title: Analysis of the initiation of viral infection under flow conditions with applications to transmission in feed

text: While kinetic models are widely used to describe viral infection at various levels, most of them are focused on temporal aspects and understanding of corresponding spatio-temporal aspects remains limited. In this work, our attention is focused on the initial stage of infection of immobile cells by virus particles (“virions”) under flow conditions with diffusion. A practical example of this scenario occurs when humans or animals consume food from virion-containing sources. Mathematically, such situations can be described by using a model constructed in analogy with those employed in chemical engineering for analysis of the function of a plug-flow reactor with dispersion. As in the temporal case, the corresponding spatio-temporal model predicts either the transition to a steady state or exponential growth of the populations of virions and infected cells. The spatial distributions of these species are similar in both of these regimes. In particular, the maximums of the populations are shifted to the upper boundary of the infected region. The results illustrating these conclusions were obtained analytically and by employing numerical calculations without and with the dependence of the kinetic parameters on the coordinate. The model proposed has also been used in order to illustrate the effect of antiviral feed additives on infection towards curbing disease transmission.


docid: stsvjqhu

title: In the search of potential epitopes for Wuhan seafood market pneumonia virus using high order nullomers

text: Abstract Alarms periodically emerge for viral pneumonia infections due to coronavirus. In all cases, these are zoonoses passing the barrier between species and infect humans. The legitimate concern of the international community is due to the fact that the new identified coronavirus, named SARS-CoV-2 (previously called 2019-nCoV), has a quite high mortality rate, around 2%, and a strong ability to spread, with an estimated reproduction number higher than 2. Even though all countries are doing their utmost to stop the pandemic, the only reliable solution to tackle the infection is the rapid development of a vaccine. For this purpose, the means of bioinformatics, applied in the context of reverse-vaccinology paradigm, can be of fundamental help to select the most promising peptides able to trigger an effective immune response. In this short report, using the concept of nullomer and introducing a distance from human self, we provide a list of peptides that could deserve experimental investigation in the view of a potential vaccine for SARS-CoV-2.


title: Risk factors and epidemiological characteristics of new neonatal porcine diarrhoea syndrome in four Danish herds

text: BACKGROUND: The epidemiology of New Neonatal Porcine Diarrhoea Syndrome (NNPDS) was studied in four selected herds. A total of 941 new born piglets in 86 litters were evaluated for five consecutive days. NNPDS is a newly emerged syndrome, characterized by diarrhoea within the first week of life, which is un-responsive to antibiotics and not associated with known pathogens. The aetiology behind the syndrome is unknown, and specific risk factors predisposing piglets to develop NNPDS also remain to be determined. The study evaluated sow and piglet-level risk factors for developing NNPDS and described the epidemiologic characteristics within four herds previously diagnosed with the syndrome. NNPDS was defined as diarrhoea at any time-point during the second to fifth day of life. RESULTS: NNPDS was observed in a total of 60% (range: 39%-89%) of first parity piglets and 36% (range: 19-65%) of piglets born by mature sows. In total of 26% of piglets had liquid faeces on the day of birth. Approximately half of these piglets developed NNPDS. In the majority of cases (50-70% of cases within herds) symptoms started on the second or third day of life. Piglets in Herd 1 had12.8 times higher probability of developing NNPDS than piglets in Herd 4. First parity piglets had a 4.1 higher probability of developing NNPDS than piglets born by mature sows. Birth weight and faecal consistency on the day of birth were minor risk factors, each significant within one herd. CONCLUSIONS: The most important factors associated with NNPDS were herd of origin and sow-parity. The reason for one of the herds experiencing a considerably more severe outbreak than the others was not explained by factors addressed in this study. The epidemiological pattern of diarrhoea varied a lot between herds; however, in all herds first parity piglets seemed predisposed. This association may be explained by an infectious background of the syndrome, but further studies are needed to explain this association.


title: Integration of aeromedicine in the response to the COVID‐19 pandemic

text: There is limited guidance on the use of helicopter medical personnel to facilitate care of critically ill COVID‐19 patients. This manuscript describes the emergence of this novel virus, its mode of transmission, and the potential impacts on patient care in the unique environment of rotor wing aircraft. It details the development of clinical and operational guidelines for flight crew members. This allows other out‐of‐hospital clinicians to utilize our framework to augment or supplement their own for the current response effort to COVID‐19. It further serves as a road map for future response to the care of high consequence infectious disease patients.


title: A case report of possible novel coronavirus 2019 reinfection

text: Since December 2019, COVID-19, the clinical syndrome associated with SARS-CoV-2 infection, has infected more than 6.2 million people and brought the function of the global community to a halt. As the number of patients recovered from COVID-19 rises and the world transitions toward reopening, the question of acquired immunity versus the possibility of reinfection are critical to anticipating future viral spread. Here, we present a case of a patient previously recovered from COVID-19 who re-presents with new respiratory, radiographical, laboratory, and RT-PCR findings concerning for re-infection. We review this case in the context of the evolving discussion and theories surrounding dynamic RT-PCR results, prolonged viral shedding, and the possibility of developed immunity.


title: Comparison between dairy cow disease incidence in data registered by farmers and in data from a disease-recording system based on veterinary reporting

text: Abstract Sweden has a national disease-recording system based on veterinary reporting. From this system, all cattle-disease records are transferred to the dairy industry cattle database (DDD) where they are used for several purposes including research and dairy-health statistics. Our objective was to evaluate the completeness of this data source by comparing it with disease data registered by dairy farmers. The proportion of veterinary-treated disease events was estimated, by diagnosis. Disease incidence in the DDD was compared, by diagnosis and age, with disease data registered by the farmers. Comparison was made, by diagnosis, for (i) all disease events and (ii) those reported as veterinary-treated. Disease events, defined as “observed deviations in health, from the normal” were recorded by the farmers during January, April, July and October 2004. For the diagnoses calving problems, peripartum disorders, puerperal paresis and retained placenta, incidence proportions (IP) with 95% confidence intervals (CIs) were estimated. For all other disease problems, incidence rates (IR) were used. In total, 177 farmers reported at least 1 month and 148 reported all 4 months. Fifty-four percent of all disease events in the farmers’ data were reported as veterinary-treated. For several of the most common diagnoses, the IRs and IPs for all events were significantly higher in farmers’ data than in the DDD. Examples are, in cows: clinical mastitis, cough, gastro-intestinal disorders and lameness in hoof and limb; and in young stock: cough and gastro-intestinal disorders. For veterinary-treated events only, significant differences with higher IR in the farmers’ data were found in young stock for sporadic cough and sporadic gastro-intestinal disorders. The diagnosis “other disorders” had significantly more events in the DDD than in farmers’ data, i.e. veterinarians tended to choose more unspecific diagnoses than the farmers. This result indicates that the true completeness is likely to be higher than our estimate. We conclude that for the time period studied there was differential under-reporting associated with the diagnosis, the age of the animal and whether the herd was served by a state-employed or private veterinarian.


title: Golgi complex localization of the Punta Toro virus G2 protein requires its association with the G1 protein

text: Abstract The glycoproteins of bunyaviruses accumulate in membranes of the Golgi complex, where virus maturation occurs by budding. In this study we have constructed a series of full length or truncated mutants of the G2 glycoprotein of Punta Toro virus (PTV), a member of the Phlebovirus genus of the Bunyaviridae, and investigated their transport properties. The results indicate that the hydrophobic domain preceding the G2 glycoprotein can function as a translocational signal peptide, and that the hydrophobic domain near the C-terminus serves as a membrane anchor. A G2 glycoprotein construct with an extra hydrophobic sequence derived from the N-terminal NSM region was stably retained in the ER, and was unable to be transported to the Golgi complex. The full-length G2 glycoprotein, when expressed on its own, was transported out of the ER and expressed on the cell surface, whereas the G1 and G2 proteins when expressed together are retained in the Golgi complex. A truncated anchor-minus form of the G2 glycoprotein was found to be secreted into the culture medium, but was retained in the Golgi complex when coexpressed with the G1 glycoprotein. These results indicate that the G2 membrane glycoprotein is a class I membrane protein which does not contain a signal sufficient for Golgi retention, and suggest that its Golgi localization is a result of association with the G1 glycoprotein.


Will the real angiotensin converting enzyme please stand up?


title: Systematic review with meta‐analysis: liver manifestations and outcomes in COVID‐19

text: BACKGROUND: The incidence of elevated liver chemistries and the presence of the pre‐existing chronic liver disease (CLD) have been variably reported in COVID‐19. AIMS: To assess the prevalence of CLD, the incidence of elevated liver chemistries and the outcomes of patients with and without underlying CLD/elevated liver chemistries in COVID‐19. METHODS: A comprehensive search of electronic databases from 1 December 2019 to 24 April 2020 was done. We included studies reporting underlying CLD or elevated liver chemistries and patient outcomes in COVID‐19. RESULTS: 107 articles (n = 20 874 patients) were included for the systematic review. The pooled prevalence of underlying CLD was 3.6% (95% CI, 2.5‐5.1) among the 15 407 COVID‐19 patients. The pooled incidence of elevated liver chemistries in COVID‐19 was 23.1% (19.3‐27.3) at initial presentation. Additionally, 24.4% (13.5‐40) developed elevated liver chemistries during the illness. The pooled incidence of drug‐induced liver injury was 25.4% (14.2‐41.4). The pooled prevalence of CLD among 1587 severely infected patients was 3.9% (3%‐5.2%). The odds of developing severe COVID‐19 in CLD patients was 0.81 (0.31‐2.09; P = 0.67) compared to non‐CLD patients. COVID‐19 patients with elevated liver chemistries had increased risk of mortality (OR‐3.46 [2.42‐4.95, P < 0.001]) and severe disease (OR‐2.87 [95% CI, 2.29‐3.6, P < 0.001]) compared to patients without elevated liver chemistries. CONCLUSIONS: Elevated liver chemistries are common at presentation and during COVID‐19. The severity of elevated liver chemistries determines the outcome of COVID‐19. The presence of CLD does not alter the outcome of COVID‐19. Further studies are needed to analyse the outcomes of compensated and decompensated liver disease.


title: Identification of Inonotus obliquus polysaccharide with broad-spectrum antiviral activity against multi-feline viruses

text: Abstract Inonotus obliquus polysaccharides (IOPs) are a potential drug for the prevention and treatment of cancer, cardiopathy, diabetes, AIDs, pancreatitis and other diseases. In this study, we found that IOP can act as a broad-spectrum antiviral drug against feline viruses in the in vitro experiment. Using cell models of feline calicivirus (FCV), we demonstrated that IOP treatment was capable of exhibiting anti-FCV strain F9 activity in cell-based assays and also showed low cytotoxicity. Investigation of the mechanism of action of the compound revealed that IOP treatment induces its inhibitory actions directly on virus particles through blocking viral binding/absorpting. The inhibitory activity against other FCV isolates from China was also identified. More importantly, we found that IOP exhibited broad-spectrum antiviral activity against the feline herpesvirus 1, feline influenza virus H3N2 and H5N6, feline panleukopenia virus and feline infectious peritonitis virus that can contribute to respiratory and gastrointestinal diseases in cats. These findings suggest that IOP may be a potential broad-spectrum antiviral drug against feline viruses.


title: The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel

text: BACKGROUND: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts. METHODS: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team. DISCUSSION: ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010).


title: Characterization of self-assembled virus-like particles of dromedary camel hepatitis e virus generated by recombinant baculoviruses

text: Abstract Dromedary camel hepatitis E virus (DcHEV), a novel hepatitis E virus, has been identified in dromedary camels in Dubai, United Arab Emirates. The antigenicity, pathogenicity and epidemiology of this virus have been unclear. Here we first used a recombinant baculovirus expression system to express the 13 and 111 N-terminus amino-acid-truncated DcHEV ORF2 protein in insect Tn5 cells, and we obtained two types of virus-like particles (VLPs) with densities of 1.300g/cm3 and 1.285g/cm3, respectively. The small VLPs (Dc4sVLPs) were estimated to be 24nm in diameter, and were assembled by a protein with the molecular mass 53kDa. The large VLPs (Dc3nVLPs and Dc4nVLPs) were 35nm in diameter, and were assembled by a 64-kDa protein. An antigenic analysis demonstrated that DcHEV was cross-reactive with G1, G3–G6, ferret and rat HEVs, and DcHEV showed a stronger cross-reactivity to G1 G3–G6 HEV than it did to rat and ferret HEV. In addition, the antibody against DcHEV-LPs neutralized G1 and G3 HEV in a cell culture system, suggesting that the serotypes of these HEVs are identical. We also found that the amino acid residue Met-358 affects the small DcHEV-LPs assembly.


title: Is there a need for improved Cryptosporidium diagnostics in Swedish calves?

text: Abstract Cryptosporidium parvum is a common pathogen in preweaned calves but in Sweden Cryptosporidium bovis, which is considered apathogenic, is the most common species in this age group and it has been identified in diarrhoeal samples, indicating that it could be a cause of diarrhoea. In routine diagnostic procedures, infection is determined by microscopy, which is not sufficient to differentiate these species. We investigated whether routine Cryptosporidium diagnostic procedures need improvement to include species determination. The relation of Cryptosporidium spp. and subtype with the clinical picture and other pathogens was also investigated. A total of 782 diarrhoeal calf samples were analysed and Cryptosporidium infection was diagnosed in 198 samples. Cryptosporidium parvum was identified in 178, C. bovis in six and mixed C. bovis/C. parvum in seven samples. Twenty-seven C. parvum subtypes were identified, of which 16 were newly described. Except for three herds, only one subtype per herd was identified. Cryptosporidium parvum-positive calves were younger than C. bovis-positive calves and most C. parvum infections were seen at 1–3weeks of age. Oocyst counts were higher in C. parvum samples. Yellow faecal colour was associated with C. parvum infection. Watery faeces had no greater association with C. parvum infection, but C. parvum subtype family IIa was more common than subtype family IId in watery faecal samples. No other pathogens were detected in the six C. bovis-infected calves, indicating a pathogenic potential. Our results show that species determination does not need to be included in routine Cryptosporidium diagnostic procedures in order to estimate the clinical relevance of infection in diarrhoeal calves. The maximum age when analysis for clinical cryptosporidiosis is performed can be lowered to 6weeks of age. However, the indicated pathogenic potential of C. bovis warrants further attention.


title: Cellular Importin-α3 Expression Dynamics in the Lung Regulate Antiviral Response Pathways against Influenza A Virus Infection

text: Importin-α adaptor proteins orchestrate dynamic nuclear transport processes involved in cellular homeostasis. Here, we show that importin-α3, one of the main NF-κB transporters, is the most abundantly expressed classical nuclear transport factor in the mammalian respiratory tract. Importin-α3 promoter activity is regulated by TNF-α-induced NF-κB in a concentration-dependent manner. High-level TNF-α-inducing highly pathogenic avian influenza A viruses (HPAIVs) isolated from fatal human cases harboring human-type polymerase signatures (PB2 627K, 701N) significantly downregulate importin-α3 mRNA expression in primary lung cells. Importin-α3 depletion is restored upon back-mutating the HPAIV polymerase into an avian-type signature (PB2 627E, 701D) that can no longer induce high TNF-α levels. Importin-α3-deficient mice show reduced NF-κB-activated antiviral gene expression and increased influenza lethality. Thus, importin-α3 plays a key role in antiviral immunity against influenza. Lifting the bottleneck in importin-α3 availability in the lung might provide a new strategy to combat respiratory virus infections.


docid: qbafkxtr

title: Porcine circovirus type 2 replication is impaired by inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway

text: Abstract Postweaning multisystemic wasting syndrome, which is primarily caused by porcine circovirus type 2 (PCV2), is an emerging and important swine disease. We have recently shown that PCV2 induces nuclear factor kappa B activation and its activation is required for active replication, but the other cellular factors involved in PCV2 replication are not well defined. The extracellular signal-regulated kinase (ERK) which served as an important component of cellular signal transduction pathways has been shown to regulate many viral infections. In this report, we show that PCV2 activates ERK1/2 in PCV2-infected PK15 cells dependent on viral replication. The PCV2-induced ERK1/2 leads to phosphorylation of the ternary complex factor Elk-1, which kinetically paralleled ERK1/2 activation. Inhibition of ERK activation with U0126, a specific MEK1/2 inhibitor, significantly reduced viral progeny release. Investigations into the mechanism of ERK1/2 regulation revealed that inhibition of ERK activation leads to decreased viral transcription and lower virus protein expression. These data indicate that the ERK signaling pathway is involved in PCV2 infection and beneficial to PCV2 replication in the cultured cells.


title: Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study

text: BACKGROUND: Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population. METHODS: We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay. RESULTS: Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%–75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 μg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 μg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 μg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 μg/L in 14/35 (40%) patients and more than 0.25 μg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 μg/L and three had a PCTmax less than 0.1 μg/L. The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 μg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 μg/L respectively, P = 0.80). CONCLUSION: The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 μg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.


title: How to Interpret and Pursue an Abnormal Complete Blood Cell Count in Adults

text: A complete blood cell count (CBC) is one of the most common laboratory tests in medicine. For example, at our institution alone, approximately 1800 CBCs are ordered every day, and 10% to 20% of results are reported as abnormal. Therefore, it is in every clinician's interest to have some understanding of the specific test basics as well as a structured action plan when confronted with abnormal CBC results. In this article, we provide practical diagnostic algorithms that address frequently encountered conditions associated with CBC abnormalities including anemia, thrombocytopenia, leukopenia, polycythemia, thrombocytosis, and leukocytosis. The objective is to help the nonhematologist recognize when a subspecialty consultation is reasonable and when it may be circumvented, thus allowing a cost-effective and intellectually rewarding practice.


title: Information available at cut rates: structure and mechanism of ribonucleases

text: Ribonucleases are counterweights in the balance of gene expression and are also involved in the maturation of functional RNA. Recent structural data reveal how ribonucleases recognize and cleave targets, in most cases with the catalytic assistance of metal cofactors. Many of these enzymes are ‘processive’, in that they make multiple scissions following the binding of substrates; crystallographic data can account for this solution behaviour. These data not only explain how ribonucleases turn over transcripts, but also provide hints about how they often play dual roles in quality control checks on structured RNA.


title: Success in the South Pacific: a case study of successful diffusion of an infection prevention and control program

text: Abstract Introduction The aim of this study was to explore the role of the Diffusion of Innovations framework in adopting an infection prevention and control program (IPCP) in a low and middle income (LMI) country, the Republic of Kiribati. Methods Case-study methodology was used to examine and contextualise the analysis of the Republic of Kiribati's adoption of the IPCP from 2003 to 2010. Data were collected from multiple sources including semi-structured interviews, IPCP documentation, program evaluation and a healthcare worker survey. Data were subjected to thematic analysis and descriptive statistics where relevant to the study design. Results It was found that the self-initiated progression of activities and stimuli has resulted in the successful adoption of a comprehensive IPCP. The process followed the staged model of the classic Diffusion of Innovations process in organisations described by Everett Rogers. Conclusion This case study provides an illustration of how a comprehensive IPCP can be adopted in a LMI country setting with little involvement from external agencies. It identifies key stimuli, opportunities and activities which could be similarly adopted and implemented by other LMI countries.


title: Application of MBR for hospital wastewater treatment in China

text: Abstract In China, the number of hospitals has increased to 19,712 in 2008, with the production of hospital wastewater reaching 1.29×106 m3/d. Membrane bioreactor (MBR) technology presents a more efficient system at removing pathological microorganism compared with existing wastewater treatment systems. In the past 8yr, over 50 MBR plants have been successfully built for hospital wastewater treatments, with the capacity ranging from 20 to 2000m3/d. MBR can effectively save disinfectant consumption (chlorine addition can decrease to 1.0mg/L), shorten the reaction time (approximately 1.5min, 2.5–5% of conventional wastewater treatment process), and attain a good effect of inactivation of microorganism. Higher disinfection efficacy is achieved in MBR effluents at lower dose of disinfectant with less disinfection by-products (DBPs). Moreover, when capacity of MBR plants increases from 20 to 1000m3/d, their operating cost decreases sharply.


title: Impact of extreme weather events on urban human flow: A perspective from location-based service data

text: This study investigates the impact of extreme weather events on urban human flow disruptions using location-based service data obtained from Baidu Map. Utilizing the 2018 Typhoon Mangkhut as an example, the spatial and temporal variations of urban human flow patterns in Shenzhen are examined using GIS and spatial flow analysis. In addition, the variation of human flow by different urban functions (e.g. transport, recreational, institutional, commercial and residential related facilities) is also examined through an integration of flow data and point-of-interest (POI) data. The study reveals that urban flow patterns varied substantially before, during, and after the typhoon. Specifically, urban flows were found to have reduced by 39% during the disruption. Conversely, 56% of flows increased immediately after the disruption. In terms of functional variation, the assessment reveals that fundamental urban functions, such as industrial (work) and institutional - (education) related trips experienced less disruption, whereas the typhoon event appears to have a relatively larger negative influence on recreational related trips. Overall, the study provides implications for planners and policy makers to enhance urban resilience to disasters through a better understanding of the urban vulnerability to disruptive events.


title: Novel Lyssavirus in Bat, Spain

text: A new tentative lyssavirus, Lleida bat lyssavirus, was found in a bent-winged bat (Miniopterus schreibersii) in Spain. It does not belong to phylogroups I or II, and it seems to be more closely related to the West Causasian bat virus, and especially to the Ikoma lyssavirus.


title: Surgical care of thoracic malignancies during the COVID‐19 pandemic in México: An expert consensus guideline from the Sociedad Mexicana de Oncología (SMeO) and the Sociedad Mexicana de Cirujanos Torácicos Generales (SMCTG)

text: To date, the impact, timeline and duration of COVID‐19 pandemic remains unknown and more than ever it is necessary to provide safe pathways for cancer patients. Multiple triage systems for nonemergent surgical procedures have been published, but potentially curative cancer procedures are essential surgery rather than elective surgery. In the present and future scenario of our country, thoracic oncology teams may have the difficult decision of weighing the utility of surgical intervention against the risk for inadvertent COVID‐19 exposure for patients and medical staff. In consequence, traditional pathways of surgical care must be adjusted to reduce the risk of infection and the use of resources. It is recommended that all thoracic cancer patients should be offered treatment according to the accepted standard of care until shortage of services require a progressive reduction in surgical cases. Here, we present a consensus of recommendations discussed by a multidisciplinary panel of experts on thoracic oncology and based on the best available evidence, and hope it will provide a modifiable framework of guidance for local strategy planners in thoracic cancer care services in Mexico. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This article provides recommendations to guarantee the continuity of surgical care for thoracic oncology cases during COVID‐19 pandemic, whilst maintaining the safety of patients and medical staff. WHAT THIS STUDY ADDS: This guideline is the result of an expert consensus on thoracic surgical oncology with recommendations adapted to medical, economic and social realities of Mexico.


title: COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up

text: Abstract Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.


title: Mannose-Binding Lectin in Severe Acute Respiratory Syndrome Coronavirus Infection

text: Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS


title: Clinical and epidemiological aspects of human bocavirus infection

text: Abstract Human bocavirus was recently described as a novel member of the Parvoviridae to infect humans. Based on accumulating clinical and epidemiological data the virus is currently being associated with respiratory infections in young children and infants and is furthermore discussed as causative agent of gastrointestinal illness.


title: Soil bacterial communities in three rice-based cropping systems differing in productivity

text: Soil microorganisms play an important role in determining productivity of agro-ecosystems. This study was conducted to compare diversity, richness, and structure (relative abundance at the phylum level) of soil bacterial communities among three rice-based cropping systems, namely, a winter fallow-rice-rice (FRR), green manure (Chinese milk vetch)-rice-rice (MRR), and oilseed rape-rice-rice (ORR), in which MRR and ORR had significantly higher productivity than FRR. A 16S rRNA gene sequence analysis showed that no significant differences were observed in diversity and richness indices (observed species, Shannon, Simpson, Chao1, abundance-based coverage estimators, and phylogeny-based metrics) of soil bacterial communities among the three cropping systems. However, relative abundances of dominant phyla in soil bacterial communities, including Proteobacteria, Acidobacteria, Nitrospirae, Gemmatimonadetes, and Verrucomicrobia, were significantly different among the three cropping systems. In particular, a significant reduction in the relative abundance of Nitrospirae was observed in both MRR and ORR compared with FRR. These results indicate that bacterial community structure was affected by cropping systems in the tested paddy soils. Based on the results of our studies and existing knowledge bases, we speculate that benefits to rice yield may be obtained by reducing the relative abundance of Nitrospirae and increasing the ratio of abundances of Proteobacteria/Acidobacteria in paddy soils.


title: Airborne Infectious Microorganisms

text: Inhalation exposes the upper and lower respiratory tracts of humans to a variety of airborne particles and vapors. Airborne transmission of pathogenic microorganisms to humans from the environment, animals, or other humans can result in disease. Inhalation is an important route of exposure as the lung is more susceptible to infection than the gastrointestinal tract. Ingested microorganisms must past through the acidic environment of the stomach before they can colonize tissue while inhaled microorganisms are deposited directly on the moist surfaces of the respiratory tract. Inhalation of microbial aerosols can elicit adverse human health effects including infection, allergic reaction, inflammation, and respiratory disease. Following inhalation, infectious viruses, bacteria, and fungi can establish in host cells of the respiratory tract. Some are translocated and infect the gastrointestinal tract and other tissues. This chapter discusses human viral, bacterial, and fungal diseases transmitted via aerosols. Viral diseases presented are influenza, severe acute respiratory syndrome (SARS), Norwalk-like viruses (NLVs) and hantavirus disease, measles, and varicella. Bacterial diseases are Legionnaires’ disease, tuberculosis, and nontubercule mycobacterial disease. Exposure to some Gram-negative and Gram-positive bacteria, endotoxin, and actinomycetes when dispersed through the air can result in disease following inhalation. Fungal diseases included are histoplasmosis, coccidiomycosis, blastomycosis, cryptococcosis, and aspergillosis. The threat of bioterrorism with airborne infectious agents is also briefly presented.


title: Review on Machine and Deep Learning Models for the Detection and Prediction of Coronavirus

text: The novel Coronavirus disease has increased rapidly in the Wuhan city of China in December 2019. This fatal virus has spread across the whole world like a fire in different stages and affecting millions of population and thousands of deaths worldwide. Therefore, it is essential to classify the infected people, so that they can take the precaution in the earlier stages. Also, due to the increasing cases spread of Coronavirus, there are only limited numbers of polymerase change reaction kits available in the hospitals for testing Coronavirus patients. That why it is extremely important to develop artificial intelligence-based automatic diagnostic tools to classify the Coronavirus outbreak. The objective of this paper is to know the novel disease epidemiology, major prevention from spreading of Coronavirus Severe Acute Respiratory Syndrome, and to assess the machine and deep learning-based architectures performance that is proposed in the present year for classification of Coronavirus images such as, X-Ray and computed tomography. Specifically, advanced deep learning-based algorithms known as the Convolutional neural network, which plays a great effect on extracting highly essential features, mostly in terms of medical images. This technique, with using CT and X-Ray image scans, has been adopted in most of the recently published articles on the Coronavirus with remarkable results. Furthermore, according to this paper, this can be noted and said that deep learning technology has potential clinical applications.


title: Bacterial pathogens were detected from human exhaled breath using a novel protocol

text: Abstract It is generally believed that influenza outbreak is associated with breath-borne transmission of viruses, however relevant evidence is little for that of respiratory bacterial infections. On another front, point-of-care infection diagnostic methods at the bedside are significantly lacking. Here, we used a newly developed protocol of integrating an exhaled breath condensate (EBC) collection device (PKU BioScreen) and Loop Mediated Isothermal Amplification (LAMP) to investigate what bacterial pathogens can be directly exhaled out from humans. Exhaled breath condensates were collected from human subjects with respiratory infection symptoms at Peking University 3rd hospital using the BioScreen. The screened bacterial pathogens included Streptococcus pneumoniae, Staphylococcus aureus, Methicillin-resistant Stphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, Haemophilus influenzae, Legionella pneumophila, Mycoplasma Pneumonia, Chlamydia pneumonia, and Mycobacterium tuberculosis. The results were further compared and validated using throat swabs from the same patients by a PCR method. Here, human bacterial pathogens such as H. influenzae, P. aeruginosa, E. coli, S. aureus and MRSA were detected in exhaled breath using the developed protocol that integrates the EBC collection and LAMP. For the patients recruited from the hospital, seven types of pathogens were detected from 36.5% of them, and for the remaining subjects none of those screened bacterial pathogens was detected. Importantly, some super resistant bacteria such as MRSA were detected from the exhaled breath, suggesting that breathing might be also an important bacterial transmission route. Results from throat swabs showed that 36.2% of the subjects were found to be infected with H. influenzae, P. aeruginosa, E. coli, S. maltophilia, S. aureus and MRSA. For the EBC samples, 33.3% were found to be infected with MRSA, E. coli and P. aeruginosa. Depending on the initial pathogen load in the sample, the entire protocol (EBC-LAMP) only takes 20–60min to complete for a respiratory infection diagnosis. For different detection methods and pathogens, the agreements between the EBC and throat swabs from the same patients were found to range from 35% to 65%. Here, we have detected several bacterial pathogens including MRSA from exhaled breath, and the developed protocol could be very useful for the bedside pathogen screening particularly in remote areas where resources are significantly limited or prohibited.


Treating COVID‐19 in Rural America


docid: hhyvbvgf

title: Evaluation of Commercial Diagnostic Assays for the Specific Detection of Avian Influenza A (H7N9) Virus RNA Using a Quality-Control Panel and Clinical Specimens in China

text: A novel avian influenza A H7N9-subtype virus emerged in China in 2013 and threatened global public health. Commercial kits that specifically detect avian influenza A (H7N9) virus RNA are urgently required to prepare for the emergence and potential pandemic of this novel influenza virus. The safety and effectiveness of three commercial molecular diagnostic assays were evaluated using a quality-control panel and clinical specimens collected from over 90 patients with confirmed avian influenza A (H7N9) virus infections. The analytical performance evaluation showed that diverse influenza H7N9 viruses can be detected with high within- and between-lot reproducibility and without cross-reactivity to other influenza viruses (H1N1 pdm09, seasonal H1N1, H3N2, H5N1 and influenza B). The detection limit of all the commercial assays was 2.83 Log(10) copies/μl [0.7 Log(10)TCID(50)/mL of avian influenza A (H7N9) virus strain A/Zhejiang/DTID-ZJU01/2013], which is comparable to the method recommended by the World Health Organization (WHO). In addition, using a WHO-Chinese National Influenza Center (CNIC) method as a reference for clinical evaluation, positive agreement of more than 98% was determined for all of the commercial kits, while negative agreement of more than 99% was observed. In conclusion, our findings provide comprehensive evidence for the high performance of three commercial diagnostic assays and suggest the application of these assays as rapid and effective diagnostic tools for avian influenza A (H7N9) virus in the routine clinical practice of medical laboratories.


title: The Pandemic Academy: Reflections of Infectious Diseases Fellows During COVID-19

text: The COVID-19 pandemic has taken over the world at an unprecedented scale. As Infectious Diseases fellows, this has come straight into the heart of our specialty and created a unique impact on our training progress and perspective. Here, we reflect on our early experiences during the first three months of battling COVID-19 in Singapore and glean some lessons for this pandemic and beyond.


title: Assessment of the Efficacy of Commercially Available and Candidate Vaccines against a Pandemic H1N1 2009 Virus

text: Background. The emergence and global spread of the pandemic H1N1 2009 influenza virus have raised questions regarding the protective effect of available seasonal vaccines and the efficacy of a newly produced matched vaccine. Methods. Ferrets were immunized with the 2008–2009 formulations of commercially available live attenuated (FluMist; MedImmune) or split-inactivated (Fluviral; GlaxoSmithKline) vaccines, a commercial swine vaccine (FluSure; Pfizer), or a laboratory-produced matched inactivated whole-virus vaccine (A/Mexico/InDRE4487/2009). Adaptive immune responses were monitored, and the animals were challenged with A/Mexico/InDRE4487/2009 after 5 weeks. Results. Only animals that received the swine or matched vaccines developed detectable hemagglutination- inhibiting antibodies against the challenge virus, whereas a T cell response was exclusively detected in animals vaccinated with FluMist. After challenge, all animals had high levels of virus replication in the upper respiratory tract. However, preexisting anti—pandemic H1N1 2009 antibodies resulted in reduced clinical signs and improved survival. Surprisingly, FluMist was associated with a slight increase in mortality and greater lung damage, which correlated with early up-regulation of interleukin-10. Conclusions. The present study demonstrates that a single dose of matched inactivated vaccine confers partial protection against a pandemic H1N1 2009 virus, and it suggests that a higher dose or prime-boost regimen may be required. The consequences of mismatched immunity to influenza merit further investigation.


Cardiac injury and mortality in COVID-19: a reappraisal


title: Microarray and real-time RT-PCR analyses of differential human gene expression patterns induced by severe acute respiratory syndrome (SARS) coronavirus infection of Vero cells

text: Abstract Vero E6 African green monkey kidney cells are highly susceptible to infection with the newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV), and they are permissive for rapid viral replication, with resultant cytopathic effects. We employed cDNA microarray analysis to characterize the cellular transcriptional responses of homologous human genes at 12 h post-infection. Seventy mRNA transcripts belonging to various functional classes exhibited significant alterations in gene expression. There was considerable induction of heat shock proteins that are crucial to the immune response mechanism. Modified levels of several transcripts involved in pro-inflammatory and anti-inflammatory processes exemplified the balance between opposing forces during SARS pathogenesis. Other genes displaying altered transcription included those associated with host translation, cellular metabolism, cell cycle, signal transduction, transcriptional regulation, protein trafficking, protein modulators, and cytoskeletal proteins. Alterations in the levels of several novel transcripts encoding hypothetical proteins and expressed sequence tags were also identified. In addition, transcription of apoptosis-related genes DENN and hIAP1 was upregulated in contrast to FAIM. Elevated Mx1 expression signified a strong host response to mediate antiviral resistance. Also expressed in infected cells was the C-terminal alternative splice variant of the p53 tumor suppressor gene encoding a modified truncated protein that can influence the activity of wild-type p53. We observed the interplay between various mechanisms to favor virus multiplication before full-blown apoptosis and the triggering of several pathways in host cells in an attempt to eliminate the pathogen. Microarray analysis identifies the critical host–pathogen interactions during SARS-CoV infection and provides new insights into the pathophysiology of SARS.


docid: copxoyqu

title: Expression and membrane integration of SARS-CoV M protein

text: SARS-CoV M gene fragment was cloned and expressed as a recombinant protein fused with a V5 tag at the C-terminus in Vero E6 cells. In addition to un-glycosylated and glycosylated proteins, one product with smaller size initiated in-frame from the third Met residues probably through ribosomal re-initiation was also detected. Translation initiated in-frame from the third Met is unusual since the sequence around the first Met of SARS-CoV M protein contains the optimal consensus Kozak sequence. The function of this smaller translated product awaits further investigation. Similar to other N-glycosylated proteins, glycosylation of SARS-CoV M protein was occurred co-translationally in the presence of microsomes. The SARS-CoV M protein is predicted as a triple-spanning membrane protein lack of a conventional signal peptide. The second and third trans-membrane regions (a.a. 46–68 and 78–100) are predicted to be the primary type helices, which will be able to penetrate into membrane by themselves, while the first trans-membrane region (a.a. 14–36) is predicted to be the secondary type helix, which is considered to be stabilized by the interaction with other trans-membrane segments. As expected, the second and third trans-membrane regions were able to insert a cytoplasmic protein into the endoplasmic reticulum membrane more efficiently than the first one. These results should be important for the study of SARS-CoV morphogenesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11373-008-9235-1) contains supplementary material, which is available to authorized users.


title: Nucleocapsid Protein as Early Diagnostic Marker for SARS

text: Serum samples from 317 patients with patients with severe acute respiratory syndrome (SARS) were tested for the nucleocapsid (N) protein of SARS-associated coronavirus, with sensitivities of 94% and 78% for the first 5 days and 6–10 days after onset, respectively. The specificity was 99.9%. N protein can be used as an early diagnostic maker for SARS.


title: An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China

text: Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.


The clinical significance of sialoderiveratives in the search for novel means of antipathogen therapy


title: Structural breaks, tourism development, and economic growth: Evidence from Taiwan

text: Abstract Our paper differs from previous studies by examining the issue of whether regime changes have broken down the stability of the long-run relationships between tourism development and real GDP in Taiwan for the 1959–2003 period. We empirically investigate the co-movements and the causal relationships among real GDP, tourism development, and the real exchange rate in a multivariate model. We use two different tourism variables—international tourism receipts and number of international tourist arrivals. To employ the unit root tests and the cointegration tests allowing for a structural break, the empirical evidence clearly shows that the causality between tourism and economic growth is bi-directional. Lastly, the international and cross-strait political change, economic shocks, and the relaxing of some tourism control and policies would break down the stability of the relationships between tourism development and economic growth. Overall, we do find the structural breakpoints, and they look to match clearly with the corresponding critical economic, political, or tourist incidents.


title: Comparative studies of the expression of creatine kinase isoforms under immune stress in Pelodiscus sinensis

text: The expression and localization of different isoforms of creatine kinase in Pelodiscus sinensis (PSCK) were studied to reveal the role of PSCK isozymes (PSCK-B, PSCK-M, PSCK-S) under bacterial infection-induced immunologic stress. The computational molecular dynamics simulations predicted that PSCK-S would mostly possess a kinase function in a structural aspect when compared to PSCK-B and PSCK-M. The assay of biochemical parameters such as total superoxide dismutase (T-SOD), lactate dehydrogenase (LDH), malondialdehyde (MDA), catalase (CAT), and the content of ATP were measured along with total PSCK activity in different tissue samples under bacterial infection. The expression detections of PSCK isozymes in vitro and in vivo were overall well-matched where PSCK isozymes were expressed differently in P. sinensis tissues. The results showed that PSCK-B mostly contributes to the spleen, followed by the liver and myocardium; PSCK-M mostly contributes to the liver, followed by the myocardium and skeletal muscle, while PSCK-S contributes to the spleen and is uniquely expressed in skeletal muscle. Our study suggests that the various alterations of PSCK isozymes in tissues of P. sinensis are prone to defense the bacterial infection and blocking energetic imbalance before severe pathogenesis turned on in P. sinensis.


title: COVID-19 in diabetic patients: related risks and specifics of management

text: Abstract Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favor of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.


title: Loss and Grief amidst COVID-19: A Path to Adaptation and Resilience

text: Abstract The COVID-19 pandemic has posed an extreme threat to global health and become a leading cause of death worldwide. Loss, as a more encompassing theme, interweaves many aspects of people’s life in this challenging time. Failure to address the pressing needs of those experiencing loss and grief may result in poor mental and physical health. Recognizing the uniqueness of each individual and their loss and grief will provide opportunities to develop tailored strategies that facilitate functional adaptation to loss and promote mental health and wellbeing in this crisis.


docid: rynndfmm

title: Immunogenicity of a neutralizing epitope from porcine epidemic diarrhea virus: M cell targeting ligand fusion protein expressed in transgenic rice calli

text: To increase immune responses of plant-based vaccines in intestine mucosal immune systems, a synthetic neutralizing epitope (sCOE) gene of porcine epidemic diarrhea virus (PEDV) was fused with M cell-targeting ligand (Co1) and introduced into a plant expression vector under the control of rice amylase 3D promoter. The sCOE–Co1 fusion gene was introduced into rice calli via the particle bombardment-mediated transformation method. The stable integration and transcriptional expression of the sCOE–Co1 fusion gene was confirmed by genomic DNA PCR amplification and Northern blot analysis, respectively. The expression of the COE–Co1 fusion protein was confirmed by immunoblot analysis. The highest expression level of the COE–Co1 fusion protein reached 0.083 % of the total soluble protein according to quantitative densitometry of Western blot analysis. Mice immunized with transgenic rice calli protein extracts induced significant serum IgG and fecal IgA antibody levels against purified bacterial COE. The systemic and mucosal immune responses were confirmed by measuring COE-specific IgG and IgA antibody-secreting cells in the lymphocytes extracted from the spleen and COE-specific IgA antibody-secreting cells in the Peyer’s patches from immunized mice. These results indicated that oral immunization of plant-produced COE–Co1 fusion protein could elicit efficient systemic and mucosal immune responses against the COE antigen. Key message Neutralizing epitope from porcine epidemic diarrhea virus-M cell targeting ligand fusion protein was produced in transgenic rice calli and elicited systemic and mucosal immune responses by oral administration in mice.


title: The virus-specific intracellular RNA species of two murine coronaviruses: MHV-A59 and MHV-JHM

text: Abstract Seven virus-specific, polyadenylated RNA species have been identified in mouse cells infected with the murine coronaviruses MHV-A59 (A59V) or MHV-JHM (JHMV). MHV-infected 17CL·1 cells were labeled with [32P]orthophosphate in the presence of actinomycin D and the cytoplasmic RNA was extracted and analyzed by agarose gel electrophoresis. These RNA species range in size from 6.3 × 105 to 6.1 × 106 daltons. The A59V and JHMV-specific RNAs have identical molecular weights and comigrate in agarose gels. The largest intracellular RNA species is identical to RNA isolated from purified virions, as determined by agarose gel electrophoresis and oligonucleotide fingerprint studies of ribonuclease T1 digests. Oligonucleotide fingerprints of the six subgenomic RNAS show that the sequences they contain are present in virion RNA, confirming their virus-specific nature. The fingerprinting studies also demonstrate that the six subgenomic RNA species make up a nested set. The sequences present in each RNA species are also present in all larger RNA species. These larger RNAs also contain additional sequences consistent with their greater size. The subgenomic RNAs fulfull many of the criteria for mRNAs. Possible mechanisms for generating these RNAs are discussed.


title: The objectives and outcomes of airport privatisation

text: Abstract Airport privatisation is a controversial yet growing trend that has been accompanied by an expanding quantity of related research. However there has been very little attempt to synthesise this research and identify overarching findings that single studies do not produce. Hence it is the aim here to apply a systematic review of all the results in the academic literature. Both the objectives and outcomes of privatisation are considered although the literature appears surprisingly lacking in assessing whether these are closely aligned. A need for improvements in efficiency, coupled with a requirement for greater investment, appear to be the key drivers of privatisation but the evidence, as to whether there are actually performance benefits, is inconclusive. Improvements need to be made to the methods used, but given that the range of airport privatisation models has now become so diverse, more focus on governance and institutional structures may also yield useful conclusions.


title: Analysis of health stories in daily newspapers in the UK

text: Summary Objectives To assess what makes a good piece of medical reporting in newspapers, to quantify what is being reported on in the major British newspapers, to identify the sources of the news threads, and to assess how these are reported. Study design Development and validation of a tool to assess the quality of reporting of health-related articles, and assessment of the quality of these articles in British newspapers. Methods Eight national daily newspapers from the UK were reviewed for 20 days over a 2-month period. All articles reporting newly emerging research pertaining to health in humans were included and reviewed independently by two raters. A descriptive analysis was performed. Subsequently, a quality assessment tool for use by a non-expert was developed and validated to objectively assess the quality of a newspaper article on a health-related topic. Results The quality assessment tool was found to have good internal consistency and inter-rater reliability. The Daily Mail published almost twice as many articles as its nearest rival, The Daily Express, and over eight times as many articles as The Guardian. Articles in The Times were, on average, more than twice as long as those in The Sun and The Daily Telegraph. The highest quality articles were in The Times and The Independent, with the lowest quality articles in The Sun. The quality scores of anonymous articles were significantly lower than those attributed to named journalists. Conclusions There are significant differences in the quality of reporting within and between major daily UK newspapers, with anonymous articles being the poorest quality, and widespread reliance on press releases from the major UK scientific journals.


SARS-CoV-2/COVID-19 und neuromuskuläre Erkrankungen: Bestandsaufnahme der DGN (Deutsche Gesellschaft für Neurologie) Kommission Motoneuron- und neuromuskuläre Erkrankungen


Sars-COV-2 and dental treatments


The Post-Acute and Long-Term Care Crisis in the Aftermath of COVID-19: a Dutch Perspective


title: Vacuolar neuronal degeneration in the ventral horns of SCID mice in naturally occurring Theiler's encephalomyelitis

text: Abstract During a spontaneous outbreak of Theiler's encephalomyelitis severe combined immunodeficient mice developed high morbidity and high mortality. Histological lesions were localized in the ventral horns of the spinal cord and brain stem. The salient features were the severe vacuolar degeneration of neurones and glial cells and the absence of inflammatory cellular infiltrates. The clinical and pathological features of this outbreak indicate that the SCID mouse would be a much improved model for studying the mechanism of poliovirus infection and of virus-induced demyelinating diseases.


title: Characterization and Pathogenicity of the Porcine Deltacoronavirus Isolated in Southwest China

text: Porcine deltacoronavirus (PDCoV) is a newly emerging enteric pathogen in swine that causes diarrhea in neonatal piglets and creates an additional economic burden on porcine industries in Asia and North America. In this study, a PDCoV isolate, CHN-SC2015, was isolated from Sichuan Province in southwest China. The isolate was characterized by a cytopathic effect, immunofluorescence, and electron microscopy. CHN-SC2015 titers in LLC-PK cells ranged from 10(4.31) to 10(8.22) TCID(50)/mL during the first 30 passages. During serial passage, 11 nucleotide mutations occurred in the S gene, resulting in nine amino acid changes. A whole genome sequencing analysis demonstrated that CHN-SC2015 shares 97.5%–99.1% identity with 59 reference strains in GenBank. Furthermore, CHN-SC2015 contained 6-nt deletion and 9-nt insertion in the ORF1ab gene, 3-nt deletion in the S gene and 11-nt deletion in its 3′UTR compared with other reference strains available in GenBank. A phylogenetic analysis showed that CHN-SC2015 is more closely related to other PDCoV strains in China than to the strains from Southeast Asia, USA, Japan, and South Korea, indicating the diversity of genetic relationships and regional and epidemic characteristics among these strains. A recombination analysis indicated that CHN-SC2015 experienced recombination events between SHJS/SL/2016 and TT-1115. In vivo infection demonstrated that CHN-SC2015 is highly pathogenic to sucking piglets, causing diarrhea, vomiting, dehydration, and death. Virus was shed daily in the feces of infected piglets and upon necropsy, was found distributed in the gastrointestinal tract and in multiple organs. CHN-SC2015 is the first systematically characterized strain from southwest China hitherto reported. Our results enrich the body of information on the epidemiology, pathogenicity and molecular evolution associated with PDCoV.


A new infectious disease challenge: Urbani severe acute respiratory syndrome (SARS) associated coronavirus


title: First experience of SARS‐CoV‐2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study

text: Immunocompromised patients may be at increased risk for complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. However, comprehensive data of SARS‐CoV‐2 infection in solid organ transplant (SOT) recipients are still lacking. We performed a multicenter nationwide observational study within the Swiss Transplant Cohort Study (STCS) to describe the epidemiology, clinical presentation, treatment and outcomes of the first microbiologically documented SARS‐CoV‐2 infection among SOT recipients. Overall, 21 patients were included with a median age of 56 years (10 kidney, 5 liver, 1 pancreas, 1 lung, 1 heart and 3 combined transplantations). The most common presenting symptoms were fever (76%), dry cough (57%), nausea (33%) and diarrhea (33%). Ninety‐five percent and 24% of patients required hospital and ICU admission, respectively, and 19% were intubated. After a median of 33 days of follow‐up, 16 patients were discharged, 3 were still hospitalized and 2 patients died. These data suggest that clinical manifestations of SARS‐CoV‐2 infection in middle‐aged SOT recipients appear to be similar to the general population without an apparent higher rate of complications. These results need to be confirmed in larger cohorts.


title: A host-range restricted parainfluenza virus type 3 (PIV3) expressing the human metapneumovirus (hMPV) fusion protein elicits protective immunity in African green monkeys

text: Human metapneumovirus (hMPV) infection causes respiratory tract disease similar to that observed during human respiratory syncytial virus infection (hRSV). hMPV infections have been reported across the entire age spectrum although the most severe disease occurs in young children. No vaccines, chemotherapeutics or antibodies are presently available for preventing or treating hMPV infections. In this study, a bovine/human chimeric parainfluenza virus type 3 (b/h PIV3) expressing the human parainfluenza type 3 (hPIV3) fusion (F) and hemagglutinin-neuraminidase (HN) proteins was engineered to express hMPV fusion (F) protein from the second genome position (b/h PIV3/hMPV F2) with the goal of generating a novel hMPV vaccine. b/h PIV3/hMPV F2 was previously shown to protect hamsters from challenge with wt hMPV (Tang RS, Schickli JH, Macphail M, Fernandes F, Bicha L, Spaete J, et al. Effects of human metapneumovirus and respiratory syncytial virus antigen insertion in two 3’ proximal genome positions of bovine/human parainfluenza virus type 3 on virus replication and immunogenicity. J Virol 2003;77:10819–28) and is here further evaluated for efficacy and immunogenicity in African green monkeys (AGMs). AGMs immunized intranasally and intratracheally with b/h PIV3/hMPV F2 generated hMPV- and hPIV3-specific humoral and cellular immune responses and were protected from wt hMPV infection. In a separate study, the host-range restriction of b/h PIV3/hMPV F2 replication relative to wt hPIV3 was performed in rhesus monkeys to demonstrate attenuation. These studies showed that b/h PIV3/hMPV F2 was immunogenic, protective and attenuated in non-human primates and warrants further evaluation in humans as a vaccine candidate for prevention of hMPV-associated respiratory tract diseases.


title: Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching

text: BACKGROUND: Antisense oligomer induced exon skipping aims to reduce the severity of Duchenne muscular dystrophy by redirecting splicing during pre-RNA processing such that the causative mutation is by-passed and a shorter but partially functional Becker muscular dystrophy-like dystrophin isoform is produced. Normal exons are generally targeted to restore the dystrophin reading frame however, an appreciable subset of dystrophin mutations are intra-exonic and therefore have the potential to compromise oligomer efficiency, necessitating personalised oligomer design for some patients. Although antisense oligomers are easily personalised, it remains unclear whether all patient polymorphisms within antisense oligomer target sequences will require the costly process of producing and validating patient specific compounds. METHODS: Here we report preclinical testing of a panel of splice switching antisense oligomers, designed to excise exon 25 from the dystrophin transcript, in normal and dystrophic patient cells. These patient cells harbour a single base insertion in exon 25 that lies within the target sequence of an oligomer shown to be effective at removing exon 25. RESULTS: It was anticipated that such a mutation would compromise oligomer binding and efficiency. However, we show that, despite the mismatch an oligomer, designed and optimised to excise exon 25 from the normal dystrophin mRNA, removes the mutated exon 25 more efficiently than the mutation-specific oligomer. CONCLUSION: This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.


title: Do we really need guidelines for HRA during COVID‐19 pandemic? ‐ Response

text: Mistrangelo et al raise a number of issues in connection with the International Anal Neoplasia Society guidelines for the practice of High Resolution Anoscopy (HRA) in the era of COVID‐19. The authors suggest that the guidelines advocate “mandatory” HRA for “screening”. On the contrary, the guidelines clearly define risk prioritisation, in terms of both potential COVID‐19 exposure and the dangers associated with delayed diagnosis of anal cancers. Centres without access to high quality HRA services may have to rely on digital anal rectal examination to eventually diagnose large anal cancers. HRA has the ability to accurately identify early anal cancers and worrisome pre‐cancerous lesions, and thus to facilitate early intervention. It therefore has the capacity to substantially improve survival and quality of life of patients. This remains true in the era of COVID‐19, and will be of increasing importance as the epidemic continues and services remain disrupted.


title: Catheter-directed thrombolysis in COVID-19 pneumonia with acute PE: Thinking beyond the guidelines

text: • Patients having COVID-19 pneumonia are at risk of venous thromboembolism. • Prophylaxis versus anticoagulation for severely ill patients is currently debated. • No specific guidelines for the management of severe pulmonary embolism exist. • Endovascular pulmonary embolism therapy may play a critical role in severe COVID-19.


title: The need for one health degree programs

text: This commentary offers suggestions for improving public health and public health education by emphasizing One Health principles, the integrating of human, veterinary, and environmental sciences. One Health is increasingly recognized as a powerful approach to the prevention and control of zoonotic diseases, increasing food productivity and safety, improving biosecurity, and enhancing many areas of biomedical research.


title: Metagenomic Sequencing for Combined Detection of RNA and DNA Viruses in Respiratory Samples from Paediatric Patients

text: Introduction Viruses are the main cause of respiratory tract infections. Metagenomic next-generation sequencing (mNGS) enables the unbiased detection of all potential pathogens in a clinical sample, including variants and even unknown pathogens. To apply mNGS in viral diagnostics, there is a need for sensitive and simultaneous detection of RNA and DNA viruses. In this study, the performance of an in-house mNGS protocol for routine diagnostics of viral respiratory infections, with single tube DNA and RNA sample-pre-treatment and potential for automated pan-pathogen detection was studied. Materials and Methods The sequencing protocol and bioinformatics analysis was designed and optimized including the optimal concentration of the spike-in internal controls equine arteritis virus (EAV) and phocine-herpes virus-1 (PhHV-1).The whole genome of PhHV-1 was sequenced and added to the NCBI database. Subsequently, the protocol was retrospectively validated using a selection of 25 respiratory samples with in total 29 positive and 346 negative PCR results, previously sent to the lab for routine diagnostics. Results The results demonstrated that our protocol using Illumina Nextseq 500 sequencing with 10 million reads showed high repeatability. The NCBI RefSeq database as opposed to the NCBI nucleotide database led to enhanced specificity of virus classification. A correlation was established between read counts and PCR cycle threshold value, demonstrating the semi-quantitative nature of viral detection by mNGS. The results as obtained by mNGS appeared condordant with PCR based diagnostics in 25 out of the 29 (86%) respiratory viruses positive by PCR and in 315 of 346 (91%) PCR-negative results. Viral pathogens only detected by mNGS, not present in the routine diagnostic workflow were influenza C, KI polyomavirus, and cytomegalovirus. Conclusions Sensitivity and analytical specificity of this mNGS protocol was comparable with PCR and higher when considering off-PCR target viral pathogens. All potential viral pathogens were detected in one single test, while it simultaneously obtained detailed information on detected viruses.


docid: urkuofmu

title: Initial impacts of global risk mitigation measures taken during the combatting of the COVID-19 pandemic

text: Abstract This paper presents an analysis of risk mitigation measures taken by countries around the world facing the current COVID-19 outbreak. In light of the current pandemic the authors collated and clustered (using harmonised terminology) the risk mitigation measures taken around the globe in the combat to contain, and since March 11 2020, to limit the spread of the SARS-CoV-2 virus known to cause the Coronavirus disease 2019 (COVID-19). This overview gathers lessons learnt, providing an update on the current knowledge for authorities, sectors and first responders on the effectiveness of said measures, and may allow enhanced prevention, preparedness and response for future outbreaks. Various measures such as mobility restrictions, physical distancing, hygienic measures, socio-economic restrictions, communication and international support mechanisms have been clustered and are reviewed in terms of the nature of the actions taken and their qualitative early-perceived impact. At the time of writing, it is still too premature to express the quantitative effectiveness of each risk mitigation cluster, but it seems that the best mitigation results are reported when applying a combination of voluntary and enforceable measures.


title: Comparison of four nasal sampling methods for the detection of viral pathogens by RT-PCR—A GA2LEN project

text: Abstract The aim of this study was to compare the efficacy and patient discomfort between four techniques for obtaining nasal secretions. Nasal secretions from 58 patients with symptoms of a common cold, from three clinical centers (Amsterdam, Lodz, Oslo), were obtained by four different methods: swab, aspirate, brush, and wash. In each patient all four sampling procedures were performed and patient discomfort was evaluated by a visual discomfort scale (scale 1–5) after each procedure. Single pathogen RT-PCRs for Rhinovirus (RV), Influenza virus and Adenovirus, and multiplex real-time PCR for RV, Enterovirus, Influenza virus, Adenovirus, Respiratory Syncytial Virus (RSV), Parainfluenza virus, Coronavirus, Metapneumovirus, Bocavirus and Parechovirus were performed in all samples. A specific viral cause of respiratory tract infection was determined in 48 patients (83%). In these, the detection rate for any virus was 88% (wash), 79% (aspirate), 77% (swab) and 74% (brush). The degree of discomfort reported was 2.54 for swabs, 2.63 for washes, 2.68 for aspirates and 3.61 for brushings. Nasal washes yielded the highest rate of viral detection without excessive patient discomfort. In contrast, nasal brushes produced the lowest detection rates and demonstrated the highest level of discomfort.


title: Crisis Symptom Management and Patient Communication Protocols Are Important Tools for All Clinicians Responding to COVID-19

text: Abstract Symptom management and skilled communication with patients and families are essential clinical services in the midst of the COVID-19 pandemic. While palliative care specialists have training in these skills, many front-line clinicians from other specialties do not. It is imperative that all clinicians responding to the COVID-19 crisis have access to clinical tools to support symptom management and difficult patient and family communication.


title: Human metapneumovirus in patients with respiratory tract infection in Kuwait

text: Human metapneumovirus (hMPV) has been recognized as an important cause of respiratory tract infections in all age groups and in all geographical area. The role of hMPV in causing respiratory tract infections in Kuwait was not yet investigated. The aim of this study was to determine the prevalence of hMPV infection in Kuwait among patients with respiratory tract infection with respect to other respiratory viruses. During January–December 2009, 460 respiratory samples from 388 patients with respiratory tract infection were collected from different hospitals. They were tested for hMPV RNA by real‐time PCR, and for other respiratory viruses by conventional PCR. Out of 388 patients, 110 (28%) were positive for viral respiratory infections; 21 (5.4%) were positive for hMPV, 29 (7.5%) were positive for rhinovirus, 13 (4%) were positive for respiratory syncytial virus, and 10 (3%) were positive for adenovirus. Most (n = 19, 90.5%) of hMPV‐positive patients were admitted to the intensive care unit, 76% of them were of age 2 years and below, and 24% of age 59 years and above. All hMPV‐positive elderly patients had pneumonia while 50% of hMPV‐positive infants had bronchopneumonia. Children with hMPV/rhinovirus co‐infection (n = 3, 1%) had recurrent chest infection and frequent intensive care unit admission. The hMPV infection was mostly detected between December and May, and genotype B was more prevalent than genotype A. This is the first study demonstrating the prevalence of hMPV infection in Kuwait, and suggests that hMPV infection is prevalent in infants and elderly patients with lower respiratory tract infection. J. Med. Virol. 83:1811–1817, 2011. © 2011 Wiley‐Liss, Inc.


title: Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2

text: COVID-19 is the most rapidly growing pandemic in modern time, and the need for serological testing is most urgent. Although the diagnostics of acute patients by RT-PCR is both efficient and specific, we are also crucially in need of serological tools for investigating antibody responses and assessing individual and potential herd immunity. We evaluated a commercially available test developed for rapid (within 15 minutes) detection of SARS-CoV-2-specific IgM and IgG by 29 PCR-confirmed COVID-19 cases and 124 negative controls. The results revealed a sensitivity of 69% and 93.1% for IgM and IgG, respectively, based solely on PCR-positivity due to the absence of a serological gold standard. The assay specificities were shown to be 100% for IgM and 99.2% for IgG. This indicates that the test is suitable for assessing previous virus exposure, although negative results may be unreliable during the first weeks after infection. More detailed studies on antibody responses during and post infection are urgently needed.


title: Pandemic spotlight on urban water quality

text: Surface water improvements associated with the COVID-19 economic slowdown illustrate environmental resiliency and societal control over urban water quality.


title: Willingness to Self-Isolate When Facing a Pandemic Risk: Model, Empirical Test, and Policy Recommendations

text: Infected people are isolated to minimize the spread of pandemic diseases. Therefore, the factors related to self-isolation (SI) should not be neglected, and it is important to investigate the factors leading the infected (or possibly infected) people to choose to self-isolate. In this paper, we tried to show that the theory of planned behavior provides a useful conceptual framework for SI when facing a pandemic risk, and a regression method with Chinese provincial (Guangdong Province) data was applied to investigate how attitude (ATT), subjective norms (SN), and perceived behavioral control (PBC) influence SI when facing a pandemic emergency. The results and the robustness tests confirm that ATT, SN, and PBC have a significant positive influence on SI when facing a pandemic emergency. ATT plays the most important role, followed by SN and then PBC. Based on the factors of SI, we found, through theoretical and empirical analyses, at least three important aspects that local governments need to consider to encourage citizens to self-isolate when facing a pandemic.


title: Antiviral activity of porcine interferon omega 7 against foot‐and‐mouth disease virus in vitro

text: Foot‐and‐mouth disease (FMD) is a disease of worldwide economic importance, and vaccines play an important role in preventing FMDV outbreaks. However, new control strategies are still needed since FMDV outbreaks still occur in some disease‐free countries. Currently, interferon (IFN)‐based strategies have been demonstrated to be an efficient biotherapeutic option against FMDV; however, interferon omega (IFN‐ω) has not yet been assessed in this capacity. Thus, this study evaluated the antiviral activity of porcine IFN omega 7 (PoIFN‐ω7) against FMDV. After the PoIFN‐ω7 was expressed and purified, cell proliferation assays and quantitative real‐time reverse transciption‐polymerase chain reaction were used to evaluate the effective anti‐cytopathic concentration of PoIFN‐ω7 and its effectiveness pre‐ and post‐infection with FMDV in swine kidney cells (IBRS‐2). Results showed the rHis‐PoIFN‐ω7 fusion protein was considerably expressed using Escherichia coli BL21 (DE3) strain, and the recombinant protein exhibited significant in vitro protection against FMDV, including two strains belonging to type O and A FMDV, respectively. In addition, PoIFN‐ω7 upregulated the transcription of Mx1, ISG15, OAS1, and PKR genes. These findings indicated that IFN‐ω has the potential for serving as a useful therapeutic agent to prevent FMDV or other viral outbreaks in pigs.


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title: Vasculitis and infections: Contribution to the issue of autoimmunity reviews devoted to “autoimmunity and infection”

text: Abstract Infections are associated with secondary forms of vasculitis. However, there is increasing evidence that microbial agents play a role also in primary systemic vasculitides. For a long time it has been noted that Hepatitis B virus (HBV) is involved in polyarteritis nodosa (PAN) although the incidence of HBV-associated PAN seems to decline. Cryoglobulinemic vasculitis has been shown to be strongly associated with Hepatitis C Virus (HCV) infection, but this is most striking in Southern Europe and less in Northern Europe. Different microbial agents have been suggested to influence disease expression in other primary vasculitides but no specific association has been established. In Wegener’s Granulomatosis (WG) chronic carriage of Staphylococcus aureus (S. aureus) is associated with a strongly increased risk for relapsing disease. Various pathogenic pathways for this association have been suggested by clinical and experimental observations. Recent studies even suggest that S. aureus derived peptides, amongst others, may induce proteinase 3-ANCA via idiotypic–anti-idiotypic interactions. Treatment with co-trimoxazole in WG localized to the upper airways may result in (temporary) remission of the disease.


title: Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination

text: Summary Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.


title: Moving past serology: Diagnostic options without serum

text: Abstract Detecting antibodies formed in serum in response to infection is the traditional function of serology. Diagnostic modalities have included complement fixation tests, agar gel immune-diffusion, radioimmunoassay, ELISA and immunofluorescence. More recent technology now allows for the direct detection of pathogens by PCR. This review details the options for diagnostic testing using specimen types other than serum, identifying the advantages and disadvantages of these options and providing evidence for more widespread use of these techniques and specimen types.


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title: POCUS to guide fluid-therapy in COVID-19


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title: Infliximab as a rescue therapy in the management of refractory typical infantile Kawasaki disease


title: Bringing together emerging and endemic zoonoses surveillance: shared challenges and a common solution

text: Early detection of disease outbreaks in human and animal populations is crucial to the effective surveillance of emerging infectious diseases. However, there are marked geographical disparities in capacity for early detection of outbreaks, which limit the effectiveness of global surveillance strategies. Linking surveillance approaches for emerging and neglected endemic zoonoses, with a renewed focus on existing disease problems in developing countries, has the potential to overcome several limitations and to achieve additional health benefits. Poor reporting is a major constraint to the surveillance of both emerging and endemic zoonoses, and several important barriers to reporting can be identified: (i) a lack of tangible benefits when reports are made; (ii) a lack of capacity to enforce regulations; (iii) poor communication among communities, institutions and sectors; and (iv) complexities of the international regulatory environment. Redirecting surveillance efforts to focus on endemic zoonoses in developing countries offers a pragmatic approach that overcomes some of these barriers and provides support in regions where surveillance capacity is currently weakest. In addition, this approach addresses immediate health and development problems, and provides an equitable and sustainable mechanism for building the culture of surveillance and the core capacities that are needed for all zoonotic pathogens, including emerging disease threats.


IN DEFENSE OF OUR PATIENTS: INDIRECT NEGATIVE NEUROLOGICAL CONSEQUENCES OF SARS-COV-2 IN THE NEW YORK EPICENTER


Cumulative index 1984–1988 volume 86 through volume 95


title: A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic

text: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00701-020-04482-8) contains supplementary material, which is available to authorized users.


title: Influenza and other emerging respiratory viruses

text: Abstract Acute lower respiratory tract infections (LRTIs) are a major worldwide health problem, particularly in childhood. About 30–50% of acute LRTIs are viral in origin with influenza A infection a key cause of explosive community outbreaks. Many different influenza A viruses occur naturally in animal reservoirs and present a constant threat of zoonotic infections and global pandemics. Since 2009, when pandemic (H1N1) influenza A emerged from a swine origin, there have been a number of different zoonotic influenza A transmissions into the human population, including H1N1 and H3N2 variant viruses in North America and H7N9 viruses in China. The segmented nature of the influenza A virus genome and the circulation of these viruses in wild bird, domestic poultry and mammalian reservoirs presents a continuous opportunity for reassortment of viral genes and the emergence of a novel pandemic virus. Constant vigilance is required. The emergence of severe acute respiratory syndrome in 2003 and Middle East respiratory syndrome coronavirus in 2012, highlights the fact that other serious respiratory viral infections in humans may originate in animals. Enhanced awareness of the potential for serious human respiratory disease in association with travel, or animal exposure, should form part of clinical assessment. Rapid developments in genomic technology improve the ability to diagnose previously undetected pathogens. Preventative measures for influenza include annual vaccination and treatment with antiviral drugs such as neuraminidase inhibitors, oseltamivir and zanamivir. Subtype-dependent resistance to antivirals can develop and should be closely monitored.


title: Virtual Morning Report During COVID‐19: A Novel Model for Case‐Based Teaching Conferences

text: Case‐based teaching conferences, such as morning report, offer trainees a forum to refine their clinical reasoning skills. The need for physical distancing during the COVID‐19 pandemic has shifted medical education towards virtual learning. Educators must now leverage digital tools to support the ongoing education of medical trainees. To meet this need, the Clinical Problem Solvers developed and implemented a multi‐institutional, online model for morning report called, “virtual morning report (VMR).”


Hidroxicloroquina en el tratamiento del COVID-19: como utilizarla a la espera de evidencia científica concluyente


title: Investigating the introduction of porcine epidemic diarrhea virus into an Ohio swine operation

text: BACKGROUND: Porcine Epidemic Diarrhea virus (PEDV) is a highly transmissible coronavirus that causes a severe enteric disease that is particularly deadly for neonatal piglets. Since its introduction to the United States in 2013, PEDV has spread quickly across the country and has caused significant financial losses to pork producers. With no fully licensed vaccines currently available in the United States, prevention and control of PEDV disease is heavily reliant on biosecurity measures. Despite proven, effective biosecurity practices, multiple sites and production stages, within and across designated production flows in an Ohio swine operation broke with confirmed PEDV in January 2014, leading the producer and attending veterinarian to investigate the route of introduction. CASE PRESENTATION: On January 12, 2014, several sows within a production flow were noted with signs of enteric illness. Within a few days, illness had spread to most of the sows in the facility and was confirmed by RT-PCR to be PEDV. Within a short time period, confirmed disease was present on multiple sites within and across breeding and post weaning production flows of the operation and mortality approached 100% in neonatal piglets. After an epidemiologic investigation, an outsourced, pelleted piglet diet was identified for assessment, and a bioassay, where naïve piglets were fed the suspected feed pellets, was initiated to test the pellets for infectious PEDV. CONCLUSIONS: The epidemiological investigation provided strong evidence for contaminated feed as the source of the outbreak. In addition, feed pellets collected from unopened bags at the affected sites tested positive for PEDV using RT-PCR. However, the bioassay study was not able to show infectivity when feeding the suspected feed pellets to a small number of naïve piglets. The results highlight the critical need for surveillance of feed and feed components to further define transmission avenues in an effort to limit the spread of PEDV throughout the U.S. swine industry.


title: Potent Antiviral Activities of Type I Interferons to SARS-CoV-2 Infection

text: The historical outbreak of COVID-19 disease not only constitutes a global public health crisis, but also has a devastating social and economic impact. The disease is caused by a newly identified coronavirus, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). There is an urgent need to identify antivirals to curtail the COVID-19 pandemic. Herein, we report the remarkable sensitivity of SARS-CoV-2 to recombinant human interferons α and β (IFNα/β). Treatment with IFN-α or IFN-β at a concentration of 50 international units (IU) per milliliter drastically reduce viral titers by 3.4 log or 4.5 log, respectively in Vero cells. The EC(50) of IFN-α and IFN-β treatment is 1.35 IU/ml and 0.76 IU/ml, respectively, in Vero cells. These results suggested that SARS-CoV-2 is more sensitive to many other human pathogenic viruses, including the SARS-CoV. Overall, our results demonstrate the potent efficacy of human Type I IFN in suppressing SARS-CoV-2 replication, a finding which could inform future treatment options for COVID-19.


title: L’organisation de la réponse de la sécurité civile : le dispositif ORSEC

text: Résumé Le dispositif ORSEC prépare, mobilise et coordonne tous les acteurs, publics ou privés, en cas de survenue de situation exceptionnelle ayant comme potentiel de compromettre la protection des populations. Summary The ORSEC plan mobilizes and coordinates all actors, public or private, in case of occurrence of any extraordinary situation that compromises the protection of populations.