Divergence of species-specific protein sex pheromone blends in two related, nonhybridizing newts (Salamandridae).
In animals that use chemical communication during courtship and reproduction, speciation is often associated with divergence of their sex pheromones. In multicomponent pheromone systems, divergence can be obtained either by adding or deleting components, or by altering the relative contribution of individual components to the mixture. Protein pheromone systems can additionally evolve by amino acid sequence divergence to produce pheromones with a species-specific effect. The sodefrin precursor-like factor (SPF) pheromone system, a blend of proteins that essentially enhances receptivity in salamanders, has had a long and dynamic evolution of gene duplications, but the mechanisms that govern interspecific divergence and the role they play in reproductive isolation remain elusive. Here, we use transcriptomics and proteomics to characterize the SPF protein repertoire of the alpine newt (Ichthyosaura alpestris), and compare it to the previously identified repertoire of SPF proteins of the palmate newt (Lissotriton helveticus), a related but nonhybridizing species. Subsequent phylogenetic analyses indicate that, despite the availability of multiple SPF gene copies, both species predominantly express the same subset of orthologs. Our study demonstrates that species specificity in the SPF protein pheromone system can be established by gradual sequence divergence of the same set of proteins alone.


The politics of health inequalities research in the United States.
In this article, based on a speech to the European Association of Health Policy, the author discusses the political context in which health inequalities research has historically operated in the United States. The discussion focuses on the limitations of research that uses income, consumption, and status as the primary categories of research practice, and demonstrates these limitations by critically analyzing The Health of Nations (by Kawachi and Kennedy). The author concludes that it is essential to use categories of analysis that focus on class relations as well as race and gender relations and their reproduction through the international and national institutions, to study their impact on the health and well-being of populations.


Functional Features of Alginates Recovered from Himanthalia elongata Using Subcritical Water Extraction.
Subcritical water extraction of Himanthalia elongata and the subsequent acetone fractionation to precipitate crude fucoidans generated a liquid phase which was used to recover alginates with a wide range of viscoelastic features and other soluble extracts with potential biological activities. The precipitated alginate was converted to sodium alginate using an environmentally friendly treatment before being characterized by Fourier transform infrared attenuated total reflectance, nuclear magnetic resonance, high performance size exclusion chromatography and rheological measurements. The cell viability of three human cell lines (A549, HCT-116, T98G) in the presence of the extracts obtained before and after acetone fractionation was assessed. Fractionation with different acetone volumes showed a slight effect in the behavior of the different tested cell lines. Results also indicated a notable effect of the processing conditions on the block structure and molar mass of the extracted biopolymer, with the subsequent impact on the rheological properties of the corresponding gelled matrices.


Effective induction of antitumor immunity by immunization with plasmid DNA encoding TRP-2 plus neutralization of TGF-beta.
Plasmid DNA vaccine is an appealing cancer immunotherapy. However, it is a weak immunogen and immunization with plasmid DNA encoding self-antigens, such as melanoma-associated antigens, could not induce antitumor immunity because of tolerance. In this study, we investigated the feasibility of using a plasmid DNA encoding Xenopus laevis transforming growth factor-beta 5 (aTGF-beta5) as an immunogen to induce neutralizing antibodies against murine TGF-beta1 (mTGF-beta1) and thus enhance the efficacy of plasmid DNA vaccine encoding murine tyrosinase-related protein 2 (mTRP-2) through neutralization of TGF-beta. The results showed that immunization with aTGF-beta5 resulted in the generation of mTGF-beta1-neutralizing antibodies, and immunization with a combination of aTGF-beta5 and mTRP-2 induced specific cytotoxic T lymphocytes (CTLs). On the contrary, immunization with mTRP-2 alone could not elicit the CTL response. Moreover, immunization of C57BL/6 wild-type mice with a combination of aTGF-beta5 and mTRP-2 induced the protective and therapeutic antitumor immunity to B16F10 melanoma, whereas the antitumor activity was abrogated in both CD4-deficient mice and CD8-deficient mice on the C57BL/6 background. Our results indicate that immunization with aTGF-beta5 is capable of breaking immune tolerance and induces mTGF-beta1-neutralizing antibodies. Neutralization of TGF-beta can enhance the efficacy of DNA vaccine encoding mTRP-2 and the induction of antitumor immunity by this immunization strategy is associated with CD4+ and CD8+ T cells.


Differential requirements for CD4+ T cells in the efficacy of the anti-PD-1+LAG-3 and anti-PD-1+CTLA-4 combinations in melanoma flank and brain metastasis models.
Although the anti-PD-1+LAG-3 and the anti-PD-1+CTLA-4 combinations are effective in advanced melanoma, it remains unclear whether their mechanisms of action overlap. We used single cell (sc) RNA-seq, flow cytometry and IHC analysis of responding SM1, D4M-UV2 and B16 melanoma flank tumors and SM1 brain metastases to explore the mechanism of action of the anti-PD-1+LAG-3 and the anti-PD-1+CTLA-4 combination. CD4+ and CD8+ T cell depletion, tetramer binding assays and ELISPOT assays were used to demonstrate the unique role of CD4+T cell help in the antitumor effects of the anti-PD-1+LAG-3 combination. The anti-PD-1+CTLA-4 combination was associated with the infiltration of FOXP3+regulatory CD4+ cells (Tregs), fewer activated CD4+T cells and the accumulation of a subset of IFNγ secreting cytotoxic CD8+T cells, whereas the anti-PD-1+LAG-3 combination led to the accumulation of CD4+T helper cells that expressed CXCR4, TNFSF8, IL21R and a subset of CD8+T cells with reduced expression of cytotoxic markers. T cell depletion studies showed a requirement for CD4+T cells for the anti-PD-1+LAG-3 combination, but not the PD-1-CTLA-4 combination at both flank and brain tumor sites. In anti-PD-1+LAG-3 treated tumors, CD4+T cell depletion was associated with fewer activated (CD69+) CD8+T cells and impaired IFNγ release but, conversely, increased numbers of activated CD8+T cells and IFNγ release in anti-PD-1+CTLA-4 treated tumors. Together these studies suggest that these two clinically relevant immune checkpoint inhibitor (ICI) combinations have differential effects on CD4+T cell polarization, which in turn, impacted cytotoxic CD8+T cell function. Further insights into the mechanisms of action/resistance of these clinically-relevant ICI combinations will allow therapy to be further personalized.


Preparation and Characterization of a Novel Room Temperature Dicationic Ionic Liquid and its Application in the Synthesis of Xanthenediones Under Solvent-Free Conditions.
In the present work, 1, 1'-sulfinyldiethylammonium bis (hydrogen sulfate) as a novel room temperature dicationic ionic liquid was synthesized and used as a catalyst for xanthenediones synthesis. The dicationic ionic liquid has been synthesized using ethylamine and thionyl chloride as precursors. Then, by the reaction of [(EtNH2)2SO]Cl2 with H2SO4, [(EtNH2)2SO][HSO4]2 was prepared and after that, it was characterized by FT-IR, 1H NMR, 13C NMR as well as Hammett acidity function. This dicationic ionic liquid was used as a catalyst for the synthesis of xanthenediones via condensation of structurally diverse aldehydes and dimedone under solvent-free conditions. The progress of the reaction was monitored by thin layer chromatography (ethyl acetate/n-hexane = 3/7). An efficient solvent-free method for the synthesis of xanthenediones has been developed in the presence of [(EtNH2)2SO][HSO4]2 as a powerful catalyst with high to excellent yields, and short reaction times. Additionally, recycling studies have demonstrated that the dicationic ionic liquid can be readily recovered and reused at least four times without significant loss of its catalytic activity. This new dicationic ionic liquid can act as a highly efficient catalyst for xanthenediones synthesis under solvent-free conditions.


Vertical liquid controlled adiabatic waveguide coupler.
A broadband vertical liquid controlled optical waveguide coupler (LCC) is demonstrated. The fabricated vertical LCC with silicon nitride (SiN) waveguides can switch light between 2 stacked photonic circuit layers with zero energy consumption in a steady switch state. In combination with low-loss interlayer waveguide crossovers they enable large scale non-volatile switch circuits with low loss. The fabricated vertical LCC has a loss less than 2.0 dB in bar state and less than 2.6 dB in cross state over the telecommunication wavelength range 1260 nm to 1630 nm. Interlayer waveguide crossovers with the same interlayer oxide thickness as the LCC have a loss less than 0.06 dB over the same wavelength range. The crosstalk of the LCC is less than -21 dB over the wavelength range 1500 nm to 1630 nm for both bar and cross state.


IL-13 from Th2-type cells suppresses induction of antigen-specific Th1 immunity in a T-cell lymphoma.
Dalton's lymphoma (DL) is a transplantable T-cell lymphoma of spontaneous origin, characterized by highly invasive and immunosuppressive property. Progression of DL cells results into an imbalance of T helper type 1 (T(h)1)/T helper type 2 (T(h)2)-type cytokine in the host, which is partly responsible for DL-induced severe immunosuppression and DL cell progression. In this study, we have shown the role of IL-13 in the regulation of T(h)1 immunity in both normal healthy and DL-bearing host. IL-13 pre-treatment inhibits the induction of 2,4-dinitro-1-fluorobenzene-induced contact hypersensitivity and delayed-type hypersensitivity (DTH) in antigen-challenged mice, which have been confirmed by neutralizing IL-13 by systemic delivery of non-signaling decoy receptor IL-13Ralpha2. Furthermore, IL-13 neutralization enhances the splenocyte proliferation, which has been inhibited by IL-13 administration. Adoptive transfer of splenocyte from IL-13-pre-treated mice and macrophages incubated with IL-13 and pulsed with antigens suppresses the DTH as well in antigen-challenged recipient mice. In addition, it also suppresses the production of pro-inflammatory cytokine and C-C chemokine in DTH footpad. Furthermore, IL-13 neutralization not only enhances the DTH reaction but also increases longevity and survival of DL-bearing host, which suggests that blocking/inactivating systemic IL-13 enhances T(h)1 immunity, and therefore, effects to diminish IL-13 production may have therapeutic value in a host bearing T-cell lymphoma.


Highly reducible π-extended copper corroles.
Di- and octa-phenylethynyl (PE) substituted π-extended copper corroles were synthesized and characterized as to their structural, electrochemical and spectroscopic properties. The addition of two or eight PE groups to the β-pyrrole positions of the corrole results in dramatic red shifts in the electronic absorption spectra and new reductions which are not seen for the parent compound lacking PE substituents. CuCor(PE)8 is reduced in four reversible one-electron transfer steps to give derivatives of [CuCor(PE)8]n- where n = 1, 2, 3 or 4. Variable temperature 1H NMR and EPR measurements were carried out and suggest that the octa- and di-PE substituted Cu-corroles can both be described as an antiferromagnetically coupled CuII corrole cation radical which is in equilibrium with a triplet state, possibly due to a lower singlet-triplet energy gap as compared to 1 and 2 at room temperature. The EPR spectra of one-electron oxidized and one electron reduced species exhibited the characteristics of Cu(ii) corroles. The products generated in the first two reductions of each π-extended corrole were characterized by thin-layer spectroelectrochemistry, thus providing new insights into how UV-vis spectra of highly reduced corroles vary as a function of the number of PE groups and overall charge on the molecule. The singly reduced and singly oxidized copper corroles were also chemically generated in CH3CN and shown to have UV-visible spectra almost identical to the spectra obtained by electroreduction or electrooxidation in PhCN or THF containing 0.1 M tetrabutylammonium perchlorate.


Metagenome-Based Exploration of Bacterial Communities Associated with Cyanobacteria Strains Isolated from Thermal Muds.
Cyanobacteria constitute a pioneer colonizer of specific environments for whom settlement in new biotopes precedes the establishment of composite microbial consortia. Some heterotrophic bacteria constitute cyanobacterial partners that are considered as their cyanosphere, being potentially involved in mutualistic relationships through the exchange and recycling of key nutrients and the sharing of common goods. Several non-axenic cyanobacterial strains have been recently isolated, along with their associated cyanospheres, from the thermal mud of Balaruc-les-Bains (France) and the biofilms of the retention basin where they develop. The community structure and relationships among the members of the isolated cyanobacterial strains were characterized using a metagenomic approach combined with taxonomic and microscopic descriptions of the microbial consortia. The results provided insights into the potential role and metabolic capabilities of the microorganisms of thermal mud-associated cyanobacterial biofilms. Thus, the physical proximity, host-specificity, and genetic potential functions advocate for their complementarity between cyanobacteria and their associated microbiota. Besides these findings, our results also highlighted the great influence of the reference protein database chosen for performing functional annotation of the metagenomes from organisms of the cyanosphere and the difficulty of selecting one unique database that appropriately covers both autotroph and heterotroph metabolic specificities.


Dietary fat, genetic predisposition, and obesity: lessons from animal models.
This review focuses on animal studies that examine the role of dietary fat in obesity. It is evident from animal experiments that the percentage of energy derived from fat in the diet is positively correlated with body fat content. With few exceptions, obesity is induced by high-fat diets in monkeys, dogs, pigs, hamsters, squirrels, rats, and mice. The mechanisms responsible for this correlation between body fat and dietary fat content are not clear. It has been proposed that a high-fat diet produces hyperphagia, which is solely responsible for the increased body fat content. However, several studies in various rodent models showed that increased body fat content still results when the hyperphagia is prevented. This suggests that some metabolic effects of high-fat diets, independent of hyperphagia, may also be contributing to the obesity induced by high-fat diets. It is also clear from animal studies that genetic factors significantly modulate the body's response to diets high in fat-derived energy. In contrast with the animal studies, studies in humans that have examined the relation between dietary fat content and body fat are inconclusive. The limitations of cross-sectional studies, the lack of controlled feeding trials, and the importance of genetic variation in response explain the absence of conclusive evidence. The lessons learned from animal models point to dietary fat as one potentially important component in the etiology of human obesity. Additional comprehensive studies are warranted to determine the role of dietary fat in the etiology of human obesity.


Modafinil and cocaine: a double-blind, placebo-controlled drug interaction study.
Modafinil is a novel compound that is approved for the treatment of narcolepsy. It is now being studied as a potential treatment for cocaine dependence. Cocaine withdrawal symptoms are associated with poor clinical outcome and are likely to be reversed by modafinil. In addition, the neurotransmitter actions of modafinil are opposite to cocaine-induced neuroadaptations affecting dopamine and glutamate reward circuits. Since cocaine-dependent subjects might use cocaine during a clinical trial with modafinil, this study tested the safety of intravenous cocaine (30 mg) in combination with modafinil. Each of seven subjects received a baseline (open-label) cocaine infusion. Three subsequent cocaine infusions were administered after subjects received 4 days of low dose modafinil (200 mg/day), high dose modafinil (400 mg/day), or placebo in randomized double-blind sequences. One subject received placebo prior to all infusions. Our results indicate that co-administering modafinil and a single dose of intravenous cocaine is not associated with medical risk in terms of blood pressure, pulse, temperature, or electrocardiogram measures. Furthermore, pretreatment with modafinil did not intensify cocaine euphoria or cocaine-induced craving. In fact, cocaine euphoria was significantly blunted (P=0.02) in one of our subjective measures.


National newspaper coverage of minority health disparities.
To assess American newspaper coverage regarding racial and ethnic minority health disparities (MHDs). LexisNexis was queried with specific word combinations to elicit all MHD articles printed in 257 newspapers from 2000-2004. The full texts were read and articles categorized by racial/ethnic group and specific MHD topics mentioned. In the five years from 2000-2004, 1188 MHD articles were published, representing 0.09% of all articles about health. Newspapers gave much attention to MHD when discussed in conferences and meetings and speeches by senior health officials and politicians. Cancer, cardiovascular disease and HIV/AIDS were most frequent among disease-specific mentions. Articles about African Americans comprised 60.4% of all race/ethnicity-mentioning articles. Despite the release of major organizational reports and the publication of many studies confirming the prevalence of MHD, few newspaper articles have been published explaining MHD to the public. Because of the general public's low rate of health literacy, the health world should collaborate with the media to present a consistent, simple message concerning gaps in care experienced by all racial/ethnic minority groups. In a time of consumer-directed healthcare, if Americans understand that MHDs exist, they may galvanize to advocate for disparity elimination and quality improvement.


Beta EEG band: a measure of functional brain damage and language reorganization in aphasic patients after recovery.
Functional reorganization of language was investigated in a group of eleven non-fluent aphasic patients after linguistic recovery and in a group of matched healthy adults. The ElectroEncephaloGram (EEG) was recorded from 38 scalp electrodes and high-beta band (21-28 Hz), an index of cognitive cortical arousal, was computed as normalized percentage across 0-100 Hz spectral range in six electrode clusters during three linguistic tasks: Phonological, Semantic and Orthographic/visuo-perceptual. During the Phonological task, controls showed greater beta activation on left versus right central cluster, whereas aphasic patients exhibited an inverted pattern of lateralization. In addition, patients' left central cluster, located over the core lesion, showed reduced beta activity with respect to controls. A similar inhibited activation was found in aphasics' left posterior cluster located over undamaged areas. At left anterior locations, aphasics, unlike controls, exhibited larger left versus right beta activity during both Phonological and Orthographic/visuo-perceptual tasks. Results point to substantial reorganization of language in recovered non-fluent aphasics at left prefrontal sites located anterior to the damaged Broca's area and inhibited language-related activation in left posterior undamaged, but disconnected, regions.


Atomically precise Au144(SR)60 nanoclusters (R = Et, Pr) are capped by 12 distinct ligand types of 5-fold equivalence and display gigantic diastereotopic effects.
For two decades, Au144(SR)60 has been one of the most studied and used thiolate (SR) protected gold nanoclusters. In many ways, however, it proved to be a challenging and elusive case, also because of the difficulties in solving its structure by single-crystal X-ray crystallography. We used very short thiols and could prepare Au144(SC2H5)60 and Au144(SC3H7)60 in a very pure form, which was confirmed by UV-vis absorption spectroscopy and very regular electrochemistry patterns. Inductively coupled plasma and electrospray ionization mass spectrometries gave definite proof of the Au144(SR)60 stoichiometry. High-resolution 1D and 2D NMR spectroscopy in the solution phase provided the result of assessing the presence of 12 ligand types in exactly the same amount (5-fold equivalence). Equally important, we found that the two protons belonging to each methylene group along the thiolate chain are diastereotopic. For the α-CH2 protons, the diastereotopic effect can be indeed gigantic, as it reaches chemical-shift differences of 2.9 ppm. DFT calculations provided insights into the relationship between structure and NMR results. In particular, the 12 ligand types and corresponding diastereotopic effects may be explained by considering the presence of C-H···S hydrogen bonds. These results thus provide fundamental insights into the structure of the thiolate layer capping this long-studied gold nanocluster.


An Ayurgenomics Approach: Prakriti-Based Drug Discovery and Development for Personalized Care.
Originating in ancient India, Ayurveda is an alternative medicinal approach that provides substantial evidence for a theoretical-level analysis of all aspects of life. Unlike modern medicine, Ayurveda is based upon tridoshas (Vata, pitta, and Kapha) and Prakriti. On the other hand, the research of all the genes involved at the proteomics, metabolomics, and transcriptome levels are referred to as genomics. Geoclimatic regions (deshanupatini), familial characteristics (kulanupatini), and ethnicity (jatiprasakta) have all been shown to affect phenotypic variability. The combination of genomics with Ayurveda known as ayurgenomics provided new insights into tridosha that may pave the way for precision medicine (personalized medicine). Through successful coordination of "omics," Prakriti-based treatments can help change the existing situation in health care. Prakriti refers to an individual's behavioral trait, which is established at the moment of birth and cannot be fully altered during one's existence. Ayurvedic methodologies are based on three Prakriti aspects: aushadhi (medication), vihara (lifestyle), and ahara (diet). A foundation of Prakriti-based medicine, preventative medicine, and improvement of life quality with longevity can be accomplished through these ayurvedic characteristics. In this perspective, we try to understand prakriti's use in personalized medicine, and how to integrate it with programs for drug development and discovery.


Emotional Dimensions of Music and Painting and their Interaction.
Usually it is accepted that human manifestations such as music or painting share a common artistic trait. However, very little is known about the genetic, behavioral, developmental and neurobiological basis of such a musical-pictorial "universal". In an attempt to approach commonalities and differences between the psychology of music and pictorial art in Experiment 1 we investigated the emotional dimensions valence and arousal in a large sample (N =156, M age = 21,44 years, SD = 3,89 years, range = 16-35 years) using a representative selection of musical and pictorial artistic stimuli. We found a stronger variability of valence and arousal with paintings and stronger effects of music on valence. In Experiment 2 (N =202, M age = 21,35 years, SD = 3,57 years, range = 16-35 years) we present first quantitative data on the interaction between the two artistic categories of stimuli on a behavioral level, again observing effects of pictorial art and music on valence and arousal. Furthermore in Experiment 2 we replicated a more pronounced effect of music on the valence of pictures, particularly on positive valence the results of the ANOVA showed an increase in group A2: F(1, 120) = 6.23, p < .05, in group C2: F(1, 120) = 89.03, p < .001, and a surprisingly emotionally negative influence of pleasant paintings on the positive valence of music, group A1: F(1, 127) = 19.69, p < .001. Despite the unresolved problem of non-representativeness of the stimuli and the sample selected these results may suggest superior emotional "power" of music over painting.


Increased sensitivity of human lymphoid lines to natural killer cells after induction of the Epstein-Barr viral cycle by superinfection or sodium butyrate.
Superinfection of latently Epstein-Barr virus (EBV)-carrying Raji cells with the P3HR-1 substrain EBV, known to induce the entry of a substantial fraction of cells into an abortively lytic cycle, increased the susceptibility of the cells to natural killer (NK) effect of human blood lymphocytes. Reciprocal cold-target competition tests with known NK-cell sensitive and -resistant lymphoid cell ines showed that the increased susceptibility is a result of the appearance of an NK-sensitive target, rather than to a general increase in membrane fragility. Lymphocytes of EBV-seropositive and -negative donors were equally effective killers against P3HR-1 virus-superinfected targets. EBV-induced NK sensitivity increased with time. It was a result of some event associated with the intracellular viral cycle, and not to the adherence of viral particles to the cell surface. Induction of EBV-carrying P3HR-1 cells to entry into the viral cycle with n-butyrate also increased their NK sensitivity. A transforming, noncytopathic prototype strain of EBV, B95-8, failed to increase the susceptibility of theRaji cells to NK-lysis, although it had some effect on the Daudi line. Because NK cells can kill virus-producing cells at an early stage of the cycle, before the virus particles are assembled, they may restrict, in vivo, the spread of the virus from latently infected cells.


Electrochemical titrations and reaction time courses monitored in situ by magnetic circular dichroism spectroscopy.
Magnetic circular dichroism (MCD) spectra, at ultraviolet-visible or near-infrared wavelengths (185-2000 nm), contain the same transitions observed in conventional absorbance spectroscopy, but their bisignate nature and more stringent selection rules provide greatly enhanced resolution. Thus, they have proved to be invaluable in the study of many transition metal-containing proteins. For mainly technical reasons, MCD has been limited almost exclusively to the measurement of static samples. But the ability to employ the resolving power of MCD to follow changes at transition metal sites would be a potentially significant advance. We describe here the development of a cuvette holder that allows reagent injection and sample mixing within the 50-mm-diameter ambient temperature bore of an energized superconducting solenoid. This has allowed us, for the first time, to monitor time-resolved MCD resulting from in situ chemical manipulation of a metalloprotein sample. Furthermore, we report the parallel development of an electrochemical cell using a three-electrode configuration with physically separated working and counter electrodes, allowing true potentiometric titration to be performed within the bore of the MCD solenoid.


Spike-timing-dependent construction.
Spike-timing-dependent construction (STDC) is the production of new spiking neurons and connections in a simulated neural network in response to neuron activity. Following the discovery of spike-timing-dependent plasticity (STDP), significant effort has gone into the modeling and simulation of adaptation in spiking neural networks (SNNs). Limitations in computational power imposed by network topology, however, constrain learning capabilities through connection weight modification alone. Constructive algorithms produce new neurons and connections, allowing automatic structural responses for applications of unknown complexity and nonstationary solutions. A conceptual analogy is developed and extended to theoretical conditions for modeling synaptic plasticity as network construction. Generalizing past constructive algorithms, we propose a framework for the design of novel constructive SNNs and demonstrate its application in the development of simulations for the validation of developed theory. Potential directions of future research and applications of STDC for biological modeling and machine learning are also discussed.


Interactive effects of light-sources, photoperiod, and strains on growth performance, carcass characteristics, and health indices of broilers grown to heavy weights1.
Effects of light sources, photoperiods, and strains on growth performance, carcass characteristics, and health indices of broilers grown to heavy weights (>3 kg) were evaluated. The experimental design was a 4 × 2 × 2 factorial treatments consisting of 4 light sources [incandescent (ICD, standard), compact fluorescent light, neutral light emitting diode (Neutral-LED), and cool poultry specific LED (Cool-poultry specific (PS)-LED)], 2 photoperiods (regular/intermittent [2L:2D], and short [8L:16D]), and 2 strains (A, B). In each trial, chicks of 2 different strains from different commercial hatcheries were equally and randomly distributed into 16 environmentally controlled rooms at 1 D of age. Each room was randomly assigned one of 16 treatments from day 1 to 56 D of age. Feed and water were provided ad libitum. Birds were provided a 4 phase-feeding program (starter, grower, finisher, withdrawal). Birds and feed were weighed on 1, 14, 28, 42, and 56 D of age for growth performance. On day 56, a total of 20 (10 males and 10 females) birds from each room were processed to determine weights and yields. The BW, BW gain, live weight, and carcass weight of birds reared under PS-LED were higher (P < 0.05) in comparison with birds reared under ICD, but feed intake, feed conversion ratio, mortality, and carcass characteristics were not affected by treatments. Also, broilers subjected to the short/non-intermittent photoperiod had the lowest (P < 0.05) growth performance and carcass characteristics compared with values obtained for regular/intermittent photoperiods. In addition, strain was significant (P < 0.05) for most of the examined variables. Feed conversion, fat, tender, and yield were not affected by treatments. There was no effect of photoperiod, light sources, or their interactions on mortality. This study shows positive impacts on alternative light sources when compared to ICD along with regular/intermittent photoperiod in commercial poultry facilities rearing the 2 strains used in this study, thereby reducing energy costs and optimizing production efficiency without compromising the welfare of broilers grown to heavy weights.


Image set based face recognition using self-regularized non-negative coding and adaptive distance metric learning.
Simple nearest neighbor classification fails to exploit the additional information in image sets. We propose self-regularized nonnegative coding to define between set distance for robust face recognition. Set distance is measured between the nearest set points (samples) that can be approximated from their orthogonal basis vectors as well as from the set samples under the respective constraints of self-regularization and nonnegativity. Self-regularization constrains the orthogonal basis vectors to be similar to the approximated nearest point. The nonnegativity constraint ensures that each nearest point is approximated from a positive linear combination of the set samples. Both constraints are formulated as a single convex optimization problem and the accelerated proximal gradient method with linear-time Euclidean projection is adapted to efficiently find the optimal nearest points between two image sets. Using the nearest points between a query set and all the gallery sets as well as the active samples used to approximate them, we learn a more discriminative Mahalanobis distance for robust face recognition. The proposed algorithm works independently of the chosen features and has been tested on gray pixel values and local binary patterns. Experiments on three standard data sets show that the proposed method consistently outperforms existing state-of-the-art methods.


The role of acceptance and job control in mental health, job satisfaction, and work performance.
Acceptance, the willingness to experience thoughts, feelings, and physiological sensations without having to control them or let them determine one's actions, is a major individual determinant of mental health and behavioral effectiveness in a more recent theory of psychopathology. This 2-wave panel study examined the ability of acceptance also to explain mental health, job satisfaction, and performance in the work domain. The authors hypothesized that acceptance would predict these 3 outcomes 1 year later in a sample of customer service center workers in the United Kingdom (N = 412). Results indicated that acceptance predicted mental health and an objective measure of performance over and above job control, negative affectivity, and locus of control. These beneficial effects of having more job control were enhanced when people had higher levels of acceptance. The authors discuss the theoretical and practical relevance of this individual characteristic to occupational health and performance.


CBP60g and SARD1 play partially redundant critical roles in salicylic acid signaling.
Arabidopsis thaliana calmodulin binding protein 60g (CBP60g) contributes to production of salicylic acid (SA) in response to recognition of microbe-associated molecular patterns (MAMPs) such as flg22, a fragment of bacterial flagellin. Calmodulin binding is required for the function of CBP60g in limiting growth of the bacterial pathogen Pseudomonas syringae pv. maculicola (Pma) ES4326 and activation of SA synthesis. Here, we describe a closely related protein, SARD1. Unlike CBP60g, SARD1 does not bind calmodulin. Growth of Pma ES4326 is enhanced in sard1 mutants. In cbp60g sard1 double mutants, growth of Pma ES4326 is greatly enhanced, and SA levels and expression of PR-1 and SID2 are dramatically reduced. Expression profiling placed the CBP60g/SARD1 node between the PAD4/EDS1 and SA nodes in the defense signaling network, and indicated that CBP60g and SARD1 affect defense responses in addition to SA production. A DNA motif bound by CBP60g and SARD1, GAAATTT, was significantly over-represented in promoters of CBP60g/SARD1-dependent genes, suggesting that expression of these genes is modulated by CBP60g/SARD1 binding. Gene expression patterns showed a stronger effect of cbp60g mutations soon after activation of a defense response, and a stronger effect of sard1 mutations at later times. The results are consistent with a model in which CBP60g and SARD1 comprise a partially redundant protein pair that is required for activation of SA production as well as other defense responses, with CBP60g playing a more important role early during the defense response, and SARD1 to playing a more important role later.


Should a diuretic always be the first choice in patients with essential hypertension? The case for no.
A more extensive use of diuretics as first-line drug for the treatment of hypertensive patients has been recommended on the basis of the results of the recent Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, yet diuretics have numerous drawbacks that may limit their undisputed ability to lower BP. These include the stimulation of the renin-angiotensin-aldosterone system with the attending negative cardiovascular effects that ensue from this activation and several metabolic alterations, namely those in glucose, lipid, and potassium metabolism. Numerous mechanistic as well as interventional trials indicate that these limitations of diuretics can adversely affect the clinical outcome of patients and their compliance to treatment and consequently the cost of therapy. In addition, there are a number of clinical conditions in which the diuretics are admittedly contraindicated as first-line drugs. Thus, the emphasis should be on obtaining optimal BP control rather on the drug used to achieve it.


Joint Attention Virtual Classroom: A Preliminary Study.
Previous studies have suggested that a virtual classroom is immersive and ecologically valid neuropsychological assessment, but those studies have limited components for social attentions. Therefore, the objective in the current study is the development of a joint attention virtual reality (JA-VR) classroom to incorporate social attentions between a participant and a virtual avatar teacher. Fifty-eight participants were recruited for current study (25 for pilot and 33 for main studies; 32.8% female, n=19; age: M=24.5, SD=4.0). We suggested a JA-VR classroom, and compared it with previous methods including a VR classroom without JA components. We conducted attention experiments with AX-version of continuous performance tasks. Our results suggest that the new JA-VR classroom had convergent validity with previous methods, and that the JA-VR classroom promoted attentional processing among participants better than both old VR and non-VR measures. We add an important social attention concept to the virtual classroom, and believe that this work is an methodological foundation for the study of social attention in school life. We hope it ultimately help people with mental handicaps in social attention.


Outcome study of the pipeline embolization device for treatment of intracranial aneurysms at a single UK institution.
The introduction of flow-diverting stents in the last decade provides an alternative endovascular treatment choice in selected intracranial aneurysms. This retrospective analysis of a UK centre's experience provides insight into clinical and radiographic outcomes. Electronic patient records, diagnostic and procedural images and written procedural records for patients treated with the PED between August 2009 and April 2014 were reviewed. Follow-up TOF MRA was performed after treatment. Clinical and radiographic outcomes were analyzed and compared with other PED studies. Twenty-nine patients with 30 attempted PED treatments were reviewed representing 3.5% of the treated aneurysm patient cohort. 63.6% (21/33) of the aneurysms were wide-necked (>4 mm), 60.6% (20/33) were large or giant (≥10 mm). The mean aneurysm sac diameter was 12.0 mm; the mean neck width was 4.5 mm. Mortality and morbidity rates were 3.3% and 10.0%, respectively. The total adequate occlusion rate was 78.1% (25/32) at 18 months. The neck width of aneurysms with residual sac filling and complete occlusion differed significantly (p = 0.04). Highly selected aneurysms treated with a PED in a UK centre have similar occlusion and complication rates when compared to non-UK studies. Again, it appeared that delayed aneurysm rupture remained a risk for PED treatment in large or giant aneurysms. Follow-up with TOF MRA gave similar occlusion results compared to those obtained with DSA in other studies. The influence of neck size on occlusion rate should be examined in future PED studies.


Monitoring osteoarthritis in the rat model using optical coherence tomography.
A need exists for an animal model to assess therapeutics for osteoarthritis (OA) without sacrificing the animal. Our goal is to assess the progression of experimentally induced osteoarthritis in the rat knee joint by monitoring articular cartilage thickness, surface abnormalities, and collagen organization using a new technology known as optical coherence tomography (OCT). OA was generated in Wistar Hanover rats via injection of sodium iodoacetate into the left articular joint of the knee while normal saline was injected as a control in the contralateral right knee. Rats were sacrificed at 1-, 2-, 3-, 4-, and 8-week intervals and the knee joints were subsequently harvested and imaged using normal and polarization sensitive OCT (PS-OCT). Treated knees were compared to normal counterparts in the contralateral leg. Following imaging, knees underwent both routine histological processing and picrosirus staining for organized collagen. OCT images indicate that injection of sodium iodoacetate resulted in a progressive decrease in cartilage thickness and loss of the bone-cartilage interface which correlated with histology. In addition, PS-OCT was able to detect collagen disorganization, an early indicator of OA. The use of OCT in combination with the induction of OA in rats is a promising new animal model for assessing articular changes with the goal of monitoring therapeutics longitudinally. Future work will extend the model to in vivo assessments.


A multi-component herbal preparation (PADMA 28) improves structure/function of corticosteroid-treated skin, leading to improved wound healing of subsequently induced abrasion wounds in rats.
PADMA 28 is a multi-component herbal mixture formulated according to an ancient Tibetan recipe. PADMA 28 is known to stimulate collagen production and reduced levels of collagen-degrading matrix metalloproteinases (MMPs). The goal of the present study was to determine whether topical treatment of rat skin with PADMA 28 would improve skin structure/function, and whether subsequently induced abrasion wounds would heal more rapidly in skin that had been pretreated with PADMA 28. Hairless rats were exposed to a potent topical corticosteroid (Temovate) in combination with either DMSO alone or with PADMA 28 given topically. At the end of the treatment period, superficial wounds were created in the skin, and time to wound closure was assessed. Collagen production and matrix-degrading MMPs were assessed. Abrasion wounds in skin that had been pretreated with PADMA 28 healed more rapidly than did wounds in Temovate plus DMSO-treated skin. Under conditions in which improved wound healing was observed, there was an increased collagen production and decreased MMP expression, but no significant epidermal hyperplasia and no evidence of skin irritation. The ability to stimulate collagen production and inhibit collagen-degrading enzymes in skin and facilitate more rapid wound closure without irritation should provide a rationale for development of the herbal preparation as a "skin-repair" agent.


Further studies on thymidine kinase: distribution pattern of the enzyme in bacteria.
Various micro-organisms (131 strains of 73 species) were studied for their ability to produce thymidine kinase (TK; EC 184.108.40.206). Taking the specific TK activity of Escherichia coli K12 [specific activity of sonicated cell extracts 95-194 pmol min-1 (mg protein)-1] as 100%, the test organisms had the following relative specific TK activities. In the Gram-positive cocci, Staphylococcus aureus (21-84%) showed higher activity than Staph. epidermidis (1-20%) and Streptococcus (1-7%) except for one strain of Strep. pyogenes (29%). Neisseria sicca, a Gram-negative coccus, lacked TK. Gram-positive endospore-forming rods showed significant activity (Bacillus, 13-51%; Clostridium perfringens, 9-18%) except for one strain of B. megaterium (2%) and C. difficile (1-3%). Among the Gram-positive asporogenous rods, Listeria monocytogenes and six species of Lactobacillus (especially L. brevis, L. buchneri and L. casei) had moderate to high activity (23-348%) but L. acidophilus, L. bulgaricus, L. lactis and L. cellobiosus had low activity (0-8%). Of the species of Pseudomonas studied, most lacked TK but Ps. fluorescens and Ps. maltophilia had significant TK activity (15-53%). Of the Gram-negative facultative anaerobes, Vibrio lacked TK, while Enterobacteriaceae, including Salmonella (148-1120%), Escherichia (59-141%), Klebsiella (78-299%) and Serratia (61-110%), had a high activity. Proteus had a somewhat lower activity (0-34%) except for 'Pr. rettgerella' (307%). Propionibacterium and Bifidobacterium and related organisms other than Streptomyces, Nocardia, Rhodococcus, Corynebacterium and Mycobacterium lacked TK. The seven species of Candida tested, and Cryptococcus neoformans, essentially lacked TK.(ABSTRACT TRUNCATED AT 250 WORDS)


Abundance and instantaneous transport of Petrolisthes armatus (Gibbes, 1850) planktonic larvae in the Catuama inlet, Northeast Brazil.
The influence of tidal and diel changes on the exchange of Petrolisthes armatus planktonic larvae was studied at the Catuama inlet, which represents an intermediate system of marine and estuarine environments in the Northeast Brazil. To characterize the larval abundance and vertical distribution, samplings were carried out in August 2001 at neap tide and 3 stations, with 3 hours interval over 24 hours. Samples were taken at three or two depths at each station, with a plankton pump coupled to a 300 µm mesh size net. Petrolisthes armatus zoea I and II showed a mean of 26.3 ± 83.6 and 12 ± 38.8 ind m-3, respectively. During flood tides, the larvae were more concentrated in the midwater and surface, which avoided the transport to internal regions. In contrast, during ebb tides when the larvae were distributed in the three layers, the higher concentrations were found in the bottom, which avoided a major exportation. The diel dynamic of the larval fluxes was characterized by vertical migration behavior associated to the tidal regime, which suggested that the development of this decapod apparently occurs in the inner shelf (instead of the outer shelf) off this peculiar ecosystem.


Equol is more active than soy isoflavone itself to compete for binding to thromboxane A(2) receptor in human platelets.
Several dietary intervention studies examining the health effect of soy isoflavones allude to the importance of equol in establishing the cardiovascular response to soy protein. Although, the specific mechanism by which this action occurs has not been established. The aim of this study was to investigate the inhibitory effect of soy-isoflavones and the metabolite of daidzein, equol, on agonist-induced platelet responses dependent on thromboxane A(2) (TxA(2)) receptor. Competitive radioligand binding assay was used to screen for affinity of these compounds to the TxA(2) receptor. The effect of equol on platelet activation, evaluate through of release of the ATP, by analogs of TxA(2) was analyzed. The effect of equol on platelet aggregation was investigated with ADP, U46619 (a TxA(2) mimic) and the calcium ionophore A23187. The data showed that aglycone isoflavones and equol bind to TxA(2) receptor in the micromol/L range, whereas their glucoside derivates had very low binding activity for this receptor. Under equilibrium conditions, the following order of the relative affinity in inhibiting [(3)H]-SQ29585 binding was: equol>genistein>daidzein>glycitein>>genistin, daidzin, glycitin. Equol interaction was reversible and competitive for labeled-SQ29548 with not apparent decrease in the number of TxA(2) binding sites. In addition, from platelet activation studies, equol effectively inhibited ATP secretion elicited by the TxA(2) analog U46619. On the other hand, equol inhibited the platelet aggregation induced by U46619 and A23187, while it failed to inhibit that induced by ADP. The aglycone isoflavones from soy, and particularly equol, have been found to have biological effects attributable to thromboxane A(2) receptor antagonism. These findings may help elucidate how dietary isoflavone modulate platelet function and explain why soy-rich foods are claimed to have beneficial effects in the prevention of thrombotic events.


Anorectal malformations (ARM): quality of life assessed in the functional, urologic and neurologic short and long term follow-up.
Imperforate anus represents a wide spectrum of anorectal malformations associated with urologic, neurologic and orthopedic malformations. The outcome from the various corrective measures has improved due to new surgical techniques as well as to a better understanding of the pathology. Other factors which influence the overall outcome include the degree of patient acceptance, family support as well as the ability of the health care structure to support the patient's needs on a clinical, functional and psychologic level. Assess (with the new techniques available) the quality of life in the adult patient with ARM and compare it to that experienced by a younger patient; also we wish to determine the correlation between the observed abnormalities with the functional, neurologic and urologic outcome. Sixty-six patients were subjected to PSARP (36 M; 30 F). Six presented with cloaca and 60 with ARM (23 high and 37 low). All patients underwent the same workup to include L/S MRI diagnostics, evaluation for incontinence (urinary and bowel), a urology screening, and if required, a subsequent urodynamic study with rehabilitation and/or bowel management. All answered questionnaires (AIMAR: Italian parent's association of ARM) in order to assess their satisfaction with the current health condition, with the information received and with the treatment and follow-up sessions. The patients were classified into one of two groups. Group A, totaled 33 patients (4 cloacae) with an age range between 2 and 12 years who were operated after 1995. The second, group B, was made up of 33 patients who had been surgically treated before 1995 (age range 15-41 years), had followed the study protocol and had also a neuropsychiatry consult. Overall fecal continence was 69% and of this number 37% were clean without constipation. Twe2nty-one patients (32%) suffered from some form of constipation. Constipation was the most common functional disorder observed in patients who have undergone PSARP. The highest incidence of constipation was found in the ARM (low type), a favorable prognostic group with 43% constipation. Patient with "high" defects and a cloaca had a lower incidence of constipation (18%). Of the 59 patients evaluated, 85% were urinary continent and 15% were incontinent. All of the incontinent patients were in the unfavorable prognostic group of malformations. Urodynamic studies showed 7 neurogenic bladders (NB) and 2 patients with a neurovescical dysfunction (NVD). Of the 50 "dry" patients. 20 had voiding disturbances due to a voiding dysfunction, in the absence of neurologic abnormalities, and presented occasional daytime or nighttime wetting. There was no correlation between the level of the anatomic defect and the urodynamic patterns in the group. Abnormal MRI findings were observed in thirty out of fifty-two patients evaluated. The MRI findings were classified as follows. Severe abnormalities: 7 patients (13%) presented with a combination of skeletal (sacral/lumbar) and spinal cord anomalies. Only spinal cord abnormalities: 12 patients (21%). Only skeletal abnormalities: 11 (19%) patients. Patients were divided into high, low and cloacal malformations. A high degree of statistical correlation was noted between the patients belonging to the cloacae and high defect groups and the abnormal MRI findings. No significant correlation was found between the low defect group and dysrafism, abnormal MRI results and the severity of the malformation. The incidence of Tethered Cord (TC) in our limited number of patients was limited in our study (9% in the high and 7% in the low defect group) when compared to the current literature. Furthermore there was no statistically conclusive evidence that TC by itself affects the urinary or fecal control in our patients. Our recommendation is nevertheless to obtain an MRI study in all patients with ARM. All patients 17 and older reported a "good quality of life". Four are married, two with children. Aclose working relationship with the medical personnel is not only necessary but is also well received by the family particularly when younger patients are involved. The adult patient easily adapts even when information is initially scarce. He quickly reaches autonomy with personalized solutions but prefers a longer follow-up time during which, specialized medical facilities will play an important role in the treatment of ARM. Our findings illustrate the importance of both global disease-specific functioning and perceived psychosocial competencies for enhancing the QL of these patients.


Family meetings in palliative care: Multidisciplinary clinical practice guidelines.
Support for family carers is a core function of palliative care. Family meetings are commonly recommended as a useful way for health care professionals to convey information, discuss goals of care and plan care strategies with patients and family carers. Yet it seems there is insufficient research to demonstrate the utlility of family meetings or the best way to conduct them. This study sought to develop multidisciplinary clinical practice guidelines for conducting family meetings in the specialist palliative care setting based on available evidence and consensus based expert opinion. The guidelines were developed via the following methods: (1) A literature review; (2) Conceptual framework; (3) Refinement of the guidelines based on feedback from an expert panel and focus groups with multidisciplinary specialists from three palliative care units and three major teaching hospitals in Melbourne, Australia. The literature review revealed that no comprehensive exploration of the conduct and utility of family meetings in the specialist palliative care setting has occurred. Preliminary clinical guidelines were developed by the research team, based on relevant literature and a conceptual framework informed by: single session therapy, principles of therapeutic communication and models of coping and family consultation. A multidisciplinary expert panel refined the content of the guidelines and the applicability of the guidelines was then assessed via two focus groups of multidisciplinary palliative care specialists. The complete version of the guidelines is presented. Family meetings provide an opportunity to enhance the quality of care provided to palliative care patients and their family carers. The clinical guidelines developed from this study offer a framework for preparing, conducting and evaluating family meetings. Future research and clinical implications are outlined.


Recent advances and perspectives of metabolomics-based investigations in Parkinson's disease.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system (CNS), which affects mostly older adults. In recent years, the incidence of PD has been dramatically increasing with the aging population expanding. Due to the lack of effective biomarkers, the accurate diagnosis and precise treatment of PD are currently compromised. Notably, metabolites have been considered as the most direct reflection of the physiological and pathological conditions in individuals and represent attractive candidates to provide deep insights into disease phenotypes. By profiling the metabolites in biofluids (cerebrospinal fluid, blood, urine), feces and brain tissues, metabolomics has become a powerful and promising tool to identify novel biomarkers and provide valuable insights into the etiopathogenesis of neurological diseases. In this review, we will summarize the recent advancements of major analytical platforms implemented in metabolomics studies, dedicated to the improvement and extension of metabolome coverage for in-depth biological research. Based on the current metabolomics studies in both clinical populations and experimental PD models, this review will present new findings in metabolomics biomarkers research and abnormal metabolic pathways in PD, and will discuss the correlation between metabolomic changes and clinical conditions of PD. A better understanding of the biological underpinning of PD pathogenesis might offer novel diagnostic, prognostic, and therapeutic approaches to this devastating disease.


Mobility status after inpatient stroke rehabilitation: 1-year follow-up and prognostic factors.
To evaluate the stability of mobility status achieved by stroke patients during hospital rehabilitation treatment over time and to identify reliable prognostic factors associated with mobility changes. Follow-up evaluation in consecutive first-ever stroke patients 1 year after hospital discharge. Multiple logistic regressions were used to analyze increases and decreases in Rivermead Mobility Index (RMI) scores (dependent variables) between discharge and follow-up. Independent variables were medical, demographic, and social factors. Rehabilitation hospital. A cohort of 155 patients with sequelae of first stroke, with a final sample of 141. Mobility status at 1-year follow-up, as measured by the RMI, and odds ratios (OR) for improvement and decline in mobility. Functionally, 19.9% improved the mobility levels achieved during the inpatient rehabilitation treatment; levels of 42.6% worsened. Patients with global aphasia (OR = 5.66; 95% confidence interval [CI], 1.50-21.33), unilateral neglect (OR = 3.01; 95% CI, 1.21-7.50), and age 75 years or older (OR = 5.77; 95% CI, 1.42-23.34) had a higher probability of mobility decline than the remaining patients. Postdischarge rehabilitation treatment (PDT), received by 52.5% of the final sample, was significantly and positively associated with mobility improvement (OR = 5.86; 95% CI, 2.02-17.00). Absence of PDT was associated with a decline in mobility (OR = 3.73; 95% CI, 1.73-8.04). In most cases, mobility status had not yet stabilized at hospital discharge. PDT was useful in preventing a deterioration in mobility improvement achieved during inpatient treatment and in helping increase the likelihood of further mobility improvement.


The role of patellar resurfacing in total knee arthroplasty.
The ideal treatment of the patella in primary total knee arthroplasty (TKA) for osteoarthritis (OA) remains unclear. Although data exist in the literature to support either resurfacing or not resurfacing the patella, evidence continues to emerge that unresurfaced patellas deteriorate with time. Recent prospective, randomized studies also favor patellar resurfacing over retaining the native patella, reporting reoperation rates to convert unresurfaced to resurfaced patellas exceeding those for complications after patellar resurfacing. In addition, the incidence of residual patellofemoral pain after secondary resurfacing is substantially higher than when patellofemoral resurfacing is done primarily. Patient selection criteria are critical in the decision-making process. Patellofemoral complications, the greatest argument against resurfacing, have been diminished with improved surgical techniques and implant design.


Genetic analysis of two female patients with incomplete Denys-Drash syndrome.
Denys-Drash syndrome (DDS) is characterized by genital anomaly, early onset nephropathy and high risk for developing Wilms' tumor (WT). Recently, mutations in exon 8 or 9 of the Wilms' tumor suppressor gene (WT1) have been found in the majority of DDS patients studied. We analyzed these two exons of the WT1 gene in genomic DNA from two female patients with DDS by using polymerase-chain reaction (PCR) and direct sequencing. The patients were accompanied with normal external genitalia, early onset renal failure between 6 and 12 months of age, and unilateral Wilms' tumor. Genomic DNA was isolated from peripheral blood leucocytes of the patients. Amplification of exons 8 and 9 of the WT1 gene by PCR was performed, and direct sequencing of the PCR product was performed using an automatic DNA sequencer. Two heterozygous missense mutations were found in these patients, including a missense mutation in exon 9 at codon 388 replacing the wild-type Cys with Phe, and a previously described mutation in exon 9 at codon 398 replacing the wild-type Leu with Pro. Cys388Phe is a novel mutation in the WT1 gene in the DDS. These cases are considered to be "incomplete DDS" with nephropathy and Wilms' tumor and without genital anomaly, the validity of which has been confirmed by mutation analysis.


Changing trends in malignant transformation of hepatocellular adenoma.
Hepatocellular adenomas (HCAs) classically develop in women who are taking oral contraceptives and have a risk of malignant transformation into hepatocellular carcinoma (HCC). HCA with malignant transformation is, however, an ill-defined entity thought to be an anecdotic pathway to HCC. The objective of this study was to characterise malignancy occurring within HCA. A series of histology proven HCAs managed between 1993 and 2008 in a tertiary hepato-biliary centre (218 patients, 184 women and 34 men) were screened to identify HCA with malignant transformation. The incidence of HCA with malignant transformation was analysed through the study period and associated conditions were retrieved. They were sub-typed according to their molecular features and the malignant compartment was mapped. Areas of HCC within HCA were observed in 23 patients and the risk of malignant transformation was 4% in women and 47% in men. The number of women whose HCA had malignant changes has remained stable during the study period and oral contraception was the only associated condition. The number of men with such transformation has markedly increased since 2000 and the metabolic syndrome has become the most frequent associated condition. Two-thirds of HCAs with malignant transformation were β-catenin activated and one-third displayed cell atypias. Both features were more prevalent in men. The median diameter of HCA with malignancy was 10 cm and only three were 5 cm or less. Prevalence of malignancy within HCA is 10 times more frequent in men than in women and management of HCA should primarily be based on gender. Whereas oral contraception is a classical cause of HCA in women but a marginal cause of HCC, the metabolic syndrome appears as an emerging condition associated with malignant transformation of HCA in men, and is the likely predisposing condition for HCC in this setting.


Hybrid foraging search: Searching for multiple instances of multiple types of target.
This paper introduces the "hybrid foraging" paradigm. In typical visual search tasks, observers search for one instance of one target among distractors. In hybrid search, observers search through visual displays for one instance of any of several types of target held in memory. In foraging search, observers collect multiple instances of a single target type from visual displays. Combining these paradigms, in hybrid foraging tasks observers search visual displays for multiple instances of any of several types of target (as might be the case in searching the kitchen for dinner ingredients or an X-ray for different pathologies). In the present experiment, observers held 8-64 target objects in memory. They viewed displays of 60-105 randomly moving photographs of objects and used the computer mouse to collect multiple targets before choosing to move to the next display. Rather than selecting at random among available targets, observers tended to collect items in runs of one target type. Reaction time (RT) data indicate searching again for the same item is more efficient than searching for any other targets, held in memory. Observers were trying to maximize collection rate. As a result, and consistent with optimal foraging theory, they tended to leave 25-33% of targets uncollected when moving to the next screen/patch. The pattern of RTs shows that while observers were collecting a target item, they had already begun searching memory and the visual display for additional targets, making the hybrid foraging task a useful way to investigate the interaction of visual and memory search.


Tiliqua scincoides: temperature-sensitive units in lizard brain.
Extracellular action potentials were recorded from units in the preoptic area of the brain of the Australian blue-tongued skink (Tiliqua scincoides) during periods of local heating and cooling of the brain (20 degrees to 36 degrees C) with water-perfused thermodes. In this temperature range most spontaneously firing neurons were temperature-insensitive, but eight showed sensitivity to the thermal stimulus. Five warm neurons increased their activity when the brain temperature was raised, and three cold neurons showed increased activity with fall in temperature.


Stressful situations in life, use and abuse of alcohol and drugs by elderly in Monterrey, Mexico.
This is a descriptive, qualitative, and correlation study with 112 elderly aged 60 years or older. This study aimed to identify differences in alcohol consumption according to gender and marital status, and differences in the consumption of medical drugs by gender. It also aims to determine differences in stressful life events by gender, and differences in stressful life events associated to alcohol and medical drugs use and abuse, as well as to know their perceptions on the most stressful life events they have experienced. The results showed significant differences in alcohol consumption by gender (U=154.0, p <0.01), in which the consumption was higher for men. It was reported that the medical drugs consumption (C2 =5.95, p <0.15) and life stress indexes (U=1038.5, p =0.10) are higher for women. The most stressful life events reported were: their health problems or those of their relatives, family and economic problems.


Integrating a 250 mL-spinner flask with other stirred bench-scale cell culture devices: a mass transfer perspective.
The bioprocess development cycle is a complex task that requires a complete understanding of the engineering of the process (e.g., mass transfer, mixing, CO(2) removal, process monitoring, and control) and its affect on cell biology and product quality. Despite their widespread use in bioprocess development, spinner flasks generally lack engineering characterization of critical physical parameters such as k(L)a, P/V, or mixing time. In this study, mass transfer characterization of a 250-mL spinner flask using optical patch-based sensors is presented. The results quantitatively show the effect of the impeller type, liquid filling volume, and agitation speed on the volumetric mass transfer coefficient (k(L)a) in a 250-mL spinner flask, and how they can be manipulated to match mass transfer capability at large culture devices. Thus, process understanding in spinner flasks can be improved, and these devices can be seamlessly integrated in a rational scale-up strategy from cell thawing to bench-scale bioreactors (and beyond) in biomanufacturing.


Mood-elevating effect of captopril in depressed patients.
The use of captopril, an inhibitor of angiotensin-converting enzyme and enkephalinase, was associated with substantial mood elevation in three depressed patients. Substances that may alter neuropeptide synthesis or degradation warrant further investigation as therapeutic agents in certain neuropsychiatric disorders.


Utilization and responsiveness of the asthma control test (ACT) at the initiation of therapy for patients with asthma: a randomized controlled trial.
The aim of this study was to assess the responsiveness of the asthma control test (ACT) to detect changes at the initiation of therapy and its utilization in the initiation of asthma treatment. This study was designed as a randomized clinical trial conducted in a primary care setting. The subjects were asthma patients who had not received controller therapy for at least two months. The patients were randomized into two groups: The Saudi Initiative for Asthma (SINA) group and the Global Initiative for Asthma (GINA) group. Treatment in the SINA group was initiated at step1 when the ACT scores ≥ 20, step 2 when the score between16-19, and step 3 when the score < 16 began at step 3. The GINA group patients were started on step 2 when they had persistent asthma symptoms or step 3 when they had severely uncontrolled disease. Forty-five patients were analyzed in each group. The improvement in ACT score after treatment initiation was significantly higher when the SINA approach was used (2.9 in the SINA group compared to 1.7 in the GINA group (p = 0.04)). The improvement in FEV1 was 5.8% in the SINA group compared to 3.4% in the GINA group (p = 0.46). The number of patients who achieved asthma control at the follow-up visit and required no treatment adjustment was 33 (73.3%) in the SINA group and 27 (60%) in the GINA group (p = 0.0125). The ACT was responsive to change at the initiation of asthma treatment and was useful for the initiation of asthma treatment. ISRCTN31998214.


Biochemical and functional abnormalities in lymphocytes from an adenosine deaminase-deficient patient during enzyme replacement therapy.
Biochemical and immunological properties of lymphocytes were measured repetitively over a period of 40 mo during enzyme replacement by transfusion in a child with adenosine deaminase (ADA) deficiency and severe combined immunodeficiency disease. Catalytically defective ADA protein is present in the child's cells. ADA activity in his lymphocytes is 7 nmol/min per 10(8) cells with 51 ng of ADA protein/10(8) cells by radioimmunoassay. ADA activities in normal cord and adult lymphocytes average 193 and 92 nmol/min per 10(8) cells, respectively, with 429 and 223 ng of ADA protein/10(8) cells. Deoxy(d)ATP accumulates in the patient's erythrocytes and lymphocytes. Transfusion of irradiated packed erythrocytes partially corrects the metabolic defects. Frank metabolic relapse occurs if transfusions are discontinued for several months. The amounts of dATP in erythrocytes and lymphocytes averaged 13 and 2 times normal, respectively, during periods when transfusions were administered every 2-4 wk. Deoxyguanosine triphosphate and deoxycytidine triphosphate in lymphocytes were normal on 11 occasions, but deoxyribosylthymine triphosphate was ninefold increased. On 11 occasions dATP was measured in lymphocytes and erythrocytes isolated simultaneously. There was a positive, but statistically insignificant, correlation between amounts of dATP in the two types of cells (r = 0.25,P > 0.1). The absolute peripheral lymphocyte count was correlated with the activity of ADA in circulating erythrocytes and with the response of lymphocytes to phytohemagglutinin (r = 0.64, P < 0.01; r = 0.49, P < 0.05). Response of lymphocytes to stimulation by phytohemagglutinin in vitro and absolute peripheral lymphocyte counts were not significantly correlated with levels of dATP in the erythrocyte or lymphocyte during periods of intensive therapy. Although there was objective improvement during enzyme replacement, the child remained immunodeficient and biochemically abnormal.


Interrelationship Between Markers of Oxidative Stress, Inflammation and Hematological Parameters Among Preeclamptic Nigerian Women.
BACKGROUND Preeclampsia is a multifaceted pregnancy-related disorder affecting women and fetuses. A link between preeclampsia, oxidative stress, and inflammation has been suggested. This study evaluated the interrelationship between biomarkers of oxidative stress, inflammation, and hematological parameters among preeclamptic Nigerian women. MATERIAL AND METHODS A cross-sectional study was conducted among 49 preeclamptic and 50 normotensive healthy pregnant women. Blood samples were obtained after 20-week gestation in all participants. Levels of superoxide dismutase (SOD), catalase, glutathione (GSH), malonaldehyde (MDA), total protein, high-sensitivity C-reactive protein (hs-CRP), and cardiac-specific troponin I (cTnI) were determined by spectrophotometric and ELISA techniques. FBC, prothrombin time, and activated partial thromboplastin time were determined using an auto-analyzer, Quick's one-stage, and Proctor's and Rappaport's modification methods, respectively. RESULTS The mean SOD (0.051±0.050 vs. 0.073±0.047, p 0.029), catalase (2.62±1.93 vs. 8.48±4.40, p<0.001), GSH (49.05±17.57 vs. 187.10±56.07 p<0.001), platelet (127.63±89.75 vs. 267.16±212.82, p<0.001 were lower in preeclampsia. MDA (7.16±5.00 vs. 2.91±2.66, p<0.001), cTnI (0.46±0.31 vs. 0.13±0.14 p<0.001), PT (19.36±4.06 vs. 13.45±1.97 p<0.001), APTT (45.53±2.92 vs. 37.49±4.99; p<0.001) were higher in preeclampsia. Negative associations between SOD and MDA (r -0.527 p<0.001), CAT and MDA (r -0.469, p 0.001) and positive associations between catalase and hs-CRP (r 0.844, p 0.029), RBC and HB (r 0.442, p 0.001), platelet, and SOD (r 0.353, p 0.013) were observed among preeclamptic volunteers. CONCLUSIONS Preeclampsia is associated with oxidative stress, derangement of hematological and coagulation homeostasis, as well as deleterious effects on the cardiovascular system.


Cytomechanics of neurite outgrowth from chick brain neurons.
Mechanical tension is a direct and immediate stimulus for neurite initiation and elongation from peripheral neurons. We report here that the relationship between tension and neurite outgrowth is equally initimate for embryonic chick forebrain neurons. Culture of forebrain neurons was unusually simple and reliable, and some of these cells undergo early events of axonal-dendritic polarity. Neurite outgrowth can be initiated de novo by experimental application of tension to the cell margin of forebrain neurons placed into culture 8-12 hours earlier, prior to spontaneous neurite outgrowth. Experimentally induced neurite elongation from these neurons shows the same robust linear relationship between elongation rate and magnitude of applied tension as peripheral neurons, i.e. both show a fluid-like growth response to tension. Although forebrain and sensory neurons manifest a similar distribution of growth sensitivity to tension (growth rate/unit tension), chick forebrain neurons initiated and elongated neurites at substantially lower net tensions than peripheral neurons. This is because, unlike peripheral neurons, there is no minimum threshold tension required for elongation in forebrain neurons; all positive tensions stimulate neurite outgrowth. Consistent with this observation, chick forebrain neurons showed weak retractile behavior in response to slackening compared to sensory neurons. Neurites that were slackened showed only transient elastic behavior and never actively produced tension, as do chick sensory neurons after slackening. We conclude that tension is an important regulator of both peripheral and central neuronal growth, but that elastic behavior is much weaker for forebrain neurons than peripheral neurons from the same developing organism. These data have significance for the understanding of the morphogenetic events of brain development.


Transesophageal two-dimensional echocardiographic identification of hiatal hernia.
We report a case of a middle-aged woman in whom a transesophageal echocardiogram showed a mass-like lesion posteriorly near the descending thoracic aorta. We were able to make a definitive diagnosis of this mass as a hiatal hernia because of a thick inner lining measuring 6-9 mm in thickness similar to the stomach mucosa, and the presence of a few microbubbles within the mass. In addition, the microbubbles increased considerably after 10 cc of agitated normal saline flush via a nasogastric tube.


Postoperative spindle cell nodules (PSCN) resembling sarcomas: an atypical granulation tissue or atypical pyogenic granuloma with exuberant myofibroblastic component?
Three cases of PSCN that developed 6-8 weeks after operations to the lower genital tract in two women, and after tooth removal in a 9-year-old boy are described. The lesions averaged 2 cm. in diameter and simulated spindle cell sarcomas because of their high mitotic rate, and marked cellularity. On follow-up (2-6 years) all patients were found to be free of disease. Immunohistochemical testing of the spindle cells showed a strong positivity for vimentin, and muscle actin and a weak, focal and inconstant positivity for F. VIII R.A., and Ulex E. The was total negativity for desmin, smooth muscle actin, S 100 Protein and Cytokeratins. We believe that these lesions represent an atypical form of granulation tissue in which the exuberant myofibroblastic component obscure the vascular elements of the lesion.


Data sets for home care organizations.
Those who predict the future see managed care as a major element in reformed health care delivery. And one tool that managed care uses increasingly is outcomes measurement. Home care has just begun to develop its role in outcomes measurement by completing a uniform minimum data set to gather and compare data. The data set as yet does not include outcomes; it is the first step toward that goal.


The m6A Writer: Rise of a Machine for Growing Tasks.
The central dogma of molecular biology introduced by Crick describes a linear flow of information from DNA to mRNA to protein. Since then it has become evident that RNA undergoes several maturation steps such as capping, splicing, 3'-end processing, and editing. Likewise, nucleotide modifications are common in mRNA and are present in all organisms impacting on the regulation of gene expression. The most abundant modification found in mRNA is N6-methyladenosine (m6A). Deposition of m6A is a nuclear process and is performed by a megadalton writer complex primarily on mRNAs, but also on microRNAs and lncRNAs. The m6A methylosome is composed of the enzymatic core components METTL3 and METTL14, and several auxiliary proteins necessary for its correct positioning and functioning, which are WTAP, VIRMA, FLACC, RBM15, and HAKAI. The m6A epimark is decoded by YTH domain-containing reader proteins YTHDC and YTHDF, but METTLs can act as "readers" as well. Eraser proteins, such as FTO and ALKBH5, can remove the methyl group. Here we review recent progress on the role of m6A in regulating gene expression in light of Crick's central dogma of molecular biology. In particular, we address the complexity of the writer complex from an evolutionary perspective to obtain insights into the mechanism of ancient m6A methylation and its regulation.


The ancient and widespread nature of the ER-mitochondria encounter structure.
Mitochondria are the result of a billion years of integrative evolution, converting a once free-living bacterium to an organelle deeply linked to diverse cellular processes. One way in which mitochondria are integrated with nonendosymbiotically derived organelles is via endoplasmic reticulum (ER)-mitochondria contact sites. The ER membrane is physically tethered to the mitochondrial outer membrane by the ER-mitochondria encounter structure (ERMES). However, to date, ERMES has only ever been found in the fungal lineage. Here, we bioinformatically demonstrate that ERMES is present in lineages outside Fungi and validate this inference by mass spectrometric identification of ERMES components in Acanthamoeba castellanii mitochondria. We further demonstrate that ERMES is retained in hydrogenosome-bearing but not mitosome-bearing organisms, yielding insight into the process of reductive mitochondrial evolution. Finally, we find that the taxonomic distribution of ERMES is most consistent with rooting the eukaryotic tree between Amorphea (Animals + Fungi + Amoebozoa) + Excavata and all other eukaryotes (Diaphoratickes).


Vision-related quality of life and symptom perception change over time in newly-diagnosed primary open angle glaucoma patients.
To evaluate the change over time of vision-related quality of life (QoL) and glaucoma symptoms in a population of newly-diagnosed primary open angle glaucoma (POAG) patients. Multicenter, prospective study. Consecutive newly-diagnosed POAG patients were enrolled and followed-up for one year. Follow-up visits were scheduled at 6 and 12 months from baseline. At each visit, vision-related QoL and glaucoma-related symptoms were assessed by the means of the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the Glaucoma Symptom Scale (GSS), respectively. Trends over time for NEI-VFQ-25 and GSS scores were evaluated with longitudinal linear mixed models. One-hundred seventy-eight patients were included in the analysis. At baseline, early to moderate glaucoma stages were associated with higher scores for most GSS and NEI-VFQ-25 items, while lower best-corrected visual acuity was associated with lower scores for 4 of the 12 NEI-VFQ-25 items. During the follow-up, all the GSS scores, the NEI-VFQ-25 total score, and 7 of the 12 NEI-VFQ-25 scores significantly improved (p < 0.05). In multivariate model, higher increases of most GSS and NEI-VFQ-25 scores were modeled in patients with low scores at baseline. Vision-related QoL and glaucoma-related symptom perception significantly improved during the one-year follow-up in this population of newly diagnosed POAG patients.


Accuracy of lower extremity arterial duplex mapping.
We performed lower extremity arterial duplex mapping from the aortic bifurcation to the ankle in 150 consecutive patients evaluated for aortic and lower extremity arterial reconstruction and compared lower extremity arterial duplex mapping in a blinded fashion to angiography. On the basis of history, physical examination, and four-cuff segmental Doppler pressures individual lower extremities were classified as normal, isolated aortoiliac disease, infrainguinal disease, and multilevel inflow and outflow disease. For vessels proximal to the tibial arteries, lower extremity arterial duplex mapping was analyzed for its ability to insonate individual arterial segments, detect a 50% or greater stenosis, and distinguish stenosis from occlusion. In the tibial arteries lower extremity arterial duplex mapping was evaluated for its ability to visualize tibial vessels and to predict interruption of tibial artery patency from origin to ankle. Lower extremity arterial duplex mapping visualized 99% of arterial segments proximal to the tibial vessels, with overall sensitivities for detecting a 50% or greater lesion ranging from 89% in the iliac vessels to 67% at the popliteal artery. Stenosis was successfully distinguished from occlusion in 98% of cases. In the tibial vessels lower extremity arterial duplex mapping was better at visualizing anterior tibial and posterior tibial artery segments (94% and 96%) than peroneal artery segments (83%), (p less than 0.001). Overall sensitivities for predicting interruption of tibial artery patency were 90% for the anterior tibial, 90% for the posterior tibial, and 82% for the peroneal. Clinical disease category did not influence in a major way the accuracy of lower extremity arterial duplex mapping in either above-knee or below-knee vessels.


Effect of propranolol on regional myocardial blood flow and oxygen consumption.
The present investigation was designed to determine the effect of propranolol on regional myocardial blood flow and oxygen consumption (MVO2) in the isolated supported dog heart preparation perfused at a constant coronary blood flow. The transmural distribution of blood flow, determined by the radioactive microsphere technique, was expressed as the epicardial/endocardial blood flow ratio (epi/endo). Propranolol (0.5 mg/kg i.v.) produced a significant decrease in heart rate and myocardial contractile force and an increase in coronary artery perfusion pressure due to an increase in coronary vascular resistance. These hemodynamic changes were accompanied by significant decreases in epi/endo (increased endocardial perfusion) and MVO2. Reduction of perfusion pressure to control by a decrease in total coronary blood flow produced no further change in epi/endo or MVO2. However, increasing heart rate to control increased epi/endo to predrug levels. Contractile force and MVO2 remained reduced below control. Norepinephrine infusion (1 mug/min intracoronary) produced a significant increase in heart rate and contractile force and decrease in perfusion pressure. These changes were accompanied by an increase in epi/endo and MVO2. Propranolol (0.5 mg/kg i.v.) abolished the response to norepinephrine. Propranolol may produce beneficial effects in angina pectoris by a decrease in epi/endo (via a reduction in heart rate) and MVO2 and by beta adrenergic blockade of the deleterious effects of catecholamines.


Release of HER2 repression of trefoil factor 3 (TFF3) expression mediates trastuzumab resistance in HER2+/ER+ mammary carcinoma.
HER2+/ER+ breast cancer, a subset of the luminal B subtype, makes up approximately 10% of all breast cancers. The bidirectional crosstalk between HER2 and estrogen receptor (ER) in HER2+/ER+ breast cancer contributes to resistance towards both anti-estrogens and HER2-targeted therapies. TFF3 promotes breast cancer progression and has been implicated in anti-estrogen resistance in breast cancer. Herein, we investigated the cross-regulation between HER2 and estrogen-responsive TFF3, and the role of TFF3 in mediating trastuzumab resistance in HER2+/ER+ breast cancer. TFF3 expression was decreased by HER2 activation, and increased by inhibition of HER2 with trastuzumab in HER2+/ER+ breast cancer cells, partially in an ERα-independent manner. In contrast, the forced expression of TFF3 activated the entire HER family of receptor tyrosine kinases (HER1-4). Hence, HER2 negatively regulates its own signalling through the transcriptional repression of TFF3, while trastuzumab inhibition of HER2 results in increased TFF3 expression to compensate for the loss of HER2 signalling. In HER2+/ER+ breast cancer cells with acquired trastuzumab resistance, TFF3 expression was markedly upregulated and associated with a corresponding decrease in HER signalling. siRNA mediated depletion or small molecule inhibition of TFF3 decreased the survival and growth advantage of the trastuzumab resistant cells without re-sensitization to trastuzumab. Furthermore, TFF3 inhibition abrogated the enhanced cancer stem cell-like behaviour in trastuzumab resistant HER2+/ER+ breast cancer cells. Collectively, TFF3 may function as a potential biomarker and therapeutic target in trastuzumab resistant HER2+/ER+ breast cancer.


Genomic analysis of CTX-M-115 and OXA-23/-72 co-producing Acinetobacter baumannii, and their potential to spread resistance genes by natural transformation.
To characterize Acinetobacter baumannii strains co-producing the ESBL CTX-M-115 and carbapenem-hydrolysing class D β-lactamases (CHDLs), and to assess the potential diffusion of their resistance genes by horizontal transfer. Nineteen CTX-M-115/CHDL-positive A. baumannii were collected between 2015 and 2019 from patients hospitalized in France. Their whole-genome sequences were determined on Illumina and Oxford Nanopore platforms and were compared through core-genome MLST (cgMLST) and SNP analyses. Transferability of resistance genes was investigated by natural transformation assays. Eighteen strains were found to harbour CHDL OXA-72, and another one CHDL OXA-23, in addition to CTX-M-115, narrow-spectrum β-lactamases and aminoglycoside resistance determinants including ArmA. cgMLST typing, as well as Oxford Scheme ST and K locus typing, confirmed that 17 out of the 18 CTX-M-115/OXA-72 isolates belonged to new subclades within clonal complex 78 (CC78). The chromosomal region carrying the blaCTX-M-115 gene appeared to vary greatly both in gene content and in length (from 20 to 79 kb) among the strains, likely because of IS26-mediated DNA rearrangements. The blaOXA-72 gene was localized on closely related plasmids showing structural variations that occurred between pdif sites. Transfer of all the β-lactamase genes, as well as aminoglycoside resistance determinants to a drug-susceptible A. baumannii recipient, was easily obtained in vitro by natural transformation. This work highlights the propensity of CC78 isolates to collect multiple antibiotic resistance genes, to rearrange and to pass them to other A. baumannii strains via natural transformation. This process, along with mobile genetic elements, likely contributes to the considerable genomic plasticity of clinical strains, and to the diversity of molecular mechanisms sustaining their multidrug resistance.


IL35-Producing B Cells Promote the Development of Pancreatic Neoplasia.
A salient feature of pancreatic ductal adenocarcinoma (PDAC) is an abundant fibroinflammatory response characterized by the recruitment of immune and mesenchymal cells and the consequent establishment of a protumorigenic microenvironment. Here, we report the prominent presence of B cells in human pancreatic intraepithelial neoplasia and PDAC lesions as well as in oncogenic Kras-driven pancreatic neoplasms in the mouse. The growth of orthotopic pancreatic neoplasms harboring oncogenic Kras was significantly compromised in B-cell-deficient mice (μMT), and this growth deficiency could be rescued by the reconstitution of a CD1d(hi)CD5(+) B-cell subset. The protumorigenic effect of B cells was mediated by their expression of IL35 through a mechanism involving IL35-mediated stimulation of tumor cell proliferation. Our results identify a previously unrecognized role for IL35-producing CD1d(hi)CD5(+) B cells in the pathogenesis of pancreatic cancer and underscore the potential significance of a B-cell/IL35 axis as a therapeutic target. This study identifies a B-cell subpopulation that accumulates in the pancreatic parenchyma during early neoplasia and is required to support tumor cell growth. Our findings provide a rationale for exploring B-cell-based targeting approaches for the treatment of pancreatic cancer.


Transesterification reaction of the fat originated from solid waste of the leather industry.
The leather industry is an industry which generates a large amount of solid and liquid wastes. Most of the solid wastes originate from the pre-tanning processes while half of it comes from the fleshing step. Raw fleshing wastes which mainly consist of protein and fat have almost no recovery option and the disposal is costly. This study outlines the possibility of using the fleshing waste as an oil source for transesterification reaction. The effect of oil/alcohol molar ratio, the amount of catalyst and temperature on ester production was individually investigated and optimum reaction conditions were determined. The fuel properties of the ester product were also studied according to the EN 14214 standard. Cold filter plugging point and oxidation stability have to be improved in order to use the ester product as an alternative fuel candidate. Besides, this product can be used as a feedstock in lubricant production or cosmetic industry.


A Feasibility Study to Assess Sleep and Subsequent Breast Milk Volume Among Mothers With Hospitalized Preterm Infants.
Sleep is essential for optimal health, and disturbed postpartum sleep is associated with compromised infant attachment. The postpartum experience of mothers with preterm infants is unlike the biological norm, as they are separated from their infants and often express breast milk. The purpose of this study was to examine the feasibility of conducting a clinical research study among women with hospitalized preterm infants. We also explored for associations between maternal sleep patterns and sleep-related psychological states and subsequent breast milk volume. Participants were recruited from Magee-Womens Hospital, located in Pittsburgh, Pennsylvania New mothers completed daily sleep and pumping logs and scales to measure stress, trauma, depression, fatigue, and sleep quality. A total of 78 women were screened, 18 women consented, and a total of 8 participants completed the study. Screening from the postpartum unit increased recruitment. The participants experience worsening sleep quality over time, moderate stress, and fatigue. Stress, postnatal depression, and fatigue are negatively associated with milk volume. Postpartum recruitment with frequent follow-ups improved recruitment and retention. We present a preliminary association between maternal stress, fatigue, and depression, and subsequent breast milk volume. Sleep-related psychological states may negatively influence milk volume.


Double-bundle "all-inside" posterior cruciate ligament reconstruction.
The procedure for repairing the posterior cruciate ligament (PCL) has a steep learning curve and entails numerous difficult steps during surgery, because of the proximity of the neurovascular bundle, difficult passage of the graft through the posterior capsule, and risk of poor tibial fixation because of the long intramedullary trajectory of the graft. The use of instruments for retrograde reaming and a new device for adjustable cortical suspensory fixation allows for a safe, reproducible all-inside double-bundle PCL reconstruction by simplifying these difficult steps. We used anterior tibial allograft or hamstring autograft together with adjustable suspensory fixation devices that allow tensioning (after fixation) of the posterolateral bundle in extension and the anteromedial bundle in flexion.


Surgical management of Necrotizing Enterocolitis in an Incredibly Low Birth Weight infant and review of the Literature.
Survival of preterm infants have dramatically improved over the last decades. Nonetheless, infants born preterm remain vulnerable to many complications, including necrotizing enterocolitis (NEC). The severity of the disease and the mortality rate are directly correlated with decreasing gestational age and birth weight. Despite surgical treatment mortality rate remains very high in extremely premature infants, especially in newborns at the lowest limit of viability. Survival of infants of birth weight (BW) below 750 g has been increasingly reported in recent years, however the overall mortality in extremely low "BW" infants (ELBW) requiring surgery for NEC has not decreased over the past years. We describe our experience with a male preterm infant who survived after an ileostomy procedure for Bell stage II NEC, with improving neuromotor skills at 2 years follow up. Although standard indication to surgery is Bell stage III, in our case the choice of minimal laparotomy, exploration of the bowel and ileostomy at Bell stage II was safe and effective. Our experience suggest that surgery has not a negative impact on survival and ileostomy could prevent further damage of the bowel in NEC. We hypothesize that indication to surgery at an earlier stage may prevent further progression of the disease without a significantly negative impact on survival. Further studies are needed to confirm the appropriateness of this approach in ELBW infants.


Results of a pragmatic effectiveness-implementation hybrid trial of the Family Check-up in community mental health agencies.
This study reports the results of a pragmatic effectiveness-implementation hybrid trial of the Family Check-Up (FCU) conducted in three community mental health agencies with 40 participating therapists. Seventy-one families with children between 5 and 17 years of age participated. Intervention fidelity and level of adoption were acceptable; families reported high service satisfaction; and therapists reported high acceptability. Families in the FCU condition experienced significantly reduced youth conduct problems in comparison to usual care and completion of the FCU resulted in larger effects. This study provides promising evidence that implementing the FCU in community mental health agencies has the potential to improve youth behavior outcomes.


Diagnostic potential of energy metabolism-related genes in heart failure with preserved ejection fraction.
Heart failure with preserved ejection fraction (HFpEF) is associated with changes in cardiac metabolism that affect energy supply in the heart. However, there is limited research on energy metabolism-related genes (EMRGs) in HFpEF. The HFpEF mouse dataset (GSE180065, containing heart tissues from 10 HFpEF and five control samples) was sourced from the Gene Expression Omnibus database. Gene expression profiles in HFpEF and control groups were compared to identify differentially expressed EMRGs (DE-EMRGs), and the diagnostic biomarkers with diagnostic value were screened using machine learning algorithms. Meanwhile, we constructed a biomarker-based nomogram model for its predictive power, and functionality of diagnostic biomarkers were conducted using single-gene gene set enrichment analysis, drug prediction, and regulatory network analysis. Additionally, consensus clustering analysis based on the expression of diagnostic biomarkers was utilized to identify differential HFpEF-related genes (HFpEF-RGs). Immune microenvironment analysis in HFpEF and subtypes were performed for analyzing correlations between immune cells and diagnostic biomarkers as well as HFpEF-RGs. Finally, qRT-PCR analysis on the HFpEF mouse model was used to validate the expression levels of diagnostic biomarkers. We selected 5 biomarkers (Chrna2, Gnb3, Gng7, Ddit4l, and Prss55) that showed excellent diagnostic performance. The nomogram model we constructed demonstrated high predictive power. Single-gene gene set enrichment analysis revealed enrichment in aerobic respiration and energy derivation. Further, various miRNAs and TFs were predicted by Gng7, such as Gng7-mmu-miR-6921-5p, ETS1-Gng7. A lot of potential therapeutic targets were predicted as well. Consensus clustering identified two distinct subtypes of HFpEF. Functional enrichment analysis highlighted the involvement of DEGs-cluster in protein amino acid modification and so on. Additionally, we identified five HFpEF-RGs (Kcnt1, Acot1, Kcnc4, Scn3a, and Gpam). Immune analysis revealed correlations between Macrophage M2, T cell CD4+ Th1 and diagnostic biomarkers, as well as an association between Macrophage and HFpEF-RGs. We further validated the expression trends of the selected biomarkers through experimental validation. Our study identified 5 diagnostic biomarkers and provided insights into the prediction and treatment of HFpEF through drug predictions and network analysis. These findings contribute to a better understanding of HFpEF and may guide future research and therapy development.