title: Global Health – emergence, hegemonic trends and biomedical reductionism

text: BACKGROUND: Global Health has increasingly gained international visibility and prominence. First and foremost, the spread of cross-border infectious disease arouses a great deal of media and public interest, just as it drives research priorities of faculty and academic programmes. At the same time, Global Health has become a major area of philanthropic action. Despite the importance it has acquired over the last two decades, the complex collective term “Global Health” still lacks a uniform use today. OBJECTIVES: The objective of this paper is to present the existing definitions of Global Health, and analyse their meaning and implications. The paper emphasises that the term “Global Health” goes beyond the territorial meaning of “global”, connects local and global, and refers to an explicitly political concept. Global Health regards health as a rights-based, universal good; it takes into account social inequalities, power asymmetries, the uneven distribution of resources and governance challenges. Thus, it represents the necessary continuance of Public Health in the face of diverse and ubiquitous global challenges. A growing number of international players, however, focus on public-private partnerships and privatisation and tend to promote biomedical reductionism through predominantly technological solutions. Moreover, the predominant Global Health concept reflects the inherited hegemony of the Global North. It takes insufficient account of the global burden of disease, which is mainly characterised by non-communicable conditions, and the underlying social determinants of health. CONCLUSIONS: Beyond resilience and epidemiological preparedness for preventing cross-border disease threats, Global Health must focus on the social, economic and political determinants of health. Biomedical and technocratic reductionism might be justified in times of acute health crises but entails the risk of selective access to health care. Consistent health-in-all policies are required for ensuring Health for All and sustainably reducing health inequalities within and among countries. Global Health must first and foremost pursue the enforcement of the universal right to health and contribute to overcoming global hegemony.


title: The biodistribution of self-assembling protein nanoparticles shows they are promising vaccine platforms

text: BACKGROUND: Because of the need to limit side-effects, nanoparticles are increasingly being studied as drug-carrying and targeting tools. We have previously reported on a scheme to produce protein-based self-assembling nanoparticles that can act as antigen display platforms. Here we attempted to use the same system for cancer-targeting, making use of a C-terminal bombesin peptide that has high affinity for a receptor known to be overexpressed in certain tumors, as well as an N-terminal polyhistidine tag that can be used for radiolabeling with technetium tricarbonyl. RESULTS: In order to increase circulation time, we experimented with PEGylated and unPEGylated varities typo particle. We also tested the effect of incorporating different numbers of bombesins per nanoparticle. Biophysical characterization determined that all configurations assemble into regular particles with relatively monodisperse size distributions, having peaks of about 33 – 36 nm. The carbonyl method used for labeling produced approximately 80% labeled nanoparticles. In vitro, the nanoparticles showed high binding, both specific and non-specific, to PC-3 prostate cancer cells. In vivo, high uptake was observed for all nanoparticle types in the spleens of CD-1 nu/nu mice, decreasing significantly over the course of 24 hours. High uptake was also observed in the liver, while only low uptake was seen in both the pancreas and a tumor xenograft. CONCLUSIONS: The data suggest that the nanoparticles are non-specifically taken up by the reticuloendothelial system. Low uptake in the pancreas and tumor indicate that there is little or no specific targeting. PEGylation or increasing the amount of bombesins per nanoparticle did not significantly improve targeting. In particular, the uptake in the spleen, which is a primary organ of the immune system, highlights the potential of the nanoparticles as vaccine carriers. Also, the decrease in liver and spleen radioactivity with time implies that the nanoparticles are broken down and cleared. This is an important finding, as it shows that the nanoparticles can be safely used as a vaccine platform without the risk of prolonged side effects. Furthermore, it demonstrates that technetium carbonyl radiolabeling of our protein-based nanoparticles can be used to evaluate their pharmacokinetic properties in vivo.


title: Medical Isolation and Solitary Confinement: Balancing Health and Humanity in US Jails and Prisons During COVID-19

text: In the face of the continually worsening COVID-19 pandemic, jails and prisons have become the greatest vectors of community transmission and are a point of heightened crisis and fear within the global crisis. Critical public health tools to mitigate the spread of COVID-19 are medical isolation and quarantine, but use of these tools is complicated in prisons and jails where decades of overuse of punitive solitary confinement is the norm. This has resulted in advocates denouncing the use of any form of isolation and attorneys litigating to end its use. It is essential to clarify the critical differences between punitive solitary confinement and the ethical use of medical isolation and quarantine during a pandemic. By doing so, then all those invested in stopping the spread of COVID-19 in prisons can work together to integrate medically sound, humane forms of medical isolation and quarantine that follow community standards of care rather than punitive forms of solitary confinement to manage COVID-19.


title: Aurintricarboxylic Acid Is a Potent Inhibitor of Influenza A and B Virus Neuraminidases

text: BACKGROUND: Influenza viruses cause serious infections that can be prevented or treated using vaccines or antiviral agents, respectively. While vaccines are effective, they have a number of limitations, and influenza strains resistant to currently available anti-influenza drugs are increasingly isolated. This necessitates the exploration of novel anti-influenza therapies. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the potential of aurintricarboxylic acid (ATA), a potent inhibitor of nucleic acid processing enzymes, to protect Madin-Darby canine kidney cells from influenza infection. We found, by neutral red assay, that ATA was protective, and by RT-PCR and ELISA, respectively, confirmed that ATA reduced viral replication and release. Furthermore, while pre-treating cells with ATA failed to inhibit viral replication, pre-incubation of virus with ATA effectively reduced viral titers, suggesting that ATA may elicit its inhibitory effects by directly interacting with the virus. Electron microscopy revealed that ATA induced viral aggregation at the cell surface, prompting us to determine if ATA could inhibit neuraminidase. ATA was found to compromise the activities of virus-derived and recombinant neuraminidase. Moreover, an oseltamivir-resistant H1N1 strain with H274Y was also found to be sensitive to ATA. Finally, we observed additive protective value when infected cells were simultaneously treated with ATA and amantadine hydrochloride, an anti-influenza drug that inhibits M2-ion channels of influenza A virus. CONCLUSIONS/SIGNIFICANCE: Collectively, these data suggest that ATA is a potent anti-influenza agent by directly inhibiting the neuraminidase and could be a more effective antiviral compound when used in combination with amantadine hydrochloride.


title: COVID-19 presenting as acute pancreatitis

text: Abstract The ongoing pandemic of Coronavirus disease-2019 (COVID-19) has spread over 200 countries worldwide, affecting >2 million people and >120,000 deaths. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The most common symptoms include cough, shortness of breath, and fever. However, gastrointestinal manifestations of COVID-19 are increasingly being recognized. Herein, we report a case of COVID-19 who presented with acute pancreatitis (AP) without any other risk factors.


The cardiovascular burden of congenital heart disease - not only in times of COVID-19


title: Functional Carbon Quantum Dots as Medical Countermeasures to Human Coronavirus

text: [Image: see text] Therapeutic options for the highly pathogenic human coronavirus (HCoV) infections are urgently needed. Anticoronavirus therapy is however challenging, as coronaviruses are biologically diverse and rapidly mutating. In this work, the antiviral activity of seven different carbon quantum dots (CQDs) for the treatment of human coronavirus HCoV-229E infections was investigated. The first generation of antiviral CQDs was derived from hydrothermal carbonization of ethylenediamine/citric acid as carbon precursors and postmodified with boronic acid ligands. These nanostructures showed a concentration-dependent virus inactivation with an estimated EC(50) of 52 ± 8 μg mL(–1). CQDs derived from 4-aminophenylboronic acid without any further modification resulted in the second-generation of anti-HCoV nanomaterials with an EC(50) lowered to 5.2 ± 0.7 μg mL(–1). The underlying mechanism of action of these CQDs was revealed to be inhibition of HCoV-229E entry that could be due to interaction of the functional groups of the CQDs with HCoV-229E entry receptors; surprisingly, an equally large inhibition activity was observed at the viral replication step.


title: Characterization of canine coronavirus spread among domestic dogs in Vietnam

text: Canine coronavirus (CCoV) is an important pathogen that causes enteritis in dogs, but there is no information on CCoV infection in Vietnam. To examine the prevalence of CCoV infection among Vietnamese dogs, 201 serum samples were analyzed by virus-neutralization (VN) test. The results showed that antibody against CCoV-II was present in 87 dogs (43.3%). To detect genes of CCoV, fecal samples collected from 30 diarrheic and 50 healthy dogs were examinated by RT-PCR, confirming that 2 diarrheic dogs and 5 healthy dogs were positive for CCoV. Nucleotide sequences of N-terminal region of spike (S) gene indicated that CCoV strains were divided into two subgenotypes, CCoV-IIa and -IIb, respectively. Furthemore, we succeeded in isolating CCoV/dog/HCM47/2015, the isolate was plaque-purified three times, and 3’-terminal one-third of the genome was analyzed. Interestingly, the plaque-purified virus had a large deletion in ORF3abc and E genes (1,165 nt), and a short deletion in ORF7b gene (60 nt), suggesting that these regions are not necessary for in vitro replication of CCoV. Next, the antigenicity between the isolated CCoV-IIb and the other CCoV-IIa was compared by VN test, revealing that antigenicty of the isolated CCoV is equal or higher than that of the other CCoV. In summary, two subgenotypes of CCoV-II are spreading among Vietnamese dogs. The isolated virus with a large deletion after in vitro passage may be useful for the development of vaccine, owing to its antigenicity and efficient viral growth in vitro.


title: Psycho-social factors associated with the nationwide lockdown in India during COVID- 19 pandemic

text: OBJECTIVE: To investigate the psycho-social factors associated with COVID-19 and the nationwide lockdown in India. STUDY DESIGN: An online survey was conducted from April 11 through April 16, 2020 in 28 states and 8 union territories (UT) of India. The potential participants were recruited using snowball sampling procedure. METHODS: A cross-sectional online survey was conducted among the people of all states in India. A spatial analysis was performed and Moran's I statistic was applied to investigate the overall clustering of locations. Fisher's exact test was used to investigate associations. GeoDa and R console were used to analyze the data. A total of [Formula: see text] responses were received. RESULTS: Those worried for their family's health were likely to follow the lockdown measures [Formula: see text] Significant association was observed [Formula: see text] between following the lockdown measures and being satisfied with the government strategy to combat the COVID-19 pandemic. A significant relation was observed between the gender (p = 0.001), job profile [Formula: see text] and physical activity [Formula: see text] were observed to be associated with the psycho-social impact. CONCLUSION: Government and public health officials should consider the sentiments of the community while planning strategies relating to the pandemic. The findings of this study will assist the policymakers in emphasizing the psychological well-being of individuals, along with physical health.


title: Early days: genomics and human responses to infection

text: DNA microarray-based gene transcript-profiling of the responses of primates to infection has begun to yield new insights into host–pathogen interactions; this approach, however, remains plagued by challenges and complexities that have yet to be adequately addressed. The rapidly changing nature over time of acute infectious diseases in a host, and the genetic diversity of microbial pathogens present unique problems for the design and interpretation of functional-genomic studies in this field. In addition, there are the more common problems related to heterogeneity within clinical samples, the complex, non-standardized confounding variables associated with human subjects and the complexities posed by the analysis and validation of highly parallel data. Whereas various approaches have been developed to address each of these issues, there are significant limitations that remain to be overcome. The resolution of these problems should lead to a better understanding of the dialogue between the host and pathogen.


Impacto de la pandemia COVID-19 en los Laboratorios de Función Pulmonar: consideraciones sobre el "hoy" y el "día después"


title: New product prompts name change for US Global Aerospace

text: Abstract US Global Aerospace Inc has introduced a range of virus and pathogen filters for aircraft environmental control systems (ECSs) and heating, ventilation and air conditioning (HVAC) systems for hospitals and buildings. With the ability to capture particulates down to 0.05 μm, the company will be targeting the product line at an air industry increasingly concerned about viruses such as severe acute respiratory syndrome (SARS). This is a short news story only. Visit www.filtsep.com for the latest filtration industry news.


title: Surgery in times of COVID-19—recommendations for hospital and patient management

text: BACKGROUND: The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeons have had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards. PURPOSE: To provide a detailed set of guidelines developed in a surgical ward at University Hospital Wuerzburg to safely accommodate the exponentially rising cases of SARS-CoV-2 infected patients without compromising the care of emergency surgery and oncological patients or jeopardizing the well-being of hospital staff. CONCLUSIONS: The dynamic prioritization of SARS-CoV-2 infected and surgical patient groups is key to preserving life while maintaining high surgical standards. Strictly segregating patient groups in emergency rooms, non-intensive care wards and operating areas prevents viral spread while adequately training and carefully selecting hospital staff allow them to confidently and successfully undertake their respective clinical duties.


title: Insights into virus capsid assembly from non‐covalent mass spectrometry

text: The assembly of viral proteins into a range of macromolecular complexes of strictly defined architecture is one of Nature's wonders. Unraveling the details of these complex structures and the associated self‐assembly pathways that lead to their efficient and precise construction will play an important role in the development of anti‐viral therapeutics. It will also be important in bio‐nanotechnology where there is a plethora of applications for such well‐defined macromolecular complexes, including cell‐specific drug delivery and as substrates for the formation of novel materials with unique electrical and magnetic properties. Mass spectrometry has the ability not only to measure masses accurately but also to provide vital details regarding the composition and stoichiometry of intact, non‐covalently bound macromolecular complexes under near‐physiological conditions. It is thus ideal for exploring the assembly and function of viruses. Over the past decade or so, significant advances have been made in this field, and these advances are summarized in this review, which covers the literature up to the end of 2007. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 27: 575–595, 2008


title: Management of the SARS-CoV-2 (Covid 19) coronavirus epidemic in hemodialysis units

text: Summary The current outbreak of SARS-CoV-2 represents a special risk for renal patients due to their comorbidities and advanced age. The usual performance of hemodialysis treatment s in collective rooms increases the risk. The specific information at this time in this regard is very limited. This manuscript includes a proposal for action to prevent infection in the N ephrology S ervices, and in particular in H emodialysis U nits, with the objective of early identification of patients who meet the definition of a suspected case of infection by SARS-CoV-2 and propose circuits and mechanisms to carry out hemodialysis treatment s. They are recommendations in continuous review and can be modified if the epidemiological situation, the diagnostic and therapeutic options so require.


title: Committed to Health: Key Factors to Improve Users’ Online Engagement through Facebook

text: Health organizations, continuously exposed to public scrutiny due to the social relevance of the services provided, have adopted social media to disseminate information about health but also about themselves, and thus, reducing uncertainty and improving communication. In this context, users’ participation in social media has become one of the main indicators of their effectiveness, highlighting the importance of analyzing which factors enhance online engagement. This research extends the number of variables identified in prior studies and analyzes 19,817 Facebook posts from 126 health organizations. Using multivariate linear regression, explanatory results show that economic and organizational attributes, and factors related to the social media posts, both contribute significantly to explain the engagement reached in social media by those organizations. According to our findings, health organizations are not taking enough advantage of social media to engage with their current and potential users. The dissemination of relevant information using visually attractive formats could help draw the attention of consumers, both to reach a higher commitment with the organization and to create value for society.


title: Bovine coronavirus in Uruguay: genetic diversity, risk factors and transboundary introductions from neighboring countries

text: Bovine coronavirus (BCoV) is a recognized cause of severe neonatal calf diarrhea, with a negative impact on animal welfare, leading to economic losses to the livestock industry. Cattle production is one of the most important economic sectors in Uruguay. The aim of this study was to determine the frequency of BCoV infections and their genetic diversity in Uruguayan calves and to describe the evolutionary history of the virus in South America. The overall detection rate of BCoV in Uruguay was 7.8% (64/824): 7.7% (60/782) in dairy cattle and 9.5% (4/42) in beef cattle. The detection rate of BCoV in samples from deceased and live calves was 10.0% (6/60) and 7.6% (58/763), respectively. Interestingly, there was a lower frequency of BCoV detection in calves born to vaccinated dams (3.3%, 8/240) than in calves born to unvaccinated dams (12.2%, 32/263) (OR: 4.02, 95%CI: 1.81–8.90; p = 0.00026). The frequency of BCoV detection was higher in colder months (11.8%, 44/373) than in warmer months (1.5%, 3/206) (OR: 9.05, 95%CI: 2.77–29.53, p = 0.000013). Uruguayan strains grouped together in two different lineages: one with Argentinean strains and the other with Brazilian strains. Both BCoV lineages were estimated to have entered Uruguay in 2013: one of them from Brazil (95%HPD interval: 2011–2014) and the other from Argentina (95%HPD interval: 2010–2014). The lineages differed by four amino acid changes, and both were divergent from the Mebus reference strain. Surveillance should be maintained to detect possible emerging strains that can clearly diverge at the antigenic level from vaccine strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04384-w) contains supplementary material, which is available to authorized users.


title: Universal laboratory testing for SARS-CoV-2 in hyperacute stroke during the COVID-19 pandemic

text: OBJECTIVE: Stroke patients are thought to be at increased risk of Coronavirus Disease 2019 (COVID-19). To evaluate yield of universal laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute stroke patients and its impact on hyperacute stroke care. METHODS: Between weeks 14 and 18 in 2020, a protected code stroke protocol including infection control screening and laboratory testing for SARS-CoV-2 was prospectively implemented for all code stroke patients upon arrival to the emergency department. If infection control screen was positive, patients received protective hygienic measures and laboratory test results were available within four hours from testing. In patients with negative screen, laboratory results were available no later than the next working day. Door-to-imaging times of patients treated with thrombolysis or thrombectomy were compared with those of patients treated during the preceding weeks 1 to 13 in 2020. RESULTS: During the 4-weeks study period, 116 consecutive code stroke patients underwent infection control screen and laboratory testing for SARS-CoV-2. Among 5 (4.3%) patients whose infection control screen was positive, no patient was tested positive for SARS-CoV-2. All patients with negative infection control screens had negative test results. Door-to-imaging times of patients treated with thrombolysis and/or thrombectomy were not different to those treated during the preceding weeks (12 [9-15] min versus 13 [11-17] min, p=0.24). CONCLUSIONS: Universal laboratory testing for SARS-CoV-2 provided useful information on patients’ infection status and its implementation into a protected code stroke protocol did not adversely affect hyperacute stroke care.


title: London 2012 Olympic and Paralympic Games: public health surveillance and epidemiology

text: Summary Mass gatherings are regarded as potential risks for transmission of infectious diseases, and might compromise the health system of countries in which they are hosted. The evidence for increased transmission of infectious diseases at international sporting mass gatherings that attract many visitors from all over the world is not clear, and the evidence base for public health surveillance, epidemiology, and response at events such as the Olympics is small. However, infectious diseases are a recognised risk, and public health planning is, and should remain, a crucial part of the overall planning of sporting events. In this Series paper, we set out the planning and the surveillance systems that were used to monitor public health risks during the London 2012 Olympic and Paralympic Games in the summer of 2012, and draw attention to the public health issues—infectious diseases and chemical, radiation, and environmental hazards—that arose. Although the absolute risk of health-protection problems, including infectious diseases, at sporting mass gatherings is small, the need for reassurance of the absence of problems is higher than has previously been considered; this could challenge conventional public health surveillance systems. Recognition of the limitations of health-surveillance systems needs to be part of the planning for future sporting events.


Coronavirus disease 2019: Mehr Sicherheit durch kompakte Fakten und Handlungsempfehlungen


title: The utility of native MS for understanding the mechanism of action of repurposed therapeutics in COVID-19: heparin as a disruptor of the SARS-CoV-2 interaction with its host cell receptor

text: The emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over six million cases and nearly four hundred thousand deaths reported world-wide by the end of May 2020. A rush to find the cures prompted re-evaluation of a range of existing therapeutics vis-à-vis their potential role in treating COVID-19, placing a premium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in supporting the mechanistic studies of drug/therapeutic target interactions, but its applications remain limited in the cases that involve systems with a high level of structural heterogeneity. Both SARS-CoV-2 spike protein (S-protein), a critical element of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, making them challenging targets for native MS. However, supplementing native MS with a gas-phase ion manipulation technique (limited charge reduction) allows meaningful information to be obtained on the non-covalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. Using this technique in combination with molecular modeling also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. Both short (pentasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with RBD, indicating the presence of a single binding site. This association alters the protein conformation (to maximize the contiguous patch of the positive charge on the RBD surface), resulting in a notable decrease of its ability to associate with ACE2. The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-pI ACE2 and the heparin segments not accommodated on the RBD surface. In addition to providing important mechanistic information on attenuation of the ACE2/RBD association by heparin, the study demonstrates the yet untapped potential of native MS coupled to gas-phase ion chemistry as a means of facilitating rational repurposing of the existing medicines for treating COVID-19.


title: Protocol for a randomized controlled trial comparing wound COmplications in elective midline laparotomies after FAscia Closure using two different Techniques Of Running sutures: COFACTOR trial

text: BACKGROUND: Wound complications following midline laparotomies are common and the main source of postoperative morbidity including superficial or deep wound infection, skin dehiscence, fascia dehiscence, and incisional hernia. Abdominal closure complications are strongly associated with suture technique and material, in addition to other factors related to the patient and type of surgery performed. The traditional technique is to place the fascia sutures 1 cm apart and at least 1 cm away from the fascia edge. A Swedish study described a new technique of placing the sutures 5 mm apart and 5 mm away from the fascia edge, resulting in lower rates of abdominal wound complications. This study has a number of limitations. There is a need for improved quality evidence to convince the surgical community to change the closure technique of abdominal wounds aiming to reduce morbidity, which is exemplified in incisional hernias and other various postop complications. METHODS: This is a 1:1 randomized, controlled, patient- and assessor-blinded, parallel design, superiority trial, with a primary endpoint of incisional hernia at 1 year. The study will be conducted at AUBMC over a 3-year period. Patients planned for a non-emergent midline laparotomy for general surgery or vascular procedure will be randomized to either fascia closure technique. In order to detect a drop of 12% in the incidence of incisional hernia, with 80% power and an alpha of 0.05, we will need to recruit 114 patients per arm. After adjusting for loss to follow-up, target recruitment is 274 subjects. We will compare both arms for the primary, secondary, and exploratory outcomes, using chi-square or t test as appropriate. Univariate and multivariate logistic regression will be done. DISCUSSION: This trial will assess postop complications following abdominal midline wound closures via two different suturing techniques. This trial will generate evidence-based conclusions that will allow surgeons to assess the role of a new abdominal closure technique in decreasing short- and long-term postoperative complications, for a commonly performed procedure. TRIAL REGISTRATION: ClinicalTrials.gov NCT03527433. Registered on 17 May 2018 before starting participant enrollment.


title: Exacerbations de l’asthme et identification virale associée à celle du Chlamydiae pneumoniae et du Mycoplasma pneumoniae : épidémiologie comparative entre nourrissons et enfants âgés de plus de deux ans

text: Résumé Objectifs. – L’utilisation des nouvelles techniques d’identification par les méthodes moléculaires apporte de nouvelles données épidémiologiques. Patients et méthodes. – Cent dix-huit aspirations nasales pratiquées chez des enfants hospitalisés pour une exacerbation aiguë d’asthme ont été colligées. Les techniques conventionnelles ont associé la culture virale et l’immunofluorescence et les techniques moléculaires une polymerase chain reaction (PCR). Résultats. – L’utilisation des techniques conventionnelles a mis en évidence un virus dans 34 % des prélèvements respiratoires (40 cas sur 118), tandis que l’étude par PCR permet une identification positive sur 68 % des prélèvements (80 cas sur 118) et l’association des deux méthodes amène la positivité à 77 % (91 cas sur 118). Les co-infections ont concerné 23 % des prélèvements positifs. L’identification virale par les outils traditionnels est significativement plus fréquente chez les jeunes asthmatiques, ainsi que lors de l’utilisation des outils de biologie moléculaire de façon non significative. L’épidémiologie comparative retrouve la prépondérance dans les deux groupes d’âge du rhinovirus (45 %), puis du virus respiratoire syncytial (28 %) et de l’entérovirus (8,5 %). Chez les enfants âgés de moins de deux ans, rhinovirus et virus respiratoire syncytial ont une prévalence proche (42 et 36 % respectivement) sensiblement différente de celle des enfants âgés de plus de deux ans (66 et 27 % respectivement). L’identification par PCR de Chlamydia pneumoniae et de Mycoplasma pneumoniae reste rare (six cas sur 118 prélèvements). Conclusion. – La prééminence du rhinovirus et du virus respiratoire syncytial est retrouvée lors des exacerbations d’asthme chez le nourrisson tandis que C. pneumoniae et M. pneumoniae ne semblent pas particulièrement impliqués. L’identification est plus forte chez les jeunes asthmatiques avec probablement une charge virale plus importante, car la positivité de la culture virale est plus fréquente chez les enfants âgés de moins de deux ans. Abstract Purpose.– Molecular processes can have a different impact on epidemiological data. Patients and methods. – The study covers 118 nasal aspirate samples taken on children hospitalized for acute asthma exacerbation for 2 years. Conventional techniques associated viral culture and immunofluorescence while molecular techniques used polymerase chain reaction (PCR). Results. – Virus presence was revealed with conventional techniques in 34% of the respiratory samples (40/118), while PCR study of viruses and genomes of Chlamydia pneumoniae and Mycoplasma pneumoniae allowed positive identification in 68% of the samples (80/118). The combination of both techniques allowed identification of an infectious agent in 77% of cases (91/118). More than one pathogenic agent was isolated in 23% of positive samples. Epidemiological study shows prevalence of rhinovirus (45%), then respiratory syncytial virus (28%) and enterovirus (8.5%). In children under 2 years of age, rhinovirus and respiratory syncytial virus have a close prevalence (respectively 42 and 36%), which is not the same result as in older children (respectively 66 and 27%). Moreover, PCR techniques allowed the identification of just a few Chlamydia pneumoniae and Mycoplasma pneumoniae (6/118). Conclusion. – In this study, molecular techniques of identification demonstrate a clear advantage in sensitivity compared to performances of viral cultures or immunofluorescence. The importance of rhinovirus and respiratory syncytial virus is remarkable while Chlamydia pneumoniae an Mycoplasma pneumoniae do not seem to be particularly involved.


title: Reducing overdose after release from incarceration (ROAR): study protocol for an intervention to reduce risk of fatal and non-fatal opioid overdose among women after release from prison

text: BACKGROUND: Drug overdose is the leading cause of death after release from prison, and this risk is significantly higher among women compared to men. Within the first 2 weeks after release, the risk of death from drug overdose is 12.7 times higher than the general population, with risk of death further elevated among females. Although female inmates have higher rates of opioid use disorder and post-release overdose fatality, justice-involved women are under-represented in studies of medications for opioid use disorder. The Reducing Overdose After Release from Incarceration (ROAR) pilot intervention and evaluation (recruitment June 2019 through December 2020) aims to reduce opioid overdose among women released to the community following incarceration in state prison. The evaluation further assesses induction, acceptance and effectiveness of extended release naltrexone in a female post-prison population. METHODS/DESIGN: In the week prior to their release, female adults in custody with moderate to severe opioid use disorder start treatment with extended release naltrexone, an injectable opioid antagonist that blocks the effects of opioids for up to 1 month. All ROAR participants receive training to use naloxone rescue kits and are provided nasal naloxone at release. Ongoing support from a certified recovery mentor to facilitate sustained engagement with treatment for substance use disorders begins in the month prior to release from prison and continues for 6 months in community. We evaluate the association between ROAR participation and the primary outcome of opioid overdose. Using administrative data provided by the Oregon Department of Corrections and the Oregon Health Authority, we compare the odds of overdose among ROAR participants versus a comparison group of females released from prison during the study period. Evaluation activities in community includes survey and qualitative interviews for 6 months post release, as well as a review of clinic records to assess retention on medication among the pilot cohort (N = 100). DISCUSSION: ROAR is a collaboration between Oregon’s public health, criminal justice, and medical communities. The ROAR intervention and evaluation provide critical information on improving interventions to prevent opioid overdose and improve retention on treatment in community in an overlooked, high-risk population: incarcerated women re-entering the community. TRIAL REGISTRATION: Clinical Trials.gov TRN: NCT03902821.


title: Bartonella spp. in Bats, Kenya

text: We report the presence and diversity of Bartonella spp. in bats of 13 insectivorous and frugivorous species collected from various locations across Kenya. Bartonella isolates were obtained from 23 Eidolon helvum, 22 Rousettus aegyptiacus, 4 Coleura afra, 7 Triaenops persicus, 1 Hipposideros commersoni, and 49 Miniopterus spp. bats. Sequence analysis of the citrate synthase gene from the obtained isolates showed a wide assortment of Bartonella strains. Phylogenetically, isolates clustered in specific host bat species. All isolates from R. aegyptiacus, C. afra, and T. persicus bats clustered in separate monophyletic groups. In contrast, E. helvum and Miniopterus spp. bats harbored strains that clustered in several groups. Further investigation is needed to determine whether these agents are responsible for human illnesses in the region.


title: Health anxiety, cyberchondria, and coping in the current COVID-19 pandemic: Which factors are related to coronavirus anxiety?

text: According to cognitive-behavioral models, traits, triggering events, cognitions, and adverse behaviors play a pivotal role in the development and maintenance of health anxiety. During virus outbreaks, anxiety is widespread. However, the role of trait health anxiety, cyberchondria, and coping in the context of virus anxiety during the current COVID-19 pandemic has not yet been studied. An online survey was conducted in the German general population (N = 1,615, 79.8% female, M(age) = 33.36 years, SD = 13.18) in mid-March 2020, which included questionnaires on anxiety associated with SARS-CoV-2, trait health anxiety, cyberchondria(Pandemic) (i.e. excessive online information search), and emotion regulation. The participants reported a significantly increasing virus anxiety in recent months (previous months recorded retrospectively), especially among individuals with heightened trait health anxiety. Cyberchondria(Pandemic) showed positive correlations with current virus anxiety (r = .09 – .48), and this relationship was additionally moderated by trait health anxiety. A negative correlation was found between the perception of being informed about the pandemic and the current virus anxiety (r=-.18), with adaptive emotion regulation being a significant moderator for this relationship. The findings suggest that trait health anxiety and cyberchondria serve as risk factors, whereas information about the pandemic and adaptive emotion regulation might represent buffering factors for anxiety during a virus pandemic.


title: Correction: Serological Evidence of MERS-CoV Antibodies in Dromedary Camels (Camelus dromedaries) in Laikipia County, Kenya

text: [This corrects the article DOI: 10.1371/journal.pone.0140125.].


title: Predicting the Potential Role of Non-human Hosts in Zika Virus Maintenance

text: Arboviruses are often maintained in complex cycles involving vertebrates such as mammals or birds and blood-feeding mosquitoes. However, the role of wildlife hosts in their emergence or re-emergence in human populations has received little attention. The recent emergence of Zika virus in America, and previous occurrences of chikungunya and dengue, forces us to confront a potential new disease-emergence phenomenon. Using a spatial data mining framework to identify potential biotic interactions, based on the degree of co-occurrence between different species, we identified those mammal species with the highest potential for establishing mammal–vector interactions, considering as principal vector Aedes aegypti. Seven of the top ten identified mammal species with highest potential were bats, with two of them having previously been confirmed as positive hosts for dengue in Mexico. We hope that this will raise interest of Mexican public health authorities and academic institutions to assess the role of wild hosts in the maintenance and spread of arboviruses.


title: Stress and burnout in health care workers during COVID-19 pandemic: validation of a questionnaire

text: AIM: To validate a questionnaire to assess stress and burnout in healthcare workers during COVID-19 pandemic. SUBJECTS AND METHODS: In this study, content validity, Cronbach’s alpha, and test–retest reliability method were utilized among 60 HCWs to evaluate the validity, internal consistency, and reliability of the questionnaire respectively. The final questionnaire was composed of four parts asking for the background information, questions about the stress caused by the COVID-19, the Depression, Anxiety and Stress Scale - 21 (DASS-21), and six questions from the Copenhagen Burnout Inventory (CBI). RESULTS: The CVR of 46 questions was equal to 1, making them acceptably valid (CVR > 0.78), so that the items could be arranged into a final questionnaire. Moreover, all items could successfully attain CVI values above 0.79, confirming the content validity of the questionnaire. The Cronbach’s alpha was between 0.80–0.95 for different sections of questionaire, confirming the stable reliability and high repeatability of the questionnaire. CONCLUSION: The results of this study showed that the DASS-21 offers adequate levels of validity and reliability for assessing the stress, anxiety, and depression among the HCWs engaged with the COVID-19 pandemic. Moreover, the six items adapted from the Copenhagen burnout inventory (CBI) were found to provide a good instrument for investigating the job burnout among the HCWs at Masih Daneshvari Hospital during the outbreak of the COVID-19 epidemic.


title: Understanding the canine intestinal microbiota and its modification by pro‐, pre‐ and synbiotics – what is the evidence?

text: Interest in the composition of the intestinal microbiota and possibilities of its therapeutic modifications has soared over the last decade and more detailed knowledge specific to the canine microbiota at different mucosal sites including the gut is available. Probiotics, prebiotics or their combination (synbiotics) are a way of modifying the intestinal microbiota and exert effects on the host immune response. Probiotics are proposed to exert their beneficial effects through various pathways, for example production of antimicrobial peptides, enhancing growth of favourable endogenous microorganisms, competition for epithelial colonisation sites and immune‐modulatory functions. Despite widespread use of pro‐, pre‐ and synbiotics, scientific evidence of their beneficial effects in different conditions of the dog is scarce. Specific effects of different strains, their combination or their potential side‐effects have not been evaluated sufficiently. In some instances, in vitro results have been promising, but could not be transferred consistently into in vivo situations. Specific canine gastrointestinal (GI) diseases or conditions where probiotics would be beneficial, their most appropriate dosage and application have not been assessed extensively. This review summarises the current knowledge of the intestinal microbiome composition in the dog and evaluates the evidence for probiotic use in canine GI diseases to date. It wishes to provide veterinarians with evidence‐based information on when and why these products could be useful in preventing or treating canine GI conditions. It also outlines knowledge about safety and approval of commercial probiotic products, and the potential use of faecal microbial transplantation, as they are related to the topic of probiotic usage.


Caring for people with heart failure and many other medical problems through and beyond the COVID‐19 pandemic: the advantages of universal access to home telemonitoring


Necessity is the mother of innovation–the time to collaborate is now


COVID-19 y Piel


title: Assessment of Coronavirus Disease 2019 Community Containment Strategies in Shenzhen, China

text: IMPORTANCE: A new outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 in Wuhan, China, is spreading rapidly around the globe. Limited information on control in community settings is available. OBJECTIVE: To detail measures enacted within a community to prevent the spread of coronavirus disease 2019 (COVID-19) and to evaluate the spread of COVID-19 associated with implementation of the program. DESIGN, SETTING, AND PARTICIPANTS: This case series study details the implementation of prevention measures in a specific community setting among community-dwelling individuals exposed to or at risk of COVID-19 in Haiyu, Shenzhen, China, from January 23 to April 10, 2020. EXPOSURES: Community containment strategies for tracking, quarantine, and management were strictly, cooperatively, and effectively implemented by a team that included a general practitioner, a community manager, and public safety bureau officials. MAIN OUTCOMES AND MEASURES: Number of locally acquired cases with indirect links to confirmed COVID-19 cases. Diagnosis with COVID-19 was confirmed when throat swab samples tested positive for severe acute respiratory syndrome coronavirus 2 on reverse transcription–polymerase chain reaction. RESULTS: Approximately 34 686 individuals live in Haiyu, including 2382 residents aged 65 years or older. Seven individuals with COVID-19 acquired outside the community (age, 20-70 years; 3 [42%] women) were moved from quarantine to a hospital for standard isolation treatment. A total of 20 people who were asymptomatic and who had had direct contact with these individuals were closely observed by health care workers at a nearby hotel. Additionally, 800 individuals considered to be at higher risk were moved from quarantine to home isolation for 14 days. There were no locally acquired cases of COVID-19 with indirect links reported in the Haiyu community from the time that the study began on January 23, 2020, to April 10, 2020. CONCLUSIONS AND RELEVANCE: These findings suggest that cooperation among the authorities of multiple sectors allowed for the implementation of preventive measures that were associated with limited community transmission.


title: Molecular targets for COVID-19 drug development: Enlightening Nigerians about the pandemic and future treatment

text: There is little or no research initiated on enlightening Nigerians about the pathogenesis, targets for drug development, and drug repositioning for SARS-CoV-2 infection. COVID-19 is a viral infection causing symptoms like dry cough, sore throat, nasal congestion, tiredness, fever, loss of taste and smell etc. Th disease was first reported in Wuhan, China, in December 2019. The infection is caused by SARS-CoV-2, which is the third introduction of a highly pathogenic coronavirus into the human population. Coronaviruses are viruses with a positive RNA envelope assigned to α, β, γ, and δ genera. Moreover, SARS-CoV-2 belongs to the β genus. The four structural proteins of β coronavirus are membrane (M), envelope (E), spike (S), and nucleocapsid (N) protein, mediation of coronavirus host infection is established by spike (S) protein. Therefore, the search for drug development targets and repositioning of existing therapeutics is essential for fighting the present pandemic. It was reviewed that therapeutics targeting SARS-CoV-2 binding to ACE2 receptor, viral RNA synthesis and replication, 3CLpro, RdRp, and helicase will play a crucial role in the development of treatment for SARS-CoV-2 infection. Furthermore, the RdRp and spike protein of SARS-CoV-2 are the most promising targets for drug development and repositioning and vaccine development. Remdesivir combination with chloroquine/hydroxychloroquine are promising drug repositioning for the treatment of COVID-19, and mRNA-1273 targeting spike protein is the promising vaccine. However, as patient management and drug repositioning are taking place, it is imperative to identify other promising targets used by SARS-CoV-2 to establish infection, to develop novel therapeutics.


title: Infection control management of patients with suspected highly infectious diseases in emergency departments: data from a survey in 41 facilities in 14 European countries

text: BACKGROUND: In Emergency and Medical Admission Departments (EDs and MADs), prompt recognition and appropriate infection control management of patients with Highly Infectious Diseases (HIDs, e.g. Viral Hemorrhagic Fevers and SARS) are fundamental for avoiding nosocomial outbreaks. METHODS: The EuroNHID (European Network for Highly Infectious Diseases) project collected data from 41 EDs and MADs in 14 European countries, located in the same facility as a national/regional referral centre for HIDs, using specifically developed checklists, during on-site visits from February to November 2009. RESULTS: Isolation rooms were available in 34 facilities (82,9%): these rooms had anteroom in 19, dedicated entrance in 15, negative pressure in 17, and HEPA filtration of exhausting air in 12. Only 6 centres (14,6%) had isolation rooms with all characteristics. Personnel trained for the recognition of HIDs was available in 24 facilities; management protocols for HIDs were available in 35. CONCLUSIONS: Preparedness level for the safe and appropriate management of HIDs is partially adequate in the surveyed EDs and MADs.


title: Zika virus: An overview

text: The Zika virus has been in the news for quite some time due to the ongoing recent outbreak in the Southern America, which started in December 2015. It has been declared a public health emergency by the World Health Organization in February 2016 owing to its association with the congenital deformities, particularly microcephaly in infants borne to the infected mothers. The rapid spread of the virus throughout the United States of America and subsequently to Asia has raised serious international concerns. Its spread to countries neighboring India is a serious threat to the Indian population. This review article gives an overview about the virus, its diagnosis, clinical features, and the management.


title: Actual Concepts in Rhinosinusitis: A Review of Clinical Presentations, Inflammatory Pathways, Cytokine Profiles, Remodeling, and Management

text: Rhinosinusitis (RS) is a heterogeneous group of diseases. It is a significant and increasing health problem that affects about 15% of the population in Western countries. It has a substantial impact on patients’ health-related quality of life and daily functioning and represents a huge financial burden to society and the health care system as a result of the direct and indirect costs. In addition, RS is not well-understood, and little is known about the etiology and pathophysiology. In the past decade, many papers have been published that have changed our understanding of RS. RS is commonly classified into acute and chronic RS based on symptom duration. In acute RS, an inflammatory reaction initiated by a viral infection characterizes most uncomplicated, mild to moderate cases. Therefore, the first line of treatment for these cases are intranasal steroids and not antibiotics. In severe and complicated cases, antibiotics combined with topical steroids remain the treatment of choice. On the other hand, chronic RS is actually subdivided into two distinct entities (chronic rhinosinusitis with and without polyps), as growing evidence indicates that these entities have specific inflammatory pathways and cytokine profiles. The authors review recent data regarding the clinical presentations, cytokine profiles, tissue remodeling, and modalities of treatment for each form of RS.


title: Safety and efficacy of attenuated classic and variant 2 infectious bronchitis virus candidate vaccines

text: Vaccination programs against infectious bronchitis virus (IBV) in Egypt depend on both classical and/or imported variant IBV strain vaccines. However, many IBV outbreaks associated with respiratory distress, nephropathy, and high mortalities were attributed to the circulation of both classical and new nephropathogenic IBV variant 2 strains. In the present study, we report the development of attenuated IBV candidate vaccines using the classic IBV strains (IBM41 and IB2) and a nephropathogenic strain (IBvar2). The wild-type (WT) viruses were attenuated through serial passages in embryonated specific pathogen free (SPF) chicken eggs. Virulence of the attenuated viruses was then tested via the ocular route inoculation and the in vivo back passage in day-old SPF chickens. Efficacy against homologous challenge was investigated also in day-old SPF chickens. Results showed that the viruses were successfully adapted to the embryo by the 100th (IBM41 and IB2) and 110th passages (IBvar2). The attenuated viruses were safe and showed no change of virulence in day-old SPF chickens up to the 10th back passages. The efficacy experiment showed that the attenuated vaccines showed 90 to 100% protection against the homologous challenge based on ciliostasis score and protection percent. The att-IBM41 and att-IB2 vaccines were able to reduce the shedding of the challenge at 3 days post-infection (DPI) and no virus shedding was detected in both vaccinated groups by 5 DPI. In the att-IBvar2 vaccinated birds, only 20% of vaccinated birds shed the challenge virus with low titers (10(2.10±0.3) EID(50)/mL) at 3 DPI. In conclusion, the attenuated strains IBM41, IB2, and IBvar2 are efficient vaccine candidates against currently circulating classic and variant IB viruses, respectively. Further studies to evaluate the field efficacy and combining these attenuated IBV strains to induce a wider protection against heterologous IBV challenge are suggested.


title: Chitinase 3‐like 1 protein plays a critical role in respiratory syncytial virus‐induced airway inflammation

text: BACKGROUND: Chitinase 3‐like 1 protein (CHI3L1) (YKL‐40 in humans and breast regression protein [BRP]‐39 in mice) is required for optimal allergen sensitization and Th2 inflammation in various chronic inflammatory diseases including asthma. However, the role of CHI3L1 in airway inflammation induced by respiratory viruses has not been investigated. The aim of this study was to investigate the relationship between CHI3L1 and airway inflammation caused by respiratory syncytial virus (RSV) infection. METHODS: We measured YKL‐40 levels in human nasopharyngeal aspirate (NPA) from hospitalized children presenting with acute respiratory symptoms. Wild‐type (WT) and BRP‐39 knockout (KO) C57BL/6 mice were inoculated with live RSV (A2 strain). Bronchoalveolar lavage fluid and lung tissue samples were obtained on day 7 after inoculation to assess lung inflammation, airway reactivity, and expression of cytokines and BRP‐39. RESULTS: In human subjects, YKL‐40 and IL‐13 levels in NPA were higher in children with RSV infection than in control subjects. Expression of BRP‐39 and Th2 cytokines, IL‐13 in particular, was increased following RSV infection in mice. Airway inflammation caused by RSV infection was reduced in BRP‐39 KO mice as compared to WT mice. Th2 cytokine levels were not increased in the lungs of RSV‐infected BRP‐39 KO mice. BRP‐39 regulated M2 macrophage activation in RSV‐infected mice. Additionally, treatment with anti‐CHI3L1 antibody attenuated airway inflammation and Th2 cytokine production in RSV‐infected WT mice. CONCLUSION: These findings suggest that CHI3L1 could contribute to airway inflammation induced by RSV infection. CHI3L1 could be a potential therapeutic candidate for attenuating Th2‐associated immunopathology during RSV infection.


title: Essentials of infection prevention in the pediatric population

text: Application of infection prevention and control (IP&C) measures is synonymous with safety, quality, resource saving, and the rights of all patients, staff and visitors. An extensive literature review was undertaken to identify key IP&C measures that address pediatric-specific requirements, taking into account age-related factors, diseases that occur most frequently among pediatric populations, and the important role of the caregiver in prevention and disease transmission. IP&C initiatives that target and incorporate both human (intrinsic) and environmental (extrinsic) sources of infection are population specific and guide practices and provide safe caring environments when used appropriately. Categories of care specifically geared to the pediatric age-group (0–14 years) are divided into two categories: within-the-healthcare system and outside-of-the-healthcare setting. By taking into account the child's developmental age; physiological, psycho-social and immunological development; differing impacts on the body's natural defense mechanisms, including procedural, device type and length of utilization; and availability of specific technologies and disciplines, the caregiver IP&C strategies can be developed and tailored to address specific needs. Within-the-healthcare setting strategies focus on surveillance, standard and transmission-based precautions, the immune system, age-related factors, institutional regulations, the family and visitation. Outside the healthcare setting preventative and protective measures are vital for providing maximum and comprehensive care. Care provided within and outside the healthcare setting can either be independent of each other or work together to maximize the health and safety of the child. This review article highlights the importance of IP&C knowledge, need for strict adherence to approved standards, and need for auditing compliance to achieve the ultimate goal of providing safe, quality care as well as an infection-free environment.


title: The many paths to frameshifting: kinetic modelling and analysis of the effects of different elongation steps on programmed –1 ribosomal frameshifting

text: Several important viruses including the human immunodeficiency virus type 1 (HIV-1) and the SARS-associated Coronavirus (SARS-CoV) employ programmed −1 ribosomal frameshifting (PRF) for their protein expression. Here, a kinetic framework is developed to describe −1 PRF. The model reveals three kinetic pathways to −1 PRF that yield two possible frameshift products: those incorporating zero frame encoded A-site tRNAs in the recoding site, and products incorporating −1 frame encoded A-site tRNAs. Using known kinetic rate constants, the individual contributions of different steps of the translation elongation cycle to −1 PRF and the ratio between two types of frameshift products were evaluated. A dual fluorescence reporter was employed in Escherichia coli to empirically test the model. Additionally, the study applied a novel mass spectrometry approach to quantify the ratios of the two frameshift products. A more detailed understanding of the mechanisms underlying −1 PRF may provide insight into developing antiviral therapeutics.


title: Viral Infections of the Lower Respiratory Tract: Old Viruses, New Viruses, and the Role of Diagnosis

text: Viral infections of the lower respiratory tract cause an enormous disease burden in children, and the role of respiratory viruses in serious lower respiratory tract infections (LRTIs) in older adults is increasingly appreciated. Although viruses are responsible for a large proportion LRTIs, antibiotics are often prescribed. New diagnostic platforms have the potential to detect a wider range of established and newly discovered viruses with greater sensitivity. This will create additional challenges. Although it is clear that influenza, parainfluenza, respiratory syncytial virus, human metapneumovirus, and adenovirus are important causes of pneumonia, the role of rhinoviruses and some of the newly described viruses, including human coronaviruses and bocavirus, is harder to determine. Better diagnostic tests that establish the cause of LRTIs in children have the potential to both reduce overall antibiotic use and to improve the targeted use of antibiotics. In addition, rapid identification of viral infections can help control nosocomial transmission.


title: Chapter 19 Pathogenic Exploitation of Fc Activity

text: While the benefits of antibody responses are widely known, pathogens are also able to exploit antibodies to facilitate cell entry and potentially alter the cellular response via interactions with Fc receptors. This phenomenon, known as antibody-dependent enhancement (ADE) of disease, is a factor in numerous human and veterinary diseases. It is thought to result from innate cellular responses to Fcγ receptor-facilitated entry of infectious microbial immune complexes, and paradoxically results in increased production of pathogenic organisms. ADE has been described in vitro in numerous settings, but the strongest data regarding the in vivo impact of this mechanism on human disease come from human disease and animal models of dengue and leishmanial infections. This chapter reviews the literature of ADE in relation to the innate immune responses to Fcγ receptor ligation by infectious IgG immune complexes and discusses the research frontiers regarding this harmful antibody activity.


title: Human Type I Interferon Antiviral Effects in Respiratory and Reemerging Viral Infections

text: Type I interferons (IFN-I) are a group of related proteins that help regulate the activity of the immune system and play a key role in host defense against viral infections. Upon infection, the IFN-I are rapidly secreted and induce a wide range of effects that not only act upon innate immune cells but also modulate the adaptive immune system. While IFN-I and many IFN stimulated genes are well-known for their protective antiviral role, recent studies have associated them with potential pathogenic functions. In this review, we summarize the current knowledge regarding the complex effects of human IFN-I responses in respiratory as well as reemerging flavivirus infections of public health significance and the molecular mechanisms by which viral proteins antagonize the establishment of an antiviral host defense. Antiviral effects and immune modulation of IFN-stimulated genes is discussed in resisting and controlling pathogens. Understanding the mechanisms of these processes will be crucial in determining how viral replication can be effectively controlled and in developing safe and effective vaccines and novel therapeutic strategies.


title: Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity

text: Innate immunity is the first line of defense against invading pathogens. Rapid and efficient detection of pathogen-associated molecular patterns via pattern-recognition receptors is essential for the host to mount defensive and protective responses. Retinoic acid-inducible gene-I (RIG-I) is critical in triggering antiviral and inflammatory responses for the control of viral replication in response to cytoplasmic virus-specific RNA structures. Upon viral RNA recognition, RIG-I recruits the mitochondrial adaptor protein mitochondrial antiviral signaling protein, which leads to a signaling cascade that coordinates the induction of type I interferons (IFNs), as well as a large variety of antiviral interferon-stimulated genes. The RIG-I activation is tightly regulated via various posttranslational modifications for the prevention of aberrant innate immune signaling. By contrast, viruses have evolved mechanisms of evasion, such as sequestrating viral structures from RIG-I detections and targeting receptor or signaling molecules for degradation. These virus–host interactions have broadened our understanding of viral pathogenesis and provided insights into the function of the RIG-I pathway. In this review, we summarize the recent advances regarding RIG-I pathogen recognition and signaling transduction, cell-intrinsic control of RIG-I activation, and the viral antagonism of RIG-I signaling.


title: Antimicrobial activity of bovine NK-lysin-derived peptides on bovine respiratory pathogen Histophilus somni

text: Bovine NK-lysins, which are functionally and structurally similar to human granulysin and porcine NK-lysin, are predominantly found in the granules of cytotoxic T-lymphocytes and NK-cells. Although antimicrobial activity of bovine NK-lysin has been assessed for several bacterial pathogens, not all the important bacterial pathogens that are involved in the bovine respiratory disease complex have been studied. Therefore the objective of the present study was to evaluate the antimicrobial activity of bovine NK-lysin-derived peptides on bovine respiratory pathogen Histophilus somni. Four, 30-mer peptides corresponding to the functional region of NK-lysin helices 2 and 3 were synthesized and assessed for antibacterial activity on four bovine pneumonic H. somni isolates. Although there were some differences in the efficiency of bactericidal activity among the NK-lysin peptides at lower concentrations (2–5 μM), all four peptides effectively killed most H. somni isolates at higher concentrations (10–30 μM) as determined by a bacterial killing assay. Confocal microscopic and flow cytometric analysis of Live/Dead Baclight stained H. somni (which were preincubated with NK-lysin peptides) were consistent with the killing assay findings and suggest NK-lysin peptides are bactericidal for H. somni. Among the four peptides, NK2A-derived peptide consistently showed the highest antimicrobial activity against all four H. somni isolates. Electron microscopic examination of H. somni following incubation with NK-lysin revealed extensive cell membrane damage, protrusions of outer membranes, and cytoplasmic content leakage. Taken together, the findings from this study clearly demonstrate the antimicrobial activity of all four bovine NK-lysin-derived peptides against bovine H. somni isolates.


The Many Faces and Fangs of COVID-19: An Editorial


title: The short-term impact of COVID-19 pandemic on spine surgeons: a cross-sectional global study

text: PURPOSE: The outbreak of COVID-19 erupted in December 2019 in Wuhan, China. In a few weeks, it progressed rapidly into a global pandemic which resulted in an overwhelming burden on health care systems, medical resources and staff. Spine surgeons as health care providers are no exception. In this study, we try to highlight the impact of the crisis on spine surgeons in terms of knowledge, attitude, practice and socioeconomic burden. METHODS: This was global, multicentric cross-sectional study on 781 spine surgeons that utilized an Internet-based validated questionnaire to evaluate knowledge about COVID-19, availability of personal protective equipment, future perceptions, effect of this crisis on practice and psychological distress. Univariate and multivariate ordinal logistic regression analyses were used to evaluate the predictors for the degree of COVID-19 effect on practice. RESULTS: Overall, 20.2%, 52% and 27.8% of the participants were affected minimally, intermediately and hugely by COVID-19, respectively. Older ages (β = 0.33, 95% CI 0.11–0.56), orthopedic spine surgeons (β = 0.30, 95% CI 0.01–0.61) and those who work in the private sector (β = 0.05, 95% CI 0.19–0.61) were the most affected by COVID-19. Those who work in university hospitals (β = − 0.36, 95% CI 0.00 to − 0.71) were affected the least. The availability of N95 masks (47%) and disposable eye protectors or face shields (39.4%) was significantly associated with lower psychological stress (p = 0.01). Only 6.9%, 3.7% and 5% had mild, moderate and severe mental distress, respectively. CONCLUSION: While it is important to recognize the short-term impact of COVID-19 pandemic on the practice of spine surgery, predicting where we will be standing in 6–12 months remains difficult and unknown. The COVID-19 crisis will probably have an unexpected long-term impact on lives and economies.


title: Human bocavirus in Iranian children with acute respiratory infections

text: Human bocavirus (HBoV), a virus discovered in Sweden in 2005, has been associated with acute respiratory infections in young children and subsequent reports suggest that HBoV may have a worldwide distribution. This report describes the frequency and clinical presentation of HBoV in 261 Iranian children<5 years old with acute respiratory infections attending two regional hospitals in Rasht, Iran in the winter of 2003–2004. Polymerase chain reaction (PCR) and reverse transcription PCR (RT‐PCR) were used for the detection of HBoV and other respiratory pathogens from nasopharyngeal specimens. HBoV was detected in 21 (8%) children. Fifteen (12%) of these children were identified among 122 children admitted to hospital and 6 (4%) from 139 outpatients (P < 0.05). Most children with HBoV were less than 2 years (17/21, 81%) and 7 (33%) were less than 1 year old. Although HBoV was identified in all ages it affected slightly older children than the respiratory syncytial virus (RSV). The frequency of the virus varied from 1 (3%) in 40 patients in November to 7 (12%) of 61 in February, suggesting a seasonal pattern during the autumn and early winter. Seven children had co‐infections with RSV, adenovirus or influenza A. The relatively high frequency of HBoV suggests that the virus may contribute substantially to acute respiratory infections in children. J. Med. Virol. 79:539–543, 2007. © 2007 Wiley‐Liss, Inc.


title: Optimal Control Design of Impulsive SQEIAR Epidemic Models with Application to COVID-19

text: quarantined individuals (Q), called SQEIAR model. The dynamic of SQEIAR model is defined by six ordinary differential equations that describe the numbers of Susceptible, Quarantined, Exposed, Infected, Asymptomatic, and Recovered individuals. The goal of this paper is to reduce the size of susceptible, infected, exposed and asymptomatic groups to consequently eradicate the infection by using two actions: the quarantine and the treatment of infected people. To reach this purpose, optimal control theory is presented to control the epidemic model over free terminal optimal time control with an optimal cost. Pontryagin's maximum principle is used to characterize the optimal controls and the optimal final time. Also, an impulsive epidemic model of SQEIAR is considered to deal with the potential suddenly increased in population caused by immigration or travel. Since this model is suitable to describe the COVID-19 pandemic, especial attention is devoted to this case. Thus, numerical simulations are given to prove the accuracy of the theoretical claims and applied to the particular data of this infection. Moreover, numerical computations of the COVID-19 are compared with diseases like Ebola and Influenza. In addition, the controller is evaluated with system parameters identified by using actual data of China. Finally, the controller tuned with the estimated parameters of the Chinese data is applied to the actual data of Spain to compare the quarantine and treatment policies in both countries.


title: Clinical and Histopathological Features and Potential Pathological Mechanisms of Skin Lesions in COVID-19: Review of the Literature

text: In recent weeks, several reports have emerged of skin lesions with different clinical presentations in COVID-19 cases All dermatologists should be aware of these cutaneous lesions, which may be early clinical symptoms of infection We reviewed the literature on cutaneous manifestations in the PubMed database from December 2019 and June 2020 From the cases described as case reports or series in 57 recent articles, it appears that skin lesions (i) are highly varied, (ii) may not be related to the severity of the condition and (iii) resolve spontaneously in a few days The frequency of these lesions in COVID-19 patients varies between 1 8% and 20 4% The major clinical forms described were maculopapular eruptions, acral areas of erythema with vesicles or pustules (pseudochilblain), urticarial lesions, other vesicular eruptions and livedo or necrosis The lesions were mainly localized in the trunk and extremities The majority of patients were male, aged between 4 5 and 89 years A minority of the patients were children presenting with acral, chilblain-like lesions, papulo-vesicular eruptions or Kawasaki disease-like pediatric inflammatory multisystem syndrome The mean duration of the lesions was a few days, but some lasting as little as 20 min and others as long as four weeks have been reported The mean latency time in the majority of cases was between 1 and 14 days;however, in some patients, lesions appeared 2 to 5 days before the onset of COVID-19 symptoms The histopathological features of these lesions also vary, corresponding to the diversity of clinical manifestations These features underline the nature of epidermal and dermal vascular lesions-and in severe cases, microvascular injury and thrombosis-associated with COVID-19, and provide important clues to their pathological mechanisms


title: Clinical characteristics of 9 cancer patients with SARS-CoV-2 infection

text: In December 2019, a cluster of pneumonia cases was caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China. Cancer patients are a special group, the immunity of them will be suppressed because of various anti-tumor treatments, and the risk of infection will be greatly increased, so we will report clinical features of 9 cancer patients with SARS-CoV-2 infection. 5 (56%) patients were ordinary type, 3 (33%) were severe type, and 1 (11%) was critical type. A total of 8 patients received combined therapy of traditional Chinese medicines and western medicines. From the clinical outcomes of these 8 patients, western combined therapy of traditional Chinese medicine was indeed an effective treatment method. D-dimmer rise, infection index rise, and chest CT(computed tomography) progression may be clinical warning indicators for severe patients, in our study, more 50% of patients had elevated levels of these indicators, but only 44% (including the dead) of patients had received treatment in the intensive care unit. 5 (56%) ordinary type patients had been discharged, while the 1 (11%) critical type patient died 3 days after admission. Cancer comorbidity seems to have no direct relationship with severe events, and the combination of traditional Chinese medicine and western medicine may be effective in the prevention and treatment of novel coronavirus-infected pneumonia (NICP).


Divided in a connected world: Reflections on COVID 19 from Hong Kong


Response: Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports (Diabetes Metab J 2020;44:349–53)


title: Quantitative high throughput screening identifies inhibitors of anthrax-induced cell death

text: Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a β-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin fusion protein and diphtheria toxin. Further efforts demonstrated that these compounds impaired the PA heptamer pre-pore to pore conversion in cells expressing the CMG2 receptor, but not the related TEM8 receptor, indicating that these compounds likely interfere with toxin internalization.


title: A low oxygen consumption pneumatic ventilator for emergency construction during a respiratory failure pandemic

text: The UK influenza pandemic plan predicts up to 750 000 additional deaths with hospitals prioritising patients against inadequate resources. We investigated three prototype low‐cost, gas‐efficient, pneumatic ventilators in a test lung model at different compliance and rate settings. Mean (SD) oxygen consumption was 0.913 (0.198) and 1.119 (0.267) l.min(−1) at tidal volumes of 500 ml and 700 ml respectively. Values of F (I) o (2) increased marginally as lung compliance reduced, reflecting the increased ventilator workload and consequent increased enrichment of breathing gas by waste oxygen from the pneumatic mechanism. We also demonstrated that a stable nitric oxide concentration could be delivered by this design following volumetric principles. It is possible to make a gas‐efficient ventilator costing less than £200 from industrial components for use where oxygen is available at 2‐4 bar, with no pressurised air or electrical requirements. Such a device could be mass‐produced for crises characterised by an overwhelming demand for mechanical ventilation and a limited oxygen supply.


title: COVID-19 and schooling: evaluation, assessment and accountability in times of crises—reacting quickly to explore key issues for policy, practice and research with the school barometer

text: The crisis caused by the COVID-19 virus has far-reaching effects in the field of education, as schools were closed in March 2020 in many countries around the world. In this article, we present and discuss the School Barometer, a fast survey (in terms of reaction time, time to answer and dissemination time) that was conducted in Germany, Austria and Switzerland during the early weeks of the school lockdown to assess and evaluate the current school situation caused by COVID-19. Later, the School Barometer was extended to an international survey, and some countries conducted the survey in their own languages. In Germany, Austria and Switzerland, 7116 persons participated in the German language version: 2222 parents, 2152 students, 1949 school staff, 655 school leaders, 58 school authority and 80 members of the school support system. The aim was to gather, analyse and present data in an exploratory way to inform policy, practice and further research. In this article, we present some exemplary first results and possible implications for policy, practice and research. Furthermore, we reflect on the strengths and limitations of the School Barometer and fast surveys as well as the methodological options for data collection and analysis when using a short monitoring survey approach. Specifically, we discuss the methodological challenges associated with survey data of this kind, including challenges related to hypothesis testing, the testing of causal effects and approaches to ensure reliability and validity. By doing this, we reflect on issues of assessment, evaluation and accountability in times of crisis.


title: Pivotal role of convalescent plasma in managing emerging infectious diseases

text: Infectious diseases remain one of the top 10 global health threats as announced by the World Health Organization [1]. The emergence of new pathogens for which there is no effective treatment has redrawn the attention to the usefulness of convalescent plasma. Indeed, convalescent plasma can be an alternate and fast therapeutic option in outbreaks of infectious diseases such as Middle East Respiratory Syndrome, Severe Acute Respiratory Syndrome (SARS), Chikungunya, Ebola and Zika [2-4]. The recent Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has prompted not only a search for effective anti-viral treatment and spread control measures, but also a reconsideration of the use of convalescent plasma for COVID-19 treatment [5, 6].


title: 15 Smartphone Apps for Older Adults to Use While in Isolation During the COVID-19 Pandemic

text: The maintenance of well-being, healthcare, and social connection is crucial for older adults (OA) and has become a topic of debate as much of the world faces lockdown during the coronavirus disease 2019 (COVID-19) pandemic. OAs have been advised to isolate themselves because they are at higher risk for developing serious complications from severe acute respiratory syndrome coronavirus. Additionally, nursing homes and assisted-living facilities across the country have closed their doors to visitors to protect their residents. Mobile technology such as applications (apps) could provide a valuable tool to help families stay connected, and to help OAs maintain mobility and link them to resources that encourage physical and mental well-being. Apps could address cognitive, visual, and hearing impairments. Our objective was to narratively summarize 15 apps that address physical and cognitive limitations and have the potential to improve OAs’ quality of life, especially during social distancing or self-quarantine.


Pathological and Virological Analyses of Severe Acute Respiratory Syndrome–Associated Coronavirus Infections in Experimantal Animals


title: Norwegian Coronavirus Disease 2019 (NO COVID-19) Pragmatic Open label Study to assess early use of hydroxychloroquine sulphate in moderately severe hospitalised patients with coronavirus disease 2019: A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: The hypothesis of the study is that treatment with hydroxychloroquine sulphate in hospitalised patients with coronavirus disease 2019 (Covid-19) is safe and will accelerate the virological clearance rate for patients with moderately severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when compared to standard care. Furthermore, we hypothesize that early treatment with hydroxychloroquine sulphate is associated with more rapid resolve of clinical symptoms as assessed by the National Early Warning Score 2 (NEWS2), decreased admission rate to intensive care units and mortality, and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide). TRIAL DESIGN: The study is a two-arm, open label, pragmatic randomised controlled group sequential adaptive trial designed to assess the effect on viral loads and clinical outcome of hydroxychloroquine sulphate therapy in addition to standard care compared to standard care alone in patients with established Covid-19. By utilizing resources already paid for by the hospitals (physicians and nurses in daily clinical practice), this pragmatic trial can include a larger number of patients over a short period of time and at a lower cost than studies utilizing traditional randomized controlled trial designs with an external study organization. The pragmatic approach will enable swift initiation of randomisation and allocation to treatment. PARTICIPANTS: Patients will be recruited from all inpatients at Akershus University Hospital, Lørenskog, Norway. Electronic real-time surveillance of laboratory reports from the Department of Microbiology will be examined regularly for SARS-CoV-2 positive subjects. All of the following conditions must apply to the prospective patient at screening prior to inclusion: (1) Hospitalisation; (2) Adults 18 years or older; (3) Moderately severe Covid-19 disease (NEWS2 of 6 or less); (4) SARS-CoV-2 positive nasopharyngeal swab; (5) Expected time of hospitalisation > 48 hours; and (6) Signed informed consent must be obtained and documented according to Good Clinical Practice guidelines of the International Conference on Harmonization, and national/local regulations. Patients will be excluded from participation in the study if they meet any of the following criteria: (1) Requiring intensive care unit admission at screening; (2) History of psoriasis; (3) Known adverse reaction to hydroxychloroquine sulphate; (4) Pregnancy; or (5) Prolonged corrected QT interval (>450 ms). Clinical data, including standard hospital biochemistry, medical therapy, vital signs, NEWS2, and microbiology results (including blood culture results and reverse transcriptase polymerase chain reaction [RT-PCR] for other upper airway viruses), will be automatically extracted from the hospital electronic records and merged with the study specific database. INTERVENTION AND COMPARATOR: Included patients will be randomised in a 1:1 ratio to (1) standard care with the addition of 400 mg hydroxychloroquine sulphate (Plaquenil(TM)) twice daily for seven days or (2) standard care alone. MAIN OUTCOMES: The primary endpoint of the study is the rate of decline in SARS-CoV-2 viral load in oropharyngeal samples as assessed by RT-PCR in samples collected at baseline, 48 and 96 hours after randomization and administration of drug for the intervention arm. Secondary endpoints include change in NEWS2 at 96 hours after randomisation, admission to intensive care unit, mortality (in-hospital, and at 30 and 90 days), duration of hospital admission, clinical status on a 7-point ordinal scale 14 days after randomization ([1] Death [2] Hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation [3] Hospitalised, on non-invasive ventilation or high flow oxygen devices [4] Hospitalized, requiring supplemental oxygen [5] Hospitalised, not requiring supplemental oxygen [6] Not hospitalized, but unable to resume normal activities [7] Not hospitalised, with resumption of normal activities), and improvement in protein biomarker profiles (C-reactive protein, markers of renal and hepatic injury, and established cardiac biomarkers like cardiac troponin and B-type natriuretic peptide) at 96 hours after randomization. RANDOMISATION: Eligible patients will be allocated in a 1:1 ratio, using a computer randomisation procedure. The allocation sequence has been prepared by an independent statistician. BLINDING (MASKING): Open label randomised controlled pragmatic trial without blinding, no active or placebo control. The virologist assessing viral load in the oropharyngeal samples and the statistician responsible for analysis of the data will be blinded to the treatment allocation for the statistical analyses. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This is a group sequential adaptive trial where analyses are planned after 51, 101, 151 and 202 completed patients, with a maximum sample size of 202 patients (101 patients allocated to intervention and standard care and 101 patients allocated to standard care alone). TRIAL STATUS: Protocol version 1.3 (March 26, 2020). Recruitment of first patient on March 26, 2020, and 51 patients were included as per April 28, 2020. Study recruitment is anticipated to be completed by July 2020. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04316377. Trial registered March 20, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: In silico fight against novel coronavirus by finding chromone derivatives as inhibitor of coronavirus main proteases enzyme

text: Novel coronavirus, 2019-nCoV is a danger to the world and is spreading rapidly. Very little structural information about 2019-nCoV make this situation more difficult for drug designing. Benzylidenechromanones, naturally occurring oxygen heterocyclic compounds, having capability to inhibit various protein and receptors, have been designed here to block mutant variety of coronavirus main protease enzyme (SARC-CoV-2 M(pro)) isolated from 2019-nCoV with the assistance of molecular docking, bioinformatics and molecular electrostatic potential. (Z)-3-(4′-chlorobenzylidene)-thiochroman-4-one showed highest binding affinity to the protein. Binding of a compound to this protein actually inhibits the replication and transcription of the virus and, ultimately, stop the virus multiplication. Incorporation of any functional groups to the basic benzylidenechromanones enhances their binding ability. Chloro and bromo substitutions amplify the binding affinity. ADME studies of all these compounds indicate they are lipophilic, high gastro intestine absorbable and blood-brain barrier permeable. The outcome reveals that the investigated benzylidenechromanones can be examined in the case of 2019-nCoV as potent inhibitory drug of SARC-CoV-2 M(pro), for their strong inhibition ability, high reactivity and effective pharmacological properties. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11224-020-01537-5) contains supplementary material, which is available to authorized users.


title: Chapter One Functional Genomic Strategies for Elucidating Human–Virus Interactions Will CRISPR Knockout RNAi and Haploid Cells?

text: Abstract Over the last several years a wealth of transformative human–virus interaction discoveries have been produced using loss-of-function functional genomics. These insights have greatly expanded our understanding of how human pathogenic viruses exploit our cells to replicate. Two technologies have been at the forefront of this genetic revolution, RNA interference (RNAi) and random retroviral insertional mutagenesis using haploid cell lines (haploid cell screening), with the former technology largely predominating. Now the cutting edge gene editing of the CRISPR/Cas9 system has also been harnessed for large-scale functional genomics and is poised to possibly displace these earlier methods. Here we compare and contrast these three screening approaches for elucidating host–virus interactions, outline their key strengths and weaknesses including a comparison of an arrayed multiple orthologous RNAi reagent screen to a pooled CRISPR/Cas9 human rhinovirus 14–human cell interaction screen, and recount some notable insights made possible by each. We conclude with a brief perspective on what might lie ahead for the fast evolving field of human–virus functional genomics.


title: Rehabilitation Medicine Response to the COVID-19 Pandemic

text: The COVID-19 pandemic has spread across the globe at a rapid rate, affecting large numbers of individuals in different countries with varying health care systems and infrastructure. In the US, New York City has been the epicenter of the COVID-19 outbreak, and the peak impact in this region has come earlier in this location than most other parts of the country. We report our experience preparing for this pandemic in a New York City academic medical center and its regional health care system, the issues confronted during the rise and peak of the number of cases, and the plans for the post-peak recovery and adjustment to the new reality of providing rehabilitation in an environment where COVID-19 remains prevalent.


title: ISHLT CONSENSUS STATEMENT FOR THE STANDARDIZATION OF BRONCHOALVEOLAR LAVAGE IN LUNG TRANSPLANTATION

text: ABSTRACT Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This ISHLT-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. Nine areas are covered: 1) bronchoscopy procedure and BAL collection, 2) sample handling, 3) sample processing for microbiology, 4) cytology, 5) research and 6) microbiome, 7) sample inventory/tracking, 8) donor bronchoscopy and 9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multi-center collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics.


title: Regulation of Human Innate Lymphoid Cells in the Context of Mucosal Inflammation

text: Since their identification as a unique cell population, innate lymphoid cells (ILCs) have revolutionized our understanding of immune responses, leaving their impact on multiple inflammatory and fibrotic pathologies without doubt. Thus, a tightly controlled regulation of local ILC numbers and their activity is of crucial importance. Even though this has been extensively studied in murine ILCs in the last few years, our knowledge of human ILCs is still lagging behind. Our review article will therefore summarize recent insights into the function of human ILCs and will particularly focus on their regulation under inflammatory conditions. The quality and intensity of ILC involvement into local immune responses at mucosal sites of the human body can potentially be modulated via three different axes: (1) activation of tissue-resident mature ILCs, (2) plasticity and local transdifferentiation of specific ILC subsets, and (3) tissue migration and accumulation of peripheral ILCs. Despite a still ongoing scientific effort in this field, already existing data on the fate of human ILCs under different pathologic conditions clearly indicate that all three of these mechanisms are of relevance for the clinical course of chronic inflammatory and autoimmune diseases and might likewise provide new target structures for future therapeutic strategies.


title: Pentair updates on Covid-19 impact

text: Pentair plc says it has experienced reduced production in a number of key facilities as the result of “shelter in place” orders and suspensions of operations in several facilities due to the Covid-19 pandemic.


title: Mycoplasma pneumoniae as a cause of vulvar ulcers in a non-sexually active girl: a case report

text: BACKGROUND: Non-sexually active young females very rarely develop genital ulcers. Such ulcers pose a diagnostic challenge as well as physical and emotional distress for patients and family; therefore, the search for their etiology requires exhaustive investigation. Several viruses such as Epstein–Barr virus have been associated with this entity; however, Mycoplasma pneumoniae has rarely been linked to such ulcers in the literature. We present a case of vulvar ulcers in a non-sexually active young girl during the course of pneumonia caused by Mycoplasma pneumoniae. CASE PRESENTATION: A 10-year-old non-sexually active girl of cypriot origin presented at a hospital with fever, dry cough, and acute vulvar ulcers. Laboratory investigations as well as imaging studies revealed Mycoplasma pneumoniae as the cause of her pneumonia and acute vulvar ulcers. CONCLUSIONS: Although a rare cause of vulvar ulcers, Mycoplasma pneumoniae should be considered in the differential diagnosis of acute vulvar ulcers coexisting with respiratory symptoms.


title: RNAi, a new therapeutic strategy against viral infection

text: RNA interference (RNAi) is an adaptive defense mechanism triggered by double-stranded RNA (dsRNA). It is a powerful reverse genetic tool that has been widely employed to silence gene expression in mammalian and human cells. RNAi-based gene therapies, especially in viral diseases have become more and more interesting and promising. Recently, small interfering RNA (siRNA) can be used to protect host from viral infection, inhibit the expression of viral antigen and accessory genes, control the transcription and replication of viral genome, hinder the assembly of viral particles, and display influences in virus-host interactions. In this review, we attempt to present recent progresses of this breakthrough technology in the above fields and summarize the possibilities of siRNA-based drugs.


title: Quadruple therapy for asymptomatic COVID-19 infection patients

text: Introduction: The novel coronavirus (COVID-19) is currently in epidemic stage. After large-scale interpersonal infection, asymptomatic patients appear. Whether asymptomatic patients are contagious or not and whether they need medication are the arguments among clinical experts. Areas covered: This paper reports a special asymptomatic couple with COVID-19, of which the male patient is an intercity bus driver but has not induced confirmed infection of his 188 passengers. The patients were treated with four combinations of lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol. Their clinical characteristics and medication were summarized and analyzed. Expert opinion: The two asymptomatic patients far away from Wuhan did not seem to be highly contagious. They improved obviously, after treatment with the quadruple therapy, but the effective drug is still unknown. It should be noted that lopinavir/ritonavir tablets have many drug interactions and are the most likely drugs to cause hyperlipidemia and hyperglycemia in these two patients. IFN-α2b is more effective in the early stage of virus infection. Arbidol instruction dose may not be sufficient to inhibit the novel coronavirus in vivo. The evidence-based medicine of Lianhuaqingwen granules for treating various viral infections is just based on Chinese patients.


title: Chemical composition and pharmacological mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction against Coronavirus Disease 2019 (COVID-19): in silico and experimental study

text: Abstract The Coronavirus Disease 2019 (COVID-19) pandemic has become a huge threaten to global health, which raise urgent demand of developing efficient therapeutic strategy. The aim of the present study is to dissect the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China. Through comprehensive analysis by liquid chromatography coupled with high resolution mass spectrometry (MS), a total of 129 compounds of QFPD were putatively identified. We also constructed molecular networking of mass spectrometry data to classify these compounds into 14 main clusters, in which exhibited specific patterns of flavonoids (45%), glycosides (15%), carboxylic acids (10%), and saponins (5%). The target network model of QFPD, established by predicting and collecting the targets of identified compounds, indicated a pivotal role of Ma Xing Shi Gan Decoction (MXSG) in the therapeutic efficacy of QFPD. Supportively, through transcriptomic analysis of gene expression after MXSG administration in rat model of LPS-induced pneumonia, the thrombin and Toll-like receptor (TLR) signaling pathway were suggested to be essential pathways for MXSG mediated anti-inflammatory effects. Besides, changes in content of major compounds in MXSG during decoction were found by the chemical analysis. We also validate that one major compound in MXSG, i.e. glycyrrhizic acid, inhibited TLR agonists induced IL-6 production in macrophage. In conclusion, the integration of in silico and experimental results indicated that the therapeutic effects of QFPD against COVID-19 may be attributed to the anti-inflammatory effects of MXSG, which supports the rationality of the compatibility of TCM.