title: Predicting mortality due to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico

text: BACKGROUND: The SARS-CoV-2 outbreak poses challenge to healthcare systems due to high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity and its role in improving risk prediction. METHODS: We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19 related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS: Among 177,133 subjects at May 18(th), 2020, we observed 51,633 subjects with SARS-CoV-2 and 5,332 deaths. Risk factors for lethality in COVID-19 include early-onset diabetes, obesity, COPD, advanced age, hypertension, immunosuppression, and CKD; we observed that obesity mediates 49.5% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for ICU admission and intubation. Our predictive score for COVID-19 lethality included age ≥65 years, diabetes, early-onset diabetes, obesity, age <40 years, CKD, hypertension, and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (c-statistic=0.823). RESULTS: Here, we propose a mechanistic approach to evaluate risk for complications and lethality attributable to COVID-19 considering the effect of obesity and diabetes in Mexico. Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first contact scenario.


docid: wjdmzmdg

title: Correlation between climate indicators and COVID-19 pandemic in New York, USA

text: Abstract This study analyzed the association between COVID-19 and climate indicators in New York City, USA. We used secondary published data from New York city health services and National weather service, USA. The climate indicators included in the study are average temperature, minimum temperature, maximum temperature, rainfall, average humidity, wind speed, and air quality. Kendall and Spearman rank correlation tests were chosen for data analysis. We find that average temperature, minimum temperature, and air quality were significantly associated with the COVID-19 pandemic. The findings of this study will help World Health Organization and health regulators such as Center for Disease Control (CDC) to combat COVID-19 in New York and the rest of the world.


title: Systems Biology Approaches to Disease Marker Discovery

text: Our understanding of human disease and potential therapeutics is improving rapidly. In order to take advantage of these developments it is important to be able to identify disease markers. Many new high-throughput genomics and proteomics technologies are being implemented to identify candidate disease markers. These technologies include protein microarrays, next-generation DNA sequencing and mass spectrometry platforms. Such methods are particularly important for elucidating the repertoire of molecular markers in the genome, transcriptome, proteome and metabolome of patients with diseases such as cancer, autoimmune diseases, and viral infections, resulting from the disruption of many biological pathways. These new technologies have identified many potential disease markers. These markers are expected to be valuable to achieve the promise of truly personalized medicine.


LA REHABILITACIÓN EN LOS TIEMPOS DEL COVID-19


title: Vascular disrupting agent DMXAA enhances the antitumor effects generated by therapeutic HPV DNA vaccines

text: Antigen-specific immunotherapy using DNA vaccines has emerged as an attractive approach for the control of tumors. Another novel cancer therapy involves the employment of the vascular disrupting agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA). In the current study, we aimed to test the combination of DMXAA treatment with human papillomavirus type 16 (HPV-16) E7 DNA vaccination to enhance the antitumor effects and E7-specific CD8+ T cell immune responses in treated mice. We determined that treatment with DMXAA generates significant therapeutic effects against TC-1 tumors but does not enhance the antigen-specific immune responses in tumor bearing mice. We then found that combination of DMXAA treatment with E7 DNA vaccination generates potent antitumor effects and E7-specific CD8+ T cell immune responses in the splenocytes of tumor bearing mice. Furthermore, the DMXAA-mediated enhancement or suppression of E7-specific CD8+ T cell immune responses generated by CRT/E7 DNA vaccination was found to be dependent on the time of administration of DMXAA and was also applicable to other antigen-specific vaccines. In addition, we determined that inducible nitric oxide synthase (iNOS) plays a role in the immune suppression caused by DMXAA administration before DNA vaccination. Our study has significant implications for future clinical translation.


docid: jwrheaph

title: Clinical trials for coronavirus disease 2019: What is being evaluated and what is not

text: Since the report of the first case of coronavirus disease 2019 (COVID-19) in China in late December 2019, there have been 204 610 cases worldwide as of 18 March, 2020. As part of the response to this outbreak, there has been an impressive amount of research undertaken to better characterize the disease and to evaluate therapeutic options. By March 12, 2020, there are more than 382 studies registered in the clinical trials databases addressing COVID-19 including more than 80 randomized controlled trials.


title: Porcine epidemic diarrhoea virus: a comprehensive review of molecular epidemiology, diagnosis, and vaccines

text: The porcine epidemic diarrhoea virus (PEDV), a member of the Coronaviridae family, causes acute diarrhoea and dehydration in pigs. Although it was first identified in Europe, it has become increasingly problematic in many Asian countries, including Korea, China, Japan, the Philippines, and Thailand. The economic impacts of the PEDV are substantial, given that it results in significant morbidity and mortality in neonatal piglets and is associated with increased costs related to vaccination and disinfection. Recently, progress has been made in understanding the molecular epidemiology of PEDV, thereby leading to the development of new vaccines. In the current review, we first describe the molecular and genetic characteristics of the PEDV. Then we discuss its molecular epidemiology and diagnosis, what vaccines are available, and how PEDV can be treated.


title: COVID-19, Fiscal Federalism and Provincial Debt: Have We Reached a Critical Juncture?

text: In 2019, Canada's gross subnational debt to GDP was well over 40 per cent, easily the highest in the world (see Figure 1). This level will only grow as the provinces grapple with the pandemic and its fiscal effects. Some believe surging provincial debts have brought Canadian federalism to a critical juncture: they have greatly increased the odds of federal measures to stabilize provincial finances. This article assesses this claim. The cleanest and most balanced path to fiscal sustainability is a combination of enhanced federal transfers, which would bolster provincial fiscal capacity, and national fiscal rules, which would constrain provincial borrowing. But the former is unlikely to restore sustainability on its own, and the latter would require a severe provincial debt crisis, which Canada's existing fiscal federal structures can avoid. COVID-19 has increased the odds of certain reforms, and it is difficult to predict their long-run effects. But any obvious paths to fiscal sustainability remain hidden.


title: Reviewing Chandipura: A Vesiculovirus in Human Epidemics

text: Chandipura virus, a member of the rhabdoviridae family and vesiculovirus genera, has recently emerged as human pathogen that is associated with a number of outbreaks in different parts of India. Although, the virus closely resembles with the prototype vesiculovirus, Vesicular Stomatitis Virus, it could be readily distinguished by its ability to infect humans. Studies on Chandipura virus while shed light into distinct stages of viral infection; it may also allow us to identify potential drug targets for antiviral therapy. In this review, we have summarized our current understanding of Chandipura virus life cycle at the molecular detail with particular interest in viral RNA metabolisms, namely transcription, replication and packaging of viral RNA into nucleocapsid structure. Contemporary research on otherwise extensively studied family member Vesicular Stomatitis Virus has also been addressed to present a more comprehensive picture of vesiculovirus life cycle. Finally, we reveal examples of protein economy in Chandipura virus life-cycle whereby each viral protein has evolved complexity to perform multiple tasks.


title: What’s New With the Old Coronaviruses?

text: Coronaviruses contribute to the burden of respiratory diseases in children, frequently manifesting in upper respiratory symptoms considered to be part of the “common cold.” Recent epidemics of novel coronaviruses recognized in the 21st century have highlighted issues of zoonotic origins of transmissible respiratory viruses and potential transmission, disease, and mortality related to these viruses. In this review, we discuss what is known about the virology, epidemiology, and disease associated with pediatric infection with the common community-acquired human coronaviruses, including species 229E, OC43, NL63, and HKU1, and the coronaviruses responsible for past world-wide epidemics due to severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus.


title: Critical paths in a metapopulation model of H1N1: Efficiently delaying influenza spreading through flight cancellation

text: Disease spreading through human travel networks has been a topic of great interest in recent years, as witnessed during outbreaks of influenza A (H1N1) or SARS pandemics. One way to stop spreading over the airline network are travel restrictions for major airports or network hubs based on the total number of passengers of an airport. Here, we test alternative strategies using edge removal, cancelling targeted flight connections rather than restricting traffic for network hubs, for controlling spreading over the airline network. We employ a SEIR metapopulation model that takes into account the population of cities, simulates infection within cities and across the network of the top 500 airports, and tests different flight cancellation methods for limiting the course of infection. The time required to spread an infection globally, as simulated by a stochastic global spreading model was used to rank the candidate control strategies. The model includes both local spreading dynamics at the level of populations and long-range connectivity obtained from real global airline travel data. Simulated spreading in this network showed that spreading infected 37% less individuals after cancelling a quarter of flight connections between cities, as selected by betweenness centrality. The alternative strategy of closing down whole airports causing the same number of cancelled connections only reduced infections by 18%. In conclusion, selecting highly ranked single connections between cities for cancellation was more effective, resulting in fewer individuals infected with influenza, compared to shutting down whole airports. It is also a more efficient strategy, affecting fewer passengers while producing the same reduction in infections. The network of connections between the top 500 airports is available under the resources link on our website http://www.biological-networks.org.


title: Management of infection control and radiological protection in diagnostic radiology examination of COVID-19 cases

text: Since the COVID-19 outbreak, diagnostic imaging has been providing valuable radiological support for disease diagnosis and prognosis prediction. Radiological staff, especially radiographers working on the front line in the battle against the COVID-19 outbreak. They are in direct contact with the patients, bearing the responsibility and pressure of both the infection prevention and control and the radiation protection. A number of relevant professionals and experts reached a consensus, which clarifies the detailed implementing rules with respective to infection control and protection of the radiation workers, disinfection of diagnostic radiology equipment and workplace, and radiological protection. The aim is to further normalize the clinical procedures of radiological staff, reduce the infection risk, especially the radiation risk to medics and patients.


title: Natural ventilation for reducing airborne infection in hospitals

text: Abstract High ventilation rate is shown to be effective for reducing cross-infection risk of airborne diseases in hospitals and isolation rooms. Natural ventilation can deliver much higher ventilation rate than mechanical ventilation in an energy-efficient manner. This paper reports a field measurement of naturally ventilated hospital wards in Hong Kong and presents a possibility of using natural ventilation for infection control in hospital wards. Our measurements showed that natural ventilation could achieve high ventilation rates especially when both the windows and the doors were open in a ward. The highest ventilation rate recorded in our study was 69.0 ACH. The airflow pattern and the airflow direction were found to be unstable in some measurements with large openings. Mechanical fans were installed in a ward window to create a negative pressure difference. Measurements showed that the negative pressure difference was negligible with large openings but the overall airflow was controlled in the expected direction. When all the openings were closed and the exhaust fans were turned on, a reasonable negative pressure was created although the air temperature was uncontrolled. The high ventilation rate provided by natural ventilation can reduce cross-infection of airborne diseases, and thus it is recommended for consideration of use in appropriate hospital wards for infection control. Our results also demonstrated a possibility of converting an existing ward using natural ventilation to a temporary isolation room through installing mechanical exhaust fans.


title: Mixing ratio optimization for functional complex extracts of Rhodiola crenulata, Panax quinquefolius, and Astragalus membranaceus using mixture design and verification of immune functional efficacy in animal models

text: Abstract We aimed to identify the optimum mixing ratio for various ingredients to obtain complex extracts with high extract yields and immune-enhancing activity in animals. The extract yield and amounts of nitric oxide (NO) and interleukin (IL)-6 were set to maximum for modeling predictions. The predicted optimum values for the mixing ratio were 49.5% for Rhodiola crenulata, 26.1% for Astragalus membranaceus, and 24.4% for Panax quinquefolius, and the predicted response values were 31.5% yield, 13.4% NO production, and 6.1% IL-6 production; actual values were 35.3% yield, 14.7% NO, and 6.6% IL-6. The optimum mixing ratio extract (OMRE) was used for the animal experiments. Treating mice with OMRE at 200 mg/kg produced significant increases in spleen indexes and T-cell/B-cell proliferation. OMRE treatment increased IL-10 and IL-6 production in concanavalin A- and lipopolysaccharide-induced T- and B- lymphocytes, respectively. These results provide a basis for the development of functional extracts and drinks.


Pertinent roles of African higher institutions in the COVID‐19 pandemic response: The University of Ilorin, Ilorin, Nigeria; An African Model


title: Taking down covid-19

text: Thousands of people are searching for coronavirus treatments. Which are most promising and when will we have them, asks Carrie Arnold


title: Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases

text: Summary WHO interim guidelines recommend offering extracorporeal membrane oxygenation (ECMO) to eligible patients with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The number of patients with COVID-19 infection who might develop severe ARDS that is refractory to maximal medical management and require this level of support is currently unknown. Available evidence from similar patient populations suggests that carefully selected patients with severe ARDS who do not benefit from conventional treatment might be successfully supported with venovenous ECMO. The need for ECMO is relatively low and its use is mostly restricted to specialised centres globally. Providing complex therapies such as ECMO during outbreaks of emerging infectious diseases has unique challenges. Careful planning, judicious resource allocation, and training of personnel to provide complex therapeutic interventions while adhering to strict infection control measures are all crucial components of an ECMO action plan. ECMO can be initiated in specialist centres, or patients can receive ECMO during transportation from a centre that is not specialised for this procedure to an expert ECMO centre. Ensuring that systems enable safe and coordinated movement of critically ill patients, staff, and equipment is important to improve ECMO access. ECMO preparedness for the COVID-19 pandemic is important in view of the high transmission rate of the virus and respiratory-related mortality.


COVID-19 in a pediatric heart transplant recipient: Emergence of Donor Specific Antibodies


title: Immunogenicity of Candidate MERS-CoV DNA Vaccines Based on the Spike Protein

text: MERS-coronavirus is a novel zoonotic pathogen which spread rapidly to >25 countries since 2012. Its apparent endemicity and the wide spread of its reservoir host (dromedary camels) in the Arabian Peninsula highlight the ongoing public health threat of this virus. Therefore, development of effective prophylactic vaccine needs to be urgently explored given that there are no approved prophylactics or therapeutics for humans or animals to date. Different vaccine candidates have been investigated but serious safety concerns remain over protein or full-length spike (S) protein-based vaccines. Here, we investigated the immunogenicity of naked DNA vaccines expressing different fragments of MERS-CoV S protein in mice. We found that plasmids expressing full-length (pS) or S1-subunit (pS1) could induce significant levels of S1-specific antibodies (Abs) but with distinct IgG isotype patterns. Specifically, pS1 immunization elicited a balanced Th1/Th2 response and generally higher levels of all IgG isotypes compared to pS vaccination. Interestingly, only mice immunized with pS1 demonstrated significant S1-specific cellular immune response. Importantly, both constructs induced cross-neutralizing Abs against multiple strains of human and camel origins. These results indicate that vaccines expressing S1-subunit of the MERS-CoV S protein could represent a potential vaccine candidate without the possible safety concerns associated with full-length protein-based vaccines.


title: Transferrin receptor 1 in the zoonosis and pathogenesis of New World hemorrhagic fever arenaviruses

text: At least five New World arenaviruses cause severe human hemorrhagic fevers. These viruses are transmitted to humans through contact with their respective South American rodent hosts. Each uses human transferrin receptor 1 (TfR1) as its obligate receptor. Accidental similarities between human TfR1 and TfR1 orthologs of arenviral host species enable zoonoses, whereas mice and rats are not infectable because they lack these TfR1 determinants of infection. All pathogenic New World arenaviruses bind to a common region of the apical domain of TfR1. The ability of a New World arenavirus to use human TfR1 is absolutely predictive of its ability to cause hemorrhagic fevers in humans. Non-pathogenic arenaviruses, closely related to hemorrhagic fever arenaviruses, cannot utilize human TfR1 but efficiently enter cells through TfR1 orthologs of their native rodent hosts. Mutagenesis studies suggest that minor changes in the entry glycoproteins of these non-pathogenic viruses may allow human transmission. TfR1 is upregulated as a result of iron sequestration during the acute phase response to infection, and the severity of disease may result from amplification of viral replication during this response.


title: Operational strategies of a trauma hub in early coronavirus disease 2019 pandemic

text: PURPOSE: The “Spedali Civili”, one of the largest hospitals in the Italian region most affected by SARS-CoV-2 infection, is managing a large number of traumatic injuries. The objective of this article is to share our operational protocols to deliver an appropriate hospital trauma care in the context of the COVID-19 pandemic. METHODS: We changed our work shifts, in consideration of the high number of patients; colleagues from smaller hospitals in the area joined us to increase the number of surgeons available. Thanks to the collaboration between orthopaedists, anaesthesiologists, and nurses, we created a flow chart and separate routes (in the emergency room, in the wards, and in the operating rooms) to optimize patient management. Our protocols allow us to always provide healthcare professionals with the correct personal protective equipment for the task they are performing. RESULTS: Our strategies proved to be practical and feasible. Having a well thought plan helped us to provide for the most robust response possible. We have not yet been able to study the effectiveness of our protocols, and our recommendations may not be applicable to all healthcare facilities. Nonetheless, sharing our early experience can help other institutions conducting and adapting such plans more quickly. CONCLUSIONS: Having a clear strategy during the COVID-19 pandemic kept our systems resilient and effective and allowed us to provide high-quality trauma care. We offer this approach for other institutions to adopt and adapt to their local setting.


title: Mutational analysis of the “slippery-sequence” component of a coronavirus ribosomal frameshifting signal

text: Abstract The ribosomal frameshift signal in the genomic RNA of the coronavirus IBV is composed of two elements, a heptanucleotide “slippery-sequence” and a downstream RNA pseudoknot. We have investigated the kinds of slippery sequence that can function at the IBV frameshift site by analysing the frameshifting properties of a series of slippery-sequence mutants. We firstly confirmed that the site of frameshifting in IBV was at the heptanucleotide stretch UUUAAAC, and then used our knowledge of the pseudoknot structure and a suitable reporter gene to prepare an expression construct that allowed both the magnitude and direction of ribosomal frameshifting to be determined for candidate slippery sequences. Our results show that in almost all of the sequences tested, frameshifting is strictly into the −1 reading frame. Monotonous runs of nucleotides, however, gave detectable levels of a −2 +1 frameshift product, and U stretches in particular gave significant levels (2% to 21%). Preliminary evidence suggests that the RNA pseudoknot may play a role in influencing frameshift direction. The spectrum of slip-sequences tested in this analysis included all those known or suspected to be utilized in vivo. Our results indicate that triplets of A, C, G and U are functional when decoded in the ribosomal P-site following slippage ( XXX YYYN) although C triplets were the least effective. In the A-site (XXY YYY N), triplets of C and G were non-functional. The identity of the nucleotide at position 7 of the slippery sequence (XXXYYY N ) was found to be a critical determinant of frameshift efficiency and we show that a hierarchy of frameshifting exists for A-site codons. These observations lead us to suggest that ribosomal frameshifting at a particular site is determined, at least in part, by the strength of the interaction of normal cellular tRNAs with the A-site codon and does not necessarily involve specialized “shifty” tRNAs.


docid: yzxpapdd

title: Methods for the discovery of emerging pathogens

text: Abstract Recently, there has been a steady increase in the number of recognized pathogenic microorganisms, specifically bacteria. The development of genetic technologies, MALDI-TOF mass spectrometry and new culturing techniques has significantly widened the repertoire of known microorganisms and therefore pathogenic microorganisms. The repertoire of infectious agents has been studied in various environments including water, soil, pets, livestock, wildlife and arthropods. Using different methods, many known pathogens can be identified in these samples; therefore, the impact of emergent pathogens on humans can be examined and novel pathogens can be identified. In this special issue, we discuss the identification of emerging pathogens in the environment and animals.


title: Prolonged viral shedding in feces of pediatric patients with coronavirus disease 2019

text: Abstract Objective To determine the dynamic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory and fecal specimens in children with coronavirus disease 2019 (COVID-19). Methods From January 17, 2020 to February 23, 2020, three paediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data were collected. Patients were followed up to March 10, 2020, and dynamic profiles of nucleic acid testing results in throat swabs and fecal specimens were closely monitored. Results Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained detectable in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days. Conclusions SARS-CoV-2 may exist in children's gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children raises the possibility that the virus might be transmitted through contaminated fomites. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.


title: Smell and Taste Dysfunction in Patients With COVID-19: A Systematic Review and Meta-analysis

text: Abstract Objective To estimate the prevalence of olfactory and gustatory dysfunctions (OGDs) among patients infected with novel coronavirus disease 2019 (COVID-19). Patients and Methods A systematic review was conducted by searching MEDLINE, EMBASE, and the preprint server MedRxiv until 11 May 2020 using the terms ‘anosmia’ or ‘hyposmia’ or ‘dysosmia’ or ‘olfactory dysfunction’ or ‘olfaction disorder’ or ‘smell dysfunction’ or ‘ageusia’ or ‘hypogeusia’ or ‘dysgeusia’ or ‘taste dysfunction’ or ‘gustatory dysfunction’ or ‘neurological’ and ‘COVID-19’ or ‘2019 novel coronavirus’ or ‘2019-nCoV’ or ‘SARS-CoV-2’. References of included studies were also manually screened. Only studies involving diagnostic-confirmed patients with COVID-19 were included. Random-effects meta-analysis was performed. Results A total of twenty-four studies with data from 8438 test-confirmed COVID-19 patients from thirteen countries were included. The pooled proportion of patients presenting with olfactory and gustatory dysfunctions was 41.0% (95% confidence interval [CI] 28.5% to 53.9) and 38.2% (95% CI 24.0 to 53.6%), respectively. Increasing mean age correlated with lower prevalence of olfactory (coefficient = -0.076; p=.02) and gustatory (coefficient = -0.073; p=.03) dysfunctions. There was a higher prevalence of olfactory dysfunctions with the use of objective measurements compared to self-reports (coefficient = 2.33; p=.01). No significant moderation of the prevalence of OGDs by gender was observed. Conclusion There is a high prevalence of OGDs among patients infected with COVID-19. Routine screening for these conditions could contribute to improved case detection in the ongoing COVID-19 pandemic. However, to better inform population screening measures, further studies are needed to establish causality.


title: Chapter 7 Environmental and Safety Issues With Nanoparticles

text: Abstract Because nanoparticles have superior surface activity and can be applied to the production of particles with various functions, they are extremely important for the future development of sophisticated material technologies. On the other hand, this superior activity of nanoparticles is a cause of trouble from the perspective of safety and does not always have a positive influence on the environment. Attention must also be paid to impact on health. Nevertheless, all technologies have negative aspects, and overcoming these kinds of problems, we will be able to utilize the superior characteristics of nanoparticles for practical purposes. To achieve this goal, it is necessary to fully understand the influence of nanoparticles on the environment and the relevant safety issues.


title: DEA allows buprenorphine inductions based on telephone only

text: Last week, the Drug Enforcement Administration (DEA) said opioid treatment programs (OTPs) and Drug Addiction Treatment Act (DATA)–waived prescribers can treat new patients with buprenorphine based on a telephone call only. The Controlled Substances Act (CSA), enforced by the DEA, requires all new patients being treated with controlled substances to have an in‐person — or, for now, telemedicine — physical exam. Now, however, because of the coexisting COVID‐19 pandemic and opioid overdose crisis, the DEA has dropped this requirement. This follows the decision of the Substance Abuse and Mental Health Services Administration (SAMHSA) to allow exemptions from the OTP take‐home regulations allowing stable patients to be given 14 or 28 days of methadone doses, instead of coming in more frequently (see DEA, SAMHSA relax OTP/OBOT regulations due to COVID‐19, ADAW March 23, https://onlinelibrary.wiley.com/doi/10.1002/adaw.32664).


title: Mobile Virology Research and Diagnostic Laboratory (MVRDL: BSL-3) for COVID-19 Screening, Virus Culturing and Vaccine Development

text: In order to prevent spread of COVID-19, World Health Organization (WHO) has specified that measures such as cleaning hands regularly with alcohol-based hand sanitizer or washing with soap and water, avoiding touching nose, eyes, mouth and social distancing should be followed by people. Another important measure for containing spread is by Testing–Testing and Testing. To conduct real-time reverse transcription polymerase chain reaction (rRT-PCR) test for diagnosing COVID-19. Possibility to test up to 2000 samples per day. For virus culturing for drug screening, convalescent plasma-derived therapy. To aid in the development of vaccine and development of diagnostic kits.


title: American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Position Statement on Pharmacy Practice Management and Clinical Management for COVID-19 in Hematopoietic Cell Transplant and Cellular Therapy Patients in the United States

text: Abstract The coronavirus-19 (COVID-19) pandemic poses a significant risk to patients undergoing hematopoietic stem cell transplant or cellular therapy. The American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Steering Committee aims to provide pharmacy practice management recommendations for how to transition clinical hematopoietic stem cell transplant (HCT) or cellular therapy pharmacy services utilizing telemedicine capabilities in the inpatient and outpatient setting to maintain an equivalent level of clinical practice but minimizing viral spread in a high risk, immunocompromised population. Additionally, the Steering Committee offers clinical management recommendations for COVID-19 in HCT and cellular therapy patients based on the rapidly developing literature. As the therapeutic and supportive care interventions for COVID-19 increase, collaboration with clinical pharmacy providers is critical to ensure safe administration in HCT patients. Attention to drug-drug interactions (DDI) and toxicity, particularly QTc prolongation, warrants close cardiac monitoring and potential cessation of concomitant QTc prolonging agents. Expanded indications for hydroxychloroquine and tocilizumab have already shown potential stress to usual supply chain. Detailed prescribing algorithms, decision pathways and specific patient population stock may be necessary. The COVID-19 pandemic has challenged every member of the healthcare team and we must continue to remain vigilant in providing pharmacy clinical services to one of the most high-risk patient populations and remain committed to providing compassionate and safe care for patients receiving HCT and cellular therapies.


Absence of Middle East respiratory syndrome coronavirus in Bactrian camels in the West Inner Mongolia Autonomous Region of China: surveillance study results from July 2015


title: Telehealth Home Support During COVID-19 Confinement for Community-Dwelling Older Adults With Mild Cognitive Impairment or Mild Dementia: Survey Study

text: BACKGROUND: The public health emergency of coronavirus disease (COVID-19) is rapidly evolving worldwide; some countries, including Spain, have implemented restrictive measures. Populations that are vulnerable to this outbreak and its physical and mental health effects include community-dwelling older adults with mild cognitive impairment or mild dementia. Telehealth is a potential tool to deliver health care and decrease exposure risk. OBJECTIVE: The aims of this study were to explore the impact of confinement on the health and well-being of community-dwelling older adults with mild cognitive impairment or mild dementia, to provide television-based and telephone-based health and social support, and to study the effects of a television-based assistive integrated technology, TV-AssistDem (TeleVision-based ASSistive Integrated Service to supporT European adults living with mild DEMentia or mild cognitive impairment). METHODS: A telephone-based survey was administered in Spain to 93 participants in the TV-AssistDem clinical trial from March 25 to April 6, 2020. RESULTS: Of the respondents, 60/93 (65%) were women. The mean age was 73.34 (SD 6.07), and 69/93 (74%) lived accompanied. Lockdown measures forced 17/93 respondents (18%) to change their living arrangements. Health status was found to be optimal in 89/93 respondents (96%), with no COVID-19 symptoms. Grocery and pharmacy outings were performed by family members of 68/93 participants (73%); 57 (61%) reported overall well-being, and 65 (70%) maintained their sleep quality. However, participants living alone reported greater negative feelings and more sleeping problems. Regarding leisure activities, 53/93 respondents (57%) took walks, 32 (35%) played memory games, 55 (60%) watched television, and 91 (98%) telephoned relatives. 58/93 (64%) respondents reported accessing moderate or too much COVID-19 information, 89 (97%) received it from television, and 56 (62%) stated that their understanding of the information was extreme. 39/93 (39%) respondents had contacted health and social services, while 29 (31%) requested information regarding these services during the telephone call. There were no significant differences in health and well-being between the intervention and control groups. Respondents with TV-AssistDem performed more memory exercises (24/93, 52% vs 8/93, 17.4%; P<.001) than control respondents. CONCLUSIONS: Our findings suggest that during COVID-19 confinement, the physical and mental health and well-being was optimal for the majority of our vulnerable population. However, those living alone reported greater negative psychological effects and sleeping problems. Measures adopted to address the negative experiences of confinement included keeping informed about the situation, accessing health and social services, having a support network that prevents risk of exposure to COVID-19 and guarantees food and medical supplies, a daily routine with maintained sleeping habits and leisure activities, staying physically and mentally active with cognitive stimulation exercises, and ensuring social connectedness using technology. Television sets were preferred technological devices to access COVID-19 information, watch television as a recreational activity, and perform memory exercises as an intellectual activity. Television-based telehealth support using TV-AssistDem demonstrated potential for cognitive stimulation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03653234; https://clinicaltrials.gov/ct2/show/NCT03653234


title: Legionella community-acquired pneumonia (CAP) presenting with spontaneous bilateral pneumothoraces

text: Legionnaires' disease is a common cause of non-zoonotic atypical community-acquired pneumonia (CAP). Legionnaires' disease has varied manifestations but may be diagnosed clinically on the basis of its characteristic pattern of extra-organ involvement. In a patient with non-zoonotic CAP, the clinical and laboratory features in a patient with CAP pointing to the diagnosis of Legionnaires' disease include relative bradycardia, mental confusion/ encephalopathy, loose stools/diarrhea, abdominal pain, mild/transient increases in serum transaminases, decreased serum phosphorous, a highly elevated C-reactive protein (CRP), elevated creatinine phosphokinase (CPK), highly elevated serum ferritin levels, or microscopic hematuria. The radiologic manifestations of Legionnaires' disease are varied and no radiographic appearance is pathopneumonic. Patchy infiltrates in Legionnaires' disease are symmetrical and rapidly progressive even on appropriate anti-Legionella antimicrobial therapy. Spontaneous unilateral pneumothorax is a rare radiographic manifestation of Legionnaires' disease. We present a case of a young male who is presenting clinical finding was that of spontaneous bilateral pneumothoraces due to Legionella CAP. We believe this is the first reported case of Legionnaires' disease presenting as spontaneous bilateral pneumothoraces. Clinicians should be aware of the protean radiological manifestations of Legionnaires' disease. In patients presenting with CAP and unilateral or bilateral spontaneous pneumothorax, clinicians should have Legionnaires' disease in the differential diagnosis.


title: Plan de contingencia para los servicios de medicina intensiva frente a la pandemia COVID-19♦

text: Resumen En enero de 2020 China identificó un nuevo virus de la familia de los Coronaviridae como causante de varios casos de neumonía de origen desconocido. Inicialmente confinado a la ciudad de Wuhan, se extendió posteriormente fuera de las fronteras chinas. En España, el primer caso se declaró el 31 de enero de 2020. El 11 de marzo, la Organización Mundial de la Salud declaró el brote de coronavirus como pandemia. El 16 de marzo había 139 países afectados. Ante esta situación, las Sociedades Científicas SEMICYUC y SEEIUC han decidido la elaboración de este plan de contingencia para dar respuesta a las necesidades que conllevará esta nueva enfermedad. Se pretende estimar la magnitud del problema e identificar las necesidades asistenciales, de recursos humanos y materiales, de manera que los servicios de medicina intensiva del país tengan una herramienta que les permita una planificación óptima y realista con que responder a la pandemia. Abstract In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC, have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.


title: Knowledge, Attitudes, Impact, and Anxiety Regarding COVID-19 Infection Among the Public in China

text: Objectives: Sufficient knowledge and positive attitudes are crucial to the prevention of COVID-19. However, little is known about public awareness and attitudes regarding COVID-19 in China. The impact of COVID-19 on the societal well-being and anxiety levels of the public has never been documented. The aim of this study was to survey the knowledge, attitudes, impact, and anxiety levels of the people of China in relation to the COVID-19 outbreak. Method: A cross-sectional population survey using an online questionnaire was undertaken between Jan 24 and Feb 24, 2020. The study participants were residents of mainland China over the age of 18 years. The attitude items in this study measured the perceived threat of COVID-19 based on the Health Belief Model. Anxiety was measured with the State-Trait Anxiety Inventory (STAI), a self-reported questionnaire that measure both state (STAI-S), and trait anxiety (STAI-T) Results: A total of 2,446 completed responses were received. The mean and standard deviation (SD) for the total knowledge score was 20.3 (SD ± 2.9) out of a possible score of 23. The social disruption and household economic impact were notable, particularly in provinces with higher cumulative confirmed cases. The majority of responses indicated a low perceived susceptibility of being infected (86.7% [95%CI 85.4–88.1]), with a fair proportion of respondents perceiving a higher severity (62.9% [95% CI 61.0–64.8]). The mean total impact score was 9.9 (SD ± 3.8) out of a possible score of 15. The mean score for STAI-S was 48.7 (SD ± 10.8), whereas the mean STAI-T score was 45.7 (SD ± 8.5). By demographics, women reported significantly higher odds for higher levels of both STAI-S (OR = 1.67) and STAI-T (OR = 1.30) compared to men. People of a younger age were also more likely to experience higher STAI-S and STAI-T. Higher perceived susceptibility and severity and impact were strong predictors of higher levels of STAI-S and STAI-T. Conclusion: Our findings can assist in tailoring public communication to change people's knowledge and attitudes. The present study also underlined the importance of the promotion of mental health during infectious disease outbreaks to help in moderating the perceived threat, social and household economic impact, targeting the vulnerable segment of the population.


title: The Coronavirus Replicase

text: Coronavirus genome replication and transcription take place at cytoplasmic membranes and involve coordinated processes of both continuous and discontinuous RNA synthesis that are mediated by the viral replicase, a huge protein complex encoded by the 20-kb replicase gene. The replicase complex is believed to be comprised of up to 16 viral subunits and a number of cellular proteins. Besides RNA-dependent RNA polymerase, RNA helicase, and protease activities, which are common to RNA viruses, the coronavirus replicase was recently predicted to employ a variety of RNA processing enzymes that are not (or extremely rarely) found in other RNA viruses and include putative sequence-specific endoribonuclease, 3′-to-5′ exoribonuclease, 2′-O-ribose methyltransferase, ADP ribose 1′-phosphatase and, in a subset of group 2 coronaviruses, cyclic phosphodiesterase activities. This chapter reviews (1) the organization of the coronavirus replicase gene, (2) the proteolytic processing of the replicase by viral proteases, (3) the available functional and structural information on individual subunits of the replicase, such as proteases, RNA helicase, and the RNA-dependent RNA polymerase, and (4) the subcellular localization of coronavirus proteins involved in RNA synthesis. Although many molecular details of the coronavirus life cycle remain to be investigated, the available information suggests that these viruses and their distant nidovirus relatives employ a unique collection of enzymatic activities and other protein functions to synthesize a set of 5′-leader-containing subgenomic mRNAs and to replicate the largest RNA virus genomes currently known.


title: Genome Wide Association Identifies PPFIA1 as a Candidate Gene for Acute Lung Injury Risk Following Major Trauma

text: Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis-regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi-center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research.


title: Tuberculosis and pneumonia in HIV-infected children: an overview

text: Pneumonia remains the most common cause of hospitalization and the most important cause of death in young children. In high human immunodeficiency virus (HIV)-burden settings, HIV-infected children carry a high burden of lower respiratory tract infection from common respiratory viruses, bacteria and Mycobacterium tuberculosis. In addition, Pneumocystis jirovecii and cytomegalovirus are important opportunistic pathogens. As the vertical transmission risk of HIV decreases and access to antiretroviral therapy increases, the epidemiology of these infections is changing, but HIV-infected infants and children still carry a disproportionate burden of these infections. There is also increasing recognition of the impact of in utero exposure to HIV on the general health of exposed but uninfected infants. The reasons for this increased risk are not limited to socioeconomic status or adverse environmental conditions—there is emerging evidence that these HIV-exposed but uninfected infants may have particular immune deficits that could increase their vulnerability to respiratory pathogens. We discuss the impact of tuberculosis and other lower respiratory tract infections on the health of HIV-infected infants and children.


title: First Confirmed Cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection in the United States, Updated Information on the Epidemiology of MERS-CoV Infection, and Guidance for the Public, Clinicians, and Public Health Authorities — May 2014

text: Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014.


title: Single-Stranded DNA Aptamers against Pathogens and Toxins: Identification and Biosensing Applications

text: Molecular recognition elements (MREs) can be short sequences of single-stranded DNA, RNA, small peptides, or antibody fragments. They can bind to user-defined targets with high affinity and specificity. There has been an increasing interest in the identification and application of nucleic acid molecular recognition elements, commonly known as aptamers, since they were first described in 1990 by the Gold and Szostak laboratories. A large number of target specific nucleic acids MREs and their applications are currently in the literature. This review first describes the general methodologies used in identifying single-stranded DNA (ssDNA) aptamers. It then summarizes advancements in the identification and biosensing application of ssDNA aptamers specific for bacteria, viruses, their associated molecules, and selected chemical toxins. Lastly, an overview of the basic principles of ssDNA aptamer-based biosensors is discussed.


title: Généralités sur l'infection du système nerveux par les virus

text: Summary Study of nervous system viral diseases is not limited to descriptions of the topography of the infection in man : it also includes studies of animal models which can help in the understanding of the physiopathology of the diseases. It is unlikely than all viruses which can infect nervous tissues are known, and new human viruses have been discovered by Neurologists. Analysis of the route of viral penetration into the brain, and of differing cell susceptibility can help our understanding of disease. Pathological modalities, other than acute infection, have been recently described. Slow virus infections can result from an atypical relationship between the virus and the cell, or the infected cell and the immunological response of the host, as well as from infection by a new category of unconventional agents which nervertheless share some common properties with known viruses.


title: Drug adherence and the incidence of coronary heart disease- and stroke-specific mortality among 218,047 patients newly prescribed an antihypertensive medication: A five-year cohort study

text: Abstract Background Randomized trials have shown that optimal adherence to antihypertensive agents could protect against cardiovascular diseases, but whether adherence reduces cardiovascular deaths in community settings has not been explored so fully. This study evaluates the association between antihypertensive adherence and cardiovascular (coronary heart disease and stroke) mortality in the primary care settings. Methods From a territory-wide database in Hong Kong, we included all patients who were prescribed their first-ever antihypertensive agents in the years between 2001 and 2005 from the public healthcare sector. All patients were followed up for five years, and assigned as having poor (Proportion of Days Covered [PDC]<40%), intermediate (40–79%), and high (≥80%) adherence to antihypertensive agents. The association between antihypertensive adherence and cardiovascular mortality was evaluated by using the Cox proportional hazard models. Results From a total of 218,047 eligible patients, 3825 patients (1.75%) died of cardiovascular disease within five years after having received their first-ever antihypertensive agents. The proportions of patients having poor, intermediate, and high medication adherence were 32.9%, 12.1%, and 55.0%, respectively. Higher adherence levels at PDC 40%–79% (HR=0.46, 95% C.I. 0.41–0.52, p<0.001) and ≥80% (HR=0.91, 95% C.I. 0.85–0.98, p=0.012) were significantly less likely to be associated with mortality than the poor adherence (PDC0.040) group. Conclusions Better antihypertensive adherence was associated with lower cardiovascular mortality. This highlights the need to promote adherence through strategies which have been proved to be effective in clinical settings.


¿Es gripe todo lo que clínicamente parece gripe?


title: A new method of assessing aerosolized bacteria generated during orthodontic debonding procedures

text: Introduction The main objective of this study was to assess the efficacy of a new and innovative method of harvesting bacteria that are aerosolized during orthodontic debonding. Additionally, the protection efficacy of several commercially available masks from such aerosols was assessed in a pilot study. Methods Twenty-six subjects were debonded during aerosol sampling, by using an innovative collection system to harvest bonding dust liberated during debonding. Dark-field microscopy, gram-stain microscopy, and chemical identification were used to determine speciation of the collected aerosol from 23 subjects. Three additional subjects were used to test 3 commercial dental or protective masks to determine whether they provide effective protection from the aerosol. Results Twenty-one species of oral bacteria were identified by the new sampling technique. Two of the 3 masks that were tested offered no protection against the aerosolized bacteria. Conclusions A new and effective method for collecting airborne bacteria is presented. Some conventional dental masks offer no protection from aerosolized organisms liberated during debonding procedures. Further assessment of mask efficacy is ongoing.


docid: zxeyjybs

title: Structural and functional characterisation of ferret interleukin-2

text: Abstract While the ferret is a valuable animal model for a number of human viral infections, such as influenza, Hendra and Nipah, evaluating the cellular immune response following infection has been hampered by the lack of a number of species-specific immunological reagents. Interleukin 2 (IL-2) is one such key cytokine. Ferret recombinant IL-2 incorporating a C-terminal histidine tag was expressed and purified and the three-dimensional structure solved and refined at 1.89 Å by X-ray crystallography, which represents the highest resolution and first non-human IL-2 structure. While ferret IL-2 displays the classic cytokine fold of the four-helix bundle structure, conformational flexibility was observed at the second helix and its neighbouring region in the bundle, which may result in the disruption of the spatial arrangement of residues involved in receptor binding interactions, implicating subtle differences between ferret and human IL-2 when initiating biological functions. Ferret recombinant IL-2 stimulated the proliferation of ferret lymph node cells and induced the expression of mRNA for IFN-γ and Granzyme A.


title: An enhanced beam search algorithm for the Shortest Common Supersequence Problem

text: Abstract The Shortest Common Supersequence Problem asks to obtain a shortest string that is a supersequence of every member of a given set of strings. It has applications, among others, in data compression and oligonucleotide microarray production. The problem is NP-hard, and the existing exact solutions are impractical for large instances. In this paper, a new beam search algorithm is proposed for the problem, which employs a probabilistic heuristic and uses the dominance property to further prune the search space. The proposed algorithm is compared with three recent algorithms proposed for the problem on both random and biological sequences, outperforming them all by quickly providing solutions of higher average quality in all the experimental cases. The Java source and binary files of the proposed IBS_SCS algorithm and our implementation of the DR algorithm and all the random and real datasets used in this paper are freely available upon request.


title: A potent germline-like human monoclonal antibody targets a pH-sensitive epitope on H7N9 influenza hemagglutinin

text: The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity (ADCC). Interestingly, immunogenetic analysis indicates that m826 is a germline antibody and m826-like sequences can be identified in H7N9-infected patients, healthy adults and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.


Emporiatrics: The growing area of concern


title: Enhanced Intrapulmonary Delivery of Anticancer siRNA for Lung Cancer Therapy Using Cationic Ethylphosphocholine-based Nanolipoplexes

text: Here, we report a cationic nanolipoplex as a pulmonary cellular delivery system for small-interfering RNA (siRNA). Six nanoliposomes differing in cationic lipids were formulated and screened in vitro and in vivo for cellular delivery functions in lung cells/tissues. Although the six nanoliposomes showed similar siRNA delivery efficiency in vitro, they exhibited significant differences in pulmonary cellular delivery functions in vivo. Among the various nanoliposomes, cationic dioleoyl-sn-glycero-3-ethylphosphocholine and cholesterol (ECL)-based nanoliposomes showed the highest pulmonary cellular delivery in vivo and the lowest cytotoxicity in vitro. The delivery efficiency of fluorescent siRNA in ECL nanoliposomes was 26.2-fold higher than that of naked siRNA in vivo. Treatment with Mcl1 (myeloid cell leukemia sequence 1)-specific siRNA (siMcl1) using ECL nanolipoplexes reduced target expression in B16F10 cell lines, whereas control, luciferase-specific siGL2 in ECL nanolipoplexes did not. In metastatic lung cancer mouse models induced by B16F10 or Lewis lung carcinoma (LLC) cells, intratracheal administration of siMcl1 in ECL nanolipoplexes significantly silenced Mcl1 mRNA and protein levels in lung tissue. Reduced formation of melanoma tumor nodules was observed in the lung. These results demonstrate the utility of ECL nanoliposomes for pulmonary delivery of therapeutic siRNA for the treatment of lung cancers and potentially for other respiratory diseases.


title: Analysis of Coronavirus Temperature-Sensitive Mutants Reveals an Interplay between the Macrodomain and Papain-Like Protease Impacting Replication and Pathogenesis

text: Analysis of temperature-sensitive (ts) mutant viruses is a classic method allowing researchers to identify genetic loci involved in viral replication and pathogenesis. Here, we report genetic analysis of a ts strain of mouse hepatitis virus (MHV), tsNC11, focusing on the role of mutations in the macrodomain (MAC) and the papain-like protease 2 (PLP2) domain of nonstructural protein 3 (nsp3), a component of the viral replication complex. Using MHV reverse genetics, we generated a series of mutant viruses to define the contributions of macrodomain- and PLP2-specific mutations to the ts phenotype. Viral replication kinetics and efficiency-of-plating analysis performed at permissive and nonpermissive temperatures revealed that changes in the macrodomain alone were both necessary and sufficient for the ts phenotype. Interestingly, mutations in the PLP2 domain were not responsible for the temperature sensitivity but did reduce the frequency of reversion of macrodomain mutants. Coimmunoprecipitation studies are consistent with an interaction between the macrodomain and PLP2. Expression studies of the macrodomain-PLP2 portion of nsp3 indicate that the ts mutations enhance proteasome-mediated degradation of the protein. Furthermore, we found that during virus infection, the replicase proteins containing the MAC and PLP2 mutations were more rapidly degraded at the nonpermissive temperature than were the wild-type proteins. Importantly, we show that the macrodomain and PLP2 mutant viruses trigger production of type I interferon in vitro and are attenuated in mice, further highlighting the importance of the macrodomain-PLP2 interplay in viral pathogenesis. IMPORTANCE Coronaviruses (CoVs) are emerging human and veterinary pathogens with pandemic potential. Despite the established and predicted threat these viruses pose to human health, there are currently no approved countermeasures to control infections with these viruses in humans. Viral macrodomains, enzymes that remove posttranslational ADP-ribosylation of proteins, and viral multifunctional papain-like proteases, enzymes that cleave polyproteins and remove polyubiquitin chains via deubiquitinating activity, are two important virulence factors. Here, we reveal an unanticipated interplay between the macrodomain and the PLP2 domain that is important for replication and antagonizing the host innate immune response. Targeting the interaction of these enzymes may provide new therapeutic opportunities to treat CoV disease.


title: Estimating the early death toll of COVID-19 in the United States

text: BACKGROUND: Efforts to track the severity and public health impact of the novel coronavirus, COVID-19, in the US have been hampered by testing issues, reporting lags, and inconsistency between states. Evaluating unexplained increases in deaths attributed to broad outcomes, such as pneumonia and influenza (P&I) or all causes, can provide a more complete and consistent picture of the burden caused by COVID-19. METHODS: We evaluated increases in the occurrence of deaths due to P&I above a seasonal baseline (adjusted for influenza activity) or due to any cause across the United States in February and March 2020. These estimates are compared with reported deaths due to COVID-19 and with testing data. RESULTS: There were notable increases in the rate of death due to P&I in February and March 2020. In a number of states, these deaths pre-dated increases in COVID-19 testing rates and were not counted in official records as related to COVID-19. There was substantial variability between states in the discrepancy between reported rates of death due to COVID-19 and the estimated burden of excess deaths due to P&I. The increase in all-cause deaths in New York and New Jersey is 1.5–3 times higher than the official tally of COVID-19 confirmed deaths or the estimated excess death due to P&I. CONCLUSIONS: Excess P&I deaths provide a conservative estimate of COVID-19 burden and indicate that COVID-19-related deaths are missed in locations with inadequate testing or intense pandemic activity.


Senegal faces the coronavirus disease −19 challenge


title: Drug repurposing against COVID-19: focus on anticancer agents

text: BACKGROUND: The very limited time allowed to face the COVID-19 pandemic poses a pressing challenge to find proper therapeutic approaches. However, synthesis and full investigation from preclinical studies to phase III trials of new medications is a time-consuming procedure, and not viable in a global emergency, such as the one we are facing. MAIN BODY: Drug repurposing/repositioning, a strategy effectively employed in cancer treatment, can represent a valid alternative. Most drugs considered for repurposing/repositioning in the therapy of the COVID-19 outbreak are commercially available and their dosage and toxicity in humans is well known, due to years (or even decades) of clinical use. This can allow their fast-track evaluation in phase II–III clinical trials, or even within straightforward compassionate use. Several drugs being re-considered for COVID-19 therapy are or have been used in cancer therapy. Indeed, virus-infected cells are pushed to enhance the synthesis of nucleic acids, protein and lipid synthesis and boost their energy metabolism, in order to comply to the “viral program”. Indeed, the same features are seen in cancer cells, making it likely that drugs interfering with specific cancer cell pathways may be effective as well in defeating viral replication. SHORT CONCLUSION: To our knowledge, cancer drugs potentially suitable for facing SARS-CoV-2 infection have not been carefully reviewed. We present here a comprehensive analysis of available information on potential candidate cancer drugs that can be repurposed for the treatment of COIVD-19.


title: Dermatological findings in SARS‐CoV‐2 positive patients: An observational study from North India

text: A novel coronavirus (severe acute respiratory syndrome corononavirus‐2; SARS‐CoV‐2) has affected millions of people across the world. The coronavirus disease (COVID‐19) resulting from SARS‐CoV‐2 manifests in variable clinical severity, featuring both respiratory and extra‐respiratory symptoms. Dermatological manifestations of COVID‐19 are sparsely reported. To study the various dermatological findings in SARS‐CoV‐2 positive patients in Indian population. This article is protected by copyright. All rights reserved.


docid: vfhggdob

title: Respiratory Conditions in Coronavirus Disease 2019 (COVID-19): Important Considerations Regarding Novel Treatment Strategies to Reduce Mortality

text: Abstract A novel virus named 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) causes symptoms that are classified as coronavirus disease (COVID-19). Respiratory conditions are extensively described among more serious cases of COVID-19, and the onset of acute respiratory distress syndrome (ARDS) is one of the hallmark features of critical COVID-19 cases. ARDS can be directly life-threatening because it is associated with low blood oxygenation levels and can result in organ failure. There are no generally recognized effective treatments for COVID-19, but treatments are urgently needed. Anti-viral medications and vaccines are in the early developmental stages and may take many months or even years to fully develop. At present, management of COVID-19 with respiratory and ventilator support are standard therapeutic treatments, but unfortunately such treatments are associated with high mortality rates. Therefore, it is imperative to consider novel new therapeutic interventions to treat/ameliorate respiratory conditions associated with COVID-19. Alternate treatment strategies utilizing clinically available treatments such as hyperbaric oxygen therapy (HBOT), packed red blood cell (pRBC) transfusions, or erthropoiesis-stimulating agent (ESA) therapy were hypothesized to increase oxygenation of tissues by alternative means than standard respiratory and ventilator treatments. It was also revealed that alternative treatments currently being considered for COVID-19 such as chloroquine and hydroxychloroquine by increasing hemoglobin production and increasing hemoglobin availability for oxygen binding and acetazolamine (for the treatment of altitude sickness) by causing hyperventilation with associated increasing levels of oxygen and decreasing levels of carbon dioxide in the blood may significantly ameliorate COVID-19 respiratory symptoms. In conclusion, is recommend, given HBOT, pRBC, and ESA therapies are currently available and routinely utilized in the treatment of other conditions, that such therapies be tried among COVID-19 patients with serious respiratory conditions and that future controlled-clinical trials explore the potential usefulness of such treatments among COVID-19 patients with respiratory conditions.


title: MCPIP1 negatively regulate cellular antiviral innate immune responses through DUB and disruption of TRAF3-TBK1-IKKε complex

text: Abstract IFNβ innate immune plays an essential role in antiviral immune. Previous reports suggested that many important regulatory proteins in innate immune pathway may be modified by ubiquitin and that many de-ubiquitination (DUB) proteins may affect immunity. Monocyte chemotactic protein-inducing protein 1 (MCPIP1), one of the CCCH Zn finger-containing proteins, was reported to have DUB function, but its effect on IFNβ innate immune was not fully understood. In this study, we uncovered a novel mechanism that may explain how MCPIP1 efficiently inhibits IFNβ innate immune. It was found that MCPIP1 negatively regulates the IFNβ expression activated by RIG-I, STING, TBK1, IRF3. Furthermore, MCPIP1 inhibits the nuclear translocation of IRF3 upon stimulation with virus, which plays a key role in type I IFN expression. Additionally, MCPIP1 interacts with important modulators of IFNβ expression pathway including IPS1, TRAF3, TBK1 and IKKε. Meanwhile, the interaction between the components in TRAF3-TBK1-IKKε complex was disrupted by MCPIP1. These results collectively suggest MCPIP1 as an innate immune regulator encoded by the host and point to a new mechanism through which MCPIP1 negatively regulates IRF3 activation and type I IFNβ expression.


title: Stem Cells and Cell Therapy Approaches in Lung Biology and Diseases

text: Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models.


title: A survey of SNOMED CT implementations

text: Abstract The Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) has been designated as the recommended clinical reference terminology for use in clinical information systems around the world and is reported to be used in over 50 countries. However, there are still few implementation details. This study examined the implementation of SNOMED CT in terms of design, use and maintenance issues involved in 13 healthcare organisations across eight countries through a series of interviews with 14 individuals. While a great deal of effort has been spent on developing and refining SNOMED CT, there is still much work ahead to bring SNOMED CT into routine clinical use.


title: Sequence of the genome RNA of rubella virus: Evidence for genetic rearrangement during togavirus evolution

text: Abstract The nucleotide sequence of the rubella virus (RUB) genomic RNA was determined. The RUB genomic RNA is 9757 nucleotides in length [excluding the poly(A) tail] and has a G/C content of 69.5%, the highest of any RNA virus sequenced to date. The RUB genomic RNA contains two long open reading frames (ORFs), a 5′-proximal ORF of 6656 nucleotides and a 3′-proximal ORF of 3189 nucleotides which encodes the structural proteins. Thus, the genomic organization of RUB is similar to that of alphaviruses, the other genus of the Togavirus family, and the 5′-proximal ORF of RUB therefore putatively codes for the nonstructural proteins. Sequences homologous to three regions of nucleotide sequence highly conserved among alphaviruses (a stem-and-loop structure at the 5′ end of the genome, a 51-nucleotide conserved sequence near the 5′ end of the genome, and a 20-nucleotide conserved sequence at the subgenomic RNA start site) were found in the RUB genomic RNA. Amino acid sequence comparisons between the nonstructural ORF of RUB and alphaviruses revealed only one short (122 amino acids) region of significant homology, indicating that these viruses are only distantly related. This region of homology is located at the NH2 terminus of nsP3 in the alphavirus genome. The RUB nonstructural protein ORF contains two global amino acid motifs conserved in a large number of positive-polarity RNA viruses, a motif indicative of helicase activity and a motif indicative of replicase activity. The order of the helicase motif and the nsP3 homology region in the RUB genome is reversed with respect to the alphavirus genome indicating that a genetic rearrangement has occurred during the evolution of these viruses.


title: Disease Management of Dairy Calves and Heifers

text: This article focuses on the most important diseases of dairy calves and heifers and presents clinical approaches that can improve detection, diagnosis, and treatment of herd-based problems. A systematic herd investigation strategy is pivotal to define the problems, understand important risk factors, develop a plan, and make recommendations for disease management accurately. A review of records, colostrum and feeding routines, housing and bedding management, routine procedures, vaccination, and treatment protocols begins the investigation and determines which diagnostic procedures and testing strategies are most useful. Disease management is most effective when the problem source is well defined and the exposure can be limited, calf immunity can be enhanced, or a combination of both. Screening examinations performed regularly or done at strategic time points improves detection of disease, can be used to monitor treatment outcomes, and can avoid disease outbreaks.


docid: atzehdpj

title: Mental health of medical professionals during the covid‐19 pandemic in Togo


title: Effect of different routes of immunization with bovine rotavirus on lactogenic antibody response in mice

text: Summary The effect of different routes of immunization with either live or killed bovine rotavirus (BRV) on the production of lactogenic antibody response in mice was evaluated. The routes of immunization were intramuscular (IM), oral (O) or intradermal in the mammary region (IMam). Following immunization, serum antibody responses were monitored by an enzyme linked immunosorbent assay (ELISA). Following whelping, the mice were allowed to stay with their mother until sacrificed on alternate days post-parturition from day 1–11. Milk from their stomach was collected for antibody titration by ELISA and virus neutralization test. Regardless of the routes of immunization, a rapid increase in serum anti-rotavirus antibody titers was observed for the first 5 wk after immunization followed by a gradual decline. After parturition, the mean antibody titer of lacteal secretions, as determined by ELISA, increased gradually for 7 days with the greatest increase on day 9, followed by a decrease in anti-rotavirus antibody. These titers also correlated with antibody titers in milk as measured by virus neutralization test. The best lactogenic antibody response was observed when IMam × IM × 2 route of immunization was used with live BRV as the antigen. Interestingly, immunization via the oral route with killed BRV also resulted in good antibody responses. In contrast, in the group where killed BRV was used, animals receiving 3× orally had the highest antibody titer. The distribution of different antibody subtypes in milk samples revealed IgG to be the predominant antibody followed by IgM and IgA. Irrespective of the route of administration, there was an increase in IgA on day 9 as compared to day 1 in most of the groups. The significant role played by mucosal immunity in passive protection and the possible ways to modulate subtype specific lactogenic immune response are discussed. Animals models; Lactogenic immunity; Rotaviruses


title: Using web search queries to monitor influenza-like illness: an exploratory retrospective analysis, Netherlands, 2017/18 influenza season

text: BACKGROUND: Despite the early development of Google Flu Trends in 2009, standards for digital epidemiology methods have not been established and research from European countries is scarce. AIM: In this article, we study the use of web search queries to monitor influenza-like illness (ILI) rates in the Netherlands in real time. METHODS: In this retrospective analysis, we simulated the weekly use of a prediction model for estimating the then-current ILI incidence across the 2017/18 influenza season solely based on Google search query data. We used weekly ILI data as reported to The European Surveillance System (TESSY) each week, and we removed the then-last 4 weeks from our dataset. We then fitted a prediction model based on the then-most-recent search query data from Google Trends to fill the 4-week gap (‘Nowcasting’). Lasso regression, in combination with cross-validation, was applied to select predictors and to fit the 52 models, one for each week of the season. RESULTS: The models provided accurate predictions with a mean and maximum absolute error of 1.40 (95% confidence interval: 1.09–1.75) and 6.36 per 10,000 population. The onset, peak and end of the epidemic were predicted with an error of 1, 3 and 2 weeks, respectively. The number of search terms retained as predictors ranged from three to five, with one keyword, ‘griep’ (‘flu’), having the most weight in all models. DISCUSSION: This study demonstrates the feasibility of accurate, real-time ILI incidence predictions in the Netherlands using Google search query data.


title: Development of non-traumatic osteonecrosis of the femoral head requires toll-like receptor 7 and 9 stimulations and is boosted by repression on nuclear factor kappa B in rats

text: Non-traumatic osteonecrosis of the femoral head (ONFH) often occurs after corticosteroid therapy in patients with inflammatory diseases. Recent studies suggest that toll-like receptor (TLR) signaling may contribute to the pathogenesis of inflammatory diseases, and that the reason for corticosteroid therapy for inflammatory diseases is related to the anti-inflammatory activities of corticosteroids through the reduction of NF-κB. We hypothesized that the administration of TLR ligands in combination with corticosteroid causes ONFH and that transcription factors may contribute to the pathogenesis of ONFH. The aim of the study was to evaluate (1) the incidence of ONFH in rats after the administration of TLR7 or TLR9 ligands together with methylprednisolone (MPSL) and (2) whether transcription factors contribute to the development of ONFH. Male Wistar rats (n=148) were divided into five groups as follows: Group 1: Saline+MPSL, Group 2: Imiquimod+Saline, Group 3: Imiquimod+MPSL, Group 4: CpG-C+MPSL, Group 5: Imiquimod+BAY11-7082+MPSL. As a result, ONFH was observed in 0 of 12 rats in Group 1, in 1 of 10 in Group 2, in 6 of 12 in Group 3, in 4 of 12 in Group 4, in 0 of 9 in Group 5. MPSL treatment did not significantly affect IRF7 activity, whereas NF-κB activity was significantly repressed in Group 2 and Group 3. Furthermore, the repression in interferon regulatory factor 7 (IRF7) activity by BAY11-7082 interfered with the development of ONFH simultaneously with the MPSL treatment-induced repression in NF-κB activity. In conclusion, in the present study, corticosteroid treatment after the administration of TLR7 or TLR9 ligands caused ONFH. Repression in NF-κB activity by corticosteroid treatment boosted the development of ONFH.


title: Importance of cholesterol for infection of cells by transmissible gastroenteritis virus

text: Abstract In this study, we addressed the question whether cholesterol is important for transmissible gastroenteritis virus (TGEV), a porcine coronavirus, in the initiation of an infection. We found that cholesterol depletion from the cellular membrane by methyl-β-cyclodextrin (MβCD) significantly impaired the efficiency of TGEV infection. Infectivity was also reduced after depleting cholesterol from the viral envelope. This finding is surprising because coronaviruses bud from a pre-Golgi compartment which is expected to be low in cholesterol compared to the plasma membrane. Addition of exogenous cholesterol resulted in a restoration of the infectivity confirming our conclusion that efficient TGEV infection requires cholesterol in both the viral and the cellular membranes. Our data raise the possibility that the viral and cellular proteins involved in the entry process may be associated with cholesterol-rich membrane microdomains.


title: Dermatologic surgery training during the COVID‐19 era

text: COVID-19, a novel coronavirus, has spread throughout the world. Because of exponential growth, social distancing is a critical strategy to decrease transmission Thus, educational medical communities from many countries have transitioned to online didactics1 . Recommendations to cancel all non-urgent visits have been proposed2 . Our dermatology department has canceled all elective outpatient visits and surgeries. Consequently, trainees' surgical skills have been severely affected. To continue our educational program, we have implemented measures to help our trainees continue learning and maintaining surgical skills.


docid: bwofzbwa

title: Current status on the development of pseudoviruses for enveloped viruses

text: Emerging and reemerging infectious diseases have a strong negative impact on public health. However, because many of these pathogens must be handled in biosafety level, 3 or 4 containment laboratories, research and development of antivirals or vaccines against these diseases are often impeded. Alternative approaches to address this issue have been vigorously pursued, particularly the use of pseudoviruses in place of wild‐type viruses. As pseudoviruses have been deprived of certain gene sequences of the virulent virus, they can be handled in biosafety level 2 laboratories. Importantly, the envelopes of these viral particles may have similar conformational structures to those of the wild‐type viruses, making it feasible to conduct mechanistic investigation on viral entry and to evaluate potential neutralizing antibodies. However, a variety of challenging issues remain, including the production of a sufficient pseudovirus yield and the inability to produce an appropriate pseudotype of certain viruses. This review discusses current progress in the development of pseudoviruses and dissects the factors that contribute to low viral yields.


Transforming food and agriculture systems with agroecology


Management strategies and role of telemedicine in a Surgery Unit during COVID-19 outbreak


title: Molecular decoys: antidotes, therapeutics and immunomodulators

text: Receptor–ligand interactions are fundamental to the regulation of cell physiology, enabling the communication between cells and their environment via signal transduction. Receptors are also exploited by toxins and infectious agents to mediate pathogenesis. Over the past 20 years, however, this bi-partite paradigm for cellular regulation, that is, receptors and their ligands, has been revised to include an unforeseen participant namely, soluble receptors or molecular decoys. Decoys function as nature's modifiers of potent responses such as inflammation, stimulation of cell proliferation and triggering apoptosis. Decoys not only provide the means to fine tune the regulation of these phenomena; they also serve as potential leads for the development of recombinant anti-toxins, anti-viral agents and novel therapeutics for combating cancer and inflammatory disease.


title: Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13

text: Abstract Severe acute respiratory syndrome (SARS) is an infectious disease with a strong potential for transmission upon close personal contact and is caused by the SARS-coronavirus (CoV). However, there are no natural or synthetic compounds currently available that can inhibit SARS-CoV. We examined the inhibitory effects of 64 purified natural compounds against the activity of SARS helicase, nsP13, and the hepatitis C virus (HCV) helicase, NS3h, by conducting fluorescence resonance energy transfer (FRET)-based double-strand (ds) DNA unwinding assay or by using a colorimetry-based ATP hydrolysis assay. While none of the compounds, examined in our study inhibited the DNA unwinding activity or ATPase activity of human HCV helicase protein, we found that myricetin and scutellarein potently inhibit the SARS-CoV helicase protein in vitro by affecting the ATPase activity, but not the unwinding activity, nsP13. In addition, we observed that myricetin and scutellarein did not exhibit cytotoxicity against normal breast epithelial MCF10A cells. Our study demonstrates for the first time that selected naturally-occurring flavonoids, including myricetin and scultellarein might serve as SARS-CoV chemical inhibitors.


title: Establishing a surveillance network for severe lower respiratory tract infections in Korean infants and young children

text: To reduce morbidity and mortality through integrated case management, a pilot study to detect respiratory viruses in patients with acute lower respiratory infections (ALRIs) was designed as part of a nationwide surveillance for this disease in Korea. The study population consisted of hospitalized patients under the age of 5 years with bronchiolitis, pneumonia, croup, or acute respiratory distress syndrome. A prospective 6-month study was performed. Two hundred and ninety-seven nasopharyngeal secretions were collected and multiplex reverse transcriptase polymerase chain reactions (RT-PCR)/polymerase chain reactions (PCR) were performed to detect respiratory viruses. If there were any positive RT-PCR/PCR results, viral cultures were proceeded for confirmation. Respiratory viruses were identified in 49.6% of 296 patients. The detection rates were as follows: respiratory syncytial virus (RSV) was the most commonly detected in 52.7% (87/165), human metapneumovirus (hMPV) in 15.8%, human corona virus (hCoV) in 5.5%, adenovirus in 9.7%, human bocavirus (hBoV) in 5.5%, parainfluenza virus (PIV) in 3.6%, rhinovirus (RV) in 4.2%, and the influenza virus in 3% of the patients with ALRIs. The consistent rate of positive results between RT-PCR and viral culture was 92% (105/114). Using our methods to detect viral causes seemed to be acceptable for the national surveillance of severe acute respiratory infections in infants and children.


title: Ebola Emergency Preparedness: Simulation Training for Frontline Health Care Professionals

text: INTRODUCTION: At Brigham and Women's Hospital, we identified the need for a comprehensive training program designed to prepare frontline staff to safely manage a patient with Ebola viral disease (EVD). The primary goal of this program was to ensure the safety of staff, patients, and the general public by training staff in the correct use of personal protective equipment (PPE) before, during, and after care of patients with EVD. METHODS: We delivered a 4-hour experiential training program to frontline health care professionals who would be expected to care for a patient with EVD. The program occurred in a simulation center with multiple flexible spaces and consisted of demonstration, multiple skills practice sessions, and a patient simulation case. We analyzed completed pre- and posttraining questionnaires. The questionnaire assessed their subjective level of confidence in three key areas: donning and doffing PPE, performing clinical skills while wearing PPE, and management of a contamination breach. RESULTS: This program was effectively deployed in the STRATUS Center for Medical Simulation over a 4-month period, with 220 health care professionals participating in the training and 195 participants completing the pre-/posttraining questionnaires. Our intervention significantly increased the confidence of participants on each primary objective (p = .001 for all three stations). DISCUSSION: This interprofessional simulation-based program has been shown to be a well-received method of training clinicians to manage patients collaboratively during an EVD outbreak. Our intent is that the skills taught in this training program would also be transferable to management of other infectious diseases in the clinical setting.


title: Better Tests, Better Care: Improved Diagnostics for Infectious Diseases

text: In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians.


title: Non‐human viruses developed as therapeutic agent for use in humans

text: Viruses usually infect a restricted set of host species, and only in rare cases does productive infection occur outside the natural host range. Infection of a new host species can manifest as a distinct disease. In this respect, the use of non‐human viruses in clinical therapy may be a cause for concern. It could provide the opportunity for the viruses to adapt to the new host and be transferred to the recipient's relatives or medical caretakers, or even to the normal host species. Such environmental impact is evidently undesirable. To forecast future clinical use of non‐human viruses, a literature study was performed to identify the viruses that are being considered for application as therapeutic agents for use in humans. Twenty‐seven non‐human virus species were identified that are in (pre)clinical development, mainly as oncolytic agents. For risk management, it is essential that the potential environmental consequences are assessed before initiating clinical use, even if the virus is not formally classified as a genetically modified organism. To aid such assessment, each of these viruses was classified in one of five relative environmental risk categories, ranging from “Negligible” to “Very High”. Canary pox virus and the Autographa californica baculovirus were assigned a “Negligible” classification, and Seneca Valley virus, murine leukemia virus, and Maraba virus to the “High” category. A complicating factor in the classification is the scarcity of publicly available information on key aspects of virus biology in some species. In such cases the relative environmental risk score was increased as a precaution. Copyright © 2011 John Wiley & Sons, Ltd.


One oral and maxillofacial surgeon’s attitude toward the COVID-19 pandemic


title: EL CUIDADO HUMANIZADO EN LA MUERTE POR COVID-19: A PROPÓSITO DE UN CASO

text: RESUMEN La población mundial está sufriendo una pandemia por infección del virus SARS-Cov-2, que provoca la enfermedad COVID-19. En España, la tasa de crecimiento de la epidemia es del 6,79% desde la activación del estado de alarma y un porcentaje de defunciones del 9,07% del total de infectados. Las recomendaciones del Ministerio de Sanidad para profesionales de la salud en contacto con personas infectadas, o sospecha de ello, incluyen la colocación de dispositivos de protección individual (mascarilla FPP2, guantes, bata impermeable, gorro, y gafas protectoras o pantalla). Una vez colocado todo el material, es necesario reflexionar acerca de la humanización de los cuidados enfermeros a las personas en situación agónica infectadas por COVID-19, a propósito de un caso. La pretensión es la puesta en valor del pensamiento enfermero para salvar esa distancia, y mantener unos cuidados lo más humanos y cercanos posibles, al final de la vida. ABSTRACT The world population is experiencing a pandemic due to infection with the SARS-Cov-2 virus, which causes the COVID-19 disease. In Spain, the growth rate of the epidemic is 6.79% since the alarm activation with 9,1% of deaths of the total infected. Recommendations of the National Government to prevent health professional contagion include the placement of personal protection devices (FPP2 mask, gloves, waterproof gown, hat, and protective glasses or screen). Once all the material is in place, it is necessary to argue about the humanization of nursing caring in people suffering dying situation, who are infected with COVID-19, regarding a clinical case. The aim is to enhance nursing thinking to bridge that distance, and maintain care as human and close as possible, at the end of life.


title: HealthMap: Global Infectious Disease Monitoring through Automated Classification and Visualization of Internet Media Reports

text: OBJECTIVE: Unstructured electronic information sources, such as news reports, are proving to be valuable inputs for public health surveillance. However, staying abreast of current disease outbreaks requires scouring a continually growing number of disparate news sources and alert services, resulting in information overload. Our objective is to address this challenge through the HealthMap.org Web application, an automated system for querying, filtering, integrating and visualizing unstructured reports on disease outbreaks. DESIGN: This report describes the design principles, software architecture and implementation of HealthMap and discusses key challenges and future plans. MEASUREMENTS: We describe the process by which HealthMap collects and integrates outbreak data from a variety of sources, including news media (e.g., Google News), expert-curated accounts (e.g., ProMED Mail), and validated official alerts. Through the use of text processing algorithms, the system classifies alerts by location and disease and then overlays them on an interactive geographic map. We measure the accuracy of the classification algorithms based on the level of human curation necessary to correct misclassifications, and examine geographic coverage. RESULTS: As part of the evaluation of the system, we analyzed 778 reports with HealthMap, representing 87 disease categories and 89 countries. The automated classifier performed with 84% accuracy, demonstrating significant usefulness in managing the large volume of information processed by the system. Accuracy for ProMED alerts is 91% compared to Google News reports at 81%, as ProMED messages follow a more regular structure. CONCLUSION: HealthMap is a useful free and open resource employing text-processing algorithms to identify important disease outbreak information through a user-friendly interface.


title: Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors

text: A small library of 36 functionalized benzophenone thiosemicarbazone analogs has been prepared by chemical synthesis and evaluated for their ability to inhibit the cysteine proteases cathepsin L and cathepsin B. Inhibitors of cathepsins L and B have the potential to limit or arrest cancer metastasis. The six most active inhibitors of cathepsin L (IC(50) < 85 nM) in this series incorporate a meta-bromo substituent in one aryl ring along with a variety of functional groups in the second aryl ring. These six analogs are selective for their inhibition of cathepsin L versus cathepsin B (IC(50) > 10,000 nM). The most active analog in the series, 3-bromophenyl-2′-fluorophenyl thiosemicarbazone 1, also efficiently inhibits cell invasion of the DU-145 human prostate cancer cell line.


COVID-19 (SARS-CoV-2 Infection) and Children: Pediatric Neurologist’s Perspective


title: The Novel Coronavirus Disease (COVID‐19) Complicated by Pulmonary Embolism and Acute Respiratory Distress Syndrome

text: Acute respiratory distress syndrome and coagulopathy played an important role in morbidity and mortality of severe COVID‐19 patients. A higher frequency of PE than expected in COVID‐19 patients was recently reported. The presenting symptoms for PE were untypical including dyspnea, which is one of the major symptoms in severe COVID‐19, especially in those patients with ARDS. We reported two COVID‐19 cases with coexisting complications of PE and ARDS, aiming to consolidate the emerging knowledge of this global health emergency and raise the awareness that the hypoxemia or severe dyspnea in COVID‐19 may be related to PE and not necessarily always due to the parenchymal disease. This article is protected by copyright. All rights reserved.