title: Individual quarantine versus active monitoring of contacts for the mitigation of COVID-19: a modelling study

text: BACKGROUND: Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible and broader mitigation measures must be implemented. METHODS: To estimate the comparative efficacy of individual quarantine and active monitoring of contacts to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit a model to the incubation period distribution (mean 5·2 days) and to two estimates of the serial interval distribution: a shorter one with a mean serial interval of 4·8 days and a longer one with a mean of 7·5 days. To assess variable resource settings, we considered two feasibility settings: a high-feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and a low-feasibility setting with 50% of contacts traced, a 2-day average delay, and 50% effective isolation. FINDINGS: Model fitting by sequential Monte Carlo resulted in a mean time of infectiousness onset before symptom onset of 0·77 days (95% CI −1·98 to 0·29) for the shorter serial interval, and for the longer serial interval it resulted in a mean time of infectiousness onset after symptom onset of 0·51 days (95% CI −0·77 to 1·50). Individual quarantine in high-feasibility settings, where at least 75% of infected contacts are individually quarantined, contains an outbreak of SARS-CoV-2 with a short serial interval (4·8 days) 84% of the time. However, in settings where the outbreak continues to grow (eg, low-feasibility settings), so too will the burden of the number of contacts traced for active monitoring or quarantine, particularly uninfected contacts (who never develop symptoms). When resources are prioritised for scalable interventions such as physical distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. Even under the shorter serial interval, if physical distancing reduces the reproductive number to 1·25, active monitoring of 50% of contacts can result in overall outbreak control (ie, effective reproductive number <1). INTERPRETATION: Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission to make data-driven policy decisions regarding the cost–benefit comparisons of individual quarantine versus active monitoring of contacts. To the extent that these interventions can be implemented, they can help mitigate the spread of SARS-CoV-2. FUNDING: National Institute of General Medical Sciences, National Institutes of Health.


Australian Hajj pilgrims’ knowledge about MERS-CoV and other respiratory infections


docid: abkpssnl

title: Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

text: The marine-derived fungus Stachylidium sp. was isolated from the sponge Callyspongia sp. cf. C. flammea. Culture on a biomalt medium supplemented with sea salt led to the isolation of three new phthalide derivatives, i.e., marilones A–C (1–3), and the known compound silvaticol (4). The skeleton of marilones A and B is most unusual, and its biosynthesis is suggested to require unique biochemical reactions considering fungal secondary metabolism. Marilone A (1) was found to have antiplasmodial activity against Plasmodium berghei liver stages with an IC(50) of 12.1 µM. Marilone B (2) showed selective antagonistic activity towards the serotonin receptor 5-HT(2B) with a K (i) value of 7.7 µM.


title: Bifidobacterium animalis ssp. lactis Bb12 induces IL‐10 through cell membrane‐associated components via TLR2 in swine

text: AIM: To investigate the role of Toll‐like receptor 2 (TLR2) in interleukin‐10 (IL‐10) production induced by Bifidobacterium animalis ssp. lactis Bb12 (Bb12) in swine immune cells. METHODS AND RESULTS: Blood‐monocytes and cells from mesenteric lymph nodes were obtained from pigs and cultured with live Bb12 for 4 and 12 h. Transcript levels of IL‐10 and TLR2 were analysed. Furthermore, TLR2 was blocked to determine its participation in IL‐10 production. TLR2 blockade was achieved with neutralizing antibodies, followed by stimulation with Bb12. Bifidobacteria induced IL‐10 production in both swine monocytes and mesenteric cells. Monocytes with TLR2 blockade had a decrease in IL‐10 transcripts, while mesenteric cells did not. Bacterial cell wall components were responsible for Bb12‐induced IL‐10 production since no IL‐10 was detected in the culture supernatant. CONCLUSIONS: We demonstrated that IL‐10 production is largely mediated through the recognition of Bb12 structures by TLR2, as bacterial metabolites in the culture supernatant failed to induce IL‐10 expression. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study provides evidence for the potential use of Bb12 in the swine industry; these bacteria can also be used as additional method to treat intestinal inflammation and enhance intestinal health in pigs.


title: Online behavioural patterns for Coronavirus disease 2019 (COVID-19) in the United Kingdom

text: The current coronavirus (COVID-19) pandemic offers a unique opportunity to conduct an infodemiological study examining patterns in online searching activity about a specific disease and how this relates to news media within a specific country. Google Trends quantifies volumes of online activity. The relative search volume was obtained for ‘Coronavirus’, ‘handwashing’, ‘face mask’ and symptom related keywords, for the United Kingdom, from the date of the first confirmed case until numbers peaked in April. The relationship between online search traffic and confirmed case numbers was examined. Search volumes varied over time; peaks appear related to events in the progression of the epidemic which were reported in the media. Search activity on ‘Coronavirus’ correlated well against confirmed case number as did ‘face mask’ and symptom-related keywords. User-generated online data sources such as Google Trends may aid disease surveillance, being more responsive to changes in disease occurrence than traditional disease reporting. The relationship between media coverage and online searching activity is rarely examined, but may be driving online behavioural patterns.


title: Comment on: Coronavirus 2019 in Geriatrics and Long‐Term Care: The ABCDs of COVID‐19

text: See the Reply by https://doi.org/10.1111/jgs.16548.


docid: blhltvns

title: Expression stability of commonly used reference genes in canine articular connective tissues

text: BACKGROUND: The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies. Real-time reverse transcription PCR and a mathematical algorithm were used to establish which reference genes were most stably expressed in normal and diseased canine articular tissues and two canine cell lines stimulated with lipolysaccaride (LPS). RESULTS: The optimal reference genes for comparing gene expression data between normal and diseased infrapatella fat pad were RPL13A and YWHAZ (M = 0.56). The ideal reference genes for comparing normal and osteoarthritic (OA) cartilage were RPL13A and SDHA (M = 0.57). The best reference genes for comparing normal and ruptured canine cranial cruciate ligament were B2M and TBP (M = 0.59). The best reference genes for normalising gene expression data from normal and LPS stimulated cell lines were SDHA and YWHAZ (K6) or SDHA and HMBS (DH82), which had expression stability (M) values of 0.05 (K6) and 0.07 (DH82) respectively. The number of reference genes required to reduce pairwise variation (V) to <0.20 was 4 for cell lines, 5 for cartilage, 7 for cranial cruciate ligament and 8 for fat tissue. Reference gene stability was not related to the level of gene expression. CONCLUSION: The reference genes demonstrating the most stable expression within each different canine articular tissue were identified, but no single reference gene was identified as having stable expression in all different tissue types. This study underlines the necessity to select reference genes on the basis of tissue and disease specific expression profile evaluation and highlights the requirement for the identification of new reference genes with greater expression stability for use in canine articular tissue gene expression studies.


title: Analysis on herbal medicines utilized for treatment of COVID-19

text: As coronavirus disease 2019 (COVID-19) pandemic poses a substantial global public health threat, traditional Chinese medicine (TCM) was used in 91.50% of the COVID-19 cases in China, showing encouraging results in improving symptom management and reducing the deterioration, mortality, and recurrence rates. A total of 166 modified herbal formulae consisting of 179 single herbal medicines were collected for treating COVID-19 in China. Glycyrrhizae Radix et Rhizome, Scutellariae Radix, and Armeniacae Semen Amarum are the most frequently utilized in clinics, most of which are antipyretic (47, 26.26%), expectorant and cough-suppressing (22, 12.29%), and dampness-resolving (21, 11.73%) from traditional descriptions. A total of 1212 chemical components containing β-sitosterol, stigmasterol, and quercetin were primarily selected. Additionally, using complex system entropy and unsupervised hierarchical clustering, 8 core herbal combinations and 10 new formulae emerged as potentially useful candidates for COVID-19. Finally, following scaffold analysis, self-organizing mapping (SOM) and cluster analysis, 12 clusters of molecules yielded 8 pharmacophore families of structures that were further screened as pharmacological targets in human metabolic pathways for inhibiting coronavirus. This article aims to make more easily accessible and share historical herbal knowledge used in contemporary treatments in a modern manner to assist researchers contain the global spread of COVID-19.


title: Clinical Characteristics of Patients Infected With the Novel 2019 Coronavirus (SARS-Cov-2) in Guangzhou, China

text: BACKGROUND: The clinical manifestations and factors associated with the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections outside of Wuhan are not clearly understood. METHODS: All laboratory-confirmed cases with SARS-Cov-2 infection who were hospitalized and monitored in Guangzhou Eighth People’s Hospital were recruited from January 20 to February 10. RESULTS: A total of 275 patients were included in this study. The median patient age was 49 years, and 63.6% had exposure to Wuhan. The median virus incubation period was 6 days. Fever (70.5%) and dry cough (56.0%) were the most common symptoms. A decreased albumin level was found in 51.3% of patients, lymphopenia in 33.5%, and pneumonia based on chest computed tomography in 86%. Approximately 16% of patients (n = 45) had severe disease, and there were no deaths. Compared with patients with nonsevere disease, those with severe disease were older, had a higher frequency of coexisting conditions and pneumonia, and had a shorter incubation period (all P < .05). There were no differences between patients who likely contacted the virus in Wuhan and those who had no exposure to Wuhan. Multivariate logistic regression analysis indicated that older age, male sex, and decreased albumin level were independently associated with disease severity. CONCLUSIONS: Most of the patients infected with SARS-CoV-2 in Guangzhou, China are not severe cases and patients with older age, male, and decreased albumin level were more likely to develop into severe ones.


title: Estimating the number of undetected COVID-19 cases exported internationally from all of China

text: During the early phase of the COVID-19 pandemic, when SARS-CoV-2 was chiefly reported in the city of Wuhan, cases exported to other locations were largely predicted using flight travel data from Wuhan. However, given Wuhan’s connectivity to other cities in mainland China prior to the lockdown, there has likely been a substantial risk of exportation of cases from other Chinese cities. It is likely that many of these exportations remained undetected because early international case definitions for COVID-19 required a recent travel history from Wuhan. Here, we combine estimates of prevalence in 18 Chinese cities with estimates of flight volume, accounting for the effects of travel bans and the timing of Lunar New Year, to approximate the number of cases exported from cities outside of Wuhan from early December 2019 to late February 2020. We predict that for every one case from Wuhan exported internationally, there were approximately 2.9 cases from large Chinese cities exported internationally that likely remained undetected. Additionally, we predict the number of exported cases in six destinations for which predictions on exported cases have yet to be made, surveillance has likely been low, and where health care systems will likely face issues in managing current or potential outbreaks. We observe heterogeneities in exported case counts across these destinations. The predicted number of cases exported to Egypt and South Africa exceeds the predicted number of cases exported to Mauritania. These trends may anticipate differences in the timing and emergence of local transmission in these countries. Our findings highlight the importance of setting accurate travel history requirements for case definition guidelines in the initial phase of an epidemic, and actively updating these guidelines as the epidemic advances.


title: Elective Surgery During the SARS-CoV-2 Pandemic (COVID-19): A Morbimortality Analysis and Recommendations on Patient Prioritisation and Security Measures

text: Abstract Introduction The spread of the SARS-CoV-2 infection (COVID-19) has required adaptation by hospitals affected by the pandemic, which has caused a reduction in elective surgical activity. Methods Retrospective study of patients operated on in the previous month and during the peak of the pandemic. We analysed the COVID-19 infection rate, the severity of respiratory infection according to the Brescia respiratory COVID-19 severity scale, the adopted therapeutic measures and the overall postoperative complications. Results From 17th February to 31st March 2020, there was a progressive decrease in surgical activity, with only 213 patients operated on. This comprised 59 (27.8%) elective operations for oncological diseases, 97 (45.5%) elective operations for benign diseases and 57 (26.7%) as urgent procedures. There was a progressive increase in the rate of infection by COVID-19, with a total of 15 cases (7%). This included 10 patients (16.9%) in the elective group for oncological disease, 1 (1%) in the elective surgery group for benign disease and 4 (7%) in the urgent surgery group (P <.001). Five patients presented with a severe respiratory infection, of which 4 were affected by oncological disease. There were 3 deaths (1.4%), which were all due to the worsening of a respiratory infection. Conclusions The patients undergoing the surgical procedures showed high rates of COVID-19 infection and postoperative complications, especially the patients with oncological diseases. Local resumption of surgical activity must be based on the prioritisation of the cases to be operated on, respecting certain premises of security and optimisation of the available resources.


Geroscience and the Coronavirus Pandemic: The Whack‐a‐Mole Approach is not Enough


title: Recombinant Newcastle Disease Virus as a Vaccine Vector for Cancer Therapy

text: Naturally occurring strains of Newcastle disease virus (NDV) are currently being investigated in multiple clinical trials for oncolytic cancer therapy in the United States and abroad. We have previously reported, for the first time, the development of recombinant NDVs designed for enhanced cancer therapeutic efficacy. Specifically, we have shown that NDV engineered to express interleukin-2 (IL-2) generates a robust therapeutic response associated with increased tumor-specific T-cell infiltration after intratumoral administration in mice. We have now demonstrated that this therapeutic response is dependent on T cells and we have investigated the potential to focus the NDV-induced immune response toward a tumor-associated antigen (TAA) to enhance the inherent therapeutic efficacy of NDV further. We found that intratumoral treatments of tumor-bearing mice with recombinant NDV expressing a model TAA elicited an enhanced tumor-specific response, resulting in a significant increase in the number of complete tumor regressions compared with control NDV. Additionally, coadministration of NDV expressing a model TAA with NDV expressing IL-2 enhanced the TAA-directed response and led to more complete tumor regressions. Our results show that TAA-directed immunotherapy by oncolytic recombinant NDV alone or in combination with IL-2 results in an enhanced therapeutic efficacy and warrant consideration in the development of cancer therapies based on the use of oncolytic NDV.


title: Fracture management during COVID-19 pandemic: A systematic review and meta-analysis

text: PURPOSE: The COVID-19 pandemic has affected orthopedic practices worldwide. Few studies focusing on epidemiology and management of fractures in COVID 19 patients have been published. We conducted a systematic review and meta-analysis to evaluate the fracture types, presentation, treatment, complications, and early outcomes of fractures occurring amidst COVID-19 pandemic. METHODS: A systematic review and meta-analysis of the all published papers was conducted with a comprehensive search of PubMed, Google Scholar, Scopus, and Cochrane Library database using keywords ‘COVID-19’, ‘Coronavirus’, ‘trauma*'and ‘fracture’ from January–April 2020. RESULTS: The searches yielded a total of ten studies with 112 Patients who were positive for COVID 19 associated with fractures. Individual patient data meta-analysis was performed as feasible, for six studies, reporting data separately for 44 patients with COVID 19 and an associated fracture. Meta-analysis showed that a diagnosis of COVID 19 was made on the basis of positive Computed Tomography scan in 39 patients and 30 patients had a positive Reverse Transcription-Polymerase Chain Reaction test. Overall, there were 29 proximal femoral fractures, 8 spine fractures, 7 fractures of the other bones. The fractures were treated surgically in 30 cases (68.18%) and the remaining 14 cases (31.82%) were managed conservatively. There were 16 patients (36.36%) who died, mostly due to respiratory failure with a median age of 82 years. CONCLUSION: COVID-19 has led to a significant reduction in a load of fracture patients globally, though the incidence of fragility fractures continues to be unaffected. There is a significantly higher risk of mortality in elderly patients with fractures and hence they should only be operated in a facility with a robust intensive care. Conservative treatment should be adopted as far as possible in non-obligatory fractures and in lesser equipped centers. Surgery in patients with proximal femur fragility fractures when judiciously selected did result in improvement in respiratory status. Reorganizing medical services is vital to deliver effective fracture care and also mitigate disease transmission.


title: Influenza risk perception and travel-related health protection behavior in the US: Insights for the aftermath of the COVID-19 outbreak

text: Abstract Influenza is a contagious virus affecting both one's health and economic productivity. This study evaluates uses a survey of 2168 individuals across the U.S. Ordered logit regressions are used to model risk perception and generalized ordered logit regressions are used to model risk mitigation travel-related decisions. Models are estimated for three influenza outbreak scenarios, specifically an individual's travel-related: 1) risk perceptions, 2) risk mitigation decisions when infected and the individual wants to prevent spreading it, and may want treatment, and 3) risk mitigation decisions when not infected and the individual wants to reduce exposure. Risk perception results show that a recent personal experience with influenza-like symptoms and being female significantly increased risk perception at mandatory and medical trip locations. Risk mitigation model results show that males are less likely to alter their travel patterns in response to the possible spreading of the virus or increasing exposure. Knowing the difference between influenza and the stomach flu is more influential in reducing travel than a recent influenza experience in one's household. Individuals proactive with their health (i.e., receive the vaccine, have health insurance) are also proactive in seeking medical attention and reducing influenza spread. Lastly, aligned with the Protection Motivation Theory, individuals reduce travel to locations in which they perceived medium or high risk. However, increased risk perceived at one's work location did not significantly reduce travel. The findings provide insight into the risk perception and mitigation behavior of the American public during the COVID-19 pandemic and after restrictions are lifted.


title: HPV caught in the tetraspanin web?

text: Tetraspanins are master organizers of the cell membrane. Recent evidence suggests that tetraspanins themselves may become crowded by virus particles and that these crowds/aggregates co-internalize with the viral particles. Using microscopy, we studied human papillomavirus (HPV) type 16-dependent aggregates on the cell surface of tetraspanin overexpressing keratinocytes. We find that aggregates are (1) rich in at least two different tetraspanins, (2) three-dimensional architectures extending up to several micrometers into the cell, and (3) decorated intracellularly by filamentous actin. Moreover, in cells not overexpressing tetraspanins, we note that obscurin-like protein 1 (OBSL1), which is thought to be a cytoskeletal adaptor, associates with filamentous actin. We speculate that HPV contact with the cell membrane could trigger the formation of a large tetraspanin web. This web may couple the virus contact site to the intracellular endocytic actin machinery, possibly involving the cytoskeletal adaptor protein OBSL1. Functionally, such a tetraspanin web could serve as a virus entry platform, which is co-internalized with the virus particle. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00430-020-00683-1) contains supplementary material, which is available to authorized users.


title: Pilocarpine Hydrochloride for the Treatment of Xerostomia in Patients with Sjögren's Syndrome in Taiwan—A Double-blind, Placebo-controlled Trial

text: Background/purpose Sjögren's syndrome (SS) is characterized by diminished exocrine secretions with the resultant symptoms of dry mouth and dry eye. As genetic predisposition and ethnicity may alter the effectiveness of drug treatment, evaluation of the efficacy and safety of the secretagogue pilocarpine hy-drochloride in the treatment of xerostomia in patients with SS in different populations is needed. Methods Forty-four patients with SS were enrolled in this double-blind, placebo-controlled trial. Patients were randomized to receive 5 mg pilocarpine (Salagen) or placebo tablet four times daily for 12 weeks. Global evaluation and subjective responses of patients were assessed by questionnaires with visual analog scales and categorical checkboxes. Saliva production was also measured by modified Saxon's test. Results Pilocarpine treatment significantly improved global assessment of dry mouth, symptoms associated with dry mouth (mouth comfort, ability to sleep and ability to speak), and saliva production compared to placebo. The drug was well tolerated and the most common adverse effect was sweating (5/23, 21.7%) resulting from the muscarinic agonist action of the drug. No serious drug-related adverse effect was found in this study. Conclusion The results of this study suggest that therapy with 5 mg pilocarpine four times daily is effective, safe and well tolerated for the relief of oral symptoms in patients with SS in Taiwan.


Personal protective equipment during the COVID‐19 pandemic: a reply


title: Spatial analysis of falls in an urban community of Hong Kong

text: BACKGROUND: Falls are an issue of great public health concern. This study focuses on outdoor falls within an urban community in Hong Kong. Urban environmental hazards are often place-specific and dependent upon the built features, landscape characteristics, and habitual activities. Therefore, falls must be examined with respect to local situations. RESULTS: This paper uses spatial analysis methods to map fall occurrences and examine possible environmental attributes of falls in an urban community of Hong Kong. The Nearest neighbour hierarchical (Nnh) and Standard Deviational Ellipse (SDE) techniques can offer additional insights about the circumstances and environmental factors that contribute to falls. The results affirm the multi-factorial nature of falls at specific locations and for selected groups of the population. CONCLUSION: The techniques to detect hot spots of falls yield meaningful results that enable the identification of high risk locations. The combined use of descriptive and spatial analyses can be beneficial to policy makers because different preventive measures can be devised based on the types of environmental risk factors identified. The analyses are also important preludes to establishing research hypotheses for more focused studies.


title: Significant Interference with Porcine Epidemic Diarrhea Virus Pandemic and Classical Strain Replication in Small-Intestine Epithelial Cells Using an shRNA Expression Vector

text: Porcine epidemic diarrhea (PED) re-emerged in China in 2010 and is now widespread. Evidence indicates that highly virulent porcine epidemic diarrhea virus (PEDV) strains belonging to genotype G2 caused a large-scale outbreak of diarrhea. Currently, vaccines derived from PEDV classical strains do not effectively prevent infection by virulent PEDV strains, and no specific drug is available to treat the disease. RNA interference (RNAi) is a novel and effective way to cure a wide range of viruses. We constructed three short hairpin RNA (shRNA)-expressing plasmids (shR-N307, shR-N463, and shR-N1071) directed against nucleocapsid (N) and determined their antiviral activities in intestine epithelial cells infected with a classical CV777 strain and LNCT2. We verified that shR-N307, shR-N463, and shR-N1071 effectively inhibited the expression of the transfected N gene in vitro, comparable to the control shRNA. We further demonstrated the shRNAs markedly reduced PEDV CV777 and LNCT2 replication upon downregulation of N production. Therefore, this study provides a new strategy for the design of antiviral methods against coronaviruses by targeting their processivity factors.


title: ‘The Microbiome and the Pathophysiology of Asthma’

text: Asthma is a chronic respiratory disease whose prevalence is increasing in the western world. Recently research has begun to focus on the role the microbiome plays in asthma pathogenesis in the hope of further understanding this respiratory disorder. Considered sterile until recently, the lungs have revealed themselves to contain a unique microbiota. A shift towards molecular methods for the quantification and sequencing of microbial DNA has revealed that the airways harbour a unique microbiota with apparent, reproducible differences present between healthy and diseased lungs. There is a hope that in classifying the microbial load of the asthmatic airway an insight may be afforded as to the possible role pulmonary microbes may have in propagating an asthmatic airway response. This could potentially pave the way for new therapeutic strategies for the treatment of chronic lung conditions such as asthma.


title: Blood Plasma Microfluidic Device: Aiming for the Detection of COVID-19 Antibodies Using an On-Chip ELISA Platform

text: COVID-19 is a public health emergency of international concern. Detection of SARS-CoV-2 virus is an important step towards containing the virus spread. Although viral detection using molecular diagnostic methods is quite common and efficient, these methods are prone to errors, laborious and time consuming. There is an urgent need for blood-based tests which are simple to use, accurate, less time consuming, portable and cost-effective. Human blood plasma contains water, proteins, organic and in-organic substances including bacteria and viruses. Blood plasma can be effectively used to detect COVID-19 antibodies. The immune system generates antibodies (IgM/IgG proteins) in response to the virus and identification of these antibodies is related to the presence of the infection in the patient in the past. Therefore, detecting and testing the presence of these antibodies will be extremely useful for monitoring and surveillance of the population (Petherick, Lancet 395:1101–1102, 2020). Herein, we describe and propose a microfluidic ELISA (enzyme-linked immunosorbent assay) system to detect COVID-19 antibodies on a lab-on-chip platform. We propose to first separate plasma from whole human blood using a microfluidic device and subsequently perform the detection of antibodies in the separated plasma using a semi-automated on-chip ELISA.


title: AMPK and the Need to Breathe and Feed: What’s the Matter with Oxygen?

text: We live and to do so we must breathe and eat, so are we a combination of what we eat and breathe? Here, we will consider this question, and the role in this respect of the AMP-activated protein kinase (AMPK). Emerging evidence suggests that AMPK facilitates central and peripheral reflexes that coordinate breathing and oxygen supply, and contributes to the central regulation of feeding and food choice. We propose, therefore, that oxygen supply to the body is aligned with not only the quantity we eat, but also nutrient-based diet selection, and that the cell-specific expression pattern of AMPK subunit isoforms is critical to appropriate system alignment in this respect. Currently available information on how oxygen supply may be aligned with feeding and food choice, or vice versa, through our motivation to breathe and select particular nutrients is sparse, fragmented and lacks any integrated understanding. By addressing this, we aim to provide the foundations for a clinical perspective that reveals untapped potential, by highlighting how aberrant cell-specific changes in the expression of AMPK subunit isoforms could give rise, in part, to known associations between metabolic disease, such as obesity and type 2 diabetes, sleep-disordered breathing, pulmonary hypertension and acute respiratory distress syndrome.


title: Establishment of the eukaryotic cell lines for inducible control of SARS-CoV nucleocapsid gene expression

text: In order to establish the eukaryotic cell lines for inducible control of SARS-CoV nucleocapsid gene expression.The recombinant plasmid of pTRE-Tight-SARS-N was constructed by using the plasmid p8S as the PCR template which contains a cDNA clone covering the nucleocapsid gene of SARS-CoV HKU-39449. Restriction enzymes digestion and sequence analysis indicated the recombinant plasmid of pTRE-Tight-SARS-N contained the nucleocapsid gene with the optimized nucleotide sequence which will improve the translation efficiency. Positive cell clones were selected by cotransfecting pTRE-Tight-SARS-N with the linear marker pPUR to BHK-21 Tet-on cells in the presence of puromycin. A set of double-stable eukaryotic cell lines (BHK-Tet-SARS-N) with inducible control of the SARS-CoV neucleocapsid gene expression was identified by using SDS-PAGE and Western-blot analysis. The expression of SARS-CoV nucleocapsid protein was tightly regulated by the varying concentration of doxcycline in the constructed double-stable cell line. The constructed BHK-Tet-SARS-N cell strains will facilitate the rescue of SARS-CoV in vitro and the further reverse genetic research of SARS-CoV.


title: A single tube RT-PCR assay for the detection of mosquito-borne flaviviruses

text: Abstract Mosquito-borne flaviviruses include several important agents of human disease and have provided striking examples of emerging infections. In this study we present the design and validation of a single tube RT-PCR assay using a pair of consensus primers for the detection of mosquito-borne flaviviruses. Sequencing of the amplicons permits the species identification. The assay was validated using RNA from the yellow fever virus vaccine strain and from representative strains of dengue viruses 1, 2, 3 and 4, West Nile virus, Kunjin virus (a clade of West Nile virus), and St. Louis encephalitis virus.


COVID‐19 special issue: Intelligent solutions for computer communication‐assisted infectious disease diagnosis


docid: qdamvwxl

title: Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic

text: The ongoing novel coronavirus disease (COVID-19) pandemic has rapidly spread in early 2020, causing tens of thousands of deaths, over a million cases and widespread socioeconomic disruption. With no vaccine available and numerous national healthcare systems reaching or exceeding capacity, interventions to limit transmission are urgently needed. While there is broad agreement that travel restrictions and closure of non-essential businesses and schools are beneficial in limiting local and regional spread, recommendations around the use of face masks for the general population are less consistent internationally. In this study, we examined the role of face masks in mitigating the spread of COVID-19 in the general population, using epidemic models to estimate the total reduction of infections and deaths under various scenarios. In particular, we examined the optimal deployment of face masks when resources are limited, and explored a range of supply and demand dynamics. We found that face masks, even with a limited protective effect, can reduce infections and deaths, and can delay the peak time of the epidemic. We consistently found that a random distribution of masks in the population was a suboptimal strategy when resources were limited. Prioritizing coverage among the elderly was more beneficial, while allocating a proportion of available resources for diagnosed infected cases provided further mitigation under a range of scenarios. In summary, face mask use, particularly for a pathogen with relatively common asymptomatic carriage, can effectively provide some mitigation of transmission, while balancing provision between vulnerable healthy persons and symptomatic persons can optimize mitigation efforts when resources are limited.


title: COVID-19: The Worst Days of Our Careers

text: Adapting to this new paradigm during this pandemic has been ever-changing and extraordinarily challenging, both personally and professionally.


title: Reverse Genetics of Measles Virus and Resulting Multivalent Recombinant Vaccines: Applications of Recombinant Measles Viruses

text: An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses from cDNA, with emphasis on nonsegmented negative-strand RNA viruses ( Mononegavirales ), as exemplified for measles virus (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects of the biology of these viruses. Concomitantly, foreign coding sequences were inserted to (a) allow localization of virus replication in vivo through marker gene expression, (b) develop candidate multivalent vaccines against measles and other pathogens, and (c) create candidate oncolytic viruses. The vector use of these viruses was experimentally encouraged by the pronounced genetic stability of the recombinants unexpected for RNA viruses, and by the high load of insertable genetic material, in excess of 6 kb. The known assets, such as the small genome size of the vector in comparison to DNA viruses proposed as vectors, the extensive clinical experience of attenuated MV as vaccine with a proven record of high safety and efficacy, and the low production cost per vaccination dose are thus favorably complemented.


title: COVID-19 pneumonia: A review of typical CT findings and differential diagnosis

text: Abstract The standard of reference for confirming COVID-19 relies on microbiological tests such as real-time polymerase chain reaction (RT-PCR) or sequencing. However, these tests might not be available in an emergency setting. Computed tomography (CT) can be used as an important complement for the diagnosis of COVID-19 pneumonia in the current epidemic context. In this review, we present the typical CT features of COVID-19 pneumonia and discuss the main differential diagnosis.


title: Cotranslocational insertion of apolipoprotein B into the inner leaflet of the endoplasmic reticulum

text: APOLIPOPROTEIN(apo) B100 is required for the distribution of hepatic triglyceride to peripheral tissues as very-low-density lipoproteins. The translocation of apo B100 into the endoplasmic reticulum (ER) and its subsequent assembly into lipoprotein particles is of particular interest as the protein is both very large (relative molecular mass 512,000) and insoluble in water. It has been proposed that apo B translocation occurs in discrete stages and is completed post-translationally(1). Several sites of arrest of translocation were reported to be present in apo B15 (the N-terminal 15% of the protein). We have re-examined this question by in vitro translation coupled with translocation into microsomes, and find no evidence for transmembrane segments in truncated apo B proteins. Translocated apo B17 is strongly associated with the membrane-of the ER, being only partially releasable with alkaline carbonate, and remaining bound to the microsomes following disruption with saponin. The efficient binding of short segments of apo B, despite the absence of transmembrane domains, suggests that apo B is cotranslationally inserted into the inner leaflet of the ER. This will obviate problems caused by the size and insolubility of apo B100, because the growing hydrophobic protein chains will never exist in a lipid-free form during translocation. From the inner leaflet, apo B in association with membrane-derived lipid can bud into the lumen of the ER to form nascent lipoprotein particles.


The aftermath of coronavirus disease of 2019: devastation or a new dawn for nephrology?


Hospital in the home: needed now more than ever: Changes in models of care elicited by COVID‐19 may improve the quality of at‐home care for patients


title: Will helminth co-infection modulate COVID-19 severity in endemic regions?

text: As COVID-19 spreads through the world, most cases to date are in middle- and high-income nations. The impact on resource-poor nations remains unknown. Amongst many factors likely to affect the impact of COVID-19 in these areas, co-infections need to be considered. Here, we discuss whether the immunomodulatory effects of helminth infections may affect COVID-19 severity.


title: Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases

text: Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.


title: Role of Atypical Pathogens in Nursing Home–Acquired Pneumonia

text: Abstract Objectives No international consensus has been reached on the empirical use of antibiotics with atypical coverage in nursing home–acquired pneumonia (NHAP). Aspiration is an important cause of NHAP, but it may not require antimicrobial treatment. This study aimed to investigate the prevalence and clinical characteristics of AP infections and review the need for empirical antibiotics with atypical coverage in NHAP. Design A prospective cohort study. Setting Four nursing homes with a total number of 772 residents. Participants Patients were aged ≥ 65 years, hospitalized for NHAP, which was defined as the presence of respiratory symptoms and abnormal chest radiographs, from April 2006 to March 2007. Measurements Demographics, clinical parameters, and investigation results were recorded. Microbial investigations comprised sputum routine and mycobacterial cultures, blood and urine cultures, serology, and nasopharyngeal aspirate viral culture and polymerase chain reaction tests. Suspected aspiration pneumonitis was arbitrarily defined as NHAP without pathogens identified. Results After excluding lone bacteriuria, 108 episodes of NHAP in 94 patients were included. Twelve APs were detected in 11 patients. There was no clinical feature to distinguish between infections caused by APs and other pathogens. The commonest APs were Mycoplasma pneumoniae (6) and Chlamydophila pneumoniae (3). No Legionella pneumophila was detected by urinary antigen test. None of the patients with AP infection received antibiotics indicated for AP infections. However, AP infections did not result in mortality. No pathogen was isolated in 31.5% of cases. Patients without pathogens isolated were less likely to have purulent sputum and crepitations on chest auscultation, compared with those with pneumonia caused by identified pathogens. Conclusions Atypical pathogens (APs) were not associated with mortality even in cases where the prescribed antibiotics did not cover APs. NHAP may not necessarily be treated with empirical antibiotics covering APs.


title: Polymorphisms in the feline TNFA and CD209 genes are associated with the outcome of feline coronavirus infection

text: Feline infectious peritonitis (FIP), caused by feline coronavirus (FCoV) infection, is a highly lethal disease without effective therapy and prevention. With an immune-mediated disease entity, host genetic variant was suggested to influence the occurrence of FIP. This study aimed at evaluating cytokine-associated single nucleotide polymorphisms (SNPs), i.e., tumor necrosis factor alpha (TNF-α), receptor-associated SNPs, i.e., C-type lectin DC-SIGN (CD209), and the five FIP-associated SNPs identified from Birman cats of USA and Denmark origins and their associations with the outcome of FCoV infection in 71 FIP cats and 93 FCoV infected non-FIP cats in a genetically more diverse cat populations. A promoter variant, fTNFA - 421 T, was found to be a disease-resistance allele. One SNP was identified in the extracellular domain (ECD) of fCD209 at position +1900, a G to A substitution, and the A allele was associated with FIP susceptibility. Three SNPs located in the introns of fCD209, at positions +2276, +2392, and +2713, were identified to be associated with the outcome of FCoV infection, with statistical relevance. In contrast, among the five Birman FIP cat-associated SNPs, no genotype or allele showed significant differences between our FIP and non-FIP groups. As disease resistance is multifactorial and several other host genes could involve in the development of FIP, the five genetic traits identified in this study should facilitate in the future breeding of the disease-resistant animal to reduce the occurrence of cats succumbing to FIP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-014-0123-6) contains supplementary material, which is available to authorized users.


title: Analysis of regional productivity growth in China: A generalized metafrontier MPI approach

text: Abstract This paper analyzes the dynamics of China's productivity for the period 1996–2004 with a newly developed methodology — generalized metafrontier Malmquist productivity index (gMMPI). Implementing the gMMPI, this paper reviews the inequality of the coastal and non-coastal provinces, as well as the latent impact of scale efficiency change (SEC) for China. Using provincial data for the years 1996–2004, the empirical results are as follows. On average, China demonstrates an annual 3.191% productivity change, which is lower than 4.729% for the conventional MPI and accounts for about 26.508% of output growth over the period 1996–2004. Most of this change is propelled by technical progress, while a fraction is driven by the adjustment in production scale, and the efficiency change has an adverse effect. Furthermore, regional inequality is also found in this empirical work, and the productivity change of the coastal region is actually stronger than that of the non-coastal region. This paper also casts some focus on the China Western Development policy. Indeed, we do not find any outstanding achievement from the policy in the sample period, except that the west region sustained its rate of productivity change after 2000. Moreover, the SEC is found to be trivial in the advanced coastal region, but plays an important role in the relatively laggard non-coastal region. The implication of the positive SEC in the non-coastal region means that China's Western Development policy will improve the scale efficiency and the TFP growth of the west region.


title: Bronchitis

text: Bronchitis is characterized by bronchial inflammation that results in …


title: Diseases affecting patients returning from abroad: Experience of a travel clinic in Japan from 2004 to 2014

text: Abstract The number of patients returning from or staying abroad is likely to increase in the future. We performed a retrospective study of patients returning from abroad in our travel clinic in Japan. All patients presenting within 6 months of traveling abroad between 2004 and 2014 were included in the present study. A total of 2374 (mean age, 35 years) patients were seen by doctors specializing in treating infectious diseases. Of these, 918 were females and 87 of them lived abroad. Diagnoses and exposure regions were recorded for all patients. The most frequent region visited before attending our clinic was Southeast Asia (n = 1050, 44%), with a median duration for staying abroad of 8 days. The major purposes for overseas travel were tourism (n = 1302, 55%) and business (n = 684, 29%). Of the 2399 individual diagnoses made, the most frequent were diseases of the gastrointestinal system (n = 1083, 45%), skin and soft tissue (n = 440, 18%), systemic febrile disease without specific systems (419, 18%), and the respiratory system (353, 15%). The relative incidences of specific diseases changed drastically due to significant disease outbreaks, such as pandemic influenza in 2009. Exposure regions remained relatively constant throughout the study period, except for Japan. Vaccine-preventable diseases accounted for 5.3% of all the diseases, and 402 (26%) patients received pre-travel consultation and prophylaxis with vaccines and/or anti-malarial drug. We should make an effort to make more people notice the risk of travel and properly perform prophylaxis.


title: Demyelination, and remyelination by Schwann cells and oligodendrocytes after kainate-induced neuronal depletion in the central nervous system

text: Abstract Excitotoxins are thought to kill neurons while sparing afferent fibers and axons of passage. The validity of this classical conclusion has recently been questioned by the demonstration of axonal demyelination. In addition, axons are submitted to a profound alteration of their glial environment. This work was, therefore, undertaken to reassess axonoglial interactions over time after an excitotoxic lesion in the rat. Ultrastructural studies were carried out in the ventrobasal thalamus two days to 18 months after neuronal depletion by in situ injections of kainic acid. In some cases, lemniscal afferents were identified by using anterograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase from the dorsal column nuclei. Two and four days after kainate injection, numerous dying axons displaying typical signs of Wallerian degeneration were observed in a neuropile characterized by the loss of neuronal somata and dendrites, an increase in number of microglia/macrophages and the disappearance of astrocytes. Ten and 12 days after kainate injection, degenerating axons were no longer observed although myelin degeneration of otherwise unaltered axons was ongoing with an accumulation of myelin remnants in the neuropile. At 16 and 20 days, the demyelination process was apparently complete and axons of different diameters were sometimes packed together. One and two months after kainate injection, the axonal environment changed again: remyelination of large-caliber axons occurred at the same time as reactive astrocytes, oligodendrocytes and numerous Schwann cells appeared in the tissue. Schwann cell processes surrounded aggregates of axons of diverse calibers, ensheathed small ones and myelinated larger ones. Axons were also remyelinated by oligodendrocytes. Horseradish peroxidase-labeled lemniscal afferents could be myelinated by either of the two cell types. After three months, the neuropile exhibited an increase in number of hypertrophied astrocytes and the progressive loss of any other cellular or axonal element. At this stage, remaining Schwann cells were surrounded by a glia limitans formed by astrocytic processes. These data indicate that although excitotoxins are sparing the axons, they are having a profound and complex effect on the axonal environment. Demyelination occurs over the first weeks, accompanying the loss of astrocytes and oligodendrocytes. Axonal ensheathment and remyelination takes place in a second period, associated with the reappearance of oligodendrocytes and recruitment of numerous Schwann cells, while reactive astrocytes appear in the tissue at a slightly later time. Over the following months, astrocytes occupy a greater proportion of the neuron-depleted territory and other elements decrease in number. These successive stages in alteration of axonoglial interactions seem to evolve in parallel to the changes in density and terminal morphology that we described earlier for myelinated afferent fibers to the excitotoxic lesion.


title: Fever in travelers returning from tropical areas: prospective observational study of 613 cases hospitalised in Marseilles, France, 1999–2003

text: Summary Background Febrile travelers may pose a diagnostic challenge for Western physicians who are frequently involved in the assessment of these patients but unfamiliar with tropical diseases. Evaluation of this situation requires an understanding of the common etiologies, which are associated with the demographics of travelers and the destinations. Methods We conducted a 5-year prospective observational study on the etiologies of fever in travelers returning from the tropics admitted to the infectious and tropical diseases unit of a university teaching hospital in Marseilles, France. Results A total of 613 patients were enrolled, including 364 migrants (59.4%), 126 travelers (20.6%), 37 visitors (6%), 24 expatriates (3.9%), and 62 patients (10.1%) who could not be classified. Malaria was the most common diagnosis (75.2%), with most cases (62%) acquired by migrants from the Comoros archipelago and who had traveled to these islands to visit friends and relatives. Agents of food-borne and water-borne infections (3.9%) and respiratory tract infections (3.4%) were also frequently identified as the cause of fever. Other infections included emerging diseases such as gnathostomiasis, hepatitis E infection and rickettsial diseases, as well as common infections or exotic diseases. Conclusions Although we have identified here various causes of imported fever, 8.2% of the fevers remained unexplained. An improved approach to diagnosis may allow for the discovery of new diseases in travelers in the future.


title: Globalization and risks to health

text: As borders disappear, people and goods are increasingly free to move, creating new challenges to global health. These cannot be met by national governments alone but must be dealt with instead by international organizations and agreements


title: Preventive Effect of Korean Red Ginseng for Acute Respiratory Illness: A Randomized and Double-Blind Clinical Trial

text: Korean Red Ginseng (KRG) is a functional food and has been well known for keeping good health due to its anti-fatigue and immunomodulating activities. However, there is no data on Korean red ginseng for its preventive activity against acute respiratory illness (ARI). The study was conducted in a randomized, double-blinded, placebo-controlled trial in healthy volunteers (Clinical Trial Number: NCT01478009). Our primary efficacy end point was the number of ARI reported and secondary efficacy end point was severity of symptoms, number of symptoms, and duration of ARI. A total of 100 volunteers were enrolled in the study. Fewer subjects in the KRG group reported contracting at least 1 ARI than in the placebo group (12 [24.5%] vs 22 [44.9%], P = 0.034), the difference was statistically significant between the two groups. The symptom duration of the subjects who experienced the ARI, was similar between the two groups (KRG vs placebo; 5.2 ± 2.3 vs 6.3 ± 5.0, P = 0.475). The symptom scores were low tendency in KRG group (KRG vs placebo; 9.5 ± 4.5 vs 17.6 ± 23.1, P = 0.241). The study suggests that KRG may be effective in protecting subjects from contracting ARI, and may have the tendency to decrease the duration and scores of ARI symptoms.


title: Network representations of immune system complexity

text: The mammalian immune system is a dynamic multi-scale system composed of a hierarchically organized set of molecular, cellular and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single cell responses to increasingly complex networks of in vivo cellular interaction, positioning and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather non-linear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multi-scale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating ‘omics’ and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks.


title: Interferon-λ3/4 genetic variants and interferon-λ3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese

text: BACKGROUND: Type III interferons (IFNs) or IFN-λs are the newly discovered cytokines that primarily target the cells of epithelial and myeloid lineages, which are major components of kidneys. The current study aimed to investigate whether IFN-λs are involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis. METHODS: TaqMan allele discrimination assays were used to determine IFNL3/4 SNP genotypes of 1620 healthy controls and 1013 SLE patients (two independent cohorts consisting of 831 and 182 subjects, respectively) from Taiwan. The distributions of IFNL3/4 SNP genotypes and allele frequencies were compared between SLE patients and healthy controls and among SLE patients stratified by clinical phenotypes. ELISA was used to determine the serum IFN-λ3 concentrations of SLE patients. RESULTS: All major IFN3/4 SNP alleles were significantly associated with the risk for lupus nephritis (rs8099917T, P(FDR) = 0.0021, OR 1.75, 95% CI 1.24–2.47; rs12979860C, P(FDR) = 0.0034, OR 1.65, 95% CI 1.18–2.30; rs4803217C, P(FDR) = 0.0021, OR 1.76, 95% CI 1.25–2.48; and ss469415590TT, P(FDR) = 0.0021, OR 1.73, 95% CI 1.23–2.42) among SLE patients. Similarly, the major IFNL3/4 SNP haplotype rs8099917T-ss469415590TT-rs12979860C-rs4803217C (or T-TT-C-C) was a significant risk factor for lupus nephritis (P = 0.0015, OR 1.68, 95% CI 1.22–2.32). Additionally, all minor IFN3/4 SNP alleles were significantly associated with SLE susceptibility in nephritis-negative SLE patients as compared to normal healthy controls (rs8099917G, P(FDR) = 0.00177, OR 1.68, 95% CI 1.24–2.28; rs12979860T, P(FDR) = 0.00299, OR 1.58, 95% CI 1.18–2.32; rs4803217A, P(FDR) = 0.00176, OR 1.65, 95% CI 1.22–2.23; and ss469415590ΔG, P(FDR) = 0.00176, OR 1.70, 95% CI 1.26–2.29). Furthermore, the elevated serum levels of IFN-λ3 were significantly correlated with the complement depression and the high SLE disease activities in SLE patients. CONCLUSIONS: IFN-λ3/4 genetic variants play a unique role in the development of lupus nephritis and SLE. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-018-1683-z) contains supplementary material, which is available to authorized users.


title: Characteristics Associated with Hospitalization Among Patients with COVID-19 — Metropolitan Atlanta, Georgia, March–April 2020

text: The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged ≥18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age ≥65 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed.


title: MMDB: annotating protein sequences with Entrez's 3D-structure database

text: Three-dimensional (3D) structure is now known for a large fraction of all protein families. Thus, it has become rather likely that one will find a homolog with known 3D structure when searching a sequence database with an arbitrary query sequence. Depending on the extent of similarity, such neighbor relationships may allow one to infer biological function and to identify functional sites such as binding motifs or catalytic centers. Entrez's 3D-structure database, the Molecular Modeling Database (MMDB), provides easy access to the richness of 3D structure data and its large potential for functional annotation. Entrez's search engine offers several tools to assist biologist users: (i) links between databases, such as between protein sequences and structures, (ii) pre-computed sequence and structure neighbors, (iii) visualization of structure and sequence/structure alignment. Here, we describe an annotation service that combines some of these tools automatically, Entrez's ‘Related Structure’ links. For all proteins in Entrez, similar sequences with known 3D structure are detected by BLAST and alignments are recorded. The ‘Related Structure’ service summarizes this information and presents 3D views mapping sequence residues onto all 3D structures available in MMDB ().


title: Psychosoziale Folgen von Quarantänemaßnahmen bei schwerwiegenden Coronavirus-Ausbrüchen: ein Rapid Review

text: Objective Review of the evidence on the psychosocial impact of quarantine measures during serious coronavirus outbreaks before COVID-19. Such information is highly relevant in regard to the COVID-19 pandemic. Methods Search of the MEDLINE database for relevant studies related to SARS-CoV and MERS-CoV outbreaks. Results Across 13 identified studies, quarantine measures were consistently associated with negative psychosocial outcomes, including depressive symptoms, anxiety, anger, stress, posttraumatic stress, social isolation, loneliness and stigmatization. Determinants comprised duration of quarantine measures and income losses. Health care workers constituted a particularly vulnerable group. Conclusion Quarantine measures during serious coronavirus outbreaks have extensive negative consequences for mental health. Prevention and intervention approaches to attenuate the psychosocial impact should be an integral component of crisis response during pandemic conditions.


title: Diabetic foot ulceration in COVID‐19 lockdown: cause for concern or unexpected benefit?

text: On 23 March 2020 the United Kingdom went into lockdown to reduce transmission of COVID-19. In order to focus on acute care capacity and maintain social distancing, there was simultaneous widespread change in the depth and breadth of National Health Service (NHS) services and a reduction in preventative care for people with diabetes [1]. We are aware of numerous mainstream media reports of reductions in the numbers of people seeking care for non-COVID emergencies and a reported reduction in referrals for suspected malignancy.


title: University students’ mental health amidst the COVID-19 quarantine in Greece

text: The COVID-19 hit also Greece but due to early measures and their exceptional success, the death toll is one of the lowest in the world. Here we report the results from the analysis of the responses to an online survey, from the first 1000 university students, concerning the impact of the lockdown on their mental health. Overall, there was a ‘horizontal’ increase in scores; 42.5% for anxiety, 74.3% for depression, and 63.3% increase in total suicidal thoughts. Quantity of sleep increased in 66.3% but quality worsened in 43.0%. Quality of life worsened in 57.0% (same in 27.9%). There was a 25-3 fold increase in possible clinical cases of depression and an almost 8-fold increase in suicidal thoughts. Almost a third accept and one fifth are open to conspiracy theories concerning COVID-19. To our knowledge this is the first study reporting data concerning the impact of lockdown and quarantine on the mental health of university students. While the acute impact seems clear, the long-term consequences are unknown and although suicidal thoughts have risen substantially, it seems unlikely this will result in deaths. However, the results constitute a clear message that vulnerable populations are at a need for specific interventions concerning their mental health issues.


title: Diagnóstico rápido de las infecciones del tracto gastrointestinal por parásitos, virus y bacterias

text: Rapid diagnostic techniques are valuable tools in the diagnosis of gastrointestinal infections, especially for the detection of some microorganisms and in certain groups of patients. While antigen detection techniques are widely used in Clinical Microbiology laboratories, for the diagnosis of viruses, some parasites and some bacteria, molecular techniques are routinely used only for some pathogens (such as Clostridium difficile). However, molecular techniques are constantly evolving, and they allow a rapid diagnosis for an increasing number of pathogens, with high sensitivity and specificity. In addition, they are also able to detect virulence factors or resistance mechanisms. Syndromic surveillance systems, which detect different pathogens simultaneously, are very promising because they enable the most frequent pathogens to be diagnosed in a few hours and they can be very useful in certain patients. For the diagnosis of Helicobacter pylori infection, molecular techniques are able to detect bacteria and its resistance to clarithromycin and levofloxacin, allowing the most appropriate treatment to be selected for each patient when bacterial culture is not possible.


title: Validity of energy social research during and after COVID-19: challenges, considerations, and responses

text: Measures to control the spread of coronavirus disease 2019 (COVID-19) are having unprecedented impacts on people’s lives around the world. In this paper, we argue that those conducting social research in the energy domain should give special consideration to the internal and external validity of their work conducted during this pandemic period. We set out a number of principles that researchers can consider to give themselves and research users greater confidence that findings and recommendations will still be applicable in years to come. Largely grounded in existing good practice guidance, our recommendations include collecting and reporting additional supporting contextual data, reviewing aspects of research design for vulnerability to validity challenges, and building in longitudinal elements where feasible. We suggest that these approaches also bring a number of opportunities to generate new insights. However, we caution that a more systemic challenge to validity of knowledge produced during this period may result from changes in the kinds of social research that it is practicable to pursue.


title: A Bibliometric Profile of Disaster Medicine Research from 2008 to 2017: A Scientometric Analysis

text: This study analyzed and assessed publication trends in articles on “disaster medicine,” using scientometric analysis. Data were obtained from the Web of Science Core Collection (WoSCC) of Thomson Reuters on March 27, 2017. A total of 564 publications on disaster medicine were identified. There was a mild increase in the number of articles on disaster medicine from 2008 (n=55) to 2016 (n=83). Disaster Medicine and Public Health Preparedness published the most articles, the majority of articles were published in the United States, and the leading institute was Tohoku University. F. Della Corte, M. D. Christian, and P. L. Ingrassia were the top authors on the topic, and the field of public health generated the most publications. Terms analysis indicated that emergency medicine, public health, disaster preparedness, natural disasters, medicine, and management were the research hotspots, whereas Hurricane Katrina, mechanical ventilation, occupational medicine, intensive care, and European journals represented the frontiers of disaster medicine research. Overall, our analysis revealed that disaster medicine studies are closely related to other medical fields and provides researchers and policy-makers in this area with new insight into the hotspots and dynamic directions. (Disaster Med Public Health Preparedness. 2019;13:165–172)


title: Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS‐CoV) in SARS patients: implications for pathogenesis and virus transmission pathways

text: We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS‐associated coronavirus (SARS‐CoV). In the present study, we used a murine monoclonal antibody specific for SARS‐CoV nucleoprotein, and probes specific for a SARS‐CoV RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect SARS‐CoV systematically in tissues from patients who died of SARS. SARS‐CoV was found in lung, trachea/bronchus, stomach, small intestine, distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas, adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen, lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus or muscle. These results suggest that, in addition to the respiratory system, the gastrointestinal tract and other organs with detectable SARS‐CoV may also be targets of SARS‐CoV infection. The pathological changes in these organs may be caused directly by the cytopathic effect mediated by local replication of the SARS‐CoV; or indirectly as a result of systemic responses to respiratory failure or the harmful immune response induced by viral infection. In addition to viral spread through a respiratory route, SARS‐CoV in the intestinal tract, kidney and sweat glands may be excreted via faeces, urine and sweat, thereby leading to virus transmission. This study provides important information for understanding the pathogenesis of SARS‐CoV infection and sheds light on possible virus transmission pathways. This data will be useful for designing new strategies for prevention and treatment of SARS. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


title: Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

text: Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.


title: Risk, uncertainty, ignorance and myopia: Their managerial implications for B2B firms

text: Abstract Rare events are common: Even though any particular type of ‘rare event’ - a world war, global economic collapse, or pandemic for that matter - should only occur once every 100 years, there are enough of those types of ‘rare events’ that overall, they commonly occur about once every 10 years. As we are currently experiencing with the COVID-19 pandemic, we do not sufficiently leverage the rich toolset that risk management offers to prepare for and mitigate the resulting uncertainty. This article highlights four aspects of risk management, and their practical and theorical implications. They are: 1) Risk (in the narrower sense), where possible future outcomes can be captured through probability distributions. 2) A situation of uncertainty, where there is transparency regarding what is not known, but probability distributions are unknown, as well as causal relationships influencing the outcome in question. 3) A situation of ignorance, where there is no understanding that certain possible future developments are even relevant. And finally: 4) The emergence of organizational and inter-organizational myopia as an effect of risk, uncertainty and ignorance on collective human behaviour.


title: Isolation and Identification of Feline Herpesvirus Type 1 from a South China Tiger in China

text: In 2012, an FHV-1-like virus was isolated from a tiger that presented with clinical signs of sialorrhea, sneezing and purulent rhinorrhea. Isolation was performed with the FK81 cell line, and the virus was identified by PCR, transmission electron microscopy (TEM), and the phylogenetic analysis of the partial thymidine kinase (TK) and glycoprotein B (gB) genes. A total of 253 bp of the TK gene and 566 bp of the gB gene were amplified from the trachea of the tiger by PCR/RT-PCR method. Phylogenetic analysis showed that the isolate belonged to the same cluster with other FHV-1 strains obtained from GenBank. Herpes-like viruses with an envelope and diameters of approximately 200 nm were observed in the culture supernatants of FK81 cells inoculated with samples from the tiger. The FHV-1 infection was confirmed by an animal challenge experiment in a cat model. Our finding extends the host range of FHV-1 and has implications for FHV-1 infection and South China tiger conservation.


title: Modeling Seasonal Rabies Epidemics in China

text: Human rabies, an infection of the nervous system, is a major public-health problem in China. In the last 60 years (1950–2010) there had been 124,255 reported human rabies cases, an average of 2,037 cases per year. However, the factors and mechanisms behind the persistence and prevalence of human rabies have not become well understood. The monthly data of human rabies cases reported by the Chinese Ministry of Health exhibits a periodic pattern on an annual base. The cases in the summer and autumn are significantly higher than in the spring and winter. Based on this observation, we propose a susceptible, exposed, infectious, and recovered (SEIRS) model with periodic transmission rates to investigate the seasonal rabies epidemics. We evaluate the basic reproduction number R (0), analyze the dynamical behavior of the model, and use the model to simulate the monthly data of human rabies cases reported by the Chinese Ministry of Health. We also carry out some sensitivity analysis of the basic reproduction number R (0) in terms of various model parameters. Moreover, we demonstrate that it is more reasonable to regard R (0) rather than the average basic reproduction number [Formula: see text] or the basic reproduction number [Formula: see text] of the corresponding autonomous system as a threshold for the disease. Finally, our studies show that human rabies in China can be controlled by reducing the birth rate of dogs, increasing the immunization rate of dogs, enhancing public education and awareness about rabies, and strengthening supervision of pupils and children in the summer and autumn.


title: Association between Hospital Nurses’ Perception of Patient Safety Management and Standard Precaution Adherence: A Cross-Sectional Study

text: Standard precautions should be applied to prevent health care-associated infections during every nursing activity. However, adherence to standard precautions was reported to be inadequate. Therefore, this study aimed to identify the rates of standard precaution adherence and the association between perception of patient safety management and standard precaution adherence. In this cross-sectional descriptive study, a convenience sample of nurses was recruited from a university-affiliated teaching hospital in Seoul, Korea. Data were collected using a structured self-report questionnaire. Among the 332 questionnaires returned (response rate: 94.9%), a total of 329 nurses were analyzed. In the present study, the overall standard precaution adherence rate was approximately 53.5%. The multiple linear regression results revealed that participants’ perceptions of patient safety management were only significantly associated with standard precaution adherence after adjusting other covariates (β = 0.412, p < 0.001). Nurse supervisors should focus more on raising awareness about nurses’ perception of patient safety management based on the specific work environment, such as the total number of nurses working together and the nurse-to-patient ratio. Nurse educators should develop integrated curricula to help graduate nurses transition smoothly into professional practice and enhance adherence to standard precautions in diverse health care settings.


title: Aerosol challenge of calves with Haemophilus somnus and Mycoplasma dispar

text: Abstract The aim of the study was to examine the ability of Haemophilus somnus and Mycoplasma dispar to induce pneumonia in healthy calves under conditions closely resembling the supposed natural way of infection, viz. by inhalation of aerosol droplets containing the microorganisms. The infections were investigated by recording clinical data, cytokine expression of peripheral blood cells and pathology. Twelve calves were included in the study: Three animals were exposed to H. somnus only, and two to M. dispar only, whereas five were challenged to M. dispar followed by exposure to H. somnus 11–14 days later. Also, one calf was exposed to M. dispar followed by exposure to a sterile saline solution 11 days later, and one calf was only exposed to a sterile saline solution. Just one animal, only challenged with H. somnus, developed a focal necrotizing pneumonia, from which H. somnus was isolated. Thus, the ability of H. somnus and M. dispar to act as primary pathogens under these conditions were minimal and inconsistent. However, a transient rise in body temperature, a marked granulocytosis and increased levels of interleukin-8 in peripheral blood after inoculation with H. somnus indicated a clear systemic response, probably as a consequence of the natural non-specific local and systemic defence mechanisms acting in healthy calves.


title: Update on infection control practices in cancer hospitals

text: Therapies in oncology have evolved rapidly over the last years. At the same pace, supportive care for patients receiving cancer therapy has also evolved, allowing patients to safely receive the newest advances in treatment in both an inpatient and outpatient basis. The recognition of the role of infection control and prevention (ICP) in the outcomes of patients living with cancer has been such that it is now a requirement for hospitals and involves multidisciplinary groups. Some unique aspects of ICP for patients with cancer that have gained momentum over the past few decades include catheter‐related infections, multidrug‐resistant organisms, community‐acquired viral infections, and the impact of the health care environment on the horizontal transmission of organisms. Furthermore, as the potential for infections to cross international borders has increased, alertness for outbreaks or new infections that occur outside the area have become constant. As the future approaches, ICP in immunocompromised hosts will continue to integrate emerging disciplines, such as antibiotic stewardship and the microbiome, and new techniques for environmental cleaning and for controlling the spread of infections, such as whole‐genome sequencing. CA Cancer J Clin 2018;000:000‐000. © 2018 American Cancer Society.


title: Colostrum-supplemented transition milk positively affects serum biochemical parameters, humoral immunity indicators and the growth performance of calves

text: Abstract The aim of this study was to determine the effect of colostrum-supplemented transition milk on the growth rate of newborn calves. Thirty-six day-old female Holstein calves with a birth weight of 43.4 ± 5.5 kg were randomly assigned to a treatment group and a control group. On day 1, all calves received one portion (3 kg) of colostrum within 2 h after birth. Between the second feeding and the age of 5 days, control calves received only transition milk that had been collected from dams shortly before feeding, and the treatment group received 1.5 kg of colostrum collected from dams on day 1 and 1.5 kg of transition milk from subsequent milkings. Monthly body weight and average daily gain were used to measure growth performance. Blood samples were collected from the jugular vein at multiple time points to evaluate the biochemical and immune status of calves. Colostrum-supplemented transition milk increased the concentrations of serum immunoglobulins, triacylglycerols, cholesterol and total protein. The activity of lactate-dehydrogenase and ceruloplasmin decreased, whereas lysozyme activity increased with time in the control group. It can be concluded that additional five days of colostrum feeding positively influences non-specific humoral immunity indicators and serum biochemical parameters in dairy calves.


docid: cqeulecp

title: SARS‐CoV‐2, the Virus that Causes COVID‐19: Cytometry and the New Challenge for Global Health


Use of Clinical Criteria and Molecular Diagnosis to More Effectively Monitor Patients Recovering after Severe Acute Respiratory Syndrome Coronavirus Infection


title: Molecular Detection of SARS-CoV-2 in Formalin Fixed Paraffin Embedded Specimens

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of human coronavirus disease 2019 (COVID-19), emerged in Wuhan, China in December 2019. The virus rapidly spread globally, resulting in a public-health crisis including more than one million cases and tens of thousands of deaths. Here, we describe the identification and evaluation of commercially available reagents and assays for the molecular detection of SARS-CoV-2 in infected formalin fixed paraffin embedded (FFPE) cell pellets. We identified a suitable rabbit polyclonal anti-SARS-CoV spike protein antibody and a mouse monoclonal anti-SARS-CoV nucleocapsid protein (NP) antibody for cross detection of the respective SARS-CoV-2 proteins by immunohistochemistry (IHC) and immunofluorescence assay (IFA). Next, we established RNAscope in situ hybridization (ISH) to detect SARS-CoV-2 RNA. Furthermore, we established a multiplex fluorescence ISH (mFISH) to detect positive-sense SARS-CoV-2 RNA and negative-sense SARS-CoV-2 RNA (a replicative intermediate indicating viral replication). Finally, we developed a dual staining assay using IHC and ISH to detect SARS-CoV-2 antigen and RNA in the same FFPE section. These reagents and assays will accelerate COVID-19 pathogenesis studies in humans and in COVID-19 animal models.


title: SnapShot: COVID-19

text: Abstract Coronavirus disease 2019 (COVID-19) is a novel respiratory illness caused by SARS-CoV-2. Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction. Most cases are mild; severe disease often involves cytokine storm and organ failure. Therapeutics including antivirals, immunomodulators, and vaccines are in development. To view this SnapShot, open or download the PDF.


title: Coronavirus disease 2019—The principles of the curve, explained simply

text: In the setting of the coronavirus disease 2019 pandemic, the concept of the disease curve has become ubiquitous in medicine and across society. Nevertheless, even among medical specialists, there are common misconception about the curve and how it affects population outcomes. This article provides a simple review of the various population dynamics at play. Principles such as the area under the curve and the threshold of capacity are discussed and simply conceptualized. Understanding the fundamental characteristics of a problem can allow us to see it with more clarity. By the end of the article, the reader will gain an effortless a sense of insight on this topic.


title: Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation

text: Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4(+) T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 profile by activating the Th17 master regulator, STAT3, which in turn bound IL-17A and F promoters. Mitophagy-targeting siRNA failed to activate the Th17 profile. We conclude that metformin improves autophagy and mitochondrial function largely in parallel to ameliorate a newly defined inflammaging profile that echoes inflammation in diabetes.


title: Regulation of Nucleotide Metabolism and Germline Proliferation in Response to Nucleotide Imbalance and Genotoxic Stresses by EndoU Nuclease

text: Nucleotide deprivation and imbalance present detrimental conditions for animals and are thus expected to trigger cellular responses that direct protective changes in metabolic, developmental, and behavioral programs, albeit such mechanisms are vastly underexplored. Following our previous finding that Caenorhabditis elegans shut down germ cell proliferation in response to pyrimidine deprivation, we find in this study that endonuclease ENDU-2 regulates nucleotide metabolism and germ cell proliferation in response to nucleotide imbalance and other genotoxic stress, and that it affects mitotic chromosomal segregation in the intestine and lifespan. ENDU-2 expression is induced by nucleotide imbalance and genotoxic stress, and ENDU-2 exerts its function in the intestine, mostly by inhibiting the phosphorylation of CTPS-1 through repressing the PKA pathway and histone deacetylase HDA-1. Human EndoU also affects the response to genotoxic drugs. Our work reveals an unknown role of ENDU-2 in regulating nucleotide metabolism and animals’ response to genotoxic stress, which may link EndoU function to cancer treatment.


docid: wlzdwtdy

title: Treatment of Covid19 ‐ Repurposing drugs commonly used in dermatology

text: For the last two decades, the outbreaks of diseases caused by coronaviruses and intermittent worldwide public health emergences have reminded us that they still represent a severe threat to global health. The recent outbreak of Corona Virus disease 19 (COVID‐19) highlighted the urgent need for effective treatment, and initiated rapid search for therapies, able to counter the most severe disease effects. Many aspects of COVID‐19 pathogenesis are unknown, but complex interplay of direct viral damage and immune response dysregulation is underline. Intensive research is undergoing for therapeutic targets of virus and high‐efficiency and low toxicity targeted drugs. There is no available specific antiviral treatment of this disease, therefore repurposing of drugs already available for the treatment of other viral and autoimmune diseases has been a part of research efforts. Well known anti‐inflammatory properties of Chloroquine and Hydroxychloroquine, agents widely used in dermatology, made them potential candidates for the treatment of COVID‐19. We review pathogenesis and clinical characteristic of COVID‐19, as well as treatment options that have been under evaluation in past several months. In addition, we focus more on Chloroquine and Hydroxychloroquine, their pharmacological properties, clinical utility, and current recommendations for their use in COVID‐19. This article is protected by copyright. All rights reserved.


title: Implementation of Influenza-like illness Sentinel Surveillance in Togo

text: BACKGROUND: The emergence of avian influenza A/H5N1 in 2003 as well as the pandemic influenza A (H1N1) pdm09 highlighted the need to establish influenza sentinel surveillance in Togo. The Ministry of Health decided to introduce Influenza to the list of diseases with epidemic potential. By April 2010, Togo was actively involved in influenza surveillance. This study aims to describe the implementation of ILI surveillance and results obtained from April 2010 to December 2012. METHODS: Two sites were selected based on their accessibility and affordability to patients, their adequate specimen storage capacity and transportation system. Patients with ILI presenting at sentinel sites were enrolled by trained medical staff based on the World Health Organization (WHO) case definitions. Oropharyngeal and nasopharyngeal samples were collected and they were tested at the National Influenza Reference Laboratory using a U.S. Centers for Disease Control and Prevention (CDC) validated real time RT-PCR protocol. Laboratory results and epidemiological data were reported weekly and shared with all sentinel sites, Ministry of Health, Division of Epidemiology, WHO and CDC/NAMRU-3. RESULTS: From April 2010 to December 2012, a total of 955 samples were collected with 52% of the study population aged between 0 and 4 years. Of the 955 samples, 236 (24.7%) tested positive for influenza viruses; with 136 (14.2%) positive for influenza A and 100 (10.5%) positive for influenza B. The highest influenza positive percentage (30%) was observed in 5–14 years old and patients aged 0–4 and >60 years had the lowest percentage (20%). Clinical symptoms such as cough and rhinorrhea were associated more with ILI patients who were positive for influenza type A than influenza type B. Influenza viruses circulated throughout the year with the positivity rate peaking around the months of January, May and again in October; corresponding respectively to the dry-dusty harmattan season and the long and then the short raining season. The pandemic A (H1N1) pdm09 was the predominantly circulating strain in 2010 while influenza B was the predominantly circulating strain in 2011. The seasonal A/H3N2 was observed throughout 2012 year. CONCLUSIONS: This study provides information on influenza epidemiology in the capital city of Togo.


title: Newly Recognized Causes of Acute Lung Injury: Transfusion of Blood Products, Severe Acute Respiratory Syndrome, and Avian Influenza

text: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a clinical syndrome that has an ever-growing list of potential causes. The transfusion of blood products is often a life-saving therapy, but it can be associated with the development of ALI/ARDS. Transfusion-related ALI is now the leading cause of transfusion-associated fatalities in the United States. Two infectious causes of ALI/ARDS, severe acute respiratory syndrome and H5N1 influenza, have recently emerged and have the potential for pandemic spread. This article discusses the clinical importance, pathogenesis, diagnosis, management, and prevention of these newly recognized causes of respiratory failure.


title: Respiratory Viruses

text: Abstract This article is an overview of the most clinically important respiratory viruses including the recently emerged highly pathogenic coronaviruses and other viruses that are transmitted via the respiratory tract. In this article, we highlight a description of the agent, its life cycle, epidemiology, pathogenesis, clinical features, diagnosis and management of the infection. The viruses in this article are respiratory syncytial virus, parainfluenza virus, human metapneumovirus, rhinovirus, seasonal and emerging coronaviruses, adenovirus, bocavirus and other viruses associated with the respiratory tract for their life cycle.


title: Protein-directed ribosomal frameshifting temporally regulates gene expression

text: Programmed −1 ribosomal frameshifting is a mechanism of gene expression, whereby specific signals within messenger RNAs direct a proportion of translating ribosomes to shift −1 nt and continue translating in the new reading frame. Such frameshifting normally occurs at a set ratio and is utilized in the expression of many viral genes and a number of cellular genes. An open question is whether proteins might function as trans-acting switches to turn frameshifting on or off in response to cellular conditions. Here we show that frameshifting in a model RNA virus, encephalomyocarditis virus, is trans-activated by viral protein 2A. As a result, the frameshifting efficiency increases from 0 to 70% (one of the highest known in a mammalian system) over the course of infection, temporally regulating the expression levels of the viral structural and enzymatic proteins.


title: The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice

text: Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Koch’s postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.