title: Real-world Scenario of Patients with Lung Cancer Amid the COVID-19 Pandemic in China

text: Abstract Background Coronavirus disease (COVID-19) outbreak throughout the world has affected billions of people in many way putting a huge burden on the healthcare system. The ongoing outbreak of this respiratory disease has posed critical challenges for the public health, research, and medical communities around the world. This study aimed to examine the impact of COVID-19 pandemic on patients with lung cancer in China. Methods We collected data on 397 inpatients from a single center during 4 weeks of the epidemic time (2020 group), and that of 2504 inpatients during the same period (4 weeks) in last 5 years (2015-2019 group). A questionnaire was used to investigate medical demands among 803 patients with lung cancer at 65 hospitals from 20 provinces in China during the epidemic. We evaluate the incidence data of COVID-19 in Guangdong to analyze the tendency of the pandemic and compared it with inpatient data. Results The number of hospitalizations and lung cancer-related surgeries had steadily increased in 2015-2019 but reduced by an average of 26.72% (133.8) and 57.18% (45.4) in 2020. The hospital capacity decreased by 28.00% (35 inpatient beds) during the SARS-CoV-2 epidemic period. The epidemic caused a greater impact on medical work related to lung cancer after the Chinese New Year holiday. Patients were most concerned about longer waiting time for outpatient services, inpatient beds, physical examinations, or surgeries (406; 50.56%), the possibility of infection with the novel coronavirus (359; 44.71%), difficulties in getting to a hospital due to transportation outages (279; 34.74%). Patients in stage I and II showed less fear about disease progression (14, 18.18%; 4, 14.81%), lower proportions of delayed medical arrangement (15, 19.48%; 6, 22.22%) and less complain about complex treatment procedures (12, 15.58%, 5, 18.52%). Patients in high-infected area (345, 56.74%) complained more frequently about longer booking periods than in low-infected area (61, 31.28%). Conclusion Treatment of patients with lung cancer has been affected by the epidemic to some extent. We provide suggestions on both clinical diagnosis and treatment strategies of lung cancer to optimize the process regarding to the currently urgent circumstances. The demand for medical support among patients with lung cancer or other life-threatening diseases should be given sufficient attention, especially during the current COVID-19 outbreak.


title: The challenge of maintaining microscopist capacity at basic levels for malaria elimination in Jiangsu Province, China

text: BACKGROUND: Local malaria transmission has decreased rapidly since the National Malaria Elimination Action Plan was launched in China in 2010. However, imported malaria cases from Africa and Southeast Asia still occur in China due to overseas laborers. Diagnosis by microscopy is the gold standard for malaria and is used in most hospitals in China. However, the current capacity of microscopists to manage malaria cases in hospitals and public health facilities to meet the surveillance needs to eliminate and prevent the reintroduction of malaria is unknown. METHODS: Malaria diagnoses were assessed by comparing the percentage of first visit and confirmed malaria diagnoses at Centers for Disease Control and Prevention (CDCs) and hospitals. The basic personnel information for public health departments and hospitals at different levels was investigated. The skills of microscopists for blood smear preparation and slide interpretation were also examined at the county and township levels. RESULTS: Inaccurate rate with 13.49% and 7.32%, respectively, in 2013 and 2014, from 341 and 355 reported cases from sub-provincial levels in Jiangsu province. Most of the 523 malaria cases reported in Nantong Prefecture from 2000 to 2014 involved patients who first visited county CDCs seeking treatment, however, none of these cases received confirmed diagnosis of malaria in townships or villages.The staff at county CDCs and hospitals with a higher education background performed better at making and interpreting blood smears than staff from townships. CONCLUSIONS: The network for malaria elimination in an entire province has been well established. However, an insufficient capacity for malaria diagnosis was observed, especially the preparing and reading the blood smears at the township and village levels, which is a challenge to achieving and maintaining malaria elimination.


title: Inhibition of herpes simplex virus by myricetin through targeting viral gD protein and cellular EGFR/PI3K/Akt pathway

text: Abstract Myricetin, a common dietary flavonoid, was reported to possess many different biological activities such as anti-oxidant, anti-inflammatory, and antiviral effects. In this study, we explored the anti-HSV effects and mechanisms of myricetin both in vitro and in vivo. The results showed that myricetin possessed anti-HSV-1 and HSV-2 activities with very low toxicity, superior to the effects of acyclovir. Myricetin may block HSV infection through direct interaction with virus gD protein to interfere with virus adsorption and membrane fusion, which was different from the nucleoside analogues such as acyclovir. Myricetin also down-regulate the cellular EGFR/PI3K/Akt signaling pathway to further inhibit HSV infection and its subsequent replication. Most importantly, intraperitoneal therapy of myricetin markedly improved mice survival and reduced virus titers in both lungs and spinal cord. Therefore, the natural dietary flavonoid myricetin has potential to be developed into a novel anti-HSV agent targeting both virus gD protein and cellular EGFR/PI3K/Akt pathway.


title: Knowledge, Attitudes, and Practices Toward COVID-19 in a Saudi Arabian Population: A Cross-Sectional Study

text: Background Preventative measures are necessary to control a pandemic such as coronavirus disease 2019 (COVID-19), and different platforms to communicate guidelines have varying levels of effectiveness. Objective At the time of this study, there were no published studies investigating knowledge, attitudes, and practices related to COVID-19 within the Saudi population. Therefore, this study aims to address this gap in current knowledge and provide baseline data to the government and other health associations for preventive measurements for future outbreaks. Methods This study was conducted among the Saudi population using an online questionnaire. The questionnaire assessed the awareness of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incubation period, the known symptoms of COVID-19, the mode of transmission of SARS-CoV-2, and infection control measures for prevention. Results The study included 6000 participants. Most respondents (84.93%) of the population reported awareness of the virus, 78.78% reported a belief that the virus leads to death, 89.47% reported a belief that 14 days is the incubation period, and 93.73% were aware of the possibility of asymptomatic carriers. Conclusions The Saudi population is aware of the attitudes and practices of prevention as well as the mode of transmission. The efforts by the Ministry of Health were effective in increasing awareness among the Saudi population toward COVID-19.


title: In Silico Computational Screening of Kabasura Kudineer - Official Siddha Formulation and JACOM against SARS-CoV-2 Spike protein

text: BACKGROUND: Siddha Medicine is a valuable therapeutic choice which is classically used for treating viral respiratory infections, this principle of medicine is proven to contain antiviral compounds. OBJECTIVE: The study is aimed to execute the In Silico computational studies of Phytoconstituents of Siddha Official Formulation Kabasura Kudineer and Novel Herbal Preparation - JACOM which are commonly used in treating viral fever and respiratory infectious diseases and could be affective against the ongoing pandemic novel coronavirus disease SARS-CoV-2. METHOD: Cresset Flare software was used for Molecular Docking studies against the Spike Protein SARS-COV-2 (PDB ID: 6VSB). Further, we also conducted In Silico prediction studies on the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates by using online pkCSM and SwissADME web servers. RESULTS: Totally 37 compounds were screened, of these 9 compounds showed high binding affinity against SARS-COV-2 Spike Protein. All the Phytoconstituents were free from carcinogenic and tumorigenic properties. Based on these, we proposed the new formulation called as “SNACK–V” CONCLUSION: Based on further experiments and clinical trials, these formulations could be used for effective treatment of COVID-19.


title: An exploration of the properties of the CORE problem list subset and how it facilitates the implementation of SNOMED CT

text: Objective Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) is the emergent international health terminology standard for encoding clinical information in electronic health records. The CORE Problem List Subset was created to facilitate the terminology’s implementation. This study evaluates the CORE Subset’s coverage and examines its growth pattern as source datasets are being incorporated. Methods Coverage of frequently used terms and the corresponding usage of the covered terms were assessed by “leave-one-out” analysis of the eight datasets constituting the current CORE Subset. The growth pattern was studied using a retrospective experiment, growing the Subset one dataset at a time and examining the relationship between the size of the starting subset and the coverage of frequently used terms in the incoming dataset. Linear regression was used to model that relationship. Results On average, the CORE Subset covered 80.3% of the frequently used terms of the left-out dataset, and the covered terms accounted for 83.7% of term usage. There was a significant positive correlation between the CORE Subset’s size and the coverage of the frequently used terms in an incoming dataset. This implies that the CORE Subset will grow at a progressively slower pace as it gets bigger. Conclusion The CORE Problem List Subset is a useful resource for the implementation of Systematized Nomenclature of Medicine Clinical Terms in electronic health records. It offers good coverage of frequently used terms, which account for a high proportion of term usage. If future datasets are incorporated into the CORE Subset, it is likely that its size will remain small and manageable.


title: Pharmacokinetics, pharmacodynamics and clinical use of trazodone and its active metabolite m‐chlorophenylpiperazine in the horse

text: Trazodone is a serotonin receptor antagonist and reuptake inhibitor used extensively as an anxiolytic in human and small animal veterinary medicine. The aims of this study were to determine the pharmacokinetics of oral trazodone in experimental horses and to evaluate the effect of oral trazodone in clinical horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg. Plasma concentrations of trazodone and its metabolite (m‐CPP) were determined via UPLC‐MS/MS. Noncompartmental pharmacokinetic analysis, sedation and ataxia scores were determined. Trazodone was rapidly absorbed after oral administration with a maximum concentration of 2.5–4.1 μg/ml and half‐life of the terminal phase of approximately 7 hr. The metabolite was present at low levels in all horses, representing only 2.5% of the total area under the curve. In experimental horses, concentration‐dependent sedation and ataxia were noted, lasting up to 12 hr. For clinical cases, medical records of horses treated with trazodone for various abnormal behaviours were reviewed and data were summarized. Trazodone was successful in modifying behavioural problems to some degree in 17 of 18 clinical cases. Tolerance and subsequent lack of drug effect occurred in two of 18 clinical cases following 14 or 21 days of use. In both populations of horses, adverse effects attributed to trazodone include oversedation, muscle fasciculations and transient arrhythmias.


title: Prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with COVID-19 in Europe: Initial report of the international RISC-19-ICU prospective observational cohort

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a high disease burden with 10% of confirmed cases progressing towards critical illness. Nevertheless, the disease course and predictors of mortality in critically ill patients are poorly understood. METHODS: Following the critical developments in ICUs in regions experiencing early inception of the pandemic, the European-based, international RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry was created to provide near real-time assessment of patients developing critical illness due to COVID-19. FINDINGS: As of April 22, 2020, 639 critically ill patients with confirmed SARS-CoV-2 infection were included in the RISC-19-ICU registry. Of these, 398 had deceased or been discharged from the ICU. ICU-mortality was 24%, median length of stay 12 (IQR, 5–21) days. ARDS was diagnosed in 74%, with a minimum P/F-ratio of 110 (IQR, 80–148). Prone positioning, ECCO2R, or ECMO were applied in 57%. Off-label therapies were prescribed in 265 (67%) patients, and 89% of all bloodstream infections were observed in this subgroup (n = 66; RR=3·2, 95% CI [1·7–6·0]). While PCT and IL-6 levels remained similar in ICU survivors and non-survivors throughout the ICU stay (p = 0·35, 0·34), CRP, creatinine, troponin, d-dimer, lactate, neutrophil count, P/F-ratio diverged within the first seven days (p<0·01). On a multivariable Cox proportional-hazard regression model at admission, creatinine, d-dimer, lactate, potassium, P/F-ratio, alveolar-arterial gradient, and ischemic heart disease were independently associated with ICU-mortality. INTERPRETATION: The European RISC-19-ICU cohort demonstrates a moderate mortality of 24% in critically ill patients with COVID-19. Despite high ARDS severity, mechanical ventilation incidence was low and associated with more rescue therapies. In contrast to risk factors in hospitalized patients reported in other studies, the main mortality predictors in these critically ill patients were markers of oxygenation deficit, renal and microvascular dysfunction, and coagulatory activation. Elevated risk of bloodstream infections underscores the need to exercise caution with off-label therapies.


Bioactive Lipids and Coronavirus (COVID-19)


title: The COVID-19 Outbreak and Affected Countries Stock Markets Response

text: This paper evaluates the short-term impact of the coronavirus outbreak on 21 leading stock market indices in major affected countries including Japan, Korea, Singapore, the USA, Germany, Italy, and the UK etc. The consequences of infectious disease are considerable and have been directly affecting stock markets worldwide. Using an event study method, our results indicate that the stock markets in major affected countries and areas fell quickly after the virus outbreak. Countries in Asia experienced more negative abnormal returns as compared to other countries. Further panel fixed effect regressions also support the adverse effect of COVID-19 confirmed cases on stock indices abnormal returns through an effective channel by adding up investors’ pessimistic sentiment on future returns and fears of uncertainties.


title: Enhancing preparation for large Nipah outbreaks beyond Bangladesh: Preventing a tragedy like Ebola in West Africa

text: Abstract The Nipah virus has been transmitted from person-to-person via close contact in non-urban parts of India (including Kerala May 2018), Bangladesh, and the Philippines. It can cause encephalitis and pneumonia, and has a high case fatality rate. Nipah is a One Health zoonotic infectious disease linked to fruit bats, and sometimes pigs or horses. We advocate anticipating and preparing for urban and larger rural outbreaks of Nipah. Immediate enhanced preparations would include standardized guidance on infection prevention and control, and personal protective equipment, from the World Health Organization (WHO) on their OpenWHO website and 2018 “Managing Epidemics” handbook, along with adding best clinical practices by experts in countries with multiple outbreaks such as Bangladesh and India. Longer-term enhanced preparations include accelerating development of field diagnostics, antiviral drugs, immune-based therapies, and vaccines. WHO-coordinated multi-partner protocols to test investigational treatments, diagnostics, and vaccines are needed, by analogy to such protocols for Ebola during the unanticipated pan-epidemic in Guinea, Liberia, and Sierra Leone. Anticipating and preparing now for urban and rural Nipah outbreaks in nations with no experience with Nipah will help avoid the potential for what the United Nations 2016 report on Ebola in West Africa called a “preventable tragedy”.


title: Indirect impact of COVID-19 on Environment: A brief study in Indian Context

text: Worldwide spread of COVID-19 in a quite short time has brought a dramatic decrease in industrial activities, road traffic and tourism. Restricted human interaction with nature during this crisis time has appeared as a blessing for nature and environment. Reports from all over the world are indicating that after the outbreak of COVID-19, environmental conditions including air quality and water quality in rivers are improving and wildlife is blooming. India has always been a hub of pollution with huge population, heavy traffics and polluting industries leading to high air quality index (AQI) values in all major cities. But after declaration of lockdown due to COVID-19, quality of air has started to improve and all other environmental parameters such as water quality in rivers have started giving a positive sign towards restoring. This paper provides evidence-based insight into improvement of air quality and environment during pre and post lockdown of this pandemic situation. An attempt has been made to visualize the improvement in the air quality using tools like satellite images of Indian atmosphere, results of onsite real-time monitoring at specific locations (Ghaziabad-highest polluting city of India) and Air quality index (AQI) calculated by central pollution control board of India.


title: Ethyl dibromofluoroacetate: a versatile reagent for the synthesis of fluorinated molecules

text: [Figure: see text]


title: The Kalgoorlie Otitis Media Research Project: rationale, methods, population characteristics and ethical considerations

text: Otitis media (OM) is one of the most common paediatric illnesses for which medical advice is sought in developed countries. Australian Aboriginal children suffer high rates of OM from early infancy. The resultant hearing loss can affect education and quality of life. As numerous factors contribute to the burden of OM, interventions aimed at reducing the impact of single risk factors are likely to fail. To identify key risk factors and understand how they interact in complex causal pathways, we followed 100 Aboriginal and 180 non‐Aboriginal children from birth to age 2 years in a semi‐arid zone of Western Australia. We collected demographic, obstetric, socio‐economic and environmental data, breast milk once, and nasopharyngeal samples and saliva on seven occasions. Ear health was assessed by clinical examination, tympanometry, transient evoked otoacoustic emissions and audiometry. We considered the conduct of our study in relation to national ethical guidelines for research in Aboriginal and Torres Strait Islander health. After 1 year of community consultation, the study was endorsed by local committees and ethical approval granted. Fieldwork was tailored to minimise disruption to people's lives and we provided regular feedback to the community. We saw 81% of non‐Aboriginal and 65% of Aboriginal children at age 12 months. OM was diagnosed on 55% and 26% of routine clinical examinations in Aboriginal and non‐Aboriginal children respectively. Aboriginal mothers were younger and less educated, fewer were employed and they lived in more crowded conditions than non‐Aboriginal mothers. Sixty‐four per cent of Aboriginal and 40% of non‐Aboriginal babies were exposed to environmental tobacco smoke. Early consultation, provision of a service while undertaking research, inclusion of Aboriginal people as active members of a research team and appropriate acknowledgement will assist in ensuring successful completion of the research.


title: Environmental contamination by SARS-CoV-2 in a designated hospital for coronavirus disease 2019

text: BACKGROUND: COVID-19 is characterized by risk of nosocomial transmission; however, the extent of environmental contamination and its potential contribution of environmental contamination to SARS-CoV-2 transmission are poorly understood. This study aimed to investigate whether environmental contamination may play a role in SARS-CoV-2 transmission. METHODS: Air samples were collected by natural precipitation, and environmental surface samples were collected by conventional surface swabbing. SARS-CoV-2 RNA detection was performed using reverse transcription polymerase chain reaction. RESULTS: Viral RNA was not detected in the 44 air samples. The positive rates in 200 environmental surface samples in medical areas (24.83%) was higher than that in living quarters (3.64%), with a significant difference (P<0.05). The positive rates were 25.00% and 37.50% for the general isolation ward and ICU, respectively, and no significant difference was observed between them (P=0.238). The top five sampling sites with a positive rate in medical areas were beepers (50.00%), water machine buttons (50.00%), elevator buttons (42.86%), computer mouses (40.00%), and telephones (40.00%). CONCLUSIONS: Most of the touchable surfaces in the designated hospital for COVID-19 were heavily contaminated, suggesting that the environment is a potential medium of disease transmission. These results emphasize the need for strict environmental surface hygiene practices and enhanced hand hygiene to prevent the spread of the virus.


title: Controlled release of PEI/DNA complexes from mannose-bearing chitosan microspheres as a potent delivery system to enhance immune response to HBV DNA vaccine

text: Abstract A novel approach involving the preparation of mannose-bearing chitosan microspheres with entrapping complexes of HBV DNA and PEI was developed to improve the delivery of DNA into antigen-presenting cells (APCs) after intramuscular (i.m.) injection. Compared with the traditional chitosan microspheres, the microspheres could quickly release intact and penetrative PEI/DNA complexes. What's more, chitosan was modified with mannose to target the primary APCs such as dendritic cells (DCs) owing to the high density of mannose receptors expressing on the surface of immature DCs. After i.m. immunization, the microspheres induced significantly enhanced serum antibody and cytotoxic T lymphocyte (CTL) responses in comparison to naked DNA.


title: Systematic review of respiratory viral pathogens identified in adults with community-acquired pneumonia in Europe

text: Abstract Community-acquired pneumonia (CAP) is an important respiratory disease and the fifth leading cause of mortality in Europe. The development of molecular diagnostic tests has highlighted the contributions of respiratory viruses to the aetiology of CAP, suggesting the incidence of viral pneumonia may have been previously underestimated. We performed a systematic review and meta-analysis to describe the overall identification of respiratory viruses in adult patients with CAP in Europe, following PRISMA guidelines (PROSPERO; CRD42016037233). We searched EMBASE, MEDLINE, CINAHL, WHOLIS, COCHRANE library and grey literature sources for relevant studies, and screened these against protocol eligibility criteria. Two researchers performed data extraction and risk of bias assessments, independently, using a piloted form. Results were synthesised narratively, and random effects meta-analyses performed to calculate pooled estimates of effect; heterogeneity was quantified using I2. Twenty-eight studies met inclusion criteria of which 21 were included in the primary meta-analysis. The pooled proportion of patients with identified respiratory viruses was 22.0% (95% CI: 18.0%–27.0%), rising to 29.0% (25.0%–34.0%) in studies where polymerase chain reaction (PCR) diagnostics were performed. Influenza virus was the most frequently detected virus in 9% (7%–12%) of adults with CAP. Respiratory viruses make a substantial contribution to the aetiology of CAP in adult patients in Europe; one or more respiratory viruses are detected in about one quarter of all cases.


title: Linking resource supplies and price drivers: Lessons from Traditional Chinese Medicine (TCM) price volatility and change, 2002–2017

text: Abstract Ethnopharmacological relevance Worldwide, one of the drivers of substitution and adulteration is the cost of the natural resources (plants, animals, fungi) that are ingredients of traditional medicines. Relatively few studies have been done that link prices of traditional medicine ingredients to what drives changes in price, yet this is an important topic. Theoretically, prices have been widely considered as an economic indicator of resource scarcity. Rare, slow growing medicinal plants sell for high prices and common, less popular species for low prices. Price levels also influence the viability of farming vs. wild harvest (and incentives to overharvest high value species when tenure is weak). Prices can also influence the harvesting or buying behaviour of harvesters, traders or manufacturers. When prices are high, then there is a greater incentive to use cheaper substitute species or adulterants. As previous studies on herbal medicine ingredients have shown, adulteration applies in a wide variety of cases, including to some Traditional Chinese Medicine (TCM) species. Aim of the study The aim of this study was to gain a better understanding of which factors influenced changes in the market prices of document prices for four popular, but very different traditional Chinese medicine (TCM) species (2002 – 2017). Materials and methods Fluctuations in market prices were followed over a 15-year period (2002–2017) for four very different TCM ingredients: two plant species (one wild harvested for fruits (Schisandra sphenanthera Rehder & E.H. Wilson) the other in a transition from wild harvest to cultivation (Paris polyphylla Smith), an animal species (the Tokay gecko (Gekko gecko L.)) and the entomophagous “caterpillar fungus” (Ophiocordyceps sinensis (Berk). G.H. Sung, J.M. Sung, Hywel-Jones & Spatafora). Results High prices of medicinal plants are widely considered to reflect resource scarcity. Real-time market prices for three of the four very different TCM species we studied all showed major price fluctuations. The exception was P. polyphylla, whose wild populations are widely known to be increasingly scarce, where there was a steady increase in price, with few fluctuations in the upward price trend. The three other species showed significant price fluctuations. These were driven by multiple factors. Ecological and biogeographic factors that influence abundance or scarcity of supply certainly played a role. But other factors were also influential. These included both national and global economic factors (the influence of the Global Financial Crisis (GFC)), national policy changes that in turn influenced businessmen giving expensive gifts (that included O. sinensis)), climate change (influencing fruiting success of S. sphenanthera), price speculation by traders and lack of information (e.g: reduction in G. gecko prices due to traders incorrectly believing that domestication would increase supplies). Conclusions Price fluctuations in the four TCM species we examined are influenced by many factors and not just resource scarcity. And the situation is more complex than the trajectory based on Homma's (1992) model, where he predicted that higher prices would result in a shift to cultivation, thus replacing wild harvest. In case of both O. sinensis and P. polyphylla, Homma (1992, 1996) was right in terms of scarcity and high prices stimulating a major investment in cultivation (P. polyphylla) and artificial production (O. sinensis). But in both cases, intensive production through cultivation or artificial propagation do not yet occur on a large enough scale to reduce harvest of wild stocks. Substitution and adulteration occur with all four species. Improving information to medicinal plant traders on the supply status of TCM stocks, whether from wild harvest or from cultivation could benefit product quality, cultivation initiatives and conservation efforts.


Coronavirus Disease 2019 Pandemic – Public Health Preparedness in Nepal and One Health Approach


title: The Frameshift Stimulatory Signal of Human Immunodeficiency Virus Type 1 Group O is a Pseudoknot

text: Abstract Human immunodeficiency virus type 1 (HIV-1) requires a programmed −1 ribosomal frameshift to produce Gag–Pol, the precursor of its enzymatic activities. This frameshift occurs at a slippery sequence on the viral messenger RNA and is stimulated by a specific structure, downstream of the shift site. While in group M, the most abundant HIV-1 group, the frameshift stimulatory signal is an extended bulged stem-loop, we show here, using a combination of mutagenesis and probing studies, that it is a pseudoknot in group O. The mutagenesis and probing studies coupled to an in silico analysis show that group O pseudoknot is a hairpin-type pseudoknot with two coaxially stacked stems of eight base-pairs (stem 1 and stem 2), connected by single-stranded loops of 2nt (loop 1) and 20nt (loop 2). Mutations impairing formation of stem 1 or stem 2 of the pseudoknot reduce frameshift efficiency, whereas compensatory changes that allow re-formation of these stems restore the frameshift efficiency to near wild-type level. The difference between the frameshift stimulatory signal of group O and group M supports the hypothesis that these groups originate from a different monkey to human transmission.


title: Role of Intelligent Computing in COVID-19 Prognosis: A State-of-the-Art Review

text: The World Health Organization (WHO) declared novel coronavirus 2019 (COVID-19), an infectious epidemic caused by SARS-CoV-2, as Pandemic in March 2020. It has affected more than 40 million people in 216 countries. Almost in all the affected countries, the number of infected and deceased patients has been enhancing at a distressing rate. As the early prediction can reduce the spread of the virus, it is highly desirable to have intelligent prediction and diagnosis tools. The inculcation of efficient forecasting and prediction models may assist the government in implementing better design strategies to prevent the spread of virus. In this paper, a state-of-the-art analysis of the ongoing machine learning (ML) and deep learning (DL) methods in the diagnosis and prediction of COVID-19 has been done. Moreover, a comparative analysis on the impact of machine learning and other competitive approaches like mathematical and statistical models on COVID-19 problem has been conducted. In this study, some factors such as type of methods(machine learning, deep learning, statistical & mathematical) and the impact of COVID research of the nature of data used for the forecasting and prediction of pandemic using computing approaches has been presented. Finally some important research directions for further research on COVID-19 are highlighted which may facilitate the researchers and technocrats to develop competent intelligent models for the prediction and forecasting of COVID-19 real time data.


title: Covid-19 in pregnant women and babies: What pediatricians need to know

text: Beginning in late 2019, a novel coronavirus labeled SARS-CoV-2 spread around the world, affecting millions. The impact of the disease on patients and on health care delivery has been unprecedented. Here, we review what is currently known about the effects of the virus and its clinical condition, Covid-19 in areas of relevance to those providing care to neonates. While aspects of pregnancy, including higher expression of the cell receptor for the virus, ACE2, could put these women at higher risk, preliminary epidemiological information does not support this. Viral carriage prevalence based on universal screening show that rates vary from 13% in “hot spots” such as New York City, to 3% in areas with lower cases. Vertical transmission risks are unknown but 3.1% of 311 babies born to mothers with Covid-19 were positive within a week of birth. The clinical description of 26 neonates < 30 days of age showed no deaths and only one requiring intensive care. Risks for breast-feeding and for milk banks are discussed.


title: Intensifying poultry production systems and the emergence of avian influenza in China: a ‘One Health/Ecohealth’ epitome

text: Several kinds of pressure can lead to the emergence of infectious diseases. In the case of zoonoses emerging from livestock, one of the most significant changes that has taken place since the mid twentieth century is what has been termed the “livestock revolution”, whereby the stock of food animals, their productivity and their trade has increased rapidly to feed rising and increasingly wealthy and urbanized populations. Further increases are projected in the future in low and middle-income countries. Using avian influenza as an example, we discuss how the emergence of avian influenza H5N1 and H7N9 in China was linked to rapid intensification of the poultry sector taking place in landscapes rich in wetland agriculture and wild waterfowls habitats, providing an extensive interface with the wild reservoir of avian influenza viruses. Trade networks and live-poultry markets further exacerbated the spread and persistence of avian influenza as well as human exposure. However, as the history of emergence of highly pathogenic avian influenza (HPAI) demonstrates in high-income countries such as the USA, Canada, Australia, the United Kingdom or the Netherlands, this is by no way specific to low and middle-income countries. Many HPAI emergence events took place in countries with generally good biosecurity standards, and the majority of these in regions hosting intensive poultry production systems. Emerging zoonoses are only one of a number of externalities of intensive livestock production systems, alongside antimicrobial consumption, disruption of nutrient cycles and greenhouse gases emissions, with direct or indirect impacts on human health. In parallel, livestock production is essential to nutrition and livelihoods in many low-income countries. Deindustrialization of the most intensive production systems in high-income countries and sustainable intensifications in low-income countries may converge to a situation where the nutritional and livelihood benefits of livestock production would be less overshadowed by its negative impacts on human an ecosystem health.


title: Case Study of Airborne Pathogen Dispersion Patterns in Emergency Departments with Different Ventilation and Partition Conditions

text: The prevention of airborne infections in emergency departments is a very important issue. This study investigated the effects of architectural features on airborne pathogen dispersion in emergency departments by using a CFD (computational fluid dynamics) simulation tool. The study included three architectural features as the major variables: increased ventilation rate, inlet and outlet diffuser positions, and partitions between beds. The most effective method for preventing pathogen dispersion and reducing the pathogen concentration was found to be increasing the ventilation rate. Installing partitions between the beds and changing the ventilation system’s inlet and outlet diffuser positions contributed only minimally to reducing the concentration of airborne pathogens.


title: The family caregiving crisis meets an actual pandemic

text: The coronavirus disease 2019 (COVID-19) pandemic presents unique challenges to those who work with the seriously ill population, including both health care providers and the family caregivers providing unpaid care. We rely on this lay workforce as health care routinely transitions care to the home, and now more than ever, we are depending on them in the current pandemic. As palliative care and other health care providers become overwhelmed with patients critically ill with COVID-19, and routine care becomes delayed, we have a charge to recognize and work with family caregivers. Our commentary provides rationale for the need to focus on family caregivers and key considerations for how to include them in pandemic clinical decision making.


title: Extracorporeal membrane oxygenation (ECMO): does it have a role in the treatment of severe COVID-19?

text: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged since December 2019 in Wuhan city, and has quickly spread throughout China and other countries. To date, no specific treatment has been proven to be effective for SARS-CoV-2 infection. According to World Health Organization (WHO), management of coronavirus disease 19 (COVID-19) has mainly focused on infection prevention, case detection and monitoring, and supportive care. Given to the previous experience, extracorporeal membrane oxygenation (ECMO) has been proven to be an effective therapy in the treatment of respiratory failure or acute respiratory distress syndrome (ARDS). On the basis of similar principle, ECMO may be also an effective therapy in the treatment of severe COVID-19. In this study, we described and discussed the clinical outcomes of ECMO for ARDS patients, ECMO use for severe COVID-19 in China, the indications of ECMO use, and some important issues associated with ECMO.


Erratum zu: Erhöhtes Risiko für tiefe Beinvenenthrombosen bei Intensivpatienten mit CoViD-19-Infektion? – Erste Daten


title: The Altered Gut Microbiome and Necrotizing Enterocolitis

text: Current evidence highlights the importance of developing a healthy intestinal microbiota in the neonate. Many aspects that promote health or disease are related to the homeostasis of these intestinal microbiota. Their delicate equilibrium could be strongly influenced by the intervention that physicians perform as part of the medical care of the neonate, especially preterm infants. As awareness of the importance of the development and maintenance of these intestinal flora increase and newer molecular techniques are developed, it will be possible to provide better care of infants with interventions that will have long-lasting effects.


title: Predictors of recovery from post-traumatic stress disorder after the dongting lake flood in China: a 13–14 year follow-up study

text: BACKGROUND: Floods are some of the most common and destructive natural disasters in the world, potentially leading to both physical injuries and psychological disorders, including post-traumatic stress disorder (PTSD). PTSD can damage functional capacity and interfere with social functioning. However, little is known about recovery from PTSD after floods. This study used 2013–2014 follow-up data on survivors of the 1998 Dongting Lake flood who were diagnosed with PTSD in 2000 to measure the prevalence rate of PTSD at follow-up and identify predictors of recovery from the PTSD diagnosis in 2000. METHODS: Participants included survivors who had been diagnosed as having PTSD in 2000 after the 1998 Dongting Lake flood. PTSD at follow-up was reassessed using the PTSD Checklist-Civilian version. Information on demographics, trauma-related stressors, post-trauma stressors, social support, and coping style were collected through face-to-face interviews. The association between the independent variables and PTSD at follow-up was analyzed using logistic regression analyses. RESULTS: A total of 201 participants with a PTSD diagnosis in 2000 were included in this study. A total of 19.4 % of the flood survivors with PTSD in 2000 continued to suffer from PTSD in 2013–2014. In the multivariable logistic regression model, individuals who had lost relatives (OR = 12.37, 95 % CI = 2.46–62.16), suffered from bodily injury (OR = 5.01, 95 % CI = 1.92–13.08), had a low level of social support (OR = 5.47, 95 % CI = 1.07–27.80), or had a negative coping style (OR = 4.92, 95 % CI = 1.89–12.81) were less likely to recover from PTSD. CONCLUSIONS: The prevalence rate of PTSD at follow-up indicates that natural disasters such as floods may have a negative influence on survivors’ mental health for an extended period of time. Individuals who have lost relatives, suffered from bodily injury, had a low level of social support, or had a negative coping style were less likely to recover from PTSD. Therefore, effective psychological intervention measures are necessary for facilitating the recovery process from PTSD, especially for individuals with adverse prognostic factors.


title: Enteropathogens and risk factors for diarrhea in Norwegian dairy calves

text: Abstract The aims of the current study were to estimate the prevalence of enteropathogens in calves in Norwegian dairy herds, evaluate the clinical consequences of protozoal infections, and identify risk factors for diarrhea. The 135 participating herds were randomly selected from those in The Norwegian Dairy Herd Recording System that had at least 15 cow-years. Each herd was followed for 1 yr. Fecal samples from calves with (n=68) or without (n=691) diarrhea were analyzed for the presence of Cryptosporidium, Giardia, and Eimeria species. Diarrheic samples (n=191) were assayed for rotavirus group A, bovine coronavirus (BCoV), Cryptosporidium, and Escherichia coli F5 by antigen ELISA. Blood samples (n=1,348) were analyzed for antibodies against BCoV and rotavirus. Potential risk factors for diarrhea were analyzed by using Cox regression analysis adjusted for herd frailty effect. Rotavirus and Cryptosporidium were the most commonly detected enteropathogens in diarrheic samples. A high level of Cryptosporidium shedding or BCoV seropositive calves in a herd was associated with an increased risk of diarrhea. Other factors found to increase the risk of diarrhea were use of slatted concrete floor in group pens versus other floor types [hazard ratio (HR)=8.9], housing of calves in free-stalls compared with tie-stalls (HR=3.7), purchasing of calves into the herd versus not purchasing calves (HR=4.1), and calves being born during winter compared with other seasons of the year (HR=1.5).


title: Hyper-activated IRF-1 and STAT1 contribute to enhanced Interferon stimulated gene (ISG) expression by Interferon α and γ co-treatment in human hepatoma cells

text: Abstract Previous reports suggest that type I and type II Interferon can co-operatively inhibit some virus replication, e.g. HCV, SARS-CoV, HSV-1. To find out the molecular mechanism underlying this phenomenon, we analyzed the transcription profile stimulated by IFN-α and IFN-γ in Huh-7 cells and found that the transcription of a subset of IFN stimulated genes (ISGs) including BclG, XAF1, TRAIL and TAP1 was enhanced when IFN-α and γ were both present. Promoter analysis of BclG revealed that IRF-1 and STAT1 were both required in this process. Enhanced IRF-1/DNA complex formation was observed in interferon co-treatment group by gel shift analysis. Furthermore, IRF-1 activation was found to be generally required in this cluster of ISGs. STAT1 tyrosine phosphorylation was elevated by IFN combination treatment, however, only the hyper-transactivation of GAS but not ISRE was observed. In conclusion, hyper-activation of IRF-1 and elevated STAT1 dimer formation may be two general switches which contribute to a much more robust antiviral symphony against virus replication when type I and type II IFNs are co-administered.


title: Twenty-five years of research on the behavioural malaise associated with influenza and the common cold

text: Summary Minor illnesses such as the common cold and influenza are frequent and widespread. As well as specific symptoms such as nasal problems and fever, these illnesses are associated with a behavioural malaise. One feature of this malaise is reduced alertness and this has been confirmed using subjective reports and objective measures of performance. Such effects have been obtained with both experimentally induced infections and in studies of naturally occurring illnesses. The mechanisms underlying the effects are unclear but possibly reflect effects of cytokines on the CNS which result in changes in neurotransmitter functioning that lead to reduced alertness. The malaise induced by these illnesses has many real-life consequences and activities such as driving and safety at work may be at risk. These illnesses not only have direct effects on performance and mood but also make the person more sensitive to effects of other negative influences such as noise, alcohol and prolonged work. Countermeasures include ingestion of caffeine and other drugs known to increase alertness.


title: Corona Virus 101

text: COVID-2019 emerged from China in late December of 2019. It follows 2 other coronavirus outbreaks, the SARS-CoV and the MERS-CoV. Coronaviruses usually circulate among animals but sometimes can jump to humans. These 3 strains have caused severe disease in humans and global transmission concerns. Symptoms of COVID-2019 include cough, fever, and shortness of breath. Related illnesses can range from mild to severe to fatal. Primary care providers must be alert to respiratory symptoms they encounter that are associated with pertinent travel history, be prepared to safely screen, examine, and possibly test and/or report suspicions to the health department for further evaluation.


title: Generation of stable monoclonal antibody-producing BCR(+) human memory B cells by genetic programming

text: B cell lymphoma (BCL)6 and Bcl-xL are expressed in germinal center (GC) B cells and enable them to endure the proliferative and mutagenic environment of the GC. By introducing these genes into peripheral blood memory B cells and culturing these cells with factors produced by follicular helper T cells, CD40L and IL-21, we convert them to highly proliferating, cell surface BCR positive, Ig-secreting B cells with features of GC B cells including expression of activation-induced cytidine deaminase. We generated cloned lines of B cells specific for respiratory syncytial virus and used these cells as a source of antibodies that effectively neutralized this virus in vivo. This method provides a new tool to study GC B cell biology, signal transduction through antigen-specific B cell receptors, and for the rapid generation of high affinity human monoclonal antibodies.


title: Psychological distress found among exposed health care workers

text: Recent research to assess the magnitude of mental health outcomes and associated factors among health care workers treating patients exposed to COVID‐19 in China has found that many are psychologically stressed, raising concerns about the psychological well‐being of physicians and nurses involved in the acute COVID‐19 outbreak.


title: Nasal cytokines as mediators of illness during the common cold

text: Identification of a pharmacologically targeted mediator of the common cold is a desirable, but, to date, elusive goal of current research. The roles of various mediators, such as histamine, leukotrienes, bradykinin, and, more recently, chemokines and cytokines, in the pathophysiology and development of complications of the common cold are the subject of previous and current investigations. Establishing causality of a mediator in the common cold has been difficult for a number of reasons, including the limitations of our research tools and protocols and the complexity of the inflammatory and immune pathways that participate during the common cold. The available evidence for mediation of the common cold is the subject of this manuscript.


title: Severe weight loss in lambs infected with Giardia duodenalis assemblage B

text: An outbreak of giardiasis was observed in a sheep farm in Central Italy. Infected lambs (30–90 days of age) showed a malabsorption syndrome, decreased weight gain and impairment in feed efficiency. The most relevant clinical sign was the excretion of malodorous and poorly formed faeces, whereas diarrhoea was rarely observed in the flock. Laboratory investigations revealed the presence of Giardia in affected animals, while no other significant viral, bacterial or parasitic pathogens were identified in faeces or tissue samples. A mild to severe infiltrative enteritis with eosinophils, lymphocytes and plasma cells was detected in histological sections of the gut. Giardia parasites collected from duodenal aspirates were typed as Giardia duodenalis Assemblage B, by PCR amplification and sequencing of the TPI gene. Treatment with fenbendazole at a dose of 10 mg/kg for 3 consecutive days, successfully cleared the infection. These results show that G. duodenalis can cause significant economic losses in sheep farming.


Lucky China: Efficient Prevention from Middle East Respiratory Syndrome and its Beyond


Could MEFV mutation carriage status have a protective role for COVID-19 pandemia?


title: Calling for an exponential escalation scheme in vaccine development for COVID-19

text: PURPOSE: COVID-19 as a pandemic calls for rapid development of vaccines. METHODS: Here a proposal of a seamless, adaptive, phase 1–3 trial for accelerated vaccine development is described. RESULTS: Starting at 10, the number of vaccinated volunteers would exponentially increase by tenfold at an interval of 2 weeks; close surveillance of antibody responses, safety and efficacy is necessary. After only 16 weeks, general vaccination would be feasible if supply meets the demand. CONCLUSION: A COVID-19 vaccine would be rapidly available at a slightly increased risk for undetected late side effects or insufficient efficacy if compared with standard vaccine development schemes.


Living Arrangements of Older Adults and COVID‐19 Risk: It Is Not Just Nursing Homes


Chapter 64 Immunodeficiency and Mucosal Immunity


title: Hospital design for better infection control

text: The physical design and infrastructure of a hospital or institution is an essential component of its infection control measure. Thus is must be a prerequisite to take these into consideration from the initial conception and planning stages of the building. The balance between designing a hospital to be an open, accessible and public place and the control to reduce the spread of infections diseases is a necessity. At Singapore General Hospital, many lessons were learnt during the SARS outbreak pertaining to this. During and subsequent to the SARS outbreak, many changes evolved in the hospital to enable us to handle and face any emerging infectious situation with calm, confidence and the knowledge that staff and patients will be in good stead. This paper will share some of our experiences as well as challenges


title: G-quadruplex-based aptamers against protein targets in therapy and diagnostics()

text: Nucleic acid aptamers are single-stranded DNA or RNA molecules identified to recognize with high affinity specific targets including proteins, small molecules, ions, whole cells and even entire organisms, such as viruses or bacteria. They can be identified from combinatorial libraries of DNA or RNA oligonucleotides by SELEX technology, an in vitro iterative selection procedure consisting of binding (capture), partitioning and amplification steps. Remarkably, many of the aptamers selected against biologically relevant protein targets are G-rich sequences that can fold into stable G-quadruplex (G4) structures. Aiming at disseminating novel inspiring ideas within the scientific community in the field of G4-structures, the emphasis of this review is placed on: 1) recent advancements in SELEX technology for the efficient and rapid identification of new candidate aptamers (introduction of microfluidic systems and next generation sequencing); 2) recurrence of G4 structures in aptamers selected by SELEX against biologically relevant protein targets; 3) discovery of several G4-forming motifs in important regulatory regions of the human or viral genome bound by endogenous proteins, which per se can result into potential aptamers; 4) an updated overview of G4-based aptamers with therapeutic potential and 5) a discussion on the most attractive G4-based aptamers for diagnostic applications. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.


Letter to the Editor Regarding 'Coronavirus Disease 2019 (COVID-19) and Neurosurgery: Literature and Neurosurgical Societies Recommendations Update'


Lutte contre les maladies respiratoires chroniques en Afrique : se concerter pour faire passer les programmes dans la pratique


title: Implementation of the cobas Liat influenza point-of-care test into an emergency department during a high-incidence season: a retrospective evaluation following real-world implementation

text: Summary The cobas Liat influenza A/B and respiratory syncytial virus (RSV) assay (Liat) was used in the adult emergency department of a large London hospital from 21st January 2018 to 14th April 2018. Influenza was detected in 308 of 1027 (30%) samples tested; influenza A in 157 (15.3%), influenza B in 149 (14.5%) and RSV in 28 (2.7%). When compared against Fast Track Diagnostics Respiratory Pathogens 21 multiplex polymerase chain reaction and Cepheid Xpert Xpress Flu/RSV assay, Liat performance for the detection of influenza A or B was: sensitivity 85% [95% confidence interval (CI) 76–92)], specificity 98% (95% CI 97–99), negative predictive value 94% (95% CI 92–96) and positive predictive value 95% (95% CI 91–97).


title: Virus-induced diabetes mellitus. X. Attachment of encephalomyocarditis virus and permissiveness of cultured pancreatic β cells to infection

text: Abstract Monolayers of pancreatic β-cells from strains of mice susceptible (SJL/J) and resistant (C57BL/6J) to the development of virus-induced diabetes mellitus were inoculated with the M variant of encephalomyocarditis (EMC) virus. Immunofluorescence showed that viral antigens appeared in up to 10 times more β cells from susceptible SJL/J mice than from resistant C57BL/6J mice. Infectious center assays revealed that 10–30 times more SJL/J β cells contained infectious virus than C57BL/6J β cells. Viral attachment experiments showed no difference in the binding of EMC virus when embryonic fibroblasts, pancreatic fibroblasts, and kidney cells from SJL/J and C57BL/6J mice were compared. However, at least twice as much virus attached to the pancreatic β cells from susceptible than from resistant strains of mice. Our data suggest that genetically determined differences in viral receptors on the surface of β cells may be one of the factors controlling susceptibility to EMC-induced diabetes mellitus.


Plasma from donors convalescent from SARS-CoV-2 infection – A matter of priorities


title: Design, synthesis and crystallographic analysis of nitrile-based broad-spectrum peptidomimetic inhibitors for coronavirus 3C-like proteases

text: Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CL(pro)) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CL(pro) of severe-acute-respiratory-syndrome-coronavirus. The IC(50) values of the inhibitors were in the range of 4.6–49 μM, demonstrating that the nitrile warhead can effectively inactivate the 3CL(pro) autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was ∼10x more potent than the other inhibitors tested. Crystal structures of the enzyme–inhibitor complexes showed that the nitrile warhead inhibits 3CL(pro) by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1–S4 substrate-binding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CL(pro) from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC(50) values ranging from 1.3 to 3.7 μM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CL(pro), and they inhibit 3CL(pro) from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection.


title: Identification and function analysis of canine stimulator of interferon gene (STING)

text: Abstract Stimulator of interferon gene (STING) plays an important role in the cyclic GMP-AMP synthase (cGAS)-mediated activation of type I IFN responses. In this study, we identified and cloned canine STING gene. Full-length STING encodes a 375 amino acid product that shares the highest similarity with feline STING. Highest levels of mRNA of canine STING were detected in the spleen and lungs while the lowest levels in the heart and muscle. Analysis of its cellular localization showed that STING is localizes to the endoplasmic reticulum. STING overexpression induced the IFN response via the IRF3 and NF-κB pathways and up-regulated the expression of ISG15 and viperin. However, knockdown of STING did not inhibit the IFN-β response triggered by poly(dA:dT), poly(I:C), or SeV. Finally, overexpression of STING significantly inhibited the replication of canine influenza virus H3N2. Collectively, our findings indicate that STING is involved in the regulation of the IFN-β pathway in canine.


title: Positive experiences of volunteers working in deployable laboratories in West Africa during the Ebola outbreak

text: The largest outbreak of Ebola virus disease ever started in West Africa in December 2013; it created a pressing need to expand the workforce dealing with it. The aim of this study was to gain insight into the experiences of volunteers from the European Union who worked in deployable laboratories in West Africa during the outbreak. This study is part of the EMERGE project. We assessed the experiences of 251 volunteers with a 19-item online questionnaire. The questions asked about positive aspects of volunteering such as learning new skills, establishing a new path in life, and changing life values. Other questionnaire subjects were the compliance to follow-up measures, the extent to which volunteers felt these measures restricted their daily activities, the fear of stigmatization, and worries about becoming infected or infecting their families. The volunteers reported positive effects that reached far beyond their daily work, such as changes in life priorities and a greater appreciation of the value of their own lives. Although the volunteers did not feel that temperature monitoring restricted their daily activities, full compliance to temperature monitoring and reporting it to the authorities was low. The volunteers did not fear Ebola infection for themselves or their families and were not afraid of stigmatization. With respect to the burden on the families, 50% reported that their family members were worried that the volunteer would be infected with Ebola virus. Altogether, the positive experiences of the volunteers in this study far outweigh the negative implications and constitute an important argument for inspiring people who intend to join such missions and for motivating the hesitant ones.


title: Effects of hypervariable regions in spike protein on pathogenicity, tropism, and serotypes of infectious bronchitis virus

text: Abstract To study the roles of hypervariable regions (HVRs) in receptor-binding subunit S1 of the spike protein, we manipulated the genome of the IBV Beaudette strain using a reverse genetics system to construct seven recombinant strains by separately or simultaneously replacing the three HVRs of the Beaudette strain with the corresponding fragments from a QX-like nephropathogenic isolate ck/CH/LDL/091022 from China. We characterized the growth properties of these recombinant IBVs in Vero cells and embryonated eggs, and their pathogenicity, tropism, and serotypes in specific pathogen-free (SPF) chickens. All seven recombinant IBVs proliferated in Vero cells, but the heterogenous HVRs could reduce their capacity for adsorption during in vitro infection. The recombinant IBVs did not significantly increase the pathogenicity compared with the Beaudette strain in SPF chickens, and they still shared the same serotype as the Beaudette strain, but the antigenic relatedness values between the recombinant strain and Beaudette strain generally decreased with the increase in the number of the HVRs exchanged. The results of this study demonstrate the functions of HVRs and they may help to develop a vaccine candidate, as well as providing insights into the prevention and control of IBV.


title: Development and Laboratory Evaluation of a Real-Time PCR Assay for Detecting Viruses and Bacteria of Relevance for Community-Acquired Pneumonia

text: Community-acquired pneumonia may present with similar clinical symptoms, regardless of viral or bacterial cause. Diagnostic assays are needed to rapidly discriminate between causes, because this will guide decisions on appropriate treatment. Therefore, a quantitative real-time PCR (qPCR) assay with duplex reactions targeting eight bacteria and six viruses was developed. Technical performance was examined with linear plasmids. Upper and lower respiratory tract specimens were used to compare the qPCR assay with standard microbiological methods. The limit of detection was 5 to 20 DNA template copies with approximately 1000-fold differences in concentrations of the two competing templates. SDs for positive controls were <5%. The use of the qPCR assay resulted in 113 positive identifications in 94 respiratory specimens compared with 38 by using standard diagnostics. Diagnostic accuracy of the qPCR assay varied between 60% positive agreement with standard tests for Streptococcus pneumoniae and 100% for Mycoplasma pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. Negative percentage of agreement was >95% for M. pneumoniae, Streptococcus pyogenes, respiratory syncytial virus, and influenza A virus; whereas it was only 56% for Haemophilus influenzae. Multiple microbial agents were identified in 19 of 44 sputum and 19 of 50 nasopharynx specimens. We conclude that in parallel qPCR detection of the targeted respiratory bacteria and viruses is feasible. The results indicate good technical performance of the assay in clinical specimens.


title: Evaluierung der Patientenzufriedenheit mit einer augenärztlichen Videosprechstunde während der COVID-19-Pandemie

text: BACKGROUND: We introduced a video consultation (VC) during the coronavirus (COVID-19) pandemic in an ophthalmology practice with eight doctors to ensure continuous ophthalmological care, infection prophylaxis and to compensate a decreased number of patient presentations. OBJECTIVE: Evaluation of the most common reasons for patient presentations in the VC, the proportion of re-presentations in the practice despite VC, practical challenges associated with the introduction of VC and patient satisfaction. MATERIAL AND METHODS: Patients with a recent acute visual deterioration and severe eye pain were excluded from the VC. The VC were carried out by a trained specialist in ophthalmology. A questionnaire with eight questions was completed after the VC appointment in order to evaluate the proportion of completed VC and patient satisfaction. RESULTS: We included 29 (13 male, Ø 52.6 years, 16 female, Ø 64.7 years) patients in this analysis. The VC could be performed with 68.97% of the participants who rated their overall experience with an average grade of 1.6 (1 very good to 6 insufficient) and all of them indicated that they would recommend the VC. Of presentations in VC 70% were related to the symptoms of the anterior eye segment. In 70% of the cases no re-presentations took place in the unit. CONCLUSION: Our study represents a significant practical application of VC for the management of non-urgent ocular conditions with maximum infection prophylaxis. The introduction of VC was severely limited by technological or user-related issues by the establishment of video connections. Patient satisfaction with VC was high to very high.


title: Acute Thrombotic Events as Initial Presentation of Patients with COVID-19 infection

text: We describe three patients with COVID-19 who presented with an acute vascular event rather than typical respiratory symptoms. These patients were all subsequently found to have laboratory confirmed COVID-19 infections as the likely etiology of their thrombotic event. The primary presentation of COVID-19 infection as a thrombotic event rather than respiratory symptoms has not been described elsewhere. Our cases and discussion highlight the thrombotic complications caused by COVID-19, management of these patients, and explores the role of anticoagulation in patients diagnosed with COVID-19.


title: Outbreaks of antimicrobial resistant Salmonella Choleraesuis in wild boars piglets from central‐western Spain

text: Salmonella enterica serovar Choleraesuis is the aetiological agent of swine paratyphoid being a highly invasive zoonotic pathogen. Wild boar natural populations are experiencing a demographical expansion as well as some farms are breeding this species to release for hunting with management sometimes identical to that of domestic pigs, including supplementation, grouping, and antibiotic treatments. This situation increases the chance of contact between wild boars and livestock, and potentially induces stress, with different sanitary consequences. The present work aims to describe the clinical features of recent outbreaks caused by S. Choleraesuis in wild boar from central‐western Spain, as well as the antimicrobial resistance and phylogenetic relationships of isolates involved. 28 strains of S. Choleraesuis were isolated from 28 different wild boars belonging to 10 different game states located in central western Spain and submitted to the Clinical Veterinary Hospital (CVH) of the University of Extremadura. Samples were taken from different organs and cultured according to the ISO 6579:2002 procedure. Suspicious colonies were identified by PCR and antimicrobial resistance was evaluated by disc diffusion susceptibility test and the presence of the main resistance genes as well as 18 plasmid replicons frequently found among the Enterobacteriaceae was verified by PCR. Pulsed field gel electrophoresis was applied to determine the genetic relationship between isolates. The outbreaks under study were characterized by high mortality (35%–84%) and a septicaemic presentation. S. Choleraesuis was isolated from all the wild boars analysed, and 26 of the 28 isolates presented resistance to at least one antibiotic. The predominant resistances found were against sulphonamide, streptomycin, tetracycline, and doxicicline and sul1, strA‐strB, and tetA were the most prevalent resistance genes among isolates. 10 strains carried FIIA, FIB+H/1 or FIIA+H/1 plasmids. PFGE classified the isolates into four different profiles, grouped into two clusters. This results show that prevention against S. Choleraesuis must be considered in the sanitary programs of the wild boar breeders.


Clinical Characteristics and 28-Day Mortality of Medical Patients Admitted with COVID-19 to a Central London Teaching Hospital


COVID-19 related liver injury: call for international consensus


title: Psychological Impact and Associated Factors During the Initial Stage of the Coronavirus (COVID-19) Pandemic Among the General Population in Spain

text: The outbreak of COVID-19 in Spain started at the end of February. By 9th April 2020 Spain was the second country in confirmed cases and in deaths. On March 14, 2020, the Spanish Government declared the state of alarm to limit viral transmission. During such state, citizens must stay confined at home with few justified exceptions. This whole situation drastically changed the life of the population, which can cause a wide range of psychosocial impacts. This study explored the psychological impact of the COVID-19 pandemic in the general adult population (N = 3055) during the first stages of the outbreak in Spain, as well as their anxiety, stress and depression levels. We also examined the extent to which the following variables were associated to participants’ mental health: (1) demographics; (2) degree of concern about the pandemic; (3) environmental conditions during the home confinement, (4) changes in daily life as a consequence of the pandemic; (5) contact with the COVID-19 disease; (6) actual and perceived severity of the crisis; (7) information about the COVID-19, (8) perceived health status and (9) leisure activities conducted within the last 24 h. Our results show that Spanish consider the current COVID-19 health crisis as fairly severe, and the majority felt that the COVID-19 crisis had greatly impacted on their daily life, including changes in their daily routines and cancelation of important activities. About 36% of the participants reported moderate to severe psychological impact, 25% showed mild to severe levels of anxiety, 41% reported depressive symptoms, and 41% felt stressed. Women, young, and those who that lost their job during the health crisis showed the strongest negative psychological symptoms. What worried Spaniards the most was the likelihood of suffering an economic crisis derived from the pandemic. We found factors associated with better mental health, such as being satisfied with the information received about the health crisis, conducting leisure activities, and the perception of being in good health. These findings can be used to design psychological interventions to help coping with COVID-19 pandemic, both in Spain and other countries.


title: The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)

text: Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.


title: Oligomerization of a membrane protein correlates with its retention in the Golgi complex

text: The first membrane-spanning domain (m1) of the M glycoprotein of avian coronavirus (formerly called E1) is sufficient to retain this protein in the cis-Golgi. When the membrane-spanning domain of a protein which is efficiently delivered to the plasma membrane (VSV G protein) is replaced with m1, the resulting chimera (Gm1) is retained in the Golgi (Swift, A. M., and C. E. Machamer. 1991. J. Cell Biol. 115:19-30). When assayed in sucrose gradients, we observed that Gm1 formed a large oligomer, and that much of this oligomer was SDS resistant and stayed near the top of the stacking gel of an SDS-polyacrylamide gel. The unusual stability of the oligomer allowed it to be detected easily. Gm1 mutants with single amino acid substitutions in the m1 domain that were retained in the Golgi complex formed SDS-resistant oligomers, whereas mutants that were rapidly released to the plasma membrane did not. Oligomerization was not detected immediately after synthesis of Gm1, but occurred gradually with a lag of approximately 10 min, suggesting that it is not merely aggregation of misfolded proteins. Furthermore, oligomerization did not occur under several conditions that block ER to Golgi transport. The lumenal domain was not required for oligomerization since another chimera (alpha m1G), where the lumenal domain of Gm1 was replaced by the alpha subunit of human chorionic gonadotropin, also formed an SDS-resistant oligomer, and was able to form hetero-oligomers with Gm1 as revealed by coprecipitation experiments. SDS resistance was conferred by the cytoplasmic tail of VSV G, because proteolytic digestion of the tail in microsomes containing Gm1 oligomers resulted in loss of SDS resistance, although the protease-treated material continued to migrate as a large oligomer on sucrose gradients. Interestingly, treatment of cells with cytochalasin D blocked formation of SDS-resistant (but not SDS- sensitive) oligomers. Our data suggest that SDS-resistant oligomers form as newly synthesized molecules of Gm1 arrive at the Golgi complex and may interact (directly or indirectly) with an actin-based cytoskeletal matrix. The oligomerization of Gm1 and other resident proteins could serve as a mechanism for their retention in the Golgi complex.


title: Phase-adjusted estimation of the number of Coronavirus Disease 2019 cases in Wuhan, China

text: An outbreak of clusters of viral pneumonia due to a novel coronavirus (2019-nCoV/SARS-CoV-2) happened in Wuhan, Hubei Province in China in December 2019. Since the outbreak, several groups reported estimated R(0) of Coronavirus Disease 2019 (COVID-19) and generated valuable prediction for the early phase of this outbreak. After implementation of strict prevention and control measures in China, new estimation is needed. An infectious disease dynamics SEIR (Susceptible, Exposed, Infectious, and Removed) model was applied to estimate the epidemic trend in Wuhan, China under two assumptions of R(t). In the first assumption, R(t) was assumed to maintain over 1. The estimated number of infections would continue to increase throughout February without any indication of dropping with R(t) = 1.9, 2.6, or 3.1. The number of infections would reach 11,044, 70,258, and 227,989, respectively, by 29 February 2020. In the second assumption, R(t) was assumed to gradually decrease at different phases from high level of transmission (R(t) = 3.1, 2.6, and 1.9) to below 1 (R(t) = 0.9 or 0.5) owing to increasingly implemented public health intervention. Several phases were divided by the dates when various levels of prevention and control measures were taken in effect in Wuhan. The estimated number of infections would reach the peak in late February, which is 58,077–84,520 or 55,869–81,393. Whether or not the peak of the number of infections would occur in February 2020 may be an important index for evaluating the sufficiency of the current measures taken in China. Regardless of the occurrence of the peak, the currently strict measures in Wuhan should be continuously implemented and necessary strict public health measures should be applied in other locations in China with high number of COVID-19 cases, in order to reduce R(t) to an ideal level and control the infection.


Commentary: Vulnerability and Resilience Demonstrated: Cardiac Surgeons During COVID-19


title: Dissecting the roles of TRBP and PACT in double‐stranded RNA recognition and processing of noncoding RNAs

text: HIV TAR RNA‐binding protein (TRBP) and Protein Activator of PKR (PACT) are double‐stranded (ds) RNA‐binding proteins that participate in both small regulatory RNA biogenesis and the response to viral dsRNA. Despite considerable progress toward understanding the structure–function relationship of TRBP and PACT, their specific roles in these seemingly distinct cellular pathways remain unclear. Both proteins are composed of three copies of the double‐stranded RNA‐binding domain, two of which interact with dsRNA, while the C‐terminal copy mediates protein–protein interactions. PACT and TRBP are found in a complex with the endonuclease Dicer and facilitate processing of immature microRNAs. Their precise contribution to the Dicing step has not yet been defined: possibilities include precursor recruitment, rearrangement of dsRNA within the complex, loading the processed microRNA into the RNA‐induced silencing complex, and distinguishing different classes of small dsRNA. TRBP and PACT also interact with the viral dsRNA sensors retinoic acid‐inducible gene I (RIG‐I) and double‐stranded RNA‐activated protein kinase (PKR). Current models suggest that PACT enables RIG‐I to detect a wider range of viral dsRNAs, while TRBP and PACT exert opposing regulatory effects on PKR. Here, the evidence that implicates TRBP and PACT in regulatory RNA processing and viral dsRNA sensing is reviewed and discussed in the context of their molecular structure. The broader implications of a link between microRNA biogenesis and the innate antiviral response pathway are also considered. WIREs RNA 2015, 6:271–289. doi: 10.1002/wrna.1272 1.. RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications; 2.. RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms; 3.. Regulatory RNAs/RNAi/Riboswitches > Biogenesis of Effector Small RNAs.


title: #EducationInTheTimeOfCOVID: Leveraging Social Media to Teach during Pandemic Pandemonium

text: Residency education has been disrupted by the coronavirus disease 2019 (COVID‐19) pandemic. Programs in pandemic status, as designated by the "Accreditation Council for Graduate Medical Education (ACGME) in the US, have substantially modified or suspended traditional educational activities to adhere to physical distancing practices and allow residents to focus on patient care. This lapse in educational events is especially challenging now, as residents and other healthcare professionals are facing a previously undocumented illness and must stay current with the deluge of new information on the disease. Hence, there is a need for simple, digestible, up‐to‐date, and accurate information on COVID‐19 that is electronically disseminated and easy to obtain.


title: Why case fatality ratios can be misleading: individual- and population-based mortality estimates and factors influencing them

text: Different ways of calculating mortality ratios during epidemics have yielded very different results, particularly during the current COVID-19 pandemic. We formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality ratios. The key parameters that affect the dynamics of the different mortality estimates are the incubation period and the time individuals were infected before confirmation of infection. We stress that none of these ratios are accurately represented by the often misinterpreted case fatality ratio (CFR), the number of deaths to date divided by the total number of confirmed infected cases to date. Using data on the recent SARS-CoV-2 outbreaks, we estimate and compare the different dynamic mortality ratios and highlight their differences. Informed by our modeling, we propose more systematic methods to determine mortality ratios during epidemic outbreaks and discuss sensitivity to confounding effects and uncertainties in the data.


title: Recurring and adaptable binding motifs in broadly neutralizing antibodies to influenza virus are encoded on the D3-9 segment of the Ig gene

text: Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA. Comparison with other influenza bnAb crystal structures indicates that the D3-9 segment provides a general mechanism for targeting HA stem. Interestingly, such bnAbs can approach the HA stem with vastly different angles and orientations. Moreover, D3-9 can be translated in different reading frames in different bnAbs, yet still target the same HA stem pocket. Thus, the D3-9 gene segment in the human immune repertoire can provide a robust defense against influenza virus.


title: Guidelines for the management of adult lower respiratory tract infections - Full version

text: This document is an update of Guidelines published in 2005 and now includes scientific publications through to May 2010. It provides evidence-based recommendations for the most common management questions occurring in routine clinical practice in the management of adult patients with LRTI. Topics include management outside hospital, management inside hospital (including community-acquired pneumonia (CAP), acute exacerbations of COPD (AECOPD), acute exacerbations of bronchiectasis) and prevention. Background sections and graded evidence tables are also included. The target audience for the Guideline is thus all those whose routine practice includes the management of adult LRTI.


title: The ATF6 branch of unfolded protein response and apoptosis are activated to promote African swine fever virus infection

text: African swine fever virus (ASFV) infection induces apoptosis in the infected cell; however, the consequences of this activation on virus replication have not been defined. In order to identify the role of apoptosis in ASFV infection, we analyzed caspase induction during the infection and the impact of caspase inhibition on viral production. Caspases 3, 9 and 12 were activated from 16 h post-infection, but not caspase 8. Indeed, caspase 3 activation during the early stages of the infection appeared to be crucial for efficient virus exit. In addition, the inhibition of membrane blebbing reduced the release of virus particles from the cell. ASFV uses the endoplasmic reticulum (ER) as a site of replication and this process can trigger ER stress and the unfolded protein response (UPR) of the host cell. In addition to caspase 12 activation, indicators of ER stress include the upregulation of the chaperones calnexin and calreticulin upon virus infection. Moreover, ASFV induces transcription factor 6 signaling pathway of the UPR, but not the protein kinase-like ER kinase or the inositol-requiring enzyme 1 pathways. Thus, the capacity of ASFV to regulate the UPR may prevent early apoptosis and ensure viral replication.


title: Quality of interaction database management systems

text: Abstract Objective To identify drug interaction databases (DID) and assess the quality of their structures. Method A search was made of the literature for DID and a series of exclusion and structural quality criteria were defined (at least 4 quality criteria: classification according to severity, classification according to level of evidence, bibliographical reference data, description of clinical management, and 11 criteria used for weighting). The level of compliance of every DID with the criteria defined was analysed, together with the level of compliance of each criteria in each DID. Results A total of 54 DID were identified, 30 of which complied with exclusion criteria and 15 of which did not meet the minimum criteria. The rest of the criteria were evaluated in 9 DID: Botplus and Medinteract (100%), SEFH Guide, Lexi-interact and Medscape (89%), Hansten (83%), Micromedex and Stockley (78%), Drug Interactions Facts (68%). Ninety-two percent of the DID describe the mechanism of action, 87% classify the information according to the active ingredient, 75% do not state they have any conflict of interest, classify according to level of severity, have electronic format, and are easy to search. A total of 67% are specific DID, 62% are classified according to level of evidence, contain bibliographical references, and describe clinical management. Conclusions A third of the DID comply with the minimum criteria. Differences were observed in the level and compliance criteria among Spanish and foreign DID. Some of the main DID used as references in the bibliography have significant structural defects: no web presentation, no multi-check function and others.


title: Physical, chemical, and biological impact (hazard) of hospital wastewater on environment: presence of pharmaceuticals, pathogens, and antibiotic-resistance genes

text: Hospital wastewater contains various pharmaceuticals and pathogens. Improper management of the wastewater has caused the leakage of these harmful materials to the environment. The presence of pathogens, pharmaceuticals, and their derivatives such as antibiotic resistance genes as the most typical one in the environment leads to physical, chemical, and biological harmful impact. This chapter has reviewed the pharmaceuticals and pathogens in the hospital; discussed the development of antibiotic resistance genes; and revealed the possible impact of these harmful materials in microorganisms, organism, and human being. In addition, the measures that can be taken to prevent the transportation of pharmaceuticals and pathogens into environment have been stated in this chapter.


Association for Molecular Pathology 2010 Meeting Abstracts


title: Open drug discovery for the Zika virus

text: The Zika virus (ZIKV) outbreak in the Americas has caused global concern that we may be on the brink of a healthcare crisis. The lack of research on ZIKV in the over 60 years that we have known about it has left us with little in the way of starting points for drug discovery. Our response can build on previous efforts with virus outbreaks and lean heavily on work done on other flaviviruses such as dengue virus. We provide some suggestions of what might be possible and propose an open drug discovery effort that mobilizes global science efforts and provides leadership, which thus far has been lacking. We also provide a listing of potential resources and molecules that could be prioritized for testing as in vitro assays for ZIKV are developed. We propose also that in order to incentivize drug discovery, a neglected disease priority review voucher should be available to those who successfully develop an FDA approved treatment. Learning from the response to the ZIKV, the approaches to drug discovery used and the success and failures will be critical for future infectious disease outbreaks.


title: Porcine deltacoronavirus: Overview of infection dynamics, diagnostic methods, prevalence and genetic evolution

text: Abstract Porcine deltacoronavirus (PDCoV) was first reported in Hong Kong, China in 2012 and reported in United States swine in February 2014. PDCoV has subsequently been detected in South Korea, mainland China, and Thailand. PDCoV has been experimentally confirmed to cause diarrhea in inoculated pigs and need to be differentially diagnosed from porcine epidemic diarrhea virus and transmissible gastroenteritis virus in the field. Rapid diagnosis is critical for the implementation of efficient control strategies against PDCoV. Developing high-quality diagnostic methods and understanding PDCoV infection dynamics to collect appropriate specimens at the appropriate time window are important to obtain reliable diagnostic results. Among the virological methods, PDCoV-specific RT-PCR remains the method of choice for the detection of PDCoV; immunohistochemistry combined with hematoxylin and eosin staining has also been commonly used to examine histopathological lesions caused by PDCoV. Serological assays can provide information about previous exposure to PDCoV and also determine antibody responses to infection or vaccination. Prevalence of PDCoV is lower compared to that of PEDV. However, among PDCoV-positive samples, co-infection with other enteric pathogen e.g. PEDV is common. It is also important to understand molecular epidemiology of PDCoV and genetic relationships of global PDCoVs. This review discusses PDCoV infection dynamics and appropriate sample collection for diagnostic testing, the commonly used virological and serological methods for PDCoV diagnosis, prevalence and genetic evolution of PDCoVs.


COVID-19: CUARENTENA, AISLAMIENTO, DISTANCIAMIENTO SOCIAL Y CONFINAMIENTO ¿SON LO MISMO?


Okuläre Post-mortem-Befunde bei an COVID-19 verstorbenen Patienten


title: A Rare Presentation of Coronavirus Disease 2019 (COVID-19) Induced Viral Myositis With Subsequent Rhabdomyolysis

text: A 38-year-old gentleman with no significant past medical history but had recent COVID-19 exposure presented to the hospital with the chief complaints of fever, shortness of breath, and generalized myalgia. He was unfortunately found to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Laboratory findings showed creatine kinase (CK) >42,670 U/L along with elevated inflammatory markers and unremarkable creatinine, cardiac troponin level. The cause of his rhabdomyolysis was discovered to be due to COVID-19 as he had no evidence of other viral infections, strenuous exercise, seizure, or other nontraumatic exertional etiologies. He received aggressive fluid resuscitation while we trended his CK levels along with other inflammatory markers throughout his hospitalization course. His diffuse myalgia improved with treatments, and he was found to maintain stable hemodynamics and was subsequently discharged home.


title: Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme

text: Abstract Rat antizyme gene expression requires programmed, ribosomal frameshifting. A novel autoregulatory mechanism enables modulation of frameshifting according to the cellular concentration of polyamines. Antizyme binds to, and destabilizes, ornithine decarboxylase, a key enzyme in polyamine synthesis. Rapid degradation ensues, thus completing a regulatory circuit. In vitro experiments with a fusion construct using reticulocyte lysates demonstrate polyamine-dependent expression with a frameshift efficiency of 19% at the optimal concentration of spermidine. The frameshift is +1 and occurs at the codon just preceding the terminator of the initiating frame. Both the termination codon of the initiating frame and a pseudoknot downstream in the mRNA have a stimulatory effect. The shift site sequence, UCC-UGA-U, is not similar to other known frameshift sites. The mechanism does not seem to involve re-pairing of peptidyl-tRNA in the new frame but rather reading or occlusion of a fourth base.


title: A mathematical model for simulating the phase-based transmissibility of a novel coronavirus

text: BACKGROUND: As reported by the World Health Organization, a novel coronavirus (2019-nCoV) was identified as the causative virus of Wuhan pneumonia of unknown etiology by Chinese authorities on 7 January, 2020. The virus was named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by International Committee on Taxonomy of Viruses on 11 February, 2020. This study aimed to develop a mathematical model for calculating the transmissibility of the virus. METHODS: In this study, we developed a Bats-Hosts-Reservoir-People transmission network model for simulating the potential transmission from the infection source (probably be bats) to the human infection. Since the Bats-Hosts-Reservoir network was hard to explore clearly and public concerns were focusing on the transmission from Huanan Seafood Wholesale Market (reservoir) to people, we simplified the model as Reservoir-People (RP) transmission network model. The next generation matrix approach was adopted to calculate the basic reproduction number (R(0)) from the RP model to assess the transmissibility of the SARS-CoV-2. RESULTS: The value of R(0) was estimated of 2.30 from reservoir to person and 3.58 from person to person which means that the expected number of secondary infections that result from introducing a single infected individual into an otherwise susceptible population was 3.58. CONCLUSIONS: Our model showed that the transmissibility of SARS-CoV-2 was higher than the Middle East respiratory syndrome in the Middle East countries, similar to severe acute respiratory syndrome, but lower than MERS in the Republic of Korea.


title: Assessment of the potential for pathogen dispersal during high-flow nasal therapy

text: Summary High-flow nasal therapy is increasingly used in hospitals because of its effectiveness and patient comfort. However, pathogens in the patient's nasal and oral cavities may be dispersed by forced air. This study aimed to investigate the risk of pathogen dispersal during high-flow nasal therapy. Liquid and bacterial dispersal were assessed via in-vitro experimental set-ups using a manikin. Thickened water or fresh yeast solution mimicked saliva and nasal mucus secretions. Dispersal was limited to the proximal area of the face and nasal cannula, suggesting that high-flow nasal therapy does not increase the risk of droplet and contact infection.


Detection of viral pathogens of the lower respiratory tract using a comprehensive multiplexed PCR-based system in two sample matrices


title: Enteric Viruses

text: Many viruses use the enteric tract as a route of entry to the human, animal, or avian host. The onset of acute enteritis is associated with infection by viruses that replicate at or near the site of entry into the intestinal mucosa, including caliciviruses, rotaviruses, adenoviruses, astroviruses, and coronaviruses. These ‘enteric’ viruses occur globally and share similar features. Most are RNA viruses that replicate in the cytoplasm of mature absorptive epithelial cells lining the villi of the small intestine, leading to inflammation and villus atrophy. Vomiting and diarrhea can result in dehydration and death if untreated. Despite abundant growth in vivo, they initially proved difficult or impossible to grow in vitro. Most are genetically diverse, species specific, highly infectious within species and transmitted by the fecal–oral route. Severe symptoms are most commonly associated with primary infections of young animals, and are followed by short-lived immunity. Reinfections are common throughout life, but are often only mildly symptomatic. Safe and effective vaccines have been developed to prevent severe rotavirus disease in young children. In addition to these enterotropic viruses, enteric disease can also result from spread to the intestine of HIV or cytomegaloviruses during the later stages of systemic disease in immunocompromised hosts.


title: Immune response and onset of protection from Bovine viral diarrhea virus 2 infection induced by modified-live virus vaccination concurrent with injectable trace minerals administration in newly received beef calves

text: Abstract Strategies to improve the onset of protective immunity induced by vaccination against respiratory pathogens may have a significant impact on health of newly received beef calves. The objective was to determine if the use of injectable trace minerals (ITM; Se, Zn, Cu, and Mn) concurrent with a modified-live virus (MLV) vaccine enhances the immune response and onset of protection in beef calves challenged with BVDV2 five days after vaccination. Forty-five calves were randomly assigned to one of three groups (15/group): VAC + ITM, received MLV-vaccine and ITM (Multimin®90) subcutaneously (SC); VAC + SAL, received the same vaccine and saline SC; or UNVAC, unvaccinated. Five days after vaccination (d.0), calves were challenged with BVDV2 strain 890. Health status was evaluated and blood samples were collected for leukocyte counts, BVDV1 and 2 serum neutralizing antibody (SNA), BVDV-PCR, percentage of CD4+, CD8+, WC1+ and CD25+ T-cells. VAC + ITM had lower health scores than UNVAC (d.8 and 9). VAC + ITM had higher BVDV1 & 2 SNA titers than VAC + SAL and UNVAC on d.21 and 28. Lymphocyte counts decreased in UNVAC but not in VAC + ITM or VAC + SAL (d.3 to 11). CD4+ T-cells significantly decreased in UNVAC and VAC + SAL (d.3). VAC + ITM had higher percentage of CD4+ cells than UNVAC (d.3 and 7). VAC + ITM had lower percentage of activated CD4+ and CD8+ than UNVAC (d.7). In summary, vaccination induced a rapid protection against BVDV2 infection. Administration of ITM was associated with increased SNA response to BVDV1 & 2, enhanced health status, mitigation of CD4+ T-cells decreased, and reduction of T-cell activation in calves challenged with BVDV2 five days after immunization. These results support the strategic use of ITM concurrent with vaccination, especially when a rapid protection is needed in newly received beef calves.


My Kingdom for a Denominator, or at Least Enough Data