title: Provision of Continuous Dental Care for Oral Oncology Patients during & after COVID-19 Pandemic

text: • Role of Dental team in assessing the risk prior to oncotherapy. • Dentist’s role involving prevention and alleviation of pain in the oral cavity. • Disruption of dental care to all patients, including those receiving oncotherapy. • Dentists to operate tele-triage and plan video consultations. • Counseling and support via tele-dentistry to improve quality of life.


Limitación terapéutica en pacientes ancianos: Reflexiones a propósito del COVID19


title: Head and neck oncology during the COVID-19 pandemic: Reconsidering traditional treatment paradigms in light of new surgical and other multilevel risks

text: Abstract The COVID-19 pandemic demands reassessment of head and neck oncology treatment paradigms. Head and neck cancer (HNC) patients are generally at high-risk for COVID-19 infection and severe adverse outcomes. Further, there are new, multilevel COVID-19-specific risks to patients, surgeons, health care workers (HCWs), institutions and society. Urgent guidance in the delivery of safe, quality head and neck oncologic care is needed. Novel barriers to safe HNC surgery include: 1) imperfect presurgical screening for COVID-19; 2) prolonged SARS-CoV-2 aerosolization; 3) occurrence of multiple, potentially lengthy, aerosol generating procedures (AGPs) within a single surgery; 4) potential incompatibility of enhanced personal protective equipment (PPE) with routine operative equipment; 5) existential or anticipated PPE shortages. Additionally, novel, COVID-19-specific multilevel risks to HNC patients, HCWs and institutions, and society include: use of immunosuppressive therapy, nosocomial COVID-19 transmission, institutional COVID-19 outbreaks, and, at some locations, societal resource deficiencies requiring health care rationing. Traditional head and neck oncology doctrines require reassessment given the extraordinary COVID-19-specific risks of surgery. Emergent, comprehensive management of these novel, multilevel surgical risks are needed. Until these risks are managed, we temporarily favor nonsurgical therapy over surgery for most mucosal squamous cell carcinomas, wherein surgery and nonsurgical therapy are both first-line options. Where surgery is traditionally preferred, we recommend multidisciplinary evaluation of multilevel surgical-risks, discussion of possible alternative nonsurgical therapies and shared-decision-making with the patient. Where surgery remains indicated, we recommend judicious preoperative planning and development of COVID-19-specific perioperative protocols to maximize the safety and quality of surgical and oncologic care.


title: Introducing a model for communicable diseases surveillance: Cell phone surveillance (CPS)

text: BACKGROUND AND GOAL: Surveillance systems for communicable diseases are primarily passive in most countries, including Iran. Laboratory-based surveillance and use of cell phone surveillance may be a useful method. MATERIAL AND METHOD: We established a new model for gathering data directly from district laboratories to regional laboratories and from them to national manager of public health laboratories by using cell phone. We assessed the coverage of Mobile and Cell phone in the laboratory Technicians, and Directors of Public Health in 27 universities in Iran by a simple data collection form to evaluate the feasibility of this method. And then this method was piloted for the last Cholera out break in Iran in 2005. RESULT: From data of 27 universities with 184 cities, we gathered 769 data health directors’ mobile , total mobile penetrating rate, SMS users, and SMS penetrating rate was 57.9%, 77.1%, and 44.6% between Directors in Medical Universities of Iran and 54.5%, 54.9% and 29.9% in Directors of Laboratory. In the Cholera epidemic in Iran in summer 2005, CDC of MOH registered near 900 cases of cholera from 70000 rectal soap’s exam in whole of country. The median reporting interval was under one day. CONCLUSION: Although the advent of the cell phone will probably change the way in which surveillance is delivered by health system, further studies are warranted to evaluate this method for laboratory based surveillance of lethal infections.


title: The value of flexible bronchoscopy in pulmonary infections of immunosuppressed children

text: OBJECTIVES: To demonstrate the value of flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) when determining causes of lung infection in immunocompromised children; to investigate differences in causes and radiological features of lung infections following bone marrow transplantation (BMT) compared to other immunosuppressive conditions; to evaluate the reliability of radiological findings when predicting the pathogen. METHODS: We retrospectively evaluated 132 immunosuppressed children who underwent FB and BAL because pulmonary complications between January 1999 and May 2014 at the Hacettepe University Hospital Pediatric Pulmonology Unit. Two groups, Group I (n = 106) and Group II (n = 26), consisted of patients who had primary or secondary immunodeficiency and those who were immunosuppressed because BMT, respectively. Radiological findings before FB and macroscopic and microscopic findings of the procedure were evaluated. RESULTS: FB and BAL were diagnostic in 86/132 patients (65.1%) and the antimicrobial treatment changed for 75/132 patients (56.8%). The most common pathogen was bacteria (Streptococcus pneumoniae was the leading one). Bacteria were more frequent in Group I than Group II (P = .008). No significant difference in radiological findings between Groups I and II was found. Considering all patients, a significant association was detected between viral pathogens and radiologically interstitial infiltration and a ground‐glass appearance (P = .003). However, no significant association was detected between bacterial and fungal pathogens and the radiological findings. CONCLUSION: In immunosuppressed patients, FB and BAL should be evaluated early for clarifying the causative agents. Then, appropriate treatments can be utilised and the side effects and high cost of unnecessary treatment may be mitigated.


title: Determinants of Severity in Cancer Patients with COVID-19 Illness

text: New York State had 180,458 cases of SARS-CoV-2 and 9385 reported deaths as of April 10th, 2020. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher COVID-19 death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-19 disease4. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. Since March 10th, 2020 Memorial Sloan Kettering Cancer Center performed diagnostic testing for SARS-CoV-2 in symptomatic patients. Overall, 40% out of 423 patients with cancer were hospitalized for COVID-19 illness, 20% developed severe respiratory illness, including 9% that required mechanical ventilation, and 9% that died. On multivariate analysis, age [≥] 65 years and treatment with immune checkpoint inhibitors (ICI) within 90 days were predictors for hospitalization and severe disease, while receipt of chemotherapy within 30 days and major surgery were not. Overall, COVID-19 illness is associated with higher rates of hospitalization and severe outcomes in patients with cancer. Association between ICI and COVID-19 outcomes will need interrogation in tumor-specific cohorts.


title: SARS‐COV‐2 children transmission: the evidence is that today we do not have enough evidence

text: I have read with interest the review by Ludvigsson on the role of children as transmitters of the new coronavirus (SARS‐COV‐2). An in‐depth review of the current literature focused on 40 published articles and 7 non‐peer reviewed papers(1). All the papers included have been done under lockdown conditions. As a consequence, we should not ignore a main bias of this review(1). The main conclusion we can draw now is that under confined conditions, children are not the main drivers of the COVID‐19 pandemic. And “Confined" is not a normal situation.


title: Trends in DNA biosensors

text: Abstract Biosensors have witnessed an escalating interest nowadays, both in the research and commercial fields. Deoxyribonucleic acid (DNA) biosensors (genosensors) have been exploited for their inherent physico-chemical stability and suitability to discriminate different organism strains. The main principle of detection among genosensors relies on specific DNA hybridization, directly on the surface of a physical transducer. This review covers the main DNA immobilization techniques reported so far, new micro- and nanotechnological platforms for biosensing and the transduction mechanisms in genosensors. Clinical applications, in particular, demand large-scale and decentralized DNA testing. New schemes for DNA diagnosis include DNA chips and microfluidics, which couples DNA detection with sample pretreatment under in vivo-like hybridization conditions. Higher sensitivity and specificity may arise from nanoengineered structures, like carbon nanotubes (CNTs) and DNA/protein conjugates. A new platform for universal DNA biosensing is also presented, and its implications for the future of molecular diagnosis are argued.


title: Optimizing treatment of respiratory tract infections in nursing homes: Nurse-initiated polymerase chain reaction testing

text: Background Diagnostic testing using polymerase chain reaction (PCR) is infrequently initiated for diagnosis of respiratory tract infections (RTIs) in nursing homes. The objectives of this study were to determine the feasibility of implementing nurse-initiated PCR testing of respiratory specimens in nursing home settings and to compare antibiotic prescribing prior to and during the implementation. Methods This was a pragmatic, historically controlled study in 3 nursing homes (181 total beds) in Melbourne, Australia. Results The number of PCR tests of respiratory specimens (over 12 months) increased from 5 to 67 when nurses could initiate the tests. Residents with RTI symptoms had a virus identified by PCR in 50.7% of tests, including 14 positive for influenza. Six outbreaks were identified. When clustering was taken into consideration, incidence rates of antibiotic days of therapy did not change (incidence rate ratio = 0.94, 95% confidence interval, 0.25-3.35, P = .92) despite identification of more viral pathogens. Conclusions In nursing homes, nurse-initiated PCR testing of respiratory specimens is feasible and useful in terms of identifying the cause of many RTIs and outbreaks, and viruses are common in this context. However, the current study suggests the availability of these test results alone does not impact antibiotic prescribing.


No country for old men: five prevalent stereotypes affecting the life of the elderly


title: Low back pain revealing a primary small cell neuroendocrine carcinoma of the upper urinary tract: A case report and review of the literature

text: Small cell carcinoma of the upper urinary tract is very rare. Their aggressiveness and their poor prognosis make it grave. We report the management of a patient who consulted in the emergency room for low back pain and to whom the radiological and endoscopic assessments found a tumor of the upper urinary tract with lung, liver, bone and adrenal damage. Anatomopathological study of biopsies obtained by flexible ureteroscopy and percutaneous liver biopsy confirmed the diagnosis and the metastatic nature of secondary lesions.


title: Identification of correlated inter-residue interactions in protein complex based on the fragment molecular orbital method

text: A theoretical scheme to systematically describe correlated (network-like) interactions between molecular fragments is proposed within the framework of the fragment molecular orbital (FMO) method. The method is mathematically based on the singular value decomposition (SVD) of the inter-fragment interaction energy (IFIE) matrix obtained by the FMO calculation, and can be applied to a comprehensive description of protein-protein interactions in the context of molecular recognition. In the present study we apply the proposed method to a complex of measles virus hemagglutinin and human SLAM receptor, thus finding a usefulness for efficiently eliciting the correlated interactions among the amino-acid residues involved in the two proteins. Additionally, collective interaction networks by amino-acid residues important for mutation experiments can be clearly visualized.


In Coronazeiten


title: Isolation of a human monoclonal antibody specific for the receptor binding domain of SARS-CoV-2 using a competitive phage biopanning strategy

text: The infection of the novel coronavirus SARS-CoV-2 has caused more than 200,000 deaths, but no vaccine or therapeutic monoclonal antibody is currently available. SARS-CoV-2 relies on its spike protein, in particular the receptor binding domain (RBD), to bind human cell receptor angiotensin-converting enzyme 2 (ACE2) for viral entry, and thus targeting RBD holds the promise for preventing SARS-CoV-2 infection. In this work, a competitive biopanning strategy of a phage display antibody library was applied to screen blocking antibodies against RBD. High-affinity antibodies were enriched after the first round using a standard panning process in which RBD-His was immobilized as a bait. At the next two rounds, immobilized ACE2-Fc and free RBD-His were mixed with the enriched phage antibodies. Antibodies binding to RBD at epitopes different from ACE2-binding site were captured by the immobilized ACE2-Fc, forming a “sandwich” complex. Only antibodies competed with ACE2 can bind to the free RBD-His in the supernatant and be subsequently separated by the Ni-NTA magnetic beads. Top 1 lead from the competitive biopanning of our synthetic antibody library, Lib AB1, was produced as the full-length IgG1 format. It was proved to competitively block the binding of RBD to ACE2 and potently inhibit SARS-CoV-2 pseudovirus infection with IC(50) values of 12 nM. Nevertheless, top 1 lead from the standard biopanning can only bind to RBD in vitro, but not have the blocking or neutralization activity. Our strategy can efficiently isolate the blocking antibodies of RBD, and it would speed up the discovery of neutralizing antibodies against SARS-CoV-2.


In Response to COVID‐19 and the Otolaryngologist: Preliminary Evidence‐Based Review


title: Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors

text: Abstract Trifluoromethyl-β-amino alcohol 11 [(4S)-tert-butyl 4-amino-6,6,6-trifluoro-5-hydroxyhexanoate] was synthesized in five steps starting from Cbz-l-Glu-OH 5 where the key step involved the introduction of the trifluoromethyl (CF3) group to oxazolidinone 7, resulting in the formation of silyl ether 8 [(4S,5S)-benzyl 4-(2-(tert-butoxycarbonyl)ethyl)-5-(trifluoromethyl)-5-(trimethylsilyloxy)oxazolidine-3-carboxylate]. Compound 11 was then converted into four tri- and tetra-glutamic acid and glutamine peptides (1–4) possessing a CF3-ketone group that exhibited inhibitory activity against severe acute respiratory syndrome coronavirus protease (SARS-CoV 3CLpro).


title: Are the relative variation rates (RVRs) of energy consumption approximate in different cities for the same increase of ventilation rate?

text: Abstract This paper makes simulations on the annual heating and cooling energy consumption of four kinds of buildings under the climatic conditions of 19 background cities in China, USA and Europe when ventilation rates increase from 0 to 1.5vol/h, respectively by, CTM, DOE-2 and DeST-h. The simulation results by CTM show that the increments of annual heating and cooling may differ up to 10s of times or even more than 100 times in different cities for the same building with the same increase of ventilation rates, while the annual heating and cooling RVRs are both approximate in different cities. For the same building with the same increase of ventilation rate in the same city, its annual heating RVRs are far higher than its annual cooling RVRs. The above conclusion can be reached for any building whether with various envelopes or with different shape coefficients.


title: Lack of inflammatory gene expression in bats: a unique role for a transcription repressor

text: In recent years viruses similar to those that appear to cause no overt disease in bats have spilled-over to humans and other species causing serious disease. Since pathology in such diseases is often attributed to an over-active inflammatory response, we tested the hypothesis that bat cells respond to stimulation of their receptors for viral ligands with a strong antiviral response, but unlike in human cells, the inflammatory response is not overtly activated. We compared the response of human and bat cells to poly(I:C), a viral double-stranded RNA surrogate. We measured transcripts for several inflammatory, interferon and interferon stimulated genes using quantitative real-time PCR and observed that human and bat cells both, when stimulated with poly(I:C), contained higher levels of transcripts for interferon beta than unstimulated cells. In contrast, only human cells expressed robust amount of RNA for TNFα, a cell signaling protein involved in systemic inflammation. We examined the bat TNFα promoter and found a potential repressor (c-Rel) binding motif. We demonstrated that c-Rel binds to the putative c-Rel motif in the promoter and knocking down c-Rel transcripts significantly increased basal levels of TNFα transcripts. Our results suggest bats may have a unique mechanism to suppress inflammatory pathology.


title: “Differential risk of hospitalization among single virus infections causing influenza‐like illnesses”

text: BACKGROUND: Acute respiratory infections are a major cause of morbidity in children and are often caused by viruses. However, the relative severity of illness associated with different viruses is unclear. The objective of this study was to evaluate the risk of hospitalization from different viruses in children presenting with an influenza‐like illness (ILI). METHODS: Data from children 5 years old or younger participating in an ILI natural history study from April 2010 to March 2014 was analyzed. The adjusted odds ratio for hospitalization was estimated in children with infections caused by respiratory syncytial virus (RSV), metapneumovirus, bocavirus, parainfluenza viruses, rhinovirus/enterovirus, coronavirus, adenovirus, and influenza. RESULTS: A total of 1486 children (408 outpatients and 1078 inpatients) were included in this analysis. At least one virus was detected in 1227 (82.6%) patients. The most frequent viruses detected as single pathogens were RSV (n = 286), rhinovirus/enterovirus (n = 251), parainfluenza viruses (n = 104), and influenza A or B (n = 99). After controlling for potential confounders (age, sex, recruitment site, days from symptom onset to enrollment, and underlying illnesses), children with RSV and metapneumovirus infections showed a greater likelihood of hospitalization than those infected by parainfluenza viruses (OR 2.7 and 1.9, respectively), rhinovirus/enterovirus (OR 3.1 and 2.1, respectively), coronaviruses (OR 4.9 and 3.4, respectively), adenovirus (OR 4.6 and 3.2, respectively), and influenza (OR 6.3 and 4.4, respectively). CONCLUSIONS: Children presenting with ILI caused by RSV and metapneumovirus were at greatest risk for hospitalization, while children with rhinovirus/enterovirus, parainfluenza, coronavirus, adenovirus, and influenza were at lower risk of hospitalization.


Should we continue using laparoscopy amid the COVID‐19 pandemic?


title: Stress Induced Cardiomyopathy Precipitated by COVID-19 and Influenza A Co-Infection

text: Abstract Myocardial injury is associated with excess mortality in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections, but the mechanisms of injury are diverse. We describe a case of stress induced cardiomyopathy in the setting of SARS-CoV-2 and Influenza A coinfection.


title: Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a cause of severe respiratory infection in humans, specifically the elderly and people with comorbidities. The re-emergence of lethal coronaviruses calls for international collaboration to produce coronavirus vaccines, which are still lacking to date. Ongoing efforts to develop MERS-CoV vaccines should consider the different target populations (dromedary camels and humans) and the correlates of protection. Extending on our current knowledge of MERS, vaccination of dromedary camels to induce mucosal immunity could be a promising approach to diminish MERS-CoV transmission to humans. In addition, it is equally important to develop vaccines for humans that induce broader reactivity against various coronaviruses to be prepared for a potential next CoV outbreak.


title: Gene-silencing suppressors for high-level production of the HIV-1 entry inhibitor griffithsin in Nicotiana benthamiana

text: Abstract The exploration of emerging host organisms for the economic and efficient production of protein microbicides against HIV is urgently needed in resource-poor areas worldwide. In this study, the production of the novel HIV entry inhibitor candidate, griffithsin (GRFT), was investigated using Nicotiana benthamiana as the expression platform based on a non-viral vector. To increase the yield of recombinant GRFT, the RNA silencing defense mechanism of N. benthamiana was abolished by using three gene silencing suppressors. A transient expression system was used by transferring the GRFT gene, which encodes 122 amino acids, under the control of the enhanced CaMV 35S promoter. The presence of correctly assembled GRFT in transgenic leaves was confirmed using immunoglobulin-specific sandwich ELISA. The data demonstrated that the use of three gene silencing suppressors allowed the highest accumulation of GRFT, with a yield of 400 μg g−1 fresh weight, and this amount was reduced to 287 μg g−1 after purification, representing a recovery of 71.75%. The analysis also showed that the ability of GRFT expressed in N. benthamiana to bind to glycoprotein 120 is close to that of the GRFT protein purified from E. coli. Whole-cell assays using purified GRFT showed that our purified GRFT was potently active against HIV. This study provides the first high-level production of the HIV-1 entry inhibitor griffithsin with a non-viral expression system and illustrates the robustness of the co-agroinfiltration expression system improved through the use of three gene silencing suppressors.


title: Characterization and Clinical Course of 1000 Patients with COVID-19 in New York: retrospective case series

text: Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient floors, and intensive care units (ICUs). Design: Retrospective manual medical record review. Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19. Methods: We identified patients with a positive RT-SARS-CoV-2 PCR receiving care at NYP/CUIMC from March 1 through April 15. Patient data was manually abstracted from the electronic medical record. Main outcome measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, outcomes, and disposition. Results: Among the first 1000 patients with confirmed COVID-19, 151 patients were discharged from or died in the ED, 618 were admitted to the floor, and 231 were admitted or transferred to the ICU; 195 remained hospitalized and 172 had died in the hospital. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (62.9%). Compared to Chinese and Italian cohorts, hospitalized patients and ICU patients in particular had more baseline comorbidities including hypertension, diabetes, and obesity and higher rates of acute kidney injury (AKI) and dialysis. ICU patients were older and predominantly male (67.5%); 75.3% developed AKI and 31.2% required dialysis. Notably, of patients who required mechanical ventilation, only 5.9% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset. Patients in this large sample have more baseline comorbidities and more complications than previous Italian and Chinese cohorts.


title: Structure of the Respiratory Syncytial Virus Polymerase Complex

text: Summary Numerous interventions are in clinical development for respiratory syncytial virus (RSV) infection, including small molecules that target viral transcription and replication. These processes are catalyzed by a complex comprising the RNA-dependent RNA polymerase (L) and the tetrameric phosphoprotein (P). RSV P recruits multiple proteins to the polymerase complex and, with the exception of its oligomerization domain, is thought to be intrinsically disordered. Despite their critical roles in RSV transcription and replication, structures of L and P have remained elusive. Here, we describe the 3.2-Å cryo-EM structure of RSV L bound to tetrameric P. The structure reveals a striking tentacular arrangement of P, with each of the four monomers adopting a distinct conformation. The structure also rationalizes inhibitor escape mutants and mutations observed in live-attenuated vaccine candidates. These results provide a framework for determining the molecular underpinnings of RSV replication and transcription and should facilitate the design of effective RSV inhibitors.


title: Triiodothyronine for the treatment of critically ill patients with COVID-19 infection: A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: Tissue hypoxia is the main cause of multi-organ dysfunction in sepsis. However, effective pharmacological treatments to combat sepsis-induced tissue hypoxia are not available. Emerging experimental and clinical evidence reveals an evolutionary conserved action of thyroid hormone (TH) to adapt injured tissue to hypoxic conditions via its action on p38 MAPK, Akt signaling pathways. In addition, TH has favorable effects on the immune system and viral load in infected tissue. Non-Thyroid Illness Syndrome is common in sepsis, acute myocardial infarction and trauma and is associated with increased mortality. Thus, TH may be a novel treatment in the setting of critical illness due to viral infection in which hypoxia prevails. The present study aims to address the efficacy and safety of acute administration of triiodothyronine (T3) in critically ill COVID-19 infected patients requiring mechanical respiratory support or Extra Corporeal Membrane Oxygenation (ECMO). TRIAL DESIGN: This study is a phase II, parallel, 2-arm (1:1 ratio), multi-centre, prospective, randomized, double-blind, placebo controlled trial. PARTICIPANTS: Male and female patients aged over 18 years old who are diagnosed with pulmonary infection due to COVID-19, admitted to Intensive Care Unit and requiring mechanical ventilation or ECMO will be enrolled in this trial. Patients will be excluded in cases of pregnancy, severe systemic disease with life expectancy less than 6 months, participation in another trial of an investigational drug or device, corticosteroid and/or sympathomimetic use before initiation of treatment. All data will be collected in electronic CRF files. Participants will start to be recruited from the ICU center of “ATTIKO” University Hospital in Greece. We aim to include two more clinical sites in the trial one from Greece and one from Germany INTERVENTION AND COMPARATOR: Intervention: T3 Solution for injection 10 μg/ml. The dose administered will be 0.8g/kg i.v. bolus and will be followed by an infusion of 0.113g. kg-1.h-1 i.v. for 48 hours (therapeutic dose). After the first 48h, a maintenance dose will be administered corresponding to 50% of the therapeutic dose (0.057g. kg-1.h-1 i.v.). Drug administration will stop after successful weaning or end of follow up (maximum 30 days). Comparator: Placebo with composition and dosage identical apart from the active substance. MAIN OUTCOMES: The primary outcome assessed in the present study will be the percentage of patients successfully weaned after 30 days of follow-up. Successful weaning is defined as no requirement for ventilatory support after extubation (mechanical support) or support from ECMO for 48 hours. RANDOMISATION: An allocation sequence to one of the groups will be prepared by the Sponsor of the study. A 1:1 treatment allocation will be adopted. An electronic CRF will be used incorporating IWRS in order to assure proper randomization and unblinding in emergency cases. The representative of the sponsor will get a copy of randomization codes. The information of the randomization codes will then be locked in the database until the time at which an interim analysis or final analysis is performed. BLINDING (MASKING): Participants, caregivers, and all investigators assessing the outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size of 60 patients (that indicates 30 subjects for each group) will have 84% power to detect the estimated difference between the two study groups. The criterion for significance (alpha) has been set at 0.05 and the test is 2-tailed. TRIAL STATUS: Protocol number T3inj-02/ThySupport, version 03, May 11, 2020. The trial is not recruiting yet. The trial will start recruitment June 18(th) 2020. Estimated recruitment will finish June 18(th), 2021. TRIAL REGISTRATION: Triiodothyronine for the Treatment of Critically Ill Patients With COVID-19 Infection (Thy-Support), ClinicalTrials.gov Identifier: NCT04348513, date of trial registration: April 16, 2020, EudraCT Identifier: 2020-001623-13, date of trial registration: April 22, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Balancing aesthetic and conventional dermatology practice in the COVID‐19 era


title: Pneumomediastinum, pneumorrhachis and subcutaneous emphysema associated with viral infections: Report of three cases

text: Spontaneous pneumomediastinum is usually secondary to alveolar rupture in the pulmonary interstitium, associated with subcutaneous emphysema and occasionally with pneumothorax, but is rarely associated with pneumorrhachis. The leaked air into the pulmonary perivascular interstitium follows the path of least resistance from the mediastinum to the fascial planes of the neck. Air freely communicates via the neural foramina and collects in the epidural space. Pneumorrhachis is defined as the presence of air in the spinal canal, either in the intradural and/or extradural spaces. It is a very rare clinical entity and mostly asymptomatic, hence most probably underdiagnosed. Many pathological and physiological events can lead to alveolar rupture, and these clinical findings can be related to various, mainly traumatic and iatrogenic etiologies. Herein we report three cases of pneumomediastinum, subcutaneous emphysema, interstitial emphysema and pneumorrhachis in two cases, which were related to rhinovirus, human bocavirus and respiratory syncytial virus infection.


The political economy of the European Union


title: Virion Background and Efficiency of Virion Incorporation Determine Susceptibility of Simian Immunodeficiency Virus Env-Driven Viral Entry to Inhibition by IFITM Proteins

text: Interferon-induced transmembrane proteins (IFITMs) can inhibit the cellular entry of several enveloped viruses, including simian immunodeficiency virus (SIV). The blockade of SIV by IFITMs is isolate specific, raising the question of which parameters impact sensitivity to IFITM. We show that the virion context in which SIV-Env is presented and the efficiency of virion incorporation determine Env susceptibility to inhibition by IFITMs. Thus, determinants other than the nature of the envelope protein can impact the IFITM sensitivity of viral entry. IMPORTANCE The host cell-encoded IFITM proteins can block viral entry and are an important component of the innate defenses against viral infection. However, the determinants controlling whether a virus is susceptible to blockade by IFITM proteins are incompletely understood. Our study shows that the amount of envelope proteins incorporated into virions as well as the nature of the virion particle itself can impact the sensitivity of viral entry to IFITMs. These results show for the first time that determinants other than the viral envelope protein can impact sensitivity to IFITM and have implications for the interpretation of previously published data on inhibition of viruses by IFITM proteins. Moreover, our findings might help to define the mechanism underlying the antiviral activity of IFITM proteins.


title: Understanding nurses’ dual practice: a scoping review of what we know and what we still need to ask on nurses holding multiple jobs

text: BACKGROUND: Mounting evidence suggests that holding multiple concurrent jobs in public and private (dual practice) is common among health workers in low- as well as high-income countries. Nurses are world’s largest health professional workforce and a critical resource for achieving Universal Health Coverage. Nonetheless, little is known about nurses’ engagement with dual practice. METHODS: We conducted a scoping review of the literature on nurses’ dual practice with the objective of generating hypotheses on its nature and consequences, and define a research agenda on the phenomenon. The Arksey and O’Malley’s methodological steps were followed to develop the research questions, identify relevant studies, include/exclude studies, extract the data, and report the findings. PRISMA guidelines were additionally used to conduct the review and report on results. RESULTS: Of the initial 194 records identified, a total of 35 met the inclusion criteria for nurses’ dual practice; the vast majority (65%) were peer-reviewed publications, followed by nursing magazine publications (19%), reports, and doctoral dissertations. Twenty publications focused on high-income countries, 16 on low- or middle-income ones, and two had a multi country perspective. Although holding multiple jobs not always amounted to dual practice, several ways were found for public-sector nurses to engage concomitantly in public and private employments, in regulated as well as in informal, casual fashions. Some of these forms were reported as particularly prevalent, from over 50% in Australia, Canada, and the UK, to 28% in South Africa. The opportunity to increase a meagre salary, but also a dissatisfaction with the main job and the flexibility offered by multiple job-holding arrangements, were among the reported reasons for engaging in these practices. DISCUSSION AND CONCLUSIONS: Limited and mostly circumstantial evidence exists on nurses’ dual practice, with the few existing studies suggesting that the phenomenon is likely to be very common and carry implications for health systems and nurses’ welfare worldwide. We offer an agenda for future research to consolidate the existing evidence and to further explore nurses’ motivation; without a better understanding of nurse dual practice, this will continue to be a largely ‘hidden’ element in nursing workforce policy and practice, with an unclear impact on the delivery of care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12960-018-0276-x) contains supplementary material, which is available to authorized users.


title: RIG-I Like Receptors and Their Signaling Crosstalk in the Regulation of Antiviral Immunity

text: During virus infection, multiple immune signaling pathways are triggered, both within the host cell and bystander cells of an infected tissue. These pathways act in concert to mediate innate antiviral immunity and to initiate the inflammatory response against infection. The RIG-I-like receptor (RLR) family of pattern recognition receptors (PRRs) is a group of cytosolic RNA helicase proteins that can identify viral RNA as nonself via binding to pathogen associated molecular patter (PAMP) motifs within RNA ligands that accumulate during virus infection. This interaction then leads to triggering of an innate antiviral response within the infected cells through RLR induction of downstream effector molecules such as type I interferon (IFN) and other pro-inflammatory cytokines that serve to induce antiviral and inflammatory gene expression within the local tissue. Cellular regulation of RLR signaling is a critical process that can direct the outcome of infection and is essential for governance of the overall immune response and avoidance of immune toxicity. Mechanisms of positive and negative regulation of RLR signaling have been identified that include signaling crosstalk between RLR pathways and Nuclear Oligomerization Domain (NOD)-Like Receptor (NLR) pathways and Caspase networks. Furthermore, many viruses have evolved mechanisms to target these pathways to promote enhanced replication and spread within the host. These virus-host interactions therefore carry important consequences for host immunity and viral pathogenesis. Understanding the pivotal role of RLRs in immune regulation and signaling crosstalk in antiviral immunity may provide new insights into therapeutic strategies for the control of virus infection and immunity.


title: Prolonged SARS‐CoV‐2 shedding and mild course of COVID‐19 in a patient after recent heart transplantation

text: In the coronavirus disease 2019 (COVID‐19) pandemic, organ transplant recipients are considered to be at high risk for unfavorable outcome. However, in particular the role of immunosuppression in patients infected with SARS‐CoV‐2 remains undetermined. Here, we present a 62‐year old male COVID‐19 patient with recent heart transplantation who developed only mild symptoms, but had prolonged virus shedding, and summarize the available data on COVID‐19 in cardiac allograft recipients. Initially the patient presented with a transient episode of fever and sore throat but no other symptoms, in particular no cough or dyspnea at rest. After diagnosis, immunosuppression was continued unchanged. On day 7, temperature increased again with concurrent mild rise of CRP, IL‐6 and proBNP levels. Hydroxychloroquine was started and continued for 7 days. While the patient had no clinical symptoms anymore 20 days after initial presentation, virus culture of throat swabs on days 18 and 21 confirmed active virus replication and SARS‐CoV‐2 PCR remained positive on day 35 with copy numbers similar to the onset of infection. In conclusion, immunosuppression regimen in transplant recipients with mild COVID‐19 associated symptoms may be continued unchanged. However, it may contribute to delayed virus PCR conversion and thus possible prolonged infectivity.


COVID‐19 testing and the Soviet biowarfare project


title: Chapter 15 Health Technology, Quality, Law, and Ethics

text: Abstract Technology assessment capability is vital in determining health policy and priorities because science and technology changes occur rapidly and are essential for progress. Quality is promoted by high professional education and practice standards, accreditation by state and non governmental authorities for health provider institutions, public health departments as well as educational program for public health, health policy and health management. Quality is an ongoing challenge in health care and public health. New innovations and therapies change the nature of care and prevention, with important epidemic and epidemiologic effects. Adoption of new evidence based methods of prevention, diagnosis and therapy have and will continue to improve quality of life and longevity. Translation of scientific and technological advances into applied practice requires education of public health policy makers, and practitioners to be well trained to evaluate new evidence and keep up with rapidly changing capacity to address old and new challenges in public health. The context of public health is set in legal frameworks and ethical standards developed over many millennia, centuries and decades which need continuous revision in keeping with societal changes and norms. Law and ethics in public health reflect the societal values in the context of social, economic, demographic, epidemiologic and political changes, while facing new health challenges and new technologies. Health ethics needed to be reexamined in the light of medical participation in 20th century genocides in the name of racial purity and industrialized murder of millions in World War II. The Nuremberg Trials redefined ethics of health research and bioethics. Public health works to protect the population from illness and premature death, often with restrictions such as in cigarette advertisement and smoking. Failure to act in protection of public health can be unethical by denying best practices in health protection and health promotion.


title: In vitro diagnostics of coronavirus disease 2019: technologies and application

text: Abstract Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19.


title: Infidelity in the Time of COVID‐19

text: Infidelity occurs in approximately 25% of marriages and is associated with various negative consequences for individuals (e.g., depression, anxiety, posttraumatic stress), the couple relationship (e.g., financial loss, increased conflict and aggression), and the couple’s children (e.g., internalizing and externalizing behaviors). Infidelity is also one of the most frequently cited reasons for divorce. The increased stress brought on by the pandemic may be putting couples at an increased risk for experiencing infidelity and data collected during the pandemic have shown that people across the United States are engaging in behaviors that are associated with a high likelihood of experiencing infidelity. The negative consequences of infidelity are also likely to be exacerbated for couples during the pandemic due to the intersection with the social, emotional, and financial consequences of COVID‐19. Furthermore, couples are likely to experience disruptions and delays to the affair recovery process during the pandemic, which can negatively impact their ability to heal. Therefore, recommendations for navigating affair recovery during the pandemic, including adaptations for therapy, are also discussed.


title: The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection

text: In severe SARS-CoV-2 infections, emerging data including recent histopathological studies have emphasized the crucial role of endothelial cells (ECs) in vascular dysfunction, immunothrombosis, and inflammation. Histopathological studies have evidenced direct viral infection of ECs, endotheliitis with diffuse endothelial inflammation, and micro- and macrovascular thrombosis both in the venous and arterial circulations. Venous thrombotic events, particularly pulmonary embolism, with elevated D-dimer and coagulation activation are highly prevalent in COVID-19 patients. The pro-inflammatory cytokine storm, with elevated levels of interleukin-6 (IL-6), IL-2 receptor, and tumor necrosis factor-α, could also participate in endothelial dysfunction and leukocyte recruitment in the microvasculature. COVID-19-induced endotheliitis may explain the systemic impaired microcirculatory function in different organs in COVID-19 patients. Ongoing trials directly and indirectly target COVID-19-related endothelial dysfunctions: i.e., a virus-cell entry using recombinant angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS-2) blockade, coagulation activation, and immunomodulatory therapies, such as anti-IL-6 strategies. Studies focusing on endothelial dysfunction in COVID-19 patients are warranted as to decipher their precise role in severe SARS-CoV-2 infection and organ dysfunction and to identify targets for further interventions.


Mechanisms of virus persistence


title: Defining Protective Epitopes for COVID‐19 Vaccination Models

text: Recent papers in the Journal provide tangible avenues for COVID‐19 vaccine production as immunoreactive epitopes are brought to the forefront in these and many other emerging studies.(1,2) The development of a consistent predictable animal model of COVID‐19 infection is evidently also a welcome event for preliminary antiviral and vaccine assessments and surely brings us to another level of progression.(3) This article is protected by copyright. All rights reserved.


title: The matrix segment of the “Spanish flu” virus originated from intragenic recombination between avian and human influenza A viruses

text: The 1918 Spanish flu virus has claimed more than 50 million lives. However, the mechanism of its high pathogenicity remains elusive; and the origin of the virus is controversial. The matrix (M) segment regulates the replication of influenza A virus, thereby affecting its virulence and pathogenicity. This study found that the M segment of the Spanish flu virus is a recombinant chimera originating from avian influenza virus and human influenza virus. The unique mosaic M segment might confer the virus high replication capacity, showing that the recombination might play an important role in inducing high pathogenicity of the virus. In addition, this study also suggested that the NA and NS segments of the virus were generated by reassortment between mammalian and avian viruses. Direct phylogenetic evidence was also provided for its avian origin.


title: The severe acute respiratory syndrome: Impact on travel and tourism

text: Summary SARS and travel are intricately interlinked. Travelers belonged to those primarily affected in the early stages of the outbreak, travelers became vectors of the disease, and finally, travel and tourism themselves became the victims. The outbreak of SARS created international anxiety because of its novelty, its ease of transmission in certain settings, and the speed of its spread through jet travel, combined with extensive media coverage. The psychological impacts of SARS, coupled with travel restrictions imposed by various national and international authorities, have diminished international travel in 2003, far beyond the limitations to truly SARS hit areas. Governments and press, especially in non SARS affected areas, have been slow to strike the right balance between timely and frequent risk communication and placing risk in the proper context. Screening at airport entry points is costly, has a low yield and is not sufficient in itself. The low yield in detecting SARS is most likely due to a combination of factors, such as travel advisories which resulted in reduced travel to and from SARS affected areas, implementation of effective pre-departure screening at airports in SARS-hit countries, and a rapid decline in new cases at the time when screening was finally introduced. Rather than investing in airport screening measures to detect rare infectious diseases, investments should be used to strengthen screening and infection control capacities at points of entry into the healthcare system. If SARS reoccurs, the subsequent outbreak will be smaller and more easily contained if the lessons learnt from the recent epidemic are applied. Lessons learnt during the outbreak in relation to international travel will be discussed.


title: It's Not All in Your Head: Thoracic Manifestations of Neurologic Diseases and Disorders

text: Myriad conditions may affect both the neurologic system and the thorax, while other diseases primarily affecting the thorax may manifest with neurologic abnormalities. Correlation of signs, symptoms, and imaging findings in the neurological system with those in the thorax can help diagnose certain conditions and/or guide further diagnostic work-up and treatment. We will review and illustrate the imaging appearance of several systemic/neurological diseases with thoracic manifestations as well as discuss conditions in the thorax that can lead to neurologic symptoms.


title: COVID-19: Challenges and its consequences for rural health care in India

text: Abstract This commentary highlights the potential consequences of the COVID-19 pandemic for India’s rural population in India. The rural health care system is not adequate or prepared to contain COVID-19 transmission, especially in many densely populated northern Indian States because of the shortage of doctors, hospital beds, and equipment. The COVID-19 epidemic creates a special challenge due to the paucity of testing services, weak surveillance system and above all poor medical care. The impacts of this pandemic, and especially the lockdown strategy, are multi-dimensional. We argue for the need to take immediate steps to control the spread and aftereffects and to use this opportunity to strengthen and improve its primary health care system.


Santé publique


title: COVID-19: Pulse oximeters in the spotlight

text: From home to intensive care units, innovations in pulse oximetry are susceptible to improve the monitoring and management of patients developing acute respiratory failure, and particularly those with the coronavirus disease 2019 (COVID-19). They include self-monitoring of oxygen saturation (SpO(2)) from home, continuous wireless SpO(2) monitoring on hospital wards, and the integration of SpO(2) as the input variable for closed-loop oxygen administration systems. The analysis of the pulse oximetry waveform may help to quantify respiratory efforts and prevent intubation delays. Tracking changes in the peripheral perfusion index during a preload-modifying maneuver may be useful to predict preload responsiveness and rationalize fluid therapy.


title: A Systematic Review and Meta-Analysis Of Outcomes for Patients with COVID-19 and Acute Kidney Injury

text: INTRODUCTION: There is limited data on the association of kidney dysfunction with prognosis in COVID-19, and the extent to which acute kidney injury (AKI) predisposes patients to severe illness and inferior outcomes is unclear. We aim to assess the incidence of AKI among patients with COVID-19 and examine their associations with patient outcomes as reported in the available literature thus far. METHODS: We systematically searched MEDLINE, EMBASE, SCOPUS, and MedRxiv databases for full-text articles available in English published from December 1, 2019 to May 24, 2020. Clinical information was extracted and examined from 20 cohorts that met inclusion criteria, covering 13137 mostly hospitalized patients confirmed to have COVID-19. Two authors independently extracted study characteristics, results, outcomes, study-level risk of bias, and strength of evidence across studies. Neither reviewer was blind to journal titles, study authors, or institutions. RESULTS: Median age was 56 years, with 55% male patients. Approximately 43% of patients had severe COVID-19 infection, and approximately 11% died. Prevalence of AKI was 17%; 77% of patients with AKI experienced severe COVID-19 infection, and 52% died. AKI was associated with increased odds of death among COVID-19 patients (pooled odds ratio 15.27, 95% CI 4.82-48.36), although there was considerable heterogeneity across studies and among different regions in the world. Approximately 5% of all patients required use of renal replacement therapy (RRT) CONCLUSIONS: Kidney dysfunction is common among patients with COVID-19, and patients who develop AKI have inferior outcomes. Additional research into management and potential mechanisms of this association is needed.


title: Ventricular Arrhythmia Risk Based on Ethnicity in COVID-19 Patients on Hydroxychloroquine and Azithromycin Combination: Viewpoint

text: There are many reports available now, which are mostly observational or registry trial outcomes having varied results on coronavirus 2019 (COVID-19) patients put on hydroxychloroquine and azithromycin combination. Some are showing increased in-hospital mortality and ventricular arrhythmia increase, while some are showing overall benefit with significant viral RNA load reduction. Everyday things are getting more complicated with the publication of these different outcomes. This needs to be addressed.


title: Carbohydrate Moieties as Vaccine Candidates

text: Carbohydrate epitopes or glycotopes are structurally diverse, occur in a variety of chemical contexts, and are present on the surfaces of cells in the body and on the surfaces of pathogens. These various structures and modes of presentation affect how they are perceived and processed by the body and dictate the outcome of the immune response directed against them. This review focuses on mechanisms of carbohydrate immunity, with an emphasis on carbohydrate vaccines that have been or are being developed for protection against encapsulated bacterial pathogens. We discuss the cellular basis of carbohydrate immunity, newly identified glycotope processing pathways and recognition capabilities, and the synthetic and microarray technologies that are being developed that will permit new experimental approaches to carbohydrate vaccine development and the exploration of the interaction of the immune system with self and nonself glycans.


title: Maintaining high quality multidisciplinary pain medicine fellowship programs: Part I: Innovations in pain fellows’ education, research, applicant selection process, wellness and ACGME implementation during the Covid-19 pandemic

text: BACKGROUND: Pain fellowship programs are facing unique challenges during the COVID-19 pandemic. Restrictions from state governments and the Centers for Disease Control and Prevention have resulted in a rapidly changing and evolving learning environment for todays’ fellows. Innovative solutions must be sought to guarantee proper education is maintained and ensure the well-being of our trainees. METHODS: We assembled a panel of pain program directors who serve as officers/board members of the Association of Pain Program Directors to provide guidance and formulate recommendations to pain fellowship directors nationally. This guidance is based on reviewing current changes to Accreditation Council Graduate Medical Education (ACGME) and American Board Anesthesiology policies and best available evidence and expert opinion on use of remote educational activities, research endeavors, and trainee wellness. CONCLUSIONS: The country is in the midst of an unprecedented pandemic. The impact on pain management fellowships has been severe and will likely last for months, resulting in extraordinary challenges to the administration of pain fellowship programs and the education of our fellows. Understanding revisions in ACGME policies, use of technology to promote remote learning opportunities, and providing trainees with opportunities to alleviate their anxieties and encourage mental health are beneficial strategies to implement. Together, we can implement innovative solutions to help overcome these challenges.


title: Online Information Exchange and Anxiety Spread in the Early Stage of the Novel Coronavirus (COVID-19) Outbreak in South Korea: Structural Topic Model and Network Analysis

text: BACKGROUND: In case of a population-wide infectious disease outbreak, such as the novel coronavirus disease (COVID-19), people’s online activities could significantly affect public concerns and health behaviors due to difficulty in accessing credible information from reliable sources, which in turn causes people to seek necessary information on the web. Therefore, measuring and analyzing online health communication and public sentiment is essential for establishing effective and efficient disease control policies, especially in the early stage of an outbreak. OBJECTIVE: This study aimed to investigate the trends of online health communication, analyze the focus of people’s anxiety in the early stages of COVID-19, and evaluate the appropriateness of online information. METHODS: We collected 13,148 questions and 29,040 answers related to COVID-19 from Naver, the most popular Korean web portal (January 20, 2020, to March 2, 2020). Three main methods were used in this study: (1) the structural topic model was used to examine the topics in the online questions; (2) word network analysis was conducted to analyze the focus of people’s anxiety and worry in the questions; and (3) two medical doctors assessed the appropriateness of the answers to the questions, which were primarily related to people’s anxiety. RESULTS: A total of 50 topics and 6 cohesive topic communities were identified from the questions. Among them, topic community 4 (suspecting COVID-19 infection after developing a particular symptom) accounted for the largest portion of the questions. As the number of confirmed patients increased, the proportion of topics belonging to topic community 4 also increased. Additionally, the prolonged situation led to a slight increase in the proportion of topics related to job issues. People’s anxieties and worries were closely related with physical symptoms and self-protection methods. Although relatively appropriate to suspect physical symptoms, a high proportion of answers related to self-protection methods were assessed as misinformation or advertisements. CONCLUSIONS: Search activity for online information regarding the COVID-19 outbreak has been active. Many of the online questions were related to people’s anxieties and worries. A considerable portion of corresponding answers had false information or were advertisements. The study results could contribute reference information to various countries that need to monitor public anxiety and provide appropriate information in the early stage of an infectious disease outbreak, including COVID-19. Our research also contributes to developing methods for measuring public opinion and sentiment in an epidemic situation based on natural language data on the internet.


title: Ebola Virus: Sensationalism, Science, and Human Rights

text: Outbreaks of the filoviruses, Ebola and Marburg, usually garner immense public attention, often with a sensationalist bent in the lay press, focused on the apparently mysterious origins of the outbreak and the high mortality rates. The scientific community may present a more objective viewpoint, but usually with a rather technical focus on identifying epidemiological risk factors and experimental therapies and vaccines. Often lost in the discussion are the human rights elements that consistently underlie large outbreaks of these dangerous viruses.


title: SOCS proteins in infectious diseases of mammals

text: Abstract As for most biological processes, the immune response to microbial infections has to be tightly controlled to remain beneficial for the host. Inflammation is one of the major consequences of the host's immune response. For its orchestration, this process requires a fine-tuned interplay between interleukins, endothelial cells and various types of recruited immune cells. Suppressors of cytokine signalling (SOCS) proteins are crucially involved in the complex control of the inflammatory response through their actions on various signalling pathways including the JAK/STAT and NF-κB pathways. Due to their cytokine regulatory functions, they are frequent targets for exploitation by infectious agents trying to escape the host's immune response. This review article aims to summarize our current knowledge regarding SOCS family members in the different mammalian species studied so far, and to display their complex molecular interactions with microbial pathogens.


title: Assessing the Presence of Post-Traumatic Stress and Turnover Intention Among Nurses Post–Middle East Respiratory Syndrome Outbreak: The Importance of Supervisor Support

text: Background: South Korea faced the Middle East Respiratory Syndrome (MERS) outbreak for the first time in 2015, which resulted in 186 infected patients and 39 deaths. This study investigated the level of post-traumatic stress disorder (PTSD) and turnover intention, the relationship between PTSD and turnover intention, and the buffering effect of supervisor support among nurses post-MERS outbreak. Methods: In total, 300 nurses from three of 15 isolation hospitals in South Korea were invited to participate. We collected data pertaining to PTSD, turnover intention, supervisor support, work-related factors, and socio-demographic factors through a structured survey distributed to the nurses at the hospitals after the outbreak. For the statistical analyses, descriptive statistics and multiple regression were employed. Findings: Of the 147 participants, 33.3% were involved in the direct care of the infected patients, whereas 66.7% were involved in the direct care of the suspected patients. More than half (57.1%) of the nurses experienced PTSD, with 25.1% experienced full PTSD and 32.0% with moderate or some level of PTSD. The mean score of turnover intention was 16.3, with the score range of 4 to 20. The multiple regression analysis revealed that PTSD was positively associated with turnover intention, and supervisor support had a strong buffering effect. Conclusion/Application to Practice: These findings confirmed that after a fatal infectious disease outbreak like MERS, nurses experience high level of PTSD and show high intention to leave. Organizational strategies to help nurses to cope with stress and to prevent turnover intention, especially using supervisor support, would be beneficial.


title: Immunomodulatory and anti-SARS activities of Houttuynia cordata

text: Abstract Background Severe acute respiratory syndrome (SARS) is a life-threatening form of pneumonia caused by SARS coronavirus (SARS-CoV). From late 2002 to mid 2003, it infected more than 8000 people worldwide, of which a majority of cases were found in China. Owing to the absence of definitive therapeutic Western medicines, Houttuynia cordata Thunb. (Saururaceae) (HC) was shortlisted by Chinese scientists to tackle SARS problem as it is conventionally used to treat pneumonia. Aim of the study The present study aimed to explore the SARS-preventing mechanisms of HC in the immunological and anti-viral aspects. Results Results showed that HC water extract could stimulate the proliferation of mouse splenic lymphocytes significantly and dose-dependently. By flow cytometry, it was revealed that HC increased the proportion of CD4+ and CD8+ T cells. Moreover, it caused a significant increase in the secretion of IL-2 and IL-10 by mouse splenic lymphocytes. In the anti-viral aspect, HC exhibited significant inhibitory effects on SARS-CoV 3C-like protease (3CLpro) and RNA-dependent RNA polymerase (RdRp). On the other hand, oral acute toxicity test demonstrated that HC was non-toxic to laboratory animals following oral administration at 16g/kg. Conclusion The results of this study provided scientific data to support the efficient and safe use of HC to combat SARS.


title: Estimating the daily trend in the size of the COVID-19 infected population in Wuhan

text: BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has become a pandemic causing global health problem. We provide estimates of the daily trend in the size of the epidemic in Wuhan based on detailed information of 10 940 confirmed cases outside Hubei province. METHODS: In this modelling study, we first estimate the epidemic size in Wuhan from 10 January to 5 April 2020 with a newly proposed model, based on the confirmed cases outside Hubei province that left Wuhan by 23 January 2020 retrieved from official websites of provincial and municipal health commissions. Since some confirmed cases have no information on whether they visited Wuhan before, we adjust for these missing values. We then calculate the reporting rate in Wuhan from 20 January to 5 April 2020. Finally, we estimate the date when the first infected case occurred in Wuhan. RESULTS: We estimate the number of cases that should be reported in Wuhan by 10 January 2020, as 3229 (95% confidence interval [CI]: 3139–3321) and 51 273 (95% CI: 49 844–52 734) by 5 April 2020. The reporting rate has grown rapidly from 1.5% (95% CI: 1.5–1.6%) on 20 January 2020, to 39.1% (95% CI: 38.0–40.2%) on 11 February 2020, and increased to 71.4% (95% CI: 69.4–73.4%) on 13 February 2020, and reaches 97.6% (95% CI: 94.8–100.3%) on 5 April 2020. The date of first infection is estimated as 30 November 2019. CONCLUSIONS: In the early stage of COVID-19 outbreak, the testing capacity of Wuhan was insufficient. Clinical diagnosis could be a good complement to the method of confirmation at that time. The reporting rate is very close to 100% now and there are very few cases since 17 March 2020, which might suggest that Wuhan is able to accommodate all patients and the epidemic has been controlled.


title: Fibrinous pericarditis secondary to bacterial infection in a cat

text: A three-year-old spayed domestic short-haired cat presented for evaluation of weight loss, cardiomegaly and pleural effusion. Echocardiographic examination demonstrated a thickened pericardium with mild pericardial effusion and a large volume of pleural effusion characterized by exudate. Although the cat was treated with antibiotics, the clinical symptoms did not improve. The cat developed dyspnea and died on day 7. Necropsy revealed a large amount of modified transudates ascites, pleural effusion and markedly dilated pericardium. Histopathological examination revealed severe exudation of fibrin and granulation tissue in a thick layer of the epicardium. The cat was diagnosed with fibrinous pericarditis secondary to bacterial infection.


title: SARS-CoV-2 epidemiology and control, different scenarios for Turkey

text: BACKGROUND/AIM: Coronavirus Infectious Disease 2019 (COVID-19) is now a pandemic spreading in most countries including Turkey. MATERIALS AND METHODS: The current knowledge of COVID-19 and the virus causing it, SARS-CoV-2, was reviewed. The epidemiology and control in different countries was compared and the differences discussed. RESULTS: The population attack rates and case fatality rates vary from country to country with Lombardy in northern Italy reporting an attack rate in the general population of 0.37% compared to 0.004% in Hong Kong. The differences are caused by different testing strategies and reporting systems. CONCLUSION: Turkey is early in the outbreak. Different control strategies are available with South Korea, Hong Kong and Singapore being models to follow.


title: COVID-19 in Children: An Ample Review

text: The aim of this review was to describe the current knowledge about coronavirus disease 2019 (COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) in children, from epidemiological, clinical, and laboratory perspectives, including knowledge on the disease course, treatment, and prognosis. An extensive literature search was performed to identify papers on COVID-19 (SARS-CoV-2 infection) in children, published between January 1, 2020 and April 1, 2020. There were 44 relevant papers on COVID-19 in children. The results showed that COVID-19 occurs in 0.39–12.3% of children. Clinical signs and symptoms are comparable to those in adults, but milder forms and a large percentage of asymptomatic carriers are found among children. Elevated inflammatory markers are associated with complications and linked to various co-infections. Chest computed tomography (CT) scans in children revealed structural changes similar to those found in adults, with consolidations surrounded by halos being somewhat specific for children with COVID-19. The recommended treatment includes providing symptomatic therapy, with no specific drug recommendations for children. The prognosis is much better for children compared to adults. This review highlights that COVID-19 in children is similar to the disease in the adult population, but with particularities regarding clinical manifestations, laboratory test results, chest imaging, and treatment. The prognosis is much better for children compared to adults, but with the progression of the pandemic; the cases in children might change in the future.


title: Curing of HeLa cells persistently infected with equine arteritis virus by a peptide-conjugated morpholino oligomer

text: Abstract A significant consequence of equine arteritis virus (EAV) infection of horses is persistence of the virus in a variable percentage of infected stallions. We recently established an in vitro model of EAV persistence in cell culture for the purpose of furthering our understanding of EAV biology in general and viral persistence in the stallion in particular. In this study we investigated whether persistently infected HeLa cells could be cured of EAV infection by treatment with an antisense peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) designed to target the 5′-terminal region of the EAV genome. We found that persistently infected HeLa cells passaged three times in the presence of 5–10μM EAV-specific PPMO produced no detectable virus. The PPMO-cured HeLa cells were free of infectious virus, viral antigen and EAV RNA as measured by plaque assay, indirect immunofluorescence assay and RT-PCR, respectively. Furthermore, when re-challenged with EAV at several passages after discontinuation of PPMO treatments, PPMO-cured HeLa cells were found to be refractory to re-infection and to the re-establishment of viral persistence. While these findings demonstrate that PPMO can be used to eliminate persistent EAV infection in cell culture, the efficacy of PPMO against EAV in vivo remains to be addressed.


title: Distant Relatives of Severe Acute Respiratory Syndrome Coronavirus and Close Relatives of Human Coronavirus 229E in Bats, Ghana

text: We tested 12 bat species in Ghana for coronavirus (CoV) RNA. The virus prevalence in insectivorous bats (n = 123) was 9.76%. CoV was not detected in 212 fecal samples from Eidolon helvum fruit bats. Leaf-nosed bats pertaining to Hipposideros ruber by morphology had group 1 and group 2 CoVs. Virus concentrations were <45,000 copies/100 mg of bat feces. The diversified group 1 CoV shared a common ancestor with the human common cold virus hCoV-229E but not with hCoV-NL63, disputing hypotheses of common human descent. The most recent common ancestor of hCoV-229E and GhanaBt-CoVGrp1 existed in ≈1686–1800 ad. The GhanaBt-CoVGrp2 shared an old ancestor (≈2,400 years) with the severe acute respiratory syndrome–like group of CoV.


title: From genotype to phenotype: can systems biology be used to predict Staphylococcus aureus virulence?

text: With the advent of high-throughput whole-genome sequencing, it is now possible to sequence a bacterial genome in a matter of hours. However, although the presence or absence of a particular gene can be determined, we do not yet have the tools to extract information about the true virulence potential of an organism from sequence data alone. Here, we focus on the important human pathogen Staphylococcus aureus and present a framework for the construction of a broad systems biology-based tool that could be used to predict virulence phenotypes from S. aureus genomic sequences using existing technology.


title: Vitamin D Levels and COVID-19 Susceptibility: Is there any Correlation?

text: Coronavirus disease (COVID-19) is a major pandemic and now a leading cause of death worldwide. Currently, no drugs/vaccine is available for the treatment of this disease. Future preventions and social distancing are the only ways to prevent this disease from community transmission. Vitamin D is an important micronutrient and has been reported to improve immunity and protect against respiratory illness. This short review highlights the important scientific link between Vit D levels and susceptibility to COVID-19 in patients. This review also discusses recommendations for Vit D dose required for healthy as well as COVID-19 susceptible patients for protection and prevention.


title: CT in coronavirus disease 2019 (COVID-19): a systematic review of chest CT findings in 4410 adult patients

text: OBJECTIVE: The objective of this systematic review was to evaluate the key imaging manifestations of COVID-19 on chest CT in adult patients by providing a comprehensive review of the published literature. METHODS: We performed a systematic literature search from the PubMed, Google Scholar, Embase, and WHO databases for studies mentioning the chest CT imaging findings of adult COVID-19 patients. RESULTS: A total of 45 studies comprising 4410 patients were included. Ground glass opacities (GGO), in isolation (50.2%) or coexisting with consolidations (44.2%), were the most common lesions. Distribution of GGOs was most commonly bilateral, peripheral/subpleural, and posterior with predilection for lower lobes. Common ancillary findings included pulmonary vascular enlargement (64%), intralobular septal thickening (60%), adjacent pleural thickening (41.7%), air bronchograms (41.2%), subpleural lines, crazy paving, bronchus distortion, bronchiectasis, and interlobular septal thickening. CT in early follow-up period generally showed an increase in size, number, and density of GGOs, with progression into mixed areas of GGOs plus consolidations and crazy paving, peaking at 10–11 days, before gradually resolving or persisting as patchy fibrosis. While younger adults more commonly had GGOs, extensive/multilobar involvement with consolidations was prevalent in the older population and those with severe disease. CONCLUSION: This review describes the imaging features for diagnosis, stratification, and follow-up of COVID-19 patients. The most common CT manifestations are bilateral, peripheral/subpleural, posterior GGOs with or without consolidations with a lower lobe predominance. It is pertinent to be familiar with the various imaging findings to positively impact the management of these patients. KEY POINTS: • Ground glass opacities (GGOs), whether isolated or coexisting with consolidations, in bilateral and subpleural distribution, are the most prevalent chest CT findings in adult COVID-19 patients. • Follow-up CT shows a progression of GGOs into a mixed pattern, reaching a peak at 10–11 days, before gradually resolving or persisting as patchy fibrosis. • Younger people tend to have more GGOs. Older or sicker people tend to have more extensive involvement with consolidations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-06975-7) contains supplementary material, which is available to authorized users.


title: ‘Primed’ Mesenchymal Stem Cells: a Potential Novel Therapeutic for COVID19 Patients

text: The COVID19 pandemic, designated as a public health crisis by the World Health Organization (WHO), is rapidly spreading around the world impacting the health and economy of almost all the countries. The data of hospitalized COVID19 patients, especially those with serious illness, indicate the involvement of immunopathological complications. As no effective treatment is currently available, we propose ‘Primed’ Mesenchymal Stem Cells (MSCs) as a therapeutic alternative to tackle devastating epidemic. The individual response to MSCs treatment is heterogeneous. During the treatment of infectious pathology, the effectiveness of the treatment may vary based on the disease scenario. Interestingly, when transplanted in vivo, MSCs are governed by the locally regulated microenvironment, suggesting that the restorative variability could be tailored by choosing a priming regimen to specifically correct a given pathology. Therefore, in our opinion, the priming of MSCs could be a novel approach to improve the responses of COVID19 patients.


title: Polysaccharide microarray technology for the detection of Burkholderia pseudomallei and Burkholderia mallei antibodies

text: Abstract A polysaccharide microarray platform was prepared by immobilizing Burkholderia pseudomallei and Burkholderia mallei polysaccharides. This polysaccharide array was tested with success for detecting B. pseudomallei and B. mallei serum (human and animal) antibodies. The advantages of this microarray technology over the current serodiagnosis of the above bacterial infections were discussed.


title: Impact of COVID-19 related healthcare crisis on treatments for patients with lysosomal storage disorders, the first Italian experience

text: Abstract The direct and indirect effects of Coronavirus Disease-19 (COVID-19) pandemic, on Italian patients with lysosomal storage disorders receiving therapy, were analyzed by a phone questionnaire. No proved COVID-19 emerged among 102 interviewed. No problems were reported by patients receiving oral treatments. Forty-nine% of patients receiving enzyme replacement therapy in hospitals experienced disruptions, versus 6% of those home-treated. The main reasons of missed infusions were fear of infection (62.9%) and re-organization of the infusion centers (37%).


title: Ubiquitin in Influenza Virus Entry and Innate Immunity

text: Viruses are obligatory cellular parasites. Their mission is to enter a host cell, to transfer the viral genome, and to replicate progeny whilst diverting cellular immunity. The role of ubiquitin is to regulate fundamental cellular processes such as endocytosis, protein degradation, and immune signaling. Many viruses including influenza A virus (IAV) usurp ubiquitination and ubiquitin-like modifications to establish infection. In this focused review, we discuss how ubiquitin and unanchored ubiquitin regulate IAV host cell entry, and how histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase with ubiquitin-binding activity, mediates IAV capsid uncoating. We also discuss the roles of ubiquitin in innate immunity and its implications in the IAV life cycle.


title: Clostridium perfringens type A netF and netE positive and Clostridium difficile co-infection in two adult dogs

text: Abstract The aim of this study was to report two cases of Clostridium perfringens type A and Clostridium difficile co-infection in adult dogs. Both animals were positive for A/B toxin. Toxigenic C. difficile and C. perfringens type A positive for NetE and NetF-encoding genes were isolated. This report reinforces the necessity of studying a possible synergism of C. difficile and C. perfringens in enteric disorders.


title: Pattern transitions in spatial epidemics: Mechanisms and emergent properties

text: Abstract Infectious diseases are a threat to human health and a hindrance to societal development. Consequently, the spread of diseases in both time and space has been widely studied, revealing the different types of spatial patterns. Transitions between patterns are an emergent property in spatial epidemics that can serve as a potential trend indicator of disease spread. Despite the usefulness of such an indicator, attempts to systematize the topic of pattern transitions have been few and far between. We present a mini-review on pattern transitions in spatial epidemics, describing the types of transitions and their underlying mechanisms. We show that pattern transitions relate to the complexity of spatial epidemics by, for example, being accompanied with phenomena such as coherence resonance and cyclic evolution. The results presented herein provide valuable insights into disease prevention and control, and may even be applicable outside epidemiology, including other branches of medical science, ecology, quantitative finance, and elsewhere.


title: Clinical features and outcome of HIV/SARS‐CoV‐2 coinfected patients in The Bronx, New York city

text: Coronavirus disease 2019 (COVID-19) is a highly contagious disease with millions of people have been infected. However, there is limited data regarding clinical features, disease courses and outcomes of COVID-19 in patients with human immunodeficiency virus (HIV). Herein, we presented the demographic data, clinical characteristics and outcomes of nine confirmed COVID-19 patients with HIV infection admitted to our hospital located in south Bronx, New York City. Our study revealed very high mortality rate at 78%, which may contradict to the hypothesis that immunosuppression from HIV infection prevents against severe COVID-19. More research is needed to determine the impact of HIV on the clinical course of COVID-19. This article is protected by copyright. All rights reserved.


title: Prediction of final infarct volume from native CT perfusion and treatment parameters using deep learning

text: CT Perfusion (CTP) imaging has gained importance in the diagnosis of acute stroke. Conventional perfusion analysis performs a deconvolution of the measurements and thresholds the perfusion parameters to determine the tissue status. We pursue a data-driven and deconvolution-free approach, where a deep neural network learns to predict the final infarct volume directly from the native CTP images and metadata such as the time parameters and treatment. This would allow clinicians to simulate various treatments and gain insight into predicted tissue status over time. We demonstrate on a multicenter dataset that our approach is able to predict the final infarct and effectively uses the metadata. An ablation study shows that using the native CTP measurements instead of the deconvolved measurements improves the prediction.


Lessons from history: viral surveillance in 1940s East Africa: Epidemiological notes on some viruses isolated in Uganda, G. W. A. Dick, Transactions of the Royal Society of Tropical Medicine and Hygiene, 1953;47(1):13–48


title: Chapter 5 Expression

text: Publisher Summary This chapter focuses on the mechanisms by which cells express the information stored in genes, and examines the genome coding struggles of different virus groups. Control of gene expression is a vital element of virus replication. Coordinate expression of groups of virus genes results in successive phases of gene expression. Immediate–early genes encode activator proteins, early genes encode further regulatory proteins, and late genes encode virus structural proteins. Viruses make use of the biochemical apparatus of their host cells to express their genetic information as proteins and, consequently, utilize the appropriate biochemical language recognized by the cell. Thus viruses of prokaryotes produce polycistronic mRNAs, while viruses with eukaryotic hosts produce more monocistronic mRNAs. Some viruses of eukaryotes do produce polycistronic mRNA to assist with the coordinate regulation of multiple genes. Viruses rely on specific cis- and trans-acting mechanisms to manipulate the biology of their host cells, and to enhance and coordinate the expression of their genetic information. The chapter discusses control of prokaryote gene expression, expression in bacteriophage λ, eukaryote gene expression, and also discusses genome coding strategies. The chapter ends with a discussion of the transcription and post-transcriptional methods of control of gene expression.


title: A Reusable Mask for Coronavirus Disease 2019 (COVID-19)

text: Abstract The outbreak of Novel Coronavirus is causing an intensely feared globally. World Health Organization has even declared that it is a global health emergency. The simplest method to limit the spread of this new virus and for people to protect themselves as well as the others is to wear a mask in crowded places. The sudden increase demand on face mask has caused manufacturers the inability to not provide enough products in a short time and the situation properly will stay the same for a period of time. In this article, we aim to give an idea on how to save the number of face masks used but still provides the same protective values using a Cardiopulmonary resuscitation (CPR) mask and a common surgical facemask.


title: Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation

text: BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. PKR activity is regulated by a 58 kilo Dalton cellular inhibitor (P58(IPK)), which is present in inactive state as a complex with Hsp40 under normal conditions. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. However the influenza virus component responsible for PKR inhibition through P58(IPK) activation was hitherto unknown. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. This interaction was confirmed by co-immunoprecipitation studies from mammalian cells transfected with IAV NP expressing plasmid. Further, the IAV NP-Hsp40 interaction was validated in mammalian cells infected with various seasonal and pandemic strains of influenza viruses. Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation. We observed that, plasmid based expression of NP in mammalian cells leads to decrease in PKR phosphorylation. Furthermore, inhibition of NP expression during influenza virus replication led to PKR activation and concomitant increase in eIF2α phosphorylation. Inhibition of NP expression also led to reduced IRF3 phosphorylation, enhanced IFN β production and concomitant reduction of virus replication. Taken together our data suggest that NP is the viral factor responsible for P58(IPK) activation and subsequent inhibition of PKR-mediated host response during IAV infection. SIGNIFICANCE: Our findings demonstrate a novel role of IAV NP in inhibiting PKR-mediated anti-viral host response and help us understand P58(IPK) mediated inhibition of PKR activity during IAV infection.


title: Insights into the Microbiological Safety of Wooden Cutting Boards Used for Meat Processing in Hong Kong’s Wet Markets: A Focus on Food-Contact Surfaces, Cross-Contamination and the Efficacy of Traditional Hygiene Practices

text: Hong Kong’s wet markets play a crucial role in the country’s supply of safe, fresh meat to satisfy the dietary needs of its population. Whilst food safety regulations have been introduced over the past few years to maintain the microbial safety of foods sold from these wet markets, it remains unclear whether the hygiene maintenance that is performed on the wooden cutting boards used for meat-processing is effective. In fact, hygiene maintenance may often be overlooked, and hygiene standards may be insufficient. If so, this may lead to the spread of harmful pathogens through cross-contamination, thereby causing severe risks to public health. The aim of this study was to determine the level of microbial transfer between wooden cutting boards and swine meat of various qualities, using 16S metagenomic sequencing, strain identification and biofilm screening of isolated strains. The results established that: (a) the traditional hygiene practices used for cleaning wooden cutting boards in Hong Kong’s wet markets expose the surfaces to potentially harmful microorganisms; (b) the processing of microbially contaminated meat on cutting boards cleaned using traditional practices leads to cross-contamination; and (c) several potentially pathogenic microorganisms found on the cutting boards have good biofilm-forming abilities. These results reinforce the need to review the traditional methods used to clean wooden cutting boards after the processing of raw meat in Hong Kong’ wet markets so as to prevent cross-contamination events. The establishment of proper hygiene protocols may reduce the spread of disease-causing microorganisms (including antibiotic-resistant microorganisms) in food-processing environments.


title: No association of Angiotensin-Converting enzyme 2 gene (ACE2) polymorphisms with essential hypertension

text: Abstract Recent intriguing findings from genetic linkage, knockout, and physiologic studies in mice and rats led us to conduct the first investigation of the novel angiotensin-converting enzyme 2 gene (ACE2) in human hypertension (HT). We genotyped four single nucleotide polymorphisms (SNP) (A→G at nucleotide 1075 in intron 1, G→A at nucleotide 8790 in intron 3, C→G at nucleotide 28330 in intron 11, and G→C at nucleotide 36787 in intron 16) in HT (n = 152) and normotensive (NT, n = 193) groups having inherently high biological power (>80%) due to our inclusion only of subjects whose parents had the same BP status as themselves. The SNPs were in linkage disequilibrium (D′ = 54% to 100%, P = .05 to 0.0001). Because ACE2 is on the X chromosome, data for each sex were analyzed separately. Minor allele frequencies in HT versus NT were as follows: for the intron 1 variant 0.21 versus 0.17 in female subjects (P = .31) and 0.25 versus 0.29 in male subjects (P = .60); intron 3 variant 0.22 versus 0.18 in female subjects (P = .35) and 0.15 versus 0.20 in male subjects (P = .47); intron 11 variant 0.39 versus 0.46 in male subjects (P = 0.17) and 0.31 versus 0.30 in male subjects (P = .96); intron 16 variant 0.20 versus 0.19 in female subjects (P = .72) and 0.17 versus 0.17 in male subjects (P = .95). Haplotype analysis was also negative. These data provide little support for ACE2 in genetic predisposition to HT.


title: Association News COVID-19 and anesthetic considerations for head and neck surgeries and bronchoscopic and dental procedures

text: After an outbreak in Wuhan, China in December 2019, coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2, rapidly spread worldwide and has been threatening public health During this pandemic, health care providers, particularly anesthesiologists, are at increased risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when they care for COVID-19 patients and/or asymptomatic carriers especially when they participate in and/or perform aerosol-generating procedures These are commonly encountered in head and neck surgeries and bronchoscopic and dental procedures This article will discuss these procedures’ characteristics and the mechanisms by which they pose increased risk to health care provider especially the anesthesiologists, and recommendations for mitigating these risks based on the current state of knowledge and experience


title: Cell Tropism Predicts Long-term Nucleotide Substitution Rates of Mammalian RNA Viruses

text: The high rates of RNA virus evolution are generally attributed to replication with error-prone RNA-dependent RNA polymerases. However, these long-term nucleotide substitution rates span three orders of magnitude and do not correlate well with mutation rates or selection pressures. This substitution rate variation may be explained by differences in virus ecology or intrinsic genomic properties. We generated nucleotide substitution rate estimates for mammalian RNA viruses and compiled comparable published rates, yielding a dataset of 118 substitution rates of structural genes from 51 different species, as well as 40 rates of non-structural genes from 28 species. Through ANCOVA analyses, we evaluated the relationships between these rates and four ecological factors: target cell, transmission route, host range, infection duration; and three genomic properties: genome length, genome sense, genome segmentation. Of these seven factors, we found target cells to be the only significant predictors of viral substitution rates, with tropisms for epithelial cells or neurons (P<0.0001) as the most significant predictors. Further, one-tailed t-tests showed that viruses primarily infecting epithelial cells evolve significantly faster than neurotropic viruses (P<0.0001 and P<0.001 for the structural genes and non-structural genes, respectively). These results provide strong evidence that the fastest evolving mammalian RNA viruses infect cells with the highest turnover rates: the highly proliferative epithelial cells. Estimated viral generation times suggest that epithelial-infecting viruses replicate more quickly than viruses with different cell tropisms. Our results indicate that cell tropism is a key factor in viral evolvability.


title: Involvement of cystatin C in immunity and apoptosis

text: Abstract As an abundantly expressed cysteine protease inhibitor widely distributed in the organisms, cystatin C is involved in various physiological processes. Due to its relatively small molecular weight and easy detection, cystatin C is commonly used as a measure for glomerular filtration rate. In pathological conditions, however, growing evidences suggest that cystatin C is associated with various immune responses against either exogenous or endogenous antigens, which ultimately result in inflammatory autoimmune diseases or tumor development if not properly controlled. Thus the fluctuation of cystatin C levels might have more clinical implications than a reflection of kidney functions. Here, we summarize the latest development of studies on the pathophysiological functions of cystatin C, with focus on its immune regulatory roles at both cellular and molecular levels including antigen presentation, secretion of cytokines, synthesis of nitric oxide, as well as apoptosis. Finally, we discuss the clinical implications and therapeutic potentials of what this predominantly expressed protease inhibitor can bring to us.


Family medicine in times of ‘COVID-19’: A generalists' voice


title: Efficacy of a pharmaceutical preparation based on glycyrrhizic acid in a challenge study of white spot syndrome in white shrimp (Litopenaeus vannamei)

text: Abstract There is a lack of preventive and therapeutic drug-based treatments for the shrimp viral disease known as white spot syndrome (WSSV). Thus a challenge study inducing WSSV in juvenile white shrimp (Litopenaeus vannamei) was established, setting 4 groups: challenged — not treated and unchallenged, untreated control groups and two experimental ones (E1 and E2) both treated with diammonium glycyrrhizic acid, extracted from licorice with added vitamins and oligoelements, and as in-feed medication. Group E1 received diammonium glycyrrhizic acid included in their daily feed, starting 17days before challenge with WSSV and maintaining the treatment for further 5days after the end of the trial, which was set on day 18. Group E2 received this medication as group E1 throughout the trial, but starting 1day before the challenge with WSSV. The group with highest surviving median values was E1, amounting two times the survival median in comparison with the control groups (P=0.007). Also a statistical difference was found in terms of survival means in favor of group E1 as compared to group E2. Macroscopic and histopathological findings revealed lesions compatible with WSSV and similar mortality in the challenged untreated group. These findings were highly reduced or inexistent in mortality analyzed from groups E1 as well as in the unchallenged — untreated control group and greatly reduced in group E2. Considering the apparent high efficacy observed and that glycyrrhizic acid and mineral and vitamin components added as treatment, and taking as an advantage that this preparation has been regarded as nutraceuticals, it is here proposed that large scale trials should be conducted to evaluate the effects here observed in commercial and larger scale shrimp farms.


title: Viral upper respiratory tract infection and otitis media complication in young children

text: BACKGROUND: The common cold or upper respiratory infection (URI) is highly prevalent in young children and often results in otitis media (OM). Incidence and characteristics of OM complicating URI by specific viruses have not been well studied. METHODS: We performed a prospective, longitudinal, cohort study of 294 healthy children (6 mos. to 3 yrs. of age). Each child was followed for 1 year for the occurrences of URI and acute otitis media (AOM) and otitis media with effusion (OME) complicating URI by specific viruses. RESULTS: There were 1295 URI episodes (5.06 episodes/child-year) and 440 AOM episodes (1.72 episodes/child-year) documented. Virus studies were performed in 864 URI episodes; 63% were virus positive. Rhinovirus and adenovirus were most commonly detected during URI. The overall incidence of OM complicating URI was 61%, including 37% AOM and 24% OME. Young age was the most important predictor for AOM complicating URI. AOM occurred in about half of children with URI associated with adenovirus, respiratory syncytial virus (RSV), and coronavirus, and about one-third of those with influenza, parainfluenza, enterovirus and rhinovirus. CONCLUSIONS: More than 60% of symptomatic URI episodes in young children were complicated by AOM and/or OME. Young age and specific virus types were predictors of AOM complicating URI. Preventive strategy for OM should be through preventing viral URI in young children. The strategy may be more effective if the priority is given to development of ways to prevent URI associated with adenovirus and RSV.