title: Neutralizing Human Monoclonal Antibodies to Severe Acute Respiratory Syndrome Coronavirus: Target, Mechanism of Action and Therapeutic Potential

text: The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) led to a rapid response not only to contain the outbreak but also to identify possible therapeutic interventions, including the generation of human monoclonal antibodies (hmAbs). Human mAbs may be used therapeutically without the drawbacks of chimeric or animal Abs. Several different methods have been used to generate SARS-CoV specific neutralizing hmAbs including the immunization of transgenic mice, cloning of small chain variable regions from naïve and convalescent patients, and the immortalization of convalescent B cells. Irrespective of the techniques used, the majority of hmAbs specifically reacted with the receptor binding domain (RBD) of the spike (S) protein and likely prevented receptor binding. However, several hmAbs that can bind to epitopes either within the RBD, located N terminal of the RBD or in the S2 domain and neutralize the virus with or without inhibiting receptor binding have been identified. Therapeutic utility of hmAbs has been further elucidated through the identification of potential combinations of hmAbs that could neutralize viral variants including escape mutants selected using hmAbs. These results suggest that a cocktail of hmAbs which can bind to unique epitopes and have different mechanisms of action might be of clinical utility against SARS-CoV infection, and indicate that a similar approach may be applied to treat other viral infections.


Sleep labs, lung function tests and COVID-19 pandemic – Only emergencies allowed!


title: MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study

text: BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. METHODS: We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. FINDINGS: 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% [23/117] vs 5% [3/58] in group B vs 1% [4/500] in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2–17, IQR 5–10). The median incubation period was significantly shorter in group A than in group C (5 days [IQR 4–8] vs 11 days [6–12]; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure. INTERPRETATION: Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. FUNDING: None.


title: Modeling and prediction of COVID-19 pandemic using Gaussian mixture model

text: COVID-19 is caused by a novel coronavirus and has played havoc on many countries across the globe. A majority of the world population is now living in a restricted environment for more than a month with minimal economic activities, to prevent exposure to this highly infectious disease. Medical professionals are going through a stressful period while trying to save the larger population. In this paper, we develop two different models to capture the trend of a number of cases and also predict the cases in the days to come, so that appropriate preparations can be made to fight this disease. The first one is a mathematical model accounting for various parameters relating to the spread of the virus, while the second one is a non-parametric model based on the Fourier decomposition method (FDM), fitted on the available data. The study is performed for various countries, but detailed results are provided for the India, Italy, and United States of America (USA). The turnaround dates for the trend of infected cases are estimated. The end-dates are also predicted and are found to agree well with a very popular study based on the classic susceptible-infected-recovered (SIR) model. Worldwide, the total number of expected cases and deaths are 12.7 × 10(6) and 5.27 × 10(5), respectively, predicted with data as of 06-06-2020 and 95% confidence intervals. The proposed study produces promising results with the potential to serve as a good complement to existing methods for continuous predictive monitoring of the COVID-19 pandemic.


title: Nasopharyngeal Microbiota in Infants With Acute Otitis Media

text: Background. Interspecies interactions of the nasopharyngeal microbiota are likely to be involved in the pathogenesis of acute otitis media (AOM). Capturing the breadth of microbial interactions requires a detailed description of the microbiota during health and AOM. Methods. The nasopharyngeal microbiota of 163 infants with (n = 153) or without (n = 10) AOM was characterized using nasopharyngeal swabs and multiplexed pyrosequencing of 16S rRNA. Nasopharyngeal swab specimens were collected during 4 winter seasons from 2004 through 2010 for infants with AOM and during 2010 for controls. Results. Fifty-eight bacterial families were identified, of which Moraxellaceae, Streptococcaceae, and Pasteurellaceae were the most frequent. Commensal families were less prevalent in infants with AOM than in controls. In infants with AOM, prior exposure to antimicrobials and administration of the heptavalent conjugated pneumococcal polysaccharide vaccine (PCV7) were also associated with reduced prevalence of distinct commensal families (Streptococcaceae and Corynebacteriaceae). In addition, antimicrobial exposure increased the prevalence of Enterobacteriaceae and the abundance of Pasteurellaceae. Other factors, such as age, sex, day care, and a history of recurrent AOM, did not influence the microbiota. Conclusions. Infants’ nasopharyngeal microbiota undergoes significant changes during AOM and after exposure to antimicrobials and PCV7, which is mainly attributable to reduced prevalence of commensal bacterial families.


title: (1)H, (13)C, (15)N resonance assignments of murine hepatitis virus nonstructural protein 3a

text: Nonstructural protein (nsp) 3 is the largest of 16 nsps translated from the murine hepatitis virus (MHV) genome. The N-terminal most domain of nsp3, nsp3a, has been identified by reverse genetics as a likely binding partner of MHV nucleocapsid protein. Here we report the backbone and side chain resonance assignments of MHV nsp3a (residues 1–114).


title: Estimation of the Excess COVID-19 Cases in Seoul, South Korea by the Students Arriving from China

text: Background: In March 2020, overall, 37,000 international students from China, a country at risk of the 2019-novel coronavirus (COVID-19) infection has arrived in Seoul, South Korea. Individuals from the country at risk of COVID-19 infection have been included in the Korean home-quarantine program, but the efficacy of the program is uncertain. Methods: To estimate the possible number of infected individuals within the large influx of international students from China, we used a deterministic compartmental model for epidemic and performed a simulation-based search of different rates of compliance with home-quarantine. Results: Under the home-quarantine program, the number of the infected individuals would reach 40–72 from 12 March–24 March with the arrival of 0.2% of pre-infectious individuals. Furthermore, the number of isolated individuals would peak at 40–64 from 13 March–27 March in Seoul, South Korea. Our findings indicated when incoming international students showed strict compliance with quarantine, epidemics by the international student from China were less likely to occur in Seoul, South Korea. Conclusions: To mitigate possible epidemics, additional efforts to improve the compliance of home-quarantine of the individuals from countries with the virus risk are warranted along with other containment policies.


title: Controlling disease outbreaks in wildlife using limited culling: modelling classical swine fever incursions in wild pigs in Australia

text: Disease modelling is one approach for providing new insights into wildlife disease epidemiology. This paper describes a spatio-temporal, stochastic, susceptible- exposed-infected-recovered process model that simulates the potential spread of classical swine fever through a documented, large and free living wild pig population following a simulated incursion. The study area (300 000 km(2)) was in northern Australia. Published data on wild pig ecology from Australia, and international Classical Swine Fever data was used to parameterise the model. Sensitivity analyses revealed that herd density (best estimate 1-3 pigs km(-2)), daily herd movement distances (best estimate approximately 1 km), probability of infection transmission between herds (best estimate 0.75) and disease related herd mortality (best estimate 42%) were highly influential on epidemic size but that extraordinary movements of pigs and the yearly home range size of a pig herd were not. CSF generally established (98% of simulations) following a single point introduction. CSF spread at approximately 9 km(2 )per day with low incidence rates (< 2 herds per day) in an epidemic wave along contiguous habitat for several years, before dying out (when the epidemic arrived at the end of a contiguous sub-population or at a low density wild pig area). The low incidence rate indicates that surveillance for wildlife disease epidemics caused by short lived infections will be most efficient when surveillance is based on detection and investigation of clinical events, although this may not always be practical. Epidemics could be contained and eradicated with culling (aerial shooting) or vaccination when these were adequately implemented. It was apparent that the spatial structure, ecology and behaviour of wild populations must be accounted for during disease management in wildlife. An important finding was that it may only be necessary to cull or vaccinate relatively small proportions of a population to successfully contain and eradicate some wildlife disease epidemics.


title: Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study

text: Summary Background Since December, 2019, an outbreak of coronavirus disease 2019 (COVID-19) has spread globally. Little is known about the epidemiological and clinical features of paediatric patients with COVID-19. Methods We retrospectively retrieved data for paediatric patients (aged 0–16 years) with confirmed COVID-19 from electronic medical records in three hospitals in Zhejiang, China. We recorded patients' epidemiological and clinical features. Findings From Jan 17 to March 1, 2020, 36 children (mean age 8·3 [SD 3·5] years) were identified to be infected with severe acute respiratory syndrome coronavirus 2. The route of transmission was by close contact with family members (32 [89%]) or a history of exposure to the epidemic area (12 [33%]); eight (22%) patients had both exposures. 19 (53%) patients had moderate clinical type with pneumonia; 17 (47%) had mild clinical type and either were asymptomatic (ten [28%]) or had acute upper respiratory symptoms (seven [19%]). Common symptoms on admission were fever (13 [36%]) and dry cough (seven [19%]). Of those with fever, four (11%) had a body temperature of 38·5°C or higher, and nine (25%) had a body temperature of 37·5–38·5°C. Typical abnormal laboratory findings were elevated creatine kinase MB (11 [31%]), decreased lymphocytes (11 [31%]), leucopenia (seven [19%]), and elevated procalcitonin (six [17%]). Besides radiographic presentations, variables that were associated significantly with severity of COVID-19 were decreased lymphocytes, elevated body temperature, and high levels of procalcitonin, D-dimer, and creatine kinase MB. All children received interferon alfa by aerosolisation twice a day, 14 (39%) received lopinavir–ritonavir syrup twice a day, and six (17%) needed oxygen inhalation. Mean time in hospital was 14 (SD 3) days. By Feb 28, 2020, all patients were cured. Interpretation Although all paediatric patients in our cohort had mild or moderate type of COVID-19, the large proportion of asymptomatic children indicates the difficulty in identifying paediatric patients who do not have clear epidemiological information, leading to a dangerous situation in community-acquired infections. Funding Ningbo Clinical Research Center for Children's Health and Diseases, Ningbo Reproductive Medicine Centre, and Key Scientific and Technological Innovation Projects of Wenzhou.


title: The ABC of society: Perceived similarity in agency/socioeconomic success and conservative-progressive beliefs increases intergroup cooperation

text: Abstract The dimensions that explain which societal groups cooperate more with which other groups remain unclear. We predicted that perceived similarity in agency/socioeconomic success and conservative-progressive beliefs increases cooperation across groups. Self-identified members (N = 583) of 30 society-representative U.S. groups (gays, Muslims, Blacks, upper class, women, Democrats, conservatives etc.) played an incentivized one-time continuous prisoner's dilemma game with one self-identified member of each of these groups. Players knew nothing of each other except one group membership. Consistent with the ABC (agency-beliefs-communion) model of spontaneous stereotypes, perceived self-group similarity in agency and beliefs independently increased expected and actual cooperation across groups, controlling for shared group membership. Similarity in conservative-progressive beliefs had a stronger effect on cooperation than similarity in agency, and this effect of similarity in beliefs was stronger for individuals with extreme (progressive or conservative) compared to moderate beliefs.


title: Cellular immune status of coronavirus-infected neonatal calves

text: Abstract A preliminary study was conducted to determine the cellular immune status of neonatal, colostrum-deprived calves following inoculation with either attenuated or virulent bovine coronavirus (BCV). Uninfected calves served as controls. To determine the intestinal and systemic cellular immune status, we performed MHC-restricted cytotoxic lymphocyte (CTL) assay on mesenteric lymphocytes, enumerated T cell subsets in peripheral blood lymphocytes, and examined histopathological alterations in mesenteric lymph nodes and gut-associated lymphoid tissue. Target cells for the CTL assay were autologous testicular cells and effector cells were mesenteric lymphocytes from calves infected with BCV. No appreciable specific lysis was observed in any group of calves indicating the absence of demonstrable CTL responses. The TC/TS population was severely depressed in the calf inoculated with the virulent virus but not in those inoculated with either the attenuated virus or placebo. The mesenteric lymph nodes and Peyer's patches of calves inoculated with the virulent virus showed severe depletion of lymphocytes. These calves developed intestinal antibody responses in the acute phase of infection (1 week after infection) but were immunosuppressed in the later stage of infection.


title: Requirements for the induction and adoptive transfer of cyclosporine- induced syngeneic graft-versus-host disease

text: These studies further delineate the requirements for the establishment and transfer of SGVHD. We show that (a) two mechanisms distinguishable by radiation and drug sensitivities exist, (b) lethal irradiation correlates with a 100% incidence in the induction of SGVHD, whereas (c) both sublethal or lethal irradiation and cytoxan therapy are effective in ablating the host autoregulatory system in order to transfer autoreactivity, (d) unfractionated as well as nylon wool-nonadherent splenocytes effectively inhibit the transfer of autoimmunity, and (e) OX19 depletion of that population, however, destroys the autoregulatory effect present in normal splenocytes. To demonstrate complete inhibition of immune reactivity, twice the number of unfractionated splenocytes from normal animals was required for every splenocyte from autoimmune donors. Last, the infusion of effector splenocytes on 4, 7, and 14 d after transplantation correlates to a decrease from 100%, 70 to 0% incidence of SGVHD, thus emulating the incidence obtained in a pretransplant rat within 2 wk. These findings further clarify the immunobiological complexity of SGVHD and suggest that since autoregulatory cells already exist in normal animals that CsA-induced autoimmunity is a reflection of not an induced reactivity specific to one therapeutic reagent but the uncoupling of normal immunologic mechanisms essential in controlling autoimmunity.


title: Closure of medical departments during nosocomial outbreaks: data from a systematic analysis of the literature

text: Summary A total closure of an affected medical department is one of the most expensive infection control measures during investigation of a nosocomial outbreak. However, until now there has been no systematic analysis of typical characteristics of outbreaks, for which closure was considered necessary. This article presents data on features of such nosocomial epidemics published during the past 40 years in the medical literature. A search of the Outbreak Database (1561 nosocomial outbreaks in file) revealed a total of 194 outbreaks that ended up with some kind of closure of the unit (median closure time: 14 days). Closure rates (CRs) were calculated and stratified for medical departments, for causative pathogens, for outbreak sources, and for the assumed mode of transmission. Data were then compared to the overall average CR of 12.4% in the entire database. Wards in geriatric patient care were closed significantly more frequently (CR: 30.3%; P <0.001) whereas paediatric wards showed a significantly lower CR (6.1%; P =0.03). Pathogen species with the highest CR were norovirus (44.1%; P <0.001) and influenza/parainfluenza virus (38.5%; P <0.001). If patients were the source of the outbreak, the CR was significantly increased (16.7%; P =0.03). Infections of the central nervous system were most often associated with closure of the ward (24.2%; P =001). A systematic evaluation of nosocomial outbreaks can be a valuable tool for education of staff in the absence of an outbreak, but may be even more helpful for potentially cost-intensive decisions in the acute outbreak setting on the ward.


COVID-19 Pandemic: The Concerns of Pediatric Neurologists


title: Using multiplex real time PCR in order to streamline a routine diagnostic service

text: Abstract An increasing number of virology laboratories are now utilising in house real time PCR assays as the frontline diagnostic tests. As the number of tests on offer increases the natural progression from this will be to rationalise their service via multiplexing. Since 2003 we have introduced a large number of qualitative and quantitative multiplex real time PCR assays into our routine testing service. This paper describes the development of the multiplex assays, the problems encountered and the resultant benefits to the routine service.


title: Age effects in monetary valuation of reduced mortality risks: the relevance of age-specific hazard rates

text: This paper highlights the relevance of age-specific hazard rates in explaining the age variation in “value of statistical life” (VSL) figures. The analysis—which refers to a stated preference framework—contributes to the ongoing discussion of whether benefits resulting from reduced mortality risk should be valued differently depending on the age of the beneficiaries. By focussing on a life-threatening environmental phenomenon I show that the consideration of the individual’s age-specific hazard rate is important. If a particular risk affects all individuals regardless of their age so that their hazard rate is age-independent, VSL is rather constant for people at different age; if hazard rate varies with age, VSL estimates are sensitive to age. The results provide an explanation for the mixed outcomes in empirical studies and illustrate in which cases an adjustment to age may or may not be justified. Efficient provision of live-saving measures requires that such differences to be taken into account.


Semen banking: consideration on viral contamination in the era of new emerging viral infection


title: COVID-19: Understanding the science of antibody testing and lessons from the HIV epidemic

text: Abstract Potential pitfalls in the development, deployment and interpretation of antibody tests for COVID-19 are discussed. Lessons learned from the experience with the introduction of antibody tests for HIV are highlighted.


title: Marine pharmacology in 2007–8: Marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous system, and other miscellaneous mechanisms of action

text: Abstract The peer-reviewed marine pharmacology literature in 2007–8 is covered in this review, which follows a similar format to the previous 1998–2006 reviews of this series. The preclinical pharmacology of structurally characterized marine compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 74 marine natural products. Additionally, 59 marine compounds were reported to affect the cardiovascular, immune and nervous systems as well as to possess anti-inflammatory effects. Finally, 65 marine metabolites were shown to bind to a variety of receptors and miscellaneous molecular targets, and thus upon further completion of mechanism of action studies, will contribute to several pharmacological classes. Marine pharmacology research during 2007–8 remained a global enterprise, with researchers from 26 countries, and the United States, contributing to the preclinical pharmacology of 197 marine compounds which are part of the preclinical marine pharmaceuticals pipeline. Sustained preclinical research with marine natural products demonstrating novel pharmacological activities, will probably result in the expansion of the current marine pharmaceutical clinical pipeline, which currently consists of 13 marine natural products, analogs or derivatives targeting a limited number of disease categories.


title: Safety management in urgent endonasal trans-sphenoidal surgery for pituitary adenoma during the COVID-19 pandemic in Japan – A case report

text: We report a 72-year-old woman who required urgent endonasal trans-sphenoidal surgery (eTSS) because of progressive visual field disturbance due to pituitary adenoma, in whom we conducted reverse-transcriptase-polymerase-chain-reaction (RT-PCR) for COVID-19 and chest CT before eTSS. We took care of her by following the rule for suspected infection patient, and safely completed her treatment without medical staff infection. Under COVID-19 pandemic state, essentially careful management including RT-PCR test and chest CT should be taken for the high infection risk surgeries to avoid the outbreak through the hospital. And the cost of RT-PCR test for the patients should be covered by the government budget.


title: Preparing for a COVID-19 pandemic: a review of operating room outbreak response measures in a large tertiary hospital in Singapore

text: The coronavirus disease 2019 (COVID-19) outbreak has been designated a public health emergency of international concern. To prepare for a pandemic, hospitals need a strategy to manage their space, staff, and supplies so that optimum care is provided to patients. In addition, infection prevention measures need to be implemented to reduce in-hospital transmission. In the operating room, these preparations involve multiple stakeholders and can present a significant challenge. Here, we describe the outbreak response measures of the anesthetic department staffing the largest (1,700-bed) academic tertiary level acute care hospital in Singapore (Singapore General Hospital) and a smaller regional hospital (Sengkang General Hospital). These include engineering controls such as identification and preparation of an isolation operating room, administrative measures such as modification of workflow and processes, introduction of personal protective equipment for staff, and formulation of clinical guidelines for anesthetic management. Simulation was valuable in evaluating the feasibility of new operating room set-ups or workflow. We also discuss how the hierarchy of controls can be used as a framework to plan the necessary measures during each phase of a pandemic, and review the evidence for the measures taken. These containment measures are necessary to optimize the quality of care provided to COVID-19 patients and to reduce the risk of viral transmission to other patients or healthcare workers.


title: The pulmonary virome, bacteriological and histopathological findings in bovine respiratory disease from western Canada

text: The aetiology and pathogenesis of bovine respiratory disease (BRD) are complex and involve the interplay of infectious agents, management and environmental factors. Previous studies of BRD focused on ante‐mortem samples from the upper respiratory tract and identified several unconventional viruses. The lung, however, is the primary location where significant BRD lesions are usually found and is a common post‐mortem diagnostic specimen. In this study, results of high‐throughput virome sequencing, bacterial culture, targeted real‐time PCR and histological examination of 130 bovine pneumonic lungs from western Canadian cattle were combined to explore associations of microorganisms with different types of pneumonia. Fibrinous bronchopneumonia (FBP) was the predominant type of pneumonia (46.2%, 60/130) and was associated with the detection of Mannheimia haemolytica. Detection of Histophilus somni and Pasteurella multocida was associated with suppurative bronchopneumonia (SBP) and concurrent bronchopneumonia and bronchointerstitial pneumonia (BP&BIP), respectively. Sixteen viruses were identified, of which bovine parvovirus 2 (BPV2) was the most prevalent (11.5%, 15/130) followed by ungulate tetraparvovirus 1 (UTPV1, 8.5%, 11/130) and bovine respiratory syncytial virus (BRSV, 8.5%, 11/130). None of these viruses, however, were significantly associated with a particular type of pneumonia. Unconventional viruses such as influenza D virus (IDV) and bovine rhinitis B virus (BRBV) were detected, although sparsely, consistent with our previous findings in upper respiratory tract samples. Taken together, our results show that while virus detection in post‐mortem lung samples is of relatively little diagnostic value, the strong associations of H. somni and M. haemolytica with SBP and FBP, respectively, indicate that histopathology can be useful in differentiating bacterial aetiologies.


Algunas consideraciones sobre la ética del triaje en UCI durante la pandemia COVID-19


Knowledge gaps in therapeutic and non-therapeutic research on the Middle East respiratory syndrome


title: Purity and the dangers of regenerative medicine: Regulatory innovation of human tissue-engineered technology

text: This paper examines the development of innovation in human tissue technologies as a form of regenerative medicine, firstly by applying ‘pollution ideas’ to contemporary trends in its risk regulation and to the processes of regulatory policy formation, and secondly by analysing the classificatory processes deployed in regulatory policy. The analysis draws upon data from fieldwork and documentary materials with a focus on the UK and EU (2002–05) and explores four arenas: governance and regulatory policy; commercialisation and the market; ‘evidentiality’ manifest in evidence-based policy; and publics’ and technology users’ values and ethics. The analysis suggests that there is a trend toward ‘purification’ across these arenas, both material and socio-political. A common process of partitioning is found in stakeholders’ attempts to define a clear terrain, which the field of tissue-engineered technology might occupy. We conclude that pollution ideas and partitioning processes are useful in understanding regulatory ordering and innovation in the emerging technological zone of human tissue engineering.


title: Network-inference-based prediction of the COVID-19 epidemic outbreak in the Chinese province Hubei

text: At the moment of writing, the future evolution of the COVID-19 epidemic is unclear. Predictions of the further course of the epidemic are decisive to deploy targeted disease control measures. We consider a network-based model to describe the COVID-19 epidemic in the Hubei province. The network is composed of the cities in Hubei and their interactions (e.g., traffic flow). However, the precise interactions between cities is unknown and must be inferred from observing the epidemic. We propose the Network-Inference-Based Prediction Algorithm (NIPA) to forecast the future prevalence of the COVID-19 epidemic in every city. Our results indicate that NIPA is beneficial for an accurate forecast of the epidemic outbreak.


title: Analysis of complications of prone position in acute respiratory distress syndrome: Quality standard, incidence and related factors

text: Abstract Introduction The monitoring system based on standards of quality allows clinicians to evaluate and improve the patient's care. According to the quality indicators recommended by Sociedad Española de Medicina Intensiva Crítica y Unidades Coronarias, and due to the importance of prone position (PP) as a treatment in patients with acute respiratory distress syndrome, it is fundamental to keep accurate record of serious adverse events occurring during the prone position procedure and its posterior analysis. Objectives To establish fulfilment of the Sociedad Española de Medicina Intensiva Crítica y Unidades Coronarias standards of quality according to the register of serious complications. To identify the incidence of serious complications registered as well as to identify possible factors related to these complications. Method Retrospective, cross-sectional descriptive study, polyvalent ICU (16 beds). Study population Patients with acute respiratory distress syndrome treated with PP (January 2012–December 2013). Study variables PP recording, accidental extubation, removal of catheters, decubitus ulcers (DU), ETT obstruction, urgency of the procedure, hours in PP, nutritional intake, type of feeding tube, food regurgitation/retention and use of prokinetics/muscle relaxant. Results The study sample comprised 38 cases, with an adequate record of complications in 92.1% of the cases. DU were the only serious complication recorded, with a 25.7% incidence. Possible factors related to DU: more hours in PP in patients developing DU (p =0.067). Less incidence of DU in well-nourished patients (p =0.577). 82.9% of patients were not appropriately nourished. Conclusions The percentage of records duly completed is very high. The presence of DU (grade 1–2 mostly) is to be noted. There is no statistical significance, although a trend is obsersed, between DU and hours in PP.


title: 新型冠状病毒肺炎疫情期间肺癌患者临床管理

text: In December 2019, China diagnosed the first patient with 2019 novel coronavirus disease (COVID-19), and the following development of the epidemic had a huge impact on China and the whole world. For patients with lung occupying lesions, the whole process of diagnosis and treatment can not be carried out as usual due to the epidemic. For thoracic surgeons, the timing of surgical intervention should be very carefully considered. All thoracic surgeons in China should work together to develop the proper procedures for the diagnosis and treatment in this special situation, and continuously update the recommendations based on epidemic changes and further understanding of COVID-19. Here, we only offer some preliminary suggestions based on our own knowledge for further reference and discussion.


title: Clinical manifestations in infants and children with Mycoplasma pneumoniae infection

text: BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in older children. Pulmonary and extra-pulmonary symptoms associated with M. pneumoniae infection are reported. M. pneumoniae is mainly epidemic in Denmark with the recurrence every 4-7(th) year. AIMS: Retrospectively, to describe the epidemiology and clinical features, in infants and children, during the M. pneumoniae epidemic in 2010 and 2011. METHODS: All children under the age of 16 that were tested for M. pneumoniae during the period 01.02.2010–31.01.2012 were included. Medical charts, as well as radiological findings, were reviewed for all children with M. pneumoniae. A post-hoc analysis of viral co-infections was done on part of the cohort. RESULTS: 134 of 746 children were tested positive for M. pneumoniae by PCR or serology. Positive tests were found in 65% of children seven years and older, in 30% of 2-6-year-olds and 4% of infants (less than two years of age). Viral co-infection was found in 27% of the tested samples. The clinical presentation was a cough, asthma-like symptoms and low-grade fever. Extra-pulmonary symptoms were common and presented as nausea/vomiting by 33% of the children and skin manifestations by 25%. 84% of the children had a chest x-ray taken, and there were positive radiological findings in 94% of these. CONCLUSION: M. pneumoniae also affected infants and young children and symptoms were similar to infections with respiratory viruses, but severe LRTI were also seen. During an up-coming epidemic, assessment of extra-pulmonary manifestations can be helpful when diagnosing M. pneumoniae infections.


title: Facing the possibility of bioterrorism

text: Abstract The possibility of bioterrorism has been met by significant financial outlays to map out public health responses. These have included comprehensive audits of potential agents, as well as exploring mechanisms for counteracting their impact. Psychological intervention and communication have been identified as key areas requiring further work, as fear of infection could pose a greater strain on social resources than the pathogens themselves. Bioterrorism provides a powerful metaphor for élite fears of social corrosion from within. Accordingly, a broader historical and cultural perspective is required to understand why individuals and societies feel so vulnerable to what remain largely speculative scenarios.


Disaster risk reduction and sustainable development: the role for occupational health


title: Characterization of an internal ribosome entry site within mRNA 5 of murine hepatitis virus

text: The unique region of mRNA 5 of murine hepatitis virus contains two open reading frames, ORF 5a and ORF 5b. The downstream ORF 5b encodes the envelope (E) protein, an integral membrane protein of the virus. We have shown previously that the expression of ORF 5b is mediated by the internal entry of ribosomes. In the experiments reported here, we have used the in vitro translation of synthetic mRNAs to identify the region of mRNA 5 that mediates internal ribosome entry. Our results show that the 5′ border of the MHV mRNA 5 IRES element is located between nucleotides 227 and 244 in ORF 5a, while the 3′ border is located between nucleotides 140 and 172 in ORF 5b. The MHV mRNA 5 IRES element, therefore, contains not more than 280 nucleotides and encompasses the ORF 5b initiation codon. As evidenced by electrophoretic mobility shift assays, the IRES element of mRNA 5 interacts specifically with protein factors present in an L-cell lysate.


title: Adequate Lymphadenectomy as a Quality Measure in Esophageal Cancer: Is there an Association with Treatment Approach?

text: BACKGROUND: The national comprehensive cancer network defines adequate lymphadenectomy as evaluation of ≥ 15 lymph nodes in esophageal cancer. However, varying thresholds have been suggested following neoadjuvant therapy. OBJECTIVES: Our objectives were to (1) explore trends in adequate lymphadenectomy rates over time; (2) evaluate unadjusted lymphadenectomy yield by treatment characteristics; and (3) identify independent factors associated with adequate lymphadenectomy. METHODS: The National Cancer Data Base was used to identify patients who underwent esophagectomy for cancer from 2004 to 2015. Adequate lymphadenectomy trends over time were evaluated using the Cochrane–Armitage test, and lymph node yield by treatment approach was compared using the Mann–Whitney U and Kruskal–Wallis tests. Associations with treatment factors were assessed by multivariable logistic regression. RESULTS: Among 24,413 patients, 9919 (40.6%) had adequate lymphadenectomy. Meeting the nodal threshold increased over time (52.6% in 2015 vs. 26.0% in 2004; p < 0.01). Lymph node yield did not differ based on neoadjuvant therapy (median 12 [interquartile range 7–19] with and without neoadjuvant therapy; p = 0.44). Adequate lymphadenectomy was not associated with neoadjuvant therapy (40.5% vs. 40.8%, odds ratio [OR] 0.94, 95% confidence interval [CI] 0.82–1.07), but was associated with surgical approach (52.7% of laparoscopic cases, OR 1.28, 95% CI 1.06–1.56; 61.2% of robotic cases, OR 1.71, 95% CI 1.34–2.19, vs. 43.5% of open cases), and increasing annual esophagectomy volume (55.6% in the fourth quartile vs. 32.6% in the first quartile; OR 3.57, 95% CI 2.35–5.43). CONCLUSIONS: Despite increases over time, only 50% of patients undergo adequate lymphadenectomy during esophageal cancer resection. Adequate lymphadenectomy was not associated with neoadjuvant therapy. Focusing on surgical approach and esophagectomy volume may further improve adequate lymphadenectomy rates.


title: Relationship between serotypes and genotypes based on the hypervariable region of the S1 gene of infectious bronchitis virus

text: To group infectious bronchitis virus (IBV) isolates, a genetic grouping method based on hypervariable region 1 (HVR 1, nucleotides 168 to 197) was compared with that based on the whole S1 gene. Both methods resulted in the same grouping data. So the grouping method based on HVR 1 could represent the grouping method based on the whole S1 gene. Taiwan isolates could not be placed within the existing groups. In order to test the correlation between genotype and serotype, a one-way neutralization test was used to compare 9 Taiwan isolates selected from different genotypes with Massachusetts (Mass) (H120) and Connecticut (Conn) standard strains. In addition, a two-way cross-neutralization test was performed in embryonated eggs with the β method (constant-virus, diluted-serum) and the reciprocal neutralization titers were calculated to give the relatedness (r) values. The results of two kinds of neutralizing tests showed that the serotypes of 9 isolates were different from Mass or Conn. Based on the r-values, 9 isolates were divided into two serotypes which were correlated with their genotypes. From pathogenicity tests, IBV Taiwan isolates could be divided into high, intermediate, and low pathogenicity according to their pathogenicity indexes. However, no relationship exists between pathotype and genotype. In conclusion, the genetic typing method based on HVR 1 can be used for typing IBV isolates.


title: Detection of respiratory viruses on air filters from aircraft

text: Aims: To evaluate the feasibility of identifying viruses from aircraft cabin air, we evaluated whether respiratory viruses trapped by commercial aircraft air filters can be extracted and detected using a multiplex PCR, bead‐based assay. Methods and Results: The ResPlex II assay was first tested for its ability to detect inactivated viruses applied to new filter material; all 18 applications of virus at a high concentration were detected. The ResPlex II assay was then used to test for 18 respiratory viruses on 48 used air filter samples from commercial aircraft. Three samples tested positive for viruses, and three viruses were detected: rhinovirus, influenza A and influenza B. For 33 of 48 samples, internal PCR controls performed suboptimally, suggesting sample matrix effect. Conclusion: In some cases, influenza and rhinovirus RNA can be detected on aircraft air filters, even more than 10 days after the filters were removed from aircraft. Significance and Impact of the Study: With protocol modifications to overcome PCR inhibition, air filter sampling and the ResPlex II assay could be used to characterize viruses in aircraft cabin air. Information about viruses in aircraft could support public health measures to reduce disease transmission within aircraft and between cities.


title: CT Manifestations of Novel Coronavirus Pneumonia: A Case Report

text: BACKGROUND: Since December 2019, the outbreak of the novel coronavirus has impacted nearly >90,000 people in more than 75 countries. In this case report, we aim to define the chest computed tomography findings of 2019-novel coronavirus associated with pneumonia and its successful resolution after treatment. CASE REPORT: A fifty-year-old female patient, who is a businesswoman, presented with chief complaints of “fever for one week, diarrhea, anorexia, and asthenia.” Initially, she was given Tamiflu. The influenza A virus serology was negative. Three days later, levofloxacin was started because the patient’s symptoms did not improve. The novel coronavirus nucleic acid test was negative. It was noted that before the onset of the disease, the patient went to Wuhan on a business trip. Despite the given treatment, her body temperature rose to 39.2°C and she was referred to our clinic for further evaluation. Then, chest computed tomography was performed and showed bilateral multifocal ground glass opacities with consolidation which suggested viral pneumonia as a differential diagnosis, and the subsequent 2019-novel coronavirus pneumonia nucleic acid test was positive. CONCLUSION: Chest computed tomography offers fast and convenient evaluation of patients with suspected 2019-novel coronavirus pneumonia.


title: Antigenic homology among coronaviruses related to transmissible gastroenteritis virus

text: Abstract The antigenic homology of 26 coronavirus isolates, of which 22 were antigenically related to transmissible gastroenteritis virus (TGEV), was determined with 42 monoclonal antibodies. Type, group, and interspecies specific epitopes were defined. Two group specific MAbs distinguished the enteric TGEV isolates from the respiratory variants. An antigenic subsite involved in neutralization was conserved in porcine, feline, and canine coronavirus. The classification of the human coronavirus 229E in a taxonomic cluster distinct from TGEV group is suggested.


title: Equine proliferative enteropathy – a review of recent developments

text: Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This emerging disease affects mainly weanling foals and causes fever, lethargy, peripheral oedema, diarrhoea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinaemia, thickening of segments of the small intestinal wall observed upon abdominal ultrasonography, positive serology and molecular detection of L. intracellularis in faeces. Although the clinical entity, diagnostic approach and treatment of EPE are well established and described, the epidemiology for this disease has remained largely unaddressed. This article focuses on new developments in the field of EPE, including epidemiology, pathophysiology, clinical signs, diagnosis, treatment and prevention. The Summary is available in Chinese – see Supporting information.


title: Nasal cytokine responses to natural colds in asthmatic children

text: BACKGROUND: The mechanisms by which viruses induce asthma exacerbations are not well-understood. OBJECTIVE: We characterized fluctuations in nasal aspirate cytokines during naturally-occurring respiratory viral infections in children with asthma. METHODS: Sixteen children underwent home collections of nasal aspirates when they were without cold symptoms and again during self-reported respiratory illnesses. The presence of viral infection was ascertained by multiplex PCR. Cytokines were measured by multiplex immune assay. mRNA expression for selected markers of viral infection was measured by RT-PCR. A cumulative respiratory symptom score was calculated for each day of measurement. Generalized estimated equations were used to evaluate associations between viral infection and marker elevation, and between marker elevation and symptom score. RESULTS: The 16 patients completed a total of 37 weeks of assessment (15 “well” weeks; 22 self-assessed “sick” weeks). Viral infections were detected in three of the “well” weeks and 17 of the “sick” weeks (10 rhinovirus, 3 coronavirus, 2 influenza A, 2 influenza B, 2 respiratory syncytial virus, 1 parainfluenza). Compared to virus-negative well weeks, nasal aspirate IFN-γ, CXCL8/IL-8, CXCL10/IP-10, CCL5/RANTES, CCL11/eotaxin-1, CCL2/MCP-1, CCL4/MIP-1β, CCL7/MCP-3 and CCL20/MIP3α protein levels increased during virus-positive sick weeks. Only a subset of cytokines (IFN-γ, CXCL8, CCL2, CCL4, CCL5 and CCL20) correlated with self-reported respiratory tract symptoms. While many aspirates were dilute and showed no mRNA signal, viral infection significantly increased the number of samples that were positive for IFN-λ1, IFN-λ2/3, TLR3, RIG-I and IRF7 mRNA. CONCLUSIONS & CLINICAL RELEVANCE: We conclude that, in children with asthma, naturally-occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs and IFN-responsive genes.


title: COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach

text: The novel coronavirus disease 2019 (COVID-19) pandemic has urged the development and implementation of guidelines and protocols on diagnosis, management, infection control strategies, and discharge planning. However, very little is currently known about neonatal COVID-19 and severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2) infections. Thus, many questions arise with regard to respiratory care after birth, necessary protection to health care workers (HCW) in the delivery room and neonatal intensive care unit (NICU), and safety of bag and mask ventilation, noninvasive respiratory support, deep suctioning, endotracheal intubation, and mechanical ventilation. Indeed, these questions have created tremendous confusion amongst neonatal HCW. In this manuscript, we comprehensively reviewed the current evidence regarding COVID-19 perinatal transmission, respiratory outcomes of neonates born to mothers with COVID-19 and infants with documented SARS-CoV-2 infection, and the evidence for using different respiratory support modalities and aerosol-generating procedures in this specific population. The results demonstrated that to date, neonatal COVID-19 infection is uncommon, generally acquired postnatally, and associated with favorable respiratory outcomes. The reason why infants display a milder spectrum of disease remains unclear. Nonetheless, the risk of severe or critical illness in young patients exists. Currently, the recommended respiratory approach for infants with suspected or confirmed infection is not evidence based but should include all routinely used types of support, with the addition of viral filters, proper personal protective equipment, and placement of infants in isolation rooms, ideally with negative pressure. As information is changing rapidly, clinicians should frequently watch out for updates on the subject. Key Points: Novel coronavirus disease 2019 (COVID-19) pandemic urged development of guidelines. Neonatal COVID-19 disease is uncommon. Respiratory outcomes in neonates seems favorable. Current neonatal respiratory care should continue. Clinicians should watch frequently for updates.


title: Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry

text: The discovery of SARS-like coronavirus in bats suggests that bats could be the natural reservoir of SARS-CoV. However, previous studies indicated the angiotensin-converting enzyme 2 (ACE2) protein, a known SARS-CoV receptor, from a horseshoe bat was unable to act as a functional receptor for SARS-CoV. Here, we extended our previous study to ACE2 molecules from seven additional bat species and tested their interactions with human SARS-CoV spike protein using both HIV-based pseudotype and live SARS-CoV infection assays. The results show that ACE2s of Myotis daubentoni and Rhinolophus sinicus support viral entry mediated by the SARS-CoV S protein, albeit with different efficiency in comparison to that of the human ACE2. Further, the alteration of several key residues either decreased or enhanced bat ACE2 receptor efficiency, as predicted from a structural modeling study of the different bat ACE2 molecules. These data suggest that M. daubentoni and R. sinicus are likely to be susceptible to SARS-CoV and may be candidates as the natural host of the SARS-CoV progenitor viruses. Furthermore, our current study also demonstrates that the genetic diversity of ACE2 among bats is greater than that observed among known SARS-CoV susceptible mammals, highlighting the possibility that there are many more uncharacterized bat species that can act as a reservoir of SARS-CoV or its progenitor viruses. This calls for continuation and expansion of field surveillance studies among different bat populations to eventually identify the true natural reservoir of SARS-CoV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-010-0729-6) contains supplementary material, which is available to authorized users.


title: HEART BRAKE-An unusual cardiac manifestation of Coronavirus disease 2019 (COVID-19)

text: Abstract: A 49-year-old male presented with worsening high-grade fevers, dry cough and shortness of breath, tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and was noted to have bradycardia with intermittent high-degree AV block. However, cardiac biomarkers and echocardiography were normal, making this an unusual and interesting manifestation showing myocardial involvement of this novel coronavirus.


title: Evaluation of a web-based self-reporting method for monitoring international passengers returning from an area of emerging infection

text: Abstract Objectives. Emerging infectious diseases are a public health issue of international concern. Identifying methods to limit their expansion is essential. We assessed the feasibility of a screening strategy in which each traveler would actively participate in the screening process after an intercontinental flight by reporting their own health status via a web-based self-administered questionnaire. Patients and methods. In 2015 and 2017, we invited passengers arriving at or departing from Pointe-à-Pitre international airport to answer an online health questionnaire during the four days following their arrival from or at Paris-Orly international airport. SPIRE 1 was intended for passengers arriving at Pointe-à-Pitre and was conceived as a pilot study. SPIRE 2 was an improved version of SPIRE 1 and consisted in three parts, which permitted to further assess the benefits of pre-flight request and email follow-up. Endpoints were the connection rates and response rates to online health questionnaire. Results. For SPIRE 1, 4/1,038 travelers (0.4%) completed the two steps of the online health questionnaire. In SPIRE 2, response rates ranged from 3/1,059 (0.3%) to 19/819 (2.3%). Response rates were significantly better when passengers were approached before their flight. Conclusions. The yield of an online health questionnaire was unexpectedly low.


title: Psychological status of parents of hospitalized children during the COVID-19 epidemic in China

text: Abstract A series of unexplained pneumonia appeared in Wuhan, Hubei Province, China, which is highly contagious. The virus is prone to nervous and anxious psychological reactions. In the objective environment of complex and densely populated hospitals, it is a high-risk area for virus-transmitted infections and children generally have lower immunity who are more likely to develop infections. The results showed that the mental health problems of parents of hospitalized children during the epidemic were more serious, and the anxiety and depression were more obvious.


title: Community acquired respiratory virus infections in cancer patients—Guideline on diagnosis and management by the Infectious Diseases Working Party of the German Society for haematology and Medical Oncology

text: Abstract Background Community acquired viruses (CRVs) may cause severe disease in cancer patients. Thus, efforts should be made to diagnose CRV rapidly and manage CRV infections accordingly. Methods A panel of 18 clinicians from the Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology have convened to assess the available literature and provide recommendations on the management of CRV infections including influenza, respiratory syncytial virus, parainfluenza virus, human metapneumovirus and adenovirus. Results CRV infections in cancer patients may lead to pneumonia in approximately 30% of the cases, with an associated mortality of around 25%. For diagnosis of a CRV infection, combined nasal/throat swabs or washes/aspirates give the best results and nucleic acid amplification based-techniques (NAT) should be used to detect the pathogen. Hand hygiene, contact isolation and face masks have been shown to be of benefit as general infection management. Causal treatment can be given for influenza, using a neuraminidase inhibitor, and respiratory syncytial virus, using ribavirin in addition to intravenous immunoglobulins. Ribavirin has also been used to treat parainfluenza virus and human metapneumovirus, but data are inconclusive in this setting. Cidofovir is used to treat adenovirus pneumonitis. Conclusions CRV infections may pose a vital threat to patients with underlying malignancy. This guideline provides information on diagnosis and treatment to improve the outcome.


title: Ecotoxic response of nematodes to ivermectin, a potential anti-COVID-19 drug treatment

text: At the end of March 2020, ivermectin was confirmed as a drug for COVID-19 treatment. A significant amount of ivermectin could deposit into sediments of the semi-closed Mediterranean Sea, where three European COVID-19 epicenters are located: Italy, Spain, and France. Meiobenthic nematodes were exposed to three ivermectin doses (1.8 ng.g(−1), 9 ng.g(−1), and 18 ng.g(−1)) for 10 days. Ivermectin caused a great reduction in abundance. However, the diversity indices decreased only at high doses. Ivermectin disadvantaged the 1B-Cr-Id functional type (non-selective deposit feeders and nematodes with circular or indistinct amphids) and benefited the 2A-REL-Sp type (epistrate feeders and nematodes with rounded or elongated loop amphids). Thus, Trophic Diversity and Amphideal Diversity index values increased with sedimentary ivermectin enrichment. Large amphideal foveas were more efficient for 2A-REL-Sp nematodes to avoid ivermectin. The responses of the functional type 2A-REL-Sp and corresponding taxa predict post-COVID-19 environmental concerns and the bioaccumulation of ivermectin in seafoods.


title: Impact of COVID-19 Pandemic on Gynecological Oncology Care: Glimpse into Association of Gynecological Oncologists of India (AGOI) Perspective

text: PURPOSE: The notorious COVID 19 pandemic has caused rapid and drastic changes in cancer care worldwide in 2020. This online survey aims to assess the extent to which the pandemic has affected cancer care in gynecological oncology amongst members of the Association of Gynecological Oncologists of India (AGOI), a registered professional society founded in 1991. METHODS: We developed and administered a cross-sectional, flash survey to members of AGOI in the first week of April 2020. Data were analyzed using Microsoft Office Excel 2016. Results were expressed as percentages of total responses excluding blank or unattended response. Overall theme-specific responses were described as a spectrum of findings, and related inferences were drawn. RESULTS: Among approached practitioners, 90 responded to the survey, more than 80% were practicing consultants, and more than 50% from academic institutions. The results of the study showed that the ongoing pandemic had severely affected gynecological oncology practice and care amongst all respondents. There were modifications in diagnostic pathways, interventions, and follow-ups across all organ sites. There was a near-unanimous opinion on the use of general safety measures to combat the virus and to use complete PPEs in a high-risk situation. There were mixed responses to alternative educational activities, especially using electronic technology and distant learning methods. There was optimism among respondents with regards to the current situation normalizing in 3–6 months. CONCLUSION: This study documents the pandemic affected scenario of gynecological cancer care and perceptions of Gynecological Oncologists in India. A significant effect on all aspects of cancer care was observed. Technological learning methods, both for patient care and educational activities, were being adopted by many respondents. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40944-020-00421-8) contains supplementary material, which is available to authorized users.


title: A dissection of SARS-CoV2 with clinical implications (Review)

text: We are being confronted with the most consequential pandemic since the Spanish flu of 1918-1920 to the extent that never before have 4 billion people quarantined simultaneously; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS-CoV2 structure and functions, immune responses and known treatments. Based on literature and our own experience we propose new interventions, including the use of amiodarone, simvastatin, pioglitazone and curcumin. In mild infections (sore throat, cough) we advocate prompt local treatment for the naso-pharynx (inhalations; aerosols; nebulizers); for moderate to severe infections we propose a tried-and-true treatment: the combination of arginine and ascorbate, administered orally or intravenously. The material is organized in three sections: i) Clinical aspects of COVID-19; acute respiratory distress syndrome (ARDS); known treatments; ii) Structure and functions of SARS-CoV2 and proposed antiviral drugs; iii) The combination of arginine-ascorbate.


title: Alpha and lineage C betaCoV infections in Italian bats

text: AlphaCoV and lineage C betaCoV, genetically similar to those identified in Spanish related bat species, have been detected in Italian Myotis blithii and Eptesicus serotinus, respectively, out of 75 anal swabs collected from Vespertilionidae between 2009 and 2012. Sequence analysis of the 816-bp obtained RdRp sequence fragment indicates a 96.9 % amino acid identity of the Italian lineage C betaCoV with the recent Middle East Respiratory Syndrome Coronavirus (MERS-CoV, Genbank accession number KF192507). This is the first documented occurrence of a lineage C betaCoV in the Italian bat population, notably in E. serotinus.


title: Modulation of gut microbiota through nutritional interventions in Behçet’s syndrome patients (the MAMBA study): study protocol for a randomized controlled trial

text: BACKGROUND: Behçet’s syndrome (BS) is a systemic inflammatory disorder of unknown etiology, and it is characterized by a wide range of potential clinical manifestations. Recent evidence suggests that the gut microbiota (GM) in BS has low biodiversity with a significant depletion in butyrate producers. The aim of the present project is to investigate whether a dietary intervention could ameliorate the clinical manifestations and modulate the GM of individuals with BS. METHODS: This is a randomized, open, cross-over study that involves 90 individuals with BS, who will be randomly assigned to one of three different diets for 3 months: a lacto-ovo-vegetarian diet (VD), a Mediterranean diet (MD), or a Mediterranean diet supplemented with butyrate (MD-Bt). The VD will contain inulin-resistant and resistant-starch-rich foods, eggs, and dairy in addition to plant-based food, but it will not contain meat, poultry, or fish. The MD will contain all food categories and will provide two portions per week of fish and three portions per week of fresh and processed meat. The MD-Bt will be similar to the MD but supplemented with 1.8 g/day of oral butyrate. The three different diets will be isocaloric and related to the participants’ nutritional requirements. Anthropometric measurements, body composition, blood, and fecal samples will be obtained from each participant at the beginning and the end of each intervention phase. The primary outcomes will be represented by the change from baseline of the BS gastrointestinal and systemic symptoms. Changes from baseline in GM composition, short-chain fatty acid (SCFA) production, and the inflammatory and antioxidant profile will be considered as secondary outcomes. DISCUSSION: BS is a rare disease, and, actually, not all the available treatments are target therapies. A supportive treatment based on dietary and lifestyle issues, able to restore immune system homeostasis, could have a high impact on cost sustainability for the treatment of such a chronic and disabling inflammatory condition. TRIAL REGISTRATION: clinicaltrials.gov: NCT03962335. Registered on 21 May 2019.


title: Hajj in the Time of COVID-19

text: Abstract The recent outbreak of the novel COVID-19 is posing a severe public health risk across the globe. The Kingdom of Saudi Arabia (KSA) is one of the greatest destinations of religious congregations of Muslims. One of the largest religious gatherings is the Hajj that is anticipated to produce serious challenges of mass level exposures and spread to every corner of the world. Therefore, it is highly recommended that the Ministry of Hajj and Umrah (KSA), must regularly analyze the prevailing situation of COVID-19, and involve the religious scholars to make appropriate decisions about Hajj 2020. Although the Saudi government has been continuously taking all possible measures to contain the pandemic, people's cooperation is crucial in the fight against COVID-19.


title: Demineralized bone matrix in bone repair: History and use

text: Abstract Demineralized bone matrix (DBM) is an osteoconductive and osteoinductive commercial biomaterial and approved medical device used in bone defects with a long track record of clinical use in diverse forms. True to its name and as an acid-extracted organic matrix from human bone sources, DBM retains much of the proteinaceous components native to bone, with small amounts of calcium-based solids, inorganic phosphates and some trace cell debris. Many of DBM's proteinaceous components (e.g., growth factors) are known to be potent osteogenic agents. Commercially sourced as putty, paste, sheets and flexible pieces, DBM provides a degradable matrix facilitating endogenous release of these compounds to the bone wound sites where it is surgically placed to fill bone defects, inducing new bone formation and accelerating healing. Given DBM's long clinical track record and commercial accessibility in standard forms and sources, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopedic repair and regenerative medicine contexts are attractive.


title: SARS‐CoV‐2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens

text: PURPOSE: The purpose of this study was to detect severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) ribonucleic acid (RNA) in urine and blood specimens, and anal and oropharyngeal swabs from patients with confirmed SARS‐CoV‐2 infection, and correlated positive results with clinical findings. METHODS: Patients with confirmed SARS‐CoV‐2 infections were included in this study. Patients' demographic and clinical data were recorded. Quantitative real‐time polymerase chain reaction was used to detect SARS‐CoV‐2 RNA in urine and blood specimens, and anal and oropharyngeal swabs. The study is registered at http://ClinicalTrials.gov (No. NCT04279782, 19 February, 2020). RESULTS: SARS‐CoV‐2 RNA was present in all four specimen types, though not all specimen types were positive simultaneously. The presence of viral RNA was not necessarily predictive of clinical symptoms, for example, the presence of viral RNA in the urine did not necessarily predict urinary tract symptoms. CONCLUSIONS: SARS‐CoV‐2 can infect multiple systems, including the urinary tract. Testing different specimen types may be useful for monitoring disease changes and progression, and for establishing a prognosis.


title: Design, synthesis and primary activity evaluation of l-arginine derivatives as amino-peptidase N/CD13 inhibitors

text: Abstract A series of l-arginine derivatives were designed, synthesized and assayed for their activities against amino-peptidase N (APN)/CD13 and metalloproteinase-2 (MMP-2). The results showed that most compounds exhibited high inhibitory activities against APN and low activities against MMP-2. Within this series, two compounds 5q and 5s (IC50 =5.3 and 5.1μM) showed similar inhibitory activities compared with bestatin (IC50 =3.8μM), which could be used as novel lead compounds for the future APN inhibitors development as anticancer agents.


title: Monitoring Disease Trends using Hospital Traffic Data from High Resolution Satellite Imagery: A Feasibility Study

text: Challenges with alternative data sources for disease surveillance include differentiating the signal from the noise, and obtaining information from data constrained settings. For the latter, events such as increases in hospital traffic could serve as early indicators of social disruption resulting from disease. In this study, we evaluate the feasibility of using hospital parking lot traffic data extracted from high-resolution satellite imagery to augment public health disease surveillance in Chile, Argentina and Mexico. We used archived satellite imagery collected from January 2010 to May 2013 and data on the incidence of respiratory virus illnesses from the Pan American Health Organization as a reference. We developed dynamical Elastic Net multivariable linear regression models to estimate the incidence of respiratory virus illnesses using hospital traffic and assessed how to minimize the effects of noise on the models. We noted that predictions based on models fitted using a sample of observations were better. The results were consistent across countries with selected models having reasonably low normalized root-mean-squared errors and high correlations for both the fits and predictions. The observations from this study suggest that if properly procured and combined with other information, this data source could be useful for monitoring disease trends.


title: A Role for H/ACA and C/D Small Nucleolar RNAs in Viral Replication

text: We have employed gene-trap insertional mutagenesis to identify candidate genes whose disruption confer phenotypic resistance to lytic infection, in independent studies using 12 distinct viruses and several different cell lines. Analysis of >2,000 virus-resistant clones revealed >1,000 candidate host genes, approximately 20 % of which were disrupted in clones surviving separate infections with 2–6 viruses. Interestingly, there were 83 instances in which the insertional mutagenesis vector disrupted transcripts encoding H/ACA-class and C/D-class small nucleolar RNAs (SNORAs and SNORDs, respectively). Of these, 79 SNORAs and SNORDs reside within introns of 29 genes (predominantly protein-coding), while 4 appear to be independent transcription units. siRNA studies targeting candidate SNORA/Ds provided independent confirmation of their roles in infection when tested against cowpox virus, Dengue Fever virus, influenza A virus, human rhinovirus 16, herpes simplex virus 2, or respiratory syncytial virus. Significantly, eight of the nine SNORA/Ds targeted with siRNAs enhanced cellular resistance to multiple viruses suggesting widespread involvement of SNORA/Ds in virus–host interactions and/or virus-induced cell death.


title: Synthesis of stilbene derivatives with inhibition of SARS coronavirus replication

text: Stilbene derivatives have wide range of activities. In an effort to find other potential activities of this kind of compounds, 17 derivatives, including resveratrol, were synthesized. Twelve of them were evaluated for their antiviral potential against severe acute respiratory syndrome (SARS)-CoV-induced cytopathicity in Vero E6 cell culture. The result showed that SARS virus was totally inhibited by compounds 17 and 19 ( ≤ 0.5 mg ml(–1)) and no significant cytotoxic effects were observed in vitro.


Ocular Pathology Recommendations during COVID-19 from the American Association of Ophthalmic Oncologists and Pathologists (AAOOP)


title: Stillbirth During Infection With Middle East Respiratory Syndrome Coronavirus

text: We conducted an epidemiologic investigation among survivors of an outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in Jordan. A second-trimester stillbirth occurred during the course of an acute respiratory illness that was attributed to MERS-CoV on the basis of exposure history and positive results of MERS-CoV serologic testing. This is the first occurrence of stillbirth during an infection with MERS-CoV and may have bearing upon the surveillance and management of pregnant women in settings of unexplained respiratory illness potentially due to MERS-CoV. Future prospective investigations of MERS-CoV should ascertain pregnancy status and obtain further pregnancy-related data, including biological specimens for confirmatory testing.


title: Machine intelligence design of 2019-nCoV drugs

text: Wuhan coronavirus, called 2019-nCoV, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by January 30, 2020. Currently, there is no effective treatment for this epidemic. However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV) is as high as 96.1%. We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV are almost identical, which means all potential anti-SARS-CoV chemotherapies are also potential 2019-nCoV drugs. Here, we report a family of potential 2019-nCoV drugs generated by a machine intelligence-based generative network complex (GNC). The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed.


title: COMPANION ANIMALS SYMPOSIUM: Microbes and gastrointestinal health of dogs and cats

text: Recent molecular studies have revealed complex bacterial, fungal, archaeal, and viral communities in the gastrointestinal tract of dogs and cats. More than 10 bacterial phyla have been identified, with Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, and Actinobacteria constituting more than 99% of all gut microbiota. Microbes act as a defending barrier against invading pathogens, aid in digestion, provide nutritional support for enterocytes, and play a crucial role in the development of the immune system. Of significance for gastrointestinal health is their ability to ferment dietary substrates into short-chain fatty acids, predominantly to acetate, propionate, and butyrate. However, microbes can have also a detrimental effect on host health. Specific pathogens (e.g., Salmonella, Campylobacter jejuni, and enterotoxigenic Clostridium perfringens) have been implicated in acute and chronic gastrointestinal disease. Compositional changes in the small intestinal microbiota, potentially leading to changes in intestinal permeability and digestive function, have been suggested in canine small intestinal dysbiosis or antibiotic-responsive diarrhea. There is mounting evidence that microbes play an important role in the pathogenesis of canine and feline inflammatory bowel disease (IBD). Current theories for the development of IBD favor a combination of environmental factors, the intestinal microbiota, and a genetic susceptibility of the host. Recent studies have revealed a genetic susceptibility for defective bacterial clearance in Boxer dogs with granulomatous colitis. Differential expression of pathogen recognition receptors (i.e., Toll-like receptors) were identified in dogs with chronic enteropathies. Similarly to humans, a microbial dysbiosis has been identified in feline and canine IBD. Commonly observed microbial changes are increased Proteobacteria (i.e., Escherichia coli) with concurrent decreases in Firmicutes, especially a reduced diversity in Clostridium clusters XIVa and IV (i.e., Lachnospiraceae, Ruminococcaceae, Faecalibacterium spp.). This would indicate that these bacterial groups, important short-chain fatty acid producers, may play an important role in promoting intestinal health.


title: Acute Viral Hepatitis

text: Acute viral hepatitis refers to hepatic infection by the hepatotropic viruses hepatitis A–E. The acute infections look similar with regard to histologic features, with spotty necrosis throughout the lobules, hepatocyte unrest, swelling and apoptosis, and portal tract and intrasinusoidal inflammation, chiefly lymphocytes. The differential diagnosis histologically includes drug-induced liver injury. Structural differences and epidemiology define the major differences in the course of each of these viral infections. Hepatitis A and E are similar in causing only acute hepatitis, while some cases of hepatitis B and many of hepatitis C become chronic. The prevalence of hepatitis D virus (HDV) infection has seen a reduction worldwide due to hepatitis B vaccination programs. Nonetheless, major cities with continued intravenous drug use remain reservoirs with a rate of approximately 8% in Europe. The availability of direct-acting viral agents is spearheading efforts by WHO to eliminate new and chronic HCV infections by 2019. Histologic cholestasis may be a particular feature of acute hepatitis E. It should be noted that hepatitis E virus has four major genotypes of which 1 and 2 infect humans (resulting in travel/endemic-related hepatitis with cholestasis and high mortality in pregnant women) and 3 and 4 are zoonotic and infect pigs, boar and several other animal and avian species (and may cause hepatitis associated with poorly or uncooked meat).


title: Regulating gene expression in animals through RNA endonucleolytic cleavage

text: The expression of any gene must be precisely controlled for appropriate function. This expression can be controlled at various levels. This includes epigenetic regulation through DNA methylation or histone modifications. At the posttranscriptional level, regulation can be via alternative splicing or controlling messenger RNA (mRNA) stability. RNA cleavage is one way to control mRNA stability. For example, microRNA (miRNA)-induced mRNA cleavage has long been recognised in plants. RNA cleavage also appears to be widespread in other kingdoms of life, and it is now clear that mRNA cleavage plays critical functions in animals. Although miRNA-induced mRNA cleavage can occur in animals, it is not a widespread mechanism. Instead, mRNA cleavage can be induced by a range of other mechanisms, including by endogenous short inhibitory RNAs (endo-siRNAs), as well as the Ribonuclease III (RNase III) enzymes Drosha and Dicer. In addition, RNA cleavage induced by endo-siRNAs and PIWI-interacting RNAs (piRNAs) is important for genome defence against transposons. Moreover, several RNase has been identified as important antiviral mediators. In this review, we will discuss these various RNA endonucleolytic cleavage mechanisms utilised by animals to regulate the expression of genes and as a defence against retrotransposons and viral infection.


title: Psychophysical Effects of Nasal and Oral Inflammation

text: Olfactory disorders are common in “nasal inflammation” even though the term is comprehensive and subsumes different kinds of entities which have to be differentiated. The most common cause of olfactory disorders are sinonasal disorders, which are defined as secondary smell disorders caused by diseases/pathologies in the nose/paranasal sinuses. According to the literature, sinonasal disorders represent—depending on the examined population—up to 72% of all olfactory disorders. In general, noninflammatory and inflammatory disorders are differentiated. Inflammatory disorders can be further classified into infectious or noninfectious disorders, both forms in which olfactory disorders can be present. For the clinician examining patients, the exact classification of the olfactory disorder is mandatory in order to choose appropriate treatment and counseling. Among the most common inflammatory disorders are acute rhinitis, allergic rhinitis, post‐upper respiratory tract infection and chronic rhinosinusitis, which are discussed in detail. In contrast to nasal inflammation, only little is known about oral inflammation and its psychophysical effects on taste function. Taste disorders following oral inflammation are briefly discussed.


title: The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells

text: Virus-host interactions in the respiratory epithelium during long term influenza virus infection are not well characterized. Therefore, we developed an air-liquid interface culture system for differentiated porcine respiratory epithelial cells to study the effect of virus-induced cellular damage. In our well-differentiated cells, α2,6-linked sialic acid is predominantly expressed on the apical surface and the basal cells mainly express α2,3-linked sialic acid. During the whole infection period, release of infectious virus was maintained at a high titre for more than seven days. The infected epithelial cells were subject to apoptosis resulting in the loss of ciliated cells together with a thinner thickness. Nevertheless, the airway epithelium maintained trans-epithelial electrical resistance and retained its barrier function. The loss of ciliated cells was compensated by the cells which contained the KRT5 basal cell marker but were not yet differentiated into ciliated cells. These specialized cells showed an increase of α2,3-linked sialic acid on the apical surface. In sum, our results help to explain the localized infection of the airway epithelium by influenza viruses. The impairment of mucociliary clearance in the epithelial cells provides an explanation why prior viral infection renders the host more susceptible to secondary co-infection by another pathogen.


title: Delaying the International Spread of Pandemic Influenza

text: BACKGROUND: The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics. METHODS AND FINDINGS: To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected. CONCLUSIONS: Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks.


Reorganize and survive—a recommendation for healthcare services affected by COVID-19—the ophthalmology experience


title: A Systematic Review of therapeutic agents for the treatment of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

text: Abstract Background The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first described in 2012 and attracted a great international attention due to multiple healthcare associated outbreaks. The disease carries a high case fatality rate of 34.5%, and there is no internationally or nationally recommended therapy. Method We searched MEDLINE, Science Direct, Embase and Scopus databases for relevant papers published till March 2019 describing in vitro, in vivo or human therapy of MERS. Results Initial search identified 62 articles: 52 articles were from Medline, 6 from Embase, and 4 from Science Direct. Based on the inclusions and exclusions criteria, 30 articles were included in the final review and comprised: 22 in vitro studies, 8 studies utilizing animal models, 13 studies in humans, and one study included both in vitro and animal model. There are a few promising therapeutic agents on the horizon. The combination of lopinavir/ritonavir and interferon-beta- 1b showed excellent results in common marmosets and currently is in a randomized control trial. Ribavirin and interferon were the most widely used combination and experience comes from a number of observational studies. Although, the data are heterogenous, this combination might be of potential benefit and deserve further investigation. There were no randomized clinical trials to recommend specific therapy for the treatment of MERS-CoV infection. Only one such study is planned for randomization and is pending completion. The study is based on a combination of lopinavir/ritonavir and interferon-beta- 1b. A fully human polyclonal IgG antibody (SAB-301) was safe and well tolerated in healthy individuals and this agent may deserve further testing for efficacy. Conclusion Despite multiple studies in humans there is no consensus on the optimal therapy for MERS-CoV. Randomized clinical trials are needed and potential therapies should be evaluated only in such clinical trials. In order to further enhance the therapeutic aroma for MERS-CoV infection, repurposing old drugs against MERS-CoV is an interesting strategy and deserves further consideration and use in clinical settings.


Reduction in ST-Segment Elevation Cardiac Catheterization Laboratory Activations in the United States during COVID-19 Pandemic


title: Antagonizing Interferon-Mediated Immune Response by Porcine Reproductive and Respiratory Syndrome Virus

text: Interferons (IFNs) are important components in innate immunity involved in the first line of defense to protect host against viral infection. Porcine reproductive and respiratory syndrome virus (PRRSV) leads to severe economic losses for swine industry since being first identified in early 1990s. PRRSV interplays with host IFN production and IFN-activated signaling, which may contribute to the delayed onset and low level of neutralizing antibodies, as well as weak cell-mediated immune response in infected pigs. PRRSV encodes several proteins that act as antagonists for the IFN signaling. In this review, we summarized the various strategies used by PRRSV to antagonize IFN production and thwart IFN-activated antiviral signaling, as well as the variable interference with IFN-mediated immune response by different PRRSV strains. Thorough understanding of the interaction between PRRSV and host innate immune response will facilitate elucidation of PRRSV pathogenesis and development of a better strategy to control PRRS.


title: Experimental infection of cattle, sheep and pigs with ‘Hobi’-like pestivirus

text: Abstract To date, limited information is available on the ability of ‘Hobi’-like pestiviruses (putative bovine viral diarrhoea 3) to infect and cause disease in animal species traditionally affected by pestiviruses. In order to obtain new insights into host range and pathogenic potential of this atypical pestivirus, BVDV-seronegative calves (n =5), lambs (n =5) and piglets (n =5) were experimentally infected with the European ‘Hobi’-like strain Italy-1/10-1, whereas two animals per species served as uninfected controls. Appearance of clinical signs, leukopenia, viremia, viral shedding and seroconversion were monitored for 28 days post-infection. Calves and lambs were successfully infected, displaying respiratory signs (nasal discharge), moderate hyperthermia and leukopenia, viremia and viral shedding through the nasal and faecal routes. Antibody responses were observed in both animal species by ELISA and virus neutralisation assays. In contrast, inoculated piglets did not display any clinical signs nor leukopenia and viral RNA was not detected in any biological samples. Nevertheless, the presence of detectable antibodies by virus neutralisation accounted for a successful, albeit limited infection of these animals.


title: A Real‐World Evidence Framework for Optimising Dosing in All Patients with COVID‐19

text: The SARS‐CoV‐2 pandemic and associated COVID‐19 disease are straining healthcare systems around the world with large numbers of patients becoming ill in a very short period of time, overwhelming healthcare systems in many countries. Several drugs are being repurposed into clinical trials in COVID‐19 patients, ranging from drugs already well established in other diseases, such as chloroquine/hydroxychloroquine, lopinavir+ ritonavir, azithromycin and tocilizumab/sarilumab, to those such as remdesivir still in development for their initial indication (1). The opportunities for clinical pharmacology to contribute to the development of new treatments have already been described by others in Clinical Pharmacology & Therapeutics (2).


title: Biosafety and biosecurity approaches to restrain/contain and counter SARS-CoV-2/COVID-19 pandemic: a rapid-review

text: Emergence and reemergence of infectious diseases pose significant public health risks that are continuously haunting human civilization in the past several decades. Such emerging pathogens should be considered as a high threat to humans, animals, and environmental health. The year 2020 was welcomed by another significant virus from family Coronaviridae called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease 2019 (COVID-19). The disease was first reported in the city of Wuhan, Hubei province, China. Within a short time, this disease attained the status of the Public Health Emergency of International Concern. Presently, COVID-19 has spread to more than 150 countries, therefore, the World Health Organization (WHO) called it a pandemic. The Chinese government, along with WHO, other health agencies, and many nations, are monitoring the current situation closely to analyze the impact of SARS-CoV-2/COVID-19 on humans, animals, and environmental health. In the context of the current situation, biosafety and biosecurity measure that focus on One Health aspects of the disease outbreaks and the SARS-CoV-2 spread are of great importance to restrain this pathogen. Along with these efforts, standard precaution and control measures should also be taken at personal and community level to prevent the spreading of any contagion diseases, including COVID-19. Researchers are putting their very high efforts to develop suitable vaccines and therapeutics/drugs to combat COVID-19. This review aims to highlight the importance of biosafety, biosecurity, One Health approach, and focusing on recent developments and the ways forward to prevent and control COVID-19 in a useful way.


title: Voices from the frontline: findings from a thematic analysis of a rapid online global survey of maternal and newborn health professionals facing the COVID-19 pandemic

text: INTRODUCTION: The COVID-19 pandemic has substantially impacted maternity care provision worldwide. Studies based on modelling estimated large indirect effects of the pandemic on services and health outcomes. The objective of this study was to prospectively document experiences of frontline maternal and newborn healthcare providers. METHODS: We conducted a global, cross-sectional study of maternal and newborn health professionals via an online survey disseminated through professional networks and social media in 12 languages. Information was collected between 24 March and 10 April 2020 on respondents’ background, preparedness for and response to COVID-19 and their experience during the pandemic. An optional module sought information on adaptations to 17 care processes. Descriptive statistics and qualitative thematic analysis were used to analyse responses, disaggregating by low-income and middle-income countries (LMICs) and high-income countries (HICs). RESULTS: We analysed responses from 714 maternal and newborn health professionals. Only one-third received training on COVID-19 from their health facility and nearly all searched for information themselves. Half of respondents in LMICs received updated guidelines for care provision compared with 82% in HICs. Overall, 47% of participants in LMICs and 69% in HICs felt mostly or completely knowledgeable in how to care for COVID-19 maternity patients. Facility-level responses to COVID-19 (signage, screening, testing and isolation rooms) were more common in HICs than LMICs. Globally, 90% of respondents reported somewhat or substantially higher levels of stress. There was a widespread perception of reduced use of routine maternity care services, and of modification in care processes, some of which were not evidence-based practices. CONCLUSIONS: Substantial knowledge gaps exist in guidance on management of maternity cases with or without COVID-19. Formal information-sharing channels for providers must be established and mental health support provided. Surveys of maternity care providers can help track the situation, capture innovations and support rapid development of effective responses.


title: Segmentation with Area Constraints

text: Image segmentation approaches typically incorporate weak regularity conditions such as boundary length or curvature terms, or use shape information. High-level information such as a desired area or volume, or a particular topology are only implicitly specified. In this paper we develop a segmentation method with explicit bounds on the segmented area. Area constraints allow for the soft selection of meaningful solutions, and can counteract the shrinking bias of length-based regularization. We analyze the intrinsic problems of convex relaxations proposed in the literature for segmentation with size constraints. Hence, we formulate the area-constrained segmentation task as a mixed integer program, propose a branch and bound method for exact minimization, and use convex relaxations to obtain the required lower energy bounds on candidate solutions. We also provide a numerical scheme to solve the convex subproblems. We demonstrate the method for segmentations of vesicles from electron tomography images.


title: Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

text: A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.


Teaching anatomy at the time of COVID‐19


title: DAS181 treatment of severe parainfluenza type 3 pneumonia in a lung transplant recipient

text: Parainfluenza virus (PIV) may cause life‐threatening pneumonia in lung transplant patients and there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, to treat severe PIV type 3 pneumonia in a lung transplant patient. Treatment was well tolerated and associated with improvement in oxygenation and symptoms, along with rapid clearance of PIV. DAS181 should be systematically evaluated for treatment of PIV infection in transplant recipients.


title: Guidelines for prevention of hospital acquired infections

text: These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments.


title: Sero-prevalence, cross-species infection and serological determinants of prevalence of Bovine Coronavirus in Cattle, Sheep and Goats in Ghana

text: Abstract Cattle, goats and sheep are dominant livestock species in sub-Saharan Africa, with sometimes limited information on the prevalence of major infectious diseases. Restrictions due to notifiable epizootics complicate the exchange of samples in surveillance studies and suggest that laboratory capacities should be established domestically. Bovine Coronavirus (BCoV) causes mainly enteric disease in cattle. Spillover to small ruminants is possible. Here we established BCoV serology based on a recombinant immunofluorescence assay for cattle, goats and sheep, and studied the seroprevalence of BCoV in these species in four different locations in the Greater Accra, Volta, Upper East, and Northern provinces of Ghana. The whole sampling and testing was organized and conducted by a veterinary school in Kumasi, Ashanti Region of Ghana. Among sampled sheep (n = 102), goats (n = 66), and cattle (n = 1495), the seroprevalence rates were 25.8 %, 43.1 % and 55.8 %. For cattle, seroprevalence was significantly higher on larger farms (82.2 % vs 17.8 %, comparing farms with >50 or <50 animals; p = 0.027). Highest prevalence was seen in the Northern province with dry climate, but no significant trend following the north-south gradient of sampling sites was detected. Our study identifies a considerable seroprevalence for BCoV in Ghana and provides further support for the spillover of BCoV to small ruminants in settings with mixed husbandry and limited separation between species.