title: Net woody vegetation increase confined to seasonally inundated lowlands in an Australian tropical savanna, Victoria River District, Northern Territory

text: Abstract Georeferenced digital aerial photographs were used to assess changes in overstorey vegetation cover since 1948 in the Victoria River District, Northern Territory, Australia, across a range of lowland tropical savanna habitats and with explicit consideration of known and variable site‐specific grazing and fire management histories. Vegetation surveys at corresponding locations on the ground identified five distinct woody vegetation communities defined primarily by water drainage and secondarily by soil characteristics. Air‐photo analyses revealed that, contrary to popular perceptions and in contrast to results from other habitats, there has been no generalized net increase in overstorey woody vegetation cover across the full range of lowland savanna habitats. Rather, different habitats exhibited distinctly different vegetation change mechanisms: low‐lying seasonally inundated ‘wet’ habitats have experienced woody vegetation increase since 1948, whereas well‐drained ‘dry’ habitats have experienced overstorey vegetation stability or loss. In almost every instance woody vegetation increase could be attributed to the invasion or proliferation of a single species, Melaleuca minutifolia F.Muell. The extent of M. minutifolia increase was unrelated to historical grazing/fire regime. Demographic analyses for this species revealed that recruitment was often episodic and that synchronized recruitment events occurred uniformly across the full range of historical management treatments, most likely as a consequence of favourable climatic conditions in years with an extended wet season. Heavy grazing facilitated juvenile survival and/or recruitment, most likely by reducing grassy fuel loads and eliminating landscape fire. We conclude that while there has been no generalized net increase in overstorey woody vegetation cover in lowland environments, savanna dynamics are complex, and multiple change mechanisms have occurred simultaneously in different habitats, some of which have been significantly transformed since 1948. Where net woody vegetation increase has occurred it is primarily a natural consequence of episodic M. minutifolia establishment in climatically favourable years, but the extent and magnitude of this effect is likely mediated by fire/grazing regime.


title: Habitat structure is more important than vegetation composition for local‐level management of native terrestrial reptile and small mammal species living in urban remnants: A case study from Brisbane, Australia

text: Abstract As urban areas continue to expand and replace natural and agricultural landscapes, the ability to manage and conserve native wildlife within urban environments is becoming increasingly important. To do so we first need to understand species' responses to local‐level habitat attributes in order to inform the decision‐making process and on‐ground conservation actions. Patterns in the occurrence of native terrestrial reptile and small mammal species in 59 sites located in remnant urban habitat fragments of Brisbane City were assessed against local‐level environmental characteristics of each site. Cluster analysis, multidimensional scaling ordination, and principal axis correlation were used to investigate relationships between species' occurrences and environmental characteristics. Native reptiles were most strongly associated with the presence of termite mounds, a high amount of fallen woody material, and a moderate amount of weed cover. Native small mammals were most strongly associated with the presence of grass trees (Xanthorrhoea spp.), and both reptiles and small mammals were negatively influenced by increased soil compaction. Significant floristic characteristics were considered to be important as structural, rather than compositional, habitat elements. Therefore, habitat structure, rather than vegetation composition, appears to be most important for determining native, terrestrial reptile and small mammal species assemblages in urban forest fragments. We discuss the management implications in relation to human disturbances and local‐level management of urban remnants.


title: The loss of aquatic and riparian plant communities: Implications for their consumers in a riverine food web

text: Abstract Human induced alterations to rivers and steams have resulted in significant changes to the structure and diversity of riparian and aquatic plant communities. These changes will impact on the dynamics of riverine carbon cycles and food web structure and function. Here we investigate the principal sources of organic carbon supporting local shredder communities across a gradient in different levels of anthropogenic development along riverine reaches, in South Australia. In forested/wooded reaches with minimum to limited development, semi‐emergent macrophytes were the principal sources of organic carbon supporting the local shredder communities. However, in developed reaches, course particulate organic matter and filamentous algae were the principal food sources. The C:N ratios of the food sources in developed reaches were higher than those of their consumers indicating a stoichiometric mismatch. This imbalanced consumer‐resource nutrient ratio in those developed reaches is likely to impose constraints on the growth and reproduction of their aquatic shredder communities with probable knock‐on effects to higher trophic levels.


title: Structure and environmental relationships of insectivorous bat assemblages in tropical Australian savannas

text: Abstract Patterns in the composition of assemblages of microbat species sampled during the late dry season (the ‘build‐up’) in north Australian savannas were assessed against a range of environmental factors as well as four a priori defined habitat types (riparian, escarpments, coastal and woodlands). Distinct species assemblages were most strongly associated with topographic and climatic variables. There were also limited associations with vegetation structure, fire and local roost potential but no associations with insects or water availability. Total species diversity at sample sites was associated with distance to rivers and rainfall. In general, species assemblages were not clearly defined and the number of significant environmental associations was relatively few. We compare these associations with those reported for bat assemblages elsewhere in Australia.


title: Relationship between species in the genus Rosa, section Pimpinellifoliae

text: The morphology of twelve species of Rosa is described and similarities between these species are assessed. Possible origins of the tetraploid species from diploid species are indicated on grounds of comparative morphology. The wild origins of living and herbarium specimens are given in order to supplement published data on geographical distribution. Meiosis in pollen mother cells, viability of pollen grains at anthesis and ability to set seed was studied in several F(1) hybrids: no indication of complete or even partial sterility was found. Reproductive isolation is therefore unlikely to be maintained by reduced fertility of interspecific hybrids. Three species are reduced to synonymy with three other species, being retained as subspecific taxa. Two species are transferred from section Pimpinellifoliae to section Cinnamomeae.


title: Study on Prediction Model of HIV Incidence Based on GRU Neural Network Optimized by MHPSO

text: Acquired Immune Deficiency Syndrome (AIDS) is still one of the most life-threatening diseases in the world. Moreover, new infections are still potentially increasing. This difficult problem must be solved. Early warning is the most effective way to solve this problem. Here, we aim to determine the best performing model to track the epidemic of AIDS, which will provide a methodological basis for testing the time characteristics of the disease. From January 2004 to January 2018, we built four computing methods based on AIDS dataset: BPNN model, RNN model, LSTM model and MHPSO-GRU model. Compare the final estimated performance to determine the preferred method. Result. Considering the root mean square error (RMSE), mean absolute error (MAE), mean error rate (MER) and mean absolute percentage error (MAPE) in the simulation and prediction subsets, the MHPSO-GRU model is determined as the best performance technology. Estimates for the period from May 2018 to December 2020 suggest that the event appears to continue to increase and remain high.


title: Next Generation Technology for Epidemic Prevention and Control: Data-Driven Contact Tracking

text: Contact tracking is one of the key technologies in prevention and control of infectious diseases. In the face of a sudden infectious disease outbreak, contact tracking systems can help medical professionals quickly locate and isolate infected persons and high-risk individuals, preventing further spread and a large-scale outbreak of infectious disease. Furthermore, the transmission networks of infectious diseases established using contact tracking technology can aid in the visualization of actual virus transmission paths, which enables simulations and predictions of the transmission process, assessment of the outbreak trend, and further development and deployment of more effective prevention and control strategies. Exploring effective contact tracking methods will be significant. Governments, academics, and industries have all given extensive attention to this goal. In this paper, we review the developments and challenges of current contact tracing technologies regarding individual and group contact from both static and dynamic perspectives, including static individual contact tracing, dynamic individual contact tracing, static group contact tracing, and dynamic group contact tracing. With the purpose of providing useful reference and inspiration for researchers and practitioners in related fields, directions in multi-view contact tracing, multi-scale contact tracing, and AI-based contact tracing are provided for next-generation technologies for epidemic prevention and control.


title: Modeling Behavioral Response to Vaccination Using Public Goods Game

text: Epidemics of infectious disease can be traced back to the early days of mankind. Only in the last two centuries vaccination has become a viable strategy to prevent such epidemics. In addition to the clinical efficacy of this strategy, the behavior and public attitudes affect the success of vaccines. This paper describes modeling the efficacy of vaccination considering the cost and benefit of vaccination to individual players. The model is based on the public goods game and is presented as a spatial game on a lattice. Using this model, individuals can contribute to the public health by paying the cost of vaccination or choose to be protected by the public who is vaccinated rather than pay the cost and share the risk of vaccination. Thus, in this model individuals can choose to stay susceptible, can become infected, or choose to vaccinate once in each episode. This paper presents the behavioral changes of the population and the cost to the society as a function of the cost of vaccines, cost of being infected, and the “fear factor” created by the public media.


title: Uncertainty Assisted Robust Tuberculosis Identification With Bayesian Convolutional Neural Networks

text: Tuberculosis (TB) is an infectious disease that can lead towards death if left untreated. TB detection involves extraction of complex TB manifestation features such as lung cavity, air space consolidation, endobronchial spread, and pleural effusions from chest x-rays (CXRs). Deep learning based approach named convolutional neural network (CNN) has the ability to learn complex features from CXR images. The main problem is that CNN does not consider uncertainty to classify CXRs using softmax layer. It lacks in presenting the true probability of CXRs by differentiating confusing cases during TB detection. This paper presents the solution for TB identification by using Bayesian-based convolutional neural network (B-CNN). It deals with the uncertain cases that have low discernibility among the TB and non-TB manifested CXRs. The proposed TB identification methodology based on B-CNN is evaluated on two TB benchmark datasets, i.e., Montgomery and Shenzhen. For training and testing of proposed scheme we have utilized Google Colab platform which provides NVidia Tesla K80 with 12 GB of VRAM, single core of 2.3 GHz Xeon Processor, 12 GB RAM and 320 GB of disk. B-CNN achieves 96.42% and 86.46% accuracy on both dataset, respectively as compared to the state-of-the-art machine learning and CNN approaches. Moreover, B-CNN validates its results by filtering the CXRs as confusion cases where the variance of B-CNN predicted outputs is more than a certain threshold. Results prove the supremacy of B-CNN for the identification of TB and non-TB sample CXRs as compared to counterparts in terms of accuracy, variance in the predicted probabilities and model uncertainty.


title: Variable-Gain Control for Respiratory Systems

text: In this paper, we introduce a variable-gain control strategy for mechanical ventilators in the respiratory systems. Respiratory systems assist the patients who have difficulty breathing on their own. For the comfort of the patient, fast pressure buildup (and release) and a stable flow response are desired. However, linear controllers typically need to balance between these conflicting objectives. In order to balance this tradeoff in a more desirable manner, a variable-gain controller is proposed, which switches the controller gain based on the magnitude of the patient flow. The effectiveness of the control strategy is demonstrated in experiments on different test lungs.


title: Information Diffusion on Social Media During Natural Disasters

text: Social media analytics has drawn new quantitative insights of human activity patterns. Many applications of social media analytics, from pandemic prediction to earthquake response, require an in-depth understanding of how these patterns change when human encounter unfamiliar conditions. In this paper, we select two earthquakes in China as the social context in Sina-Weibo (or Weibo for short), the largest Chinese microblog site. After proposing a formalized Weibo information flow model to represent the information spread on Weibo, we study the information spread from three main perspectives: individual characteristics, the types of social relationships between interactive participants, and the topology of real interaction networks. The quantitative analyses draw the following conclusions. First, the shadow of Dunbar’s number is evident in the “declared friends/followers” distributions, and the number of each participant’s friends/followers who also participated in the earthquake information dissemination show the typical power-law distribution, indicating a rich-gets-richer phenomenon. Second, an individual’s number of followers is the most critical factor in user influence. Strangers are very important forces for disseminating real-time news after an earthquake. Third, two types of real interaction networks share the scale-free and small-world property, but with a looser organizational structure. In addition, correlations between different influence groups indicate that when compared with other online social media, the discussion on Weibo is mainly dominated and influenced by verified users.


title: Development and validation of a portable, point-of-care canine distemper virus qPCR test

text: Canine distemper virus (CDV) is a multi-host pathogen that can cause significant mortality in domestic, wild terrestrial and marine mammals. It is a major conservation threat in some endangered species. Infection can result in severe respiratory disease and fatal encephalitis. Diagnosis and disease monitoring in wildlife, and differentiation of CDV from rabies (a life-threatening zoonotic disease that can produce similar neurologic signs), would benefit from the availability of a portable, point-of-care (POC) diagnostic test. We therefore developed a quantitative RT-PCR assay for CDV using shelf-stable, lyophilized reagents and target-specific primers and probes for use with the handheld Biomeme two3(™) qPCR thermocycler. Biomeme’s extraction methodology, lyophilized reagents, and thermocycler were compared to our standard laboratory-based methods to assess sensitivity, efficiency and overall test performance. Results using a positive control plasmid for CDV showed comparable sensitivity (detection of 50 copies) and PCR efficiency between the two platforms, and CDV detection was similar between platforms when tested using a modified live CDV vaccine. Significantly higher Ct values (average Ct = 5.1 cycles) were observed using the Biomeme platform on known CDV positive animal samples. CDV detection using the Biomeme platform was similar in 25 of 26 samples from suspect CDV cases when compared to standard virology laboratory testing. One false positive was observed that was negative upon retest. The Biomeme methodology can be adapted for detection of specific targets, and this portable technology saves time by eliminating the need for local or international sample transport for laboratory-based diagnostics. However, results of our testing suggest that decreased diagnostic sensitivity (higher Ct values) relative to laboratory-based methods was observed using animal samples, so careful validation and optimization are essential. Portable qPCR platforms can empower biologists and wildlife health professionals in remote and low-resource settings, which will greatly improve our understanding of CDV disease ecology and associated conservation threats in wildlife.


Protecting Medical Trainees on the Coronavirus Disease 2019 (COVID-19) Frontlines Saves Us All


The fight against stroke must go on


Obesity-related stigma—hiding in plain sight


title: A Unified Approach for EIT Imaging of Regional Overdistension and Atelectasis in Acute Lung Injury

text: Patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS) are vulnerable to ventilator-induced lung injury. Although this syndrome affects the lung heterogeneously, mechanical ventilation is not guided by regional indicators of potential lung injury. We used electrical impedance tomography (EIT) to estimate the extent of regional lung overdistension and atelectasis during mechanical ventilation. Techniques for tidal breath detection, lung identification, and regional compliance estimation were combined with the Graz consensus on EIT lung imaging (GREIT) algorithm. Nine ALI/ARDS patients were monitored during stepwise increases and decreases in airway pressure. Our method detected individual breaths with 96.0% sensitivity and 97.6% specificity. The duration and volume of tidal breaths erred on average by 0.2 s and 5%, respectively. Respiratory system compliance from EIT and ventilator measurements had a correlation coefficient of 0.80. Stepwise increases in pressure could reverse atelectasis in 17% of the lung. At the highest pressures, 73% of the lung became overdistended. During stepwise decreases in pressure, previously-atelectatic regions remained open at sub-baseline pressures. We recommend that the proposed approach be used in collaborative research of EIT-guided ventilation strategies for ALI/ARDS.


title: Impact of Model Shape Mismatch on Reconstruction Quality in Electrical Impedance Tomography

text: Electrical impedance tomography (EIT) is a low-cost, noninvasive and radiation free medical imaging modality for monitoring ventilation distribution in the lung. Although such information could be invaluable in preventing ventilator-induced lung injury in mechanically ventilated patients, clinical application of EIT is hindered by difficulties in interpreting the resulting images. One source of this difficulty is the frequent use of simple shapes which do not correspond to the anatomy to reconstruct EIT images. The mismatch between the true body shape and the one used for reconstruction is known to introduce errors, which to date have not been properly characterized. In the present study we, therefore, seek to 1) characterize and quantify the errors resulting from a reconstruction shape mismatch for a number of popular EIT reconstruction algorithms and 2) develop recommendations on the tolerated amount of mismatch for each algorithm. Using real and simulated data, we analyze the performance of four EIT reconstruction algorithms under different degrees of shape mismatch. Results suggest that while slight shape mismatch is well tolerated by all algorithms, using a circular shape severely degrades their performance.


title: A SARS Method for Reliable Spectrum Sensing in Multiband Communication Systems

text: This paper introduces a novel method of spectrum sensing in communication systems that utilizes nonuniform sampling in conjunction with a suitable spectral analysis tool. It is referred to here as spectral analysis for randomized sampling (SARS). Owing to the deployment of nonuniform sampling, the proposed technique can accomplish the sensing task by using sampling rates well below the ones demanded by uniform-sampling-based digital signal processing (DSP). The effect of the cyclostationary nature of the incoming digital communication signal on the adequacy of the adopted periodogram-type estimator for the spectrum sensing operation is addressed. The statistical characteristics of the estimator are presented. General reliability conditions on the length of the required signal observation window, i.e., sensing time, for a chosen sampling rate or vice versa are provided amid a sought system performance. The impact of the presence of noise and processing transmissions with various power levels on the derived dependability recommendations is given. The analytical results are illustrated by numerical examples. This paper establishes a new framework for efficient spectrum sensing where considerable savings on the sampling rate and number of processed samples can be attained.


title: Absolute Electrical Impedance Tomography (aEIT) Guided Ventilation Therapy in Critical Care Patients: Simulations and Future Trends

text: Thoracic electrical impedance tomography (EIT) is a noninvasive, radiation-free monitoring technique whose aim is to reconstruct a cross-sectional image of the internal spatial distribution of conductivity from electrical measurements made by injecting small alternating currents via an electrode array placed on the surface of the thorax. The purpose of this paper is to discuss the fundamentals of EIT and demonstrate the principles of mechanical ventilation, lung recruitment, and EIT imaging on a comprehensive physiological model, which combines a model of respiratory mechanics, a model of the human lung absolute resistivity as a function of air content, and a 2-D finite-element mesh of the thorax to simulate EIT image reconstruction during mechanical ventilation. The overall model gives a good understanding of respiratory physiology and EIT monitoring techniques in mechanically ventilated patients. The model proposed here was able to reproduce consistent images of ventilation distribution in simulated acutely injured and collapsed lung conditions. A new advisory system architecture integrating a previously developed data-driven physiological model for continuous and noninvasive predictions of blood gas parameters with the regional lung function data/information generated from absolute EIT (aEIT) is proposed for monitoring and ventilator therapy management of critical care patients.


title: Computational Study of Interdependence Between Hemagglutinin and Neuraminidase of Pandemic 2009 H1N1

text: Influenza type A viruses are classified into subtypes based on their two surface proteins, hemagglutinin (HA) and neuraminidase (NA). The HA protein facilitates the viral binding and entering a host cell and the NA protein helps the release of viral progeny from the infected cell. The complementary roles of HA and NA entail their collaboration, which has important implications for viral replication and fitness. The HA protein from early strains of pandemic 2009 H1N1 of swine origin preferentially binds to human type receptors with a weak binding to avian type receptors. This virus caused several human deaths in December 2013 in Texas, USA, which motivated us to investigate the changes of genetic features that might contribute to the surged virulence of the virus. Our time series analysis on the strains of this virus collected from 2009 to 2013 implied that the HA binding preference of this virus in USA, Europe, and Asia has been the characteristic of swine H1N1 virus since 2009. However, its characteristic of seasonal human H1N1 and its binding avidity for avian type receptors both were on steady rise and had a clear increase in 2013 with American strains having the sharpest surge. The first change could enhance the viral transmission and replication in humans and the second could increase its ability to cause infection deep in lungs, which might account for the recent human deaths in Texas. In light of HA and NA coadaptation and evolutionary interactions, we also explored the NA activity of this virus to reveal the functional balance between HA and NA during the course of virus evolution. Finally we identified amino acid substitutions in HA and NA of the virus that were critical for the observed evolution.


title: Pandemic Influenza Detection by Electrically Active Magnetic Nanoparticles and Surface Plasmon Resonance

text: Influenza A virus (FLUAV), the causative agent of influenza infection, has received extensive attention due to the recent swine-origin H1N1 pandemic. FLUAV has long been the cause of annual epidemics as well as less frequent but more severe global pandemics. Here, we describe a biosensor utilizing electrically active magnetic (EAM) polyaniline-coated nanoparticles as the transducer in an electrochemical biosensor for rapidly identifying FLUAV strains based on receptor specificity, which will be useful to monitor animal influenza infections and to characterize pandemic potential of strains that have transmitted from animals to humans. Pandemic potential requires human-to-human transmissibility, which is dependent upon FLUAV hemagglutinin (HA) specificity for host glycan receptors. Avian FLUAV preferentially bind to α2,3-linked receptors, while human FLUAV bind to α2,6-linked receptors. EAM nanoparticles were prepared by synthesizing aniline monomer around gamma iron (III) oxide (γ-Fe(2)O(3)) cores, yielding 25–100-nm diameter nanoparticles that were structurally characterized by transmission electron microscopy and electron diffraction. The EAM nanoparticles were coated with monoclonal antibodies specific to H5N1 (A/Vietnam/1203/04). Specificity of binding between glycans and H5 was demonstrated. The biosensor results were correlative to supporting data from a surface plasmon resonance assay that characterized HA/glycan binding and α-H5 antibody activity. This novel study applies EAM nanoparticles as the transducer in a specific, portable, easy-to-use biosensor with great potential for disease monitoring and biosecurity applications.


title: Identification of Adequate Neurally Adjusted Ventilatory Assist (NAVA) During Systematic Increases in the NAVA Level

text: Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (P(aw)) in proportion to the electrical activity of the diaphragm (EAdi) using an adjustable proportionality constant (NAVA level, cm⋅H (2)O/ [Formula: see text] V). During systematic increases in the NAVA level, feedback-controlled down-regulation of the EAdi results in a characteristic two-phased response in P(aw) and tidal volume (Vt). The transition from the 1st to the 2nd response phase allows identification of adequate unloading of the respiratory muscles with NAVA (NAVA(AL)). We aimed to develop and validate a mathematical algorithm to identify NAVA(AL). P(aw), Vt, and EAdi were recorded while systematically increasing the NAVA level in 19 adult patients. In a multistep approach, inspiratory P(aw) peaks were first identified by dividing the EAdi into inspiratory portions using Gaussian mixture modeling. Two polynomials were then fitted onto the curves of both P(aw) peaks and Vt. The beginning of the P(aw) and Vt plateaus, and thus NAVA (AL), was identified at the minimum of squared polynomial derivative and polynomial fitting errors. A graphical user interface was developed in the Matlab computing environment. Median NAVA(AL) visually estimated by 18 independent physicians was 2.7 (range 0.4 to 5.8) cm⋅H (2)O/ [Formula: see text] V and identified by our model was 2.6 (range 0.6 to 5.0) cm⋅H (2)O/ [Formula: see text] V. NAVA(AL) identified by our model was below the range of visually estimated NAVA(AL) in two instances and was above in one instance. We conclude that our model identifies NAVA(AL) in most instances with acceptable accuracy for application in clinical routine and research.


title: Unobtrusive Sensing and Wearable Devices for Health Informatics

text: The aging population, prevalence of chronic diseases, and outbreaks of infectious diseases are some of the major challenges of our present-day society. To address these unmet healthcare needs, especially for the early prediction and treatment of major diseases, health informatics, which deals with the acquisition, transmission, processing, storage, retrieval, and use of health information, has emerged as an active area of interdisciplinary research. In particular, acquisition of health-related information by unobtrusive sensing and wearable technologies is considered as a cornerstone in health informatics. Sensors can be weaved or integrated into clothing, accessories, and the living environment, such that health information can be acquired seamlessly and pervasively in daily living. Sensors can even be designed as stick-on electronic tattoos or directly printed onto human skin to enable long-term health monitoring. This paper aims to provide an overview of four emerging unobtrusive and wearable technologies, which are essential to the realization of pervasive health information acquisition, including: 1) unobtrusive sensing methods, 2) smart textile technology, 3) flexible-stretchable-printable electronics, and 4) sensor fusion, and then to identify some future directions of research.


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title: Ensuring Equitable Access to School Meals


title: Plasma Donors in the Southwestern United States Positively Contribute to the Diverse Therapeutic Antibody Profile of Immune Globulin Products

text: Human-plasma-derived immune globulin (IG) is used in augmentation therapy to provide protective levels of antibodies to patients with primary immune deficiency diseases (PIDD) and for prophylaxis against infectious diseases. To maintain the breadth of antibodies necessary for clinical protection, it is important to understand regional patterns of antibody seroprevalence in source plasma from which IG products are manufactured. In this study, source plasma from donation centers in various locations of the Southwestern quarter of the United States was surveyed for antibody titers to hepatitis A virus (HAV), measles virus (MeV), and cytomegalovirus (CMV). A broad range of anti-HAV Ig plasma titers was observed among these centers, with some centers exhibiting 3–5 times the titers of the others. Minor to no differences were observed for levels of anti-MeV and anti-CMV, respectively. Importantly, elevated anti-HAV Ig titers were broadly observed across plasma units obtained from the centers exhibiting high titers, indicative of a potential regional phenomenon among donors as opposed to few donors with singularly high titers. Plasma from these high-titer centers conferred significantly greater neutralization against HAV in vitro. The outcomes of this study give a glimpse of the antibody diversity inherent in human plasma used to manufacture IG products..


title: Development of a Yeast Two-Hybrid Screen for Selection of Human Ras-Raf Protein Interaction Inhibitors

text: A yeast two-hybrid screening system was developed to screen for small molecules that inhibit the interaction of the Ras and the Raf proteins. Hyperpermeable yeast strains useful for high-throughput screening (HTS) for the two-hybrid system were created. Differential inhibition of the Ras-Raf vs the hsRPB4-hsRPB7 interaction allowed the identification of selective inhibitors.


title: Acute Hemorrhagic Rectal Ulcer Syndrome: A New Clinical Entity? Report of 19 Cases and Review of the Literature

text: PURPOSE: Acute hemorrhagic rectal ulcer syndrome is characterized by sudden onset, painless, and massive hemorrhage from rectal ulcer(s) in patients with serious underlying illnesses. It is a matter of controversy whether acute hemorrhagic rectal ulcer syndrome is a distinct clinical entity. This is the first Asian report on acute hemorrhagic rectal ulcer syndrome to be made outside Japan. METHODS: From January 1989 to December 1999, 8,085 patients underwent total colonoscopy at our institution. We retrospectively analyzed the medical records and colonoscopic files. The diagnosis of acute hemorrhagic rectal ulcer syndrome was made by means of the clinical, histologic, and colonoscopic findings. RESULTS: Among the 8,085 patients, 19 patients (11 males; mean age, 71.2 ± 10.1 years) were diagnosed with acute hemorrhagic rectal ulcer syndrome, which accounted for 2.8 percent of the patients with massive lower gastrointestinal bleeding. The duration from hospitalization to the onset of massive bleeding ranged from 3 to 14 (mean, 9 ± 3.3) days. Characteristics of colonoscopic appearance were solitary or multiple rectal ulcer(s), with round, circumferential, geographical, or Dieulafoy-like lesions located within a mean of 4.7 cm ± 1.5 cm from the dentate line. Histopathologically, the lesions appeared as necrosis with denudation of covering epithelium, hemorrhage, and multiple thrombi in the vessels of the mucosa and underlying stroma, which is considered to be similar to stress-related mucosa injury. Successful hemostasis was obtained in 74 percent (14/19) of patients with direct therapeutic maneuvers. Prognosis was largely dependent on accurate diagnosis and management of the underlying disorders. CONCLUSIONS: We assert that acute hemorrhagic rectal ulcer syndrome is a rare but important entity and stress that awareness of this clinical entity should lead to a high index of suspicion resulting in early detection, diagnosis, and appropriate therapy.


title: Culture, institutions and democratization*

text: We construct a model of revolution and transition to democracy under individualistic and collectivist cultures. The main result is that, despite facing potentially more challenging collective action problems, countries with individualistic cultures are more likely to end up adopting democracy earlier than countries with collectivist cultures. Our empirical analysis suggests a strong and robust association between individualistic cultures and average polity scores and durations of democracy, even after controlling for other determinants of democracy emphasized in the literature. We provide evidence that countries with collectivist cultures also are more likely to experience autocratic breakdowns and transitions from autocracy to autocracy.


Reply to the letter to the editor by Tuuminen et al. (2020), “Indoor air nontoxicity should be proven with special techniques prior claiming that it may cause a variety of mental disorders.”


title: Investigating the Strategies Adopted by Emergency Nurses to Address Uncertainty and Change in the Event of Emerging Infectious Diseases: A Grounded Theory Study

text: Emergency nurses frequently encounter uncertainty and changes during the management of emerging infectious diseases, which challenge their capability to perform their duties in a well-planned and systematic manner. To date, little is known about the coping strategies adopted by emergency nurses in addressing uncertainty and changes during an epidemic event. The present study explored emergency nurses’ behaviours and strategies in handling uncertainty and practice changes during an epidemic event. A qualitative study based on the Straussian grounded theory approach was established. Semi-structured, face-to-face, individual interviews were conducted with 26 emergency nurses for data collection. Adapting protocol to the evolving context of practice was revealed as the core category. Four interplaying subcategories were identified: (1) Completing a comprehensive assessment, (2) continuing education for emerging infectious disease management, (3) incorporating guideline updates and (4) navigating new duties and competencies. The nurses demonstrated the prudence to orientate themselves to an ambiguous work situation and displayed the ability to adapt and embrace changes in their practice and duties. These findings offer insights into the need for education and training schemes that allow emergency nurses to acquire and develop the necessary decision-making and problem-solving skills to handle a public health emergency.


title: The Relationship Exploration between Public Migration Attention and Population Migration from a Perspective of Search Query

text: Rapid population migration has been viewed as a critical factor impacting urban network construction and regional sustainable development. The supervision and analysis of population migration are necessary for guiding the optimal allocation of urban resources and for attaining the high efficiency development of region. Currently, the explorations of population migration are often restricted by the limitation of data. In the information era, search engines widely collect public attention, implying potential individual actions, and freely provide open, timelier, and large-scope search query data for helping explore regional phenomena and problems. In this paper, we endeavor to explore the possibility of adopting such data to depict population migration. Based on the search query from Baidu search engine, three migration attention indexes (MAIs) are constructed to capture public migration attention in cyber space. Taking three major urban agglomerations in China as case study, we conduct the correlation analysis among the cyber MAIs and population migration in geographical space. Results have shown that external-MAI and local-MAI can positively reflect the population migration inner regions and across regions from a holistic lens and that intercity-MAI can be a helpful supplement for the delineation of specific population flow. Along with the accumulation of cyber search query data, its potential in exploring population migration can be further reinforced.


title: Validation of age, PaO(2)/FlO(2) and plateau pressure score in Korean patients with acute respiratory distress syndrome: a retrospective cohort study

text: BACKGROUND: A predictive scoring system for acute respiratory distress syndrome (ARDS) patients, which incorporates age, PaO(2)/FlO(2), and plateau pressure, APPS, was developed recently. It was validated externally in a Caucasian population but has not been studied in Asian populations. The aim of this study was to validate APPS in Korean ARDS patients. METHODS: We retrospectively reviewed the medical records of patients who were diagnosed with ARDS using the Berlin criteria and admitted to the medical ICU at Seoul National University Hospital from January 2015 to December 2016. The validation of the APPS was performed by evaluating its calibration and predictive accuracy. Its calibration was plotted and quantified using the Hosmer–Lemeshow test. Its predictive accuracy was assessed by calculating the area under the receiver operating characteristics (AUC–ROC) curve. RESULTS: A total of 116 patients were analyzed, 32 of whom survived. Of the 116 patients, 11 (9.5%) were classified as APPS grade 1 (score 3–4), 88 (75.9%) as grade 2 (score 5–7) and 17 (14.6%) as grade 3 (score 8–9). In-hospital mortality was 27.3% for grade 1, 73.9% for grade 2 and 94.1% for grade 3 (P for trend < 0.001). The APPS was well calibrated (Hosmer–Lemeshow test, P = 0.578) and its predictive accuracy was acceptable (AUC–ROC 0.704, 95% confidence interval 0.599–0.809). CONCLUSIONS: The APPS predicted in-hospital mortality in Korean patients with ARDS with similar power to its application in a Western population and with acceptable predictive accuracy. TRIAL REGISTRATION: Retrospectively registered.


title: H2 influenza A virus is not pathogenic in Tmprss2 knock-out mice

text: The host cell protease TMPRSS2 cleaves the influenza A virus (IAV) hemagglutinin (HA). Several reports have described resistance of Tmprss2(−/−) knock-out (KO) mice to IAV infection but IAV of the H2 subtype have not been examined yet. Here, we demonstrate that TMPRSS2 is able to cleave H2-HA in cell culture and that Tmprss2(−/−) mice are resistant to infection with a re-assorted PR8_HA(H2) virus. Infection of KO mice did not cause major body weight loss or death. Furthermore, no significant increase in lung weights and no virus replication were observed in Tmprss2(−/−) mice. Finally, only minor tissue damage and infiltration of immune cells were detected and no virus-positive cells were found in histological sections of Tmprss2(−/−) mice. In summary, our studies indicate that TMPRSS2 is required for H2 IAV spread and pathogenesis in mice. These findings extend previous results pointing towards a central role of TMPRSS2 in IAV infection and validate host proteases as a potential target for antiviral therapy.


title: Immunization with a fusion protein vaccine candidate generated from truncated peptides of human enterovirus 71 protects mice from lethal enterovirus 71 infections

text: BACKGROUND: Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. Children aged less than 5 years are especially susceptible to EV71 infections. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens also constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. We previously developed a fusion protein composed with truncated peptides of the EV71 capsid protein, which assembled into spherical particles. This study aimed to assess the immunoprotective effects of this fusion protein as a vaccine candidate in a mouse model of EV71 infection. METHODS: To evaluate the protective effect of fusion protein vaccine candidate, neonatal mice born by immunized female mice, as well as normal neonatal mice immunized twice were infected with EV71 virus. Whereafter, the survival rates, clinical scores and viral loads were measured. RESULTS: The high dosage and booster immunization helped induce specific serum antibodies with high neutralization titers, which were transferred to neonatal mice, thereby facilitating effective resistance towards EV71 infection. An active immune response was also observed in neonatal mice which generated following immunization. CONCLUSIONS: The present results suggest that this fusion protein is a suitable vaccine candidate in treating EV71 infections.


title: Synthesis and Bioactivity Assessment of Novel Spiro Pyrazole-Oxindole Congeners Exhibiting Potent and Selective in vitro Anticancer Effects

text: The present work aims to design and synthesize novel series of spiro pyrazole-3,3’-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7; colon, HCT-116 and liver, HepG-2) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and proapoptotic protein markers. The analytical and spectral data of the all synthesized target congeners were compatible with their structures. Synthesized compounds showed diverse moderate to powerful antimicrobial and antioxidant activities. Results of MTT assay revealed that seven synthesized compounds (i.e., 11a, 11b, 12a, 12b, 13b, 13c and 13h) particularly exhibited significant cytotoxicity against the three cancerous cell lines under investigation. Ranges of IC(50) values obtained were 5.7–21.3 and 5.8–37.4 µg/mL against HCT-116 and MCF-7, respectively; which is 3.8 and 6.5-fold (based on the least IC(50) values) more significant relative to the reference chemotherapeutic drug doxorubicin. In HepG-2 cells, the analogue 13h exhibited the highest cytotoxicity with IC(50) value of 19.2µg/mL relative to doxorubicin (IC(50) = 21.6µg/mL). The observed cytotoxicity was specific to cancerous cells, as evidenced by the minimal toxicity in the noncancerous control skin-fibroblast cells. ELISA results indicated that the observed antiproliferative effect against examined cancer cell lines is mediated via engaging the activation of apoptosis as illustrated by the significant increase in proapoptotic protein markers (p53, bax and caspase-3) and reduction in the antiapoptotic marker bcl-2. Taken together, results of the present study emphasize the potential of spiro pyrazole-oxindole analogues as valuable candidate anticancer agents against human cancer cells.


Mitteilungen des Berufsverbands der Pneumologen in Baden-Württemberg


Agenda


Deep phenotyping: Embracing complexity and temporality—Towards scalability, portability, and interoperability


Remote Treatment Delivery in Response to the COVID-19 Pandemic.


title: Resistance of Enteric Viruses on Fomites

text: Human enteric viruses are associated with several clinical features, especially gastroenteritis. Large amounts of these viruses can be released in the environment and spread to people. Enteric viruses are nonenveloped viruses and have displayed good survival in the environment. They can be significantly resistant in food and water but also on fomites, and this is thought to play a role in transmission, leading to sporadic cases or outbreaks. The survival of enteric viruses on fomites relies on many factors including the virus itself, fomite properties, and extrinsic environmental factors such as temperature or relative humidity. Several reports in the literature have found an association with gastroenteritis cases or outbreaks and fomites naturally contaminated by enteric viruses. However, the study of virus survival following natural contamination is challenging, and most published studies are laboratory based, using experimental contamination. In addition, recent and detailed data on the resistance of each of the main enteric viruses on fomites are scarce. Many approaches, both physical and chemical, can be used to inactivate enteric viruses, the efficacy of which depends on the virus and the disinfection conditions.


title: Effects of Age on Voice Onset Time and Variability in Children with Repaired Cleft Palate

text: OBJECTIVE: To examine the effect of age on voice onset time (VOT) and VOT variability in children with repaired cleft palate. METHODS: Twenty-two children with repaired cleft palate were allocated into two age groups: younger children (YC: n = 13) and older children (OC: n = 9). VOT measurements from monosyllabic words (/pa/, /ta/, and /ka/) and intraspeaker VOT variability estimated by coefficients of variation (CoV) of two age groups were compared. RESULTS: Age was found to have a statistically significant effect on VOT and VOT variability. Specifically, OC had significantly longer VOT (F(1,66) = 4.196, p < 0.05) and less VOT variability (F(1,66) = 6.007, p < 0.05) for English voiceless stops than YC. No statistically significant main effect for speech sample or age by speech sample interaction was observed. CONCLUSIONS: Our data supplement the existing literature by adding VOT and VOT variability information for older children/adolescents with repaired cleft palate. Findings from the study suggest VOT patterns acquired at younger age appear to be further exaggerated and stabilized during the adolescent period among children with repaired cleft palate. A future study is necessary to determine different sources of VOT variability in children with a history of cleft palate, which may have clinical therapeutic implications.


title: Prognostic factors for ARDS: clinical, physiological and atypical immunodeficiency

text: BACKGROUND: Risk factors affecting the prognosis of acute respiratory distress syndrome (ARDS) in adults were investigated. The aim was to identify new predictors for ARDS patient prognosis, including those with clinical, pathophysiological, and atypical immunodeficiency. METHODS: ARDS patients were retrospectively included. The patients were grouped and analysed according to different oxygenation index grades and prognosis, and factors influencing prognosis and survival were examined. Adolescent patients, patients with typical immunodeficiency and patients who died within 24 h after being diagnosed with ARDS were excluded. The predictive value for mortality was determined by Cox proportional hazard analysis. RESULTS: In total, 201 patients who fulfilled the Berlin definition of ARDS were included. The severity of critical illness on the day of enrolment, as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.016), Sequential Organ Failure Assessment (SOFA) score (P = 0.027), and PaO(2)/FiO(2) (P = 0.000), worsened from mild to severe ARDS cases. Compared with survivors, non-survivors were significantly older and had higher APACHE II and SOFA scores. Moreover, significantly lower lymphocyte/neutrophil ratios and leukocyte counts were found among non-survivors than survivors (P = 0.008, P = 0.012). A moderate positive correlation between the lymphocyte/neutrophil and PaO(2)/FiO(2) ratios (P = 0.023) was observed. In predicting 100-day survival in patients with ARDS, the area under the curve (AUC) for the lymphocyte/neutrophil ratio was significantly higher than those for the PaO(2)/FiO(2) ratio alone, body mass index (BMI) alone, and the lymphocyte count alone (P = 0.0062, 0.0001, and 0.0154). Age (per log(10) years), BMI < 24, SOFA score, leukocyte count, and the lymphocyte/neutrophil ratio were independent predictors of 28-day mortality in ARDS patients. Additionally, ARDS patients with a lymphocyte/neutrophil ratio < 0.0537 had increased 28-day mortality rates (P = 0.0283). Old age affected both 28-day and 100-day mortality rates (P = 0.0064,0.0057). CONCLUSIONS: Age (per log(10) years), BMI < 24, SOFA score, lymphocytes, and the lymphocyte/neutrophil ratio were independent predictors of 100-day mortality in patients with ARDS. The lymphocyte/neutrophil ratio may represent a potential molecular marker to evaluate atypical immunosuppression or impairment in patients with ARDS.


Understanding health spending for SDG 3


India under COVID-19 lockdown


docid: hfpmelrn

title: Understanding spending trends for tuberculosis


“Carbon Pricing” Special Issue in the European Economic Review


'We will have a lot to do when this is over'


docid: vkihskox

title: 'I do not know when I will practise again'


Online resource created to support redeployed dentists


BDJ offers support to dental companies


Alternative teaching aids


Caution with NSAIDs


Initial experience of DCTs


'We are all awaiting our call to the frontline'


Head Dental Officer appointed


Remain positive and proactive


Young colleagues need support


Out of our comfort zone


Skincare experts offer advice for those wearing face masks for long periods


Mitteilungen der Gesellschaft für Gastroenterologie in NRW


docid: mbeyduzy

title: Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

text: Despite being a leading cause of severe respiratory disease, there remains no licensed respiratory syncytial virus (RSV) vaccine. Neutralizing antibodies reduce the severity of RSV-associated disease, but are not sufficient for preventing reinfection. In contrast, the role of memory CD8 T cells in protecting against a secondary RSV infection is less established. We recently demonstrated that high-magnitude memory CD8 T cells efficiently reduced lung viral titers following RSV infection, but induced fatal immunopathology that was mediated by IFN-γ. To evaluate the ability of RSV-specific neutralizing antibodies to prevent memory CD8 T cell-mediated immunopathology, mice with high-magnitude memory CD8 T cell responses were treated with neutralizing antibodies prior to RSV challenge. Neutralizing antibody treatment significantly reduced morbidity and prevented mortality following RSV challenge compared with IgG-treated controls. Neutralizing antibody treatment restricted early virus replication, which caused a substantial reduction in memory CD8 T cell activation and IFN-γ production, directly resulting in survival. In contrast, therapeutic neutralizing antibody administration did not impact morbidity, mortality, or IFN-γ levels, despite significantly reducing lung viral titers. Therefore, only pre-existing neutralizing antibodies prevent memory CD8 T cell-mediated immunopathology following RSV infection. Overall, our results have important implications for the development of future RSV vaccines.


Protect Healthcare Workers and Patients from COVID-19: The Experience of Two Tertiary Ophthalmology Care Referral Centers in Italy.


title: Effectiveness comparison of indocyanine green retention test with the cirrhotic severity scoring in evaluating the pathological severity of liver cirrhosis in patients with hepatocellular carcinoma and Child-Pugh grade A liver function

text: BACKGROUND: Evaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown. METHODS: Overall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared. RESULTS: Patients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality. CONCLUSIONS: CSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades.


title: Pilot test of an online training module on near-infrared spectroscopy monitoring for the randomised clinical trial SafeBoosC-III

text: BACKGROUND: SafeBoosC-III is an international randomised clinical trial to evaluate the effect of treatment of extremely preterm infants during the first 3 days of life based on cerebral near-infrared spectroscopy (NIRS) monitoring versus treatment and monitoring as usual. To ensure high quality of the trial intervention as well as of patient care, we have developed a multilingual web-based training program to train relevant staff and test their competence. As we enter an under-explored area of e-learning, we have conducted a pilot study on the first of the five modules comprising the web-based training program to test the feasibility of developing such a program for an international trial with limited resources. METHODS: The module in this study focuses on the principles and practice of NIRS monitoring. The pedagogical idea was to integrate training and certification. One-hundred doctors and nurses from five Neonatal Intensive Care Units across China, Spain and Denmark were invited to participate in the pilot study. Upon completion of the NIRS module, participants were invited to evaluate their experience by completing an online survey. Data from closed-ended questions were analysed using descriptive statistics while data from open-ended questions underwent thematic analysis. RESULTS: In total, 81 of 100 invited staff members entered the training module and completed the online survey. The median time and the number of questions to pass the module was 15 minutes and seven questions, respectively. Most staff found the academic level of the learning material and quiz appropriate (85% and 93% of all staff members, respectively), as well as agreeing that the module was relevant to prepare them to ‘use the NIRS device’ (90%). Thematic analysis revealed issues such as a discrepancy between learning material and quiz questions, lack of clarity, and technical issues. CONCLUSION: We provide evidence of the feasibility of developing a multilingual web-based training program for an international trial, despite challenges such as low budget, language barriers and possibly differences in the clinical training of staff. Exploring the integration of training and certification for international trials, the positive results of this study motivate further developments. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03770741. Registered 10 December 2018.


title: Update on Ebola Treatment Center Costs and Sustainability, United States, 2019

text: We surveyed 56 Ebola treatment centers (ETCs) in the United States and identified costs incurred since 2014 ($1.76 million/ETC) and sustainability strategies. ETCs reported heavy reliance on federal funding. It is uncertain if, or for how long, ETCs can maintain capabilities should federal funding expire in 2020.


docid: djcdvdhq

title: New trends in Manufacturing Systems Research 2020


Update to Our Reader, Reviewer, and Author Communities—April 2020


docid: plpghewn

title: Association of early viral lower respiratory infections and subsequent development of atopy, a systematic review and meta-analysis of cohort studies

text: INTRODUCTION: Existing evidence on the relationship between childhood lower respiratory tract infections (LRTI) and the subsequent atopy development is controversial. We aimed to investigate an association between viral LRTI at <5 years and the development of atopy at > 2 years. METHODS: We conducted a search at Embase, Pubmed, Web of Science, and Global Index Medicus. We collected data from the included articles. We estimated the odds ratio and the 95% confidence intervals with a random effect model. We determined factors associated with atopy development after childhood LRTI using univariate and multivariate meta-regression analyses. We recorded this systematic review at PROSPERO with the number CRD42018116955. RESULTS: We included 24 studies. There was no relationship between viral LRTI at <5 years and skin prick test-diagnosed-atopy (OR = 1.2, [95% CI = 0.7–2.0]), unknown diagnosed-atopy (OR = 0.7, [95% CI = 0.4–1.3]), atopic dermatitis (OR = 1.2, [95% CI = 0.9–1.6]), hyperreactivity to pollen (OR = 0.8, [95% CI = 0.3–2.7]), food (OR = 0.8, [95% CI = 0.3–2.5]), or house dust mite (OR = 1.1, [95% CI = 0.6–2.2]). Although not confirmed in all studies with a symmetric distribution of the 23 confounding factors investigated, the overall analyses showed that there was a relationship between childhood viral LRTI at < 5 years and serum test diagnosed-atopy (OR = 2.0, [95% CI = 1.0–4.1]), allergic rhinoconjunctivitis (OR = 1.7, [95% CI = 1.1–2.9]), hyperreactivity diagnosed by serum tests with food (OR = 5.3, [1.7–16.7]) or inhaled allergens (OR = 4.2, [95% CI = 2.1–8.5]), or furred animals (OR = 0.6, [95% CI = 0.5–0.9]). CONCLUSION: These results suggest that there is no association between viral LRTI at < 5 years and the majority of categories of atopy studied during this work. These results, however, are not confirmed for the remaining categories of atopy and more particularly those diagnosed by serum tests. There is a real need to develop more accurate atopy diagnostic tools.


title: Comparative characterization of flavivirus production in two cell lines: Human hepatoma-derived Huh7.5.1-8 and African green monkey kidney-derived Vero

text: The Flaviviridae is a family of enveloped viruses with a positive-sense single-stranded RNA genome. It contains many viruses that threaten human health, such as Japanese encephalitis virus (JEV) and yellow fever virus (YFV) of the genus Flavivirus as well as hepatitis C virus of the genus Hepacivirus. Cell culture systems highly permissive for the Flaviviridae viruses are very useful for their isolation, propagation, and diagnosis, an understanding of their biology, and the development of vaccines and antiviral agents. Previously, we isolated a human hepatoma HuH-7-derived cell clone, Huh7.5.1–8, which is highly permissive to hepatitis C virus infection. Here, we have characterized flavivirus infection in the Huh7.5.1–8 cell line by comparing with that in the African green monkey kidney-derived Vero cell line, which is permissive for a wide spectrum of viruses. Upon infection with JEV, Huh7.5.1–8 cells produced a higher amount of virus particles early in infection and were more susceptible to virus-induced cell death than Vero cells. Similar outcomes were obtained when the cells were infected with another flavivirus, YFV (17D-204 strain). Quantification of cellular and extracellular viral RNA revealed that high JEV production in Huh7.5.1–8 cells can be attributed to rapid viral replication kinetics and efficient virus release early in infection. In a plaque assay, Huh7.5.1–8 cells developed JEV plaques more rapidly than Vero cells. Although this was not the case with YFV plaques, Huh7.5.1–8 cells developed higher numbers of YFV plaques than Vero cells. Sequence analysis of cDNA encoding an antiviral RNA helicase, RIG-I, showed that Huh7.5.1–8 cells expressed not only a full-length RIG-I mRNA with a known dominant-negative missense mutation but also variants without the mutation. However, the latter mRNAs lacked exon 5/6−12, indicating functional loss of RIG-I in the cells. These characteristics of the Huh7.5.1–8 cell line are helpful for flavivirus detection, titration, and propagation.


title: The CD1 family and T cell recognition of lipid antigens

text: Abstract: For many years it was thought that T lymphocytes recognized only peptide antigens presented by MHC class I or class II molecules. Recently, it has become clear that a wide variety of lipids and glycolipids are also targets of the T cell response. This novel form of cell‐mediated immune recognition is mediated by a family of lipid binding and presenting molecules known as CD1. The CD1 proteins represent a small to moderate sized family of β2‐microglobulin‐associated transmembrane proteins that are distantly related to MHC class I and class II molecules. They are conserved in most or all mammals, and control the development and function of T cell populations that participate in innate and adaptive immune responses through the recognition of self and foreign lipid antigens. Here we review the current state of our understanding of the structure and function of CD1 proteins, and the role of CD1‐restricted T cell responses in the immune system.


title: Detection of blood‐transmissible agents: can screening be miniaturized?

text: Transfusion safety relating to blood‐transmissible agents is a major public health concern, particularly when faced with the continuing emergence of new infectious agents. These include new viruses appearing alongside other known reemerging viruses (West Nile virus, Chikungunya) as well as new strains of bacteria and parasites (Plasmodium falciparum, Trypanosoma cruzi) and finally pathologic prion protein (variant Creutzfeldt‐Jakob disease). Genomic mutations of known viruses (hepatitis B virus, hepatitis C virus, human immunodeficiency virus) can also be at the origin of variants susceptible to escaping detection by diagnostic tests. New technologies that would allow the simultaneous detection of several blood‐transmissible agents are now needed for the development and improvement of screening strategies. DNA microarrays have been developed for use in immunohematology laboratories for blood group genotyping. Their application in the detection of infectious agents, however, has been hindered by additional technological hurdles. For instance, the variability among and within genomes of interest complicate target amplification and multiplex analysis. Advances in biosensor technologies based on alternative detection strategies have offered new perspectives on pathogen detection; however, whether they are adaptable to diagnostic applications testing biologic fluids is under debate. Elsewhere, current nanotechnologies now offer new tools to improve the sample preparation, target capture, and detection steps. Second‐generation devices combining micro‐ and nanotechnologies have brought us one step closer to the potential development of innovative and multiplexed approaches applicable to the screening of blood for transmissible agents.


Letter to the editor concerning “Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version)” by Zhao et al., Journal of Orthopaedic Translation, 2019, https://doi.org/10.1016/j.jot.2019.12.004


title: Retinopathy of prematurity in Rwanda: a prospective multi-centre study following introduction of screening and treatment services

text: OBJECTIVES: To investigate risk factors for retinopathy of prematurity (ROP) in a newly established ROP screening and management programme in Rwanda, Africa. METHODS: In this multi-centre prospective study 795/2222 (36%) babies fulfilled the inclusion criteria (gestational age (GA) < 35 weeks or birth weight (BW) < 1800 g or unstable clinical course), 424 (53%) of whom were screened for ROP. 270 died before the first screening. ROP and treatment-warranted ROP were classified using the revised International Classification of ROP (2005). Data on maternal and perinatal risk factors were collected from daily neonatal notes. RESULTS: 31 babies (7.3%, CI 5.0–10.2) developed any ROP, 13 of whom (41.9%, CI 24.5–60.9) required treatment. ROP was seen in six neonates with GA > 30 weeks and BW > 1500 g, one of whom required treatment. In univariate analysis the following were associated with any ROP: increasing number of days on supplemental oxygen (OR 2.1, CI 1.5–3.0, P < 0.001), low GA (OR 3.4, CI 1.8–6.4, P < 0.001), low BW (OR 2.3, CI 1.5–3.4, P < 0.001), at least one episode of hyperglycaemia ≥ 150 mg/dl (OR 6.6, CI 2.0–21.5, P < 0.001), blood transfusion (OR 3.5, CI 1.6–7.4, P < 0.001) or sepsis (OR 3.2, CI 1.2–8.6, P = 0.01). In multivariate analysis longer exposure to supplemental oxygen (OR 2.1, CI 1.2–3.6, P = 0.01) and hyperglycaemia (OR 3.5, CI 1.0–12.4, P = 0.05) remained significant. CONCLUSIONS: ROP has become an emerging health problem in Rwanda, requiring programmes for screening and treatment. ROP screening is indicated beyond the 2013 American Academy guidelines. Improved quality of neonatal care, particularly oxygen delivery and monitoring is needed.


title: Coronaviridae1

text: The family Coronavirtdae comprises a monogeneric group of 11 viruses which infect vertebrates. The main characteristics of the member viruses are: (i) Morphological: Enveloped pleomorphic particles typically 100 nm in diameter (range 60-220 nm), bearing about 20 nm long club-shaped surface projections, (ii) Structural: A single-stranded infectious molecule of genomic RNA of about (5-7) × 10(6) molecular weight. A phosphorylated nucleocapsid protein [mol.wt. (50-60) × 10(3)] complexed with the genome as a helical ribonucleoprotein; a surface (peplomer) protein, associated with one or two glycosylated polypeptides [mol.wt. (90-180) × 10(3)]; a transmembrane (matrix) protein, associated with one polypeptide which may be glycosylated to different degrees [mol.wt. (20-35) × 10(3)]. (iii) Replicative: Production in infected cells of multiple 3′ coterminal sub genomic mRNAs extending for different lengths in the 5′ direction. Virions bud intracytoplasmically. (iv) Antigenic: 3 major antigens, each corresponding to one class of virion protein, (v) Biological: Predominantly restricted to infection of natural vertebrate hosts by horizontal transmission via the fecal/oral route. Responsible mainly for respiratory and gastrointestinal disorders.


title: Predictive factors for successful INTELLiVENT-ASV® use: a retrospective observational study

text: BACKGROUND: INTELLiVENT-ASV® (I-ASV) is a closed-loop ventilation mode that automatically controls the ventilation settings. Although a number of studies have reported the usefulness of I-ASV, the clinical situations in which it may be useful have not yet been clarified. We aimed to report our initial 3 years of experience using I-ASV, particularly the clinical conditions and the technical and organizational factors associated with its use. Furthermore, we evaluated the usefulness of I-ASV and determined the predictive factors for successful management with I-ASV. METHODS: This single-center, retrospective observational study included patients who were ventilated using the Hamilton G5® ventilator (Hamilton Medical AG, Rhäzüns, Switzerland) from January 2016 to December 2018. The patients were categorized into the “I-ASV success” group and “I-ASV failure” group (those receiving mechanical ventilation with I-ASV along with any other mode). Multivariate analysis was performed to identify factors associated with successful I-ASV management. RESULTS: Of the 189 patients, 135 (71.4%) were categorized into the I-ASV success group. In the I-ASV success group, the reasons for ICU admission included post-elective surgery (94.1%), post-emergent surgery (81.5%), and other medical reasons (55.6%). I-ASV failure was associated with a low P/F ratio (278 vs. 167, P = 0.0003) and high Acute Physiology and Chronic Health Evaluation (APACHE) II score (21 vs. 26, P < 0.0001). The main reasons for not using I-ASV included strong inspiratory effort and asynchrony. The APACHE II score was an independent predictive factor for successful management with I-ASV, with an odds ratio of 0.92 (95% confidential interval 0.87–0.96, P = 0.0006). The area under the receiver operating curve for the APACHE II score was 0.722 (cut-off: 24). CONCLUSIONS: In this study, we found that 71.4% of the fully mechanically ventilated patients could be managed successfully with I-ASV. The APACHE II score was an independent factor that could help predict the successful management of I-ASV. To improve I-ASV management, it is necessary to focus on patient-ventilator interactions.


title: Effect of mechanical ventilation versus spontaneous breathing on abdominal edema and inflammation in ARDS: an experimental porcine model

text: BACKGROUND: Mechanical ventilation (MV), compared to spontaneous breathing (SB), has been found to increase abdominal edema and inflammation in experimental sepsis. Our hypothesis was that in primary acute respiratory distress syndrome (ARDS) MV would enhance inflammation and edema in the abdomen. METHODS: Thirteen piglets were randomized into two groups (SB and MV) after the induction of ARDS by lung lavage and 1 h of injurious ventilation. 1. SB: continuous positive airway pressure 15 cmH(2)O, fraction of inspired oxygen (FIO(2)) 0.5 and respiratory rate (RR) maintained at about 40 cycles min(− 1) by titrating remifentanil infusion. 2. MV: volume control, tidal volume 6 ml kg(− 1), positive end-expiratory pressure 15 cmH(2)O, RR 40 cycles min(− 1), FIO(2) 0.5. Main outcomes: abdominal edema, assessed by tissues histopathology and wet-dry weight; abdominal inflammation, assessed by cytokine concentration in tissues, blood and ascites, and tissue histopathology. RESULTS: The groups did not show significant differences in hemodynamic or respiratory parameters. Moreover, edema and inflammation in the abdominal organs were similar. However, blood IL6 increased in the MV group in all vascular beds (p < 0.001). In addition, TNFα ratio in blood increased through the lungs in MV group (+ 26% ± 3) but decreased in the SB group (− 17% ± 3). CONCLUSIONS: There were no differences between the MV and SB group for abdominal edema or inflammation. However, the systemic increase in IL6 and the TNFα increase through the lungs suggest that MV, in this model, was harmful to the lungs.


title: Leptospirosis as an important differential of pulmonary haemorrhage on the intensive care unit: a case managed with VV-ECMO

text: BACKGROUND: Leptospirosis is a potentially fatal zoonosis. It can cause a wide range of symptoms, including diffuse alveolar haemorrhage which occurs in a minority of cases but carries a mortality of over 70%. These patients may present with severe acute respiratory failure. The differential diagnosis for diffuse alveolar haemorrhage is broad whereas prompt diagnosis and treatment can be lifesaving. CASE PRESENTATION: A 20-year-old previously fit and well trout farm worker presented with a 3-day history of malaise, fevers, diarrhoea, vomiting and jaundice. He developed haemoptysis, severe headaches, neck stiffness and photophobia on the day of emergency admission. He was anaemic and thrombocytopenic. Anuric acute kidney injury (urea 32, creat 507) required immediate haemofiltration. In view of progressive respiratory failure with four-quadrant lung infiltrates on imaging, he was given broad spectrum antibiotics and pulsed methylprednisolone empirically, in case of a vasculitic pulmonary-renal presentation. He was intubated within 48 h of admission. Despite attempted protective ventilatory management, he remained hypoxaemic and developed pneumomediastinum. He was retrieved to a specialist cardiorespiratory intensive care unit on femoro-femoral mobile VV-ECMO. Three days from admission, results showed positive Leptospira IgM and real-time PCR. Serial bronchoscopies showed old and fresh clots, but not the classical progressive late red tinge of the returned lavage fluid. After eight days, VV-ECMO was weaned, he was extubated three days later, and made a full recovery. At 9 months follow-up, he was clinically better, with resolution of the CT scan findings and near normal lung function, albeit with low normal gas transfer. CONCLUSIONS: Leptospirosis is a rare but important differential to be considered in diffuse alveolar haemorrhage presenting to the ICU, especially in young males. A thorough history for occupational or recreational risk factors may offer the diagnostic clue. Most patients recover fully with antibiotics. However, resulting acute severe respiratory failure can ensue. In this situation, early consideration for respiratory ECMO support offers time for clearance of endobronchial clot, parenchymal recovery, and prevention of ventilator-induced lung injury. Steroids have no clear evidence but may be used to avoid delay in treating suspected vasculitic or autoimmune causes of diffuse alveolar haemorrhage.


title: Low occurrence of extended-spectrum cephalosporinase producing Enterobacteriaceae and no detection of methicillin-resistant coagulase-positive staphylococci in healthy dogs in Sweden

text: Sweden has a long tradition of monitoring occurrence of antibiotic resistant bacteria in both animals and humans, but there currently is no organised and harmonized monitoring on carriage of Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase (pAmpC), or methicillin-resistant coagulase positive staphylococci e.g. methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs. The aim of the current study was therefore to determine the prevalence of ESBL/pAmpC producing Enterobacteriaceae and methicillin-resistant coagulase positive staphylococci in healthy dogs in Sweden, and to phenotypically and genotypically characterize any identified isolates. It was shown that 0.9% (95% confident interval 0.3–2.7%) of the dogs (n = 325) carried multi-resistant ESBL-producing Escherichia coli, but that no methicillin-resistant coagulase positive staphylococci could be detected. In conclusion, the occurrence of multi-drug resistant bacteria remains rare among healthy dogs in Sweden. In addition, the ESBL-producing E. coli identified showed genetic characteristics related to those reported from humans.


docid: bqemkljl

title: Diagnostic Experience from an Epidemic of Canine Parvoviral Enteritis

text: SUMMARY: Hemagglutination (HA) test and electron microscopy (EM) were used to diagnose canine parvoviral enteritis on fecal samples from 58 hospitalized dogs of a huge epidemic. By HA‐tests the presence of the canine parvovirus (CPV) involved was shown in samples from 15 dogs (∼ 26%). A reference antiserum was used to identify the virus of each sample by hemagglutination inhibition (HI). By EM parvovirus‐like particles were seen in samples from 28 dogs (∼ 48%). Particles in six samples were identified as CPV by immunoaggregation. Sera from 17 out of 19 dogs examined showed specific HI titers during the acute stage of illness. A high incidence of concomitant infection with Campylobacter spp was found by the bacteriologists. ZUSAMMENFASSUNG: Diagnostische Erfahrungen während einer Epidemie von Parvovirus‐Enteritis der Hunde Während einer grossen Epidemie von Parvovirus‐Enteritis der Hunde (in Schweden) wurde der Nachweis von Virus in Kotproben mit Hilfe der Hëmagglutination (HA) und Elektronenmikroskopie (EM) versucht; die Kotproben stammten von 58 hospitalisierten Hunden. Mit dem HA‐Test ließ sich das ursächliche Parvovirus in den Proben von 15 Hunden nachweisen (= ∼ 26%). In jeder von diesen Proben wurde das Virus durch Hämagglutination‐Hemmung (HAH) mit einem Referenzserum identifiziert. Mit der EM waren Parvovirus‐ähnliche Partikel in den Proben von 28 Hunden zu finden (= ∼ 48%). In 6 von diesen Proben wurden die Partikel mittels der Immunaggregation als das ursächlichen Parvovirus identifiziert. In 17 Serumproben von 19 untersuchten Hunden wurden spezifische HAH‐Titer während der akuten Krankheitsphase festgestellt. Die Bakteriologen wiesen ein gehäuftes Vorkommen von gleichzeitiger Infektion mit Campylobacter spp nach. RÉSUMÉ: Expériences de diagnostic durant une épidémie d'entérite à Parvovirus chez des chiens On a recherché la mise en évidence du virus dans des matières fécales à l'aide de l'hémagglutination (HA) et de la microscopie électronique (EM) durant une forte épidémie d'entérite à Parvovirus chez des chiens en Suède. Les échantillons d'excréments provenaient de 58 chiens hospitalisés. Le Parvovirus a été mis en évidence par test HA dans les échantillons de 15 chiens (∼ 26%). Le virus a été identifié dans chacun de ces échantillons au moyen de l'inhibition de l'hémagglutination (HAH) avec un sérum de référence. On a trouvé des particules identiques au microscope électronique dans les échantillons de 28 chiens (∼ 48%). Les particules dans 6 de ces prélèvements furent identifiées comme Parvovirus au moyen de l'immunoaggrégation. Un titre HAH spécifique a été établi durant la phase aiguë de la maladie dans 17 échantillons sérologiques sur 19 chiens examinés. La bactériologie a montré la présence fréquente d'une infection simultanée à Campylobacter spp. RESUMEN: Experiencias en el diagnóstico de una epidemia de parvovirus‐enteritis en caninos Mediante pruebas de hemaglutinación y microscopía electrónica se diagnosticó parvovirus‐enteritis en caninos en muestras fecales de 58 caninos hospitalizados a raiz de una extensa epidemia. Con la prueba de hemaglutinación se detectó la presencia de virus en muestras fecales de 15 caninos (∼ 26%). Un antisuero de referencia se utilizó para la identificación del virus (prueba de inhibición de la hemaglutinación). Con microscopía electrónica se identificó parvovirus en muestras fecales de 28 caninos (∼ 48%). El virus fué identificado en seis muestras fecales utilizando la prueba de inmunoagregación. Sueros de 17 de 19 caninos examinados demostraron títulos específicos de inhibición de la hemaglutinación durante la etapa aguda de la enfermedad. Se demostró también una alta incidencia de infección concomitante con Campylobacter spp.


Telehealth’s Time Has Come


Bladder Cancer Guidelines: Let Not the Cure Be Worse than the Disease


The Wuhan COVID-19 intubation experience


Keep Taking Your ACE Inhibitors and ARBs During the COVID 19 Pandemic


Safety Considerations in the Laboratory Testing of Specimens Suspected or Known to Contain the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)


COVID-19: Keine Entwarnung im Sommer?


docid: cnygzwkw

title: Hydrops fetalis and neonatal abdominal compartment syndrome continuum from immature gastric teratoma: a case report

text: BACKGROUND: Hydrops fetalis as well as abdominal compartment syndrome (ACS) are conditions that are associated with high mortality rates. A rare case of immature gastric teratoma causing fetal hydrops and subsequent ACS is presented. The related pathophysiologic mechanisms are discussed, and the importance of timely recognition and appropriate interventions are highlighted. CASE PRESENTATION: The male patient was born preterm, weighing 3.9 kg., by Cesarean section. Prior prenatal ultrasounds were normal, but a scan done just before delivery had findings indicating polyhydramnios, fetal ascites, and meconium peritonitis. Upon delivery, the patient had respiratory distress, anasarca and a massively distended abdomen. Resuscitation measures, including ventilatory support, were instituted. Imaging studies showed ascites as well as a large, complex intra-abdominal lesion with calcifications. In the succeeding hours, anuria persisted, anasarca worsened, the abdomen became more distended, and inotrope requirements increased. The occurrence of ACS, from what was presumed to be a retroperitoneal teratoma, was therefore considered. Laparotomy was done on the 28th hour of life, with en bloc excision of a massive tumor and attached section of the greater curvature of the stomach. Passage of urine occurred intra-operatively, and the patient was soon after weaned off inotropes and ventilator support. The histopathologic result was immature gastric teratoma. No chemotherapy was given, and the patient’s serum AFP is at normal levels 15 months following surgery. CONCLUSION: The presence of a massive intra-abdominal lesion can result in the pathophysiologic continuum of hydrops fetalis and neonatal ACS. The early recognition of such an association can enable appropriate expectant management of similarly affected neonates, including emergent decompression laparotomy.


title: Noninvasive oxygenation strategies in adult patients with acute respiratory failure: a protocol for a systematic review and network meta-analysis

text: BACKGROUND: Acute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and is associated with high mortality. Noninvasive oxygenation strategies such as high-flow nasal cannula, standard oxygen therapy, and noninvasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of noninvasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. METHODS: We will search key databases for randomized controlled trials assessing the effect of noninvasive oxygenation strategies in adult patients with acute hypoxemic respiratory failure. We will exclude studies in which the primary focus is either acute exacerbations of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. The primary outcome will be all-cause mortality (longest available up to 90 days). The secondary outcomes will be receipt of invasive mechanical ventilation (longest available up to 30 days). We will assess the risk of bias for each of the outcomes using the Cochrane Risk of Bias Tool. Bayesian network meta-analyses will be conducted to obtain pooled estimates of head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and 95% credible intervals. Subgroup analyses will be conducted examining key populations including immunocompromised hosts. Sensitivity analyses will be conducted by excluding those studies with high risk of bias and different etiologies of acute respiratory failure. We will assess certainty in effect estimates using GRADE methodology. DISCUSSION: This study will help to guide clinical decision-making when caring for adult patients with acute hypoxemic respiratory failure and improve our understanding of the limitations of the available literature assessing noninvasive oxygenation strategies in acute hypoxemic respiratory failure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121755


title: Age Limit in Bronchiolitis Diagnosis: 6 or 12 Months?

text: Aim: The most frequent cause of lower respiratory tract infection in infants is bronchiolitis. Up to now there is no agreement on the upper limit age of bronchiolitis. Our aim was to identify if there are clinical differences in infants hospitalized for bronchiolitis between 0–6 months and 6–12 months of age. A secondary aim was to establish whether there was differences in terms of recurrent wheezing at 12, 24, and 36 months of follow-up. Methods: We retrospectively analyzed clinical and virological records of 824 infants hospitalized for bronchiolitis during 11 consecutive epidemic seasons. From each infant at admission to the hospital nasopharyngeal washing was collected, clinical severity was assessed and clinical data were extracted from a structured questionnaire. At 12–24–36 months after discharge, parents were interviewed seeking information on recurrent wheezing. Results: A total of 773 infants (Group1) were ≤6 months of age, while 51 were >6 months (Group 2). No differences between family history for atopy and passive smoking exposure were observed between the two groups. Respiratory syncyzial virus was detected more frequently in Group 1 and human bocavirus in Group 2. The clinical severity score (p = 0.011) and the use of intravenous fluids (p = 0.0001) were higher in Group 1 with respect to Group 2 infants. At 36 months follow-up 163/106 (39.4%) Group 1 and 9/9 Group 2 infants experienced recurrent wheezing (p = 0.149). Conclusion: We demonstrated that 0-6 months old infants bronchiolitis differs from > 6 months bronchiolitis.


Esperanza de vida al nacer. Contribuciones y desafíos de la microbiología


title: Immunocytochemical Localization of the Menkes Copper Transport Protein (ATP7A) to the Trans-Golgi Network

text: We have generated polyclonal antibodies against the amino-terminal third of the Menkes protein (ATP7A; MNK) by immunizing rabbits with a histidine-tagged MNK fusion construct containing metal-binding domains 1–4. The purified antibodies were used in Western analysis of cell lysates and in indirect immunofluorescence experiments on cultured cells. On Western blots, the antibodies recognized the ∼165 kDa MNK protein in CHO cells and human fibroblasts. No MNK signal could be detected in fibroblasts from a patient with Menkes disease or in Hep3B hepatocellular carcinoma cells, confirming the specificity of the antibodies. Immunocytochemical analysis of CHO cells and human fibroblasts showed a distinct perinuclear signal corresponding to the pattern of the Golgi complex. This staining pattern was similar to that of α-mannosidase II which is a known resident enzyme of the Golgi complex. Using brefeldin A, a fungal inhibitor of protein secretion, we further demonstrated that the MNK protein is localized to the trans-Golgi network. This data provides direct evidence for a subcellular localization of the MNK protein which is similar to the proposed vacuolar localization of Ccc2p, the yeast homolog of MNK and WND (ATP7B), the Wilson disease gene product. In light of the proposed role of MNK both in subcellular copper trafficking and in copper efflux, these data suggest a model for how these two processes are linked and represent an important step in the functional analysis of the MNK protein.


Confronting infectious diseases is a perpetual struggle, top official says


title: Amenity Migration and Public Lands: Rise of the Protected Areas

text: Rural amenity migration, or the relocation for quality of life purposes as opposed to monetary enhancement, has been occurring for decades and has been particularly pronounced in the American West where the phenomenon peaked in the 1990s. Researchers have illustrated that some places are more attractive for migrants than others and that certain regional amenities hold considerable influence on where migrants relocate. Increased migration levels typically result in increased economic growth indicators, making amenity migration an attractive rural development strategy. But comprehensive econometric analysis focused on amenity migration in the American West has been lacking. To address this, we conducted an econometric analysis of attributes that influenced migration to rural Western counties from 1980 to 2010. Over 20 potential amenity supply categories were collated for 356 rural counties from 11 Western states, with a focus on public lands. Descriptive statistics and OLS regressions were estimated and interpreted. Traditional amenities of climate, water area, and regional access were highly associated with migration levels, while designated natural amenities of Wilderness and National Monuments were the most influential public lands for migration to rural Western counties. Farming and oil and gas dependency were negatively associated with migration levels. Increasing the amount of protected areas, and branding campaigns based on natural amenities, can be a critical development strategy for rural communities.


Harnessing Cross-Reactive CD8(+) T(RM) Cells for Long-Standing Protection Against Influenza A Virus


This Scientific Life


title: Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN

text: CIRE/mDC-SIGN is a C-type lectin we originally identified as a molecule differentially expressed by mouse dendritic cell (DC) populations. Immunostaining with a CIRE/mDC-SIGN-specific mAb revealed that CIRE/mDC-SIGN is indeed on the surface of some CD4(+), CD4(−)8(−) DCs and plasmacytoid pre-DCs, but not on CD8(+) DCs. It has been proposed that CIRE/mDC-SIGN is the functional orthologue of human DC-SIGN (hDC-SIGN), a molecule that both enhances T cell responses and facilitates antigen uptake. We assessed if CIRE/mDC-SIGN and hDC-SIGN exhibit functional similarities. CIRE/mDC-SIGN is down-regulated upon activation, but unlike hDC-SIGN, incubation with IL-4 and IL-13 did not enhance CIRE/mDC-SIGN expression, indicating differences in gene regulation. Like hDC-SIGN, CIRE/mDC-SIGN bound mannosylated residues. However, we could detect no role for CIRE/mDC-SIGN in T cell–DC interactions and the protein did not bind to pathogens known to interact with hDC-SIGN, including Leishmania mexicana, cytomegalovirus, HIV and lentiviral particles bearing the Ebolavirus glycoprotein. The binding of CIRE/mDC-SIGN to hDC-SIGN ligands was not rescued when CIRE/mDC-SIGN was engineered to express the stalk region of hDC-SIGN. We conclude that there are significant differences in the fine specificity of the C-type lectin domains of hDC-SIGN and CIRE/mDC-SIGN and that these two molecules may not be functional orthologues.


title: Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9

text: Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but the underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions in patients with multiple sclerosis are associated with increased glial expression of fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination and remyelination in vitro. This inhibitory activity is associated with the appearance of multi-branched ‘pre-myelinating’ MBP(+)/PLP(+) oligodendrocytes that interact with axons but fail to assemble myelin sheaths; an oligodendrocyte phenotype described previously in chronically demyelinated multiple sclerosis lesions. This inhibitory activity is not due to a direct effect of FGF9 on cells of the oligodendrocyte lineage but is mediated by factors secreted by astrocytes. Transcriptional profiling and functional validation studies demonstrate that these include effects dependent on increased expression of tissue inhibitor of metalloproteinase-sensitive proteases, enzymes more commonly associated with extracellular matrix remodelling. Further, we found that FGF9 induces expression of Ccl2 and Ccl7, two pro-inflammatory chemokines that contribute to recruitment of microglia and macrophages into multiple sclerosis lesions. These data indicate glial expression of FGF9 can initiate a complex astrocyte-dependent response that contributes to two distinct pathogenic pathways involved in the development of multiple sclerosis lesions. Namely, induction of a pro-inflammatory environment and failure of remyelination; a combination of effects predicted to exacerbate axonal injury and loss in patients.


title: Perspectives on Fatigue from the Study of Chronic Fatigue Syndrome and Related Conditions

text: Fatigue is a symptom whose causes are protean and whose phenotype includes physical, mood, and behavioral components. Chronic fatigue syndrome (CFS) is an illness that has strong biological underpinnings and no definite etiology. Diagnostic criteria established by the Centers for Disease Control and Prevention have helped classify CFS as an overlap of mood, behavioral, and biological components. These include the presence of fatigue for more than 6 months associated with a diminution of functional activity and somatic symptoms, and pain not attributable to a specific diagnosis or disease. Four of the following criteria need to be present: sore throat, impaired memory or cognition, unrefreshing sleep, postexertional fatigue, tender glands, aching stiff muscles, joint pain, and headaches. Many researchers have observed that CFS shares features in common with other somatic syndromes, including irritable bowel syndrome, fibromyalgia, and temporomandibular joint dysfunction. Correlations between inflammation and infection, augmented sensory processing, abnormalities of neurotransmitters, nerve growth factors, low levels of serotonin and norepinephrine, abnormalities of homeostasis of the stress system, and autonomic dysfunction may be hallmarks of CFS. The relative contributions of each of these abnormalities to the profound fatigue associated with CFS need to be explored further to better evaluate and treat the syndrome.


Pediatric Patient Safety in the Ambulatory Setting


title: LRRK2 Expression in Normal and Pathologic Human Brain and in Human Cell Lines

text: Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently identified in families with autosomal-dominant late-onset Parkinson disease. We report that by reverse transcriptase-polymerase chain reaction, the mRNA of LRRK2 is expressed in soluble extracts of human brain, liver, and heart and in cultured human astrocytes, microglia, and oligodendroglia as well as in human neuroblastoma cell lines. We find by Western blotting using a polyclonal antibody of the leucine-rich repeat kinase 2 protein (Lrrk2) specific for C-terminal residues 2511-2527 that an apparent full-length protein and several of its fractions are expressed in soluble extracts of normal human brain. By immunocytochemistry, the antibody recognizes neurons, and more weakly astrocytes and microglia, in normal brain tissue. It intensely labels Lewy bodies in Parkinson disease and related neurodegenerative disorders. It also labels a subset of neurofibrillary tangles in Alzheimer disease and the Parkinsonism dementia complex of Guam (PDCG). It labels thorn-shaped astrocytes and oligodendroglial coiled bodies in PDCG; oligodendroglial inclusions in multiple system atrophy; Pick bodies in Pick disease; nuclear and cytoplasmic inclusions in Huntington disease; and intraneuronal and glial inclusions in amyotrophic lateral sclerosis. In summary, LRRK2 is constitutively expressed in neurons and also in glial cells of human brain. It strongly associates with pathological inclusions in several neurodegenerative disorders.