title: Pathogenesis of GIII.2 bovine norovirus, CV186-OH/00/US strain in gnotobiotic calves

text: The pathogenesis of GIII.2 bovine norovirus (BoNoV) is not well understood. Our study demonstrated persisting diarrhea and prolonged fecal shedding, but with a lack of significant intestinal lesions in gnotobiotic (Gn) calves infected with GIII.2 BoNoV, CV186-OH/00/US strain. Nine 4 to 7-day-old Angus/Jersey crossbred Gn calves were orally inoculated with 10.0-11.9 log(10) genomic equivalents (GE)/calf of CV186-OH (n=7) or mock (n=2). Calves were euthanized at post-inoculation day (PID) 1 (n=1) when moderate to severe lethargy was observed and at PIDs 2-6 (n=4) after lethargy had subsided. Two calves were kept longer term (until PID 30) for monitoring fecal shedding patterns by TaqMan real-time RT-PCR (qRT-PCR). Most infected calves exhibited two clinical signs: i) acute but persisting diarrhea and ii) acute moderate to severe lethargy. The two infected calves, followed longer-term, had prolonged fecal viral RNA shedding [peak average titer of 11.8 (± 0.2) log(10) GE/ml] at least until PID 20. By qRT-PCR, 5 infected calves had low viral RNA titers in serum, ranging from 4.0 to 5.8 log(10) GE/ml, at PIDs 1-5, but not (<2.7 log(10) GE/ml) at PIDs 6-30. The latter observation coincided with the presence of serum IgG antibody to BoNoV at PIDs 8-30. Collectively, the GIII.2 BoNoV strain CV186-OH induced only mild enteropathogenicity, evident by the lack of significant intestinal lesions, but it led to persisting mild diarrhea and prolonged fecal virus shedding in Gn calves. The prolonged fecal shedding of GIII.2 BoNoV might partially explain how this virus is maintained as endemic infections in cattle.


Atypical presentation of Covid-19 in an older adult with severe Alzheimer Disease


The calendar of epidemics: Seasonal cycles of infectious diseases


title: Diskussion um NSAR in Zeiten von Covid-19: Fiebersenkung und Schmerztherapie

text: Im Zusammenhang mit der Corona-Pandemie tauchten alarmierende Meldungen auf, die vor dem Einsatz von Ibuprofen und anderen NSAR bei einer vermuteten SARS-CoV-2-Infektion warnen. Diese Medikamente, so wird spekuliert, könnten den Verlauf der Infektion verschlimmern. Was hinter solchen Spekulationen steckt und wie der aktuelle Stand der Empfehlungen ist, erläutert der Schmerzexperte Prof. Hartmut Göbel, Kiel.


title: Seasonal trends of diagnosis of childhood malignant diseases and viral prevalence in South Korea

text: Abstract Background Several studies have reported a seasonal trend in the diagnosis of childhood cancer suggesting seasonal factors such as infection. The present study aimed to analyze the diagnosis pattern of childhood malignant diseases using public health data, and to compare this pattern with seasonal viral infection trends. Method Using the open data source of the Health Insurance Review and Assessment Service, we extracted data regarding all patients under 21 years of age and who had any cancer, aplastic anemia or myelodysplastic syndrome between September 2009 and December 2013. The positive detection rates of 11 viruses was collected from the surveillance data of Korea Centers for Disease Control and Prevention, and seasonality analysis were conducted with both data. Results In total, 9085 patients were diagnosed with malignant disease during the study period; there were about 175 new cases per month on average. Monthly stacked time series by year showed an apparent seasonal variation with the highest monthly average in January as 236, and the lowest in September as 120. In winter, significantly more patients were diagnosed with acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma, and Hodgkin’s lymphoma than in other seasons. There was a temporal correlation with the diagnostic trends of several diseases and the prevalence of recent human parainfluenza virus. Conclusion This study tentatively suggests that the diagnosis of childhood malignancy follows a seasonal trend in Korea, and has a possible correlation with viral prevalence in several diseases. Further long-term analysis of epidemiological data is needed to explore possible causality.


title: Long-term Psychological and Occupational Effects of Providing Hospital Healthcare during SARS Outbreak

text: Healthcare workers (HCWs) found the 2003 outbreak of severe acute respiratory syndrome (SARS) to be stressful, but the long-term impact is not known. From 13 to 26 months after the SARS outbreak, 769 HCWs at 9 Toronto hospitals that treated SARS patients and 4 Hamilton hospitals that did not treat SARS patients completed a survey of several adverse outcomes. Toronto HCWs reported significantly higher levels of burnout (p = 0.019), psychological distress (p<0.001), and posttraumatic stress (p<0.001). Toronto workers were more likely to have reduced patient contact and work hours and to report behavioral consequences of stress. Variance in adverse outcomes was explained by a protective effect of the perceived adequacy of training and support and by a provocative effect of maladaptive coping style and other individual factors. The results reinforce the value of effective staff support and training in preparation for future outbreaks.


Rapid advice guidelines for management of children with COVID-19.


title: An antibody response to human polyomavirus 15-mer peptides is highly abundant in healthy human subjects

text: BACKGROUND: Human polyomaviruses (HPyV) infections cause mostly unapparent or mild primary infections, followed by lifelong nonpathogenic persistence. HPyV, and specifically JCPyV, are known to co-diverge with their host, implying a slow rate of viral evolution and a large timescale of virus/host co-existence. Recent bio-informatic reports showed a large level of peptide homology between JCPyV and the human proteome. In this study, the antibody response to PyV peptides is evaluated. METHODS: The in-silico analysis of the HPyV proteome was followed by peptide microarray serology. A HPyV-peptide microarray containing 4,284 peptides was designed and covered 10 polyomavirus proteomes. Plasma samples from 49 healthy subjects were tested against these peptides. RESULTS: In-silico analysis of all possible HPyV 5-mer amino acid sequences were compared to the human proteome, and 1,609 unique motifs are presented. Assuming a linear epitope being as small as a pentapeptide, on average 9.3% of the polyomavirus proteome is unique and could be recognized by the host as non-self. Small t Ag (stAg) contains a significantly higher percentage of unique pentapeptides. Experimental evidence for the presence of antibodies against HPyV 15-mer peptides in healthy subjects resulted in the following observations: i) antibody responses against stAg were significantly elevated, and against viral protein 2 (VP2) significantly reduced; and ii) there was a significant correlation between the increasing number of embedded unique HPyV penta-peptides and the increase in microarray fluorescent signal. CONCLUSION: The anti-peptide HPyV-antibodies in healthy subjects are preferably directed against the penta-peptide derived unique fraction of the viral proteome.


title: Fish disease dynamics in changing rivers: Salmonid Ceratomyxosis in the Klamath River

text: Abstract The myxozoan parasite Ceratomyxa shasta has been identified as the main contributor of mortality in salmon in the Klamath River, California. The life cycle of the parasite is complex, involving a polychaete and a salmonid host. Infection dynamics are greatly influenced by environmental factors, such as temperature and water velocity. If we are to control the disease it is important to predict the impact of environmental scenarios on spore concentration and infection prevalence. Here, we introduce a model based on partial differential equations to study the spore concentration in the river and the infection prevalence of returning salmon. The analysis of the model shows that for current climate conditions, additional dam release can reduce the actinospore concentration up to 48% and the prevalence up to 40% thus providing a potential disease management option. However, the infection risk is likely to increase for future climate conditions by 10–54% and this will lead to an infection level comparable to that of a recent high-disease year. Our simulations show that dam removal cannot be assumed to mitigate the effect of climate change or to have influence on infection prevalence. We show that our detailed model system can be reduced to a simpler exponential dose-response function, which predicts infection levels based on transmission rates, travel time and mean spore concentration, quantities that can be measured in-situ or given empirically. The dose-response function may therefore be a useful tool in disease management.


title: Animal models: an important tool in mycology

text: Animal models of fungal infections are, and will remain, a key tool in the advancement of the medical mycology. Many different types of animal models of fungal infection have been developed, with murine models the most frequently used, for studies of pathogenesis, virulence, immunology, diagnosis, and therapy. The ability to control numerous variables in performing the model allows us to mimic human disease states and quantitatively monitor the course of the disease. However, no single model can answer all questions and different animal species or different routes of infection can show somewhat different results. Thus, the choice of which animal model to use must be made carefully, addressing issues of the type of human disease to mimic, the parameters to follow and collection of the appropriate data to answer those questions being asked. This review addresses a variety of uses for animal models in medical mycology. It focuses on the most clinically important diseases affecting humans and cites various examples of the different types of studies that have been performed. Overall, animal models of fungal infection will continue to be valuable tools in addressing questions concerning fungal infections and contribute to our deeper understanding of how these infections occur, progress and can be controlled and eliminated.


title: Strategy for the practice of digestive and oncological surgery during the Covid-19 epidemic()()

text: The Covid-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery–go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer–colon, pancreas, oesogastric, hepatocellular carcinoma–morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3-4 and/or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting period) to reduce time of exposure in the hospital and to prevent infections. Most complex surgery with high morbidity and mortality–oesogastric, hepatic or pancreatic–is most often best deferred.


title: New tools for the study and direct surveillance of viral pathogens in water

text: Half a century ago scientists attempted the detection of poliovirus in water. Since then other enteric viruses responsible for gastroenteritis and hepatitis have replaced enteroviruses as the main target for detection. However, most viral outbreaks are restricted to norovirus and hepatitis A virus, making them the main targets in water. The inclusion of virus analysis in regulatory standards for viruses in water samples must overcome several shortcomings such as the technical difficulties and high costs of virus monitoring, the lack of harmonised and standardised assays and the challenge posed by the ever-changing nature of viruses. However, new tools are nowadays available for the study and direct surveillance of viral pathogens in water that may contribute to fulfil these requirements.


docid: ibnizdpu

title: COVID-19: Una pandemia de valores y algo más


title: Arthroplasty During the COVID-19 Pandemic

text: This article aims to give a brief outline of the pathogenesis and transmission of SARS-CoV-2 and how to safely navigate an arthroplasty practice during and after the pandemic.


Clinical management of a Nigerian patient affected by sickle cell disease with rare blood group and persistent SARS‐CoV‐2 positivity


The effect of mite allergen-impermeable covers in adult asthma: The SMAC study


title: Complete Genome Sequences of Porcine Deltacoronavirus Strains DH1/2016 and DH2/2016 Isolated in South Korea

text: Two porcine deltacoronavirus (PDCoV) strains, named DH1/2016 and DH2/2016, were isolated from feces of piglets which had severe watery diarrhea symptoms. A comparison of the complete genome sequences suggested that the DH1/2016 and DH2/2016 strains are highly homologous to each other and to PDCoVs isolated in early 2014 from the United States.


title: Catastrophic Risk: Waking Up to the Reality of a Pandemic?

text: Will a major shock awaken the US citizens to the threat of catastrophic pandemic risk? Using a natural experiment administered both before and after the 2014 West African Ebola Outbreak, our evidence suggests “no.” Our results show that prior to the Ebola scare, the US citizens were relatively complacent and placed a low relative priority on public spending to prepare for a pandemic disease outbreak relative to an environmental disaster risk (e.g., Fukushima) or a terrorist attack (e.g., 9/11). After the Ebola scare, the average citizen did not over-react to the risk. This flat reaction was unexpected given the well-known availability heuristic—people tend to over-weigh judgments of events more heavily toward more recent information. In contrast, the average citizen continued to value pandemic risk less relative to terrorism or environmental risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10393-020-01479-8) contains supplementary material, which is available to authorized users.


title: Adapting re‐usable elastomeric respirators to utilise anaesthesia circuit filters using a 3D‐printed adaptor ‐ a potential alternative to address N95 shortages during the COVID‐19 pandemic

text: The COVID‐19 pandemic has increased the demand for disposable N95 respirators. Re‐usable elastomeric respirators may provide a suitable alternative. Proprietary elastomeric respirator filters may become depleted as demand increases. An alternative may be the virus/bacterial filters used in anaesthesia circuits, if they can be adequately fitted onto the elastomeric respirators. In addition, many re‐usable elastomeric respirators do not filter exhaled breaths. If used for sterile procedures, this would also require modification. We designed a 3D‐printed adaptor that permits elastomeric respirators to interface with anaesthesia circuit filters and created a simple modification to divert exhaled breaths through the filter. We conducted a feasibility study evaluating the performance of our modified elastomeric respirators. A convenience sample of eight volunteers was recruited. Quantitative fit testing, respiratory rate and end‐tidal carbon dioxide were recorded during fit testing exercises and after 1 h of wear. All eight volunteers obtained excellent quantitative fit testing throughout the trial. The mean (SD) end‐tidal carbon dioxide was 4.5 (0.5) kPa and 4.6 (0.4) kPa at baseline and after 1 h of wear (p = 0.148). The mean (SD) respiratory rate was 17 (4) breaths.min(−1) and 17 (3) breaths.min(−1) at baseline and after 1 h of wear (p = 0.435). Four out of eight subjects self‐reported discomfort; two reported facial pressure, one reported exhalation resistance and one reported transient dizziness on exertion. Re‐usable elastomeric respirators to utilise anaesthesia circuit filters through a 3D‐printed adaptor may be a potential alternative to disposable N95 respirators during the COVID‐19 pandemic.


title: Early Phylogenetic Diversification of SARS-CoV-2: Determination of Variants and the Effect on Epidemiology, Immunology, and Diagnostics.

text: The phylogenetic clustering of 95 SARS-CoV-2 sequences from the first 3 months of the pandemic reveals insights into the early evolution of the virus and gives first indications of how the variants are globally distributed. Variants might become a challenge in terms of diagnostics, immunology, and effectiveness of drugs. All available whole genome sequence data from the NCBI database (March 16, 2020) were phylogenetically analyzed, and gene prediction as well as analysis of selected variants were performed. Antigenic regions and the secondary protein structure were predicted for selected variants. While some clusters are presenting the same variant with 100% identical bases, other SARS-CoV-2 lineages show a beginning diversification and phylogenetic clustering due to base substitutions and deletions in the genomes. First molecular epidemiological investigations are possible with the results by adding metadata as travelling history to the presented data. The advantage of variants in source tracing can be a challenge in terms of virulence, immune response, and immunological memory. Variants of viruses often show differences in virulence or antigenicity. This must also be considered in decisions like herd immunity. Diagnostic methods might not work if the variations or deletions are in target regions for the detection of the pathogen. One base substitution was detected in a primer binding site.


title: A tale of two countries: how decentralized organization and long-term investment build resilient healthcare systems

text: Healthcare systems are faced with unique challenges during the ongoing Covid-19 pandemic. This viewpoint compares the response to the Covid-19 pandemic in the UK and in Germany. Despite being two large European countries of comparable size with good healthcare systems and similar patterns of exposure to Covid-19, Covid-19 related deaths in the UK currently far outnumber those in Germany. This has several reasons, but two explanations stick out: 1. lower long-term investment into healthcare in the UK rendered the NHS more vulnerable to Covid-19; 2. the existence of a well-governed decentralised and partially redundant organisation of healthcare increased resilience in Germany’ s healthcare systems, enhancing the ability to adapt in response to unexpected challenges to healthcare. The response to the current pandemic also illustrates the power and the necessity to learn from each other through transparent communication of successes and mistakes.


title: Neonatal Diseases in Llamas and Alpacas

text: This article attempts to cover the most common problems likely to present in neonatal crias and to give guidance on how to approach these cases, particularly how to stabilize the acute presentation of a sick neonate. It is impossible to cover every eventuality and it is important to keep an open mind when evaluating and treating sick neonatal camelids. Despite the often moribund presentation of sick neonatal crias, they may be highly rewarding to treat, although hospitalization and 24-hour care is recommended.


title: Diagnosis and Management of Lung Infections

text: This article describes contemporary methods of diagnosis and current treatment regimens for most pulmonary infections. Modern techniques used to improve diagnostic yield in pulmonary infection include bronchoscopy, ultrasound- and electromagnetic-guided endoscopy, transthoracic needle biopsy, and samples obtained with thoracoscopy. The spectrum of bacterial, mycobacterial, fungal, and viral pathogens implicated in pulmonary disease is discussed. Treatment strategies and guideline recommendations for antimicrobial selection are described for community-acquired, health care–associated, hospital-acquired, and ventilator-associated pneumonia, and for the most common fungal, mycobacterial, and viral infections. The state-of-the art in topical and aerosolized anti-infective therapy and an algorithm for managing hemoptysis are also presented.


title: Cooperative virus propagation underlies COVID-19 transmission dynamics

text: The global pandemic due to the emergence of a novel coronavirus (COVID-19) is a threat to the future health of humanity. There remains an urgent need to understand its transmission characteristics and design effective interventions to mitigate its spread. In this study, we define a non-linear (known in biochemistry models as allosteric or cooperative) relationship between viral shedding, viral dose and COVID-19 infection propagation. We develop a mathematical model of the dynamics of COVID-19 to link quantitative features of viral shedding, human exposure and transmission in nine countries impacted by the ongoing COVID-19 pandemic. The model was then used to evaluate the efficacy of interventions against virus transmission. We found that cooperativity was important to capture country-specific transmission dynamics and leads to resistance to mitigating transmission in mild or moderate interventions. The behaviors of the model emphasize that strict interventions greatly limiting both virus shedding and human exposure are indispensable to achieving effective containment of COVID-19.


title: What we are watching—five top global infectious disease threats, 2012: a perspective from CDC’s Global Disease Detection Operations Center

text: Disease outbreaks of international public health importance continue to occur regularly; detecting and tracking significant new public health threats in countries that cannot or might not report such events to the global health community is a challenge. The Centers for Disease Control and Prevention’s (CDC) Global Disease Detection (GDD) Operations Center, established in early 2007, monitors infectious and non-infectious public health events to identify new or unexplained global public health threats and better position CDC to respond, if public health assistance is requested or required. At any one time, the GDD Operations Center actively monitors approximately 30–40 such public health threats; here we provide our perspective on five of the top global infectious disease threats that we were watching in 2012: (1) avian influenza A (H5N1), (2) cholera, (3) wild poliovirus, (4) enterovirus-71, and (5) extensively drug-resistant tuberculosis.


title: Broad-spectrum antiviral agents

text: Development of highly effective, broad-spectrum antiviral agents is the major objective shared by the fields of virology and pharmaceutics. Antiviral drug development has focused on targeting viral entry and replication, as well as modulating cellular defense system. High throughput screening of molecules, genetic engineering of peptides, and functional screening of agents have identified promising candidates for development of optimal broad-spectrum antiviral agents to intervene in viral infection and control viral epidemics. This review discusses current knowledge, prospective applications, opportunities, and challenges in the development of broad-spectrum antiviral agents.


title: Viruses

text: Abstract Increased knowledge has been gained into the aetiology and pathogenesis of viral gastroenteritis during the past two decades. There are now thought to be four major subclassifications of gastroenteritis-causing viruses; these include rotavirus, enteric adenovirus, calicivirus, including Norwalk and Norwalk-like viruses, and astrovirus. The association of these agents with gastroenteritis has been made by their electron microscopic detection in stool and intestinal biopsy specimens from affected patients, the inability to detect the viruses after recovery from disease, and the subsequent development of immunoglobulin responses after infection; in some instances disease transmission was achieved in human volunteers. The association of these viral agents with gastroenteritis has facilitated the study of classification, epidemiology, immunity, diagnostic tests, methods of treatment and, most importantly, disease prevention strategies such as vaccine development for rotavirus. This chapter highlights the major features of these agents, with special attention being given to the pertinent molecular biology as well as current and future prospects for vaccination. Enteric viral infections of the gastrointestinal tract in patients with AIDS are also discussed.


title: Detection and genetic characterization of canine astroviruses in pet dogs in Guangxi, China

text: BACKGROUND: Astroviruses (AstVs) have been reported to infect and cause gastroenteritis in most animal species. Human AstVs were regarded the causative agent of viral diarrhea in children. In dogs, little is known about the epidemiology and clinical significance of AstV infection. FINDINGS: In this study, we collected and tested 253 rectal swabs from pet dogs; of which 64 samples (25.3%) tested positive for AstVs with diarrhea and 15 more samples (5.9%) also was identified as AstVs, however without any clinical signs. Phylogenetic analysis of 39 partial ORF1b sequences from these samples revealed that they are similar to AstVs, which can be subdivided into three lineages. Interestingly, out of the 39 isolates sequenced, 16 isolates are shown to be in the Mamastrovirus 5/canine astrovirus (CAstV) lineage and the remaining 23 isolates displayed higher similarities with known porcine astrovirus (PoAstV) 5 and 2. Further, analysis of 13 capsid sequences from these isolates showed that they are closely clustered with Chinese or Italy CAstV isolates. CONCLUSIONS: The findings indicate that CAstVs commonly circulate in pet dogs, and our sequencing results have shown the genomic diversity of CAstVs leading to increasing number of clusters.


title: Anti-Inflammatory Effect of Quercetin on RAW 264.7 Mouse Macrophages Induced with Polyinosinic-Polycytidylic Acid

text: Quercetin (3,3′,4′,5,6-pentahydroxyflavone) is a well-known antioxidant and a flavonol found in many fruits, leaves, and vegetables. Quercetin also has known anti-inflammatory effects on lipopolysaccharide-induced macrophages. However, the effects of quercetin on virus-induced macrophages have not been fully reported. In this study, the anti-inflammatory effect of quercetin on double-stranded RNA (dsRNA)-induced macrophages was examined. Quercetin at concentrations up to 50 μM significantly inhibited the production of NO, IL-6, MCP-1, IP-10, RANTES, GM-CSF, G-CSF, TNF-α, LIF, LIX, and VEGF as well as calcium release in dsRNA (50 µg/mL of polyinosinic-polycytidylic acid)-induced RAW 264.7 mouse macrophages (p < 0.05). Quercetin at concentrations up to 50 μM also significantly inhibited mRNA expression of signal transducer and activated transcription 1 (STAT1) and STAT3 in dsRNA-induced RAW 264.7 cells (p < 0.05). In conclusion, quercetin had alleviating effects on viral inflammation based on inhibition of NO, cytokines, chemokines, and growth factors in dsRNA-induced macrophages via the calcium-STAT pathway.


title: Regulatory interplay between deubiquitinating enzymes and cytokines

text: Abstract Deubiquitinating enzymes (DUBs) are cysteine protease proteins that reverse the ubiquitination by removing ubiquitins from the target protein. With over 100 DUBs identified and categorized into at least 7 families, many DUBs interact with one or more cytokines, influencing cellular processes, such as antiviral responses, inflammatory responses, apoptosis, etc. While some DUBs influence cytokine pathway or production, some DUBs are cytokine-inducible. In this article, we summarize a list of DUBs, their interaction with cytokines, target proteins and mechanisms of action.


title: Recrudescence of Ebola virus disease outbreak in West Africa, 2014–2016

text: Abstract Objectives There have been errors in determining the end of the Ebola virus disease (EVD) epidemic when adhering to the criteria of the World Health Organization. The present study aimed to review and learn from all known recrudescence events in West Africa occurring in 2014–2016. Methods Background mechanisms of five erroneous declarations in Guinea, Liberia, and Sierra Leone during 2014–2016 were reviewed. Results Three cases of recrudescence were suspected to have been caused by sexual contact with survivors, one to be due to international migration, and one was linked to a potentially immunocompromised mother. The three sexual transmission events involving survivors—the first two in Liberia and one in Sierra Leone—required 164 days, >150 days, and approximately 180 days, respectively, from discharge of the survivors to confirmation of the recrudescent case. Conclusions The events of recrudescence were associated with relatively uncommon routes of transmission other than close contact during burial or care-giving, including sexual transmission, possible immunocompromise, and migration. Recognition of the sexual transmission risk among survivors could potentially involve discrimination, which may lead to under-ascertainment.


title: Idiopathic sterile pyogranuloma in three domestic cats

text: Pyogranulomatous inflammation has been extensively described in cats, in particular in cases of feline infectious peritonitis and also associated with Mycobacteria, Actinomyces, Nocardia, Rhodococcus and fungal infections. Idiopathic sterile pyogranulomatous dermatitis has also been described. In this case series we describe the clinical presentation, histopathology and outcome of three cases of feline idiopathic sterile steroid‐responsive pyogranuloma with different presentation and different locations of the lesion, but with the common feature of having a mass with no superficial skin involvement.


title: Comprehensive Identification and Isolation Policies Have Effectively Suppressed the Spread of COVID-19

text: The outbreak of COVID-19 has caused severe life and economic damage worldwide. Since the absence of medical resources or targeted therapeutics, systemic containment policies have been prioritized but some critics query what extent can they mitigate this pandemic. We construct a fine-grained transmission dynamics model to forecast the crucial information of public concern, therein using dynamical coefficients to quantify the impact of the implement schedule and intensity of the containment policies on the spread of epidemic. Statistical evidences show the comprehensive identification and quarantine policies eminently contributed to reduce casualties during the phase of a dramatic increase in diagnosed cases in Wuhan and postponing or weakening such policies would undoubtedly exacerbate the epidemic. Hence we suggest that governments should swiftly execute the forceful public health interventions in the initial stage until the pandemic is blocked.


title: Modulation of metabolic functions through Cas13d-mediated gene knockdown in liver

text: RNA knockdown in vivo carries significant potential for disease modelings and therapies. Despite the emerging approaches of CRISPR/Cas9-mediated permanent knock out of targeted genes, strategies targeting RNA for disruption are advantageous in the treatment of acquired metabolic disorders when permanent modification of the genome DNA is not appropriate, and RNA virus infection diseases when pathogenic DNA is not available (such as SARS-Cov-2 and MERS infections). Recently, Cas13d, a family of RNA-targeting CRISPR effectors, has been shown to accomplish robust down-regulation of cellular RNAs in mammalian cells in vitro. Among the various Cas13d subtypes, CasRx (RfxCas13d) showed the most potent RNA knockdown efficiency in HEK293T cells. However, the RNA-targeting activity of Cas13d still needs to be verified in vivo. In this study, the CasRx system was demonstrated to efficiently and functionally knock down genes related to metabolism functions, including Pten, Pcsk9 and lncLstr, in mouse hepatocytes. CasRx-mediated simultaneous knockdown of multiple genes was also achieved by sgRNA arrays, providing a useful strategy to modulate complex metabolism networks. Moreover, the AAV (adeno-associated virus)-mediated delivery of CasRx and Pcsk9 sgRNAs into mouse liver successfully decreased serum PCSK9, resulting in significant reduction of serum cholesterol levels. Importantly, CasRx-mediated knockdown of Pcsk9 is reversible and Pcsk9 could be repeatedly down-regulated, providing an effective strategy to reversibly modulate metabolic genes. The present work supplies a successful proof-of-concept trial that suggests efficient and regulatory knockdown of target metabolic genes for a designed metabolism modulation in the liver.


title: Determination of microsomal lauric acid hydroxylase activity by HPLC with flow-through radiochemical quantitation

text: Abstract An assay for the microsomal hydroxylation of lauric acid (LA), based on HPLC with flow-through radiochemical detection, has been developed. Conditions were optimized for resolution and quantitation of three microsomal metabolites of LA, one of which has not been reported previously as a metabolite of LA in mammalian microsomal incubations. These products, 12-(ω)-hydroxy-LA, 11-(ω-1)-hydroxy-LA, and a novel metabolite, 10-(ω-2)-hydroxy-LA, were isolated by HPLC and identified by gas chromatography/mass spectrometry. In the presence of NADPH, the formation of all three metabolites was linear with time and microsomal protein concentration. Hydrogen peroxide also supported the microsomal metabolism of LA, although the ratio of metabolites was substantially different than that produced by NADPH-supported microsomes. Several biochemical probes (metyrapone, α-naphthoflavone, 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride, and 10-undecynoic acid) were used to dissociate the three LA hydroxylase activities. These experiments suggest that the site-specific hydroxylation [ω-, (ω-1)-, (ω-2)-] of LA may be catalyzed by different isozymes of cytochrome P-450.


title: SAROTUP: Scanner and Reporter of Target-Unrelated Peptides

text: As epitope mimics, mimotopes have been widely utilized in the study of epitope prediction and the development of new diagnostics, therapeutics, and vaccines. Screening the random peptide libraries constructed with phage display or any other surface display technologies provides an efficient and convenient approach to acquire mimotopes. However, target-unrelated peptides creep into mimotopes from time to time through binding to contaminants or other components of the screening system. In this study, we present SAROTUP, a free web tool for scanning, reporting and excluding possible target-unrelated peptides from real mimotopes. Preliminary tests show that SAROTUP is efficient and capable of improving the accuracy of mimotope-based epitope mapping. It is also helpful for the development of mimotope-based diagnostics, therapeutics, and vaccines.


title: Human polyomavirus type six in respiratory samples from hospitalized children with respiratory tract infections in Beijing, China

text: BACKGROUND: HPyV6 is a novel human polyomavirus (HPyV), and neither its natural history nor its prevalence in human disease is well known. Therefore, the epidemiology and phylogenetic status of HPyV6 must be systematically characterized. METHODS: The VP1 gene of HPyV6 was detected with an established TaqMan real-time PCR from nasopharyngeal aspirate specimens collected from hospitalized children with respiratory tract infections. The HPyV6-positive specimens were screened for other common respiratory viruses with real-time PCR assays. RESULTS: The prevalence of HPyV6 was 1.7 % (15/887), and children ≤ 5 years of age accounted for 80 % (12/15) of cases. All 15 HPyV6-positive patients were coinfected with other respiratory viruses, of which influenza virus A (IFVA) (8/15, 53.3 %) and respiratory syncytial virus (7/15, 46.7 %) were most common. All 15 HPyV6-positive patients were diagnosed with lower respiratory tract infections, and their viral loads ranged from 1.38 to 182.42 copies/μl nasopharyngeal aspirate specimen. The most common symptoms were cough (100 %) and fever (86.7 %). The complete 4926-bp genome (BJ376 strain, GenBank accession number KM387421) was amplified and showed 100 % identity to HPyV6 strain 607a. CONCLUSIONS: The prevalence of HPyV6 was 1.7 % in nasopharyngeal aspirate specimens from hospitalized children with respiratory tract infections, as analyzed by real-time PCR. Because the coinfection rate was high and the viral load low, it was not possible to establish a correlation between HPyV6 and respiratory diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0390-5) contains supplementary material, which is available to authorized users.


docid: tmdljsao

title: Respiratory infections in elderly people: Viral role in a resident population of elderly care centers in Lisbon, winter 2013–2014

text: Abstract Objective The aim of this study was to analyze the etiology and clinical consequences of viral respiratory infections in 18 elderly care centers (ECC) in Lisbon, which housed a total of 1022 residents. Methods Nasopharyngeal swabs were collected whenever an elderly had symptoms of acute respiratory infections (ARI). PCR and RT-PCR were performed for influenza A/B, human parainfluenza virus 1–4, adenovirus, human metapneumovirus (HMPV), respiratory syncytial virus (RSV), rhinovirus, enterovirus, human coronavirus and human Bocavirus (HBoV). Array cards for atypical bacteria were also used in severe cases. Results In total, 188 episodes of ARI were reported, being rhinovirus the most frequently detected (n=53), followed by influenza A(H3) (n=19) and HBoV (n=14). Severe infections were reported in 19 patients, 11 of which were fatal, Legionela pneumophila, rhinovirus, HMPV and RSV associated with these fatalities. Nine influenza strains were analyzed, all antigenically dissimilar from vaccine strain 2013/14. “Age”, “HMPV” and “Respiratory disease” showed an association with severe infection. Conclusions In this study an etiologic agent could be found in 60% of the acute respiratory episodes. These data provides information about the circulating viruses in ECC and highlights the importance of searching both viruses and atypical bacteria in severe ARI.


docid: jlhykfbf

title: Phosphatidylserine treatment relieves the block to retrovirus infection of cells expressing glycosylated virus receptors

text: BACKGROUND: A major determinant of retrovirus host range is the presence or absence of appropriate cell-surface receptors required for virus entry. Often orthologs of functional receptors are present in a wide range of species, but amino acid differences can render these receptors non-functional. In some cases amino acid differences result in additional N-linked glycosylation that blocks virus infection. The latter block to retrovirus infection can be overcome by treatment of cells with compounds such as tunicamycin, which prevent the addition of N-linked oligosaccharides. RESULTS: We have discovered that treatment of cells with liposomes composed of phosphatidylserine (PS) can also overcome the block to infection mediated by N-linked glycosylation. Importantly, this effect occurs without apparent change in the glycosylation state of the receptors for these viruses. This effect occurs with delayed kinetics compared to previous results showing enhancement of virus infection by PS treatment of cells expressing functional virus receptors. CONCLUSION: We have demonstrated that PS treatment can relieve the block to retrovirus infection of cells expressing retroviral receptors that have been rendered non-functional by glycosylation. These findings have important implications for the current model describing inhibition of virus entry by receptor glycosylation.


Searching for a traumatic brain injury biomarker to aid clinical decision making in the Emergency Department


title: The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope glycoproteins

text: OBJECTIVES: Many enveloped viruses carry carbohydrate-containing proteins on their surface. These glycoproteins are key to the infection process as they are mediators of the receptor binding and membrane fusion of the virion with the host cell. Therefore, they are attractive therapeutic targets for the development of novel antiviral therapies. Recently, carbohydrate-binding agents (CBA) were shown to possess antiviral activity towards coronaviruses. The current study further elucidates the inhibitory mode of action of CBA. METHODS: Different strains of two coronaviruses, mouse hepatitis virus and feline infectious peritonitis virus, were exposed to CBA: the plant lectins Galanthus nivalis agglutinin, Hippeastrum hybrid agglutinin and Urtica dioica agglutinin (UDA) and the non-peptidic mannose-binding antibiotic pradimicin A. RESULTS AND CONCLUSIONS: Our results indicate that CBA target the two glycosylated envelope glycoproteins, the spike (S) and membrane (M) protein, of mouse hepatitis virus and feline infectious peritonitis virus. Furthermore, CBA did not inhibit virus–cell attachment, but rather affected virus entry at a post-binding stage. The sensitivity of coronaviruses towards CBA was shown to be dependent on the processing of the N-linked carbohydrates. Inhibition of mannosidases in host cells rendered the progeny viruses more sensitive to the mannose-binding agents and even to the N-acetylglucosamine-binding UDA. In addition, inhibition of coronaviruses was shown to be dependent on the cell-type used to grow the virus stocks. All together, these results show that CBA exhibit promising capabilities to inhibit coronavirus infections.


Akute infektiöse Diarrhoe


title: Mice protected by oral immunization with Lactobacillus reuteri secreting fusion protein of Escherichia coli enterotoxin subunit protein

text: A green fluorescent protein (gfp) gene was ligated to the Lactobacillus reuteri-specific nisin-inducible expression-secretion vector pNIES, generating a pNIES-GFP vector capable of secreting the cloned gene as a GFP-fusion protein with fluorescent activity. To develop this system as a live vehicle carrying the heat-stable enterotoxin (ST) and heat-labile enterotoxin B (LT(B)) of the enterotoxigenic Escherichia coli (ETEC), a recombinant 5′-ST-LT(B)-3′ DNA fragment was cloned into pNIES-GFP. The resulting L. reuteri/pNIES-GFP:STLT(B) system was found to possess the capability of adhering to the mice gut, secreting GFP:STLT(B) product at 0.14 and 0.026 pgcell(−1) under induced and noninduced conditions, respectively. Further analysis of the GFP:STLT(B) product confirmed its ganglioside-binding ability, LT(B) antigenicity and relative freedom from the ST-associated toxicity, making it suitable for use as an oral vaccine in mice. Oral inoculation of the L. reuteri/pNIES-GFP:STLT(B) culture in mice elicited significant (P<0.01) serum IgG and mucosal IgA antibodies against the STLT(B) antigen. These immunized mice were subsequently challenged with ETEC and showed full protection against the fluid influx response in the gut. This is the first report of using L. reuteri as a vaccine carrier to induce complete immunologic protection against ETEC.


title: Web-based electronic patient records for collaborative medical applications

text: Abstract We developed a web-based system to interactively display electronic patient records (EPR), such as DICOM images, graphics, and structure reports and therapy records, for intranet and internet collaborative medical applications. This system has three major components, a C/S (client/server) architecture for EPR data acquisition and authoring, and a Web B/S architecture for data delivering. The Web viewer of this system integrates multi-media display modules and remote control module together to provide interactive EPR display and manipulation functions for collaborative applications. We have successfully used this system two times to provide teleconsultation for severe acute respiratory syndrome (SARS) patients in Shanghai Infection Hospital and Xinhua Hospital. During the consultation, both the physicians in infection control area and the experts outside the control area could use this system interactively to manipulate and navigate the EPR objects of the SARS patients to facilitate a more precise diagnosis. This paper gives a new approach to create and manage image-based EPR from actual patient records, and also presents a novel method to use Web technology and DICOM standard to build an open architecture for collaborative medical applications. The system can be used for both intranet and internet medical applications such as tele-diagnosis, teleconsultation, and distant learning.


COVID-19: an overview of worldwide recommendations for management of patients with liver diseases or liver transplantation


title: Nidovirales: Evolving the largest RNA virus genome

text: Abstract This review focuses on the monophyletic group of animal RNA viruses united in the order Nidovirales. The order includes the distantly related coronaviruses, toroviruses, and roniviruses, which possess the largest known RNA genomes (from 26 to 32kb) and will therefore be called ‘large’ nidoviruses in this review. They are compared with their arterivirus cousins, which also belong to the Nidovirales despite having a much smaller genome (13–16kb). Common and unique features that have been identified for either large or all nidoviruses are outlined. These include the nidovirus genetic plan and genome diversity, the composition of the replicase machinery and virus particles, virus-specific accessory genes, the mechanisms of RNA and protein synthesis, and the origin and evolution of nidoviruses with small and large genomes. Nidoviruses employ single-stranded, polycistronic RNA genomes of positive polarity that direct the synthesis of the subunits of the replicative complex, including the RNA-dependent RNA polymerase and helicase. Replicase gene expression is under the principal control of a ribosomal frameshifting signal and a chymotrypsin-like protease, which is assisted by one or more papain-like proteases. A nested set of subgenomic RNAs is synthesized to express the 3′-proximal ORFs that encode most conserved structural proteins and, in some large nidoviruses, also diverse accessory proteins that may promote virus adaptation to specific hosts. The replicase machinery includes a set of RNA-processing enzymes some of which are unique for either all or large nidoviruses. The acquisition of these enzymes may have improved the low fidelity of RNA replication to allow genome expansion and give rise to the ancestors of small and, subsequently, large nidoviruses.


title: Hip Fracture Outcomes During the COVID-19 Pandemic: Early Results From New York

text: OBJECTIVE: To evaluate inpatient outcomes among patients with hip fracture treated during the COVID-19 pandemic in New York City. DESIGN: Multicenter retrospective cohort study. SETTING: One Level 1 trauma center and one orthopaedic specialty hospital in New York City. PATIENTS/PARTICIPANTS: Fifty-nine consecutive patients (average age 85 years, range: 65–100 years) treated for a hip fracture (OTA/AO 31, 32.1) over a 5-week period, March 20, 2020, to April 24, 2020, during the height of the COVID-19 crisis. MAIN OUTCOME MEASUREMENTS: COVID-19 infection status was used to stratify patients. The primary outcome was inpatient mortality. Secondary outcomes were admission to the intensive care unit, unexpected intubation, pneumonia, deep vein thrombosis, pulmonary embolus, myocardial infarction, cerebrovascular accident, urinary tract infection, and transfusion. Baseline demographics, comorbidities, treatment characteristics, and COVID-related symptomatology were also evaluated. RESULTS: Ten patients (15%) tested positive for COVID-19 (COVID+) (n = 9; 7 preoperatively and 2 postoperatively) or were presumed positive (n = 1), 40 (68%) patients tested negative, and 9 (15%) patients were not tested in the primary hospitalization. American Society of Anesthesiologists' scores were higher in the COVID+ group (d = −0.83; P = 0.04); however, the Charlson Comorbidity Index was similar between the study groups (d = −0.17; P = 0.63). Inpatient mortality was significantly increased in the COVID+ cohort (56% vs. 4%; odds ratio 30.0, 95% confidence interval 4.3–207; P = 0.001). Including the one presumed positive case in the COVID+ cohort increased this difference (60% vs. 2%; odds ratio 72.0, 95% confidence interval 7.9–754; P < 0.001). CONCLUSIONS: Hip fracture patients with concomitant COVID-19 infection had worse American Society of Anesthesiologists' scores but similar baseline comorbidities with significantly higher rates of inpatient mortality compared with those without concomitant COVID-19 infection. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


title: Mandating influenza vaccinations for health care workers: analysing opportunities for policy change using Kingdon’s agenda setting framework

text: BACKGROUND: The consequences of annual influenza outbreaks are often underestimated by the general public. Influenza poses a serious public health threat around the world, particularly for the most vulnerable populations. Fortunately, vaccination can mitigate the negative effects of this common infectious disease. Although inoculating frontline health care workers (HCWs) helps minimize disease transmission, some HCWs continue to resist participating in voluntary immunization programs. A potential solution to this problem is government-mandated vaccination for HCWs; however, in practice, there are substantial barriers to the adoption of such policies. The purpose of this paper is to identify the likelihood of adopting a policy for mandatory immunization of HCWs in Ontario based on a historical review of barriers to the agenda setting process. METHODS: Documents from secondary data sources were analysed using Kingdon’s agenda setting framework of three converging streams leading to windows of opportunity for possible policy adoption. RESULTS: The problems, politics, and policies streams of Kingdon’s framework have converged and diverged repeatedly over an extended period (policy windows have opened and closed several times). In each instance, a technically feasible solution was available. However, despite the evidence supporting the value of HCW immunization, alignment of the three agenda setting streams occurred for very short periods of time, during which, opposition lobby groups reacted, making the proposed solution less politically acceptable. CONCLUSIONS: Prior to the adoption of any new policies, issues must reach a government’s decision agenda. Based on Kingdon’s agenda setting framework, this only occurs when there is alignment of the problems, politics, and policies streams. Understanding this process makes it easier to predict the likelihood of a policy being adopted, and ultimately implemented. Such learning may be applied to policy issues in other jurisdictions. In the case of mandatory influenza vaccinations for HCWs in Ontario, it seems highly unlikely that a new policy will be adopted until perception of the problem’s importance is sufficient to overcome the political opposition to implementing a solution and thus, create a window of opportunity that is open long enough to support change.


title: A duplex real-time RT-PCR assay for the detection of St. Louis encephalitis and Eastern equine encephalitis viruses

text: A duplex TaqMan real-time RT-PCR assay was developed for the detection of St. Louis encephalitis virus (SLEV) and Eastern equine encephalitis virus (EEEV), for use in human and vector surveillance. The respective targets selected for the assay were the conserved NS5 and E1 genes of the two viruses. Due to the insufficient number of NS5 sequences from SLEV strains in the GenBank database, we determined the sequence of an approximately 1-kb region for each of 25 strains of SLEV in order to select primers and probes in a conserved region. Our assay has a sensitivity of 5 gene copies/reaction for EEEV and 10 gene copies/reaction for SLEV, and it’s performance is linear over at least 6 log(10) gene copies. The assay is specific and detected all strains of SLEV (69) and EEEV (12) that were tested. An internal control ensures detection of efficient nucleic acid extraction and possible PCR inhibition.


title: Congruent epidemic models for unstructured and structured populations: Analytical reconstruction of a 2003 SARS outbreak

text: Abstract Both the threat of bioterrorism and the natural emergence of contagious diseases underscore the importance of quantitatively understanding disease transmission in structured human populations. Over the last few years, researchers have advanced the mathematical theory of scale-free networks and used such theoretical advancements in pilot epidemic models. Scale-free contact networks are particularly interesting in the realm of mathematical epidemiology, primarily because these networks may allow meaningfully structured populations to be incorporated in epidemic models at moderate or intermediate levels of complexity. Moreover, a scale-free contact network with node degree correlation is in accord with the well-known preferred mixing concept. The present author describes a semi-empirical and deterministic epidemic modeling approach that (a) focuses on time-varying rates of disease transmission in both unstructured and structured populations and (b) employs probability density functions to characterize disease progression and outbreak controls. Given an epidemic curve for a historical outbreak, this modeling approach calls for Monte Carlo calculations (that define the average new infection rate) and solutions to integro-differential equations (that describe outbreak dynamics in an aggregate population or across all network connectivity classes). Numerical results are obtained for the 2003 SARS outbreak in Taiwan and the dynamical implications of time-varying transmission rates and scale-free contact networks are discussed in some detail.


title: Clinical presentation, diagnostic findings, and outcome of adult horses with equine coronavirus infection at a veterinary teaching hospital: 33 cases (2012–2018)

text: Abstract Equine coronavirus (ECoV) is a recently described enteric virus with worldwide outbreaks; however, there are little data available on clinical presentation, diagnosis, and outcome. The study objective was to document case management of ECoV in adult horses presented to a referral hospital and compare to a cohort of horses that tested negative for ECoV. A retrospective case series was performed based on positive real-time quantitative PCR results for ECoV on faeces from horses treated at the UC Davis Veterinary Medical Teaching Hospital from 1 March 2012 to 31 March 2018. Horses negative for ECoV were matched to the ECoV-positive group as controls. Data collected included signalment, history, exam findings, diagnostics, treatment, and follow-up. Thirty-three horses (median age, 11 years; range, 2–37 years) tested ECoV-positive, including three horses with co-infections. Presenting complaints for ECoV-infected horses included historic fevers (n = 25/30; 83%), anorexia (n = 14/30; 47%), and colic (n = 13/30; 43%). ECoV-positive horses had significantly lower white blood cell (median, 3.0 × 109/L; range, 0.68–16.2 × 109/L), neutrophil (median, 1.26 × 109/L; range, 0.15–14.4 × 109/L), and lymphocyte (median, 0.86 × 109/L; range, 0.42–3.47 × 109/L) counts than ECoV-negative horses. Electrolyte and metabolic derangements and scant faeces were common. Twenty-seven horses were hospitalised for a median of 5 days (range, 0.5–14 days), with 26/27 (96%) horses surviving to discharge. ECoV infection should be a differential diagnosis for adult horses with fever, colic, anorexia, and leukopenia. The disease has a low mortality rate, but horses may require intensive care to resolve severe leukopenia, systemic inflammation, and metabolic disturbances.


title: Improved Prediction of MHC Class I Binders/Non-Binders Peptides Through Artificial Neural Network Using Variable Learning Rate: SARS Corona Virus, a Case Study

text: Fundamental step of an adaptive immune response to pathogen or vaccine is the binding of short peptides (also called epitopes) to major histocompatibility complex (MHC) molecules. The various prediction algorithms are being used to capture the MHC peptide binding preference, allowing the rapid scan of entire pathogen proteomes for peptide likely to bind MHC, saving the cost, effort, and time. However, the number of known binders/non-binders (BNB) to a specific MHC molecule is limited in many cases, which still poses a computational challenge for prediction. The training data should be adequate to predict BNB using any machine learning approach. In this study, variable learning rate has been demonstrated for training artificial neural network and predicting BNB for small datasets. The approach can be used for large datasets as well. The dataset for different MHC class I alleles for SARS Corona virus (Tor2 Replicase polyprotein 1ab) has been used for training and prediction of BNB. A total of 90 datasets (nine different MHC class I alleles with tenfold cross validation) have been retrieved from IEDB database for BNB. For fixed learning rate approach, the best value of AROC is 0.65, and in most of the cases it is 0.5, which shows the poor predictions. In case of variable learning rate, of the 90 datasets the value of AROC for 76 datasets is between 0.806 and 1.0 and for 7 datasets the value is between 0.7 and 0.8 and for rest of 7 datasets it is between 0.5 and 0.7, which indicates very good performance in most of the cases.


title: Caring for children and adolescents with eating disorders in the current COVID-19 pandemic: A Singapore perspective

text: Abstract Our public pediatric tertiary hospital in Singapore has been a part of a robust public heath response to COVID-19 that has been calibrated in a timely manner to the evolving international situation. As of mid-March, Singapore remains in a containment mode with enhanced surveillance and limited community spread. Within this context, our service for pediatric eating disorder care has had to make significant adaptations to our models of service delivery as well as respond to the changing psychosocial needs of our patients. Given infection control requirements, we have instituted modular staffing for our inpatient and outpatient settings, necessitating task shifting and an increased use of technology for communication. Due to reduced outpatient capacity and the need to minimize non-urgent trips to the hospital, we have implemented telemedicine and have leveraged on partnerships with school counselors and other community partners. “Coronaphobia” has influenced our patients’ willingness to attend visits and worsened existing health anxiety for some. Responsiveness to families’ and patients’ health and financial concerns has been essential. As COVID-19 impacts more countries, our institution’s experience can provide insight into challenges and possible adaptations to providing ongoing care for eating disorder patients in this environment.


A clear 'wake-up call' from Korea


HIPERTENSIÓN Y COVID 19: CUIDADOS CON LOS MANGUITOS DE PRESIÓN ARTERIAL


title: Naringenin, a flavanone with antiviral and anti‐inflammatory effects: A promising treatment strategy against COVID‐19

text: At the end of 2019, a novel flu‐like coronavirus named COVID‐19 (coronavirus disease 2019) was recognized by World Health Organization. No specific treatments exist for COVID‐19 at this time. New evidence suggests that therapeutic options focusing on antiviral agents may alleviate COVID‐19 symptoms as well as those that lead to the decrease in the inflammatory responses. Flavonoids, as phenolic compounds, have attracted considerable attention due to their various biological properties. In this review, the promising effects and possible mechanisms of action of naringenin, a citrus‐derived flavonoid, against COVID‐19 were discussed. We searched PubMed/Medline, Science direct, Scopus, and Google Scholar databases up to March 2020 using the definitive keywords. The evidence reviewed here indicates that naringenin might exert therapeutic effects against COVID‐19 through the inhibition of COVID‐19 main protease, 3‐chymotrypsin‐like protease (3CLpro), and reduction of angiotensin converting enzyme receptors activity. One of the other mechanisms by which naringenin might exert therapeutic effects against COVID‐19 is, at least partly, by attenuating inflammatory responses. The antiviral activity of the flavanone naringenin against some viruses has also been reported. On the whole, the favorable effects of naringenin lead to a conclusion that naringenin may be a promising treatment strategy against COVID‐19.


title: Environmental Contamination and Viral Shedding in MERS Patients During MERS-CoV Outbreak in South Korea

text: Background. Although Middle East Respiratory Syndrome coronavirus (MERS-CoV) is characterized by a risk of nosocomial transmission, the detailed mode of transmission and period of virus shedding from infected patients are poorly understood. The aims of this study were to investigate the potential role of environmental contamination by MERS-CoV in healthcare settings and to define the period of viable virus shedding from MERS patients. Methods. We investigated environmental contamination from 4 patients in MERS-CoV units of 2 hospitals. MERS-CoV was detected by reverse transcription polymerase chain reaction (PCR) and viable virus was isolated by cultures. Results. Many environmental surfaces of MERS patient rooms, including points frequently touched by patients or healthcare workers, were contaminated by MERS-CoV. Viral RNA was detected up to five days from environmental surfaces following the last positive PCR from patients’ respiratory specimens. MERS-CoV RNA was detected in samples from anterooms, medical devices, and air-ventilating equipment. In addition, MERS-CoV was isolated from environmental objects such as bed sheets, bedrails, IV fluid hangers, and X-ray devices. During the late clinical phase of MERS, viable virus could be isolated in 3 of the 4 enrolled patients on day 18 to day 25 after symptom onset. Conclusions. Most of touchable surfaces in MERS units were contaminated by patients and health care workers and the viable virus could shed through respiratory secretion from clinically fully recovered patients. These results emphasize the need for strict environmental surface hygiene practices, and sufficient isolation period based on laboratory results rather than solely on clinical symptoms.


title: Antisense downregulation of SARS‐CoV gene expression in Vero E6 cells

text: BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS‐CoV). It is an enveloped, single‐stranded, plus‐sense RNA virus with a genome of ∼30 kb. The structural proteins E, M and N of SARS‐CoV play important roles during host cell entry and viral morphogenesis and release. Therefore, we have studied whether expression of these structural proteins can be down‐regulated using an antisense technique. METHODS: Vero E6 cells were transfected with plasmid constructs containing exons of the SARS‐CoV structural protein E, M or N genes or their exons in frame with the reporter protein EGFP. The transfected cell cultures were treated with antisense phosphorothioated oligonucleotides (antisense PS‐ODN, 20mer) or a control oligonucleotide by addition to the culture medium. RESULTS: Among a total of 26 antisense PS‐ODNs targeting E, M and N genes, we obtained six antisense PS‐ODNs which could sequence‐specifically reduce target genes expression by over 90% at the concentration of 50 µM in the cell culture medium tested by RT‐PCR. The antisense effect was further proved by down‐regulating the expression of the fusion proteins containing the structural proteins E, M or N in frame with the reporter protein EGFP. In Vero E6 cells, the antisense effect was dependent on the concentrations of the antisense PS‐ODNs in a range of 0–10 µM or 0–30 µM. CONCLUSIONS: The antisense PS‐ODNs are effective in downregulation of SARS. The findings indicate that antisense knockdown of SARS could be a useful strategy for treatment of SARS, and could also be suitable for studies of the pathological function of SARS genes in a cellular model system. Copyright © 2004 John Wiley & Sons, Ltd.


title: Development and application of an indirect ELISA for the detection of antibodies to porcine epidemic diarrhea virus based on a recombinant spike protein

text: BACKGROUND: As the major causative agent of swine viral diarrhea, porcine epidemic diarrhea virus (PEDV) has caused massive losses to the economies of swine raising countries. Accordingly, the serological detection of corresponding antibodies would be beneficial to diagnose PEDV indirectly to control the disease. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) based on the recombinant truncated spike (S) protein of PEDV was developed and validated. RESULTS: The reaction conditions of the developed indirect ELISA were optimized. This indirect ELISA was compared to indirect immunoinfluscent assay (IFA), and the overall coincidence rate was 96.74% based on testing 368 clinical serum samples with different PEDV antibody levels. No cross-reactivity with other common swine pathogens was detected for the developed S1 indirect ELISA. Finally, the S1 indirect ELISA was applied to detect serum antibodies of 3304 field samples collected from different pig farms in eastern China, and it presented an overall substantial agreement on the PEDV infection status. CONCLUSIONS: This established S1 indirect ELISA is capable of detecting serum antibodies against PEDV, and due to its high sensitivity and specificity, it could be applied for serological evaluation and indirect diagnosis of PEDV infection.


title: Detection and characterization of subgenomic RNAs in hepatitis A virus particles

text: Abstract Defective viral particles containing deleted genomes were detected in harvests of cell cultures infected with various HAV isolates. The most prominent deletions were identified within the region of the genome coding for structural proteins. In this location three different deletions spanning nts 930–4380 (A), 1140–3820 (B), and 1370–3240 (C) were characterized. In addition to these internal deletions, various truncated RNAs were detected lacking either partially or completely the 3′ terminal region which is supposed to code for viral replicase. RNA molecules with internal deletions as well as those with 3′ terminal truncations could also be extracted directly from infected cells. During multiple consecutive passages of a given HAV strain, deletions A, B, and C accumulated and a quantitative increase of deleted RNAs occurred. Type and predominance of deletions varied with virus strains (CLF, GBM, MBB11/5, HM175, CR326, H141) and with the type of cells used for propagation (MRC-5, BGM, HELF, PLC/PRF/5). However, within the limits of the reliability of S1 analysis the endpoints of deletions A, B, and C were conserved. The mechanisms leading to formation of deletions remain unclear. Yet, some sequences flanking internal deletions showed homology with common splice signals and 3′ terminal truncations proved to be confined to a distinct region within the genome.


title: Clinical characteristics and diagnostic challenges of pediatric COVID-19: A systematic review and meta-analysis

text: Background/Purpose Current studies on pediatric coronavirus disease 2019 (COVID-19) are rare. The clinical characteristics and spectrum are still unknown. Facing this unknown and emerging pathogen, we aimed to collect current evidence about COVID-19 in children. Methods We performed a systematic review in PubMed and Embase to find relevant case series. Because some reports were published in Chinese journals, the journals and publications of the Chinese Medical Association related to COVID-19 were completely reviewed. A random effects model was used to pool clinical data in the meta-analysis. Results Nine case series were included. In the pooled data, most of patients (75%) had a household contact history. The disease severity was mainly mild to moderate (98%). Only 2 children (2%) received intensive care. Fever occurred in 59% of the patients, while cough in 46%. Gastrointestinal symptoms (12%) were uncommon. There are 26% children are asymptomatic. The most common radiographic finding was ground glass opacities (48%). Currently, there is no evidence of vertical transmission to neonates born to mothers with COVID-19. Compared with the most relevant virus, SARS-CoV, SARS-CoV-2 causes less severe disease. Conclusion COVID-19 has distinct features in children. The disease severity is mild. Current diagnosis is based mainly on typical ground glass opacities on chest CT, epidemiological suspicion and contact tracing.


title: Laparoscopic-assisted myomectomy with uterine artery occlusion at a freestanding ambulatory surgery center: a case series

text: BACKGROUND: Non-hysteroscopic myomectomy is infrequently performed in a freestanding ambulatory setting, in part due to risks of intraoperative hemorrhage. There are also concerns about increased surgical risks for morbidly obese patients in this setting. The purpose of this study is to report the surgical outcomes of a series of laparoscopic-assisted myomectomy (LAM) cases at a freestanding ambulatory surgery center (ASC), including a comparative analysis of outcomes in morbidly obese patients (BMI > 40 kg/m(2)). METHODS: A retrospective comparative analysis was performed of 969 women, age 18 years or older, non-pregnant, who underwent LAM by one of two high volume, laparoscopic gynecologic surgical specialists at a freestanding ambulatory surgery center serving the Washington, DC area, between October 2013 and February 2019. Reversible occlusion was performed laparoscopically by placing a latex-based rubber catheter as a tourniquet around the isthmus of the uterus, causing a temporary occlusion of the bilateral uterine arteries. Permanent occlusion was performed laparoscopically via retroperitoneal dissection and uterine artery ligation at the origin of the anterior branch of the internal iliac artery. Minilaparotomy was performed for specimen removal in all cases. No power morcellation was used. Postoperative complications were graded using the Clavien-Dindo Classification system. Outcomes were compared across BMI categories using Pearson Chi-Square. RESULTS: Average myoma weight and size were 422.7 g and 8.3 cm, respectively. Average estimated blood loss (EBL) was 192.1 mL; intraoperative and grade 3 postoperative complication rates were 1.4% and 1.6%, respectively. While EBL was significantly higher in obese and morbidly obese patients, this difference was not clinically meaningful, with no significant difference in blood transfusion rates. There were no statistically significant intraoperative or postoperative complication rates across BMI categories. There was a low rate of hospital transfers (0.7%) for all patients. CONCLUSION: Laparoscopic-assisted myomectomy can be performed safely in a freestanding ambulatory surgery setting, including morbidly obese patients. This is especially important in the age of COVID-19, as elective surgeries have been postponed due to the 2020 pandemic, which may lead to a dramatic and permanent shift of outpatient surgery from the hospital to the ASC setting.


SARS-CoV-2: a new virus but a familiar inflammation brain pattern


Selective C‐reactive protein (CRP) apheresis for Covid‐19 patients suffering from organ damage


title: COVID-19 among community pharmacists during the 2020 SARS-CoV-2 outbreak in Italy: Results from a cross-sectional survey

text: INTRODUCTION: Since the beginning of the 2020 Sars-CoV-2 Italian outbreak, healthcare workers have been among the most exposed categories. There is little information about community pharmacists’ on occupational exposure, symptoms development, and testing practices in the community pharmacist cohort. METHODS: Between April 30th and May 10th, a questionnaire was administered through social media to Italian community pharmacists. From 67000 pharmacists currently working in community pharmacies, 1632 answered the survey. RESULTS: The survey population reflected the general Italian community pharmacists population in terms of age, gender, and number of co-workers. Protective measures were adopted in up to 99.9% of pharmacies. 624 pharmacists (38.2%) developed at least one COVID-19 related symptom in the period between February 28th and May 10th. Also, 102 pharmacists (6.2%) were tested for COVID-19 and 15, the 15% of the tested population and 0.92% of the whole survey population, resulted positive on nasopharyngeal swab. However, while the number of symptomatic pharmacists decreased, a higher number of tests were performed, thus COVID-19 prevalence among community pharmacists could have been underestimated and is probably intermediate between other healthcare workers and the general population (0.31%). CONCLUSION: Community pharmacists have probably been one of the first categories to experience increased contact risk to SARS-CoV-2. COVID-19 prevalence among pharmacists could have been underestimated. In addition, the rates of protection measures adoption might have helped to reduce the spread of COVID-19 among co-workers and the community.


title: Respiratory viral pathogens among Singapore military servicemen 2009 – 2012: epidemiology and clinical characteristics

text: BACKGROUND: Few studies have comprehensively described tropical respiratory disease surveillance in military populations. There is also a lack of studies comparing clinical characteristics of the non-influenza pathogens with influenza and amongst themselves. METHODS: From May 2009 through October 2012, 7733 consenting cases of febrile respiratory illness (FRI) (temperature [greater than or equal to]37.5degreesC with cough or sorethroat) and controls in the Singapore military had clinical data and nasal washes collected prospectively. Nasal washes underwent multiplex PCR, and the analysis was limited to viral mono-infections. RESULTS: 49% of cases tested positive for at least one virus, of whom 10% had multiple infections. 53% of the FRI cases fulfilled the definition of influenza-like illness (ILI), of whom 52% were positive for at least one virus. The most frequent etiologies for mono-infections among FRI cases were Influenza A(H1N1)pdm09 (13%), Influenza B (13%) and coxsackevirus (9%). The sensitivity, specificity, positive predictive value and negative predictive value of ILI for influenza among FRI cases were 72%, 48%, 40% and 69% respectively. On logistic regression, there were marked differences in the prevalence of different symptoms and signs between viruses with fever more prevalent amongst influenza and adenovirus infections than other viruses. CONCLUSION: There are multiple viral etiologies for FRI and ILI with differing clinical symptoms in the Singapore military. Influenza and coxsackevirus were the most common etiology for FRI, while influenza and adenoviruses displayed the most febrile symptoms. Further studies should explore these differences and possible interventions.


title: Exacerbations asthmatiques : spécificités pédiatriques (en dehors du traitement)

text: Résumé L’asthme aurait déjà concerné plus de 10 % des enfants âgés de dix ans. Ce constat mérite une discussion pneumopédiatrique à part entière. Malgré des similitudes entre l’asthme de l’adulte et celui de l’enfant, la population pédiatrique présente certaines spécificités notamment concernant les exacerbations. L’asthme du nourrisson est une entité particulière dont la définition a bénéficié récemment d’une mise à jour officielle. Les étiologies d’exacerbations asthmatiques restent les infections, avec en tête les virus dont le typage joue un rôle pronostique. L’environnement intérieur et extérieur peut aggraver l’asthme, notamment par de fortes concentrations de polluants atmosphériques. Les nutriments semblent jouer un rôle pronostique par le biais de la vitamine D ou de la présence d’allergie alimentaire. La recherche de facteurs prédictifs ou de marqueurs inflammatoires de l’asthme est la clé de voûte pour la maîtrise de ces exacerbations, mais les techniques actuelles ne sont pas encore totalement performantes comme la mesure de l’oxyde nitrique exhalé (eNO), l’étude des crachats/exhalas ou encore de simples questionnaires. La prise en charge précoce et continue avec l’éducation thérapeutique des enfants et de leur famille demeure un outil efficace en termes de prévention de rechute des exacerbations. Summary Asthma concerns more than 10% of 10-year-old children. Despite the similarities between adult and childhood asthma, the pediatric population presents some specific characteristics, notably in relation to exacerbations. Asthma in the newborn infant is a specific entity, the definition of which has recently been officially recognized. In exacerbations, the most important trigger factors are respiratory virus infections, the strain having prognostic importance. The indoor and outdoor environments are risk factors, particularly high levels of atmospheric pollution. Nutrients seem to play a prognostic role through vitamin D or food allergy. Measurement of exhaled nitric oxide and examination of induced sputum may help in diagnosis and adjustment of treatment but these tools are not yet effective as predictive factors in asthma exacerbations. Prevention, early management and continued education of children and their families remain the best methods to improve asthma control.


Miocarditis fulminante por COVID-19


title: A Novel Mechanism Underlying the Innate Immune Response Induction upon Viral-Dependent Replication of Host Cell mRNA: A Mistake of +sRNA Viruses' Replicases

text: Viruses are lifeless particles designed for setting virus-host interactome assuring a new generation of virions for dissemination. This interactome generates a pressure on host organisms evolving mechanisms to neutralize viral infection, which places the pressure back onto virus, a process known as virus-host cell co-evolution. Positive-single stranded RNA (+sRNA) viruses are an important group of viral agents illustrating this interesting phenomenon. During replication, their genomic +sRNA is employed as template for translation of viral proteins; among them the RNA-dependent RNA polymerase (RdRp) is responsible of viral genome replication originating double-strand RNA molecules (dsRNA) as intermediates, which accumulate representing a potent threat for cellular dsRNA receptors to initiate an antiviral response. A common feature shared by these viruses is their ability to rearrange cellular membranes to serve as platforms for genome replication and assembly of new virions, supporting replication efficiency increase by concentrating critical factors and protecting the viral genome from host anti-viral systems. This review summarizes current knowledge regarding cellular dsRNA receptors and describes prototype viruses developing replication niches inside rearranged membranes. However, for several viral agents it's been observed both, a complex rearrangement of cellular membranes and a strong innate immune antiviral response induction. So, we have included recent data explaining the mechanism by, even though viruses have evolved elegant hideouts, host cells are still able to develop dsRNA receptors-dependent antiviral response.


title: Acute Respiratory Tract Infection in Daycare Centers for Older Persons

text: OBJECTIVE: To evaluate the rate of specific pathogens and clinical syndromes associated with acute respiratory tract infections (ARTI) in frail older persons attending daycare. DESIGN: Prospective descriptive study, without intervention. SETTING: Two sites of a senior daycare program providing all‐inclusive care for the older persons in Rochester, New York. PARTICIPANTS: Staff members and participants of the daycare. MEASUREMENTS: Demographic, medical, and physical findings were collected from older subjects at baseline and while ill with respiratory illnesses. Nasopharyngeal specimens for viral and Chlamydia culture and sputum for bacterial culture were obtained from subjects when ill. Acute and convalescent sera were also collected with each illness and examined for viral, chlamydial, and mycoplasma infection. MAIN RESULTS: One hundred sixty‐five illnesses were documented in 165 older daycare participants as well as 113 illnesses among 67 staff members during the 15‐month study. The rate of ARTI in the elderly group was 10.8 per 100 person months. The most common etiologies in both the staff and elderly participants were respiratory syncytial virus (RSV), Influenza A, and coronavirus. The etiologies of illnesses in the staff compared with those in elderly group were similar except that bacterial infections were significantly more common among the elderly (7% vs. 0, P = 0.05). Multiple pathogens were found to cocirculate within centers, and no clear outbreak of a predominant organism was noted. Cough and nasal congestion characterized most illnesses. The elderly experienced significantly more cough, dyspnea, and sputum production than did the staff. There were 10 hospitalizations related to respiratory infections and four deaths during the acute illness among the elderly group and none in staff. CONCLUSIONS: Acute respiratory infections are a common occurrence in both the staff and participants of a senior daycare center and are the cause of substantial morbidity in frail older persons.


title: Antivirals become a broader enterprise

text: Small molecules have dominated antivirals for decades, but other approaches are needed and biologics could show the way.


title: Effect of stochasticity on coinfection dynamics of respiratory viruses

text: BACKGROUND: Respiratory viral infections are a leading cause of mortality worldwide. As many as 40% of patients hospitalized with influenza-like illness are reported to be infected with more than one type of virus. However, it is not clear whether these infections are more severe than single viral infections. Mathematical models can be used to help us understand the dynamics of respiratory viral coinfections and their impact on the severity of the illness. Most models of viral infections use ordinary differential equations (ODE) that reproduce the average behavior of the infection, however, they might be inaccurate in predicting certain events because of the stochastic nature of viral replication cycle. Stochastic simulations of single virus infections have shown that there is an extinction probability that depends on the size of the initial viral inoculum and parameters that describe virus-cell interactions. Thus the coinfection dynamics predicted by the ODE might be difficult to observe in reality. RESULTS: In this work, a continuous-time Markov chain (CTMC) model is formulated to investigate probabilistic outcomes of coinfections. This CTMC model is based on our previous coinfection model, expressed in terms of a system of ordinary differential equations. Using the Gillespie method for stochastic simulation, we examine whether stochastic effects early in the infection can alter which virus dominates the infection. CONCLUSIONS: We derive extinction probabilities for each virus individually as well as for the infection as a whole. We find that unlike the prediction of the ODE model, for similar initial growth rates stochasticity allows for a slower growing virus to out-compete a faster growing virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2793-6) contains supplementary material, which is available to authorized users.


To cite this article: Turchiarelli V, Schinkel J, Molenkamp R, Foschino Barbaro MP, Carpagnano GE, Spanevello A, Lutter R, Bel EH, Sterk PJ. Repeated virus identification in the airways of patients with mild and severe asthma during prospective follow‐up. Allergy 2011; 66: 1099–1106. ABSTRACT: Background: Respiratory viruses may persist in the airways of asthmatics between episodes of clinical worsening. We hypothesized that patients with clinically stable, severe asthma exhibit increased and more prolonged viral presence in the airways as compared to mild asthmatics and healthy controls. Methods: Thirty‐five subjects (no cold symptoms >4 weeks) entered a 12‐week prospective study using three groups: clinically stable mild asthma (GINA 2) (n = 12, age 34.1 ± 13.4 year), severe asthma (GINA 4) (n = 12, age 49.3 ± 14.8 year) and healthy controls (n = 11, age 37.9 ± 14.2 year). All subjects underwent spirometry and completed a written questionnaire on asthma symptoms at baseline. Nasal and throat swabs, induced sputum samples, exhaled breath condensate and gelatine‐filtered expired air were analysed at 0, 6 and 12 weeks by a multiplex real‐time PCR assay for 14 respiratory viruses using adequate positive and negative controls. Results: Thirty‐two of 525 patient assessments (6%) showed a virus‐positive sample. Among the 14 respiratory viruses examined, HRV, adenovirus, respiratory syncytial virus, parainfluenza 3&4, human bocavirus, influenza B and coronavirus were detected. When combining all sampling methods, on average 18% of controls and 30% of mild and severe asthmatics were virus positive, which was not different between the groups (P = 0.34). The longitudinal data showed a changing rather than persistent viral presence over time. Conclusion: Patients with clinically stable asthma and healthy controls have similar detection rates of respiratory viruses in samples from nasopharynx, sputum and exhaled air. This indicates that viral presence in the airways of stable (severe) asthmatics varies over time rather than being persistent.


title: SARS coronavirus E protein forms cation-selective ion channels

text: Abstract Severe Acute Respiratory Syndrome (SARS) is caused by a novel coronavirus (SARS-CoV). Coronaviruses including SARS-CoV encode an envelope (E) protein, a small, hydrophobic membrane protein. We report that, in planar lipid bilayers, synthetic peptides corresponding to the SARS-CoV E protein forms ion channels that are more permeable to monovalent cations than to monovalent anions. Affinity-purified polyclonal antibodies recognizing the N-terminal 19 residues of SARS-CoV E protein were used to establish the specificity of channel formation by inhibiting the ion currents generated in the presence of the E protein peptides.


title: Bilateral spontaneous pneumothorax in SARS-CoV-2 infection: A very rare, life-threatening complication

text: In the coronavirus disease 2019 (COVID-19) era, the presence of acute respiratory failure is generally associated with acute respiratory distress syndrome; however, it is essential to consider other differential diagnoses that require different, and urgent, therapeutic approaches. Herein we describe a COVID-19 case complicated with bilateral spontaneous pneumothorax. A previously healthy 45-year-old man was admitted to our emergency department with sudden-onset chest pain and progressive shortness of breath 17 days after diagnosis with uncomplicated COVID-19 infection. He was tachypneic and presented severe hypoxemia (75% percutaneous oxygen saturation). Breath sounds were diminished bilaterally on auscultation. A chest X-ray revealed the presence of a large bilateral pneumothorax. A thoracic computed tomography (CT) scan confirmed the large bilateral pneumothorax, with findings consistent with severe COVID-19 infection. Chest tubes were inserted, with immediate clinical improvement. Follow-up chest CT scan revealed resolution of bilateral pneumothorax, reduction of parenchymal consolidation, and formation of large bilateral pneumatoceles. The patient remained under observation and was then discharged home. Bilateral spontaneous pneumothorax is a very rare, potentially life-threatening complication in patients with COVID-19. This case highlights the importance of recognizing this complication early to prevent potentially fatal consequences.


title: Membrane-associated zinc peptidase families: comparing ACE and ACE2

text: Abstract In contrast to the relatively ubiquitous angiotensin-converting enzyme (ACE), expression of the mammalian ACE homologue, ACE2, was initially described in the heart, kidney and testis. ACE2 is a type I integral membrane protein with its active site domain exposed to the extracellular surface of endothelial cells and the renal tubular epithelium. Here ACE2 is poised to metabolise circulating peptides which may include angiotensin II, a potent vasoconstrictor and the product of angiotensin I cleavage by ACE. To this end, ACE2 may counterbalance the effects of ACE within the renin–angiotensin system (RAS). Indeed, ACE2 has been implicated in the regulation of heart and renal function where it is proposed to control the levels of angiotensin II relative to its hypotensive metabolite, angiotensin-(1–7). The recent solution of the structure of ACE2, and ACE, has provided new insight into the substrate and inhibitor profiles of these two key regulators of the RAS. As the complexity of this crucial pathway is unravelled, there is a growing interest in the therapeutic potential of agents that modulate the activity of ACE2.


title: iPPBS-Opt: A Sequence-Based Ensemble Classifier for Identifying Protein-Protein Binding Sites by Optimizing Imbalanced Training Datasets

text: Knowledge of protein-protein interactions and their binding sites is indispensable for in-depth understanding of the networks in living cells. With the avalanche of protein sequences generated in the postgenomic age, it is critical to develop computational methods for identifying in a timely fashion the protein-protein binding sites (PPBSs) based on the sequence information alone because the information obtained by this way can be used for both biomedical research and drug development. To address such a challenge, we have proposed a new predictor, called iPPBS-Opt, in which we have used: (1) the K-Nearest Neighbors Cleaning (KNNC) and Inserting Hypothetical Training Samples (IHTS) treatments to optimize the training dataset; (2) the ensemble voting approach to select the most relevant features; and (3) the stationary wavelet transform to formulate the statistical samples. Cross-validation tests by targeting the experiment-confirmed results have demonstrated that the new predictor is very promising, implying that the aforementioned practices are indeed very effective. Particularly, the approach of using the wavelets to express protein/peptide sequences might be the key in grasping the problem’s essence, fully consistent with the findings that many important biological functions of proteins can be elucidated with their low-frequency internal motions. To maximize the convenience of most experimental scientists, we have provided a step-by-step guide on how to use the predictor’s web server (http://www.jci-bioinfo.cn/iPPBS-Opt) to get the desired results without the need to go through the complicated mathematical equations involved.


title: Epidemiology and clinical features of coronavirus disease 2019 in children

text: Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.


title: Congenital cardiac interventions during the peak phase of COVID-19 pandemics in the country in a pandemics hospital in Istanbul

text: INTRODUCTION: In this report, we aim to present our algorithm and results of patients with congenital cardiac disorders who underwent surgical or interventional procedures during the peak phase of the pandemics in our country. PATIENTS AND METHODS: The first COVID-19 case was diagnosed in Turkey on 11 March, 2020, and the peak phase seemed to end by the end of April. All the patients whom were referred, treated, or previously operated but still at the hospital during the peak phase of COVID-19 pandemics in the country were included into this retrospective study. Patient’s diagnosis, interventions, adverse events, and early post-procedural courses were studied. RESULTS: Thirty-one patients with various diagnoses of congenital cardiovascular disorders were retrospectively reviewed. Ages of the patients ranged between 2 days and 16 years. Seventeen cases were males and 14 cases were females. Elective cases were postponed. Priority was given to interventional procedures, and five cases were treated percutaneously. Palliative procedures were preferred in patients whom presumably would require long hospital stay. Corrective procedures were not hesitated in prioritised stable patients. Mortality occurred in one patient. Eight patients out of 151 ICU admissions were diagnosed with COVID-19, and they were transferred to COVID-19 ICU immediately. Three nurses whom also took care of the paediatric cases became infected with SARS-CoV-2; however, the children did not catch the disease. CONCLUSION: Mandatory and emergent congenital cardiac percutaneous and surgical procedures may be performed with similar postoperative risks as there are no pandemics with meticulous care and preventive measures.


title: DeepTracer: Predicting Backbone Atomic Structure from High Resolution Cryo-EM Density Maps of Protein Complexes

text: Accurately determining the atomic structure of proteins represents a fundamental problem in the field of structural bioinformatics. A solution would be significant as protein structure information could be utilized in the medical field, e.g. in the development of vaccines for new viruses. This paper focuses on predicting the protein structure based on 3D images of the proteins captured through cryogenic electron microscopes (cryo-EM). A fully automated computationally efficient protein structure prediction method would be particularly beneficial in the field of cryo-EM as the technology allows researchers to photograph multiple large protein complexes in a single study, which means that a fast prediction method could allow for a high throughput of derived protein structures. We present a deep learning approach, DeepTracer, for predicting locations of the backbone atoms, secondary structure elements, and the amino acid types. In order to connect the predicted amino acids into chains, we applied a modified traveling salesman algorithm. We trained our deep learning model on experimental cryo-EM density maps and tested it on a set of 50 density maps. We found that our new approach predicted protein structures with an average RMSD value of 1.18 and a coverage of 87.5%. Furthermore, we detected secondary structure information for 87.2% of amino acids correctly. We also showed preliminarily that 25.2% of amino acid types could be predicted directly from the 3D cryo-EM density map, considering 20 different types in total. Finally, we noted that the prediction runtime of DeepTracer is significantly improved compared to other methods. It predicts a large protein complex structure of more than 30,000 amino acids in only 2 hours. The repository of this project will be published. dongsi@uw.edu Supplementary data will be available at Bioinformatics online.


title: Repurposing approved drugs on the pathway to novel therapies

text: The time and cost of developing new drugs have led many groups to limit their search for therapeutics to compounds that have previously been approved for human use. Many “repurposed” drugs, such as derivatives of thalidomide, antibiotics, and antivirals have had clinical success in treatment areas well beyond their original approved use. These include applications in treating antibiotic‐resistant organisms, viruses, cancers and to prevent burn scarring. The major theoretical justification for reusing approved drugs is that they have known modes of action and controllable side effects. Coadministering antibiotics with inhibitors of bacterial toxins or enzymes that mediate multidrug resistance can greatly enhance their activity. Drugs that control host cell pathways, including inflammation, tumor necrosis factor, interferons, and autophagy, can reduce the “cytokine storm” response to injury, control infection, and aid in cancer therapy. An active compound, even if previously approved for human use, will be a poor clinical candidate if it lacks specificity for the new target, has poor solubility or can cause serious side effects. Synergistic combinations can reduce the dosages of the individual components to lower reactivity. Preclinical analysis should take into account that severely ill patients with comorbidities will be more sensitive to side effects than healthy trial subjects. Once an active, approved drug has been identified, collaboration with medicinal chemists can aid in finding derivatives with better physicochemical properties, specificity, and efficacy, to provide novel therapies for cancers, emerging and rare diseases.


Application of Article 107(2)(b) TFEU to Covid-19 Measures: State Aid to Make Good the Damage Caused by an Exceptional Occurrence