Increasing buprenorphine access for veterans with opioid use disorder in rural clinics using telemedicine.
Background:Having prescribers use clinical video teleconferencing (telemedicine) to prescribe buprenorphine to people with opioid use disorder (OUD) has shown promise but its implementation is challenging. We describe barriers, facilitators and lessons learned while implementing a system to remotely prescribe buprenorphine to Veterans in rural settings. Methods: We conducted a quality improvement project aimed at increasing the availability of medications for OUD (MOUD) to Veterans. This project focused on tele-prescribing buprenorphine to rural sites via a hub (centralized prescribers) and spoke (rural clinics) model. After soliciting a wide-range of inputs from site visits, qualitative interviews of key stakeholders at rural sites, and review of preliminary cases, a "how-to" toolkit was developed and iteratively refined to guide tele-prescribing of buprenorphine. After internal and external facilitation strategies were employed, Veterans with OUD at three clinics were transitioned to buprenorphine treatment via telemedicine. Results: Factors impacting adoption of the tele-prescribing intervention were mapped to the Consolidated Framework for Implementation Research (CFIR) constructs. Barriers to adoption included concerns about legality of tele-prescribing a controlled substance, conflicting interests between different stakeholders, and coordination with an existing buprenorphine program requiring more attendance and abstinence from Veterans than the tele-prescribing program required. Factors facilitating adoption included a sense of mission around combating the opioid epidemic, preexisting use of and comfort with tele-prescribing, and rural sites' control over Veterans referred to tele-prescribers. A total of 12 patients from rural areas were successfully transitioned onto buprenorphine, of whom 9 remained on buprenorphine 6 months after initiation of treatment. Conclusions: Implementing tele-prescribing was negotiated with stakeholders at the target clinics and operationalized in a toolkit to guide future efforts. Implementation issues can be addressed by activities that foster collaboration between hubs (centralized prescribers) and spokes (rural clinics) and by a toolkit that operationalizes tele-prescribing procedures.


Aerosol survival of Pasteurella tularensis and the influence of relative humidity.
The aerosol survival in air was determined for Pasteurella tularensis live vaccine strain (LVS) as a function of relative humidity (RH). Three different preparations of bacteria were used: (i) liquid suspension of P. tularensis LVS in spent culture medium; (ii) powders of P. tularensis LVS freeze-dried in spent culture fluid; (iii) P. tularensis LVS freeze-dried in spent culture fluid and then reconstituted with distilled water and disseminated as a liquid suspension. Preparation (i) gave greatest survival at high RH and lowest survival at intermediate RH. Preparation (ii), in contrast, gave greatest survival at low RH and minimum survival at 81% RH. Preparation (iii) was the same as preparation (i), i.e., the process of freeze-drying and reconstituting with distilled water before aerosol formation had little or no effect upon aerosol survival as a function of RH. Hence, control of aerosol survival appears to be through the water content of P. tularensis LVS at the moment of aerosol generation rather than the water content of the bacteria in the aerosol phase.


Emphysema quantification by combining percentage and size distribution of low-attenuation lung regions.
The purpose of this study was to investigate efficacy of two types of emphysema quantification: percentage of low-attenuation lung regions (%LA); and size distribution of these regions. On a log-log plot, cumulative frequency-size distribution of low-attenuation lung regions can be fitted by a straight line whose slope (D) has been reported to reflect diffusing capacity. In this study, %LA and D were compared with pulmonary function test (PFT) parameters, especially with ratio of diffusing capacity of carbon monoxide to effective alveolar ventilation (i.e., DLCO/VA). Thin-section unenhanced CT images were acquired from 30 patients (25 men, five women; mean [SD] age, 70.1 ± 12.1 years), of whom 25 had received diagnosis of COPD, and %LA and D were calculated at 20 thresholds, ranging from -995 to -900 HU. To determine utility of %LA and D, we used Pearson's correlation for emphysema quantification and PFT. Significance of the coefficients was determined with Bonferroni correction (p < 0.0025). Finally, the relationships between emphysema quantification and DLCO/VA were examined by linear models and Akaike information criterion (AIC). The correlation coefficients for %LA and DLCO/VA were statistically significant at all the thresholds (optimal coefficient, -0.761). The correlation coefficients for D and DLCO/VA were statistically significant at the thresholds from -945 to -900 HU (optimal coefficient, -0.646). AIC values showed that the most accurate prediction of DLCO/VA was obtained by the model incorporating both %LA and D. Both %LA and D showed significant correlation with DLCO/VA. Combining %LA and D resulted in more accurate evaluation of DLCO/VA than did using %LA or D alone.


Molecular simulations for dynamic nuclear polarization in liquids: a case study of TEMPOL in acetone and DMSO.
A computational strategy for calibrating, validating and analyzing molecular dynamics (MD) simulations to predict dynamic nuclear polarization (DNP) coupling factors and relaxivities of proton spins is presented. Simulations of the polarizing agent TEMPOL in liquid acetone and DMSO are conducted at low (infinite dilution) and high (1 M) concentrations of the free radical. Because DNP coupling factors and relaxivities are sensitive to the time scales of the molecular motions, the MD simulations are calibrated to reproduce the bulk translational diffusion coefficients of the pure solvents. The simulations are then validated by comparing with experimental dielectric relaxation spectra, which report on the rotational dynamics of the molecular electric dipole moments. The analysis consists of calculating spectral density functions (SDFs) of the magnetic dipole-dipole interaction between the electron spin of TEMPOL and nuclear spins of the solvent protons. Here, MD simulations are used in combination with an analytically tractable model of molecular motion. While the former provide detailed information at relatively short spin-spin distances, the latter includes contributions at large separations, all the way to infinity. The relaxivities calculated from the SDFs of acetone and DMSO are in excellent agreement with experiments at 9.2 T. For DMSO we calculate a coupling factor in agreement with experiment while for acetone we predict a value that is larger by almost 50%, suggesting a possibility for experimental improvement.


Using electronic health record alerts to provide public health situational awareness to clinicians.
Alerting providers to public health situations requires timeliness and context-relevance, both lacking in current systems. Incorporating decision support tools into electronic health records may provide a way to deploy public health alerts to clinicians at the point of care. A timely process for responding to Health Alert Network messages sent by the New York City Department of Health and Mental Hygiene was developed by a network of community health centers. Alerts with order sets and recommended actions were created to notify primary care providers of local disease outbreaks. The process, effect, and lessons learned from alerts for Legionella, toxogenic E coli, and measles outbreaks are described. Electronic alerts have the potential to improve management of diseases during an outbreak, including appropriate laboratory testing, management guidance, and diagnostic assistance as well as to enhance bi-directional data exchange between clinical and public health organizations.


[Prophylaxis in hemophilia: situation analysis and call-to-action in Latin America. A report from the GLAITH group].
Prophylactic treatment in the management of hemophilia has been a crucial factor in improving the prognosis and quality of life for people with hemophilia (PCH). However, it is not globally implemented. In Latin America it is difficult to assess the status of PCH and the its management does not conform to ideal standards. The GLAITH group discussed the problem in Latin America. A survey of its members and its findings were discussed at a meeting in Bogota in May 2013. Proportions of hemophilia A and B were 75-90% and 10-25% respectively. Severe hemophilia represents 26-55% of cases. A high percentage of PCH have hemophilic arthropathy. The general care and specific treatments of PCH vary by country, only 50-60% of the treatment is covered and in 85-95% of the cases are performed on an on- demand basis. Just 5-15% receives prophylaxis, most of them secondary. Few countries have a national program or homogeneous records. Finally the GLAITH group proceeded to develop a conclusion and call to action for the region where the following points are recommended: the establishment of a unified Latin American registry; prospective cost-effectiveness studies and evaluation criteria related to secondary prophylaxis; comparative studies of quality of life with and without prophylaxis in the region; promotion of individualization of treatment and, the increase of primary and secondary prophylaxis globally in Latin America.


Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence.
We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.


Macrophages and MHC class II positive dendritiform cells in the iris and choroid of the pig.
Macrophages and dendritic cells (DC) are considered to play an important role in the initiation and propagation of uveitis. Little is known about these cells in the normal pig uveal tract, despite the fact that the pig eye shares many similarities with the human eye and is considered as a suitable species to investigate the pathogenesis of human ocular disease. The aim of this study was to investigate the presence of immunocompetent cells in the uveal tract of the normal pig. Iris and choroid wholemounts and cryostat sections were obtained from normal pig eyes. Single and double immunohistochemistry was performed by using anti-porcine leukocyte (CD45), anti-porcine macrophage (CD163, CD14), anti-porcine MHC class II (MCA1335), anti-human MHC class II (MCA379G), anti-porcine B lymphocyte (IgM), anti-porcine T lymphocyte (CD6) and anti-porcine granulocyte (MCA1219) monoclonal antibodies. A rich network of dendritiform CD163 positive tissue macrophages was observed in normal pig iris and choroid wholemounts (368 + 84/mm(2), 402 + 97/mm(2), respectively). Approximately 50% of the CD163 positive tissue macrophages in the iris coexpressed MHC class II. Double immunostaining revealed that a small population of the MHC class II positive cells, did not express macrophage markers, and probably represent classical DCs. B lymphocytes and granulocytes were not detected in iris and choroid wholemounts. An occasional T cell could be observed per high power field in iris wholemounts but not in the choroid. The present study reveals that the normal pig uveal tract contains a rich network of tissue macrophages and MHC class II positive dendritiform cells. At least three populations could be distinguished: MHC class II positive and negative tissue macrophages and MHC class II+ dendritiform cells lacking tissue macrophage markers.


Entrainment and Control of Bacterial Populations: An in Silico Study over a Spatially Extended Agent Based Model.
We extend a spatially explicit agent based model (ABM) developed previously to investigate entrainment and control of the emergent behavior of a population of synchronized oscillating cells in a microfluidic chamber. Unlike most of the work in models of control of cellular systems which focus on temporal changes, we model individual cells with spatial dependencies which may contribute to certain behavioral responses. We use the model to investigate the response of both open loop and closed loop strategies, such as proportional control (P-control), proportional-integral control (PI-control) and proportional-integral-derivative control (PID-control), to heterogeinities and growth in the cell population, variations of the control parameters and spatial effects such as diffusion in the spatially explicit setting of a microfluidic chamber setup. We show that, as expected from the theory of phase locking in dynamical systems, open loop control can only entrain the cell population in a subset of forcing periods, with a wide variety of dynamical behaviors obtained outside these regions of entrainment. Closed-loop control is shown instead to guarantee entrainment in a much wider region of control parameter space although presenting limitations when the population size increases over a certain threshold. In silico tracking experiments are also performed to validate the ability of classical control approaches to achieve other reference behaviors such as a desired constant output or a linearly varying one. All simulations are carried out in BSim, an advanced agent-based simulator of microbial population which is here extended ad hoc to include the effects of control strategies acting onto the population.


Look at the lung: can chest ultrasonography be useful in pregnancy?
This study aimed to evaluate the clinical value of chest ultrasound (US) in the detection, diagnosis and follow-up of pathologic processes of both peripheral lung parenchyma and pleural space in pregnant women. Pregnant women admitted to Obstetric Pathology Hospital Department for respiratory diseases were enrolled. Chest US examination was performed when there was a respiratory disease highly suggestive of pneumonia and/or pleural effusion and chest X-ray (CXR) should have been obtained. Three chest US patterns were identified: lung consolidation (LC), pleural effusion (PE) and focal sonographic interstitial syndromes (SIS). When chest US pathologic signs were reported, one or more subsequent chest US examinations were performed to follow-up the patient until their complete resolution. Sixteen inpatients underwent 54 chest US evaluations. We identified: 9 LCs, 6 PEs and 11 SISs. Total number of CXRs was 7 (10 females avoided X-rays exposure and one underwent 2 CXR evaluations on the advice of Gynecologist). Chest US follow-up, during and after therapy, showed complete resolution of echographic patterns previously described. Chest US evaluation during pregnancy is a useful diagnostic tool to detect and monitor respiratory diseases, avoiding excessive X-rays exposure.


Bioreducible Zinc(II)-Dipicolylamine Functionalized Hyaluronic Acid Mediates Safe siRNA Delivery and Effective Glioblastoma RNAi Therapy.
RNA interference (RNAi) is an emerging therapeutic modality for tumors. However, lack of a safe and efficient small interfering RNA (siRNA) delivery system limits its clinical application. Here, we report a bioreducible and less-cationic siRNA delivery carrier by conjugating Zn(II)-dipicolylamine complexes (Zn-DPA) onto hyaluronic acid (HA) via a redox-sensitive disulfide (-SS-) linker. Such polymer conjugates can formulate stable siRNA nanomedicines via coordination between zinc ions of DPA and the anionic phosphate of siRNA. After the conjugates are taken up by cells, intracellular reduction stimulus subsequently triggers the release of siRNAs and elucidates the desired RNAi effect. Our studies showed the formulated siRNA nanomedicines can be efficiently delivered into tumor cells/tissues and mediates less cytotoxicities both in vitro and in vivo. More importantly, when applied in a xenograft glioblastoma tumor model, this siRNA nanomedicine demonstrated significantly enhanced antitumor ability comparing to naked siRNA. This work demonstrates that such bioreducible Zn-DPA-functionalized HA conjugates without using cationic material as a siRNA carrier represents a promising direction for RNAi-based cancer therapy.


Determinants of survival after inferior vena cava trauma.
Inferior vena cava (IVC) injuries continue to be associated with mortality rates of 21 to 66 per cent despite advances in prehospital, surgical, and critical care. The purpose of this study was to evaluate outcome of patients with IVC injury after treatment at a major urban trauma center and to identify factors predictive of survival. Between 1989 and 1995, 158 patients presented to the Los Angeles County + University of Southern California Medical Center with IVC injuries. One hundred thirty-six patient records were available for review, and 69 data points were collected and analyzed. Mean age was 26 years (range, 6-54), and 122 (90%) patients were male. Mechanism of injury included gunshot in 88 (65%) patients, stab in 23 (17%) patients, shotgun in 7 (5%) patients, and blunt trauma in 18 (13%) patients. The mean Injury Severity Score was 25. Seventy (52%) patients were hypotensive. Eleven (8%) patients died before surgical intervention, and 25 (18%) patients died before operative repair. Repair (79), ligation (20), or observation (1) was accomplished in 100 (74%) patients. Overall survival was 48 per cent and 65 per cent in the 100 patients surviving to operative repair, including 5 of 20 patients requiring IVC ligation. Significant differences (P<0.001) between survivors and nonsurvivors included Injury Severity Score, Glasgow Coma Score, hematocrit, hypotension, emergent thoracotomy, blood loss, level of injury, tamponade, and associated aortic injury. Logistic regression analysis identified hypotension, anatomic level of injury, and associated aortic injury as significant predictors of outcome (P = 0.001). Survival is predominantly determined by severity and anatomic accessibility of the IVC injury and by the absence of associated major vascular injuries. Ligation may control otherwise exsanguinating injuries and should be considered early in the management of complex injuries.


Corona-Enabled Electrostatic Printing for Ultra-fast Manufacturing of Binder-Free Multifunctional E-Skins.
As essential components in intelligent systems, printed soft electronics (PSEs) are playing crucial roles in public health, national security, and economics. Innovations in printing technologies are required to promote the broad application of high-performance PSEs at a low cost. However, current printing techniques are still facing long-lasting challenges in addressing the conflict between printing speed and performance. To overcome this challenge, we developed a new corona-enabled electrostatic printing (CEP) technique for ultra-fast (milliseconds) roll-to-roll (R2R) manufacturing of binder-free multifunctional e-skins. The printing capability and controllability of CEP were investigated through parametric studies and microstructure observation. The electric field generation, material transfer, and particle amount and size selecting mechanisms were numerically and experimentally studied. CEP-printed graphene e-skins were demonstrated to possess an outstanding strain sensing performance. The binder-free feature of the CEP-assembled networks enables them to provide pressure sensitivity as low as 2.5 Pa and capability to detect acoustic signals of hundreds of hertz in frequency. Furthermore, the CEP technique was utilized to pattern different types of functional materials (e.g., graphene and thermochromic polymers) onto different substrates (e.g., tape and textile). Overall, this study demonstrated that CEP can be a novel contactless and ultra-fast manufacturing platform compatible with the R2R process for fabricating high-performance, scalable, and low-cost soft electronics.


Infodemic Signal Detection During the COVID-19 Pandemic: Development of a Methodology for Identifying Potential Information Voids in Online Conversations.
The COVID-19 pandemic has been accompanied by an infodemic: excess information, including false or misleading information, in digital and physical environments during an acute public health event. This infodemic is leading to confusion and risk-taking behaviors that can be harmful to health, as well as to mistrust in health authorities and public health responses. The World Health Organization (WHO) is working to develop tools to provide an evidence-based response to the infodemic, enabling prioritization of health response activities. In this work, we aimed to develop a practical, structured approach to identify narratives in public online conversations on social media platforms where concerns or confusion exist or where narratives are gaining traction, thus providing actionable data to help the WHO prioritize its response efforts to address the COVID-19 infodemic. We developed a taxonomy to filter global public conversations in English and French related to COVID-19 on social media into 5 categories with 35 subcategories. The taxonomy and its implementation were validated for retrieval precision and recall, and they were reviewed and adapted as language about the pandemic in online conversations changed over time. The aggregated data for each subcategory were analyzed on a weekly basis by volume, velocity, and presence of questions to detect signals of information voids with potential for confusion or where mis- or disinformation may thrive. A human analyst reviewed and identified potential information voids and sources of confusion, and quantitative data were used to provide insights on emerging narratives, influencers, and public reactions to COVID-19-related topics. A COVID-19 public health social listening taxonomy was developed, validated, and applied to filter relevant content for more focused analysis. A weekly analysis of public online conversations since March 23, 2020, enabled quantification of shifting interests in public health-related topics concerning the pandemic, and the analysis demonstrated recurring voids of verified health information. This approach therefore focuses on the detection of infodemic signals to generate actionable insights to rapidly inform decision-making for a more targeted and adaptive response, including risk communication. This approach has been successfully applied to identify and analyze infodemic signals, particularly information voids, to inform the COVID-19 pandemic response. More broadly, the results have demonstrated the importance of ongoing monitoring and analysis of public online conversations, as information voids frequently recur and narratives shift over time. The approach is being piloted in individual countries and WHO regions to generate localized insights and actions; meanwhile, a pilot of an artificial intelligence-based social listening platform is using this taxonomy to aggregate and compare online conversations across 20 countries. Beyond the COVID-19 pandemic, the taxonomy and methodology may be adapted for fast deployment in future public health events, and they could form the basis of a routine social listening program for health preparedness and response planning.


Cloning and characterization of pathogenicity genes from Xanthomonas campestris pv. glycines.
Nonpathogenic mutants of Xanthomonas campestris pv. glycines 8ra were generated with N-methyl-N-nitro-N'-nitrosoguanidine to identify and characterize pathogenicity genes of the bacterium. A total of 16 nonpathogenic mutants were isolated from 2,000 colonies. One mutant, NP1, was chosen for further study. NP1 did not multiply in soybean cotyledons. A genomic library of strain 8ra was constructed in the cosmid pLAFR3, and the cosmids were tested for complementation in NP1. One cosmid clone, pIH1, which contained a 31-kb insert, complemented mutant NP1. A restriction map of pIH1 was constructed, and deletion analyses identified a 10-kb HindIII fragment that restored pathogenicity to NP1. Southern hybridization analysis indicated that DNA sequences in the 10-kb HindIII fragment are conserved among other X. campestris pathovars tested. Three regions responsible for restoring pathogenicity have been identified by Tn3-HoHo1 mutagenesis. A 2.7-kb ClaI fragment was sequenced, and two possible open reading frames (ORF1 and ORF2) were found. Results indicated that ORF2 but not ORF1 may be expressed in Escherichia coli and in X. campestris pv. glycines. The carboxy terminus of the potential polypeptide encoded by ORF2 has an amino acid sequence similar to that of the gamma subunit of oxaloacetate decarboxylase, which is involved in sodium ion transport in Klebsiella pneumoniae.


Effect of 67Cu-2IT-BAT-Lym-1 therapy on BCL-2 gene and protein expression in a lymphoma mouse model.
Radioimmunotherapy using monoclonal antibodies against tumor-associated antigens has been particularly promising in the treatment of radiosensitive malignancies such as lymphoma. 67Cu has excellent physical and biochemical properties for radioimmunotherapy. 67Cu-2IT-BAT-Lym-1 has been used in preclinical and clinical trials, where an exceptionally long residence time of 67Cu on tumor was observed. BCL-2, a proto-oncogene that promotes cell survival by blocking apoptotic cell death, is overexpressed in most B-cell lymphomas including Raji human Burkitt's lymphoma cells. In this study, therapeutic efficacy and BCL-2 gene and protein expression levels were examined in Raji xenografts in mice after 67Cu-2IT-BAT-Lym-1 radioimmunotherapy. 67Cu-2IT-BAT-Lym-1 therapy induced a response rate (complete and partial responses) of approximately 50%. BCL-2 gene expression was decreased 3 h after radioimmunotherapy, followed by a decrease in Bcl-2 protein by 24 h. Decreases in BCL-2 gene and protein expression preceding observations of 67Cu-2IT-BAT-Lym-1 therapeutic effect suggest that down-regulation of BCL-2 leaves cells more likely to be killed by low dose-rate radiation from radioimmunotherapy.


Microorganisms in Whole Botanical Fermented Foods Survive Processing and Simulated Digestion to Affect Gut Microbiota Composition.
Botanical fermented foods have been shown to improve human health, based on the activity of potentially beneficial lactic acid bacteria (LAB) and yeasts and their metabolic outputs. However, few studies have explored the effects of prolonged storage and functional spices on microbial viability of whole fermented foods from fermentation to digestion. Even fewer have assessed their impact on the gut microbiota. Our study investigated the effects of production processes on LAB and yeast microbial viability and gut microbiota composition. We achieved this by using physicochemical assessments and an in vitro gastrointestinal and a porcine gut microbiota model. In low-salt sauerkraut, we assessed the effects of salt concentration, starter cultures, and prolonged storage, and in tibicos, prolonged storage and the addition of spices cayenne, ginger, and turmeric. In both food matrices, LAB counts significantly increased (p<0.05), reaching a peak of 7-8 log cfu/g, declining to 6-6.5 log cfu/g by day 96. Yeast viability remained at 5-6 log cfu/g in tibicos. Ginger tibicos had significantly increased LAB and yeast viability during fermentation and storage (p<0.05). For maximum microbial consumption, tibicos should be consumed within 28days, and sauerkraut, 7weeks. Simulated upper GI digestion of both products resulted in high microbial survival rates of 70-80%. The 82% microbial survival rate of cayenne tibicos was significantly higher than other treatments (p<0.05). 16S rRNA sequencing of simulated porcine colonic microbiota showed that both spontaneously fermented sauerkraut and tibicos increase the relative abundance of Megasphaera 85-fold. These findings will inform researchers, producers, and consumers about the factors that affect the microbial content of fermented foods, and their potential effects on the gut.


Viral cystatin evolution and three-dimensional structure modelling: a case of directional selection acting on a viral protein involved in a host-parasitoid interaction.
In pathogens, certain genes encoding proteins that directly interact with host defences coevolve with their host and are subject to positive selection. In the lepidopteran host-wasp parasitoid system, one of the most original strategies developed by the wasps to defeat host defences is the injection of a symbiotic polydnavirus at the same time as the wasp eggs. The virus is essential for wasp parasitism success since viral gene expression alters the immune system and development of the host. As a wasp mutualist symbiont, the virus is expected to exhibit a reduction in genome complexity and evolve under wasp phyletic constraints. However, as a lepidopteran host pathogenic symbiont, the virus is likely undergoing strong selective pressures for the acquisition of new functions by gene acquisition or duplication. To understand the constraints imposed by this particular system on virus evolution, we studied a polydnavirus gene family encoding cyteine protease inhibitors of the cystatin superfamily. We show that cystatins are the first bracovirus genes proven to be subject to strong positive selection within a host-parasitoid system. A generated three-dimensional model of Cotesia congregata bracovirus cystatin 1 provides a powerful framework to position positively selected residues and reveal that they are concentrated in the vicinity of actives sites which interact with cysteine proteases directly. In addition, phylogenetic analyses reveal two different cystatin forms which evolved under different selective constraints and are characterized by independent adaptive duplication events. Positive selection acts to maintain cystatin gene duplications and induces directional divergence presumably to ensure the presence of efficient and adapted cystatin forms. Directional selection has acted on key cystatin active sites, suggesting that cystatins coevolve with their host target. We can strongly suggest that cystatins constitute major virulence factors, as was already proposed in previous functional studies.


Enhancement of slow-wave sleep by tumor necrosis factor-alpha is mediated by cyclooxygenase-2 in rats.
Tumor necrosis factor-alpha (TNFalpha) was infused into the subarachnoid space of the rat rostral basal forebrain, which was previously defined as a prostaglandin (PG) D2-sensitive, sleep-promoting zone. TNFalpha increased the amount of slow-wave sleep (SWS), decreased that of paradoxical sleep (PS), and caused fever and anorexia. The TNFalpha-induced SWS enhancement, fever and anorexia were all blocked by co-infusion of diclofenac, a non-selective cyclooxygenase (COX) inhibitor, and by pretreatment with NS-398, a COX-2-specific inhibitor. In striking contrast, the TNFalpha-induced suppression of PS was not affected by the inhibitors. These results indicate that COX-2-mediated hyperproduction of PGs is critically involved in the enhancement of SWS, fever, and anorexia but not in the suppression of PS, caused by TNFalpha infused into the PGD2-sensitive zone.


Combinatorial organization of the transcriptional regulatory machinery in biological control and cancer.
The architecturally associated subnuclear organization of nucleic acids and cognate regulatory factors suggests functional interrelationships between nuclear structure and gene expression. Mechanisms that contribute to the spatial distribution of transcription factors within the three dimensional context of nuclear architecture control the sorting and integration of regulatory information as well as the combinatorial assembly, organization and activities of transcriptional machinery at scaffold-associated subnuclear sites that support gene expression. During the past several years our laboratory has been addressing intranuclear trafficking mechanisms that direct transcription factors to transcriptionally active nuclear microenvironments. We are pursuing these studies using the AML/Runx/Cbfa transcription factors that govern hematopoietic and bone-specific transcription as a paradigm. Our objective is to gain insight into linkage of intranuclear organization of genes, transcripts, and regulatory proteins with fidelity of biological control and contributions of aberrant nuclear structure/function relationships to the onset and progression of tumorigenesis.


Applying a PC accelerator board for medical imaging.
An AT-compatible computer was used to expand X-ray images that had been compressed and stored on optical data cards. Initially, execution time for expansion of a single X-ray image was 25 min. The requirements were for an expansion time of under 10 s and costs of under $1000 for computing hardware. This meant a computational speed increase of over 150 times was needed. Tests showed that incorporating an 80287 coprocessor would only give a speed increase of five times. The DSP32-PC-160 floating-point accelerator board was selected as a cost-effective solution to the need for more computing power. This board provided adequate processor speed, onboard memory, and data bus width; floating-point math precision; and a high-level language compiler for code development.


Microbe-specific unconventional T cells induce human neutrophil differentiation into antigen cross-presenting cells.
The early immune response to microbes is dominated by the recruitment of neutrophils whose primary function is to clear invading pathogens. However, there is emerging evidence that neutrophils play additional effector and regulatory roles. The present study demonstrates that human neutrophils assume Ag cross-presenting functions and suggests a plausible scenario for the local generation of APC-like neutrophils through the mobilization of unconventional T cells in response to microbial metabolites. Vγ9/Vδ2 T cells and mucosal-associated invariant T cells are abundant in blood, inflamed tissues, and mucosal barriers. In this study, both human cell types responded rapidly to neutrophils after phagocytosis of Gram-positive and Gram-negative bacteria producing the corresponding ligands, and in turn mediated the differentiation of neutrophils into APCs for both CD4(+) and CD8(+) T cells through secretion of GM-CSF, IFN-γ, and TNF-α. In patients with acute sepsis, circulating neutrophils displayed a similar APC-like phenotype and readily processed soluble proteins for cross-presentation of antigenic peptides to CD8(+) T cells, at a time when peripheral Vγ9/Vδ2 T cells were highly activated. Our findings indicate that unconventional T cells represent key controllers of neutrophil-driven innate and adaptive responses to a broad range of pathogens.


Engineered Human Muscle Tissue from Multilayered Aligned Myofiber Sheets for Studies of Muscle Physiology and Predicting Drug Response.
In preclinical drug testing, human muscle tissue models are critical to understanding the complex physiology, including drug effects in the human body. This study reports that a multilayering approach to cell sheet-based engineering produces an engineered human muscle tissue with sufficient contractile force suitable for measurement. A thermoresponsive micropatterned substrate regulates the biomimetic alignment of myofiber structures enabling the harvest of the aligned myofibers as a single cell sheet. The functional muscle tissue is produced by layering multiple myofiber sheets on a fibrin-based gel. This gel environment promotes myofiber maturation, provides the tissue an elastic platform for contraction, and allows the attachment of a measurement device. Since this multilayering approach is effective in enhancing the contractile ability of the muscle tissue, this muscle tissue generates a significantly high contractile force that can be measured quantitatively. The multilayered muscle tissue shows unidirectional contraction from electrical and chemical stimulation. In addition, their physiological responses to representative drugs can be determined quantitatively in real time by changes in contractile force and fatigue resistance. These physiological properties indicate that the engineered muscle tissue can become a promising tissue model for preclinical in vitro studies in muscle physiology and drug discovery.


Effect of a Chinese herb medicine formulation, as an alternative for antibiotics, on performance of broilers.
1. A total of 720 female broiler chicks was used to test the effects of 4 dietary concentrations of a Chinese herbal medicine (CHM) formulation (0.25, 0.5, 1 and 2g/kg), as an alternative for virginiamycin (VRG), on growth performance in broilers. 2. A total of 72 birds from non-supplemented, VRG and 0.5 g/kg CHM groups was selected and killed and the relative weights of the intestinal segments were assessed. 3. The CHM dietary treatments produced increased body weight gain at 7 to 21 d of age but not at 21 to 28 d of age compared with the non-supplemented and VRG groups. The CHM groups had a higher feed intake and a higher feed conversion ratio (FCR) than the VRG group between 21 and 28 d. 4. The dissection results showed that the liver colour of the birds in the CHM group varied less between animals than that of the VRG and the non-supplemented groups. Neither CHM nor VRG had any significant effects on either liver or intestinal tract weights. 5. It was concluded that the birds of the CHM group had better growth performance from d 7 to 21 but not thereafter. Further experiments are needed to elucidate the mechanisms underlying enhanced growth performance by CHM in broilers.


Evaluation of Urea-motility-indole medium for recognition and differentiation of Salmonella and Shigella species in stool cultures.
A semisolid urea-motility-indole medium designed for detection in Enterobacteriaceae of urease activity, motility, and indole production in one tube was prepared and evaluated. The formulation of the medium was similar to that of Christensen urea agar, but the agar concentration was 0.2%, and 1% tryptone was added. Results with 687 strains of Enterobacteriaceae were the same as those obtained with standard test media (98% overall agreement). The urea-motility-indole medium was also used in combination with Kligler iron agar for the recognition and differentiation of Salmonella and Shigella species from colonies picked from plating media in fecal cultures. This combination was compared with the combination of Kligler iron agar and lysine iron agar with 507 strains of non-lactose-fermenting Enterobacteriaceae. Although both combinations enabled the presumptive recognition and differentiation of Salmonella and Shigella species, an analysis of data indicated that the combination of Kligler iron agar and urea-motility-indole medium performed better than the combination of Kligler iron agar and lysine iron agar in detecting Salmonella and Shigella species.


Utility of Transbronchial Lung Cryobiopsy in Non-Interstitial Diseases.
Transbronchial lung cryobiopsy (TLCB), performed with a flexible cryoprobe, is an interventional pulmonology procedure that has proved its diagnostic value for interstitial pulmonary disease. However, it has not been explored extensively as a diagnostic tool for patients with non-interstitial lung pathology, including infectious and malignant diseases. To evaluate the diagnostic yield and safety of an interventional pulmonology approach that integrates TLCB and bronchoalveolar lavage (BAL) for the diagnosis of non-interstitial pulmonary disease. TLCB and BAL were performed under general anesthesia through the same bronchoscopic access on 103 adult patients (including immunocompromised HIV+ individuals) with clinical/radiological evidence of non-interstitial lung disease admitted to the Interventional Pulmonology Service between May 2015 and April 2016. Samples obtained were sent to pathology and microbiology laboratories for standard diagnostic analysis. Samples of TLCB allowed the diagnosis of 75.7% of patients, while 39.8% were diagnosed from BAL. The global diagnostic yield from the dual sampling was 92.2%. TLCB allowed the diagnosis of 94.7% of cancer cases and 60.0% of infectious cases, while BAL samples identified 77.5% of infectious cases and 21.2% of malignant lesions. The incidence of complications was 4.9% with full recovery in all cases. Simultaneous TLCB and BAL constitute a safe and useful diagnostic procedure for non-interstitial pulmonary disease, with a global diagnostic yield of 92.2%. Complementary advantages of samples obtained by each technique result in a robust diagnostic strategy for infectious and malignant disease in adults, including HIV+ individuals.


Molecular population genetics of the alcohol dehydrogenase locus in the Hawaiian drosophilid D. mimica.
Sequence variation among 10 alleles of the alcohol dehydrogenase (Adh) gene of the Hawaiian drosophilid D. mimica was analyzed with reference to the evolutionary history of the Hawaiian subgroup as well as to levels and patterns of polymorphism of the Adh gene in continental drosophilid species. The Adh gene of D. mimica is less polymorphic than that of other drosophilid species, and no replacement substitutions were found. Statistical analyses of the Adh alleles suggested the action of balancing selection and revealed significant linkage disequilibrium among three of the variable sites. The effective population size was estimated to be only slightly smaller than that of continental species and, surprisingly, on the same order of magnitude as the actual size.


Potentiation of radiation cytotoxicity by recombinant interferons, a phenomenon associated with increased blockage at the G2-M phase of the cell cycle.
Radiation sensitivity of human hypernephroma tumor cells, ACHN, was evaluated in the presence or absence of various recombinant interferons (IFNs): alpha D (rHuIFN-alpha D), beta ser (rHuIFN-beta ser), and gamma (rHuIFN-gamma). Exponentially growing monolayers of ACHN cells were incubated with IFNs (10(3) units/ml) for 2, 6, and 24 h prior to irradiation. The effects of IFNs on the growth inhibition, radiation cell survival, and cell cycle redistribution were determined from growth curves, colony-forming efficiency, and flow cytometric analysis. rHuIFN-alpha D and rHuIFN-beta ser were associated with a modest inhibition in cell growth and the growth delay was reversible upon the removal of IFNs. However, rHuIFN-gamma exhibited the greatest inhibitory effect on both cell growth delay and rate. IFN and radiation have an additive effect on cell growth inhibition. Although IFN treatments alone (0-1000 IU/ml) did not have a significant effect on cell survival, radiation killing was increased by IFN pretreatment. The enhancing factor measured at a survival level of 0.1 for rHuIFN-alpha D, rHuIFN-beta ser, and rHuIFN-gamma was 1.21, 1.28, and 1.44, respectively. In addition, this potentiation effect was dependent on the dose of radiation and exposure time to IFN with the maximal effect observed after 24 h of treatment with IFN at 12 Gy. When the distributions of G1, S, and G2-M cells were measured 24 and 48 h after combined IFN and radiation treatment, there was a significant increase in the accumulation of cells at the G2-M phase of the cell cycle compared to either IFN or radiation treatment alone. We conclude that IFNs and radiation have an additional inhibitory effect on ACHN cell growth, that IFN can potentiate radiation cytotoxicity, and that this phenomenon is associated with an increased blockage at G2-M phase of the cell cycle.


Impaired Glucocorticoid Suppression of TGFβ Signaling in Human Omental Adipose Tissues Limits Adipogenesis and May Promote Fibrosis.
Visceral obesity is associated with insulin resistance and higher risk of type 2 diabetes and metabolic diseases. A limited ability of adipose tissues to remodel through the recruitment and differentiation of adipose stem cells (ASCs) is associated with adipose tissue inflammation and fibrosis and the metabolic syndrome. We show that the lower adipogenesis of omental (Om) compared with abdominal subcutaneous (Abdsc) ASCs was associated with greater secretion of TGFβ ligands that acted in an autocrine/paracrine loop to activate SMAD2 and suppress adipogenesis. Inhibition of TGFβ signaling rescued Om ASC differentiation. In Abdsc ASCs, low concentrations of dexamethasone suppressed TGFβ signaling and enhanced adipogenesis, at least in part by increasing TGFBR3 protein that can sequester TGFβ ligands. Om ASCs were resistant to these dexamethasone effects; recombinant TGFBR3 increased their differentiation. Pericellular fibrosis, a hallmark of dysfunctional adipose tissue, was greater in Om and correlated with higher level of tissue TGFβ signaling activity and lower ASC differentiation. We conclude that glucocorticoids restrain cell-autonomous TGFβ signaling in ASCs to facilitate adipogenesis and healthy remodeling in Abdsc and these processes are impaired in Om. Therapies directed at overcoming glucocorticoid resistance in visceral adipose tissue may improve remodeling and help prevent metabolic complications of visceral obesity.


Oxidative Stress Modulation Through Habitual Physical Activity.
Oxidative stress is involved in different pathophysiological states, such as aging, inflammatory, cardiovascular and neurodegenerative diseases, by damaging several cellular and tissue components including proteins, DNA and lipids. On the other hand, free radicals generated during physical activity are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair. Indeed, ROS, generated during physical activity, are likely main mediators of antioxidant molecules upregulation, as reflected by increased glutathione reductase levels after exercise training. The aim of this review is to summarize the main mechanisms responsible for ROS-dependent adaptations to exercise training. Regular moderate exercise seems to counteract oxidative stress-related detrimental changes and to promote a healthy lifestyle. Conversely, acute and strenuous exercise can generate an excess of free radicals production. Moreover, regular habitual physical activity is related to reduced risk of coronary heart disease and death, whereas vigorous exercise has been shown to favour sudden cardiac death in sedentary individuals with preexisting vascular disease. New specific markers of mitochondrial or ER dysfunction may be better clues of oxidative stress, and their application to clinical practice may help set up the optimal dose, intensity and modality of exercise training for every single subject. The relationship between exercise and oxidative stress is extremely complex, depending on the mode, intensity, and duration of exercise. These conflicting effects and outcomes may be explained by the hormesis theory, in which low doses of an agent that is detrimental at high doses, induces an adaptive beneficial effect on the cells or organism.


Mosquito (Diptera: Culicidae) surveillance for arboviruses in an area endemic for West Nile (Lineage Rabensburg) and Tahyna viruses in Central Europe.
Six viral isolates were obtained from 23,243 female mosquitoes (examined in 513 pools) belonging to 16 species and collected along the lower reaches of the Dyje River in South Moravia (Czech Republic, central Europe) during 2006-2008: five isolates of Orthobunyavirus Tahyna (TAHV, California group, family Bunyaviridae: three isolations from Aedes vexans (Meigen), one from Ae. sticticus (Meigen), one from Culex modestus Ficalbi); and one isolation of Flavivirus West Nile (WNV, Japanese encephalitis group, family Flaviviridae)-strain Rabensburg (proposed lineage 3 of WNV) from Ae. rossicus (Dolbeshkin et al). All viral isolates were recovered from mosquitoes collected in 2006 (15,882 mosquitoes examined), while no virus was isolated from mosquitoes trapped in 2007 and 2008, when 1,555 and 5,806 mosquitoes were examined, respectively. The population density of local mosquitoes was very low in 2007 and 2008 because of warm and dry summer including a considerably low water table, compared with environmental conditions favorable for mosquito development in 2006. The virus isolation procedure was based on intracerebral inoculation of newborn mice. In parallel, more than one-third of the samples (183 pools consisting of 8,470 individual mosquitoes) were also examined by inoculating Vero cell cultures in Leighton tubes. However, the latter method detected only three of the six virus isolates (including WNV-Rabensburg). Ae. rossicus is a new potential vector for WNV-Rabensburg. This species feeds mostly on mammals including man; this raises the question whether this virus lineage is not adapted to an alternative mosquito-mammal cycle in the South-Moravian natural focus.


Oesophageal perforation complicating intraoperative transoesophageal echocardiography: suspicion can save lives.
Oesophageal injury is an extremely rare complication of intra-operative transoesophageal echocardiography (TOE) associated with cardiac surgery. We report a case of delayed presentation (19 days after surgery) of oesophageal injury that was likely due to TOE following an aortic valve replacement. Lack of suspicion led to a delay in diagnosis but the patient fortunately survived. We advocate that in the event of postoperative hydropneumothorax, the differential diagnosis must include iatrogenic oesophageal injury from transoesophageal echo.


Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19.
The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.


Comparison of livestock-associated and community-associated Staphylococcus aureus pathogenicity in a mouse model of skin and soft tissue infection.
Industrial hog operation (IHO) workers are at increased risk of carrying Staphylococcus aureus in their nares, particularly strains that are livestock-associated (LA) and multidrug-resistant. The pathogenicity of LA-S. aureus strains remains unclear, with some prior studies suggesting reduced transmission and virulence in humans compared to community-associated methicillin-resistant (CA-MRSA) S. aureus. The objective of this study was to determine the degree to which LA-S. aureus strains contracted by IHO workers cause disease relative to a representative CA-MRSA strain in a mouse model of skin and soft tissue infection (SSTI). Mice infected with CC398 LA-S. aureus strains (IHW398-1 and IHW398-2) developed larger lesion sizes with higher bacterial burden than mice infected with CA-MRSA (SF8300) (p < 0.05). The greatest lesion size and bacterial burden was seen with a CC398 strain that produced a recurrent SSTI in an IHO worker. The LA-S. aureus infected mice had decreased IL-1β protein levels compared with CA-MRSA-infected mice (p < 0.05), suggesting a suboptimal host response to LA-S. aureus SSTIs. WGSA revealed heterogeneity in virulence factor and antimicrobial resistance genes carried by LA-S. aureus and CA-MRSA strains. The observed pathogenicity suggest that more attention should be placed on preventing the spread of LA-S. aureus into human populations.


Integration of energy systems.
This article in MRS Bulletin and the framework set out in the introductory article articulate a scenario of renewable electrons and electrification of end use appliances and industrial processes as a plausible paradigm to realize a carbon-free energy economy. The subsequent articles cover specific sectoral or chemical applications of those renewable electrons (e.g., for hydrogen, transportation, building use, electrochemical storage, and within the chemical industry). This article addresses the intersections among and across those sectors. We describe the importance of considering integrated systems and systems of systems as we consider pathways to a decarbonized energy economy. Further, we review and summarize key insights into the innovation challenges that reside at the particular integration interfaces among sectors, and highlight the opportunity for advances in materials and processes that will be critical to successful achievement of economy-wide, low-carbon energy systems.


Can a 10-Minute Questionnaire Identify Significant Psychological Issues in Patients With Temporomandibular Joint Disease?
For patients with disc displacement disorders (DDDs), psychiatric illness increases the risk of worsening postsurgical pain, postoperative delirium, postoperative incomplete recovery, and worse postoperative life quality. This study provides a fast and practical protocol to evaluate psychological conditions of patients with DDDs of the temporomandibular joint (TMJ) in clinical care. The populations under investigation in this cross-sectional study included patients with DDD who received treatment from October 2012 through June 2016. Variables included age, gender, education level, and TMJ (Axis I) and psychological (Axis II) evaluations. The 13-item protocol of Axis II evaluations contained a 5-item Brief Symptom Rating Scale (BSRS-5), a pain visual analog scale (VAS; 1 item), major life events (3 items), suicidal risk (3 items), and substance use (1 item). Analysis of variance, χ2 test, and multivariate logistic regression were used for analyses. Of 177 patients, 75.14% were women (mean age, 37.46 ± 14.06 yr). Pain VAS scores clearly supported the following ranking of psychosocial discomforts: disc displacement without reduction with limited opening (DDWORWLO) > disc displacement without reduction without limited opening > disc displacement with reduction. Pain VAS and BSRS-5 correlated with 5 variables in Axis I (trismus, acute TMJ pain, chronic awake bruxism, chronic sleep bruxism, and deep bite). The DDD study indicated that 9.6% of patients required urgent referrals to mental health resources (MHRs) for their moderate and high suicidal risk DDD and 77% required nonurgent referrals to MHRs for their psychiatric morbidity. This study found that patients with DDD showed a prevalence of suicidal ideation and mean BSRS scores that were higher for anxiety, hostility, depression, interpersonal hypersensitivity, and insomnia than in the general population. Patients with trismus or acute TMJ pain could have a higher pain VAS score; chronic awake bruxism could involve greater hostility and lower depression; chronic sleep bruxism could increase sensitivity to interpersonal interactions; and deep bite could involve a higher anxiety level. DDWORWLO produced the highest pain VAS score in patients with DDD. The 13-item Axis II evaluations can offer useful clues for oral and maxillofacial surgeons and other specialists to collaborate with MHRs.


Learning-based ventricle detection from cardiac MR and CT images.
The objective of this work is to investigate the issue of automatically detecting regions of interest (ROI's) in medical images. It is assumed that the regions to be detected can be roughly segmented by a threshold based on a likelihood measure of the ROI. First, an analysis of the global histogram is used to compute a preliminary threshold that is likely near the optimal one. The histogram analysis is motivated by the analytical result of a bell image intensity model proposed in this work. Then, the preliminary threshold is used to segment the input image, resulting in an attention map, which contains an attention region that approximates the ROI as well as many spurious ones. Due to the nonoptimality of the preliminary threshold, it can happen that the attention region contains a part of, or more regions than, the ROI. Learning takes place in two stages: 1) learning for automatic selection of the preliminary threshold value and 2) learning for automatically selecting the ROI from the attention map while dynamically tuning the threshold according to the learned-likelihood function. Experiments have been conducted to approximately locate the endocardium boundaries of the left and right ventricles from gradient-echo magnetic resonance (MR) images. Cardiac computed tomography (CT) images have also been used for testing. The boundary of the segmented region provided by this algorithm is not very accurate and is meant to be used for further fine tuning based on other application-specific measures.


Retinal nerve fiber layer thickness and visual hallucinations in Parkinson's Disease.
Defective visual information processing from both central and peripheral pathways is one of the suggested mechanisms of visual hallucination in Parkinson's disease (PD). To investigate the role of retinal thinning for visual hallucination in PD, we conducted a case-control study using spectral domain optical coherence tomography. We examined a representative sample of 61 patients with PD and 30 healthy controls who had no history of ophthalmic diseases. General ophthalmologic examinations and optical coherence tomography scans were performed in each participant. Total macular thickness and the thickness of each retinal layer on horizontal scans through the fovea were compared between the groups. In a comparison between patients with PD and healthy controls, there was significant parafoveal inner nuclear layer thinning, whereas other retinal layers, including the retinal nerve fiber layer, as well as total macular thicknesses were not different. In terms of visual hallucinations among the PD subgroups, only retinal nerve fiber layer thickness differed significantly, whereas total macular thickness and the thickness of other retinal layers did not differ. The retinal nerve fiber layer was thinnest in the group that had hallucinations without dementia, followed by the group that had hallucinations with dementia, and the group that had no hallucinations and no dementia. General ophthalmologic examinations did not reveal any significant correlation with hallucinations. There were no significant correlations between retinal thicknesses and duration or severity of PD and medication dosages. The results indicate that retinal nerve fiber layer thinning may be related to visual hallucination in nondemented patients with PD. Replication studies as well as further studies to elucidate the mechanism of thinning are warranted.


Application of the Second Law of Thermodynamics in Brazilian Residential Appliances towards a Rational Use of Energy.
This article proposes the utilization of the concepts of destroyed exergy and exergy efficiency for equipment and process performance indicators that are related to the current energy planning scenario in Brazil, more specifically with energy-efficiency labelling. Several indicators associated with these concepts are discussed, including one national program that is based on labeling the energy efficiency of several residential, commercial and industrial appliances. The grades are indicated in the equipment using values from A to G. This labeling system is useful for discriminating similar technologies used for the same function; nevertheless produced by different enterprises. For this complementary analysis, two types of refrigeration methods were compared, absorption and vapor compression; however, these energy indexes alone are not sufficient parameters to select among these two technologies, because their performance indexes definition are different. To address this, our research considers the second law of thermodynamics through exergy analysis as a proper sub-index to obtain a systematic comparison between these various indicators. It is significant to highlight that seldom research studies addressed to this problem so explicitly, in an actual governmental working solution, aiming at discussing to the society the advantage of the usage of the "quality of the energy" as a complementary index to governmental and personal choices. Results indicate that it is possible to use the destroyed exergy and exergy efficiency to help select the technology that better utilizes natural resources, considering the energy matrix of the country. Appliances for water heating and air conditioning were compared from energy and exergy viewpoint, where the last gave additional information about the quality of energy conversion process, giving a completely different trend from the energy analysis alone, without the necessity to think about the energy matrix. Later this issue is addressed from both points of view. Future studies may suggest an exergy based index. The energy efficiency suggests that electrical shower (values higher than 95%) are better than gas water heaters (83% ) in using natural resources, whereas the exergy efficiency shares similar magnitudes (about 3%). A related pattern is shown for the theoretical air conditioning systems. The vapor compression systems have an energy index higher than 3, and absorption systems lower than 1. For these circumstances, the exergy efficiency shows figures nearby 30%.


A randomized controlled trial to assess the effect of a ketamine infusion on tourniquet hypertension during general anaesthesia in patients undergoing upper and lower limb surgery.
Tourniquet hypertension arising from tourniquet inflation remains a primary concern to the anaesthetist. One drug commonly used to manage tourniquet hypertension is ketamine. No studies have examined the effect of ketamine on tourniquet hypertension for a period of more than one hour or an infusion of the same. To compare the effect of an intravenous infusion of ketamine versus placebo on tourniquet induced hypertension in patients undergoing upper and lower limb surgery under general anaesthesia. Forty six adult patients scheduled for upper and lower limb surgery under general anaesthesia were randomized into two equal groups. The ketamine group received an intravenous bolus of 0.1mg/kg of ketamine followed by an infusion of 2ug/kg/min. The saline group received an intravenous bolus of physiological saline followed by an infusion of saline. All the patients were reviewed post-operatively. Data of the baseline characteristics, haemodynamic changes, post-tourniquet pain and side effects were collected. If post-tourniquet pain was present post-operatively, a visual analogue scale (VAS) was used to assess its severity. 46 patients successfully completed the trial. There were no significant differences between the groups for baseline patient demographics. The incidence of tourniquet hypertension was higher in the saline group (26.1%) compared with ketamine group (4.6%) with a 95% confidence interval. The difference was shown to be statistically significant ('P'<0.05). There was an increase in systolic blood pressure after 60 minutes of tourniquet inflation in the saline group but the difference was not statistically significant('P'>0.866). There were no significant differences between the groups as regards diastolic blood pressure and heart rate. VAS scores did not differ between the two groups. Statistically, there was no difference found between the two groups. Side effects were minimal in the ketamine group whilst in the saline group, nausea and vomiting were predominant but were also not statistically significant. Based on the results of this study, there was a difference in the proportion of tourniquet hypertension between the ketamine and saline groups for patients undergoing upper and lower limb orthopaedic surgery under general anaesthesia.


Synthesis and biological activity of LH-RH analogs modified at the carboxyl terminus.
Des(Pro9,Gly10)-LH-RH ethylamide, des(Pro9,Gly10)-LH-RH butylamide, desGly10-LH-RH 2-aminoethylamide, and desGly10-LH-RH hydrazide were synthesized by a solid-phase method involving cleavage of protected peptide intermediates from their resin support by reaction with ethylamine, butylamine, ethylenediamine, and hydrazine, respectively. In the assay utilizing steroid pretreated, ovariectomized rats, the peptides were found to have the following LH-releasing activities when compared with natural LH-RH: ethylamide, 0.2%; butylamide, 0,1%; 2-aminoethylamide, 2.4%; hydrazide, 12%. DesGly10-LH-RH hydrazide was used as a precursor in the synthesis of desGly10-LH-RH allylamide and desGly10-LH-RH propargylamide by conversion to the azide and reaction with allylamine and propargylamine, respectively. LH and FSH levels were measured over a 4-hr period after subcutaneous injection of these two peptides into immature male rats in order to detect any prolongation of activity. The allylamide analog was quite active, releasing 1.7 times more LH and 1.3 times more FSH than the same dose of LH-RH. The propargylamide analog was considerably less active, exhibiting 50% LH-releasing activity and 64% FSH-releasing activity. Neither peptide appeared to be longer acting than LH-RH.


The Pharmaceutical Device Prisma® Skin Promotes in Vitro Angiogenesis through Endothelial to Mesenchymal Transition during Skin Wound Healing.
Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma® Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with mesoglycan and Prisma® Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that mesoglycan and Prisma® Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma® Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses.


Parallel evolutionary trajectories underlie the origin of giant suspension-feeding whales and bony fishes.
Giant suspension feeders such as mysticete whales, basking and whale sharks, and the extinct (indicated by '†') †pachycormiform teleosts are conspicuous members of modern and fossil marine vertebrate faunas. Whether convergent anatomical features common to these clades arose along similar evolutionary pathways has remained unclear because of a lack of information surrounding the origins of all groups of large-bodied suspension feeders apart from baleen whales. New investigation reveals that the enigmatic ray-finned fish †Ohmdenia, from the Lower Jurassic (Toarcian, 183.0-175.6 Ma) Posidonia Shale Lagerstätte, represents the immediate sister group of edentulous †pachycormiforms, the longest lived radiation of large vertebrate suspension feeders. †Ohmdenia bisects the long morphological branch leading to suspension-feeding †pachycormiforms, providing information on the sequence of anatomical transformations preceding this major ecological shift that can be compared to changes associated with the origin of modern mysticetes. Similarities include initial modifications to jaw geometry associated with the reduction of dentition, followed by the loss of teeth. The evolution of largest body sizes within both radiations occurs only after the apparent onset of microphagy. Comparing the fit of contrasting evolutionary models to functionally relevant morphological measurements for whales and †pachycormiform fishes reveals strong support for a common adaptive peak shared by suspension-feeding members of both clades.


Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice.
The glycoprotein CD47 (integrin-associated protein, IAP) is present on the surface of virtually all cells, including red blood cells (RBCs). CD47 acts like a marker of self by ligating the macrophage inhibitory receptor signal regulatory protein alpha (SIRPalpha). In this manner mild reactivity of wild-type RBCs with macrophage phagocytic receptors is tolerated, whereas otherwise identical CD47-deficient RBCs are rapidly eliminated. We show here that virtually all CD47-deficient nonobese diabetic (NOD) mice spontaneously develop severe lethal autoimmune hemolytic anemia (AIHA) at 180 to 280 days of age, whereas none of the control CD47(+) NOD mice develop lethal AIHA at least during the first year of life. This phenotype is at least partially due to a markedly increased rate of elimination of opsonized CD47(-/-) compared to CD47(+) RBCs. Similarly, CD47(-/-)C57BL/6 mice were much more sensitive than their wild-type counterparts to experimental passive AIHA induced by anti-RBC monoclonal antibodies. Thus, CD47-SIRPalpha signaling can have a profound influence on the severity of AIHA, making manipulation of this signaling pathway a theoretically appealing avenue in the treatment of the disease.


Effect of cochlear nerve electrocautery on the adult cochlear nucleus.
Electrocauterization and subsequent transection of the cochlear nerve induce greater injury to the cochlear nucleus than sharp transection alone. Some studies show that neurofibromatosis Type 2 (NF2) patients fit with auditory brainstem implants (ABIs) fail to achieve speech perception abilities similar to ABI recipients without NF2. Reasons for these differences remain speculative. One hypothesis posits poorer performance to surgically induced trauma to the cochlear nucleus from electrocautery. Sustained electrosurgical depolarization of the cochlear nerve may cause excitotoxic-induced postsynaptic nuclear injury. Equally plausible is that cautery in the vicinity of the cochlear nucleus induces necrosis. The cochlear nerve was transected in anesthetized adult gerbils sharply with or without bipolar electrocautery at varying intensities. Gerbils were perfused at 1, 3, 5, and 7 days postoperatively; their brainstem and cochleas were embedded in paraffin and sectioned at 10 μm. Alternate sections were stained with flourescent markers for neuronal injury or Nissl substance. In additional experiments, anterograde tracers were applied directly to a sectioned eighth nerve to verify that fluorescent-labeled profiles seen were terminating auditory nerve fibers. Cochlear nerve injury was observed from 72 hours postoperatively and was identical across cases regardless of surgical technique. Postsynaptic cochlear nucleus injury was not seen after distal transection of the nerve. By contrast, proximal transection was associated with trauma to the cochlear nucleus. Distal application of bipolar electrocautery seems safe for the cochlear nucleus. Application near the root entry zone must be used cautiously because this may compromise nuclear viability needed to support ABI stimulation.


The assignment-dial-a-ride-problem.
In this paper, we present the first Assignment-Dial-A-Ride problem motivated by a real-life problem faced by medico-social institutions in France. Every day, disabled people use ride-sharing services to go to an appropriate institution where they receive personal care. These institutions have to manage their staff to meet the demands of the people they receive. They have to solve three interconnected problems: the routing for the ride-sharing services; the assignment of disabled people to institutions; and the staff size in the institutions. We formulate a general Assignment-Dial-A-Ride problem to solve all three at the same time. We first present a matheuristic that iteratively generates routes using a large neighborhood search in which these routes are selected with a mixed integer linear program. After being validated on two special cases in the literature, the matheuristic is applied to real instances in three different areas in France. Several managerial results are derived. In particular, it is found that the amount of cost reduction induced by the people assignment is equivalent to the amount of cost reduction induced by the sharing of vehicles between institutions.


Investigation of the mechanism of gelatin to enhance 3D printing accuracy of corn starch gel: From perspective of phase morphological changes.
The study examined the impact of phase morphological transformations within the corn starch/gelatin system, induced by varying gelatin content, on its rheological properties and 3D printing performance. Gelatin addition inhibited the gelatinization and retrogradation of starch, which leaded to the transformation of continuous phase structure. The transition process from starch continuous phase to gelatin continuous phase promoted a thinner wall structure of the gel and loosed its dense network, resulting in reduced flow stress (τf) and storage modulus (G'). These changes improved the extrusion and "extrusion swelling" of gel ink materials, which made the print size of printed product closer to the set model. The formation of a gelatin continuous phase in the gel was helpful in increasing τf and G', resulting in enhanced support capacity of the printed product. This study presented meaningful information for the application of 3D printing to starch-gelatin complex foods.


Polyester Textiles as a Source of Microplastics from Households: A Mechanistic Study to Understand Microfiber Release During Washing.
Microplastic fibers make up a large proportion of microplastics found in the environment, especially in urban areas. There is good reason to consider synthetic textiles a major source of microplastic fibers, and it will not diminish since the use of synthetic fabrics, especially polyester, continues to increase. In this study we provide quantitative data regarding the size and mass of microplastic fibers released from synthetic (polyester) textiles during simulated home washing under controlled laboratory conditions. Consideration of fabric structure and washing conditions (use of detergents, temperature, wash duration, and sequential washings) allowed us to study the propensity of fiber shedding in a mechanistic way. Thousands of individual fibers were measured (number, length) from each wash solution to provide a robust data set on which to draw conclusions. Among all the variables tested, the use of detergent appeared to affect the total mass of fibers released the most, yet the detergent composition (liquid or powder) or overdosing of detergent did not significantly influence microplastic release. Despite different release quantities due to the addition of a surfactant (approximately 0.025 and 0.1 mg fibers/g textile washed, without and with detergent, respectively), the overall microplastic fiber length profile remained similar regardless of wash condition or fabric structure, with the vast majority of fibers ranging between 100 and 800 μm in length irrespective of wash cycle number. This indicates that the fiber staple length and/or debris encapsulated inside the fabric from the yarn spinning could be directly responsible for releasing stray fibers. This study serves as a first look toward understanding the physical properties of the textile itself to better understand the mechanisms of fiber shedding in the context of microplastic fiber release into laundry wash water.


Investigation of Chlorhexidine Tolerance and its Association with Antibiotic Resistance in Clinical Gram-Negative Bacilli Isolates.
Chlorhexidine (CHX) is one of the most frequently used antiseptic agents in challenging multidrug-resistant (MDR) isolates. There is an increasing number of reports on reduced susceptibility (tolerance) to CHX in MDR isolates. We aimed to investigate CHX tolerance in Gram-negative bacilli (GNB) and its possible association with antibiotic resistance. A total of 84 enteric GNB (ENT) and 40 non-fermentative GNB (NFGNB) isolates were collected from different clinical specimens. Disk diffusion method was performed to differentiate between MDR and non-MDR isolates and tolerance to CHX was determined by a modified agar dilution method. In GNB isolates, CHX tolerance was defined as a minimum inhibitory concentration (MIC) ≥ 4 mg/L. We detected that 26.2% (22/84) of ENT and 50.0% (20/40) of NFGNB were MDR and the rest were non-MDR isolates. The CHX tolerance rate was detected as 50.0% (10/20) in MDR-NFGNB and 15.0% (3/20) in non-MDR-NFGNB, and this difference was statistically significant (p < 0.05). Conversely, the tolerance rate was observed as 4.5% (1/22) in MDR-ENT and 1.6% (1/62) in non-ENT, and this difference was not statistically significant (p ˃ 0.05). NFGNB isolates had a higher tendency to CHX tolerance than ENT, and antibiotic resistance facili-tates the selection of CHX tolerance in NFGNB but not in ENT isolates.


COMT Val158Met and cognitive and functional outcomes after traumatic brain injury.
There is significant variability in long-term outcomes after traumatic brain injury (TBI), making accurate prognosis difficult. In seeking to enhance understanding of outcomes, this study aimed to investigate whether COMT Val(158)Met allele status was associated with performance on neuropsychological measures of attention and working memory, executive functioning, learning and memory, and speed of information processing in the early rehabilitation phase. The study also aimed to examine whether the COMT polymorphism was associated with longer-term functional outcomes. A total of 223 participants (71.3% male) with moderate-to-severe TBI were recruited as rehabilitation inpatients to participate in a prospective, longitudinal head injury outcome study. The three COMT genotype groups (Val/Val, Val/Met, and Met/Met) were well matched for estimated full-scale IQ, years of education, age at injury, and injury severity. Results showed no significant difference between genotypes on neuropsychological measures (all p>0.05) or functional outcome, as measured by the Glasgow Outcome Scale-Extended (GOS-E), after controlling for age, education, and severity of injury. The presence of frontal lobe pathology was also not associated with cognitive performance. Those with greater injury severity (i.e., longer duration of post-traumatic amnesia) performed more poorly on measures of processing speed and verbal new learning and recall. It was concluded that there was little support for the influence of COMT Val(158)Met on cognitive function, or functional outcome measures, in the acute rehabilitation phase after TBI.


Particle shape dependence of CD8+ T cell activation by artificial antigen presenting cells.
Previous work developing particle-based acellular, artificial antigen presenting cells (aAPCs) has focused exclusively on spherical platforms. To explore the role of shape, we generated ellipsoidal PLGA microparticles with varying aspect ratios (ARs) and synthesized aAPCs from them. The ellipsoidal biomimetic aAPCs with high-AR showed significantly enhanced in vitro and in vivo activity above spherical aAPCs with particle volume and antigen content held constant. Confocal imaging indicates that CD8+ T cells preferentially migrate to and are activated by interaction with the long axis of the aAPC. Importantly, enhanced activity of high-AR aAPCs was seen in a mouse melanoma model, with high-AR aAPCs improving melanoma survival compared to non-cognate aAPCs (p = 0.004) and cognate spherical aAPCs (p = 0.05). These findings indicate that particle geometry is a critical design criterion in the generation of aAPCs, and may offer insight into the essential role of geometry in the interaction between CD8+ T cells and biological APCs.


Comorbid Depressive Symptoms and Chronic Medical Conditions Among US Chinese Older Adults.
The prevalence and health consequences of comorbid depressive symptoms (DSs) and chronic medical conditions (CMCs) among older ethnic minority populations remain poorly understood. To bridge this gap, the present cross-sectional study examined the prevalence of comorbid DS-CMC and the association between such comorbidity and health services use among US Chinese older adults. Data were from the Population Study of Chinese Elderly in Chicago (N = 3157). The relationship between comorbid DS-CMC and health service use (ie, emergency department [ED] visits and hospitalizations) was investigated by stratifying the sample into four groups: (1) neither DSs nor CMCs (ie, heart disease, stroke, cancer, high cholesterol, diabetes, high blood pressure, hip fraction, thyroid, and osteoarthritis); (2) DSs only; (3) CMCs only; and (4) comorbid DS-CMC. Multivariate negative binomial regression models were conducted to determine the relationship between comorbid DS-CMC and health service use. Participants were 73 years old on average. The prevalence of comorbid DSs ranged between 0.7% and 4.6% across various CMCs. The odds of DSs were at least twice as high among US Chinese older adults with CMCs than those without the various conditions. Compared with US Chinese older adults with neither DSs nor CMCs, those with comorbid DS-CMC had more ED visits (rate ratio [RR] = 3.32; 95% confidence interval [CI] = 2.03-5.42) and hospitalizations (RR = 3.12; 95% CI = 1.95-4.97). Recognition and treatment of comorbid DS-CMC warrant increased policy and clinical attention. The findings underscore the potential need to develop effective services targeting DSs among US Chinese older adults with CMCs. J Am Geriatr Soc 67:S545-S550, 2019.


Apolipoprotein E polymorphism in ischemic cerebrovascular diseases and vascular dementia patients in Taiwan.
This study aims to clarify the association between apolipoprotein E gene (ApoE) polymorphism, ischemic cerebrovascular diseases (ICVD) and vascular dementia (VaD) in Taiwan Chinese. 277 patients with ICVD, 49 patients with probable VaD and 112 controls were recruited for this study. Distributions of ApoE epsilon4 carriers and allele frequencies were 28.5 and 14.5% for patients with ICVD, 20.4 and 10.2% for patients with VaD, whereas these values were 22.9 and 11.6% for controls. Distributions of ApoE epsilon2 carriers and allele frequencies were 10.1 and 5.2% for ICVD patients, 6.1 and 3.1% for VaD patients, but 12.5 and 8.0% for controls. There were no differences between ICVD patients and controls, or VaD patients and controls in their epsilon4 carriers. Those patients aged 65 and under, carrying the epsilon2 allele, had a lower risk of developing ICVD and VaD than did their counterparts. These findings suggest that ApoE epsilon4 plays no significant role in the development of ICVD and VaD, but that ApoE epsilon2 has a protective effect with regard to the development of ICVD and VaD for Taiwan Chinese below the age of 65.


[The passive coagglutination reaction as a method of determining the fibronectin-binding properties of microorganisms].
The authors suggest a method for the detection of S. aureus and S. epidermidis strains fibronectin-binding ability (FNBA), based on a new principle--the passive coagglutination test. Using this test, FNBA was detected at 16 of the 20 tested S. aureus strains and in 6 of the 11 S. epidermidis strains. This method yields more demonstrable results than the flake-formation test on the glass in the presence of fibronectin. A nonagglutinating fibronectin form may be used in the test.


Association of physician's sex with risk factor control in treated hypertensive patients from Swedish primary healthcare.
To study the association of physician's sex with blood pressure, lipid control, and cardiovascular risk factors in treated hypertensive men and women, stratified for the sex of their physician. In a cross-sectional survey of hypertensive patients, 264 primary care physicians (PCPs), 187 men and 77 women from across Sweden, recruited 6537 treated hypertensive patients (48% men) during 2002-2005, consecutively collected from medical records and registered on a web-based form connected to a central database. Patients were included consecutively in the same order as they visited the healthcare centre. Hypertensive women more often reached target systolic/diastolic blood pressure levels (<140/90 mmHg) when treated by female PCPs than when they were treated by male PCPs (32 vs. 24%, P < 0.001). This difference remained when comparing female and male physicians' nondiabetic female patients. Both male and female patients had better control of total cholesterol and low-density lipoprotein cholesterol levels when treated by female PCPs than when treated by male PCPs (total cholesterol <5 mmol/l: women 30 vs. 24%, P < 0.001; men 42 vs. 34%, P < 0.001; low-density lipoprotein cholesterol <3 mmol/l: women 39 vs. 33%, P < 0.01; men 41 vs. 35%, P < 0.05). Female PCPs had a higher proportion of treated hypertensive patients with diabetes than did male PCPs but male PCPs had a higher prevalence of treated hypertensive men with microalbuminuria compared with female PCPs. Female physicians appeared more often to reach the treatment goal for blood pressure in female patients and cholesterol levels in all patients than did male physicians.


Standardized senna in the management of constipation in the puerperium: A clinical trial.
Successful treatment of constipation in the immediate postpartum period in 93% of White patients and 96% of Coloured patients was achieved in a clinical trial of standardized senna tablets (Senokot; Reckitt & Colman). This is significantly better than the success rates of 51% and 59% achieved in White and Coloured controls treated with a placebo. Minor abdominal cramps occurred in some 13% of the patients treated with standardized senna, and in 4% of the controls given the placebo. There is no evidence to suggest that standardized senna has any effect whatsoever on a breast-fed baby if taken by the mother.


Manipulation of culture conditions alters lipid content and fatty acid profiles of a wide variety of known and new oleaginous yeast species.
Oleaginous yeasts have been studied for oleochemical production for over 80 years. Only a few species have been studied intensely. To expand the diversity of oleaginous yeasts available for lipid research, we surveyed a broad diversity of yeasts with indicators of oleaginicity including known oleaginous clades, and buoyancy. Sixty-nine strains representing 17 genera and 50 species were screened for lipid production. Yeasts belonged to Ascomycota families, Basidiomycota orders, and the yeast-like algal genus Prototheca. Total intracellular lipids and fatty acid composition were determined under different incubation times and nitrogen availability. Thirteen new oleaginous yeast species were discovered, representing multiple ascomycete and basidiomycete clades. Nitrogen starvation generally increased intracellular lipid content. The fatty acid profiles varied with the growth conditions regardless of taxonomic affiliation. The dominant fatty acids were oleic acid, palmitic acid, linoleic acid, and stearic acid. Yeasts and culture conditions that produced fatty acids appropriate for biodiesel were identified.


The social skills problems of victims of bullying: self, peer and teacher perceptions.
A small number of prior studies have found that victims of school bullying tend to exhibit poor social skills. Few of these have examined this issue from multiple perspectives, and there has been a focus on a restricted range of social skills. To determine the extent to which self, peers, and teachers regard victims as having poorer social skills than non-victims across 20 behaviours/competencies. A convenience sample of 330 pupils aged between 9 and 11 years (162 girls and 168 boys) provided self-report and peer-report data. They were drawn from 12 classes from 6 junior schools in the UK. Additionally, 11 of the class teachers provided data. Three separate methods were employed and in each case, participants were provided with 20 short statements that described a different social skill: (1) participants who were classified as either 'victims' or 'non-victims' (using peer nominations) rated themselves on a 3-point scale in terms of how like them each description was, (2) participants were asked to think of a victim and a non-victim in their class and to rate both of these people on each description, and (3) teachers were asked to rate a previously identified victim and a non-victim from their class on each description. Using a direct discriminant function analysis of the self-ratings, six of the social skills items were found to discriminate between victims and non-victims, and the discriminant function was able to correctly classify 80% of the participants. For 18 of the items, peer ratings indicated significantly more pronounced social skills problems for victims than for non-victims. Teacher ratings were significant for eight of the social skill items, and in each case, victims were rated as having greater problems. The finding that victims are perceived by three different sources to have poor social skills has important implications for interventions to support victims of bullying.


Prevalence, risk factors and antimicrobial susceptibility test of Staphylococcus aureus in Bovine cross breed mastitic milk in and around Asella town, Oromia regional state, southern Ethiopia.
A cross sectional study was undertaken from November 2016 to March 2017 in and around Asella town, Oromia regional state, southern Ethiopia, to determine the prevalence, associated risk factors and antimicrobial susceptibility of Staphylococcus aureus, in Bovine cross breed mastitis milk. A total of 384 lactating dairy cows were screened for mastitis based on clinical examinations and California mastitis test (CMT). Out of 230 lactating crossbred cows with either clinical or subclinical mastitis examined for the involvement of Staphylococcus aureus. Staphylococcus aureus was isolated at a rate of 47.2% (N=92) and 42.9% (N=15) of the sub- clinical and clinical cases, respectively. The overall prevalence of Staphylococcus aureus scored in this study was 46.5% (N=107). Descriptive statistics and chi-square were used in order to assess the magnitude of the difference of comparable variables, as a result, among risk factors considered, Age, parity, and lactation stage were found significantly associated with the occurrence of S. aureus in mastitis milk (p<0.05). The current study revealed that S. aureus has 0% susceptibility to penicillinG, followed by tetracycline (14.2%). However, these randomly selected isolates were found to be totally (100%) susceptible to the Kanamycin. The possible justification for, low antimicrobial susceptibility to these commonly used antimicrobials might be repeated and uncontrolled use of these drugs without veterinarian's prescription. Proper provention and regular antimicrobial sensitivity testing helps to select effective antibiotics and ultimately reduce the development of resistance towards commonly used antibiotics. To conclude, the study was able to show that, mastitis caused by S. aureus is one of the major problems of dairy cows in milk production and imposing public health hazard in study area. Hence, every possible control and prevention strategies should be implemented.


Efficient community detection of network flows for varying Markov times and bipartite networks.
Community detection of network flows conventionally assumes one-step dynamics on the links. For sparse networks and interest in large-scale structures, longer timescales may be more appropriate. Oppositely, for large networks and interest in small-scale structures, shorter timescales may be better. However, current methods for analyzing networks at different timescales require expensive and often infeasible network reconstructions. To overcome this problem, we introduce a method that takes advantage of the inner workings of the map equation and evades the reconstruction step. This makes it possible to efficiently analyze large networks at different Markov times with no extra overhead cost. The method also evades the costly unipartite projection for identifying flow modules in bipartite networks.


Diverse Malaria Presentations across National Institutes of Health South Asia International Center for Excellence in Malaria Research Sites in India.
The Malaria Evolution in South Asia (MESA) International Center for Excellence in Malaria Research (ICEMR) was established by the US National Institutes of Health (US NIH) as one of 10 malaria research centers in endemic countries. In 10 years of hospital-based and field-based work in India, the MESA-ICEMR has documented the changing epidemiology and transmission of malaria in four different parts of India. Malaria Evolution in South Asia-ICEMR activities, in collaboration with Indian partners, are carried out in the broad thematic areas of malaria case surveillance, vector biology and transmission, antimalarial resistance, pathogenesis, and host response. The program integrates insights from surveillance and field studies with novel basic science studies. This is a two-pronged approach determining the biology behind the disease patterns seen in the field, and generating new relevant biological questions about malaria to be tested in the field. Malaria Evolution in South Asia-ICEMR activities inform local and international stakeholders on the current status of malaria transmission in select parts of South Asia including updates on regional vectors of transmission of local parasites. The community surveys and new laboratory tools help monitor ongoing efforts to control and eliminate malaria in key regions of South Asia including the state of evolving antimalarial resistance in different parts of India, new host biomarkers of recent infection, and molecular markers of pathogenesis from uncomplicated and severe malaria.


The Divide-and-Conquer Approach to Delaying Age-Related Functional Decline: Where Are We Now?
Over 20 years ago, together with seven illustrious colleagues, the author proposed that efforts to postpone the decline and debilitation of aging might most promisingly be pursued by tackling the various lifelong processes of accumulation of damage through a panel of interventions, rather than seeking a magic bullet that would retard them all. A decade later, this approach was embraced in a paper that rapidly became, and is still, by far the most highly cited publication in the biology of aging this century. Here I survey the progress that the field has made in relation to this philosophy and the challenges that remain.


Understanding polycystic ovarian syndrome pathogenesis: an updated of its genetic aspects.
Polycystic ovary syndrome (PCOS) is the most frequent cause of female infertility. It is also characterized by metabolic defects that raise the risk for cardiovascular disease. Despite the progress in the definition of the clinical aspects of the syndrome, only very few definite data are available about the ethiopathogenetic mechanisms that subtend PCOS. It is likely that the PCOS phenotype derives from the interaction between environmental and genetic factors. While environmental factors have easily been investigated, the individuation of the genetic factors seem to be more complex. Indeed, PCOS appears to be inherited as a complex, polygenic trait. Several family studies have been conducted with the aim to clarify the genetic aspects of PCOS, but their findings are often conflicting and not conclusive.Moreover, it is difficult to establish with certainty which genes are involved and their effective role in the development of the syndrome because in PCOS, genetic analysis is hampered by low fecundity, lack of a male phenotype, absence of an animal model, and dissimilarity of the diagnostic criteria used to select the patients. Since multiple biochemical pathways are implicated in PCOS pathogenesis, genes of steroid hormone metabolism, gonadotropin release and action, insulin secretion and action, adipose tissue metabolism and others have been investigated. Nevertheless, none of them seems to play a key role in the ethiopathogenesis of PCOS. This article reviews the large body of literature generated to support the presence of genetic abnormalities in PCOS women by taking in consideration the most important studies regarding PCOS candidate genes.