Community Participation and Strengthening in a Reconstruction Context After a Natural Disaster.
During the first academic term of 2010, participatory action investigation processes were conducted in three communities affected by the 2007 high magnitude earthquake that occurred in the province of Chincha (Ica, Peru). In the process, members of the communities identified, as core problems, aspects related to the community coexistence, emphasizing the attention of the most vulnerable segments (children and adolescents) in the context of economic constraints and problems aggravated by the earthquake. Results include an analysis of the needs and reactions following the earthquake, the leadership and the power relations visible in the post disaster context and, finally, the community participation throughout the reconstruction process. This article also proposes some topics resulting from the analysis, aiming to contribute to interventions focused on community participation and strengthening of local resources in contexts of great vulnerability to natural disasters.


Rapid and high-precision displacement sensing based on the multiple mode dip areas in a SNAP microresonator.
Whispering gallery mode (WGM) microresonators offer significant potential for precise displacement measurement owing to their compact size, ultrahigh sensitivity, and rapid response. However, conventional WGM displacement sensors are prone to noise interference, resulting in accuracy loss, while the demodulation process for displacement often exhibits prolonged duration. To address these limitations, this study proposes a rapid and high-precision displacement sensing method based on the dip areas of multiple resonant modes in a surface nanoscale axial photonics microresonator. By employing a neural network to fit the nonlinear relationship between displacement and the areas of multiple resonant dips, we achieve displacement prediction with an accuracy better than 0.03 µm over a range of 200 µm. In comparison to alternative sensing approaches, this method exhibits resilience to temperature variations, and its sensing performance remains comparable to that in a noise-free environment as long as the signal-to-noise ratio is greater than 25 dB. Furthermore, the extraction of the dip area enables significantly enhanced speed in displacement measurement, providing an effective solution for achieving rapid and highly accurate displacement sensing.


Low serum selenium is associated with the severity of organ failure in critically ill children.
Low concentration of serum selenium is associated with the inflammatory response and multiple organ failure in adult ICU-patients. Critically ill children are less well characterized. In this study, serum selenium concentration and its possible relation to multiple organ failure as well as glutathione status was investigated in pediatric intensive care (PICU) patients. A prospective consecutive cohort of critically ill children (n = 100) admitted to the PICU of a tertiary university hospital, and in addition an age stratified reference group of healthy children (n = 60) were studied. The concentrations of serum selenium and reduced and total glutathione were determined at admission and at day 5 for patients still in the PICU. Low concentration of serum selenium as well as a high-reduced fraction of glutathione (GSH/tGSH) was associated with multiple organ failure (p < 0.001 and p < 0.01) respectively. A correlation between low serum selenium concentration and high-reduced fraction of glutathione (GSH/tGSH) was also seen (r = -0.19 and p = 0.03). The serum selenium concentrations in the pediatric reference group in a selenium poor area were age dependent with lower concentrations in infants as compared to older children (p < 0.001). Both low serum selenium concentration and high reduced fraction of glutathione (GSH/tGSH) were associated with the development of multiple organ failure. The association between low serum selenium concentration and high fraction of reduced glutathione in whole blood favour the hypothesis that selenium is of critical importance for the scavenge capacity of glutathione peroxidase (GPX).


Determination of total folates in infant formula and adult nutritionals by trienzyme extraction and UPLC-MS/MS Quantitation: First Action 2011.06.
The method for "Determination of Total Folates in Infant Formula and Adult Nutritionals by Trienzyme Extraction and UPLC-MS/MS Quantitation" was submitted to the Folate Working Group for consideration for adoption as Official First Action by AOAC INTERNATIONAL. This method uses ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) to determine the total folates in infant formulas and adult nutritionals after trienzyme digestion. Deconjugation of the various folate polyglutamates to folate monoglutamates is achieved by using rat plasma conjugase after the sample digestion with protease and a-amylase during the trienzyme digestion process. This method shows linearity of folate concentrations in the range of 10-19 100 microg/100 g. Extension of the range to cover folate concentrations of 5-2 000 000 microg/100 g can be achieved with appropriate adjustment of the sample weight and SPE cleanup loading volume. The recoveries ranged from 94.10 to 101.34%.


[Are systemic diseases of infectious origin?].
Defined as diffuse inflammatory disorders, theoretically of unknown origin, systemic diseases would thus not be of infectious origin. Nevertheless, a series of examples shows that it is possible for some, and probable for others, that a parasitic, bacterial or especially viral infection would be a triggering or maintaining factor. In addition, better means of investigation have already and will certainly lead to more precise study of this interaction. New pathophysiological mechanisms are predicted and sometimes already shown. The results have already influenced therapy. It can therefore be concluded that at least some diseases considered to by systemic are probably of infectious origin.


Displaced honey bees perform optimal scale-free search flights.
Honey bees (Apis mellifera) are regularly faced with the task of navigating back to their hives from remote food sources. They have evolved several methods to do this, including compass-directed "vector" flights and the use of landmarks. If these hive-centered mechanisms are disrupted, bees revert to searching for the hive, but the nature and efficiency of their searching strategy have hitherto been unknown. We used harmonic radar to record the flight paths of honey bees that were searching for their hives. Our subsequent analysis of these paths revealed that they can be represented by a series of straight line segments that have a scale-free, Lévy distribution with an inverse-square-law tail. We show that these results, combined with the "no preferred direction" characteristic of the segments, demonstrate that the bees were flying an optimal search pattern. Lévy movements have already been identified in a number of other animals. Our results are the best reported example where the movements are mostly attributable to the adoption of an optimal, scale-free searching strategy.


Behaviour Real-Time Spatial Tracking Identification (BeRSTID) used for Cat Behaviour Monitoring in an Animal Shelter.
Efficiently tracking animal behaviour in an animal shelter has direct lifesaving applications. Individualized care and early recognition of distress in cats are often missed. However, monitoring behaviour is a challenge as time and financial resources are often limited, and the size and needs of animal populations within shelters are commonly in flux. Our research required a method of behavioural observation that was simple, accessible, used limited human and computer resources and allowed for real-time feedback. Here, we present BeRSTID, an open-source behaviour real-time spatial tracking identification system demonstrated on six cats in an animal shelter using unique 2D fiducial markers. The markers were attached to custom veterinary paper identification collars for feedback on individual animal behaviour over time. Our findings show that BeRSTID correlated closely to human-coded data in both real-time and post-event processing modes of eating and drinking behaviours of cats in naturalistic shelter environments. By building upon a lateral concept of marker tracking for direct applied use in a new context, we present a low-barrier user-friendly solution using common technologies that can track animals for research and, with further development, may help improve welfare in animal care facilities such as shelters. Extensions of BeRSTID may be generalized to track unique subjects in varied environments for multiple use cases.


A Cryptic Invasion in the Western Atlantic: Presence of the Fouling Barnacle Megabalanus zebra (Darwin, 1854) (Crustacea, Cirripedia) in the Caribbean Sea.
The barnacle Megabalanus zebra is largely known from ship hulls, with little information on its biology, ecology, and natural range. We identify M. zebra here from the southern Caribbean, based upon specimens collected as early as 2002. Challenges associated with identifying megabalinine species have delayed recognition of this species as distinct from other Caribbean Megabalanus. Sequenced material of M. zebra from Curaçao did not match M. zebra GenBank sequences that could be verified by descriptions or vouchered material. The presence of young M. zebra on vessels that have not left the Caribbean, as well as on pier pilings and resident buoys, indicate that this species is established in the tropical Western Atlantic Ocean, but the timing of its invasion remains unknown.


Cardiac protection by volatile anesthetics in non-cardiac surgery? A meta-analysis of randomized controlled studies on clinically relevant endpoints.
Volatile anesthetics improve post-ischemic recovery. A meta-analysis suggested that the cardioprotective properties of desflurane and sevoflurane could reduce mortality and cardiac morbidity in cardiac surgery. Recent American College of Cardiology / American Heart Association Guidelines recommended volatile anesthetic agents during non-cardiac surgery for the maintenance of general anesthesia in patients at risk for myocardial infarction but whether these cardioprotective properties exist in non-cardiac surgery settings is controversial. We therefore performed a meta-analysis of randomized studies to investigate this issue. Two investigators independently searched PubMed. Inclusion criteria were random allocation to treatment, comparison of a total intravenous anesthesia regimen vs an anesthesia plan including desflurane or sevoflurane, performed on adult patients undergoing non-cardiac surgery. The primary endpoints were the incidence of perioperative myocardial infarction and death. A total of 6219 patients from 79 randomized trials were identified. No myocardial infarctions or deaths were reported in any of the studies we examined. This meta-analysis highlights a weakness in the literature and the results can be used to design future studies: the cardioprotective properties of desflurane and sevoflurane have never been studied in noncardiac surgery. No randomized study, among those which compared desflurane or sevoflurane to intravenous anesthetics, has addressed major outcomes such as myocardial infarction or mortality. Large, multicentre, randomized clinical trials including patients undergoing high-risk non-cardiac surgery and reporting clinically relevant outcomes such as myocardial infarction and mortality are needed.


MicroRNA Regulation of Epigenetic Modifiers in Breast Cancer.
Epigenetics refers to the heritable changes in gene expression without a change in the DNA sequence itself. Two of these major changes include aberrant DNA methylation as well as changes to histone modification patterns. Alterations to the epigenome can drive expression of oncogenes and suppression of tumor suppressors, resulting in tumorigenesis and cancer progression. In addition to modifications of the epigenome, microRNA (miRNA) dysregulation is also a hallmark for cancer initiation and metastasis. Advances in our understanding of cancer biology demonstrate that alterations in the epigenome are not only a major cause of miRNA dysregulation in cancer, but that miRNAs themselves also indirectly drive these DNA and histone modifications. More explicitly, recent work has shown that miRNAs can regulate chromatin structure and gene expression by directly targeting key enzymes involved in these processes. This review aims to summarize these research findings specifically in the context of breast cancer. This review also discusses miRNAs as epigenetic biomarkers and as therapeutics, and presents a comprehensive summary of currently validated epigenetic targets in breast cancer.


[Thrombocytopenia and other extrahepatic manifeststions of hepatitis C virus infection--case report].
Authors present a case of forty seven years old woman with thrombocytopenia in the course of hepatitis C virus infection. Thrombocytopenia might be related to immunological mechanisms or be an effect of hypersplenism. Moreover mixed cryoglobulinemia, lymphocytic autoimmune thyroiditis with hypothyroidism and other laboratory abnormalities (impaired rate of lymphocytes CD4 to CD8, increase of B cells and natural killer cells, hypocomplementemia, hypergammaglobulinemia, increase of immune complexes concentration) were revealed. Above-mentioned abnormalities might be an effect of hepatitis C virus infection.


Accumulation of abasic sites induces genomic instability in normal human gastric epithelial cells during Helicobacter pylori infection.
Helicobacter pylori infection of the human stomach is associated with inflammation that leads to the release of reactive oxygen and nitrogen species (RONs), eliciting DNA damage in host cells. Unrepaired DNA damage leads to genomic instability that is associated with cancer. Base excision repair (BER) is critical to maintain genomic stability during RONs-induced DNA damage, but little is known about its role in processing DNA damage associated with H. pylori infection of normal gastric epithelial cells. Here, we show that upon H. pylori infection, abasic (AP) sites accumulate and lead to increased levels of double-stranded DNA breaks (DSBs). In contrast, downregulation of the OGG1 DNA glycosylase decreases the levels of both AP sites and DSBs during H. pylori infection. Processing of AP sites during different phases of the cell cycle leads to an elevation in the levels of DSBs. Therefore, the induction of oxidative DNA damage by H. pylori and subsequent processing by BER in normal gastric epithelial cells has the potential to lead to genomic instability that may have a role in the development of gastric cancer. Our results are consistent with the interpretation that precise coordination of BER processing of DNA damage is critical for the maintenance of genomic stability.


Exercise Training and Cognitive Rehabilitation: A Symbiotic Approach for Rehabilitating Walking and Cognitive Functions in Multiple Sclerosis?
The current review develops a rationale and framework for examining the independent and combined effects of exercise training and cognitive rehabilitation on walking and cognitive functions in persons with multiple sclerosis (MS). To do so, we first review evidence for improvements in walking and cognitive outcomes with exercise training and cognitive rehabilitation in MS. We then review evidence regarding cognitive-motor coupling and possible cross-modality transfer effects of exercise training and cognitive rehabilitation. We lastly present a macro-level framework for considering mechanisms that might explain improvements in walking and cognitive dysfunction with exercise and cognitive rehabilitation individually and combined in MS. We conclude that researchers should consider examining the effects of exercise training and cognitive rehabilitation on walking, cognition, and cognitive-motor interactions in MS and the possible physiological and central mechanisms for improving these functions.


Dietary Crocin Inhibits Colitis and Colitis-Associated Colorectal Carcinogenesis in Male ICR Mice.
A natural carotenoid crocin is contained in saffron and gardenia flowers (crocuses and gardenias) and is used as a food colorant. This study reports the potential inhibitory effects of crocin against inflammation-associated mouse colon carcinogenesis and chemically induced colitis in male ICR mice. In the first experiment, dietary crocin significantly inhibited the development of colonic adenocarcinomas induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) in mice by week 18. Crocin feeding also suppressed the proliferation and immunohistochemical expression of nuclear factor- (NF-) κB but increased the NF-E2-related factor 2 (Nrf2) expression, in adenocarcinoma cells. In the second experiment, dietary feeding with crocin for 4 weeks was able to inhibit DSS-induced colitis and decrease the mRNA expression of tumor necrosis factor α, interleukin- (IL-) 1β, IL-6, interferon γ, NF-κB, cyclooxygenase-2, and inducible nitric oxide synthase in the colorectal mucosa and increased the Nrf2 mRNA expression. Our results suggest that dietary crocin suppresses chemically induced colitis and colitis-related colon carcinogenesis in mice, at least partly by inhibiting inflammation and the mRNA expression of certain proinflammatory cytokines and inducible inflammatory enzymes. Therefore, crocin is a candidate for the prevention of colitis and inflammation-associated colon carcinogenesis.


A novel Norrie disease pseudoglioma gene mutation, c.-1_2delAAT, responsible for Norrie disease in a Chinese family.
To investigate the genetic findings and phenotypic characteristics of a Chinese family with Norrie disease (ND). Molecular genetic analysis and clinical examinations were performed on a Chinese family with ND. Mutations in the Norrie disease pseudoglioma (NDP) gene were detected by direct sequencing. Haplotypes were constructed and compared with the phenotypes in the family. Evolutionary comparisons and mutant open reading frame (ORF) prediction were also undertaken. Two family members with ocular manifestations were diagnosed with ND. No signs of sensorineural hearing loss were observed in either patient, while one of them showed signs of mild mental retardation. A novel heterozygous mutation in the NDP gene, c.-1_2delAAT, was detected in both patients. The mutation and the mutation bearing haplotype co-segregated with the ND phenotype in males and was transmitted from their mothers and/or grandmothers (II:2). The male without ND did not harbor the mutation. The mutation occurred at the highly conserved nucleotides. ORF finder predicted that the mutation would lead to the production of a truncated protein that lacks the first 11 N-terminal amino acids. A novel mutation, c.-1_2delAAT in the NDP gene, was identified in a Chinese family with ND. This mutation caused ND without obvious sensorineural hearing loss. Mental disorder was found in one but not the other patients. The clinical heterogeneity in the family indicated that other genetic variants and epigenetic factors may also play a role in the disease presentation.


Unique Immune Blood Markers Between Severe Dengue and Sepsis in Children.
Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies. We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease. During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate. Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.


Chemistry of Renieramycins. 15. Synthesis of 22-O-Ester Derivatives of Jorunnamycin A and Their Cytotoxicity against Non-Small-Cell Lung Cancer Cells.
Eighteen 22-O-ester derivatives of jorunnamycin A (2) were prepared via 2, and their cytotoxicity against human non-small-cell lung cancer (NSCLC) cells was evaluated. Preliminary study of the structure-cytotoxicity relationship revealed that the ester part containing a nitrogen-heterocyclic ring elevated the cytotoxicity of the 22-O-ester derivatives. Among them, 22-O-(4-pyridinecarbonyl) ester 6a is the most potent compound (IC50 1.1 and 1.6 nM), exhibiting 21-fold and 5-fold increases in cytotoxicity against the H292 and H460 NSCLC cell lines, respectively, relative to renieramycin M (1), the major cytotoxic bistetrahydroisoquinolinequinone alkaloid of the Thai blue sponge Xestospongia sp.


Partial trisomy 17q and partial monosomy 20q in a boy with craniosynostosis.
Craniosynostosis is defined as a premature fusion of at least one cranial suture, which can be accompanied by other findings. Of syndromic cases, 14-22% have been associated with chromosomal rearrangements. This report describes a Brazilian boy with syndromic craniosynostosis who also presented with intellectual disability, microcephaly, frontal bossing, bitemporal narrowing, short neck, syndactyly, and cardiac defects. Chromosome banding showed an apparently normal male karyotype. Subsequent chromosomal microarray analysis (CMA) using the Affymetrix CytoScan 750 K Array showed a duplication of 2.1 Mb on chromosome 17q and a deletion of 1.4 Mb on chromosome 20q. The data suggested an unbalanced translocation, which was confirmed by fluorescence in-situ hybridization analysis (FISH). While there are several reports in the literature of chromosome 17q duplication syndrome accompanied by partial monosomies of other chromosomes, this is the first case featuring partial monosomy of 20q. The patient́s phenotype is generally consistent with 17q duplication syndrome, however craniosynostosis has rarely been associated with this chromosomal anomaly.


Recent advances in TPGS-based nanoparticles of docetaxel for improved chemotherapy.
Docetaxel (DTX) is one of the important antitumor drugs, being used in several common chemotherapies to control leading cancer types. Severe toxicities of the DTX are prominent due to sudden parenteral exposure of desired loading dose to maintain the therapeutic concentration. Field of nanotechnology is leading to resist sudden systemic exposure of DTX with more specific delivery to the site of cancer. Further nanometric size range of the formulation aid for prolonged circulation, thereby extensive exposure results better efficacy. In this article, we extensively reviewed the therapeutic benefit of incorporating d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS, or simply TPGS) in the nanoparticle (NP) formulation of DTX for improved delivery, tumor control and tolerability. TPGS is well accepted nonionic-ampiphilic polymer which has been identified in the role of emulsifier, stabilizer, penetration enhancer, solubilizer and in protection in micelle. Simultaneously, P-glycoprotein inhibitory activity of TPGS in the multidrug resistant (MDR) cancer cells along with its apoptotic potential are the added advantage of TPGS to be incorporated in nano-chemotherapeutics. Thus, it could be concluded that TPGS based nanoparticulate application is an advanced approach to improve therapeutic efficacy of chemotherapeutic agents by better internalization and sustained retention of the NPs.


Representation scaffolds improve diagnostic efficiency in medical students.
Diagnostic efficiency is important in daily clinical practice as doctors have to face problems within a limited time frame. To foster the clinical reasoning of students is a major challenge in medical education research. Little is known about students' diagnostic efficiency. On the basis of current theories, scaffolds for case representation (statement of the case as far as it is summarised in the mind) could be a promising approach to make the diagnostic reasoning of intermediate medical students more efficient. Clinical case processing of 88 medical students in their fourth and fifth years was analysed in a randomised, controlled laboratory study. Cases dealing with dyspnoea were provided in an electronic learning environment (CASUS). Students could freely choose the time, amount and sequence of clinical information. During the learning phase the intervention group was asked to write down case representation summaries while working on the cases. In the assessment phase diagnostic efficiency was operationalised as the number of correct diagnoses divided by the time spent on diagnosing. Diagnostic efficiency was significantly improved by the representation scaffolding (M = 0.12 [SD = 0.07], M = 0.09 [SD = 0.06] correct cases/time, p = 0.045), whereas accuracy remained unchanged (M = 2.28 [SD = 1.10], M = 2.09 [SD = 1.08], p = 0.52). Both groups screened the same amount of clinical information, but the scaffolding group did this faster (M = 20.8 minutes [SD = 7.15], M = 24.6 minutes [SD = 7.42], p = 0.01; Cohen's d = 0.5). Diagnostic efficiency is an important outcome variable in clinical reasoning research as it corresponds to workplace challenges. Scaffolding for case representations significantly improved the diagnostic efficiency of fourth and fifth-year medical students, most likely because of a more targeted screening of the available information.


Plant proteins as binders in cellulosic paper composites.
Plant proteins are used - for the first time - in this work as bulk binders for cellulosic fibers in paper composites. Soy bean protein and wheat gluten were denatured by two methods, namely by: urea+NaOH and by urea+NaOH+acrylamide. Addition of increased amounts of the denatured proteins resulted in a significant increase in all paper strength properties. Soy protein led, in addition, to a remarkable enhancement in opacity. The use of proteins increased kaolin retention in the paper composites, while keeping the paper strength higher than the blank protein-free paper. The results show that plant proteins are favorable than synthetic adhesives; because they are biodegradable and do not cause troubles in paper recycling i.e. they are environmentally friendly.


Molecular modeling of HIV-1 reverse transcriptase drug-resistant mutant strains: implications for the mechanism of polymerase action.
A computer model of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) either alone, or complexed with a non-nucleoside inhibitor (NNI), was constructed using crystal coordinate data from a subset of the protein surrounding the binding pocket region. Molecular mechanics calculations were carried out on solvated wild-type RT and RT that contained modifications corresponding to resistance-engendering mutations. Results from the calculations revealed that the r.m.s. difference between 12 modified proteins and that of wild-type RT could be qualitatively correlated with the measured polymerase activity of the enzyme in the presence of these mutations. In addition, the level of activity was related to the measured distance between the primer grip and dNTP binding regions of the protein. These data suggest a direct correlation between RT structure and function. Complexes of RT-8-C1 TIBO and RT-alpha-APA were also minimized in models containing modifications corresponding to key drug-resistant mutants. The variant complexes all showed weaker binding than wild-type RT, while giving rise to similar, but critical changes in the protein. Therefore, the design of new inhibitors should center on obtaining stronger binding drugs to key drug-resistant RT variants.


New conformal mapping for adaptive resolving of the complex singularities of Stokes wave.
A new highly efficient method is developed for computation of travelling periodic waves (Stokes waves) on the free surface of deep water. A convergence of numerical approximation is determined by the complex singularities above the free surface for the analytical continuation of the travelling wave into the complex plane. An auxiliary conformal mapping is introduced which moves singularities away from the free surface thus dramatically speeding up numerical convergence by adapting the numerical grid for resolving singularities while being consistent with the fluid dynamics. The efficiency of that conformal mapping is demonstrated for the Stokes wave approaching the limiting Stokes wave (the wave of the greatest height) which significantly expands the family of numerically accessible solutions. It allows us to provide a detailed study of the oscillatory approach of these solutions to the limiting wave. Generalizations of the conformal mapping to resolve multiple singularities are also introduced.


Contribution of endothelin receptors in renal microvessels in acute cyclosporine-mediated vasoconstriction in rats.
Cyclosporine A (CsA), a widely used immunosuppressive agent, causes renal vasoconstriction and systemic hypertension. Recent data suggest that the renal effect of CsA is possibly mediated by endothelin (ET). We investigated the effects of CsA on renal microvessels and the efficacy of ETA or ETA/ETB receptor antagonists in ameliorating CsA effects in the hydronephrotic rat kidney. Infusion of CsA (30 mg.kg-1) induced a transient increase (20%) in mean arterial pressure (MAP) and a sustained reduction (85%) in glomerular blood flow (GBF) due to preferential constriction of the arcuate artery (39%) and the proximal segment of the interlobular artery (23%). Under basal conditions the ETA receptor antagonist BQ-123 had marginal effects consisting of reduction in MAP, rise in GBF and dilation of preglomerular vessels. The non-selective ETA/ETB receptor antagonist PD 145065 also reduced MAP, but tended to decrease GBF and constrict large preglomerular vessels. The difference in effects of the two antagonists indicated that under basal conditions ETB blockade constricts large preglomerular vessels and reduces GBF. After BQ-123 or PD 145065, the constriction of large preglomerular vessels and reduction in GBF induced by CsA was attenuated by about 50%, but the rise in MAP was not influenced. Our data indicate that a sizable part of renal vasoconstriction due to CsA is mediated via ET production in large preglomerular arteries and can be avoided by the blockade of ETA receptors. Additional blockade of ETB receptors does not attenuate the CsA effects further, possibly because ETB receptors mediate both vasoconstriction and dilation.


Expression of intercellular adhesion molecule-1 and infiltration of lymphocytes in glomeruli of patients with IgA nephropathy.
Using immunofluorescence, we studied 19 patients with IgA nephropathy to determine whether the expression of intercellular adhesion molecule (ICAM)-1 in glomeruli might reflect the disease activity. The relationship between the expression of ICAM-1 and the infiltration of lymphocytes, monocytes and polymorphonuclear leukocytes (PMN) in glomeruli of IgA nephropathy cases was examined. The expression of ICAM-1 in patients in the advanced stage was significantly higher than that in patients in the mild stage. In double immunofluorescence, the distribution of ICAM-1 expression in glomeruli was different from that of IgA deposition in patients in both stages. Glomeruli which showed increases of ICAM-1 expression had marked infiltration of lymphocytes (OKT4+, OKT8+ T cells), and monocytes (OKM1+ cells). Increase of urinary protein and decreases in renal function were observed in patients in the advanced stage. It appears that the expression of ICAM-1 is closely linked to glomerular cell proliferation, and infiltration of lymphocytes and monocytes in patients with IgA nephropathy. However, the expression of ICAM-1 in glomeruli might not be correlated with IgA-dominant immune complexes in this disease.


Characterization of the key antigenic components and pre-clinical immune responses to a meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles.
Serogroup B strains are now responsible for over 80% of meningococcal disease in the UK and no suitable vaccine is available that confers universal protection against all serogroup B strains. Neisseria lactamica shares many antigens with the meningococcus, except capsule and the surface protein PorA. Many of these antigens are thought to be responsible for providing cross-protective immunity to meningococcal disease. We have developed an N. lactamica vaccine using methods developed for meningococcal outer membrane vesicle (OMV) vaccines. The major antigenic components were identified by excision of 11 major protein bands from an SDS-PAGE gel, followed by mass spectrometric identification. These bands contained at least 22 proteins identified from an unassembled N. lactamica genome, 15 of which having orthologues in published pathogenic Neisseria genomes. Western blotting revealed that most of these bands were immunogenic, and antibodies to these proteins generally cross-reacted with N. meningitidis proteins. Sera from mice and rabbits immunized with either N. lactamica or N. meningitidis OMVs produced comparable cross-reactive ELISA titres against OMVs prepared from a panel of diverse meningococcal strains. Mice immunized with either N. meningitidis or N. lactamica OMVs showed no detectable serum bactericidal activity against the panel of target strains except N. meningitidis OMV sera against the homologous strain. Similarly, rabbit antisera to N. lactamica OMVs elicited little or no bactericidal antibodies against the panel of serogroup B meningococcal strains. However, such antisera did mediate opsonophagocytosis, suggestingthat this may did mediate opsonophagocytosis, suggesting that this may be a mechanism by which this vaccine protects in a mouse model of meningococcal bacteraemia.


Ligand binding to heme proteins: the effect of light on ligand binding in myoglobin.
Extended illumination slows the rebinding of CO to myoglobin after photodissociation at cryogenic temperatures. Two types of models have been put forward to explain the effect: motions of the CO within the heme pocket or conformational transitions of the protein. To resolve this ambiguity, we have studied the effect of extended illumination on ligand binding to horse and sperm whale myoglobin (hMb and swMb) with temperature-derivative spectroscopy, monitoring the reaction in the CO stretch bands in the infrared and the conformation-sensitive band III near 760 nm. The experiments show that the stretch frequency of the photodissociated CO does not change upon illumination, implying that the slowing of the CO rebinding is caused by conformational relaxation of Mb from the bound state toward the deoxy structure. The light-induced relaxation (LIR) depends on the number of photons absorbed but not on the light intensity or duration separately. LIR occurs on photon absorption in either the bound or photodissociated state and depends on the temperature at which the MbCO is illuminated. The LIR proceeds in jumps through a small number of conformational substates. The effective barrier for rebinding increases with each step. The substates populated are similar to those found in the thermally-induced relaxation (TIR) that is observed above 160 K. LIR depends markedly on the structural details; it differs for swMbCO and hMbCO and even for the three A substates of swMbCO. Pronounced differences exist between the effects in MbCO and MbO2. The similarity of LIR and TIR leads to a revised model for ligand binding to swMbCO and hMbCO, in which the relaxation is crucial for the escape of the ligand from the pocket, as was first suggested by Friedman [Friedman, J. M. (1985) Science 228, 1273-1280].


The Adverse Effects of Motherhood on Substance Use Treatment Program Outcomes Among Adolescent Women.
Adolescent mothers have differing risks and responsibilities compared to adolescent women without children that may impact substance use treatment. This study sought to describe characteristics of adolescent women in a substance use treatment program and determine the effect of adolescent motherhood on treatment program outcomes. Data were collected from standardized interviews of female adolescents in a case management criminal justice diversion program for substance-using adolescents and adults. Variables included sociodemographic factors (ie, race/ethnicity, age, financial support, education, insurance, marital status, sexual abuse), Diagnostic and Statistical Manual-IV (DSM-IV) substance use disorder diagnoses, and motherhood (ie, childbirth and residence with a child). Treatment program outcome was documented by case workers at the end of the participants' time in the program. Chi-square analyses and analysis of variances determined associations between variables. Logistic regression was used to assess characteristics associated with negative treatment program outcome. Data from 1080 adolescent women aged 16-21 years (mean 19.7 years, SD = 1.16) were analyzed; 403 (37%) were mothers. After controlling for sociodemographic factors and substance use disorder diagnoses, adolescent mothers were less likely to successfully complete the treatment program than nonmothers. Adolescent women with reliance on family or friends for financial support, lower education status, and cannabis and cocaine use disorders had worse treatment program outcomes. Childbirth and parenting adversely affect substance use treatment outcomes for adolescent women in the criminal justice system. Future research should explore tailored substance use treatments for adolescents with children. Job training and educational support may improve outcomes.


Meta-Ribosomalomics: RNA Sequencing Is an Unbiased Method for Parasite Detection of Different Sample Types.
In this perspective article, we review the past use of ribosomal sequences to address scientific and diagnostic questions. We highlight a variety of sequencing approaches including metagenomics and DNA barcoding and their different demands and requirements. Meta-ribosomalomics is introduced as an unbiased approach to exploit high-throughput sequencing datasets for eukaryotic and prokaryotic ribosomal sequences. Prerequisites, benefits, drawbacks, and future perspectives are elaborated and compared to other sequencing approaches.


Anomalous Reflection of Gold: A Novel Platform for Biochips.
The importance of protein detection system for protein functions analyses in recent post-genomic era is rising with the emergence of label-free protein detection methods. We are focusing on a simple and practical label-free optical-detection method called anomalous reflection (AR) of gold. When a molecular layer forms on the gold surface, significant reduction in reflectivity can be observed at wavelengths of 400-500 nm. This allows the detection of molecular interactions by monitoring changes in reflectivity. In this chapter, we describe the AR method with three different application platforms: (1) gold, (2) gold containing alloy/composite (AuAg2O), and (3) metal-insulator-metal (MIM) thin layers. The AuAg2O composite and MIM are implemented as important concepts for signal enhancement process for the AR technique. Moreover, the observed molecular adsorption and activity is aided by a three-dimensional surface geometry, performed using poly(amidoamine) or PAMAM dendrimer modification. The described system is suitable to be used as a platform for high-throughput detection system in a chip format.


[Childhood passive smoking and purulent meningitis].
The relationship between purulent meningitis and passive smoking were investigated in 63 children with purulent meningitis aged 1-12 years against 63 children with non-purulent meningitis as control. It was found that the odds ratio of purulent meningitis for children receiving passive smoking was 3.0, and the 95% confident limit was greater than 1 (P < 0.05). There was significant dose-effect relationship between the daily dosage of cigarette smoked by family members and the odds ratio of purulent meningitis (P < 0.005). It suggests that passive smoking is one of the risk factors for purulent meningitis.


[Asymmetric synthesis of aromatic L-amino acids catalyzed by transaminase].
Aromatic L-Amino acids are important chiral building blocks for the synthesis of many drugs, pesticides, fine chemicals and food additives. Due to the high activity and steroselectivity, enzymatic synthesis of chiral building blocks has become the main research direction in asymmetric synthesis field. Guided by the phylogenetic analysis of transaminases from different sources, two representative aromatic transaminases TyrB and Aro8 in type I subfamily, from the prokaryote Escherichia coli and eukaryote Saccharomyces cerevisia, respectively, were applied for the comparative study of asymmetric transamination reaction process and catalytic efficiency of reversely converting keto acids to the corresponding aromatic L-amino acid. Both TyrB and Aro8 could efficiently synthesize the natural aromatic amino acids phenylalanine and tyrosine as well as non-natural amino acid phenylglycine. The chiral HPLC analysis showed the produced amino acids were L-configuration and the e.e value was 100%. L-alanine was the optimal amino donor, and the transaminase TyrB and Aro8 could not use D-amino acids as amino donor. The optimal molar ratio of amino donor (L-alanine) and amino acceptor (aromatic alpha-keto acids) was 4:1. Both of the substituted group on the aromatic ring and the length of fatty acid carbon chain part in the molecular structure of aromatic substrate alpha-keto acid have the significant impact on the enzyme-catalyzed transamination efficiency. In the experiments of preparative-scale transamination synthesis of L-phenylglycine, L-phenylalanine and L-tyrosine, the specific production rate catalyzed by TryB were 0.28 g/(g x h), 0.31 g/(g x h) and 0.60 g/(g x h) and the specific production rate catalyzed by Aro8 were 0.61 g/(g x h), 0.48 g/(g x h) and 0.59 g/(g x h). The results obtained here were useful for applying the transaminases to asymmetric synthesis of L-amino acids by reversing the reaction balance in industry.


Successful Treatment of Necrotizing Fasciitis and Streptococcal Toxic Shock Syndrome with the Addition of Linezolid.
Necrotizing fasciitis is a deep-seated subcutaneous tissue infection that is commonly associated with streptococcal toxic shock syndrome (TSS). Surgical debridement plus penicillin and clindamycin are the current standard of care. We report a case of necrotizing fasciitis and streptococcal TSS where linezolid was added after a failure to improve with standard therapy. Briefly after isolation of Streptococcus pyogenes from tissue cultures, the patient underwent two surgical debridement procedures and was changed to standard of care therapy. While the patient was hemodynamically stable, the patient's wounds, leukocytosis, and thrombocytopenia all progressively worsened. After initiation of linezolid, the patient slowly improved clinically. The present report is the first to highlight the role of linezolid in streptococcal necrotizing fasciitis and TSS not improving with standard therapy.


Small toxic proteins and the antisense RNAs that repress them.
There has been a great expansion in the number of small regulatory RNAs identified in bacteria. Some of these small RNAs repress the synthesis of potentially toxic proteins. Generally the toxin proteins are hydrophobic and less than 60 amino acids in length, and the corresponding antitoxin small RNA genes are antisense to the toxin genes or share long stretches of complementarity with the target mRNAs. Given their short length, only a limited number of these type I toxin-antitoxin loci have been identified, but it is predicted that many remain to be found. Already their characterization has given insights into regulation by small RNAs, has suggested functions for the small toxic proteins at the cell membrane, and has led to practical applications for some of the type I toxin-antitoxin loci.


Craniofacial changes in Icelandic children between 6 and 16 years of age - a longitudinal study.
The aim of the present study was to describe the craniofacial changes between 6 and 16 years of age in a sample of Icelandic children. Complete sets of lateral cephalometric radiographs were available from 95 males and 87 females. Twenty-two reference points were digitized and processed by standard methods, using the Dentofacial Planner computer software program. Thirty-three angular and linear variables were calculated, including: basal sagittal and vertical measurements, facial ratio, and dental, cranial base and mandibular measurements. For the angular measurements, gender differences were not statistically different for any of the measurements, in either age group, except for the variable s-n-na, which was larger in the 16-year-old boys (P < or = 0.001). Linear variables were consistently larger in the boys compared with the girls at both age levels. During the observation period mandibular prognathism increased but the basal sagittal jaw relationship, the jaw angle, the mandibular plane angle and cranial base flexure (n-s-ba) decreased in both genders (P < or = 0.001). Maxillary prognathism increased only in the boys from 6 to 16 years. Inclination of the lower incisors and all the cranial base dimensions increased in both genders during the observation period. When the Icelandic sample was compared with a similar Norwegian sample, small differences could be noted in the maxillary prognathism, mandibular plane angle and in the inclination of the maxilla. Larger differences were identified in the inclination of the lower incisors. These findings could be used as normative cephalometric standards for 6- and 16-year-old Icelandic children.


Cholesterol 25-Hydroxylase Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication through Enzyme Activity-Dependent and -Independent Mechanisms.
Cholesterol 25-hydroxylase (CH25H) has recently been identified as a host restriction factor that exerts antiviral effects by catalyzing the production of 25-hydroxycholesterol (25HC). CH25H can be rapidly induced upon infection with some viruses. Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, has ranked among the most important swine pathogens since it was discovered in the late 1980s. In this study, we found that PRRSV infection significantly downregulated the expression of CH25H in cells by a so-far unknown mechanism, suggesting that CH25H exerts antiviral activity against PRRSV. Indeed, overexpression of CH25H inhibited PRRSV replication, whereas knockdown of CH25H by short interfering RNA (siRNA) promoted PRRSV infection. The anti-PRRSV effect of 25HC operates via inhibition of viral penetration. Interestingly, a CH25H mutant (CH25H-M) lacking hydroxylase activity still inhibited PRRSV infection. Screening using a yeast two-hybrid system followed by coimmunoprecipitation and immunofluorescence colocalization analyses confirmed that both CH25H and CH25H-M interact with the nonstructural protein 1 alpha (nsp1α) of PRRSV. Unexpectedly, the expression of nsp1α decreased following coexpression with CH25H or CH25H-M. Detailed analyses demonstrated that CH25H/CH25H-M could degrade nsp1α through the ubiquitin-proteasome pathway and that site K169 in the nsp1α protein is the key site of ubiquitination. Taken together, our findings demonstrate that CH25H restricts PRRSV replication by targeting viral penetration as well as degrading nsp1α, revealing a novel antiviral mechanism used by CH25H.IMPORTANCE PRRSV has been a continuous threat to the global swine industry, and current vaccines are insufficient to provide sustainable control. CH25H has been found to exert a broad antiviral effect; thus, it is an attractive target for the development of anti-PRRSV drugs. Here, we demonstrate that CH25H is an interferon-stimulated gene that is highly expressed in porcine alveolar macrophages. CH25H exerts its anti-PRRSV effect not only via the production of 25HC to inhibit viral penetration but also by degrading viral protein through the ubiquitin-proteasome pathway, suggesting that CH25H is a candidate for the development of antiviral therapeutics. However, PRRSV infection appears to actively decrease CH25H expression to promote viral replication, highlighting the complex game between PRRSV and its host.


Artificial Intelligence in Renal Cell Carcinoma Histopathology: Current Applications and Future Perspectives.
Renal cell carcinoma (RCC) is characterized by its diverse histopathological features, which pose possible challenges to accurate diagnosis and prognosis. A comprehensive literature review was conducted to explore recent advancements in the field of artificial intelligence (AI) in RCC pathology. The aim of this paper is to assess whether these advancements hold promise in improving the precision, efficiency, and objectivity of histopathological analysis for RCC, while also reducing costs and interobserver variability and potentially alleviating the labor and time burden experienced by pathologists. The reviewed AI-powered approaches demonstrate effective identification and classification abilities regarding several histopathological features associated with RCC, facilitating accurate diagnosis, grading, and prognosis prediction and enabling precise and reliable assessments. Nevertheless, implementing AI in renal cell carcinoma generates challenges concerning standardization, generalizability, benchmarking performance, and integration of data into clinical workflows. Developing methodologies that enable pathologists to interpret AI decisions accurately is imperative. Moreover, establishing more robust and standardized validation workflows is crucial to instill confidence in AI-powered systems' outcomes. These efforts are vital for advancing current state-of-the-art practices and enhancing patient care in the future.


Reirradiation with stereotactic body radiation therapy after prior conventional fractionation radiation for locally recurrent pancreatic adenocarcinoma.
Locally recurrent pancreatic cancer after prior radiotherapy is a therapeutic challenge with limited treatment options. This study examines the safety and efficacy of stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma after prior conventional fractionation radiotherapy (CRT). Outcomes from all patients treated with SBRT for locally recurrent pancreatic adenocarcinoma after prior CRT at our institution were reviewed. A total of 23 patients were identified. Prior CRT median dose was 50.4 Gy (range, 30-60 Gy). Twelve patients (52%) had previously undergone surgery and received CRT as neo- or adjuvant treatment. Nine patients (39.1%) were reirradiated with SBRT with a dose of 25 Gy in a single fraction, and 14 patients (60.8%) received a 5-fraction SBRT schedule with a median dose of 25 Gy (range, 20-33 Gy) in 5 fractions (1-5 fractions). Median follow-up time was 28 months (range, 9-77 months). The median planning target volume was 46 cm3 (range, 14-89 cm3). Median overall survival from diagnosis and from reirradiation were 27.5 months (range, 10-77 months) and 8.5 months (range, 1 month to not reached) respectively. The cumulative incidence of local failures at the last follow-up was 19%. For the 4 patients who presented with local failure, one was treated with a single fraction of 25 Gy, and the other 3 were treated with 25 Gy in 5 fractions. Three patients presented regional failure, with a cumulative incidence of 14%, all with concurrent distant progression. The cumulative incidence of distant progression was 64% at last follow-up. After reirradiation, 6 patients (26.1%) developed a grade 2 or 3 gastrointestinal toxicity, 4 of them occurring among patients treated with a single-fraction SBRT regimen. Our report shows that SBRT for reirradiation of locally recurrent pancreas adenocarcinoma is a feasible option with good local control and acceptable toxicity rates, especially with a multifraction schedule.


Analytical electron microscopy of Bacterionema matruchotii calcification.
The morphology and elemental analyses of calcification occurring in Bacterionema matruchotii were studied by analytical electron microscopy. Early electron densities were found associated with metachromatic granules and cell membranes. Amorphous calcium phosphate appeared before apatite was detected.


Mixed connective tissue disease: a follow-up study of 12 patients with special reference to cold sensitivity and skin manifestations.
A great variety of skin manifestations and the frequent occurrence of cold sensitivity, vascular symptoms with peripheral painful ulcerations, headache of migraine type, and muscle and joint symptoms are described in a series of 12 patients with an overlap syndrome compatible with mixed connective tissue disease (MCTD). The patients have been followed up for an average of 7 years. The peripheral symptoms on the extremities in particular were exacerbated by exposure to cold and caused much inconvenience and early disability for the patients. In addition to the symptoms generally connected with MCTD, some of the patients presented signs of other diseases of autoimmune type as well. For instance 2 of the patients presented autoimmune thyroiditis and one patient developed myasthenia gravis and cold agglutinin syndrome.


E2F1‑mediated RAB34 upregulation accelerates the proliferation and inhibits the cell cycle arrest and apoptosis of acute myeloid leukemia cells.
Acute myeloid leukemia (AML) is a malignant disease that is mainly arisen from myeloid stem/progenitor cells. The pathogenesis of AML is complex. Ras-related protein member RAS oncogene GTPases (RAB) 34 protein has been reported to serve an important role in the development of cancer. However, to the best of our knowledge, the role of RAB34 in AML has not been previously reported. The GEPIA database was used to predict the expression levels of RAB34 in patients with AML. Reverse transcription-quantitative PCR and western blotting were used to detect the expression of RAB34 in AML cell lines. Cell transfection with short hairpin (sh)RNAs targeting RAB34 was used to interfere with RAB34 expression. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining were used to measure cell proliferation. Flow cytometry was used to investigate cell cycle distribution and apoptosis. Western blotting was used to assess the protein expression levels of RAB34 and E2F transcription factor 1 (E2F1), and cell cycle- and apoptosis-associated proteins, including Bcl-2, Bax, CDK4, CDK8 and cyclin D1. The potential binding between E2F1 and RAB34 was then verified by luciferase reporter and chromatin immunoprecipitation assays. Subsequently, cells were co-transfected with RAB34 shRNA and the E2F1 overexpression plasmid before cell proliferation, cell cycle and apoptosis were analyzed further. The expression of RAB34 was found to be significantly increased in AML cell lines. Knocking down RAB34 expression in AML cells was found to significantly inhibit cell proliferation, induce cell cycle arrest and promote apoptosis. E2F1 activated the transcription of RAB34 and E2F1 elevation reversed the impacts of RAB34 silencing on cell proliferation, cell cycle and apoptosis in AML. Therefore, these findings suggest that E2F1-mediated RAB34 upregulation may accelerate the malignant progression of AML.


The Centers for Disease Control and Prevention's New Definitions for Complications of Mechanical Ventilation Shift the Focus of Quality Surveillance and Predict Clinical Outcomes in a PICU.
The Centers for Disease Control and Prevention shifted the focus of surveillance paradigm for adult patients receiving mechanical ventilation, moving from the current standard of ventilator-associated pneumonia to broader complications. The surveillance definitions were designed to enable objective measures and efficient processes, so as to facilitate quality improvement initiatives and enhance standardized benchmark comparisons. We evaluated the surveillance definitions in term of their ability to predict clinical outcomes and ease of surveillance in a PICU. Retrospective cohort study. A PICU at a university-affiliated children's hospital. Eight hundred thirty-six patients receiving mechanical ventilation over 1-year period. None. We applied the definition for ventilator-associated condition (i.e., a sustained increase in ventilator setting after a period of stable or decreasing support) to our database. Of total 606 patients, 14.5% had ventilator-associated condition (20.9/1,000 ventilator days) and 8.1% had an infection-related ventilator-associated condition (12.9/1,000 ventilator days). The patients with infection-related ventilator-associated condition were classified into probable pneumonia (55%), possible pneumonia (28.6%), and undetermined infection (16.3%). A large portion of patients with ventilator-associated condition (44%) had other noninfectious etiologies (e.g., atelectasis, pulmonary edema, and shock). Patients who developed ventilator-associated condition had significantly longer ventilatory, ICU, and hospital days compared with those who did not. The ventilator-associated condition group had increased hospital mortality compared with the non-ventilator-associated condition group (19.3% vs 6.9%; p=0.0007). Multivariate regression analysis identified ventilator-associated condition as one of the predictors of hospital mortality with an adjusted odds ratio of 2.14 (95% CI, 1.03-4.42). Risk factors for developing a ventilator-associated condition included immunocompromised status (odds ratio, 2.90; 95% CI, 1.57-5.33), tracheostomy dependence (odds ratio, 2.78; 95% CI, 1.40-5.51), and chronic respiratory disease (odds ratio, 1.85; 95% CI, 1.03-3.3). The definitions for the various ventilator-associated conditions are good predictors of outcomes in children and adults and are amenable to automated surveillance. Based on the study findings, we suggest consideration for shifting the focus of surveillance for ventilator-associated events from only pneumonia to a broader range of complications.


On the solution of the Helmholtz equation on regions with corners.
In this paper we solve several boundary value problems for the Helmholtz equation on polygonal domains. We observe that when the problems are formulated as the boundary integral equations of potential theory, the solutions are representable by series of appropriately chosen Bessel functions. In addition to being analytically perspicuous, the resulting expressions lend themselves to the construction of accurate and efficient numerical algorithms. The results are illustrated by a number of numerical examples.


The influence of haemoglobin types on reproduction and production in Hungarian Merino sheep.
Fewer Hb A and AB lambs were born than expected in the investigated Hungarian Merino population but the factors responsible for these differences could not be identified. The Hb A and AB breeding ewes were not inferior to their B type herd mates with respect to average daily weight gain (when lambs), reproductive performance (prolificacy) and survival rate. Their reproductive performance was, in some cases, even better than that of the ewes with other haemoglobin types. The haemoglobin types cannot be used as markers when selecting for higher prolificacy.


Pancreatic cancer circulating tumor cells: applications for personalized oncology.
Pancreatic cancer (PC) is a highly lethal disease, in part because of early metastasis, late diagnosis, and limited treatment options. Circulating tumor cells (CTCs) are cancer cells that have achieved the metastatic step of intravasation, and are thus a unique source of biomarkers with potential applications in the staging, prognostication, and treatment of PC. Areas covered: This review describes the use of CTCs in PC, including isolation methods, the significance of CTC enumeration, and studies examining phenotypic and molecular characteristics of CTCs. We also speculate on future directions for PC CTC research such as single-cell analysis and CTC culture. Expert commentary: CTCs represent a potential unique serial source of cancer tissue via a convenient and minimally invasive blood draw. Recent development of isolation methods that allow for the release of viable CTCs with unaltered molecular characteristics has set the stage for single-cell analysis and ex vivo culture. Although there is significant potential for CTCs as a biomarker to impact PC from diagnosis to therapy, there still remain a number of challenges to the routine implementation of CTCs in the clinical management of PC.


Polygenic Risk Score Effectively Predicts Depression Onset in Alzheimer's Disease Based on Major Depressive Disorder Risk Variants.
Depression is a common, though heterogenous, comorbidity in late-onset Alzheimer's Disease (LOAD) patients. In addition, individuals with depression are at greater risk to develop LOAD. In previous work, we demonstrated shared genetic etiology between depression and LOAD. Collectively, these previous studies suggested interactions between depression and LOAD. However, the underpinning genetic heterogeneity of depression co-occurrence with LOAD, and the various genetic etiologies predisposing depression in LOAD, are largely unknown. Major Depressive Disorder (MDD) genome-wide association study (GWAS) summary statistics were used to create polygenic risk scores (PRS). The Religious Orders Society and Rush Memory and Aging Project (ROSMAP, n = 1,708) and National Alzheimer's Coordinating Center (NACC, n = 10,256) datasets served as discovery and validation cohorts, respectively, to assess the PRS performance in predicting depression onset in LOAD patients. The PRS showed marginal results in standalone models for predicting depression onset in both ROSMAP (AUC = 0.540) and NACC (AUC = 0.527). Full models, with baseline age, sex, education, and APOEε4 allele count, showed improved prediction of depression onset (ROSMAP AUC: 0.606, NACC AUC: 0.581). In time-to-event analysis, standalone PRS models showed significant effects in ROSMAP (P = 0.0051), but not in NACC cohort. Full models showed significant performance in predicting depression in LOAD for both datasets (P < 0.001 for all). This study provided new insights into the genetic factors contributing to depression onset in LOAD and advanced our knowledge of the genetics underlying the heterogeneity of depression in LOAD. The developed PRS accurately predicted LOAD patients with depressive symptoms, thus, has clinical implications including, diagnosis of LOAD patients at high-risk to develop depression for early anti-depressant treatment.


The ratio of alpha-galactosidase to beta-glucuronidase activities in dried blood for the identification of female Fabry disease patients.
Female heterozygous patients with Fabry disease are difficult to identify because of the relatively high residual activity of alpha-galactosidase. We systematically evaluated the activities of various lysosomal enzymes in dried blood samples from Fabry patients and found that the beta-glucuronidase activity was frequently elevated. The ratio of alpha-galactosidase to beta-glucuronidase proved to be a helpful tool for the diagnosis of female Fabry disease patients.


Lithium effects on the mechanical and electronic properties of germanium nanowires.
Semiconductor nanowire arrays promise rapid development of a new generation of lithium (Li) batteries because they can store more Li atoms than conventional crystals due to their large surface areas. During the charge-discharge process, the electrodes experience internal stresses that fatigue the material and limit the useful life of the battery. The theoretical study of electronic and mechanical properties of lithiated nanowire arrays allows the designing of electrode materials that could improve battery performance. In this work, we present a density functional theory study of the electronic band structure, formation energy, binding energy, and Young's modulus (Y) of hydrogen passivated germanium nanowires (H-GeNWs) grown along the [111] and [001] crystallographic directions with surface and interstitial Li atoms. The results show that the germanium nanowires (GeNWs) with surface Li atoms maintain their semiconducting behavior but their energy gap size decreases when the Li concentration grows. In contrast, the GeNWs can have semiconductor or metallic behavior depending on the concentration of the interstitial Li atoms. On the other hand, Y is an indicator of the structural changes that GeNWs suffer due to the concentration of Li atoms. For surface Li atoms, Y stays almost constant, whereas for interstitial Li atoms, the Y values indicate important structural changes in the GeNWs.


Inhibitory effect of interleukin-10 on human leukocyte interferon-alpha production by Sendai virus.
Treatment of human peripheral blood leukocytes (hPBL) with Sendai virus induces significant production of human interferon-alpha (IFN-alpha). Addition of human recombinant interleukin-10 (IL-10) to hPBL in vitro prior to treatment with Sendai virus resulted in considerable inhibition of IFN-alpha production. Downregulation of IFN-alpha production was IL-10 concentration-dependent and observed at IL-10 concentrations of as low as 0.05 ng/ml, with a median effective dose (ED50) of about 5 ng/ml. Inhibition of IFN-alpha production by IL-10 occurred at an early stage of Sendai virus induction. The inhibitory effect of IL-10 on leukocyte interferon production was specific and blocked by pretreatment with neutralizing polyclonal anti-IL-10 antibody. This downregulatory effect is at the transcriptional level, since IL-10 inhibits IFN-alpha mRNA accumulation upon Sendai virus treatment. These data suggest that leukocyte IFN-alpha production is a highly regulated process that is modulated by cytokines such as IL-10 during early immunological response to infection.


[Perspectives on pharmacological and clinical benefits from sirtuin 1 activators in oxidative damage].
Sirtuins, named after their homology to the Saccharomyces cerevisiae Silent Information Regulator Two, constitute a family of highly conserved nicotinamide adenine dinucleotide-dependent enzymes that deacetylate histones and residues of acetylated lysine. The main aim of this article is to put forward the pharmacological importance of major sirtuin 1 activators of natural or synthetic origin tested in last years in cases of oxidative tissue damage. The related bioactivity of these activators as "leading" compounds in the search for new drugs and remedies is also described. With the recent development of our knowledge on the cross talks between sirtuin 1 and its modulators (e.g. resveratrol), pharmacological and clinical research on this topic is getting a new horizon.


Cell therapy for cardiac repair.
Cardiovascular diseases remain the leading cause of morbidity and mortality in Western society. Among these diseases, congestive heart failure continues to be a significant health care burden. Recent medical and surgical advances in therapy have improved the quality and quantity of life for patients with heart failure. However, none of these therapies address the fundamental problem of loss of functional cardiomyocytes. Cell regeneration therapies have become an exciting potential treatment for heart failure and other cardiovascular diseases. This emerging therapeutic field has been pursued experimentally with both embryonic-derived stem cells and adult-derived progenitor cells. The identification of resident cardiac progenitor cells has propelled the field of cardiac regenerative biology forward at astonishing rates. This review will examine current findings of various stem and progenitor cells that have been proposed as potential sources for cardiac regeneration, and the recent therapeutic findings from preliminary clinical trials using some of these cell types for cardiovascular repair.


Relative toxicological ranking of eight polybrominated diphenyl ether congeners using cytotoxicity, chemical properties and exposure data.
Polybrominated diphenyl ethers are widely used flame retardants which persist and diffuse in the environment thus entering the food chain. Eight congeners, most relevant for human exposure (BDE-28, 47, 99, 100, 153, 154, 183 and 209), were analyzed in vitro and in silico to derive a relative toxicological ranking. Cytotoxicity was assessed on human liver (HepG2) and colon (DLD-1) cell lines, by three assays (MTS, ATP and DNA content) in a range of realistic concentration (1pM - 10 nM). Jejunum and Caco-2 passive absorptions were calculated in silico. Exposure estimates were calculated using EFSA database. By ToxPi we integrated the overall data. No reduction of DNA content was observed, supporting absence of cytotoxicity. Otherwise, hormetic effects were exerted by all the congeners, except BDE-183. BDE-28, 47, 99, 100 differently affected the ATP content inducing a dose-related increase in HepG2 and depletion in DLD-1. Jejunum coefficients did not differ among congeners, whereas a higher Caco-2 coefficient indicates rapid absorption of BDE-28. ToxPi relative rankings support the toxicological relevance of BDE-153 and 28 congeners for their potential hazard; the inclusion of exposure data in young and adult populations shifted BDE-209 and BDE-47 as top ranked due to their widespread occurrence in the diet.


Treating triple negative breast cancer cells with erlotinib plus a select antioxidant overcomes drug resistance by targeting cancer cell heterogeneity.
Among breast cancer patients, those diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst prog-nosis. TNBC does not express estrogen receptor-alpha, progesterone receptor, or the HER2 oncogene; therefore, TNBC lacks targets for molecularly-guided therapies. The concept that EGFR oncogene inhibitor drugs could be used as targeted treatment against TNBC has been put forth based on estimates that 30-60% of TNBC express high levels of EGFR. However, results from clinical trials testing EGFR inhibitors, alone or in combination with cytotoxic chemotherapy, did not improve patient outcomes. Results herein offer an explanation as to why EGFR inhibitors failed TNBC patients and support how combining a select antioxidant and an EGFR-specific small molecule kinase inhibitor (SMKI) could be an effective, novel therapeutic strategy. Treatment with CAT-SKL-a re-engineered protein form of the antioxidant enzyme catalase-inhibited cancer stem-like cells (CSCs), and treatment with the EGFR-specific SMKI erlotinib inhibited non-CSCs. Thus, combining the antioxidant CAT-SKL with erlotinib targeted both CSCs and bulk cancer cells in cultures of EGFR-expressing TNBC-derived cells. We also report evidence that the mechanism for CAT-SKL inhibition of CSCs may depend on antioxidant-induced downregulation of a short alternative mRNA splicing variant of the methyl-CpG binding domain 2 gene, isoform MBD2c.


The effect of digitisation of the humeral epicondyles on quantifying elbow kinematics during cricket bowling.
In the sport of cricket the objective of the "no-ball" law is to allow no performance advantage through elbow extension during ball delivery. However, recently it has been shown that even bowlers with actions that are considered within the law show some elbow extension. The objective of this study was to investigate: [1] the effect of elbow orientation during anatomical landmark digitisation and [2] the choice of upper arm tracking cluster on the measurement of elbow angles during cricket bowling. We compared the mean elbow angles for four different elbow postures; with the joint flexed at approximately 130°, 90°, in full extension and with the elbow flexed with the humerus internally rotated, and two upper arm clusters in two different situations: [1] during a controlled movement of pure flexion-extension and [2] during cricket bowling. The digitised postures of the anatomical landmarks where the elbow was extended and at 90° of flexion were more repeatable than the other two postures. The recommendation of this study when analysing cricket bowling is to digitise the humeral epicondyles with the joint flexed at 90°, or in full extension, and to relate their positions to an upper arm cluster fixed close to the elbow.


Seed morphometric characteristics of European species of Elatine (Elatinaceae).
Elatine L. contains ca. 25 small, herbaceous, annual species distributed in ephemeral waters in both hemispheres. All species are amphibious and characterized by a high degree of morphological variability. The importance of seed morphology in Elatine taxonomy has been emphasized by many authors. The degree of seed curvature and seed coat reticulation have been traditionally considered very important in recognizing individual species of this genus. Seed morphometric characteristics of 10 Elatine species, including all European native taxa, are provided on the basis of material from two or three populations of each species. A total of 24-50 seeds were studied from each population, altogether 1,260 images were used for the morphometric study. In total, six parameters were measured from SEM pictures: object surface area, profile specific perimeter (object circuit), rectangle of the object (a) length, rectangle of the object (b) width, angle of the seed curvature, and number of pits in the seed coat counted in the middle row. Our study shows that the range of morphological variation of seeds in European species of Elatine is great, both between the species and the populations. Discrimination analysis showed that all six traits significantly differentiate the populations studied (λ = 0.001, p < 0.001), and the greatest contributions were "number of pits", "rectangle_a", and "the angle curvature". Multidimensional scaling based on a correlation matrix of Mahalanobis distance of the six features studied revealed the greatest similarity between the three populations of E. alsinastrum, E. macropoda, and E. hexandra. Regarding interspecific differences, a Kruskal-Wallis tests showed that, in many cases, lack of statistically significant differences between species relative to the studied seed traits. If distinction of species is only based on seeds, especially if only a few seeds are evaluated, the following species pairs can be easily confused: E. alsinastrum and E. orthosperma, E. hexandra and E. macropoda, E. campylosperma and E. hydropiper, as well and E. gussonei and E. hungarica. We found no diversity in seed coat micromorphology within pits that could have potential taxonomic importance. An identification key and descriptions of species are provided on the basis of seeds traits.


Epithelial ovarian cancer is infiltrated by activated effector T cells co-expressing CD39, PD-1, TIM-3, CD137 and interacting with cancer cells and myeloid cells.
Despite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity. In this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs). Activated T cells showing features of partial exhaustion with a CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ signature. These data demonstrate that EOC is enriched in CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches.


[Future developments in genetic research. I. Technological possibilities].
The attention in genetic research is shifting from the determination' of (rare) monogenic disorders to identification of genetic risk factors for important diseases at adult age. Mapping of all man's 80,000-100,000 genes will also provide more insight into the gene polymorphisms and mutations that are associated with various types of cancer, certain cardiovascular diseases, diabetes and neurodegenerative disorders, including Alzheimer dementia. Apart from new diagnostic possibilities, the DNA techniques create new prospects for the study of the pathogenesis of diseases and the devising of new strategies for treatment. Examples are familial hypercholesterolaemia, diabetes, breast cancer and colorectal carcinoma.


Work-Related Upper Limb Disorders: A Case Report.
In this study the complex interrelationship between physical factors, job stress, lifestyle and genetic factors on symptoms of work-related musculoskeletal disorders of the upper limbs is demonstrated by a case report and discussion of the literature. A 58 year old woman with long lasting complaints of the upper limbs with increasing intensity and duration, generalisation, combined with skin thickness, Raynaud's phenomenon, joint disorders, arterial and pulmonary hypertension, metabolic lipid dysfunctions is presented. Occupational history proves continuous duration of service at a job with occupational physical static load with numerous repetitive monotonous systematic motions of fingers and hands as a weaver of Persian rugs followed by work at an automated loom and variable labour activities. Though the complaints dated since the time she was a manual weaver, the manifestations of generalized joint degenerative changes, system sclerosis with Raynaud's phenomenon with similar upper extremities signs and symptoms discount upper limbs musculoskeletal disorder as caused only or mainly by occupational risk factors. The main principles and criteria for occupational diagnosis of musculoskeletal upper limb disorders and legislative requirements for their reglamentation are discussed.


Quincke Oscillations of Colloids at Planar Electrodes.
Dielectric particles in weakly conducting fluids rotate spontaneously when subject to strong electric fields. Such Quincke rotation near a plane electrode leads to particle translation that enables physical models of active matter. In this Letter, we show that Quincke rollers can also exhibit oscillatory dynamics, whereby particles move back and forth about a fixed location. We explain how oscillations arise for micron-scale particles commensurate with the thickness of a field-induced boundary layer in the nonpolar electrolyte. This work enables the design of colloidal oscillators.


Circulating tumor DNA detection: A potential tool for colorectal cancer management.
Colorectal cancer (CRC) is frequently diagnosed at an advanced stage of the disease, the pathogenesis of which is influenced by genetic and epigenetic events. Circulating tumor DNA (ctDNA) is extracellular DNA that is present in a number of bodily fluids, including blood, synovial fluid and cerebrospinal fluid. Compared with performing a tissue biopsy, ctDNA examination presents the advantages of minimal invasion and greater convenience. ctDNA is commonly used to identify actionable genomic alterations, monitor treatment responses, unravel therapeutic resistance and potentially detect disease progression prior to clinical and radiological confirmation. The technique can potentially serve as a non-invasive diagnostic tool in personalized medicine, as it demonstrates prognostic value in the management of patients with CRC. ctDNA detection continues to demonstrate inherent advantages compared with other methods, thus serving an increasingly important role in tumor monitoring and oncotherapy. The aim of the current review was to explore the clinical applications of ctDNA in patients with CRC, including early detection and screening, medication guidance, resistance prediction, and residual lesion and recurrence monitoring. Furthermore, several technical methods for ctDNA detection and analysis are explored, as well as other potential biomarkers.


Varying Cognitive Scars - Differential Associations Between Types of Childhood Maltreatment and Facial Emotion Processing.
Distorted cognitive processing has been found among survivors of child maltreatment. However, different types of abuse and neglect may bring about differences in emotion and attention processing. The present study aimed to detect differential associations between various types of childhood maltreatment and attentional biases in facial emotion processing. A non-clinical sample was recruited on University campus and consisted of 67 individuals with varying degrees of maltreatment. In an evaluative conditioning task, images of faces with neutral emotional expressions were either associated with short videos of intense negative statements, or associated with neutral videos. Subsequently, these faces were used as stimuli in a face in the crowd recognition task in which the familiar faces had to be recognized within a crowd of unfamiliar neutral faces. In multiple linear regression analyses controlling for the intercorrelatedness of types of maltreatment, differential relationships between types of maltreatment and attentional bias were found. While emotional abuse was associated with faster detection of negatively associated faces, emotional neglect was associated with an impaired recognition of familiar stimuli regardless of the emotional content. Results indicated that interindividual differences in cognitive biases may be due to the activation of diverse cognitive schemas based on differential experiences of maltreatment.


Impact of alcohol consumption on survival in patients with esophageal carcinoma: a large cohort with long-term follow-up.
Alcohol is a well-established cause of esophageal carcinoma, but its effect on survival is little known and contradictory. To clarify whether drinking is an independent predictor of survival in esophageal carcinoma, 2151 Chinese patients, receiving surgical resection from January 1997 to December 2008, were followed until March 2014. Cox proportional hazards analysis was applied to evaluate the prognostic effect of alcohol consumption. The median follow-up was 64 months. The median overall survival (OS; 42 months) and disease-free survival (DFS; 33 months) for never-drinkers were significantly higher than ever-drinkers (27 and 22 months, respectively). In the multivariate Cox model that was adjusted for age, weight loss, stage according to criteria set by the American Joint Committee on Cancer, radicality of surgery, adjuvant treatment, smoking status, and gender, the hazard ratios of ever-drinking were 1.22 (1.06-1.41, P = 0.005) on OS, and 1.16 (1.01-1.34, P = 0.037) on DFS. The hazardous effect on OS and DFS of drinking grew statistically significantly in a dose-dependent manner with increasing amount of alcohol consumption per day (both P-value for trend < 0.05). The predictive effect of drinking on OS (P = 0.596) or DFS (P = 0.207) was not significant in the subgroup with esophageal adenocarcinoma (n = 195). The current study revealed that the survival is shortened, of those patients who consume alcohol before diagnosis of esophageal squamous cell carcinoma, which are not attributable to differences in stage, smoking status, and gender. Alcohol control should be emphasized to reduce mortality of esophageal carcinoma, and further outcome studies should include alcohol as a potential prognosticator.


Strategies on aroma formation in Chardonnay sparkling base wine: Different Saccharomyces cerevisiae strains, co-inoculation with Torulaspora delbrueckii and utilization of bentonite.
The worldwide production of sparkling wines has been growing annually, driven by a market demand for high quality and more complex products. The present study aimed to evaluate the fermentation of Chardonnay must using two different Saccharomyces cerevisiae yeasts, either alone (from commercial brands A and B) or in combination with Torulaspora delbrueckii (ScA + Td and ScB + Td, respectively), as well as the addition of bentonite to the fermentation with ScA (ScA + Ben), to investigate their impact on aroma formation in sparkling base wine. Enological parameters, volatile composition, and sensory profile were evaluated. The results showed notable differences in total sulfur dioxide and volatile acidity among the S. cerevisiae strains. Moreover, the esters ethyl acetate, isoamyl acetate, hexyl acetate, and phenethyl acetate showed significant differences among treatments. Esters are recognized for their contribution to fruity and floral aromas, making them an essential part of the aromatic profile of wines. The descriptive analysis revealed that ScB + Td had the highest intensity of floral and tropical fruit notes, as well as aromatic clarity. The use of bentonite did not affect the aromatic composition or sensory profile of the wine. Therefore, the co-inoculation of S. cerevisiae with T. delbrueckii can lead to a base wine with a higher intensity of important volatile compounds and sensory attributes, providing an important alternative to produce winery products with a more complex aroma profile.


SNAT4 isoform of system A amino acid transporter is expressed in human placenta.
The system A amino acid transporter is encoded by three members of the Slc38 gene family, giving rise to three subtypes: Na+-coupled neutral amino acid transporter (SNAT)1, SNAT2, and SNAT4. SNAT2 is expressed ubiquitously in mammalian tissues; SNAT1 is predominantly expressed in heart, brain, and placenta; and SNAT4 is reported to be expressed solely by the liver. In the placenta, system A has an essential role in the supply of neutral amino acids needed for fetal growth. In the present study, we examined expression and localization of SNAT1, SNAT2, and SNAT4 in human placenta during gestation. Real-time quantitative PCR was used to examine steady-state levels of system A subtype mRNA in early (6-10 wk) and late (10-13 wk) first-trimester and full-term (38-40 wk) placentas. We detected mRNA for all three isoforms from early gestation onward. There were no differences in SNAT1 and SNAT2 mRNA expression with gestation. However, SNAT4 mRNA expression was significantly higher early in the first trimester compared with the full-term placenta (P < 0.01). We next investigated SNAT4 protein expression in human placenta. In contrast to the observation for gene expression, Western blot analysis revealed that SNAT4 protein expression was significantly higher at term compared with the first trimester (P < 0.05). Immunohistochemistry and Western blot analysis showed that SNAT4 is localized to the microvillous and basal plasma membranes of the syncytiotrophoblast, suggesting a role for this isoform of system A in amino acid transport across the placenta. This study therefore provides the first evidence of SNAT4 mRNA and protein expression in the human placenta, both at the first trimester and at full term.


Direct measurement of vertical binding energy of a hydrated electron.
We present the first measurement of the vertical binding energy (VBE) of a hydrated electron in bulk water by the time-resolved photoelectron spectroscopy (TRPES) of the charge-transfer-to-solvent (CTTS) reaction in aqueous NaI solution. Our best estimate of VBE is 3.27 +/- 0.10 eV for H(2)O and 3.20 +/- 0.10 eV for D(2)O.


The Molecular Cloud Lifecycle.
Giant molecular clouds (GMCs) and their stellar offspring are the building blocks of galaxies. The physical characteristics of GMCs and their evolution are tightly connected to galaxy evolution. The macroscopic properties of the interstellar medium propagate into the properties of GMCs condensing out of it, with correlations between e.g. the galactic and GMC scale gas pressures, surface densities and volume densities. That way, the galactic environment sets the initial conditions for star formation within GMCs. After the onset of massive star formation, stellar feedback from e.g. photoionisation, stellar winds, and supernovae eventually contributes to dispersing the parent cloud, depositing energy, momentum and metals into the surrounding medium, thereby changing the properties of galaxies. This cycling of matter between gas and stars, governed by star formation and feedback, is therefore a major driver of galaxy evolution. Much of the recent debate has focused on the durations of the various evolutionary phases that constitute this cycle in galaxies, and what these can teach us about the physical mechanisms driving the cycle. We review results from observational, theoretical, and numerical work to build a dynamical picture of the evolutionary lifecycle of GMC evolution, star formation, and feedback in galaxies.


Microneedle pH Sensor: Direct, Label-Free, Real-Time Detection of Cerebrospinal Fluid and Bladder pH.
Acid-base homeostasis (body pH) inside the body is precisely controlled by the kidneys and lungs and buffer systems, such that even a minor pH change could severely affect many organs. Blood and urine pH tests are common in day-to-day clinical trials and require little effort for diagnosis. There is always a great demand for in vivo testing to understand more about body metabolism and to provide effective diagnosis and therapy. In this article, we report the simple fabrication of microneedle-based direct, label-free, and real-time pH sensors. The reference and working electrodes were Ag/AgCl thick films and ZnO thin films on tungsten (W) microneedles, respectively. The morphological and structural characteristics of microneedles were carefully investigated through various analytical methods. The developed sensor exhibited a Nernstian response of -46 mV/pH. Different conditions were used to test the sensor to confirm their accuracy and stability, such as various buffer solutions, with respect to time, and we compared the reading with commercial pH electrodes. Besides that, the fabricated microneedle sensor ability is proven by in vivo testing in mouse cerebrospinal fluid (CSF) and bladders. The pH sensor procedure reported here is totally reversible, and results were reproducible after several rounds of testing.


[Urticarial skin reaction to codeine, a measure of mast cell reactivity].
The reactivity of skin mast cells was tested in 86 probands. Introduction of various concentrations of codeine phosphate, either by intradermal injection or by prick test, produced an immediate wheal and flare response. Since the codeine skin test depends on both release of and response to histamine, it may be more useful than the conventional skin test with histamine for assessment of skin reactivity, and also for preliminary evaluation of anti-allergic agents in man.


Enhanced light extraction from AlGaInP-based red light-emitting diodes with photonic crystals.
The photonic crystal (PC) has been demonstrated to be very effective in improving the extraction efficiency of light-emitting diodes (LEDs). In this paper, high-brightness AlGaInP-based vertical LEDs (VLEDs) with surface PC (SPCLED) and embedded PC (EPCLED) were successfully fabricated. Compared with normal LED (NLED), photoluminescence intensities of SPCLED and EPCLED have been improved up to 30% and 60%, respectively. And the reflection patterns of SPCLED and EPCLED were periodic bright points array, showing the ability to control light in PC. Electroluminescent measurements show that three kinds of LEDs have similar threshold voltages. Simultaneously, the light output power (LOP) of SPCLED and EPCLED has been improved up to 24% and 11% at 200 mA, respectively, in comparison to NLEDs. But the LOP decays earlier for EPCLED due to the excessive heat production. Furthermore, it is demonstrated that the SPCLED and EPCLED luminous uniformity is better. This kind of high brightness PCLED is promising in improving the properties of all kinds of LEDs, especially mini LEDs and micro LEDs.


Simvastatin Inhibits IL-5-Induced Chemotaxis and CCR3 Expression of HL-60-Derived and Human Primary Eosinophils.
IL-5-induced chemotaxis of eosinophils is an important feature of allergic airway inflammatory diseases. Simvastatin, a lipid lowering agent, has been shown to exhibit anti-inflammatory and anti-allergic effects. Our aim was to investigate the effect of simvastatin on IL-5-induced eosinophil chemotaxis and its regulatory mechanisms. Eosinophils were derived by treating HL-60 clone 15 (HC15) cells with butyric acid (BA) in an alkaline condition or through direct isolation from human peripheral blood. The expressions of CC chemokine receptor 3 (CCR3) and interleukin (IL)-5 receptors (IL5Rα and β) were analyzed using RT/real-time PCR. The granular proteins were stained using fast green. Eotaxin-induced chemotaxis was measured using a transwell migration assay. CCR3 protein expression was revealed by immunocytochemistry. An animal model of allergic rhinitis was established by challenging Sprague-Dawley® rats repeatedly with ovalbumin. Butyric acid significantly increased the expression of IL5Rα and IL5Rβ, CCR3 and granular proteins in HC15 cells, indicating the maturation of eosinophils (BA-E cells). IL-5 further enhanced the CCR3 expression at both the mRNA and protein levels and the eotaxin-induced chemotaxis of BA-E cells. Simvastatin inhibited the effects of IL-5 on BA-E cells, but not in the presence of mevalonate. Similar results were also exhibited in human primary eosinophils. In vivo animal studies further confirmed that oral simvastatin could significantly suppress the infiltration of eosinophils into turbinate tissues of allergic rats. Therefore, simvastatin was demonstrated to inhibit IL-5-induced CCR3 expression and chemotaxis of eosinophils mediated via the mevalonate pathway. We confirmed that simvastatin also reduced eosinophilic infiltration in allergic rhinitis.


Microelectric Current Treatment Enhanced Biodegradation of Pumpkin Lignocelluloses by Trichoderma reesei RUT-C30.
A homemade microcurrent reactor was used to treat the fermentation of Trichoderma reesei. Results indicated that the yield of saccharides for T. reesei RUT-C30 cultivated in pumpkin lignocellulose broth reaches 38.86% (w/w) when a microcurrent treatment (20 mA, at the 48th hour for 60 min) was carried out, which is significantly higher than the control group (p < 0.05). Additionally, activities of endoglucanase, cellobiohydrolase, xylanase, and pectinase were significantly increased in days 3-7. Furthermore, the fungal growth was facilitated by microelectric treatment, showing a 0.57-fold increase of spore numbers at the sixth day of cultivation. Besides, the monosaccharide composition, including glucose (1.03 mg/mL), xylose (0.12 mg/mL), arabinose (0.31 mg/mL), and fructose (0.13 mg/mL), extracted from the reactor was higher than that without the current treatment. In this work, we improved the biodegradation of lignocellulosic wastes by applying a microcurrent to lignocellulose-degrading fungal cultures and provided a new idea for the lignocellulose material pretreatment and bioconversion.


Ankylos implant system: concept and clinical application.
The Ankylos system was developed in 1985 and has been in clinical use since 1987. Some of its significant design features include (1) a progressive thread structure of the endosseous implant body for targeted load distribution to the apically positioned spongy bone; and (2) the gap-free subgingival tapered connection to the abutments. The purpose of this report is to demonstrate that the Ankylos Implant System meets both the patients' and the dentists' standards of success and is suitable for use as single tooth replacements, bridge abutments, and retention elements for all regions and prosthetic indications. The data from 5439 implants were evaluated between October 1991 and October 2002. The implants were considered successful if the following criteria were met: (1) clinical stability and function; (2) no inflammation of the peri-implant hard and soft tissue; (3) no progressive loss of the peri-implant bone; (4) no progressive loss of the peri-implant mucosa; and (5) satisfaction of the patient. All implants placed during this period were included in the evaluation as a prospective study. The average loading period was 56.8 months. Postoperative follow-ups were made once a year by a standardized protocol. The results were classified by prosthetic application in Table 1. A total of 943 implants were placed as single tooth restoration and were followed for the duration of the study. The success rate for this type of restoration was 98.7%. For free-end implant restorations, there were 1679 implants placed with a 97.9% success rate. When the edentulous area involved a large gap, a total of 805 implants were placed with a 97.3% success rate. For cases involving reduced dentition, 606 implants were used with a 95.8% success rate. Another significant finding was that the success rates classified by maxilla and mandible showed no differences.