title: Impact of a Multidisciplinary Sepsis Initiative on Knowledge and Behavior in a Pediatric Center

text: OBJECTIVE: Our institution performed an educational initiative targeting previously identified barriers to pediatric sepsis recognition and treatment. We hypothesized that provider knowledge, attitude, and behavior would be improved 1 year after implementation. METHODS: This was a prospective, observational study of a multi-faceted quality initiative introduced to providers in the Emergency Department, inpatient wards, and Pediatric Intensive Care Unit of a tertiary care children’s hospital. Educational platforms consisted of quarterly electronic sepsis “newsletters,” brightly colored posters highlighting protocol and screening strategies displayed throughout the hospital, and low-fidelity simulation sessions (drills) led by trained staff and incorporated into daily workflows. The content was driven by feedback from a baseline needs assessment of sepsis education. One year after implementation, the needs assessment was repeated. RESULTS: Over 3 months, facilitators conducted 197 drills and captured a majority of nurses (89%), pediatrics residents (96%), and respiratory therapists (62%). By 6 months, 241 sessions had been completed. Approximately 55.4% of the 442 eligible staff participated in our post-intervention survey. Overall, knowledge of diagnostic criteria for pediatric sepsis and septic shock increased from pre-intervention levels (P = 0.015). Among post-implementation respondents, drill participants outperformed their colleagues (P = 0.001). A greater percentage of post-intervention respondents indicated comfort with sepsis recognition (P < 0.001), and fewer reported hesitating to bring sepsis concerns to their care team (P < 0.01). CONCLUSIONS: Our findings suggest that a multidisciplinary curriculum balancing active education—through brief, targeted simulation—and general awareness—through electronic resources and a poster campaign—can improve sepsis-related knowledge, attitude, and behavior among pediatric practitioners.


title: Reduction of Central Line-associated Bloodstream Infection Through Focus on the Mesosystem: Standardization, Data, and Accountability

text: INTRODUCTION: Efforts to reduce central line-associated bloodstream infection (CLABSI) rates require strong microsystems for success. However, variation in practices across units leads to challenges in ensuring accountability. We redesigned the organization’s mesosystem to provide oversight and alignment of microsystem efforts and ensure accountability in the context of the macrosystem. We implemented an A3 framework to achieve reductions in CLABSI through adherence to known evidence-based bundles. METHODS: We conducted this CLABSI reduction improvement initiative at a 395-bed freestanding, academic, university-affiliated children’s hospital. A mesosystem-focused A3 emphasized bundle adherence through 3 key drivers (1) practice standardization, (2) data transparency, and (3) accountability. We evaluated the impact of this intervention on CLABSI rates during the pre-intervention (01/15-09/17) and post-intervention (07/18–06/19) periods using a Poisson model controlling for baseline trends. RESULTS: Our quarterly CLABSI rates during the pre-intervention period ranged from 1.0 to 2.3 CLABSIs per 1,000 central line-days. With the mesosystem in place, CLABSI rates ranged from 0.4 to 0.7 per 1,000 central line days during the post-intervention period. Adjusting for secular trends, we observed a statistically significant decrease in the post versus pre-intervention CLABSI rate of 71%. CONCLUSION: Our hospital-wide CLABSI rate declined for the first time in many years after the redesign of the mesosystem and a focus on practice standardization, data transparency, and accountability. Our approach highlights the importance of alignment across unit-level microsystems to ensure high-fidelity implementation of practice standards throughout the healthcare-delivery system.


title: The health case for urgent action on climate change

text: Health professionals have a leading role


Actualités profession


Lassa fever outbreak continues across Nigeria


The resurgence of convalescent plasma therapy


Rebalancing Redux: the Final NICE Guidelines on Abdominal Aortic Aneurysm (AAA) Disease


Radiological findings for diagnosis of SARS-CoV-2 pneumonia (COVID-19)()


Redistributing working schedules using the infective principle in the response to COVID-19


STELLAR 3 and STELLAR 4: Lessons From the Fall of Icarus


title: Evolution of ARDS biomarkers: Will metabolomics be the answer?

text: To date, there is no clinically agreed-upon diagnostic test for acute respiratory distress syndrome (ARDS): the condition is still diagnosed on the basis of a constellation of clinical findings, laboratory tests, and radiological images. Development of ARDS biomarkers has been in a state of continuous flux during the past four decades. To address ARDS heterogeneity, several studies have recently focused on subphenotyping the disease on the basis of observable clinical characteristics and associated blood biomarkers. However, the strong correlation between identified biomarkers and ARDS subphenotypes has yet to establish etiology; hence, there is a need for the adoption of other methodologies for studying ARDS. In this review, we will shed light on ARDS metabolomics research in the literature and discuss advances and major obstacles encountered in ARDS metabolomics research. Generally, the ARDS metabolomics studies focused on identification of differentiating metabolites for diagnosing ARDS, but they were performed to different standards in terms of sample size, selection of control cohort, type of specimens collected, and measuring technique utilized. Virtually none of these studies have been properly validated to identify true metabolomics biomarkers of ARDS. Though in their infancy, metabolomics studies exhibit promise to unfold the biological processes underlying ARDS and, in our opinion, have great potential for pushing forward our present understanding of ARDS.


Letter to the Editor: Resources and recommendations for a quick transition to online instruction in physiology


Fever: Role of Pyrogens and Cryogens


title: Chemokines in acute respiratory distress syndrome

text: A characteristic feature of all inflammatory disorders is the excessive recruitment of leukocytes to the site of inflammation. The loss of control in trafficking these cells contributes to inflammatory diseases. Leukocyte recruitment is a well-orchestrated process that includes several protein families including the large cytokine subfamily of chemotactic cytokines, the chemokines. Chemokines and their receptors are involved in the pathogenesis of several diseases. Acute lung injury that clinically manifests as acute respiratory distress syndrome (ARDS) is caused by an uncontrolled systemic inflammatory response resulting from clinical events including major surgery, trauma, multiple transfusions, severe burns, pancreatitis, and sepsis. Systemic inflammatory response syndrome involves activation of alveolar macrophages and sequestered neutrophils in the lung. The clinical hallmarks of ARDS are severe hypoxemia, diffuse bilateral pulmonary infiltrates, and normal intracardiac filling pressures. The magnitude and duration of the inflammatory process may ultimately determine the outcome in patients with ARDS. Recent evidence shows that activated leukocytes and chemokines play a key role in the pathogenesis of ARDS. The expanding number of antagonists of chemokine receptors for inflammatory disorders may hold promise for new medicines to combat ARDS.


title: Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury

text: Acute respiratory distress syndrome (ARDS) is a common cause of death in the intensive care unit, with mortality rates of ~30–40%. To reduce invasive diagnostics such as bronchoalveolar lavage and time-consuming in-hospital transports for imaging diagnostics, we hypothesized that particle flow rate (PFR) pattern from the airways could be an early detection method and contribute to improving diagnostics and optimizing personalized therapies. Porcine models were ventilated mechanically. Lipopolysaccharide (LPS) was administered endotracheally and in the pulmonary artery to induce ARDS. PFR was measured using a customized particles in exhaled air (PExA 2.0) device. In contrast to control animals undergoing mechanical ventilation and receiving saline administration, animals who received LPS developed ARDS according to clinical guidelines and histologic assessment. Plasma levels of TNF-α and IL-6 increased significantly compared with baseline after 120 and 180 min, respectively. On the other hand, the PFR significantly increased and peaked 60 min after LPS administration, i.e., ~30 min before any ARDS stage was observed with other well-established outcome measurements such as hypoxemia, increased inspiratory pressure, and lower tidal volumes or plasma cytokine levels. The present results imply that PFR could be used to detect early biomarkers or as a clinical indicator for the onset of ARDS.


title: Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue

text: Chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are associated with changes in extracellular matrix (ECM) composition and abundance affecting the mechanical properties of the lung. This study aimed to generate ECM hydrogels from control, severe COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) IV], and fibrotic human lung tissue and evaluate whether their stiffness and viscoelastic properties were reflective of native tissue. For hydrogel generation, control, COPD GOLD IV, and fibrotic human lung tissues were decellularized, lyophilized, ground into powder, porcine pepsin solubilized, buffered with PBS, and gelled at 37°C. Rheological properties from tissues and hydrogels were assessed with a low-load compression tester measuring the stiffness and viscoelastic properties in terms of a generalized Maxwell model representing phases of viscoelastic relaxation. The ECM hydrogels had a greater stress relaxation than tissues. ECM hydrogels required three Maxwell elements with slightly faster relaxation times (τ) than that of native tissue, which required four elements. The relative importance (R(i)) of the first Maxwell element contributed the most in ECM hydrogels, whereas for tissue the contribution was spread over all four elements. IPF tissue had a longer-lasting fourth element with a higher R(i) than the other tissues, and IPF ECM hydrogels did require a fourth Maxwell element, in contrast to all other ECM hydrogels. This study shows that hydrogels composed of native human lung ECM can be generated. Stiffness of ECM hydrogels resembled that of whole tissue, while viscoelasticity differed.


title: Worldwide clinical practices in perioperative antibiotic therapy for lung transplantation

text: BACKGROUND: Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices. METHODS: We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period. RESULTS: We received a total of 99 responses from 24 countries, mostly from Western Europe (n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin / tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%). CONCLUSION: Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients.


title: Potential prognostic roles of serum lactate and Creatine kinase levels in poisoned patients

text: BACKGROUND: Examination of serum lactate level and its changes, as an indicator of tissue oxygenation, as well as level of creatine kinase (CK) inhibitors, as a factor of mortality which partially expresses heart, brain, and muscle damage, may be considered as tools to determine prognosis in critically ill patients. We aimed to evaluate these two factors as potential prognostic factors in critically poisoned patients admitted to our toxicology ICU. METHOD: This is a cross-sectional descriptive-analytic study that was performed on poisoned patients referred to emergency department of Loghman Hakim Hospital. One-hundred critically poisoned patients who had been admitted to ICU were conveniently chosen using a random number table and included into the study after obtaining consent forms from their next of kin. Their serum lactate and CK levels were checked on admission. These levels were compared subsequently between survivors and non-survivors to seek for their potential prognostic role. RESULTS: In a total of 100 patients enrolled, 61 were male. Serum level of lactate (with a cut off of 26 mg/dL) and serum CK with a cutoff point of 169 U/L could have prognosticated death with sensitivity and specificity of 78 and 77% (for lactate) and 74 and 62% (for serum CK), respectively. CONCLUSIONS: In poisoned patients, serum lactate and CK can be used as possible prognostic factors because they rapidly increase in the serum and are easily detectable.


A tribute to Stephen M. Schwartz, MD, PhD


title: Point-of-Care Technologies for Health Care

text: The increasingly global focus on health care issues continues to underline the importance of point-of-care technologies and their ability to provide cost-effective solutions that address many unmet health care needs. Further, the current crisis in health care costs has critically underscored the need for research and development into highly effective, but low cost means of delivering health care. With a focus on providing clinically actionable information at or near the patient, point-of-care devices provide clinicians with information that is critical to the management of patient care while they are still with the patient. Rapid information results in various advantages for POC testing in different kinds of health care settings. In primary care settings in developed countries, the shortened timeline between testing and availability of results reduces the need for extra office visits or follow-up phone calls to convey testing results and adjust clinical intervention. This strategy can reduce cost and increase access of otherwise underserved populations to medical care. For diseases that are infectious, such as sexually transmitted infections or respiratory diseases, POC testing can facilitate treatment modalities quickly, thus preventing further spread of the infection for better and timely clinical management. In acute care settings, timely access to diagnostic information is most critical for providing an effective medical response. In disaster settings, POC diagnostics can speed triage and enable rapid establishment and delivery of medical services.


title: Pandemic response lessons from influenza H1N1 2009 in Asia

text: During April 2009, a novel H1N1 influenza A virus strain was identified in Mexico and the USA. Within weeks the virus had spread globally and the first pandemic of the 21st Century had been declared. It is unlikely to be the last and it is crucial that real lessons are learned from the experience. Asia is considered a hot spot for the emergence of new pathogens including past influenza pandemics. On this occasion while preparing for an avian, highly virulent influenza virus (H5N1 like) originating in Asia in fact the pandemic originated from swine, and was less virulent. This discrepancy between what was planned for and what emerged created its own challenges. The H1N1 pandemic has tested national health‐care infrastructures and exposed shortcomings in our preparedness as a region. Key health challenges include communication throughout the region, surge capacity, access to reliable information and access to quality care, health‐care worker skills, quality, density and distribution, access to essential medicines and lack of organizational infrastructure for emergency response. Despite years of preparation the public health and clinical research community were not ready to respond and opportunities for an immediate research response were missed. Despite warm words and pledges efforts to engage the international community to ensure equitable sharing of limited resources such as antivirals and vaccines fell short and stockpiles in the main remained in the rich world. This manuscript with authors from across the region describes some of the major challenges faced by Asia in response to the pandemic and draws lessons for the future.


title: The function of a ribosomal frameshifting signal from human immunodeficiency virus‐1 in Escherichia coli

text: A 15‐17 nucleotide sequence from the gag‐pol ribosome frameshift site of HIV‐1 directs analogous ribosomal frameshifting in Escherichia coli. Limitation for leucine, which is encoded precisely at the frameshift site, dramatically increased the frequency of leftward frameshifting. Limitation for phenylaianine or arginine, which are encoded just before and just after the frameshift, did not significantly affect frameshifting. Protein sequence analysis demonstrated the occurrence of two closeiy related frameshift mechanisms. In the first, ribosomes appear to bind leucyl‐tRNA at the frameshift site and then slip leftward. This is the 'simultaneous slippage’mechanism. In the second, ribosomes appear to slip before binding amlnoacyl‐tRNA, and then bind phenylaianyl‐tRNA, which is encoded in the left‐shifted reading frame. This mechanism is identicai to the‘overlapping reading’we have demonstrated at other bacterial frameshift sites. The HIV‐1 sequence is prone to frame‐shifting by both mechanisms in E. coli.


title: Limited polymorphism at major histocompatibility complex (MHC) loci in the Swedish moose A. alces

text: The Swedish moose was analysed for genetic variability at major histocompatibility complex (MHC) class I and class II DQA, DQB and DRB loci using restriction fragment length polymorphism (RFLP) and single strand conformation polymorphism (SSCP) techniques. Both methods revealed limited amounts of polymorphism. Since the SSCP analysis concerned an expressed DRB gene it can be concluded that the level of functional MHC class II polymorphism, at least at the DRB locus, is low in Swedish moose. DNA fingerprinting was used to determine if the unusual pattern of low MHC variability could be explained by a low degree of genome‐wide genetic diversity. Hybridizations with two minisatellite probes gave similarity indices somewhat higher than the average for other natural population, but the data suggest that the low MHC variability cannot be explained by a recent population bottleneck. However, since minisatellite sequences evolve more rapidly than MHC sequences, the low levels of MHC diversity may be attributed to a bottleneck of more ancient origin. The selection pressure for MHC variability in moose may also be reduced and we discuss the possibility that its solitary life style may reduce lateral transmission of pathogens in the population.


title: Analysis of Benthic Communities in the Cyclades Plateau (Aegean Sea) Using Ecological and Paleoecological Data Sets

text: Abstract. In the Cyclades plateau (Aegean Sea), a qualitative and quantitative analysis of macro‐benthic fauna was carried out in 1986. Standard multivariate analysis techniques were applied to both ecological (living benthic fauna) and paleoecological data sets in order to distinguish distribution patterns. Results showed that caution must prevail in drawing conclusions from a limited data set. The clearest classification was obtained using total living fauna, while the dead molluscan fauna gave a similar pattern; this indicates similar response to the environmental conditions of the area. In the analysis of the living molluscan fauna, the groups failed to show any clusters, probably as an effect of some impoverished sites. In the two groups delineated, depth seems to be the major factor in the distribution of species. The fact that two distinct data sets (subfossil assemblages and living communities), when treated separately, produce similar grouping indicates that the subfossil assemblages could be reliably used as a first approach for determination of the living communities' distribution patterns.


title: Mycelial compatibility groups and pathogenic diversity in Sclerotium rolfsii populations from sugar beet crops in Mediterranean‐type climate regions

text: The population structure of Sclerotium rolfsii from autumn‐sown sugar beet crops in Mediterranean‐type climate regions of Chile, Italy, Portugal and Spain was determined by analyses of mycelial compatibility groups (MCGs) and pathogenicity to 11 economically important plant species. Twelve MCGs (i–xii) were identified among 459 S. rolfsii isolates. MCG iii was the most prevalent group in all countries except Italy. MCG i, the most abundant group (64·7% of isolates) was identified in Portugal and Spain. The remaining MCGs were restricted to various regions within one country (ii, vi, ix) or different countries (v), or to specific localities (iv, vii, viii, x, xi, xii). MCGs iv, vii and x each comprised one isolate. Fields extensively sampled in southern Spain were infected with one to three MCGs. Plant species differed in susceptibility to MCG tester isolates with a MCG by species interaction. Cluster analyses allowed selection into five MCG groupings and grouped plant species into species‐groups 1 (broccoli, chickpea, sunflower, tomato) and 2 (cotton, pepper, sugar beet, watermelon). MCG groupings 1 (i, ix), 2 (ii, iii, vi, viii) and 5 (x, xii) were moderately virulent to species‐group 1 and mildly virulent to species‐group 2. MCG groupings 3 (iv, v, xi) and 4 (vii) were mildly virulent to both species‐groups. Across MCG groups, species were rated highly susceptible (chickpea, sunflower), susceptible (cotton, pepper, tomato, watermelon), moderately resistant (broccoli, melon, sugar beet) and resistant (corn, wheat). Establishing the MCG population structure and virulence variability among S. rolfsii isolates should help in the management of sclerotium root rot diseases.


title: Correlation between relative growth rate and specific leaf area requires associations of specific leaf area with nitrogen absorption rate of roots

text: • . Close correlations between specific leaf area (SLA) and relative growth rate (RGR) have been reported in many studies. However, theoretically, SLA by itself has small net positive effect on RGR because any increase in SLA inevitably causes a decrease in area‐based leaf nitrogen concentration (LNC(a)), another RGR component. It was hypothesized that, for a correlation between SLA and RGR, SLA needs to be associated with specific nitrogen absorption rate of roots (SAR), which counteracts the negative effect of SLA on LNC(a). • . Five trees and six herbs were grown under optimal conditions and relationships between SAR and RGR components were analyzed using a model based on balanced growth hypothesis. • . SLA varied 1.9‐fold between species. Simulations predicted that, if SAR is not associated with SLA, this variation in SLA would cause a 47% decrease in LNC(a) along the SLA gradient, leading to a marginal net positive effect on RGR. In reality, SAR was positively related to SLA, showing a 3.9‐fold variation, which largely compensated for the negative effect of SLA on LNC(a). Consequently, LNC(a )values were almost constant across species and a positive SLA–RGR relationship was achieved. • . These results highlight the importance of leaf–root interactions in understanding interspecific differences in RGR.


title: Seasonal and pandemic influenza during pregnancy and risk of fetal death: A Norwegian registry-based cohort study

text: Previous studies of fetal death with maternal influenza have been inconsistent. We explored the effect of maternal influenza-like illness (ILI) in pregnancy on the risk of fetal death, distinguishing between diagnoses during regular influenza seasons and the 2009/2010 pandemic and between trimesters of ILI. We used birth records from the Medical Birth Registry of Norway to identify fetal deaths after the first trimester in singleton pregnancies (2006–2013). The Norwegian Directorate of Health provided dates of clinical influenza diagnoses by primary-health-care providers, whereas dates of laboratory-confirmed influenza A (H1N1) diagnoses were provided by the Norwegian Surveillance System for Communicable Diseases. We obtained dates and types of influenza vaccinations from the Norwegian Immunisation Registry. Cox proportional-hazards regression models were fitted to estimate hazard ratios (HRs) of fetal death, with associated 95% confidence intervals (CIs), comparing women with and without an ILI diagnosis in pregnancy. There were 2510 fetal deaths among 417,406 eligible pregnancies. ILI during regular seasons was not associated with increased risk of fetal death: adjusted HR = 0.90 (95% CI 0.64–1.27). In contrast, ILI during the pandemic was associated with substantially increased risk of fetal death, with an adjusted HR of 1.75 (95% CI 1.21–2.54). The risk was highest following first-trimester ILI (adjusted HR = 2.28 [95% CI 1.45–3.59]). ILI during the pandemic—but not during regular seasons—was associated with increased risk of fetal death in the second and third trimester. The estimated effect was strongest with ILI in first trimester. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10654-020-00600-z) contains supplementary material, which is available to authorized users.


title: Neutrophil chemoattractant receptors in health and disease: double-edged swords

text: Neutrophils are frontline cells of the innate immune system. These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential. Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis, for inflammation modulation and resolution, wound healing and tissue repair. After fulfilling the appropriate effector functions, however, dampening neutrophil activation and infiltration is crucial to prevent damage to the host. In humans, chemoattractant molecules can be categorized into four biochemical families, i.e., chemotactic lipids, formyl peptides, complement anaphylatoxins and chemokines. They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs. Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors (GPCRs). In addition, emerging evidence suggests an important role for atypical chemoattractant receptors (ACKRs) that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses. The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation, with a pivotal modulatory role for the (inflammatory) environment. Here, we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease. Depending on the (patho)physiological context, specific chemoattractant receptors may be up- or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences, thus opening new windows for the identification of disease biomarkers and potential drug targets.


title: Polymorphisms in PARP1 predict disease-free survival of triple-negative breast cancer patients treated with anthracycline/taxane based adjuvant chemotherapy

text: Triple-negative breast cancer (TNBC) is a highly aggressive disease and of poor prognosis. It is very important to identify novel biomarkers to predict therapeutic response and outcome of TNBC. We investigated the association between polymorphisms in PARP1 gene and clinicopathological characteristics or survival of 272 patients with stage I-III primary TNBC treated with anthracycline/taxane based adjuvant chemotherapy. We found that after adjusted by age, grade, tumor size, lymph node status and vascular invasion, rs7531668 TA genotype carriers had significantly better DFS rate than TT genotype carriers, the 5 y DFS was 79.3% and 69.2% (P = 0.046, HR 0.526 95% CI 0.280–0.990). In lymph node negative subgroup, DFS of rs6664761 CC genotype carriers was much better than TT genotype carriers (P = 0.016, HR 0.261 95% CI 0.088–0.778) and DFS of rs7531668 AA genotype carriers was shorter than TT genotype carriers (P = 0.015, HR 3.361 95% CI 1.259–8.969). In subgroup of age ≤ 50, rs6664761 TC genotype predicted favorable DFS than TT genotype (P = 0.042, HR 0.405 95% CI 0.170–0.967). Polymorphisms in PARP1 gene had no influence on treatment toxicities. After multivariate analysis, tumor size (P = 0.037, HR = 2.829, 95% CI: 1.063–7.525) and lymph node status (P < 0.001, HR = 9.943, 95% CI: 2.974–33.243) were demonstrated to be independent prognostic factors. Our results suggested that polymorphisms in PARP1 gene might predict the DFS of TNBC patients treated with anthracycline/taxane based adjuvant chemotherapy.


title: Under-the-Radar Dengue Virus Infections in Natural Populations of Aedes aegypti Mosquitoes

text: The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort concerning the dengue mosquito vector, Aedes aegypti, and its microbiome, which has been shown to influence virus transmission success. We examined the “metavirome” of four populations of Aedes aegypti mosquitoes collected in 2016 to 2017 in Manatee County, FL. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a 2-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, and explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of the DENV4 infections in A. aegypti that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak. IMPORTANCE Since 1999, dengue outbreaks in the continental United States involving local transmission have occurred only episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from countries where the disease is endemic. To date, the U.S. public health response to dengue outbreaks has been largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of DENV4 transmission to and maintenance within a local mosquito vector population in the continental United States in the absence of a human case during two consecutive years. Our data suggest that molecular surveillance of mosquito populations in high-risk, high-tourism areas of the United States may enable proactive, targeted vector control before potential arbovirus outbreaks.


title: Epitope-Based Peptide Vaccine against Glycoprotein G of Nipah Henipavirus Using Immunoinformatics Approaches

text: BACKGROUND: Nipah belongs to the genus Henipavirus and the Paramyxoviridae family. It is an endemic most commonly found at South Asia and has first emerged in Malaysia in 1998. Bats are found to be the main reservoir for this virus, causing disease in both humans and animals. The last outbreak has occurred in May 2018 in Kerala. It is characterized by high pathogenicity and fatality rates which varies from 40% to 70% depending on the severity of the disease and on the availability of adequate healthcare facilities. Currently, there are no antiviral drugs available for NiV disease and the treatment is just supportive. Clinical presentations for this virus range from asymptomatic infection to fatal encephalitis. OBJECTIVE: This study is aimed at predicting an effective epitope-based vaccine against glycoprotein G of Nipah henipavirus, using immunoinformatics approaches. METHODS AND MATERIALS: Glycoprotein G of the Nipah virus sequence was retrieved from NCBI. Different prediction tools were used to analyze the epitopes, namely, BepiPred-2.0: Sequential B Cell Epitope Predictor for B cell and T cell MHC classes II and I. Then, the proposed peptides were docked using Autodock 4.0 software program. Results and Conclusions. The two peptides TVYHCSAVY and FLIDRINWI have showed a very strong binding affinity to MHC class I and MHC class II alleles. Furthermore, considering the conservancy, the affinity, and the population coverage, the peptide FLIDRINWIT is highly suitable to be utilized to formulate a new vaccine against glycoprotein G of Nipah henipavirus. An in vivo study for the proposed peptides is also highly recommended.


title: Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine

text: BACKGROUND: There is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to determine such “functional metabolites” in ARDS using metabolomics and in vivo experiments in a mouse model. METHODS: Metabolomic profiles of blood plasma from 42 ARDS patients and 28 healthy controls were captured using Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Univariate and multivariate statistical analysis were performed on metabolomic profiles from blood plasma of ARDS patients and healthy controls to screen for “functional metabolites”, which were determined by variable importance in projection (VIP) scores and P value. Pathway analysis of all the metabolites was performed. The mouse model of ARDS was established to investigate the role of “functional metabolites” in the lung injury and mortality caused by the respiratory disorder. RESULTS: The metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool. Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS. Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS. CONCLUSION: Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma Phenylalanine. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800015930. Registered 29 April 2018, http://www.chictr.org.cn/edit.aspx?pid=25609&htm=4


title: In vivo evidence for extracellular DNA trap formation

text: Extracellular DNA trap formation is a cellular function of neutrophils, eosinophils, and basophils that facilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form extracellular traps, granulocytes release a scaffold consisting of mitochondrial DNA in association with granule proteins. As we understand more about the molecular mechanism for the formation of extracellular DNA traps, the in vivo function of this phenomenon under pathological conditions remains an enigma. In this article, we critically review the literature to summarize the evidence for extracellular DNA trap formation under in vivo conditions. Extracellular DNA traps have not only been detected in infectious diseases but also in chronic inflammatory diseases, as well as in cancer. While on the one hand, extracellular DNA traps clearly exhibit an important function in host defense, it appears that they can also contribute to the maintenance of inflammation and metastasis, suggesting that they may represent an interesting drug target for such pathological conditions.


title: Tolerance of coffee (Coffea spp.) seeds to ultra‐low temperature exposure in relation to calorimetric properties of tissue water, lipid composition, and cooling procedure

text: The effect of exposure to ultra‐low temperature (liquid nitrogen, LN) on viability of seeds desiccated to various water contents was investigated in 9 coffee species. Three groups of species could be distinguished based on seed survival after LN exposure. In group 1 species, no seedling production could be obtained after LN exposure due to endosperm injury. In group 2 species, recovery was very low or nil after rapid cooling, and only moderate after slow cooling. In group 3 species, very high percentages of seedling development were observed after both rapid and slow cooling. A high interspecific variability for the high moisture freezing limit was observed within the species of groups 2 and 3, since it ranged from 0.14 to 0.26 g H(2)O g(−1) dry weight. A very highly significant correlation was found for those species between the unfreezable water content, as determined from DSC analysis, and the high moisture freezing limit of their seeds. No significant correlation was found between seed lipid content, which varied from 9.8 to 34.6% dry weight, and survival after LN exposure. However, a negative relationship was found between seed unfreezable water content and lipid content. Interspecific differences in fatty acid composition of seed lipids resulted in a high variability in the percentage of unsaturated fatty acids, which ranged from 28.7 to 54.4% among the 9 species studied. For all species studied, a highly significant correlation was found between the percentage of unsaturated fatty acids and the percentage of seedling recovery after rapid or slow cooling.


title: Resource Allocation and Priority Setting

text: There has been much discussion of resource allocation in medical systems, in the United States and elsewhere. In large part, the discussion is driven by rising costs and the resulting budget pressures felt by publicly funded systems and by both public and private components of mixed health systems. In some publicly funded systems, resource allocation is a pressing issue because resources expended on one disease or person cannot be spent on another disease or person. Some of the same concern arises in mixed medical systems with multiple funding sources.


title: International Collaboration for Global Public Health

text: There is a long tradition of global collaboration in biomedicine and public health. Examples range from medical outposts in rural communities run by foreign missionaries (Good 1991) to the early infectious disease programs of the Rockefeller Foundation (Fosdick 1989) and from medical services and training programs for indigenous populations set up by colonial authorities (Marks 1997) to the Pan American Health Organization (PAHO) established by a collective of sovereign governments (Cueto 2007).


Addressing Burnout: Symptom Management Versus Treating the Cause


To our global neonatal nursing community


title: Functional richness of local hoverfly communities (Diptera, Syrphidae) in response to land use across temperate Europe

text: Environmental change is not likely to act on biodiversity in a random manner, but rather according to species traits that affect assembly processes, thus, having potentially serious consequences on ecological functions. We investigated the effects of anthropogenic land use on functional richness of local hoverfly communities of 24 agricultural landscapes across temperate Europe. A multivariate ordination separated seven functional groups based on resource use, niche characteristics and response type. Intensive land use reduced functional richness, but each functional group responded in a unique way. Species richness of generalist groups was nearly unaffected. Local habitat quality mainly affected specialist groups, while land use affected intermediate groups of rather common species. We infer that high species richness within functional groups alone is no guarantee for maintaining functional richness. Thus, it is not species richness per se that improves insurance of functional diversity against environmental pressures but the degree of dissimilarity within each functional group.


title: Character‐ and tree‐based delimitation of species in the ‘Cichlasoma’ facetum group (Teleostei, Cichlidae) with the description of a new genus

text: The ‘Cichlasoma’ facetum group is part of the taxonomically complex group of Neotropical cichlid fishes of the tribe Heroini. Many species groups and unplaced species of heroines are still left without a generic name following the revision of the genus Cichlasoma. We describe here the ‘Cichlasoma’ facetum group as a new genus, Australoheros, and provide evidence for its monophyly based on phylogenetic analyses of morphological and mtDNA characters. Australoheros is morphologically characterized by the lowest values in meristic characters among heroines and by three apomorphic characters in coloration pattern. In addition to the three described species of Australoheros, our results of species delimitation based on a combination of tree‐ and character‐based approaches identify seven putatively new species of Australoheros. Several coding schemes of morphological characters are used to recover the intrageneric relationships within the genus, resulting in very similar topologies. Discovery of additional species within the genus is expected once material from the whole distribution area is studied.


title: In vitro susceptibility of Escherichia coli strains isolated from diarrhoeic lambs and goat kids to 14 antimicrobial agents

text: The in vitro activities of 14 anti‐microbial agents were determined against 92 strains of E. coli isolated from lambs (60 strains) and kids (32 strains) affected by neonatal diarrhoea. The overall percentage of resistant strains to streptomycin, sulphadimethoxine and tetracycline was very high (above 70%). A high level of resistance (from 30% to 50%) to ampicillin, kanamycin, neomycin and chloramphenicol was also detected. The E. coli strains were highly susceptible to cephalosporins, polymyxin and quinolones. Most of the strains showed multiresistance: 77.2% of isolates were resistant to at least two antibiotics, 55.4% were resistant to at least four antibiotics and 33.7% were resistant to at least six antibiotics. A total of 34 antibiotypes could be distinguished.


title: Graptoloid feeding efficiency, rotation and astogeny

text: Two methods are used to examine feeding strategies in graploloids; the first profiles different sets of zooids on the colony, the second treats the colony as a whole. Both of these techniques have advantages. The choice between them brings into question our concepts of the degree of coloniality shown by graptoloids. Using a whole colony model. graptoloids can be shown to have sampled the water with variable efficiency. as defined in this paper. Planar forms were relatively inefficient, generally sampling less than 10% of the available water. Inclined forms frequently approached 75% efficiency. Biserial forms and strdight monograptids roulinely exceeded 100%. sampling each unit of water more than once. Rotation of the rhabdosome during movement increased the efficiency of horizontal and inclined forms. It reduced the efficiency of scandent biserials and straight monograptids. These were both advantageous effects. Astogenetic changes in colony size and form would have had a profound effect on feeding efficiency.□Graptoloid, ecology, astogeny


title: Propagation of Hemagglutinating Encephalomyelitis Virus in Porcine Cell Cultures

text: SUMMARY: This study reports some cultural characteristics of the VW 572 strain of hemagglutinating encephalomyelitis virus (HEV) in primary pig kidney (PPK) cells, primary pig testicle (PPT) cells, secondary pig thyroid (SPTh) cells and the cell lines PK‐15 (pig kidney), SK−6 (swine kidney) and ST (swine testicle). A growth curve, based on cytopathic effect (CPE), immunofluorescence (IF), hemadsorption (Hads) and hemagglutination (HA), showed that SPTh and PPK cells were most susceptible for cultivation and quantitation of the virus. For the detection of replication in tubes inoculated with small amounts of virus, CPE, Hads and HA appeared to be useful and sensitive criteria. Repeated virus quantitation trials revealed a high variation in titration end‐points, even in the most susceptible cell types. The optimal procedure for the isolation of HEV from clinical specimens is preferably to inoculate the material on SPTh or PPK cells and to make a blind passage if the HA test at 7 days post inoculation is negative. ZUSAMMENFASSUNG: Züchtung von Hemagglutinating Encephalomyelitis Virus (HEV) in porcinen Zellkulturen Kulturelle Eigenschaften des HEV‐Stammes VW 572 in primären Schweinenierenzellen (PPK), primären Schweinehodenzellen (PPT), sekundären Schweineschilddrüsenzellen (SPTh) und in den Zellinien PK‐15 (Schweinenieren), SK−6 (Schweinenieren) und ST (Schweinehoden) werden beschrieben. Vermehrungskurven, die mit Hilfe des cytopatischen Effektes (CPE), der Immunofluoreszenz (IF), der Hämadsorption (Hads) und der Hämagglutination als Kriterien für die Virusreplikation erstellt wurden, zeigten, daß SPTh und PPK‐Zellen am empfindlichsten für die Züchtung und Titration des Virus sind. Zum Nachweis der Virusvermehrung in Röhrchen, die mit kleinen Virusmengen beimpft wurden, waren CPE, Hads und HA empfindliche und brauchbare Kriterien. Wiederholte Virustitrationen zeigten eine hohe Variation der Titerendpunkte auch in hochempfänglichen Zellkulturen. Die optimale Methode für die Isolierung von HEV von klinischem Material ist die Verimpfung auf SPTh oder PPK mit anschließender Blindpassage, wenn der HA‐Test sieben Tage p. inf. negativ ist. RÉSUMÉ: Culture du virus hémagglutinant de l'encéphalomyélite (HEV) dans des cultures de cellules de porc On décrit les propriétés de culture de la souche HEV VW 572 dans des cellules primaires de reins de pores (PPK), dans des cellules primaires de testicules de porcs (PPT), dans des cellules secondaires de glandes tyroïdes de porcs (SPTh) et dans les lignées cellulaires PK‐15 (reins de porcs), SK−6 (reins de porcs) et ST (testicules de porcs). Les courbes de multiplication établies avec l'effet cytopathique (CPE), l'immunofluorescence (IF), l'hémadsorption (Hads) et l'hémagglutination (HA) comme critères pour la réplication du virus ont montré que les cellules SPTh et PPK étaient les plus sensibles pour la culture et la titration du virus. CPE, Hads et HA furent les critères sensibles et utilisables pour la mise en évidence de la multiplication virale en tubes inoculés avec de petites quantités de virus. Des titrations du virus répétées ont montré une forte variation du titre final également dans les cultures cellulaires hautement réceptrices. La méthode optimale pour l'isolement de HEV à partir d'un matériel clinique est l'inoculation sur SPTh ou PPK avec passages à l'aveugle si le test HA est négatif 7 jours après l'infection. RESUMEN: Propagación del virus hemoaglutinante de la encefalomielitis (HEV) en los cultivos de células de cerdos Se describen las propiedades culturales de la estirpe HEV VW 572 en células renales primarias de cerdo (PPK), células testiculares primarias de cerdo, células tiroideas secundarias de cerdo (SPTh) y en las líneas celulares PK‐15 (riñones de cerdo), SK−6 (riñones porcinos) y ST (testículos de cerdo). Las curvas de multiplicación, las cuales se establecieron con ayuda del efecto citopático (CPE), la inmunofluorescencia (IF), la hemoadsorción (Hads) y la hemoaglutinación como criterios para la replicación virósica, mostraban que las células SPTh y PPK son las más sensibles para el cultivo y titulación del virus. Para la puesta en evidencia de la multiplicación virósica en tubitos, los cuales se inocularon con cantidades pequeñas de virus, eran CPE, Hads y HA criterios sensibles y útiles. Titulaciones repetidas de virus mostraban una variación elevada de los puntos finales de títulos incluso en cultivos celulares harto receptibles. El método óptimo para el aislamiento de HEV a partir de material clínico consiste en la inoculación a SPTH o PPK con pase ciego inmediato si la prueba HA es negativa 7 días después de la infección.


title: Necrotizing enterocolitis in very low birthweight infants: a four‐year experience

text: Fifty (13%) of 375 infants who weighed 1500 g or less at birth had necrotizing enterocolitis (NEC). Haematological changes suggestive of sepsis occurred in 83% and positive bacteriological cultures were found in 38%, the most common organism isolated being Clostridium perfringens. Complications included intestinal perforation in six patients and recurrence of NEC in five, of whom one subsequently developed an intestinal stricture. Five of the eight nursery deaths were secondary to peritonitis and overwhelming sepsis from NEC. In spite of the discontinuation of milk feeds for prolonged periods, satisfactory caloric intake and weight gain were achieved with parenteral nutrition in the survivors. Of the 41 long‐term survivors, six (15%) were found to have a disability at 2 years of ago, corrected for prematurity, compared with 48 (20%) of 241 very low birthweight survivors from the same study period who did not have NEC. None had evidence of gastrointestinal dysfunction. Six (15%) children remained below the 10th percentile for both weight and height. This study showed that early diagnosis and therapy for NEC in very tow birthweight infants were associated with a favourable short‐ and long‐term outcome.


title: The Evolutionary History of the Genus Acanthamoeba and the Identification of Eight New 18S rRNA Gene Sequence Types

text: ABSTRACT The 18S rRNA gene (Rns) phylogeny of Acanthamoeba is being investigated as a basis for improvements in the nomenclature and taxonomy of the genus. We previously analyzed Rns sequences from 18 isolates from morphological groups 2 and 3 and found that they fell into four distinct evolutionary lineages we called sequence types T1‐T4. Here, we analyzed sequences from 53 isolates representing 16 species and including 35 new strains. Eight additional lineages (sequence types T5‐T12) were identified. Four of the 12 sequence types included strains from more than one nominal species. Thus, sequence types could be equated with species in some cases or with complexes of closely related species in others. The largest complex, sequence type T4, which contained six closely related nominal species, included 24 of 25 keratitis isolates. Rns sequence variation was insufficient for full phylogenetic resolution of branching orders within this complex, but the mixing of species observed at terminal nodes confirmed that traditional classification of isolates has been inconsistent. One solution to this problem would be to equate sequence types and single species. Alternatively, additional molecular information will be required to reliably differentiate species within the complexes. Three sequence types of morphological group 1 species represented the earliest divergence in the history of the genus and, based on their genetic distinctiveness, are candidates for reclassification as one or more novel genera.


title: Influences of El Niño on assemblages of mesopelagic fish larvae along the Pacific coast of Baja California Sur

text: Seasonal assemblages of mesopelagic fish larvae and changes related with environmental factors (plankton biomass, sea surface temperature anomaly, upwelling, and the multivariate El Niño index) were investigated. From 1982 to 1987, 16 oceanographic cruises were carried out along the Pacific coast of Baja California Sur, Mexico. Larvae of 42 mesopelagic fish taxa were collected. Larval abundance was highly variable during the studied period, but summer months coincided with higher abundance (>200 larvae under 10 m(2)). Larval assemblages were dominated by three of the most common species of tropical (Vinciguerria lucetia, Diogenichthys laternatus) and subtropical affinity (Triphoturus mexicanus). A group of species of tropical affinity (Diplophos proximus, Diaphus pacificus, Benthosema panamense) was useful for distinguishing the 1982–84 El Niño event, and an assemblage of larvae of temperate affinity (Symbolophorus californiensis, Melamphaes lugubris, Bathylagus ochotensis, Leuroglossus stilbius, Protomyctophum crockeri) characterized ‘normal’ years (mid‐1984 to mid‐1987).


title: Land use affects the relationship between species diversity and productivity at the local scale in a semi‐arid steppe ecosystem

text: 1.. The accelerating extinction rate of plant species and its effect on ecosystem functioning is a hotly debated topic in ecological research. Most research projects concerning the relationship between species diversity and productivity have been conducted in artificial plant communities, with only a few in natural ecosystems. In this study we examined the relationship between species diversity and above‐ground net primary productivity (ANPP) over two consecutive growth seasons (2004 and 2005) in a semi‐arid steppe ecosystem of northern China, that were subjected to different land uses. 2.. Land use affected the relationship between species diversity and ANPP in this semi‐arid steppe ecosystem. Exclusion of grazing without or with biomass removal by mowing increased ANPP, species richness and species diversity compared with free grazing; the effect was reflected mainly as enhanced importance of the perennial forbs functional group in terms of their relative contributions to ANPP, plant cover and plant abundance. 3.. Many mechanisms regulate the relationship between species diversity and productivity. Differential effects of anthropogenic activities on biodiversity and ecosystem functioning greatly complicate the analysis of such relationships. On grazing‐exclusion sites the relationship between ANPP and species richness can be best described as an exponential growth function (R (2) = 0·99, P < 0·001, n = 24); whereas on the free‐grazing site the relationship takes the form of exponential decay (R (2) = 0·96, P < 0·001, n = 24). Our study concludes that the mode and severity of disturbance are important factors for interpreting the relationship between species diversity and productivity in semi‐arid steppe ecosystems.


title: Assessment of periradicular microbiota by DNA‐DNA hybridization

text: Abstract – In the present study the “checkerboard” DNA‐DNA hybridization technique was used to identify bacteria in periapical endodontic lesions of asymptomatic teeth. Thirty‐four patients with root‐filled teeth and apical periodontitis were divided into two groups, each containing 17 patients. In Group 1, a marginal incision was performed during surgery to expose the lesion, and in Group 2, a submarginal incision was applied. The gingiva and mucosa were swabbed with an 0.2% chlorhexidine gluconate solution prior to surgery. Bacterial DNA was identified in all samples from the two groups using 40 different whole genomic probes. The mean number (±SD) of species detected was 33.7±3.3 in Group 1 and 21.3±6.3 in Group 2 (P<0.001). The majority of the probe‐detected bacteria were present in more lesions from Group1 than from Group 2. The differences were most notable for Campylobacter gracilis, Porphyromonas endodontalis, Propionibacterium acnes, Capnocytophaga gingivalis, Fusobacterium nucleatum ssp. nucleatum, Fusobacterium nucleatum ssp. polymorphum, Prevotella intermedia, Treponema denticola, Streptococcus constellatus and Actinomyces naeslundii I. Bacterial species such as Actinobacillus actinomycetemcomitans and Bacteroides forsythus were detected in more than 60% of the lesions from both groups. Also, P. endodontalis was abundant in periapical tissue. The data supported the idea that following a marginal incision, bacteria from the periodontal pocket might reach the underlying tissues by surgeon‐released bacteremia. The study provided solid evidence that bacteria invade the periapical tissue of asymptomatic teeth with apical periodontitis. The detection of much more bacteria with the “checkerboard” DNA‐DNA hybridization method than has previously been recovered by anaerobic culture indicated that the endodontic (and periodontal) microfloras should be redefined using molecular methods.


title: Immunogenicity and Efficacy of a Commercial Feline Leukemia Virus Vaccine

text: Twenty young adult specific pathogen‐free cats were randomly divided into two groups of 10 animals each. One group was vaccinated with two doses of feline leukemia virus vaccine according to the manufacturer's recommendations. All 20 cats were challenge exposed oronasally (4 times over a 1‐week period), beginning 3 weeks after immunization, with a virulent subgroup A strain of FeLV (CT600‐FeLV). The severity of the FeLV infection was enhanced by treating the cats with methylprednisolone acetate at the time of the last FeLV exposure. Ten of 10nonvaccinated cats became persistently viremic compared with 0/10 of the vaccinates. ELISA antibodies to whole FeLV were present at high concentrations after immunization in all of the vaccinated cats, and there was no observable anamnestic antibody response after challenge exposure. ELISA antibodies to whole FeLV appeared at low concentrations in the serum of nonvaccinated cats after infection but disappeared as the viremia became permanently established. Virus neutralizing antibodies were detected in 3/10 vaccinates and 0/10 nonvaccinates immediately before FeLV challenge exposure, and in 8/10 vaccinates and 1/10 nonvaccinates 5 weeks later. Although vaccination did not consistently evoke virus neutralizing antibodies, it appeared to immunologically prime cats for a virus‐neutralizing antibody response after infection. Active FeLV infection was detected in bone marrow cells taken 14 weeks after infection from 10/10 nonvaccinates and 0/10 vaccinates. Latent FeLV infection was not detected in bone marrow cells from any of the vaccinated cats 14 weeks after challenge exposure.


title: Monotonicity properties for a ratio of finite many gamma functions

text: In the paper, the authors consider a ratio of finite many gamma functions and find its monotonicity properties such as complete monotonicity, the Bernstein function property, and logarithmically complete monotonicity.


title: Urbanization interferes with the use of amphibians as indicators of ecological integrity of wetlands

text: 1. Wetlands are ecologically and economically important ecosystems but are threatened globally by many forms of human disturbance. Understanding the responses of wetland species to human disturbance is essential for effective wetland management and conservation. 2. We undertook a study to determine (i) whether anurans can be used effectively to assess the ecological integrity of wetlands affected by groundwater withdrawal and, if so, (ii) what effect increasing urbanization might have on the utility of anurans as wetland indicators. We monitored the intensity of anuran calls at 42 wetlands in south‐western Florida throughout 2001–2002 and 2005–2009. 3. We first validated the use of anurans to assess wetland integrity using a small group of wetlands by comparing anuran calling and subsequent tadpole development with an established index employing vegetation composition and structure. We then verified that the results could be expanded to a variety of sites throughout the region. Finally, we focused on urbanized wetlands to determine whether urbanization could interfere with the use of anurans to assess wetland integrity. 4. We used PRESENCE to estimate occupancy and detection probabilities and to examine the relationship between occupancy and five covariates expected to influence individual species occurrence. We used FRAGSTATS to calculate the mean proximity index for urbanized wetlands, which assesses the size and distribution of land use types within a specified area. 5. Our results showed that the group of species including oak toad Anaxyrus quercicus, southern cricket frog Acris gryllus, pinewoods treefrog Hyla femoralis, barking treefrog Hyla gratiosa, and little grass frog Pseudacris ocularis is a reliable indicator of wetland integrity. However, this same group of species, which is sensitive to wetland health, is selectively excluded from urbanized wetlands. 6. Synthesis and applications. Although anurans are effective indicators of wetland health and complement vegetation surveys, the usefulness of this group for monitoring the ecological integrity of wetlands can be substantially reduced, or eliminated, as a consequence of urbanization. We urge for careful consideration of confounding factors in any studies examining the utility of indicator species.


title: Acanthamoeba healyi N. Sp. and the Isoenzyme and Immunoblot Profiles of Acanthamoeba spp., Groups 1 and 3

text: ABSTRACT Two strains of Acanthamoeba isolated from human brain tissue and a strain of Acanthamoeba isolated from a fish were compared with 10 species of Acanthamoeba belonging to groups 1, 2 and 3 based on their isoenzyme profiles and antigenic characteristics. A total of 12 enzymes were studied. The isoenzymes and antigens were electrophoretically separated on polyacrylamide gradient gels, and the patterns obtained were compared after appropriate staining for particular enzymes and reactivities with homologous and heterologous rabbit anti‐Acanthamoeba antisera. One of the human strains (CDC:1283:V013) was identified as A. healyi n. sp. because of its unique isoenzyme profiles for 11 of the 12 enzymes tested. The other human isolate was reidentified as A. culbertsoni because its isoenzyme profiles for 10 of 12 enzymes resembled those of A. culbertsoni, Lilly A‐1 strain. Since the isoenzyme profiles and the antigenic patterns of the fish isolate as well were remarkably similar to those of A. royreba, it was considered as a strain of A. royreba. Polyacrylamide gradient gel electrophoresis appears to be a powerful technique for the study of isoenzymes and antigens of Acanthamoeba.


title: An Ultrastructural Study of Vairimorpha necatrix (Microspora, Microsporida) with Particular Reference to Episporontal Inclusions During Octosporogony

text: ABSTRACT. The life cycle of Vairimorpha necatrix was studied by electron microscopy. Disporous development has two distinct stages: 1) diplokaryotic meronts which are actively mitotic, and 2) diplokaryotic sporonts which are distinguished by reduced ribosome density and a thickened plasmalemma. After final division of the sporont, sporoblasts form spores which are ovocylindrical and measure 4.4 ± 0.08 × 2.3 ± 0.05 μm (mean ± SE). Octosporous development results in eight haploid spores being formed in a sporophorous vesicle. The uninucleate octospores were smaller than the binucleate dispores and the exospore was thicker but less crenulate in outline. Early in octosporogony, tubules are produced from the sporont plasmalemma and electron‐dense material accumulates in the episporontal space. The latter may be amorphous, vesiculated, or vacuolated in appearance and in later stages may take a stacked, lamellar form. At sporoblast formation, exospore material coats the plasmalemma and attached tubules; all inclusions in the episporontal space gradually disappear as spores are formed. These secretory products may have application to taxonomic distinction at the species level.


title: Multiplication of rubella and measles viruses in primary rat neural cell cultures: relevance to a postulated triggering mechanism for multiple sclerosis

text: Rubella virus multiplied to low titre and produced a partial cytopathic effect in rat glial cell cultures. Anti‐galactocerebroside staining showed that this cytopathic effect involved the disintegration of oligodendrocytes. A similar effect was produced following infection of myelinating neural cell cultures with rubella virus, but virus multiplication could not be detected in pure neuron cultures. Measles virus was found to multiply and produce a cytopathic effect in primary cultures of both neurons and glial cells. These results are discussed in relation to the ability of measles and rubella viruses to trigger human multiple sclerosis.


title: Aspects of canine distemper virus and measles virus encephalomyelitis

text: Canine distemper (CD) is a frequently fatal, systemic morbillivirus infection in the dog and other carnivores: encephalomyelitis is the common cause of death. Susceptibility to canine distemper virus (CDV) is now recognized in a wide range of non–domestic animals, most recently in captive lions, tigers and leopards. Furthermore, closely related viruses have produced CD–like diseases in marine mammals. CDV induces an inclusion–body encephalomyelitis in the dog and demyelination is often a conspicuous feature. Myelin injury is associated with the presence of virus but the mechanism of demyelination remains incompletely understood. Oligodendrocyte infection may be defective, as has been shown in vitro. CDV and measles virus (MV) produce similar systemic disorders in their respective hosts but differ markedly in the frequency of central nervous system (CNS) involvement, and in the pathogenesis of the more common neurological sequelae. Both CDV and MV have been considered as multiple sclerosis agents, and the association of CDV with other human disease has been suggested.


Food Insecure and Allergic in a Pandemic: A Vulnerable Population


No Time for Tears


WHO launches crowdfund for COVID-19 response


Probable aircraft transmission of Covid-19 in-flight from the Central African Republic to France


Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 2019) Treatment


COVID-19 cacophony: is there any orchestra conductor?


Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): A multi-center study in Wenzhou city, Zhejiang, China


Applying the ethical principles of resource allocation to drugs in limited supply during a public health crisis


Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement


Anti-Microbial Coating Innovations to prevent infectious disease: a consensus view from the AMiCl COST Action.


Correction to Lancet Glob Health 2020; 8: e452–53


Can #PlayOurpartTogether help prevent miscommunication?


Multiple parameters required for diagnosis of COVID-19 in clinical practice


title: Avian macrophage and immune response: an overview

text: 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.


Letter from the Guest Editors


Editorial comment to Finkelstein et al. – Original reference JPUROL-D-20-00181


Coronavirus Disease 2019 and Educational Engagement


We all need a yellow submarine!


title: A non-static quantum inspired spacetime in f(R) gravity: Gravity's rainbow

text: 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.


Physical activity for immunity protection: Inoculating populations with healthy living medicine in preparation for the next pandemic()


title: Artificial Intelligence (AI) applications for COVID-19 pandemic

text: Abstract 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.


From the editor: Confronting a pandemic or two


Why WHO needs a feminist economic agenda


Whatever happened to universal/standard precautions?


Leadership Evolution: The Academy's Sustained and Growing Contribution


Pandemic school closures: risks and opportunities


Editorial: safe healthcare teams during the coronavirus outbreak


title: Validation of RESP and PRESERVE score for ARDS patients with pumpless extracorporeal lung assist (pECLA)

text: 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.


De-intensification of treatment in human papilloma virus related oropharyngeal carcinoma: Patient choice still matters for de-escalation and for the COVID era


Missed or Delayed Diagnosis of Kawasaki Disease During the 2019 Novel Coronavirus Disease (COVID-19) Pandemic


The Generation of Virtual Defenders


title: The Secretome Profiling of a Pediatric Airway Epithelium Infected with hRSV Identified Aberrant Apical/Basolateral Trafficking and Novel Immune Modulating (CXCL6, CXCL16, CSF3) and Antiviral (CEACAM1) Proteins

text: The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remain poorly understood. To investigate the hRSV-associated apical and basolateral secretomes, a proteomics approach was combined with an ex vivo pediatric human airway epithelial (HAE) model of hRSV infection (data are available via ProteomeXchange and can be accessed at https://www.ebi.ac.uk/pride/ with identifier PXD013661). Following infection, a skewing of apical/basolateral abundance ratios was identified for several individual proteins. Novel modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) were detected in infected, but not in uninfected cultures. Importantly, CXCL6, CXCL16, CSF3 were also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not healthy controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome and was associated with immune modulating proteins (CXCL6, CXCL16, CSF3) never linked with this virus before. In addition, the antiviral activity of CEACAM1 against hRSV had also never been previously characterized. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium.


Maurizio Galderisi. In Memoriam


title: Comparison of ATP Bioluminescence and Aerobic Bacterial Count for Evaluating Surface Cleanliness in an Italian Hospital

text: 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.


title: Analysis of Residual Chemicals on Filtering Facepiece Respirators After Decontamination

text: 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.


title: Health Care Workers’ Mobile Phones: A Potential Cause of Microbial Cross-Contamination Between Hospitals and Community

text: 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.


title: 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

text: 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.


title: A Study Quantifying the Hand-to-Face Contact Rate and Its Potential Application to Predicting Respiratory Tract Infection

text: 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.


title: Discomfort and Exertion Associated with Prolonged Wear of Respiratory Protection in a Health Care Setting

text: 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.


title: ATP as a Marker for Surface Contamination of Biological Origin in Schools and as a Potential Approach to the Measurement of Cleaning Effectiveness

text: 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.


title: Toward Understanding the Risk of Secondary Airborne Infection: Emission of Respirable Pathogens

text: 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.


title: Performance of an N95 Filtering Facepiece Particulate Respirator and a Surgical Mask During Human Breathing: Two Pathways for Particle Penetration

text: 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.


title: St. Corona – eine Fürsprecherin gegen Seuchen?: Eine Miszelle aus der Medizin- und Urologiegeschichte

text: 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.


title: Gold nanoparticles for preparation of antibodies and vaccines against infectious diseases

text: 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.


title: Pathogenic variants in CDC45 on the remaining allele in patients with a chromosome 22q11.2 deletion result in a novel autosomal recessive condition

text: 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.


title: Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids

text: 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.