title: RNA transcription analysis and completion of the genome sequence of yellow head nidovirus

text: Abstract Yellow head virus (YHV) is a pathogen of the black tiger shrimp (Penaeus monodon) and, with gill-associated virus (GAV), is one of two known invertebrate nidoviruses. We describe sequences of the large replicase gene (ORF1a) and 5′- and 3′-terminal UTRs, completing the 26,662nt sequence of the YHV genome. ORF1a (12,219nt) encodes a ∼462,662Da polypeptide containing a putative 3C-like protease and a putative papain-like protease with the canonical C/H catalytic dyad and α+β fold. The read-through pp1ab polyprotein contains putative uridylate-specific endoribonuclease and ribose-2′-O-methyl transferase domains, and an exonuclease domain incorporating unusual dual Zn2+-binding fingers. Upstream of ORF1a, the 71nt 5′-UTR shares 82.4% identity with the 68nt 5′-UTR of GAV. The 677nt 3′-terminal region contains a single 60nt ORF, commencing 298nt downstream of ORF3, that is identical to N-terminal coding region of the 249nt GAV ORF4. Northern blots using RNA from YHV-infected shrimp and probes directed at ORF1a, ORF1b, ORF2 and ORF3 identified a nested set of 3′-coterminal RNAs comprising the full-length genomic RNA and two sub-genomic (sg) mRNAs. Intergenic sequences upstream of ORF2 and ORF3 share high identity with GAV, particularly in the conserved domains predicted to mediate sgmRNA transcription.


title: Management learning from air purifier tests in hotels: Experiment and action research

text: Abstract Recently, indoor air quality (IAQ) has become an important issue as it affects people's comfort and health. To mitigate the problem, application of some innovative air filtering devices has been generally recognized as one of the effective ways. This study adopted an action research-dominated approach to test whether the indoor air quality in the tested hotel rooms meets the recognized standard, and measure the pollutant removal efficiency of three types of air purifiers. Focus group discussion was carried out to ascertain the difference in hotel managers’ understanding of indoor air quality research before the experiment and management response after the experiment. The result of field test indicates that the actual performance of the purifiers is not as good as the manufactures claim. The management response study also ascertains that hotel department heads’ awareness, exposure and training in relation to IAQ testing is limited.


title: Health care–associated infections in the neonatal intensive care unit

text: Neonates represent a unique and highly vulnerable patient population. Advances in medical technology that have occurred over the last few decades have improved the survival and quality of life for neonates, particularly those infants born with extreme prematurity or with congenital defects. Although immunologic immaturity and altered cutaneous barriers play some role in the vulnerability of neonates to nosocomial infections, clearly, therapeutic interventions that have proven to be lifesaving for these fragile infants also appear to be associated with the majority of infectious complications resulting in neonatal morbidity and mortality. Rates of infections in neonatal intensive care units (NICUs) have varied from 6% to 40% of neonatal patients, with the highest rates in those facilities having larger proportions of very low-birth-weight infants (birthweight ≤1000 grams) or neonates requiring surgery. Efforts to protect the vulnerable NICU infants include the following: (1) optimal infection control practices, especially good hand hygiene and good nursery design; (2) prudent use of invasive interventions with particular attention to early removal of invasive devices after they are no longer essential; and (3) judicious use of antimicrobial agents, with an emphasis on targeted (narrow spectrum) rather than broad-spectrum antibiotics and appropriate indications (proven or suspected bacterial infections).


title: Epidemiological and clinical characteristics of 333 confirmed cases with coronavirus disease 2019 in Shanghai, China

text: Coronavirus disease 2019 (COVID‐19) is an emerging infectious disease first identified in Wuhan City, Hubei Province, China. As of 19 February 2020, there had been 333 confirmed cases reported in Shanghai, China. This study elaborates on the epidemiological and clinical characteristics of COVID‐19 based on a descriptive study of the 333 patients infected with COVID‐19 in Shanghai for the purpose of probing into this new disease and providing reference. Among the 333 confirmed cases in Shanghai, 172 (51.7%) were males and 161 (48.3%) were females, with a median age of 50 years. 299 (89.8%) cases presented mild symptoms. 139 (41.7%) and 111 (33.3%) cases were infected in Wuhan and Shanghai, respectively. 148 (44.4%) cases once had contact with confirmed cases before onset, while 103 (30.9%) cases had never contacted confirmed cases but they had a sojourn history in Wuhan. The onset date of the first case in Shanghai was 28 December, with the peak appearing on 27 January. The median incubation period of COVID‐19 was estimated to be 7.2 days. 207 (62.2%) cases had fever symptoms at the onset, whereas 273 (82.0%) cases experienced fever before hospitalization. 56 (18.6%) adults experienced a decrease in white blood cell and 84 (42.9%) had increased C‐reactive protein after onset. Elderly, male and heart disease history were risk factors for severe or critical pneumonia. These findings suggest that most cases experienced fever symptoms and had mild pneumonia. Strengthening the health management of elderly men, especially those with underlying diseases, may help reduce the incidence of severe and critical pneumonia. Time intervals from onset to visit, hospitalization and diagnosis confirmed were all shortened after Shanghai's first‐level public health emergency response. Shanghai's experience proves that COVID‐19 can be controlled well in megacities.


title: Complete Genome Sequence of a 2019 Novel Coronavirus (SARS-CoV-2) Strain Isolated in Nepal

text: A complete genome sequence was obtained for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from an oropharyngeal swab specimen of a Nepalese patient with coronavirus disease 2019 (COVID-19), who had returned to Nepal after traveling to Wuhan, China.


Maintaining the HIV care continuum during the COVID-19 pandemic


title: The anti‐HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV‐2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID‐19 infections

text: Severe acute respiratory syndrome coronavirus‐2 (SARS CoV‐2) is the causative agent of the coronavirus disease‐2019 (COVID‐19) pandemic. Coronaviruses enter cells via fusion of the viral envelope with the plasma membrane and/or via fusion of the viral envelope with endosomal membranes after virion endocytosis. The spike (S) glycoprotein is a major determinant of virus infectivity. Herein, we show that the transient expression of the SARS CoV‐2 S glycoprotein in Vero cells caused extensive cell fusion (formation of syncytia) in comparison to limited cell fusion caused by the SARS S glycoprotein. Both S glycoproteins were detected intracellularly and on transfected Vero cell surfaces. These results are in agreement with published pathology observations of extensive syncytia formation in lung tissues of patients with COVID‐19. These results suggest that SARS CoV‐2 is able to spread from cell‐to‐cell much more efficiently than SARS effectively avoiding extracellular neutralizing antibodies. A systematic screening of several drugs including cardiac glycosides and kinase inhibitors and inhibitors of human immunodeficiency virus (HIV) entry revealed that only the FDA‐approved HIV protease inhibitor, nelfinavir mesylate (Viracept) drastically inhibited S‐n‐ and S‐o‐mediated cell fusion with complete inhibition at a 10‐μM concentration. In‐silico docking experiments suggested the possibility that nelfinavir may bind inside the S trimer structure, proximal to the S2 amino terminus directly inhibiting S‐n‐ and S‐o‐mediated membrane fusion. Also, it is possible that nelfinavir may act to inhibit S proteolytic processing within cells. These results warrant further investigations of the potential of nelfinavir mesylate to inhibit virus spread at early times after SARS CoV‐2 symptoms appear.


title: Outbreak of Middle East respiratory syndrome coronavirus, Saudi Arabian experience

text: Abstract Objective MERS-CoV infection is uncommonly identified among patients visiting healthcare facilities & we were vigilant in screening all patients entering our hospital to prevent cross infection among patients, visitors & healthcare providers and aiming to prevent potential outbreaks with MERS-CoV infection. In spite of our efforts on practicing Failure Mode Effect Analysis for MERS-CoV infection management we ended up having an outbreak with MERS-CoV. Based on our experience, we actively implemented policies, procedures & practices on early identification & appropriate isolation practices along with supplemental infection prevention & control measures for preventing future outbreaks at our healthcare facility. Methods Retrospectively we analyzed our failure in preventing the outbreak of MERS-CoV infection among our hospitalized patients by identifying the outbreak & actively intervening as a team to control the outbreak with the support of Hospital Higher management, Administrators, Quality improvement team, Infection prevention & control team & the active support of all healthcare workers of the facility. Results Following the early identification of MERS-CoV outbreak, we could successfully prevent large scale outbreak both in the hospital & the community. Conclusion Continuous implementation of infection prevention & control standards along with early clinical diagnosis of MERS-CoV infections based on the case definition as laid out by the Ministry of Health will prevent infectious outbreaks at healthcare facilities.


title: Asymptomatic and Presymptomatic SARS-CoV-2 Infections in Residents of a Long-Term Care Skilled Nursing Facility — King County, Washington, March 2020

text: Older adults are susceptible to severe coronavirus disease 2019 (COVID-19) outcomes as a consequence of their age and, in some cases, underlying health conditions (1). A COVID-19 outbreak in a long-term care skilled nursing facility (SNF) in King County, Washington that was first identified on February 28, 2020, highlighted the potential for rapid spread among residents of these types of facilities (2). On March 1, a health care provider at a second long-term care skilled nursing facility (facility A) in King County, Washington, had a positive test result for SARS-CoV-2, the novel coronavirus that causes COVID-19, after working while symptomatic on February 26 and 28. By March 6, seven residents of this second facility were symptomatic and had positive test results for SARS-CoV-2. On March 13, CDC performed symptom assessments and SARS-CoV-2 testing for 76 (93%) of the 82 facility A residents to evaluate the utility of symptom screening for identification of COVID-19 in SNF residents. Residents were categorized as asymptomatic or symptomatic at the time of testing, based on the absence or presence of fever, cough, shortness of breath, or other symptoms on the day of testing or during the preceding 14 days. Among 23 (30%) residents with positive test results, 10 (43%) had symptoms on the date of testing, and 13 (57%) were asymptomatic. Seven days after testing, 10 of these 13 previously asymptomatic residents had developed symptoms and were recategorized as presymptomatic at the time of testing. The reverse transcription-polymerase chain reaction (RT-PCR) testing cycle threshold (Ct) values indicated large quantities of viral RNA in asymptomatic, presymptomatic, and symptomatic residents, suggesting the potential for transmission regardless of symptoms. Symptom-based screening in SNFs could fail to identify approximately half of residents with COVID-19. Long-term care facilities should take proactive steps to prevent introduction of SARS-CoV-2 (3). Once a confirmed case is identified in an SNF, all residents should be placed on isolation precautions if possible (3), with considerations for extended use or reuse of personal protective equipment (PPE) as needed (4).


Caring for Patients with Venous Insufficiency During the COVID-19 Pandemic at a Tertiary Care Center


title: Treatment of cancer patients during the COVID-19 pandemic in the Philippines

text: The COVID-19 pandemic has caused disruptions in cancer care around the world due to logistical and psychosocial reasons. This paper was written with the primary objective of providing a guide for medical oncologists in addressing concerns in the management of adult patients with solid tumours in the Philippines and for those working under similar circumstances. These recommendations are divided into prioritisation of cancer care, ensuring a safe work environment, organising the transition of cancer care, and maintaining cohesion in a time of isolation.


title: Quality & Safety in the time of Coronavirus—Design Better, Learn Faster

text: The COVID-19 pandemic has required health systems to change much faster than normal. Many staff have experienced training in quality improvement and patient safety methods which can be used to support the design of new systems and to accelerate learning about new and adapted practices. This article sets out the principles of quality improvement and patient safety science, applying them in a selection of approaches, methods and tools which may be useful in crisis situations such as the current pandemic. The article also makes reference to several resources which may be of use to those keen to advance their knowledge.


Abstract Recent advances in electrochemical biosensors for pathogen detection are reviewed. Electrochemical biosensors for pathogen detection are broadly reviewed in terms of transduction elements, biorecognition elements, electrochemical techniques, and biosensor performance. Transduction elements are discussed in terms of electrode material and form factor. Biorecognition elements for pathogen detection, including antibodies, aptamers, and imprinted polymers, are discussed in terms of availability, production, and immobilization approach. Emerging areas of electrochemical biosensor design are reviewed, including electrode modification and transducer integration. Measurement formats for pathogen detection are classified in terms of sample preparation and secondary binding steps. Applications of electrochemical biosensors for the detection of pathogens in food and water safety, medical diagnostics, environmental monitoring, and bio-threat applications are highlighted. Future directions and challenges of electrochemical biosensors for pathogen detection are discussed, including wearable and conformal biosensors, detection of plant pathogens, multiplexed detection, reusable biosensors for process monitoring applications, and low-cost, disposable biosensors.


title: Apes, lice and prehistory

text: Although most epidemic human infectious diseases are caused by recently introduced pathogens, cospeciation of parasite and host is commonplace for endemic infections. Occasional host infidelity, however, provides the endemic parasite with an opportunity to survive the potential extinction of its host. Such infidelity may account for the survival of certain types of human lice, and it is currently exemplified by viruses such as HIV.


Immunopathology of lung diseases: introduction for the special issue


title: A Fluorogenic Peptide Containing the Processing Site of Human SARS Corona Virus S‐Protein: Kinetic Evaluation and NMR Structure Elucidation

text: Human severe acute respiratory syndrome coronavirus (hSARS‐CoV) is the causative agent for SARS infection. Its surface glycoprotein (spike protein) is considered to be one of the prime targets for SARS therapeutics and intervention because its proteolytic maturation by a host protease is crucial for host–virus fusion. Using intramolecularly quenched fluorogenic (IQF) peptides based on hSARS‐CoV spike protein (Abz‐(755)Glu‐Gln‐Asp‐Arg‐Asn‐Thr‐Arg‐Glu‐Val‐Phe‐Ala‐Gln(766)‐Tyx‐NH(2)) and in vitro studies, we show that besides furin, other PCs, like PC5 and PC7, might also be involved in this cleavage event. Through kinetic measurements with recombinant PCs, we observed that the peptide was cleaved efficiently by both furin and PC5, but very poorly by PC7. The cleavage could be blocked by a PC‐inhibitor, α1‐PDX, in a dose‐dependent manner. Circular dichroism spectra indicated that this peptide possesses a high degree of sheet structure. Following cleavage by furin, the sheet content increased, possibly at the expense of turn and random structures. (1)H NMR spectra from 2D COSY and ROESY experiments under physiological buffer and pH conditions indicated that this peptide possesses a structure with a turn at its C‐terminal segment, close to the cleavage site. The data suggest that the cleavable peptide bond is located within the most exposed domain; this is supported by the nearby turn structure. Several strong to weak NMR ROESY correlations were detected, and a 3D structure of the spike IQF peptide that contains the crucial cleavage site R(761)↓E has been proposed.


title: Utilization of the respiratory virus multiplex reverse transcription-polymerase chain reaction test for adult patients at a Korean tertiary care center

text: BACKGROUND/AIMS: Respiratory viruses (RVs) are considered to be important respiratory pathogens in adult patients, and the multiplex reverse transcription-polymerase chain reaction (RT-PCR) test is used frequently in adult patients with respiratory infections. However, clinical data regarding utilization of the multiplex RT-PCR test for RVs are lacking. METHODS: We investigated the utilization of the multiplex RT-PCR test for RVs at Chung-Ang University Hospital in Seoul, Korea, between January 2012 and April 2013. RESULTS: During the study period, the multiplex RT-PCR test was performed for 291 adult patients. The test frequency was 4.9% of rapid influenza antigen detection tests and 0.8% of respiratory bacterial culture studies. A turnaround time of < 48 hours was observed in 25.9% of positive tests. Most of the tests were performed for admitted patients (97.9%) with a community-acquired infection (84.2%) during the flu season (82.5%). RVs were detected in 81 of 291 cases (27.8%). The RV positivity rates for community- and hospital-acquired infections did not differ (28.6% vs. 23.9%, p = 0.52). Of 166 patients with pneumonia, 44 (26.5%) had a viral infection. Among the patients with RV-associated pneumonia, an RV other than influenza was detected in 20 patients (45.4%). CONCLUSIONS: The multiplex RT-PCR test for RVs was infrequently performed at a tertiary care center, and the test results were often reported late. The test was most often performed for admitted adult patients with community-acquired infections during the flu season. The utilization of multiplex RT-PCR testing for RVs in current clinical practice should be improved.


title: High throughput virtual screening reveals SARS-CoV-2 multi-target binding natural compounds to lead instant therapy for COVID-19 treatment

text: The present-day world is severely suffering from the recently emerged SARS-CoV-2. The lack of prescribed drugs for the deadly virus has stressed the likely need to identify novel inhibitors to alleviate and stop the pandemic. In the present high throughput virtual screening study, we used in silico techniques like receptor-ligand docking, Molecular dynamic (MD), and ADME properties to screen natural compounds. It has been documented that many natural compounds display antiviral activities, including anti–SARS-CoV effect. The present study deals with compounds of Natural Product Activity and Species Source (NPASS) database with known biological activity that probably impedes the activity of six essential enzymes of the virus. Promising drug-like compounds were identified, demonstrating better docking score and binding energy for each druggable targets. After an extensive screening analysis, three novel multi-target natural compounds were predicted to subdue the activity of three/more major drug targets simultaneously. Concerning the utility of natural compounds in the formulation of many therapies, we propose these compounds as excellent lead candidates for the development of therapeutic drugs against SARS-CoV-2.


title: Novel Pharmacological Activity of Artesunate and Artemisinin: Their Potential as Anti-Tubercular Agents

text: Tuberculosis is a major infectious disease that globally causes the highest human mortality. From this aspect, this study was carried out to evaluate novel pharmacological activities/effects of artesunate and artemisinin causing anti-tubercular activity/effects against Mycobacterium tuberculosis (Mtb). The anti-Mtb activities/effects of artesunate and artemisinin were evaluated using different anti-Mtb indicator assays, such as the resazurin microtiter assay, the Mycobacteria Growth Indicator Tube (MGIT) 960 system assay, and the Ogawa slant medium assay, as well as in vivo tests. Artesunate showed selective anti-Mtb effects by strongly inhibiting the growth of Mtb compared to artemisinin, and consistently induced anti-Mtb activity/effects by effectively inhibiting Mtb in the MGIT 960 system and in Ogawa slant medium for 21 days with a single dose; its minimum inhibitory concentration was 300 µg/mL in in vitro testing. Furthermore, artesunate demonstrated an anti-tubercular effect/action with a daily dose of 3.5 mg/kg in an in vivo test for four weeks, which did not indicate or induce toxicity and side effects. These results demonstrate that artesunate effectively inhibits the growth and/or proliferation of Mtb through novel pharmacological activities/actions, as well as induces anti-Mtb activity. This study shows its potential as a potent candidate agent for developing new anti-tuberculosis drugs of an effective/safe next generation, and suggests novel insights into its effective use by repurposing existing drugs through new pharmacological activity/effects as one of the substantive alternatives for inhibiting tuberculosis.


title: Recovery of divergent avian bornaviruses from cases of proventricular dilatation disease: Identification of a candidate etiologic agent

text: BACKGROUND: Proventricular dilatation disease (PDD) is a fatal disorder threatening domesticated and wild psittacine birds worldwide. It is characterized by lymphoplasmacytic infiltration of the ganglia of the central and peripheral nervous system, leading to central nervous system disorders as well as disordered enteric motility and associated wasting. For almost 40 years, a viral etiology for PDD has been suspected, but to date no candidate etiologic agent has been reproducibly linked to the disease. RESULTS: Analysis of 2 PDD case-control series collected independently on different continents using a pan-viral microarray revealed a bornavirus hybridization signature in 62.5% of the PDD cases (5/8) and none of the controls (0/8). Ultra high throughput sequencing was utilized to recover the complete viral genome sequence from one of the virus-positive PDD cases. This revealed a bornavirus-like genome organization for this agent with a high degree of sequence divergence from all prior bornavirus isolates. We propose the name avian bornavirus (ABV) for this agent. Further specific ABV PCR analysis of an additional set of independently collected PDD cases and controls yielded a significant difference in ABV detection rate among PDD cases (71%, n = 7) compared to controls (0%, n = 14) (P = 0.01; Fisher's Exact Test). Partial sequence analysis of a total of 16 ABV isolates we have now recovered from these and an additional set of cases reveals at least 5 distinct ABV genetic subgroups. CONCLUSION: These studies clearly demonstrate the existence of an avian reservoir of remarkably diverse bornaviruses and provide a compelling candidate in the search for an etiologic agent of PDD.


title: Respiratory viruses in patients and employees in an intensive care unit

text: PURPOSE: To evaluate the frequency of respiratory viruses in a nonselected population of intensive care unit patients and employees and to investigate the clinical as well as the epidemiological association with virological findings. METHODS: Between 12 January and 5 March 2009, nasopharyngeal swabs were collected from 55 intensive care unit (ICU) patients and 41 medical personnel at 16 different time-points and tested for 11 respiratory viruses by single real-time PCR using TaqMan or MGB probes. RESULTS: Among the 55 ICU patients tested, there were 30 virus-positive respiratory specimens (30/173, 17.3%) and 23 patients who tested positive at least once for respiratory viruses (23/55, 41.8%). Only the time from admission to the ICU was associated with the probability of testing positive, with the probability of testing positive decreasing with increasing length of stay (P < 0.001). Of the 418 respiratory specimens collected from the healthcare personnel, 27 (6.5%) tested positive. Seventeen employees tested positive at least once for respiratory viruses (17/41, 41.5%). Among the employees, calendar time (P = 0.03) and having sick contacts at home (P = 0.006) were significantly associated with swab positivity. Among the study population, patients had a significantly higher probability of having a positive swab result than employees. The distribution of viruses differed between the two groups. CONCLUSIONS: Our results suggest that when hygiene precautions are adopted, the possibility of transmitting selected respiratory viruses between patients and personnel is limited. They also point to a greater importance of the community over the hospital environment for acquisition of viral respiratory infections by ICU patients and employees. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s15010-012-0245-6) contains supplementary material, which is available to authorized users.


title: Enteropathogen infections in canine puppies: (Co-)occurrence, clinical relevance and risk factors

text: Abstract Laboratory confirmation of the causative agent(s) of diarrhoea in puppies may allow for appropriate treatment. The presence of potential pathogens however, does not prove a causal relationship with diarrhoea. The aim of this study was to identify specific enteropathogens in ≤12 month old puppies with and without acute diarrhoea and to assess their associations with clinical signs, putative risk factors and pathogen co-occurrence. Faecal samples from puppies with (n=113) and without (n=56) acute diarrhoea were collected and screened for Canine Parvovirus (CPV), Canine Coronavirus (CCoV), Salmonella spp., Campylobacter spp., Clostridium perfringens, Clostridium difficile, β-hemolytic Eschericha coli (hEC), Giardia spp., Toxocara spp., Cystoisospora spp., and Cyniclomyces guttulatus. One or more pathogens were detected in 86.5% of diarrhoeic puppies and in 77.8% of asymptomatic puppies. Significant positive associations were found between CPV and CCoV, CPV and Cystoisospora spp., Toxocara spp. and hEC, Giardia spp. and C. guttulatus. Only CPV and CCoV were significantly associated with diarrhoea, hEC with a subset of puppies that had diarrhoea and severe clinical signs. CPV was more prevalent in puppies under 3 months of age. Puppies from high-volume dog breeders were significantly at increased risk for CPV (OR 4.20), CCoV (OR 4.50) and Cystoisospora spp. (OR 3.60). CCoV occurred significantly more often in winter (OR 3.35), and CPV in winter (OR 3.78) and spring (OR 4.72) as compared to summer. We conclude that routine screening for CPV, CCoV and hEC is recommended in puppies with acute diarrhoea, especially if they are under 3 months of age and originate from high-volume dog breeders. Routine screening for other pathogens may lead to less conclusive results.


title: Early career psychiatrists’ perspectives on the mental health impact and care of the COVID-19 pandemic across the world

text: Abstract The emergence of mental health (MH) problems during a pandemic is extremely common, though difficult to address due to the complexities of pandemics and the little evidence about the epidemiology of pandemic-related MH problems and the potential interventions to tackle them. Little attention has been devoted so far to this topic from policymakers, stakeholders and researchers, what could be due to a lack of replicable, scalable and applicable frameworks to plan, develop and deliver MH care during pandemics. As a response, we have attempted to develop a conceptual framework (CF) that could guide the development, implementation, and evaluation of MH interventions during the ongoing COVID-19 pandemic. This CF was developed by early career psychiatrists, from 16 countries that cover all the WHO regions. Their opinions were elicited via semi-structured questionnaire. They were asked to provide their views about the current MH situation of their countries, existing myths and misinformation, and the possible resources available. They were also asked to propose solutions and approaches to provide accessible and affordable care. The CF’s were prepared based on the extant literature and the views expressed; they illustrate the epidemiology of MH issues, preparedness plans, stage-specific plans/innovative solutions, opportunities to integrate those plans and probable outcomes at policy level. This CF can serve as a technical guide for future research in pandemic. It can be used to monitor trends and to optimize efforts and to develop evidence based MH interventions. However further research focusing on the individual components of this framework is needed.


title: Race, socioeconomic deprivation, and hospitalization for COVID-19 in English participants of a national biobank

text: Preliminary reports suggest that the Coronavirus Disease 2019 (COVID− 19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. We investigate the racial and socioeconomic associations of COVID− 19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both Black participants (odds ratio 3.7; 95%CI 2.5–5.3) and Asian participants (odds ratio 2.2; 95%CI 1.5–3.2) were at substantially increased risk as compared to White participants. We further observed a striking gradient in COVID− 19 hospitalization rates according to the Townsend Deprivation Index − a composite measure of socioeconomic deprivation − and household income. Adjusting for socioeconomic factors and cardiorespiratory comorbidities led to only modest attenuation of the increased risk in Black participants, adjusted odds ratio 2.4 (95%CI 1.5–3.7). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-White individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study.


Specialty Grand Challenge for NeuroRehabilitation Research


title: Coronavirus mouse hepatitis virus (MHV)-A59 causes a persistent, productive infection in primary glial cell cultures

text: Abstract MHV-A59 causes a chronic demyelinating disease in mice which is accompanied by persistence of viral genome in white matter. As part of the investigation into the mechanism of viral persistence, infection of glial cells, probable targets for chronic infection, was studied by the use of mixed glial, enriched oligodendrocyte and enriched astrocyte cultures. Following MHV-A59 infection in vitro, approximately 10% of oligodendrocytes and 30% of astrocytes expressed viral antigens in the absence of overt cytopathic effect. All cultures released infectious virus for the lifetime of the cultures, for at least 45 days in the case of mixed glial cultures. Cultures derived from previously infected mice were similar to those infected in vitro with respect to percentage of cells expressing viral antigen and levels of infectious virus produced. These results show (1) that glial cells are early sites of infection in vivo as well as sites of infection in in vitro cultures, and (2) that glial cells support a non-lytic but productive infection in vitro and thus may contribute to viral persistence in vivo.


title: Host protein chaperones, RNA helicases and the ubiquitin network highlight the arms race for resources between tombusviruses and their hosts

text: Positive-strand RNA viruses need to arrogate many cellular resources to support their replication and infection cycles. These viruses co-opt host factors, lipids and subcellular membranes and exploit cellular metabolites to built viral replication organelles in infected cells. However, the host cells have their defensive arsenal of factors to protect themselves from easy exploitation by viruses. In this review, the author discusses an emerging arms race for cellular resources between viruses and hosts, which occur during the early events of virus-host interactions. Recent findings with tomato bushy stunt virus and its hosts revealed that the need of the virus to exploit and co-opt given members of protein families provides an opportunity for the host to deploy additional members of the same or associated protein family to interfere with virus replication. Three examples with well-established heat shock protein 70 and RNA helicase protein families and the ubiquitin network will be described to illustrate this model on the early arms race for cellular resources between tombusviruses and their hosts. We predict that arms race for resources with additional cellular protein families will be discovered with tombusviruses. These advances will fortify research on interactions among other plant and animal viruses and their hosts.


title: The Effect of Hospital Isolation Precautions on Patient Outcomes and Cost of Care: A Multi-Site, Retrospective, Propensity Score-Matched Cohort Study

text: BACKGROUND: Isolation precautions have negative effects on patient safety, psychological well-being, and healthcare worker contact. However, it is not known whether isolation precautions affect certain hospital-related outcomes. OBJECTIVE: To examine the effect of isolation precautions on hospital-related outcomes and cost of care. DESIGN: Retrospective, propensity-score matched cohort study of inpatients admitted to general internal medicine (GIM) services at three academic hospitals in Toronto, Ontario, Canada between January 2010 and December 2012. PARTICIPANTS: Adult (≥18 years of age) patients on isolation precautions for respiratory illnesses and methicillin-resistant Staphylococcus aureus (MRSA) were matched to controls based on propensity scores derived from nine covariates: age, sex, Resource Intensity Weight, number of hospital readmissions within 90 days, total length of stay for hospital admissions within 90 days, site of admission, month of isolation, year of isolation, and Case Mix Group. MAIN MEASURES: Thirty-day readmission rates and emergency department visits, hospital length of stay, expected length of stay, adverse events, in-hospital mortality, patient complaints, and cost of care in Canadian doll ars (CAD). KEY RESULTS: A total of 17,649 non-isolated patients were admitted to the participating hospitals during the study period. We identified 1506 patients isolated for respiratory illnesses and 745 patients isolated for MRSA. Compared to non-isolated individuals, those on isolation precautions for respiratory illnesses stayed 17 % longer (95 % CI: 9 %, 25 %), stayed 9 % longer than expected (95 % CI: 3 %, 15 %), and had 23 % higher cost of care (95 % CI: 14 %, 32 %). Patients isolated for MRSA had similar outcomes, but they also had a 4.4 % higher (95 % CI: 1.4 %, 7.3 %) rate of readmission to hospital within 30 days. CONCLUSIONS: Isolation precautions are associated with adverse effects which may result in poorer hospital outcomes. Balancing the benefits for the many with the harms to the few will be a future challenge.


title: ARMAX modelling of international tourism demand

text: Abstract Box–Jenkins (1970) models are often used to capture the autoregressive moving average of past observations of tourist arrivals from Japan to Taiwan and New Zealand. However, other explanatory variables, such as real income in the origin country, have also affected the demand for international travel. The purpose of this paper is to use the ARMAX model to investigate the dynamic relationship between tourism demand and real income of Japan, and to compare the findings with the single-equation model. Unit root tests and diagnostics are performed before estimating the income elasticity of travel demand by Japan for New Zealand and Taiwan based on seasonally unadjusted quarterly data for 1980(1) to 2004(2). The empirical results of the ARMAX model support the economic theory that the demand for international travel is positively related to income of the origin country.


title: Estimation of the reproductive number of novel coronavirus (COVID-19) and the probable outbreak size on the Diamond Princess cruise ship: A data-driven analysis

text: Abstract Backgrounds Up to February 16, 2020, 355 cases have been confirmed as having COVID-19 infection on the Diamond Princess cruise ship. It is of crucial importance to estimate the reproductive number (R0) of the novel virus in the early stage of outbreak and make a prediction of daily new cases on the ship. Method We fitted the reported serial interval (mean and standard deviation) with a gamma distribution and applied “earlyR” package in R to estimate the R0 in the early stage of COVID-19 outbreak. We applied “projections” package in R to simulate the plausible cumulative epidemic trajectories and future daily incidence by fitting the data of existing daily incidence, a serial interval distribution, and the estimated R0 into a model based on the assumption that daily incidence obeys approximately Poisson distribution determined by daily infectiousness. Results The Maximum-Likelihood (ML) value of R0 was 2.28 for COVID-19 outbreak at the early stage on the ship. The median with 95% confidence interval (CI) of R0 values was 2.28 (2.06–2.52) estimated by the bootstrap resampling method. The probable number of new cases for the next ten days would gradually increase, and the estimated cumulative cases would reach 1514 (1384–1656) at the tenth day in the future. However, if R0 value was reduced by 25% and 50%, the estimated total number of cumulative cases would be reduced to 1081 (981–1177) and 758 (697–817), respectively. Conclusion The median with 95% CI of R0 of COVID-19 was about 2.28 (2.06–2.52) during the early stage experienced on the Diamond Princess cruise ship. The future daily incidence and probable outbreak size is largely dependent on the change of R0. Unless strict infection management and control are taken, our findings indicate the potential of COVID-19 to cause greater outbreak on the ship.


title: Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study

text: BACKGROUND: Brain MRI parenchymal signal abnormalities have been in association with SARS-CoV-2. PURPOSE: Describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe COVID-19 infection. METHODS: This was a retrospective study of patients evaluated from March 23th, 2020 to April 27th, 2020 at 16 hospitals. Inclusion criteria were: (i) positive nasopharyngeal or lower respiratory tract reverse transcriptase-polymerase chain reaction assays; (ii) severe COVID infection defined as requirement for hospitalization and oxygen therapy; (iii) neurologic manifestations; (iv) abnormal brain MRI. Exclusion criteria were patients with missing or non-contributory data regarding brain MRI or a brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using Fisher exact test. Quantitative data were compared using Student’s t-test or Wilcoxon test. A p-value lower than 0.05 was considered significant. RESULTS: Thirty men (81%) and 7 women (19%) met inclusion criteria, with a mean age of 61+/- 12 years (range: 8-78). The most common neurologic manifestations were alteration of consciousness (27/37, 73%), pathological wakefulness when the sedation was stopped (15/37, 41%), confusion (12/37, 32%), and agitation (7/37, 19%). The most frequent MRI findings were: signal abnormalities located in the medial temporal lobe in 16/37 (43%, 95% CI 27-59%) patients, non-confluent multifocal white matter hyperintense lesions on FLAIR and diffusion sequences, with variable enhancement, with associated hemorrhagic lesions in 11/37 patients (30%, 95% CI 15-45%), and extensive and isolated white matter microhemorrhages in 9/37 patients (24%, 95% CI 10-38%). A majority of patients (20/37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation: higher admission rate in intensive care units, 20/20 patients, 100% versus 12/17 patients, 71%, p=0.01; development of the acute respiratory distress syndrome in 20/20 patients, 100% versus 11/17 patients, 65%, p=0.005. Only one patient was positive for SARS-CoV-2 RNA in the cerebrospinal fluid. CONCLUSION: Patients with severe COVID-19 and without ischemic infarcts had a wide range of neurologic manifestations that were be associated with abnormal brain MRIs. Eight distinctive neuroradiological patterns were described.


title: Novel outbreak of acral lesions in times of COVID‐19: A description of 74 cases from a tertiary university hospital in Spain

text: Since the outbreak of novel Coronavirus Disease 2019 (COVID‐19), reports concerning suspicious COVID‐19 skin manifestations are progressively increasing. Morbilliform, varicelliform or urticarial rashes were firstly described(1). Later, acral erythematous or purpuric lesions(2‐4) were reported.


Reply to “Statins may decrease the Fatality Rate of MERS Infection”


title: Novel Norovirus in Dogs with Diarrhea

text: To identify the prevalence and genetic variability of noroviruses in dogs, we tested fecal samples by using reverse transcription–PCR. We found canine norovirus in 40% and 9% of dogs with and without diarrhea, respectively. The virus was genetically unrelated to other noroviruses and constitutes a tentative new genogroup.


title: Don't forget shared decision‐making in the COVID‐19 crisis

text: Mechanical ventilation as a resource is limited and may lead to poor outcomes in at‐risk populations. Critical care supports may not be preferred by those at risk of deterioration in the COVID‐19 setting. Patient‐centred communication and shared decision‐making should continue to remain central to clinical practice.


title: Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation

text: For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are key mediators of neutrophilic inflammation in influenza-induced exacerbations of chronic lung inflammation. Using a mouse model of disease, our data shows a role for IL-1β in mediating lung dysfunction, and in driving neutrophilic inflammation during the whole phase of viral infection. We further report a role for IL-17A as a mediator of IL-1β induced neutrophilia at early time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1 resulted in a significant abrogation of neutrophil recruitment to the airways in the initial phase of infection or at the peak of viral replication, respectively. Therefore, IL-17A and IL-1β are potential targets for therapeutic treatment of viral exacerbations of chronic lung inflammation


title: Genomics, the origins of agriculture, and our changing microbe‐scape: Time to revisit some old tales and tell some new ones

text: Though agriculture is often viewed as one of humanity's crowning achievements, skeletal evidence indicates that dependence on domesticated plants and animals was accompanied by an increase in infectious disease. Scientists have proposed that many important infections emerged in the period following the advent of agriculture, as a result of newly dense populations and novel proximity to domestic animals that served as reservoirs for novel pathogens. Here, we review genomic evidence regarding pathogen origins, analyzing these data using the epidemiological transition framework. Genetic information has forced us to reconsider how and when many important pathogens emerged; it appears that a number of infections thought to result from contact with domesticated animals arose much earlier than agriculture was adopted. We also consider the broader effect of agriculture upon the microbiome, exploring potential consequences for human health. We end by discussing the changes in the human microbe‐scape we are likely to see in the future. Am J Phys Anthropol 57:135–152, 2013. © 2013 Wiley Periodicals, Inc.


title: Trypanosoma teixeirae: A new species belonging to the T. cruzi clade causing trypanosomosis in an Australian little red flying fox (Pteropus scapulatus)

text: Abstract Little is known about the genetic diversity and pathogenicity of trypanosomes in Australian bats. Recently a novel trypanosome species was identified in an adult female little red flying fox (Pteropus scapulatus) with clinical and pathological evidence of trypanosomosis. The present study used morphology and molecular methods to demonstrate that this trypanosome is a distinct species and we propose the name Trypanosoma teixeirae sp. n. Morphological comparison showed that its circulating trypomastigotes were significantly different from those of Trypanosoma pteropi and Trypanosoma hipposideri, two species previously described from Australian bats. Genetic information was not available for T. pteropi and T. hipposideri but phylogenetic analyses at the 18S ribosomal RNA (rRNA) and glycosomal glyceraldehyde phosphate dehydrogenase (gGAPDH) loci indicated that T. teixeirae sp. n. was genetically distinct and clustered with other bat-derived trypanosome species within the Trypanosoma cruzi clade.


title: Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers

text: RNA viruses pose a threat to public health that is exacerbated by the dearth of antiviral therapeutics. The RNA-dependent RNA polymerase (RdRp) holds promise as a broad-spectrum, therapeutic target because of the conserved nature of the nucleotide-substrate-binding and catalytic sites. Conventional, quantitative, kinetic analysis of antiviral ribonucleotides monitors one or a few incorporation events. Here, we use a high-throughput magnetic tweezers platform to monitor the elongation dynamics of a prototypical RdRp over thousands of nucleotide-addition cycles in the absence and presence of a suite of nucleotide analog inhibitors. We observe multiple RdRp-RNA elongation complexes; only a subset of which are competent for analog utilization. Incorporation of a pyrazine-carboxamide nucleotide analog, T-1106, leads to RdRp backtracking. This analysis reveals a mechanism of action for this antiviral ribonucleotide that is corroborated by cellular studies. We propose that induced backtracking represents a distinct mechanistic class of antiviral ribonucleotides.


title: Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2

text: We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.


Intranasal Protollin Formulated Recombinant SARS-CoV S Protein Elicits Respiratory and Serum Neutralizing Antibodies


title: Serological tests facilitate identification of asymptomatic SARS‐CoV‐2 infection in Wuhan, China

text: The Wuhan City has ended the lockdown and people have been allowed to resume working since April 8 if meeting a set of COVID‐19‐associated tests including SARS‐CoV‐2 nucleic acid test (NAT) of nasopharyngeal swabs, chest CT scan or a SARS‐CoV‐2‐specific serological test. Here, we reported the positive rate of COVID‐19 tests based on NAT, chest CT scan and a serological SARS‐CoV‐2 test, from April 3 to 15 in one hospital in Qingshan Destrict, Wuhan. We observed a ~10% SARS‐CoV‐2‐specific IgG positive rate from 1,402 tests. Combination of SARS‐CoV‐2 NAT and a specific serological test might facilitate the detection of COVID‐19 infection, or the asymptomatic SARS‐CoV‐2‐infected subjects. Large‐scale investigation is required to evaluate the herd immunity of the city, for the resuming people and for the re‐opened city. This article is protected by copyright. All rights reserved.


title: Study about the Effect of Addition of Carbon Nanofibers on the Strain-Rate Sensitivity of Thermoplastic Polymer Matrix Nanocomposites Manufactured by Ultrasonic Processing

text: Abstract Polymer nanocomposites based on polypropylene (PP) reinforced with carbon nanofibers (CNFs) at a fixed concentration of 0.5% w/w were prepared by precipitation from liquid solutions of PP and CNFs. Ultrasonic processing was used as the primary process for mixing both PP and CNFs in the the solvent, while mechanical stirring was also used as a control process to prepare similar samples. Thermogravimetric analysis (TGA) shows that the ultrasonic processing influences little on the thermal stability of the polymer material. Moreover, ultrasonically-processed PP shows higher tensile strength and better ductility, compared to those of the neat PP. Although the mechanically-processed PP has about 10% higher tensile strength than the ultrasonically-processed one, it is observed that there is a significant deterioration in its ductility due to the dissolution of calcium carbonate which is used as an additive for the neat PP. The advantage of significantly reduced material processing time, increased mixing efficiency, and increase in thermal stability and mechanical properties of ultrasonically-processed PPs indicated that the ultrasonic processing is relatively more effective and efficient mixing process compared to mechanical stirring for preparation of the polymer and its nanocomposite. Tensile tests were also conducted using quasi-static strain rates from 10-4 to 10-1 s-1 in order to obtain the tensile strength, elongation at fracture, and the elastic modulus of injection molded polymer and its nanocomposite. PP-CNF nanocomposites exhibited higher strain-rate sensitivity within the tested strain range, compared to the neat PP. Both the neat PP and PP-CNF nanocomposite exhibited strain-rate dependent material properties, showing an increase in tensile strength, and decrease in elongation with increasing strain rates.


Chemotherapy directly followed by PARP inhibition as an alternative to surgery in patients with BRCA- mutated ovarian cancer – a potential management strategy in the era of COVID-19


title: Identification of novel and diverse rotaviruses in rodents and insectivores, and evidence of cross-species transmission into humans

text: Abstract Rotaviruses are an important cause of severe diarrheal illness in children globally. We characterized rotaviruses sampled in humans, insectivores (shrews) and rodents from urban and rural regions of Zhejiang province, China. Phylogenetic analyses revealed seven genotypic constellations of human rotaviruses with six different combinations of G and P genotypes – G3P[8] (50.06%), G9P[8] (36.16%), G1P[8] (8.92%), G2P[4] (4.63%), G3P[3] (0.12%), and G3P[9] (0.12%). In rodents and shrews sampled from the same locality we identified a novel genotype constellation (G32-P[46]-I24-R18-C17-M17-A28-N17-T19-E24-H19), a novel P genotype (P[45]), and two different AU-1-like rotaviruses associated with a G3P[3] genotype combination. Of particular note was a novel rotavirus from a human patient that was closely related to viruses sampled from rodents in the same region, indicative of a local species jump. In sum, these data are suggestive of the cross-species transmission of rodent rotaviruses into humans and for reassortment among human and animal rotaviruses.


Coronavirus Disease 2019 (Covid-19) and Acute Cardiovascular Disease Management: A Chinese Perspective on Striking the Balance


title: Case of the Index Patient Who Caused Tertiary Transmission of Coronavirus Disease 2019 in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Pneumonia Monitored by Quantitative RT-PCR

text: Since mid-December of 2019, coronavirus disease 2019 (COVID-19) has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.


title: Digital transformation during a lockdown

text: These are indeed exceptional and historic times, a global pandemic and public health emergency sitting side by side with heightened public awareness of the injustices of decades of institutional racism. This article considers the current pandemic and lockdown period through a VUCA lens and offers reflection on how the pandemic revealed the fragility of digitally immature organisations. VUCA, a managerial catchall acronym for Volatility, Uncertainty, Complexity and Ambiguity is a litmus test for recognising unpredictable external environments. We offer business leaders a caveat, it is dangerous to ignore the impact of VUCA on the smooth functioning of an organisation. In terms of digital transformation during lockdown this article offers three key lessons that can so far be discerned from the pandemic period, firstly organisations must improve their digital maturity, secondly, less digitally mature organisations are more fragile and finally organisations with higher levels of digital maturity are generally more flexible.


title: Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease

text: Abstract In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD.


title: Mucosal Immune Response to Feline Enteric Coronavirus Infection

text: Feline infectious peritonitis is a devastating, fatal disease of domestic cats caused by a pathogenic mutant virus derived from the ubiquitous feline enteric coronavirus (FECV). Infection by FECV is generally subclinical, and little is known about the mucosal immune response that controls and eliminates the virus. We investigated the mucosal immune response against FECV in an endemically infected breeding colony over a seven-month period. Thirty-three cats were grouped according to FECV seropositivity and fecal virus shedding into naïve/immunologically quiescent, convalescent and actively infected groups. Blood, fecal samples and colon biopsies were collected to assess the mucosal and systemic immunologic and virologic profile. Results showed that cats with active FECV infections have strong systemic IgG and mucosal IgA responses that wane after virus clearance. Significant FECV-specific mucosal T cell IFNγ responses were not detected in any of the three groups. A shift toward an inflammatory state in the mucosa was suggested by increased IL17:FoxP3 expression. However, no histologic abnormalities were observed, and no shifts in lymphocyte subpopulation phenotype or proliferation were noted. Together, the results suggest that control of FECV is mediated by humoral mucosal and systemic responses and that perturbations in the primary reservoir organ (colon) are minimal.


title: Genetic diversity of porcine sapoviruses

text: Abstract Sapoviruses (SaVs) within the Caliciviridae family are an important cause of gastroenteritis in both humans and animals. Although the widespread occurrence of divergent human SaV strains has been reported, there have only been a few studies of porcine SaVs examining their genetic diversity. The aim of this study was to assess the genetic diversity of porcine SaVs in piglets with diarrhea in South Korea. Two hundred and thirty-seven fecal specimens from piglets with diarrhea were examined from 78 farms over a 2-year period from six provinces in South Korea. Overall, 69 (29.1%) of the samples from five provinces tested positive for porcine SaVs by either RT-PCR or nested PCR with the primer pairs specific to porcine SaVs. An analysis of the partial capsid gene (757bp) of 12 porcine SaVs detected from fecal samples showed genetic divergence, not only among the Korean porcine SaVs (67.7–99.1%), but also between Korean and American porcine SaVs (69.1–90.2%). Interestingly, one strain (Po/SaV/JN-MA113/05/Korea), formed a second porcine SaV/GIII genotype, and is tentatively called GIII/2. This strain had a 0.236–0.405 inter-cluster distance with the other strains in the same genogroup, which is comparable to the distances between the established GI and GII SaVs. Furthermore, two potential recombinant porcine SaVs were identified. In conclusion, porcine SaV infections are common in diarrheic piglets in South Korea. The infecting strains are genetically diverse, and include a newly recognized genotype and recombinant viruses within genogroup III.


title: Translational research in immunology: Japanese perspectives

text: Japan has a formidable tradition in immunological research, starting with Shibasaburo Kitasato (1852–1931), who, after returning to Japan from his studies with Robert Koch, went on to build almost single-handedly a research tradition in investigative medical research, while engaging himself in the fight against infectious diseases(1). Over the past few decades, Japanese immunologists have been involved in many important discoveries at the forefront of immunological research, yet, when it comes to the translation of new discoveries into clinical innovations and new therapies, Japan's track record seems more modest.


title: Coronaviruses Hijack the LC3-I-Positive EDEMosomes, ER-Derived Vesicles Exporting Short-Lived ERAD Regulators, for Replication

text: Summary Coronaviruses (CoV), including SARS and mouse hepatitis virus (MHV), are enveloped RNA viruses that induce formation of double-membrane vesicles (DMVs) and target their replication and transcription complexes (RTCs) on the DMV-limiting membranes. The DMV biogenesis has been connected with the early secretory pathway. CoV-induced DMVs, however, lack conventional endoplasmic reticulum (ER) or Golgi protein markers, leaving their membrane origins in question. We show that MHV co-opts the host cell machinery for COPII-independent vesicular ER export of a short-living regulator of ER-associated degradation (ERAD), EDEM1, to derive cellular membranes for replication. MHV infection causes accumulation of EDEM1 and OS-9, another short-living ER chaperone, in the DMVs. DMVs are coated with the nonlipidated LC3/Atg8 autophagy marker. Downregulation of LC3, but not inactivation of host cell autophagy, protects cells from CoV infection. Our study identifies the host cellular pathway hijacked for supplying CoV replication membranes and describes an autophagy-independent role for nonlipidated LC3-I.


title: Fetal heart rate changes on the cardiotocograph trace secondary to maternal COVID-19 infection

text: OBJECTIVE: To determine the cardiotocograph (CTG) changes in women with symptomatic COVID-19 infection. STUDY DESIGN: 12 anonymised CTG traces from 2 hospitals in Spain were retrospectively analysed by 2 independent assessors. CTG parameters were studied based on fetal pathophysiological responses to inflammation and hypoxia that would be expected based on the pathogenesis of COVID-19 patients. Correlation was made with perinatal outcomes (Apgar score at 5 min and umbilical cord pH). RESULTS: All fetuses showed an increased baseline FHR > 10 percent compared to the initial recording, in addition to absence of accelerations. 10 out of 12 CTG traces (83.3 percent) demonstrated late or prolonged decelerations and 7 out of 12 fetuses (58.3 percent) showed absence of cycling. Not a single case of sinusoidal pattern was observed. ZigZag pattern was found in 4 CTG traces (33 percent). Excessive uterine activity was observed in all CTG traces where uterine activity was monitored (10 out of 12). Apgar scores at 5 min were normal (>7) and absence of metabolic acidosis was found in the umbilical cord arterial pH (pH > 7.0) in the cases that were available (11 and 9, respectively). CONCLUSION: Fetuses of COVID-19 patients showed a raised baseline FHR (>10 percent), loss of accelerations, late decelerations, ZigZag pattern and absence of cycling probably due to the effects of maternal pyrexia, maternal inflammatory response and the “cytokine storm”. However, the perinatal outcomes appear to be favourable. Therefore, healthcare providers should optimise the maternal environment first to rectify the reactive CTG changes instead of performing an urgent operative intervention.


Recent findings on cardiovascular safety with the use of chloroquine and hydroxychloroquine for COVID-19.


title: Impacts of allergic airway inflammation on lung pathology in a mouse model of influenza A virus infection

text: Influenza A virus is the respiratory pathogen responsible for influenza. Infection by the 2009 pandemic influenza A (H1N1) virus caused severe lower airway inflammation and pneumonia. Asthma is a chronic inflammatory disorder of the airways that affects the entire brachial tree, and was one of the commonest underlying medical conditions among patients hospitalized with the 2009 pandemic influenza virus infection. Although respiratory virus infections are the major causes of asthma exacerbation, the mechanism by which influenza exacerbates asthma is poorly understood. Animal models of disease comorbidity are crucial to understanding host-pathogen interactions and elucidating complex pathologies. Existing murine models of influenza virus infection in asthmatics show that asthmatic mice are highly resistant to influenza virus infection, which contradicts clinical observations in humans. Here, we developed a murine model of influenza virus/asthma comorbidity using NC/Nga mice, which are highly sensitive to allergic reactions such as atopic dermatitis and allergic airway inflammation. This model was then used to examine the impact of allergic airway inflammation on lung pathology in the 2009 pandemic influenza virus infected mice. The results showed that induction of acute allergic airway inflammation in pre-existing influenza virus infection had additive effects on exacerbation of lung pathology, which mirrors findings in human epidemiological studies. In contrast, pre-existing allergic airway inflammation protected from subsequent influenza virus infection, which was compatible with those of previous murine models of influenza virus infection in asthmatic mice. These variable outcomes of this murine model indicate that the temporal relation between allergic airway inflammation and influenza virus infection might play a critical role in asthma and influenza comorbidity. Thus, this murine model will further our understanding of how influenza virus infection affects an asthmatic host and may aid the development of strategies to improve treatments and outcomes for asthmatics harboring influenza virus infection.


title: Interactions Between Enteroviruses and the Inflammasome: New Insights Into Viral Pathogenesis

text: Enteroviruses (EVs) have emerged a substantial threat to public health. EVs infection range from mild to severe disease, including mild respiratory illness, diarrhea, poliomyelitis, hand, foot, and mouth disease, aseptic meningitis, and encephalitis. In the Asia-Pacific region, for example, one of the best studied enterovirus 71 (EV71) has been associated with pandemics of hand, foot, and mouth disease (HFMD) in children, particularly those under the age of five. Serious HFMD cases are associated with neurological complications, such as aseptic meningitis, acute flaccid paralysis, brainstem encephalitis, and have been associated with as many as 1000s of deaths in children and infants from 2008 to 2017, in China. More than 90% of laboratory confirmed deaths due to HMFD are associated with EV71. However, little is known about the pathogenesis of EVs. Studies have reported that EVs-infected patients with severe complications show elevated serum concentrations of IL-1β. The secretion of IL-1β is mediated by NLRP3 inflammasome during EV71 and CVB3 infection. Enteroviruses 2B and 3D proteins play an important role in activation of NLRP3 inflammasome, while 3C and 2A play important roles in antagonizing the activation of NLRP3 and the secretion of IL-1β. In this review, we summarize current knowledge regarding the molecular mechanisms that underlie the activation and regulation of the NLRP3 inflammasome, particularly how viral proteins regulate NLRP3 inflammasome activation. These insights into the relationship between the NLRP3 inflammasome and the pathogenesis of EVs infection may ultimately inform the development of novel antiviral drugs.


title: A reformulated contextual model of psychotherapy for treating anxiety and depression

text: This paper describes a reformulated contextual model that uses cognitive theory (dual process theory), motivation theory (personality) and behavioral adaptation (self-correcting control systems) to show how anxiety and depression are caused, treated and prevented by an interaction between people and contexts. Depression and anxiety are the result of implicit beliefs (not cognitions) that all experience is unrewarding and threatening, these being components of the implicit belief that life is bad. Implicit beliefs are formed automatically from contextual cues and in healthy individuals are consistent with rational appraisal. They become more negative than reality through a process of adaptation when behaviors, directed by rational thinking, repeatedly create cues that signify lack of reward or threat. Such behaviors occur when social or other obligations lead people to choose behaviors that fail to satisfy their own unique goals in life and approach threatening situations, contrary to their automatic reactions. Therapeutic interventions and lifestyle change reverse these adaptive processes by positive experiences that create positive implicit beliefs, a change effected in different ways by contextual and specific mechanisms both of which correct the same fault of negative implicit beliefs. Effective therapeutic relationships and interventions are achieved by detecting and responding to a patient's unique needs and goals and their associated implicit beliefs. Mental health requires not only that people experience life as good as defined by their own goals and beliefs but also the avoidance of contexts where social and other pressures induce people to behave in ways inconsistent with their automatically generated feelings.


title: Host Cell Factors in Filovirus Entry: Novel Players, New Insights

text: Filoviruses cause severe hemorrhagic fever in humans with high case-fatality rates. The cellular factors exploited by filoviruses for their spread constitute potential targets for intervention, but are incompletely defined. The viral glycoprotein (GP) mediates filovirus entry into host cells. Recent studies revealed important insights into the host cell molecules engaged by GP for cellular entry. The binding of GP to cellular lectins was found to concentrate virions onto susceptible cells and might contribute to the early and sustained infection of macrophages and dendritic cells, important viral targets. Tyrosine kinase receptors were shown to promote macropinocytic uptake of filoviruses into a subset of susceptible cells without binding to GP, while interactions between GP and human T cell Ig mucin 1 (TIM-1) might contribute to filovirus infection of mucosal epithelial cells. Moreover, GP engagement of the cholesterol transporter Niemann-Pick C1 was demonstrated to be essential for GP-mediated fusion of the viral envelope with a host cell membrane. Finally, mutagenic and structural analyses defined GP domains which interact with these host cell factors. Here, we will review the recent progress in elucidating the molecular interactions underlying filovirus entry and discuss their implications for our understanding of the viral cell tropism.


title: Identification of a novel astrovirus in domestic sheep in Hungary

text: The family Astroviridae consists of two genera, Avastrovirus and Mamastrovirus, whose members are associated with gastroenteritis in avian and mammalian hosts, respectively. We serendipitously identified a novel ovine astrovirus in a fecal specimen from a domestic sheep (Ovis aries) in Hungary by viral metagenomic analysis. Sequencing of the fragment indicated that it was an ORF1b/ORF2/3′UTR sequence, and it has been submitted to the GenBank database as ovine astrovirus type 2 (OAstV-2/Hungary/2009) with accession number JN592482. The unique sequence characteristics and the phylogenetic position of OAstV-2 suggest that genetically divergent lineages of astroviruses exist in sheep.


title: Sasa quelpaertensis Nakai extract suppresses porcine reproductive and respiratory syndrome virus replication and modulates virus-induced cytokine production

text: Although Sasa quelpaertensis Nakai, a dwarf bamboo, is known to exert a variety of beneficial effects on health, its antiviral effect remains to be elucidated. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating viral pathogens of swine and has a substantial economic impact on the global pork industry. Therefore, the present study was conducted to determine whether Sasa quelpaertensis Nakai extract (SQE) inhibits PRRSV infection in cultured porcine alveolar macrophages (PAMs). Our results demonstrated that SQE treatment suppressed the replication of PRRSV in a dose-dependent manner. The antiviral activity of SQE on PRRSV replication was found to be primarily exerted at early times postinfection. Treatment with SQE resulted in marked reduction of viral genomic and subgenomic RNA synthesis, viral protein expression, and progeny virus production. Notably, pro-inflammatory cytokine production in PAM cells infected with PRRSV was shown to be modulated in the presence of SQE. Taken together, our data indicate that SQE has potential as a therapeutic agent against PRRSV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-015-2469-0) contains supplementary material, which is available to authorized users.


title: Comparison of three multiplex PCR assays for the detection of respiratory viral infections: evaluation of xTAG respiratory virus panel fast assay, RespiFinder 19 assay and RespiFinder SMART 22 assay

text: BACKGROUND: A broad spectrum of pathogens is causative for respiratory tract infections, but symptoms are mostly similar. Therefore, the identification of the causative viruses and bacteria is only feasible using multiplex PCR or several monoplex PCR tests in parallel. METHODS: The analytical sensitivity of three multiplex PCR assays, RespiFinder-19, RespiFinder-SMART-22 and xTAG-Respiratory-Virus-Panel-Fast-Assay (RVP), were compared to monoplex real-time PCR with quantified standardized control material. All assays include the most common respiratory pathogens. RESULTS: To compare the analytical sensitivity of the multiplex assays, samples were inoculated with 13 different quantified viruses in the range of 10(1) to 10(5) copies/ml. Concordant results were received for rhinovirus, whereas the RVP detected influenzavirus, RSV and hMPV more frequently in low concentrations. The RespiFinder-19 and the RespiFinder-SMART-22 showed a higher analytical sensitivity for adenoviruses and coronaviruses, whereas the RVP was incapable to detect adenovirus and coronavirus in concentrations of 10(4) copies/ml. The RespiFinder-19 and RespiFinder-SMART-22A did not detect influenzaviruses (10(4) copies/ml) and RSV (10(3) copies/ml). The detection of all 13 viruses in one sample was only achieved using monoplex PCR. To analyze possible competitive amplification reactions between the different viruses, samples were further inoculated with only 4 different viruses in one sample. Compared to the detection of 13 viruses in parallel, only a few differences were found. The incidence of respiratory viruses was compared in tracheal secretion (TS) samples (n = 100) of mechanically ventilated patients in winter (n = 50) and summer (n = 50). In winter, respiratory viruses were detected in 32 TS samples (64%) by RespiFinder-19, whereas the detection rate with RVP was only 22%. The most frequent viruses were adenovirus (32%) and PIV-2 (20%). Multiple infections were detected in 16 TS samples (32%) by RespiFinder-19. Fewer infections were found in summer (RespiFinder-19: 20%; RVP: 6%). All positive results were verified using monoplex PCR. CONCLUSIONS: Multiplex PCR tests have a broad spectrum of pathogens to test at a time. Analysis of multiple inoculated samples revealed a different focus of the detected virus types by the three assays. Analysis of clinical samples showed a high concordance of detected viruses by the RespiFinder-19 compared to monoplex tests.


title: Weathering COVID-19 Storm: Successful Control Measures of Five Asian Countries

text: • COVID-19 control measures taken by five Asian countries first hit by coronavirus; • China took extremely aggressive measures of lockdowns and closing business; • Singapore took proactive measures of border controls and extensive contact tracing; • Taiwan seized border control and strict home quarantine with the use of big data; • South Korea executed widespread testing and contact tracing; • Japan promoted measures of social distancing.


title: MANAGEMENT OF NATURAL AND BIOTERRORISM INDUCED PANDEMICS

text: A recent approach for bioterrorism risk management calls for stricter regulations over biotechnology as a way to control subversion of technology that may be used to create a man‐made pandemic. This approach is largely unworkable given the increasing pervasiveness of molecular techniques and tools throughout society. Emerging technology has provided the tools to design much deadlier pathogens but concomitantly the ability to respond to emerging pandemics to reduce mortality has also improved significantly in recent decades. In its historical context determining just how ‘risky’ biological weapons is an important consideration for decision making and resource allocation. Management should attempt to increase capacity, share resources, provide accurate infectious disease reporting, deliver information transparency and improve communications to help mitigate the magnitude of future pandemics.


title: Dam characteristics associated with pre-weaning diarrhea in mink (Neovison vison)

text: BACKGROUND: Pre-weaning diarrhea (PWD) in mink, also known as “sticky kits”, is a frequently occurring syndrome in suckling mink kits on commercial mink farms. Outbreaks of PWD result in weakened kits, increased mortality and reduced growth and welfare as well as considerable economic losses for the farmers. The syndrome is regarded as multifactorial with a complex etiology, and studies have focused on associations with environment, management and dam characteristics. The present study was conducted from May to June 2015 and included 70 dams with mink litters with and without PWD. The aims were to examine associations between PWD and mastitis (bacterial infection and histological signs of inflammation or other lesions in the mammary gland), and to examine associations between PWD and other dam-related characteristics (age, litter size, body mass index, and weight and number of active mammary glands of the dam). RESULTS: Using multivariable mixed logistic regression analyses with farm id as a random intercept, we found that the odds for PWD in the litter were significantly higher in 1 year old dams versus > 1 year old (OR = 13.3, CI 2.0–90.2, P = 0.01), higher if litter size observed after birth was > 5 kits versus ≤ 5 kits (OR = 16.5, CI 2.2–123.7, P = 0.01), higher if the number of active mammary glands per kit was ≤ 1.5 versus > 1.5 glands per kit (OR = 6.5, CI 1.2–36.0), P = 0.03), and higher in farms with high prevalence of PWD versus low prevalence (OR = 16.8, CI 2.9–97.6, P = 0.002). There were no significant associations between PWD and bacterial infection, histological signs of inflammation or other lesions of the mammary gland, body mass index or weight of mammary gland per kit. CONCLUSION: Pre-weaning diarrhea had a statistically significant association with age of the dam, litter size and the number of active mammary glands per kit. However, PWD was not associated with mastitis, body mass index and weight of mammary gland tissue per kit.


title: Virologie : l’apport de la biologie moléculaire dans le diagnostic microbiologique en pneumopédiatrie

text: Résumé Les outils traditionnels du diagnostic virologique comprennent la recherche antigénique directe par immunofluorescence (IF) ou test immunoenzymatique (EIA), et l’isolement en culture. Les techniques d’IF ou EIA ont une sensibilité en général légèrement inférieure à celle de la culture, mais elles permettent de détecter également une fraction d’échantillons faussement négatifs en culture. Les résultats de plusieurs équipes, utilisant des techniques de reverse transcription-polymerase chain reaction (RT-PCR), montrent que les méthodes moléculaires détectent plus d’échantillons positifs que les méthodes traditionnelles. Le travail est en cours pour élargir le nombre de virus identifiés par des RT-PCR multiplex et découvrir de nouveaux virus, tels le métapneumovirus humain, en cause dans les atteintes respiratoires de l’enfant. En conclusion, afin de concilier rapidité, contrôle des coûts et un fort taux de détection des virus respiratoires, l’utilisation combinée de l’IF et de la RT-PCR multiplex semble ce jour la meilleure façon de progresser dans le diagnostic des maladies respiratoires de l’enfant. Summary The conventionnal tools used for virological diagnosis include direct antigen detection by immunofluorescence (IFA) or an immunoenzymatic test (EIA), and viral isolation technique (VIT). In most cases, IFA and EIA have a slightly lower sensitivity than VIT but are also able to detect some VIT-negative samples. Results of several teams using RT-PCR technologies show that the molecular methods detect more positive cases than the conventional tools. Work is under way to expand the number of viruses detected by multiplex RT-PCR and to determine wether newly discovered viruses, such as human metapneumovirus, contribute to burden of paediatric lower respiratory infections. In conclusion, according to requirements of speed, low cost of the methods, and to achieve the highest rate of detection of respiratory viruses, the combined use of IFA and multiplex RT-PCR is today likely to be the best way to improve diagnosis of respiratory illnesses in children.


title: COVID-19 Outbreak: Infection Control and Management Protocol for Vascular and Interventional Radiology Departments—Consensus Document

text: COVID-19 (SARS-CoV-2 virus) pandemic was recently declared by the WHO as a global health emergency. A group of interventional radiology senior experts developed a consensus document for infection control and management of patients with COVID-19 in interventional radiology (IR) departments. This consensus statement has been brought together at short notice with the help of different protocols developed by governmental entities and scientific societies to be adapted to the current reality and needs of IR Departments. Recommendations are the specific strategies to follow in IR departments, preventive measures and regulations, step by step for donning and doffing personal protective equipment, specific IR procedures which can not be delayed, and aerosol-generating procedures in IR with COVID-19 patients. It is advisable with this document to be adapted to local workplace policies.


Chloroquin gegen Corona?


title: Potential of SARS-CoV-2 to Cause CNS Infection: Biologic Fundamental and Clinical Experience

text: SARS-CoV-2 is a novel coronavirus leading to serious respiratory disease and is spreading around the world at a raging speed. Recently there is emerging speculations that the central nervous system (CNS) may be involved during SARS-CoV-2 infection, contributing to the respiratory failure. However, the existence of viral replication in CNS has not been confirmed due to the lack of evidence from autopsy specimens. Considering the tropism of SARS-CoV-2, ACE2, is prevailing in CNS, and the neuro-invasive property of human coronavirus was widely reported, there is a need to identified the possible complications during COVID-19 for CNS. In this review, we conduct a detailed summary for the potential of SARS-CoV-2 to infect central nervous system from latest biological fundamental of SARS-CoV-2 to the clinical experience of other human coronaviruses. To confirm the neuro-invasive property of SARS-CoV-2 and the subsequent influence on patients will require further exploration by both virologist and neurologist.


title: Comparing Neural-Network Scoring Functions and the State of the Art: Applications to Common Library Screening

text: [Image: see text] We compare established docking programs, AutoDock Vina and Schrödinger’s Glide, to the recently published NNScore scoring functions. As expected, the best protocol to use in a virtual-screening project is highly dependent on the target receptor being studied. However, the mean screening performance obtained when candidate ligands are docked with Vina and rescored with NNScore 1.0 is not statistically different than the mean performance obtained when docking and scoring with Glide. We further demonstrate that the Vina and NNScore docking scores both correlate with chemical properties like small-molecule size and polarizability. Compensating for these potential biases leads to improvements in virtual screen performance. Composite NNScore-based scoring functions suited to a specific receptor further improve performance. We are hopeful that the current study will prove useful for those interested in computer-aided drug design.


title: Highly Efficient Transgenesis in Ferrets Using CRISPR/Cas9-Mediated Homology-Independent Insertion at the ROSA26 Locus

text: The domestic ferret (Mustela putorius furo) has proven to be a useful species for modeling human genetic and infectious diseases of the lung and brain. However, biomedical research in ferrets has been hindered by the lack of rapid and cost-effective methods for genome engineering. Here, we utilized CRISPR/Cas9-mediated, homology-independent insertion at the ROSA26 “safe harbor” locus in ferret zygotes and created transgenic animals expressing a dual-fluorescent Cre-reporter system flanked by PhiC31 and Bxb1 integrase attP sites. Out of 151 zygotes injected with circular transgene-containing plasmid and Cas9 protein loaded with the ROSA26 intron-1 sgRNA, there were 23 births of which 5 had targeted integration events (22% efficiency). The encoded tdTomato transgene was highly expressed in all tissues evaluated. Targeted integration was verified by PCR analyses, Southern blot, and germ-line transmission. Function of the ROSA26-CAG-(LoxP)tdTomato(StopLoxP)EGFP (ROSA-TG) Cre-reporter was confirmed in primary cells following Cre expression. The Phi31 and Bxb1 integrase attP sites flanking the transgene will also enable rapid directional insertion of any transgene without a size limitation at the ROSA26 locus. These methods and the model generated will greatly enhance biomedical research involving lineage tracing, the evaluation of stem cell therapy, and transgenesis in ferret models of human disease.


title: Maneuvering for advantage: the genetics of mouse susceptibility to virus infection

text: Abstract Genetic studies of host susceptibility to infection contribute to our understanding of an organism's response to pathogens at the immunological, cellular, and molecular levels. In this review we describe how the study of host genetics in mouse models has helped our understanding of host defense mechanisms against viral infection, and how this knowledge can be extended to human infections. We focus especially on the innate mechanisms that function as the host's first line of defense against infection. We also discuss the main issues that confront this field, as well as its future.


title: Mink (Neovison vison) kits with pre-weaning diarrhea have elevated serum amyloid A levels and intestinal pathomorphological similarities with New Neonatal Porcine Diarrhea Syndrome

text: BACKGROUND: Pre-weaning diarrhea (PWD) is a syndrome affecting farm-raised neonatal mink kits. Apart from diarrhea it causes greasy skin exudation, dehydration, and distressed behavior and can ultimately lead to death. No specific causative agents have been identified and the syndrome is regarded as multifactorial. The aim of the present study was to investigate a possible inflammatory state in mink kits with PWD, as indicated by raised serum concentrations of the acute phase protein serum amyloid A (SAA) and by changes in intestinal pathomorphology and intestinal contents of bacteria. Samples collected from 20 diarrheic mink kits with PWD and 20 age-matched non-diarrheic control mink kits from two commercial Danish farms during the pre-weaning period (April–May) in 2016 were analyzed. RESULTS: Concentrations of SAA in serum samples from mink kits with PWD were significantly higher (up to 1000-fold) compared to non-diarrheic control mink kits. Significant features of enterocytic vacuolization, atrophy and fusion of villi in jejunum and mucosal atrophy of the colon of kits with PWD were found. Moreover, attachment of coccoid bacteria to enterocytes was more often found in kits suffering from PWD, while intra-cytoplasmic eosinophil bodies were more frequently observed in control kits. Cellular infiltrations with mononuclear and neutrophil leukocytes were not associated with disease status. Bacteria from the Staphylococcus intermedius group, such as Staphylococcus delphini, were more frequently cultivated from control mink kits, whereas Enterococcus spp. dominated in mink kits with PWD. Escherichia coli was cultivated from both control and mink kits with PWD, but with a higher frequency from mink kits with PWD. CONCLUSION: A significant increase in circulating concentrations of SAA was found in PWD affected mink kits from 6 to 23 days old compared to controls. The histopathological changes in PWD mink kits suggest that the type of diarrhea is secretory. Attachment of coccoid bacteria, therefore, might be responsible for an enterotoxic effect causing a loss of balance in movements of ions and water leading to the vacuolization and swelling of the enterocytes. The slight to moderate infiltrations of neutrophils irrespectively of diarrheic status and the attachment of coccoid bacteria to enterocytes are comparable to observations found in piglets suffering from New Neonatal Porcine Diarrhea Syndrome. Mechanisms behind the correlation between increased SAA levels and the observed pathological intestinal features remain obscure.


title: Correlation between the migration scale index and the number of new confirmed coronavirus disease 2019 cases in China

text: In late December 2019, patients of atypical pneumonia due to an unidentified microbial agent were reported in Wuhan, Hubei Province, China. Subsequently, a novel coronavirus was identified as the causative pathogen which was named SARS-CoV-2. As of 12 February 2020, more than 44 000 cases of SARS-CoV-2 infection have been confirmed in China and continue to expand. Provinces, municipalities and autonomous regions of China have launched first-level response to major public health emergencies one after another from 23 January 2020, which means restricting movement of people among provinces, municipalities and autonomous regions. The aim of this study was to explore the correlation between the migration scale index and the number of confirmed coronavirus disease 2019 (COVID-19) cases and to depict the effect of restricting population movement. In this study, Excel 2010 was used to demonstrate the temporal distribution at the day level and SPSS 23.0 was used to analyse the correlation between the migration scale index and the number of confirmed COVID-19 cases. We found that since 23 January 2020, Wuhan migration scale index has dropped significantly and since 26 January 2020, Hubei province migration scale index has dropped significantly. New confirmed COVID-19 cases per day in China except for Wuhan gradually increased since 24 January 2020, and showed a downward trend from 6 February 2020. New confirmed COVID-19 cases per day in China except for Hubei province gradually increased since 24 January 2020, and maintained at a high level from 24 January 2020 to 4 February 2020, then showed a downward trend. Wuhan migration scale index from 9 January to 22 January, 10 January to 23 January and 11 January to 24 January was correlated with the number of new confirmed COVID-19 cases per day in China except for Wuhan from 22 January to 4 February. Hubei province migration scale index from 10 January to 23 January and 11 January to 24 January was correlated with the number of new confirmed COVID-19 cases per day in China except for Hubei province from 22 January to 4 February. Our findings suggested that people who left Wuhan from 9 January to 22 January, and those who left Hubei province from 10 January to 24 January, led to the outbreak in the rest of China. The ‘Wuhan lockdown’ and the launching of the first-level response to this major public health emergency may have had a good effect on controlling the COVID-19 epidemic. Although new COVID-19 cases continued to be confirmed in China outside Wuhan and Hubei provinces, in our opinion, these are second-generation cases.


title: epic3: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England

text: Executive Summary National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were originally commissioned by the Department of Health and developed during 1998–2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were first published in January 2001 1 and updated in 2007. 2 A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective for the prevention of HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. The Department of Health commissioned a review of new evidence and we have updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the epic2 guidelines published in 2007 remain robust, relevant and appropriate, but some guideline recommendations required adjustments to enhance clarity and a number of new recommendations were required. These have been clearly identified in the text. In addition, the synopses of evidence underpinning the guideline recommendations have been updated. These guidelines (epic3) provide comprehensive recommendations for preventing HCAI in hospital and other acute care settings based on the best currently available evidence. National evidence-based guidelines are broad principles of best practice that need to be integrated into local practice guidelines and audited to reduce variation in practice and maintain patient safety. Clinically effective infection prevention and control practice is an essential feature of patient protection. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of health care in NHS hospitals in England can be minimised.


title: The cytoplasmic tail of hantavirus Gn glycoprotein interacts with RNA

text: Abstract We recently characterized the interaction between the intraviral domains of envelope glycoproteins (Gn and Gc) and ribonucleoprotein (RNP) of Puumala and Tula hantaviruses (genus Hantavirus, family Bunyaviridae). Herein we report a direct interaction between spike-forming glycoprotein and nucleic acid. We show that the envelope glycoprotein Gn of hantaviruses binds genomic RNA through its cytoplasmic tail (CT). The nucleic acid binding of Gn-CT is unspecific, as demonstrated by interactions with unrelated RNA and with single-stranded DNA. Peptide scan and protein deletions of Gn-CT mapped the nucleic acid binding to regions that overlap with the previously characterized N protein binding sites and demonstrated the carboxyl-terminal part of Gn-CT to be the most potent nucleic acid-binding site. We conclude that recognition of the RNP complex by the Gn-CT could be mediated by interactions with both genomic RNA and the N protein. This would provide the required selectivity for the genome packaging of hantaviruses.


How much “Thinking” about COVID-19 is Clinically Dysfunctional?


title: Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells

text: BACKGROUND: The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs) might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS. RESULTS: Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs. CONCLUSION: The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted.


title: Correction to: Epidemiological and clinical characteristics of patients with suspected COVID-19 admitted in Metro Manila, Philippines

text: [This corrects the article DOI: 10.1186/s41182-020-00241-8.].


title: “War to the knife” against thromboinflammation to protect endothelial function of COVID-19 patients

text: In this viewpoint, we summarize the relevance of thromboinflammation in COVID-19 and discuss potential mechanisms of endothelial injury as a key point for the development of lung and distant organ dysfunction, with a focus on direct viral infection and cytokine-mediated injury. Entanglement between inflammation and coagulation and resistance to heparin provide a rationale to consider other therapeutic approaches in order to preserve endothelial function and limit microthrombosis, especially in severe forms. These strategies include nebulized heparin, N-acetylcysteine, plasma exchange and/or fresh frozen plasma, plasma derivatives to increase the level of endogenous anticoagulants (tissue factor pathway inhibitor, activated protein C, thrombomodulin, antithrombin), dipyridamole, complement blockers, different types of stem cells, and extracellular vesicles. An integrated therapy including these drugs has the potential to improve outcomes in COVID-19.