title: Early use of tocilizumab in the prevention of adult respiratory failure in SARS‐CoV‐2 infections and the utilization of interleukin‐6 levels in the management

text: BACKGROUND: Respiratory failure in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection appears related to cytokine release syndrome (CRS) that often results in mechanical ventilation (MV). We investigated the role of tocilizumab (TCZ) on interleukin‐6 (IL‐6) trends and MV in SARS‐CoV‐2 patients. METHODS: In this longitudinal observational study, 112 patients were evaluated from 2/1/2020 ‐ 5/31/2020. TCZ was administered followed by methylprednisolone to patients with > 3L oxygen (O2) requirement and pneumonia severity index (PSI) score ≤ 130 with CT scan changes. IL‐6, C‐reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), D‐dimer, and procalcitonin were monitored on days 0, 3, and 6 of therapy. Statistical analyses were performed with significance ≤ 0.05. RESULTS: 80/112 SARS‐CoV‐2‐positive patients (45 males, 56.96%; 34 females, 43.04%) were included in this study. Seven patients expired (8.75%) and nine patients required MV (11.25%). Median IL‐6 levels pre‐administration of TCZ was 342.50 (78.25 ‐ 666.25) pg/mL compared to post‐administration on day 3 (563; 162 ‐ 783) pg/mL (P < 0.00001). On day 6, the median dropped to 545 (333.50 ‐ 678.50) pg/mL compared to day 3 (P = 0.709). CRP, ferritin, LDH, and D‐dimer levels were reduced following TCZ therapy. CONCLUSIONS: Early use of TCZ may reduce the need for MV and decrease CRP, ferritin, LDH, and D‐dimer levels. The sequential use of methylprednisolone for 72 hours seems to potentiate the effect and prolong the suppression of the cytokine storm. IL‐6 levels may be helpful as a prognostic tool. This article is protected by copyright. All rights reserved.


title: Geburtshilfliche Anästhesie während der SARS-CoV-2-Pandemie: Übersicht der Handlungsempfehlungen

text: The most common human corona viruses cause common colds. But three of these viruses cause more serious, acute diseases; Middle East Respiratory Syndrome (MERS by MERS-CoV), Severe Acute Respiratory Syndrome (SARS) by SARS-CoV and COVID-19 by SARS-CoV-2. The current outbreak was classified by the WHO as a “global public health emergency”. Despite all efforts to reduce the surgical lists and to cancel or postpone non-time-critical surgical interventions, some surgical and anesthetic interventions outside of intensive care medicine are still necessary and must be performed. This is particularly true for obstetric interventions and neuraxial labor analgesia. Workload in the delivery room is presumably not going to decrease and planned cesarean sections cannot be postponed. In the meantime, the clinical course and outcome of some COVID-19 patients with an existing pregnancy or peripartum courses have been reported. There are already numerous recommendations from national and international bodies regarding the care of such patients. Some of these recommendations will be summarized in this manuscript. The selection of aspects should by no means be seen as a form of prioritization. The general treatment principles in dealing with COVID-19 patients and the recommendations for action in intensive care therapy also apply to pregnant and postpartum patients. In this respect, there are naturally considerable redundancies and only a few aspects apply strictly or exclusively to the cohort of obstetric patients. In summary, at present it must be stated that the general care recommendations that also apply to non-COVID-19 patients are initially valid with regard to obstetric anesthesia. Nevertheless, the special requirements on the part of hygiene and infection protection result in special circumstances that should be taken into account when caring for pregnant patients from an anesthetic point of view. These relate to both medical aspects, but also to a particular extent logistics issues with regard to spatial separation, staffing and material resources.


title: Rapid and Sensitive Detection of Novel Avian-Origin Influenza A (H7N9) Virus by Reverse Transcription Loop-Mediated Isothermal Amplification Combined with a Lateral-Flow Device

text: A severe disease in humans caused by a novel avian-origin influenza A (H7N9) virus emerged in China recently, which has caused at least 128 cases and 26 deaths. Rapid detection of the novel H7N9 virus is urgently needed to differentiate the disease from other infections, and to facilitate infection control as well as epidemiologic investigations. In this study, a reverse transcription loop-mediated isothermal amplification combined with a lateral flow device (RT-LAMP-LFD) assay to rapidly detect H7N9 virus was developed and evaluated. The RT-LAMP primers were designed to target the haemagglutinin (HA) and neuraminidase (NA) genes of H7N9 virus. Results of 10-fold dilution series assays showed that analysis of RT-LAMP products by the LFD method was as sensitive as real-time turbidity detection, and that the analytic sensitivities of the HA and NA RT-LAMP assays were both 10 copies of synthetic RNA. Furthermore, both the assays showed 100% clinical specificity for identification of H7N9 virus. The performance characteristics of the RT-LAMP-LFD assay were evaluated with 80 clinical specimens collected from suspected H7N9 patients. The NA RT-LAMP-LFD assay was more sensitive than real time RT-PCR assay. Compared with a combination of virus culture and real-time RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value of the RT-LAMP-LFD assay were all 100%. Overall, The RT-LAMP-LFD assay established in this study can be used as a reliable method for early diagnosis of the avian-origin influenza A (H7N9) virus infection.


On Lung Ultrasound Patterns Specificity in the Management of COVID‐19 Patients


title: Forecast and evaluation of COVID-19 spreading in USA with Reduced-space Gaussian process regression

text: In this report, we analyze historical and forecast infections for COVID-19 death based on Reduced-Space Gaussian Process Regression associated to chaotic Dynamical Systems with information obtained in 82 days with continuous learning, day by day, from January 21(th), 2020 to April 12(th). According last results, COVID-19 could be predicted with Gaussian models mean-field models can be meaning- fully used to gather a quantitative picture of the epidemic spreading, with infections, fatality and recovery rate. The forecast places the peak in USA around July 14(th) 2020, with a peak number of 132,074 death with infected individuals of about 1,157,796 and a number of deaths at the end of the epidemics of about 132,800. Late on January, USA confirmed the first patient with COVID-19, who had recently traveled to China, however, an evaluation of states in USA have demonstrated a fatality rate in China (4%) is lower than New York (4.56%), but lower than Michigan (5.69%). Mean estimates and uncertainty bounds for both USA and his cities and other provinces have increased in the last three months, with focus on New York, New Jersey, Michigan, California, Massachusetts,... (January e April 12(th)). Besides, we propose a Reduced-Space Gaussian Process Regression model predicts that the epidemic will reach saturation in USA on July 2020. Our findings suggest, new quarantine actions with more restrictions for containment strategies implemented in USA could be successfully, but in a late period, it could generate critical rate infections and death for the next 2 month.


title: Clinical decision making in the emergency department setting using rapid PCR: Results of the CLADE study group

text: Abstract Background Emergency Departments (ED) are challenged during influenza season by patients who present acutely during sporadic ED visits. ED management is largely empiric, often occurring without reliable diagnostics needed for targeted therapies, safe outpatient discharge, or hospital admissions. Objective To evaluate the impact of the influenza diagnosis on physician decision making during ED visits using the Cobas Liat® influenza A + B assay. Study design Prospective study assessing the impact of rapid (<30 min), reverse-transcriptase polymerase chain reaction (RT-PCR) influenza testing on physician decision making in the ED. Physician responses established pre-and post-diagnosis management courses which required confirmation via secondary documentation in the medical record. Changes in physician decision making were analyzed across four clinical touchpoints: (i) admission/discharge status, (ii) medical procedures, (iii) antiviral and antibiotic prescribing, and (iv) laboratory studies. Results An influenza diagnosis changed patient management courses, relative to empiric, pre-diagnosis plans, in in 61% of the cases resulting in cost savings of $49,420-to-$42,270 over 143 patients and 104 days during influenza season resulting in a cost savings of $200.40/ED visit. Evaluation over 2000 ED patient visits projects cost savings > $578,000 due to deferred admissions, and reduction in antiviral prescribing. Sensitivity of ED-based influenza testing using the Cobas Liat® assay was equivalent to centralized lab testing at 98.8% sensitivity and 98.5% specificity respectively. Conclusion Providing rapid, RT-PCR influenza testing to ED settings is actionable and used to guide patient care decisions. Understanding the cascade of events linked to the influenza diagnosis in the ED provides overall cost savings which offset the cost of providing ED-based testing.


title: Erste Ergebnisse zu Untersuchungen der menschlichen Hornhaut auf SARS-CoV‑2-RNA

text: Preliminary investigations of human corneal tissues from coronavirus disease 2019 (COVID-19) cadaveric donors indicated that no severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is present. Current eye banking guidelines do not recommend any type of routine testing for SARS-CoV‑2 RNA in post-mortem donor tissue. This is partly based on factors that can influence the test results of the reverse transcription polymerase chain reaction (RT-PCR).


title: Comprehensive update on current outbreak of novel coronavirus infection (2019-nCoV).

text: Recently, a new coronavirus disease (COVID-19) has emerged as a respiratory infection with significant concern for global public health hazards. With an initial suspicion of the animal to the human transmission for earlier cases, now the paradigm has shifted towards human to human transmission via droplets, contacts and/or through fomites. with each passing day, more and more confirmed cases are being reported worldwide which has alarmed the global authorities including World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) and the National Health Commission of the People's Republic of China to take immediate action in order to reduce the transmission and subsequent mortalities associated with COVID-19 to as minimum as possible. Unfortunately, like the previous Coronavirus outbreaks, there is no definite antiviral therapy for the treatment of confirmed cases and hence preventing ourselves from contracting 2019-nCoV is the best way to prevent it from becoming pandemic. Herein, we aim to discuss the latest updates on the origin, genomic characteristics, diagnosis, treatment options and current efforts being made by international health organizations with regards to the 2019-nCoV outbreak.


title: Asthme et usage de cannabis, de cocaïne ou d’héroïne

text: INTRODUCTION: The use of cannabis, cocaine or heroin can be responsible for many respiratory complications including asthma. OBJECTIVES: The aim of this systematic literature review of data was to expose the relations between cannabis, cocaine or heroin use and asthma. RESULTS: Cannabis, cocaine or heroin use by inhalation may be responsible for respiratory symptoms (cough, wheezing), asthma onset, acute asthma exacerbations (which may require intubation and invasive ventilation) or deaths related to asthma. Lower adherence to asthma treatment is also observed. Cannabis induces a rapid bronchodilator effect. In contrast, its chronic use may induce a decrease in specific airway conductance. Studies on forced expiratory volume in one second (FEV1) reduction or decline are discordant. CONCLUSION: Cannabis, cocaine or heroin use must be considered in cases of acute respiratory symptoms or asthma exacerbation in young persons and practitioners must help illicit substance users to stop their consumption.


title: Transmissible gastroenteritis virus infection decreases arginine uptake by downregulating CAT-1 expression

text: Transmissible gastroenteritis virus (TGEV) is a coronavirus that causes severe diarrhea in suckling piglets. TGEV primarily targets and infects porcine intestinal epithelial cells, which play an important role in nutrient absorption. However, the effects of TGEV infection on nutrient absorption in swine have not yet been investigated. In this study, we evaluated the impact of TGEV infection on arginine uptake using the porcine small intestinal epithelial cell line IPEC-J2 as a model system. High performance liquid chromatography (HPLC) analyses showed that TGEV infection leads to reduced arginine uptake at 48 hours post-infection (hpi). Expression of cationic amino acid transporter 1 (CAT-1) was attenuated as well. TGEV infection induced activation of phospho-protein kinase C α (p-PKC α), phospho-epidermal growth factor receptor (p-EGFR), and enhanced the expression of caveolin-1, all of which appear to be involved in down-regulating arginine uptake and CAT-1 expression. These results illuminate the relationship between TGEV infection and nutrient absorption, and further our understanding of the mechanisms of TGEV infection.


title: Late-Life Depression: A Model for Medical Classification

text: Geriatric psychiatric syndromes might serve as the starting point for a medical classification of psychiatric disorders, because their medical and neurological comorbidity and their clinical, neuropsychological, and neuroimaging features often reflect specific brain abnormalities. Geriatric syndromes, however, consist of complex behaviors that are unlikely to be caused by single lesions. We propose a model in which aging-related changes in specific brain structures increase the propensity for the development of certain psychiatric syndromes. The predisposing factors are distinct from the mechanisms mediating the expression of a syndromic state, much like hypertension is distinct from stroke, but constitutes a morbid vulnerability. We argue that research seeking to identify both brain abnormalities conferring vulnerability as well as the mediating mechanisms of symptomatology has the potential to lead to a medical classification of psychiatric disorders. In addition, a medical classification can guide the effort to improve treatment and prevention of psychiatric disorders as it can direct therapeutic efforts to the underlying predisposing abnormalities, the syndrome-mediating mechanisms, and to development of behavioral skills needed for coping with adversity and disability.


title: Recent development of multi-dimensional chromatography strategies in proteome research

text: Abstract As a complementary approach to two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), multi-dimensional chromatography separation methods have been widely applied in all kinds of biological sample investigations. Multi-dimensional liquid chromatography (MDLC) coupled with bio-mass spectrometry (MS) is playing important roles in proteome research due to its high speed, high resolution and high sensitivity. Proteome analysis strategies mainly include bottom-up and top-down approaches which carry out biological sample separation based on peptide and protein levels, respectively. Electrophoretic methods combined with liquid chromatography like IEF-HPLC and HPLC-SDS-PAGE have been successful applied for protein separations. As for MDLC strategy, ion-exchange chromatography (IEX) together with reversed phase liquid chromatography (RPLC) is still a most widely used chromatography in proteome analysis, other chromatographic methods are also frequently used in protein pre-fractionations, while affinity chromatography is usually adopted for specific functional protein analysis. Recent MDLC technologies and applications to variety of proteome analysis have been achieved great development. A digest peptide-based approach as so-called “bottom-up” and intact protein-based approach “top-down” analysis of proteome samples were briefly reviewed in this paper. The diversity of combinations of different chromatography modes to set up MDLC systems was demonstrated and discussed. Novel developments of MDLC techniques such as high-abundance protein depletion and chromatography array were also included in this review.


title: Systemic fatal type II coronavirus infection in a dog: Pathological findings and immunohistochemistry

text: Abstract A case of fatal systemic coronavirus infection is described in a 53-day-old Pekinese dog. Pathological findings and immunohistochemical identification using a monoclonal anti-canine Coronavirus antibody are included. Visceral lesions consisted of extensive fibrinopurulent bronchopneumonia, multiple renal cortical infarcts, severe coalescing centrilobular hepatic fatty change with minimal random hepatic necrosis, and multifocal splenic haemorrhage with lymphoid depletion. Moderate chronic diffuse enteritis was associated with intraluminal adult ascarids. Identification of type I and type II coronavirus in this subject had been previously confirmed by genotype-specific real-time reverse transcription-polymerase chain reaction (RT-PCR) assays of the intestinal contents, while only Coronavirus type II was detected in visceral organs. This case represents the first description of morphological lesions associated with a type II pantropic fatal coronavirus infection in the dog.


title: The Battle Against Coronavirus Disease 2019 (COVID-19): Emergency Management and Infection Control in a Radiology Department

text: Abstract Objective To describe the strategy and the emergency management and infection control procedure of our radiology department during the coronavirus disease 2019 (COVID-19) outbreak. Methods We set up emergency management and sensing control teams. The team formulated various measures: reconfiguration of the radiology department, personal protection and training of staff, examination procedures for patients suspected of or confirmed with COVID-19 as well as patients without an exposure history or symptoms. Those with suspected or confirmed COVID-19 infection were scanned in the designated fever-CT unit. Results From January 21, 2020, to March 9, 2020, 3,083 people suspected or confirmed to be infected with COVID-19 underwent fever-CT examinations. Including initial examinations and re-examinations, the total number of fever-CT examinations numbered 3,340. As a result of our precautions, none of the staff of the radiology department were infected with COVID-19. Conclusion Strategic planning and adequate protections can help protect patients and staff against a highly infectious disease while maintaining function at a high-volume capacity.


title: Optimization of bovine coronavirus hemagglutinin-estrase glycoprotein expression in E3 deleted bovine adenovirus-3

text: Abstract Adenoviral vectors expressing foreign genes have many desirable properties in applications such as vaccination. Recently, we have generated replication-competent (E3 deleted) bovine adenovirus-3 (BAV-3) recombinants expressing significant amounts of glycoprotein D (gD) of bovine herpesvirus-1 (a DNA virus). However, attempts to express the RNA virus genes using the same strategy were not successful. In an effort to optimize the expression, we have constructed several BAV-3 recombinants carrying the hemagglutinin esterase (HE) gene of bovine coronavirus (BCV) in the E3 region with or without exogenous transcription control elements. The expression studies suggest that the introduction of a 137 bp chimeric intron upstream of the HE cDNA is able to increase the level of HE gene expression. The introduction of a SV40 early promoter or human cytomegalovirus (HCMV) immediate early (IE) promoter into the expression cassette changed the kinetics of the HE expression. However, the recombinant BAV-3 containing HE under the HCMV IE promoter replicated less efficiently than the wild-type BAV-3. These studies should prove useful in expression of other RNA viral genes in the E3 region of BAV-3 expression system.


Reply to Leow


The “piecework anesthetists” solution to the lack of ventilators during the COVID-19 pandemic


title: COVID-19-driven endothelial damage: complement, HIF-1, and ABL2 are potential pathways of damage and targets for cure

text: COVID-19 pandemia is a major health emergency causing hundreds of deaths worldwide. The high reported morbidity has been related to hypoxia and inflammation leading to endothelial dysfunction and aberrant coagulation in small and large vessels. This review addresses some of the pathways leading to endothelial derangement, such as complement, HIF-1α, and ABL tyrosine kinases. This review also highlights potential targets for prevention and therapy of COVID-19-related organ damage and discusses the role of marketed drugs, such as eculizumab and imatinib, as suitable candidates for clinical trials.


title: Etiology of bronchiolitis in a hospitalized pediatric population: Prospective multicenter study

text: Abstract Background In 2006, bronchiolitis due to adenovirus nosocomial infections resulted in the closure of a pediatric department in northern Portugal. Objectives To determine the etiology of bronchiolitis in northern Portugal. Study design It was a prospective multicenter study on the etiology of bronchiolitis during the respiratory syncytial virus (RSV) season (November–April). Children ≤24 months of age admitted for a first wheezing episode were included. Nasopharyngeal specimens were analyzed by an indirect immunofluorescent-antibody assay (IFA) for RSV, adenovirus (HAdV), parainfluenza (PIV) 1–3 and influenza (IV) A and B and by polymerase chain reaction (PCR) or reverse transcription-PCR for the same viruses and for human metapneumovirus (hMPV), bocavirus (HBoV), rhinovirus (HRV), coronaviruses (229/E; NL63; OC43; HKU1) and enterovirus. Results During this period, 253 children were included, 249 IFA analyses and 207 PCRs were performed. IFA detected RSV in 58.1%; PCR increased it to 66.7%. IFA detected HAdV in 3.2%, PCR 10.0%. PCR detected IV A in 5; IV B in 2; PIV 1 in 6, PIV 2 in 4 and PIV 3 in 11 cases. HBoV, as single agent in 2 cases, and HRV were positive in 8 samples and hMPV in 11. With this virus panel, 19.7% remained without etiology. Conclusions The most frequent agent was RSV, followed by HAdV. PCR can be cost-effective and more accurate than IFA, which is crucial for HAdV that may be associated with significant mortality (IFA alone did not detect 2/3 of the cases).


title: Pandemic response protocol of a non-frontline specialty in a multispecialty tertiary health care centre—a pilot model in orthopaedics

text: BACKGROUND: 3,181,642 cases and 224,301 deaths in 212 regions of the world—this is the status of COVID-19 (Coronavirus Disease 2019) pandemic as of May 1, 2020. This pandemic has managed to overwhelm the health care system of the most advanced countries in the world. As the whole of the medical fraternity stands robed as health care professionals to fight against COVID-19, specialty emergencies like trauma continue to pester the already overburdened health care community. This situation calls for the need for a pandemic response protocol (PREP) in each specialty that helps the doctors to manage specialty emergencies without chaos and at the same time allowing them to play their part in pandemic management. CONCLUSION: PREP as an integrated pragmatic approach is essential in containing pandemics as they need international cooperation at various levels starting from knowledge sharing to monetary support. PREP which is in line with the WHO action plan, will be an essential minimum response of a non-frontline pandemic response specialty like orthopedics to combat and curtail the effects of a pandemic in a multispecialty tertiary health care centre.


title: Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease-19

text: BACKGROUND: Whether angiotensin-converting enzyme (ACE) Inhibitors and angiotensin receptor blockers (ARBs) mitigate or exacerbate SARS-CoV-2 infection remains uncertain. In a national study, we evaluated the association of ACE inhibitors and ARB with coronavirus disease-19 (COVID-19) hospitalization and mortality among individuals with hypertension. METHODS: Among Medicare Advantage and commercially insured individuals, we identified 2,263 people with hypertension, receiving ≥1 antihypertensive agents, and who had a positive outpatient SARS-CoV-2 test (outpatient cohort). In a propensity score-matched analysis, we determined the association of ACE inhibitors and ARBs with the risk of hospitalization for COVID-19. In a second study of 7,933 individuals with hypertension who were hospitalized with COVID-19 (inpatient cohort), we tested the association of these medications with in-hospital mortality. We stratified all our assessments by insurance groups. RESULTS: Among individuals in the outpatient and inpatient cohorts, 31.9% and 29.8%, respectively, used ACE inhibitors and 32.3% and 28.1% used ARBs. In the outpatient study, over a median 30.0 (19.0 - 40.0) days after testing positive, 12.7% were hospitalized for COVID-19. In propensity score-matched analyses, neither ACE inhibitors (HR, 0.77 [0.53, 1.13], P = 0.18), nor ARBs (HR, 0.88 [0.61, 1.26], P = 0.48), were significantly associated with risk of hospitalization. In analyses stratified by insurance group, ACE inhibitors, but not ARBs, were associated with a significant lower risk of hospitalization in the Medicare group (HR, 0.61 [0.41, 0.93], P = 0.02), but not the commercially insured group (HR: 2.14 [0.82, 5.60], P = 0.12; P-interaction 0.09). In the inpatient study, 14.2% died, 59.5% survived to discharge, and 26.3% had an ongoing hospitalization. In propensity score-matched analyses, neither use of ACE inhibitor (0.97 [0.81, 1.16]; P = 0.74) nor ARB (1.15 [0.95, 1.38]; P = 0.15) was associated with risk of in-hospital mortality, in total or in the stratified analyses. CONCLUSIONS: The use of ACE inhibitors and ARBs was not associated with the risk of hospitalization or mortality among those infected with SARS-CoV-2. However, there was a nearly 40% lower risk of hospitalization with the use of ACE inhibitors in the Medicare population. This finding merits a clinical trial to evaluate the potential role of ACE inhibitors in reducing the risk of hospitalization among older individuals, who are at an elevated risk of adverse outcomes with the infection.


title: Molecular Epidemiology of Human Adenovirus–Associated Febrile Respiratory Illness in Soldiers, South Korea(1)

text: During January 2013–April 2014, we subjected nasopharyngeal specimens collected from patients with acute febrile respiratory illness in a military hospital to PCR testing to detect 12 respiratory viruses and sequence a partial hexon gene for human adenovirus (HAdV) molecular typing. We analyzed the epidemiologic characteristics of HAdV infections and compared clinical characteristics of HAdV types. Among the 305 patients with acute febrile respiratory illness, we detected respiratory viruses in 139 (45.6%) patients; HAdV was the most prevalent virus (69 cases). Of the 40 adenoviruses identified based on type, HAdV-55 (29 cases) was the most prevalent, followed by HAdV-4 (9 cases). HAdV-55 was common in patients with pneumonia (odds ratio 2.17; 95% CI 0.48–9.86) and hospitalized patients (odds ratio 5.21; 95% CI 1.06–25.50). In soldiers with HAdV infection in Korea, HAdV-55 was the most prevalent type and might be associated with severe clinical outcomes.


title: How to Influence Rural Tourism Intention by Risk Knowledge during COVID-19 Containment in China: Mediating Role of Risk Perception and Attitude

text: With both cost and safety taken into account in the context of the life-threatening COVID-19 pandemic globally, rural tourism is expected to be the top choice for Chinese residents for relaxation and enhancing parent-child relationships. In this paper, a structural equation (SEM) model was proposed to compare risk knowledge, risk perception, risk aversion attitudes and behavioral intentions towards rural tourism. According to the empirical results, there was a large proportion of tourists showing preference for rural tourism recently. Potential participants in rural tourism paid most attention to the performance realization and time cost of scenic spots, while the psycho-social risk posed by COVID-19 had little impact. The inherent risk nature of risk aversion attitudes made knowledge of the pneumonia risk less effective in reducing tourists’ intentions, while knowledge of the pneumonia risk was more effective in alleviating the risk perception that potential tourists have towards rural tourism. With regard to travel intention and recommendation intention of rural tourism, the negative impacts of risk aversion attitude were more considerable compared to risk perception. Meanwhile, the parallel mediating effect of risk perception and risk aversion attitude in rural tourism needed to be taken into consideration together.


title: Avoiding collateral mortality in a pandemic — time to change our mindset in surgical oncology

text: The coronavirus disease 19 (COVID-19) pandemic has become the focus of attention worldwide, and herein we seek to highlight the potential problem of ‘collateral mortality’ from delayed or deferred treatments in patients with cancer. We propose potential solutions to ensure continuity of care in the field of surgical oncology.


COVID‐19, Dugnad and productive incompleteness: volunteer labour and crisis loans in Norway


title: Assessing the potential of upper respiratory tract point-of-care testing: a systematic review of the prognostic significance of upper respiratory tract microbes

text: Abstract Objectives Microbial point-of-care testing (POCT) has potential to revolutionize clinical care. Understanding the prognostic value of microbes identified from the upper respiratory tract (a convenient sampling site) is a necessary first step to understand potential for upper respiratory tract POCTs in assisting antimicrobial treatment decisions for respiratory infections (RTIs). The aim was to investigate the relationship between upper respiratory tract microbial detection and disease prognosis, including effects of antimicrobial use. Methods Data sources were the MEDLINE and Embase databases. Study eligibility criteria consisted of quantitative studies reporting microbiological and prognostic data from patients of all age groups presenting with RTI. Patients presenting to healthcare or research settings with RTI participated. Interventions included upper respiratory tract swab. The methods used were systematic review and meta-analysis. Results Searches identified 5156 articles, of which 754 were duplicates and 4258 excluded on title or abstract. A total of 144 full texts were screened; 21 articles were retained. Studies reported data for 15 microbes and 26 prognostic measures (390 potential associations). One hundred and seven (27%) associations were investigated statistically, of which 38 (36%) were significant. Most studies reported only prognostic value of test positive results. Meta-analyses suggested hospitalization duration was longer for patients with respiratory syncytial virus than adenovirus and influenza, but significant heterogeneity was observed between studies. Conclusions A quarter of potential prognostic associations have been investigated. Of these, a third were significant, suggesting considerable potential for POCT. Future research should investigate prognostic value of positive and negative tests, and interactions between test results, use of antimicrobials and microbial resistance.


title: SARS and hospital priority setting: a qualitative case study and evaluation

text: BACKGROUND: Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS) in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'. METHODS: This study was conducted at a large tertiary hospital in Toronto, Canada. There were two data sources: 1) over 200 key documents (e.g. emails, bulletins), and 2) 35 interviews with key informants. Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. RESULTS: Participants described the types of priority setting decisions, the decision making process and the reasoning used. Although the hospital leadership made an effort to meet the conditions of 'accountability for reasonableness', they acknowledged that the decision making was not ideal. We described good practices and opportunities for improvement. CONCLUSIONS: 'Accountability for reasonableness' is a framework that can be used to guide fair priority setting in health care organizations, such as hospitals. In the midst of a crisis such as SARS where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less.


title: Occurrence of infectious bronchitis in layer birds in Plateau state, north central Nigeria

text: A flock of 54 wk-old layer birds exhibiting signs of respiratory distress, greenish diarrhea, and drop in egg production was investigated. A marked drop in egg production (55%) was recorded with eggs appearing white and soft-shelled. Mortality was in the range of 1%–2% with post-mortem lesions revealing cloudy air sacs, frothy, and congested lungs. Viral RNA was extracted from pooled tissue samples (trachea, lungs, spleen, and liver) and tested for Avian influenza virus (AIV), Newcastle disease virus (NDV), and infectious bronchitis virus (IBV) by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, virus isolation was attempted in 9–11 day-old embryonating chicken eggs (ECE). In order to determine the prevalence of IBV serotype(s) in the flock, serum samples were screened by hemagglutination-inhibition (HI) test using IBV antigens and antisera (Arkansas, Connecticut, and Massachusetts). Neither AIV nor NDV but IBV was detected in the tissue samples by RT-PCR. In addition, virus isolate obtained after four serial passages in ECE produced dwarfed, stunted, and hemorrhagic embryos, and the isolate was confirmed by RT-PCR to be IBV. The serum samples were 100% seropositive for three serotypes with HI titres ranging from 5 to 12 Log(2). In this study, IBV was confirmed as the causative agent of the observed respiratory distress and drop in egg production. Also, the evidence of co-circulation of multiple IBV serotypes was established, this to the best of our knowledge is the first of such report in Nigeria. We recommend extensive molecular and sero-epidemiology of circulating IBV genotypes and serotypes in Nigeria with the aim of developing better control strategies, including vaccination.


title: Detection and spike gene characterization in porcine deltacoronavirus in China during 2016–2018

text: Abstract Porcine deltacoronavirus (PDCoV) has been emerging in several swine-producing countries for years. In our study, 719 porcine diarrhoea samples from 18 provinces in China were collected for PDCoV and porcine epidemic diarrhoea virus (PEDV) detection. The epidemiological survey revealed that the positive rates of PDCoV, PEDV and coinfection were 13.07%, 36.72% and 4.73%, respectively. The entire spike (S) genes of eleven detected PDCoV strains were sequenced. Phylogenetic analysis showed that the majority of PDCoVs could be divided into three lineages: the China lineage, the USA/Japan/South Korea lineage and the Viet Nam/Laos/Thailand lineage. The China and the Viet Nam/Laos/Thailand lineages showed much greater genetic divergences than the USA/Japan/South Korea lineage. The present study detected one new monophyletic branch that contained three PDCoVs from China, and this branch was separated from the China lineage but closely related to the Viet Nam/Laos/Thailand lineage. The strain CH-HA2-2017, which belongs to this new branch, had a possible recombination event between positions 27 and 1234. Significant amino acid substitutions of PDCoV S proteins were analysed and displayed with a three-dimensional cartoon diagram. The visual spatial location of these substitutions gave a conformational-based reference for further studies on the significance of critical sites on the PDCoV S protein.


title: CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens

text: Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.


title: The development of a multiplex real-time RT-PCR for the detection of adenovirus, astrovirus, rotavirus and sapovirus from stool samples

text: Abstract Viral gastroenteritis is a major health problem with significant morbidity and economic consequences. Viral gastroenteritis is caused by a number of viruses, including norovirus, rotavirus, adenovirus, astrovirus, and sapovirus. Conventional diagnosis is based on direct antigen detection and electron microscopy, however enzyme immunoassay’s are insensitive and not available for all relevant pathogens, and electron microscope (EM) is no longer routinely carried out in most laboratories. Most laboratories now offer norovirus real-time PCR testing however the availability of other assays is variable. Commercial methods for the detection of inflectional intestinal disease (IID) are available but these can be expensive and are not commonly used. This paper describes the development of a single multiplex assay for the simultaneous detection of adenovirus, astrovirus, rotavirus and sapovirus from stool samples. The multiplex was evaluated by assessing endpoint sensitivity, specificity, panel of clinical samples, quality control (QC) panel and the robustness and reproducibility of the multiplex.


title: Inhibition of viral RNA polymerases by nucleoside and nucleotide analogs: therapeutic applications against positive-strand RNA viruses beyond hepatitis C virus

text: A number of important human infections are caused by positive-strand RNA viruses, yet almost none can be treated with small molecule antiviral therapeutics. One exception is the chronic infection caused by hepatitis C virus (HCV), against which new generations of potent inhibitors are being developed. One of the main molecular targets for anti-HCV drugs is the viral RNA-dependent RNA polymerase, NS5B. This review summarizes the search for nucleoside and nucleotide analogs that inhibit HCV NS5B, which led to the FDA approval of sofosbuvir in 2013. Advances in anti-HCV therapeutics have also stimulated efforts to develop nucleoside analogs against other positive-strand RNA viruses. Although it remains to be validated in the clinic, the prospect of using nucleoside analogs to treat acute infections caused by RNA viruses represents an important paradigm shift and a new frontier for future antiviral therapies.


In Response to: In Reference to Anosmia and Ageusia: Common Findings in COVID‐19 Patients


title: Evaluation of the efficacy of a trivalent vaccine mixture against a triple challenge with Mycoplasma hyopneumoniae, PCV2, and PRRSV and the efficacy comparison of the respective monovalent vaccines against a single challenge

text: BACKGROUND: The objective of this study was to assess the efficacy of a trivalent vaccine mixture and compare it to the respective monovalent vaccines against Mycoplasma hyopneumoniae, porcine circovirus type 2 (PCV2), and porcine reproductive and respiratory syndrome virus (PRRSV). RESULTS: Pigs that were triple challenged with M. hyopneumoniae, PCV2, and PRRSV following vaccination with the trivalent vaccine mixture exhibited a significantly better growth performance when compared to unvaccinated and challenged pigs. A statistical difference was not found when comparing pig populations which were vaccinated with the trivalent vaccine followed by a triple challenge and pigs vaccinated with monovalent M hyopneumoniae vaccine followed by mycoplasmal single challenge in the following areas: M. hyopneumoniae nasal shedding, the number of M. hyopneumoniae-specific interferon-γ secreting cells (IFN-γ-SC), and mycoplasmal lung lesion scores. Pigs vaccinated with the trivalent vaccine mixture followed by a triple challenge resulted in a similar reduction of PCV2 viremia, an increase in the number of PCV2-specific IFN-γ-SC and reduction in interstitial lung lesion scores when compared to pigs vaccinated with a PCV-2 vaccine and challenged with PCV2 only. Lastly, there was a significant difference in the reduction of PRRSV viremia, an increase in PRRSV-specific IFN-γ-SC and a reduction of interstitial lung lesion scores between pigs vaccinated with the trivalent vaccine mixture followed by a triple challenge and pigs vaccinated with a monovalent PRRSV vaccine followed by PRRSV challenge only. CONCLUSION: The trivalent vaccine mixture was efficacious against a triple challenge of M. hyopneumoniae, PCV2, and PRRSV. The trivalent vaccine mixture, however, did not result in equal protection when compared against each respective monovalent vaccine, with the largest vaccine occurring within PRRSV.


title: AANA20: The 2020 Annual Meeting of the Arthroscopy Association of North America

text: Abstract Arthroscopy, Arthroscopy Techniques, and Arthroscopy, Sports Medicine, and Rehabilitation will be in attendance in force at the 2020 Annual Meeting of the Arthroscopy Association of North America (AANA20). Program highlights and innovations include surgery simulcasts, “Great Debates,” award-winning papers, Feature Lectures, and sessions glimpsing what is On the Horizon—and perhaps over and beyond.


title: Spatiotemporal Interplay of Severe Acute Respiratory Syndrome Coronavirus and Respiratory Mucosal Cells Drives Viral Dissemination in Rhesus Macaques

text: Innate immune responses play a critical role in the control of early virus replication and dissemination. It remains unknown, however, how SARS-CoV evades respiratory innate immunity to establish a systemic infection. Here, we show in Chinese macaques that SARS-CoV traversed the mucosa through the respiratory tract within 2 days, resulting in extensive mucosal infiltration by T cells, MAC387(+) and CD163(+) monocytes/macrophages followed by limited viral replication in the lung but persistent viral shedding into the upper airway. Mucosal monocytes/macrophages sequestered virions in intracellular vesicles together with infected Langerhans cells (LCs) and migrated into the tonsils and/or draining lymph nodes (LNs) within 2 days. In lymphoid tissues, viral RNA and proteins were detected in infected monocytes upon differentiation into dendritic cells (DCs) within 3 days. Systemic viral dissemination was observed within 7 days. This study provides a comprehensive overview of the spatiotemporal interactions of SARS-CoV, monocytes/macrophages and the dendritic cell network in mucosal tissues and highlights the fact that while these innate cells contribute to viral clearance, they probably also serve as shelters and vehicles to provide a mechanism for the virus to escape host mucosal innate immunity and disseminate systemically.


title: Uncertainty and sensitivity analysis of the basic reproduction number of diphtheria: a case study of a Rohingya refugee camp in Bangladesh, November–December 2017

text: BACKGROUND: A Rohingya refugee camp in Cox’s Bazar, Bangladesh experienced a large-scale diphtheria epidemic in 2017. The background information of previously immune fraction among refugees cannot be explicitly estimated, and thus we conducted an uncertainty analysis of the basic reproduction number, R(0). METHODS: A renewal process model was devised to estimate the R(0) and ascertainment rate of cases, and loss of susceptible individuals was modeled as one minus the sum of initially immune fraction and the fraction naturally infected during the epidemic. To account for the uncertainty of initially immune fraction, we employed a Latin Hypercube sampling (LHS) method. RESULTS: R(0) ranged from 4.7 to 14.8 with the median estimate at 7.2. R(0) was positively correlated with ascertainment rates. Sensitivity analysis indicated that R(0) would become smaller with greater variance of the generation time. DISCUSSION: Estimated R(0) was broadly consistent with published estimate from endemic data, indicating that the vaccination coverage of 86% has to be satisfied to prevent the epidemic by means of mass vaccination. LHS was particularly useful in the setting of a refugee camp in which the background health status is poorly quantified.


title: Bridging the gap between guidelines and practice in the management of emerging infectious diseases: a qualitative study of emergency nurses

text: AIMS AND OBJECTIVES: To explore the difficulties and strategies regarding guideline implementation among emergency nurses. BACKGROUND: Emerging infectious diseases remain an underlying source of global health concern. Guidelines for accident and emergency departments would require adjustments for infectious disease management. However, disparities between guidelines and nurses' practice are frequently reported, which undermines the implementation of these guidelines into practice. This article explores the experience of frontline emergency nurses regarding guideline implementation and provides an in‐depth account of their strategies in bridging guideline‐practice gaps. DESIGN: A qualitative descriptive design was used. METHODS: Semi‐structured, face‐to‐face, individual interviews were conducted between November 2013–May 2014. A purposive sample of 12 frontline emergency nurses from five accident and emergency departments in Hong Kong were recruited. The audio‐recorded interviews were transcribed verbatim and analysed with a qualitative content analysis approach. RESULTS: Four key categories associated with guideline‐practice gaps emerged, including getting work done, adapting to accelerated infection control measures, compromising care standards and resolving competing clinical judgments across collaborating departments. The results illustrate that the guideline‐practice gaps could be associated with inadequate provision of corresponding organisational supports after guidelines are established. CONCLUSIONS: The nurses' experiences have uncovered the difficulties in the implementation of guidelines in emergency care settings and the corresponding strategies used to address these problems. The nurses' experiences reflect their endeavour in adjusting accordingly and adapting themselves to their circumstances in the face of unfeasible guidelines. RELEVANCE TO CLINICAL PRACTICE: It is important to customise guidelines to the needs of frontline nurses. Maintaining cross‐departmental consensus on guideline interpretation and operation is also indicated as an important component for effective guideline implementation.


title: Medical Anthropology

text: Medical anthropology is an interdisciplinary subfield of anthropology with a long history of research on environmental health-related issues, especially those pertaining to human health within environments of risk, consequences of ecological degradation, and the way patterns of development and globalization impact environmental (and therefore human) health. In this article, the authors provide an introduction to the scope of medical anthropology research, its relevance to the field of environmental health, and the methods anthropologists use in their analyses. They conclude by elaborating on some of the key conceptual frameworks that guide current research and highlight topical areas in environmental health (broadly defined) where medical anthropology research is warranted.


title: Incidencia de la patología abdominal quirúrgica urgente durante la pandemia por SARS-CoV-2[[[en]]]Incidence of surgical abdominal emergencies during SARS-CoV-2 pandemic

text: Resumen Introducción: Desde la aparición en diciembre de 2019 del SARS-CoV-2 en la ciudad china de Wuhan, hemos experimentado un descenso en los ingresos en nuestro Servicio y disminución de la actividad quirúrgica urgente. Por ello, el objetivo de este estudio fue analizar la incidencia de la patología abdominal urgente potencialmente quirúrgica en nuestro centro durante la epidemia por COVID-19. Métodos: Se diseñó un estudio retrospectivo que incluyó todos los pacientes ingresados por patología abdominal urgente potencialmente quirúrgica en nuestro Servicio de Cirugía General y del Aparato Digestivo desde el 24 de febrero de 2020 hasta el 19 de abril de 2020. Resultados: Se incluyeron 89 pacientes con una edad media de 58,85±22,2. La mediana de tiempo transcurrido desde el inicio de los síntomas hasta la consulta en el Servicio de Urgencias fue de 48 (P25-P75 = 24-96) horas. A su llegada a Urgencias 18 (20%) pacientes presentaban criterios de SRIS (síndrome de respuesta inflamatoria sistémica). Se realizaron 51 (57%) intervenciones quirúrgicas. La tasa de complicaciones postquirúrgicas a los 30 días fue del 31% y la tasa de mortalidad de 2%. Con respecto al mismo período de tiempo de los años 2017 a 2019, la media de ingresos desde Urgencias en nuestro Servicio descendió un 14% durante el período de epidemia. Conclusiones: Se ha producido un descenso del número de pacientes que son ingresados por patología abdominal urgente potencialmente quirúrgica durante el período de epidemia por COVID-19 en nuestro centro. Abstract Introduction: Since the appearance of SARS-CoV-2 in December 2019 in the Chinese city of Wuhan, we have experienced a reduction in admissions in our Service and a decrease in urgent surgical activity. Therefore, this study aimed to assess the incidence of potentially surgical abdominal emergency in our center during the epidemic of COVID-19. Methods: A retrospective study was designed. It included all patients admitted for urgent abdominal pathology with potential surgical treatment in our General and Digestive Surgery Department from February 24, 2020 to April 19, 2020. Results: Eighty-nine patients with a mean age of 58.85±22.2 were included. The median time from symptom onset to the Emergency Department (ED) visit was 48 (P25-P75 = 24-96) hours. On arrival at the ED, 18 (20%) patients presented with systemic inflammatory response syndrome criteria. Fifty-one (57%) surgical procedures were performed. The rate of post-surgical complications at 30 days was 31% and the mortality rate was 2%. Concerning the same period from 2017 to 2019, the mean number of admissions from the ED to our Department decreased by 14% during the epidemic period. Conclusion: There has been a decrease in the number of patients admitted for urgent, potentially surgical, abdominal pathology during the period of the COVID-19 epidemic in our center.


title: Echinacea can help with Azithromycin in prevention of recurrent tonsillitis in children

text: PURPOSE: Recurrent tonsillitis in children is a common disease affecting children quality of life and extends to their families. The aim of this study was to assess the effect of combined use of oral Azithromycin (AZT) plus Echinacea compared to exclusive use of AZT in children with recurrent tonsillitis. MATERIAL AND METHODS: A prospective comparative study including three groups of children with recurrent tonsillitis. Group 1: (100 patients) had no prophylactic treatment. Group 2 (100 patients) received [60 mg/kg] prophylactic dose of AZT divided as (10 mg/kg/day) over 6 consecutive days every month for 6 consecutive months. Group 3 (100 patients) received AZT as in group 2 plus commercially available Echinacea in a dose of 5 ml oral suspension; 3 times daily for 10 consecutive days every month for 6 consecutive months. Number of tonsillitis attacks and severity of tonsillitis symptoms were assessed and compared in different groups. RESULTS: Group 2 and group 3 had significant less number of tonsillitis attacks and severity of assessed symptoms during 6 months of prophylactic treatment with significant better results in group 3 (i.e. AZT plus Echinacea) compared to group 2 (I.e. AZT alone). However; there was no significant difference in patients with any prophylaxis. CONCLUSION: The combined use of Echinacea with Azithromycin produced favorable outcome than Azithromycin alone in pediatric patients with recurrent tonsillitis.


title: The IRIDICA BAC BSI Assay: Rapid, Sensitive and Culture-Independent Identification of Bacteria and Candida in Blood

text: Bloodstream infection (BSI) and sepsis are rising in incidence throughout the developed world. The spread of multi-drug resistant organisms presents increasing challenges to treatment. Surviving BSI is dependent on rapid and accurate identification of causal organisms, and timely application of appropriate antibiotics. Current culture-based methods used to detect and identify agents of BSI are often too slow to impact early therapy and may fail to detect relevant organisms in many positive cases. Existing methods for direct molecular detection of microbial DNA in blood are limited in either sensitivity (likely the result of small sample volumes) or in breadth of coverage, often because the PCR primers and probes used target only a few specific pathogens. There is a clear unmet need for a sensitive molecular assay capable of identifying the diverse bacteria and yeast associated with BSI directly from uncultured whole blood samples. We have developed a method of extracting DNA from larger volumes of whole blood (5 ml per sample), amplifying multiple widely conserved bacterial and fungal genes using a mismatch- and background-tolerant PCR chemistry, and identifying hundreds of diverse organisms from the amplified fragments on the basis of species-specific genetic signatures using electrospray ionization mass spectrometry (PCR/ESI-MS). We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. The assay generated matching results in 80% of culture-positive cases (86% when common contaminants were excluded from the analysis), and twice the total number of positive detections. The described method is capable of providing organism identifications directly from uncultured blood in less than 8 hours. Disclaimer: The IRIDICA BAC BSI Assay is not available in the United States.


title: Chapter 18 Assessment of Medication Dispensing and Extended Community Pharmacy Services

text: Abstract Individuals who visit community pharmacies are regarded as customers rather than patients. The public tends to view community pharmacists as businesspeople. Several factors influence individuals' willingness to patronize and to continue visiting such pharmacies. On the supply side, community pharmacists' responsibilities and duties center on the health and well-being of society. In this chapter, an assessment of community pharmacy practices in developing countries is particularly interesting in terms of medication dispensing and extended pharmacy services that promote public wellness. Community pharmacists in developing countries, who are supposedly strategically positioned in the community to provide public health, are not taking advantage on this opportunity. Although several studies have noted the services provided by community pharmacists, in general, the practice is far from meeting expectations due to several barriers. Pharmacists need to realize their opportunities and potential for success as both professionals and businesspeople.


title: Molecular epidemiology of chicken anaemia virus in sick chickens in China from 2014 to 2015

text: Chicken anaemia virus (CAV), a member of the genus Gyrovirus, is the etiological agent of chicken infectious anaemia. CAV infects bone marrow-derived cells, resulting in severe anaemia and immunosuppression in young chickens and a compromised immune response in older birds. We investigated the molecular epidemiology of CAV in sick chickens in China from 2014 to 2015 and showed that the CAV-positive rate was 13.30%, in which mixed infection (55.56%) was the main type of infection. We isolated and identified 15 new CAV strains using different methods including indirect immunofluorescence assay and Western Blotting. We used overlapping polymerase chain reaction to map the whole genome of the strains. Phylogenetic analyses of the obtained sequences and related sequences available in GenBank generated four distinct groups (A–D). We built phylogenetic trees using predicted viral protein (VP) sequences. Unlike CAV VP2s and VP3s that were well conserved, the diversity of VP1s indicated that the new strains were virulent. Our epidemiological study provided new insights into the prevalence of CAV in clinical settings in recent years in China.


title: Inactivation of hepatitis A HM‐175/18f, reovirus T1 Lang and MS2 during alkaline stabilization of human biosolids

text: Aim: To compare the inactivation rates of male‐specific bacteriophage‐2 (MS2), hepatitis A HM‐175/18f (HM‐175) and reovirus T1 Lang (T1 L) during alkaline stabilization of wastewater residues. Methods and Results: A bench scale alkaline stabilization model was used to evaluate the inactivation of MS2 seeded into raw sludge simultaneously with HM‐175 or T1 L. Stabilization was performed in triplicate at 28 and 4°C for both viral combinations. During stabilization at 28 and 4°C, MS2 and T1 L concentrations were similar at each time point (t = 0·1, 2, 12 and 24 h). MS2 and HM‐175 concentrations were also similar at each time point during stabilization at 28°C. At 4°C, MS2 and HM‐175 concentrations were not similar at the first two time points (t = 0·1 and 2 h), but were similar at later time points (t = 12 and 24 h). Conclusions: The inactivation rates of T1 L at 4°C and both T1 L and HM‐175 at 28°C were similar to the inactivation rate of MS2 at all time points. At 4°C, MS2 was inactivated at a faster rate during the first two time points (t = 0·1 and 2 h) than HM‐175, but was inactivated similarly at later time points (t = 12 and 24 h). Significance and Impact of the Study: Phages, such as MS2, would be ideal indicators for the presence of enteric viruses in wastewater residues because of their ubiquity, nonpathogenic nature, low cost and time associated with their detection. The findings of this study suggest that MS2 could serve as an indicator for monitoring the persistence of enteric viruses, such as HM‐175 and T1 L, during alkaline stabilization performed at moderate temperatures (28°C), but may not serve as an indicator for HM‐175 at reduced temperature (4°C). The utility of MS2 as an indicator of viral persistence during biosolids treatment should be further evaluated, as the increased efficiency and frequency of pathogen monitoring associated with their use may reduce the potential public health risk associated with biosolids, facilitating a greater acceptance for their land application.


Targeting vascular leakage in lung inflammation


title: Prevalence of dental caries and associated factors among primary school children: a population-based cross-sectional study in Riyadh, Saudi Arabia

text: BACKGROUND: Dental caries is a preventable childhood disease, but public health efforts are hampered due to limited information on associated factors in vulnerable populations. Our study was aimed at estimating the prevalence of dental caries and identifying key associated factors in four major risk domains, including socioeconomic factors, child oral health behavior and practices, child feeding practices, and dietary habits among primary school children in Saudi Arabia. METHODS: A cross-sectional study design was used to recruit 578 male Saudi primary school children, aged 6–8 years, from 12 primary schools in five different regions of Riyadh. Children were clinically screened to detect carious lesions in primary teeth according to World Health Organization’s criteria. Structured self-administered questionnaire was used to collect information on social and individual factors from the parents. The odds ratios and 95% confidence intervals of associated factors for dental caries were computed using logistic regression models; key factors were identified by systematic selection process that accounted for multicollinearity and bias correction. RESULTS: Dental caries was prevalent among children (83%, 95% confidence interval 79.7–86.0%). Individual factors, including irregular brushing, late adoption of brushing habit, consulting dentist for symptomatic treatment, lack of breast feeding, sleeping with a bottle in mouth, habit of snacking between meals, low consumption of fruits, and frequent consumption of soft drinks and flavored milk, were predominantly associated with dental caries in children, instead of socioeconomic factors (p < 0.05, adjusted R-square 80%). CONCLUSION: Dental caries were prevalent in school children, and individual factors were predominantly associated with the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12199-018-0750-z) contains supplementary material, which is available to authorized users.


title: Pathogens Causing Respiratory Tract Infections in Children Less Than 5 Years of Age in Senegal

text: INTRODUCTION: While acute respiratory tract infections are the main cause of paediatric mortality and morbidity worldwide, pathogen patterns shift due to factors such as hygiene, vaccinations, and antibiotic resistance. Knowledge about current cause of respiratory infections is lacking, particularly in low- and middle-income countries. The aim of this study was to identity the various respiratory pathogens causing acute respiratory tract infections in children below 5 years of age visiting a sub-urban primary care clinic in Senegal. METHODS: A case-control study was performed in September and October 2018. Oropharyngeal swabs were collected from cases; infants with fever and respiratory symptoms, and controls; children involved in the vaccination programme. Viral identification was conducted by polymerase chain reaction for 21 different viruses; bacteria were identified by culture studies. Associations between microorganisms, acute respiratory infection and severity of disease were calculated by multivariate regression adjusting for confounders such as age, sex, and living area. RESULTS: Overall, 102 cases and 96 controls were included. Microorganisms were detected in 90.1% of cases and 53.7% of controls (P < .001). Influenza virus A (including H1N1), influenza virus B, respiratory syncytial virus (RSV), and Streptococcus pneumoniae were independently associated with acute respiratory tract infections. Co-detection of two or more pathogens was present in 49.5% of cases; 31.7% of cases had a pneumonia and 90.2% was treated with antibiotics. CONCLUSIONS: This case-control study in a primary care setting in sub-Saharan Africa found influenza virus A and B, RSV, and S pneumoniae to be the main causes of acute respiratory tract infections in children below 5 years of age. We recommend evaluation of antibiotics prescription behaviour in this setting.


title: Bending the epidemic curve: advancements and opportunities to reduce the threat of emerging pathogens

text: This invited editorial introduces a special issue of Epidemiology & Infection while also discussing advances in emerging infectious diseases.


title: Metagenomic Nanopore Sequencing of Influenza Virus Direct from Clinical Respiratory Samples

text: Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential for a diagnostic test for influenza virus which also provides insights on transmission, evolution, and drug resistance and simultaneously detects other viruses. We therefore set out to apply the Oxford Nanopore Technologies sequencing method to metagenomic sequencing of respiratory samples. We generated influenza virus reads down to a limit of detection of 10(2) to 10(3) genome copies/ml in pooled samples, observing a strong relationship between the viral titer and the proportion of influenza virus reads (P = 4.7 × 10(−5)). Applying our methods to clinical throat swabs, we generated influenza virus reads for 27/27 samples with mid-to-high viral titers (cycle threshold [C(T)] values, <30) and 6/13 samples with low viral titers (C(T) values, 30 to 40). No false-positive reads were generated from 10 influenza virus-negative samples. Thus, Nanopore sequencing operated with 83% sensitivity (95% confidence interval [CI], 67 to 93%) and 100% specificity (95% CI, 69 to 100%) compared to the current diagnostic standard. Coverage of full-length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza virus titers, we were able to reconstruct >99% complete sequences for all eight gene segments. We also detected a human coronavirus coinfection in one clinical sample. While further optimization is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza virus and other respiratory viruses.


Paediatric aspects of COVID-19: an update


title: Pharmacological plasticity—How do you hit a moving target?

text: Paul Ehrlich's concept of the magic bullet, by which a single drug induces pharmacological effects by interacting with a single receptor has been a strong driving force in pharmacology for a century. It is continually thwarted, though, by the fact that the treated organism is highly dynamic and the target molecule(s) is (are) never static. In this article, we address some of the factors that modify and cause the mobility and plasticity of drug targets and their interactions with ligands and discuss how these can lead to unexpected (lack of) effects of drugs. These factors include genetic, epigenetic, and phenotypic variability, cellular plasticity, chronobiological rhythms, time, age and disease resolution, sex, drug metabolism, and distribution. We emphasize four existing approaches that can be taken, either singly or in combination, to try to minimize effects of pharmacological plasticity. These are firstly, to enhance specificity using target conditions close to those in diseases, secondly, by simultaneously or thirdly, sequentially aiming at multiple targets, and fourthly, in synchronization with concurrent dietary, psychological, training, and biorhythm‐synchronizing procedures to optimize drug therapy.


title: Critical role of cholesterol in bovine herpesvirus type 1 infection of MDBK cells

text: Abstract Cholesterol is involved in the life cycle of many viruses. Here, we examined the role of cholesterol for both viral envelope and target cell membrane for bovine herpesvirus type 1 (BoHV-1) infection. Cholesterol depletion by pretreatment of Madin–Darby bovine kidney (MDBK) cells with a cholesterol-sequestering drug methyl-β-cyclodextrin (MβCD), inhibited the production of BoHV-1 in a dose-dependent manner. This inhibitory effect was partially reversed by cholesterol replenishment, indicating that the reduction was caused by cholesterol depletion. Cholesterol depletion at the post-entry stage only had a mild effect on the virus production. However, cell membrane cholesterol depletion did not reduce the virus attachment. In addition, treatment of BoHV-1 particles with MβCD also reduced the virus infectivity significantly and the effect was partially reversed by addition of exogenous cholesterol. Taken together, these data implicated that cell membrane cholesterol mainly contributed to BoHV-1 entry into MDBK cells and the viral envelope cholesterol was also essential for the virus infectivity.


title: An Unconventional Role for Cytoplasmic Disulfide Bonds in Vaccinia Virus Proteins

text: Previous data have shown that reducing agents disrupt the structure of vaccinia virus (vv). Here, we have analyzed the disulfide bonding of vv proteins in detail. In vv-infected cells cytoplasmically synthesized vv core proteins became disulfide bonded in the newly assembled intracellular mature viruses (IMVs). vv membrane proteins also assembled disulfide bonds, but independent of IMV formation and to a large extent on their cytoplasmic domains. If disulfide bonding was prevented, virus assembly was only partially impaired as shown by electron microscopy as well as a biochemical assay of IMV formation. Under these conditions, however, the membranes around the isolated particles appeared less stable and detached from the underlying core. During the viral infection process the membrane proteins remained disulfide bonded, whereas the core proteins were reduced, concomitant with delivery of the cores into the cytoplasm. Our data show that vv has evolved an unique system for the assembly of cytoplasmic disulfide bonds that are localized both on the exterior and interior parts of the IMV.


title: Analysis and prediction of protective continuous B-cell epitopes on pathogen proteins

text: BACKGROUND: The application of peptide based diagnostics and therapeutics mimicking part of protein antigen is experiencing renewed interest. So far selection and design rationale for such peptides is usually driven by T-cell epitope prediction, available experimental and modelled 3D structure, B-cell epitope predictions such as hydrophilicity plots or experience. If no structure is available the rational selection of peptides for the production of functionally altering or neutralizing antibodies is practically impossible. Specifically if many alternative antigens are available the reduction of required synthesized peptides until one successful candidate is found is of central technical interest. We have investigated the integration of B-cell epitope prediction with the variability of antigen and the conservation of patterns for post-translational modification (PTM) prediction to improve over state of the art in the field. In particular the application of machine-learning methods shows promising results. RESULTS: We find that protein regions leading to the production of functionally altering antibodies are often characterized by a distinct increase in the cumulative sum of three presented parameters. Furthermore the concept to maximize antigenicity, minimize variability and minimize the likelihood of post-translational modification for the identification of relevant sites leads to biologically interesting observations. Primarily, for about 50% of antigen the approach works well with individual area under the ROC curve (AROC) values of at least 0.65. On the other hand a significant portion reveals equivalently low AROC values of < = 0.35 indicating an overall non-Gaussian distribution. While about a third of 57 antigens are seemingly intangible by our approach our results suggest the existence of at least two distinct classes of bioinformatically detectable epitopes which should be predicted separately. As a side effect of our study we present a hand curated dataset for the validation of protectivity classification. Based on this dataset machine-learning methods further improve predictive power to a class separation in an equilibrated dataset of up to 83%. CONCLUSION: We present a computational method to automatically select and rank peptides for the stimulation of potentially protective or otherwise functionally altering antibodies. It can be shown that integration of variability, post-translational modification pattern conservation and B-cell antigenicity improve rational selection over random guessing. Probably more important, we find that for about 50% of antigen the approach works substantially better than for the overall dataset of 57 proteins. Essentially as a side effect our method optimizes for presumably best applicable peptides as they tend to be likely unmodified and as invariable as possible which is answering needs in diagnosis and treatment of pathogen infection. In addition we show the potential for further improvement by the application of machine-learning methods, in particular Random Forests.


title: APN-mediated phosphorylation of BCKDK promotes hepatocellular carcinoma metastasis and proliferation via the ERK signaling pathway

text: Hepatocellular carcinoma (HCC) is one of the most prevalent human malignancies worldwide and has high morbidity and mortality. Elucidating the molecular mechanisms underlying HCC recurrence and metastasis is critical to identify new therapeutic targets. This study aimed to determine the roles of aminopeptidase N (APN, also known as CD13) in HCC proliferation and metastasis and its underlying mechanisms. We detected APN expression in clinical samples and HCC cell lines using immunohistochemistry, flow cytometry, real-time PCR, and enzyme activity assays. The effects of APN on HCC metastasis and proliferation were verified in both in vitro and in vivo models. RNA-seq, phosphoproteomic, western blot, point mutation, co-immunoprecipitation, and proximity ligation assays were performed to reveal the potential mechanisms. We found that APN was frequently upregulated in HCC tumor tissues and high-metastatic cell lines. Knockout of APN inhibited HCC cell metastasis and proliferation in vitro and in vivo. Functional studies suggested that a loss of APN impedes the ERK signaling pathway in HCC cells. Mechanistically, we found that APN might mediate the phosphorylation at serine 31 of BCKDK (BCKDK(S31)), promote BCKDK interacting with ERK1/2 and phosphorylating it, thereby activating the ERK signaling pathway in HCC cells. Collectively, our findings indicate that APN mediates the phosphorylation of BCKDK(S31) and activates its downstream pathway to promote HCC proliferation and metastasis. Therefore, the APN/BCKDK/ERK axis may serve as a new therapeutic target for HCC therapy, and these findings may be helpful to identify new biomarkers in HCC progression.


title: The NIAID Integrated Research Facility at Frederick, Maryland: A unique international resource to facilitate medical countermeasure development for BSL-4 pathogens

text: Scientists at the National Institute of Allergy and Infectious Diseases Integrated Research Facility at Fort Detrick, Frederick, Maryland coordinate and facilitate preclinical research on infectious diseases to develop medical countermeasures for high consequence pathogens. This facility is unique in that it is the only maximum containment laboratory in the world where conventional and molecular medical imaging equipment are incorporated into the design of the facility. This capability provides investigators with unique tools to dissect disease pathogenesis, evaluate the ability of animal models to recapitulate human disease, and test candidate countermeasures. Importantly, advanced molecular imaging has the potential to provide alternative endpoints to lethality. By using these alternative endpoints, investigators can reduce the number of animals used in experiments and evaluate countermeasures in sublethal models. With the incorporation of medical imaging modalities, a clinical laboratory modeled after those existing in hospitals, and a highly trained veterinary medicine team, IRF Frederick is uniquely suited to advance our understanding of emerging infectious diseases and to facilitate the development of medical countermeasures and clinical care paradigms previously considered impossible.


title: The Immediate Impact of COVID-19 on Law Enforcement in the United States

text: During pandemics, like COVID-19, law enforcement agencies are responsible for working with government and public health officials to contain spread, serve the local community, and maintain public order. Given the person-to-person spread of COVID-19 through respiratory droplets, law enforcement officers are also at a heightened risk of exposure due to their close contact with members of the public. To protect officers, the Centers for Disease Control and Prevention (CDC) and other agencies have made numerous recommendations for law enforcement agencies to protect officers and the public. Departments around the country have responded to the pandemic in various ways, such as reassigning personnel to high-traffic areas, suspending training, roll calls, and community outreach initiatives, only issuing citations for low-level crimes, implementing safety precautions for officers, and limiting access to department facilities. The COVID-19 pandemic also has exposed some key obstacles for law enforcement, related to communication, resource management, the enforcement of public health restrictions, and changes to crime and service patterns. Based on these early/initial responses and obstacles during the COVID-19 outbreak, the current paper highlights directions for future responses to pandemics to ensure the safety and security of police officers and the communities they serve.


title: NALT- versus PEYER'S-patch-mediated mucosal immunity

text: Recent studies indicate that the mechanism of nasopharynx-associated lymphoid tissue (NALT) organogenesis is different from that of other lymphoid tissues. NALT has an important role in the induction of mucosal immune responses, including the generation of T helper 1 and T helper 2 cells, and IgA-committed B cells. Moreover, intranasal immunization can lead to the induction of antigen-specific protective immunity in both the mucosal and systemic immune compartments. Therefore, a greater understanding of the differences between NALT and other organized lymphoid tissues, such as Peyer's patches, should facilitate the development of nasal vaccines.


title: Wild-type human coronaviruses prefer cell-surface TMPRSS2 to endosomal cathepsins for cell entry

text: Abstract Human coronaviruses (HCoVs) enter cells via two distinct pathways: the endosomal pathway using cathepsins to activate spike protein and the cell-surface or early endosome pathway using extracellular proteases such as transmembrane protease serine 2 (TMPRSS2). We previously reported that clinical isolates of HCoV-229E preferred cell-surface TMPRSS2 to endosomal cathepsin for cell entry, and that they acquired the ability to use cathepsin L by repeated passage in cultured cells and were then able to enter cells via the endosomal pathway. Here, we show that clinical isolates of HCoV-OC43 and -HKU1 preferred the cell-surface TMRRSS2 to endosomal cathepsins for cell entry, similar to HCoV-229E. In addition, the cell-culture-adapted HCoV-OC43 lost the ability to infect and replicate in air-liquid interface cultures of human bronchial tracheal epithelial cells. These results suggest that circulating HCoVs in the field generally use cell-surface TMPRSS2 for cell entry, not endosomal cathepsins, in human airway epithelial cells.


title: Enhanced protective efficacy of H5 subtype influenza vaccine with modification of the multibasic cleavage site of hemagglutinin in retroviral pseudotypes

text: Traditionally, the multibasic cleavage site (MBCS) of surface protein H5-hemagglutinin (HA) is converted to a monobasic one so as to weaken the virulence of recombinant H5N1 influenza viruses and to produce inactivated and live attenuated vaccines. Whether such modification benefits new candidate vaccines has not been adequately investigated. We previously used retroviral vectors to generate wtH5N1 pseudotypes containing the wild-type HA (wtH5) from A/swine/Anhui/ca/2004 (H5N1) virus. Here, we generated mtH5N1 pseudotypes, which contained a mutant-type HA (mtH5) with a modified monobasic cleavage site. Groups of mice were subcutaneously injected with the two types of influenza pseudotypes. Compared to the group immunized with wtH5N1 pseudotypes, the inoculation of mtH5N1 pseudotypes induced significantly higher levels of HA specific IgG and IFN-γ in immunized mice, and enhanced protection against the challenge of mouse-adapted avian influenza virus A/Chicken/Henan/12/2004 (H5N1). This study suggests modification of the H5-hemagglutinin MBCS in retroviral pseudotypes enhances protection efficacy in mice and this information may be helpful for development of vaccines from mammalian cells to fight against H5N1 influenza viruses.


The next big threat to global health? 2019 novel coronavirus (2019-nCoV): What advice can we give to travellers? – Interim recommendations January 2020, from the Latin-American society for Travel Medicine (SLAMVI)


title: CLINICAL AND MAGNETIC RESONANCE IMAGING FEATURES OF INFLAMMATORY VERSUS NEOPLASTIC MEDIAL RETROPHARYNGEAL LYMPH NODE MASS LESIONS IN DOGS AND CATS

text: Medial retropharyngeal lymph node (MRLN) mass lesions are a common cause of cranial cervical masses in dogs and cats, and are predominantly due to metastatic neoplasia, primary neoplasia, or inflammatory lymphadenitis. The purpose of this retrospective cross‐sectional study was to test the hypothesis that clinical and magnetic resonance imaging (MRI) characteristics for dogs and cats with MRLN mass lesions would differ for inflammatory vs. neoplastic etiologies. Dogs and cats with MRLN mass lesions that had undergone MRI and had a confirmed cytological or histopathological diagnosis were recruited from medical record archives. Clinical findings were recorded by one observer and MRI characteristics were recorded by two other observers who were unaware of clinical findings. A total of 31 patients were sampled, with 15 in the inflammatory lymphadenitis group and 16 in the neoplasia group. Patients with inflammatory lymphadenitis were more likely to be younger and present with lethargy (P = 0.001), pyrexia (P = 0.000), and neck pain (P = 0.006). Patients with inflammatory lymphadenitis were also more likely to have a leukocystosis (P = 0.02) and segmental neutrophilia (P = 0.001). Inflammatory masses were more likely to have moderate or marked MRI perinodal contrast enhancement (P = 0.021) and local muscle contrast enhancement (P = 0.03) whereas the neoplastic masses were more likely to have greater MRI width (P = 0.002) and height (P = 0.009). In conclusion, findings indicated that some clinical and MRI characteristics differed for dogs and cats with inflammatory vs. neoplastic medial retropharyngeal lymph node masses. Although histopathological or cytological diagnosis remains necessary for confirmation, these findings may help with the ranking of differential diagnoses of future cases.


title: Coronavirus disease 2019 (COVID-19) imaging reporting and data system (COVID-RADS) and common lexicon: a proposal based on the imaging data of 37 studies

text: BACKGROUND: In the vast majority of the laboratory-confirmed coronavirus disease 2019 (COVID-19) patients, computed tomography (CT) examinations yield a typical pattern and the sensitivity of this modality has been reported to be 97% in a large-scale study. Structured reporting systems simplify the interpretation and reporting of imaging examinations, serve as a framework for consistent generation of recommendations, and improve the quality of patient care. PURPOSE: To compose a comprehensive lexicon for description of the imaging findings and propose a grading system and structured reporting format for CT findings in COVID-19. MATERIAL AND METHODS: We updated our published systematic review on imaging findings in COVID-19 to include 37 published studies pertaining to diagnostic features of COVID-19 in chest CT. Using the reported imaging findings of 3647 patients, we summarized the typical chest CT findings, atypical features, and temporal changes of COVID-19 in chest CT. Subsequently, we extracted a list of descriptive terms and mapped it to the terminology that is commonly used in imaging literature. RESULTS: We composed a comprehensive lexicon that can be used for documentation and reporting of typical and atypical CT imaging findings in COVID-19 patients. Using the same data, we propose a grading system with five COVID-RADS categories. Each COVID-RADS grade corresponds to a low, moderate, or high level of suspicion for pulmonary involvement of COVID-19. CONCLUSION: The proposed COVID-RADS and common lexicon would improve the communication of findings to other healthcare providers, thus facilitating the diagnosis and management of COVID-19 patients. KEY POINTS: • Chest CT has high sensitivity in diagnosing the coronavirus disease 2019 (COVID-19). • Structured reporting systems simplify the interpretation and reporting of imaging examinations, serve as a framework for consistent generation of recommendations, and improve the quality of patient care. • The proposed COVID-RADS and common lexicon would improve the communication of findings to other healthcare providers, thus facilitating the diagnosis and management of COVID-19 patients.


title: Grippe aviaire : la menace se précise T.T. Hien M. De Jong

text: Unknown


Epidemiological update on SARS-CoV-2 infection in Spain. Comments on the management of infection in pediatrics


title: Characterization of eae + Escherichia coli isolated from healthy and diarrheic calves

text: Abstract Strains of Escherichia coli from 101 healthy and 114 diarrheic calves were screened by PCR for the eae (intimin) gene and Shiga toxin genes (stx). Each eae + and eae/stx + strain was examined for antimicrobial susceptibility, enterohemolysin activity, and the somatic O antigen was determined. An immunoassay was used to detect Shiga toxin antigens for the eae/stx + E. coli. Significantly more (p =0.005) of the healthy calves carried eae + and eae/stx + E. coli in their feces when compared to strains from diarrheic calves. Moreover, Shiga toxin antigens were detected significantly more (p =0.001) often among the eae/stx + strains from healthy calves when compared to eae/stx + strains from diarrheic calves. However, significantly more (p =0.001) of the eae + and eae/stx + strains from diarrheic calves were resistant to at least one of the antimicrobials tested, and the strains from diarrheic calves had a significantly (p =0.05) higher rate of antimicrobial resistance to at least two different antimicrobial classes. No significant difference (p ≥0.05) was detected among the eae + and eae/stx + strains from healthy and diarrheic calves for enterohemolysin production. Serogroups O-negative, O5, O26, and O111 were predominate among both healthy and diarrheic calves.


title: Interferon-induced ISG15 pathway: an ongoing virus–host battle

text: ISG15 is an interferon-induced ubiquitin-like protein that is conjugated to target proteins via the sequential action of three enzymes that are also induced by interferon. Unlike ubiquitin, which is highly conserved, the sequence of ISG15 varies between species. ISG15 conjugation inhibits many viruses, and free (unconjugated) ISG15 can also act as an antiviral protein. Here we focus on the antiviral role of ISG15 conjugation and on countermeasures employed by several viruses. The countermeasure by influenza B virus is unique in that it exhibits species-specificity. Only the antiviral activity of human and non-human primate ISG15s can be blocked, providing one possible explanation for the restriction of influenza B virus to humans.


title: Management of blood supply and demand during the COVID-19 pandemic in King Abdullah Hospital, Bisha, Saudi Arabia

text: Abstract Background Maintaining blood supply is essential since blood transfusions are lifesaving in many conditions. The 2003 infectious outbreak of SARS-CoV had a negative impact on blood supply. This study aimed to measure donor attendance and blood demand in order to help find efficient ways of managing blood supply and demand during the COVID-19 pandemic and similar public emergencies in the future. Materials and methods Data from donor attendance, mobile blood drives and blood inventory records were retrospectively obtained for the period between 1 September 2019 and 1 May 2020 to assess the impact of COVID-19 on donor attendance and the management of blood supply and demand in King Abdullah Hospital, Bisha, Saudi Arabia. Data were analysed using SPSSStatistics, version 25.0. Categorical variables were described using frequencies and percentages. Results After imported cases of COVID-19 were reported in Saudi Arabia, donor attendance and blood supply at blood bank-based collections showed a drop of 39.5%. On the other hand, blood demand during the same period was reduced by 21.7%. Conclusions The COVID-19 pandemic had a negative impact on donor attendance and blood supply and adversely affected blood transfusion services. Guidelines that prioritize blood transfusion should prepare at the beginning of emergencies similar to this pandemic. Close monitoring of blood needs and blood supply and appropriate response is essential for avoiding sudden blood shortage. An evidence-based emergency blood management plan and flexible regulatory policy should be ready to deal with any disaster and to respond quickly in the case of blood shortage.


title: Efficacy and gastrointestinal risk of aspirin used for the treatment of pain and cold

text: Aims To analyse major sources of evidence-based information on the efficacy and gastrointestinal tolerability of aspirin, used short-term, in over-the-counter (OTC) doses, to relieve acute pain and cold symptoms, including associated feverishness. Methods Evidence was largely collected from published meta-analyses and systematic reviews that focused on randomised, controlled, double-blind clinical trials, in which aspirin was compared to placebo and, in some cases also, to active comparators such as OTC doses of paracetamol or ibuprofen. Results Across a large number of comparisons, aspirin was superior to placebo in treating pain, cold or fever. Efficacy was essentially similar to that of comparators used in equivalent doses. There was no serious GI adverse event attributed to ASA in any study, but mild-to-moderate dyspepsia in small percentages of cases was commonly reported. Conclusion OTC aspirin is safe and effective. Safety concerns should not limit brief use to relieve acute pain, cold or fever.


title: Generation of a recombinant avian coronavirus infectious bronchitis virus using transient dominant selection

text: Abstract A reverse genetics system for the avian coronavirus infectious bronchitis virus (IBV) has been described in which a full-length cDNA, corresponding to the IBV (Beaudette-CK) genome, was inserted into the vaccinia virus genome following in vitro assembly of three contiguous cDNAs [Casais, R., Thiel, V., Siddell, S.G., Cavanagh, D., Britton, P., 2001. Reverse genetics system for the avian coronavirus infectious bronchitis virus. J. Virol. 75, 12359–12369]. The method has subsequently been used to generate a recombinant IBV expressing a chimaeric S gene [Casais, R., Dove, B., Cavanagh, D., Britton, P., 2003. Recombinant avian infectious bronchitis virus expressing a heterologous spike gene demonstrates that the spike protein is a determinant of cell tropism. J. Virol. 77, 9084–9089]. Use of vaccinia virus as a vector for the full-length cDNA of the IBV genome has the advantage that modifications can be made to the IBV cDNA using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. We describe the use of homologous recombination as a method for modifying the Beaudette full-length cDNA, within the vaccinia virus genome, without the requirement for in vitro assembly of the IBV cDNA. To demonstrate the feasibility of the method we exchanged the ectodomain of the Beaudette spike gene for the corresponding region from IBV M41 and generated two recombinant infectious bronchitis viruses (rIBVs) expressing the chimaeric S protein, validating the method as an alternative way for generating rIBVs.


title: Rapid Diagnosis of Influenza State of the Art

text: Much effort has been expended developing testing modalities for influenza viruses that are capable of providing rapid results to clinicians. Antigen-detection techniques, historically the only methods able to deliver results quickly, are still widely used despite concerns about sensitivity. Recently, nucleic acid amplification tests (NAATs), which can achieve rapid turnaround times and high sensitivity, have become available. In addition, NAATs can detect other respiratory pathogens. Although there are many theoretical advantages to rapid influenza testing, the clinical impact of testing in various patient populations must be considered against the cost and the analytical performance of the tests.


title: Supporting pandemic response using genomics and bioinformatics: A case study on the emergent SARS‐CoV‐2 outbreak

text: Pre‐clinical responses to fast‐moving infectious disease outbreaks heavily depend on choosing the best isolates for animal models that inform diagnostics, vaccines and treatments. Current approaches are driven by practical considerations (e.g. first available virus isolate) rather than a detailed analysis of the characteristics of the virus strain chosen, which can lead to animal models that are not representative of the circulating or emerging clusters. Here, we suggest a combination of epidemiological, experimental and bioinformatic considerations when choosing virus strains for animal model generation. We discuss the currently chosen SARS‐CoV‐2 strains for international coronavirus disease (COVID‐19) models in the context of their phylogeny as well as in a novel alignment‐free bioinformatic approach. Unlike phylogenetic trees, which focus on individual shared mutations, this new approach assesses genome‐wide co‐developing functionalities and hence offers a more fluid view of the ‘cloud of variances’ that RNA viruses are prone to accumulate. This joint approach concludes that while the current animal models cover the existing viral strains adequately, there is substantial evolutionary activity that is likely not considered by the current models. Based on insights from the non‐discrete alignment‐free approach and experimental observations, we suggest isolates for future animal models.


title: Chapter 3.5 Chemokine Responses in Virus-Induced Neurologic Disease Balancing Host Defense and Neuropathology

text: Publisher Summary This chapter focuses on the chemokine response to viral infection of the central nervous system (CNS) with an emphasis on the functional significance of chemokine expression as it relates to both host defense and neuropathology. Available evidence demonstrates clearly that viral infection of the CNS results in a dramatic increase in chemokine gene expression. Moreover, production of chemokines in response to infection is highly focused within areas of viral replication early in the disease process and areas of viral RNA persistence during the chronic stages of disease. Resident glial cells are capable of generating a robust chemokine response following viral infection in the absence of inflammatory cells suggesting that this response may reflect an innate CNS response against viral infection analogous to the response of phagocytic cells in the periphery. Differences in virus and cellular tropism are likely explanations for the slight differences in chemokine profiles and duration of expression observed in the different models. The non-ELR CXC chemokine CXCL10 is often the predominant chemokine expressed early following viral infection suggesting an important role as a sentinel molecule in initiating neuroinflammation. Based on the studies presented in this chapter, it is clear that targeting chemokines during either acute or chronic viral-induced CNS disease may offer exciting new insights into potentially novel interventional mechanisms in treating human neuroinflammatory diseases.