Biodegradation of tricalcium phosphate ceramics by osteoclasts.
Biodegradation of tricalcium phosphate (TCP) ceramics was observed through mixed culture of osteoclasts and TCP discs in vitro in this study. Osteoclasts were isolated from newborn SD rat's marrow of long bone and cultured on TCP discs. The culture terminated at the 48th h and 96th h respectively. Under an inverted microscope, the osteoclasts imparted round or oval body with multinuclear and many thin processes. These cells were positively stained for tartrate-resistance acid phosphatase (TRAP). Scanning electron microscope showed that many resorption lacunae on TCP disc surface and their diameters were smaller than 20 microns. Osteoclasts were located in the lacunae. At the 96th h, the resorption lacunae become larger and osteoclasts showed degeneration. It is suggested that osteoclasts possess ability to re-absorb TCP ceramics under in vitro culturing condition.


Modulation of DNA repair and recombination by the bacteriophage lambda Orf function in Escherichia coli K-12.
The orf gene of bacteriophage lambda, fused to a promoter, was placed in the galK locus of Escherichia coli K-12. Orf was found to suppress the recombination deficiency and sensitivity to UV radiation of mutants, in a Delta(recC ptr recB recD)::P(tac) gam bet exo pae cI DeltarecG background, lacking recF, recO, recR, ruvAB, and ruvC functions. It also suppressed defects of these mutants in establishing replication of a pSC101-related plasmid. Compared to orf, the recA803 allele had only small effects on recF, recO, and recR mutant phenotypes and no effect on a ruvAB mutant. In a fully wild-type background with respect to known recombination and repair functions, orf partially suppressed the UV sensitivity of ruvAB and ruvC mutants.


Structural studies of biologically active glycosylated polyamidoamine (PAMAM) dendrimers.
The partial modification of carboxylic acid terminated polyamidoamine (PAMAM) dendrimers with glucosamine has been reported to give dendrimer glucosamine conjugates novel immuno-modulatory and anti-angiogenic properties. Experimental analysis of these glycosylated dendrimers showed that, on average, eight glucosamine molecules were covalently bound to each dendrimer. In order to better understand the surface loading and distribution of these glucosamine molecules, molecular reactivity was determined by evaluation of electronic properties using frontier molecular orbital theory (FMOT) and molecular dynamics simulations. It was shown that the surface loading and distribution of zero length amide bond-conjugated glucosamine molecules was determined by both electronic effects and by the different dynamic conformations adopted by the modified dendrimer during the incremental addition of glucosamine. Importantly, the structural features and the dynamic behavior of the partially glycosylated generation 3.5 PAMAM dendrimer showed that its flexibility and polarity changed with the incremental addition of glucosamine. These peripheral glucosamine molecules remained available on the dendrimer's surface for interaction with the biological target.


Morphological abnormalities of the thalamus in youths with attention deficit hyperactivity disorder.
The role of the thalamus in the genesis of attention deficit hyperactivity disorder (ADHD) remains poorly understood. The authors used anatomical MRI to examine the morphology of the thalamus in youths with ADHD and healthy comparison youths. The authors examined 46 youths with ADHD and 59 comparison youths 8-18 years of age in a cross-sectional case-control study. Conventional volumes and measures of surface morphology of the thalamus served as the main outcome measures. A mixed-effects model comparing whole thalamic volumes revealed no significant differences between groups. Maps of the thalamic surface revealed significantly smaller regional volumes bilaterally in the pulvinar in youths with ADHD relative to comparison subjects. Post hoc analyses showed that ADHD patients who received stimulants (N=31) had larger conventional thalamic volumes than untreated youths with ADHD, and maps of the thalamic surface showed enlargement over the pulvinar in those receiving stimulants. Smaller regional volumes in the right lateral and left posterior thalamic surfaces were associated with more severe hyperactivity symptoms, whereas larger regional volumes in the right medial thalamic surfaces were associated with more severe symptoms of inattention. These findings demonstrate reduced pulvinar volumes in youths with ADHD and indicate that this same area is relatively enlarged in patients treated with stimulants compared to those untreated. Associations of hyperactivity scores with smaller regional volumes on the lateral thalamic surface and inattention scores with larger regional volumes on the medial thalamic surface suggest the differential involvement of thalamic subcircuits in the pathogenesis of differing ADHD symptoms.


Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex.
The "beta-catenin destruction complex" is central to canonical Wnt/beta-catenin signaling. The scaffolding protein Axin and the tumor suppressor adenomatous polyposis coli protein (APC) are critical components of this complex, required for rapid beta-catenin turnover. We determined the crystal structure of a complex between beta-catenin and the beta-catenin-binding domain of Axin (Axin-CBD). The Axin-CBD forms a helix that occupies the groove formed by the third and fourth armadillo repeats of beta-catenin and thus precludes the simultaneous binding of other beta-catenin partners in this region. Our biochemical studies demonstrate that, when phosphorylated, the 20-amino acid repeat region of APC competes with Axin for binding to beta-catenin. We propose that a key function of APC in the beta-catenin destruction complex is to remove phosphorylated beta-catenin product from the active site.


Reproducibility of drug-induced effects on the contractility of an engineered heart tissue derived from human pluripotent stem cells.
Introduction: Engineered heart tissues (EHTs) are three-dimensional culture platforms with cardiomyocytes differentiated from human pluripotent stem cells (hPSCs) and were designed for assaying cardiac contractility. For drug development applications, EHTs must have a stable function and provide reproducible results. We investigated these properties with EHTs made with different tissue casting batches and lines of differentiated hPSC-cardiomyocytes and analyzed them at different times after being fabricated. Methods: A video-optical assay was used for measuring EHT contractile outputs, and these results were compared with results from motion traction analysis of beating hPSC-cardiomyocytes cultured as monolayers in two-dimensional cultures. The reproducibility of induced contractile variations was tested using compounds with known mechanistic cardiac effects (isoproterenol, EMD-57033, omecamtiv mecarbil, verapamil, ranolazine, and mavacamten), or known to be clinically cardiotoxic (doxorubicin, sunitinib). These drug-induced variations were characterized at different electrical pacing rates and variations in intracellular calcium transients were also assessed in EHTs. Results: To ensure reproducibility in experiments, we established EHT quality control criteria based on excitation-contraction coupling and contractile sensitivity to extracellular calcium concentration. In summary, a baseline contractile force of 0.2 mN and excitation-contraction coupling of EHTs were used as quality control criteria to select suitable EHTs for analysis. Overall, drug-induced contractile responses were similar between monolayers and EHTs, where a close relationship was observed between contractile output and calcium kinetics. Contractile variations at multiple time points after adding cardiotoxic compounds were also detectable in EHTs. Discussion: Reproducibility of drug-induced effects in EHTs between experiments and relative to published work on these cellular models was generally observed. Future applications for EHTs may require additional mechanistic criteria related to drug effects and cardiac functional outputs to be measured in regard to specific contexts of use.


A simple method to estimate photosynthetic radiation use efficiency of canopies.
Photosynthetic radiation use efficiency (PhRUE) over the course of a day has been shown to be constant for leaves throughout a general canopy where nitrogen content (and thus photosynthetic properties) of leaves is distributed in relation to the light gradient. It has been suggested that this daily PhRUE can be calculated simply from the photosynthetic properties of a leaf at the top of the canopy and from the PAR incident on the canopy, which can be obtained from weather-station data. The objective of this study was to investigate whether this simple method allows estimation of PhRUE of different crops and with different daily incident PAR, and also during the growing season. The PhRUE calculated with this simple method was compared with that calculated with a more detailed model, for different days in May, June and July in California, on almond (Prunus dulcis) and walnut (Juglans regia) trees. Daily net photosynthesis of 50 individual leaves was calculated as the daylight integral of the instantaneous photosynthesis. The latter was estimated for each leaf from its photosynthetic response to PAR and from the PAR incident on the leaf during the day. Daily photosynthesis of individual leaves of both species was linearly related to the daily PAR incident on the leaves (which implies constant PhRUE throughout the canopy), but the slope (i.e. the PhRUE) differed between the species, over the growing season due to changes in photosynthetic properties of the leaves, and with differences in daily incident PAR. When PhRUE was estimated from the photosynthetic light response curve of a leaf at the top of the canopy and from the incident radiation above the canopy, obtained from weather-station data, the values were within 5 % of those calculated with the more detailed model, except in five out of 34 cases. The simple method of estimating PhRUE is valuable as it simplifies calculation of canopy photosynthesis to a multiplication between the PAR intercepted by the canopy, which can be obtained with remote sensing, and the PhRUE calculated from incident PAR, obtained from standard weather-station data, and from the photosynthetic properties of leaves at the top of the canopy. The latter properties are the sole crop parameters needed. While being simple, this method describes the differences in PhRUE related to crop, season, nutrient status and daily incident PAR.


Identifying Correlates of Peer and Faculty/Staff Sexual Harassment in US Students.
Sexual harassment and its negative consequences continue to affect a large percentage of higher education students in the US. Previous research has identified a limited number of harassment risk factors, and has generally not examined them in combination. In this study, an expanded set of individual, relationship, and community-level risk factors were examined using hurdle models and classification and regression tree (CART) analyses to identify key risk factors for peer and faculty/staff sexual harassment. Secondary data analysis was conducted using data from a sample of 9,285 students from 18 two-year and four-year schools in Minnesota. CART analyses indicated that, for peer sexual harassment, being younger; consuming alcohol more than once a month; attending a four-year school; being transgender, genderqueer, self-identified, or a cisgender woman; and having experienced bullying were the most important risk factors for peer harassment on campus. For faculty/staff harassment, being gay, lesbian, bisexual, questioning, or having a self-identified sexual orientation was the most important risk factor. These and other risk factors were significant in the hurdle models. More research is needed to understand why these factors are associated with harassment. Limitations and implications for prevention programming at higher education institutions are discussed.


Superhydrophobic Nickel-Electroplated Carbon Fibers for Versatile Oil/Water Separation with Excellent Reusability and High Environmental Stability.
Superhydrophobic filtrating materials have been widely developed for rapid removal or collection of oils from oil/water mixture due to the increasing water pollution caused by oil spills and oil-contaminated wastewater. However, poor reusability, superhydrophobic failure in harsh environments, and that only heavy oil or light oil was separated from water seriously restricted their practical application. Herein, superhydrophobic carbon fibers were first fabricated using a novel nickel electroplating for versatile oil/water separation with excellent reusability and high environmental stability. The interconnected nanometer-scale nickel grains formed on the micrometer-scale fibers and fluoroalkylsilane molecules enabled the fibers to be superhydrophobic with the water contact angle (CA) of ∼159.1° and superoleophilic with the oil CA of ∼0°. The nickel coating contributed to the improvement of the bonding strength, tensile strength, and oxidation resistance of the fibers. The as-prepared fibers could be applied for the separation of heavy or light oil/water mixtures with separation efficiencies above 99.1%, during which the oil content in the separated water all remained below 78 ppm. The fibers also realized the highly efficient separation of dichloromethane and various harsh environmental solutions such as hot water, acid, alkali, and salt. The superhydrophobicity of the fluorinated nickel-coated carbon fibers still remained even after 100 cycles of separation and 24 months of storage in air, demonstrating outstanding durability of the fibers. These novel superhydrophobic carbon fibers had promising potentials for versatile oil/water separation in practical applications.


From FHB Resistance QTLs to Candidate Genes Identification in Triticum aestivum L.
Fusarium head blight (FHB) caused by Fusarium graminearum is a worldwide destructive disease affecting cereals such as wheat. FHB resistance is a quantitative trait, and information for FHB resistance QTLs in wheat is available. However, little is known about genes underlying the FHB resistance QTL regions. Using a computational approach in this study, we have mined eight FHB resistance QTLs in wheat and predicted the candidate genes falling within these QTL intervals based on the available sequences and markers. A total of 18 genomic scaffolds located at chromosomes 2AL, 2DL, 3B and 4BS were prioritized to harbor FHB-resistant candidate genes. These genes are mainly involved in plant defense response, immune regulation and cellular detoxification. We believe that our results constitute a starting point for further validation to improve FHB-resistant bread wheat varieties.


[The relations between atrial natriuretic factor release and adrenergic activation in hypertrophic cardiomyopathy].
Atrial natriuretic factor (ANF) is a potent natriuretic and vasoactive (vasorelaxant) peptide localized in the secretory-like atrial specific granules. The main peptide in this storage granules is the 126 amino acid proatrial natriuretic peptide, but the principal circulating form in human plasma is the 28 amino acid, alpha-human natriuretic peptide. Animal and in vitro studies have suggested that ANF modulates autonomic circulatory control, probably with a dose-dependent mechanism. Moreover, recent human studies have resulted contradictory. In particular, it is still unclear if high circulating levels of ANF, which are present in congestive heart diseases constantly, may be correlated with sympathetic nervous system activity in man. Previously we have shown that in congestive diseases there is a relation between ANF and catecholamine secretion. From these basis, the aim of this study was to investigate on the pathophysiological relations between atrial natriuretic factor (ANF) release and adrenergic activation in patients with obstructive hypertrophic cardiomyopathy (n = 6) and non obstructive hypertrophic cardiomyopathy (n = 4). Sympathetic activation in physiologic way was induced by cycloergometer sub-maximal exercise. Then specimens of venous blood were achieved for plasma determination of ANF and catecholamines pre- and post-exercise. Results have shown that in obstructive hypertrophic cardiomyopathy patients basal levels of ANF and catecholamines were higher than levels of these parameters in non obstructive hypertrophic cardiomyopathy patients.(ABSTRACT TRUNCATED AT 250 WORDS)


MCP-1 and MIP-1alpha are most efficient in recruiting T cells into the skin in vivo.
To analyze T cell recruitment by chemokines in vivo, we used SCID mice grafted with human skin onto their backs and human T cells into their peritoneal cavities. rh MIP-1alpha and rh MCP-1, as well as mouse MCP-1, attracted significant amounts of human T cells into human skin grafts, whereas effects of rh RANTES, rh SDF-1, or rh IP-10 were minimal. Human T cells were found in a striking perivascular position exclusively at sites of human endothelium. None of the chemokines recruited human T cells across mouse endothelial barriers. For control purposes, chemokines were injected into the abdominal wall directly above the peritoneal cavity, where human T cells had been injected and were not subjected to flow. At this site all tested chemokines attracted human T cells to an equal extent. In summary, our experiments point towards an important role for MCP-1 and MIP-1alpha as T cell chemoattractants for skin inflammatory conditions.


Effects of NMDA and AMPA receptor antagonists on corticosterone facilitation of long-term memory in the chick.
Long-term memory formation for a weak passive avoidance task in day-old chicks is facilitated by corticosterone administration. Since (i) glutamatergic systems, through different receptor types, play a key role in learning and memory processes, and (ii) glucocorticoids increase glutamate concentrations in learning-related regions of the mammalian brain, we reasoned that glutamatergic activation might be a mechanism by which corticosterone facilitates the formation of an enduring memory. To assess this hypothesis, long-term retention was evaluated in chicks trained on a weak passive avoidance task and intracerebrally injected with NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists (MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione) with regard to training and corticosterone injection respectively. The results indicated that either of the antagonists prevented the facilitating effect of corticosterone when administered before the training trial, but failed to interfere with the steroid effect when injected before corticosterone administration in the post-training period, suggesting that their early effectiveness was not related to corticosterone-induced actions but to training-triggered mechanisms. In addition, administration of the AMPA antagonist, 5.5 h after training, was also effective in impairing the long-term memory-potentiating effect of corticosterone. These results support the view that corticosterone facilitates the formation of an enduring memory in this learning model, through the modulation of late events during the consolidation period, including the activation of the AMPA receptor type.


Regeneration of murine megakaryocytopoiesis and the hematopoietic inductive microenvironment after sublethal whole body irradiation by treatment with an anabolic steroid.
The ability of the anabolic steroid nandrolone decanoate (ND) to increase megakaryocytopoiesis (MP) and the hematopoietic-inductive microenvironment (HIM) after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation (2 Gy) and on the next 2 days, mice were injected with 1.25 mg of ND in propylene glycol intraperitoneally. Irradiated control mice received only vehicle. Compared to controls, drug-treated mice showed a 151% increase in the platelet level on day 14. Drug-treated mice also demonstrated a significant rebound in MP, as colony-forming progenitor stem cells (CFU-Mk) from bone marrow rose to 288% of control by day 8 and from spleen to 599% by day 1 following the last drug injection. In addition, drug-treated mice produced a 286% increase in bone marrow and a 378% in splenic stromal cell colonies on day 5 following drug treatment. These results demonstrate that ND enhances MP and HIM following sublethal irradiation. After hematopoietic suppression, ND may serve to stimulate MP and HIM recovery both at the stem cell level and in peripheral blood.


Experience of compounding total parenteral nutrition admixtures for preterm infants in a hospital pharmacy: evidence of calcium and phosphate compatibility problem.
Parenterally fed preterm newborn infants require large amounts of calcium and phosphate in a low volume of solution. The lower the volume of solution, the higher is the possibility of precipitation of calcium hydrogen phosphate (CaHPO4). Precipitation could cause respiratory distress and pulmonary embolism, and the use of organic salts of calcium and phosphorus may reduce the likelihood of this problem. To date, no previous work on the stability of solutions with organic salts has been published in the literature. This study aims to evaluate the visible precipitation of calcium and phosphorus in total parenteral nutrition solutions. 20 parenteral nutrition solutions were aseptically prepared in a laminar airflow hood in a clean room. The solutions are intended to facilitate precipitation, with the amino acid ratio below the standard concentration and other parameters also modulated to promote the precipitation of CaHPO4. The solutions contained dextrose, amino acids, calcium gluconate and fructose 1,6-bisphosphate. We did not use lipid emulsion so that we could see all precipitations. No visible precipitation was observed during 4 weeks of observation at 25°C. The only observed event was the change in colour of the solution, which became yellow, maybe because of a Maillard reaction. This study evaluated the compatibility of organic calcium and phosphorus in order to prevent the precipitation of CaHPO4 when preparing total parenteral nutrition solutions. The fact that no precipitation was observed is very significant as it indicates the compatibility of the ions, even though no instrumental analysis was performed.


Molecular Analyses of the Distribution and Function of Diazotrophic Rhizobia and Methanotrophs in the Tissues and Rhizosphere of Non-Leguminous Plants.
Biological nitrogen fixation (BNF) by plants and its bacterial associations represent an important natural system for capturing atmospheric dinitrogen (N2) and processing it into a reactive form of nitrogen through enzymatic reduction. The study of BNF in non-leguminous plants has been difficult compared to nodule-localized BNF in leguminous plants because of the diverse sites of N2 fixation in non-leguminous plants. Identification of the involved N2-fixing bacteria has also been difficult because the major nitrogen fixers were often lost during isolation attempts. The past 20 years of molecular analyses has led to the identification of N2 fixation sites and active nitrogen fixers in tissues and the rhizosphere of non-leguminous plants. Here, we examined BNF hotspots in six reported non-leguminous plants. Novel rhizobia and methanotrophs were found to be abundantly present in the free-living state at sites where carbon and energy sources were predominantly available. In the carbon-rich apoplasts of plant tissues, rhizobia such as Bradyrhizobium spp. microaerobically fix N2. In paddy rice fields, methane molecules generated under anoxia are oxidized by xylem aerenchyma-transported oxygen with the simultaneous fixation of N2 by methane-oxidizing methanotrophs. We discuss the effective functions of the rhizobia and methanotrophs in non-legumes for the acquisition of fixed nitrogen in addition to research perspectives.


The microbial biosynthesis of methionine.
1. The enzymes leading to the methylation of homocysteine have been examined in three micro-organisms: a cobalamin-producing bacterium, Bacillus megaterium; a yeast, Candida utilis; and a basidiomycete fungus, Coprinus lagopus. The yeast and the fungus contain negligible endogenous cobalamin. 2. Extracts of each organism catalyse C(1)-transfer from serine to homocysteine with a polyglutamate folate coenzyme. 3. The enzymes generating the methyl group of methionine from C-3 of serine have similar properties in each case, but different mechanisms of homocysteine transmethylation from 5-methyltetrahydrofolates were found. 4. B. megaterium contains an enzyme with properties suggestive of a vitamin B(12)-dependent homocysteine transmethylase, whereas Cand. utilis and Cop. lagopus transfer the methyl group by a reaction characteristic of the cobalamin-independent mechanism established for Escherichia coli. 5. The specificity of each transmethylase for a 5-methyltetrahydropteroylpolyglutamate is consistent with the results of analyses of endogenous folates in these organisms, which showed only conjugated forms. 6. None of the extracts catalysed methionine production from S-adenosylmethionine and homocysteine. 7. These results are compared with results now available for methionine synthesis in other organisms, which show a considerable diversity of mechanisms.


Neonatology for the generalist: human milk banks and evidence-based medicine.
Human milk (HM) banks provide pasteurised milk from screened donors for infants in many countries but not in Australia. There are potential benefits and risks from feeding donor milk with the benefits most likely for preterm infants. A randomized clinical trial is required to provide conclusive evidence. Promotion of breast-feeding with the establishment of HM banks may prove to be an important primary health care activities for infants in Australia.


Biomarkers in idiopathic pulmonary fibrosis.
This review examines the recent literature on molecular biomarkers of idiopathic pulmonary fibrosis (IPF). Specific attention is dedicated to the recent studies that identified the genes associated with IPF and the peripheral blood biomarkers that predict outcome in IPF. Multiple studies attempted to identify diagnostic and predictive biomarkers in IPF. Until recently, these studies were limited in size and lacked replication, but still when taken together provided convincing evidence that changes in blood proteins (KL-6, SP-A, MMP-7, CCL-18, among others) or cells (fibrocytes and T-cell subpopulations) are indicative of the disease presence and outcome. More recently, larger studies have identified gene polymorphisms associated with IPF, as well as protein markers and integrated clinical and molecular prediction rules that accurately predict outcome in patients with IPF. The peripheral blood contains disease presence and outcome relevant information, and suggests distinct biologically defined outcome trajectories in patients with IPF. Although recently identified biomarkers should still be validated in multiple clinical contexts, there is sufficient evidence to suggest that collection of peripheral blood biomarkers needs to be incorporated in the design of drug studies and that some of these markers be clinically evaluated in lung transplant prioritization.


Platelet activation induced by porcine factor VIII (Hyate:C).
We studied the effects of porcine factor VIII (P-FVIII; Hyate:C) and other coagulation products employed in the management of patients with hemophilia A, on platelet activation in vitro. Exposure of normal resting platelets to P-FVIII resulted in platelet activation, as manifested by increased expression of the platelet surface activation markers CD62, CD63, and activated-GPIIbIIIa, and by activation-induced modulation of expression of normal platelet membrane glycoproteins CD41, CD42, and CD36. In contrast, platelet activation was not observed after exposure of the platelets to human FVIII, FEIBA, recombinant FVIIa, or cryosupernatant plasma. As with thrombin, exposure of platelets to P-FVIII resulted in the generation of platelet microparticles, an effect not seen not with the other products. In contrast to the characteristic reduction in expression in the number of CD42 molecules detected on thrombin-activated platelets, P-FVIII-stimulated platelets showed a small increase in CD42 expression. In contrast to thrombin, P-FVIII did not cause platelet dense granule release. The results indicate that therapeutic P-FVIII activates platelets, likely in ways that are different from the platelet activation seen with thrombin. The observed platelet activation and microparticle generation may provide a "hypercoagulable" mechanism for hemostasis with P-FVIII therapy separate from, and additional to, that due to increased circulating FVIII levels.


68Ga-DOTATATE Uptake in Solitary Pancreatic Metastasis From Clear Cell Renal Cancer.
A 64-year-old man with a lesion of the pancreatic tail was referred for Ga-DOTATATE PET/CT imaging. His medical history included previous metastatic clear cell renal cell cancer. Ga-DOTATATE PET/CT demonstrated increased DOTATATE uptake (SUVmax 10.5) in a pancreatic tail lesion. Histopathology of the resected lesion confirmed clear renal cell cancer metastasis. This case illustrates that clear cell renal cancer metastasis can demonstrate Ga-DOTATATE accumulation.


Once-daily therapy with ceftriaxone compared with daily multiple-dose therapy with cefotaxime for serious bacterial infections: a randomized, double-blind study.
A randomized, double-blind study was done to compare the efficacy and toxicity of daily single-dose therapy with intravenous ceftriaxone (2 g every 24 h) with daily multiple-dose therapy with cefotaxime (2 g every 6 h) for treatment of serious bacterial infections in nonneutropenic patients. Of the 325 patients who were evaluable for toxicity, 241 (74.2%) were evaluable for efficacy. Infection sites included lung (106), urinary tract (42), skin and soft tissue (43), bone and joint (23), bacteremia (21), and hepatobiliary (5). Definite infections were present in 173 cases (71.8%) and possible infections in 68 (28.2%). Analysis of clinical and bacteriologic responses and adverse drug reactions showed no significant differences between the regimens. Values for 95% confidence limits on the differences between regimens for positive clinical and bacteriological outcomes in definite infections were -0.8% to 3.0% and -1.9% to 9.1%, respectively. Thus, daily single-dose therapy with ceftriaxone was comparable to daily multiple-dose therapy with cefotaxime in treating these bacterial infections.


Conditions for equilibrium solid-stabilized emulsions.
Particular types of solid-stabilized emulsions can be thermodynamically stable as evidenced by their spontaneous formation and monodisperse droplet size, which only depends on system parameters. Here, we investigate the generality of these equilibrium solid-stabilized emulsions with respect to the basic constituents: aqueous phase with ions, oil, and stabilizing particles. From systematic variations of these constituents, we identify general conditions for the spontaneous formation of monodisperse solid-stabilized emulsions droplets. We conclude that emulsion stability is achieved by a combination of solid particles as well as amphiphilic ions adsorbed at the droplet surface, and low interfacial tensions of the bare oil-water interface of order 10 mN/m or below. Furthermore, preferential wetting of the colloidal particles by the oil phase is necessary for thermodynamic stability. We demonstrate the sufficiency of these basic requirements by extending the observed thermodynamic stability to emulsions of different compositions. Our findings point to a new class of colloid-stabilized meso-emulsions with a potentially high impact on industrial emulsification processes due to the associated large energy savings.


Renal hemodynamic effects of ketanserin therapy in essential hypertension.
Ketanserin is a novel agent that has been shown to be a specific 5-HT2-serotonergic antagonist. It has useful antihypertensive properties. Owing to its unique mechanism of action, it has been suggested that ketanserin may have a favorable effect on tissue blood flow during chronic therapy for hypertension. This double-blind study was designed to evaluate the acute (1 week) and chronic (8 weeks) effects of ketanserin on renal hemodynamic parameters and renin-aldosterone axis in patients with uncomplicated hypertension. Compared to placebo, ketanserin caused a significant blood pressure reduction at the end of the 8-week study period. Despite the reduction in systematic arterial pressure, glomerular filtration rate and renal plasma flow were preserved. Ketanserin therapy induced a slight reduction in plasma renin activity and a marginal increase in the sodium excretion. Although the results of this study are limited by the small number of patients, it appears that ketanserin may have favorable renal hemodynamic effects in uncomplicated essential hypertension.


Sequence determination and phylogenetic analysis of the Akabane bunyavirus S RNA genome segment.
The nucleotide sequence of the small (S) RNA segment of Akabane (AKA) bunyavirus was determined. The segment is 858 nucleotides long and contains two overlapping open reading frames (ORFs), which encode the nucleocapsid (N) and nonstructural (NSs) proteins, consistent with other bunyaviruses. Comparisons with the Aino virus S RNA sequence indicated that there is 73.5% identity in nucleotide sequence. However, the sequence identity of the 5' non-coding region of the genomic RNA between these two viruses is only 55%. The N ORFs from 20 Japanese and 2 Australian isolates of AKA virus were sequenced and subjected to phylogenetic analysis. This suggested that AKA virus has evolved in multiple lineages. Twenty-three isolates were grouped into three major clusters, and the cluster which includes recent isolates was subdivided into two branches. Thus, phylogenetic analysis of the AKA virus N protein gene gives a greater insight into bunyavirus evolution.


Possible instability of one-step replica symmetry breaking in p-spin Ising models outside mean-field theory.
The fully connected Ising p-spin model has for p>2 a discontinuous phase transition from the paramagnetic phase to a stable state with one-step replica symmetry breaking (1RSB). However, simulations in three dimension do not look like these mean-field results and have features more like those which would arise with full replica symmetry breaking (FRSB). To help understand how this might come about we have studied in the fully connected p-spin model the state of two-step replica symmetry breaking (2RSB). It has a free energy degenerate with that of 1RSB, but the weight of the additional peak in P(q) vanishes. We expect that the state with full replica symmetry breaking (FRSB) is also degenerate with that of 1RSB. We suggest that finite-size effects will give a nonvanishing weight to the FRSB features, as also will fluctuations about the mean-field solution. Our conclusion is that outside the fully connected model in the thermodynamic limit, FRSB is to be expected rather than 1RSB.


Simultaneous left atrium anatomy and scar segmentations via deep learning in multiview information with attention.
Three-dimensional late gadolinium enhanced (LGE) cardiac MR (CMR) of left atrial scar in patients with atrial fibrillation (AF) has recently emerged as a promising technique to stratify patients, to guide ablation therapy and to predict treatment success. This requires a segmentation of the high intensity scar tissue and also a segmentation of the left atrium (LA) anatomy, the latter usually being derived from a separate bright-blood acquisition. Performing both segmentations automatically from a single 3D LGE CMR acquisition would eliminate the need for an additional acquisition and avoid subsequent registration issues. In this paper, we propose a joint segmentation method based on multiview two-task (MVTT) recursive attention model working directly on 3D LGE CMR images to segment the LA (and proximal pulmonary veins) and to delineate the scar on the same dataset. Using our MVTT recursive attention model, both the LA anatomy and scar can be segmented accurately (mean Dice score of 93% for the LA anatomy and 87% for the scar segmentations) and efficiently ( ∼ 0.27 s to simultaneously segment the LA anatomy and scars directly from the 3D LGE CMR dataset with 60-68 2D slices). Compared to conventional unsupervised learning and other state-of-the-art deep learning based methods, the proposed MVTT model achieved excellent results, leading to an automatic generation of a patient-specific anatomical model combined with scar segmentation for patients in AF.


E2F6 functions as a competing endogenous RNA, and transcriptional repressor, to promote ovarian cancer stemness.
Ovarian cancer is the most lethal cancer of the female reproductive system. In that regard, several epidemiological studies suggest that long-term exposure to estrogen could increase ovarian cancer risk, although its precise role remains controversial. To decipher a mechanism for this, we previously generated a mathematical model of how estrogen-mediated upregulation of the transcription factor, E2F6, upregulates the ovarian cancer stem/initiating cell marker, c-Kit, by epigenetic silencing the tumor suppressor miR-193a, and a competing endogenous (ceRNA) mechanism. In this study, we tested that previous mathematical model, showing that estrogen treatment of immortalized ovarian surface epithelial cells upregulated both E2F6 and c-KIT, but downregulated miR-193a. Luciferase assays further confirmed that microRNA-193a targets both E2F6 and c-Kit. Interestingly, ChIP-PCR and bisulphite pyrosequencing showed that E2F6 also epigenetically suppresses miR-193a, through recruitment of EZH2, and by a complex ceRNA mechanism in ovarian cancer cell lines. Importantly, cell line and animal experiments both confirmed that E2F6 promotes ovarian cancer stemness, whereas E2F6 or EZH2 depletion derepressed miR-193a, which opposes cancer stemness, by alleviating DNA methylation and repressive chromatin. Finally, 118 ovarian cancer patients with miR-193a promoter hypermethylation had poorer survival than those without hypermethylation. These results suggest that an estrogen-mediated E2F6 ceRNA network epigenetically and competitively inhibits microRNA-193a activity, promoting ovarian cancer stemness and tumorigenesis.


Using metabarcoding to compare the suitability of two blood-feeding leech species for sampling mammalian diversity in North Borneo.
The application of high-throughput sequencing (HTS) for metabarcoding of mixed samples offers new opportunities in conservation biology. Recently, the successful detection of prey DNA from the guts of leeches has raised the possibility that these, and other blood-feeding invertebrates, might serve as useful samplers of mammals. Yet little is known about whether sympatric leech species differ in their feeding preferences, and whether this has a bearing on their relative suitability for monitoring local mammalian diversity. To address these questions, we collected spatially matched samples of two congeneric leech species Haemadipsa picta and Haemadipsa sumatrana from lowland rainforest in Borneo. For each species, we pooled ~500 leeches into batches of 10 individuals, performed PCR to target a section of the mammalian 16S rRNA locus and undertook sequencing of amplicon libraries using an Illumina MiSeq. In total, we identified sequences from 14 mammalian genera, spanning nine families and five orders. We found greater numbers of detections, and higher diversity of OTUs, in H. picta compared with H. sumatrana, with rodents only present in the former leech species. However, comparison of samples from across the landscape revealed no significant difference in mammal community composition between the leech species. We therefore suggest that H. picta is the more suitable iDNA sampler in this degraded Bornean forest. We conclude that the choice of invertebrate sampler can influence the detectability of different mammal groups and that this should be accounted for when designing iDNA studies.


Measuring Racial Discrimination Remotely: A Contemporary Review of Unobtrusive Measures.
Social-science researchers have increasingly moved from conducting their studies in a face-to-face format to an online format. Although new and innovative remote platforms afford researchers generalizability and scale, many of these platforms also tend to solicit socially desirable responses. This pattern of socially desirable responding is evident in examinations of racial discrimination, in which participants are particularly determined to present themselves as ethical and moral. In the current article, we rectify the concern between remote platforms and inauthentic participant responses by reviewing unobtrusive measures of racial discrimination. First, we conceptualize unobtrusive measures as measurements that assess a participant's discriminatory action without the participant's knowledge that the specific discriminatory action is under observation. Next, we review the landscape of unobtrusive studies conducted within three broad categories-audit, helping, and friendly interaction-and discuss how these measures have changed over time. Finally, we discuss how to adapt classic face-to-face measures to remote platforms and provide recommendations for implementing unobtrusive measures into remote examinations of discrimination.


Minimally invasive aortic valve replacement: the "Miami Method".
For patients undergoing aortic valve replacement (AVR), a minimally invasive approach performed via a right anterior thoracotomy is the preferred method at our institution. This method has evolved over a 10-year span, being applied to over 1,500 patients with the commitment of one surgeon seeking to offer a simplistic and reproducible minimally invasive alternative. We believe that this is truly the least invasive approach to the aortic valve since it avoids sternal invasion. By virtue of being less traumatic, the morbidity is diminished and therefore the recovery is enhanced. We believe that this approach is most beneficial in the high risk patient such as the elderly, the obese, those with chronic obstructive pulmonary, chronic kidney disease and those requiring re-operative surgery. This method has proven to be safe and effective in all patients requiring isolated AVR surgery. The only relative exclusion criteria would be a porcelain aorta with the inability to cannulate the patient.


Addiction-related genes in gambling disorders: new insights from parallel human and pre-clinical models.
Neurobiological research supports the characterization of disordered gambling (DG) as a behavioral addiction. Recently, an animal model of gambling behavior was developed (rat gambling task, rGT), expanding the available tools to investigate DG neurobiology. We investigated whether rGT performance and associated risk gene expression in the rat's brain could provide cross-translational understanding of the neuromolecular mechanisms of addiction in DG. We genotyped tagSNPs (single-nucleotide polymorphisms) in 38 addiction-related genes in 400 DG and 345 non-DG subjects. Genes with P<0.1 in the human association analyses were selected to be investigated in the animal arm to determine whether their mRNA expression in rats was associated with the rat's performance on the rGT. In humans, DG was significantly associated with tagSNPs in DRD3 (rs167771) and CAMK2D (rs3815072). Our results suggest that age and gender might moderate the association between CAMK2D and DG. Moderation effects could not be investigated due to sample power. In the animal arm, only the association between rGT performance and Drd3 expression remained significant after Bonferroni correction for 59 brain regions. As male rats were used, gender effects could not be investigated. Our results corroborate previous findings reporting the involvement of DRD3 receptor in addictions. To our knowledge, the use of human genetics, pre-clinical models and gene expression as a cross-translation paradigm has not previously been attempted in the field of addictions. The cross-validation of human findings in animal models is crucial for improving the translation of basic research into clinical treatments, which could accelerate neurobiological and pharmacological investigations in addictions.


Long-term cognitive deficits in patients after surgery on aneurysms of the anterior communicating artery.
The long term recovery of a series of 27 patients who had undergone rupture and repair of an aneurysm of the anterior communicating artery was assessed using a number of neuropsychological measures. Testing took place 12 to 84 months post surgery. On the basis of the results from tests of intellect, memory, and conceptual learning, three subgroups of patients were identified: those with persuasive cognitive defects, those with evidence of residual frontal lobe damage and those who showed no evidence of dysfunction. The occurrence of cerebral vasospasm was the most consistent predictor of long term cognitive deficit.


PyLipID: A Python Package for Analysis of Protein-Lipid Interactions from Molecular Dynamics Simulations.
Lipids play important modulatory and structural roles for membrane proteins. Molecular dynamics simulations are frequently used to provide insights into the nature of these protein-lipid interactions. Systematic comparative analysis requires tools that provide algorithms for objective assessment of such interactions. We introduce PyLipID, a Python package for the identification and characterization of specific lipid interactions and binding sites on membrane proteins from molecular dynamics simulations. PyLipID uses a community analysis approach for binding site detection, calculating lipid residence times for both the individual protein residues and the detected binding sites. To assist structural analysis, PyLipID produces representative bound lipid poses from simulation data, using a density-based scoring function. To estimate residue contacts robustly, PyLipID uses a dual-cutoff scheme to differentiate between lipid conformational rearrangements while bound from full dissociation events. In addition to the characterization of protein-lipid interactions, PyLipID is applicable to analysis of the interactions of membrane proteins with other ligands. By combining automated analysis, efficient algorithms, and open-source distribution, PyLipID facilitates the systematic analysis of lipid interactions from large simulation data sets of multiple species of membrane proteins.


Alfaxalone-Xylazine Anesthesia in Laboratory Mice (Mus musculus).
Since its recent reformulation, alfaxalone has gained popularity as an injectable veterinary anesthetic, including promising studies demonstrating the use of alfaxalone-xylazine for anesthesia in mice. Here we sought to expand these studies by testing additional dose ranges, elaborating on physiologic monitoring, testing sex- and strain-associated differences, and evaluating efficacy during actual surgical conditions. C57BL/6J mice showed significant sex-associated differences in anesthetic sensitivity, with males requiring higher doses of alfaxalone (80-120 mg/kg IP alfaxalone with 10 mg/kg IP xylazine) than females (40-80 mg/kg IP alfaxalone with 10 mg/kg IP xylazine) to achieve a surgical plane of anesthesia. In addition, female outbred CD1 mice were less sensitive to alfaxalone than female inbred C57BL/6J mice. When used during actual surgery, alfaxalone-xylazine administered intraperitoneally provided adequate anesthesia for a model of orthopedic surgery, whereas the same anesthetic regimen during laparotomy resulted in unacceptably high mortality; survival during laparotomy increased when drugs were administered subcutaneously. These results indicate that alfaxalone-xylazine may be a viable option for injectable surgical anesthesia in mice, although strain- and sex-associated differences and alternative routes of administration should be considered when optimizing the anesthetic regimen for specific experimental conditions.


Evidence of enzymatic catalysis of oxygen reduction on stainless steels under marine biofilm.
Cathodic current trends on stainless steel samples with different surface percentages covered by biofilm and potentiostatically polarized in natural seawater were studied under oxygen concentration changes, temperature increases, and additions of enzymic inhibitors to the solution. The results showed that on each surface fraction covered by biofilm the oxygen reduction kinetics resembled a reaction catalyzed by an immobilised enzyme with high oxygen affinity (apparent Michaelis-Menten dissociation constant close to K(O(2))(M) ≈ 10 μM) and low activation energy (W ≈ 20 KJ mole(-1)). The proposed enzyme rapidly degraded when the temperature was increased above the ambient (half-life time of ∼1 day at 25°C, and of a few minutes at 50°C). Furthermore, when reversible enzymic inhibitors (eg sodium azide and cyanide) were added, the cathodic current induced by biofilm growth was inhibited.


Plasma iohexol clearance in automated peritoneal dialysis--its role in adequacy determination.
To compare the relationship of plasma iohexol clearance to standard adequacy measures in an automated peritoneal dialysis (APD) population. Prospective, nonrandomized, open label, simultaneous clearance studies of novel (iohexol) and traditional (urea and creatinine) markers of dialysis quantitation. Outpatient peritoneal dialysis units associated with tertiary care university hospitals. Eighteen stable patients, 13 undergoing continuous cycling peritoneal dialysis (CCPD) and 5 receiving intermittent dialysis, who underwent 24-hour clearance studies were enrolled in and completed the study. Each subject received 15 mL of iohexol intravenously the morning of a scheduled dialysis night. Blood was obtained for determination of serum concentrations of urea nitrogen and creatinine, and plasma iohexol concentration. Dialysate and urine were collected over 24 hours. Urea and creatinine data from the total pooled dialysate and from the 24-hour urine collection were used to calculate daily Kt/Vurea and normalized total daily creatinine clearance (CrCl). Total plasma iohexol clearance was calculated using a one-compartment model with the Brochner-Mortensen correction. Normalized [to 1.73 m2 body surface area (BSA)] iohexol clearance correlated very well with normalized CrCl (r2 = 0.777; p < 0.001). A weaker correlation was observed between Kt/Vurea and normalized iohexol clearance (r2 = 0.213; 0.05 < p < 0.1). When data are not normalized using BSA or urea distribution volume, the regressions are improved for both creatinine (r2 = 0.820) and urea (r2 = 0.533). These results were comparable between those on CCPD and those on intermittent therapy. Total plasma iohexol clearance provides a simple assessment for APD adequacy by eliminating collection problems inherent to the methodologies currently employed. Such simplicity allows for more frequent assessments of delivered dialysis dose and efficacy of prescription changes.


Myokine Response to High-Intensity Interval vs. Resistance Exercise: An Individual Approach.
Purpose: This study aimed to compare the response to acute exercise of several myokines/hormones involved in metabolic function between two types of training sessions that are growing in popularity for their purported cardiometabolic benefits, high-intensity interval (HIIT) and resistance training (RT). Methods: Seventeen healthy, non-athletic men (23 ± 3 years) participated in this cross-over study. They randomly performed a HIIT [with short (HIIT1) or long (HIIT2) intervals] or a RT session. The concentration of fibroblast-growth factor (FGF) 21, follistatin, ghrelin, interleukin-15, irisin, myostatin, and peptide YY was measured at baseline and 0, 1, 3, 24, 48, and 72 h post-exercise. An individual approach was adopted to determine the rate of responsiveness to each specific cytokine and training mode. Results: A significant condition (session type) by time interaction (p = 0.004) effect was observed for FGF21, with RT eliciting a greater area under the curve (AUC) concentration than HIIT1 (p = 0.02). The AUC for follistatin was significantly greater after HIIT2 compared with RT (p = 0.02). Individual responsiveness to all session types ranged between 19 and 93% depending on the cytokine. However, most subjects (71-100%) responded positively for all cytokines (except for irisin, with only 53% of responders) after 1+ session type. Conclusion: Except for FGF21, our results show no overall differences in the myokine response to HIIT or RT. A considerable individual variability was observed, with some subjects responding to some but not other training session types. Notwithstanding, most responded to at least one training session. Thus, it is mostly the individual response of each subject rather than general recommendations on type of training session (i.e., RT vs. HIIT or HIIT subtypes) that must be taken into consideration for maximizing cardiometabolic benefits in the context of personalized exercise prescription.


Effect of Previous Anticoagulant Treatment on Risk of COVID-19.
Little is known about the role played by anticoagulants in COVID-19. The aim of this study was to assess the impact of previous anticoagulant treatment on risk of hospitalization due to COVID-19, progression to severe COVID-19 and susceptibility to COVID-19 infection. We conducted a multiple population-based case-control study in northwest Spain, in 2020, to assess (1) risk of hospitalization: cases were all patients admitted due to COVID-19 with PCR confirmation, and controls were a random matched sample of subjects without a positive PCR; (2) progression: cases were hospitalized COVID-19 subjects, and controls were all non-hospitalized COVID-19 patients; and (3) susceptibility: cases were patients with a positive PCR (hospitalized and non-hospitalized), and the controls were the same as for the hospitalization model. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a generalized linear mixed model. The consumption of antivitamin K and direct-acting anticoagulants apparently was not associated with the risk of progression to severe COVID-19 (OR 0.93 [95% CI 0.74-1.17] and OR 1.04 [95% CI 0.79-1.36], respectively). Antivitamin K anticoagulants were associated with a significantly lower risk of hospitalization (OR 0.77 [95% CI 0.64-0.93]), which, in part, can be explained by a decreased risk of susceptibility to infection (OR 0.83 [95% CI 0.74-0.92]). The use of direct-acting anticoagulants was not associated with the risk of hospitalization, although it also seems to decrease susceptibility (OR 0.85 [95% CI 0.74-0.98]). It has also been observed that low-molecular-weight heparins were associated with an increased risk of progression to severe COVID-19 (OR 1.25 [95% CI 1.01-1.55]). The results of this study have shown that antivitamin K anticoagulants and direct-acting anticoagulants do not increase the risk of progression to more severe stages. Antivitamin K consumption was associated with a lower risk of hospitalization and susceptibility to infection.


An emerging role for the delta opioid receptor in the regulation of mu opioid receptor function.
Morphine and related opiates are commonly used in the clinical management of various types of pain. However, the antinociceptive properties of morphine are often overshadowed by the development of tolerance and dependence following its chronic use. The mechanisms underlying opiate tolerance are not fully understood, but appear to involve numerous and complex physiological adaptations. Recently, a role for the heterodimerization of mu and delta opioid receptors in the development of morphine tolerance has been proposed. This novel mechanism could help us to understand several observations, such as the critical role of delta opioid receptor regulation, the impact of delta opioid receptor binding site occupancy, and the participation of beta-arrestin2, in the development of morphine tolerance.


Coastal Synechococcus metagenome reveals major roles for horizontal gene transfer and plasmids in population diversity.
The extent to which cultured strains represent the genetic diversity of a population of microorganisms is poorly understood. Because they do not require culturing, metagenomic approaches have the potential to reveal the genetic diversity of the microbes actually present in an environment. From coastal California seawater, a complex and diverse environment, the marine cyanobacteria of the genus Synechococcus were enriched by flow cytometry-based sorting and the population metagenome was analysed with 454 sequencing technology. The sequence data were compared with model Synechococcus genomes, including those of two coastal strains, one isolated from the same and one from a very similar environment. The natural population metagenome had high sequence identity to most genes from the coastal model strains but diverged greatly from these genomes in multiple regions of atypical trinucleotide content that encoded diverse functions. These results can be explained by extensive horizontal gene transfer presumably with large differences in horizontally transferred genetic material between different strains. Some assembled contigs showed the presence of novel open reading frames not found in the model genomes, but these could not yet be unambiguously assigned to a Synechococcus clade. At least three distinct mobile DNA elements (plasmids) not found in model strain genomes were detected in the assembled contigs, suggesting for the first time their likely importance in marine cyanobacterial populations and possible role in horizontal gene transfer.


Extending the use of the conceptions of learning and teaching (COLT) instrument to the postgraduate setting.
Several studies have shown that conceptions of teachers on teaching and learning can influence the teaching practices and behavior in higher education. This association is also found in undergraduate medical education but not yet established in postgraduate medical setting. An instrument, Conceptions of Learning and Teaching (COLT) was developed to measure conception of teachers in undergraduate medical education. COLT is a 3-factor 18-item questionnaire. The objective of this study is to evaluate if COLT is valid for postgraduate medical education. We invited postgraduate clinical faculty from 3 hospitals in the Netherlands to fill out the COLT. Confirmatory and exploratory factor analysis were performed to evaluate the fit of the postgraduate clinical faculty data to the COLT. Analysis of variance was done to evaluate if there was difference among the 3 hospitals in terms of the response by the clinical faculty. Confirmatory factor analysis showed that the postgraduate faculty data had a 2 factor structure after removal of five items. These factors were Teacher Centeredness (TC) and combined Appreciation of Active Learning and Orientation to Professional Practice (A-P) and were considered as comparable to the factors in the original COLT, expressing the post-graduate learning and teaching setting. As several items were removed, the fit was suboptimal, yet did suggest validity for use of the COLT for postgraduate medical education. The modified COLT can be used to measure conceptions of teaching and learning in postgraduate medical education. We recommend further study to improve the factor structure of the modified COLT.


Alcohol consumption patterns and growth differentiation factor 15 among life-time drinkers aged 65+ years in Spain: a cross-sectional study.
To examine the association of alcohol consumption patterns with growth differentiation factor 15 (GDF-15) in older drinkers, separately among individuals with cardiovascular disease (CVD)/diabetes and those without them, as GDF-15 is a strong biomarker of chronic disease burden. Cross-sectional study. Population-based study in Madrid (Spain). A total of 2051 life-time drinkers aged 65+ years included in the Seniors-ENRICA-2 study in 2015-17. Participants' mean age was 71.4 years and 55.4% were men. According to their average life-time alcohol intake, participants were classified as occasional (≤ 1.43 g/day), low-risk (men: > 1.43-20 g/day; women: > 1.43-10 g/day), moderate-risk (men: > 20-40 g/day; women: > 10-20 g/day) and high-risk drinkers (men: > 40 g/day; women: > 20 g/day; or binge drinkers). We also ascertained wine preference (> 80% of alcohol derived from wine), drinking with meals and adherence to a Mediterranean drinking pattern (MDP) defined as low-risk drinking, wine preference and one of the following: drinking only with meals; higher adherence to the Mediterranean diet; or any of these. In participants without CVD/diabetes, GDF-15 increased by 0.27% [95% confidence interval (CI) = 0.06%, 0.48%] per 1 g/day increment in alcohol among high-risk drinkers, but there was no clear evidence of association in those with lower intakes or in the overall group, or across categories of alcohol consumption status. Conversely, among those with CVD/diabetes, GDF-15 rose by 0.19% (95% CI = 0.05%, 0.33%) per 1 g/day increment in the overall group and GDF-15 was 26.89% (95% CI = 12.93%, 42.58%) higher in high-risk versus low-risk drinkers. Drinking with meals did not appear to be related to GDF-15, but among those without CVD/diabetes, wine preference and adherence to the MDP were associated with lower GDF-15, especially when combined with high adherence to the Mediterranean diet. Among older life-time drinkers in Madrid, Spain, high-risk drinking was positively associated with growth differentiation factor 15 (a biomarker of chronic disease burden). There was inconclusive evidence of a beneficial association for low-risk consumption.


New trends in medical education. The clinical skills laboratories.
A clinical skills laboratory or center is a facility in which students, physicians, nurses and other health care professionals learn clinical, communication and information technology skills to a specified level of competence prior to or coordinated with direct patient contact. The purpose of the clinical skill laboratory is to support the acquisition, maintenance and enhancement of the clinical skills of students in health care professions. Within this non-threatening environment, patient volunteers, simulated patients, mannequins and information technology are employed to provide hands-on learning experiences for the practice of the essential clinical skills. The skills laboratory helps to ensure that all students have necessary learning opportunities and appropriate assessment and feedback before approaching real patients. As more and more schools integrate skills laboratories into their curricula, it is important to review this new trend, to introduce the reader to its nature, factors that led to its development, advantages and problems related to its implementation. This review will also suggest some guidelines that may help in overcoming the implementation problems.


Laser resonators folded by diffraction gratings.
A grating may be employed to fold a laser resonator, thereby enabling the simultaneous extraction of several frequencies from the laser. This limits the range of useful grating constants as compared to the Littrow case. The astigmatism introduced by the grating is examined through the use of sigma-circle diagrams. It will be seen that the grating performs an angle-dependent transformation on the sigma-circle representative of the plane of diffraction to make the mode astigmatic. Some consequences of this related to the design of similar resonators are discussed.


The V beta 17+ T cell repertoire: skewed J beta usage after thymic selection; dissimilar CDR3s in CD4+ versus CD8+ cells.
To ascertain how the actual repertoire of T cell receptors (TCRs) deviates from the theoretical, we have generated a large number of junctional region sequences from TCRs carrying the V beta 17 variable region. The greater than 600 sequences analyzed represent transcripts from nine different cell populations, permitting several comparisons: transcripts from an expressed vs. a non-expressed V beta 17 allele, those from E+ vs. E- mice, transcripts from immature vs. mature thymocytes, those from thymic vs. peripheral T cells, and those from CD4+ vs. CD8+ cells. These comparisons have allowed us to distinguish between the influence of molecular events involved in TCR gene rearrangement and that of various selection events that shape the T cell repertoire. Our most striking findings are: (a) that J beta usage is markedly skewed, partly due to recombination mechanics and partly due to selection forces: in particular, those mediated by the class II E molecule in the thymus; and (b) that TCRs on CD4+ and CD8+ cells show intriguing dissimilarities. In addition, we present evidence that N nucleotide additions occur with clear biases, probably due to idiosyncrasies of the recombination enzymes, and provide arguments that TCR and immunoglobulin CDR3s have distinct structures.


Parameters of spikes in human epilepsy.
The parameters of 600 spikes were studied in 100 epileptic patients. Spikes were subdivided morphologically into: monophasic spikes, diphasic spikes, spike-slow wave complexes, polyspike-slow wave complexes and spike followed by spike. The following parameters were analyzed: polarity, amplitude, duration and sequence, 88% of spikes were negative. 98% of spikes raised 30% above the background activity. Spike duration varied, the shortest spike had a 9 msec duration. The range of duration varied from 9 to 200 msec with a mean of 45.06. 75% of spikes were followed by a deflection lasting from 130 to 200 msec. No evidence was found in our study for the differentiation of sharp waves from spikes.


In vivo miniature robots for natural orifice surgery: State of the art and future perspectives.
Natural orifice translumenal endoscopic surgery (NOTES) is the integration of laparoscopic minimally invasive surgery techniques with endoscopic technology. Despite the advances in NOTES technology, the approach presents several unique instrumentation and technique-specific challenges. Current flexible endoscopy platforms for NOTES have several drawbacks including limited stability, triangulation and dexterity, and lack of adequate visualization, suggesting the need for new and improved instrumentation for this approach. Much of the current focus is on the development of flexible endoscopy platforms that incorporate robotic technology. An alternative approach to access the abdominal viscera for either a laparoscopic or NOTES procedure is the use of small robotic devices that can be implanted in an intracorporeal manner. Multiple, independent, miniature robots can be simultaneously inserted into the abdominal cavity to provide a robotic platform for NOTES surgery. The capabilities of the robots include imaging, retraction, tissue and organ manipulation, and precise maneuverability in the abdominal cavity. Such a platform affords several advantages including enhanced visualization, better surgical dexterity and improved triangulation for NOTES. This review discusses the current status and future perspectives of this novel miniature robotics platform for the NOTES approach. Although these technologies are still in pre-clinical development, a miniature robotics platform provides a unique method for addressing the limitations of minimally invasive surgery, and NOTES in particular.


Incidence and characteristics of venous thromboembolic disease during pregnancy and the postnatal period: a contemporary series.
To evaluate the incidence and characteristics of venous thromboembolic events (VTE) associated with pregnancy in a contemporary patient series. We performed a retrospective review of 33,311 deliveries between June 2003 and June 2008. Patients with objective documentation of a VTE during pregnancy or the 3-month postnatal period were identified from hospital discharge International Classification of Disease Codes edition 9 codes. Diagnosis of deep venous thrombosis (DVT) was largely made by a Duplex ultrasound, whereas pulmonary embolism (PE) was diagnosed by a computerized tomographic angiography (CTA). Of 33,311 deliveries during the study period, 74 patients (0.22%) had a VTE. There were 40 incidents of DVT (0.12%) and 37 of PE (0.11%). DVT involved the iliac veins (6), the femoral or popliteal veins (16), the infrapopliteal veins (17), and the axillary vein (1). Most (57.5%) of the DVTs involved the left lower extremity. Thirty-eight (51.6%) of the VTEs occurred in the postnatal period, and of those 33 (87%) occurred within 1 week of delivery. Most of the postnatal VTEs (68%) were seen in patients who underwent a cesarean section. Among patients with VTE during pregnancy, there were 28% in the first trimester, 25% in the second, and 47% in the third. Events were distributed among maternal age groups as follows: 26% aged 13-24, 50% aged 25-34, and 24% aged 35-54. Of the 35 patients tested for a hypercoagulable disorder, 12 were found to have a positive test result. Five (6.8%) of these 74 patients had a prior history of VTE, with two having a hypercoagulable disorder. In addition, 45 of the 74 patients were on oral contraceptive therapy or received hormonal stimulation therapy before pregnancy. Patients with a VTE during pregnancy were treated with low molecular weight or unfractionated heparin. Most postnatal patients were treated with subcutaneous low molecular weight heparin and coumadin. Six inferior vena cava filters were placed in patients with bleeding complications as a result of anticoagulation. There were no deaths during the study period. Comparing our results with historic controls (DVT: 0.04-0.14% and PE: 0.003-0.04%), the incidence of DVT in pregnancy has not changed significantly. We note, however, that the incidence of pulmonary embolus in our series is higher than previously reported. CTA has been used for the diagnosis of PE since the past decade. The increase in the rate of PE in the current series may be because of the higher sensitivity of CTA when compared with previous diagnostic modalities.


Microbiosensors based on DNA modified single-walled carbon nanotube and Pt black nanocomposites.
Glucose and ATP biosensors have important applications in diagnostics and research. Biosensors based on conventional materials suffer from low sensitivity and low spatial resolution. Our previous work has shown that combining single-walled carbon nanotubes (SWCNTs) with Pt nanoparticles can significantly enhance the performance of electrochemical biosensors. The immobilization of SWCNTs on biosensors remains challenging due to the aqueous insolubility originating from van der Waals forces. In this study, we used single-stranded DNA (ssDNA) to modify SWCNTs to increase solubility in water. This allowed us to explore new schemes of combining ssDNA-SWCNT and Pt black in aqueous media systems. The result is a nanocomposite with enhanced biosensor performance. The surface morphology, electroactive surface area, and electrocatalytic performance of different fabrication protocols were studied and compared. The ssDNA-SWCNT/Pt black nanocomposite constructed by a layered scheme proved most effective in terms of biosensor activity. The key feature of this protocol is the exploitation of ssDNA-SWCNTs as molecular templates for Pt black electrodeposition. The glucose and ATP microbiosensors fabricated on this platform exhibited high sensitivity (817.3 nA/mM and 45.6 nA/mM, respectively), wide linear range (up to 7 mM and 510 μM), low limit of detection (1 μM and 2 μM) and desirable selectivity. This work is significant to biosensor development because this is the first demonstration of ssDNA-SWCNT/Pt black nanocomposite as a platform for constructing both single-enzyme and multi-enzyme biosensors for physiological applications.


A Health System's Pilot Experience with Using Social Knowledge Networking (SKN) Technology to Enable Meaningful Use of EHR Medication Reconciliation Technology.
Similar to issues faced in health systems across USA, AU Health, based in Augusta, Georgia, faced a scenario of low physician engagement in, and limited-use of its Electronic Health Record (EHR) Medication Reconciliation (MedRec) technology, which translated to high rates of medication discrepancies and low accuracy of the patient's active medication list, during transitions of care. In fall 2016, a two-year grant was secured from the U.S. Agency for Healthcare Research and Quality (AHRQ), to pilot a Social Knowledge Networking (SKN) system pertaining to "EHR-MedRec," to enable AU Health to progress from "limited use" of EHR MedRec technology, to "meaningful use." The rationale behind an SKN system, is that it could provide a platform for inter-professional knowledge exchange on practice issues related to EHR MedRec, across diverse provider subgroups and care settings, to highlight adverse consequences of gaps in practice for patient safety, and emphasize the value of adhering to best-practices in EHR MedRec. This, in turn, is expected to increase provider engagement in addressing issues related to EHR MedRec, and promote inter-professional learning of best-practices, to create a foundation for practice change or improvement (e.g., Meaningful Use of EHR MedRec technology). This Case Report describes AU Health's experiences with this novel initiative to pilot an SKN system for enabling Meaningful Use of EHR MedRec technology. It also discusses lessons learned in regard to the potential of an SKN system to enable inter-professional learning and practice improvement in the context of EHR MedRec, which, in turn, helps identify strategies and practice implications for healthcare managers.


Leflunomide improves psoriasis in patients with psoriatic arthritis: an in-depth analysis of data from the TOPAS study.
Leflunomide has shown promise in the treatment of psoriasis. To provide an in-depth analysis of the effect of leflunomide on psoriasis in patients with psoriatic arthritis (PsA). 190 patients with plaque psoriasis (at least 3% skin involvement) and active PsA were randomized to double-blind treatment with leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. As previously reported, leflunomide resulted in a significantly higher Psoriatic Arthritis Response Criteria response rate than placebo (58.9 vs. 29.7%; p < 0.0001). Significant differences in favor of leflunomide were also observed in the Psoriasis Area and Severity Index (PASI 50 in 30.4% of patients vs. 18.9% for placebo; p = 0.05), target lesion response (46.4 vs. 25.3%; p = 0.0048), combined skin and joint response (27.2 vs. 8.9%; p < 0.0001), Dermatology Life Quality Index (improvement of 1.9 points vs. 0.2; p = 0.0173) and certain SF-36 subdomains. Dermatological responses were observed at the earliest examination (4 weeks) and increased throughout the 24-week study. Once-daily oral leflunomide is an effective and convenient treatment for PsA and plaque psoriasis.


Increasing independent decision-making skills of women with mental retardation in simulated interpersonal situations of abuse.
The effectiveness of two decision-making training approaches in increasing independent decision-making skills of 36 women with mild mental retardation in response to hypothetical social interpersonal situations involving abuse was evaluated. Participants were randomly assigned to a control or one of two training conditions (a decision-making training approach that either addressed both cognitive and motivational aspects of decision-making or included only instruction on the cognitive aspect of decision-making). Although both approaches were effective relative to a control condition, the combined cognitive and motivational training approach was superior to the cognitive only training approach. The superiority of this approach was also reflected on a verbally presented generalization task requiring participants to respond to a decision-making situation involving abuse from their own perspective and on a locus of control scale that measured perceptions of control.


Aerosol derived airway morphometry in healthy subjects.
Monodisperse aerosol particles can be used to non-invasively probe intrapulmonary airspace dimensions. In this study, the aerosol-derived airway morphometry technique was used to study airspace dimensions in 79 healthy subjects, in order to assess reference data for the future clinical application of aerosol-derived airway morphometry, and to investigate the effect of lung inflation, anthropometric, and lung function parameters on aerosol-derived airway morphometry. Intrapulmonary airspace dimensions were assessed by measuring the deposition of monodisperse, hydrophobic submicron aerosol particles during breathholding. Additionally, measurements of spirometric and body plethysmographic lung function were performed. Airspace dimensions were in good agreement with morphometric lung data. Airspace dimensions increased with increasing lung inflation. Interindividual variation of airspace dimensions was lowest in the lung periphery, at high levels of lung inflation, and when the volumetric lung depth was normalized to the end-inspiratory lung volume. Analysis of variance showed an increase of airspace dimensions with age. The results of this study indicate that aerosol-derived airway morphometry is dependent on the level of lung inflation and the age of the subject. These results suggest that in contrast to conventional lung function techniques, aerosol-derived airway morphometry might be a powerful tool for the detection of small changes in peripheral airway geometry.


Performance of Maximum Likelihood estimation of Mueller matrices taking into account physical realizability and Gaussian or Poisson noise statistics.
We address constrained estimation of the Mueller matrices from noisy measurements, taking into account the physical realizability. Physical realizability is enforced based on the positive semi-definite Hermitian coherency matrix, and the statistics of the noise is taken into account by employing Maximum Likelihood (ML) method. We consider two types of noise sources frequently encountered in optical imaging systems: additive Gaussian noise and Poisson shot noise. In both cases, we demonstrate reduction of estimation error by enforcing the physical realizability constraint, and superiority of the ML constrained solutions compared to empirically constrained ones. The ML constrained estimation method proposed in this paper provides a justified and effective way to exploit experimental measurements of Mueller matrices.


Elucidation of the Molecular Determinants for Optimal Perfluorooctanesulfonate Adsorption Using a Combinatorial Nanoparticle Library Approach.
Perfluorooctanesulfonate (PFOS) persistently accumulates in the environment and in humans, causing various toxicities. To determine the key molecular determinants for optimal PFOS specificity and efficiency, we designed and synthesized a combinatorial gold nanoparticle (GNP) library consisting of 18 members with rationally diversified hydrophobic, electrostatic, and fluorine-fluorine interaction components for PFOS bindings. According to our findings, the electrostatic and F-F interactions between PFOS and nanoparticles are complementary. When F-F attractions are relatively weak, the electrostatic interactions are dominant. As F-F interactions increase, the electrostatic contributions are reduced to as low as 20%, demonstrating that F-F binding may overpower even electrostatic interactions. Furthermore, F-F interactions (28-79% binding efficiency) are 2-fold stronger than regular hydrophobic interactions (15-39% binding efficiency) for PFOS adsorption, explaining why these novel PFOS-binding nanoparticles are superior to other conventional materials based on either hydrophobic or electrostatic binding. The PFOS adsorption by the optimized nanoparticles performs well in the presence of ionic interferences and in environmental wastewater. This library mapping approach can potentially be applied to recognition mechanism investigation of other pollutants and facilitate the discovery of effective monitoring probes and matrices for their removal.


Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: a randomized clinical trial.
Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment. While the clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial to date. To determine the efficacy and tolerability of low-dose oral 17β-estradiol and low-dose venlafaxine extended release in alleviating vasomotor symptoms (VMS). In total, 339 perimenopausal and postmenopausal women with at least 2 bothersome VMS per day (mean, 8.1 per day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites between December 5, 2011, and October 15, 2012. Participants were randomized to double-blind treatment with low-dose oral 17β-estradiol (0.5 mg/d) (n = 97), low-dose venlafaxine hydrochloride extended release (75 mg/d) (n = 96), or placebo (n = 146) for 8 weeks. The primary outcome was the mean daily frequency of VMS after 8 weeks of treatment. Secondary outcomes were VMS severity, bother, and interference with daily life. Intent-to-treat analyses compared the change in VMS frequency between each active intervention and placebo and between the 2 active treatments. Compared with baseline, the mean VMS frequency at week 8 decreased to 3.9 (95% CI, 2.9-4.9) VMS per day (52.9% reduction) in the estradiol group, to 4.4 (95% CI, 3.5-5.3) VMS per day (47.6% reduction) in the venlafaxine group, and to 5.5 (95% CI, 4.7-6.3) VMS per day (28.6% reduction) in the placebo group. Estradiol reduced the frequency of symptoms by 2.3 more per day than placebo (P < .001), and venlafaxine reduced the frequency of symptoms by 1.8 more per day than placebo (P = .005). The results were consistent for VMS severity, bother, and interference. Low-dose estradiol reduced the frequency of symptoms by 0.6 more per day than venlafaxine (P = .09). Treatment satisfaction was highest (70.3%) for estradiol (P < .001 vs placebo), lowest (38.4%) for placebo, and intermediate (51.1%) for venlafaxine (P = .06 vs placebo). Both interventions were well tolerated. Low-dose oral estradiol and venlafaxine are effective treatments for VMS in women during midlife. While the efficacy of low-dose estradiol may be slightly superior to that of venlafaxine, the difference is small and of uncertain clinical relevance. clinicaltrials.gov Identifier: NCT01418209.


The risk of high-grade squamous intraepithelial lesions in women with low serum levels of vitamin A.
The progression of the cervical squamous intraepithelial lesion (SIL) is associated with many cofactors, and nutritional aspects are gradually assuming an important role in understanding the physiopathogenesis. To assess the serum levels of retinol in women from a poor region of Brazil with a histological diagnosis of cervical high-grade SIL (HSIL). A cross-sectional study was conducted in 62 women aged 14-48 years who had a cervical biopsy and were treated at the Federal University of Ceara in Fortaleza, Brazil. Serum retinol levels were measured in peripheral blood by a spectrophotometry technique. Values were categorized as subnormal (<20 µg/dl) or normal (≥20 µg/dl). Multivariate logistic regression was used to determine the association between serum levels of retinol and HSIL for a confidence interval of 95%. Twenty-six out of 62 women (42%) had a negative histopathological result for SIL and 36 (58%) were diagnosed with SIL (20 low SIL and 16 high SIL). The level of retinol was more frequently low in women with HSIL, but there was no statistical significance [p = 0.409, OR: 2.26 (0.33-15.59)]. There was no association between high SIL and low levels of retinol in peripheral blood.


Surgical sequelae of abnormal eustachian tube function.
Mechanical, neural, and immunologic factors controlling eustachian tube function are discussed in detail. Relationships of normal tubal function to the development of otitis media with effusion and its pathologic sequelae are reviewed.


Integrin alpha6beta1-laminin interactions regulate early myotome formation in the mouse embryo.
We addressed the potential role of cell-laminin interactions during epaxial myotome formation in the mouse embryo. Assembly of the myotomal laminin matrix occurs as epaxial myogenic precursor cells enter the myotome. Most Myf5-positive and myogenin-negative myogenic precursor cells localise near assembled laminin, while myogenin-expressing cells are located either away from this matrix or in areas where it is being assembled. In Myf5(nlacZ/nlacZ) (Myf5-null) embryos, laminin, collagen type IV and perlecan are present extracellularly near myogenic precursor cells, but do not form a basement membrane and cells are not contained in the myotomal compartment. Unlike wild-type myogenic precursor cells, Myf5-null cells do not express the alpha6beta1 integrin, a laminin receptor, suggesting that integrin alpha6beta1-laminin interactions are required for myotomal laminin matrix assembly. Blocking alpha6beta1-laminin binding in cultured wild-type mouse embryo explants resulted in dispersion of Myf5-positive cells, a phenotype also seen in Myf5(nlacZ/nlacZ) embryos. Furthermore, inhibition of alpha6beta1 resulted in an increase in Myf5 protein and ectopic myogenin expression in dermomyotomal cells, suggesting that alpha6beta1-laminin interactions normally repress myogenesis in the dermomyotome. We conclude that Myf5 is required for maintaining alpha6beta1 expression on myogenic precursor cells, and that alpha6beta1 is necessary for myotomal laminin matrix assembly and cell guidance into the myotome. Engagement of laminin by alpha6beta1 also plays a role in maintaining the undifferentiated state of cells in the dermomyotome prior to their entry into the myotome.


Resonance control of a silicon micro-ring resonator modulator under high-speed operation using the intrinsic defect-mediated photocurrent.
A method to stabilize the resonance wavelength of a depletion-type silicon micro-ring resonator modulator during high-speed operation is described. The method utilizes the intrinsic defect-mediated photo-absorption of a silicon waveguide and results in a modulator chip fabrication process that is free of heterogeneous integration (for example using germanium), thus significantly reducing the complexity and cost of manufacture. Residual defects, present after p-n junction formation, are found to produce an adequate photocurrent for use as a feedback signal, while an integrated heater is used to compensate for thermal drift via closed-loop control. The photocurrent is measured by a source-meter, which simultaneously provides a DC bias to the integrated heater during high-speed operation. A drop-port or an integrated extrinsic detector is not needed. This feedback control method is experimentally demonstrated via a computer-aided proportional-integral-differential loop. The resonance locking is validated for 12.5 Gb/s intensity modulation in a back-to-back bit-error-rate measurement. The stabilization method described is not limited to a specific modulator design and is compatible with speeds greatly in excess of 12.5 Gb/s, in contrast to the bandwidth limitation of other stabilization methods that rely on intrinsic photo-carrier generation through non-linear processes such as two-photon-absorption. Further, the use of intrinsic defects present after standard fabrication insures that no excess loss is associated with this stabilization method.


Epigenetic switch reshapes epithelial progenitor cell signatures and drives inflammatory pathogenesis in hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a complex inflammatory skin disease with undefined mechanistic underpinnings. Here, we investigated HS epithelial cells and demonstrated that HS basal progenitors modulate their lineage restriction and give rise to pathogenic keratinocyte clones, resulting in epidermal hyperproliferation and dysregulated inflammation in HS. When comparing to healthy epithelial stem/progenitor cells, in HS, we identified changes in gene signatures that revolve around the mitotic cell cycle, DNA damage response and repair, as well as cell-cell adhesion and chromatin remodeling. By reconstructing cell differentiation trajectory and CellChat modeling, we identified a keratinocyte population specific to HS. This population is marked by S100A7/8/9 and KRT6 family members, triggering IL1, IL10, and complement inflammatory cascades. These signals, along with HS-specific proinflammatory cytokines and chemokines, contribute to the recruitment of certain immune cells during the disease progression. Furthermore, we revealed a previously uncharacterized role of S100A8 in regulating the local chromatin environment of target loci in HS keratinocytes. Through the integration of genomic and epigenomic datasets, we identified genome-wide chromatin rewiring alongside the switch of transcription factors (TFs), which mediated HS transcriptional profiles. Importantly, we identified numerous clinically relevant inflammatory enhancers and their coordinated TFs in HS basal CD49fhigh cells. The disruption of the S100A enhancer using the CRISPR/Cas9-mediated approach or the pharmacological inhibition of the interferon regulatory transcription factor 3 (IRF3) efficiently reduced the production of HS-associated inflammatory regulators. Our study not only uncovers the plasticity of epidermal progenitor cells in HS but also elucidates the epigenetic mechanisms underlying HS pathogenesis.


Genetic effects of air pollution on forest tree species of the Carpathian Mountains.
The effects of air pollution on the genetic structure of Norway spruce, European silver fir and European beech were studied at four polluted sites in Slovakia, Romania and Czech Republic. In order to reduce potential effects of site heterogeneity on the health condition, pair-wise sampling of pollution-tolerant and sensitive trees was applied. Genotypes of sampled trees were determined at 21 isozyme gene loci of spruce, 18 loci of fir and 15 loci of beech. In comparison with Norway spruce, fewer genetic differences were revealed in beech and almost no differentiation between pollution-tolerant and sensitive trees was observed in fir. In adult stands of Norway spruce, sensitive trees exhibited higher genetic multiplicity and diversity. The decline of pollution-sensitive trees may result thus in a gradual genetic depletion of pollution-exposed populations of Norway spruce through the loss of less frequent alleles with potential adaptive significance to altered stressing regimes in the future. Comparison of the subsets of sensitive and tolerant Norway spruce individuals as determined by presence or absence of discolorations ("spruce yellowing") revealed different heterozygosity at 3 out of 11 polymorphic loci.


[Aortoenteric fistula secondary to aortobifemoral prosthesis infection].
We present the case of a 76 year-old man, intervened of an obstruction bilateral iliac by means of placement of a prosthesis aortobifemoral that presented pain in the grave left iliac and fever in needles of 39 degrees C to the five years of the intervention. In the physical exploration it highlighted a painful abdomen in the grave left iliac with signs of peritoneal irritation. In the laboratory tests a leukocytosis was detected with neutrophilia and negative culture. The computed thomography (CT) show the presence of gas bubbles around the prosthesis, as well as a liquid collection with areas necrotics in their interior that affected to the psoas and iliac muscles. In the same exploration the aspirative puncture with drainage of the absces demonstrated in the cultivations carried out in aerobic means the presence of Enterococcus faecalis and Enterobacter cloacae. When presenting a high gastrointestinal hemorrhage abruptly, he was practiced and gastroduodenal endoscope in which a aortoduodenal fistula was evidenced with having bled active. When a bypass extra-anatomic, the sick person will practice it died when presenting a shock abrupt hipovolemic that he didn't respond to the pertinent treatment. We analyze the approaches current diagnoses of infection of the vascular prosthesis and their more serious complication, the aortoenteric fistula (AEF) that either appears in the 0.3-5.9% of the patients who undergo prosthetic reconstruction of the abdominal aorta, for occlusive or aneurismal disease. We highlight the importance of carrying out a precocious diagnosis of the infection of the portion retroperitoneal of the vascular graft that, often, it is manifested with subtle and not specific clinical signs, with the techniques at the moment available as: the CT, fine needle aspiration guided by her, and to diminish the rates of mortality, from the current of 43%, until the most optimistic estimated in 19%.


Economic evaluation of enhanced staff contact for the promotion of breastfeeding for low birth weight infants.
There is evidence that breastmilk feeding reduces mortality and short and long-term morbidity among infants born too soon or too small. The aim of this study was to evaluate the cost-effectiveness of enhanced staff contact for mothers with infants in a neonatal unit with a birth weight of 500-2,500 g from the perspective of the UK National Health Service. A decision-tree model linked clinical outcomes with long-term health outcomes. The study population was divided into three weight bands: 500-999 g, 1000-1,749 g, and 1,750-2,500 g. Clinical and resource use data were obtained from literature reviews. The measure of benefit was quality-adjusted life-years. Uncertainty was evaluated using cost-effectiveness acceptability curves and sensitivity analyses. The intervention was less costly and more effective than the comparator in the base-case analysis for each birth weight group. The results were quite robust to the sensitivity analyses performed. This is the first economic evaluation in this complex field and offers a model to be developed in future research. The results provide preliminary indications that enhanced staff contact may be cost-effective. However, the limited evidence available, and the limited UK data in particular, suggest that further research is required to provide results with confidence.


Methylobacterium populi VP2: plant growth-promoting bacterium isolated from a highly polluted environment for polycyclic aromatic hydrocarbon (PAH) biodegradation.
The use of microorganisms to accelerate the natural detoxification processes of toxic substances in the soil represents an alternative ecofriendly and low-cost method of environmental remediation compared to harmful incineration and chemical treatments. Fourteen strains able to grow on minimal selective medium with a complex mixture of different classes of xenobiotic compounds as the sole carbon source were isolated from the soil of the ex-industrial site ACNA (Aziende Chimiche Nazionali Associate) in Cengio (Savona, Italy). The best putative degrading isolate, Methylobacterium populi VP2, was identified using a polyphasic approach on the basis of its phenotypic, biochemical, and molecular characterisation. Moreover, this strain also showed multiple plant growth promotion activities: it was able to produce indole-3-acetic acid (IAA) and siderophores, solubilise phosphate, and produce a biofilm in the presence of phenanthrene and alleviate phenanthrene stress in tomato seeds. This is the first report on the simultaneous occurrence of the PAH-degrading ability by Methylobacterium populi and its multiple plant growth-promoting activities. Therefore, the selected indigenous strain, which is naturally present in highly contaminated soils, is good candidate for plant growth promotion and is capable of biodegrading xenobiotic organic compounds to remediate contaminated soil alone and/or soil associated with plants.


[Different stages of hyperostosis of the heads of the ribs in spondylosis hyperostotica].
Hyperostosis of the heads of the ribs represents a rare pattern and localization of spondylosis hyperostotica. The latter is combined with asymmetric extensions of the costovertebral surfaces, which are different from arthrotic alterations. A distinct preference is given to the upper glenoid surfaces. The scleroses of the heads of the ribs are also more pronounced in their cranial parts. Because of the pattern and different extent of the reported alterations a classification in five degrees of development and severity was possible.