Correlating the Diffusion of Water to Performance in Model Reverse Osmosis Polyamides with Controlled Crosslink Densities.
We systematically reduce the cross-link density of a PA network based on m-phenylene diamine by substituting a fraction of the trifunctional trimesoyl chloride cross-linking agent with a difunctional isophthaloyl analog that promotes chain extension, in order to elucidate robust design cues for improving the polyamide (PA) separation layer in reverse osmosis (RO) membranes for desalination. Thin films of these model PA networks are fully integrated into a composite membrane and evaluated in terms of their water flux and salt rejection. By incorporating 15 mol % of the difunctional chain extender, we reduce the cross-link density of the network by a factor of two, which leads to an 80 % increase in the free or unreacted amine content. The resulting swelling of the PA network in liquid water increases by a factor of two accompanied by a 30 % increase in the salt passage through the membrane. Surprisingly, this leads to a 30 % decrease in the overall permeance of water through the membrane. This conundrum is resolved by quantifying the microscopic diffusion coefficient of water inside the PA network with quasi-elastic neutron scattering. In the highest and lowest cross-link density networks, water shows strong signatures of confined diffusion. At short length scales, the water exhibits a translational diffusion that is consistent with the jump-diffusion mechanism. This translational diffusion coefficient is approximately five times slower in the lowest cross-linked density network, consistent with the reduced water permeance. This is interpreted as water molecules interacting more strongly with the increased free amine content. Over longer length scales the water diffusion is confined, exhibiting mobility that is independent of length scale. The length scales of confinement from the quasi-elastic neutron scattering experiments at which this transition from confined to translational diffusion occurs is on the order of (5 to 6) Å, consistent with complementary X-ray scattering, small angle neutron scattering, and positron annihilation lifetime spectroscopy measurements. The confinement appears to come from heterogeneities in the average inter-atomic distances, suggesting that diffusion occurs by water bouncing between chains and occasionally sticking to the polar functional groups. The results obtained here are compared with similar studies of water diffusion through both rigid porous silicates and ion exchange membranes, revealing robust design cues for engineering high-performance RO membranes.


Sources of Information on Postgraduate Medical Training Programs--2002 update.
This is the biennial update listing directories, journal articles, Web sites, and general books that aid the librarian, house officer, or medical student in finding information on medical residency and fellowship programs. The World Wide Web continues to surpass print resources as the most current and complete source of information about postgraduate training programs and specialties. The Web has become a marketing tool for hospitals seeking to recruit the best and brightest for their residency and fellowship programs.


Hospital breastfeeding support and exclusive breastfeeding by maternal prepregnancy body mass index.
Overweight and obese mothers in the United States have disproportionately lower rates of exclusive breastfeeding than mothers of normal weight. The Ten Steps to Successful Breastfeeding (Ten Steps), a series of evidence-based practices designed to support breastfeeding initiation, duration, and exclusivity, demonstrate effectiveness at the population level. It is unknown, however, whether they are consistently provided to women across all maternal body mass index (BMI) categories. We sought to determine whether pre-pregnancy BMI is associated with the implementation and effectiveness of the Ten Steps. We used data from Listening to Mothers III, a cross-sectional survey administered to a sample of mothers who delivered in U.S. hospitals between July 2011 and June 2012. Measures of the Ten Steps were based on maternal self-report on Listening to Mothers III. Our analytic sample was limited to mothers of term infants intending to breastfeed (N = 1,506, weighted). We conducted chi-square testing and constructed weighted multivariable logistic regression models to account for potential confounders. Results suggest that two practices (i.e., holding their babies skin-to-skin for the first time and being encouraged to breastfeed on demand) were more strongly associated with exclusive breastfeeding among mothers with obesity than other mothers. Additionally, mothers with obesity reported holding babies skin-to-skin significantly less often than other mothers. Thus, interventions aimed at helping mothers with obesity to hold their babies skin-to-skin in the first hour and teaching them to breastfeed on demand have the potential to decrease the breastfeeding disparities in this population.


Meta Learning for Low-Resource Molecular Optimization.
The goal of molecular optimization (MO) is to discover molecules that acquire improved pharmaceutical properties over a known starting molecule. Despite many recent successes of new approaches for MO, these methods were typically developed for particular properties with rich annotated training examples. Thus, these approaches are difficult to implement in real scenes where only a small amount of pharmaceutical data is usually available due to the expense and significant effort required for the data collection. Here, we propose a new approach, Meta-MO, for molecular optimization with a handful of training samples based on the well-recognized first-order meta-learning algorithms. By using a set of meta tasks with rich training samples, Meta-MO trains a meta model through the meta-learning optimization and adapts the learned model to new low-resource MO tasks. Meta-MO was shown to consistently outperform several pretraining and multitask training procedures, providing an average improvement in the success rate of 4.3% on a large-scale bioactivity data set with diverse target variations. We also observed that Meta-MO resulted in the best performing models across fine-tuning sets with only dozens of samples. To the best of our knowledge, this is the first study to apply meta learning to MO tasks. More importantly, such a strategy could be further extended to many low-resource scenarios in real-world drug design.


Oncolytic virus therapy: A new era of cancer treatment at dawn.
Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic virus drug in the USA and Europe. The phase III trial proved that local intralesional injections with T-Vec in advanced malignant melanoma patients can not only suppress the growth of injected tumors but also act systemically and prolong overall survival. Other oncolytic viruses that are closing in on drug approval in North America and Europe include vaccinia virus JX-594 (pexastimogene devacirepvec) for hepatocellular carcinoma, GM-CSF-expressing adenovirus CG0070 for bladder cancer, and Reolysin (pelareorep), a wild-type variant of reovirus, for head and neck cancer. In Japan, a phase II clinical trial of G47∆, a third-generation oncolytic HSV-1, is ongoing in glioblastoma patients. G47∆ was recently designated as a "Sakigake" breakthrough therapy drug in Japan. This new system by the Japanese government should provide G47∆ with priority reviews and a fast-track drug approval by the regulatory authorities. Whereas numerous oncolytic viruses have been subjected to clinical trials, the common feature that is expected to play a major role in prolonging the survival of cancer patients is an induction of specific antitumor immunity in the course of tumor-specific viral replication. It appears that it will not be long before oncolytic virus therapy becomes a standard therapeutic option for all cancer patients.


An Intelligent Classification Method of Multisource Enterprise Financial Data Based on SAS Model.
An enterprise is often faced with a large amount of financial information and data information. It is inefficient to rely solely on manual work, and the accuracy is difficult to guarantee. For the multisource data of corporate finance, it is more difficult for financial personnel to accurately analyze the connections between the data. For the multisource financial data of enterprise, this is also a time-consuming and laborious task for financial personnel. At the same time, it is difficult to find the correlation between multiple sources of data and then formulate financial data that guides the development of the enterprise. With the advancement of intelligent algorithms, an intelligent classification algorithm similar to the SAS model has emerged, which can realize the intelligent classification of enterprise financial multisource data and accurately predict the future development trend, which is extremely beneficial to the development and performance of the enterprise. This article mainly combines the financial intelligence classification model SAS with clustering and decision tree methods to classify the financial multisource information and uses the neural network method to carry out the future development trend of corporate finance. The research results show that the maximum error of enterprise financial classification after using the intelligent classification method is only 3.71% and that the forecast error of the future development trend of enterprise finance is only 1.77%. This is an acceptable error range, and this intelligent classification method is also greatly improving the efficiency of corporate financial management.


Site-Specific Chemical Modification of a Cytokine Mimic for Small Molecule-Based Tumor Targeting.
The targeted delivery of bioactive proteins, such as cytokines, for cancer immunotherapy approaches mostly relies on antibodies or antibody fragments. However, fusion proteins may display low tissue penetration due to a large molecular size. Small molecule ligands with high affinity toward tumor-associated antigens provide a promising alternative for the selective delivery of cytokines to tumor lesions. We developed a one-pot procedure for the site-specific thiazolidine formation between an aldehyde bearing small molecule and the in situ generated N-terminal cysteine of a bioactive protein. Thereby, neoleukin-2/15 (Neo-2/15), a computationally engineered interleukin-2 and -15 mimic, was chemically conjugated to acetazolamide plus, a potent carbonic anhydrase IX (CAIX) ligand. The conjugate retained the biological activity of Neo-2/15 and revealed its ability to accumulate in renal cell carcinoma (SK-RC-52) xenografts upon systemic intravenous administration. The results highlight the potential of small molecule targeting moieties to drive the accumulation of a protein cargo to the respective disease site while conserving the small construct size.


New species of Victoriopisa Karaman Barnard, 1979 (Crustacea: Amphipoda: Eriopisidae) from Vembanad backwaters, Southwest coast of India.
The new species is the third of genus Victoriopisa from Indian waters.The species is described from the Valanthakad mangrove area of Vembanad backwater. Victoriopisa cusatensis sp. nov differs from other species of Victoriopisa by presenting: (1) a characteristic projection at dorsolateral margin of peduncle article 2 of antenna 1in male while smooth in female; (2) broad, triangular lateral cephalic lobe; (3) posteroventral tooth in epimeral plates; (4) presence of lateral and subapical spines in telson (5) smooth palm of gnathopod 2 without any excavations.


Digital analysis of the pharmacological effects of in vitro ischemia on rabbit corpus cavernosum.
Regulation of corporal smooth muscle tone is essential for the initiation of penile erection. In recent years, in vitro isometric tension studies using isolated corpus cavernosal tissue have been used extensively to investigate the mechanisms regulating corporal smooth muscle tone and tension. In the present study, we utilized digital analysis of contractile data generated from investigation of contractile and relaxation responses of isolated rabbit corpus cavenosum to various forms of stimulation. Digital analysis of the contractile and relaxation data allows quantitation of both maximal and mean rates of tension change, and time elapsed to maximal response. Rates of tension changes may provide additional important information regarding cellular events that mediate corporal tone and tension changes. Sexually mature male New Zealand White rabbits were used. Each corpus cavernosum was dissected sharply from the removed penis, then two longitudinal strips were prepared for isometric tension studies and placed in individual baths. Tension was monitored continually using an 8-channel Grass Polygraph. The Grass PolyVIEW system simultaneously converted analog signals to digital information and stored data using a 486 PC computer. Each corporal strip was prestimulated with 300 mumol/l phenylephrine to produce a maximal contraction, then field stimulation (FS), carbachol and nitroprusside were applied consecutively to determine relaxation effects. This procedure was repeated after strips were deprived of glucose and oxygen (in vitro ischemia) for 1 h. The following parameters were quantitated for all responses: maximal tension change; maximal and mean rates of tension change, and time to maximal response. Effects of 1-hour in vitro ischemia on rabbit corporal tissue were as follows: (1) an 85% decrease in contractile response to phenylephrine, and (2) a marked increase in rate of contractile response to phenylephrine. Phenylephrine precontracted strips exhibited: (3) no change in relaxant response to FS; (4) increased relaxant responses to carbachol and nitroprusside; (5) no change in rates of relaxation in response to FS; (6) increased rates of relaxation in response to carbachol and nitroprusside, (7) no change in elapsed time to maximal relaxation in response to FS, and (8) decreased elapsed time to maximal relaxation in response to carbachol and nitroprusside. Digital analysis of the data generated facilitates recording, reviewing and analyzing of in vitro isometric tension studies on rabbit corpus cavernosum. Digital analysis allows quantification of additional parameters that have important implications for determination of mechanisms by which specific pathological processes occur.


Blood levels of 25-hydroxyvitamin D in nephrotic syndrome. Studies in 26 patients.
The blood levels of 25-hydroxyvitamin D (25-HCC) in 26 patients with nephrotic syndrome (proteinuria of 6.5 g/24 h +/- 0.8 SEM) ranged between 1 and 18.6 ng/ml (8.6 +/- 1.0 SEM). This value was significantly lower (P less than 0.01) than that in normal subjects (21.8 +/- 2.3 ng/ml) and patients with chronic renal failure (24.8 +/- 2.3 ng/ml). There was inverse correlation (P less than 0.01) between levels of 25-HCC and magnitude of proteinuria and a direct relation (P less than 0.01) with serum albumin. Reduction in proteinuria was rapidly followed by a rise in blood 25-HCC toward normal. Ionized calcium levels were low in 16 of 26 nephrotic patients irrespective of degree of renal failure. In four of seven nephrotic patients with normal renal function, ionized calcium levels were low and showed an inverse relation with levels of parathyroid hormone. These data show that patients with nephrotic syndrome have low blood levels of 25-HCC probably due to its loss in urine. This derangement is probably responsible for the disorders of calcium metabolism in nephrosis.


APP+ T lymphocytes selectively sorted to endomysial tubes in polymyositis displace NCAM-expressing muscle fibers.
The characteristic pathogenic feature of polymyositis (PM) is muscle invasion by T lymphocytes penetrating the basal lamina and displacing the sarcolemma of normal muscle fibers (T cell invasion of endomysial tubes). Active forward movement of these T cells is indicated by cell extensions interdigitating with the muscle fiber surface. Here we describe for the first time high abundance of Alzheimer amyloid protein precursor (APP) in invasive T cells contacting the border of muscle fibers in PM. These are the sites of muscle fiber displacement. The percentage of APP+ T cells at these sites is significantly higher than in other neuromuscular disorders with inflammatory infiltrates suggesting a specific pathogenic function of these cells in PM. By using a new multiparameter immunofluorescence imaging procedure and confocal laser scanning microscopy, we show that APP+ T cells in PM are invasive front cells that penetrate the basal lamina of the endomysial tube and displace the muscle fiber. Mononuclear cells behind the invasive front are negative for APP or show much lower APP levels. Front T cells either express the CD8-CD4+APP+ or CD8+CD4-APP+ phenotypes, or are CD4+CD8+APP+ T cell chimeras. The highest APP concentration is found at the tip of T cell extensions interdigitating with the fiber surface. Although normal by morphological criteria, the same fibers show intense staining for the regeneration marker NCAM. This reactivity is highest at sites contacted by the APP+ T cells. The findings indicate that APP is specifically upregulated in T cells displacing muscle fibers in PM and suggest that NCAM, which may be abnormally regulated in these fibers, is a candidate molecule for interaction with APP.


Computational fluid dynamics analysis of cold plasma carrier gas injected into a fluid using level set method.
A promising application of plasma medicine is to treat living cells and tissues with cold plasma. In cold plasmas, the fraction of neutrals dominates, so the carrier gas could be considered the main component. In many realistic situations, the treated cells are covered by a fluid. The present paper developed models to determine the temperature of the fluid at the positions of the treated cells. Specifically, the authors developed a three-phase-interaction model which was coupled with heat transfer to examine the injection of the helium carrier gas into water and to investigate both the fluid dynamics and heat transfer output variables, such as temperature, in three phases, i.e., air, helium gas, and water. Our objective was to develop a model to perform complete fluid dynamics and heat transfer computations to determine the temperature at the surface of living cells. Different velocities and plasma temperatures were also investigated using finite element method, and the model was built using the comsol multiphysics software. Using the current model to simulate plasma injection into such systems, the authors were able to investigate the temperature distributions in the domain, as well as the surface and bottom boundary of the medium in which cells were cultured. The temperature variations were computed at small time intervals to analyze the temperature increase in cell targets that could be highly temperature sensisitve. Furthermore, the authors were able to investigate the volume of the plasma plume and its effects on the average temperature of the medium layer/domain. Variables such as temperature and velocity at the cell layer could be computed, and the variations due to different plume sizes could be determined. The current models would be very useful for future design of plasma medicine devices and procedures involving cold plasmas.


Psychometric evaluation of the HIV stigma scale in a Swedish context.
HIV-related stigma has negative consequences for infected people's lives and is a barrier to HIV prevention. Therefore valid and reliable instruments to measure stigma are needed to enable mapping of HIV stigma. This study aimed to evaluate the psychometric properties of the HIV stigma scale in a Swedish context with regard to construct validity, data quality, and reliability. The HIV stigma scale, developed by Berger, Ferrans, and Lashley (2001), was distributed to a cross-sectional sample of people living with HIV in Sweden (n = 194). The psychometric evaluation included exploratory factor analysis together with an analysis of the distribution of scores, convergent validity by correlations between the HIV stigma scale and measures of emotional well-being, and an analysis of missing items and floor and ceiling effects. Reliability was assessed using Cronbach's α. The exploratory factor analysis suggested a four-factor solution, similar to the original scale, with the dimensions personalised stigma, disclosure concerns, negative self-image, and concerns with public attitudes. One item had unacceptably low loadings and was excluded. Correlations between stigma dimensions and emotional well-being were all in the expected direction and ranged between -0.494 and -0.210. The instrument generated data of acceptable quality except for participants who had not disclosed their HIV status to anybody. In line with the original scale, all subscales demonstrated acceptable internal consistency with Cronbach's α 0.87-0.96. A 39-item version of the HIV stigma scale used in a Swedish context showed satisfactory construct validity and reliability. Response alternatives are suggested to be slightly revised for items assuming the disclosure of diagnosis to another person. We recommend that people that have not disclosed should skip all questions belonging to the dimension personalised stigma. Our analysis confirmed construct validity of the instrument even without this dimension.


From social liminality to cultural negotiation: Transformative processes in immigrant mental wellbeing.
The underlying psychosocial processes that produce immigrant mental wellbeing are understudied in anthropology and medicine. This paper provides insights into these processes by describing culturally diverse immigrants' perceptions of mental health and adaptation strategies. Qualitative data were collected from 21 focus groups as part of a large, multidisciplinary, participatory action research project about mental health with five ethnolinguistic groups (Mandarin-speaking Chinese, Polish, Punjabi Sikh, Somali and Spanish-speaking Latin American) in Ontario, Canada. In framing the analysis, transformative concepts are applied to address dimensions of power and culture - social liminality and cultural negotiation - to the ongoing psychosocial processes of coping with mental distress. 'Social liminality' describes how immigrants perceive themselves to be in a psychologically stressful, transitional state, whereas 'cultural negotiation' describes how they actively cope with cultural tensions and respond to mental health challenges. Study findings show that while social liminality and cultural negotiation are stressful, they also have the potential to help individuals adapt by producing a positive synthesis of ideas about mental health in new social and cultural contexts. The study contributes to the shift from problem identification using a biomedical model of mental illness to a more psychosocial and ecological approach that reveals the potential for resolving some mental health problems experienced in immigrant communities. Describing active psychosocial process of adaptation also reinforces the therapeutic and educational value of partnerships between practitioners and clients and immigrant communities and mental health systems.


Macrophages in gastrointestinal homeostasis and inflammation.
Monocyte-derived mononuclear phagocytes, particularly macrophages, are crucial to maintain gastrointestinal homeostasis in the steady state but are also important for protection against certain pathogens. However, when uncontrolled, they can promote immunopathology. Broadly two subsets of macrophages can be considered to perform the vast array of functions to complete these complex tasks: resident macrophages that dominate in the healthy gut and inflammation-elicited (inflammatory) macrophages that derive from circulating monocytes infiltrating inflamed tissue. Here, we discuss the features of resident and inflammatory intestinal macrophages, complexities in identifying and defining these populations and the mechanisms involved in their differentiation. In particular, focus will be placed on describing their unique ontogeny as well as local gastrointestinal signals that instruct specialisation of resident macrophages in healthy tissue. We then explore the very different roles of inflammatory macrophages and describe new data suggesting that they may be educated not only by the gut microenvironment but also by signals they receive during development in the bone marrow. Given the high degree of plasticity of gut macrophages and their multifaceted roles in both healthy and inflamed tissue, understanding the mechanisms controlling their differentiation could inform development of improved therapies for inflammatory diseases such as inflammatory bowel disease (IBD).


Appearance-based trust behaviour is reduced in children with autism spectrum disorder.
Typical individuals make rapid and reliable evaluations of trustworthiness from facial appearances, which can powerfully influence behaviour. However, the same may not be true for children with autism spectrum disorder. Using an economic trust game, the current study revealed that like typical children, children with autism spectrum disorder rationally modulate their trust behaviour based on non-face cues to partner trustworthiness (e.g. reputation information). Critically, however, they are no more likely to place their trust in partners with faces that look trustworthy to them, than those that look untrustworthy. These results cannot be accounted for by any group differences in children's conceptualization of trustworthiness, ability to read trustworthiness from faces or understanding of the experimental paradigm. Instead, they seem to suggest that there may be a selective failure to spontaneously use facial cues to trustworthiness to guide behaviour in an ecologically valid context.


Protocol for Determination of the Persister Subpopulation in Candida Albicans Biofilms.
In contrast to planktonic cultures of the human fungal pathogen Candida albicans, C. albicans biofilms can contain a persister subpopulation that is tolerant to high concentrations of currently used antifungals. In this chapter, the method to determine the persister fraction in a C. albicans biofilm treated with an antifungal compound is described. To this end, a mature biofilm is developed and subsequently treated with a concentration series of the antifungal compound of interest. Upon incubation, the fraction of surviving biofilm cells is determined by plating and plotted versus the used concentrations of the antifungal compound. If a persister subpopulation in the biofilm is present, the dose-dependent killing of the biofilm cells results in a biphasic killing pattern.


Intrascleral haptic fixation for haptic exposure after Yamane technique.
A 55-year-old patient presented with exposure of both the haptics beyond the conjunctiva of the scleral fixated multipiece intraocular lens (IOL). Two diagonally opposite scleral pockets were created, and the exposed haptics was redirected and repositioned aseptically into these pockets to facilitate intrascleral fixation. Herein, we report a simple rescue method for management of exposed haptic after Yamane technique of scleral fixated IOL.


Antioxidant activity of nitro derivative of aspirin against ischemia-reperfusion in hamster cheek pouch microcirculation.
Aspirin that has been chemically combined with a nitric oxide (NO) donor (NCX-4016) has been shown to inhibit cyclooxygenase and prostaglandin generation while maintaining the inhibitory effects of aspirin. The possible role of reactive oxygen species (ROS) in the action of NCX-4016 in ischemia-reperfusion (I/R) has not been studied. Furthermore, we were interested in comparing the effects of a conventional NO donor [2,2'-hydroxynitrosohydrazino-bis-etanamine (DETA/NO)] and NCX-4016 at the microvascular level in the hamster cheek pouch visualized by using an intravital fluorescent microscopy technique. Microvascular injury was assessed by measuring diameter change, the perfused capillary length (PCL), and leukocyte adhesion. Animals were treated with NCX-4016 (100 mg/kg or 30 mg.kg(-1).day(-1) for 5 days po) or DETA-NO (0.5 mg/kg). Mean arterial blood pressure increased slightly but significantly after NCX-4016 treatment. During 5- and 15-min reperfusion, lipid peroxides in the systemic blood increased by 72 and 89% vs. baseline, respectively, and were still higher than in basal conditions after 30-min reperfusion in the I/R group. Pretreatment with NCX-4016 maintained ROS at normal levels; increased arteriolar diameter, blood flow, and PCL; and decreased leukocyte adhesion (P < 0.05). DETA-NO decreased ROS during 30-min reperfusion; however, later there was a significant increase during reperfusion. DETA-NO decreased leukocyte adhesion (P < 0.05) but microvascular permeability increased after 30 min of reperfusion. In conclusion, NCX-4016 attenuates oxidative stress and prevents arteriolar constriction during I/R, whereas DETA-NO increases lipid peroxides in the systemic blood and permeability after reperfusion.


Routine use of color Doppler in fetal heart scanning in a low-risk population.
Objectives. To investigate the detection rate of major fetal heart defects in a low-risk population implementing routine use of color Doppler. Material and Methods. In a prospective observational study, all women undergoing fetal heart scanning (including 6781 routine examinations in the second trimester) during a three-year period were included. First a gray-scale scanning was performed including assessment of the four-chamber view and the great vessels. Thereafter three cross-sectional planes through the fetal thorax were assessed with color Doppler. Results. Thirty-nine fetuses had major heart defects, and 26 (67%) were prenatally detected. In 9/26 (35%) of cases the main ultrasound finding was related to the use of color Doppler. The survival rate of live born children was 91%. Conclusions. Routine use of color Doppler in fetal heart scanning in a low-risk population may be helpful in the detection of major heart defects; however, still severe malformations were missed prenatally.


Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity.
We have previously observed that Sp1, a ubiquitous zinc finger transcription factor, is phosphorylated during terminal differentiation in the whole animal, and this results in decreased DNA binding activity (Leggett, R. W., Armstrong, S. A., Barry, D., and Mueller, C. R. (1995) J. Biol. Chem. 270, 25879-25884). In this study, we demonstrate that casein kinase II (CKII) is able to phosphorylate the C terminus of Sp1 and results in a decrease in DNA binding activity. This suggests that CKII may be responsible for the observed regulation of Sp1. Mutation of a consensus CKII site at amino acid 579, within the second zinc finger, eliminates phosphorylation of this site and the CKII-mediated inhibition of Sp1 binding. Phosphopeptide analysis confirms the presence of a CKII site at Thr-579 as well as additional sites within the C terminus. No gross changes in CKII subunit levels were seen during de-differentiation associated with liver regeneration. The serine/threonine phosphatase PP1 was identified as the endogenous liver nuclear protein able to dephosphorylate Sp1 but again no gross changes in activity were observed in the regenerating liver. Okadaic acid treatment of K562 cells increases Sp1 phosphorylation and inhibits its DNA binding activity suggesting that steady state levels of Sp1 phosphorylation are established by a balance between kinase and phosphatase activities.


Aromatase activity in a rat Leydig cell tumor.
Male Wistar-Furth rats bearing the transplantable LTW(m) Leydig cell tumor have elevated serum estradiol (E2) concentrations. We measured the ability of these tumors to aromatize testosterone (T) to E2 by two methods. First, tumor minces were incubated with [7-3H]T, and the resultant [3H]E2 and [3H]estrone were purified and measured. In addition, tumor cell cultures were incubated with [1 beta-3H]T, and the resultant [3H]H2O was determined as a measure of aromatization. Tumor minces aromatized more actively than normal rat testicular tissue (3.30 +/- 0.15% of the T added was converted to E2 by the tumor vs. 0.30 +/- 0.25% by normal testis). Most of the aromatizing actitivity was localized to the microsomes. Using cell cultures the maximum velocity was 6.1 pmol/h X 5 X 10(5) cells, and the Km was 98 nM. In neither minces nor cell cultures were we able to show stimulation of aromatization with hCG, (Bu)2cAMP, or phorbol esters, although we could show stimulation by these agents in normal testicular cells. We were unable to inhibit the aromatase activity with human beta-endorphin or stimulate it with naloxone. However, we were able to inhibit the aromatase activity with 4-hydroxy-4-androstene-3,17-dione. We conclude that the LTW(m) rat Leydig cell tumor has an active autonomous aromatase system that is not responsive to compounds affecting the adenylate cyclase-cAMP system. It can be inhibited by 4-hydroxy-4-androstene-3,17-dione, a competitive-suicide inhibitor of the aromatase enzyme(s).


Solvent-mediated self-assembly of nanocube superlattices.
Self-organization of colloidal Pt nanocubes into two types of distinct ordered superlattices, simple-cubic and body-centered-tetragonal structures, has been achieved using a home-built setup. Detailed translational and orientational characteristics of these superstructures were determined using a transmission electron microscopy tomographic technique with 3D reconstruction analysis. The formation of these distinct superlattices is the result of a delicate choice of solvent (i.e., aliphatic hexane or aromatic toluene hydrocarbons), which serves as a dispersion medium to fine-tune the relative strengths of ligand-ligand and ligand-solvent interactions during the self-assembly process. This work provides important insights into the effects of ligand-solvent interactions on superlattice formation from nonspherical nanoparticles.


Viability of Salmonella and Listeria monocytogenes in delicatessen salads and hummus as affected by sodium content and storage temperature.
A study was conducted to determine survival and growth behavior of Salmonella and Listeria monocytogenes in commercially prepared mayonnaise-based potato salad, macaroni salad, and coleslaw and in hummus (initial mean pH values were 4.80 to 4.94, 4.18 to 4.31, 3.87, and 4.50 to 4.52, respectively) as affected by sodium concentration (133 to 364, 190 to 336, 146 to 272, and 264 to 728 mg/100 g, respectively) and storage at 4 or 10°C for up to 27 days. Salmonella did not grow in any of the test products. Initial populations (2.02 to 2.38 log CFU/g) decreased in coleslaw to undetectable levels (<1 CFU/25 g) within 13 days and in most formulations of macaroni salad within 20 to 27 days. Salmonella survived in highest numbers in potato salad and hummus. The presence of added sodium in macaroni salad stored at 4°C and hummus stored at 4 or 10°C appeared to protect Salmonella against inactivation. L. monocytogenes, at an initial population of 1.86 to 2.23 log CFU/g, did not grow in test products, but with the exception of coleslaw containing sodium at a concentration used in the standard (control) recipe, this pathogen was detected by direct plating (≥ 1.0 log CFU/g) in all products stored at 4 or 10°C for 27 days. L. monocytogenes populations were significantly (P < 0.05) lower in potato salad and hummus with no added sodium than in test products with added sodium after storage at 4°C. Sodium concentration did not markedly affect aerobic plate counts over the 27-day storage period. Results confirm that the acidic pH of mayonnaise-based salads and hummus is a major factor preventing growth and influencing rates of inactivation of Salmonella and L. monocytogenes. In the absence of added sodium, death of these bacteria may be more rapid. However, in general decreasing or increasing the sodium concentration in selected delicatessen salad and hummus recipes does not markedly affect the behavior of Salmonella and L. monocytogenes when products are stored at 4 or 10°C for up to 27 days.


Endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance in human ovarian cancer cells.
Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins. CDDP, tunicamycin, and BEZ235 acted synergistically to enhance these effects. We also detected lower expression of the ERS-related proteins caspase-3, LC3 II and Beclin 1 in ovarian cancer tissues than adjacent normal tissues. By contrast, expression of Bcl-2 and PI3K/AKT/mTOR pathway-related proteins was higher in ovarian cancer tissues than adjacent normal tissues. Lastly, expression of the ERS-related proteins Beclin 1, caspase-3 and LC3 II was higher in the sensitive group than the resistant group, while expression of Bcl-2, LC3 I, P62 and PI3K/AKT/mTOR pathway-related proteins was decreased. These results show that ERS promotes cell autophagy and apoptosis while reversing chemoresistance in ovarian cancer cells by inhibiting activation of the PI3K/AKT/mTOR signaling pathway.


[COVID-19 : Intensive care management].
The SARS-coronavirus 2 disease initially reported in December 2019 in China (COVID-19) represents a major challenge for intensive care medicine, due to the high number of ICU admission and the prolonged stay for many patients. Up to 5 % of COVID-19 infected patients develop severe acute hypoxemic respiratory failure requiring invasive mechanical ventilation as supportive treatment. Apart from early antiviral and anti-inflammatory treatment, the management of COVID-19 patients is mainly applying protective mechanical ventilation, to support the injured lungs. However recently acquired data and clinical experience suggest that COVID-19-related ARDS presents some specificities that will be summarized in the present article.


Coupled cluster valence bond theory for open-shell systems with application to very long range strong correlation in a polycarbene dimer.
The Coupled Cluster Valence Bond (CCVB) method, previously presented for closed-shell (CS) systems, is extended to open-shell (OS) systems. The theoretical development is based on embedding the basic OS CCVB wavefunction in a fictitious singlet super-system. This approach reveals that the OS CCVB amplitude equations are quite similar to those of CS CCVB, and thus that OS CCVB requires the same level of computational effort as CS CCVB, which is an inexpensive method. We present qualitatively correct CCVB potential energy curves for all low-lying spin states of P2 and Mn2+. CCVB is successfully applied to the low-lying spin states of some model linear polycarbenes, systems that appear to be a hindrance to standard density functionals. We examine an octa-carbene dimer in a side-by-side orientation, which, in the monomer dissociation limit, exhibits maximal strong correlation over the length of the polycarbene.


MacroEvoLution: A New Method for the Rapid Generation of Novel Scaffold-Diverse Macrocyclic Libraries.
Macrocycles are a structural class bearing great promise for future challenges in medicinal chemistry. Nevertheless, there are few flexible approaches for the rapid generation of structurally diverse macrocyclic compound collections. Here, an efficient method for the generation of novel macrocyclic peptide-based scaffolds is reported. The process, named here as "MacroEvoLution", is based on a cyclization screening approach that gives reliable access to novel macrocyclic architectures. Classification of building blocks into specific pools ensures that scaffolds with orthogonally addressable functionalities are generated, which can easily be used for the generation of structurally diverse compound libraries. The method grants rapid access to novel scaffolds with scalable synthesis (multi gram scale) and the introduction of further diversity at a late stage. Despite being developed for peptidic systems, the approach can easily be extended for the synthesis of systems with a decreased peptidic character.


A Survey of Location-Allocation of Points of Dispensing During Public Health Emergencies.
Public health emergencies such as disease outbreaks and bioterrorism attacks require immediate response to ensure the safety and well-being of the affected community and prevent the further spread of infection. The standard method to increase the efficiency of mass dispensing during health emergencies is to create emergency points called points of dispensing (PODs). PODs are sites for distributing medical services such as vaccines or drugs to the affected population within a specific time constraint. These PODs need to be sited in optimal locations and have people (demand points) assigned to them simultaneously; this is known as the location-allocation problem. PODs may need to be selected to serve the entire population (full allocation) or different priority or needs groups (partial allocation). Several previous studies have focused on location problems in different application domains, including healthcare. However, some of these studies focused on healthcare facility location problems without specifying location-allocation problems or the exact domain. This study presents a survey of the PODs location-allocation problem during public health emergencies. This survey aims to review and analyse the existing models for PODs location-allocation during public health emergencies based on full and partial demand points allocation. Moreover, it compares existing models based on their key features, strengths, and limitations. The challenges and future research directions for PODs location-allocation models are also discussed. The results of this survey demonstrated a necessity to develop a variety of techniques to analyse, define and meet the demand of particular groups. It also proved essential that models be developed for different countries, including accounting for variations in population size and density. Moreover, the model constraints, such as those relating to time or prioritizing certain groups, need to be considered in the solution. Finally, additional comparative studies are required to clarify which methods or models are adequate based on predefined criteria.


Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens.
Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top 10 signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here.


[Possible roles of certain special pathogens in male chronic prostatitis / chronic pelvic pain syndrome].
The etiology and pathogenesis of chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) have not been fully understood so far. It is indicated that pathogen infection may play a significant role in the development of this disease. In addition to typical pathogens such as Escherichia coli and Staphylococcus aureus, many special pathogens are difficult to be identified and isolated by conventional methods and are easily ignored in clinical practice. This review summarizes the possible roles of potential pathogens in CP/CPPS, in order to arouse the attention of clinicians and help solve related clinical problems. Clinicians are advised to attend better to the screening and study of abacterial prostatitis with dominant clinical characteristics of chronic inflammation, recurrence or aggravation, especially the cases receiving long-term broad-spectrum antibiotics, suggesting prostatic infection caused by special pathogens.


Mapping the 3D orientation of nanocrystals and nanostructures in human bone: Indications of novel structural features.
Bone is built from collagen fibrils and biomineral nanoparticles. In humans, they are organized in lamellar twisting patterns on the microscale. It has been a central tenet that the biomineral nanoparticles are co-aligned with the bone nanostructure. Here, we reconstruct the three-dimensional orientation in human lamellar bone of both the nanoscale features and the biomineral crystal lattice from small-angle x-ray scattering and wide-angle x-ray scattering, respectively. While most of the investigated regions show well-aligned nanostructure and crystal structure, consistent with current bone models, we report a localized difference in orientation distribution between the nanostructure and the biomineral crystals in specific bands. Our results show a robust and systematic, but localized, variation in the alignment of the two signals, which can be interpreted as either an additional mineral fraction in bone, a preferentially aligned extrafibrillar fraction, or the result of transverse stacking of mineral particles over several fibrils.


Nutritional and metabolic support in patients with amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is the most common form of progressive motor neuron disease and the most devastating neurodegenerative disorder. ALS is characterized by progressive paralysis and respiratory failure leading to death within 3 to 5 years after its onset. Protein-energy malnutrition is a frequent finding in ALS. The pathogenesis of protein-energy malnutrition in ALS is multifactorial. Muscle atrophy, hypophagia, dysphagia, and hypermetabolism play a role in determining the deterioration of nutritional status. A multidisciplinary approach is crucial to set an appropriate plan for metabolic and nutritional support in ALS. Nutritional management incorporates a continuous assessment and implementation of dietary modifications throughout the duration of the disease. The nutritional and metabolic approaches to ALS should start when the diagnosis of ALS is made and should become an integral part of the continuous care to the patient, including nutritional surveillance, dietary counseling, management of dysphagia, and enteral nutrition when needed. Parenteral nutrition is rarely indicated. Standard polymeric enteral formulas are routinely used, usually providing 25 to 30 kcal/kg and protein 0.8 to 1.2 g /kg per day. The use of fiber-enriched formulas may help prevent constipation. However, considering the complex metabolic abnormalities of ALS, standard and/or fiber-enriched formulas might not be sufficient to achieve optimal metabolic and nutritional support. Based on the most recent clinical and experimental evidence, it is tempting to hypothesize that personalized nutritional support including specific nutritional substrates could act on disease progression and improve the quality of life and the response to the few and yet scarcely effective, currently available pharmacologic therapies.


Parasitism and Suitability of Different Egg Ages of the Leguminivora glycinivorella (Lepidoptera: Tortricidae) for Three Indigenous Trichogramma Species.
Pod borers are economically important soybean pests in temperate and tropical regions. However, the biological control of these pests using their natural insect enemies has been poorly studied to date. Indigenous natural populations of three Trichogramma (Hymenoptera: Trichogrammatidae) species, Trichogramma chilonis Ishii, Trichogramma ostriniae Pang & Chen, and Trichogramma leucaniae Pang & Chen, were collected from Leguminivora glycinivorella (Matsumura) (Lepidoptera: Tortricidae) eggs in soybean fields in China. In this study, we compare the parasitic capacities and suitabilities of three indigenous Trichogramma species on L. glycinivorella eggs at various ages. Host eggs of all ages were accepted by T. chilonis, T. ostriniae, and T. leucaniae. T. chilonis tended to parasitize 0-2-d-old eggs more than 3-4-d-old eggs. There were no significant differences in parasitism between the 0-2-d-old eggs and the 1-4-d-old eggs for T. ostriniae and T. leucaniae. For eggs at various ages, T. chilonis parasitized the smallest number of eggs, while T. leucaniae and T. ostriniae exhibited similar parasitic capacities. With 0-d-old host eggs, T. ostriniae developed over the longest time period (8.7 d), and T. leucaniae produced the most female progeny (87.9%). Both T. leucaniae and T. ostriniae had similar developmental times, survival rates and percentages of female progeny with 1-3-d-old eggs. These results show that T. leucaniae can parasitize host eggs at varying ages with the best development and suggest that it may be a valuable biological control agent for soybean pod borers.


Dorsal horn volume loss and pain pathway changes in Cavalier King Charles Spaniels with syringomyelia, signs of pain, and phantom scratching.
Central neuropathic pain is a core clinical sign of syringomyelia in humans and Cavalier King Charles Spaniel (CKCS) dogs. This histopathological study used spinal cords from CKCS dogs with syringomyelia to investigate the following conditions: (1) whether specific structural cervical spinal cord entities involved in nociception were affected by loss of neuroparenchyma or other pathological changes in CKCS dogs with pain-related behaviour and phantom scratching, (2) whether pain-related behaviour or phantom scratching correlated with loss of a specific anatomical entity or upregulation of glia cells, and (3) whether syringomyelia-related lesions affected specific functional spinal cord units of nociception. Spinal cord segments C1-C8 from CKCS dogs with magnetic resonance imaging-confirmed syringomyelia and clinical signs of pain and phantom scratching (n = 8) were compared with those from CKCS dogs without syringomyelia (n = 4). Dogs with unilateral scratching (n = 7) had a volume loss ( P = 0.043) of the dorsal horn laminae I-III in the ipsilateral side compared with the contralateral dorsal horn. A clear pattern of ipsilateral changes in the dorsal root entry zone characterised by deafferentation and reorganization of first-order axons into deeper laminae was found in cases with lateralised scratching. Significant changes in cell number density were not found for astrocytes or microglia, suggesting that the dogs represented cases of end-stage syringomyelia and thus could not reveal astrogliosis and microgliosis, which may be involved in the early phases of syrinx development and phantom scratching. The present relationship between clinical findings and dorsal horn and pain pathway pathology in CKCS dogs suggests that these dogs may be of interest as a supplement to experimental model pain research.


Fimasartan: A New Angiotensin Receptor Blocker.
Fimasartan is the ninth, and most recent, angiotensin II receptor antagonist approved as an antihypertensive agent. Fimasartan, a pyrimidin-4(3H)-one derivative of losartan with the imidazole ring replaced, which enables higher potency and longer duration than losartan. Fecal elimination and biliary excretion are the predominant elimination pathways of fimasartan and the urinary excretion was found to be less than 3 % 24 h after administration. Fimasartan is primarily catabolized by cytochrome P450 isoform 3A and no significant drug interaction was observed when used in combination with hydrochlorothiazide, amlodipine, warfarin, or digoxin. Fimasartan at a dosage range of 60-120 mg once daily showed an antihypertensive effect over 24 h. In a large, population-based observational study, fimasartan showed an excellent safety profile. Anti-inflammatory and organ-protecting effects of fimasartan have been shown in various preclinical studies, including aortic balloon injury, myocardial infarct ischemia/reperfusion, doxorubicin cardiotoxicity, and ischemic stroke models.


CLADOGRAM VERSATILITY: EVOLUTION AND BIOGEOGRAPHY OF ACANTHUROID FISHES.
A highly corroborated cladogram of acanthuroid fishes is used to explore several aspects of the biogeographic and microevolutionary events during the evolution of the group. Five events in acanthuroid evolution are documented here, which demonstrate not only the power of cladograms to provide adaptational hypotheses, but also how they can be used to frame significant questions for further research. Biogeographic analysis indicates that basal cladogenesis of the acanthuroids must have occurred prior to the Eocene (50-55 mya), because at least the basal lineages of the Acanthuridae, one of the last acanthuroid families to have evolved, were present at that time. In addition, optimization of current distributions suggests that the ancestors of the Acanthurinae, of the Acanthuridae, and of the Acanthuroidei each had an Indo-West Pacific distribution. Subsequent dispersion and/or speciation in one or more of these lineages may have been related either to the closure of the Tethys (ca 20 mya), or to colonization from the Pacific of the Caribbean/Atlantic prior to the formation of the Panamanian isthmus. Hypotheses about adaptation in acanthuroids begin with a discussion of several cases of dietary plasticity. The importance of information from fossils is illustrated in an investigation of predorsal bone evolution. Morphologically divergent and convergent tendencies in the modification of the pelvic fins concludes the examples. The morphologically most derived genus, Ctenochaetus, seems the least active taxon evolutionarily in the characters investigated.


Role of voltage dependent calcium channels and cholinergic receptors in the convulsant action of BAY k-8644.
The study was designed to investigate the effects of administration of cholinomimetic agents and nifedipine on seizures induced by BAY k-8644 in rats. Injection of pilocarpine (3 mg/kg) increased seizures induced by BAY k-8644 (2 mg/kg). Administration of nifedipine (10 mg/kg) did not affect the convulsions and mortality elicited by coadministration of BAY k-8644 and pilocarpine. However, the facilitating effect of pilocarpine on BAY k-8644-induced seizures was fully prevented by pretreatment of rats with a cholinergic antagonist atropine (5 mg/kg). No similar effects were observed after injection of another cholinomimetic agent physostigmine (0.3 mg/kg). This finding implies, that facilitation of convulsant action of BAY k-8644 by pilocarpine may be related to activity of cholinergic system, but not strictly to activity of voltage dependent calcium channels.


Prognostic Role of microRNA-205 in Human Gynecological Cancer: A Meta-Analysis of Fourteen Studies.
Several studies have revealed that miR-205 plays important roles in the development of gynecological cancers and thus may serve as a potential prognostic biomarker, but the current conclusions remain controversial. Therefore, the goal of this study was to explore the prognostic significance and functional mechanisms of miR-205 based on a meta-analysis and bioinformatics investigation. A total of 14 published studies containing 5835 patients were enrolled by searching the PubMed, EMBASE, and Cochrane library databases, 13 (14 datasets) and 5 (6 datasets) of which evaluated the correlations between the expression level of miR-205 and overall survival (OS) or disease-free survival (DFS)/disease-specific survival (DSS)/progression-free survival (PFS)/distant metastasis-free survival (DMFS), respectively. Furthermore, the use of online Kaplan-Meier plotter database analysis supplemented another seven results for OS. Then, a meta-analysis using these 21 and 6 datasets was performed. As a result, the overall analysis failed to demonstrate any significant associations between miR-205 expression and OS (p = 0.267) or DSS/DFS/DMFS/PFS (p = 0.457), but the subgroup analysis suggested that elevated miR-205 predicted a reduced OS for breast cancer (BC) patients (hazard ratio [HR] = 0.84, 95% confidence interval [CI] = 0.72-0.98; p = 0.022), while higher miR-205 was associated with a poor DSS for endometrial cancer (EC) patients (HR = 2.19, 95% CI = 1.45-3.32; p < 0.001). Function prediction analysis indicated that miR-205 may be involved in BC by negatively influencing hub genes, SMARCA5 and SIAH1, whereas miR-205 may participate in EC by negatively modulating BMPR1B because of the presence of interactions of miR-205 with them at 3'-untranslated region and their opposite prognosis outcomes with miR-205. In conclusion, our findings suggest miR-205 may be a promising prognostic biomarker and therapeutic target for BC and EC patients.


Dietary diversity and possible sarcopenia among older people in China: a nationwide population-based study.
Sarcopenia is a common geriatric disease. Many dietary factors may contribute to the development of sarcopenia. Few studies have been conducted on dietary diversity and sarcopenia in Chinese older adults. Among a nationwide sample, the objective of this study is to assess the association between the dietary diversity score (DDS) and the prevalence of possible sarcopenia. We considered the different patterns of dietary diversity in relation to possible sarcopenia. We conducted this analysis utilizing the cross-sectional data from the 2012, 2014, and 2018 waves of the Chinese longitudinal healthy longevity survey (CLHLS). A standard developed by the Asian Working Group for Sarcopenia 2019 (AWGS2019) was used to assess the possibility of sarcopenia. On the basis of the DDS generated by previous studies, we have constructed four new indicators as follows: total diet, animal-based diet, plant-based diet, and plant-based diet without the consumption of legume products and nuts. We used the generalized estimation equation (GEE) model to evaluate the associations between the DDS of the total diet, animal-based diet, plant-based diet, and plant-based diet without the intake of legume products and nuts and possible sarcopenia. These associations were statistically adjusted for a variety of potential confounders. Sensitivity analysis was performed by excluding some participants who were long-term bedridden, had Alzheimer's disease, or were terminally ill. The analysis included 6,624 participants (mean age 83.4 years at baseline). In our study, we found that participants with a higher DDS of the total diet (OR = 0.62; 95% CI: 0.51-0.77), animal-based diet (OR = 0.62; 95% CI: 0.49-0.79), and plant-based diet (OR = 0.64;95% CI: 0.51-0.80) were at a lower risk of developing sarcopenia. In sensitivity analyses, the associations remained unchanged. Taking a diversified diet, including animal foods, may reduce the risk of developing sarcopenia. According to the findings of this study, adopting a diversified diet might reduce the risk of sarcopenia for older adults.


Salient Object Detection with Lossless Feature Reflection and Weighted Structural Loss.
Salient object detection (SOD), which aims to identify and locate the most salient pixels or regions in images, has been attracting more and more interest due to its various realworld applications. However, this vision task is quite challenging, especially under complex image scenes. Inspired by the intrinsic reflection of natural images, in this paper we propose a novel feature learning framework for large-scale salient object detection. Specifically, we design a symmetrical fully convolutional network (SFCN) to effectively learn complementary saliency features under the guidance of lossless feature reflection. The location information, together with contextual and semantic information, of salient objects are jointly utilized to supervise the proposed network for more accurate saliency predictions. In addition, to overcome the blurry boundary problem, we propose a new weighted structural loss function to ensure clear object boundaries and spatially consistent saliency. The coarse prediction results are effectively refined by these structural information for performance improvements. Extensive experiments on seven saliency detection datasets demonstrate that our approach achieves consistently superior performance and outperforms the very recent state-of-the-art methods with a large margin.


[Personalized medicine, privatized medicine? legal and public health stakes].
Personalized medicine is booming. It tends to provide a medical management "tailored" for groups of patients, or for one unique patient, but also to identify risk groups to develop public health strategies. In this context, some radicalization phenomenon can emerge, leading to not only personalized medicine but also privatized medicine, which can lead to a capture of the medical public resource. If the "privatization" of medicine is not limited to producing adverse effects, several potentially destabilizing phenomena for patients still remain. First, some objective factors, like the adjustment of scientific prerequisites, are emerging from personalized medicine practices (clinical trial, public health policy) and are interfering with the medical doctor/patient relationship. Another risk emerges for patients concomitantly to their demand for controlling their own health, in terms of patients' security although these risks are not clearly identified and not effectively communicated. These practices, related to a privatized medicine, develop within the healthcare system but also outside, and the government and legislators will have to take into account these new dimensions in drafting their future regulations and policies.


Cloning and characterization of the gene for amylosucrase from Neisseria polysaccharea: production of a linear alpha-1,4-glucan.
The gene for the amylosucrase from Neisseria polysaccharea (ATCC 43768) was cloned by use of a functional expression system in Escherichia coli XL1-Blue. The deduced amino acid sequence of the protein has homology to the sequences of the alpha-amylase class of enzymes, with the highest similarities being found to the sequences of the trehalose synthase from Pimelobacter sp. strain R48 (17) and amylomaltase from Thermotoga maritima (11). However, the regions of highest homology within the alpha-amylase class of enzymes, which are essential for the catalytic activity, are only scarcely found in the sequence of amylosucrase. By using the enzyme isolated from culture supernatants of transformed E. coli cells, it is possible to synthesize linear alpha-1,4-glucans from sucrose, indicating that the enzyme is not capable of producing alpha-1,6-glycosidic linkages on its own.


Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine.
Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-α, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA.


Allergic contact dermatitis from ethyl chloride and sensitization to dichlorodifluoromethane (CFC 12).
Despite the widespread use of ethyl chloride as a local anesthetic and chlorofluorocarbons as propellants in medical and cosmetic aerosols, contact allergy to these 2 gases is rare. In a 30-year-old woman, an unusual itchy dermatitis appeared at all skin sites where a medical aerosol containing ethyl chloride had been briefly applied. Subsequent re-exposure to the spray and patch tests revealed contact sensitization to ethyl chloride and dichlorodifluoromethane (CFC 12). Histologic and immunohistochemical examinations of the test reaction were consistent with a T-cell-mediated allergic reaction. The low incidence of contact allergy to ethyl chloride and chlorofluorocarbons may be due to the rapid evaporation of these volatile gases, thus preventing intense and prolonged contact with the skin and consequently contact sensitization. A modified patch test procedure using perforated plastic chambers to allow gas evaporation is necessary to test volatile agents.


Tissue engineered scaffolds for corneal endothelial regeneration: a material's perspective.
Currently, the treatment of corneal diseases caused by damage to the corneal endothelium requires a donor cornea. Because of their limited availability (1 donor cornea for 70 patients in need), researchers are investigating alternative approaches that are independent of donor tissue. One of them includes the development of a tissue engineered scaffold onto which corneal endothelial cells are seeded. In order to function as a suitable substrate, some of its essential properties including thickness, permeability, transparency and mechanical strength should meet certain demands. Additionally, the membrane should be biocompatible and allow the formation of a functional endothelium on the surface. Many materials have already been investigated in this regard including natural, semi-synthetic and synthetic polymers. In the current review, we present an overview of their characteristics and provide a critical view on the methods exploited for material characterization. Next, also the suitability of scaffolds to serve their purpose is discussed along with an overview of natural tissues (e.g. amniotic membrane and lens capsule) previously investigated for this application. Eventually, we propose a consistent approach to be exploited ideally for membrane characterization in future research. This will allow a scientifically sound comparison of materials and membranes investigated by different research groups, hence benefitting research towards the creation of a suitable/optimal tissue engineered endothelial graft.


Estimating perimenstrual distress: a comparison of two methods.
The purpose of this study was to compare two methods of measuring menstrual distress. Seventy-three women, 18 to 35 years of age, selected from lower-middle to upper-middle income neighborhoods kept a daily diary for a two-month period. Following completion of the diary, the women responded to the Moos Menstrual Distress Questionnaire (MDQ) with reference to their last menstrual period. Estimates for all symptoms on the MDQ exceeded those in the diary. The greatest discrepancies between the two methods were found for water retention and negative affect symptoms. Concordance of perimenstrual symptom reporting across the two measures was statistically significant only for menstrual cramps, K = .248, p less than .021, and premenstrual backache, K = .203, p less than .036). Although these results suggest that estimates of dysmenorrhea symptoms are least affected by the data collection method, they are consistent with the hypothesized joint effects of menstrual stereotypes and recall bias on retrospective symptom reports; these sources of bias should be considered in future menstrual, distress research.


[A case of Foix-Chavany-Marie syndrome and crossed aphasia after right corona radiata infarction with history of left hemispheric infarction].
Foix-Chavany-Marie syndrome (FCMS) is a syndrome that presents facio-pharyngo-glosso-masticatory diplegia with automatic voluntary dissociation. Its most common etiology is stroke in the regions of bilateral opercula. We described a 75-year-old woman with FCMS and crossed aphasia. She had cerebral infarction of left middle cerebral artery territory 23 years before. At that time she had transient right hemiparesis, but no aphasia. This time, she suddenly became mute and was brought to our hospital. Neurological examination revealed severe weakness in her bilateral lower face, pharynx, tongue, and sternocleidomastoideus. She had no weakness of limbs. Her listening comprehension was moderately disturbed and handwriting was paragraphic. Her emotional facial movement was maintained despite of disturbed volitional facial movement. CT scan disclosed fresh infarction at the right corona radiata and old infarction at the left middle cerebral artery territory. In this patient, lesions at the left operculum and right corona radiata with the preserved right operculum gave rise to FCMS. This implies following possibilities: 1) the corticobulbar tract and corticospinal tract run separately at the corona radiata, 2) volitional and emotional tracts of facial movement run separately at the corona radiata. It was demonstrated that FCMS is not always caused by bilateral operculum lesions. Our patient did not show aphasia after the first stroke including left language area, but became severely aphasic after the right corona radiata infarction. Simultaneous occurrence of FCMS and aphasia after corona radiata lesion suggested that the corticobulbar tract and a tract that conducts linguistic information are running adjacently in the corona radiata. Our case suggested that restricted corona radiata lesion may cause severe subcortical aphasia and in case of additional contralateral corticobulbar tract lesion, severe dysarthria may occur.


Pancreatic peptide YY in alloxan diabetic mice.
Peptide YY (PYY) immunoreactive material was detected in the splenic and duodenal portions of the adult mouse pancreas, using immunocytochemical and immunochemical methods. Cells displaying PYY immunoreactivity generally occurred at the islet periphery. Double immunostaining enabled localization of PYY to a major subpopulation of the glucagon cells and to subpopulations of the pancreatic polypeptide (PP) cells and the somatostatin cells. In contrast, no PYY immunoreactivity occurred in the insulin cells. In alloxan-treated hyperglycemic mice, PYY immunoreactive cells were increased in number and distributed throughout the islets, in parallel with the glucagon, PP, and somatostatin cells. Analysis by radioimmunoassay indicated a significant increase in the concentration of pancreatic PYY after alloxan treatment in the splenic portion of the pancreas, but not in the duodenal portion. Pancreatic glucagon concentrations were not significantly changed. It is concluded that the islet content of PYY increases in alloxan diabetes, which might contribute to the accompanying alterations in islet function.


Immune Checkpoint in Glioblastoma: Promising and Challenging.
Glioblastoma (GBM) is a severe malignant brain cancer with poor overall survival. Conventional intervention remains dismal to prevent recurrence and deterioration of GBM cell. Recent years have witnessed exciting breakthroughs in novel immune strategies, especially checkpoint inhibitors, some of which have become adjuvant setting after standard of care in melanoma. Several clinical trials of checkpoint inhibitors are ongoing in glioblastoma and other brain carcinomas. Plus, synergistic combinations of checkpoint inhibitors with conventional therapy strategies-radiotherapy, temozolomide, bevacizumab, and corticosteroids are now being exploited and applied in clinical settings. This review highlights the recent developments of checkpoints in GBM immunotherapy to provide a brief and comprehensive review of current treatment options. Furthermore, we will discuss challenges remained, such as unique immune system of central nervous system (CNS), immune-related toxicities, synergies, and adverse interactions of combination therapies.


Predicting the Adult Clinical and Academic Outcomes in Boys With ADHD: A 7- to 10-Year Follow-Up Study in China.
Background: Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood and causes adverse effects on social functioning. The present study aimed to widely investigate the predictors, particularly childhood intelligence quotient (IQ) and family environment factors, on adult clinical and academic outcomes in boys with ADHD. Methods: A total of 101 boys with ADHD in a Chinese Han ADHD cohort were followed up 7-10 years later. Baseline ADHD symptoms were evaluated using the parent version of the ADHD Rating Scale-IV (ADHD-RS-IV) and the Chinese version of the Conners' Parent Rating Scale-Revised (CPRS-48). The intelligence of the child was tested by the China-Wechsler Intelligence Scale for Children (C-WISC), and family function was assessed by the Family Environment Scale-Chinese Edition (FES-CV). Adult ADHD persistence was defined using DSM-IV criteria for ADHD, and academic outcome fell into two categories: higher academic level group (studying in senior middle school or above) and lower academic level group (studying in vocational secondary schools or below). Results: Stepwise multiple logistic regression analysis revealed that the father's character, impulsive-hyperactive index as measured by the CPRS-48, and intellectual-cultural index as measured by the FES-CV independently predicted clinical outcomes in adults, with an AUC of 0.770 (p < 0.001, 95% CI = 0.678-0.863). The corresponding sensitivity and specificity were 0.743 and 0.727, respectively. The father's education level, family economic level, and verbal IQ (VIQ) on the C-WISC independently predicted adult academic outcomes, with an AUC of 0.870 (p < 0.001, 95% CI = 0.796-0.944). The corresponding sensitivity and specificity were 0.813 and 0.783, respectively. Conclusion: Initial ADHD symptom severity and IQ, father's character and education level, and family atmosphere and function affect adult clinical and academic outcomes. Addressing these areas early may help to improve the prognosis of ADHD into adulthood.


Development of a functional human induced pluripotent stem cell-derived nociceptor MEA system as a pain model for analgesic drug testing.
The control of severe or chronic pain has relied heavily on opioids and opioid abuse and addiction have recently become a major global health crisis. Therefore, it is imperative to develop new pain therapeutics which have comparable efficacy for pain suppression but lack of the harmful effects of opioids. Due to the nature of pain, any in vivo experiment is undesired even in animals. Recent developments in stem cell technology has enabled the differentiation of nociceptors from human induced pluripotent stem cells. This study sought to establish an in vitro functional induced pluripotent stem cells-derived nociceptor culture system integrated with microelectrode arrays for nociceptive drug testing. Nociceptors were differentiated from induced pluripotent stem cells utilizing a modified protocol and a medium was designed to ensure prolonged and stable nociceptor culture. These neurons expressed nociceptor markers as characterized by immunocytochemistry and responded to the exogenous toxin capsaicin and the endogenous neural modulator ATP, as demonstrated with patch clamp electrophysiology. These cells were also integrated with microelectrode arrays for analgesic drug testing to demonstrate their utilization in the preclinical drug screening process. The neural activity was induced by ATP to mimic clinically relevant pathological pain and then the analgesics Lidocaine and the opioid DAMGO were tested individually and both induced immediate silencing of the nociceptive activity. This human-based functional nociceptive system provides a valuable platform for investigating pathological pain and for evaluating effective analgesics in the search of opioid substitutes.


Müller and macrophage-like cell interactions in an organotypic culture of porcine neuroretina.
To analyze the in vitro Müller cell modifications in an organotypic culture of porcine neuroretina in response to the addition of a blood-derived mononuclear fraction (MNF; monocytes and lymphocytes) as a source of macrophages. Control and MNF-stimulated neuroretinal explants were examined at 3, 6, and 9 days of culture. Specimens were processed for epoxy-resin embedding and cryosectioning. Light and immunofluorescence microscopy were performed, using toluidine blue staining and antibodies against glial fibrillary acidic protein (GFAP), as a reactive gliosis marker, and cellular retinaldehyde-binding protein (CRALBP), as a Müller cell marker. Compared to controls, explants cocultured with MNF displayed increased cellular disorganization and larger tissue invasion of the subretinal space at 9 days of culture. Immunostaining of the MNF-treated explants revealed evidence of more reactive gliosis and greater number of GFAP-immunoreactive Müller cells that had increased width and processes extending into the subretinal space and forming a multilayer tissue. Astrocytes also responded to the MNF addition, producing extensions that invaded the neuroretinal outer layers. Addition of MNF stimulates modifications of Müller cells, producing a wider intraretinal reactive gliosis and tissue proliferation at the subretinal space (outer layers of the retina). These findings emphasize the role of macrophage-like cells in the production of changes in retinal structure observed after retinal detachment in humans.


Regulatory Roles of Sortilin and SorLA in Immune-Related Processes.
Sortilin, also known as Neurotensin Receptor-3, and the sorting-related receptor with type-A repeats (SorLA) are both members of the Vps10p domain receptor family. Initially identified in CNS cells, they are expressed in various other cell types where they exert multiple functions. Although mostly studied for its involvement in Alzheimer's disease, SorLA has recently been shown to be implicated in immune response by regulating IL-6-mediated signaling, as well as driving monocyte migration. Sortilin has been shown to act as a receptor, as a co-receptor and as an intra- and extracellular trafficking regulator. In the last two decades, deregulation of sortilin has been demonstrated to be involved in many human pathophysiologies, including neurodegenerative disorders (Alzheimer and Parkinson diseases), type 2 diabetes and obesity, cancer, and cardiovascular pathologies such as atherosclerosis. Several studies highlighted different functions of sortilin in the immune system, notably in microglia, pro-inflammatory cytokine regulation, phagosome fusion and pathogen clearance. In this review, we will analyze the multiple roles of sortilin and SorLA in the human immune system and how their deregulation may be involved in disease development.


Prevention of wound infection in elective colorectal surgery by local application of a gentamicin-containing collagen sponge.
Preoperative antibiotic prophylaxis is known to significantly reduce the incidence of postoperative wound infection in elective colorectal surgery, and is a recognized part of surgical management. Antibiotics are usually given systemically or orally, or by a combination of the two routes. Local antibiotic delivery to the wound site using an implanted, reabsorbable, gentamicin-containing collagen sponge is a novel concept. We compared postoperative wound infection rates in 221 colorectal surgery patients randomized to receive systemic gentamicin/metronidazole with (Group I, n = 107) or without (Group II, n = 114) the gentamicin-collagen sponge. The two patient groups were identical on the basis of demographics and operations undergone. The postoperative wound infection rate was significantly lower in Group I patients than Group II 5.6% (6/107) and 18.4% (21/ 114), respectively (p < 0.01). The mean duration of hospital stay was 13.8 days in Group I and 16.3 days in Group II, which did not represent a statistically significant difference. The gentamicin collagen sponge was well tolerated and no adverse events were reported that were attributable to its use. This new method for delivering gentamicin directly to the operative site may represent a significant method for reducing postoperative wound infection rates to levels lower than those currently achieved with systemic antibiotics alone.


Withdrawing and withholding treatment in intensive care. Part 3. Practical aspects.
A major goal of intensive care units should be to provide an environment in which death may occur with dignity if cure is impossible. The key issues in providing such an environment are the establishment of consensus that cure is impossible, and the provision of a resource person who has been a major participant in efforts to cure the patient. This person leads discussion with the patient or relatives, seeking concurrence rather than permission when the withdrawing or withholding of care is under consideration. We present problems which may arise in facilitating a dignified demise, and a practical approach to these problems.


Evidence-Based Medicine for Ballistic Maxillofacial Trauma.
Ballistic trauma is a serious health issue with significant costs to physical, psychosocial, economic, and societal well-being. It may be caused from firearms, explosive devices, or any other projectile forces, and is characterized by severe tissue loss and evolving tissue devitalization. This review covers mechanism, diagnosis, and management of ballistic maxillofacial trauma, specifically. Initial evaluation includes stabilization of airway, bleeding, and circulation, followed by assessment of other injuries. The overall degree of tissue damage is determined by intrinsic patient factors and extrinsic projectile factors. Management of ballistic injuries has shifted toward advocation for early operative repair with the advent of antibiotics and advanced techniques in maxillofacial reconstruction. Appropriate timing and method of reconstruction should be carefully selected on a case-by-case basis. While ballistic trauma research is limited to studies biased by institutional practices, areas for further study identified from current literature include guidelines directing timing of reconstructive surgery; thresholds for free tissue transfer; handling of retained projectiles; incidence of surgical complications; and clinical outcomes for computer-aided surgical repair of these highly destructive injuries.


A biosphere assessment of high-level radioactive waste disposal in Sweden.
Licence applications to build a repository for the disposal of Swedish spent nuclear fuel have been lodged, underpinned by myriad reports and several broader reviews. This paper sketches out the technical and administrative aspects and highlights a recent review of the biosphere effects of a potential release from the repository. A comprehensive database and an understanding of major fluxes and pools of water and organic matter in the landscape let one envisage the future by looking at older parts of the site. Thus, today's biosphere is used as a natural analogue of possible future landscapes. It is concluded that the planned repository can meet the safety criteria and will have no detectable radiological impact on plants and animals. This paper also briefly describes biosphere work undertaken after the review. The multidisciplinary approach used is relevant in a much wider context and may prove beneficial across many environmental contexts.


Photochemical Nickel-Catalyzed Reductive Migratory Cross-Coupling of Alkyl Bromides with Aryl Bromides.
A novel method to access 1,1-diarylalkanes from readily available, nonactivated alkyl bromides and aryl bromides via visible-light-driven nickel and iridium dual catalysis, wherein diisopropylamine ( iPr2NH) is used as the terminal stoichiometric reductant, is reported. Both primary and secondary alkyl bromides can be successfully transformed into the migratory benzylic arylation products with good selectivity. Additionally, this method showcases tolerance toward a wide array of functional groups and the presence of bases.


Effect of different implant placement depths on crestal bone levels and soft tissue behavior: a randomized clinical trial.
This randomized clinical trial analyzed crestal bone changes and soft tissue dimensions surrounding implants with an internal tapered connection placed in the mandible anterior region at different depths (equicrestal and subcrestal). Eleven edentulous patients (five implants per patient) were randomly divided in a split-mouth design: G1, 28 equicrestal implants; and G2, 27 subcrestal implants. All implants were immediately loaded. Correlation between keratinized tissue width (KTW) and vertical mucosa thickness (MT) with soft tissue recession was analyzed. Intraoral radiographs were used to evaluate crestal bone changes. Patients were assessed immediately, 4-, and 8-months after implant placement. Rank-based ANOVA-type statistical test was used for comparison between groups (α = 0.05). Fifty-five implants (G1 = 28 and G2 = 27) were assessed in 11 patients. Implant survival rate was 100% for both groups. Both tested implant placement depths presented similar crestal bone loss (P > 0.05). Significant crestal bone loss for each group was found in the different measurement times (T4 and T8) (P < 0.05). Implant placement depths, KTW, and vertical MT had no effect on soft tissue recession (P > 0.05). Different implant placement depths do not influence crestal bone changes. Soft tissue behavior is not influenced by different implant placement depths or by the amount of keratinized tissue.


Incorporating mutations and bone marrow fibrosis into the revised international prognostic scoring system in myelodysplastic syndromes.
The independent prognostic significance of bone marrow fibrosis (BMF) in myelodysplastic syndromes (MDS) is challenged under currently molecular prognostic models. In this study, the clinical and genetic data from 438 MDS patients were analyzed retrospectively. The patients were randomly divided into training (n = 306) and validation (n = 132) cohorts. The independent significant prognostic factors included age, IPSS-R, BMF, TP53 and U2AF1. Using their weighted coefficients, we developed a simplified prognostic system. Four risk groups were produced: low, intermediate, high and very high. The new model yielded more clearly separated survival curves than the IPSS-R. In addition, our model achieved higher C-indexes (0.61 in the training cohort and 0.63 in the validation cohort) than the IPSS-RM model (0.59 and 0.58) and IPSS-R (0.57 and 0.56). In conclusion, BMF was an independent significant prognostic factor for MDS, and adding BMF into the IPSS-R improved its predictive capability.


Loss of mitochondrial protein CHCHD10 in skeletal muscle causes neuromuscular junction impairment.
The neuromuscular junction (NMJ) is a synapse between motoneurons and skeletal muscles to control motor behavior. Acetylcholine receptors (AChRs) are restricted at the synaptic region for proper neurotransmission. Mutations in the mitochondrial CHCHD10 protein have been identified in multiple neuromuscular disorders; however, the physiological roles of CHCHD10 at NMJs remain elusive. Here, we report that CHCHD10 is highly expressed at the postsynapse of NMJs in skeletal muscles. Muscle conditional knockout CHCHD10 mice showed motor defects, abnormal neuromuscular transmission and NMJ structure. Mechanistically, we found that mitochondrial CHCHD10 is required for ATP production, which facilitates AChR expression and promotes agrin-induced AChR clustering. Importantly, ATP could effectively rescue the reduction of AChR clusters in the CHCHD10-ablated muscles. Our study elucidates a novel physiological role of CHCHD10 at the peripheral synapse. It suggests that mitochondria dysfunction contributes to neuromuscular pathogenesis.


Sudden appearance of anti-protein IgG1-forming cell precursors early during primary immunization.
The anti-keyhole limpet hemocyanin (KLH) B-cell repertoire of unimmunized adult mice was examined by culture of splenocytes (generally 100-3000) at limiting dilution. Cells were polyclonally stimulated with Escherichia coli lipopolysaccharide (LPS) and an interleukin-4-containing lymphokine mixture in the presence of 3T3 fibroblast filler cells. After 7 days of culture, supernatants were examined for their content of anti-KLH IgM and IgG1 antibody by an enzyme-linked immunosorbent assay (ELISA). Parallel cultures of smaller numbers (generally 1-15) of splenocytes were examined to determine the cloning efficiency of B cells in terms of total IgM and IgG1 production. Whereas one spleen cell in 370 produced clones secreting anti-KLH IgM, only 1% of these produced IgG1 that could bind to KLH, despite the fact that about half of the clones switched to IgG1 production with these stimuli. In mice immunized with KLH, this situation did not change until day 5, when there was a sudden, explosive emergence of B cells that could form clones secreting anti-KLH IgG1. The absolute number of such cells in the spleen was found to rise by a factor of 350 between days 3 and 7 of immunization. Moreover, the median amount of IgG1 antibody formed per clone and binding to KLH also rose markedly. In contrast, neither the numbers nor the median KLH-binding antibody content of anti-KLH IgM clones changed significantly after immunization. The results show that the repertoire of anti-protein B cells detected through IgM formation in ELISA consists chiefly of cells producing antibody of low avidity and of doubtful in vivo significance. Assuming that the small proportion of these cells making antibody that is of sufficient avidity to bind as the IgG1 isotype are the ancestors of the many such cells found on day 7 of the primary immune response, one would have to postulate a very high recruitment and/or division rate to account for the increase in numbers and avidity that occurs. It is possible that the anti-KLH IgG1 precursors that suddenly emerge are the results of early variable region gene (V) mutations in B cells. Moreover, it is not excluded that they represent products of a subset of B cells different from those that give rise to the primary in vitro anti-KLH IgM response. The findings have implications for theories of B-cell tolerance.


Archaea appear to dominate the microbiome of Inflatella pellicula deep sea sponges.
Microbes associated with marine sponges play significant roles in host physiology. Remarkable levels of microbial diversity have been observed in sponges worldwide through both culture-dependent and culture-independent studies. Most studies have focused on the structure of the bacterial communities in sponges and have involved sponges sampled from shallow waters. Here, we used pyrosequencing of 16S rRNA genes to compare the bacterial and archaeal communities associated with two individuals of the marine sponge Inflatella pellicula from the deep-sea, sampled from a depth of 2,900 m, a depth which far exceeds any previous sequence-based report of sponge-associated microbial communities. Sponge-microbial communities were also compared to the microbial community in the surrounding seawater. Sponge-associated microbial communities were dominated by archaeal sequencing reads with a single archaeal OTU, comprising ~60% and ~72% of sequences, being observed from Inflatella pellicula. Archaeal sequencing reads were less abundant in seawater (~11% of sequences). Sponge-associated microbial communities were less diverse and less even than any other sponge-microbial community investigated to date with just 210 and 273 OTUs (97% sequence identity) identified in sponges, with 4 and 6 dominant OTUs comprising ~88% and ~89% of sequences, respectively. Members of the candidate phyla, SAR406, NC10 and ZB3 are reported here from sponges for the first time, increasing the number of bacterial phyla or candidate divisions associated with sponges to 43. A minor cohort from both sponge samples (~0.2% and ~0.3% of sequences) were not classified to phylum level. A single OTU, common to both sponge individuals, dominates these unclassified reads and shares sequence homology with a sponge associated clone which itself has no known close relative and may represent a novel taxon.


Screening of cytoplasmic DNA diversity between and within Lupinus mutabilis Sweet and Lupinus albus sensu lato by restriction fragment length polymorphism (RFLP).
Seven populations and five mutant lines of the Andean lupin and four species from the section Albus were screened for their mitochondrial and chloroplast polymorphisms. For this purpose the RFLP method with EcoRI as a restriction enzyme was used. Lupinus luteus, Lupinus albus and Phaseolus vulgaris organellar clones as well as amplified fragments were used as probes. We found that mitochondrial probes were more suitable than chloroplast probes for identification of inter- and intra-specific variations within the examined material. Most mitochondrial probes differentiate the two species investigated. A high level of mitochondrial polymorphism was observed among the populations of L. mutabilis in contrast to monomorphism among the species in the section Albus. A limited polymorphism was detected between the mutant lines of L. mutabilis. We conclude from this study that the mitochondrial RFLP analysis is a valuable tool for identification of variability among Andean lupin populations.


Preventing construction worker injury incidents through the management of personal stress and organizational stressors.
Construction workers (CWs) are positioned at the lowest level of an organization and thus have limited control over their work. For this reason, they are often deprived of their due rewards and training or sometimes are even compelled to focus on production at the expense of their own safety. These organizational stressors not only cause the CWs stress but also impair their safety behaviors. The impairment of safety behaviors is the major cause of CW injury incidents. Hence, to prevent injury incidents and enhance safety behaviors of CWs, the current study aimed to identify the impact of various organizational stressors and stress on CW safety behaviors and injury incidents. To achieve this aim, we surveyed 395 CWs. Using factor analysis, we identified five organizational stressors (unfair reward and treatment, inappropriate safety equipment, provision of training, lack of goal setting, and poor physical environment), two types of stress (emotional and physical), and safety behaviors. The results of correlation and regression analyses revealed the following: (1) injury incidents were minimized by safety behaviors but escalated by a lack of goal setting, (2) safety behaviors were maximized by moderate levels of emotional stress (i.e., an inverted U-shape relationship between these two variables) and increased in line with physical stress and inappropriate safety equipment, (3) emotional stress was positively predicted by the provision of training and inappropriate safety equipment, and (4) physical stress was predicted only by inappropriate safety equipment. Based on these results, we suggest various recommendations to construction stakeholders on how to prevent CW injury incidents.


Fatigue of Metallic Stents: From Clinical Evidence to Computational Analysis.
The great success of stents in treating cardiovascular disease is actually undermined by their long-term fatigue failure. The high variability of stent failure incidence suggests that it is due to several correlated aspects, such as loading conditions, material properties, component design, surgical procedure, and patient functional anatomy. Numerical and experimental non-clinical assessments are included in the recommendations and requirements of several regulatory bodies and they are thus exploited in the analysis of stent fatigue performance. Optimization-based simulation methodologies have been developed as well, to improve the fatigue endurance of novel designs. This paper presents a review on the fatigue issue in metallic stents, starting from a description of clinical evidence about stent fracture up to the analysis of computational approaches available from the literature. The reported discussion on both the experimental and numerical framework aims at providing a general insight into stent lifetime prediction as well as at understanding the factors which affect stent fatigue performance for the design of novel components.