title: Asymptomatic Summertime Shedding of Respiratory Viruses

text: To determine rates of both symptomatic and asymptomatic infection among ambulatory adults, we collected nasopharyngeal swab specimens, demographic characteristics, and survey information from 1477 adult visitors to a New York City tourist attraction during April–July 2016. Multiplex polymerase chain reaction analysis was used to identify specimens positive for common respiratory viruses. A total of 7.2% of samples tested positive for respiratory viruses; among positive samples, 71.0% contained rhinovirus, and 21.5% contained coronavirus. Influenza virus, respiratory syncytial virus, and parainfluenza virus were also detected. Depending on symptomatologic definition, 57.7%–93.3% of positive samples were asymptomatic. These findings indicate that significant levels of asymptomatic respiratory viral shedding exist during summer among the ambulatory adult population.


title: Evaluation of two commercial and two non-commercial immunoassays for the detection of prior infection to SARS-CoV-2

text: BACKGROUND: Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2 but many immunoassays have not been externally validated raising questions about reliability of study findings. To ensure meaningful data, particularly in a low seroprevalence population, assays need to be rigorously characterized with high specificity. METHODS: We evaluated two commercial (Roche Diagnostics and Epitope Diagnostics IgM/IgG) and two non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 68 confirmed positive and 232 pre-pandemic negative controls. Sensitivity was stratified by time from symptom onset. The Simoa multiplex assay applied three pre-defined algorithm models to determine sample result. RESULTS: The Roche and Ragon/MGH IgG assays each registered 1/232 false positive, the primary Simoa model registered 2/232 false positives, and the Epitope registered 2/230 and 3/230 false positives for the IgG and IgM assays respectively. Sensitivity >21 days post symptom-onset was 100% for all assays except Epitope IgM, but lower and/or with greater variability between assays for samples collected 9–14 days (67–100%) and 15–21 days (69–100%) post-symptom onset. The Simoa and Epitope IgG assays demonstrated excellent sensitivity earlier in the disease course. The Roche and Ragon/MGH assays were less sensitive during early disease, particularly among immunosuppressed individuals. CONCLUSIONS: The Epitope IgG demonstrated good sensitivity and specificity. The Roche and Ragon/MGH IgG assays registered rare false positives with lower early sensitivity. The Simoa assay primary model had excellent sensitivity and few false positives.


docid: ssmfhoew

title: Rapid detection of three rabbit pathogens by use of the Luminex x-TAG assay

text: BACKGROUND: Domestic rabbits especially New Zealand white rabbits play an important role in biological research. The disease surveillance and quality control are essential to guarantee the results of animal experiments performed on rabbits. Rabbit hemorrhagic disease virus, rabbit rotavirus and Sendai virus are the important pathogens that needed to be eliminated. Rapid and sensitive method focus on these three viruses should be established for routine monitoring. The Luminex x-TAG assay based on multiplex PCR and fluorescent microsphere is a fast developing technology applied in high throughput detection. Specific primers modified with oligonucleotide sequence/biotin were used to amplify target fragments. The conjugation between oligonucleotide sequence of the PCR products and the MagPlex-TAG microspheres was specific without any cross-reaction, and the hybridization products could be analyzed using the Luminex 200 analyzer instrument. Recombinant plasmids were constructed to estimate the detection limit of the viruses. Furthermore, 40 clinical samples were used to evaluate the efficiency of this multiplex PCR based Luminex x-TAG assay. RESULTS: According to the results, this new method showed high specificity and good stability. Assessed by the recombinant plasmids, the detection limit of three viruses was 100copies/μl. Among 40 clinical specimens, 18 specimens were found positive, which was completely concordant with the conventional PCR method. CONCLUSIONS: The new developed Luminex x-TAG assay is an accurate, high throughput method for rapid detection of three important viruses of rabbits.


title: Functions and Biosynthesis of O-Acetylated Sialic Acids

text: Sialic acids have a pivotal functional impact in many biological interactions such as virus attachment, cellular adhesion, regulation of proliferation, and apoptosis. A common modification of sialic acids is O-acetylation. O-Acetylated sialic acids occur in bacteria and parasites and are also receptor determinants for a number of viruses. Moreover, they have important functions in embryogenesis, development, and immunological processes. O-Acetylated sialic acids represent cancer markers, as shown for acute lymphoblastic leukemia, and they are known to play significant roles in the regulation of ganglioside-mediated apoptosis. Expression of O-acetylated sialoglycans is regulated by sialic acid-specific O-acetyltransferases and O-acetylesterases. Recent developments in the identification of the enigmatic sialic acid-specific O-acetyltransferase are discussed.


Comment on Gross and MacDougall “Roles of the clinical pharmacist during the COVID‐19 pandemic”


title: Public health in practice: the three domains of public health

text: Summary This paper outlines a conceptual model for public health practice by proposing the three domains as a framework to organize and to deliver public health programmes. The model builds on the recognition that public health is everybody's business and therefore, needs a common definitional base. Different levels of skill and a wide range of contributions are needed if public health programmes are to make the most impact. The different domains of practice help to construct a basis for understanding the necessary elements of the public health system and their interactions. Using teenage pregnancy as a case study of a public health programme highlights the characteristics of the model. It demonstrates not only the importance of the role of directors of public health in taking a population-based overview, but also the need for multisectoral, multidisciplinary working. The relevance of the public health approach not only to primary care but also to the hospital-based sector becomes apparent, as does its relevance to communities, voluntary sector and local government. Integration of the three domains, a common definition and the framework for the public health system will support effective delivery of health improvement.


Acute, infectious diarrhea among children in developing countries


Editorial – COVID‐19


“What, me worry?” Businesses and AIDS at Davos


title: Toona sinensis Roem tender leaf extract inhibits SARS coronavirus replication

text: Abstract Aim of the study Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by the SARS coronavirus (SARS-CoV). The development of new antiviral agents for SARS-CoV is an important issue. We tried to find potential resource from Traditional Chinese medicine (TCM) for development of new drugs against SARS-CoV. Materials and Methods Our team recruited the potential TCM formulae (also known as Kampo) from two TCM books, Shang-Han Lun (Discussion of Cold-Induced Disorders) and Wen-Bing Tiau-Bein (Differential Management of Febrile Diseases). Several herbs, which were believed to be beneficial for SARS by experienced TCM doctors were also recruited. In addition, a vegetable polular in Taiwan, China and Malaysia, the tender leaf of Toona sinensis Roem (also known as Cedrela sinensis, belongs to the family Meliacceae) was also recruited under the suggestion of botanic experts. These TCM products and plant extrats were then tested for the effectiveness against SARS-CoV in vitro. Results Only TSL-1, the extract from tender leaf of Toona sinensis Roem was found to have an evident effect against SARS-CoV with selectivity index 12∼17. Conclusion This paper reports for the first time that extract from a vegetable, the tender leaf of Toona sinensis Roem, can inhibit SARS-CoV in vitro. Thererfore, the tender leaf of Toona sinensis Roem may be an important resource agninst SARS-CoV.


title: Is Tuberculosis Treatment Really Free in China? A Study Comparing Two Areas with Different Management Models

text: OBJECTIVE: China has implemented a free-service policy for tuberculosis. However, patients still have to pay a substantial proportion of their annual income for treatment of this disease. This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. METHODS: There are three tuberculosis management models in China: the tuberculosis dispensary model, specialist model and integrated model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which correspond to areas implementing the integrated model and dispensary model, respectively. Patients diagnosed and treated for tuberculosis since January 2010 were recruited as study subjects. A total of 590 patients (316 patients from ZJG and 274 patients from TX) were interviewed with a response rate of 81%. The economic burden attributed to tuberculosis, including direct costs and indirect costs, was estimated and compared between the two study sites. The Mann-Whitney U Test was used to compare the cost differences between the two groups. Potential factors related to the total out-of-pocket costs were analyzed based on a step-by-step multivariate linear regression model after the logarithmic transformation of the costs. RESULTS: The average (median, interquartile range) total cost was 18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range: 983–6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY in TX. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. CONCLUSION: Under the current “free of diagnosis and treatment” policy, the financial burden remains heavy on tuberculosis patients. Policy makers need to consider appropriate steps to lessen the burden of out-of-pocket costs for tuberculosis patients in China and how best to improve service delivery for poor patients.


title: Sleep apnoea management in Europe during the COVID-19 pandemic: data from the European Sleep Apnoea Database (ESADA)

text: Sleep disordered breathing (SDB) is highly prevalent with a male to female predominance of two to one, and is more common in middle-aged and elderly subjects [1]. Affected patients often present with comorbidities such as obesity, cardiovascular disease (systemic hypertension, heart failure, atrial fibrillation), and diabetes mellitus Type II [2]. The strong overlap between the profile for SDB patients and the identified risk factors for adverse outcomes of COVID-19 infection that include age, male gender, and cardio-metabolic comorbidity [3] suggest that SDB patients may benefit from effective therapy if confronted with COVID-19 infection [4].


title: Maternal immunity enhances Mycoplasma hyopneumoniae vaccination induced cell-mediated immune responses in piglets

text: BACKGROUND: Passively acquired maternal derived immunity (MDI) is a double-edged sword. Maternal derived antibody-mediated immunity (AMI) and cell-mediated immunity (CMI) are critical immediate defenses for the neonate; however, MDI may interfere with the induction of active immunity in the neonate, i.e. passive interference. The effect of antigen-specific MDI on vaccine-induced AMI and CMI responses to Mycoplasma hyopneumoniae (M. hyopneumoniae) was assessed in neonatal piglets. To determine whether CMI and AMI responses could be induced in piglets with MDI, piglets with high and low levels of maternal M. hyopneumoniae-specific immunity were vaccinated against M. hyopneumoniae at 7 d of age. Piglet M. hyopneumoniae-specific antibody, lymphoproliferation, and delayed type hypersensitivity (DTH) responses were measured 7 d and 14 d post vaccination. RESULTS: Piglets with M. hyopneumoniae-specific MDI failed to show vaccine-induced AMI responses; there was no rise in M. hyopneumoniae antibody levels following vaccination of piglets in the presence of M. hyopneumoniae-specific MDI. However, piglets with M. hyopneumoniae-specific MDI had primary (antigen-specific lymphoproliferation) and secondary (DTH) M. hyopneumoniae-specific CMI responses following vaccination. CONCLUSIONS: In this study neonatal M. hyopneumoniae-specific CMI was not subject to passive interference by MDI. Further, it appears that both maternal derived and endogenous CMI contribute to M. hyopneumoniae-specific CMI responses in piglets vaccinated in the face of MDI.


title: Teledermatology for COVID‐19 cutaneous lesions: substitute or supplement?

text: In the context of COVID‐19 pandemic, teledermatology is being favored over in‐person consultation in order to avoid the possibility of virus transmission(1). In France, COVID‐19 wasn't known to cause cutaneous manifestations before April 6(th) 2020, when an alert about possible associated skin symptoms was raised to the general public and the professional social network(2–4). We aimed to assess the impact of alerting about COVID‐associated lesions on the activity of urgent teledermatology (TD) and the activity of dermatologic emergencies unit (DEU) of two university hospitals during this pandemic.


title: Newborn calf welfare: A review focusing on mortality rates

text: Calf mortality control is vitally important for farmers, not only to improve animal welfare, but also to increase productivity. High calf mortality rates can be related to larger numbers of calves in a herd, employee performance, severe weather, and the neonatal period covering the first 4 weeks of life. Although the basic premise of preventing newborn calf mortality is early detection and treatment of calves at risk for failure of passive transfer of immunoglobulins, calf mortality due to infectious diseases such as acute diarrhea increases in the presence of these physical and psychological stressors. This suggests that farmers should not ignore the effects of secondary environmental factors. For prevention rather than cure, the quality of the environment should be improved, which will improve not only animal welfare but also productivity. This paper presents a review of the literature on newborn calf mortality and discusses its productivity implications.


title: MicroRNome Analysis Unravels the Molecular Basis of SARS Infection in Bronchoalveolar Stem Cells

text: Severe acute respiratory syndrome (SARS), caused by the coronavirus SARS-CoV, is an acute infectious disease with significant mortality. A typical clinical feature associated with SARS is pulmonary fibrosis and associated lung failure. In the aftermath of the SARS epidemic, although significant progress towards understanding the underlying molecular mechanism of the infection has been made, a large gap still remains in our knowledge regarding how SARS-CoV interacts with the host cell at the onset of infection. The rapidly changing viral genome adds another variable to this equation. We have focused on a novel concept of microRNA (miRNA)–mediated host–virus interactions in bronchoalveolar stem cells (BASCs) at the onset of infection by correlating the “BASC–microRNome” with their targets within BASCs and viral genome. This work encompasses miRNA array data analysis, target prediction, and miRNA–mRNA enrichment analysis and develops a complex interaction map among disease-related factors, miRNAs, and BASCs in SARS pathway, which will provide some clues for diagnostic markers to view an overall interplay leading to disease progression. Our observation reveals the BASCs (Sca-1+ CD34+ CD45- Pecam-), a subset of Oct-4+ ACE2+ epithelial colony cells at the broncho-alveolar duct junction, to be the prime target cells of SARS-CoV infection. Upregulated BASC miRNAs-17*, -574-5p, and -214 are co-opted by SARS-CoV to suppress its own replication and evade immune elimination until successful transmission takes place. Viral Nucleocapsid and Spike protein targets seem to co-opt downregulated miR-223 and miR-98 respectively within BASCs to control the various stages of BASC differentiation, activation of inflammatory chemokines, and downregulation of ACE2. All these effectively accounts for a successful viral transmission and replication within BASCs causing continued deterioration of lung tissues and apparent loss of capacity for lung repair. Overall, this investigation reveals another mode of exploitation of cellular miRNA machinery by virus to their own advantage.


title: Classification analysis of dual nucleotides using dimension reduction

text: Abstract We introduce a new approach to investigate the dual nucleotides compositions of 11 Gram-positive and 12 Gram-negative eubacteria recently studied by Sorimachi and Okayasu. The approach firstly obtains a 16-dimension vector set of dual nucleotides by PN-curve from the complete genome of organism. Each vector of the set corresponds to a single gene of genome. Then we reduce the 16-dimension vector set to 2-dimension by principal components analysis (PCA). The reduction avoids possible loss of information averaging all 16-dimension vectors. Then we suggest a 2D graphical representation based on the 2-dimension vector to investigate the classification patters among different organisms.


title: Prevalence of Pathogens Related to Bovine Respiratory Disease Before and After Transportation in Beef Steers: Preliminary Results

text: SIMPLE SUMMARY: Bovine respiratory disease (BRD) affects the lower respiratory tract of cattle, causing high mortality. The syndrome has a multifactorial etiology and transport seems to favor pathogen proliferation. This study investigated the prevalence of different pathogens involved in BRD, in the nasal microbiota of beef steers collected before and after a long-distance journey. A total of 56 Limousine animals were included, travelling in three different shipments, on the same route from France to southern Italy in a semitrailer, on three different days from February to April. Prior to shipment (T0) and four days after arrival (T1), two deep nasopharyngeal swabs (DNS)/steer were collected and tested by bimolecular analysis. Neither bovine viral diarrhea virus (BVDV) nor bovine herpesvirus type 1 (BoHV-1) were detected. A higher prevalence of Histophilus somni was observed in the DNS collected during the third shipment in comparison with those registered during the first and the second one, probably due to a higher prevalence at departure. Conversely, the prevalence of bovine coronavirus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis and Pasteurella multocida was higher on arrival in comparison with departure, confirming data reported in the literature. Overall, there were nasal microbiota changes in beef steers, with an increase in the prevalence of pathogens associated with BRD after travelling. ABSTRACT: Bovine respiratory disease (BRD) is a serious health and economic problem in the beef industry, which is often associated with transportation and caused by different pathogens. The prevalence of bovine herpesvirus type 1 (BoHV-1), bovine adenovirus (BAdV), bovine viral diarrhea virus (BVDV), bovine coronavirus (BCoV), bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus (BPiV), Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, in the nasal microbiota of beef steers before and after the same long-distance journey from France to southern Italy was documented. Fifty-six Limousine animals of three different shipments, travelling on three different days from February to April, were included. Prior to shipment (T0) and four days after arrival (T1), two DNS/animal were collected and tested by Real Time quantitative PCR (qPCR). Univariate logistic regression was carried out, considering time and day as fixed factors and the outcome of qPCR for each pathogen as a dependent categorical dichotomous variable (positive/negative, 1/0). The fact that the number of H. somni positive animals were found to be higher in the third shipment than the first and second one, indicating that this pathogen was already present before loading, is relevant. The prevalence of BCoV, BRSV, M. haemolytica, M. bovis, P. multocida was higher at T1 than T0, suggesting that other factors, such as stress and the epidemiological status of the arrival farm, played a role. The tested animals were not treated before and after transport, and our results are in agreement with the current literature, supporting the hypothesis that the prevalence of pathogens related to BRD would increase after travelling, with an increased risk of pathogens shedding.


title: Osteoporosis in the age of COVID-19

text: As the world grapples with the crisis of COVID-19, established economies and healthcare systems have been brought to their knees. Tough decisions regarding redirection of resources away from the management of conditions deemed “nonessential” are being made. How can we balance urgent resourcing of our acute crisis while not abandoning the real need of patients with osteoporosis? This article offers a few practical solutions.


title: Dynamic interventions to control COVID-19 pandemic: a multivariate prediction modelling study comparing 16 worldwide countries

text: To date, non-pharmacological interventions (NPI) have been the mainstay for controlling the coronavirus disease-2019 (COVID-19) pandemic. While NPIs are effective in preventing health systems overload, these long-term measures are likely to have significant adverse economic consequences. Therefore, many countries are currently considering to lift the NPIs—increasing the likelihood of disease resurgence. In this regard, dynamic NPIs, with intervals of relaxed social distancing, may provide a more suitable alternative. However, the ideal frequency and duration of intermittent NPIs, and the ideal “break” when interventions can be temporarily relaxed, remain uncertain, especially in resource-poor settings. We employed a multivariate prediction model, based on up-to-date transmission and clinical parameters, to simulate outbreak trajectories in 16 countries, from diverse regions and economic categories. In each country, we then modelled the impacts on intensive care unit (ICU) admissions and deaths over an 18-month period for following scenarios: (1) no intervention, (2) consecutive cycles of mitigation measures followed by a relaxation period, and (3) consecutive cycles of suppression measures followed by a relaxation period. We defined these dynamic interventions based on reduction of the mean reproduction number during each cycle, assuming a basic reproduction number (R(0)) of 2.2 for no intervention, and subsequent effective reproduction numbers (R) of 0.8 and 0.5 for illustrative dynamic mitigation and suppression interventions, respectively. We found that dynamic cycles of 50-day mitigation followed by a 30-day relaxation reduced transmission, however, were unsuccessful in lowering ICU hospitalizations below manageable limits. By contrast, dynamic cycles of 50-day suppression followed by a 30-day relaxation kept the ICU demands below the national capacities. Additionally, we estimated that a significant number of new infections and deaths, especially in resource-poor countries, would be averted if these dynamic suppression measures were kept in place over an 18-month period. This multi-country analysis demonstrates that intermittent reductions of R below 1 through a potential combination of suppression interventions and relaxation can be an effective strategy for COVID-19 pandemic control. Such a “schedule” of social distancing might be particularly relevant to low-income countries, where a single, prolonged suppression intervention is unsustainable. Efficient implementation of dynamic suppression interventions, therefore, confers a pragmatic option to: (1) prevent critical care overload and deaths, (2) gain time to develop preventive and clinical measures, and (3) reduce economic hardship globally. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10654-020-00649-w) contains supplementary material, which is available to authorized users.


title: Coronavirus-related nosocomial viral respiratory infections in a neonatal and paediatric intensive care unit: a prospective study

text: Abstract The incidence of nosocomial viral respiratory infections (NVRI) in neonates and children hospitalized in paediatric and neonatal intensive care units (PNICU) is unknown. Human coronaviruses (HCoV) have been implicated in NVRI in hospitalized preterm neonates. The objectives of this study were to determine the incidence of HCoV-related NVRI in neonates and children hospitalized in a PNICU and the prevalence of viral respiratory tract infections in staff. All neonates (age≤28 days) and children (age>28 days) hospitalized between November 1997 and April 1998 were included. Nasal samples were obtained by cytological brush at admission and weekly thereafter. Nasal samples were taken monthly from staff. Virological studies were performed, using indirect immunofluorescence, for HCoV strains 229E and OC43, respiratory syncytial virus (RSV), influenza virus types A and B, paramyxoviruses types 1, 2 and 3 and adenovirus. A total of 120 patients were enrolled (64 neonates and 56 children). Twenty-two samples from 20 patients were positive (incidence 16.7%). In neonates, seven positive samples, all for HCoV, were detected (incidence 11%). Risk factors for NVRI in neonates were: duration of hospitalization, antibiotic treatment and duration of parenteral nutrition (P<0.01). Monthly prevalence of viral infections in staff was between 0% and 10.5%, mainly with HCoV. In children, 15 samples were positive in 13 children at admission (seven RSV, five influenza and three adenovirus) but no NVRI were observed. In spite of a high rate of community-acquired infection in hospitalized children, the incidence of NVRI with common respiratory viruses appears low in neonates, HCoV being the most important pathogen of NRVI in neonates during this study period. Further research is needed to evaluate the long-term impact on pulmonary function.


Development of potential COVID-19 vaccines continues to accelerate


docid: iqepytyd

title: Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

text: Abstract Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin–angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.


title: Role of Neutralizing Antibodies in Adults With Community-Acquired Pneumonia by Respiratory Syncytial Virus

text: Background. Respiratory syncytial virus (RSV) has been implicated in the etiology of adult community-acquired pneumonia (CAP). We investigated RSV infection in Chilean adults with CAP using direct viral detection, real-time reverse-transcription polymerase chain reaction (rtRT-PCR), and serology (microneutralization assay). Methods. RSV, other respiratory viruses, and bacteria were studied by conventional and molecular techniques in adults aged ≥18 years presenting with CAP to the healthcare facilities in Santiago, Chile from February 2005 through December 2007. Results. All 356 adults with CAP enrolled had an acute blood sample collected at enrollment, and 184 had a convalescent blood sample. RSV was detected in 48 cases (13.4%). Immunofluorescence assay and viral isolation each detected only 1 infection (0.2%), whereas rtRT-PCR was positive in 32 (8.9%) cases and serology was positive in 20 (10.8%) cases. CAP clinical characteristics were similar in RSV-infected and non-RSV-infected cases. RSV-specific geometric mean serum-neutralizing antibody titer (GMST) was significantly lower at admission in the 48 RSV-infected cases compared with 308 non-RSV-infected adults (GMST in log(2): RSV/A 8.1 vs 8.9, and RSV/B 9.3 vs 10.4; P < .02). Conclusions. RSV infection is frequent in Chilean adults with CAP. Microneutralization assay was as sensitive as rtRT-PCR in detecting RSV infection and is a good adjunct assay for diagnostic research. High RSV-specific serum-neutralizing antibody levels were associated with protection against common and severe infection. The development of a vaccine could prevent RSV-related CAP in adults.


title: Influenza D Virus in Cattle, Ireland

text: We detected influenza D virus in 18 nasal swab samples from cattle in Ireland that were clinically diagnosed with respiratory disease. Specimens were obtained from archived samples received for routine diagnosis during 2014–2016. Sequencing showed that viruses from Ireland clustered with virus sequences obtained in Europe within the D/swine/OK/1334/2011 clade.


Virus interactions with bacteria: Partners in the infectious dance


Chloroquine and hydroxychloroquine for COVID‐19: A word of caution


title: Catastrophic acute bilateral lower limbs necrosis associated with COVID‐19 as a likely consequence of both vasculitis and coagulopathy

text: A‐83‐year‐old man was admitted on the 3(rd) of April 2020 for respiratory distress. He had presented with fever the 20th of march. On the 2nd of April he had an acute pain of both legs associated with discoloration. He was admitted to the emergency room on the following day. His temperature was 38°C, he was dyspneic despite oxygen. He had bilateral and symmetrical well limited black skin on both legs (Figure).


title: Restablecimiento de la actividad en los servicios de Digestivo. Recomendaciones de la SEPD, AEEH, GETECCU y AEG

text: ABSTRACT The set of measures proposed by SEPD, AEEH, GETECCU and AEG are aimed to help departments in their resumption of usual activity. We have prepared a number of practical recommendations regarding patient management and the stepwise resumption of healthcare activity. These recommendations are based on the sparse, changing evidence available, and will be updated in the future according to daily needs and the availability of expendable materials to suit them; in each department they will be implemented depending upon the cumulative incidence of SARS-CoV-2 infection in each region, and the burden the pandemic has represented for each hospital. The general objectives of these recommendations include: To protect our patients against the risks of infection with SARS-CoV-2 and to provide them with high-quality care. To protect all healthcare professionals against the risks of infection with SARS-CoV-2.To resume normal functioning of our departments in a setting of ongoing risk for infection with SARS-CoV-2.


Heart Retransplantation Following COVID-19 Illness in a Heart Transplant Recipient


SARS Preparedness and Response Planning


Déjà vu All Over Again: Koch's Postulates and Virology in the 21(st) Century


title: COVID‐19 and islet transplantation: different twins

text: For those who work in the field of islet transplantation, the micro vascular COVID‐19 lung vessels obstructive thrombo‐inflammatory syndrome (recently referred to as MicroCLOTS) is familiar, as one cannot fail to recognize the presence of similarities with the instant blood mediated inflammatory reaction (IBMIR) occurring in the liver hours and days after islet infusion. Evidences in both MicroCLOTS and IBMIR suggest the involvement of the coagulation cascade and complement system activation, and proinflammatory chemokines/cytokines release. Identification and targeting of pathway(s) playing a role as “master regulator(s)” in the post‐islet transplant detrimental inflammatory events could be potentially useful to suggest innovative COVID‐19 treatments and vice versa. All the scientific organizations across the world are fighting the COVID‐19 pandemic. Islet transplantation, and more generally the transplantation scientific community, could contribute suggesting strategies for innovative approaches. At the same time, in the near future, clinical trials in COVID‐19 patients will produce an enormous quantity of clinical and translational data on the control of inflammation, and complement/microthrombosis activation. These data will represent a legacy to be transformed into innovation in the transplant field. It will be our contribution to change a dramatic event into advancement for the transplant field, and ultimately for our patients.


title: Staffing With Disease-Based Epidemiologic Indices May Reduce Shortage of Intensive Care Unit Staff During the COVID-19 Pandemic

text: BACKGROUND: Health care worker (HCW) safety is of pivotal importance during a pandemic such as Coronavirus Disease 2019 (COVID-19), and employee health and well-being ensure functionality of health care institutions. This is particularly true for an intensive care unit (ICU), where highly specialized staff cannot be readily replaced. In the light of lacking evidence for optimal staffing models in a pandemic, we hypothesized that staff shortage can be reduced when staff scheduling takes the epidemiology of a disease into account. METHODS: Various staffing models were constructed, and comprehensive statistical modeling was performed. A typical routine staffing model was defined that assumed full-time employment (40 h/wk) in a 40-bed ICU with a 2:1 patient-to-staff ratio. A pandemic model assumed that staff worked 12-hour shifts for 7 days every other week. Potential in-hospital staff infections were simulated for a total period of 120 days, with a probability of 10%, 25%, and 40% being infected per week when at work. Simulations included the probability of infection at work for a given week, of fatality after infection, and the quarantine time, if infected. RESULTS: Pandemic-adjusted staffing significantly reduced workforce shortage, and the effect progressively increased as the probability of infection increased. Maximum effects were observed at week 4 for each infection probability with a 17%, 32%, and 38% staffing reduction for an infection probability of 0.10, 0.25, and 0.40, respectively. CONCLUSIONS: Staffing along epidemiologic considerations may reduce HCW shortage by leveling the nadir of affected workforce. Although this requires considerable efforts and commitment of staff, it may be essential in an effort to best maintain staff health and operational functionality of health care facilities and systems.


title: PEDV ORF3 encodes an ion channel protein and regulates virus production

text: Several studies suggest that the open reading frame 3 (ORF3) gene of porcine epidemic diarrhea virus (PEDV) is related to viral infectivity and pathogenicity, but its function remains unknown. Here, we propose a structure model of the ORF3 protein consisting of four TM domains and forming a tetrameric assembly. ORF3 protein can be detected in PEDV-infected cells and it functions as an ion channel in both Xenopus laevis oocytes and yeast. Mutation analysis showed that Tyr170 in TM4 is important for potassium channel activity. Furthermore, viral production is reduced in infected Vero cells when ORF3 gene is silenced by siRNA. Interestingly, the ORF3 gene from an attenuated PEDV encodes a truncated protein with 49 nucleotide deletions, which lacks the ion channel activity.


title: Beyond protein structure determination with MicroED

text: Microcrystal electron diffraction (MicroED) was first coined and developed in 2013 at the Janelia Research Campus as a new modality in electron cryomicroscopy (cryoEM). Since then, MicroED has not only made important contributions in pushing the resolution limits of cryoEM protein structure characterization but also of peptides, small-organic and inorganic molecules, and natural-products that have resisted structure determination by other methods. This review showcases important recent developments in MicroED, highlighting the importance of the technique in fields of studies beyond protein structure determination where MicroED is beginning to have paradigm shifting roles.


title: Lactate dehydrogenase and C-reactive protein as predictors of respiratory failure in CoVID-19 patients

text: OBJECTIVE: The dramatic worldwide CoVID-19 infection requires the identification of a reliable and inexpensive tool to quickly discriminate patients with a more unfavorable outcome. METHODS: We performed routine laboratory tests suitable to identify tissue damage and inflammatory status in 123 consecutive CoVID-19 patients admitted to the Emergency Department of the hospital of Piacenza (Emilia-Romagna, Northern Italy). The results were correlated with patients’ respiratory function evaluated by the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2). Results: The most common laboratory abnormalities were lymphocytopenia and elevated values of C-reactive protein (CRP) and lactate dehydrogenase (LDH). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) were also increased. The respiratory performance (PaO2/FiO2) showed a strong inverse correlation with LDH (r= 0.62, r(2) 0.38, p value< 0.0001) and CRP (r= 0.55, r(2) 0.31, p value< 0.0001). PaO2/FiO2 values also showed a significant inverse correlation with age (r= -0.37, p< 0.0001), AST (r= -0.31, p<0.01), WBC (r= -0.49, p<0.0001), neutrophils count (r= -0.5, p<0.001). ROC curves showed a sensitivity of 75% and specificity of 70% for the LDH cut-off value of 450 U/L and a sensitivity of 72% and specificity of 71% for the CRP cut-off value of 11 mg/dl in identifying CoVID-19 with moderate-severe ARDS. CONCLUSIONS: LDH and CRP may be related to respiratory function (PaO2/FiO2) and be a predictor of respiratory failure in CoVID-19 patients. LDH and CRP should be considered a useful test for the early identification of patients who require closer respiratory monitoring and more aggressive supportive therapies to avoid poor prognosis.


title: Mortality of Life‐Insured Swedish Cats during 1999–2006: Age, Breed, Sex, and Diagnosis

text: Background: A cat life insurance database can potentially be used to study feline mortality. Hypothesis: The aim was to describe patterns of mortality in life‐insured Swedish cats. Cats: All cats (<13 years of age) with life insurance during the period 1999–2006 were included. Methods: Age‐standardized mortality rates (MR) were calculated with respect to sex (males and females), age, breed, and diagnosis. Survival to various ages is presented by time period and breed. Results: The total number of cats insured was 49,450 and the number of cat‐years at risk (CYAR) was 142,049. During the period, 6,491 cats died and of these 4,591 cats (71%) had a diagnosis, ie, were claimed for life insurance. The average annual MR was 462 deaths per 10,000 CYAR (95% confidence interval, 431–493). Sex‐specific rates did not differ significantly. The overall mortality of the Persian and the Siamese groups was higher than that of several other breeds. Overall and breed‐specific (for most breeds) survival increased with time when analyzed by 2‐year periods. The 6 most common diagnostic categories (ignoring cats recorded as dead with no diagnosis) were urinary, traumatic, neoplastic, infectious, cardiovascular, and gastrointestinal. The MR within diagnostic categories varied by age and breed. Conclusions and Clinical Importance: In this mainly purebred, insured cat population, the overall mortality varied with age and breed but not with sex. The increase in survival over time is likely a reflection of willingness to keep pet cats longer and increased access to and sophistication of veterinary care.


RWANDA: Lockdown Support


title: CHAPTER 12 MICE AND RATS

text: Publisher Summary This chapter focuses on mice and rats, and provides detailed information that may be useful for veterinarians treating these animals. Mice are continuous, polyestrous rodents that should be bred in polygamous or monogamous setups because of the males' aggressive territoriality behavior. When breeding mice that have been housed in a polygamous ratio, there may be one male with two to six females. Females are removed from a polygamous cage before parturition, whereas the monogamous pair is maintained together with the young until weaning. Mice are maintained in environments that are similar to other small rodents but require a thorough cleaning of their cage more often because of their malodorous urine. Ventilation is essential for small rodent housing to prevent irritation of the respiratory tract from ammonia vapors generated by urine. Quarantining is important when a new animal is being introduced into a setting in which there is an established group. As with other animals, a 30-day quarantine period is recommended, along with a physical examination and fecal parasite check. To maintain oversight of breeding animals' health and reduce the exposure of young animals to infectious disease and parasites, routine screening of representative animals within the colony is recommended. In very large colonies, special caging, food, and water may be necessary to prevent exposure to disease organisms.


title: Cross–strait interactions on the South China Sea issues: a need for CBMs

text: Abstract Recent developments in the South China Sea (SCS) and the actions expected to be taken by China and member states of ASEAN in accordance with the Declaration on the Conduct of Parties in the SCS have the potential to further marginalize Taiwan's role in any serious discussion on SCS issues and then deprive Taiwan of its legitimate rights and interest in the area. These developments will also force Taiwan to respond by taking more active actions for the sole purpose of safeguarding its sovereignty and maritime jurisdiction in the SCS. This article discusses a number of possible confidence-building measures that could be considered for adoption by China to help engage Taiwan in the regional security dialogue process and enable Taiwan to participate in the planned joint co-operative activities in the SCS. The co-operative actions taken in the SCS area could enhance mutual trust between the two sides of the Taiwan Strait.


title: Aktuelle Handlungsempfehlungen der Deutschen Gesellschaft für Rheumatologie für die Betreuung von Patienten mit rheumatischen Erkrankungen während der SARS-CoV‑2/Covid 19-Pandemie

text: In the current SARS-CoV-2 pandemic there are many questions regarding the safe treatment of patients with inflammatory rheumatic diseases. Many of these questions cannot yet be answered on an evidence-based basis and this does not make patient care easy. The German Society for Rheumatology (DGRh) hopes that these initial recommendations will provide support for specific issues in the care of patients with inflammatory rheumatic diseases in view of the current threat posed by SARS-CoV-2. In order to take advantage of the dynamic worldwide gain in knowledge for our patients, the recommendations will be updated regularly. The updated versions of the recommendations are deposited on the homepage of the DGRh.


title: Should SARS‐CoV‐2 influence immunosuppressive therapy for autoimmune blistering diseases?

text: In this dramatic period where the whole world is affected by the outbreak of coronavirus disease 19 (COVID‐19), scientific data relating to the causative virus SARS‐CoV‐2 as well as the subsequent therapeutic repercussions on the management of other diseases should be divulged in order to share as much information as possible among experts in a timely manner.


title: A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III

text: Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate.


title: Coronavirus disease (COVID-19) in neurology and neurosurgery: A scoping review of the early literature

text: Coronavirus disease 2019 (COVID-19) is a devastating respiratory illness that has dramatically changed the medical landscape around the world. In parallel with a rise in the number of cases globally, the COVID-19 literature has rapidly expanded with experts around the world disseminating knowledge and collaborating on best practices. To date, the literature has predominantly consisted of case reports, case series, and systemic protocols for dealing with this deadly disease from a plethora of specialties with larger observational and randomized studies only now starting to emerge. This scoping review of MEDLINE, EMBASE, SCOPUS, and the Cochrane Library aims to evaluate and summarize the current status of the COVID-19 literature at it applies to neurology and neurosurgery. Neurological symptomatology, neurological risk factors for poor prognosis, pathophysiology for neuroinvasion, and actions taken by neurological or neurosurgical services to manage the current COVID-19 crisis are reviewed.


The Critical Role of Futility Analysis in the Pursuit of Effective Treatments for COVID-19


title: Statistical Properties of Stepped Wedge Cluster-Randomized Trials in Infectious Disease Outbreaks

text: Randomized controlled trials are crucial for the evaluation of interventions such as vaccinations, but the design and analysis of these studies during infectious disease outbreaks is complicated by statistical, ethical, and logistical factors. Attempts to resolve these complexities have led to the proposal of a variety of trial designs, including individual randomization and several types of cluster randomization designs: parallel-arm, ring vaccination, and stepped wedge designs. Because of the strong time trends present in infectious disease incidence, however, methods generally used to analyze stepped wedge trials may not perform well in these settings. Using simulated outbreaks, we evaluate various designs and analysis methods, including recently proposed methods for analyzing stepped wedge trials, to determine the statistical properties of these methods. While new methods for analyzing stepped wedge trials can provide some improvement over previous methods, we find that they still lag behind parallel-arm cluster-randomized trials and individually-randomized trials in achieving adequate power to detect intervention effects. We also find that these methods are highly sensitive to the weighting of effect estimates across time periods. Despite the value of new methods, stepped wedge trials still have statistical disadvantages compared to other trial designs in epidemic settings.


title: Automated real time constant-specificity surveillance for disease outbreaks

text: BACKGROUND: For real time surveillance, detection of abnormal disease patterns is based on a difference between patterns observed, and those predicted by models of historical data. The usefulness of outbreak detection strategies depends on their specificity; the false alarm rate affects the interpretation of alarms. RESULTS: We evaluate the specificity of five traditional models: autoregressive, Serfling, trimmed seasonal, wavelet-based, and generalized linear. We apply each to 12 years of emergency department visits for respiratory infection syndromes at a pediatric hospital, finding that the specificity of the five models was almost always a non-constant function of the day of the week, month, and year of the study (p < 0.05). We develop an outbreak detection method, called the expectation-variance model, based on generalized additive modeling to achieve a constant specificity by accounting for not only the expected number of visits, but also the variance of the number of visits. The expectation-variance model achieves constant specificity on all three time scales, as well as earlier detection and improved sensitivity compared to traditional methods in most circumstances. CONCLUSION: Modeling the variance of visit patterns enables real-time detection with known, constant specificity at all times. With constant specificity, public health practitioners can better interpret the alarms and better evaluate the cost-effectiveness of surveillance systems.


title: Sodium chromo-glycate and palmitoylethanolamide: A possible strategy to treat mast cell-induced lung inflammation in COVID-19

text: A novel human coronavirus SARS‐CoV‐2 (also referred to as CoV-19) that emerged in late 2019 causes Covid-19 disease a respiratory tract infection which provokes about 4 million deaths per year. Unfortunately, to date, there is no specific antiviral treatment for COVID-19. Mast cells (MCs) are immune cells implicated in the pathogenesis of viral infections, where they mediate inflammation. Microbes, including virus, activate MCs through TLR releasing chemical pro-inflammatory compounds and cytokines. Although, in biomedical literature there are only few reports on MCs activation by SARS-CoV-2 infection. The production of pro-inflammatory cytokines by MC viral activation leads to increase pulmonary inflammation and fibrosis. Sodium Chromo-Glycate (SCG) described as a MC stabilizer, prevents the release of inflammatory chemical compounds, improve mouse survival and respiratory pathological changes in lung viral infection and suppresses inflammation. Furthermore, palmitoylethanolamide (PEA) a nuclear factor agonist, an endogenous fatty acid amide, which exerts a variety of biological effects, related to chronic inflammation and pain, is involved also in MCs homeostasis with an inhibitory and protective effect on the respiratory tract during viral infections. Here, we hypothesize for the first time, that SCG and/or PEA suppress MC activation and pro-inflammatory mediators release, playing an anti-inflammatory therapeutic role in the inflamed lung of patients with COVID-19.


title: Unmasking Influenza Virus Infection in Patients Attended to in the Emergency Department

text: BACKGROUND: Infection by the influenza virus may pass undetected in many adult patients attended to in the emergency department because its diagnosis usually relies on clinical manifestations, which can be distorted by symptoms of a preexisting disease, superposed complications or nontypical manifestations of influenza virus infection (confusing symptoms). PATIENTS AND METHODS: We performed this observational, prospective study with an antigen detection test by indirect immunofluorescence assay (IFA) to estimate the presence of influenza virus infection in such patients. No confirmatory test was performed to validate a positive or negative IFA result. Then we compared those who were antigen positive to those who were negative and also analyzed those who were positive classified by age, comorbidity and clinical presentation. We also evaluated the use of medical and hospital resources and vaccination status. Posterior pharynx swab specimens from 136 consecutive adult patients, 74 women and 62 men with a mean age of 68.7 ± 17.9 (range: 18–97) years attended to in the emergency department of a university hospital in Barcelona during the 1999–2000 influenza epidemic were examined. Tested patients presented either a classical influenza syndrome, a deterioration of a previous condition or any abrupt onset of symptoms without an obvious cause. RESULTS: Influenza A virus antigen was detected in 99 (72.8%) of the 136 patients included in the study. Confusing symptoms were present in 86 patients with laboratoryconfirmed influenza and 40 of them lacked influenza syndrome. Prostration, aching and fever out of proportion to catarrhal symptoms (disproportionate prostration) and cough were independent predictors for this diagnosis (OR = 5.14; 95% CI: 1.98–13.35, p = 0.001 and OR = 4.40, 95% CI, 1.65–11.75, p = 0.03, respectively). Among the 99 patients who tested positive, 72 were ≥ 65 years of age. This older positive group compared to the 27 also positive < 65 (non-old) had a tendency to show symptoms mediated by cytokines less frequently: malaise was present in 76.4% of the older positive patients vs 92.6% in the non-old positive ones, p = 0.07. The equivalent percentages for muscle ache were: 56.9% vs 77.8%, p = 0.06; for dysthermia: 54.2% vs 70.4%, p = 0.08; for headache: 35.2% vs 66.7%, p = 0.005, and for disproportionate prostration: 47.2% vs 66.7%, p = 0.08. Cough was more frequent in the older positive group: 94.4% vs 77.8%, p = 0.02. Older positive patients were also hospitalized and received antibiotics more frequently than the non-old positive ones: 65.3% vs 40.7%, p = 0.03 and 81.9% vs 63.0%, p = 0.046, respectively. Hospitalization was independently correlated with the presence of complications (OR = 4.5, 95% IC 1.27–15.95, p = 0.02). Patients with the highest comorbidity, evaluated with the Charlson scale, were more inadequately vaccinated than those with moderate or low comorbidity. CONCLUSION: Influenza virus infection has a great and underestimated impact in the emergency department during influenza epidemics. High frequency of confusing symptoms, which overcome classical influenza syndrome in adult people with comorbidity, may explain this effect. Disproportionate prostration and cough are symptoms that independently predict its diagnosis in the global adult population, whereas in the elderly, fever and cough should arouse this suspicion whether or not they present classic symptoms. In our setting, individuals with high comorbidity are inadequately vaccinated.


title: Are Cost Advantages from a Modern Indian Hospital Transferable to the US?

text: Abstract Background Multiple modern Indian hospitals operate at very low cost while meeting US-equivalent quality accreditation standards. Though US hospitals face intensifying pressure to lower their cost, including proposals to extend Medicare payment rates to all admissions, the transferability of Indian hospitals’ cost advantages to US peers remains unclear. Methods Using time-driven activity-based costing methods, we estimate the average cost of personnel and space for an elective coronary artery bypass graft (CABG) surgery at two American hospitals and one Indian hospital (NH). All three hospitals are Joint Commission accredited and have reputations for use of modern performance management methods. Our case study applies several analytic steps to distinguish transferable from non-transferable sources of NH’s cost savings. Results After removing non-transferable sources of efficiency, NH’s residual cost advantage primarily rests on shifting tasks to less-credentialed and/or less-experienced personnel who are supervised by highly-skilled personnel when perceived risk of complications is low. NH’s high annual CABG volume facilitates such supervised work “downshifting.” The study is subject to limitations inherent in case studies, does not account for the younger age of NH’s patients, or capture savings attributable to NH’s negligible frequency of re-admission or post-acute care facility placement. Conclusions Most transferable bases for a modern Indian hospital’s cost advantage would require more flexible American states’ hospital and health professional licensing regulations, greater family participation in inpatient care, and stronger support by hospital executives and clinicians for substantially lowering the cost of care via regionalization of complex surgeries and weekend use of costly operating rooms.


title: Health-Care Data Collecting, Sharing, and Using in Thailand, China Mainland, South Korea, Taiwan, Japan, and Malaysia

text: Abstract This article sought to describe the health-care data situation in six selected economies in the Asia-Pacific region. Authors from Thailand, China mainland, South Korea, Taiwan, Japan, and Malaysia present their analyses in three parts. The first part of the article describes the data-collection process and the sources of data. The second part of the article presents issues around policies of data sharing with the stakeholders. The third and final part of the article focuses on the extent of health-care data use for policy reform in these different economies. Even though these economies differ in their economic structure and population size, they share some similarities on issues related to health-care data. There are two main institutions that collect and manage the health-care data in these economies. In Thailand, China mainland, Taiwan, and Malaysia, the Ministry of Health is responsible through its various agencies for collecting and managing the health-care data. On the other hand, health insurance is the main institution that collects and stores health-care data in South Korea and Japan. In all economies, sharing of and access to data is an issue. The reasons for limited access to some data are privacy protection, fragmented health-care system, poor quality of routinely collected data, unclear policies and procedures to access the data, and control on the freedom on publication. The primary objective of collecting health-care data in these economies is to aid the policymakers and researchers in policy decision making as well as create an awareness on health-care issues for the general public. The usage of data in monitoring the performance of the heath system is still in the process of development. In conclusion, for the region under discussion, health-care data collection is under the responsibility of the Ministry of Health and health insurance agencies. Data are collected from health-care providers mainly from the public sector. Routinely collected data are supplemented by national surveys. Accessibility to the data is a major issue in most of the economies under discussion. Accurate health-care data are required mainly to support policy making and evidence-based decisions.


title: Coronavirus envelope (E) protein remains at the site of assembly

text: Abstract Coronaviruses (CoVs) assemble at endoplasmic reticulum Golgi intermediate compartment (ERGIC) membranes and egress from cells in cargo vesicles. Only a few molecules of the envelope (E) protein are assembled into virions. The role of E in morphogenesis is not fully understood. The cellular localization and dynamics of mouse hepatitis CoV A59 (MHV) E protein were investigated to further understanding of its role during infection. E protein localized in the ERGIC and Golgi with the amino and carboxy termini in the lumen and cytoplasm, respectively. E protein does not traffic to the cell surface. MHV was genetically engineered with a tetracysteine tag at the carboxy end of E. Fluorescence recovery after photobleaching (FRAP) showed that E is mobile in ERGIC/Golgi membranes. Correlative light electron microscopy (CLEM) confirmed the presence of E in Golgi cisternae. The results provide strong support that E proteins carry out their function(s) at the site of budding/assembly.


title: Sampling and Mass Detection of a Countable Number of Microparticles Using on-Cantilever Imprinting

text: Liquid-borne particles sampling and cantilever-based mass detection are widely applied in many industrial and scientific fields e.g., in the detection of physical, chemical, and biological particles, and disease diagnostics, etc. Microscopic analysis of particles-adsorbed cantilever-samples can provide a good basis for measurement comparison. However, when a particles-laden droplet on a solid surface is vaporized, a cluster-ring deposit is often yielded which makes particles counting difficult or impractical. Nevertheless, in this study, we present an approach, i.e., on-cantilever particles imprinting, which effectively defies such odds to sample and deposit countable single particles on a sensing surface. Initially, we designed and fabricated a triangular microcantilever sensor whose mass m(0), total beam-length L, and clamped-end beam-width w are equivalent to that of a rectangular/normal cantilever but with a higher resonant frequency (271 kHz), enhanced sensitivity (0.13 Hz/pg), and quality factor (~3000). To imprint particles on these cantilever sensors, various calibrated stainless steel dispensing tips were utilized to pioneer this study by dipping and retracting each tip from a small particle-laden droplet (resting on a hydrophobic n-type silicon substrate), followed by tip-sensor-contact (at a target point on the sensing area) to detach the solution (from the tip) and adsorb the particles, and ultimately determine the particles mass concentration. Upon imprinting/adsorbing the particles on the sensor, resonant frequency response measurements were made to determine the mass (or number of particles). A minimum detectable mass of ~0.05 pg was demonstrated. To further validate and compare such results, cantilever samples (containing adsorbed particles) were imaged by scanning electron microscopy (SEM) to determine the number of particles through counting (from which, the lowest count of about 11 magnetic polystyrene particles was obtained). The practicality of particle counting was essentially due to monolayer particle arrangement on the sensing surface. Moreover, in this work, the main measurement process influences are also explicitly examined.


title: Evaluation of ocular symptoms and tropism of SARS‐CoV‐2 in patients confirmed with COVID‐19

text: PURPOSE: The SARS‐CoV‐2 RNA has been detected in tears and conjunctival samples from infected individuals. Conjunctivitis is also reported in a small number of cases. We evaluated ocular symptoms and ocular tropism of SARS‐CoV‐2 in a group of patients with COVID‐19. METHOD: Fifty‐six patients infected with SARS‐CoV‐2 were recruited as subjects. Relevant medical histories were obtained from the electronic medical record system. Ocular history and ocular symptoms data were obtained by communicating directly with the subjects. The Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ) were used to assess the anterior ocular surface condition before and after the onset of disease. RESULTS: Patients classified as severe COVID‐19 cases were more likely to have hypertension compared to mild cases (p = 0.035). Of the 56 subjects, thirteen patients (23%) were infected in Wuhan, 32 patients (57%) were community‐infected, 10 patients (18%) were unknown origin, 1 (2%) was a physician likely infected by a confirmed patient. Three patients wore face mask with precaution when contacting the confirmed patients. Fifteen (27%) had aggravated ocular symptoms, of which 6 (11%) had prodromal ocular symptoms before disease onset. The differences in mean scores of OSDI questionnaire and SEEQ between before and after onset of COVID‐19 were all significant (p < 0.05 for both). CONCLUSIONS: Ocular symptoms are relatively common in COVID‐19 disease and may appear just before the onset of respiratory symptoms. Our data provided the anecdotal evidences of transmission of SARS‐CoV‐2 via ocular surface.


title: 8.25 Modeling Genetic Susceptibility to Disease☆

text: Abstract As we transition to an era of personalized medicine, it has become imperative to integrate genomics with pharmacological and toxicological discoveries to provide individualized care to patients. Animal models are extremely important in understanding this interface as well as in bridging the gap between basic science discoveries and clinical medicine. The complex nature of pharmacological and toxicological research involving exposure to xenobiotic and therapeutic compounds necessitates the use of animal models to better understand how these compounds interact with multiple organ systems and cell types. As genomics has expanded, we have become increasingly aware of the impact an individual’s genetic makeup influences these responses. Novel methods have emerged that allow for the rapid development of animal models containing mutant alleles, allowing investigators to model these complex genetic interactions in a dramatically shortened timeline. In this chapter, we emphasize the methods and approaches that can be used in gene targeting, screening strategies, and a variety of genetically modified model organisms. The goal is to provide toxicologists an up to date review on the creation of genetically engineered animal models, which can be used to model genetic susceptibility to disease.


New developments in acute diarrhea


title: ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions

text: Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates. Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28). Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions. Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy.


title: OX40:OX40L axis: emerging targets for improving poxvirus-based CD8(+) T-cell vaccines against respiratory viruses

text: The human respiratory tract is the entry point for over 200 known viruses that collectively contribute to millions of annual deaths worldwide. Consequently the World Health Organization has designated respiratory viral infections as a priority for vaccine development. Despite enormous advances in understanding the attributes of a protective mucosal antiviral immune response, current vaccines continue to fail in effectively generating long-lived protective CD8(+) T-cell immunity. To date, the majority of licensed human vaccines afford protection against infectious pathogens through the generation of specific immunoglobulin responses. In recent years, the selective manipulation of specific costimulatory pathways, which are critical in regulating T-cell-mediated immune responses, has generated increasing interest. Impressive results in animal models have shown that the tumor necrosis factor receptor (TNFR) family member OX40 (CD134) and its binding partner OX40L (CD252) are key costimulatory molecules involved in the generation of protective CD8(+) T-cell responses at mucosal surfaces such as the lung. In this review, we highlight these new findings with a particular emphasis on their potential as immunological adjuvants to enhance poxvirus-based CD8(+) T-cell vaccines.


title: Prioritising Urological Surgery in the COVID-19 Era: A Global Reflection on Guidelines

text: Abstract Background Determining whether members follow guidelines, including guidelines prepared to help direct practice management during the coronavirus disease 2019 (COVID-19) pandemic, is an important goal for medical associations. Objective To determine whether practice of urologists is in line with guidelines for the management of common urological conditions during the COVID-19 pandemic produced by leading (inter)national urological associations. Design, setting, and participants Self-selected urologists completed a voluntary survey available online from March 27 to April 11, 2020 and distributed globally by the Société Internationale d’Urologie. Outcome measurements and statistical analysis Responses to two survey questions on the (1) management of 14 common urological procedures and (2) priority scoring of 10 common urological procedures were evaluated by practice setting and geographical region using chi-square and one-way analysis of variance analyses, respectively. Results and limitations There were 2494 respondents from 76 countries. Oncological conditions were prioritised over benign conditions, and benign conditions were deferred when feasible and safe. Oncological conditions with the greatest malignant potential were prioritised over less aggressive cancers. Respondents from Europe were least likely to postpone and most likely to prioritise conditions identified by guidelines as being of the highest priority. Respondents’ priority scoring of urological procedures closely matched the priorities assigned by guidelines. The main limitation of this study is that respondents were self-selected, and access to the survey was limited by language and technology barriers. Conclusions Prioritisation and management of urological procedures during the COVID-19 pandemic are in line with current guidelines. The greatest agreement was reported in Europe. Observed differences may be related to limited resources in some settings. Patient summary When deciding how best to treat patients during the coronavirus disease 2019 (COVID-19) pandemic, urologists are taking into account both expert recommendations and the availability of important local resources.


title: 7.10 Viruses and Viral Diseases

text: More than 40 compounds have been formally licensed for clinical use as antiviral drugs, and half of these are used for the treatment of human immunodeficiency virus (HIV) infections. The others have been approved for the therapy of herpesvirus (herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV)), hepadnavirus (hepatitis B virus (HBV)), hepacivirus (hepatitis C virus (HCV)), and myxovirus (influenza, respiratory synctural virus (RSV)) infections. New compounds are in clinical development or under preclinical evaluation, and, again, half of these target HIV infections. Yet, quite a number of important viral pathogens (i.e., human papilloma virus (HPV), HCV, hemorrhagic fever viruses) remain in need of effective and/or improved antiviral therapies.


STUDIES ON NEW VIRUS ISOLATES RECOVERED IN TRACHEAL ORGAN CULTURE


docid: zxnmylkw

title: RNA helicases and remodeling proteins

text: It is becoming increasingly clear that RNA molecules play a major role in all aspects of metabolism. The conformational state and stability of RNA are controlled by RNA remodeling proteins, which are ubiquitous motor proteins in the cell. Here, we review advances in our understanding of the structure and function of three major structural families of RNA remodeling proteins, the hexameric ring proteins, the processive monomeric RNA translocase/helicases, and the functionally diverse DEAD-box remodeling proteins. New studies have revealed molecular mechanisms for coupling between ATP hydrolysis and unwinding, the physical basis for regulatory control by cofactors, and novel functions for RNA remodeling proteins.


title: Human coronavirus 229E encodes a single ORF4 protein between the spike and the envelope genes

text: BACKGROUND: The genome of coronaviruses contains structural and non-structural genes, including several so-called accessory genes. All group 1b coronaviruses encode a single accessory protein between the spike and envelope genes, except for human coronavirus (HCoV) 229E. The prototype virus has a split gene, encoding the putative ORF4a and ORF4b proteins. To determine whether primary HCoV-229E isolates exhibit this unusual genome organization, we analyzed the ORF4a/b region of five current clinical isolates from The Netherlands and three early isolates collected at the Common Cold Unit (CCU) in Salisbury, UK. RESULTS: All Dutch isolates were identical in the ORF4a/b region at amino acid level. All CCU isolates are only 98% identical to the Dutch isolates at the nucleotide level, but more closely related to the prototype HCoV-229E (>98%). Remarkably, our analyses revealed that the laboratory adapted, prototype HCoV-229E has a 2-nucleotide deletion in the ORF4a/b region, whereas all clinical isolates carry a single ORF, 660 nt in size, encoding a single protein of 219 amino acids, which is a homologue of the ORF3 proteins encoded by HCoV-NL63 and PEDV. CONCLUSION: Thus, the genome organization of the group 1b coronaviruses HCoV-NL63, PEDV and HCoV-229E is identical. It is possible that extensive culturing of the HCoV-229E laboratory strain resulted in truncation of ORF4. This may indicate that the protein is not essential in cell culture, but the highly conserved amino acid sequence of the ORF4 protein among clinical isolates suggests that the protein plays an important role in vivo.


docid: hpejohle

title: Alternative Global Health Security Indexes for Risk Analysis of COVID-19

text: Given the volume of research and discussion on the health, medical, economic, financial, political, and travel advisory aspects of the SARS-CoV-2 virus that causes the COVID-19 disease, it is essential to enquire if an outbreak of the epidemic might have been anticipated, given the well-documented history of SARS and MERS, among other infectious diseases. If various issues directly related to health security risks could have been predicted accurately, public health and medical contingency plans might have been prepared and activated in advance of an epidemic such as COVID-19. This paper evaluates an important source of health security, the Global Health Security Index (2019), which provided data before the discovery of COVID-19 in December 2019. Therefore, it is possible to evaluate how countries might have been prepared for a global epidemic, or pandemic, and acted accordingly in an effective and timely manner. The GHS index numerical scores are calculated as the arithmetic (AM), geometric (GM), and harmonic (HM) means of six categories, where AM uses equal weights for each category. The GHS Index scores are regressed on the numerical score rankings of the six categories to check if the use of equal weights of 0.167 in the calculation of the GHS Index using AM is justified, with GM and HM providing a check of the robustness of the arithmetic mean. The highest weights are determined to be around 0.244–0.246, while the lowest weights are around 0.186–0.187 for AM. The ordinal GHS Index is regressed on the ordinal rankings of the six categories to check for the optimal weights in the calculation of the ordinal Global Health Security (GHS) Index, where the highest weight is 0.368, while the lowest is 0.142, so the estimated results are wider apart than for the numerical score rankings. Overall, Rapid Response and Detection and Reporting have the largest impacts on the GHS Index score, whereas Risk Environment and Prevention have the smallest effects. The quantitative and qualitative results are different when GM and HM are used.


title: Characterization of gene expression in naturally occurring feline degenerative joint disease-associated pain

text: Abstract Degenerative joint disease (DJD) associated-pain is a clinically relevant and common condition affecting domesticated cats and other species including humans. Identification of the neurobiological signature of pain is well developed in rodent pain models, however such information is lacking from animals or humans with naturally occurring painful conditions. In this study, identification of housekeeping genes (HKG) for neuronal tissue and expression levels of genes considered associated with chronic pain in rodent models were explored in cats with naturally occurring osteoarthritic pain. Fourteen adult cats were evaluated — seven without clinical signs of osteoarthritic pain, and seven with hind limb radiographic DJD and pain. Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). HKG identified as the most stable across all tissue samples were many of the ribosomal protein genes, such as RPL30 and RPS19. qPCR results showed ATF3 and CX3CL1 up-regulated in DJD-affected dorsal root ganglia compared to clinically healthy controls. In spinal cord, CX3CL1 was up-regulated and NGF was down-regulated when DJD-affected samples were compared to healthy samples. Further work is needed to understand the neurobiology of pain in naturally occurring disease and what rodent models are predictive of these changes in more heterogeneous populations such as domestic cats.


title: Functional incorporation of green fluorescent protein into hepatitis B virus envelope particles

text: Abstract The envelope of hepatitis B virus (HBV), containing the L, M, and S proteins, is essential for virus entry and maturation. For direct visualization of HBV, we determined whether envelope assembly could accommodate the green fluorescent protein (GFP). While the C-terminal addition of GFP to S trans-dominant negatively inhibited empty envelope particle secretion, the N-terminal GFP fusion to S (GFP.S) was co-integrated into the envelope, giving rise to fluorescent particles. Microscopy and topogenesis analyses demonstrated that the proper intracellular distribution and folding of GFP.S, required for particle export were rescued by interprotein interactions with wild-type S. Thereby, a dual location of GFP, inside and outside the envelope, was observed. GFP.S was also efficiently packaged into the viral envelope, and these GFP-tagged virions retained the capacity for attachment to HBV receptor-positive cells in vitro. Together, GFP-tagged virions should be suitable to monitor HBV uptake and egress in live hepatocytes.


title: Antiviral agents in the critically ill child

text: Abstract The treatment for most viral infections in children primarily is supportive. Severe viral illnesses and significant secondary complications that require treatment in the intensive care unit may occur in immunocompromised patients and also in infants and children who were previously healthy. Antiviral agents with specific activity against certain respiratory viruses, herpesviruses, and enteric viruses are available. New drugs are under development, and their use in pediatric patients is a subject of active research. The clinician's knowledge of the mechanisms of action, spectrum of activity, and side effects of these drugs is an important tool for their judicious use in the treatment of the critically ill child. Copyright © 2000 by W.B. Saunders Company


title: Clones of MRC-C cells may be superior to the parent line for the culture of 229E-like strains of human respiratory coronavirus

text: Abstract A clone was selected from the MRC-C continuous heteroploid cell line which was significantly better than MRC-C for the culture of human respiratory coronavirus (HCV) 229E, strain LP. Such clones could prove generally useful for the isolation of HCV-229E from clinical specimens, and for the propagation and assay of laboratory adapted strains.


title: Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant

text: BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann–Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2–5], otherwise they have a median of 1 mutation [range: 0–3] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.


title: Current Approaches on Viral Infection: Proteomics and Functional Validations

text: Viruses could manipulate cellular machinery to ensure their continuous survival and thus become parasites of living organisms. Delineation of sophisticated host responses upon virus infection is a challenging task. It lies in identifying the repertoire of host factors actively involved in the viral infectious cycle and characterizing host responses qualitatively and quantitatively during viral pathogenesis. Mass spectrometry based proteomics could be used to efficiently study pathogen-host interactions and virus-hijacked cellular signaling pathways. Moreover, direct host and viral responses upon infection could be further investigated by activity-based functional validation studies. These approaches involve drug inhibition of secretory pathway, immunofluorescence staining, dominant negative mutant of protein target, real-time PCR, small interfering siRNA-mediated knockdown, and molecular cloning studies. In this way, functional validation could gain novel insights into the high-content proteomic dataset in an unbiased and comprehensive way.


title: A Peptide-Based Virus Inactivator Protects Male Mice Against Zika Virus-Induced Damage of Testicular Tissue

text: Zika virus (ZIKV) was a re-emerging arbovirus associated with Guillain–Barré Syndrome in adult and congenital Zika syndrome in fetus and infant. Although ZIKV was mainly transmitted by mosquito bites, many sexual transmission cases have been reported since the outbreak in 2015. ZIKV can persist in testis and semen for a long time, causing testicular tissue damage and reducing sperm quality. However, no drug has been approved for prevention or treatment of ZIKV infection, especially infection in male testicular tissue. Previously reported peptide Z2 could inactivate ZIKV, inhibiting ZIKV infection in vitro and in vivo. Importantly, Z2 could inhibit vertical transmission of ZIKV in pregnant mice, reducing ZIKV infection in fetus. Here we showed that intraperitoneally administered Z2 could also be distributed to testis and epididymis, resulting in the reduction of ZIKV RNA copies in testicular tissue and protection of testis and epididymis against ZIKV-induced pathological damage and poor sperm quality in type I interferon receptor-deficient A129 mice. Thus, Z2, a ZIKV inactivator, could serve as an antiviral agent for treatment of ZIKV infection and attenuation of ZIKV-induced testicular tissue damage.


title: Olfactory dysfunction from acute upper respiratory infections: relationship to season of onset

text: BACKGROUND: Acute viral upper respiratory tract infections are the most common cause of chronic olfactory dysfunction. In light of the seasonality of numerous viruses, the question arises as to whether the frequency and magnitude of postviral olfactory disorders (PVODs) are similarly seasonal. We sought to determine whether olfactory deficits due to influenza and non–influenza‐related viruses (I‐PVODs and NI‐PVODs) vary in frequency or magnitude across seasons in a North American population and whether they are more prevalent or produce more severe olfactory dysfunction during colder months when host susceptibility may be increased. METHODS: This was a retrospective study of 587 patients presenting to an academic smell and taste center with either I‐PVOD–related or NI‐PVOD–related olfactory deficits. Chi‐square and analysis of covariance (age = covariate) compared dysfunction prevalence frequencies and scores on the University of Pennsylvania Smell Identification Test (UPSIT) across calendar months and between months with the coldest and warmest air temperatures. RESULTS: For I‐PVOD–related cases, both the prevalence and magnitude of smell dysfunction were highest in the colder months. However, for NI‐PVOD–related cases, prevalence was higher in warmer months but, paradoxically, the magnitude of dysfunction was higher in colder months. CONCLUSION: This study shows that seasonal variations occur in both the prevalence and magnitude of PVOD‐related olfactory deficits in a North American population, and that such variations differ between NI‐PVOD and I‐PVOD cases. The findings suggest multiple viruses are involved in producing PVOD‐related olfactory deficits.


title: Targeted Release in the COVID-19 Correctional Crisis: Using the RNR Model to Save Lives

text: While the COVID-19 pandemic has dramatically affected the lives of people around the world, select populations (e.g., elderly, immune-compromised, and incarcerated individuals) are among the most likely to contract the virus and among the least likely to overcome the illness and regain full health. This paper focuses on the incarcerated individuals and how the coronavirus has added a new and unprecedented threat to correctional facilities that are already overcrowded and ill-equipped to identify and address the medical needs of the inmate population. The risk-need-responsivity model (RNR) should be used to make empirically-informed decisions about the targeted release. The identification and release of inmates who pose the least threat to society will help alleviate some of the burdens associated with prison crowding. Specifically, with fewer inmates, correctional facilities can comply with social distancing guidelines, introduce enhanced cleaning measures, and make necessary institutional adjustments. In so doing they will limit the transmission of COVI-19 within correctional institutions, ensure the safety of staff and their charges, and enable prisons and jails to better accommodate the needs of the inmate population.


title: Effect of Underlying Comorbidities on the Infection and Severity of COVID-19 in Korea: a Nationwide Case-Control Study

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an emerging threat worldwide. It remains unclear how comorbidities affect the risk of infection and severity of COVID-19. METHODS: This is a nationwide retrospective case-control study of 219,961 individuals, aged 18 years or older, whose medical costs for COVID-19 testing were claimed until May 15, 2020. COVID-19 diagnosis and infection severity were identified from reimbursement data using diagnosis codes and on the basis of respiratory support use, respectively. Odds ratios (ORs) were estimated using multiple logistic regression, after adjusting for age, sex, region, healthcare utilization, and insurance status. RESULTS: The COVID-19 group (7,341 of 219,961) was young and had a high proportion of female. Overall, 13.0% (954 of 7,341) of the cases were severe. The severe COVID-19 group had older patients and a proportion of male ratio than did the non-severe group. Diabetes (odds ratio range [ORR], 1.206–1.254), osteoporosis (ORR, 1.128–1.157), rheumatoid arthritis (ORR, 1.207–1.244), substance use (ORR, 1.321–1.381), and schizophrenia (ORR, 1.614–1.721) showed significant association with COVID-19. In terms of severity, diabetes (OR, 1.247; 95% confidential interval, 1.009–1.543), hypertension (ORR, 1.245–1.317), chronic lower respiratory disease (ORR, 1.216–1.233), chronic renal failure, and end-stage renal disease (ORR, 2.052–2.178) were associated with severe COVID-19. CONCLUSION: We identified several comorbidities associated with COVID-19. Health care workers should be more careful while diagnosing and treating COVID-19 when patients have the abovementioned comorbidities.


title: PreDicta chip-based high resolution diagnosis of rhinovirus-induced wheeze

text: Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD). The occurrence of numerous RV types is a major challenge for the identification of the culprit virus types and for the improvement of virus type-specific treatment strategies. Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology. Importantly, we identify RV-A and RV-C species as giving rise to most severe respiratory symptoms. Thus, we have generated a chip for the serological identification of RV-induced respiratory illness which should be useful for the rational development of preventive and therapeutic strategies targeting the most important RV types.


title: Letter to the Editor Regarding the Viewpoint “Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanism”

text: I have read with interest the article entitled Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms by Baig et al. 1. This letter is supposed to supplement the aforementioned article with expanded scope on pathophysiological mechanisms which could prove salient in elucidating pathogenesis, seeking treatment, or considering clinical implications.


title: Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry

text: Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.


title: Metronomic oral vinorelbine and lung cancer therapy during the COVID 19 pandemic: a single-center experience

text: • Intravenous vinorelbine is a standard treatment for advanced NSCLC; • Oral vinorelbine is equally effective as compared to intravenous vinorelbine; • Metronomic oral formulation of vinorelbine is a safe and active treatment for advanced NSCLC; • No established treatment is a “gold standard” during COVID19 era; • Metronomic oral vinorelbine permitted to carry on active treatment during COVID Emergency; • Metronomic oral vinorelbine reduce side effects and hospital visits to lung cancer patients; • Management of lung cancer patients may be improved by metronomic oral vinorelbine.


title: Memory immune responses and protection of chickens against a nephropathogenic infectious bronchitis virus strain by combining live heterologous and inactivated homologous vaccines

text: In this study, we evaluated antibody and cell-mediated immune (CMI) responses in the mucosal and systemic compartments and protection against challenge with a nephropathogenic Brazilian (BR-I) strain of infectious bronchitis virus (IBV) in chickens submitted to a vaccination regime comprising a priming dose of heterologous live attenuated Massachusetts vaccine followed by a booster dose of an experimental homologous inactivated vaccine two weeks later. This immunization protocol elicited significant increases in serum and lachrymal levels of anti-IBV IgG antibodies and upregulated the expression of CMI response genes, such as those encoding CD8β chain and Granzyme homolog A in tracheal and kidney tissues at 3, 7, and 11 days post-infection in the vaccinated chickens. Additionally, vaccinated and challenged chickens showed reduced viral loads and microscopic lesion counts in tracheal and kidney tissues, and their antibody and CMI responses were negatively correlated with viral loads in the trachea and kidney. In conclusion, the combination of live attenuated vaccine containing the Massachusetts strain with a booster dose of an inactivated vaccine, containing a BR-I IBV strain, confers effective protection against infection with nephropathogenic homologous IBV strain because of the induction of consistent memory immune responses mediated by IgG antibodies and TCD8 cells in the mucosal and systemic compartments of chickens submitted to this vaccination regime.


title: Integration of telemedicine into the public health response to COVID‐19 must include dentists

text: Dentists are among the medical professionals, who are particularly exposed to Covid-19 (Meng et al. 2020, Yu et al. 2020). Indeed, in additional to the nasal passages the mouth is a privileged place of contamination; urgent or emergent dental care is often invasive and requires aerosolization (Ather et al 2020). Dental practitioners are then exposed to saliva which plays a role in the human-to-human transmission of diseases, in particular respiratory coronaviruses (Sabino-Silva et al. 2020, Lu et al. 2010, Liu et al. 2011). We believe that dental surgeons are at the forefront of practitioner-patient cross-transmission. It is imperative that dental surgeons stay abreast of this outbreak and appreciate essential precautionary practices that are potentially crucial to protect themselves, their relatives and their patients during this outbreak.


Management of breast cancer in an EUSOMA‐accredited Breast Unit in Lombardy, Italy, during the COVID‐19 pandemic