[High frequency transthoracic echocardiography in diagnosis of chronic occlusions of major coronary arteries].
Comparative analysis of possibilities of transthoracic echocardiography (TTE) and coronary angiography in diagnosis of chronic occlusions of anterior descending (ADA), circumflex (CA), and right coronary (RA) arteries was carried out in 100 patients (90 men, 10 women, mean age 51 +/- 11 years). With the help of TTE we analyzed direction, structural and temporal parameters of coronary blood flow in zones of potential epicardial and intramyocardial collateral filling: for ADA - in distal segment (dADA) and septal branches (SBADA), for CA - in obtuse marginal branches (OMB), for RCA - in posterior interventricular artery (PIA) and septal branches (SBRCA). We found that TTE was a sensitive and highly specific method of diagnosis of ADA and RCA occlusions, but did not allow to diagnose adequately occlusions of CA. We proved that main criterion of ADA occlusion was registration of retrograde or retroanterograde collateral blood flow in dADA or SBADA. Sensitivity of detection of inverted blood flow in dADA without consideration of direction of blood flow in SBADA in diagnosis of ADA occlusions was 77%, with consideration of SBRCA - 85%, specificity - 97%. Detection of retrograde or retroanterograde blood flow in SBADA was indicative of proximal level of artery lesion with sensitivity 100% and specificity 75%. Detection of retrograde or collateral flow in PIA or SBRCA was found to be main criterion of RCA occlusion. Sensitivity of detection of inverted blood flow in PIA without taking into account direction of blood flow in SBRCA in diagnosis of RCA occlusions was 77%, with consideration of SBRCA - 88%, specificity - 98%. The study of lat flow in SBRCA did not allow to determine accurately the level of artery lesion.


[Endogenous Aspergillus endophthalmitis in AIDS].
We present the course of an endogenous Aspergillus endophthalmitis in a 38-year-old HIV-positive man. HISTORY AND CLINICAL SIGNS: The first examination because of a sudden visual loss in the right eye showed a central subretinal infiltration, peripheral vascular sheeting and retinal hemorrhages. In spite of high-dose systemic antifungal therapy we could not prevent the penetration of the posterior wall of the eye and infiltration of adjacent orbital structures. Enucleation had to be performed. In case of scleral involvement in Aspergillus endophthalmitis the necessity of enucleation has to be considered.


Centrality measures and thermodynamic formalism for complex networks.
In the study of small and large networks it is customary to perform a simple random walk where the random walker jumps from one node to one of its neighbors with uniform probability. The properties of this random walk are intimately related to the combinatorial properties of the network. In this paper we propose to use the Ruelle-Bowens random walk instead, whose probability transitions are chosen in order to maximize the entropy rate of the walk on an unweighted graph. If the graph is weighted, then a free energy is optimized instead of the entropy rate. Specifically, we introduce a centrality measure for large networks, which is the stationary distribution attained by the Ruelle-Bowens random walk; we name it entropy rank. We introduce a more general version, which is able to deal with disconnected networks, under the name of free-energy rank. We compare the properties of those centrality measures with the classic PageRank and hyperlink-induced topic search (HITS) on both toy and real-life examples, in particular their robustness to small modifications of the network. We show that our centrality measures are more discriminating than PageRank, since they are able to distinguish clearly pages that PageRank regards as almost equally interesting, and are more sensitive to the medium-scale details of the graph.


Triclosan resistance in clinical isolates of Acinetobacter baumannii.
The susceptibility to triclosan of 732 clinical Acinetobacter baumannii isolates obtained from 25 hospitals in 16 cities in China from December 2004 to December 2005 was screened by using an agar dilution method. Triclosan MICs ranged between 0.015 and 16 mg l(-1), and the MIC(90) was 0.5 mg l(-1), lower than the actual in-use concentration of triclosan. Twenty triclosan-resistant isolates (MICs >or=1 mg l(-1)) were characterized by antibiotic susceptibility, clonal relatedness, fabI mutation, fabI expression, and efflux pump phenotype and expression to elucidate the resistance mechanism of A. baumannii to triclosan. The resistance rates of triclosan-resistant isolates to imipenem, levofloxacin, amikacin and tetracycline were higher than those of triclosan-sensitive isolates. Triclosan resistance was artificially classified as low level (MICs 1-2 mg l(-1)) or high level (MICs >or=4 mg l(-1)). High-level triclosan resistance could be explained by a Gly95Ser mutation of FabI, whilst wild-type fabI was observed to be overexpressed in low-level resistant isolates. Active efflux did not appear to be a major reason for acquired triclosan resistance, but acquisition of resistance appeared to be dependent on a background of intrinsic triclosan efflux.


Linking governance mechanisms to health outcomes: a review of the literature in low- and middle-income countries.
We conducted a synthesis of peer-reviewed literature to shed light on links between governance mechanisms and health outcomes in low- and middle-income countries. Our review yielded 30 studies, highlighting four key governance mechanisms by which governance may influence health outcomes in these settings: Health system decentralization that enables responsiveness to local needs and values; health policymaking that aligns and empowers diverse stakeholders; enhanced community engagement; and strengthened social capital. Most, but not all, studies found a positive association between governance and health. Additionally, the nature of the association between governance mechanisms and health differed across studies. In some studies (N = 9), the governance effect was direct and positive, while in others (N = 5), the effect was indirect or modified by contextual factors. In still other studies (N = 4), governance was found to have a moderating effect, indicating that governance mechanisms influenced other system processes or structures that improved health. The remaining studies reported mixed findings about the association between governance and health (N = 6), no association between governance and health (N = 4), or had inconclusive results (N = 2). Further exploration is needed to fully understand the relationship between governance and health and to inform the design and delivery of evidence-based, effective governance interventions around the world.


2 kW incoherent beam combining of four narrow-linewidth photonic crystal fiber amplifiers.
We report on beam combining of four narrow-linewidth fiber amplifier chains, running at different wavelengths and each delivering 500 W optical output power. The main amplifier stage consists of a large mode area photonic crystal fiber. The four output beams of the amplifier chains are spectrally (incoherent) combined using a polarization-independent dielectric reflective diffraction grating to form an output beam of 2 kW continuous-wave optical power with good beam quality (M(2)x = 2.0, M(2)y = 1.8).


Computer-aided drug design at Boehringer Ingelheim.
Computer-Aided Drug Design (CADD) is an integral part of the drug discovery endeavor at Boehringer Ingelheim (BI). CADD contributes to the evaluation of new therapeutic concepts, identifies small molecule starting points for drug discovery, and develops strategies for optimizing hit and lead compounds. The CADD scientists at BI benefit from the global use and development of both software platforms and computational services. A number of computational techniques developed in-house have significantly changed the way early drug discovery is carried out at BI. In particular, virtual screening in vast chemical spaces, which can be accessed by combinatorial chemistry, has added a new option for the identification of hits in many projects. Recently, a new framework has been implemented allowing fast, interactive predictions of relevant on and off target endpoints and other optimization parameters. In addition to the introduction of this new framework at BI, CADD has been focusing on the enablement of medicinal chemists to independently perform an increasing amount of molecular modeling and design work. This is made possible through the deployment of MOE as a global modeling platform, allowing computational and medicinal chemists to freely share ideas and modeling results. Furthermore, a central communication layer called the computational chemistry framework provides broad access to predictive models and other computational services.


Evaluation of the immunoprotective effects of porcine deltacoronavirus subunit vaccines.
Porcine deltacoronavirus (PDCoV), a new porcine enteric coronavirus, has seriously endangered the pig breeding industry and caused great economic losses. However, a PDCoV vaccine is not commercially available. Therefore, new and efficient PDCoV vaccines must be developed without delay. In this study, we used the ExpiCHO eukaryotic expression system to express and purify the following 3 structural proteins of PDCoV: S, N and M. Subsequently, the level of humoral and cellular immunity induced by the S protein (immunization with the S protein alone) and a protein mixture (immunization with a mixture of S, N and M proteins) were evaluated in mice and piglets, respectively, and the performances of the 2 immunizations in a challenge protection test were assessed in piglets. The results showed that both the S protein and the protein mixture induced the production of high levels of specific IgG antibodies and neutralizing antibodies and effectively neutralized PDCoV-infected LLC-PK cells in vitro. Furthermore, compared with the S protein, the N and M proteins in the protein mixture promoted the expression of CD8+ T cells and IFN-γ, induced a stronger cellular immune response, and effectively protected 4/5 of the piglets from PDCoV infection. In conclusion, the results of this study showed that the N and M proteins play important roles in inducing an immunoprotective response. Using N and M antigens as effective antigenic components in the development of PDCoV vaccines in the future will effectively increase the immune efficacy of the vaccines.


Updates in prognostication and treatment of Waldenström's macroglobulinemia.
Waldenström's macroglobulinemia (WM) is a rare, incurable hematologic disorder with a relatively indolent course in a majority of the patients. Despite this, a significant proportion of patients require treatment because of hypersecretion of immunoglobulin M and the invasion of bone marrow and peripheral organs by neoplastic lymphoplasmacytic lymphoma cells. Historically, there has been a dearth of research and therapeutic advancements in the field of WM, with most understanding based on other, related B-cell lymphoid malignancies, including multiple myeloma, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Recently, there has been an increase in dedicated work to better explain the pathobiology of WM, which has identified several clinical and genetic markers that serve to prognosticate disease course and patient outcomes. Furthermore, this has led to dedicated clinical trials and the development of novel drugs/regimens including the first Food and Drug Administration-approved agent for this diagnosis, ibrutinib. This review aims to document some of the recent advancements with respect to prognostic markers and therapeutic options for patients with WM, as well as certain selected novel treatments with unique mechanisms of action, that are currently under development.


Fluctuations in intracellular calcium responses to action potentials in single en passage presynaptic boutons of layer V neurons in neocortical slices.
The release of neurotransmitter from a nerve terminal on invasion by an action potential shows large trial-to-trial fluctuations. The factors contributing to this variability have not been elucidated clearly. Here, simultaneous patch-clamp and optical measurements from layer V neocortical pyramidal neurons have been used to assess the extent to which the fluctuations in transmitter release may be caused by variability in calcium rise in presynaptic structures. Boutons on axon collaterals were visualized and increases in intracellular calcium, assessed by Fura-2, were observed in response to single action potentials. In some boutons, calcium responses showed trial-to-trial variability and occasional apparent failures despite the faithful conduction of the action potential. These results suggest that a factor contributing to the fluctuation in transmitter release may be the variability with which depolarization of a presynaptic bouton produces an increase in intrabouton calcium.


[The maternal-fetal immune relationship in pregnancy].
The mother establishes with the fetus a special interaction in pregnancy allowing his normal survival in spite of the different HLA antigens. The main factors contributing to these favourable conditions for the fetus are an efficient local immunosuppression and the formation of a protective barrier between the mother and the fetus. A number of substances are responsible for the local immunosuppression and include cytokines, prostaglandins, hormones as well as various other proteins of pregnancy. In addition, cytokines produced by TH2 lymphocytes seem to be predominant with respect to those of TH1 cells. An effective protection is provided by the trophoblast layer, which not only forms a physical barrier between the mother and the fetus but evades the immune attack of the mother by expressing inhibitory molecules of the complement system and by down regulating the expression of HLA antigens. Data obtained from murine models and clinical observation in pathological pregnancies suggest that an abnormal immune response of the mother against the feto-placental unit may be responsible for the occurrence of recurrent spontaneous abortions. This is proved by the ability of the partner's lymphocytes administered to females in the mouse model prior to mating to reduce the incidence of abortions. Unfortunately, similar treatment in women with recurrent abortion does not appear to be very effective.


ON THE RESULTS OF A SYSTEMIC MULTIFACTOR ANALYSIS WITH MATHEMATICAL MODELING OF THE INDICATORS OF MEDICAL EXPERTISE OF YOUNG MALES WITH SURGICAL DISEASES IN THE REPUBLIC OF ARMENIA.
Medical aspects of the organization of replenishment of the Armed Forces with healthy and physically strong personnel are of great importance, and the deficit in the number of conscripts and their low-quality condition have become one of the main and important problems for the Armed Forces. The aim of the study was to improve the medical care of male conscripts aged 18-27 years by revealing the regularities and peculiarities of the expert assessment of surgical diseases among this category of young men on the basis of mathematical modeling. The object of the research was the study of the names of surgical profile articles, according to which these people were recognized as unfit or restricted fit for service, and the results of military medical expertise. Descriptive, social, and statistical methods were applied in the course of the study. The final stage was to conduct a systemic multifactor analysis in order to obtain a mathematical model of the process under study. The values of the influence coefficients of the mentioned indicators for 2013-2019 on the obtained mathematical models from the point of view of military-medical expertise of young men with surgical diseases both in the Republic of Armenia as a whole and in its separate regions are presented. Summarizing, it can be stated that from the point of view of military-medical expertise of young men with surgical diseases it is impossible to consider Yerevan city and the regions of RA as separate parts of the Republic of Armenia. Yerevan and the regions of the Republic of Armenia as separate parts, as they appear as a single whole according to the results of systemic multifactor analysis with mathematical modeling.


Expression of the vitamin K-dependent proteins GAS6 and protein S and the TAM receptor tyrosine kinases in human atherosclerotic carotid plaques.
The GAS6/ProS-TAM system is composed of two vitamin K-dependent ligands (GAS6 and protein S) and their three protein tyrosine kinase receptors TYRO3, AXL and MERTK, known as the TAM receptors. The system plays a prominent role in conditions of injury, inflammation and repair. In murine models of atherosclerotic plaque formation, mutations in its components affect atherosclerosis severity. Here we used Taqman low-density arrays and immunoblotting to study mRNA and protein expression of GAS6, ProS and the TAM receptors in human carotid arteries with different degrees of atherosclerosis. The results show a clear down-regulation of the expression of AXL in atheroma plaques with respect to normal carotids that is matched by decreased abundance of AXL in protein extracts detected by immunoblotting. A similar decrease was observed in PROS1 mRNA expression in atherosclerotic carotids compared to the normal ones, but in this case protein S (ProS) was clearly increased in protein extracts of carotid arteries with increasing grade of atherosclerosis, suggesting that ProS is carried into the plaque. MERTK was also increased in atherosclerotic carotid arteries with respect to the normal ones, suggesting that the ProS-MERTK axis is functional in advanced human atherosclerotic plaques. MERTK was expressed in macrophages, frequently in association with ProS, while ProS was abundant also in the necrotic core. Our data suggest that the ProS-MERTK ligand-receptor pair was active in advanced stages of atherosclerosis, while AXL signalling is probably down-regulated.


Flt3high and Flt3low CD34+ progenitor cells isolated from human bone marrow are functionally distinct.
We generated monoclonal antibodies against the human Flt3 receptor and used them to study the characteristics of normal human bone marrow cells resolved based on Flt3 expression. Human CD34+ or CD34+lin- marrow cells were sorted into two populations: cells expressing high levels of Flt3 receptor (Flt3high) and cells with little or no expression of Flt3 receptor (Flt3low). Flt3 receptor was detected on a subset of CD34+CD38- marrow cells, as well as on CD34+CD19+ B lymphoid progenitors and CD34+CD14+CD64+ monocytic precursors. Flt3 receptor was also present on more mature CD34-CD14+ monocytes. In colony-forming assays, Flt3high cells gave rise mainly to colony-forming unit-granulocyte-macrophage (CFU-GM) colonies, whereas Flt3low cells produced mostly burst-forming unit-erythroid colonies. There was no difference in the number of multilineage CFU-Mix colonies between the two cell fractions. Cell cycle analysis showed that a large number of the Flt3low cells were in the G0 phase of the cell cycle, whereas Flt3high cells were predominantly in G1. Cell numbers in the suspension cultures initiated with Flt3high cells were maintained in the presence of Flt3 ligand (FL) alone, and increased in response to FL plus kit ligand (KL). In contrast, cell numbers in the suspension cultures started with Flt3low cells did not increase in the presence of FL, or FL plus KL. Upregulation of Flt3 receptor on Flt3low cells was not detected during suspension culture. CD14+ monocytes were the major cell type generated from CD34+lin-Flt3high cells in liquid suspension culture, whereas cells generated from CD34+lin-Flt3low cells were mainly CD71+GlycA+ erythroid cells. These results show clear functional differences between CD34+Flt3high and CD34+Flt3low cells and may have implications concerning the in vitro expansion of human hematopoietic progenitor cells.


Anxiety, depression, and oral health: A population-based study in Southeast of Iran.
Depression and anxiety are two psychosocial illnesses that mostly are comorbid. The prevalence of these diseases is increasing worldwide. Both can affect general health also oral and dental health. The effects can be physiological and behavioral. Patients with these disorders are not willing to keep oral hygiene. The purpose of this study was to investigate the association between depression/anxiety and oral health indices in the 15-75-year-old population of Kerman. This cross-sectional study recruited 5900 people aged 15-75 years through one-stage cluster sampling (Kerman coronary artery disease risk factors study, KERCADRS). Data were collected through beck questionnaires for anxiety and depression and clinical examinations. Oral health indices including decayed, missing, filled teeth, gingival index (GI), and community periodontal index (CPI) were also measured. Data were analyzed by SPSS 21 software. Chi-square, t-test and regression analysis were used to determine the relationship between the variables. P ≤0.05 was considered as the level of statistical significance. In the study, 1975 (33.6%) of patients showed moderate-to-severe anxiety and 3502 (59.5%) got the scores as depressed. There was a significant difference between GI and CPI indices of the normal and depressed group (P < 0.01), but the difference in the anxious and normal group was not statistically significant (P > 0.05). The results of the study showed a significant relationship between depression and oral health indices but not with anxiety. Therefore, the present study suggests that more attention should be paid to the oral health of people with a history of depression.


Aging is associated with increased regulatory T-cell function.
Regulatory T-cell (Treg, CD4(+) CD25(+)) dysfunction is suspected to play a key role in immune senescence and contributes to increased susceptibility to diseases with age by suppressing T-cell responses. FoxP3 is a master regulator of Treg function, and its expression is under control of several epigenetically labile promoters and enhancers. Demethylation of CpG sites within these regions is associated with increased FoxP3 expression and development of a suppressive phenotype. We examined differences in FoxP3 expression between young (3-4 months) and aged (18-20 months) C57BL/6 mice. DNA from CD4(+) T cells is hypomethylated in aged mice, which also exhibit increased Treg numbers and FoxP3 expression. Additionally, Treg from aged mice also have greater ability to suppress effector T-cell (Teff) proliferation in vitro than Tregs from young mice. Tregs from aged mice exhibit greater redox remodeling-mediated suppression of Teff proliferation during coculture with DCs by decreasing extracellular cysteine availability to a greater extent than Tregs from young mice, creating an adverse environment for Teff proliferation. Tregs from aged mice produce higher IL-10 levels and suppress CD86 expression on DCs more strongly than Tregs from young mice, suggesting decreased T-cell activity. Taken together, these results reveal a potential mechanism of higher Treg-mediated activity that may contribute to increased immune suppression with age.


Stuck in a (literal) tight spot: Cycling between tram rails, sharrows and parked cars.
Cyclists riding next to parked vehicles are at risk of crashes with opening vehicle doors. A central position, out of this dooring zone, decreases such a risk but comes with other problems like potentially smaller passing distances kept by overtaking motorists or having to cross tram rails. Factors influencing cyclists' choice of position were investigated by showing a total of 3,444 German cyclists different traffic situations in two online surveys. In the first study (N = 1,850), parked cars, the position of a cyclist riding ahead in the presented images (towards the curb/center of the lane), and presence and kind of sharrows were varied. As the variation in results for the different sharrow types was negligible, in Study 2 (N = 1,594), only the most common type was used. Whether cyclists prefer to accept the risk of falling while crossing tram rails or the risk of being too close to the curb or parked cars was investigated, varying the presence of tram rails, which has not been previously researched. In both studies, respondents indicated which position on the road they would choose in the depicted situations and answered questions about subjective safety, a factor closely related to cyclists' choice of position. Cyclists chose positions farther towards the center of the road if there were parked cars and they chose an even more central position with tram rails. Respondents felt safer with sharrows on the road as well as in situations without parked cars and in situations without tram rails. Discussion and practical implications: The results indicate that, in addition to infrastructure characteristics, other cyclists' behavior (descriptive norm) influences cyclists' position on the road as well as their perceived safety. Implications for infrastructure design, especially regarding (the removal of) parked cars, are discussed.


Application of High Hydrostatic Pressure in fresh purple smoothie: Microbial inactivation kinetic modelling and qualitative studies.
The inactivation kinetics of Listeria monocytogenes during High Hydrostatic Pressure (HHP) treatments was studied in a purple smoothie based of fresh fruit and vegetables. Pressure intensity studied was 300, 350, 400 and 450 MPa. Untreated samples were used as control. Furthermore, the effects on quality attributes (sensory, total soluble solids content, colour, titratable acidity, pH, vitamin C and total phenolics content) were also monitored. Microbial inactivation was modelled as a function of the HHP intensity using the Geeraerd model. Shoulder and tail effects were observed only for the 300 MPa pressure assayed, supporting a multiple hit kinetic inactivation of critical factors. Increasing the HHP intensity resulted in a faster inactivation with tailing. A strong positive correlation was observed between the pressure level and the inactivation rate (k). Hence, a linear model was used to describe the relationship between both variables. Nevertheless, further data are required to confirm this secondary model. Quality was mostly unaffected by the HHP treatments, except for the vitamin C content, which reported reductions of 26 and 21% after 300 and 350 MPa, respectively. In conclusion, HHP can be a viable technology for processing fruit and vegetable-based smoothies to preserve quality and safety. A pressure of 400 MPa is advisable to ensure an efficient microbial inactivation with the best sensory and nutritional quality retention.


Airborne reduced nitrogen: ammonia emissions from agriculture and other sources.
Ammonia is a basic gas and one of the most abundant nitrogen-containing compounds in the atmosphere. When emitted, ammonia reacts with oxides of nitrogen and sulfur to form particles, typically in the fine particle size range. Roughly half of the PM(2.5) mass in eastern United States is ammonium sulfate, according to the US EPA. Results from recent studies of PM(2.5) show that these fine particles are typically deposited deep in the lungs and may lead to increased morbidity and/or mortality. Also, these particles are in the size range that will degrade visibility. Ammonia emission inventories are usually constructed by multiplying an activity level by an experimentally determined emission factor for each source category. Typical sources of ammonia include livestock, fertilizer, soils, forest fires and slash burning, industry, vehicles, the oceans, humans, pets, wild animals, and waste disposal and recycling activities. Livestock is the largest source category in the United States, with waste from livestock responsible for about 3x10(9) kg of ammonia in 1995. Volatilization of ammonia from livestock waste is dependent on many parameters, and thus emission factors are difficult to predict. Despite a seasonal variation in these values, the emission factors for general livestock categories are usually annually averaged in current inventories. Activity levels for livestock are from the USDA Census of Agriculture, which does not give information about animal raising practices such as housing types and grazing times, waste handling systems, and approximate animal slurry spreading times or methods. Ammonia emissions in the United States in 1995 from sources other than livestock are much lower; for example, annual emissions are roughly 8x10(8) kg from fertilizer, 7x10(7) kg from industry, 5x10(7) kg from vehicles and 1x10(8) kg from humans. There is considerable uncertainty in the emissions from soil and vegetation, although this category may also be significant. Recommendations for future directions in ammonia research include designing experiments to improve emission factors and their resolution in all significant source categories, developing mass balance models, and refining of the livestock activity level data by eliciting judgment from experts in this field.


PERSPECTIVE: SUSTAINING EFFECTIVE MALARIA CONTROL DURING THE COVID-19 PANDEMIC.
The COVID-19 pandemic has spread to many malaria endemic countries in sub Saharan Africa. There is little or no experience on how the impact of policies put in place to curtail further spread of the pandemic will affect the epidemiology of malaria during the malaria season. The objective of this write-up is to put in perspective, the need to ensure effective malaria control in the midst of the COVID-19 crises. Proper integration of the COVID-19 safety and treatment guidelines with malaria control policies and effective diagnosis in malaria endemic countries in sub Saharan Africa are important in mitigating morbidity and mortality rates which may rise if malaria cases are neglected due to the current burden of the COVID-19 pandemic.


Scalable Synthesis of Photoluminescent Single-Chain Nanoparticles by Electrostatic-Mediated Intramolecular Crosslinking.
We report the large-scale synthesis of photoluminescent single-chain nanoparticles (SCNPs) by electrostatic-mediated intramolecular crosslinking in a concentrated solution of 40 mg mL-1 by continuous addition of the free radical initiator. Poly(vinyl benzyl chloride) was charged by quaternization with vinyl-imidazolium for the intramolecular crosslinking by using 2,2-dimethoxy-2-phenylacetophenone (DMAP) as the radical initiator. Under the electrostatic repulsion thus interchain isolation, the intrachain crosslinking experiences the transition from coil through pearl-necklace to globular state. The SCNPs demonstrate strong photoluminescence in the visible range when the non-emissive units are confined thereby. Composition and microstructure of the SCNPs are tunable. The photoluminescent tadpole-like Janus SCNP can be used to selectively illuminate interfacial membranes while stabilizing the emulsions.


Pathways to community living in practice: Local development and adaptation within an older peoples mental health service.
To describe the local adaptation of the Pathways to Community Living (PCLI) program in an Older Peoples Mental Health (OPMH) service to guide other services. A retrospective observational study was conducted. Data were obtained from service planning meetings and newly developed documents, Clinical Advisory Committee meetings, and OPMH PCLI database. The PCLI program was adapted for the local OPMH service through development of an assessment template, creating a Memorandum of Understanding with a partner Residential Aged Care Facility (RACF) and establishing processes for collaboration and regular review. Between 2019 and March 2023, 20 mental health consumers were referred to the OPMH PCLI program. Their demographic and clinical characteristics are described. Adaptation of the PCLI program for OPMH consumers required consideration of specific older adult needs to develop a bespoke plan for assessment and partnership with the PCLI-funded RACF. The development phase and ongoing processes for review facilitated engagement of key stakeholders across health and RACF sectors, highlighting issues with consumer engagement. Similar models could be used by other health services to implement the PCLI in their local context.


Avian pathogenic Escherichia coli infection causes infiltration of heterophilic granulocytes of chick tracheal by the complement and coagulation cascades pathway.
Avian pathogenic Escherichia coli (APEC) causes tracheal damage and heterophilic granulocytic infiltration and inflammation in infected chicks. In this study, we infected chick tracheal tissue with strain AE17 and produced pathological sections with proteomic sequencing. We compared the results of pathological sections from the APEC-infected group with those from the PBS control group; the pathological sections from the experimental group showed hemorrhage, fibrinization, and infiltration of heterophilic granulocytes in the tracheal tissue. In order to explore the effect on proteomics on inflammation and to further search for the caus. The tandem mass tag-based (TMT) sequencing analysis showed 224 upregulated and 140 downregulated proteins after infection with the AE17 strain. Based on the results of KEGG in Complement and coagulation cascades, differential protein expression in the Protein export pathway was upregulated. With these results, we found that chemokines produced by the Complement and coagulation cascades pathway may cause infiltration of heterophilic granulocytes involved in inflammation, as well as antimicrobial factors produced by the complement system to fight the infection together.These results suggest that APEC causes the infiltration of heterophilic granulocytes through the involvement of the complement system with serine protease inhibitors.


Formation mechanism of Mn x Co3-x O4 yolk-shell structures.
Formation of Mn x Co3-x O4 yolk-shell microspheres via a solvothermal reaction of hydrated cobalt and manganese nitrates in ethanol is investigated. Spinel nanocrystals of cobalt oxide or cobalt-rich ternary oxide preferentially develop in the system, while manganese-rich hydroxide form Mn(OH)2-type nanosheets. Instead of continuing to grow individually, the nanocrystallites and nanosheets aggregate into large microspheres due to their strong inter-particle interaction. When the proportion of Mn-rich nanosheets is high, therefore the overall density is low, dehydration of hydroxide nanosheets and a surface re-crystallisation lead to formation of a dense and rigid shell, which is separated from a solid or hollow core via a further Ostwald ripening process. The proposed formation mechanism of the yolk-shell structures based on electron microscopic studies would help us to develop yolk-shell structure based multifunctional materials.


Enhanced proliferation of pancreatic acinar cells in MRL/MpJ mice is driven by severe acinar injury but independent of inflammation.
Adult pancreatic acinar cells have the ability to re-enter the cell cycle and proliferate upon injury or tissue loss. Despite this mitotic ability, the extent of acinar proliferation is often limited and unable to completely regenerate the injured tissue or restore the initial volume of the organ, thus leading to pancreatic dysfunction. Identifying molecular determinants of enhanced proliferation is critical to overcome this issue. In this study, we discovered that Murphy Roths Large (MRL/MpJ) mice can be exploited to identify molecular effectors promoting acinar proliferation upon injury, with the ultimate goal to develop therapeutic regimens to boost pancreatic regeneration. Our results show that, upon cerulein-induced acinar injury, cell proliferation was enhanced and cell cycle components up-regulated in the pancreas of MRL/MpJ mice compared to the control strain C57BL/6. Initial damage of acinar cells was exacerbated in these mice, manifested by increased serum levels of pancreatic enzymes, intra-pancreatic trypsinogen activation and acinar cell apoptosis. In addition, MRL/MpJ pancreata presented enhanced inflammation, de-differentiation of acinar cells and acinar-to-ductal metaplasia. Manipulation of inflammatory levels and mitogenic stimulation with the thyroid hormone 5,3-L-tri-iodothyronine revealed that factors derived from initial acinar injury rather than inflammatory injury promote the replicative advantage in MRL/MpJ mice.


Prevalence of and risk factors for minor and major depression among community-dwelling older adults in Taiwan.
This study was conducted to estimate prevalence rates and risk factors for late-life depression in a large nationwide representative sample from Taiwan. A total of 5,664, randomly sampled individuals aged ≥55 years were enrolled. Clinically, relevant depressive symptoms were classified using the Center for Epidemiological Studies Depression Scale (CES-D score ≥16), and major depression was confirmed using the Primary Care Evaluation of Mental Disorders. Individuals with clinically relevant depressive symptoms, who did not meet the strict diagnostic criteria for major depression, were considered to have minor depression. Multinomial logistic regression analyses were conducted to identify risk factors for major and minor depression, including socio-demographic characteristics, medical conditions, lifestyle behaviors, social support network, and life events. The prevalence rates of minor and major depression were 3.7% and 1.5%, respectively. Major depression was associated with personal vulnerability factors, such as poor social support, cognitive impairment, comorbid pain conditions, and sleep disturbance. However, minor depression was more likely to be related to adverse life events, including increased burden on families, changes in health status, or relationship problem. Approximately, 20.0% of individuals with major depression received antidepressant treatment. Late-life depression was less prevalent among community-dwelling older adults in Taiwan than among populations in other countries. Our findings may aid the early detection and treatment of late-life depression and provide a basis for future investigations.


The complementary use of glycoprotein IIb/IIIa inhibitors and drug-eluting stents in contemporary percutaneous coronary intervention.
The percutaneous treatment of symptomatic, obstructive coronary artery disease continues to undergo evolutionary changes that have led to an increase in the number of procedures performed each year. Studies on the adjunctive use of thienopyridines and glycoprotein (GP) IIb/IIIa inhibitors during and following percutaneous coronary intervention (PCI) have demonstrated a reduction in the ischemic complications following PCI. One of the GP IIb/IIIa inhibitors, abciximab, has been shown to reduce mortality one year after successful PCI compared with placebo. Despite the reduction in ischemic complications and a potential reduction in mortality at one year, the antiplatelet agents have not consistently been shown to affect the rates of restenosis following PCI. Recent, exciting data on the use of drug-eluting stents (DES) in diseased coronary vessels has generated immense enthusiasm within the interventional community about the future ability to dramatically reduce the rates of restenosis following PCI with the use of this novel stent technology. With the introduction and assumed widespread use of these new stents, it appears that the contemporary interventional cardiologist will now have two complementary therapies available for use during percutaneous revascularization: GP IIb/IIIa inhibitors for the reduction of ischemic complications during and immediately following PCI, and DES for the prevention of long-term restenosis within the treated vessel segment. Caution should be taken not to view these valuable therapies as mutually exclusive but rather to recognize that each addresses critical aspects of percutaneous revascularization that have been improved upon after being studied in thousands of patients in controlled, randomized clinical trials.


Personal reflections on the multichannel cochlear implant and a view of the future.
The multichannel cochlear implant is the first neural prosthesis to effectively and safely bring electronic technology into a direct physiological relation with the central nervous system and human consciousness. It is also the first cochlear implant to give speech understanding to tens of thousands of persons with profound deafness and spoken language to children born deaf in more than 80 countries. In so doing, it is the first major advance in research and technology to help deaf children communicate since Sign Language of the Deaf was developed at the Paris deaf school (L'Institut National de Jeunes Sourds de Paris) >200 years ago. Furthermore, biomedical research has been fundamental for ensuring that the multielectrode implant is safe as well as effective. More recent research has also shown that bilateral implants confer the benefits of binaural hearing. Future research using nanotechnology should see high-fidelity sound received, which would help deaf persons communicate in noise and enjoy music. Research should also lead to implants in ears with useful hearing.


Effect of Multi-Directional Forging on the Microstructure and Mechanical Properties of β-Solidifying TiAl Alloy.
This study systematically investigated the influence of multi-directional forging (MDF) on the microstructural evolution, hot deformation behavior, and tensile properties of a β-solidifying TiAl alloy. The initial lamellar microstructure of an as-cast alloy was remarkably refined and homogenized by three-step MDF. High temperatures and multi-pass deformations were conducive to the decomposition of lamellae. A crack-free billet was obtained through three-step MDF, with a deformation temperature of 1250 °C and a forging speed of 0.1 mm/s, indicating that MDF can be applied to β-solidifying TiAl alloys by the proper control of the alloy composition and process parameters. Microstructural observation showed that the billet mainly consists of fine and equiaxed γ grains and a small amount of β phase. The tensile properties of the multi-directional forged alloy were also significantly improved, due to microstructure refinement. The ultimate tensile strength (UTS) and elongation (δ) at room temperature were 689.4 MPa, and 0.83%, respectively. The alloy exhibits excellent ductility at 700 °C. When the temperature was increased to 700 °C, the UTS decreased to 556 MPa and δ increased to 5.98%, indicating that the alloy exhibits excellent ductility at 700 °C. As the temperature further increased to 750 °C, δ dramatically increased to 46.65%, indicating that the ductile-brittle transition temperature of the alloy is between 700 °C and 750 °C.


Genomic sequencing and analyses of Lymantria xylina multiple nucleopolyhedrovirus.
Outbreaks of the casuarina moth, Lymantria xylina Swinehoe (Lepidoptera: Lymantriidae), which is a very important forest pest in Taiwan, have occurred every five to 10 years. This moth has expanded its range of host plants to include more than 65 species of broadleaf trees. LyxyMNPV (L. xylina multiple nucleopolyhedrovirus) is highly virulent to the casuarina moth and has been investigated as a possible biopesticide for controlling this moth. LdMNPV-like virus has also been isolated from Lymantria xylina larvae but LyxyMNPV was more virulent than LdMNPV-like virus both in NTU-LY and IPLB-LD-652Y cell lines. To better understand LyxyMNPV, the nucleotide sequence of the LyxyMNPV DNA genome was determined and analysed. The genome of LyxyMNPV consists of 156,344 bases, has a G+C content of 53.4% and contains 157 putative open reading frames (ORFs). The gene content and gene order of LyxyMNPV were similar to those of LdMNPV, with 151 ORFs identified as homologous to those reported in the LdMNPV genome. Two genes (Lyxy49 and Lyxy123) were homologous to other baculoviruses, and four unique LyxyMNPV ORFs (Lyxy11, Lyxy19, Lyxy130 and Lyxy131) were identified in the LyxyMNPV genome, including a gag-like gene that was not reported in baculoviruses. LdMNPV contains 23 ORFs that are absent in LyxyMNPV. Readily identifiable homologues of the gene host range factor-1 (hrf-1), which appears to be involved in the susceptibility of L. dispar to NPV infection, were not present in LyxyMNPV. Additionally, two putative odv-e27 homologues were identified in LyxyMNPV. The LyxyMNPV genome encoded 14 bro genes compared with 16 in LdMNPV, which occupied more than 8% of the LyxyMNPV genome. Thirteen homologous regions (hrs) were identified containing 48 repeated sequences composed of 30-bp imperfect palindromes. However, they differed in the relative positions, number of repeats and orientation in the genome compared to LdMNPV. The gene parity plot analysis, percent identity of the gene homologues and a phylogenetic analysis suggested that LyxyMNPV is a Group II NPV that is most closely related to LdMNPV but with a highly distinct genomic organisation.


Primate occurrence across a human-impacted landscape in Guinea-Bissau and neighbouring regions in West Africa: using a systematic literature review to highlight the next conservation steps.
West African landscapes are largely characterised by complex agroforest mosaics. Although the West African forests are considered a nonhuman primate hotspot, knowledge on the distribution of many species is often lacking and out-of-date. Considering the fast-changing nature of the landscapes in this region, up-to-date information on primate occurrence is urgently needed, particularly of taxa such as colobines, which may be more sensitive to habitat modification than others. Understanding wildlife occurrence and mechanisms of persistence in these human-dominated landscapes is fundamental for developing effective conservation strategies. In this paper, we aim to review current knowledge on the distribution of three threatened primates in Guinea-Bissau and neighbouring regions, highlighting research gaps and identifying priority research and conservation action. We conducted a systematic literature review of primate studies from 1976 to 2016 in Guinea-Bissau, southern Senegal and western Guinea (Boké Region). We mapped historical observation records of chimpanzee (Pan troglodytes verus), Temminck's red colobus (Pilicolobus badius temminckii) and king colobus (Colobus polykomos), including our preliminary survey data from Dulombi, a newly established National Park (NP) in Guinea-Bissau. We found 151 documents, including 87 journal articles, that contained field data on primates in this region. In Guinea-Bissau, nearly all studies focussed south of the Corubal River, including mainly Cantanhez, Cufada, and Boé NP's. In Senegal, most of the data came from Fongoli and Niokolo-Koba NP. In Boké (Guinea) studies are few, with the most recent data coming from Sangarédi. In Dulombi NP we recorded eight primate species, including chimpanzees, red colobus and king colobus. Across the selected region, chimpanzees, red colobus and king colobus were reported in eleven, twelve and seven protected areas, respectively. Our study demonstrates large geographical research gaps particularly for the two colobines. For the first time after more than two decades, we confirm the presence of red colobus and king colobus north of the Corubal River in Guinea-Bissau. The little information available from large parts of the red colobus range raises questions regarding levels of population fragmentation in this species, particularly in Casamance and across northern Guinea-Bissau. There are still no records demonstrating the occurrence of king colobus in Senegal, and the presence of a viable population in north-eastern Guinea-Bissau remains uncertain. While the occurrence of chimpanzees in Guinea-Bissau and Senegal is well documented, data from Boké (Guinea) are sparse and out-of-date. Our approach-the mapping of data gathered from a systematic literature review-allows us to provide recommendations for selecting future geographical survey locations and planning further research and conservation strategies in this region.


Inflammatory and antimicrobial properties differ between vaginal Lactobacillus isolates from South African women with non-optimal versus optimal microbiota.
Female genital tract (FGT) inflammation increases HIV infection susceptibility. Non-optimal cervicovaginal microbiota, characterized by depletion of Lactobacillus species and increased bacterial diversity, is associated with increased FGT cytokine production. Lactobacillus species may protect against HIV partly by reducing FGT inflammation. We isolated 80 lactobacilli from South African women with non-optimal (Nugent 4-10; n = 18) and optimal microbiota (Nugent 0-3; n = 14). Cytokine production by vaginal epithelial cells in response to lactobacilli in the presence and absence of Gardnerella vaginalis was measured using Luminex. Adhesion to vaginal epithelial cells, pH, D/L-lactate production and lactate dehydrogenase relative abundance were assessed. Lactobacilli from women with non-optimal produced less lactic acid and induced greater inflammatory cytokine production than those from women with optimal microbiota, with IL-6, IL-8, IL-1α, IL-1β and MIP-1α/β production significantly elevated. Overall, lactobacilli suppressed IL-6 (adjusted p < 0.001) and IL-8 (adjusted p = 0.0170) responses to G. vaginalis. Cytokine responses to the lactobacilli were inversely associated with lactobacilli adhesion to epithelial cells and D-lactate dehydrogenase relative abundance. Thus, while cervicovaginal lactobacilli reduced the production of the majority of inflammatory cytokines in response to G. vaginalis, isolates from women with non-optimal microbiota were more inflammatory and produced less lactic acid than isolates from women with optimal microbiota.


Isolation of mutants of Hansenula polymorpha defective in the assembly of octameric alcohol oxidase.
Alcohol oxidase (AO) is a peroxisomal enzyme that catalyses the first step in methanol metabolism in yeast. Monomeric, inactive AO protein is synthesised in the cytosol and subsequently imported into peroxisomes, where the enzymatically active, homo-octameric form is found. The mechanisms involved in AO octamer assembly are largely unclear. Here we describe the isolation of Hansenula polymorpha mutants specifically affected in AO assembly. These mutants are unable to grow on methanol and display reduced AO activities. Based on their phenotypes, three major classes of mutants were isolated. Three additional mutants were isolated that each displayed a unique phenotype. Complementation analysis revealed that the isolated AO assembly mutants belonged to 10 complementation groups.


Radiation-induced lung injury. Assessment, management, and prevention.
Radiation therapy (RT) is an important treatment modality for multiple thoracic malignancies. Incidental irradiation of the lungs, which are particularly susceptible to injury, is unavoidable and often dose-limiting. The most radiosensitive subunit of the lung is the alveolar/capillary complex, and RT-induced lung injury is often described as diffuse alveolar damage. Reactive oxygen species generated by RT are directly toxic to parenchymal cells and initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating a self-sustaining cycle of inflammation and chronic oxidative stress. Replacement of normal lung parenchyma by fibrosis is the culminating event. Depending on the dose and volume of lung irradiated, acute radiation pneumonitis may develop, characterized by dry cough and dyspnea. Fibrosis of the lung, which can also cause dyspnea, is the late complication. Imaging studies and pulmonary function tests can be used to quantify the extent of lung injury. While strict dose-volume constraints to minimize the risk of injury are difficult to impose, substantial data support some general guidelines. New modalities such as intensity-modulated radiation therapy and stereotactic body radiation therapy provide new treatment options but also pose new challenges in safely delivering thoracic RT.


Challenges in diagnosis, treatment and follow-up of patients presenting with central nervous system infections in a resource-limited setting.
Central Nervous System (CNS) infections are associated with significant mortality and morbidity. Accurate diagnosis is necessary for prompt treatment and increased chances of survival. However, there are many challenges to correct diagnoses in resource-limited settings, including the HIV epidemic, late presentation of symptomatic individuals, limited availability of laboratory diagnostic tests as well as treatment, and inadequate access to funds accompanied by lack of financial support from developed countries. This article presents case reports of patients admitted to the Mulago Hospital in Kampala, Uganda that exemplify challenging diagnoses of tuberculous meningitis (TBM), cryptococcal meningitis (CM), toxoplasmosis, and primary CNS lymphoma (PCNSL). Also included is a literature review of the pathology, diagnosis, and treatment of TBM, CM, toxoplasmosis, and PCNSL in immunocompromised patients.


The Theobroma cacao B3 domain transcription factor TcLEC2 plays a duel role in control of embryo development and maturation.
The Arabidopsis thaliana LEC2 gene encodes a B3 domain transcription factor, which plays critical roles during both zygotic and somatic embryogenesis. LEC2 exerts significant impacts on determining embryogenic potential and various metabolic processes through a complicated genetic regulatory network. An ortholog of the Arabidopsis Leafy Cotyledon 2 gene (AtLEC2) was characterized in Theobroma cacao (TcLEC2). TcLEC2 encodes a B3 domain transcription factor preferentially expressed during early and late zygotic embryo development. The expression of TcLEC2 was higher in dedifferentiated cells competent for somatic embryogenesis (embryogenic calli), compared to non-embryogenic calli. Transient overexpression of TcLEC2 in immature zygotic embryos resulted in changes in gene expression profiles and fatty acid composition. Ectopic expression of TcLEC2 in cacao leaves changed the expression levels of several seed related genes. The overexpression of TcLEC2 in cacao explants greatly increased the frequency of regeneration of stably transformed somatic embryos. TcLEC2 overexpressing cotyledon explants exhibited a very high level of embryogenic competency and when cultured on hormone free medium, exhibited an iterative embryogenic chain-reaction. Our study revealed essential roles of TcLEC2 during both zygotic and somatic embryo development. Collectively, our evidence supports the conclusion that TcLEC2 is a functional ortholog of AtLEC2 and that it is involved in similar genetic regulatory networks during cacao somatic embryogenesis. To our knowledge, this is the first detailed report of the functional analysis of a LEC2 ortholog in a species other then Arabidopsis. TcLEC2 could potentially be used as a biomarker for the improvement of the SE process and screen for elite varieties in cacao germplasm.


Patients With Inflammatory Bowel Diseases Are at Higher Risk for Meningitis.
The epidemiology of meningitis is unknown in inflammatory bowel disease (IBD) patients. We aimed to determine the incidence of and risk factors for meningitis in IBD patients. We conducted a retrospective cohort and nested case-control study in the Quintiles IMS Legacy PharMetrics Adjudicated Claims Database from January 2001 to June 2016. We matched IBD patients to those without IBD on age, sex, enrollment, and region. Meningitis was defined as one code for meningitis associated with an emergency department visit or hospitalization. Meningitis risk was calculated with incidence rate ratios. In a nested case-control study of IBD patients, predictors for meningitis were determined with multivariable conditional logistic regression models. We identified 50,029 patients with Crohn's disease (CD) and 59,830 patients with ulcerative colitis (UC) matched to 296,801 non-IBD comparators. There were 85 CD patients, 77 UC patients, and 235 comparators with meningitis. CD patients had 2.17 times the rate of meningitis and UC patients had 1.63 times the rate of meningitis as non-IBD comparators. After adjusting for relevant covariates among those with IBD, treatment with mesalamine was associated with a significantly lower odds of a meningitis claim (odds ratio: 0.40, 95% confidence interval: 0.26-0.62). Having at least one comorbidity was associated with a significantly higher odds of a meningitis claim (odds ratio: 2.21, 95% confidence interval: 1.76-2.77). Although the overall rate of meningitis is low, IBD patients are at an increased risk compared with non-IBD comparators. Comorbidities are a risk factor for meningitis in IBD patients. Pneumococcal and meningococcal vaccinations should be discussed.


Contractures induced by reversed Na+/Ca2+ exchange in rat portal vein: effects of calcium antagonists.
Spontaneous electrical and mechanical activity was abolished in isolated preparations of rat portal vein by exposure to K+-free Krebs solution. This procedure probably also increased the intracellular [Na+] owing to interference with the active transmembrane Na+-K+ transport. Contractures could be induced under these conditions by lowering extracellular [Na+] from the control level of 144 to 17 mM using sucrose, TrisCl, or LiCl as NaCl substitutes. Contractile force depended on the type of substitute: sucrose greater than TrisCl greater than LiCl. These contractures are thought to be caused by influx of extracellular Ca2+ through the Na+/Ca2+ exchanger, which otherwise transports Ca2+ in the opposite direction at normal transmembrane Na+ gradient. The contractile response to low Na+ was rapidly and completely abolished in nominally Ca2+-free medium; it was strongly inhibited by 0.4 mM MnCl2 but was not affected by high concentrations of the organic calcium antagonists, felodipine (10(-6) M), verapamil (10(-5) M), or diltiazem (10(-5) M). We conclude that the Na+/Ca2+-exchanger is an effective pathway for Ca2+ transport over vascular smooth muscle cell membrane; this pathway is not blocked by calcium antagonists.


Dietary Interventions for Gastroparesis: A Systematic Review.
Gastroparesis (Gp) is a delay in gastric emptying in the absence of a mechanical obstruction and has the capacity to cause symptoms that significantly impact a patient's quality of life. Dietary interventions are the first-line treatment in Gp, but the efficacy of different diets is unclear. This systematic review seeks to determine the effectiveness of dietary interventions on clinical outcomes in Gp. A literature search of MEDLINE Ovid from 1 March 2008 to 1 October 2021 was conducted to identify randomized controlled trials, cohort studies, and cross-sectional studies that reported dietary interventions in Gp. From the initial search, 2789 studies resulted. These were assessed by 2 independent reviewers and selected based on the primary outcomes of interest: changes in symptom-specific patient-reported outcomes and changes in gastric emptying time. A third reviewer resolved any discrepancies. Six adult studies (185 subjects) met the inclusion criteria, whereas no pediatric study did. Five of the included studies were randomized controlled trials and one was an observational study. The systematic review suggested low-fat diets, small-particle diets, diets with isoflavones, and foods considered bland, starchy, sweet, and salty did not exacerbate Gp symptoms. Small-particle diets and diets with isoflavones were found to improve gastric emptying time in patients. Additionally, small-particle diets were shown to reduce anxiety in comparison to large-particle diets. Of the randomized controlled trials, 80% were low risk of bias and 20% were fair risk of bias. The observational study was considered fair quality. The data presented in this review suggest specific dietary interventions could potentially improve Gp symptoms and gastric emptying in adult patients, particularly low-fat and small-particle diets. For pediatric Gp, data are lacking. The limited data available highlights a critical gap in the literature.


Gender differences in the historical trauma response among the Lakota.
The historical trauma response is a constellation of characteristics associated with massive cumulative group trauma across generations, similar to those found among Jewish Holocaust survivors and descendants. Trauma response features include elevated mortality rates and health problems emanating from heart disease, hypertension, alcohol abuse, and suicidal behavior. This article explores gender differences in the historical trauma response among the Lakota (Teton Sioux) and the correlation with health and mental health statistics. The theory of a Lakota historical trauma response is first explained. Traditional gender roles are described in combination with modifications engendered by traumatic Lakota history. Then, data from a study on Lakota historical trauma are presented, including gender differences in response to an experimental intervention aimed at facilitating a trauma resolution process. The data revealed significant gender differences. The sample of women presented initially with a greater degree of conscious affective experience of historical trauma. In contrast, the men reported more lifespan trauma associated with boarding school attendance and appeared to be at an earlier stage of grief. However, at the end of the intervention, women's experience of survivor guilt--a significant trauma response feature-decreased while men's consciousness of historical trauma and unresolved grief increased. Degree of traditional presentation-of-self, including phenotype, appeared to interact with gender to place male participants at greater risk for being traumatized over the lifespan and perhaps subsequently utilizing more rigid defenses against the conscious experience of the trauma with the exception of survivor guilt. The article concludes with a discussion of health and mental health implications for prevention and treatment of the trauma response which could positively impact the health status of the Lakota. Recommendations for future research are suggested.


Analysis of Consumers' Preferences and Price Sensitivity to Native Chickens.
This study analyzed consumers' preferences and price sensitivity to native chickens. A survey was conducted from Jan 6 to 17, 2014, and data were collected from consumers (n=500) living in Korea. Statistical analyses evaluated the consumption patterns of native chickens, preference marketing for native chicken breeds which will be newly developed, and price sensitivity measurement (PSM). Of the subjects who preferred broilers, 24.3% do not purchase native chickens because of the dryness and tough texture, while those who preferred native chickens liked their chewy texture (38.2%). Of the total subjects, 38.2% preferred fried native chickens (38.2%) for processed food, 38.4% preferred direct sales for native chicken distribution, 51.0% preferred native chickens to be slaughtered in specialty stores, and 32.4% wanted easy access to native chickens. Additionally, the price stress range (PSR) was 50 won and the point of marginal cheapness (PMC) and point of marginal expensiveness (PME) were 6,980 won and 12,300 won, respectively. Evaluation of the segmentation market revealed that consumers who prefer broiler to native chicken breeds were more sensitive to the chicken price. To accelerate the consumption of newly developed native chicken meat, it is necessary to develop a texture that each consumer needs, to increase the accessibility of native chickens, and to have diverse menus and recipes as well as reasonable pricing for native chickens.


Emergence of Fermi's Golden Rule.
Fermi's golden rule applies in the limit where an initial quantum state is weakly coupled to a continuum of other final states overlapping its energy. Here we investigate what happens away from this limit, where the set of final states is discrete, with a nonzero mean level spacing; this question arises in a number of recently investigated many-body systems. For different symmetry classes, we analytically and/or numerically calculate the universal crossovers in the average decay of the initial state as the level spacing is varied, with the golden rule emerging in the limit of a continuum. Among the corrections to the exponential decay of the initial state given by Fermi's golden rule is the appearance of the spectral form factor in the longtime regime for small but nonzero level spacing.


Rab35 is translocated from Arf6-positive perinuclear recycling endosomes to neurite tips during neurite outgrowth.
Small GTPase Rab35 is a key regulator of neurite outgrowth, and its activation dramatically enhances nerve growth factor (NGF)-induced neurite outgrowth. We recently reported finding that Rab35 and its effector molecules recruit EHD1, a facilitator of vesicle formation, to Arf6-positive perinuclear recycling endosomes (hereafter simply referred to as recycling endosomes) in response to NGF stimulation. Although Rab35 is likely to promote the formation of transport vesicles from recycling endosomes that contributes to neurite outgrowth, the destination of the vesicles during neurite outgrowth remains unknown. Here we report finding that Rab35 is translocated from recycling endosomes to neurite tips in a late phase of NGF stimulation. We found that Rab35 immunofluorescence signals accumulated at recycling endosomes during the first 6 h, i.e., the early phase of NGF stimulation and then translocated to neurite tips during the late phase of NGF stimulation (i.e., >6 h to <36 h after NGF stimulation). These findings suggest that Rab35 regulates membrane trafficking from recycling endosomes to neurite tips during neurite outgrowth.


Accuracy of cardiac function and volume status estimates using the bedside echocardiographic assessment in trauma/critical care.
Critically ill patients often require invasive monitoring to evaluate and optimize cardiac function and preload. With questionable outcomes associated with pulmonary artery catheters (PACs), some have evaluated the role of less invasive monitors. We hypothesized that the Bedside Echocardiographic Assessment in Trauma (BEAT) examination would generate cardiac index (CI) and central venous pressure (CVP) estimates that correlate with that of a PAC. BEAT was performed on all SICU patients with a PAC in place. Prospective data included stroke volume and the inferior vena cava (IVC) diameter. The CI was calculated and correlated with that from the PAC. Each CI was then categorized as low, normal, or high. The IVC diameter was used to estimate the CVP. The association between the BEAT and PAC estimates of CI and CVP was evaluated using chi. Eighty-five BEAT examinations were performed, 57% on trauma and 37% on general surgery patients. Fifty-nine percent of the CI examinations and 97% of the IVC examinations contained quality images. Of these, the overall correlation coefficient was 0.70 (p < 0.0001). When CI was categorized, there was a significant association between the BEAT and PAC (p = 0.021). There was a significant association between the CVP estimate from the BEAT examination and the PAC (p = 0.031). Our data show a significant correlation between the CI and CVP estimates obtained from the BEAT examination and that from a PAC. BEAT provides a noninvasive method of evaluating cardiac function and volume status. Bedside echocardiography is teachable and should become a part of future critical care curricula.


Isolation, characterization and chromosomal localization of cDNA clones for the E1 beta subunit of the pyruvate dehydrogenase complex.
A full-length cDNA clone for the E1 beta subunit of the human pyruvate dehydrogenase (PyrDH) complex was isolated from a human skin fibroblast cDNA library. When sequenced, it showed differences from the nucleotide sequence already published [Koike, K., Ohta, S., Urata, Y., Kagawa, Y. & Koike, M. (1988) Proc. Natl Acad. Sci. USA 85, 41-45], such that 19 amino acids were different in the translated open reading frame. Northern blotting of human fibroblast cell lines revealed a major mRNA species of 1.6 kb and a weaker band of 5.5 kb. In a series of nine PyrDH-complex-deficient cell lines from patients with this deficiency, no patients had severely reduced amounts of mRNA, but there was one patient cell line with an increased amount of abnormal-size mRNA. Chromosome localization carried out with DNA blots from man-mouse hybrid cell lines indicated that the E1 beta subunit of pyruvate dehydrogenase is located on chromosome 3. A motif AXGXXXXGL(R/K)X15(D/E)Q was found in common with a variety of other oxo-acid oxidoreductases, but its function is not known.


Modulation of endothelial cell functions by different molecular species of interleukin 1.
Different molecular species of interleukin 1 (IL 1) were examined for the spectrum of responses elicited in human endothelial cells (HEC), including synthesis of prostacyclin (PGI2), tissue-type procoagulant activity (PCA), platelet activating factor (PAF), and plasminogen activator inhibitor (PA-I). The IL 1 preparations utilized for the present study included a natural, partially purified IL 1, a preparation purified to homogeneity with extensive homology with the derived aminoacid IL 1 beta (pI7) sequence denominated "22K factor," murine recombinant IL 1 alpha, human recombinant IL 1 alpha (pI5) and beta (pI7). Natural, partially purified IL 1, a mixture of alpha and beta species, induced the entire spectrum of responses in HEC. Production of PA-I was elicited by all forms of IL 1 tested. PGI2 and PCA were elicited by "22K factor" and by human recombinant IL 1 beta and alpha but not by murine recombinant IL 1 alpha. PAF synthesis was stimulated by murine and human recombinant IL 1 alpha but not by human recombinant IL 1 beta and 22K factor. Thus the available different molecular forms of IL 1 elicit largely but not completely overlapping patterns of responses in HEC. The IL 1 pathway of regulation of HEC functions might provide a basis for novel strategies in therapeutically oriented research on vessel wall disorders.


A focus group study of veterinarians' and pet owners' perceptions of veterinarian-client communication in companion animal practice.
To compare veterinarians' and pet owners' perceptions of client expectations with respect to veterinarian-client communication and to identify related barriers and challenges to communication. Qualitative study based on focus group interviews. 6 pet owner focus groups (32 owners) and 4 veterinarian focus groups (24 companion animal veterinarians). Independent focus group sessions were conducted with standardized open-ended questions and follow-up probes. Content analysis was performed on transcripts of the focus group discussions. Five themes related to veterinarian-client communication were identified: educating clients (ie, explaining important information, providing information up front, and providing information in various forms), providing choices (ie, providing pet owners with a range of options, being respectful of owners' decisions, and working in partnership with owners), using 2-way communication (ie, using language clients understand, listening to what clients have to say, and asking the right questions), breakdowns in communication that affected the client's experience (ie, owners feeling misinformed, that they had not been given all options, and that their concerns had not been heard), and challenges veterinarians encountered when communicating with clients (ie, monetary concerns, client misinformation, involvement of > 1 client, and time limitations). Results suggested that several factors are involved in providing effective veterinarian-client communication and that breakdowns in communication can have an adverse effect on the veterinarian-client relationship.


Synbiotic formulation of probiotic and lactulose combination for hepatic encephalopathy treatment: a realistic hope?
Gut-produced ammonia plays a vital role in the pathogenesis of hepatic encephalopathy because cirrhotic liver fails to clear toxic metabolites. Small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhosis add to the pathogenesis. Lactulose is a mainstay in the treatment of hepatic encephalopathy. Another benefit of lactulose is its prebiotic effect on probiotics that reduce the activity of bacterial urease, resulting in decreased hyperammoneamia and increased elimination of ammonia and other nitrogenous waste through enteric toxin reduction technology. Synbiotic formulation of probiotic and lactulose can synergistically/additively reduce ammonia production, increase utilization and excretion of ammonia and other nitrogenous wastes, thereby improving the well-being of patients with hepatic encephalopathy. We hypothesize that oral administration of a synbiotic formulation prepared from a combination of selected microbial strains of probiotics and lactulose will offer additional protection against hepatic encephalopathy via intra-intestinal extraction of toxic solutes in patients with cirrhosis.


Migraine--treatment of acute attack.
The treatment of an acute attack of classical or common migraine is sleep, an antinauseant such as metoclopramide, an analgesic, either aspirin or paracetamol, and in some patients 1 or 2 mg of ergotamine tartrate. Treatment should be given as early in the attack as possible and all drugs should, if possible, be given in a soluble or effervescent form. When vomiting occurs early in the attack, treatment is best given by suppository, inhalation or intramuscular injection. Ergotamine tartrate is only necessary in about one third of attacks and when used is best given by suppository or inhalation. Doses of ergotamine tartrate higher than 2 mg per attack or 6 mgs per week may cause toxic symptoms as may the abuse of analgesics.


Large indoor cage study of the suppression of stable Aedes aegypti populations by the release of thiotepa-sterilised males.
The sterile insect technique (SIT) is a promising pest control method in terms of efficacy and environmental compatibility. In this study, we determined the efficacy of thiotepa-sterilised males in reducing the target Aedes aegypti populations. Treated male pupae were released weekly into large laboratory cages at a constant ratio of either 5:1 or 2:1 sterile-to-fertile males. A two-to-one release ratio reduced the hatch rate of eggs laid in the cage by approximately a third and reduced the adult catch rate by approximately a quarter, but a 5:1 release drove the population to elimination after 15 weeks of release. These results indicate that thiotepa exposure is an effective means of sterilising Ae. aegypti and males thus treated are able to reduce the reproductive capacity of a stable population under laboratory conditions. Further testing of the method in semi-field enclosures is required to evaluate the mating competitiveness of sterile males when exposed to natural environmental conditions. If proven effective, SIT using thiotepa-sterilised males may be incorporated into an integrated programme of vector control to combat dengue in Cuba.


Metabolomic and ecdysteroid variations in Anopheles gambiae s.l. mosquitoes exposed to the stressful conditions of the dry season in Burkina Faso, West Africa.
This study explored the metabolic adjustments prompted by a switch between the rainy and dry season conditions in the African malaria mosquitoes Anopheles gambiae (M and S molecular forms) and Anopheles arabiensis. Mosquitoes were reared in contrasted experimental conditions reflecting environmental variation in Burkina Faso. Thirty-five metabolites (including sugars, polyols, and amino acids) were monitored in newly emerged males and females, and their ecdysteroid titers were determined. Metabolomic signatures were remarkably similar across species, when specimens of same age and sex were reared under identical experimental conditions. In males and females, amino acids (including glycine, leucine, phenylanine, serine, threonine, and valine) were accumulated in 1-h-old mosquitoes, then decreased 24 h after emergence, probably reflecting adult maturation and the amino acid-consuming process of cuticle sclerotisation. In turn, elevated amounts of alanine and proline in 24-h-old mosquitoes may assist the development of flight ability. Lower concentration of tricarboxylic acid cycle intermediates and isoleucine characterized older females reared under dry season conditions, suggesting metabolic and reproduction depression. In all cases, ecdysteroid concentration was much higher in males than in females, with significant seasonal variation in males. This might reflect a unique role of these hormones in shaping reproductive strategies and population demography in the An. gambiae s.l. species complex, further contributing to local adaptation in a highly fluctuating environment.


Glucose intolerance, hyperinsulinaemia and cognitive function in a general population of elderly men.
Cognitive impairment is highly prevalent among the elderly. Subjects with disturbed glucose metabolism may be at risk of impaired cognitive function, as these disturbances can influence cognition through atherosclerosis, thrombosis and hypertension. We therefore studied the cross-sectional association of cognitive function with hyperinsulinaemia, impaired glucose tolerance and diabetes mellitus in a population-based cohort of 462 men aged 69 to 89 years. Cognitive function was measured by the 30-point Mini-Mental State Examination. Results were expressed as the rate ratio (95% confidence interval) of the number of erroneous answers given on the Mini-Mental State Examination by the index compared to the reference group. Compared to subjects with normal glucose tolerance, known diabetic patients had a rate ratio of 1.23 (1.04-1.46), newly-diagnosed diabetic patients of 1.16 (0.91-1.48) and subjects with impaired glucose tolerance of 1.18 (0.98-1.41), after adjustment for confounding due to age, occupation and cigarette smoking (p-trend = 0.01). Non-diabetic subjects in the highest compared to the lowest quartile of the area under the insulin curve had a rate ratio of 1.24 (1.03-1.50), after adjustment for confounding (p-trend = 0.02). The results did not change appreciably when potentially mediating factors, including cardiovascular diseases and risk factors associated with the insulin resistance syndrome, were taken into account. These results suggest that diabetes, as well as impaired glucose tolerance and hyperinsulinaemia in non-diabetic subjects are associated with cognitive impairment.


Gastrotomy closure with the lock-it system and the Padlock-G clip: a survival study in a porcine model.
The success of natural orifice surgery depends on secure closure of the transmural gut opening, so a rapid, secure, and easy-to-place closure method is desirable. Our aim was to determine whether a gastrotomy can be closed safely and effectively from within the stomach in a survival model by using a novel, endoscopically placed device: the Padlock-G system. This was a pilot study of 4 survival animals in an animal laboratory setting. Gastrotomies were made in the stomachs of laboratory swine, and the abdomen was explored by using a standard gastroscope. Gastrotomies were then closed by using the Padlock-G system. Survival for 2 or 6 weeks was the primary outcome measurement. Secondary outcomes included ease of use, visual assessment of closure integrity immediately and at necropsy, presence of adhesions, evidence of infection, and histologic appearance at the closure sites. All animals thrived, ate normally, and gained weight. None developed fever, tachycardia, or signs of peritoneal irritation. Closure-site inspection at necropsy revealed excellent healing, with epithelial growth over the Padlock-G. There were no ulcers, serosal surfaces were tightly closed, and no defects could be seen. There were no signs of peritoneal inflammation, intra-abdominal adhesions, or gastric spillage. Histologic evaluation showed organizing granulation tissue with fibrosis, vascular proliferation, and mild chronic inflammatory infiltrate (i.e., scar). The Padlock-G is easy to place, provides a durable closure, and allows survival animals to thrive without adverse sequellae. This device provides a suitable closure system for transgastric NOTES.


The platelets' perspective to pathogen reduction technologies.
A wide variety of clinical conditions, associated with low circulating platelet counts, require platelet transfusion in order to normalize hemostatic function. Although single-donor apheresis platelets bear the lowest risk of transfusion-transmitted infections, pathogen reduction technologies (PRT) are being implemented worldwide to reduce this risk further through inactivation of known, emergent and as yet to be discovered nucleic acid-based pathogens. Human blood platelets are now known to harbor a diverse transcriptome, important to their function and comprised of >5000 protein-coding messenger RNAs and different classes of non-coding RNAs, including microRNAs. Our appreciation of the nucleic acid-dependent functions of platelets is likely to increase. On the other hand, the side effects of PRT on platelet function are underappreciated. Recent evidences suggest that PRT may compromise platelets' responsiveness to agonists, and induce platelet activation. For instance, platelets have the propensity to release proinflammatory microparticles (MPs) upon activation, and the possibility that PRT may enhance the production of platelet MPs in platelet concentrates (PCs) appears likely. With this in mind, it would be timely and appropriate to investigate other means to inactivate pathogens more specifically, or to modify the currently available PRT so to better preserve the platelet function and improve the safety of PCs; platelets' perspective to PRT deserves to be considered.


Finite amplitude distortion-based inhomogeneous pulse echo ultrasonic imaging.
Ultrasonic pulse echo imaging in inhomogeneous media suffers from significant lateral and contrast resolution losses due to the defocusing effects of the inhomogeneities. The losses in lateral and contrast resolution are associated with increases in the width of the mainbeam and increases in sidelobe levels, respectively. These two forms of resolution loss represent significant hurdles to improving the clinical utility of biomedical ultrasonic imaging. A number of research efforts are currently under way to investigate the defocusing effects of tissue and to consider corrective measures. All of these efforts assume linear propagation, and base the image-formation process on the reception of the transmitted pulse. A novel pulse echo imaging scheme in which the image is formed using the finite amplitude distortion components of the received pulse is considered here. Alternatively, this could be described as image formation using the nonlinearly-generated higher harmonics. In homogeneous beam propagations, it has been established that the sidelobes of nonlinearly-generated higher harmonics are much lower than their linear counterparts. Computations considered here suggest that this relationship also holds for the case of propagations through abdominal wall and breast wall tissue. These computations also suggest that the lateral resolution limits imposed by abdominal wall and breast wall tissue are slightly smaller for nonlinearly-generated second harmonics than for their linear counterparts. The resulting potential of these higher harmonics to improve image resolution is investigated.


Cytosolic localization of Fox proteins in motor neurons of G93A SOD1 mice.
NeuN is a nuclear protein expressed exclusively in mature neurons and has served for many years as a reliable neuronal marker in immunohistochemical labeling studies. In 2009, NeuN was identified as Fox3, one of three closely related RNA binding proteins important in pre-mRNA splicing. During the course of a previous study using G93A SOD1 mice, a model of amyotrophic lateral sclerosis (ALS), we observed that NeuN was significantly redistributed to the cytosol. Since altered splicing may be important in the pathogenesis of ALS, we compared the localization (predominantly nuclear or cytosolic) of all three Fox proteins in the lumbar spinal cord of wild-type and G93A SOD1 mice before and after the development of clinical signs of disease. The Fox proteins regulate their own splicing, and we also examined the major Fox protein isoforms in nuclear and cytosolic fractions of lumbar spinal cord by Western blotting. We report here that Fox3 and Fox2 undergo a major cytosolic relocalization in this ALS model that increases with age and that is associated with progressive alterations in the splicing profiles of all three Fox proteins.


Glomus tumor of uncertain malignant potential of the brachial plexus: A case report.
Glomus tumor is an uncommon benign tumor usually presenting with a small mass occurring in the dermis or soft tissue of an extremity, especially subungual region. However, intraneural glomus tumor is sporadic. While most of the glomus tumors are benign, atypical glomus tumors with unusual features can be occasionally found, leading to distinctive malignant potential required different therapeutic approaches. Glomus tumor of uncertain malignant potential is one type of atypical glomus tumor with limited criteria for malignancy and without metastasis. Herein, we report a case of a 48-year-old Thai male with a large painful mass in his axilla for one year without apparent neurological deficit. Magnetic resonance imaging showed a large heterogeneous mass encasing entire posterior cord of left brachial plexus and axillary artery. The tumor tissue from core needle biopsy histologically demonstrated the sheets and cords of relatively uniform tumor cells with foamy cytoplasm and round to oval hyperchromatic nuclei without atypia. The mitotic count was 0 per 50 high power field. A final diagnosis of glomus tumor of uncertain malignant potential was rendered. Complete surgical resection was performed, followed by adjuvant radiation due to positive margin. Neither local recurrence nor distant metastasis was observed at 2-year follow up. Unfortunately, postoperative incomplete brachial plexopathy without signs of re-innervation by electromyography was persisted. Later nerve grafting reconstruction was performed, followed by ongoing neurological rehabilitation. Glomus tumor of uncertain malignant potential is exceedingly rare, especially around brachial plexus. Although the prognosis is good, careful histological diagnosis and treatment are needed to achieve an optimal outcome with lower morbidity.


Secretion and mammary gland uptake of prolactin in dairy cows during lactogenesis.
Mammary arteriovenous differences of prolactin concentration and net mammary uptake of prolactin from blood were quantified near parturition in 9 dairy cows. Six cows were milked once daily for at least 6 d before parturition, and prepartum lactogenesis occurred in 3 of 6 cows. Prepartum milking 2 or more d before parturition abruptly increased secretion of prolactin into blood, but milkings within 1 d before or after parturition did not increase prolactin secretion. Concentrations of prolactin in whole milk sampled over 8 d before parturition (64.5 ng/ml) were substantially greater than those occurring several days after parturition (19 ng/ml). Milk prolactin concentrations were unaffected by the successful induction of prepartum lactogenesis, which greatly increased prepartum yields of milk (2 to 8 kg/milking). Therefore, the alveolar lumenal content of prolactin was greatest in pregnant cows with prepartum lactogenesis. This enhanced content of intraalveolar prolactin before parturition was associated with an absence of mammary uptake of prolactin immediately prior to ejection of the prolactin-containing milk from the alveoli. However, prolactin uptake was quickly restored to about 2 micrograms/min per half udder shortly after milk ejection. During the prepartum period, an enhanced intraalveolar reservoir of 200 to 400 micrograms prolactin, due to induction of prepartum lactogenesis, appears to saturate temporarily all putative sites for uptake of prolactin from blood.


Mechanism of T5-induced DNA polymerase. I. Replication of short primer templates.
Bacteriophage T5-induced DNA polymerase shows an initial phase of rapid synthesis, followed by a slower steady rate for much longer periods, with short DNA primer-templates (400 to 600 nucleotides long), in vitro. On extrapolating the line of steady rate back to 0 min, an intercept is obtained on the ordinate. With large DNA primer-templates, such as denatured T5 DNA (average chain length approximately 50,000 bases), the rate of synthesis remains constant and is equal to the initial rate obtained with short primer-templates. The zero time intercept was proportional to the amount of enzyme used and independent of temperature. Polymer challenge experiments indicate that the initial phase of rapid synthesis can be attributed to the processive mode of synthesis by T5 DNA polymerase. After synthesizing a stretch of DNA processively for about 200 nucleotide residues, the enzyme apparently forms a "dead-end complex" with the primer-templates used and must dissociate from the primer-template in order to resume synthesis. The average size of the product made processively, during various phase of synthesis, remains invariant and is in good agreement with the size of the zero time intercept per enzyme molecule.


Tudor domains bind symmetrical dimethylated arginines.
The Tudor domain is an approximately 60-amino acid structure motif in search of a function. Herein we show that the Tudor domains of the spinal muscular atrophy gene product SMN, the splicing factor 30 kDa (SPF30), and the Tudor domain-containing 3 (TDRD3) proteins interacted with arginine-glycine-rich motifs in a methylarginine-dependent manner. The Tudor domains also associated with methylarginine-containing cellular proteins, providing evidence that methylated arginines represent physiological ligands for this protein module. In addition, we report that spliceosomal small nuclear ribonucleoprotein particles core Sm proteins accumulated in the cytoplasm when arginine methylation was inhibited with adenosine dialdehyde or in the presence of an excessive amount of unmethylated arginine-glycine-rich peptides. These data provide in vivo evidence in support of a role for arginine methylation in the proper assembly and localization of spliceosomal Sm proteins.


Latency type-specific distribution of epigenetic marks at the alternative promoters Cp and Qp of Epstein-Barr virus.
Transcripts for the Epstein-Barr virus (EBV)-encoded nuclear antigens are initiated at the alternative promoters Wp, Cp and Qp. Although the host cell-dependent activity of Cp is regulated by DNA methylation, Qp is unmethylated independently of its activity. Because histone modifications affect the chromatin structure, we compared the levels of diacetylated histone H3, tetraacetylated histone H4 and histone H3 dimethylated on lysine 4 (H3K4me2) at Cp and Qp, in well characterized cell lines representing the major EBV latency types. We found an activity-dependent histone code: acetylated histones marked active Cp, whereas active Qp was selectively enriched both in acetylated histones and H3K4me2. We concluded that active (but not silent) Cp and Qp are located to 'acetylation islands' in latent, episomal EBV genomes, similar to the active chromatin domains of the human genome.


Stress-induced ATP release from and growth modulation of human lens and retinal pigment epithelial cells.
ATP release has been shown to occur following stimulation in several cellular systems. This study was undertaken to determine if lens and retinal epithelial cells release ATP in response to physiological stresses and to elucidate a possible role for ATP. Analysis of human aqueous humour samples showed a mean ATP level of 37.8+/-7.7 nM. Hyper-osmotic stress induced a dose- and time-dependent release of ATP. Both cell types were found to proliferate in serum-free medium, and the addition of ATP and adenosine at concentrations as low as 0.1 nM inhibited growth. Gene profiling also demonstrated the presence of the ectonucleotidases CD39 and CD73 and the A1 adenosine receptor on both cell types.


Experiences and problems pre-operative anti-CD20 monoclonal antibody infusion therapy with splenectomy and plasma exchange for ABO-incompatible living-donor liver transplantation.
ABO-incompatible living-donor liver transplantation (LDLT) requires a reduction of the anti-ABO antibody titer to <16 before transplantation, which is usually achieved by pre-operative plasma exchange (PE) or double-filtration plasmapheresis. ABO-incompatible transplantations have been performed after a splenectomy with heavy drug immunosupression plus B-cell-specific drugs. Here, we evaluated a pre-transplantation infusion protocol with an anti-CD20 monoclonal antibody (rituximab) for ABO-incompatible LDLT. Between March 2002 and December 2005, 73 adult patients underwent LDLT without retransplantation in our institution. Among these cases, 57 were ABO-identical, 11 were ABO-compatible and five were ABO-incompatible. The rituximab infusion protocol consisted of a weekly infusion of rituximab (375 mg/m(2)) for three wk, which was administered to three of the five ABO-incompatible LDLT patients. All three patients underwent a pre-operative PE, as well as a splenectomy during the operation. A triple immunosuppression protocol of tacrolimus, low-dose steroids and mycophenolate mofetil (1500 mg/d) was administered post-operatively. In addition, the patients received a continuous intra-arterial infusion of prostaglandin E(1) and methylprednisolone, and a continuous intra-portal infusion of a protease inhibitor for three and two wk after transplantation, respectively. After the first rituximab infusion, the peripheral blood CD19(+) B cell count rapidly decreased to <1%. All three patients treated with rituximab subsequently received an ABO-incompatible LDLT, with donor/recipient blood groups of B/O, A(1)/B and A(1)/O. In two cases, the ABO-antibody level transiently increased post-operatively, then decreased and remained low. Rituximab infusion therapy did not develop any direct side effect except for mild allergic reaction to the first infusion, but post-operatively all three patients suffered a cytomegalovirus and were successfully treated with ganciclovir, and one patient had a MRSA-positive intra-abdominal abscess. Two patients are currently alive at 20 and 18 months respectively, and show normal graft-liver function. But one patient died of sepsis because of intra-abdominal abscess. Although the protocol of rituximab administration is a conventional and safe regimen with no major side effects, the development of a new protocol is needed for prevention of the infection with bone suppression.


Aquatic insect community structure under the influence of small dams in a stream of the Mogi-Guaçu river basin, state of São Paulo.
The fragmentation of lotic systems caused by construction of dams has modified many aquatic communities. The objective of this study was to analyse changes in the aquatic insect community structure by discontinuity of habitat created by dams along the Ribeirão das Anhumas, a sub-basin of the Mogi-Guaçu River (state of São Paulo, Brazil). Entomofauna collection was carried out in 10 segments upstream and downstream of five dams along the longitudinal profile of the stream, with a quick sampling method using a D net (mesh 250 mm) with 2 minutes of sampling effort. The insects were sorted and identified to the lowest possible taxonomic level and analysed by the Shannon diversity index, β diversity, richness estimated by rarefaction curves and relative participation of functional feeding groups. The results showed a slight reduction in diversity in the downstream segments, as well as along the longitudinal profile of the stream. However, there were no significant differences in abundance and richness between the upstream and downstream segments, indicating that the dams did not influence these variables. Differences were observed in the functional feeding groups along the longitudinal profile. Predator and gatherer insects were dominant in all segments analysed. The feeding group of shredders was more abundant in the segment DSIII with the participation of Marilia Müller (Odontoceridae - Trichoptera), although we observed a decrease of shredders and scrapers with the decrease of the canopy cover reducing values of β diversity in the continuum of Ribeirão das Anhumas. This result demonstrated the importance of the conservation of the riparian vegetation in order to maintain the integrity of the stream.


[Characteristics of the perception and imagination of emotions in patients with focal brain pathology].
Voluntary components of the emotion perception were shown to be related to the left hemisphere temporal area in patients with focal lesions of postero-frontal and temporal areas of both hemispheres, whereas the involuntary components required involvement of the right hemisphere temporal area. The voluntary components of the emotion reproduction are associated with involvement of the left hemisphere postero-frontal area, whereas involuntary components of perception are related to work of the right hemisphere postero-frontal area. The data obtained suggest that the voluntary (conscious) recognition and reproduction of emotions are mainly related to the sensory and motor speech centres of the left hemisphere, whereas involuntary those involve symmetrical areas of the opposite hemisphere.