title: Risks to healthcare workers following tracheal intubation of patients with COVID‐19: a prospective international multicentre cohort study

text: Healthcare workers involved in aerosol‐generating procedures, such as tracheal intubation, may be at elevated risk of acquiring COVID‐19. However, the magnitude of this risk is unknown. We conducted a prospective international multicentre cohort study recruiting healthcare workers participating in tracheal intubation of patients with suspected or confirmed COVID‐19. Information on tracheal intubation episodes, personal protective equipment use, and subsequent provider health status was collected via self‐reporting. The primary endpoint was the incidence of laboratory‐confirmed COVID‐19 diagnosis or new symptoms requiring self‐isolation or hospitalisation after a tracheal intubation episode. Cox regression analysis examined associations between the primary endpoint and healthcare worker characteristics, procedure‐related factors, and personal protective equipment use. Between 23 March and 2 June 2020, 1718 healthcare workers from 503 hospitals in 17 countries reported 5148 tracheal intubation episodes. The overall incidence of the primary endpoint was 10.7% over a median (IQR [range]) follow‐up of 32 (18–48 [0–116]) days. The cumulative incidence within 7, 14 and 21 days of the first tracheal intubation episode was 3.6%, 6.1%, and 8.5%, respectively. The risk of the primary endpoint varied by country and was higher in females, but was not associated with other factors. Around 1 in 10 healthcare workers involved in tracheal intubation of patients with suspected or confirmed COVID‐19 subsequently reported a COVID‐19 outcome. This has human resource implications for institutional capacity to deliver essential healthcare services, and wider societal implications for COVID‐19 transmission.


title: Regional and interregional integrative dynamics of ASEAN and EU in response to the avian influenza

text: The article explores the European Union’s and the Association of Southeast Asian Nation’s regional and interregional integrative dynamics in response to the avian influenza outbreak in East Asia of 7 years ago. It sketches the collaborative efforts from an institutionalist perspective and outlines the variables influencing the behaviour of regional organisations. To explain and predict behavioural patterns, the article takes into account the following moderating variables: the kind of affectedness, mode of regional and interregional cooperation, the degree of institutionalisation and the role of international actors. The independent variable is the crisis itself. It replaces goal formulation for action and interaction during periods of normalcy. The succeeding paragraphs argue that a transnational crisis may trigger integrative dynamics and institutional change, but, that the mode of regional and interregional cooperation and the degree of institutionalisation matter in the long run and are the essential factors in differentiating the cooperative dynamics. These two variables are vital elements contributing to the institutional design of a regional organisation. In the end, the article views the institutional design to be the central and constant determinant of integrative behaviour both in times of and in absence of crises.


title: Selection of SARS-Coronavirus-specific B cell epitopes by phage peptide library screening and evaluation of the immunological effect of epitope-based peptides on mice

text: Abstract Antibodies to SARS-Coronavirus (SARS-CoV)-specific B cell epitopes might recognize the pathogen and interrupt its adherence to and penetration of host cells. Hence, these epitopes could be useful for diagnosis and as vaccine constituents. Using the phage-displayed peptide library screening method and purified Fab fragments of immunoglobulin G (IgG Fab) from normal human sera and convalescent sera from SARS-CoV-infected patients as targets, 11 B cell epitopes of SARS-CoV spike glycoprotein (S protein) and membrane protein (M protein) were screened. After a bioinformatics tool was used to analyze these epitopes, four epitope-based S protein dodecapeptides corresponding to the predominant epitopes were chosen for synthesis. Their antigenic specificities and immunogenicities were studied in vitro and in vivo. Flow cytometry and ELISPOT analysis of lymphocytes as well as a serologic analysis of antibody showed that these peptides could trigger a rapid, highly effective, and relatively safe immune response in BALB/c mice. These findings might aid development of SARS diagnostics and vaccines. Moreover, the role of S and M proteins as important surface antigens is confirmed.


title: Metagenomic analysis of viral diversity in respiratory samples from patients with respiratory tract infections in Kuwait

text: A metagenomic approach based on target independent next‐generation sequencing has become a known method for the detection of both known and novel viruses in clinical samples. This study aimed to use the metagenomic sequencing approach to characterize the viral diversity in respiratory samples from patients with respiratory tract infections. We have investigated 86 respiratory samples received from various hospitals in Kuwait between 2015 and 2016 for the diagnosis of respiratory tract infections. A metagenomic approach using the next‐generation sequencer to characterize viruses was used. According to the metagenomic analysis, an average of 145, 019 reads were identified, and 2% of these reads were of viral origin. Also, metagenomic analysis of the viral sequences revealed many known respiratory viruses, which were detected in 30.2% of the clinical samples. Also, sequences of non‐respiratory viruses were detected in 14% of the clinical samples, while sequences of non‐human viruses were detected in 55.8% of the clinical samples. The average genome coverage of the viruses was 12% with the highest genome coverage of 99.2% for respiratory syncytial virus, and the lowest was 1% for torque teno midi virus 2. Our results showed 47.7% agreement between multiplex Real‐Time PCR and metagenomics sequencing in the detection of respiratory viruses in the clinical samples. Though there are some difficulties in using this method to clinical samples such as specimen quality, these observations are indicative of the promising utility of the metagenomic sequencing approach for the identification of respiratory viruses in patients with respiratory tract infections.


title: Synthesis and anti-HCMV activity of 1-[ω-(phenoxy)alkyl]uracil derivatives and analogues thereof

text: Abstract HCMV infection represents a life-threatening condition for immunocompromised patients and newborn infants and novel anti-HCMV agents are clearly needed. In this regard, a series of 1-[ω-(phenoxy)alkyl]uracil derivatives were synthesized and examined for antiviral properties. Compounds 17, 20, 24 and 28 were found to exhibit highly specific and promising inhibitory activity against HCMV replication in HEL cell cultures with EC50 values within 5.5–12μM range. Further studies should be undertaken to elucidate the mechanism of action of these compounds and the structure–activity relationship for the linker region.


title: Comparative nucleic acid chaperone properties of the nucleocapsid protein NCp7 and Tat protein of HIV-1

text: Abstract RNA chaperones are proteins able to rearrange nucleic acid structures towards their most stable conformations. In retroviruses, the reverse transcription of the viral RNA requires multiple and complex nucleic acid rearrangements that need to be chaperoned. HIV-1 has evolved different viral-encoded proteins with chaperone activity, notably Tat and the well described nucleocapsid protein NCp7. We propose here an overview of the recent reports that examine and compare the nucleic acid chaperone properties of Tat and NCp7 during reverse transcription to illustrate the variety of mechanisms of action of the nucleic acid chaperone proteins.


title: No Room for Error: Empiric Treatment for Fulminant Pneumonia

text: Early antibiotic administration is critical in cases of sepsis and severe community-acquired pneumonia, which is frequently due to Streptococcus pneumoniae, Staphylococcus aureus, Legionella species, or influenza. We describe the case of a 29-year-old previously healthy man who presented to an urban emergency department (ED) in the North Central U.S. with fever, hip pain, severe hypoxemia, and diffuse pulmonary infiltrates. He was intubated and received piperacillin/tazobactam, levofloxacin, vancomycin, and oseltamivir; given his fulminant presentation and predicted high mortality, doxycycline, methylprednisolone, and amphotericin B were also administered empirically in the ED. A respiratory culture eventually grew Blastomyces dermatitidis, and the patient survived. Severe acute respiratory distress syndrome due to fulminant pneumonitis carries a high mortality. Faced with this scenario and no room for error, it is important that the emergency physician cover for all possible pathogens, including zoonotic bacteria and endemic fungi.


title: Recommendations for the surgical management of gynecological cancers during the COVID-19 pandemic - FRANCOGYN group for the CNGOF

text: Abstract Introduction In the context of the COVID-19 pandemic, specific recommendations are required for the management of patients with gynecologic cancer. Materials and method The FRANCOGYN group of the National College of French Gynecologists and Obstetricians (CNGOF) convened to develop recommendations based on the consensus conference model. Results If a patient with a gynecologic cancer presents with COVID-19, surgical management should be postponed for at least 15 days. For cervical cancer, radiotherapy and concomitant radiochemotherapy could replace surgery as first-line treatment and the value of lymph node staging should be reviewed on a case-by-case basis. For advanced ovarian cancers, neoadjuvant chemotherapy should be preferred over primary cytoreduction surgery. It is legitimate not to perform hyperthermic intraperitoneal chemotherapy during the COVID-19 pandemic. For patients who are scheduled to undergo interval surgery, chemotherapy can be continued and surgery performed after 6 cycles. For patients with early stage endometrial cancer of low and intermediate preoperative ESMO risk, hysterectomy with bilateral adnexectomy combined with a sentinel lymph node procedure is recommended. Surgery can be postponed for 1–2 months in low-risk endometrial cancers (FIGO Ia stage on MRI and grade 1–2 endometrioid cancer on endometrial biopsy). For patients of high ESMO risk, the MSKCC algorithm (combining PET-CT and sentinel lymph node biopsy) should be applied to avoid pelvic and lumbar-aortic lymphadenectomy. Conclusion During the COVID-19 pandemic, management of a patient with cancer should be adapted to limit the risks associated with the virus without incurring loss of chance.


title: The 1995 Kikwit Ebola outbreak: lessons hospitals and physicians can apply to future viral epidemics

text: Abstract Objective This article looks at lessons learned from the 1995 Kikwit Ebola outbreak and suggests how modern hospitals should apply these lessons to the next lethal viral epidemic that occurs. Method The 1995 Kikwit Ebola outbreak in the Democratic Republic of the Congo (formally Zaire) is one of the most well studied epidemics to have occurred to date. Many of the lessons learned from identifying, containing and treating that epidemic are applicable to future viral outbreaks, natural disasters and bioterrorist attacks. This is due to Ebola's highly contagious nature and high mortality rate. Results When an outbreak occurs, it often produces fear in the community and causes the basic practice of medicine to be altered. Changes seen at Kikwit included limited physical examinations, hesitance to give intravenous medications and closure of supporting hospital facilities. The Kikwit Ebola outbreak also provided beneficial psychological insight into how patients, staff and the general community respond to a biological crisis and how this will affect physicians working in an epidemic. Conclusions General lessons from the outbreak include the importance of having simple, well-defined triage procedures; staff who are flexible and able to adapt to situations with unknowns; and the need to protect staff physically and emotionally to ensure a sustained effort to provide care.


title: Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice

text: Rice leaf blight, which is caused by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), results in huge losses in grain yield. Here, we show that Xoo-induced rice leaf blight is effectively controlled by niclosamide, an oral antihelminthic drug and molluscicide, which also functions as an anti-tumor agent. Niclosamide directly inhibited the growth of the three Xoo strains PXO99, 10208 and K3a. Niclosamide moved long distances from the site of local application to distant rice tissues. Niclosamide also increased the levels of salicylate and induced the expression of defense-related genes such as OsPR1 and OsWRKY45, which suppressed Xoo-induced leaf wilting. Niclosamide had no detrimental effects on vegetative/reproductive growth and yield. These combined results indicate that niclosamide can be used to block bacterial leaf blight in rice with no negative side effects.


title: Measurement of Angiotensin Converting Enzyme 2 Activity in Biological Fluid (ACE2)

text: Angiotensin-converting enzyme 2 (ACE2) is a recently described member of the renin-angiotensin system that hydrolyzes angiotensin (Ang) II to Ang-(1-7), and may thereby protect against cardiovascular and renal diseases. ACE2 is a type 1 integral membrane protein and contains a catalytically active ectodomain that can be shed from the cell surface into the extracellular space, via cleavage by a disintegrin and metalloproteinase-17 (ADAM-17). ACE2 enzymatic activity and protein can be detected in biological fluids, including urine, plasma, and conditioned cell culture media. We present a detailed method for measurement of ACE2 activity in biological fluids, using hydrolysis of an intramolecularly quenched fluorogenic ACE2 substrate, in the absence or presence of the ACE2 inhibitors MLN-4760 or DX600. Recombinant human or mouse ACE2 is used to generate standard curves for this assay, with ACE2 detection ranging from 1.56 to 50 ng/ml. While MLN-4760 potently inhibits the activity of both human and mouse ACE2, DX600 (linear form) only effectively blocks human ACE2 activity in this assay. In biological samples of human and mouse urine, cell culture medium from mouse proximal tubular cells, and mouse plasma, the mean intra- and inter-assay coefficients of variation (CVs) of the assay range from 1.43 to 4.39 %, and from 7.01 to 13.17 %, respectively. We present data on the time and substrate concentration dependence of the assay, and show that exogenous d -glucose, creatinine, urea, and albumin do not interfere with its performance. In biological fluids, this assay is a simple and reliable method to study the role of ACE2 and its shed fragments in cardiovascular and renal diseases.


docid: yjaedzxm

title: Innate immune signaling in the olfactory epithelium reduces odorant receptor levels: modeling transient smell loss in COVID-19 patients

text: Post-infectious anosmias typically follow death of olfactory sensory neurons (OSNs) with a months-long recovery phase associated with parosmias. While profound anosmia is the leading symptom associated with COVID-19 infection, many patients regain olfactory function within days to weeks without distortions. Here, we demonstrate that sterile induction of anti-viral type I interferon signaling in the mouse olfactory epithelium is associated with diminished odor discrimination and reduced odor-evoked local field potentials. RNA levels of all class I, class II, and TAAR odorant receptors are markedly reduced in OSNs in a non-cell autonomous manner. We find that people infected with COVID-19 rate odors with lower intensities and have odor discrimination deficits relative to people that tested negative for COVID-19. Taken together, we propose that inflammatory-mediated loss of odorant receptor expression with preserved circuit integrity accounts for the profound anosmia and rapid recovery of olfactory function without parosmias caused by COVID-19.


title: Genotyping of human bocavirus using a restriction length polymorphism

text: Sequencing analysis of the isolates of a recently identified pathogen associated with respiratory infections, human bocavirus (HBoV), allowed for identification of two virus genotypes of the virus. In the current article a new method for a simple and fast differentiation of HBoV genotypes in clinical materials is described. The test includes an amplification of a 309 bp fragment of VP1/VP2 gene of HBoV from nasopharyngeal aspirates with a subsequent incubation of a PCR mix with the BstAPI endonuclease. Upon such a digestion, the DNA fragment derived from the genotype I HBoV isolates forms two fragments of 150 and 159 bp, while that obtained from genotype 2 isolates remains unrestricted. The developed technique may be used in epidemiological studies of HBoV infection and analysis of the potential differences in biological characteristics of HboV genotypes.


title: Forecasting the Future of Urology Practice: A Comprehensive Review of the Recommendations by International and European Associations on Priority Procedures During the COVID-19 Pandemic

text: Abstract Context The unprecedented health care scenario caused by the coronavirus disease 2019 (COVID-19) pandemic has revolutionized urology practice worldwide. Objective To review the recommendations by the international and European national urological associations/societies (UASs) on prioritization strategies for both oncological and nononcological procedures released during the current emergency scenario. Evidence acquisition Each UAS official website was searched between April 8 and 18, 2020, to retrieve any document, publication, or position paper on prioritization strategies regarding both diagnostic and therapeutic urological procedures, and any recommendations on the use of telemedicine and minimally invasive surgery. We collected detailed information on all urological procedures, stratified by disease, priority (higher vs lower), and patient setting (outpatient vs inpatient). Then, we critically discussed the implications of such recommendations for urology practice in both the forthcoming “adaptive” and the future “chronic” phase of the COVID-19 pandemic. Evidence synthesis Overall, we analyzed the recommendations from 13 UASs, of which four were international (American Urological Association, Confederation Americana de Urologia, European Association of Urology, and Urological Society of Australia and New Zealand) and nine national (from Belgium, France, Germany, Italy, Poland, Portugal, The Netherlands, and the UK). In the outpatient setting, the procedures that are likely to impact the future burden of urologists’ workload most are prostate biopsies and elective procedures for benign conditions. In the inpatient setting, the most relevant contributors to this burden are represented by elective surgeries for lower-risk prostate and renal cancers, nonobstructing stone disease, and benign prostatic hyperplasia. Finally, some UASs recommended special precautions to perform minimally invasive surgery, while others outlined the potential role of telemedicine to optimize resources in the current and future scenarios. Conclusions The expected changes will put significant strain on urological units worldwide regarding the overall workload of urologists, internal logistics, inflow of surgical patients, and waiting lists. In light of these predictions, urologists should strive to leverage this emergency period to reshape their role in the future. Patient summary Overall, there was a large consensus among different urological associations/societies regarding the prioritization of most urological procedures, including those in the outpatient setting, urological emergencies, and many inpatient surgeries for both oncological and nononcological conditions. On the contrary, some differences were found regarding specific cancer surgeries (ie, radical cystectomy for higher-risk bladder cancer and nephrectomy for larger organ-confined renal masses), potentially due to different prioritization criteria and/or health care contexts. In the future, the outpatient procedures that are likely to impact the burden of urologists’ workload most are prostate biopsies and elective procedures for benign conditions. In the inpatient setting, the most relevant contributors to this burden are represented by elective surgeries for lower-risk prostate and renal cancers, nonobstructing stone disease, and benign prostatic hyperplasia.


docid: njdtfcjo

title: The European network of Biosafety-Level-4 laboratories: enhancing European preparedness for new health threats

text: Abstract Emerging and re-emerging infections and possible bioterrorism acts will continue to challenge both the medical community and civilian populations worldwide, urging health authorities to respond rapidly and effectively. Established in 2005, the European Community (EC)-funded European Network of Biosafety-Level-4 laboratories (Euronet-P4), which brings together the laboratories in Porton Down, London, Hamburg, Marburg, Solna, Lyon and Rome, seeks to increase international collaboration in the areas of high containment laboratory biosafety and viral diagnostic capability, to strengthen Europe's capacity to respond to an infectious disease emergency, and to offer assistance to countries not equipped with such costly facilities. Network partners have agreed on a common strategy to fill the gaps identified in the field of risk group-4 agents’ laboratory diagnosis, namely the lack of standardization and of reference samples. The network has received a further 3-year funding, to offer assistance to external laboratories, and to start the planning of field activities.


title: Nine challenges in modelling the emergence of novel pathogens

text: Abstract Studying the emergence of novel infectious agents involves many processes spanning host species, spatial scales, and scientific disciplines. Mathematical models play an essential role in combining insights from these investigations and drawing robust inferences from field and experimental data. We describe nine challenges in modelling the emergence of novel pathogens, emphasizing the interface between models and data.


title: Yeast Proteomics and Protein Microarrays

text: Our understanding of biological processes as well as human diseases has improved greatly thanks to studies on model organisms such as yeast. The power of scientific approaches with yeast lies in its relatively simple genome, its facile classical and molecular genetics, as well as the evolutionary conservation of many basic biological mechanisms. However, even in this simple model organism, systems biology studies, especially proteomic studies had been an intimidating task. During the past decade, powerful high-throughput technologies in proteomic research have been developed for yeast including protein microarray technology. The protein microarray technology allows the interrogation of protein-protein, protein-DNA, protein-small molecule interaction networks as well as post-translational modification networks in a large-scale, high-throughput manner. With this technology, many groundbreaking findings have been established in studies with the budding yeast Saccharomyces cerevisiae, most of which could have been unachievable with traditional approaches. Discovery of these networks has profound impact on explicating biological processes with a proteomic point of view, which may lead to a better understanding of normal biological phenomena as well as various human diseases.


title: The Indian perspective of COVID-19 outbreak

text: The emerging infection of COVID-19 was initiated from Wuhan, China, have been spread to more than 210 countries around the globe including India. The clinical symptoms of COVID-19 are very similar to other respiratory viruses. The number of laboratory-confirmed cases and associated deaths are increasing regularly in various parts of the World. Seven coronaviruses (229E, NL63, OC43, HKU1, SARS, MERS and, COVID-19) can naturally infect human beings. Out of these four (229E-CoV, NL63-CoV, OC43-CoV, HKU1-CoV) are responsible for mild upper respiratory infections, while SARS-CoV, MERS-CoV, and COVID-19 are well known for their high mortality. Few mild strains of coronaviruses are circulating in India but there is no evidence of SARS and MERS outbreaks. The COVID-19 is an emerging viral infection responsible for pandemics. Fortunately, the mortality of COVID-19 is low as compared with SARS and MERS, the majority of its cases are recovered. The death toll of COVID-19 is high even after its low mortality because COVID-19 causes a pandemic while SARS-CoV and MERS-CoV cause epidemics only. COVID-19 influenced the large segments of the world population, which led to a public health emergency of international concern, putting all health organizations on high alert. COVID-19 is the first coronavirus after Spanish Flu 1918–1919, who has extremely influenced the health system, economy, and psychology of India. The present study review is on the general continent, virology, pathogenesis, global epidemiology, clinical presentation, diagnosis, treatment and control of COVID-19 with the reference to India.


title: Deaths in healthcare workers due to COVID‐19: the need for robust data and analysis

text: The novel coronavirus SARS-CoV-2 has rapidly spread across the world from its origin in Wuhan, China in late 2019. The resultant disease (COVID-19) has placed an enormous burden on healthcare systems because of the high transmission rates, prevalence of severe disease and mortality [1]. The risk of viral transmission to healthcare workers has been a concern since the start of the outbreak and the first person to raise concerns about the illness to the international community was Dr Li Wen-Liang, an ophthalmologist in Wuhan who sadly died of the disease that he likely contracted whilst at work [2].


title: Multiplex PCR point of care testing versus routine, laboratory-based testing in the treatment of adults with respiratory tract infections: a quasi-randomised study assessing impact on length of stay and antimicrobial use

text: BACKGROUND: Laboratory-based respiratory pathogen (RP) results are often available too late to influence clinical decisions such as hospitalisation or antibiotic treatment due to time delay in transport of specimens and testing schedules. Ward-based i.e. point of care (POC) testing providing rapid results may alter the clinical management pathway. METHODS: FilmArray® RP polymerase chain reaction (PCR) systems were placed in three in-patient and out-patient medical areas. Patients presenting with influenza-like illness /upper respiratory tract infection +/− lower RTI were recruited between January–July 2015. FilmArray® POC testing occurred on even days of the month (intervention) or routine, laboratory-based RP PCR testing +/− atypical serology on odd days (control). The primary outcome was length of hospital stay. The secondary outcomes were impact on the use of antimicrobials, readmissions, all-cause mortality, length of ward stay and turn-around time (TAT) (time to result from admission). RESULTS: Of 606 eligible patients, 545 (89.9%) were included; 211 in the control arm and 334 in the intervention arm. 20% of control arm patients and 24% of intervention arm patients had an RP detected. POC testing was not associated with the primary outcome measure, length of stay, but reduced the TAT from 39.5 h to 19.0 h, p < 0.001. Only the prescribing decision differed between study arms, p < 0.001. When antivirals were given, the intervention was associated with a reduction in the median time to the first dose of 36 h and allowed appropriate treatment of mycoplasma infection. CONCLUSIONS: We found no association between respiratory PCR POC testing and length of stay or most of the secondary outcomes except the antimicrobial prescribing decision. This was probably due to a delay in initiating FilmArray® testing. Despite this, POC testing allowed time-critical antivirals to be given significantly faster, appropriate mycoplasma treatment and results were available considerably faster than routine, laboratory-based testing. Ward-staff of all grades performed POC testing without difficulty suggesting potential use across many divergent healthcare settings. Further studies evaluating the implementation of rapid respiratory PCR POC testing and the effect on length of stay and antimicrobial use are required. TRIAL REGISTRATION: ISRCTN10470967, Retrospectively Registered, 30/6/2015.


title: Activation of Transgene-specific T Cells Following Lentivirus-mediated Gene Delivery to Mouse Lung

text: Integrating lentiviral vectors based on the human immunodeficiency virus type-1 (HIV-1) can transduce quiescent cells, which in lung account for almost 95% of the epithelial cell population. Pseudotyping lentiviral vectors with the envelope glycoprotein from the Ebola Zaire virus, the lymphocytic choriomeningitis virus (LCMV), the Mokola virus, and the vesicular stomatitis virus (VSV-G) resulted in transduction of mouse alveolar epithelium, but gene expression in the lung of C57BL/6 and BALB/c mice waned within 90 days of vector injection. Intratracheal delivery of the four pseudotyped lentiviral vectors resulted in transgene-specific T-cell activation in both mouse strains, albeit lower than that achieved by intramuscular injection of the vectors. We performed an adoptive transfer of luciferase-specific T cells, isolated from spleen or lung of donor mice injected with VSV-G-pseudotyped lentivirus vector expressing luciferase into the muscle or lung, respectively, into recipient recombination-activating gene (RAG)–deficient mice transduced in lung with adenovirus expressing firefly luciferase (ffluc2). Gene expression declined within 7 days of adoptive transfer approaching background levels by day 36. Taken together, our results suggest that the loss of transduced cells in lung is due to VSV-G.HIV vector–mediated activation of transgene-specific T cells rather than as result of normal turnover of airway cells.


title: Cervical lymphadenitis: Etiology, diagnosis, and management

text: Cervical lymphadenopathy is a common problem in children. The condition most commonly represents a transient response to a benign local or generalized infection. Acute bilateral cervical lymphadenitis is usually caused by a viral upper respiratory tract infection or streptococcal pharyngitis. Acute unilateral cervical lymphadenitis is caused by streptococcal or staphylococcal infection in 40% to 80% of cases. Common causes of subacute or chronic lymphadenitis include cat-scratch disease and mycobacterial infection. Generalized lymphadenopathy is often caused by a viral infection, and less frequently by malignancies, collagen vascular diseases, and medications. Laboratory tests are not necessary in most children with cervical lymphadenopathy. Most cases of cervical lymphadenitis are self-limited and require no treatment. The treatment of acute bacterial cervical lymphadenitis without a known primary source should provide adequate coverage for both Staphylococcus aureus and Streptococcus pyogenes.


title: X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy

text: Abstract The hepatitis B virus X protein (HBV-X) is a multifunctional regulatory protein associated with the pathogenesis of liver disease in chronic HBV infection. Basal core promoter mutations (BCP), associated with the clinical course of chronic HBV infection, affect HBV-X at 130–131 positions. The role of these mutations on HBV-X biological activity remains largely unknown. The aim of this study was to analyze the impact of the presence of different amino acids at 130–131 positions of HBV-X on the biological activity of the protein. Transient expression of wild type and mutant F1b and F4 HBV-X increased cell mortality by the induction of apoptosis in human hepatoma cells. The wild type and mutant HBV-X differentially modulate the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2 and Bcl-X) regulatory proteins of the Bcl-2 family. Furthermore, the expression of HBV-X variants of both subgenotypes induced autophagy of human tumoral hepatocytes. In conclusion, HBV-X variants of the Latin American HBV F genotype promotes human hepatocytes death by the induction of apoptosis and autophagy. The results of this work describe some of the molecular mechanisms by which HBV-X variants contribute to the pathogenesis of liver diseases in the infected liver and help to the biological characterization of genotype F, responsible of the majority of HBV infections in Argentina.


title: Political Intrusions into the International Health Regulations Treaty and Its Impact on Management of Rapidly Emerging Zoonotic Pandemics: What History Tells Us

text: For a large number of health care providers world-wide, the coronavirus disease 2019 (COVID-19) pandemic is their first experience in population-based care. In past decades, lower population densities, infectious disease outbreaks, epidemics, and pandemics were rare and driven almost exclusively by natural disasters, predatory animals, and war. In the early 1900s, Sir William Osler first advanced the knowledge of zoonotic diseases that are spread from reservoir animals to human animals. Once rare, they now make up 71% or more of new diseases. Globally, zoonotic spread occurs for many reasons. Because the human population has grown in numbers and density, the spread of these diseases accelerated though rapid unsustainable urbanization, biodiversity loss, and climate change. Furthermore, they are exacerbated by an increasing number of vulnerable populations suffering from chronic deficiencies in food, water, and energy. The World Health Organization (WHO) and its International Health Regulation (IHR) Treaty, organized to manage population-based diseases such as Influenza, severe acute respiratory syndrome (SARS), H1N1, Middle East respiratory syndrome (MERS), HIV, and Ebola, have failed to meet population-based expectations. In part, this is due to influence from powerful political donors, which has become most evident in the current COVID-19 pandemic. The global community can no longer tolerate an ineffectual and passive international response system, nor tolerate the self-serving political interference that authoritarian regimes and others have exercised over the WHO. In a highly integrated globalized world, both the WHO with its IHR Treaty have the potential to become one of the most effective mechanisms for crisis response and risk reduction world-wide. Practitioners and health decision-makers must break their silence and advocate for a stronger treaty, a return of the WHO’s singular global authority, and support highly coordinated population-based management. As Osler recognized, his concept of “one medicine, one health” defines what global public health is today.


title: Oral mucosa lesions in COVID‐19

text: SARS‐CoV‐2 marks a new era in the medical field. The literature has outlined several signs and symptoms of COVID‐19 (Lake, 2020), but there are some manifestations not yet confirmed or not entirely described. There have been reported several dermatological conditions associated with COVID‐19: rash, urticaria and chickenpox‐like vesicles (Recalcati, 2020) and studies on cutaneous manifestations of COVID‐19 have been announced (Fernandez‐Nieto et al., 2020). The main path of COVID‐19 transmission is through droplets (The Chinese Preventive Medicine Association, 2020) from the oral cavity. This is why dental professionals are widely exposed to be infected, but they could also be the first ones to identify SARS‐CoV‐2 positive patients. Carreras‐Presas et al. published a paper presenting three case reports describing oral mucosa vesiculobullous lesions developed by COVID‐19 positive or suspected to be positive patients.


title: Emerging infectious disease outbreaks: Old lessons and new challenges for obstetrician-gynecologists

text: Objective The purpose of this study was to summarize 3 recent high-profile infectious disease threats that have affected the United States: severe acute respiratory syndrome, West Nile virus, and anthrax. Study design A systematic review was conducted with the use of Medline searches, searches of the Centers for Disease Control and Prevention website, and review by experts at the Centers for Disease Control and Prevention. Results The 3 emerging infectious diseases pose very different threats: Severe acute respiratory syndrome is a newly identified pathogen that caused an international pandemic; the West Nile virus investigation involved an old pathogen that was identified in a new location; and the anthrax attacks involved the intentional introduction of a pathogen. Conclusion All 3 outbreaks highlight the importance of obstetrician-gynecologists keeping current with new information as it emerges. In this global environment, it is likely that novel disease threats will continue to emerge in the United States.


title: Trypanosomiasis in an Australian little red flying fox (Pteropus scapulatus)

text: CASE REPORT: An adult female Australian little red flying fox (Pteropus scapulatus) presented with icterus and anaemia. Examination of a blood smear revealed numerous trypanosomes 20.4–30.8 µm long with tapered ends. Necropsy and histological findings were consistent with trypanosome infection of lymphoid tissue and intravascular haemolysis. Sequence and phylogenetic analysis demonstrated this trypanosome species to be genetically distinct and most similar to Trypanosoma minasense and Trypanosoma rangeli (with a genetic distance of 1% at the 18S rRNA locus for both). CONCLUSION: To the authors’ knowledge this is the first report of a trypanosome infection associated with clinical disease in bats.


title: Antigenicity Analysis of Different Regions of the Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein

text: Background: The widespread threat of severe acute respiratory syndrome (SARS) to human health has made urgent the development of fast and accurate analytical methods for its early diagnosis and a safe and efficient antiviral vaccine for preventive use. For this purpose, we investigated the antigenicity of different regions of the SARS coronavirus (SARS-CoV) nucleocapsid (N) protein. Methods: The cDNA for full-length N protein and its various regions from the SARS-CoV was cloned and expressed in Escherichia coli. After purification, all of the protein fragments were printed on glass slides to fabricate a protein microarray and then probed with the sera from SARS patients to determine the reactivity of these protein fragments. Results: The full-length protein and two other fragments reacted with all 52 sera tested. Four important regions with possible epitopes were identified and named as EP1 (amino acids 51–71), EP2 (134–208), EP3 (249–273), and EP4 (349–422), respectively. EP2 and EP4 possessed linear epitopes, whereas EP1 and EP2 were able to form conformational epitopes that could react with most (>80%) of the tested sera. EP3 and EP4 also formed conformational epitopes, and antibodies against these epitopes existed in all 52 of the sera tested. Conclusion: The N protein is a highly immunogenic protein of the SARS-CoV. Conformational epitopes are important for this protein, and antigenicity of the COOH terminus is higher than that of the NH(2) terminus. The N protein is a potential diagnostic antigen and vaccine candidate for SARS-CoV.


title: Chapter 99 Ocular Mucosal Immunity

text: Abstract Mucosal immunity defends the ocular surface against antigenic challenge and microbial invasion. The principal effector site is the lacrimal gland, where immunoglobulin A (IgA) antibodies are produced. Nasal-associated lymphoid tissue and posterior cervical lymph nodes function as major inductive sites for tear IgA responses. Neural connections and systemic hormones maintain the integrity and function of the ocular surface. Neuroenzyme activities in the lacrimal gland are influenced by ocular infections, leading to reduced expression of acetylcholine and modulation of receptors on acinar cells and on plasma cells, thereby decreasing fluid and immunoglobulin secretion. T lymphocyte-dependent responses result in production of interleukin-4 in lacrimal glands, thereby influencing cholinergic enzyme activity affecting immune processes and lacrimal physiology. Furthermore, neuropeptides released into lymphoid structures or inflamed tissues are chemotactic for antigen-presenting cells and affect their interactions with T cells. Thus, in developing therapeutic approaches for treating dry-eye conditions and vaccination strategies to elicit protective ocular mucosal immune responses, the entire lacrimal functional unit should be considered.


Symptomatic COVID-19 Infection in Eye Professionals in Wuhan China


title: Differential domain structure stability of the severe acute respiratory syndrome coronavirus papain-like protease

text: Abstract Papain-like protease (PLpro) from severe acute respiratory syndrome (SARS) coronavirus is one of the two proteases involved in the proteolytic processing of the virion polyproteins. In addition, PLpro shows significant in vitro deubiquitinating and de-ISGylating activities. All these findings demonstrated the multifunctional nature of the PLpro. Here we report the sensitivity of PLpro to denaturant urea. An increase in urea concentration induced a reversible biphasic unfolding of the enzyme. Differently, the unfolding of the catalytic triad region located within the palm and thumb domains followed a monophasic unfolding curve. Further observations suggest that the zinc-binding domain may start to unfold during the first transition. An 80% lost of its enzymatic activity at a urea concentration lower than 1M showed a close correlation with unfolding of the zinc-binding domain. The enzyme was also characterized in terms of hydrophobicity and size-and-shape distribution. We have demonstrated that PLpro displayed differential domain structure stability and molten globule state in its folding. These studies will not only assist in our understanding of the folding of this viral enzyme, but also that of other deubiquitinating enzymes with a similar scaffold.


title: The need for neurologists in the care of COVID‐19 patients

text: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulting in severe acute respiratory syndrome in a substantial number of patients. Approximately 5% to 10% of patients need intensive care unit (ICU) admission and mechanical ventilation [1]. The primary symptoms of COVID-19 include fever, dry cough and fatigue [2]. However, a recent report from Shandong, China, disclosed that a subset of patients did not suffer from respiratory symptoms but had neurologic signs and symptoms [3]. Moreover, in a retrospective study from Wuhan, China, neurologic symptoms were observed in 36.4% of the hospitalized patients with COVID-19 infection and pertained to both the central and peripheral nervous system [4].


title: Characteristics of COVID-19 infection in Beijing

text: Abstract Background Since the first case of a novel coronavirus (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Beijing. We analyzed the data of 262 confirmed cases to determine the clinical and epidemiological characteristics of COVID-19 in Beijing. Methods We collected patients who were transferred by Beijing Emergency Medical Service to the designated hospitals. The information on demographic, epidemiological, clinical, laboratory test for the COVID-19 virus, diagnostic classification, cluster case and outcome were obtained. Furthermore we compared the characteristics between severe and common confirmed cases which including mild cases, no-pneumonia cases and asymptomatic cases, and we also compared the features between COVID-19 and 2003 SARS. Findings By Feb 10, 2020, 262 patients were transferred from the hospitals across Beijing to the designated hospitals for special treatment of the COVID-19 infected by Beijing emergency medical service. Among of 262 patients, 46 (17.6%) were severe cases, 216 (82.4%) were common cases, which including 192 (73.3%) mild cases, 11(4.2%) non-pneumonia cases and 13 (5.0%) asymptomatic cases respectively. The median age of patients was 47.5 years old and 48.5% were male. 192 (73.3%) patients were residents of Beijing, 50 (26.0%) of which had been to Wuhan, 116 (60.4%) had close contact with confirmed cases, 21 (10.9%) had no contact history. The most common symptoms at the onset of illness were fever (82.1%), cough (45.8%), fatigue (26.3%), dyspnea (6.9%) and headache (6.5%). The median incubation period was 6.7 days, the interval time from between illness onset and seeing a doctor was 4.5 days. As of Feb 10, 17.2% patients have discharged and 81.7% patients remain in hospital in our study, the fatality of COVID-19 infection in Beijing was 0.9%. Interpretation On the basis of this study, we provided the ratio of the COVID-19 infection on the severe cases to the mild, asymptomatic and non-pneumonia cases in Beijing. Population was generally susceptible, and with a relatively low fatality rate. The measures to prevent transmission was very successful at early stage, the next steps on the COVID-19 infection should be focused on early isolation of patients and quarantine for close contacts in families and communities in Beijing. Funding Beijing Municipal Science and Technology Commission and Ministry of Science and Technology.


docid: tfkhptdg

title: Why are pregnant women susceptible to COVID-19? An immunological viewpoint

text: Abstract The 2019 novel coronavirus disease (COVID-19) was first detected in December 2019 and became epidemic in Wuhan, Hubei Province, China. COVID-19 has been rapidly spreading out in China and all over the world. The virus causing COVID-19, SARS-CoV-2 has been known to be genetically similar to severe acute respiratory syndrome coronavirus (SARS-CoV) but distinct from it. Clinical manifestation of COVID-19 can be characterized by mild upper respiratory tract infection, lower respiratory tract infection involving non-life threatening pneumonia, and life-threatening pneumonia with acute respiratory distress syndrome. It affects all age groups, including newborns, to the elders. Particularly, pregnant women may be more susceptible to COVID-19 since pregnant women, in general, are vulnerable to respiratory infection. In pregnant women with COVID-19, there is no evidence for vertical transmission of the virus, but an increased prevalence of preterm deliveries has been noticed. The COVID-19 may alter immune responses at the maternal-fetal interface, and affect the well-being of mothers and infants. In this review, we focused on the reason why pregnant women are more susceptible to COVID-19 and the potential maternal and fetal complications from an immunological viewpoint.


Fatal Pulmonary Thromboembolism in SARS-CoV-2-Infection


title: Secretory Nanoparticles of Neospora caninum Profilin-Fused with the Transmembrane Domain of GP64 from Silkworm Hemolymph

text: Neosporosis, which is caused by Neospora caninum, is a well-known disease in the veterinary field. Infections in pregnant cattle lead to abortion via transplacental (congenitally from mother to fetus) transmission. In this study, a N. caninum profilin (NcPROF), was expressed in silkworm larvae by recombinant Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid and was purified from the hemolymph. Three NcPROF constructs were investigated, native NcPROF fused with an N-terminal PA tag (PA-NcPROF), PA-NcPROF fused with the signal sequence of bombyxin from B. mori (bx-PA-NcPROF), and bx-PA-NcPROF with additional C-terminal transmembrane and cytoplasmic domains of GP64 from BmNPV (bx-PA-NcPROF-GP64TM). All recombinant proteins were observed extra- and intracellularly in cultured Bm5 cells and silkworm larvae. The bx-PA-NcPROF-GP64TM was partly abnormally secreted, even though it has the transmembrane domain, and only it was pelleted by ultracentrifugation, but PA-NcPROF and bx-PA-NcPROF were not. Additionally, bx-PA-NcPROF-GP64TM was successfully purified from silkworm hemolymph by anti-PA agarose beads while PA-NcPROF and bx-PA-NcPROF were not. The purified bx-PA-NcPROF-GP64TM protein bound to its receptor, mouse Toll-like receptor 11 (TLR-11), and formed unique nanoparticles. These results suggest that profilin fused with GP64TM was secreted as a nanoparticle with binding affinity to its receptor and this nanoparticle formation is advantageous for the development of vaccines to N. caninum.


title: Rhinoviruses

text: Rhinovirus is the major cause of common colds in humans. For many years, common colds were considered a trivial disease, but more recent evidence suggests that the many serotypes of rhinovirus are responsible for triggering the development of acute viral otitis media and sinusitis, exacerbation of asthma in children and adults, and exacerbation of chronic bronchitis in patients with chronic obstructive pulmonary disease. In addition to improved symptomatic treatment of colds, new treatment strategies are needed to reduce the morbidity of rhinovirus infections. Further understanding of the pathogenesis of rhinovirus infection in the ear, sinus, and lower airways is warranted.


title: Kingdom-agnostic Metagenomics and the Importance of Complete Characterization of Enteric Microbial Communities

text: Advanced sequencing techniques have shown that bacteria are not the only complex and important microbes in the human intestine. Non-bacterial organisms, particularly the virome and the mycobiome, are important regulators of intestinal immunity and inflammation. The virome is mucosal and systemic; it can alter the host response to bacteria and interact with host genes and bacteria to contribute to disease pathogenesis. The human mycobiome is also complex and can contribute to intestinal inflammation. We review what has recently been learned about the non-bacterial and non-archaeal microbes in the gastrointestinal tract, discussing their potential effects on health and disease and analytical approaches for their study. Studies of associations between the microbiome and intestinal pathology should incorporate kingdom-agnostic approaches if we are to fully understand intestinal health and disease.


title: The ubiquitous role of ubiquitin in the DNA damage response

text: Abstract Protein ubiquitylation has emerged as an important regulatory mechanism that impacts almost every aspect of the DNA damage response. In this review, we discuss how DNA repair and checkpoint pathways utilize the diversity offered by the ubiquitin conjugation system to modulate the response to genotoxic lesions in space and time. In particular, we will highlight recent work done on the regulation of DNA double-strand breaks signalling and repair by the RNF8/RNF168 E3 ubiquitin ligases, the Fanconi anemia pathway and the role of protein degradation in the enforcement and termination of checkpoint signalling. We also discuss the various functions of deubiquitylating enzymes in these processes along with potential avenues for exploiting the ubiquitin conjugation/deconjugation system for therapeutic purposes.


title: A unified personal protective equipment ensemble for clinical response to possible high consequence infectious diseases: A consensus document on behalf of the HCID programme

text: Summary The importance of appropriate personal protective equipment (PPE) as a component of healthcare worker (HCW) protection was highlighted during the Ebola virus disease (EVD) outbreak in West Africa. The large number of HCW deaths in Africa was in part due to lack of resources or prior training in PPE usage. As part of the Ebola legacy, the High Consequence Infectious Disease (HCID) programme was initiated by NHS England and Public Health England (PHE) to improve preparedness for Ebola and other infections that not only endanger the life of the patient, but also pose particular dangers to HCWs. A systematic review identified national standardisation of PPE protocols as a priority, but recognised that a lack of safety data limited the ability to mandate any one protocol. A simulation-based exercise was developed to assess the safety of PPE ensembles in use in the UK during first assessment of a patient with a possible HCID. A mannequin was adapted to expose volunteer HCWs to synthetic bodily fluids (vomit, sweat, diarrhoea and cough), each with a different coloured fluorescent tracer, invisible other than under ultraviolet (UV) light. After exposure, HCWs were examined under UV lights to locate fluorescent contamination, and were screened again after removing PPE (doffing) to detect any personal contamination. The exercise was videoed, allowing retrospective analysis of contamination events and user errors. The simulation testing identified significant HCW contamination events after doffing, related to protocol failure or complications in PPE doffing, providing conclusive evidence that improvements could be made. At a workshop with an expert stakeholder group, the data were examined and a unified PPE ensemble agreed. This ensemble was then tested in the same simulation exercise and no evidence of any HCW contamination was seen after doffing. Following further review by the working group, a consensus agreement has been reached and a unified ‘HCID assessment PPE’ ensemble, with accompanying donning and doffing protocols, is presented here.


title: Structural basis of sialidase in complex with geranylated flavonoids as potent natural inhibitors

text: Sialidase catalyzes the removal of a terminal sialic acid from glycoconjugates and plays a pivotal role in nutrition, cellular interactions and pathogenesis mediating various infectious diseases including cholera, influenza and sepsis. An array of antiviral sialidase agents have been developed and are commercially available, such as zanamivir and oseltamivir for treating influenza. However, the development of bacterial sialidase inhibitors has been much less successful. Here, natural polyphenolic geranylated flavonoids which show significant inhibitory effects against Cp-NanI, a sialidase from Clostridium perfringens, are reported. This bacterium causes various gastrointestinal diseases. The crystal structure of the Cp-NanI catalytic domain in complex with the best inhibitor, diplacone, is also presented. This structure explains how diplacone generates a stable enzyme–inhibitor complex. These results provide a structural framework for understanding the interaction between sialidase and natural flavonoids, which are promising scaffolds on which to discover new anti-sialidase agents.


title: Possible Role of Aerosol Transmission in a Hospital Outbreak of Influenza

text: Background. We examined the role of aerosol transmission of influenza in an acute ward setting. Methods. We investigated a seasonal influenza A outbreak that occurred in our general medical ward (with open bay ward layout) in 2008. Clinical and epidemiological information was collected in real time during the outbreak. Spatiotemporal analysis was performed to estimate the infection risk among patients. Airflow measurements were conducted, and concentrations of hypothetical virus-laden aerosols at different ward locations were estimated using computational fluid dynamics modeling. Results. Nine inpatients were infected with an identical strain of influenza A/H3N2 virus. With reference to the index patient's location, the attack rate was 20.0% and 22.2% in the “same” and “adjacent” bays, respectively, but 0% in the “distant” bay (P=.04). Temporally, the risk of being infected was highest on the day when noninvasive ventilation was used in the index patient; multivariate logistic regression revealed an odds ratio of 14.9 (95% confidence interval, 1.7–131.3; P=.015). A simultaneous, directional indoor airflow blown from the “same” bay toward the “adjacent” bay was found; it was inadvertently created by an unopposed air jet from a separate air purifier placed next to the index patient's bed. Computational fluid dynamics modeling revealed that the dispersal pattern of aerosols originated from the index patient coincided with the bed locations of affected patients. Conclusions. Our findings suggest a possible role of aerosol transmission of influenza in an acute ward setting. Source and engineering controls, such as avoiding aerosol generation and improving ventilation design, may warrant consideration to prevent nosocomial outbreaks.


title: Epigenetic and epitranscriptomic regulation of viral replication

text: Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. However, viruses have evolved countermeasures that prevent the epigenetic silencing of their genes during lytic replication, and they can also take advantage of epigenetic silencing to establish latent infections. By contrast, the various covalent modifications added to RNAs, termed epitranscriptomic modifications, can positively regulate mRNA translation and/or stability, and both DNA and RNA viruses have evolved to utilize epitranscriptomic modifications as a means to maximize viral gene expression. As a consequence, both chromatin and RNA modifications could serve as novel targets for the development of antivirals. In this Review, we discuss how host epigenetic and epitranscriptomic processes regulate viral gene expression at the levels of chromatin and RNA function, respectively, and explore how viruses modify, avoid or utilize these processes in order to regulate viral gene expression.


title: Experience of 16 years and its associated challenges in the Field Epidemiology Training Program in Korea

text: OBJECTIVES: The field epidemiologist system of South Korea, which employs public health doctors who are relatively more readily available, was created in 1999 to ensure a ready supply of experts for epidemiological investigations and enable an effective response for new and reemerging infectious diseases. However, the 2015 outbreak of Middle East Respiratory Syndrome revealed limitations in the existing systems of management of field epidemiologists and communicable diseases. METHODS: The present study aims to evaluate data on current states, administrative reports, and other literature on the field epidemiologist system that has been in place in South Korea for 16 years since 1999 and to suggest appropriate future improvements in this system. RESULTS: By suggesting methods to evaluate the field epidemiologist system and training programs and by suggesting ways for the Korea Centers for Disease Control and Prevention to conduct evaluations on its own, the present study provides supporting evidence for improvement of systems for training of experts in epidemiological investigations. Moreover, based on the findings, this study also suggests methods to systematically train experts in communicable diseases management and a sustainable system to establish the basis of and develop strategies for a systematic and phased management of field epidemiologist training programs. CONCLUSIONS: The present study suggests the possibility of establishing dedicated training facilities, revising the guidelines on training and improvement of the competency of public health experts, while not limiting the scope of application to communicable diseases.


title: International HRM insights for navigating the COVID-19 pandemic: Implications for future research and practice

text: We show the relevance of extant international business (IB) research, and more specifically work on international human resources management (IHRM), to address COVID-19 pandemic challenges. Decision-makers in multinational enterprises have undertaken various types of actions to alleviate the impacts of the pandemic. In most cases these actions relate in some way to managing distance and to rethinking boundaries, whether at the macro- or firm-levels. Managing distance and rethinking boundaries have been the primary focus of much IB research since the IB field was established as a legitimate area of academic inquiry. The pandemic has led to increased cross-border distance problems (e.g., as the result of travel bans and reduced international mobility), and often also to new intra-firm distancing challenges imposed upon previously co-located employees. Prior IHRM research has highlighted the difficulties presented by distance, in terms of employee selection, training, support, health and safety, as well as leadership and virtual collaboration. Much of this thinking is applicable to solve pandemic-related distance challenges. The present, extreme cases of requisite physical distancing need not imply equivalent increases in psychological distance, and also offer firms some insight into the unanticipated benefits of a virtual workforce – a type of workforce that, quite possibly, will influence the ‘new normal’ of the post-COVID world. Extant IHRM research does offer actionable insight for today, but outstanding knowledge gaps remain. Looking ahead, we offer three domains for future IHRM research: managing under uncertainty, facilitating international and even global work, and redefining organizational performance.


title: A universal microarray for detection of SARS coronavirus

text: Abstract Severe acute respiratory syndrome (SARS) is caused by the SARS coronavirus (SARS-CoV). There are many point mutations among SARS-CoV genome sequences. Previous studies suggested that the mutations are correlated closely with the SARS epidemic. It was found that the bases of six nucleotide positions (nt9404, nt9479, nt19838, nt21721, nt22222 and nt27827) with high-mutation rate have an important relationship with the SARS epidemic. For viral detection as well as genotyping, a universal microarray system was developed that combines RT-PCR and ligase detection reaction (LDR). The Zip Codes attached covalently to a slide remain constant and their complementary Zip Codes (cZip Codes) can be used for tagging target sequence, making the microarrays universal. The discriminating oligonucleotides contain on the 5′ end “cZip Codes” that are used to direct LDR product to specific Zip Codes attached covalently to a slide. Since Zip Codes have no homology to either the target sequence or to other sequences in the genomes of both human host and SARS-CoV, there was no false signal due to mismatch hybridizations. 20 samples assayed with the universal microarray were confirmed by DNA sequencing, demonstrating that this microarray system is a promising diagnostic tool for detection and genotyping of the SARS-CoV.


Chronic Liver Disease and COVID‐19: Alcohol Use Disorder/Alcohol‐Associated Liver Disease, Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis, Autoimmune Liver Disease, and Compensated Cirrhosis


title: Structural basis for human coronavirus attachment to sialic acid receptors

text: Coronaviruses cause respiratory tract infections in humans and outbreaks of deadly pneumonia worldwide. Infections are initiated by the transmembrane spike (S) glycoprotein, which binds to host receptors and fuses the viral and cellular membranes. To understand the molecular basis of coronavirus attachment to oligosaccharide receptors, we determined cryo-EM structures of coronavirus OC43 S glycoprotein trimer in isolation and in complex with a 9-O-acetylated sialic acid. We demonstrate that the ligand binds with fast kinetics to a surface-exposed groove and interactions at the identified site are essential for S-mediated viral entry into host cells, but free monosaccharide did not trigger fusogenic conformational changes. The receptor-interacting site is conserved in all coronavirus S glycoproteins that engage 9-O-acetyl-sialogycans, with an architecture similar to the ligand-binding pockets of coronavirus hemagglutinin esterases and influenza virus C/D hemagglutinin-esterase-fusion glycoproteins. Our results demonstrate these viruses evolved similar strategies to engage sialoglycans at the surface of target cells.


title: Coast-to-coast spread of SARS-CoV-2 in the United States revealed by genomic epidemiology

text: Since its emergence and detection in Wuhan, China in late 2019, the novel coronavirus SARS-CoV-2 has spread to nearly every country around the world, resulting in hundreds of thousands of infections to date. The virus was first detected in the Pacific Northwest region of the United States in January, 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the U.S., we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated impacts of federal travel restrictions. This study provides evidence for widespread, sustained transmission of SARS-CoV-2 within the U.S. and highlights the critical need for local surveillance.


title: Chest CT for detecting COVID-19: a systematic review and meta-analysis of diagnostic accuracy

text: OBJECTIVE: The purpose of this article was to perform a systematic review and meta-analysis regarding the diagnostic test accuracy of chest CT for detecting coronavirus disease 2019 (COVID-19). METHODS: PubMed, Embase, Web of Science, and CNKI were searched up to March 12, 2020. We included studies providing information regarding diagnostic test accuracy of chest CT for COVID-19 detection. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity were pooled. RESULTS: Sixteen studies (n = 3186 patients) were included. The risks of bias in all studies were moderate in general. Pooled sensitivity was 92% (95% CI = 86–96%), and two studies reported specificity (25% [95% CI = 22–30%] and 33% [95% CI = 23–44%], respectively). There was substantial heterogeneity according to Cochran’s Q test (p < 0.01) and Higgins I(2) heterogeneity index (96% for sensitivity). After dividing the studies into two groups based on the study site, we found that the sensitivity of chest CT was great in Wuhan (the most affected city by the epidemic) and the sensitivity values were very close to each other (97%, 96%, and 99%, respectively). In the regions other than Wuhan, the sensitivity varied from 61 to 98%. CONCLUSION: Chest CT offers the great sensitivity for detecting COVID-19, especially in a region with severe epidemic situation. However, the specificity is low. In the context of emergency disease control, chest CT provides a fast, convenient, and effective method to early recognize suspicious cases and might contribute to confine epidemic. KEY POINTS: • Chest CT has a high sensitivity for detecting COVID-19, especially in a region with severe epidemic, which is helpful to early recognize suspicious cases and might contribute to confine epidemic.


title: Fatal outcome of human coronavirus NL63 infection despite successful viral elimination by IFN‐alpha in a patient with newly diagnosed ALL

text: INTRODUCTION: Human coronavirus NL63 (HCoV‐NL63) is one of four common human respiratory coronaviruses. Despite high incidence, HCoV infections are grossly understudied. We here report a case of HCoV infection in a leukemia patient with fatal ARDS despite successful virus elimination by pegylated interferon‐alpha (PEG‐IFN‐α). CASE: The 27‐year‐old female pre‐T‐ALL patient was treated according to the German‐Multicenter Trial for Adult ALL protocol. No relevant infectious complications were seen until day 35 when the neutropenic patient developed fever without any clinical focus. Antibiotic prophylaxis was switched to meropenem. The patient deteriorated rapidly with respiratory failure due to ARDS. Anti‐infectious therapy was escalated to additional linezolid and liposomal amphotericine‐B. BAL revealed a significant viral load of HCoV‐NL63. Based on successful application of PEG‐IFN against the related SARS coronavirus in animal experiments, a single injection of 180 μg PEG‐IFN‐α2b was applied. Despite immediate initiation of treatment and elimination of virus in subsequent tests, the progressive lung failure led to death 7 d after onset of fever with massive lung bleeding as a consequence of diffuse alveolar hemorrhage. CONCLUSION: This report emphasizes the fatal consequences of common respiratory virus infections in immunocompromised patients. HCoV‐NL63 replication can be reduced by treatment with peg‐IFN if diagnosed early.


title: Rapid approach to identify an unrecognized viral agent

text: Abstract For epidemic control, rapid identification and characterization of the responsible unknown agent are crucial. To address this critical question, a method was developed for virus discovery based on a flexible nested-PCR subtraction hybridization. As a positive control, we used hepatitis C virus as a hypothetical unrecognized virus and “discover” it in the sample. Using template-switching universal long-PCR to produce large quantities of cDNA, our nested-PCR-based subtractive hybridization coupled with a single-strand deletion technology removed most of the common cDNA. Following subtraction hybridization, a cDNA library was constructed and displayed by differential reverse dot blot hybridization. This new genomic subtraction hybridization method will be ideally suited to identify rapidly any previously unrecognized viral agent.


title: Pharmaceutical patents: reconciling the human right to health with the incentive to invent

text: In developed countries that protect core aspects of the fundamental human right to the highest attainable standard of health, how does that right intersect with intellectual property rights? Here, the human rights implication of providing access to all cancer drugs recommended by experts in a developed country is considered in the context of conflict between the incentive to invent and the rights of others to access medicines. Effective incentives to innovate in developed countries can lead to global improvements in access to medicine if the intellectual property system is calibrated to permit this. This depends partly on the usefulness of compulsory licensing and alternative mechanisms facilitating global access to drugs. This review considers tensions between fundamental rights to access essential medicines and rights of the inventor and investors, including the pharmaceutical industry.


title: The successful use of extra-corporeal membrane oxygenation in the management of a pregnant woman with severe H1N1 2009 influenza complicated by pneumonitis and adult respiratory distress syndrome

text: Abstract We report a case of H1N1 2009 influenza A, in a previously fit woman at 24weeks of gestation, who presented atypically with abdominal pain. The infection was complicated by severe respiratory failure and acute respiratory distress syndrome, requiring ventilatory support, including extra-corporeal membrane oxygenation (ECMO). This was one of the first cases of severe H1N1 disease presenting in the UK. Use of extra-corporeal membrane oxygenation for the complications of H1N1 resulted in full maternal recovery and subsequent delivery of a healthy infant.


title: Only 7% of the variation in feed efficiency in veal calves can be predicted from variation in feeding motivation, digestion, metabolism, immunology, and behavioral traits in early life

text: ABSTRACT High interindividual variation in growth performance is commonly observed in veal calf production and appears to depend on milk replacer (MR) composition. Our first objective was to examine whether variation in growth performance in healthy veal calves can be predicted from early life characterization of these calves. Our second objective was to determine whether these predictions differ between calves that are fed a high- or low-lactose MR in later life. A total of 180 male Holstein-Friesian calves arrived at the facilities at 17 ± 3.4 d of age, and blood samples were collected before the first feeding. Subsequently, calves were characterized in the following 9 wk (period 1) using targeted challenges related to traits within each of 5 categories: feeding motivation, digestion, postabsorptive metabolism, behavior and stress, and immunology. In period 2 (wk 10–26), 130 calves were equally divided over 2 MR treatments: a control MR that contained lactose as the only carbohydrate source and a low-lactose MR in which 51% of the lactose was isocalorically replaced by glucose, fructose, and glycerol (2:1:2 ratio). Relations between early life characteristics and growth performance in later life were assessed in 117 clinically healthy calves. Average daily gain (ADG) in period 2 tended to be greater for control calves (1,292 ± 111 g/d) than for calves receiving the low-lactose MR (1,267 ± 103 g/d). Observations in period 1 were clustered per category using principal component analysis, and the resulting principal components were used to predict performance in period 2 using multiple regression procedures. Variation in observations in period 1 predicted 17% of variation in ADG in period 2. However, this was mainly related to variation in solid feed refusals. When ADG was adjusted to equal solid feed intake, only 7% of the variation in standardized ADG in period 2, in fact reflecting feed efficiency, could be explained by early life measurements. This indicates that >90% of the variation in feed efficiency in later life could not be explained by early life characterization of the calves. It is speculated that variation in health status explains a substantial portion of variation in feed efficiency in later life. Significant relations between fasting plasma glucose concentrations, fecal pH, drinking speed, and plasma natural antibodies in early life (i.e., not exposed to the lactose replacer) and feed efficiency in later life depended on MR composition. These measurements are therefore potential tools for screening calves in early life on their ability to cope with MR varying in lactose content.


title: Infections Caused by Influenza Viruses Among Children in Poland During the 2017/18 Epidemic Season

text: Influenza is an infectious disease that is a threat to both children and adults. The most effective way to prevent infections among children is seasonal vaccination in every epidemic season, which is recommended from the age of 6 months onward. This study is a report of the prevalence of influenza infection in the population of children up to the age of 14 years and of the type of influenza virus involved during the 2017/18 epidemic season in Poland. We found that influenza A and B viruses co-dominated in the season. Among the influenza A viruses, A/H1N1/ pdm09 subtype was a more frequent source of infection than A/H3N2/ subtype. In addition, the prevalence of infection was re-analyzed in children stratified into the age groups of 0–4, 5–9, and 10–14 years old. We found a relation between the age of a child and the type of influenza virus causing infection. The youngest children under 4 years were the most vulnerable to both influenza and influenza-like infections; the former caused mostly by influenza A and the latter by RSV. In contradistinction, influenza B dominated in the oldest children aged 10–14 and RSV infections were not present in this age group. The characteristics of influenza viruses may however vary on the seasonal basis.


title: Perceptions of postoutbreak management by management and healthcare workers of a Middle East respiratory syndrome outbreak in a tertiary care hospital: a qualitative study

text: OBJECTIVES: This study examines perceptions of the operational and organisational management of a major outbreak of Middle East Respiratory Syndrome (MERS) caused by a novel coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia (KSA). Perspectives were sought from key decision-makers and clinical staff about the factors perceived to promote and inhibit effective and rapid control of the outbreak. SETTING: A large teaching tertiary healthcare centre in KSA; the outbreak lasted 6 weeks from June 2015. PARTICIPANTS: Data were collected via individual and focus group interviews with 28 key informant participants (9 management decision-makers and 19 frontline healthcare workers). DESIGN: We used qualitative methods of process evaluation to examine perceptions of the outbreak and the factors contributing to, or detracting from successful management. Data were analysed using qualitative thematic content analysis. RESULTS: Five themes and 15 subthemes were found. The themes were related to: (1) the high stress of the outbreak, (2) factors perceived to contribute to outbreak occurrence, (3) factors perceived to contribute to success of outbreak control, (4) factors inhibiting outbreak control and (5) long-term institutional gains in response to the outbreak management. CONCLUSION: Management of the MERS-CoV outbreak at King Abdulaziz Medical City-Riyadh was widely recognised by staff as a serious outbreak of local and national significance. While the outbreak was controlled successfully in 6 weeks, progress in management was inhibited by a lack of institutional readiness to implement infection control (IC) measures and reduce patient flow, low staff morale and high anxiety. Effective management was promoted by greater involvement of all staff in sharing learning and knowledge of the outbreak, developing trust and teamwork and harnessing collective leadership. Future major IC crises could be improved via measures to strengthen these areas, better coordination of media management and proactive staff counselling and support.


title: Multiple Contact Dates and SARS Incubation Periods

text: Many severe acute respiratory syndrome (SARS) patients have multiple possible incubation periods due to multiple contact dates. Multiple contact dates cannot be used in standard statistical analytic techniques, however. I present a simple spreadsheet-based method that uses multiple contact dates to calculate the possible incubation periods of SARS.


Viral abundance and its public health implications


Viral pathogenesis and immune control


Salt Poisoning as a Cause of Morbidity and Mortality in Neonatal Dairy Calves


title: Forty Years of Canine Vaccination

text: During the last 40 years vaccines have been developed that have greatly reduced the incidence of infectious diseases of dogs. In general, modified live products have been superior to inactivated vaccines for dogs. It can be expected that recombinant and/or DNA vaccines may dominate the market in the future. Although most vaccines on the market are safe and efficacious, there have been exceptions where disease was induced by vaccination or dogs were not protected. The failure of protection may in part be due to variations in individual vaccine batches. Only potency tests but not efficacy tests are required, which may not be sufficient. For example, a virus titer in a vaccine may be meaningless if the minimum protective dose is not known. Overattenuated virus (e.g., CDV-Ond or parvovirus in cat cells) may have a high titer in tissue culture but is not immunogenic. The question of frequency of vaccination of dogs should be addressed. Annual revaccinations for CDV, CPV, and CAV are probably not needed. However, it would be desirable to collect more data to support less frequent vaccinations. Annual immunization for bacterial diseases such as kennel cough, Lyme disease, and leptospirosis should continue. It also would be desirable to develop more oro/nasal vaccines, perhaps combined with newly developed vectors that are less likely to induce undesirable side effects that may be seen after parenteral vaccination. Finally a word of warning against homeopathic "nosodes" to replace tested canine vaccines. They will appear highly effective as long as the majority of dogs remain vaccinated. As soon as a nonvaccinated dog population is large enough to allow virulent agents to spread, disease outbreaks will occur and we will be back where we began 40 years ago.


title: Microstructure, pathophysiology and potential therapeutics of COVID‐19: A comprehensive review

text: There have been over 7 million cases and almost 413,372 deaths globally due to the novel coronavirus (2019‐nCoV) associated disease COVID‐19, as of June 11, 2020. Phylogenetic analysis suggests that there is a common source for these infections. The overall sequence similarities between the spike protein of 2019‐nCoV and that of SARS‐CoV are known to be around 76‐78% and 73‐76% for whole protein and receptor‐binding domain (RBD), respectively. Thus, they have the potential to serve as drug and/ or vaccine candidate. However, the individual response against 2019‐nCoV differs due to genetic variations in the human population. Understanding the variations in Angiotensin‐converting enzyme 2 (ACE2) and human leukocyte antigen (HLA) that may affect the severity of 2019‐nCoV infection could help in identifying individuals at higher risk from the COVID‐19. A number of potential drugs/vaccines as well as antibody/cytokine‐based therapeutics are running in various developmental stages of preclinical/clinical trials against SARS‐CoV, MERS‐CoV and 2019‐nCoV with substantial cross‐reactivity, which may be used against COVID‐19. For diagnosis, reverse transcription polymerase chain reaction (RT‐PCR) is the gold standard test for initial diagnosis of COVID‐19. Kit based on serological tests are also recommended for investigating the spread of COVID‐19 but it is challenging due to antibodies cross‐reactivity. This review comprehensively summarizes the recent reports available regarding the host‐pathogen interaction, morphological and genomic structure of the virus, and the diagnostic techniques as well as available and potential therapeutics against COVID‐19. This article is protected by copyright. All rights reserved.


title: The role of antigen-presenting cells in filoviral hemorrhagic fever: gaps in current knowledge

text: The filoviruses, ebolavirus (EBOV) and marburgvirus (MARV), are highly lethal zoonotic agents of concern as emerging pathogens and potential bioweapons. Antigen-presenting cells (APCs), particularly macrophages and dendritic cells, are targets of filovirus infection in vivo. Infection of these cell types has been proposed to contribute to the inflammation, activation of coagulation cascades and ineffective immune responses characteristic of filovirus hemorrhagic fever. However, many aspects of filovirus-APC interactions remain to be clarified. Among the unanswered questions: What determines the ability of filoviruses to replicate in different APC subsets? What are the cellular signaling pathways that sense infection and lead to production of copious quantities of cytokines, chemokines and tissue factor? What are the mechanisms by which innate antiviral responses are disabled by these viruses, and how may these mechanisms contribute to inadequate adaptive immunity? A better understanding of these issues will clarify the pathogenesis of filoviral hemorrhagic fever and provide new avenues for development of therapeutics.


title: A Lego®-like swappable fluidic module for bio-chem applications

text: Abstract A Lego®-like swappable fluidic module (SFM) is proposed in this research. We designed and fabricated selected modular fluidic components, including functional and auxiliary types that can be effortlessly swapped and integrated into a variety of modular devices to rapidly assemble a fully-portable, disposable fluidic system. In practice, an integrated SFM uses finger-operated, electricity-free pumps to deliver fluids. Using a swirling mechanism, the vortex mixer can rapidly mix two liquids in a one-shot mixing event. We demonstrate the successful application of this SFM in several microfluidic applications, such as the synthesis of gold nanoparticles (AuNPs) from chloroauric acid (HAuCl4), and nucleic acid amplification from the Hepatitis B virus (HBV) with a capillary convective polymerase chain reaction (ccPCR).


title: Non-pharmaceutical interventions for the prevention of respiratory tract infections during Hajj pilgrimage

text: Summary Overcrowding during the yearly Hajj mass gatherings is associated with increased risk of spreading infectious diseases, particularly respiratory diseases. Non-pharmaceutical interventions (e.g., hand hygiene, wearing face masks, social distancing) are known to reduce the spread of respiratory viruses from person to person and are therefore recommended to pilgrims by public health agencies. The implementation of effective public health policies and recommendations involves evaluating the adherence to and effectiveness of these measures in the specific context of the Hajj. This review summarizes the evidence related to the effectiveness of non-pharmaceutical interventions in preventing the spread of respiratory infectious diseases during the Hajj. Overall, although hand hygiene compliance is high among pilgrims, face mask use and social distancing remain difficult challenges. Data about the effectiveness of these measures at the Hajj are limited, and results are contradictory, highlighting the need for future large-scale studies.


title: Elucidating the Interaction of CF Airway Epithelial Cells and Rhinovirus: Using the Host-Pathogen Relationship to Identify Future Therapeutic Strategies

text: Chronic lung disease remains the primary cause of mortality in cystic fibrosis (CF). Growing evidence suggests respiratory viral infections are often more severe in CF compared to healthy peers and contributes to pulmonary exacerbations (PEx) and deterioration of lung function. Rhinovirus is the most prevalent respiratory virus detected, particularly during exacerbations in children with CF <5 years old. However, even though rhinoviral infections are likely to be one of the factors initiating the onset of CF lung disease, there is no effective targeted treatment. A better understanding of the innate immune responses by CF airway epithelial cells, the primary site of infection for viruses, is needed to identify why viral infections are more severe in CF. The aim of this review is to present the clinical impact of virus infection in both young children and adults with CF, focusing on rhinovirus infection. Previous in vitro and in vivo investigations looking at the mechanisms behind virus infection will also be summarized. The review will finish on the potential of transcriptomics to elucidate the host-pathogen responses by CF airway cells to viral infection and identify novel therapeutic targets.


title: CoV3D: A database of high resolution coronavirus protein structures

text: The SARS-CoV-2 virus is the cause of the current COVID-19 pandemic, and exemplifies the general threat to global health posed by coronaviruses. The urgent need for effective vaccines and therapies is leading to a rapid rise in the number of high resolution structures of SARS-CoV-2 proteins that collectively reveal a map of virus vulnerabilities. To assist structure-based design of vaccines and therapeutics against SARS-CoV-2 and other coronaviruses, we developed CoV3D, a database and molecular viewer of SARS-CoV-2 and other coronavirus protein structures updated weekly. CoV3D annotates structures of coronavirus proteins and their complexes with antibodies, receptors, and small molecules. Additionally, CoV3D provides information on spike glycoprotein sequence variability and polymorphisms, and maps these features onto the spike structure in the integrated molecular viewer. In order to further aid structure-based design and analysis, CoV3D includes viewable and downloadable spike glycoprotein structures with modeled glycosylation from Rosetta. CoV3D is available at: https://cov3d.ibbr.umd.edu.


title: Locked nucleic acid (LNA): High affinity targeting of RNA for diagnostics and therapeutics

text: Locked nucleic acid (LNA) is a nucleic acid analogue containing one or more LNA nucleotide monomers with a bicyclic furanose unit locked in an RNA mimicking sugar conformation. This conformational restriction results in unprecedented hybridization affinity towards complementary single stranded RNA and thus, makes LNA uniquely suited for mimicking RNA structures and sequence specific targeting of RNA in vitro or in vivo. The focus of this paper is on LNA-antisense, LNA-modified siRNA (siLNA), and detection and analysis of microRNAs by LNA-modified oligonucleotide probes. Section editors: Steve Gullans – RxGen, Inc., New Haven, CT, USA Robert Zivin – Johnson and Johnson, New Brunswick, NJ, USA


title: The Heart in COVID19: Primary Target or Secondary Bystander?

text: Summary: In the throes of the current COVID-19 pandemic, interest has burgeoned in the cardiovascular complications of this virulent viral infection. As troponin, a biomarker of cardiac injury, often rises in hospitalized patients, its interpretation and actionability require careful consideration. Fulminant myocarditis due to direct viral infection can certainly occur, but patients with increased oxygen demands due to tachycardia and fever, and reduced oxygen delivery due to hypotension and hypoxemia can cause myocardial injury indirectly. Cytokines released during the acute infection can elicit activation of cells within pre-existing atherosclerotic lesions, augmenting thrombotic risk and risk of ischemic syndromes. Moreover, microvascular activation by cytokines can cause not only myocardial injury but harm other organ systems commonly involved in COVID-19 infections including the kidneys. Dealing with the immense challenge of COVID-19 disease, confronted with severely ill patients in dire straits with virtually no rigorous evidence base to guide our therapy, we must call upon our clinical skills and judgment. These touchstones can help guide us in selecting patients who might benefit from the advanced imaging and invasive procedures that present enormous logistical challenges in the current context. Lacking a robust evidence base, pathophysiologic reasoning can help guide our choices of therapy for individual clinical scenarios. We must exercise caution and extreme humility, as often plausible interventions fail when tested rigorously. But act today we must, and understanding the multiplicity of mechanisms of myocardial injury in COVID-19 infection will help us meet our mission unsupported by the comfort of strong data.


title: Objective olfactory evaluation of self‐reported loss of smell in a case series of 86 COVID‐19 patients

text: OBJECTIVE: To investigate olfactory dysfunction (OD) in patients with mild coronavirus disease 2019 (COVID‐19) through patient‐reported outcome questionnaires and objective psychophysical testing. METHODS: COVID‐19 patients with self‐reported sudden‐onset OD were recruited. Epidemiological and clinical data were collected. Nasal complaints were evaluated with the sinonasal outcome‐22. Subjective olfactory and gustatory status was evaluated with the National Health and Nutrition Examination Survey. Objective OD was evaluated using psychophysical tests. RESULTS: Eighty‐six patients completed the study. The most common symptoms were fatigue (72.9%), headache (60.0%), nasal obstruction (58.6%), and postnasal drip (48.6%). Total loss of smell was self‐reported by 61.4% of patients. Objective olfactory testings identified 41 anosmic (47.7%), 12 hyposmic (14.0%), and 33 normosmic (38.3%) patients. There was no correlation between the objective test results and subjective reports of nasal obstruction or postnasal drip. CONCLUSION: A significant proportion of COVID‐19 patients reporting OD do not have OD on objective testing.


title: Adaptation of the Bangla Version of the COVID-19 Anxiety Scale

text: The Coronavirus Anxiety Scale (CAS) is among the first few published screening tools for assessing dysfunctional anxiety induced by the current COVID-19 pandemic. The CAS was translated into the Bangla language following the International Test Commission’s guidelines for this adaptation study and placed in an online survey (N = 737, with a mean age of 26.55 (SD = 7.166 years) to assess the psychometric properties of the Bangla version of the scale. Results suggested that all items had a good item discrimination index and single-factor structure with good factor loadings. The CAS Bangla version was found to have good internal consistency reliabilities, test-retest reliability, and composite reliability (≥ 0.7). The measurement invariance suggested invariances across age groups and gender. The CAS Bangla version showed a high correlation to the anxiety subscale of the short form of the Depression Anxiety Stress Scale (DASS-21) and a moderate correlation to the depression subscale of the DASS-21 and the COVID-19 Worry Scale. This validation of a Bangla CAS scale would be helpful for mental health practitioners to assess pandemic anxiety among the Bangladeshi people.


title: Leukoencephalopathy and cerebral edema as the presenting manifestations of SLE in an ANA-negative adolescent female: a case report and review of literature

text: BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with various clinical manifestations involving multiple organ systems. Neuropsychiatric manifestations of SLE have been associated with increased morbidity and mortality, thus it is important to recognize and diagnose the disease entity and treat early. When neuropsychiatric symptoms are involved, typically there are many other systemic features to aid in the diagnosis of SLE. Many autoantibodies have been discovered and are used to help diagnose SLE. The antibody present in most cases of pediatric SLE, as well as in many other rheumatic diseases, is the nonspecific antinuclear antibody (ANA). The ANA is a commonly used screening tool by primary care physicians when evaluating a patient with a possible rheumatic disorder. However, a small subset of SLE patients, 1–5%, present with a negative ANA, and it is important to keep SLE on the differential diagnosis in specific instances when a thorough infectious, metabolic and neurological workup has been completed and proven to be inconclusive. CASE PRESENTATION: This case involves a Hispanic adolescent female with a negative ANA who presented with diffuse cerebral edema secondary to leukoencephalopathy due to SLE with central nervous system involvement. She was normotensive on presentation and relatively symptom free aside from headache. She had an extensive workup while inpatient involving metabolic, infectious disease, rheumatology, and neurology prior to obtaining the diagnosis of SLE. She was treated with cyclophosphamide and rituximab with appropriate disease response. CONCLUSIONS: A review of the literature revealed 12 cases with SLE presenting with or developing diffuse cerebral edema and/or leukoencephalopathy. Our patient’s case differs in that she was also ANA negative despite other autoantibody positivity. While she did have low complements and transient leukopenia, she did not present with other signs of organ involvement, which made the diagnosis of SLE with neuropsychiatric involvement quite challenging. We discuss the importance of keeping SLE on the differential diagnosis despite a negative ANA in complex cases after thorough workup has been unrevealing, and to consider initial screening with not only the ANA but also dsDNA and complements to avoid missed diagnoses.


title: Crystallization and preliminary X-ray characterization of aminopeptidase N from Escherichia coli

text: A recombinant form of aminopeptidase N (molecular weight 99 kDa) from Escherichia coli was crystallized by the hanging-drop vapour-diffusion method using ammonium sulfate as a precipitating agent. The crystals belong to the hexagonal space group P3(1)21, with unit-cell parameters a = b = 120.5, c = 171.0 Å. The crystals are most likely to contain one molecule in the asymmetric unit, with a V (M) value of 3.62 Å(3) Da(−1). Diffraction data were collected to 2.0 Å resolution using Cu Kα radiation from a rotating-anode X-ray generator.


The role of physical and rehabilitation medicine in the COVID-19 pandemic: the clinician's view


title: Plasma enteroglucagon and neurotensin levels in gnotobiotic calves infected with enteropathogenic and non-enteropathogenic viruses

text: Five gnotobiotic calves were each infected with five viruses. Each calf was inoculated with Coronavirus at seven days old, followed by astrovirus, Newbury agent, Parainfluenzavirus type 3 and rotavirus at intervals of two weeks. Three of the viruses were enteropathogenic (bovine Coronavirus, bovine calici-like virus and bovine rotavirus) and two were not (bovine astrovirus and Parainfluenzavirus type 3). Plasma levels of the peptide hormones enteroglucagon and neurotensin and faecal output were measured daily and xylose absorption was studied before and after each infection. A close correlation was found between a rise in plasma enteroglucagon and neurotensin and infection with enteropathogenic viruses. The three enteropathogenic viruses caused increased daily faecal output, and elevated plasma levels of enteroglucagon and neurotensin, while the non-enteropathogens did not. The calici-like virus and rotavirus but not the Coronavirus caused xylose malabsorption.