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Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement
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701
Department of Error
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Correction to Lancet Glob Health 2020; 8: e452–53
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703
Multiple parameters required for diagnosis of COVID-19 in clinical practice
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704
Avian macrophage and immune response: an overview
Macrophages belong to the mononuclear phagocytic system lineage. This cell type is unique in that it is a crucial player in both the innate and adaptive immune responses. The material described in this overview is a brief description of what I presented as a World's Poultry Science Association-sponsored lecture at the annual meetings of the Poultry Science Association in 2002. Therefore, I have not attempted to present an up-to-date review of literature on this topic. Rather, I have summarized some salient research accomplishments made by our research group over the years in the area of avian macrophage biology and function.
705
Letter from the Guest Editors
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706
Clinical and CT imaging features of 2019 novel coronavirus disease (COVID-19)
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707
HEALTH STATUS OF LIVER TRANSPLANTED PATIENTS DURING THE CORONAVIRUS OUTBREAK IN ITALY: A LARGE SINGLE CENTER EXPERIENCE FROM MILAN
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708
A non-static quantum inspired spacetime in f(R) gravity: Gravity's rainbow
In this note we explore a non-static spacetime in quantum regime in the background of [Formula: see text] gravity. The time dependent Vaidya metric which represents the spacetime of a radiating body like star is studied in an energy dependent gravity's rainbow, which is a UV completion of General Relativity. In our quest we have used gravitational collapse as the main tool. The focus is to probe the nature of singularity (black hole or naked singularity) formed out of the collapsing procedure. This is achieved via a geodesic study. For our investigation we have considered two different models of [Formula: see text] gravity, namely the inflationary Starobinsky's model and the power law model. Our study reveals the fact that naked singularity is as good a possibility as black hole as far as the central singularity is concerned. Via a proper fine tuning of the initial data, we may realize both black hole or naked singularity as the end state of the collapse. Thus this study is extremely important and relevant in the light of the Cosmic Censorship hypothesis. The most important result derived from the study is that gravity's rainbow increases the tendency of formation of naked singularities. We have also deduced the conditions under which the singularity will be a strong or weak curvature singularity. Finally in our quest to know more about the model we have performed a thermodynamical study. Throughout the study we have obtained results which involve deviation from the classical set-up. Such deviations are expected in a quantum evolution and can be attributed to the quantum fluctuations that our model suffers from. It is expected that this study will enhance our knowledge about quantization of gravity and subsequently about the illusive theory of quantum gravity.
709
Physical activity for immunity protection: Inoculating populations with healthy living medicine in preparation for the next pandemic()
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710
Artificial Intelligence (AI) applications for COVID-19 pandemic
BACKGROUND AND AIMS: Healthcare delivery requires the support of new technologies like Artificial Intelligence (AI), Internet of Things (IoT), Big Data and Machine Learning to fight and look ahead against the new diseases. We aim to review the role of AI as a decisive technology to analyze, prepare us for prevention and fight with COVID-19 (Coronavirus) and other pandemics. METHODS: The rapid review of the literature is done on the database of Pubmed, Scopus and Google Scholar using the keyword of COVID-19 or Coronavirus and Artificial Intelligence or AI. Collected the latest information regarding AI for COVID-19, then analyzed the same to identify its possible application for this disease. RESULTS: We have identified seven significant applications of AI for COVID-19 pandemic. This technology plays an important role to detect the cluster of cases and to predict where this virus will affect in future by collecting and analyzing all previous data. CONCLUSIONS: Healthcare organizations are in an urgent need for decision-making technologies to handle this virus and help them in getting proper suggestions in real-time to avoid its spread. AI works in a proficient way to mimic like human intelligence. It may also play a vital role in understanding and suggesting the development of a vaccine for COVID-19. This result-driven technology is used for proper screening, analyzing, prediction and tracking of current patients and likely future patients. The significant applications are applied to tracks data of confirmed, recovered and death cases.
711
Leadership Evolution: The Academy's Sustained and Growing Contribution
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712
Pandemic school closures: risks and opportunities
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713
Validation of RESP and PRESERVE score for ARDS patients with pumpless extracorporeal lung assist (pECLA)
BACKGROUND: RESP score and PRESERVE score have been validated for veno-venous Extracorporeal Membrane Oxygenation in severe ARDS to assume individual mortality risk. ARDS patients with low-flow Extracorporeal Carbon Dioxide Removal, especially pumpless Extracorporeal Lung Assist, have also a high mortality rate, but there are no validated specific or general outcome scores. This retrospective study tested whether these established specific risk scores can be validated for pumpless Extracorporeal Lung Assist in ARDS patients in comparison to a general organ dysfunction score, the SOFA score. METHODS: In a retrospective single center cohort study we calculated and evaluated RESP, PRESERVE, and SOFA score for 73 ARDS patients with pumpless Extracorporeal Lung Assist treated between 2002 and 2016 using the XENIOS iLA Membrane Ventilator. Six patients had a mild, 40 a moderate and 27 a severe ARDS according to the Berlin criteria. Demographic data and hospital mortality as well as ventilator settings, hemodynamic parameters, and blood gas measurement before and during extracorporeal therapy were recorded. RESULTS: Pumpless Extracorporeal Lung Assist of mechanical ventilated ARDS patients resulted in an optimized lung protective ventilation, significant reduction of P(aCO2), and compensation of acidosis. Scoring showed a mean score of alive versus deceased patients of 3 ± 1 versus − 1 ± 1 for RESP (p < 0.01), 3 ± 0 versus 6 ± 0 for PRESERVE (p < 0.05) and 8 ± 1 versus 10 ± 1 for SOFA (p < 0.05). Using receiver operating characteristic curves, area under the curve (AUC) was 0.78 (95% confidence interval (CI) 0.67–0.89, p < 0.01) for RESP score, 0.80 (95% CI 0.70–0.90, p < 0.0001) for PRESERVE score and 0.66 (95% CI 0.53–0.79, p < 0.05) for SOFA score. CONCLUSIONS: RESP and PRESERVE scores were superior to SOFA, as non-specific critical care score. Although scores were developed for veno-venous ECMO, we could validate RESP and PRESERVE score for pumpless Extracorporeal Lung Assist. In conclusion, RESP and PRESERVE score are suitable to estimate mortality risk of ARDS patients with an arterio-venous pumpless Extracorporeal Carbon Dioxide Removal.
714
The Generation of Virtual Defenders
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715
Maurizio Galderisi. In Memoriam
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716
Comparison of ATP Bioluminescence and Aerobic Bacterial Count for Evaluating Surface Cleanliness in an Italian Hospital
Contaminated hospital surfaces have been demonstrated to be an important environmental reservoir of microorganisms that can increase the risk of nosocomial infection in exposed patients. As a consequence, cleaning and disinfecting hospital environments play an important role among strategies for preventing healthcare-associated colonization and infections. The aim of the present study was to evaluate whether adenosine triphosphate (ATP) presence, measured by bioluminescence methods, can predict microbiological contamination of hospital surfaces. The study was carried out between September and December 2012 at the University Hospital “P. Giaccone” of Palermo. A total of 193 randomly selected surfaces (tables, lockers, furnishings) were sampled and analyzed in order to assess ATP levels (expressed as relative light units or RLU) and aerobic colony count (ACC) or presence of S. aureus. ACC had median values of 1.85 cfu/cm(2) (interquartile range = 4.16) whereas ATP median was 44.6 RLU/cm(2) (interquartile range = 92.3). Overall, 85 (44.0%) surfaces exceeded the established microbial benchmark: 73 (37.8%) exceeded the 2.5 cfu/cm(2) ACC standard, 5 (2.6%) surfaces were positive for S. aureus and 7 (3.6%) showed both the presence of S. aureus and an ACC of more than 2.5 cfu/cm(2). ACC and bioluminescence showed significant differences in the different surface sites (p < 0.001). A significant correlation was found between ACC and RLU values (p-value < 0.001; R(2) = 0.29) and increasing RLU values were significantly associated with a higher risk of failing the benchmark (p < 0.001). Our data suggest that bioluminescence could help in measuring hygienic quality of hospital surfaces using a quick and sensitive test that can be an useful proxy of microbial contamination; however, further analysis will be necessary to assess the cost-efficacy of this methodology before requiring incorporation in hospital procedures.
717
Analysis of Residual Chemicals on Filtering Facepiece Respirators After Decontamination
The N95 filtering facepiece respirator (FFR) is commonly used to protect individuals from infectious aerosols. Health care experts predict a shortage of N95 FFRs if a severe pandemic occurs, and an option that has been suggested for mitigating such an FFR shortage is to decontaminate and reuse the devices. Before the effectiveness of this strategy can be established, many parameters affecting respiratory protection must be measured: biocidal efficacy of the decontamination treatment, filtration performance, pressure drop, fit, and toxicity to the end user post treatment. This research effort measured the amount of residual chemicals created or deposited on six models of FFRs following treatment by each of 7 simple decontamination technologies. Measured amounts of decontaminants retained by the FFRs treated with chemical disinfectants were small enough that exposure to wearers will be below the permissible exposure limit (PEL). Toxic by-products were also evaluated, and two suspected toxins were detected after ethylene oxide treatment of FFR rubber straps. The results provide encouragement to efforts promoting the evolution of effective strategies for decontamination and reuse of FFRs.
718
Health Care Workers’ Mobile Phones: A Potential Cause of Microbial Cross-Contamination Between Hospitals and Community
This study evaluated the microbial contamination of health care workers’ (HCWs) mobile phones. The study was conducted at a secondary referral hospital in July 2010. Samples were taken from all surfaces of the mobile phones using a sterile swab, and incubated on Brain Heart Infusion agar at 37.5°C for 24 hr. Any isolated microorganisms were grown aerobically on 5% sheep blood agar and eosin methylene-blue agar medium at 37.5°C for 24–48 hr. The Sceptor microdilution system was used to identify the microorganisms, together with conventional methods. The oxacillin disc diffusion test and double-disc synergy test were used to identify methicillin-resistant Staphylococcus aureus (MRSA) and expanded-spectrum beta-lactamase (ESBL)-producing Gram-negative bacilli, respectively. The mobile phones were also categorized according to whether the HCWs used them in the intensive care unit (ICU). Overall, 183 mobile phones were screened: 94 (51.4%) from nurses, 32 (17.5%) from laboratory workers, and 57 (31.1%) from health care staff. In total, 179 (97.8%) culture-positive specimens were isolated from the 183 mobile phones, including 17 (9.5%) MRSA and 20 (11.2%) ESBL-producing Escherichia coli, which can cause nosocomial infections. No statistical difference was observed in the recovery of MRSA (p = 0.3) and ESBL-producing E. coli (p = 0.6) between the HCW groups. Forty-four (24.6%) of the 179 specimens were isolated from mobile phones of ICU workers, including two MRSA and nine ESBL-producing E. coli. A significant (p = 0.02) difference was detected in the isolation of ESBL-producing E. coli between ICU workers and non-ICU workers. HCWs’ mobile phones are potential vectors for transferring nosocomial pathogens between HCWs, patients, and the community.
719
Inactivation of Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus faecium (VRE) on Various Environmental Surfaces by Mist Application of a Stabilized Chlorine Dioxide and Quaternary Ammonium Compound-Based Disinfectant
Contaminated environmental surfaces are important reservoirs in the transmission of many human pathogens. Although several options exist for disinfecting contaminated environmental surfaces, few are compatible with use on both hard smooth non-porous (hard) and soft porous surfaces (soft) while still offering significant disinfection of the contaminating organisms. This study evaluated the efficacy of mist application of a stabilized chlorine dioxide and quaternary ammonium compound-based disinfectant (Cryocide20) for inactivation of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) on various environmental surfaces. MRSA and VRE were applied to hard and soft surfaces (glass, steel, tile, carpet, and cotton fabric), allowed to dry, and exposed to a uniform mist application of the disinfectant solution. After 1 hr of contact time, the residual disinfectant was neutralized, and the bacteria were recovered and enumerated on brain heart infusion (BHI) agar. Reduction of both test bacteria was observed on most of the hard and soft surfaces tested. Log(10) reduction of the organisms tended to be higher on steel, tile, and carpet than glass or cotton. Overall, these results suggest that mist application of Cryocide20 disinfectant may be an effective option for reduction of low levels of infectious bacterial pathogens from contaminated environmental surfaces.
720
A Study Quantifying the Hand-to-Face Contact Rate and Its Potential Application to Predicting Respiratory Tract Infection
A substantial portion of human respiratory tract infection is thought to be transmitted via contaminated hand contact with the mouth, eyes, and/or nostrils. Thus, a key risk factor for infection transmission should be the rate of hand contact with these areas termed target facial membranes. A study was conducted in which 10 subjects were each videotaped for 3 hr while performing office-type work in isolation from other persons. The number of contacts to the eyes, nostrils, and lips was scored during subsequent viewing of the tapes. The total contacts per subject had sample mean x = 47 and sample standard deviation s = 34. The average total contact rate per hour was 15.7. The authors developed a relatively simple algebraic model for estimating the dose of pathogens transferred to target facial membranes during a defined exposure period. The model considers the rate of pathogen transfer to the hands via contact with contaminated environmental surfaces, and the rate of pathogen loss from the hands due to pathogen die-off and transfer from the hands to environmental surfaces and to target facial membranes during touching. The estimation of infection risk due to this dose also is discussed. A hypothetical but plausible example involving influenza A virus transmission is presented to illustrate the model.
721
Discomfort and Exertion Associated with Prolonged Wear of Respiratory Protection in a Health Care Setting
The nature of discomfort and level of exertion associated with wearing respiratory protection in the health care workplace are not well understood. Although a few studies have assessed these topics in a laboratory setting, little is known about the magnitude of discomfort and the level of exertion experienced by workers while they deliver health care to patients for prolonged periods. The purpose of this study was to determine the magnitude of discomfort and level of exertion experienced by health care workers while wearing respiratory protection for periods up to 8 hr when performing their typical occupational duties. This project was a multiple cross-over field trial of 27 health care workers, aged 24–65, performing their typical, hospital-based occupational duties. Each participant served as his/her own control and wore one of seven respirators or a medical mask for 8 hr (or as long as tolerable) with interposed doffing periods every 2 hr. Self-perceived discomfort and exertion were quantified before each doffing: self-perceived level of discomfort using a visual analog scale, and self-perceived level of exertion using a Borg scale. Overall, and as would be expected, discomfort increased over time with continual respirator use over an 8-hr period. Interestingly, exertion increased only marginally over the same time period. The relatively low level of exertion associated with eight respiratory protective devices, including models commonly used in the U.S. health care workplace, is not likely to substantially influence workers’ tolerability or occupational productivity. However, the magnitude of discomfort does appear to increase significantly over time with prolonged wear. These results suggest that respirator-related discomfort, but not exertion, negatively influences respirator tolerance over prolonged periods. Discomfort may also interfere with the occupational duties of workers.
722
ATP as a Marker for Surface Contamination of Biological Origin in Schools and as a Potential Approach to the Measurement of Cleaning Effectiveness
To address the need for a quantitative approach to the measurement of cleaning effectiveness, related to biologically derived surface contamination, three commercially available adenosine triphosphate (ATP) test systems were used to collect multiple samples measured in relative light units (RLUs) from 27 elementary schools in the southwestern United States before and after a standardized cleaning protocol. The database consisted of 6480 ATP measurements from four critical surfaces (student desktops, cafeteria tabletops, and restroom sinks and stall doors). Data was assessed according to ranges of ATP values before and after cleaning. Results showed the potential for such data to provide the basis for a standardized approach to the measurement of cleaning effectiveness, based on detection and quantification of pollutant loads of biological origin, across critical surfaces in school building environments. It is anticipated that verification of this data in school buildings across different geographic and climatic regions will lead to the establishment of “acceptable” ranges of ATP values that can be used as a practice-based approach to improving cleaning practices and contributing to healthier school environments.
723
Toward Understanding the Risk of Secondary Airborne Infection: Emission of Respirable Pathogens
Certain respiratory tract infections are transmitted through air. Coughing and sneezing by an infected person can emit pathogen-containing particles with diameters less than 10 μm that can reach the alveolar region. Based on our analysis of the sparse literature on respiratory aerosols, we estimated that emitted particles quickly decrease in diameter due to water loss to one-half the initial values, and that in one cough the volume in particles with initial diameters less than 20 μm is 6 × 10(−8) mL. The pathogen emission rate from a source case depends on the frequency of expiratory events, the respirable particle volume, and the pathogen concentration in respiratory fluid. Viable airborne pathogens are removed by exhaust ventilation, particle settling, die-off, and air disinfection methods; each removal mechanism can be assigned a first-order rate constant. The pathogen concentration in well-mixed room air depends on the emission rate, the size distribution of respirable particles carrying pathogens, and the removal rate constants. The particle settling rate and the alveolar deposition fraction depend on particle size. Given these inputs plus a susceptible person's breathing rate and exposure duration to room air, an expected alveolar dose μ is estimated. If the infectious dose is one organism, as appears to be true for tuberculosis, infection risk is estimated by the expression: R = 1 − exp(−μ). Using published tuberculosis data concerning cough frequency, bacilli concentration in respiratory fluid, and die-off rate, we illustrate the model via a plausible scenario for a person visiting the room of a pulmonary tuberculosis case. We suggest that patients termed “superspreaders” or “dangerous disseminators” are those infrequently encountered persons with high values of cough and/or sneeze frequency, elevated pathogen concentration in respiratory fluid, and/or increased respirable aerosol volume per expiratory event such that their pathogen emission rate is much higher than average.
724
Performance of an N95 Filtering Facepiece Particulate Respirator and a Surgical Mask During Human Breathing: Two Pathways for Particle Penetration
The protection level offered by filtering facepiece particulate respirators and face masks is defined by the percentage of ambient particles penetrating inside the protection device. There are two penetration pathways: (1) through the faceseal leakage, and the (2) filter medium. This study aimed at differentiating the contributions of these two pathways for particles in the size range of 0.03–1 μm under actual breathing conditions. One N95 filtering facepiece respirator and one surgical mask commonly used in health care environments were tested on 25 subjects (matching the latest National Institute for Occupational Safety and Health fit testing panel) as the subjects performed conventional fit test exercises. The respirator and the mask were also tested with breathing manikins that precisely mimicked the prerecorded breathing patterns of the tested subjects. The penetration data obtained in the human subject- and manikin-based tests were compared for different particle sizes and breathing patterns. Overall, 5250 particle size- and exercise-specific penetration values were determined. For each value, the faceseal leakage-to-filter ratio was calculated to quantify the relative contributions of the two penetration pathways. The number of particles penetrating through the faceseal leakage of the tested respirator/mask far exceeded the number of those penetrating through the filter medium. For the N95 respirator, the excess was (on average) by an order of magnitude and significantly increased with an increase in particle size (p < 0.001): ∼7-fold greater for 0.04 μm, ∼10-fold for 0.1 μm, and ∼20-fold for 1 μm. For the surgical mask, the faceseal leakage-to-filter ratio ranged from 4.8 to 5.8 and was not significantly affected by the particle size for the tested submicrometer fraction. Facial/body movement had a pronounced effect on the relative contribution of the two penetration pathways. Breathing intensity and facial dimensions showed some (although limited) influence. Because most of the penetrated particles entered through the faceseal, the priority in respirator/mask development should be shifted from improving the efficiency of the filter medium to establishing a better fit that would eliminate or minimize faceseal leakage.
725
St. Corona – eine Fürsprecherin gegen Seuchen?: Eine Miszelle aus der Medizin- und Urologiegeschichte
The knowledge of hagiography and hagiotherapy still plays an important role in the history of science, especially when focusing on specific aspects of history. While knowledge about St. Liborius persists in urology, knowledge about patron saints for pandemics, especially those who were called upon to treat venereal diseases, has diminished due to the association with nonappropriate sexual behavior.
726
Gold nanoparticles for preparation of antibodies and vaccines against infectious diseases
Introduction: Vaccination remains very effective in stimulating protective immune responses against infections. An important task in antibody and vaccine preparation is to choose an optimal carrier that will ensure a high immune response. Particularly promising in this regard are nanoscale particle carriers. An antigen that is adsorbed or encapsulated by nanoparticles can be used as an adjuvant to optimize the immune response during vaccination. a very popular antigen carrier used for immunization and vaccination is gold nanoparticles, with are being used to make new vaccines against viral, bacterial, and parasitic infections. Areas covered: This review summarizes what is currently known about the use of gold nanoparticles as an antigen carrier and adjuvant to prepare antibodies in vivo and design vaccines against viral, bacterial, and parasitic infections. The basic principles, recent advances, and current problems in the use of gold nanoparticles are discussed. Expert opinion: Gold nanoparticles can be used as adjuvants to increase the effectiveness of vaccines by stimulating antigen-presenting cells and ensuring controlled antigen release. Studying the characteristics of the immune response obtained from the use of gold nanoparticles as a carrier and an adjuvant will permit the particles’ potential for vaccine design to be increased.
727
Pathogenic variants in CDC45 on the remaining allele in patients with a chromosome 22q11.2 deletion result in a novel autosomal recessive condition
PURPOSE: The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion in humans, with highly variable phenotypic expression. Whereas congenital heart defects, palatal anomalies, immunodeficiency, hypoparathyroidism, and neuropsychiatric conditions are observed in over 50% of patients with 22q11DS, a subset of patients present with additional “atypical” findings such as craniosynostosis and anorectal malformations. Recently, pathogenic variants in the CDC45 (Cell Division Cycle protein 45) gene, located within the LCR22A–LCR22B region of chromosome 22q11.2, were noted to be involved in the pathogenesis of craniosynostosis. METHODS: We performed next-generation sequencing on DNA from 15 patients with 22q11.2DS and atypical phenotypic features such as craniosynostosis, short stature, skeletal differences, and anorectal malformations. RESULTS: We identified four novel rare nonsynonymous variants in CDC45 in 5/15 patients with 22q11.2DS and craniosynostosis and/or other atypical findings. CONCLUSION: This study supports CDC45 as a causative gene in craniosynostosis, as well as a number of other anomalies. We suggest that this association results in a condition independent of Meier–Gorlin syndrome, perhaps representing a novel condition and/or a cause of features associated with Baller–Gerold syndrome. In addition, this work confirms that the phenotypic variability observed in a subset of patients with 22q11.2DS is due to pathogenic variants on the nondeleted chromosome.
728
Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids
Strategies for selectively imaging and delivering drugs to tumours typically leverage differentially upregulated surface molecules on cancer cells. Here, we show that intravenously injected carbon quantum dots, functionalized with multiple paired α-carboxyl and amino groups that bind to the large neutral amino acid transporter 1 (which is expressed in most tumours), selectively accumulate in human tumour xenografts in mice and in an orthotopic mouse model of human glioma. The functionalized quantum dots, which structurally mimic large amino acids and can be loaded with aromatic drugs through π–π stacking interactions, enabled—in the absence of detectable toxicity—near-infrared fluorescence and photoacoustic imaging of the tumours and a reduction in tumour burden after the targeted delivery of chemotherapeutics to the tumours. The versatility of functionalization and high tumour selectivity of the quantum dots make them broadly suitable for tumour-specific imaging and drug delivery.
729
Outcome of patients with cirrhosis requiring intensive care unit support: Prospective assessment of predictors of mortality
Determinants of outcome and the utility of the Child-Pugh score and the acute physiology and chronic health evaluation (APACHE) II score as predictors of outcome were prospectively assessed in 54 consecutive patients with cirrhosis requiring intensive care unit (ICU) management. Overall mortality in the ICU was 43% (23/54). Child-Pugh scores did not differ between survivors or nonsurvivors (12.8 versus 12.3, P = 0.26), however APACHE II scores (P = 0.007), acute physiology scores (P = 0.006), and Karnofsky scores (P = 0.001) were significant predictors of outcome. By univariate analysis, requirement of mechanical ventilation analysis (P = 0.001), duration of mechanical ventilation (P = 0.001), pulmonary infiltrates (P = 0.0001), infections (P = 0.047), gastrointestinal bleeding (P = 0.005), and serum creatinine ≥1.5 mg/dl (P = 0.0005) were significantly associated with mortality. By logistic regression analysis only pulmonary infiltrates (P = 0.0001) and renal dysfunction (P = 0.041) were independent predictors of mortality. When controlled for the severity of illness (APACHE II scores), the mortality in patients with cirrhosis caused by alcohol was significantly lower than that in patients with liver disease not caused by alcohol (P = 0.01). Our study not only identified predictors of poor outcome in patients with cirrhosis requiring ICU care but also provided data that may have implications for optimal timing for transplantation.
730
Vaping induced pneumonitis: a small community hospital’s case series and analysis
BACKGROUND: Electronic cigarettes/e-cigarettes (ECs), or vaping, is currently the most popular form of smoking amongst youth in the United States. ECs are battery-powered devices that vaporize a liquid that comes in small cartridges, or pods, that contain various chemicals, nicotine, and an array of flavors that can be modified to include cannabinoids (THC). With increasing popularity, however, there is an epidemic of pulmonary and gastrointestinal illnesses associated with vaping in the continental U.S.A. METHODS: We analyzed medical charts of three patients who were active users of ECs and presented with pneumonitis to our community medical center between January and August 2019. RESULTS: We report three cases of vaping pneumonitis in young adults, ages 18 to 21, who presented with similar symptoms, profiles, imaging studies, and disease progression. The average length of stay was approximately one week, and all patients had an extensive work-up in addition to a relapsing and remitting course of their condition. CONCLUSIONS: Early recognition and diagnosis of vaping pneumonitis are essential in the treatment of the ongoing epidemic. Extensive unnecessary work up may lead to increased healthcare costs. Our case series echoes the concerns of the CDC such that ECs should be avoided, and those with any pulmonary or gastrointestinal symptoms should seek medical attention promptly.
731
Adjuvant Immunotherapy of Feline Fibrosarcoma with Recombinant Feline Interferon‐ω
Background: Recombinant feline interferon‐ω (rFeIFN‐ω) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility. Hypothesis: Treatment with rFeIFN‐ω in cats with fibrosarcoma is safe and feasible. Animals: Twenty domestic cats. Methods: In an open‐labeled uncontrolled clinical trial 12 injections of 1 × 10(6) U/kg rFeIFN‐ω were administered over a 5‐week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN‐ω. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN‐ω and recombinant feline interferon‐γ was performed to assess the biological effect of rFeIFN‐ω. Results: Changes in blood cell count, increases in serum aspartate‐amino‐transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P= .025), neutropenia (P= .021), and weight loss (P < .001) were statistically correlated with rFeIFN‐ω‐treatment (analysis of parameters before treatment and after 3 injections of rFeIFN‐ω). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P= .026) in response to in vitro incubation with rFeIFN‐ω, whereas expression of MHC class II molecules was not affected significantly. Conclusions and Clinical Importance: RFeIFN‐ω for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo‐controlled trial.
732
Shutting Up Infected Houses: Infectious Disease Control, Past and Present
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733
Return to the Past: The Case for Antibody-Based Therapies in Infectious Diseases
In the preantibiotic era, passive antibody administration (serum therapy) was useful for the treatment of many infectious diseases. The introduction of antimicrobial chemotherapy in the 1940s led to the rapid abandonment of many forms of passive antibody therapy. Chemotherapy was more effective and less toxic than antibody therapy. In this last decade of the 20th century the efficacy of antimicrobial chemotherapy is diminishing because of the rapidly escalating number of immunocompromised individuals, the emergence of new pathogens, the reemergence of old pathogens, and widespread development of resistance to antimicrobial drugs. This diminishment in the effectiveness of chemotherapy has been paralleled by advances in monoclonal antibody technology that have made feasible the generation of human antibodies. This combination of factors makes passive antibody therapy an option worthy of serious consideration. We propose that for every pathogen there exists an antibody that will modify the infection to the benefit of the host. Such antibodies are potential antimicrobial agents. Antibody-based therapies have significant advantages and disadvantages relative to standard chemotherapy. The reintroduction of antibody-based therapy would require major changes in the practices of infectious disease specialists.
734
Hot hearts on bone scintigraphy are not all amyloidosis: hydroxychloroquine-induced restrictive cardiomyopathy
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735
Selection of an aminoglycoside antibiotic for administration to horses
The serum concentrations of the aminoglycosides neomycin, kanamycin and streptomycin were determined after intravenous (iv) and intramuscular (im) administration. These values were then related to the minimum inhibitory concentrations (MIC) of a number of equine pathogenic bacteria to determine the duration of therapeutic serum concentrations of the aminoglycosides in the horse. Pharmacokinetic analysis of the data using neomycin as the example revealed a mean (± sd) peak serum concentration of 23.2 ± 10.2 μg/ml present at 30 mins, and at 8 h the serum concentration was 2.8 ± 0.8 μg/ml. From the pharmacological analysis of concentration‐time data it was shown that neomycin was very rapidly absorbed from the im injection site, with an absorption half‐time of 0.16 ± 0.05 and was well absorbed (systemic availability was 73.7 ± 26.9 per cent). A peak tissue level, which represented 40 per cent of the amount of drug in the body, was obtained at 32 mins after injection of the drug. At 8 h, the fractions of the dose in the central and peripheral compartments of the model were 1.5 per cent and 2.5 per cent respectively, and 96 per cent was the cumulative amount eliminated up to that time. Based on the MIC values of the majority of isolates of Corynebacterium equi, and only a few isolates of Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Streptococcus equi, one would expect a serum concentration of more than 2 μg neomycin/ml up to 8 h following im dosage (10 mg/kg) to be therapeutically effective.
736
Ingestion of sugar beet fiber enhances irradiation-induced aberrant crypt foci in the rat colon under an apoptosis-suppressed condition
The induction of aberrant crypt foci (ACF) by irradiation of γ-rays ((60)Co), and the effect of dietary sugar beet fiber (SBF) on irradiation-induced ACF were examined. We found that abdominal irradiation of γ-rays could induce ACF in the rat colon. The irradiation was performed once a week at a dose rate of 2 or 3 Gy per irradiation. Irradiation-induced ACF were observed in the colon at 10 weeks after the first irradiation at dose of 2 Gy for six times or 3 Gy for four times. Dietary SBF had no effect on the number of ACF, aberrant crypts (AC) or AC/focus induced by abdominal γ-irradiation. However, an ingestion of SBF resulted in an increase in the number of these parameters in apoptosis-suppressed rats by cycloheximide (CHX). An injection of CHX suppressed irradiation-induced apoptosis of the colonic epithelial cells for at least 6 h after the irradiation. In CHX-injected rats, an ingestion of SBF significantly increased the number of ACF, AC and AC/focus compared with fiber-free fed rats at 9 weeks after the first irradiation. On the other hand, in saline-injected rats, no significant difference was found between SBF and fiber-free diets in the number of ACF, AC and AC/focus through the experimental period. These results suggest that dietary SBF may be involved in the elimination of abnormal cells from an irradiated colon through the apoptosis of colonic epithelial cells. In this study, we have shown a new method for inducing ACF by using γ-rays which were not influenced by luminal contents such as bacterial enzyme, at least in the initiation stage.
737
Hyperkalemic Atrial Standstill in Neonatal Calf Diarrhea
Hyperkalemia has been associated with cardiac abnormalities and muscular disorders. Hyperkalemia is a common problem associated with the acid‐base and electrolyte disturbances that occur in neonatal calves having acute diarrhea. Occasional calves with acute neonatal diarrhea, metabolic acidosis, and hyperkalemia have cardiac rate or rhythm abnormalities. Bradycardia observed in three such calves was found to represent atrial standstill and was attributed to hyperkalemia. (Journal of Veterinary Internal Medicine 1992; 6:294–297)
738
Evaluation of murine norovirus as a surrogate for human norovirus and hepatitis A virus in heat inactivation studies
Aims: To determine the suitability of murine norovirus (MNV) as a surrogate for human norovirus (HuNoV) in heat inactivation studies. Methods and Results: MNV, hepatitis A virus (HAV) and HuNoV genogroup I and II (GI and GII) specific real‐time quantitative reverse transcription (qRT)‐PCR assays were used to determine the effects of heat exposure (63 and 72°C) for up to 10 min in water and milk. Using culture assays, MNV and HAV showed similar reductions in infectivity over time. Both HuNoV GI and GII showed lower log reductions in qRT‐PCR titre following heat exposure than either MNV or HAV. No significant protective effect of milk was observed for any virus. Conclusions: MNV is as suitable a surrogate for HuNoV as HAV. In heat inactivation studies at 63 and 72°C, qRT‐PCR results indicate that HuNoV is less susceptible to heat than either HAV or MNV and so neither virus may be an appropriate surrogate for HuNoV. Significance and Impact of the Study: Caution should be used when extrapolating surrogate virus data for HuNoV. Although not conclusive, our results suggest that HuNoV may be more resistant to heat than either HAV or MNV.
739
ARHGAP24 inhibits cell proliferation and cell cycle progression and induces apoptosis of lung cancer via a STAT6-WWP2-p27 axis
Rho GTPase-activating proteins (RhoGAPs) have been reported to be of great importance in the initiation and development of many different cancers. However, their biological roles and regulatory mechanisms in lung cancer development and progression are poorly defined. Real-time PCR or western blotting analysis was used to detect Rho GTPase-activating protein 24 (ARHGAP24), WWP2, p27, p-STAT6 and STAT6 expression levels as well as the activity of RhoA and Rac1 in lung cancer. Cell proliferation, apoptosis and cell cycle were measured by CCK-8 and flow cytometry analysis. Tumor growth of lung cancer cells was measured using a nude mouse xenograft experiment model in vivo. The correlation between WWP2 and p27 was measured by co-immunoprecipitation and ubiquitination analysis. We found that ARHGAP24 expression was lower in lung cancer tissues collected from the The Cancer Genome Atlas and independent hospital database. Overexpression of ARHGAP24 significantly suppressed cell proliferation and the activity of RhoA and Rac1, induced cell apoptosis and arrested cell cycle at the G(0)–G(1) phase. ARHGAP24 overexpression also inhibited tumor growth in nude mice, whereas knockdown of ARHGAP24 significantly promoted cell proliferation and WWP2 expression and inhibited cell cycle arrest at G(1) phase through activating STAT6 signaling. ARHGAP24 overexpression inhibited WWP2 overexpression-induced cell proliferation, cell cycle progression and the decreased p27 expression. Moreover, WWP2 was found interacted with p27, and WWP2 overexpression promoted the ubiquitination of p27. In conclusion, our findings suggest that ARHGAP24 inhibits cell proliferation and cell cycle progression and induces cell apoptosis of lung cancer via a STAT6-WWP2-p27 axis.
740
Microbial contamination in kitchens and bathrooms of rural Cambodian village households
Aims: To quantify microbial contamination on kitchen and bathroom surfaces (fomites) in rural Cambodian homes and to compare these concentrations to similar data from the United States and Japan. Methods and Results: This study monitored the numbers of faecal coliforms (i.e. thermotolerant coliforms), total coliforms, Escherichia coli and heterotrophic plate count bacteria on household surfaces in a rural village of Cambodia. Faecal coliform levels in Cambodia were highest on moist locations such as the plastic ladle used for sink water, the toilet seat surface and the cutting board surface with 100‐fold higher levels of faecal coliform bacteria than E. coli and 100‐fold higher levels of faecal coliforms than the US and Japanese studies. Conclusions: A single public health intervention barrier, such as an improved latrine, is only partially effective for household sanitation. For complete sanitation, multiple environmental barriers may be necessary. These barriers occur in a house constructed with easily washable surfaces, a chlorinated water distribution system, house climate control and cleaning product availability. Significance and Impact of the Study: Results of this study can be used to emphasize the importance of increasing household environmental sanitation barriers.
741
Seroepidemiology of Chronic Fatigue Syndrome: A Case-Control Study
We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We did not find any agent associated with CFS. In addition, we did not find elevated levels of antibody to any of a wide range of agents examined. In particular, we did not find elevated titers of antibody to any herpesvirus, nor did we find evidence of enteroviral exposure in this group of patients.
742
Correction to Lancet Oncol 2020; published online April 30. https://doi.org/10.1016/S1470-2045(20)30265-5
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743
Correction to Lancet Infect Dis 2020; published online March 30. https://doi.org/10.1016/S1473-3099(20)30243-7
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Issue Highlights
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745
Safe Reintroduction of Cardiovascular Services during the COVID-19 Pandemic: Guidance from North American Society Leadership
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746
Cancelling a Major Meeting is never an Easy Decision
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747
Leadership Essentials During a Disaster
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748
Chloroquine-induced torsade de pointes in a COVID-19 patient
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749
Inflammatory dilated cardiomyopathy: Etiology and clinical management
Inflammatory dilated cardiomyopathy (DCMi) is a syndrome, not an etiological disease entity. The infective etiology and the immunopathology can be best determined through endomyocardial biopsy with a complete work-up by light microscopy, immunohistology, and polymerase chain reaction for microbial agents. This review focuses on the methodological advances in diagnosis in the past few years and exemplifies the importance of an etiology-orientated treatment in different case scenarios. In fulminant nonviral myocarditis, immunosuppressive treatment together with hemodynamic stabilization of the patient via mechanical circulatory support (e.g., microaxial pumps, extracorporeal membrane oxygenation, left ventricular assist device) can be life-saving. For viral inflammatory cardiomyopathy, intravenous immunoglobulin treatment can resolve inflammation and often eradicate the virus.
750
Analysis of Expression Profiles of Long Noncoding RNAs and mRNAs in A549 Cells Infected with H3N2 Swine Influenza Virus by RNA Sequencing
Long noncoding RNAs (lncRNAs) participate in regulating many biological processes. However, their roles in influenza A virus (IAV) pathogenicity are largely unknown. Here, we analyzed the expression profiles of lncRNAs and mRNAs in H3N2-infected cells and mock-infected cells by high-throughput sequencing. The results showed that 6129 lncRNAs and 50,031 mRNA transcripts in A549 cells displayed differential expression after H3N2 infection compared with mock infection. Among the differentially expressed lncRNAs, 4963 were upregulated, and 1166 were downregulated. Functional annotation and enrichment analysis using gene ontology and Kyoto Encyclopedia of Genes and Genomes databases (KEGG) suggested that target genes of the differentially expressed lncRNAs were enriched in some biological processes, such as cellular metabolism and autophagy. The up- or downregulated lncRNAs were selected and further verified by quantitative real-time polymerase chain reaction (RT-qPCR) and reverse transcription PCR (RT-PCR). To the best of our knowledge, this is the first report of a comparative expression analysis of lncRNAs in A549 cells infected with H3N2. Our results support the need for further analyses of the functions of differentially expressed lncRNAs during H3N2 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00170-9) contains supplementary material, which is available to authorized users.
751
Structural equation modeling the “control of gut overgrowth” in the prevention of ICU-acquired Gram-negative infection
BACKGROUND: Conceptually, the “control of gut overgrowth” (COGO) is key in mediating prevention against infection with Gram-negative bacilli by topical antibiotic prophylaxis, a common constituent of selective digestive decontamination (SDD) regimens. However, the relative importance of the other SDD components, enteral and protocolized parenteral antibiotic prophylaxis, versus other methods of infection prevention and versus other contextual exposures cannot be resolved within individual studies. METHODS: Seven candidate generalized structural equation models founded on COGO concepts were confronted with Pseudomonas and Acinetobacter bacteremia as well as ventilator-associated pneumonia data derived from > 200 infection prevention studies. The following group-level exposures were included in the models: use and mode of antibiotic prophylaxis, anti-septic and non-decontamination methods of infection prevention; proportion receiving mechanical ventilation; trauma ICU; mean length of ICU stay; and concurrency versus non-concurrency of topical antibiotic prophylaxis study control groups. RESULTS: In modeling Pseudomonas and Acinetobacter gut overgrowth as latent variables, anti-septic interventions had the strongest negative effect against Pseudomonas gut overgrowth but no intervention was significantly negative against Acinetobacter gut overgrowth. Strikingly, protocolized parenteral antibiotic prophylaxis and concurrency each have positive effects in the model, enteral antibiotic prophylaxis is neutral, and Acinetobacter bacteremia incidences are high within topical antibiotic prophylaxis studies, moreso with protocolized parenteral antibiotic prophylaxis exposure. Paradoxically, topical antibiotic prophylaxis (moreso with protocolized parenteral antibiotic prophylaxis) appears to provide the strongest summary prevention effects against overall bacteremia and overall VAP. CONCLUSIONS: Structural equation modeling of published Gram-negative bacillus infection data enables a test of the COGO concept. Paradoxically, Acinetobacter and Pseudomonas bacteremia incidences are unusually high among studies of topical antibiotic prophylaxis.
752
An automated aquatic rack system for rearing marine invertebrates
BACKGROUND: One hundred years ago, marine organisms were the dominant systems for the study of developmental biology. The challenges in rearing these organisms outside of a marine setting ultimately contributed to a shift towards work on a smaller number of so-called model systems. Those animals are typically non-marine organisms with advantages afforded by short life cycles, high fecundity, and relative ease in laboratory culture. However, a full understanding of biodiversity, evolution, and anthropogenic effects on biological systems requires a broader survey of development in the animal kingdom. To this day, marine organisms remain relatively understudied, particularly the members of the Lophotrochozoa (Spiralia), which include well over one third of the metazoan phyla (such as the annelids, mollusks, flatworms) and exhibit a tremendous diversity of body plans and developmental modes. To facilitate studies of this group, we have previously described the development and culture of one lophotrochozoan representative, the slipper snail Crepidula atrasolea, which is easy to rear in recirculating marine aquaria. Lab-based culture and rearing of larger populations of animals remain a general challenge for many marine organisms, particularly for inland laboratories. RESULTS: Here, we describe the development of an automated marine aquatic rack system for the high-density culture of marine species, which is particularly well suited for rearing filter-feeding animals. Based on existing freshwater recirculating aquatic rack systems, our system is specific to the needs of marine organisms and incorporates robust filtration measures to eliminate wastes, reducing the need for regular water changes. In addition, this system incorporates sensors and associated equipment for automated assessment and adjustment of water quality. An automated feeding system permits precise delivery of liquid food (e.g., phytoplankton) throughout the day, mimicking real-life feeding conditions that contribute to increased growth rates and fecundity. CONCLUSION: This automated system makes laboratory culture of marine animals feasible for both large and small research groups, significantly reducing the time, labor, and overall costs needed to rear these organisms.
753
Long Noncoding RNA NRAV Promotes Respiratory Syncytial Virus Replication by Targeting the MicroRNA miR-509-3p/Rab5c Axis To Regulate Vesicle Transportation
Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long noncoding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from the lncRNA database, and we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. Quantitative PCR (qPCR) detection indicated that the expression of lncRNA negative regulator of antiviral response (NRAV) in RSV-positive patients was significantly lower than that in uninfected patients, but lncRNA psoriasis-associated non-protein coding RNA induced by stress (PRINS), nuclear paraspeckle assembly transcript 1 (NEAT1), and Nettoie Salmonella pas Theiler’s (NeST) showed no difference in vivo and in vitro. Meanwhile, overexpression of NRAV promoted RSV proliferation in A549 and BEAS-2B cells, and vice versa, indicating that the downregulation of NRAV was part of the host antiviral defense. RNA fluorescent in situ hybridization (FISH) confirmed that NRAV was mainly located in the cytoplasm. Through RNA sequencing, we found that Rab5c, which is a vesicle transporting protein, showed the same change trend as NRAV. Subsequent investigation revealed that NRAV was able to favor RSV production indirectly by sponging microRNA miR-509-3p so as to release Rab5c and facilitate vesicle transportation. The study provides a new insight into virus-host interaction through noncoding RNA, which may contribute to exploring potential antivirus targets for respiratory virus. IMPORTANCE The mechanism of interaction between RSV and host noncoding RNAs is not fully understood. In this study, we found that the expression of long noncoding RNA (lncRNA) negative regulator of antiviral response (NRAV) was reduced in RSV-infected patients, and overexpression of NRAV facilitated RSV production in vitro, suggesting that the reduction of NRAV in RSV infection was part of the host antiviral response. We also found that NRAV competed with vesicle protein Rab5c for microRNA miR509-3p in cytoplasm to promote RSV vesicle transport and accelerate RSV proliferation, thereby improving our understanding of the pathogenic mechanism of RSV infection.
754
Korotnevella hemistylolepis N. Sp. and Korotnevella monacantholepis N. Sp. (Paramoebidae), Two New Scale‐covered Mesohaline Amoebae
ABSTRACT. Two new species of Korotnevella Goodkov, 1988, Korotnevella hemistylolepis n. sp. and Korotnevella monacantholepis n. sp., are described from mesohaline ecosystems. The amoebae are characterized on the basis of light and electron microscopy with special emphasis on the structure of the basket scales, which have species‐specific architecture. The two new species are the second and third ones recovered from environments other than freshwater. In terms of scale morphology they most closely resemble a freshwater species, Korotnevella bulla (Schaeffer, 1926) Goodkov, 1988. Two genus names, Dactylamoeba Korotnev, 1880 and Korotnevella Goodkov, 1988, are in current use. The latter name is preferred, pending rediscovery and characterization of Dactylamoeba elongata Korotnev, 1880, the type species of the genus. Korotnevella species can be divided into three groups on the basis of scale morphology, suggesting that the genus may not be monophyletic. A key to species is provided.
755
A case of cow's milk allergy in the neonatal period‐evidence for intrauterine sensitization?
Clinical manifestations of cow's milk allergy rarely occur in the first days after birth. We report on a newborn presenting with hemorrhagic mecon‐ium in the first hour of life followed by bloody diarrhea in the next few days. At day 14, an elevaled total IgE, specific IgE to cow's milk and an eosinophilia in peripheral blood were found. Symptoms disappeared when the milk feed was changed to an extensively hydrolyzed casein formula. Two challenges with cow's milk formula (on day 30 and at 7 months of age) were followed by recurrence of vomiting, watery diarrhea and failure to thrive. At the age of 17 months cow's milk was tolerated well. Although other pathogenetic mechanisms cannot completely be ruled out, there is strong evidence that cow's milk allergy— induced by intrauterine sensiti‐zation—explains the symptoms in our patient. In conclusion, cow's milk allergy can occur even in the first days of life, and our clinical observation supports the concept of intra‐uterine sensitization to allergens.
756
The importance of ultrasonographic pneumatosis intestinalis in equine neonatal gastrointestinal disease
Reasons for performing study: Recognising the presence of a necrotising component of the gastrointestinal disease may be clinically useful in ill equine neonates. Objectives: To study the importance of abdominal sonograms in neonatal foals suffering from gastrointestinal conditions and to describe the clinical features of necrotising gastrointestinal disease. Hypothesis: There is a subgroup of neonates with sonographically detectable pneumatosis intestinalis (PI), reflecting a necrotising disease. Methods: Records of foals aged ≤7 days hospitalised from 2005 to 2009 with signs of gastrointestinal disease were evaluated (n = 89). The association of sonographic, clinical and clinicopathological signs with necrotising gastrointestinal disease and outcome was determined. Results: PI was imaged in 19 foals. Twenty‐seven foals were classified as having necrotising gastrointestinal disease based on the presence of gastrointestinal signs (colic, diarrhoea, gastric reflux or abdominal distension) and sonographic PI (n = 19), surgical (n = 2) or pathological (n = 6) evidence of gastrointestinal necrosis. There was a difference between survival rate in foals with and without necrotising disease (33.3 and 69.4%, respectively, P = 0.005) or foals with and without PI detected sonographically (36.8 and 72.1%, respectively, P = 0.023). PI was the only sonographic finding associated with outcome. Prematurity, the presence of blood in the faeces, gastric reflux, abdominal distension, abnormal echogenicity of the colon and the lowest white blood cell count during hospitalisation were associated with necrotising gastrointestinal disease (P<0.05). Conclusions and potential relevance: Abdominal sonograms have prognostic value in neonatal gastrointestinal disease. PI and the presence of necrotising gastrointestinal disease were common and associated with a poor prognosis.
757
Caring for Pediatric Patients with Diabetes amidst the COVID-19 Storm
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758
Managing FPIES during the COVID-19 pandemic-expert recommendations
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759
The use of PET in COVID 19 cases
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760
Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI)-Associated Interstitial Lung Disease During the COVID-19 Pandemic
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761
The Clinical Observation of a CVID Patient Infected with COVID-19
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762
Efficacy and Safety of Oral Pleconaril for Treatment of Colds Due to Picornaviruses in Adults: Results of 2 Double-Blind, Randomized, Placebo-Controlled Trials
The novel capsid-binding antiviral pleconaril inhibits in vitro replication of most rhinoviruses and enteroviruses. Oral pleconaril treatment was studied in 2 parallel randomized, double-blind, placebo-controlled trials. Among 1363 picornavirus-infected participants (65%) in the studies combined, the median time to alleviation of illness was 1 day shorter for pleconaril recipients than for placebo recipients (P > .001). Cold symptom scores and frequency of picornavirus cultured from nasal mucus specimens were lower among pleconaril recipients by day 2 of treatment. No treatment effects were seen in those without picornavirus infection. Pleconaril was associated with a higher incidence of nausea (6% vs. 4%) and diarrhea (9% vs. 7%) and with small increases in mean serum cholesterol levels and platelet counts, compared with baseline measurements. A subsequent 6-week prophylaxis study found that pleconaril induces cytochrome P-450 3A enzymes, which metabolize a variety of drugs, including ethinyl estradiol. Early pleconaril treatment was well tolerated and significantly reduced the duration and severity of colds due to picornaviruses in adults.
763
Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings
BACKGROUND: Human respiratory system infected with influenza A virus (IAV) elicited a robust pro-inflammatory response that resulted in severe illness and even death. Currently, limited immunomodulator is available to counteract IAV-associated pneumonia in the clinic. Sinensetin, a polymethoxylated flavone with five methoxy groups, has been found to possess anti-agiogenesis, anti-inflammatory and anti-diabetic activities. However, the effects of sinensetin on IAV-triggered pro-inflammatory response remain unclear. In the present study, the anti-inflammatory effects and corresponding possible mechanism of sinensetin in IAV-infected A549 cells were subjected to investigations. METHODS: The cytotoxic effects of sinensetin towards A549 cells was detected by MTT and LDH assays. The antiviral activity of sinensetin against influenza A virus was assayed in A549 cells with an engineered replication-competent influenza A virus carrying Gaussia luciferase reporter gene infection. The effect of sinensetin on influenza A virus-triggered inflammatory reaction was determined by qRT-PCR, Luminex assays, ELISA and Western blot. RESULTS: Our results showed that sinensetin did not exhibit antiviral activity against A/PR/8/34 (H1N1). Meanwhile, sinensetin treatment significantly decreased IAV-induced expression of pro-inflammatory mediators at mRNA and protein levels, including IL-6, TNF-α, IP-10, IL-8 and MCP-1. Additionally, levels of cyclooxygenase (COX)-2 and the downstream product prostaglandin E(2) (PGE(2)) up-regulated by IAV infection were dramatically suppressed by sinensetin. The mechanistic investigation revealed that sinensetin treatment suppressed the NF-κB transcriptional activity using the NF-κB reporter stable HEK293 cell line stimulated with TNF-α (20 ng/mL) or influenza H1N1 virus. Furthermore, sinensetin abrogated influenza H1N1 virus-induced activation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings. CONCLUSION: Collectively, our results indicated that sinensetin has potential capacity to attenuate IAV-triggered pro-inflammatory response via inactivation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings, which implied that sinensetin may be a promising candidate drug for influenza H1N1 virus infection therapeutics.
764
A role for CIM6P/IGF2 receptor in memory consolidation and enhancement
Cation-independent mannose-6-phosphate receptor, also called insulin-like growth factor two receptor (CIM6P/IGF2R), plays important roles in growth and development, but is also extensively expressed in the mature nervous system, particularly in the hippocampus, where its functions are largely unknown. One of its major ligands, IGF2, is critical for long-term memory formation and strengthening. Using CIM6P/IGF2R inhibition in rats and neuron-specific knockdown in mice, here we show that hippocampal CIM6P/IGF2R is necessary for hippocampus-dependent memory consolidation, but dispensable for learning, memory retrieval, and reconsolidation. CIM6P/IGF2R controls the training-induced upregulation of de novo protein synthesis, including increase of Arc, Egr1, and c-Fos proteins, without affecting their mRNA induction. Hippocampal or systemic administration of mannose-6-phosphate, like IGF2, significantly enhances memory retention and persistence in a CIM6P/IGF2R-dependent manner. Thus, hippocampal CIM6P/IGF2R plays a critical role in memory consolidation by controlling the rate of training-regulated protein metabolism and is also a target mechanism for memory enhancement.
765
Witch-hunt Cannot Eradicate COVID-19
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766
Management of Travel-Related Infectious Diseases in the Emergency Department
PURPOSE OF REVIEW: Emergency physicians generally have limited exposure to internationally acquired illnesses. However, travelers can present quite ill, and delays in recognition and treatment can lead to increased morbidity and mortality. This paper aims to summarize typical presentations of common international diseases and provide the emergency physician with a practical approach based on current guidelines. RECENT FINDINGS: In the treatment of traveler’s diarrhea, azithromycin has become the treatment of choice due to the growing antibiotic resistance. Intravenous artesunate was approved in 2019 under investigational new drug protocol for the treatment of severe malaria, and artemisinin-based combination therapies (ACTs) have become the first-line treatment for most cases of uncomplicated malaria. Since the 2015 outbreak, Zika has become a concern to many travelers, but the current treatment is supportive. SUMMARY: Clinicians should be aware of a few noteworthy updates in the treatment of internationally acquired illnesses, but more importantly, they must recognize warning signs of severe illness and treat promptly. Future research on workup and disposition could help emergency physicians identify which patients need admission in well-appearing febrile travelers.
767
Post-translational modifications and stress adaptation: the paradigm of FKBP51
Adaptation to stress is a fundamental requirement to cope with changing environmental conditions that pose a threat to the homeostasis of cells and organisms. Post-translational modifications (PTMs) of proteins represent a possibility to quickly produce proteins with new features demanding relatively little cellular resources. FK506 binding protein (FKBP) 51 is a pivotal stress protein that is involved in the regulation of several executers of PTMs. This mini-review discusses the role of FKBP51 in the function of proteins responsible for setting the phosphorylation, ubiquitination and lipidation of other proteins. Examples include the kinases Akt1, CDK5 and GSK3β, the phosphatases calcineurin, PP2A and PHLPP, and the ubiquitin E3-ligase SKP2. The impact of FKBP51 on PTMs of signal transduction proteins significantly extends the functional versatility of this protein. As a stress-induced protein, FKBP51 uses re-setting of PTMs to relay the effect of stress on various signaling pathways.
768
ECR 2020 Book of Abstracts: Vienna, Austria. 15 March 2020
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769
Mitteilungen der DGRh – Veranstaltungen der Rheumaakademie
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770
Mitteilungen der DGRh
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771
Real-time, MinION-based, amplicon sequencing for lineage typing of infectious bronchitis virus from upper respiratory samples
Infectious bronchitis (IB) causes significant economic losses in the global poultry industry. Control of IB is hindered by the genetic diversity of the causative agent, infectious bronchitis virus (IBV), which has led to the emergence of several serotypes that lack complete serologic cross-protection. Although serotyping requires immunologic characterization, genotyping is an efficient means to identify IBVs detected in samples. Sanger sequencing of the S1 subunit of the spike gene is currently used to genotype IBV; however, the universal S1 PCR was created to work from cultured IBV, and it is inefficient at detecting multiple viruses in a single sample. We describe herein a MinION-based, amplicon-based sequencing (AmpSeq) method that genetically categorized IBV from clinical samples, including samples with multiple IBVs. Total RNA was extracted from 15 tracheal scrapings and choanal cleft swab samples, randomly reverse transcribed, and PCR amplified using modified S1-targeted primers. Amplicons were barcoded to allow for pooling of samples, processed per manufacturer’s instructions into a 1D MinION sequencing library, and then sequenced on the MinION. The AmpSeq method detected IBV in 13 of 14 IBV-positive samples. AmpSeq accurately detected and genotyped both IBV lineages in 3 of 5 samples containing 2 IBV lineages. Additionally, 1 sample contained 3 IBV lineages, and AmpSeq accurately detected 2 of the 3 lineages. Strain identification, including detection of different IBVs from the same lineage, was also possible with this AmpSeq method. Our results demonstrate the feasibility of using MinION-based AmpSeq for rapid and accurate identification and lineage typing of IBV from oral swab samples.
772
Mitteilungen der DGG
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773
Successful treatment of mycobacterial infection associated hemophagocytic lymphohistiocytosis with etoposide and anti-tuberculous therapy: a case report
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.
774
Scrub typhus as a rare cause of acute pyelonephritis: case report
BACKGROUND: Scrub typhus can present with atypical signs and symptoms such as those of acute kidney injury, gastroenteritis, pneumonitis, and acute respiratory distress syndrome. Meningitis, encephalitis, and hepatic dysfunction have also been reported, particularly in severe cases with multisystem involvement. Scrub typhus has never been reported in the literature to cause urinary tract infections (UTIs) which includes cystitis and pyelonephritis. CASE PRESENTATION: A 45-year old male presenting to the outpatient unit with fever, right flank pain, and burning micturition for three days was initially treated for UTI. However, he returned to the hospital on the fourth day of illness with persistent symptoms. He was hospitalized, with intravenous (IV) ceftriaxone. Computerized tomography scan of his abdomen-pelvis showed features of acute pyelonephritis, so his antibiotics were upgraded to meropenem and teicoplanin. Despite this, the patient’s condition deteriorated. Laboratory investigations showed multisystem involvement: decreasing platelets, raised creatinine, and deranged liver panel. As Kathmandu was hit by dengue epidemic during the patient’s hospitalization, on the seventh day of his illness, blood samples were sent for tropical fever investigation. All tests came out negative except for scrub typhus—IgM antibodies positive on rapid diagnostic test. The patient’s symptoms subsided after 48 h of starting doxycycline and he became fully asymptomatic four days later. Fever did not recur even after discontinuing other IV antibiotics, favoring scrub typhus disease rather than systemic bacterial sepsis. CONCLUSIONS: Scrub typhus is an emerging infectious disease of Nepal. Therefore, every unexplained fever cases (irrespective of clinical presentation) should be evaluated for potential Rickettsiosis. Moreover, for cases with acute pyelonephritis, atypical causative agents should be investigated, for example scrub typhus in this case.
775
Combining the use of Nuss procedure and rib fixation for severe flail chest: a case report
BACKGROUND: Severe flail chest is a life-threatening situation. The Nuss procedure is a new effective treatment for severe flail chest patients who cannot be weaned from prolonged mechanical ventilation in the last few years. However, the procedure is not suitable when there are multiple fractures in both the anterior and lateral chest walls. Here, we reported a rare case of severe flail chest in a patient who suffered multiple fractures in both the anterior and lateral chest walls in a traffic accident. CASE PRESENTATION: A 49-year-old patient suffered severe flail chest by a steering wheel in a traffic accident with multiple fractures in both the anterior and lateral chest walls. In the beginning, the patient was administrated with mechanical ventilation because of acute respiratory distress syndrome (ARDS) for more than 1 week. Then the patient suffered from a severe lung infection and decreased blood oxygen saturation. After a multidiscipline discussion (MDT), three rib fixation plates were first used to rebuild the stability of lateral chest walls, then two Nuss bars were inserted to eliminate paradoxical movement in the anterior chest wall. Finally, the patient recovered smoothly after the combining procedure. CONCLUSIONS: Severe flail chest patients with both the anterior and lateral chest walls after trauma are in a life-threatening situation, and require an appropriate procedure to get out of danger in time. Rib fixation is an effective treatment when the fractured sites are few and the fractured area is small. The Nuss procedure is a new effective method for severe flail chest with multiple fractures in an anterior chest wall, which is also a minimally invasive and short time-consuming procedure. However, it does not suitable for the patient with multiple fractures in lateral chest walls. Combining the use of Nuss procedure and rib fixation can solve severe flail chest with multiple ribs and sternum fractures in both the anterior and lateral chest walls, and the outcome of this procedure is satisfying in the present rare case.
776
Convalescent transfusion for pandemic influenza: preparing blood banks for a new plasma product?
Due to the potential of a severe pandemic to limit efficacy or availability of medical countermeasures, some researchers have begun a search for new interventions that could complement the planned antiviral‐ and vaccine‐based response to an influenza pandemic. One such countermeasure—the transfusion of pandemic influenza‐specific antibodies from surviving patients to the clinically ill—is the focus of this commentary. Passive immunotherapy, which includes the use of monoclonal antibodies (MoAbs), hyperimmune globulin, or convalescent plasma, had been used before the advent of antibiotics and has recently reentered the limelight due to the accelerating development of MoAb therapies against cancer, a number of microbes, allograft rejection, and a host of other conditions. After the plausible biologic mechanism and somewhat limited data supporting the efficacy for this modality against influenza are reviewed, safety and logistical concerns for utilization of this potential new product (fresh convalescent plasma against influenza [FCP‐Flu]) are discussed. FCP‐Flu could indeed prove useful in a response to a pandemic, but two necessary items must first be satisfied. Most importantly, more research should be conducted to establish FCP‐Flu efficacy against the current and other pandemic strains. Second, and also importantly, blood banks and donor centers should examine whether offering this new product would be feasible in a pandemic and begin planning before a more severe pandemic forces us to respond without adequate preparation.
777
Nineteen years of experience with autotransfusion for elective surgery in children: more troublesome than we expected
BACKGROUND: Under the rationale that children undergoing elective surgery are the best candidates for autologous blood donors because of their long life expectancy, aggressive donations of autologous blood, even from infants, have been reported. A number of problems are associated with the procedure, however, whereas the risks of homologous blood are very low. STUDY DESIGN AND METHODS: From 1987 through 2005, of 5792 patients referred to blood transfusion services at two Japanese university hospitals for autologous blood donations, 314 children younger than 16 years old served as subjects for assessment. RESULTS: Of 314 children, 7 were not suitable as autologous donors. In most cases this was due to uncooperative behavior. Over a follow‐up period of 19 years, the authors encountered 53 cases (17.3%) of donation‐related problems, and this rate was higher than the 6 percent rate recorded for adult cases (316/5305). Nine children suffered crucial complications such as vasovagal reactions, and one 14‐year‐old boy required a vasopressor drug. Important findings were that 6 of these were first‐time donors, and the amount of blood drawn was under 10 percent of their estimated blood volume. CONCLUSION: Of 53 donation‐related problems, 9 (17.0%) were accompanied by marked hypotension. Drawing autologous blood from children has become easier with advanced devices; however, lessening of anxiety and tension are essential for the safety of children's autologous blood donation programs. Aggressive donation should be avoided.
778
A phylogeographical study of the Turnip mosaic virus population in East Asia reveals an ‘emergent’ lineage in Japan
The genetic structure of populations of Turnip mosaic virus (TuMV) in East Asia was assessed by making host range and gene sequence comparisons of 118 isolates utilizing a population genetic approach. Most, but not all, isolates collected from Brassica plants in China infected only Brassica plants, whereas those from Japan infected both Brassica and Raphanus (BR) plants. Analyses of the positions of recombination sites in five regions of the genomes (one third of the full sequence) of the many recombinant isolates were fully congruent with the results of phylogenetic analysis, and at least one recombination type pattern was shared between Chinese and Japanese populations. One lineage of nonrecombinant isolates from the basal‐BR lineage was found in 2000 in Kyushu, Japan but none in China, and have since been found over the whole island. The sudden expansion of this basal‐BR population was strongly supported by calculations showing the deviations from the neutral equilibrium model for the individual geographical lineages with overall lack of nucleotide diversity, and by analysis of mismatch distribution. Our study shows that the recent Chinese and Japanese TuMV isolates are part of the same population but are discrete lineages.
779
Regeneration of monsoon rain forest in northern Australia: the sapling bank
Abstract. As part of a wider study examining regeneration pathways in monsoon rain forest vegetation in northern Australia, a one‐off, dry season census of saplings was undertaken along transects sampled at each of 33 relatively undisturbed sites broadly representative of the range of regional monsoon rain forest vegetation. Four floristic quadrat groups were derived through TWINSPAN classification. Subsequent analyses involved: (1) comparison of mean dry season stockings of juveniles occurring in different rain forest types, and their structural and environmental correlates; (2) comparison of the contributions of different life forms, and the influence of clonal reproduction in the sapling regeneration banks of different forest types; and (3) exploration of relationships between the distributions of saplings of common tree species with respect to seed bank, floristic, structural, and environmental variables. While data presented here require cautious interpretation given that processes of seedling/sapling recruitment and mortality are highly dynamic, sapling banks were found to be most dense on coarse‐textured, moist soils, and least dense on coarse‐textured, seasonally dry soils. Canopy cover and fire impact were shown to be highly influential on sapling distribution, especially for saplings of tree species and those growing on seasonally dry sites. Sapling densities were little influenced by proximity to rain forest margins, except for shrubs. The potential for clonal reproduction was significantly greater on dry sites, especially for trees. The majority of saplings sampled were derived from relatively few common, non‐clonal, canopy tree species. Sapling distributions of 20 out of 23 common tree species were clumped in the vicinity of conspecific adults; for most species the strength of this relationship was greater than that for any other variable. These data support observations in the literature concerning the distribution of sapling banks in moist and dry tropical forests.
780
In situ regeneration of Pinus strobus and P. resinosa in the Great Lakes forest communities of Canada
Abstract. Two extensive forest vegetation survey datasets are explored, using ordination and classification, for evidence of in situ regeneration by Pinus strobus (Eastern white pine) and P. resinosa (Red pine). Ordination of tree species contributions to total basal area in 320 upland northern hardwood‐ conifer stands produced distinct stand groups for P.banksiana, P. resinosa, P. strobus and mesic hardwoods in an ascending sequence along the first axis. Quercus rubra (red oak), Q. alba (white oak) and tolerant conifer groups formed segregates from the hardwood complex along the second axis. P. strobus mixes with all other forest types, but P. resinosa is restricted to its own group. Seedlings and trees of P. strobus are more abundant than saplings, which are restricted to the pine and oak forests. Therefore, seed production, dispersal and seedling establishment seem to be less of a barrier to in situ regeneration by P. strobus than subsequent survival and growth. Canonical correspondence analysis of 170 pine‐dominated stands from the Canadian Shield of Ontario, in which tree species variables are segmented into height‐class pseudo‐ species, yielded no linear relationship between environmental features or stand structure and seedling densities of P. strobus. However, total tree basal area appears to impose an upper limit to seedling density on the forest floor. Strong correlations emerged between pine seedling density and understorey vegetation. Stand classification of the understorey vegetation, using constrained indicator species analysis, yielded distinct high and low seedling groups. Low pine seedling density was associated with abundant broadleaved shrubs, herbs and seedlings as well as feathermosses and tolerant conifers. High seedling density could not be ascribed to the presence of seedbed taxa, such as Polytrichum, but is ascribed to the absence of competition and other forms of inhibition in the understorey vegetation and down through the canopy profile. In situ regeneration of P. strobus does, therefore, occur but conditions over the forest landscape are largely restrictive.
781
Reversion of vegetation following the cessation of fertilizer application
Abstract. Tadham Moor in Somerset, England, is an exceptionally rich wetland site which has been mown for hay for many years, with stock grazing the aftermath, but with no history of any fertilizer use. A randomized blocks field experiment (1986–1989) was used to study the effects of five levels of nitrogen input treatments: 0 = control, 25, 50, 100 and 200 kg of N fertilizer per ha per yr. In Phase II of the experiment (1990–1993), each plot was split into two subplots. The allocated fertilizer treatment for the plot was continued in one, randomly selected, subplot but the treatment was discontinued in the other subplot. The experiment not only identified and quantified the changes occurring in the vegetation of hay meadows under different levels of N input, it also provided valuable insight into the dynamics of the sward upon the discontinuance of the treatments. The data for Phase II were used to estimate the time required by the changed vegetation (under different nitrogen treatments) to revert to a state comparable to that prevailing in the control plots. A method for estimating reversion times is described. The main difficulties in estimating the reversion times are identified, the choice of robust vegetation variables being critical. Reversion time estimation methods are presented and used to obtain working estimates for the four nitrogen treatments, applied for 5 yr. These estimates are 3, 5, 7 and 9 yr respectively. The validity of the estimates of 3 yr for the lowest nitrogen input treatment (25 kg /ha/yr) was checked using the available post cessation data.
782
Mediterranean pasture dynamics: the role of germination
Abstract. Meteorological patterns have a decisive influence on the inter‐annual dynamics of therophyte pastures under Mediterranean climatic conditions. The germination behaviour of annual pasture species was studied by subjecting two collections of seeds taken from plants and soil‐seed banks to two phytotron‐simulated weather patterns: early and late autumn rains. Species from these pastures were arranged along a gradient of sensitivity to temperature on the arrival of the first persistent rain. This sensitivity was manifested in both the total germination success of the species and the germination time profile. The different germination patterns of the species can provide competitive advantages depending on the autumn weather conditions.
783
Nitrate reductase activity in vegetation below an arctic bird cliff, Svalbard, Norway
Abstract. Vegetated sites below bird‐nesting cliffs are uniquely nutrient‐rich habitats in the otherwise nutrient‐poor arctic environment. Plants from six distinct vegetation zones below such a cliff at 79° N, Svalbard, Norway, were collected for analysis under greenhouse conditions. Leaf nitrate reductase activity (NRA) was analysed in 42 species representing 25 % of the Svalbard vascular flora. The species mean NRA values ranged from 0.37 to 8.34 μmols of nitrite ions formed per gram of plant fresh weight per hour. Species in the vegetated zone growing closest to recent guano deposits had the highest NRA values, (mean = 4.47) whereas plants growing farther below the cliff had significantly lower values (mean = 0.55). A similar pattern was detected in a duplicate set of plants induced with 15 mM KNO(3); vegetation zone means for NRA ranged from 5.08 to 0.98 μmols of nitrite ions formed per gram of plant fresh weight per hour. Maximally induced species NRA values were highest in the first zones below the cliff and decreased downslope. This gradient paralleled the steep soil nitrate gradient, which decreased from 13.84 mg/l at the cliffbase to 1.03 mg/l downslope. Correspondingly, soil ammonium ions in the vegetation zones ranged between 1.96 mg/l at the cliff‐base to 0.03 mg/l downslope. Correlations between NRA and soil nitrate provide a systematic basis for assigning scalar ‘nitrogen figures’ as indicators of habitat preference, here for the first time applied to arctic species.
784
Assessing allergenic fungi in house dust by floor wipe sampling and quantitative PCR
Abstract In the present study, we modified an existing surface wipe sampling method for lead and other heavy metals to create a protocol to collect fungi in floor dust followed by real‐time quantitative PCR (qPCR)‐based detection. We desired minimal inconvenience for participants in residential indoor environmental quality and health studies. Accuracy, precision, and method detection limits (MDLs) were investigated. Overall, MDLs ranged from 0.6 to 25 cell/cm(2) on sampled floors. Overall measurement precisions expressed as the coefficient of variation because of sample processing and qPCR ranged 6–63%. Median and maximum fungal concentrations in house dust in study homes in Visalia, Tulare County, California, were 110 and 2500 cell/cm(2), respectively, with universal fungal primers (allergenic and nonallergenic species). The field study indicated samplings in multiple seasons were necessary to characterize representative whole‐year fungal concentrations in residential microenvironments. This was because significant temporal variations were observed within study homes. Combined field and laboratory results suggested this modified new wipe sampling method, in conjunction with growth‐independent qPCR, shows potential to improve human exposure and health studies for fungal pathogens and allergens in dust in homes of susceptible, vulnerable population subgroups. PRACTICAL IMPLICATIONS: Fungi are ubiquitous in indoor and outdoor environments, and many fungi are known to cause allergic reactions and exacerbate asthma attacks. This study established—by modifying an existing—a wipe sampling method to collect fungi in floor dust followed by real‐time quantitative PCR (qPCR)‐based detection methodologies. Results from this combined laboratory and field assessment suggested the methodology’s potential to inform larger human exposure studies for fungal pathogens and allergens in house dust as well as epidemiologic studies of children with asthma and older adults with chronic respiratory diseases.
785
Resource utilization, overlap and temporal dynamics in a guild of mountain stream insects
SUMMARY 1. Resource utilization was quantified for six mayfly (Ephemeroptera) and one caddis (Trichoptera) species comprising a lotic scraper/collector‐gatherer guild across three niche dimensions (temporal, trophic and spatial). Based on trophic differences and inferred microspatial utilization, the members of this guild separated into two groups: (1) cryptic detritivores and (2) exposed algivores. 2. Each species demonstrated a slow seasonal univoltine life cycle except for Epeorus longimanus (Eaton) and Baetis iricaudatus (Dodds) which were fast seasonal univoltine and multivoltine, respectively. 3. Temporal sequencing of periods of peak resource utilization were not demonstrated by the members of this guild. A null analysis indicated that periods of peak resource utilization were aggregated.
786
The search for reference conditions for stream vegetation in northern Europe
1. The European Water Framework Directive provides a framework for improving the ecological quality of stream ecosystems, with deviation from reference used as a measure of ecological status. 2. Here we examine the possibility of using less impacted stream sites from Latvia, Lithuania and Poland to establish a Danish reference network for macrophyte assemblages, and as a guiding image for identification of possible references sites within Denmark. Both approaches were evaluated using historical Danish records. 3. Four different macrophyte assemblages were identified for mid‐sized streams in the Central and Eastern Lowland ecoregions. Macrophyte assemblages could not be delineated using physical stream site characteristics; however a gradual change in assemblage composition was attributed to differences in alkalinity and human impact. 4. Assemblages of contemporary vegetation in Denmark were quite similar to those found in Polish, Latvian and Lithuanian streams (26–35%). However, more importantly, from species‐based predictions we noted higher similarity, particularly with Latvian and Lithuanian streams, before intensive land use commenced in Denmark (c. 1900). These results show that stream sites from these three countries can be considered in a Danish reference network. 5. Two of the four macrophyte assemblages comprised species such as Fontinalis antipyretica, Myriophyllum spicatum, Nuphar lutea, Potamogeton alpinus and P. perfoliatus that have a very scattered occurrence in the contemporary vegetation in Denmark. These groups were closely associated with the predictions from historic records, thereby lending support the conjecture that these assemblages could be part of the guiding image for the identification of potential reference sites within Denmark.
787
Ecological and historical filters constraining spatial caddisfly distribution in Mediterranean rivers
1. Contemporary species distributions are determined by a mixture of ecological and historical filters acting on several spatial and temporal scales. Mediterranean climate areas are one of the world's biodiversity hotspots with a high level of endemicity, which is linked to complex ecological and historical factors. 2. This paper explores the ecological and historical factors constraining the distribution of caddisfly species on a large regional scale. A total of 69 taxa were collected from 140 sampling sites in 10 Iberian Mediterranean river basins. Approximately 74% of taxa can be considered rare, with the southern basins (the Baetic–Riffian region) having greater endemicity. The greatest richness, involving a mixture of northern and southern species, was found in the transitional area between the Baetic–Riffian region and the Hesperic Massif. 3. The historical processes occurring during the Tertiary (i.e. the junction of the Eurasian and African plates) explained 3.1% of species distribution, whereas ecological factors accounted for 20.7%. Only 0.3% was explained by the interaction of history and ecology. A set of multi‐scale ecological variables (i.e. basin, reach and bedform characteristics) defined five river types with specific caddisfly assemblages. The commonest caddisfly species accounted for the regional distribution pattern, while rare taxa contributed to the explanation of subtle patterns not shown by common species. 4. Despite the importance of historical factors for biogeography and the large scale used in our study, ecological variables better explained caddisfly distribution. This may be explained by the length of time since the historical process we are considering, the high dispersion and colonisation capacity of many caddisfly species, and the strong environmental gradient in the area. Because of the historical and environmental complexity of Mediterranean areas, rare taxa should be included in ecological studies so that the singularity of these ecosystems is not missed.
788
An Extraordinary Issue for Extraordinary Times
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789
A chromosomal analysis of some water beetle species recently transferred from Agabus Leach to Ilybius Erichson, with particular reference to the variation in chromosome number shown by I. montanus Stephens (Coleoptera: Dytiscidae)
The karyotypes of seven Ilybius species are described and illustrated. All except I. wasastjernae have a basic karyotype of 34 autosomes plus sex chromosomes which are X0 (♂), XX (♀), with the X chromosome among the largest in the nucleus. This karyotype appears to be the norm for Ilybius and supports the transfer of the species concerned from Agabus to Ilybius. I. wasastjernae has 36 autosomes and the X chromosome is the smallest in the nucleus and its karyotype is unlike any other known karyotype in either Ilybius or Agabus. In most of the species studied no intraspecific variation has been detected. Exceptions are I. chalconatus, where there is one inversion polymorphism in one of the autosomes, and I. montanus whose autosome number has been found to vary from 29 to 34. Such variation is highly unusual among Coleoptera. The variation results from fusion‐fission polymorphisms involving three different pairs of autosomes. In each case the fusions may be homozygous, heterozygous or absent. All populations investigated were polymorphic for some of the fusions, but only one (La Salceda, Spain) included individuals lacking all fusions. The frequencies of fused and unfused chromosomes were analysed in three English populations. In only one case was there a departure from the values expected from the Hardy‐Weinberg equilibrium, and this population also showed a significant difference from the other two. Meiosis in males heterozygous for fusions involves the production of trivalents in first division, but results in the production of abundant sperm, with no evidence of chromosomal abnormalities in second metaphase, or of degenerating cells as a result of failed meiosis. The three fusions sites are consistent in all the populations studied, and it is concluded that these fusions represent unique historical events rather than current chromosomal instability.
790
Nutrition and feeding of African ungulates during quarantine at Dvur Kralove Zoo
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791
Studies on the Ephemeroptera of a Northumbrian river system: I. Serial distribution and relative abundance
The River Coquet is a clean, fast flowing, moderately calcareous river. It is young to mature in development and supports a typical torrential fauna. Marked trends in successional replacement along the river course are confined to the scarce species of Ephemeroptera and the absence of longitudinal zonation in the distribution of some common species is related to the topographical characteristics of the system. A distinct successional trend by one species is attributed to its intolerance to the lower temperatures at high altitudes. Major discontinuities in distribution are found between the Ephemeroptera of the main river and certain tributaries. The paucity of certain otherwise abundant species in one region is related to silt deposition resulting from sand and gravel excavation.
792
Infectious Diseases and Extinction Risk in Wild Mammals
Abstract: Parasite‐driven declines in wildlife have become increasingly common and can pose significant risks to natural populations. We used the IUCN Red List of Threatened and Endangered Species and compiled data on hosts threatened by infectious disease and their parasites to better understand the role of infectious disease in contemporary host extinctions. The majority of mammal species considered threatened by parasites were either carnivores or artiodactyls, two clades that include the majority of domesticated animals. Parasites affecting host threat status were predominantly viruses and bacteria that infect a wide range of host species, including domesticated animals. Counter to our predictions, parasites transmitted by close contact were more likely to cause extinction risk than those transmitted by other routes. Mammal species threatened by parasites were not better studied for infectious diseases than other threatened mammals and did not have more parasites or differ in four key traits demonstrated to affect parasite species richness in other comparative studies. Our findings underscore the need for better information concerning the distribution and impacts of infectious diseases in populations of endangered mammals. In addition, our results suggest that evolutionary similarity to domesticated animals may be a key factor associated with parasite‐mediated declines; thus, efforts to limit contact between domesticated hosts and wildlife could reduce extinction risk.
793
IMMUNOPATHOLOGY OF RHINO MOUSE, AN AUTOSOMAL RECESSIVE MUTANT WITH MURINE LUPUS‐LIKE DISEASE
Detection of high incidence of antinuclear antibodies (ANA) was reported in young homozygous rhino mice employing formalinized chicken erythrocyte nuclei as substrate for indirect immunofluorescence (IF) assay. The titers of ANA heightened with increasing age, and attained to 1:1024 by the time mice reached 5 months of age. The occurrence of ANA was associated with development of splenic and hepatic fibrosis, glomerulonephritis and abnormalities of lymphoreticular tissue. The granular deposits of IgG and C3 detected by direct IF were initially found at the basement membrane of dermal‐epidermal junction of rhino mice aged 2.5 months. These deposits distributed progressively in the fibrotic areas of spleen and liver, and renal glomerular tufts at 5 months of age. Dense deposits revealed by electron microscopy were found in the regions where IF of IgG and G3 was observed. Acid buffer eluates from liver and kidney contained IgG reactive with nuclear antigens. Importance of homozygous rhino gene was discussed in relation to development of autoimmune disorders of these mice.
794
Looking Back at TMS2020: Setting Records and Starting Trends
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795
Pulmonary Thromboembolism in Cats
Pulmonary thromboembolism (PTE) is rarely diagnosed in cats, and the clinical features of the disease are not well known. PTE was diagnosed at postmortem examination in 17 cats, a prevalence of 0.06% over a 24‐year period. The age of affected cats ranged from 10 months to 18 years, although young (<4 years) and old (10 years) cats were more commonly affected than were middleaged cats. Males and females were equally affected. The majority of cats with PTE (n = 16) had concurrent disease, which was often severe. The most common diseases identified in association with PTE were neoplasia, anemia of unidentified cause, and pancreatitis. Cats with glomerulonephritis, encephalitis, pneumonia, heart disease, and hepatic lipidosis were also represented in this study. Most cats with PTE demonstrated dyspnea and respiratory distress before death or euthanasia, but PTE was not recognized ante mortem in any cat studied. In conclusion, PTE can affect cats of any age and is associated with a variety of systemic and inflammatory disorders. It is recommended that the same clinical criteria used to increase the suspicion of PTE in dogs should also be applied to cats.
796
A comparison of some classification methods used to determine benthic macro‐invertebrate species associations in river survey work based on data obtained from the River Ely, South Wales
SUMMARY. The results of a survey of the macro‐invertebrates of the polluted River Ely, South Wales, are used as a basis for comparing several classification methods which have been used previously in river survey work to determine species groupings. The methods compared are product‐moment correlation (clustered by the nearest neighbour technique), Kendall's tau coefficient (clustered by the nearest neighbour and average linkage techniques), and Squared Euclidean‐Distance coefficient (clustered by nearest neighbour and Ward's techniques). The species groupings determined by these methods were influenced both by the association coefficient and the technique used to cluster it. Some species were grouped together by all or most of the methods. The ecological validity of these robust groups is examined. A clear recommendation regarding the most appropriate method is frustrated by incomplete knowledge of the ecological requirements of most of the aquatic macro‐invertebrates used in the data‐set. However, Kendall's tau coefficient clustered by the average linkage technique appeared to produce ecologically meaningful species groups. Product‐moment correlation was also reasonably successful and since it is based on absolute abundance data whereas Kendall's tau coefficient is based on relative abundance data, the use of the two together is recommended for determining robust groups.
797
Ciliate populations in temporary freshwater ponds: seasonal dynamics and influential factors
SUMMARY 1. The ciliate populations of two temporary ponds in southern Ontario were studied throughout their aquatic phases in 2001. Pond I (∼1 ha) held water for 98 days, whereas Pond II (∼0.25 ha) held water for 34 days. Populations were assessed both within the ponds themselves and within a series of enclosures in which invertebrate predator pressure was manipulated. 2. In the natural pond water, total ciliate abundance in Pond II rose rapidly from day 1 increasing two orders of magnitude by day 7. In contrast, total abundance in Pond I began at the same level as in Pond II but increased much more slowly, reached a plateau of around 500 individuals L(−1), and increased again late in the hydroperiod. 3. Despite being only 500 m apart, the two ponds were fairly dissimilar in terms of their species richness and species composition. Pond I contained 50 species compared with 70 species for Pond II, with only 24 species shared. Additional species occurred within the enclosures raising the total species richness to 145 species; 88 from Pond I, 104 from Pond II, with 47 species (30%) in common. Pond II contained more mid‐sized ciliates (50–200 μm), whereas Pond I was dominated by smaller ciliates, especially in mid‐May and early June. In Pond I, cumulative species richness throughout the hydroperiod was highest in the predator addition enclosures (65 ± 4 species), followed by the partial‐predator exclusion enclosures (50 ± 4). Lowest species richness was found in the control enclosures (39 ± 2) and in the pondwater controls (39 ± 0). Differences between the ciliates in the natural pond water and the enclosures appeared to be related to a greater concentration of phytoplankton within the enclosures (perhaps resulting from extensive growth of duckweed, Lemna, outside), and higher densities of zooplankters in the pond. 4. The physicochemical environment influenced species richness, total abundance and the number of rare species (27 in Pond II versus 13 in Pond I). Variation in ciliate abundance in Pond I could be explained by the number of days after filling (39%) and enclosure treatment (23%). These two parameters also explained 72% of the variation in species richness in Pond I (46 and 26%, respectively). Sixty‐five per cent of the variation in abundance in Pond II could be explained by the measured parameters: number of days after filling 27%, pH 19%, and nitrate levels 12%. Fifty‐two per cent of the variation in species richness was explained by the environmental parameters, of which pH was the most influential. Species succession was a strong feature of both ponds and its relationship to environmental variables and the presence of other organisms is discussed. 5. Addition of invertebrate predators resulted in higher abundance and higher species richness for a limited time period in one of the ponds – suggesting that differences in foodweb dynamics may influence ciliate community composition.
798
Interferon and Interferon-Induced Chemokine Expression Is Associated with Control of Acute Viremia in West Nile Virus-Infected Blood Donors
To understand early host responses controlling West Nile virus (WNV) infection, acutely viremic blood donors, identified by nucleic acid amplification testing, were enrolled and monitored for RNA-clearance and WNV-specific IgM and IgG antibodies. Viral load and chemokine and cytokine assays were performed on serial samples from donors whose index and first follow-up samples tested negative for IgM. A total of 84% of the specimens obtained from viremic donors before IgM/IgG seroconversion demonstrated a decreasing viral load. Levels of interferon (IFN)-α ere significantly increased before IgM seroconversion, relative to those in control specimens. CXCL10 and CCL2 were significantly elevated in donor specimens obtained before IgM seroconversion, compared with those obtained after IgM seroconversion. These findings suggest that IFN-mediated innate immunity plays a key role in initial control of WNV replication.
799
A Systematic Review of Tracheostomy Modifications and Swallowing in Adults
Dysphagia occurs in 11% to 93% of patients following tracheostomy. Despite its benefits, the tracheostomy often co-exists with dysphagia given its anatomical location, the shared pathway of the respiratory and alimentary systems, and the medical complexities necessitating the need for the artificial airway. When tracheostomy weaning commences, it is often debated whether the methods used facilitate swallowing recovery. We conducted a systematic review to determine whether tracheostomy modifications alter swallowing physiology in adults. We searched eight electronic databases, nine grey literature repositories and conducted handsearching. We included studies that reported on oropharyngeal dysphagia as identified by instrumentation in adults with a tracheostomy. We accepted case series (n > 10), prospective or retrospective observational studies, and randomized control trials. We excluded patients with head and neck cancer and/or neurodegenerative disease. Two independent and blinded reviewers rated abstracts and articles for study inclusion. Data abstraction and risk of bias assessment was conducted on included studies. Discrepancies were resolved by consensus. A total of 7079 citations were identified, of which, 639 articles were reviewed, with ten articles meeting our inclusion criteria. The studies were heterogeneous in study design, patient population, and outcome measures. For these reasons, we presented our findings descriptively. All studies were limited by bias risk. This study highlights the limitations of the evidence and therefore the inability to conclude whether tracheostomy modifications alter swallowing physiology.