuss the effects of certain orthodontic/orthopedic treatment approaches as well as the role of dental implants in treatment of cleft lip and palate patients.


Conservation of sigma F in mycobacteria and its expression in Mycobacterium smegmatis.
Alternate sigma factor SigF controls the expression of virulence-associated genes and is believed to contribute to the pathology of tuberculosis. It was reported to be absent in fast-growing nontuberculous mycobacteria until its orthologs were reported recently in a database. In this study, we demonstrate the presence of sigF gene in few commonly studied nonpathogenic mycobacterial species. Further, we studied the sigF expression in Mycobacterium smegmatis and observed that unlike its late-stage expression in M. tuberculosis and M. bovis, found in earlier studies, sigF is expressed throughout the growth in M. smegmatis, by and large, at the same level, but its expression varies upon exposure to different stress conditions. The presence of sigF orthologs in nontuberculous mycobacteria and its continued expression throughout the growth suggests that apart from regulating the expression of virulence factor genes in pathogenic mycobacteria, SigF is likely to have more roles in the mycobacterial physiology.


Influence of overlying soft tissues on trabecular bone acoustic measurement at various ultrasound frequencies.
Ultrasound (US) has been introduced as a promising tool for osteoporosis diagnostics. However, soft tissues overlying the bones affect reliability of the ultrasound (US) techniques. In this in vitro study, the effect of soft tissues on bone US measurements was investigated numerically and experimentally. Particularly, the dependence of the error induced by soft tissues on the applied US frequency (0.3 to 6.7 MHz) was addressed. For these aims, human trabecular bone samples (n = 25) were measured using acoustic, dual energy x-ray absorptiometry (DXA) and mechanical techniques. US attenuation, speed, reflection and backscattering were determined from the through-transmission and pulse-echo measurements. Numerical correction, based on the inclusion of acoustic characteristics of specific soft tissue components, i.e., adipose and lean tissues, was derived for the analysis of experimental measurements. Values of US parameters, interrelationships between the US parameters and mechanical properties, as well as the errors induced by the soft tissues, were significantly dependent on the US frequency. The errors induced by the soft tissues on the US measurement were typically reduced by approximately 50% after introduction of the numerical correction technique. Thereby, the acoustic prediction of mechanical properties of trabecular bone was also improved. We conclude that the numerical correction of the contribution of overlying soft tissues on acoustic measurements can reduce uncertainties related to in vivo US measurements.


Delta-aminolaevulinic acid metabolism in normal and lead-exposed humans.
The activity of the haem biosynthetic enzymes delta-aminolaevulinic acid synthetase (ALA.S) and delta-aminolaevulinic acid dehydratase (ALA.D) were measured in the peripheral blood of a group of lead workers and control subjects. The haem precursor delta-aminolaevulinic acid (ALA) was measured in blood and urine, whilst lead levels were measured in whole blood. The inter-relationships between all these parameters were examined and quantified. The results demonstrate that above a blood lead concentration of 2 mumole/l and below an erythrocyte ALA.D activity of 18 nmole ALA utlized/min/ml red blood cells (R.B.C.), Haem synthesis is depressed to such an extent that the activity of leucocyte ALA.S, the rate-limiting enzyme of haem biosynthesis, is increased by negative feedback.


Pericardial heterografts: a comparative study of suture pull-out and tissue strength.
The force required to pull sutures out of glutaraldehyde fixed bovine pericardium, for four different suture bites: 0.5 mm, 1 mm, 1.5 mm and 2.0 mm, was compared with the tissue strength. The mean suture pull-out force was significantly lower than the tissue strength for all bites, with a minimum value of 2.86 +/- 1.02 N for the 0.5 mm bite and a maximum value of 6.32 +/- 0.77 N for the 2.0 mm bite. The mean force which produced failure of the chemically modified pericardium was 15.49 +/- 8.48 N. The mean force at pull-out of the sutures lay on a regression line: force at failure = 1.68 + 2.25 x Bite. A video film of the experiments showed that the suture does not cut through the pericardium. It pulls a V-shaped band of collagen fibre bundles through the stationary pericardium. Eventually this band breaks away from the free edge of the tissue specimen. The specimens under uniaxial load failed by laminate debonding of two layers of tissue, rupture of the serosal surface layer followed by shear and fibre slippage. These results indicate that any suture which bears load, during the normal functioning of a heart valve substitute, will be a source of weakness, compared to the overall tissue strength. As a consequence the alignment/holding suture of the Standard Ionescu-Shiley valve and the modified stitch of the low profile valve are likely to be potential sites of fatigue failure.


Retinol binding protein-4 circulating levels were higher in nonalcoholic fatty liver disease vs. histologically normal liver from morbidly obese women.
We aimed to analyze the retinol binding protein-4 (RBP4) messenger RNA (mRNA) expression profiles in adipose tissues and liver of morbidly obese (MO) women with or without nonalcoholic fatty liver disease (NAFLD), and to study the relationships with other pro- and anti-inflammatory adipokines in vivo and in vitro. We performed a cross-sectional analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and liver samples from four lean and 45 MO women with or without NAFLD by enzyme-linked immunosorbent assay and real-time reverse transcription-PCR. We also studied RBP4 expression in HepG2 hepatocytes under various inflammatory stimuli. Circulating RBP4 levels were higher in MO women, and specifically, in MO subjects with NAFLD compared with normal liver controls (lean and MO). RBP4 liver expression was higher in nonalcoholic steatohepatitis (NASH)-moderate/severe than in NASHmild. Overall RBP4 gene expression was higher in liver than in adipose tissues. Among them, the higher expression corresponded to SAT. VAT expression was lower in the MO cohort. In HepG2, RBP4 mRNA expression was reduced by tumor necrosis factor (TNF)-α and increased by adiponectin treatment. The results obtained in MO women with NAFLD, brings up the use of RBP4 and other adipokines as a panel of noninvasive molecular biomarkers when NAFLD is suspected. Further studies are needed with other obesity groups.


Diagnosis, Bedside Manner and Comment Style are Predictive Factors in Online Ratings of Urologists.
We assess how urologists are rated online by patients and which factors influence these ratings. We created an anonymous database of urologists' ratings from Ontario, Canada using a popular rating website (RateMDs.com). Comments were assessed for mention of diagnosis, bedside manner and nonlinguistic emphasis devices, and the impact of these variables was analyzed. A total of 3,288 ratings were identified for 224 urologists (median 15 ratings per urologist, range 1 to 35), representing 75.4% of practicing urologists in the province. Mean rating was 3.96/5 (median 4.75, range 1 to 5). Overall 2,215 ratings (67.4%) were 4/5 or greater. Comment on good bedside manner was associated with higher ratings (mean 4.74 vs 3.92, p <0.001) and comment on poor bedside manner was associated with lower ratings (mean 2.45 vs 4.01, p <0.001). Patients mentioning surgery rated urologists higher than those who did not (4.28 vs 3.85, p <0.001). A specific diagnosis was mentioned in 1,056 cases (32.1%). Mean rating was highest for kidney cancer (4.67) and lowest for vasectomy (3.77, p <0.001). Comments with at least 1 word in full capital letters and those with a word or phrase in quotation marks were accompanied by lower ratings (mean 3.11 vs 4.03 and 3.13 vs 4.02, respectively, p <0.001). Longer comments were also associated with lower ratings (word count 1 to 50-mean rating 4.24, word count 51 to 100-mean rating 3.88, word count greater than 100-mean rating 3.29; p <0.001). Urologists are reviewed favorably online. Patients who note surgery, a cancer diagnosis or good bedside manner rate urologists highly, while longer comments, the use of all caps or quotation marks, or mention of a poor bedside manner are associated with lower ratings.


INFLUENCE OF PAPAVERINE AND COMMERCIAL DIETARY SUPPLEMENTS ON BLOOD GLUCOSE AND BODY WEIGHT IN OBESE DOGS.
Our experiments showed that papaverine inhibits sugar absorption in vivo as well as in vitro. Papaverine blocks the absorption of sugar both in healthy and diabetic animals. Oral administration of papaverine significantly reduced blood sugar level but after an hour blood sugar level showed tendency to come back to the initial levels that were characteristic for these diabetic dogs. Dietary supplement made of herbal remedies and papaverine has proven to be quite effective in reducing body weight in dogs. For a month, dogs with initial overweight lost on average more than 1 kg (10+%), that is a very good result for their size.


Molecular identification of Trypanosoma cruzi in domestic animals in municipalities of the State of Rio Grande do Norte, Brazil.
Trypanosoma cruzi, the etiologic agent of American trypanosomiasis, is a vector-borne zoonotic parasite which has been little studied regarding its infection in domestic animals. In this study, we evaluated the occurrence of natural infection by T. cruzi in farm animals using molecular markers and phylogenetic analysis in blood clot samples of 60 sheep (Ovis aires), 22 goats (Capra hircus), and 14 horses (Equus caballus) in eight municipalities located in an infection risk area in the state of Rio Grande do Norte (RN), Northeast Region of Brazil. Trypanosoma spp. infection was identified by amplifying the rRNA 18S SSU gene in 48.9% of the samples. The SH022 sample showed 99.8% similarity with the Y strain of T. cruzi in phylogeny, grouped in the DTU II clade. Blood clots of sheep, goats, and horses detected T. cruzi kDNA in 28.3% (17/60), 22.7% (5/22), and 15.4% (2/14) of the samples, respectively. These animals were distributed in the three studied mesoregions throughout the state of RN. The identification of natural infection in domestic animals contributes to expand the epidemiological transmission scenario in an area where T. brasiliensis is the main vector.


Effect of controlled-release levodopa on the microstructure of sleep in Parkinson's disease.
Dopamine is an important neurotransmitter in the regulation of the sleep-wake cycle, and parkinsonian patients suffer from prominent sleep abnormalities. Hence, the question arises whether the disrupted sleep pattern in Parkinson's disease (PD) is responsive to dopaminergic treatment. Thirty-two patients (18 women, 45-82 years old; mean 61 ± 8 years) with dopamine-responsive, akinetic-rigid PD, not taking neuroleptic medication or suffering from dementia were randomized into two groups. Both groups had to withhold their usual dopaminergic medication after noon. At bedtime, one group received 200 mg controlled-release (CR) levodopa/carbidopa, whilst the other group spent the night in the 'off'-state. Polysomnographic recordings were obtained in all patients and 16 age-matched, healthy controls. Compared to healthy controls, patients with PD suffered from significantly decreased total sleep time, REM sleep and slow wave sleep (SWS), whilst the time spent awake was increased. The administration of levodopa/carbidopa CR had no impact on any of these variables. Levodopa/carbidopa CR has previously been found effective for treating night-time akinesia, but according to this study, it has no impact on the altered sleep structure in PD.


Mid-term results of aortic valve preservation: remodelling vs. reimplantation.
Valve-preserving root replacement has become an accepted alternative to composite replacement both in dissection and in aneurysmal disease. We retrospectively analysed 5-year results comparing root remodelling and reimplantation procedures. From October 1995 to January 2001, 119 patients underwent either root remodelling (group A; n = 98; age: 61 +/- 14 years) or valve reimplantation within a vascular graft (group B; n = 21; age: 47 +/- 17 years). In group A, 26 patients were operated for aortic dissection type A and 72 for aortic valve regurgitation and aneurysmal disease. In group B, 8 patients were operated for aortic dissection type A, 13 for aortic valve regurgitation and aneurysm. Concomitant arch surgery was performed in 65 patients (group A: 57; group B: 8). Time on cardiopulmonary bypass was 121 +/- 30 min in group A, 143 +/- 24 min in group B, and aortic cross-clamp time was 87 +/- 19 min in group A and 113 +/- 24 min in group B. Average duration was therefore longer in group B (p = n.s.) Hospital mortality was 3.1 % in group A and 0 % in group B. Following elective procedures, hospital mortality was 1.1 % in group A. Freedom from aortic regurgitation over grade 2 at 4 years was 86 % in group A and 94.7 % in group B. At 4 years, freedom from proximal reoperation was 97.8 % in group A and 100 % in group B. There was no deterioration of valve function or need for reoperation observed after 1 year in either group. Five-year results are comparable and encouraging for remodelling and reimplantation procedures. If the initial valve function and geometry is adequate, the chance of secondary failure beyond the first year is minimal.


A systematic review and meta-analysis of impact of baseline thrombocytopenia on cardiovascular outcomes and mortality in patients undergoing percutaneous coronary intervention.
Thrombocytopenia (TP) is associated with higher incidence of bleeding in the setting of percutaneous coronary intervention (PCI) leading to increased morbidity and mortality. Herein, we report a meta-analysis evaluating the effects of baseline thrombocytopenia (bTP) on cardiovascular outcomes in patients undergoing PCI. Literature search was performed using PubMed, Embase, Cochrane library and clinicaltrials.gov from inception till October 2019. Patients were divided into two groups: Patients with (a) no Thrombocytopenia (nTP) (b) bTP before PCI. Primary endpoints were in-hospital, and all-cause mortality rates at the longest follow-up. The main summary estimate was random effects risk ratio (RR) with 95% confidence intervals (CIs). A total of 6,51,543 patients from 10 retrospective studies were included. There was increased in-hospital all-cause mortality (RR 2.58 [1.7-3.8], p < .001) and bleeding (RR 2.37 [1.41-3.98], p < .005), in the bTP group compared to the nTP group. There was no difference for in-hopsital major adverse cardiovascular outcomes (MACE) (RR 1.38 [0.94-2.0], p < .10), post-PCI MI (RR 1.17 [0.9-1.5], p = .19) and TVR (RR 1.65 [0.8-3.6], p = .21), respectively. Outcomes at longest follow-up showed increased incidence of all-cause mortality (RR 1.86 [1.2-2.9], p < .006) and bleeding (RR 1.72 [1.1-2.9], p = .04) in bTP group, while there was no significant difference for post-PCI MI (RR 1.07 [0.91-1.3], p = .42), MACE (RR 1.86 [0.69-1.8], p = .68) and TVR (RR 1.1 [0.9-1.2], p = .93) between both groups. bTP in patients undergoing PCI is associated with increased mortality and predicts risk of bleeding.


Morphology, molecular phenotypes and distribution of neurons in developing human corpus callosum.
The aim of this study was to investigate the morphology, molecular phenotypes, distribution and developmental history of interstitial neurons in the human corpus callosum, here defined as intracallosal neurons. We analysed 26 fetuses, three newborns, five infants and children, and eight adults [age range - 15 weeks postconception (PCW) to 59 years] by means of acetylcholinesterase (AChE) histochemistry and immunohistochemistry for neuron markers (MAP2, NeuN, NPY, calretinin and calbindin). We found a heterogeneous neuron population, positioned within the callosal trunk itself (aside from neurons present in the transient midline structures such as callosal sling, septa or subcallosal zone), which was most numerous during the second half of gestation and early postnatal years. We named these cells intracallosal neurons. At 15 PCW, the intracallosal neuron population consisted of poorly differentiated, small fusiform or bipolar, migratory-like MAP2- or calretinin-positive neurons which could be observed until mid-gestation. Later the population comprised morphologically diverse, predominantly well-differentiated MAP2-, NPY-, calbindin- and AChE-positive neurons. The morphological differentiation of intracallosal neurons culminated in the newborns and remained pronounced in infants and children. In the adult brain, the intracallosal neurons were found only sporadically, with small somata and poorly stained dendrites. Thus, intracallosal neurons form part of a transitory neuron population with a developmental peak contemporaneous to the critical period of callosal formation. Therefore, they may be involved in processes such as axon guiding or elongation, withdrawal of exuberant axons, fasciculation, or functional tuning, which occur at that time.


Modulation of pulmonary eicosanoid metabolism following exposure to sulfuric acid.
Eicosanoids (arachidonic acid metabolites) are potent biological mediators. Modulation of their metabolism by air pollutants may be a possible factor in the pathogenesis of environmentally related lung disease. Sulfuric acid (H2SO4) aerosols are components of ambient air in many areas. Rabbits were exposed to H2SO4 (0.3 microns) at 250, 500, or 1000 micrograms/m3 for 1 hr/day for 5 days. They were then euthanized, the lungs lavaged, and eicosanoid analyses performed by radioimmunoassay of acellular lavage fluid. An exposure-concentration-dependent decrease in levels of prostaglandins E2 and F2 alpha and thromboxane B2 was found; no change in leukotriene B4 was observed. Tracheal explants exposed to acidic environments in vitro also showed reduced production of PGE2, PGF2 alpha, and TxB2. Incubation with sodium sulfate (Na2SO4) showed no effect of the sulfate ion (SO4(2-)). This study, the first to examine eicosanoid production after in vivo exposure to pure H2SO4 droplets, indicates that such exposure can modulate arachidonic acid metabolism, and that this is likely due to the deposition of hydrogen ion (H+) on target tissue.


The application of strong cation exchange high-performance liquid chromatography to drug analysis.
The application of strong cation exchange (SCX) HPLC to the analysis of drugs in plasma, tissue and rodent feed is presented. This approach is shown to give useful separations allowing the separation of physiochemically diverse compounds in a simple isocratic system. The SCX columns are not as robust as standard reversed-phase materials and to ensure maximum column lifetimes the use of a guard column is recommended.


MammoSite excision volume as a predictor for residual disease.
The MammoSite catheter is a brachytherapy device used for accelerated partial breast irradiation. Currently, it is available as 2 spherically shaped balloons meant to fill 70-cc and 120-cc cavity volumes. This study was designed to define the relation of these excision volumes to the likelihood of microscopically detectable, residual disease based on tumor size, margin status, patient age, and histology. The study data base was comprised of 531 patients with Stage 0, I, and II breast carcinoma (using American Joint Committee on Cancer staging criteria) who received breast-conserving therapy and underwent surgical reexcision. Patients in the data base were stratified based on the volume of their initial excision: < or = 70 cc versus > 70 cc and < or = 120 cc versus > 120 cc. Surgical margin size was found to be a strong predictor of residual disease both for patients with smaller excision volumes (P = 0.0014) and patients with larger excision volumes (P = 0.0003); histology (extensive intraductal component [EIC] or pure ductal carcinoma in situ [DCIS]) also was a strong predictor. Tumor size was significant only for the larger volume group (P = 0.029). On multivariate analysis, only histology and initial margin status were significant correlates with residual disease. The adjusted odds ratio for residual disease with pure DCIS was 0.79, and the adjusted odds ratio for invasive ductal or lobular carcinoma (IDC/ILC) without EIC was 0.44 relative to IDC/ILC with EIC (P = 0.008). The adjusted odds ratio for residual disease with a positive initial margin versus a negative initial margin was 2.65 (P < or = 0.0001). For excisions amenable to use of the MammoSite catheter, a margin > or = 1.0 mm appeared to afford at most a 35% risk of microscopically detectable residual tumor. Evidence of EIC on excision of IDC/ILC connoted a significantly higher risk. Age did not appear to be predictive for residual disease.


Factors modifying renal tubular bicarbonate reabsorption in the dog.
1. Acute experiments were carried out on anaesthetized dogs during metabolic alkalosis produced by I.V. administration of NaHCO(3). Partial constriction of one ureter led to a significant rise in the HCO(3) (-) threshold, beyond the simultaneous value for the other kidney. The magnitude of the increase was not correlated with the reduction of glomerular filtration.2. Stop-flow analysis, following complete unilateral obstruction of urine flow, demonstrated proximal as well as distal tubular reabsorption of bicarbonate. At any given plasma P(co2) the detailed configuration of the concentration changes which developed depended on (a) the presence and concentration of mannitol, (b) the duration of urinary stasis, and (c) the plasma concentration of HCO(3) (-).3. If a solution containing 15% (w/v) mannitol was infused I.V., the HCO(3) (-) concentration in free flow urine was lower than in plasma, and it fell further during arrest of flow in the entire column of trapped fluid. If less mannitol was infused, or none at all, interruption of urine flow led to a striking increase of HCO(3) (-) concentration in the distal portion of the occluded column, and to a fall in the fluid arrested in the proximal segments.4. It was demonstrated that the HCO(3) (-) concentration attained after 2(1/2), 6, or 15 min of urinary stasis at any point in the trapped fluid column was due to the combined effects of water reabsorption and HCO(3) (-) reabsorption which proceeded independently, and with a different time course.5. If mannitol was administered the lowest urinary HCO(3) (-) concentration in the series moved progressively to a more distal location with increasing duration of urinary stasis. When HCO(3) (-) concentration peaks were present in distal fluid they were conspicuous only after short interruptions of urine flow; during extended stop-flow periods they became attenuated, or disappeared. If no mannitol was administered this did not occur.6. Provided the plasma level of HCO(3) (-) was sufficiently elevated, mannitol (15%, w/v) was administered, and the time available for reabsorption was lengthened by ureter obstruction, much larger concentration differences between plasma and trapped fluid developed than the largest that are ever found between the plasma and freely draining urine. The magnitude of the largest plasma-urine (P-U) concentration difference for HCO(3) (-) increased with intratubular ;contact time', and no limiting value was found.7. Potassium concentration in distal occluded fluid fell with prolonged duration of stasis. This was related to the slow and progressive diminution of distal HCO(3) (-) concentration. But if instead of bicarbonate a nonreabsorbable anion, such as phosphate, was the dominant distal anion, K(+) concentration in distal fractions remained high and rose further with time.


Effects of topical corticosteroid therapy on Langerhans cell antigen presenting function in human skin.
We have investigated the mechanisms by which topical corticosteroids modulate cutaneous immune reactions in man. Volunteers applied clobetasone butyrate 0.05% (Eumovate; EV), betamethasone valerate 0.1% (Betnovate; BV), clobetasol propionate 0.05% (Dermovate; DV), and control vehicles twice daily to forearm skin for 7 days. Steroid therapy significantly decreased the number of HLA-DR/T6 (CD1a) positive Langerhans cells (LCs) per mm2 in suction blister-derived epidermal sheets, expressed as a mean percentage of controls, as follows: EV 69.2%; BV 67.3%; DV 37.8%. LC antigen presenting capacity was determined in the allogeneic and autologous epidermal cell-lymphocyte reactions. The LC-dependent allostimulatory capacity of epidermal cells, expressed as a mean percentage of controls, was also significantly reduced by steroid therapy: EV 45.1%; BV 41.9%; DV 23.4%. Following therapy with clobetasol propionate 0.05%, the capacity of epidermal cells to present tetanus toxoid to, and to augment concanavalin A mediated lymphocyte stimulation of, autologous lymphocytes was reduced to 33.6% and 19.7% respectively of controls. Depression of epidermal cell allostimulatory capacity was not the result of a steroid-induced decrease in the production of epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1 by keratinocytes, since it could not be reversed by addition of exogenous interleukin 1. Indomethacin, added to block any potential prostaglandin synthesis during the culture period, did not restore the allostimulatory capacity of epidermal cells from steroid-treated sites. Addition of epidermal cells from DV-treated sites depressed the capacity of control epidermal cells to stimulate lymphocytes in the allogeneic epidermal-lymphocyte reaction. Our results demonstrate that the anti-inflammatory action of topical corticosteroids in man is associated not only with a reduction in the number of HLA-DR/T6 positive LCs, but also with a marked decrease in Langerhans cell-dependent T lymphocyte activation. The effects of the different steroids on both of these parameters correlated with their potency as determined in the standard occlusive vasoconstrictor assay. Topical corticosteroids are widely used for the treatment of inflammatory skin disorders, and inhibit not only the elicitation phase, but also the induction phase, of allergic contact dermatitis reactions.(ABSTRACT TRUNCATED AT 400 WORDS)


Genomic analysis of Thalassospira sp. SW-3-3 reveals its genetic potential for phthalate pollution remediation.
Thalassospira sp. SW-3-3 is a bacterial strain isolated from deep seawater of the Pacific Ocean at a water depth of 3112 m. It is a Gram-negative, aerobic, and curved rod-shaped bacterium belonging to the family Thalassospiraceae. In this study, we report the complete genome sequence of strain SW-3-3. It has a circular chromosome with a size of 4,764,478 bp and a G + C content of 54.7%. The genome contains 4296 protein-coding genes, 63 tRNA genes, and 12 rRNA genes. Genomic analysis shows that strain SW-3-3 contains genes and catalytic pathways relevant to phthalate metabolism. Phthalates are well-known emerging contaminants that are harmful to environments and human health. They are chemically stable compounds that are widely used in plastic products and are pervasive in our life. With the discharge of plastic pollutants, a huge number of phthalate compounds enter the ocean. The genetic information of strain SW-3-3 suggests that it has the potential to metabolize phthalates. There are 9 key enzymes in the metabolization pathway, and phthalates are finally catalyzed to produce succinyl-CoA which is further degraded through the tricarboxylic acid (TCA) cycle pathway. This genomic analysis will be helpful for further understanding of the applications of strain SW-3-3 in the remediation of phthalate pollution.


Exercise Interventions for Persistent Non-Specific Low Back Pain - Does Matching Outcomes to Treatment Targets Make a Difference? A Systematic Review and Meta-Analysis.
Exercise is a core treatment for persistent non-specific low back pain (NSLBP), but results from randomised controlled trials (RCTs) of exercise typically show only small to moderate standardised mean differences (SMDs) compared to nonexercise controls. The choice of primary outcome, and relationship to the specific targets of exercise may influence this. This systematic review aimed to explore whether primary outcomes match the exercise treatment targets used in NSLBP RCTs and the potential impact of matching on SMDs. Included RCTs were conducted with patients with persistent NSLBP, compared exercise to no exercise, with sample sizes >60 per arm. Screening, data extraction and risk of bias assessment were independently undertaken by paired reviewers. Of 19272 initial titles, 27 RCTs were included with 31 treatment targets and 6 primary outcome domains identified. Only 25% of included RCTs had primary outcomes that matched the treatment targets. SMDs of exercise versus comparison arms were observed to be larger in the matched (SMD .54 (95% Confidence Interval .23 to.85), P =.0006) compared to the unmatched category (SMD 0.22 (95% Confidence Interval .01, .44) P = .04) but this difference was not statistically significant (P = .10). These exploratory findings may have implications for future teams developing RCTs of exercise for NSLBP and warrant further investigation in larger datasets. PERSPECTIVE: This review was an exploratory study that investigated the primary outcome and treatment targets used in RCTs of exercise for NSLBP. The SMDs of the matched group were descriptively larger than those of the unmatched group, but further analysis with larger sample sizes is required to have confidence in these results.


Comparative dynamics of mixed convection heat transfer under thermal radiation effect with porous medium flow over dual stretched surface.
Due to enhanced heat transfer rate, the nanofluid and hybrid nanofluids have significant industrial uses. The principal objective of this exploration is to investigate how thermal radiation influences the velocity and temperature profile. A water-based rotational nanofluid flow with constant angular speed [Formula: see text] is considered for this comparative study. A similarity conversion is applied to change the appearing equations into ODEs. Three different nanoparticles i.e., copper, aluminum, and titanium oxide are used to prepare different nanofluids for comparison. The numerical and graphical outputs are gained by employing the bvp-4c procedure in MATLAB. The results for different constraints are represented through graphs and tables. Higher heat transmission rate and minimized skin friction are noted for triple nanoparticle nanofluid. Skin coefficients in the x-direction and y-direction have reduced by 50% in trihybrid nanofluid by keeping mixed convection levels between the range [Formula: see text]. The heat transmission coefficient with raising the levels of thermal radiation between [Formula: see text] and Prandlt number [Formula: see text] has shown a 60% increase.


The degree of certainty in brain death: probability in clinical and Islamic legal discourse.
The University of Michigan conference "Where Religion, Policy, and Bioethics Meet: An Interdisciplinary Conference on Islamic Bioethics and End-of-Life Care" in April 2011 addressed the issue of brain death as the prototype for a discourse that would reflect the emergence of Islamic bioethics as a formal field of study. In considering the issue of brain death, various Muslim legal experts have raised concerns over the lack of certainty in the scientific criteria as applied to the definition and diagnosis of brain death by the medical community. In contrast, the medical community at large has not required absolute certainty in its process, but has sought to eliminate doubt through cumulative diagnostic modalities and supportive scientific evidence. This has recently become a principal model, with increased interest in data analysis and evidence-based medicine with the intent to analyze and ultimately improve outcomes. Islamic law has also long employed a systematic methodology with the goal of eliminating doubt from rulings regarding the question of certainty. While ample criticism of the scientific criteria of brain death (Harvard criteria) by traditional legal sources now exists, an analysis of the legal process in assessing brain death, geared toward informing the clinician's perspective on the issue, is lacking. In this article, we explore the role of certainty in the diagnostic modalities used to establish diagnoses of brain death in current medical practice. We further examine the Islamic jurisprudential approach vis-à-vis the concept of certainty (yaqīn). Finally, we contrast the two at times divergent philosophies and consider what each perspective may contribute to the global discourse on brain death, understanding that the interdependence that exists between the theological, juridical, ethical, and medical/scientific fields necessitates an open discussion and active collaboration between all parties. We hope that this article serves to continue the discourse that was successfully begun by this initial interdisciplinary endeavor at the University of Michigan.


Vimentin is an important ACE2 co-receptor for SARS-CoV-2 in epithelial cells.
Vimentin is a type III intermediate filament protein, widely expressed in mesenchymal cells. Mainly located in the cytoplasm, vimentin can also appear at extracellular locations, where it may interact with bacterial or viral pathogens. In this study, we aimed at investigating the implication of vimentin in SARS-CoV-2 viral entry and the consequences on viral replication and cellular response. We showed that upon infection, vimentin was upregulated at the cell surface, where it interacts with ACE2 for SARS-CoV-2 entry. We demonstrated a direct interaction between SARS-CoV-2 spike protein, ACE2, and vimentin in epithelial cells. Inhibition of cell-surface vimentin availability resulted in reduced viral entry and cytopathogenic effects. Finally, we showed that the expression of inflammatory cytokines and chemokines was modulated by vimentin-SARS-CoV-2 interaction. In conclusion, our data suggest that cell-surface vimentin acts as a co-receptor for SARS-CoV-2.


Chemicals bathing the oxyntic gland area stimulate acid secretion in dog.
Release of gastrin is the only recognized mechanism by which chemicals in the stomach stimulate acid secretion. We report here that dietary components coming in contact only with oxyntic gland mucosa stimulate near maximal acid secretion through a local, H-sensitive mechanism that does not involve gastrin. In 4 dogs with gastric fistula and Heidenhain pouch (HP), 10% liver extract, 10% peptone, 0.4 M glycine, or Tris buffer, as control, was instilled into the HP in volumes of 40, 80, or 160 ml every 30 min. Instilled solutions were adjusted to pH 8.0 and HP acid secretion was measured by titrating a sample of the fluid recovered from the HP back to pH 8.0 with 0.2 M NaOH. Instillation of liver extract into the HP stimulated acid secretion from the HP but caused no change in serum gastrin and no change in acid secretion from the gastric fistula. The maximal response to liver extract occurred with the largest volume instilled and was 80% of the maximal response to histamine and 188% of the maximal response to pentagastrin. Expressed as per cent of maximal response to histamine, the maximal response to Tris buffer was 8%, to peptone 44%, and to glycine 14%. Intact bovine serum albumin gave no response, but after digestion by pepsin it stimulated acid secretion moderately. At pH 2.0, liver extract caused no stimulation of acid secretion. The pH threshold was about 2.5, and at pH 4.5 acid secretion was 55% of the response at pH 8.0. The response to liver extract at pH 8.0 was only minimally decreased by topical lidocaine or by intravenous atropine or metiamide. Since atropine and metiamide almost totally abolish the acid response to food in the main stomach, but do not inhibit secretion of acid evoked by instilling liver extract into the HP, there is reason to doubt whether this new mechanism operates under physiological conditions.


Effects of acute exercise on food intake and plasma free fatty acid levels.
The effects of acute exercise (swimming) on food intake (FI) and plasma free fatty acids (PFFA) were examined in male adult rats. FI decreased during the first hour after swimming; it was unchanged during the second hour; it decreased again during the third hour. Body weight decreased over the 24 hours following exercise (-1.7 +/- 1 g) while the animals gained weight during no exercise periods (+3.2 +/- 1 g). At the end of exercise, plasma glucose augmented as well as PFFA levels. An increase in sympathoadrenal activity per se and its inhibitory effect on insulin release can both be responsible for fatty acid mobilization from adipose tissue. Lipolysis could be a cause of hypophagia.


Motor cortical plasticity as a predictor of treatment response to high frequency repetitive transcranial magnetic stimulation (rTMS) for cognitive function in drug-naive patients with major depressive disorder.
There is growing evidence that repetitive transcranial magnetic stimulation (rTMS) can improve cognitive function in patients with major depressive disorder (MDD). Few biomarkers are currently available to predict cognitive response in MDD patients. This study aimed to examine whether cortical plasticity played an important role in improving cognitive deficits in MDD patients treated with rTMS. A total of 66 MDD patients and 53 healthy controls were recruited. MDD patients were randomly assigned to receive 10 Hz active or sham rTMS 5 days per week for 4 weeks. Cognitive function was assessed using the Repeatable Battery for assessing Neuropsychological Status (RBANS), while depressive symptoms were assessed with the Hamilton Rating Scale for Depression (HRSD-24) before and after treatment. We combined transcranial magnetic stimulation and muscle surface electrophysiological recording to measure plasticity in motor cortex areas in healthy controls at baseline and MDD patients before and after treatment. Compared with healthy controls, cortical plasticity was impaired in MDD patients. Moreover, cortical plasticity was correlated with RBANS total score at baseline in MDD patients. After 4-week 10 Hz rTMS treatment, the impaired cortical plasticity was restored to some extent. Interestingly, 10 Hz rTMS treatment produced effective therapeutic effects on immediate memory, attention, and RBANS total score. Pearson correlation analysis shows that improvements in plasticity were positively correlated with improvement of immediate memory and RBANS total score. Our results show for the first time that 10 Hz rTMS can effectively treat impaired cortical plasticity and cognitive impairment in MDD patients and that changes in plasticity and cognitive function are closely related, which may indicate that motor cortical plasticity may play a vital role in cognitive impairment and that cortical plasticity may serve as a potential predictive biomarker for cognitive improvement in MDD patients.


Serotonin binding in rat brain: circadian rhythm and effect of sleep deprivation.
Crude membrane fractions isolated from rat brain were used to measure specific serotonin (5-HT) binding. In untreated animals a 24 hours rhythm in 5-HT binding was evident. Sleep deprivation (SD) was applied to enhance sleep pressure. After 12, 24, and 72 hours SD the high affinity 5-HT binding, KD1 = 1-3 nM, remained unchanged, the apparent dissociation constant of the low affinity 5-HT binding, KD2 = 20-30 nM, was found to be enhanced almost by factor 2. The number of binding sites were only moderately affected by SD. If SD was followed by 1 or 4 hours recovery sleep, the dissociation constant KD2 was decreased towards control values. The brain levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were not significantly changed immediately after 72 hours SD. A statistically significant increase was found only for 5-HIAA 4 hours after 72 hours SD. The results are consistent with the hypothesis that changes in the sensitivity of 5-HT binding may be involved in the regulation of the sleep-waking cycle.


Composition and properties of the actinomycete flora in a ferralitic tropical soil (oxisol)-sugar cane ecological system.
Streptomycetes constituted about 46--48 per cent of the total aerobic microflora in the cultivated horizon of the studied ferralitic tropical soil below sugar cane plantation. This streptomycete fraction of the soil microbial community was composed of 13 (or more) species of Streptomyces (S. chromofuscus, S. chromogenus, S. diastatochromogenes, S. flavochromogenes, S. griseolus, S. nigrescens, S. phaeofaciens, S. sterilis, S. violaceus, Streptomyces sp. I--III), and Streptoverticillium (Sv. aspergilloides). None of these organisms did occur, with detectable frequency of occurrence, in the root surface region of sugar cane. Here, in the rhizoplane, we found a numerically small population of streptomycetes (about 5 per cent of the total bacterial flora), composed of two species (Streptomyces sp. IV and S. griseorubiginosus) which were, however, not detected in soil samples.


M2 Macrophage-Derived Concentrated Conditioned Media Significantly Improves Skin Wound Healing.
Macrophages, with many different phenotypes play a major role during wound healing process, secreting the cytokines crucial to angiogenesis, cell recruitment and ECM remodeling. Therefore, macrophage-derived cytokines may be attractive therapeutic resource for wound healing. To obtain a conditioned media (CM) from macrophages, human monocyte THP-1 cells were seeded on TCP or human fibroblast-derived matrix (hFDM) and they were differentiated into M1 or M2 phenotype using distinct protocols. A combination of different substrates and macrophage phenotypes produced M1- and M2-CM or M1-hFDM- and M2-hFDM-CM, respectively. Proteome microarray determines the cytokine contents in those CMs. CMs-treated human dermal fibroblast (hDFB) was analyzed using collagen synthesis and wound scratch assay. Concentrated form of the CM (CCM), obtained by high-speed centrifugation, was administered to a murine full-thickness wound model using alginate patch, where alginate patch was incubated in the M2-CCM overnight at 4 °C before transplantation. On 14 day post-treatment, examination was carried out through H&E and Herovici staining. Keratinocyte and M2 macrophages were also evaluated via immunofluorescence staining. Cytokine analysis of CMs found CCL1, CCL5, and G-CSF, where CCL5 is more dominant. We found increased collagen synthesis and faster wound closure in hDFB treated with M2-CM. Full-thickness wounds treated by M2-hFDM-CCM containing alginate patch showed early wound closure, larger blood vessels, increased mature collagen deposition, enhanced keratinocyte maturation and more M2-macrophage population. Our study demonstrated therapeutic potential of the CM derived from M2 macrophages, where the cytokines in the CM may have played an active role for enhanced wound healing.


Co-expression of vascular endothelial growth factor C (VEGF-C) and c-erbB2 in human breast carcinoma.
Vascular endothelial growth factor C (VEGF-C) has angiogenic and lymphangiogenic properties and is associated with the development of lymphatic metastases in a number of epithelial malignancies. The aim of this study was to determine VEGF-C protein expression in a series of breast carcinomas and correlate this with axillary lymph node (LN) metastases, the presence of lympho-vascular invasion (LVI), bone marrow micro-metastases (BMM) and other clinico-pathological data including oestrogen receptor (ER) and c-erbB2 status. VEGF-C expression was determined by immunohistochemistry (IHC) in 51 tumours. ER and c-erbB2 were also assessed by IHC. Bone marrow analysis was performed using a combination of immunomagnetic separation and immunocytochemistry. Overall, 30/51 (59%) of the tumours were positive for VEGF-C. There was no significant correlation between VEGF-C expression and LN status, LVI, BMM, tumour size, grade or ER status. However, there was an association between c-erbB2 and VEGF-C expression (P=0.013). The correlation between VEGF-C and c-erbB2 suggests a functional relationship and may, in part, explain the aggressive phenotype associated with c-erbB2-positive tumours.


A green approach for the extraction of diamondoids from petroleum source rock.
Extraction of adamantanes and diamantanes from petroleum source rock using nonionic surfactant was investigated and the optimum conditions for yields of the diamondoids were determined. The conventionally used accelerated solvent extraction method was compared to an innovative microwave-assisted nonionic surfactant extraction (MANSE). A three-level full factorial design of experiment (DoE) was adopted for the optimization of MANSE, involving solvent concentration, extraction temperature as well as extraction time. In-tube extraction (ITEX-2) using TENAX TA as sorbent in combination with gas chromatography-mass spectrometry (GC-MS) was used to determine the diamondoids in the extract. The results revealed that solvent concentration, extraction temperature and time have significant effects on extraction yields of the diamondoids. 0.04 M was the optimum surfactant concentration for extraction of both, adamantane and diamantane. The highest yields of the diamondoids were obtained at extraction temperature of 80 °C. The optimum extraction time for both adamantane and diamantane was 10 min. In comparison with the accelerated solvent extraction method, the results showed that MANSE is more efficient. This study has revealed that MANSE is a robust and efficient environmentally benign sample preparation method for geochemical evaluation of petroleum source rock.


[Trend in inequities in homicides in Mexico, 2000-2021: longitudinal ecological studyDesigualdades nas taxas de homicídios do México no período de 2000 a 2021: estudo ecológico longitudinal].
To document trends in inequity in homicide rates in Mexico for the period 2000-2021, at the state and national levels. An observational, longitudinal ecological study was conducted in which standardized homicide mortality rates were estimated, by municipality and sex. Municipalities were classified in five groups, according to the Social Lag Index. The absolute inequality gap was obtained, as well as differences between groups with very high and very low social lag, for each year of the study period. In the 32 states, an increase was observed in the rate of death by homicide, with higher rates among men but a greater relative increase among women (+127.86% vs. +110.03%). The absolute gap between municipalities with very high and very low social lag narrowed in the period, due to higher homicide rates in municipalities with low social lag and a modest reduction in municipalities with very high social lag. In Mexico, between 2000 and 2021, the absolute gap in deaths by homicide between municipalities with very high and very low social lag declined due to higher homicide rates in municipalities with lower social lag. It is necessary to strengthen policies and actions aimed at addressing the social determinants of interpersonal violence.


Mechanical and clinical performance of pulse-inversion tissue harmonic imaging in the superficial region.
To compare image quality between fundamental imaging (FI; transmitted and received frequencies 8.0 and 9.0 MHz, respectively) and pulse-inversion tissue harmonic imaging (PI-THI; transmitted frequencies 4.0 and 4.5 MHz, respectively) within 40 mm of the surface of the probe, we tested axial, lateral, and contrast resolution. The axial and lateral resolution were tested by use of a tissue-mimicking test object. For contrast resolution, milk agar blocks of different concentration were used for the comparison test. The lateral resolution was significantly improved by use of PI-THI at a depth of 20 to 40 mm from the surface of the phantom. Axial resolution was not reduced by use of PI-THI compared with FI. The value of the contrast index was higher in PI-THI than in FI. The researchers also evaluated the two modes clinically, by comparing the visibility of 170 cervical lymph nodes (identification of lymph node, echogenic hilus, parenchymal echogenicity). The results revealed significant advantages of PI-THI over FI for three features. This study suggests that PI-THI might be mechanically and clinically useful in the superficial region.


The potassium channel Kv4.2 regulates dendritic spine morphology, electroencephalographic characteristics and seizure susceptibility in mice.
The voltage-gated potassium channel Kv4.2 is a critical regulator of dendritic excitability in the hippocampus and is crucial for dendritic signal integration. Kv4.2 mRNA and protein expression as well as function are reduced in several genetic and pharmacologically induced rodent models of epilepsy and autism. It is not known, however, whether reduced Kv4.2 is just an epiphenomenon or a disease-contributing cause of neuronal hyperexcitability and behavioral impairments in these neurological disorders. To address this question, we used male and female mice heterozygous for a Kv.2 deletion and adult-onset manipulation of hippocampal Kv4.2 expression in male mice to assess the role of Kv4.2 in regulating neuronal network excitability, morphology and anxiety-related behaviors. We observed a reduction in dendritic spine density and reduced proportions of thin and stubby spines but no changes in anxiety, overall activity, or retention of conditioned freezing memory in Kv4.2 heterozygous mice compared with wildtype littermates. Using EEG analyses, we showed elevated theta power and increased spike frequency in Kv4.2 heterozygous mice under basal conditions. In addition, the latency to onset of kainic acid-induced seizures was significantly shortened in Kv4.2 heterozygous mice compared with wildtype littermates, which was accompanied by a significant increase in theta power. By contrast, overexpressing Kv4.2 in wildtype mice through intrahippocampal injection of Kv4.2-expressing lentivirus delayed seizure onset and reduced EEG power. These results suggest that Kv4.2 is an important regulator of neuronal network excitability and dendritic spine morphology, but not anxiety-related behaviors. In the future, manipulation of Kv4.2 expression could be used to alter seizure susceptibility in epilepsy.


Prevalence of sexually transmitted infections with Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis: findings from the National Survey of Sexual Lifestyles, Attitudes and Health, Slovenia, 2016 to 2017.
BackgroundTo inform prevention and control of sexually transmitted infections (STIs), we need reliable prevalence estimates.AimOne objective of the Slovenian National Survey of Sexual Lifestyles, Attitudes and Health was to estimate the prevalence of STIs with Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium and Trichomonas vaginalis.MethodsData were collected between October 2016 and July 2017 in a probability sample of the general population aged 18-49 years. Computer-assisted face-to-face interviewing and self-completion of questionnaires were used. Respondents were invited to provide urine samples to be tested for STIs.ResultsOf 1,929 survey participants, 1,087 individuals provided urine samples which were tested confidentially for C. trachomatis and a subset (n = 1,023) were tested anonymously for the other STIs. The prevalence of C. trachomatis was 0.5% (95% confidence interval (CI): 0.1-1.8) in men and 1.7% (95% CI: 0.9-3.2) in women. Age-specific prevalence was the highest among individuals aged 18-24 years, 2.8% (95% CI: 0.7-10.6) in men and 4.7% (95% CI: 1.7-12.3) in women. N. gonorrhoea was not detected. Prevalence of M. genitalium was 0.5% (95% CI: 0.1-2.2) in men and 0.3% (95% CI: 0.1-1.1) in women; the highest prevalence was among men aged 25-34 years (1.1%; 95% CI: 0.2-7.5) and women aged 35-49 years (0.5%; 95% CI: 0.1-2.0). T. vaginalis was detected in the sample from one woman (0.2%; 95% CI: 0.1-1.2).ConclusionThe substantial prevalence of C. trachomatis among young adults suggests gaps in testing, diagnosis and treatment.


A Comparison between Different Agro-Wastes and Carbon Nanotubes for Removal of Sarafloxacin from Wastewater: Kinetics and Equilibrium Studies.
In the current study, eco-structured and efficient removal of the veterinary fluoroquinolone antibiotic sarafloxacin (SARA) from wastewater has been explored. The adsorptive power of four agro-wastes (AWs) derived from pistachio nutshells (PNS) and Aloe vera leaves (AV) as well as the multi-walled carbon nanotubes (MWCNTs) has been assessed. Adsorbent derived from raw pistachio nutshells (RPNS) was the most efficient among the four tested AWs (%removal '%R' = 82.39%), while MWCNTs showed the best adsorptive power amongst the five adsorbents (%R = 96.20%). Plackett-Burman design (PBD) was used to optimize the adsorption process. Two responses ('%R' and adsorption capacity 'qe') were optimized as a function of four variables (pH, adsorbent dose 'AD' (dose of RPNS and MWCNTs), adsorbate concentration [SARA] and contact time 'CT'). The effect of pH was similar for both RPNS and MWCNTs. Morphological and textural characterization of the tested adsorbents was carried out using FT-IR spectroscopy, SEM and BET analyses. Conversion of waste-derived materials into carbonaceous material was investigated by Raman spectroscopy. Equilibrium studies showed that Freundlich isotherm is the most suitable isotherm to describe the adsorption of SARA onto RPNS. Kinetics' investigation shows that the adsorption of SARA onto RPNS follows a pseudo-second order (PSO) model.


Community program therapist adherence and competence in motivational enhancement therapy.
The extent to which clinicians in addiction treatment programs can implement empirically validated therapies with adequate fidelity that can be discriminated from standard counseling has rarely been evaluated. We evaluated the treatment adherence and competence of 35 therapists from five outpatient community programs who delivered either a three-session adaptation of motivational enhancement therapy (MET) or an equivalent number of drug counseling-as-usual sessions to 461 clients within a National Institute on Drug Abuse Clinical Trial Network multi-site effectiveness protocol. MET therapists were carefully prepared to implement MET using a combination of expert-led intensive workshop training followed by program-based clinical supervision. Independent rating of sessions demonstrated that the adherence and competence items were very reliable (mean interclass correlation coefficients for adherence=.89 and competence=.81) and converged to form two a priori defined skill factors conceptually related to motivational interviewing. Moreover, the factors discriminated between MET therapists and those who delivered drug counseling-as-usual sessions in predicted ways, and were significantly related to in-session change in client motivation and some client treatment outcomes (percent negative drug urine screens). These findings demonstrate the reliability and validity of evaluating motivational interviewing fidelity and suggest that the combination of expert-led workshops followed by program-based clinical supervision may be an effective method for disseminating motivational interviewing in community treatment programs.


Clinical Relevance of Sleep Duration: Results from a Cross-Sectional Analysis Using NHANES.
To assess the clinical relevance of sleep duration, hours slept were compared by health status, presence of insomnia, and presence of depression, and the association of sleep duration with BMI and cardiovascular risk was quantified. Cross-sectional analysis of subjects in the US National Health and Nutrition Examination Surveys using adjusted linear and logistic regressions. A total of 22,281 adults were included, 37% slept ≤ 6 hours, 36% were obese, and 45% reported cardiovascular conditions. Mean sleep duration was 6.87 hours. Better health was associated with more hours of sleep. Subjects with poor health reported sleeping 46 min, (95% CI -56.85 to -35.67) less than subjects with excellent health. Individuals with depression (vs. not depressed) reported 40 min less sleep, (95% CI -47.14 to -32.85). Individuals with insomnia (vs. without insomnia) reported 39 min less sleep, (95% CI -56.24 to -22.45). Duration of sleep was inversely related to BMI; for every additional hour of sleep, there was a decrease of 0.18 kg/m(2) in BMI, (95% CI -0.30 to -0.06). The odds of reporting cardiovascular problems were 6.0% lower for every hour of sleep (odds ratio = 0.94, 95% CI [0.91 to 0.97]). Compared with subjects who slept ≤ 6 h, subjects who slept more had lower odds of reporting cardiovascular problems, with the exception of subjects ≥ 55 years old who slept ≥ 9 hours. Long sleep duration is associated with better health. The fewer the hours of sleep, the greater the BMI and reported cardiovascular disease. A difference of 30 minutes of sleep is associated with substantive impact on clinical well-being.


Fetal bradycardia due to intrathecal opioids for labour analgesia: a systematic review.
To evaluate fetal and maternal adverse effects of intrathecal opioid analgesia during labour. A systematic search was performed, in Medline, Embase, the Cochrane Library, bibliographies, and personal contact with authors, in any language, up to February 2001. selection Full reports on randomised comparisons of any analgesia with intrathecal opioid (experimental group) with any non-intrathecal opioid regimen (control group) during labour. Dichotomous data from 24 trials (3513 women). With intrathecal opioids, there was a significant increase in the risk of fetal bradycardia: odds ratio 1.8 (95% confidence interval 1.0 to 3.1), number-needed-to-harm 28. The risk of caesarean section due to fetal heart rate abnormalities was similar (6.0% versus 7.8%). The incidence of pruritus was significantly higher with intrathecal opioids: relative risk 29.6 (95% CI 13.6 to 64.6), number-needed-to-harm 1.7. Intrathecal opioids for labour increase the risk of fetal bradycardia and maternal pruritus. The risk of subsequent caesarean section is not increased.


Encephalopathy in a patient with loiasis treated with albendazole: A case report.
Loiasis is a vector-borne parasitic infection endemic across many areas of Central and West Africa. Its treatment is tricky due to the risk of serious neurologic adverse events occurring after the administration of microfilaricidal drugs, like diethylcarbamazine or ivermectin, in subjects with high pre-treatment microfilarial load. Albendazole is currently recommended to slowly reduce microfilaremia before curative regimen is prescribed. We report the case of a 25-year-old man from Guinea-Conakry who was incidentally diagnosed with highly microfilaremic Loa loa infection. A three weeks regimen of albendazole was prescribed. Minor neurologic side effects occurred after two weeks of administration, while serious encephalopathy developed one week later. Clinical and electroencephalographic features of the patient resembled those of an immune-mediated encephalitis. After exclusion of other causes of encephalopathy, treatment-related Loa loa encephalopathy induced by albendazole was suspected. Corticosteroid treatment was administered and the patient recovered. Our case confirms that Loa loa treatment-related encephalopathy may occur even during albendazole treatment. The clinical and electroencephalographic similarities between Loa loa albendazole-related encephalopathy and immune-mediated encephalitis suggest the possibility of an underlying inflammation-based pathogenesis. Although corticosteroid administration is not recommended in Loa loa ivermectin-induced encephalopathy, in this case of Loa loa albendazole-induced encephalopathy it may have played a therapeutic role.


Negative Social Relationships Predict Posttraumatic Stress Symptoms Among War-Affected Children Via Posttraumatic Cognitions.
Post traumatic cognitions (PTCs) are important determinants of post traumatic stress symptoms (PTS symptoms). We tested whether risk factors of PTS symptoms (trauma, demographics, social and family-related factors) predict PTCs and whether PTCs mediate the association between risk factors and PTS symptoms among war-affected children. The participants were 240 Palestinian children 10-12 years old, half boys and half girls, and their parents. Children reported about psychological maltreatment, sibling and peer relations, war trauma, PTCs, PTS symptoms, and depression. Parents reported about their socioeconomic status and their own PTS symptoms. The associations between the variables were estimated in structural equation models. In models which included all the variables, PTCs were predicted by and mediated the effects of psychological maltreatment, war trauma, sibling conflict, and peer unpopularity on PTS symptoms. Other predictors had statistically non-significant effects. Psychological maltreatment had the largest indirect effect (b* = 0.29, p = 0.002) and the indirect effects of war trauma (b* = 0.10, p = 0.045), sibling conflict (b* = 0.10, p = 0.045), and peer unpopularity (b* = 0.10, p = 0.094) were lower and about the same size. Age-salient social relationships are potentially important in the development of both PTCs and PTS symptoms among preadolescents. Furthermore, PTCs mediate the effects of the risk factors of PTS symptoms. The causality of the associations among the variables is not established but it could be studied in the future with interventions which improve the negative aspects of traumatized children's important social relationships.


A critical review of Roxadustat formulations, solid state studies, and analytical methodology.
This review aims to collate information about the analytical methodologies, bioanalytical methodologies, pharmaceutical formulations, solid-state studies, and the current and future market scenario for a relatively new class of drugs, Roxadustat. Roxadustat is a hypoxia-inducible factor propyl hydroxylase inhibitor that significantly increases blood hemoglobin via the action of transcriptional activator HIF. As the molecule has a promising role in stimulating erythropoiesis, it is considered an ideal therapeutic agent for patients with anemia. In the current review, an attempt has been made to compile the pharmacological, pharmacokinetic, and pharmacodynamic characteristics of Roxadustat and systematically present product development data. This drug has several polymorphs of cocrystal, co-former, and salt, which have been explained in detail in the current work. The comprehensive review summarizes all the chromatographic methods and is presented in table form. This review has extensively covered Liquid chromatography-tandem mass spectrometry methods used to analyze Roxadustat in the biological matrix. The literature needs more data on forced degradation study, impurity profiling, gas chromatography, analytical methods for assay, dissolution, and different formulation aspects of Roxadustat.


Hyaluronan fragments induce IFNβ via a novel TLR4-TRIF-TBK1-IRF3-dependent pathway.
The extracellular matrix plays a critical role in insuring tissue integrity and water homeostasis. However, breakdown products of the extracellular matrix have emerged as endogenous danger signals, designed to rapidly activate the immune system against a potential pathogen breach. Type I interferons play a critical role in the immune response against viral infections. In the lungs, hylauronan (HA) exists as a high molecular weight, biologically inert extracellular matrix component that is critical for maintaining lung function. When lung tissue is injured, HA is broken down into lower molecular weight fragments that alert the immune system to the breach in tissue integrity by activating innate immune responses. HA fragments are known to induce inflammatory gene expression via TLR-MyD88-dependent pathways. Primary peritoneal macrophages from C57BL/6 wild type, TLR4 null, TLR3 null, MyD88 null, and TRIF null mice as well as alveolar and peritoneal macrophage cell lines were stimulated with HA fragments and cytokine production was assessed by rt-PCR and ELISA. Western blot analysis for IRF3 was preformed on cell lysates from macrophages stimulate with HA fragments We demonstrate for the first time that IFNβ is induced in murine macrophages by HA fragments. We also show that HA fragments induce IFNβ using a novel pathway independent of MyD88 but dependent on TLR4 via TRIF and IRF-3. Overall our findings reveal a novel signaling pathway by which hyaluronan can modulate inflammation and demonstrate the ability of hyaluronan fragments to induce the expression of type I interferons in response to tissue injury even in the absence of viral infection. This is independent of the pathway of the TLR2-MyD88 used by these matrix fragments to induce inflammatory chemokines. Thus, LMW HA may be modifying the inflammatory milieu simultaneously via several pathways.


Racial/Ethnic Disparities in Hospital Admissions from COVID-19 and Determining the Impact of Neighborhood Deprivation and Primary Language.
Background Despite past and ongoing efforts to achieve health equity in the United States, persistent disparities in socioeconomic status along with multilevel racism maintain disparate outcomes and appear to be amplified by COVID-19. Objective Measure socioeconomic factors and primary language effects on the risk of COVID-19 severity across and within racial/ethnic groups. Design Retrospective cohort study. Setting Health records of 12 Midwest hospitals and 60 clinics in the U.S. between March 4, 2020 to August 19, 2020. Patients PCR+ COVID-19 patients. Exposures Main exposures included race/ethnicity, area deprivation index (ADI), and primary language. Main Outcomes and Measures The primary outcome was COVID-19 severity using hospitalization within 45 days of diagnosis. Logistic and competing-risk regression models (censored at 45 days and accounting for the competing risk of death prior to hospitalization) assessed the effects of neighborhood-level deprivation (using the ADI) and primary language. Within race effects of ADI and primary language were measured using logistic regression. Results 5,577 COVID-19 patients were included, 866 (n=15.5%) were hospitalized within 45 days of diagnosis. Hospitalized patients were older (60.9 vs. 40.4 years, p<0.001) and more likely to be male (n=425 [49.1%] vs. 2,049 [43.5%], p=0.002). Of those requiring hospitalization, 43.9% (n=381), 19.9% (n=172), 18.6% (n=161), and 11.8% (n=102) were White, Black, Asian, and Hispanic, respectively. Independent of ADI, minority race/ethnicity was associated with COVID-19 severity; Hispanic patients (OR 3.8, 95% CI 2.72-5.30), Asians (OR 2.39, 95% CI 1.74-3.29), and Blacks (OR 1.50, 95% CI 1.15-1.94). ADI was not associated with hospitalization. Non-English speaking (OR 1.91, 95% CI 1.51-2.43) significantly increased odds of hospital admission across and within minority groups. Conclusions Minority populations have increased odds of severe COVID-19 independent of neighborhood deprivation, a commonly suspected driver of disparate outcomes. Non-English-speaking accounts for differences across and within minority populations. These results support the continued concern that racism contributes to disparities during COVID-19 while also highlighting the underappreciated role primary language plays in COVID-19 severity across and within minority groups.


Association of preoperative frailty and postoperative delirium in older cancer patients undergoing elective abdominal surgery: A prospective observational study in Taiwan.
Postoperative delirium (POD) is a common surgical complication in elderly patients. As frailty is a relatively novel concept, its clinical significance for POD has seldom been examined. This study aimed to investigate the association between frailty and POD in aged cancer patients undergoing elective abdominal surgery in Taiwan. We prospectively enrolled 345 consecutive patients aged ≥65 years with newly diagnosed cancer who underwent elective abdominal surgery between 2016 and 2018. Frailty assessment was performed using the Comprehensive Geriatric Assessment (CGA). POD was assessed daily using the Confusion Assessment Method from postoperative day 1 until discharge. Patients were allocated into fit and frail groups. POD occurred in 19 (5.5%) of 345 patients. POD incidence was 1.6%, 3.1%, 4.8%, 11.5%, and 10.0% in patients with 0, 1, 2, 3, and 4+ frail conditions, respectively, which presented a positive linear correlation among patients with an increased number of frail conditions and POD incidence. Based on CGA, 159 (46.1%) and 186 (53.9%) patients were allocated to fit and frail groups, respectively. POD incidence was 2.5% and 8.1% for the fit and frail groups, respectively. Frailty status was an independent risk factor for POD occurrence in multivariate analysis. Our study identified frailty as an independent risk factor for POD in aged Taiwanese cancer patients undergoing elective abdominal surgery. Given the high prevalence of frailty among older cancer patients, preoperative assessment is important to identify high risk of POD and to improve the quality of postoperative care.


Recent advances in gout drugs.
Gout is an autoinflammatory disease caused by the deposition of urate crystals. As the most common inflammatory arthritis, gout has a high incidence and can induce various severe complications. At present, there is no effective cure method in the world. With the deepening of medical research, gout treatment drugs continue to progress. In this review, we provide a landscape view of the current state of the research on gout treatment drugs, including the research progress of anti-inflammatory and analgesic drugs, drugs that promote uric acid excretion, and drugs that inhibit uric acid production. We mainly emphasize the understanding of gout as an auto-inflammatory disease and the discovery strategy of related gout drugs to provide a systematic and theoretical basis for the new exploration of gout drug discovery.


Chikungunya-related arthritis: case report and review of the literature.
Chikungunya fever often presents with severe arthritis/arthralgias, high fever, myalgias, headache, and maculopapular rash (Chow et al., 2011 [1]; Das et al., 2010 [2]; Mizuno et al., 2011 [3]; Powers, 2010 [4]; Sissoko et al., 2010 [5]; Staples et al., 2009 [6]). Persistent arthritis/arthralgias commonly develop after symptomatic infection and are the most common long-term complication (Chow et al., 2011 [1]; Powers, 2010 [4]; Sissoko et al., 2010 [5]; Staples et al., 2009 [6]). The small joints are most often affected in a symmetric pattern that can mimic adult rheumatoid arthritis (RA) (Mizuno et al., 2011 [3]; Bouquillard and Combe, 2009 [7]; Chabbra et al., 2008 [8]; Jaffar-Bandjee et al., 2009 [9]; Simon et al., 2007 [10]). We present a case of Chikungunya virus (CHIKV)-induced arthritis and review the literature surrounding Chikungunya-induced arthritis/arthralgias and associated musculoskeletal (MSK) manifestations. A Medline search was completed from 1946--November 2011. Key words included Chikungunya virus and arthritis. A PubMed search was completed from 1996--November 2011. Search terms included Chikungunya virus, etiology, and fever. Searches were limited to humans and English language publications. Additional relevant articles were obtained from the reference lists.


Polyphenols of Melaleuca quinquenervia leaves--pharmacological studies of grandinin.
Four polyphenolic acid derivatives and three ellagitannins were isolated from the leaves of Melaleuca quinquenervia (Clav.) S. T. Blake for the first time. Their structures were elucidated as gallic acid (1), ellagic acid (2), 3-O-methylellagic acid (3), 3,4,3'-tri-O-methylellagic acid (4), 2,3-O-hexahydroxydiphenoyl-(alpha/beta)-D-(4)C(1)-glucopyranose (5), castalin (6) and grandinin (7) on the basis of chemical, mass spectrometric (-ve ESI-MS) and spectroscopic (UV, (1)H-, (13)C NMR, (1)H,(1)H-, (1)H,(13)C-COSY, (1)H,(1)H-TOCSY and HMBC) analyses. Grandinin (the major compound) showed radical scavenging properties by its reaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical [EC(50) = 4.3 +/- 0.3 micro g mL(-1)]. It was found to be relatively nontoxic in mice [LD(50) = 316 mg Kg(-1) b.wt.]. It exhibited a significant dose-dependent (35-70 mg Kg(-1)) hypoglycemic effect by significantly reducing blood glucose level in basal condition and after heavy glucose load in normal mice. Moreover, it reduced the elevated blood glucose level in STZ-induced diabetic mice. In addition, grandinin reduced the elevated blood urea nitrogen and serum lipid peroxides in STZ-induced diabetic mice.


Cell cycle rate and sister chromatid exchange profile in polyethylene glycol-exposed/unexposed Bloom syndrome and normal cells. A co-culture study.
A delay in cell cycle progression and a decrease in sister chromatid exchange (SCE) frequency was observed in Bloom syndrome (BS) cells when exposed to polyethylene glycol (PEG) treatment followed by co-cultivation with unexposed normal cells, whereas the SCE rate of both normal and BS cells increased when PEG-exposed normal cells were co-cultured with unexposed BS high SCE cells. This indicates the role of normal cells, probably of cell membranes (which were disturbed or disrupted by PEG treatment), in complementing the deficiency of BS cells under co-culture conditions, and suggests that BS cells may be deficient in membrane bound factor(s) present in normal cells.


Molecular characterization of β-tubulin gene associated with benzimidazole resistance in larvae of field isolates of Parascaris (Nematoda: Ascarididae).
Since the past 2 decades, an increasing number of resistance to the Benzimidazoles (BZs) have been reported in nematode parasites of livestock. More recently, detection of single-nucleotide polymorphisms (SNPs) at codons of 167, 198 or 200 of the β-tubulin gene has been attributed to the occurrence of resistance. In the present study, we investigated the presence of those SNPs in the β-tubulin isotype-1 gene in different isolates of Parascaris in horse. Also, the mitochondrial (mt) and ribosomal genes were sequenced for species confirmation of the isolates. The analysis of sequences inferred from COII gene confirmed that those isolates were P. equorum. The distance between mt genes obtained here and several ascarid species in equids and other hosts suggests the need for the combination of more genetic data with morphologic and other diagnostic measures. The analysis on β-tubulin isotype-1 gene revealed no resistance-related SNPs or substitutions at the expected codon positions and selection pressure with BZs has not occurred for Parascaris worms. Although the molecular data showed the susceptibility of Parascaris isolates against BZs, other mechanisms of resistance should be also investigated to confirm the validity of molecular results.


Competence imagery: a case study treating emetophobia.
An emetophobic child is nonresponsive to conventional systematic desensitization and has her anxiety responses counterconditioned by using Competence Imagery instead of physical relaxation responses while progressing through her fear hierarchy.


Simultaneous Liver-Kidney Transplantation in Adults: A Single-center Experience Comparing Results With Isolated Liver Transplantation.
After introduction of the Model for End-Stage Liver Disease (MELD) score in 2002, a worldwide increasing number of simultaneous liver-kidney transplantations (SLKTx) has been observed. However, organ shortage puts into question the allocation of 2 grafts to 1 recipient. This retrospective, single-center study compared SLKTx results with isolated liver transplantation (LTx). Between 1995 and 2013, 37 SLKTx were performed in adult recipients. Every SLKTx was matched by donor age (±5 years) and transplantation date with 2 LTx (n = 74). Pretransplant, intraoperative, and post-transplant variables were collected; liver graft and patient survivals were calculated. As expected, donor age was similar in the 2 groups (median, 39.7 years), whereas serum creatinine level, glomerular filtration rate, and MELD and D-MELD (donor age*MELD) scores were significantly higher in the SLKTx group. SLKTx had longer waiting list time (P = .0034) as well as higher surgical difficulty, testified by more blood transfusions (P = .0083), increased use of classic caval reconstruction (P = .0024), and more frequent need of abdominal packing for bleeding control (P = .0003). In addition, duration of hospital stay (P < .0001), second-look surgery (P = .0082), post-transplant dialysis (P < .0001), and post-transplant infections (P = .04) were significantly greater in SLKTx group. Acute rejection episodes involving the liver were significantly less in SLKTx than in LTx (14% vs 41%; P = .0045). Liver graft and patient survival at 10 years after transplantation was similar in the 2 groups (liver graft: SLKTx, 80% vs LTx, 77% [P = .85]; patient: SLKTx, 86% vs LTx, 79% [P = .56]). Despite being technically challenging, SLKTx provided excellent long-term results and was shown to be an effective use of liver grafts.


Conservative management of chronic interstitial cystitis: transcutaneous electrical nerve stimulation and transurethral resection.
Transcutaneous electrical nerve stimulation was used in a prospective series of 23 patients with classical interstitial cystitis. This treatment reduced pain in 18 patients and urinary frequency returned to normal in 8. Four women with a history of cystitis for 1 or 2 decades had no symptoms during transcutaneous electrical nerve stimulation for 7 or more years and lesions disappeared or were hardly detectable. A 2 to 3-fold increase in bladder capacity with anesthesia also was registered. Complete transurethral resection of visible lesions in 30 patients resulted in initial disappearance of pain in all and a decrease in urinary frequency in 21. The mode of action of the 2 methods and registered complications are discussed.


Increase of interferon antiviral activity by exogenous cyclic adenosine-3':5'-monophosphate (cAMP).
Some effects of cAMP on replication of Semliki Forest Virus in chick embryo fibroblast cell cultures are described. Depending on concentration, the incorporation of [3H]-uridine into viral RNA or the formation of plaque-forming units is inhibited; the highest concentration tested was 8 mM. Cyclic AMP has an effect of its own and increases the Interferon action in the lower concentration ranges of Interferon (up to 1 unit/ml). The effect of cyclic AMP is fast, needs no induction and is also visible in late phases of viral replication. However, these experiments do not establish a causal relation between cAMP and Interferon.


Proteomic analysis of the periodontal pathogen Prevotella intermedia secretomes in biofilm and planktonic lifestyles.
Prevotella intermedia is an important species associated with periodontitis. Despite the remarkable clinical significance, little is known about the molecular basis for its virulence. The aim of this study was to characterize the secretome of P. intermedia in biofilm and planktonic life mode. The biofilm secretome showed 109 proteins while the planktonic secretome showed 136 proteins. The biofilm and the planktonic secretomes contained 17 and 33 signal-peptide bearing proteins, 13 and 18 lipoproteins, respectively. Superoxide reductase, sensor histidine kinase, C40 family peptidase, elongation factor Tu, threonine synthase etc. were unique to biofilm. Of the ~ 30 proteins with predicted virulence potential from biofilm and planktonic secretomes, only 6 were common between the two groups, implying large differences between biofilm and planktonic modes of P. intermedia. From Gene Ontology biofilm secretome displayed a markedly higher percent proteins compared to planktonic secretome in terms of cellular amino acid metabolic process, nitrogen compound metabolic process etc. Inflammatory cytokine profile analysis revealed that only the biofilm secretome, not the planktonic one, induced important cytokines such as MIP-1α/MIP-1β, IL-1β, and IL-8. In conclusion, the revealed differences in the protein profiles of P. intermedia biofilm and planktonic secretomes may trigger further questions about molecular mechanisms how this species exerts its virulence potential in the oral cavity.


The role of biomarkers in bladder preservation management of muscle-invasive bladder cancer.
Patients with localized muscle-invasive bladder cancer (MIBC) can choose to undergo either neoadjuvant chemotherapy followed by radical cystectomy or radiation therapy-based bladder preservation treatment modality with subsequent close cystoscopic surveillance with salvage cystectomy reserved for patients with evidence of local disease recurrence. At the present time, the decision regarding bladder-directed local therapy for MIBC is based on physicians' and patients' preferences, and does not take into account tumor biology. Predictive biomarkers, once validated, could offer a more patient-centered and biology-driven selection of bladder-directed therapies. We provide a narrative review of clinical data pertaining to the biomarkers in bladder preservation management of MIBC. There are currently no validated and clinically used biological markers used for stratification of radical bladder treatment and selection of bladder-preserving therapies. This article summarizes biomarkers that could have a potential clinical utility-PD-L1, molecular subtypes, Ki-67, MRE-11 and markers of hypoxia-and offers a hypothetical pathway model for a marker-driven precision management of medically operable patients with a newly diagnosed MIBC. When selecting the optimal cancer treatment, both patient and tumor factors need to be considered. Once validated, biological markers will help clinicians tailor the management of MIBC to individual patients.


Vesicles-on-a-chip: A universal microfluidic platform for the assembly of liposomes and polymersomes.
In this study, we present a PDMS-based microfluidic platform for the fabrication of both liposomes and polymersomes. Based on a double-emulsion template formed in flow-focusing configuration, monodisperse liposomes and polymersomes are produced in a controlled manner after solvent extraction. Both types of vesicles can be formed from the exact same combination of fluids and are stable for at least three months under ambient storage conditions. By tuning the flow rates of the different fluid phases in the flow-focusing microfluidic design, the size of the liposomes and polymersomes can be varied over at least one order of magnitude. This method offers a versatile tool for future studies, e.g., involving the encapsulation of biological agents and the functionalization of artificial cell membranes, and might also be applicable for the controlled fabrication of hybrid vesicles.