title: RSV and its propensity for causing bronchiolitis

text: Infants and young children with acute onset of wheezing and reduced respiratory airflows are often diagnosed with obstruction and inflammation of the small bronchiolar airways, i.e., bronchiolitis. The most common eitological agents causing bronchiolitis in young children are the respiratory viruses and of the commonly encountered respiratory viruses, Respiratory Syncytial Virus (RSV) has a propensity for causing bronchiolitis. Indeed, RSV bronchiolitis remains the major reason why previously healthy infants are admitted to hospital. Why RSV infection is such a predominant cause of bronchiolitis is the subject of this review. By reviewing the available histopathology of RSV bronchiolitis both in humans and relevant animal models we identify hallmark features of RSV infection of the distal airways and focus attention on the consequences of columnar cell cytopathology occurring in the bronchioles, which directly impacts the development of bronchiolar obstruction, inflammation and disease.


title: Porcine Epidemic Diarrhea Virus Shedding and Antibody Response in Swine Farms: A Longitudinal Study

text: The porcine epidemic diarrhea virus (PEDV) causes an acute and highly contagious enteric disease characterized by severe enteritis, vomiting, watery diarrhea, and a high mortality rate in seronegative neonatal piglets. In the last few years, PED had a large economic impact on the swine industries in Asia and the US, and in 2014, the PEDV also re-emerged in Europe. Two main PEDV variants circulate worldwide but only the S INDEL variant, considered a mild strain, is spreading in Europe. To gain insights into the pathogenicity of this variant, its viral load and temporal shedding pattern were evaluated in piglets from infected farms. Quantitative real-time PCR (qPCR) targeting the spike gene, was validated according to the minimum information for quantitative real-time PCR experiments guidelines. The qPCR was applied to longitudinal studies conducted in four swine farms naturally infected with the PEDV S INDEL variant. Clinical data, fecal swabs, and blood samples were collected from 103 piglets at 15–30-day intervals for 2–5 months. On all four farms, diarrhea was observed in sows during gestation and in farrowing units, and the mortality rates of piglets were 18, 25, 30, and 35%. Different clinical pictures (0-50% of diarrhea positivity), viral titer levels (mean 5.3-7.2 log(10) genome copies/mL), and antibody conditions (30-80% of positivity) were registered among sows on the four farms. The percentage of qPCR positive piglets varied greatly from the beginning (63–100%) to the end (0%) of the infection course. Clinical signs were present in 96% of the qPCR positive animals. Viral loads ranged from 8.5 log(10) to 4 log(10) genome copies/mL in suckling pigs at 3–6 days of age and were not statistically different among farms, despite the different patterns observed in sows. After 2–3 weeks, only a few piglets still showed detectable viral levels and clinical signs, and they developed antibody responses. Moreover, co-infections with other pathogens and biosecurity procedures limiting the circulation of the virus could have influenced the severity of PED infection. QPCR and clinical data were useful in understanding the dynamics of PEDV infections and, therefore, in implementing appropriate control measures.


title: Novel foods to treat food allergy and gastrointestinal infection

text: The gastrointestinal tract communicates directly with the external environment. Necessary nutrients must be absorbed and commensal bacteria tolerated, and foreign proteins, antigens, and pathogens must be simultaneously excluded or destroyed. Immaturity or disruption of the mucosal immune defenses increases vulnerability to food allergy, intolerance, and infectious disease. Diseases resulting from ingested foreign proteins and organisms are increasing and cause morbidity and mortality worldwide. There is no specific treatment for food allergy other than avoidance. Vaccination for infectious disease is limited by the cost and logistics of distribution and administration, particularly in developing countries. Novel strategies are being explored to modulate the gut mucosal immune system by altering protein expression in food. Crops are being developed to remove deleterious allergens to prevent immunogenic exposure while preserving nutritional quality. Local food plants that express protein fragments of pathogens might provide an effective means to stimulate gut mucosal immunity while increasing vaccine accessibility.


title: Avoiding student infection during a Middle East respiratory syndrome (MERS) outbreak: a single medical school experience

text: PURPOSE: In outbreaks of infectious disease, medical students are easily overlooked in the management of healthcare personnel protection although they serve in clinical clerkships in hospitals. In the early summer of 2015, Middle East respiratory syndrome (MERS) struck South Korea, and students of Sungkyunkwan University School of Medicine (SKKUSOM) were at risk of contracting the disease. The purpose of this report is to share SKKUSOM’s experience against the MERS outbreak and provide suggestions for medical schools to consider in the face of similar challenges. METHODS: Through a process of reflection-on-action, we examined SKKUSOM’s efforts to avoid student infection during the MERS outbreak and derived a few practical guidelines that medical schools can adopt to ensure student safety in outbreaks of infectious disease. RESULTS: The school leadership conducted ongoing risk assessment and developed contingency plans to balance student safety and continuity in medical education. They rearranged the clerkships to another hospital and offered distant lectures and tutorials. Five suggestions are extracted for medical schools to consider in infection outbreaks: instant cessation of clinical clerkships; rational decision making on a school closure; use of information technology; constant communication with hospitals; and open communication with faculty, staff, and students. CONCLUSION: Medical schools need to take the initiative and actively seek countermeasures against student infection. It is essential that medical schools keep constant communication with their index hospitals and the involved personnel. In order to assure student learning, medical schools may consider offering distant education with online technology.


title: Depression as a Mediator of Chronic Fatigue and Post-Traumatic Stress Symptoms in Middle East Respiratory Syndrome Survivors

text: OBJECTIVE: The relationship among chronic fatigue, depressive symptoms, and post-traumatic stress symptoms (PTSSs) among Middle East respiratory syndrome (MERS) survivors is poorly understood. METHODS: Of 148 survivors who consented to be registered and underwent assessments at 12 months (T1) and 18 months (T2) after the MERS outbreak, 72 (48.65%) were evaluated for chronic fatigue, depressive symptoms, and PTSSs based on the Impact of Event ScaleRevised (IES-R), the Patient Health Questionnaire-9 (PHQ-9), and the Fatigue Severity Scale (FSS). Data from 52 subjects, who completed both assessments, were analyzed using a regression-based serial multiple mediation model (PROCESS Model 6). RESULTS: Bootstrap analyses indicated no direct effects of T1 FSS on T2 IES-R but significant positive indirect effects of T1 FSS on T2 IESR through T1 PHQ-9 and T2 PHQ-9 (B=2.1601, SE=1.3268, 95% confidence interval=0.4250–6.1307). In other words, both T1 PHQ-9 and T2 PHQ-9 fully mediated the relationship between T1 FSS and T2 IES. CONCLUSION: Chronic fatigue 12 months after MERS had indirect effects on prolonged PTSSs 18 months after MERS via persisting depression in MERS survivors. This finding supports the need to promote interventional programs for emerging infectious disease survivors with chronic fatigue to reduce depression and prevent prolonged PTSSs.


title: Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study

text: INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. METHODS: Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) users to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study addressed confounding through large-scale propensity score adjustment and negative control experiments. RESULTS: Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 – 1.14), nor any difference for mono/combination use (1.01; 0.90 – 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated a moderately lower risk with ACE, non-significant for monotherapy (0.85; 0.69 – 1.05) and marginally significant for mono/combination users (0.88; 0.79 – 0.99). We observed, however, no significant difference between drug-classes for COVID-19 hospitalization or pneumonia risk across all comparisons. CONCLUSION: There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.


title: Recommended operating room practice during the COVID‐19 pandemic: systematic review

text: BACKGROUND: The COVID‐19 pandemic poses a critical global public health crisis. Operating room (OR) best practice in this crisis is poorly defined. This systematic review was performed to identify contemporary evidence relating to OR practice in the context of COVID‐19. METHODS: MEDLINE was searched systematically using PubMed (search date 19 March 2020) for relevant studies in accordance with PRISMA guidelines. Documented practices and guidance were assessed to determine Oxford Centre for Evidence‐Based Medicine (OCEBM) levels of evidence, and recommendations for practice within five domains were extracted: physical OR, personnel, patient, procedure, and other factors. RESULTS: Thirty‐five articles were identified, of which 11 met eligibility criteria. Nine articles constituted expert opinion and two were retrospective studies. All articles originated from the Far East (China, 9; Singapore, 2); eight of the articles concerned general surgery. Common themes were identified within each domain, but all recommendations were based on low levels of evidence (median OCEBM level 5 (range 4–5)). The highest number of overlapping recommendations related to physical OR (8 articles) and procedural factors (13). Although few recommendations related to personnel factors, consensus was high in this domain, with all studies mandating the use of personal protective equipment. CONCLUSION: There was little evidence to inform this systematic review, but there was consensus regarding many aspects of OR practice. Within the context of a rapidly evolving pandemic, timely amalgamation of global practice and experiences is needed to inform best practice.


title: Efficacy of dried colostrum powders in the prevention of diarrhea in neonatal Holstein calves

text: One hundred and twenty healthy Holstein calves were assigned randomly at birth to one of four groups; each group contained 30 calves and the calves were received as follows: group A, 85 ± 5 g of lyophilized colostrum powder dissolved in 3 kg of whole milk; group B, 85 ± 5 g of spray-dried colostrum powder dissolved in 3 kg of whole milk; group C, 750 ml frozen and thawed colostrum in 3 kg of whole milk, and group D, only 3 kg of whole milk without colostrum supplement. Each group was subdivided into 3 sub-groups of 10 calves as follows: calves fed colostrum supplement at 24 or 48 or 72 h after birth. All calves fed fresh colostrum within 6 h after birth at the amount of 5% of BW by bottle. Calves which were fed lyophilized colostrum supplement had a significant lower incidence of diarrhea in comparison to control calves. In addition, calves were received lyophilized colostrum supplement at 24 h after birth showed less incidence of diarrhea than calves fed the supplement at 48 and 72 h. According to the results of present study providing lyophilized colostrum supplement at 24 h after birth might have been preventive effect on calf diarrhea. The spray-dried colostrum supplement had not the same effect.


title: The intricate interplay between RNA viruses and NF-κB

text: Abstract RNA viruses have rapidly evolving genomes which often allow cross-species transmission and frequently generate new virus variants with altered pathogenic properties. Therefore infections by RNA viruses are a major threat to human health. The infected host cell detects trace amounts of viral RNA and the last years have revealed common principles in the biochemical mechanisms leading to signal amplification that is required for mounting of a powerful antiviral response. Components of the RNA sensing and signaling machinery such as RIG-I-like proteins, MAVS and the inflammasome inducibly form large oligomers or even fibers that exhibit hallmarks of prions. Following a nucleation event triggered by detection of viral RNA, these energetically favorable and irreversible polymerization events trigger signaling cascades leading to the induction of antiviral and inflammatory responses, mediated by interferon and NF-κB pathways. Viruses have evolved sophisticated strategies to manipulate these host cell signaling pathways in order to ensure their replication. We will discuss at the examples of influenza and HTLV-1 viruses how a fascinating diversity of biochemical mechanisms is employed by viral proteins to control the NF-κB pathway at all levels.


title: The Impact of COVID-19 on the Orthopaedic Surgery Residency Application Process

text: Over recent months, coronavirus disease 2019 (COVID-19) has swept the world as a global pandemic, largely changing the practice of medicine because it was previously known. Physician trainees have not been immune to these changes—uncertainty during this time is undeniable for medical students at all levels of training. Of particular importance is the potential impact of COVID-19 on the upcoming residency application process for rising fourth-year students; a further source of added complexity in light of the newly integrated allopathic and osteopathic match in the 2020 to 2021 cycle. Owing to the impact COVID-19 could have on the residency match, insight regarding inevitable alterations to the application process and how medical students can adapt is in high demand. Furthermore, it is very possible that programs will inquire about how applicants spent their time while not in the hospital because of COVID-19, and applicants should be prepared to provide a meaningful answer. Although competitive at a basal level, the complexity of COVID-19 now presents an unforeseen, superimposed development in the quest to match. In this article, we aim to discuss and provide potential strategies for navigating the impact of COVID-19 on the residency application process for orthopaedic surgery.


title: Why does Japan have so few cases of COVID‐19?

text: The COVID‐19 pandemic has spread to many countries around the world, but the infection and death rates vary widely. One country that appeared to have kept the infection under control despite limited societal restrictions is Japan. This commentary explores why Japan may have, up to now, been spared an escalation of the SARS‐CoV‐2 infections.[Image: see text]


title: Hematology and serum biochemistry of free‐ranging and captive Sechuran foxes (Lycalopex sechurae)

text: BACKGROUND: Hematologic and serum biochemical reference values obtained from captive or free‐ranging wildlife populations may not be comparable as there can be significant variations due to preanalytic and analytic differences, including methods of capture and restraint, overall management in captivity including diet and composition of animal groups, and analytic methods being used. Hematology and serum biochemistry have never been studied in captive or free‐ranging populations of Sechuran foxes (Lycalopex sechurae). OBJECTIVES: The purposes of the study were to determine hematologic and serum biochemical RI in Sechuran foxes and to explore differences in these variables related to sex and overall life circumstances. METHODS: Blood samples were obtained from 15 free‐ranging and 15 captive Sechuran foxes. Hematology variables were assessed by blood smear examination and automated analyzer methodology. Serum biochemical analysis was performed by automated analyzer methodology. Descriptive statistics were calculated for each variable. Data obtained from free‐ranging and captive groups were statistically compared and RIs were calculated. RESULTS: Captive Sechuran foxes had significantly (P < .05) higher MCH, MCHC, and eosinophil counts and significantly lower band neutrophil counts than free‐ranging foxes. Free‐ranging Sechuran foxes had significantly (P < .05) higher serum lipase and globulins and significantly lower albumin, total bilirubin, and indirect bilirubin than captive foxes. CONCLUSIONS: These findings suggest that there are hematologic and serum biochemical differences between captive and free‐ranging Sechuran fox populations. Hence, such differences should be considered when using these variables to assess the health status of this species.


title: Acute respiratory failure secondary to eosinophilic pneumonia following influenza vaccination in an elderly man with chronic obstructive pulmonary disease

text: Summary Acute respiratory failure with diffuse pulmonary opacities is an unusual manifestation following influenza vaccination. We report herein a patient with chronic obstructive pulmonary disease who developed fever with worsening of respiratory symptoms and severe hypoxemia requiring ventilatory support shortly after influenza vaccination. Bronchoalveolar lavage was compatible with acute eosinophilic pneumonia. Rapid clinical improvement was observed 2 weeks after systemic corticosteroid treatment, followed by radiographic improvement at 4 weeks. No disease recurrence was observed at the 6-month follow-up.


title: T cell-selective deletion of Oct1 protects animals from autoimmune neuroinflammation while maintaining neurotropic pathogen response

text: BACKGROUND: Treatments for autoimmune diseases aim to dampen autoreactivity while preserving normal immune function. In CD4(+) T cells, the transcription factor Oct1/Pou2f1 is a dispensable transcription factor for T cell development and response to primary infection, but promotes expression of target genes, including Il2 and Ifng, under conditions of antigen reencounter. As a result, they are more strongly expressed upon secondary stimulation. Such repeated antigen encounters occur in memory recall responses, in autoimmunity where self-antigen can be recognized multiple times, and in chronic infection where foreign antigen is persistent. Based on these previous findings, we hypothesized that Oct1 loss would protect animals from autoimmunity but maintain normal responses to pathogens in the CNS. OBJECTIVE: We used a conditional mouse Oct1 (Pou2f1) allele and a CD4-Cre driver to determine the effect of T cell-specific Oct1 loss on autoimmune- and viral-induced neuroinflammation using an autoantigen-driven EAE model of autoimmunity and a JHMV model of viral infection. RESULTS: Oct1 conditional deletion mitigated clinical scores and reduced infiltrating T cells and cytokine production in the EAE model. Consistently, Oct1-deficient CD4(+) T cells stimulated in vitro showed increased expression of markers associated with T cell anergy, particularly in the absence of co-stimulatory signals. In contrast, anti-viral T cell effector functions are intact in the absence of Oct1, with no changes in neuroinflammation, infiltrating T cells or cytokine production. CONCLUSION: Our findings uncover a significant difference between the effect of Oct1 loss on autoimmune and anti-pathogen responses, which potentially could be exploited for therapeutic benefit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1523-3) contains supplementary material, which is available to authorized users.


COVID-19: The importance of multidisciplinary approach


COVID-19, ACE -inhibitors and angiotensin receptor blockers-: The need to differentiate between early infection and acute lung injury


title: Bocavirus infection following paediatric liver transplantation

text: HBoV is an emergent virus, which is frequently detected as a co‐infective agent. However, it can cause disease on its own. It is associated with respiratory and diarrhoeal illness in children and adults, whether immunocompetent or immunocompromised. We report HBoV infection in a child post‐liver transplantation, who presented with persistent fever and mild tachypnea, 3 weeks after a successful transplant. She recovered spontaneously with no graft dysfunction.


title: The challenge of emerging and re-emerging infectious diseases

text: Infectious diseases have for centuries ranked with wars and famine as major challenges to human progress and survival. They remain among the leading causes of death and disability worldwide. Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. Studies of these emerging infections reveal the evolutionary properties of pathogenic microorganisms and the dynamic relationships between microorganisms, their hosts and the environment.


title: ANAKINRA, UNA ALTERNATIVA POTENCIAL EN EL TRATAMIENTO DE LA INFECCIÓN RESPIRATORIA GRAVE POR SARS-CoV-2 REFRACTARIA A TOCILIZUMAB

text: RESUMEN El virus SARS-CoV-2 es un nuevo virus RNA causante de la enfermedad COVID-19, declarada como pandemia por la Organización Mundial de la Salud (OMS). Produce un cuadro de neumonía atípica que puede desembocar en un fallo multiorgánico. La desregulación del sistema inmune secundaria a la infección produce un cuadro similar al síndrome de linfohistiocitosis hemofagocítica (SLHH). Varios estudios han definido la importancia que los inhibidores de la IL-6 (Tocilizumab) tienen en el tratamiento de la infección por SARS-CoV-2, sin embargo, la indicación de tratamiento con inhibidores de IL-1 (anakinra) no se encuentra establecida de forma clara. Presentamos el caso de un paciente de 51 años con neumonía bilateral secundaria a infección por SARS-CoV-2 refractaria al tratamiento antiviral y anti-IL-6 que presentó mejoría clínica y analítica tras el tratamiento con anti-IL-1 (anakinra). ABSTRACT SARS-CoV-2 is a new RNA virus which causes coronavirus disease 2019 (COVID-19), declared a pandemic by the World Health Organization (WHO). It triggers an atypical pneumonia that can progress to multiorgan failure. COVID-19 can cause dysregulation of the immune system, triggering an inflammatory response, and simulate haemophagocytic lymphohistiocytosis. Several studies have proposed that anti-IL-6 receptor antibodies, such as tocilizumab, play an important role in the treatment of severe acute respiratory infection associated with SARS-CoV-2. However, the role of anti-IL-1 receptor antibodies, such as anakinra, in the treatment of COVID-19 has not been established. We present a case report of a 51-year-old man diagnosed with severe respiratory infection associated with SARS-CoV-2 that was refractory to antiviral and anti-IL-6 treatment, with a favourable clinical outcome and analytical improvement after treatment with anti-IL-1 (anakinra).


title: Structure and possible function of a G-quadruplex in the long terminal repeat of the proviral HIV-1 genome

text: The long terminal repeat (LTR) of the proviral human immunodeficiency virus (HIV)-1 genome is integral to virus transcription and host cell infection. The guanine-rich U3 region within the LTR promoter, previously shown to form G-quadruplex structures, represents an attractive target to inhibit HIV transcription and replication. In this work, we report the structure of a biologically relevant G-quadruplex within the LTR promoter region of HIV-1. The guanine-rich sequence designated LTR-IV forms a well-defined structure in physiological cationic solution. The nuclear magnetic resonance (NMR) structure of this sequence reveals a parallel-stranded G-quadruplex containing a single-nucleotide thymine bulge, which participates in a conserved stacking interaction with a neighboring single-nucleotide adenine loop. Transcription analysis in a HIV-1 replication competent cell indicates that the LTR-IV region may act as a modulator of G-quadruplex formation in the LTR promoter. Consequently, the LTR-IV G-quadruplex structure presented within this work could represent a valuable target for the design of HIV therapeutics.


title: Tomographie par émission de positrons (TEP) et bilan du cancer bronchique non à petites cellules : attention aux faux positifs dans les localisations médiastinales 5, 6 et 7 R.J. Cerfolio

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title: Management of Respiratory Disorders and the Pharmacist's Role: Cough, Colds, and Sore Throats and Allergies (Including Eyes)

text: Abstract Complaints pertaining to the upper respiratory tract, such as the common cold and allergies, are a common reason for presentation to community pharmacies. This chapter explores the common cold and influenza and associated symptoms, including cough, congestion, rhinorrhea, sore throat, diarrhea, pain, and fever. This chapter will aid pharmacists in identifying the characteristics and pharmacological and nonpharmacological management of these conditions. Allergies of the nose and eyes are another common ailment encountered in the community pharmacy, and this chapter assists pharmacists in reaching a differential diagnosis and strategies to manage these conditions.


Follow your Gut: Challenges in Nutritional Therapy during the COVID-19 Pandemic


title: In vitro Inhibition of Porcine Hemagglutinating Encephalomyelitis Virus Replication with siRNAs Targeting the Spike Glycoprotein and Replicase Polyprotein Genes

text: OBJECTIVE: The specific effect of RNA interference on the replication of porcine hemagglutinating encephalomyelitis virus (PHE-CoV) was explored. METHODS: Four species of small interfering RNA (siRNA), targeting different regions of the PHE-CoV spike glycoprotein and replicase polyprotein genes, were prepared by in vitro transcription. After transfection of PK-15 cells with each of the siRNAs followed by infection with PHE-CoV, the cytopathic effect (CPE) was examined by phase-contrast microscope, and viral proliferation within cells was examined by indirect immunofluorescence microscopy, hemagglutination (HA) test, TCID(50) assay and real-time RT-PCR. RESULTS: Examination of CPE demonstrated that the four siRNAs were capable of protecting cells against PHE-CoV invasion with very high specificity and efficiency. At 48 h post-infection, only a few siRNA-treated cells were positive for viral antigen staining, whereas most untreated virus-infected cells were positive. Transfection with siRNAs also suppressed the production of infectious virus by up to 18- to 32-fold as assessed by a HA test and 93- to 494-fold as assessed by TCID(50) assay. Furthermore, treatment with siRNAs caused a 53-91% reduction in the viral genome copy number as assessed by real-time RT-PCR. CONCLUSION: These results suggested that the four species of siRNAs can efficiently inhibit PHE-CoV genome replication and infectious virus production.


Glucocorticosteroids as Dengue Therapeutics: Resolving Clinical Observations With a Primary Human Macrophage Model


title: Respiratory tract infections among French Hajj pilgrims from 2014 to 2017

text: Respiratory tract infections (RTIs) are common among Hajj pilgrims, but risk factors for RTIs and respiratory pathogen acquisition during the Hajj are not clearly identified. Based on previous studies, most frequent pathogens acquired by Hajj pilgrims were investigated: rhinovirus, human coronaviruses, influenza viruses, Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Haemophilus influenzae. 485 pilgrims were included. 82.1% presented with RTIs. Respiratory chronic diseases were associated with cough, Influenza-like illness (ILI) and the acquisition of H. influenzae. Vaccination against invasive pneumococcal diseases (IPD) and influenza was associated with a decrease in the acquisition of S. pneumoniae and prevalence of ILI (aRR = 0.53, 95%CI [0.39–0.73] and aRR = 0.69, 95%CI [0.52–0.92] respectively). Individuals carrying rhinovirus and H. influenzae-S. pneumoniae together were respectively twice and five times more likely to have respiratory symptoms. Individual with H. influenzae-K. pneumoniae carriage were twice (p = 0.04) as likely to develop a cough. The use of disposable handkerchiefs was associated with a decrease in the acquisition of S. aureus (aRR = 0.75, 95%CI [0.57–0.97]). Results could be used to identify pilgrims at increased risk of RTIs and acquisition of respiratory pathogens. Results also confirm the effectiveness of influenza and IPD vaccinations in reducing ILI symptoms and acquisition of S. pneumoniae carriage respectively.


title: Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR

text: BACKGROUND: Human papillomaviruses (HPV) are classified into high-risk HPV and low-risk HPV. The most common high-risk HPV types in cervical cancer are HPV 16 and 18, and the most common low-risk types causing genital warts are HPV 6 and HPV 11. In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. METHODS: The specificity, the sensitivity, the detection limit, the reproducibility and the standard curve of this method were examined. Finally, clinical samples that had been tested previously by TaqMan PCR and HPV GenoArray (GA) test were used to verify the accuracy and sensitivity of the method. RESULTS: The assay has a sensitivity of 10(1) to 10(2) copies/test and a linear detection range from 10(1) to 10(8) copies/test. The mean amplification efficiencies for HPV 6, 11, 16, and 18 were 0.97, 1.10, 0.93 and 1.20, respectively, and the mean correlation coefficient (r(2)) of each standard curve was above 0.99 for plasmid templates ranging from 10(3) to 10(7) copies/test. There was 100% agreement between the AllGlo quadruplex quantitative PCR, HPV GA test and TaqMan uniplex qPCR methods. CONCLUSIONS: AllGlo quadruplex quantitative PCR in a single tube has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, and a wide linear range of detection. The convenient single tube format makes this assay a powerful tool for the studies of mixed infections by multiple pathogens, viral typing and viral load quantification.


title: High mortality rate in cancer patients with symptoms of COVID-19 with or without detectable SARS-COV-2 on RT-PCR

text: BACKGROUND: Cancer patients presenting with COVID-19 have a high risk of death. In this work, predictive factors for survival in cancer patients with suspected SARS-COV-2 infection were investigated. METHODS: PRE-COVID-19 is a retrospective study of all 302 cancer patients presenting to this institute with a suspicion of COVID-19 from March 1st to April 25th 2020. Data were collected using a web-based tool within electronic patient record approved by the Institutional Review Board. Patient characteristics symptoms and survival were collected and compared in SARS-COV-2 RT-PCR positive and negative patients. RESULTS: 55 of the 302 (18.2%) patients with suspected COVID-19 had detectable SARS-COV-2 with RT-PCR in nasopharyngeal samples. RT-PCR+ patients were older, had more frequently haematological malignancies, respiratory symptoms and suspected COVID-19 pneumonia of CTscan. However, respectively 38% and 20% of SARS-COV-2 RT-PCR negative patients presented similar respiratory symptoms and CT scan images. Thirty of the 302 (9.9%) patients died during the observation period, including 24 (80%) with advanced disease. At the median follow-up of 25 days after first symptoms, the death rate in RT-PCR+ and RT-PCR-patients were 21% and 10% respectively. In both groups, independent risk factors for death were male gender, KPS<60, cancer in relapse, and respiratory symptoms. Detection of SARS-COV-2 on RT-PCR was not associated with an increased death rate (p=0.10). None of the treatment given in the previous month (including cytotoxics, PD1 Ab, anti-CD20, VEGFR2…) correlated with survival. The survival of RT-PCR positive and negative patients with respiratory symptoms and/or COVID-19 type pneumonia on CTscan was similar with a 18.4% and 19.7% death-rate at day-25. Most (22/30, 73%) cancer patients dying during this period were RT-PCR negative. CONCLUSION: The 30-day death rate of cancer patients with or without documented SARS-COV-2 infection is poor, but the majority of deaths occur in RT-PCR negative patients.


title: The emergence of influenza A H7N9 in human beings 16 years after influenza A H5N1: a tale of two cities

text: Summary Infection with either influenza A H5N1 virus in 1997 or avian influenza A H7N9 virus in 2013 caused severe pneumonia that did not respond to typical or atypical antimicrobial treatment, and resulted in high mortality. Both viruses are reassortants with internal genes derived from avian influenza A H9N2 viruses that circulate in Asian poultry. Both viruses have genetic markers of mammalian adaptation in their haemagglutinin and polymerase PB2 subunits, which enhanced binding to human-type receptors and improved replication in mammals, respectively. Hong Kong (affected by H5N1 in 1997) and Shanghai (affected by H7N9 in 2013) are two rapidly flourishing cosmopolitan megacities that were increasing in human population and poultry consumption before the outbreaks. Both cities are located along the avian migratory route at the Pearl River delta and Yangtze River delta. Whether the widespread use of the H5N1 vaccine in east Asia—with suboptimum biosecurity measures in live poultry markets and farms—predisposed to the emergence of H7N9 or other virus subtypes needs further investigation. Why H7N9 seems to be more readily transmitted from poultry to people than H5N1 is still unclear.


title: The Enigmatic Role of Viruses in Multiple Sclerosis: Molecular Mimicry or Disturbed Immune Surveillance?

text: Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability. A disturbed immune surveillance in MS would explain several experimental findings, and has important implications for prognosis and therapy.


Is the fear of Covid-19 infection the same in all subjects?


title: A memory-efficient algorithm for multiple sequence alignment with constraints

text: Motivation: Recently, the concept of the constrained sequence alignment was proposed to incorporate the knowledge of biologists about structures/functionalities/consensuses of their datasets into sequence alignment such that the user-specified residues/nucleotides are aligned together in the computed alignment. The currently developed programs use the so-called progressive approach to efficiently obtain a constrained alignment of several sequences. However, the kernels of these programs, the dynamic programming algorithms for computing an optimal constrained alignment between two sequences, run in 𝒪(γn(2)) memory, where γ is the number of the constraints and n is the maximum of the lengths of sequences. As a result, such a high memory requirement limits the overall programs to align short sequences~only. Results: We adopt the divide-and-conquer approach to design a memory-efficient algorithm for computing an optimal constrained alignment between two sequences, which greatly reduces the memory requirement of the dynamic programming approaches at the expense of a small constant factor in CPU time. This new algorithm consumes only 𝒪(αn) space, where α is the sum of the lengths of constraints and usually α ≪ n in practical applications. Based on this algorithm, we have developed a memory-efficient tool for multiple sequence alignment with constraints. Availability: http://genome.life.nctu.edu.tw/MUSICME Contact: cllu@mail.nctu.edu.tw


title: The ACE-2 in COVID-19: Foe or Friend?

text: COVID-19 is a rapidly spreading outbreak globally. Emerging evidence demonstrates that older individuals and people with underlying metabolic conditions of diabetes mellitus, hypertension, and hyperlipidemia are at higher risk of morbidity and mortality. The SARS-CoV-2 infects humans through the angiotensin converting enzyme (ACE-2) receptor. The ACE-2 receptor is a part of the dual system renin-angiotensin-system (RAS) consisting of ACE-Ang-II-AT (1) R axis and ACE-2-Ang-(1–7)-Mas axis. In metabolic disorders and with increased age, it is known that there is an upregulation of ACE-Ang-II-AT (1) R axis with a downregulation of ACE-2-Ang-(1–7)-Mas axis. The activated ACE-Ang-II-AT1R axis leads to pro-inflammatory and pro-fibrotic effects in respiratory system, vascular dysfunction, myocardial fibrosis, nephropathy, and insulin secretory defects with increased insulin resistance. On the other hand, the ACE-2-Ang-(1–7)-Mas axis has anti-inflammatory and antifibrotic effects on the respiratory system and anti-inflammatory, antioxidative stress, and protective effects on vascular function, protects against myocardial fibrosis, nephropathy, pancreatitis, and insulin resistance. In effect, the balance between these two axes may determine the prognosis. The already strained ACE-2-Ang-(1–7)-Mas in metabolic disorders is further stressed due to the use of the ACE-2 by the virus for entry, which affects the prognosis in terms of respiratory compromise. Further evidence needs to be gathered on whether modulation of the renin angiotensin system would be advantageous due to upregulation of Mas activation or harmful due to the concomitant ACE-2 receptor upregulation in the acute management of COVID-19.


title: Heated Air Delivery by Micro-Sauna: An Experimental Treatment Prototype Concept for Coronavirus Disease 2019

text: Coronavirus disease 2019 (COVID-19) has gained international attention as it poses a significant threat to global health. Currently, medical researchers are working to exhaust all strategies that may prove beneficial in combating this disease. Heat has been shown to destabilize other coronavirus strains in testing environments, and it has been hypothesized that heated air may destabilize viral pathogens in vivo as well. The present report describes the engineering of a micro-sauna prototype for the delivery of heated air. Concept formulation, process highlights, and the final prototype are all discussed. The prototype can deliver air heated to 80-90 degrees Celsius in a safe and tolerable manner. The goal of this technical report is to further encourage the study of heated air as a potential COVID-19 treatment.


The importance of challenges in COVID-19 screening and testing in the obstetric patient population


title: Transmission patterns of COVID-19 in the mainland of China and the efficacy of different control strategies: a data- and model-driven study

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has seriously endangered the health and lives of Chinese people. In this study, we predicted the COVID-19 epidemic trend and estimated the efficacy of several intervention strategies in the mainland of China. METHODS: According to the COVID-19 epidemic status, we constructed a compartmental model. Based on reported data from the National Health Commission of People’s Republic of China during January 10–February 17, 2020, we estimated the model parameters. We then predicted the epidemic trend and transmission risk of COVID-19. Using a sensitivity analysis method, we estimated the efficacy of several intervention strategies. RESULTS: The cumulative number of confirmed cases in the mainland of China will be 86 763 (95% CI: 86 067–87 460) on May 2, 2020. Up until March 15, 2020, the case fatality rate increased to 6.42% (95% CI: 6.16–6.68%). On February 23, 2020, the existing confirmed cases reached its peak, with 60 890 cases (95% CI: 60 350–61 431). On January 23, 2020, the effective reproduction number was 2.620 (95% CI: 2.567–2.676) and had dropped below 1.0 since February 5, 2020. Due to governmental intervention, the total number of confirmed cases was reduced by 99.85% on May 2, 2020. Had the isolation been relaxed from February 24, 2020, there might have been a second peak of infection. However, relaxing the isolation after March 16, 2020 greatly reduced the number of existing confirmed cases and deaths. The total number of confirmed cases and deaths would increase by 8.72 and 9.44%, respectively, due to a 1-day delayed diagnosis in non-isolated infected patients. Moreover, if the coverage of close contact tracing was increased to 100%, the cumulative number of confirmed cases would be decreased by 88.26% on May 2, 2020. CONCLUSIONS: The quarantine measures adopted by the Chinese government since January 23, 2020 were necessary and effective. Postponing the relaxation of isolation, early diagnosis, patient isolation, broad close-contact tracing, and strict monitoring of infected persons could effectively control the COVID-19 epidemic. April 1, 2020 would be a reasonable date to lift quarantine in Hubei and Wuhan.


title: Successful treatment of Providencia rettgeri cholecystitis and neutrophilic cholangitis in a cat

text: CASE SUMMARY: A 15-year-old male neutered domestic shorthair cat was presented with a recent history of seizures, diarrhoea, lethargy, fever and jaundice. Marked elevation of liver enzyme activity was present and ultrasound examination was suggestive of cholecystitis and hepatitis. Neutrophilic cholangitis was confirmed on histopathology of liver biopsies. Bile culture identified a monomicrobial infection with Providencia rettgeri, which was resistant to multiple antimicrobial agents. The cat was treated with oral pradofloxacin for 4 weeks and remained well 4 months later. RELEVANCE AND NOVEL INFORMATION: Providencia species are rarely reported in the veterinary literature and are an uncommon cause of disease in humans. The significance of this species in humans relates to the high prevalence of antimicrobial resistance. This is the first report of P rettgeri causing clinical illness in a cat and highlights the importance of bile cultures in hepatic disease.


title: A novel delivery platform based on Bacteriophage MS2 virus-like particles

text: Abstract Our objective here is to review the novel delivery platform based on Bacteriophage MS2 virus-like particles (VLPs), including introduction to their structure, their potential as a delivery platform, and their expected use in medicine and other fields. Bacteriophage MS2 VLPs are nanoparticles devoid of viral genetic material and can self-assemble from the coat protein into an icosahedral capsid. As a novel delivery platform, they possess numerous features that make them suitable and attractive for targeted delivery of RNAs or DNAs, epitope peptides, and drugs within the protein capsid. In short, as a novel delivery platform, MS2 VLPs are suitable for delivery of targeted agents and hold promise for use in diagnostics, vaccines, and therapeutic modalities.


The Various Faces of Hyperthyroidism


title: Efficacy and safety of 2-hour urokinase regime in acute pulmonary embolism: a randomized controlled trial

text: BACKGROUNDS: Urokinase (UK) 2 200 U/kg·h for 12 hours infusion(UK-12 h)is an ACCP recommended regimen in treating acute pulmonary embolism (PE). It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected PE patients. METHODS: A randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70), or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated. RESULTS: Similarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found. CONCLUSIONS: The UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE. TRIAL REGISTRATION: Clinical trial registered with http://clinicaltrials.gov/ct2/show/NCT00799968 (Identifier: NCT 00799968)


SARS – A Fast Moving Infectious Disease


A HIGH-VOLUME THORACIC SURGERY DIVISION INTO THE STORM OF THE COVID-19 PANDEMIC


title: CMR in the era of COVID-19: Evaluation of Myocarditis in the Subacute Phase

text: [Figure: see text]


title: Evaluation of a Web-Based Intervention to Promote Hand Hygiene: Exploratory Randomized Controlled Trial

text: BACKGROUND: Hand-washing is regarded as a potentially important behavior for preventing transmission of respiratory infection, particularly during a pandemic. OBJECTIVE: The objective of our study was to evaluate whether a Web-based intervention can encourage more frequent hand-washing in the home, and to examine potential mediators and moderators of outcomes, as a necessary first step before testing effects of the intervention on infection rates in the PRIMIT trial (PRimary care trial of a website based Infection control intervention to Modify Influenza-like illness and respiratory infection Transmission). METHODS: In a parallel-group pragmatic exploratory trial design, 517 nonblinded adults recruited through primary care were automatically randomly assigned to a fully automated intervention comprising 4 sessions of tailored motivational messages and self-regulation support (n = 324) or to a no-intervention control group (n = 179; ratio 2:1). Hand-washing frequency and theory of planned behavior cognitions relating to hand-washing were assessed by online questionnaires at baseline (in only half of the control participants, to permit evaluation of effects of baseline assessment on effect sizes), at 4 weeks (postintervention; all participants), and at 12 weeks. RESULTS: Hand-washing rates in the intervention group were higher at 4 weeks than in the control group (mean 4.40, n = 285 and mean 4.04, n = 157, respectively; P < .001, Cohen d = 0.42) and remained higher at 12 weeks (mean 4.45, n = 282 and mean 4.12, n = 154, respectively; P < .001, Cohen d = 0.34). Hand-washing intentions and positive attitudes toward hand-washing increased more from baseline to 4 weeks in the intervention group than in the control group. Mediation analyses revealed positive indirect effects of the intervention on change in hand-washing via intentions (coefficient = .15, 95% confidence interval [CI], .08–.26) and attitudes (coefficient = 0.16, 95% CI, .09–.26). Moderator analyses confirmed that the intervention was similarly effective for men and women, those of higher and lower socioeconomic status, and those with higher and lower levels of perceived risk. CONCLUSIONS: This study provides promising evidence that Web-based interventions could potentially provide an effective method of promoting hand hygiene in the home. Data were collected during the 2010 influenza pandemic, when participants in both groups had already been exposed to extensive publicity about the need for hand hygiene, suggesting that our intervention could add to existing public health campaigns. However, further research is required to determine the effects of the intervention on actual infection rates. TRIAL: International Standard Randomized Controlled Trial Number (ISRCTN): 75058295; http://www.controlled-trials.com/ISRCTN75058295 (Archived by WebCite at http://www.webcitation.org/62KSbkNmm)


title: The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome

text: BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-γ,TNF-α and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-γ,TNF-α and IL-10 for their associations with SARS. RESULTS: IFN-γ +874A allele was associated with susceptibility to SARS in a dose-dependent manner (P < 0.001). Individuals with IFN-γ +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-α were not associated with SARS susceptibility. CONCLUSION: IFN-γ +874A allele was shown to be a risk factor in SARS susceptibility.


Application of ‘mobile hospital’ against 2019-nCoV in China


Comment on “Are erythema multiforme and urticaria related to a better outcome of COVID 19?”. Eosinophils count in 7 patients with COVID‐19 and urticarial rash.


title: The Another Side of COVID‐19 in Alzheimer’s Disease Patients: Drug‐Drug Interactions

text: Coronavirus Disease 2019 (COVID‐19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a major public health problem. The elderly people are the most affected population by the COVID‐19 outbreak in terms of mortality and morbidity. Delirium caused by hypoxia, a prominent clinical feature of COVID‐19, may increase the need for treatment of Alzheimer's disease (AD) patients (1). Therefore, drug‐drug interactions should be considered in AD patients while receiving COVID‐19 treatment.


title: Synthesis, antiviral activity and cytotoxicity evaluation of Schiff bases of some 2-phenyl quinazoline-4(3)H-ones

text: A new series of 3-(benzylideneamino)-2-phenylquinazoline-4(3H)-ones were prepared through Schiff base formation of 3-amino-2-phenyl quinazoline-4(3)H-one with various substituted carbonyl compounds. Their chemical structures were elucidated by spectral studies. Cytotoxicity and antiviral activity were evaluated against herpes simplex virus-1 (KOS), herpes simplex virus-2 (G), vaccinia virus, vesicular stomatitis virus, herpes simplex virus-1 TK- KOS ACVr, para influenza-3 virus, reovirus-1, Sindbis virus, Coxsackie virus B4, Punta Toro virus, feline corona virus (FIPV), feline herpes virus, respiratory syncytial virus, influenza A H1N1 subtype, influenza A H3N2 subtype, and influenza B virus. Compound 2a showed better antiviral activity against the entire tested virus.


title: Feline Foamy Virus Infection: Characterization of Experimental Infection and Prevalence of Natural Infection in Domestic Cats with and without Chronic Kidney Disease

text: Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood mononuclear cell (PBMC) phenotype, urinary parameters, and histopathology. A persistent infection of primarily lymphoid tropism was detected with no evidence of immunological or hematologic perturbations. One cat with a significant negative correlation between lymphocytes and PBMC proviral load displayed an expanded FFV tissue tropism. Significantly increased blood urea nitrogen and ultrastructural kidney changes were noted in all experimentally infected cats, though chemistry parameters were not outside of normal ranges. Histopathological changes were observed in the brain, large intestine, and other tissues. In order to determine if there is an association of FFV with Chronic Kidney Disease, we additionally screened 125 Australian pet cats with and without CKD for FFV infection and found that FFV is highly prevalent in older cats, particularly in males with CKD, though this difference was not statistically significant compared to controls. Acute FFV infection was clinically silent, and while some measures indicated mild changes, there was no overt association of FFV infection with renal disease.


title: Detection of yellow head virus in shrimp by loop-mediated isothermal amplification (LAMP)

text: Abstract Reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for detecting the structural glycoprotein gene of yellow head virus (YHV). The RT-LAMP assay is a novel method of gene amplification that amplifies nucleic acid with high specificity, sensitivity and rapidity under isothermal conditions with a set of four specially designed primers that recognize six distinct sequences of the target. The whole procedure is very simple and rapid, and reaction time and temperatures were optimized for 60min at 65°C, respectively. Detection of gene amplification could be accomplished by agarose gel electrophoresis. The standardized RT-LAMP procedure was used to detect YHV in the heart and gill from infected shrimp. Thus, the RT-LAMP assay is extremely rapid, cost-effective, sensitive and specific and has potential usefulness for rapid diagnosis for YHV detection in shrimp.


Letter to the Editor: “Embracing Disruptive Change During the SARS-CoV 2 Pandemic”


title: Visualising COVID-19 Pandemic Risk through Network Connectedness

text: Abstract With the domestic and international spread of the COVID-19, much attention has been given to estimating pandemic risk. We propose the use of a novel application of a well-established scientific approach, network analysis, to provide a direct visualisation (the infographics in Figures 1 and 2) of the COVID-19 pandemic risk. By showing visually the degree of connectedness between different regions based on reported confirmed cases of COVID-19, we demonstrate that network analysis provides a relatively simple yet powerful way to estimate the pandemic risk.


Hydroxychloroquine for the Prevention of Covid-19 — Searching for Evidence


title: Antibodies and vaccines against Middle East respiratory syndrome coronavirus

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) has spread through 27 countries and infected more than 2,200 people since its first outbreak in Saudi Arabia in 2012. The high fatality rate (35.4%) of this novel coronavirus and its persistent wide spread infectiousness in animal reservoirs have generated tremendous global public health concern. However, no licensed therapeutic agents or vaccines against MERS-CoV are currently available and only a limited few have entered clinical trials. Among all the potential targets of MERS-CoV, the spike glycoprotein (S) has been the most well-studied due to its critical role in mediating viral entry and in inducing a protective antibody response in infected individuals. The most notable studies include the recent discoveries of monoclonal antibodies and development of candidate vaccines against the S glycoprotein. Structural characterization of MERS-CoV S protein bound with these monoclonal antibodies has provided insights into the mechanisms of humoral immune responses against MERS-CoV infection. The current review aims to highlight these developments and discuss possible hurdles and strategies to translate these discoveries into ultimate medical interventions against MERS-CoV infection.


title: Lack of association between polymorphisms of MASP2 and susceptibility to SARS coronavirus infection

text: BACKGROUND: The pathogenesis of severe acute respiratory disease syndrome (SARS) is not fully understood. One case-control study has reported an association between susceptibility to SARS and mannan-binding lectin (MBL) in China. As the downstream protein of MBL, variants of the MBL-associated serine protease-2 (MASP2) gene may be associated with SARS coronavirus (SARS-CoV) infection in the same population. METHODS: Thirty individuals with SARS were chosen for analysis of MASP2 polymorphisms by means of PCR direct sequencing. Tag single nucleotide polymorphisms (tagSNPs) were chosen using pairwise tagging algorithms. The frequencies of four tag SNPs (rs12711521, rs2261695, rs2273346 and rs7548659) were ascertained in 376 SARS patients and 523 control subjects, using the Beckman SNPstream Ultra High Throughput genotyping platform. RESULTS: There is no significant association between alleles or genotypes of the MASP2 tagSNP and susceptibility to SARS-CoV in both Beijing and Guangzhou populations. Diplotype (rs2273346 and rs12711521)were analyzed for association with susceptibility to SARS, no statistically significant evidence of association was observed. The Beijing and Guangzhou sample groups were homogeneous regarding demographic and genetic parameters, a joined analysis also showed no statistically significant evidence of association. CONCLUSION: Our data do not suggest a role for MASP2 polymorphisms in SARS susceptibility in northern and southern China.


title: Pathologic Features of COVID-19: A Concise Review

text: The novel coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), first appeared in December 2019, in Wuhan, China and evolved into a pandemic. As Angiotensin-Converting Enzyme 2 (ACE2) is one of the potential target receptors for SARS-CoV-2 in human body, which is expressed in different tissues, multiple organs might become affected. In the initial phase of the current pandemic, a handful of post-mortem case-series revealed COVID-19-related pathological changes in various organs. Although pathological examination is not a feasible method of diagnosis, it can elucidate pathological changes, pathogenesis of the disease, and the cause of death in COVID-19 cases. Herein, we thoroughly reviewed multiple organs including lung, gastrointestinal tract, liver, kidney, skin, heart, blood, spleen, lymph nodes, brain, blood vessels, and placenta in terms of COVID-19-related pathological alterations. Also, these findings were compared with SARS and MERS infection, wherever applicable. We found a diverse range of pathological changes, some of which resemble those found in SARS and MERS.


title: Pedestrian-level wind conditions in the space underneath lift-up buildings

text: Abstract Lift-up buildings are advantageous in improving the wind circulation in a congested and compact city. However, the wind conditions in the void underneath a lift-up building, also known as the lift-up area, are vital for wind comfort of occupants of lift-up buildings. This study tested 28 lift-up buildings in a boundary layer wind tunnel to assess the influence of key design parameters; height and width of the main structure, and height, width, depth, and the shape of the central core on the wind conditions in the lift-up area. The results of the analyses show a significant influence of building height on the magnitude of wind speeds in the lift-up area while the width of the central core controls the area with low wind speeds. Tall buildings with short lift-up cores have small areas with acceptable pedestrian wind comfort, which can be increased by adopting corner modifications for the central core. The area of acceptable pedestrian wind comfort increases in oblique wind directions as the areas of high (>3.5 m s−1) and low (<1.5 m s−1) wind speeds are decreased. Finally, a non-linear second-order multivariable regression model is developed to predict pedestrian wind comfort in the lift-up area.


title: A systematic review of the overlap of fluid biomarkers in delirium and advanced cancer-related syndromes

text: BACKGROUND: Delirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer. Understanding of delirium pathophysiology is largely hypothetical, with some evidence for involvement of inflammatory systems, neurotransmitter alterations and glucose metabolism. To date, there has been limited empirical consideration of the distinction between delirium pathophysiology and that of the underlying disease, for example, cancer where these mechanisms are also common in advanced cancer syndromes such as pain and fatigue. This systematic review explores biomarker overlap in delirium, specific advanced cancer-related syndromes and prediction of cancer prognosis. METHODS: A systematic review (PROSPERO CRD42017068662) was conducted, using MEDLINE, PubMed, Embase, CINAHL, CENTRAL and Web of Science, to identify body fluid biomarkers in delirium, cancer prognosis and advanced cancer-related syndromes of interest. Studies were excluded if they reported delirium tremens only; did not measure delirium using a validated tool; the sample had less than 75% of participants with advanced cancer; measured tissue, genetic or animal biomarkers, or were conducted post-mortem. Articles were screened for inclusion independently by two authors, and data extraction and an in-depth quality assessment conducted by one author, and checked by two others. RESULTS: The 151 included studies were conducted in diverse settings in 32 countries between 1985 and 2017, involving 28130 participants with a mean age of 69.3 years. Seventy-one studies investigated delirium biomarkers, and 80 studies investigated biomarkers of an advanced cancer-related syndrome or cancer prognosis. Overall, 41 biomarkers were studied in relation to both delirium and either an advanced cancer-related syndrome or prognosis; and of these, 24 biomarkers were positively associated with either delirium or advanced cancer syndromes/prognosis in at least one study. The quality assessment showed large inconsistency in reporting. CONCLUSION: There is considerable overlap in the biomarkers in delirium and advanced cancer-related syndromes. Improving the design of delirium biomarker studies and considering appropriate comparator/controls will help to better understanding the discrete pathophysiology of delirium in the context of co-existing illness.


title: Global issues related to enteric viral infections

text: Acute viral gastroenteritis is a major health issue worldwide and is associated with high annual mortality, particularly in children of developing countries. Rotaviruses, caliciviruses and astroviruses are the main causes. Accurate diagnoses are possible by recently developed molecular techniques. In many setups, zoonotic transmission is an important epidemiological factor. Treatment consists of rehydration and is otherwise symptomatic. The worldwide introduction of universal rotavirus vaccination of infants has significantly reduced rotavirus disease and mortality.


title: Clinical Characteristics and Outcome in Patients with Combined Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State Associated with COVID-19: A Retrospective, Hospital-Based Observational Case Series

text: AIM: One of the risk factors for poor outcome with SARS-CoV-2 infection is diabetes mellitus; diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the most serious complications of diabetes mellitus. We aimed to explore the clinical characteristics and outcomes of COVID-19 patients presenting with combined DKA/HHS to our institution. METHODS: A retrospective, hospital based observation case series was performed on patients with SARS-CoV-2 admitted to Intensive Care Unit between 3/20/2020 and 4/20/2020. Inclusion criteria were: 1) Blood Glucose >250mg/dL; 2) Serum bicarbonate <18 mmol/L; 3) Anion Gap >10; 4) serum pH <7.3 ; 4) ketonemia or ketonuria; 5) effective/calculated plasma osmolality >304 mOsm/kg. and 6) positive SARS-CoV-2 RT-PCR RESULTS: We reported 6 patients who presented during this period with combined DKA/HHS. Their median age was 50 years, all males, three Hispanic, and three African American. Hispanic patients, had more severe acidosis, and multiple comorbidities, with a higher mortality. The striking feature was that combined DKA/HHS was the initial presentation for COVID-19 for most of the cases. DISCUSSION: Our observational retrospective case series shows that diabetic patients are at risk of developing combined DKA/ HHS associated with COVID-19 and a substantial mortality. To our knowledge, we are first to report the clinical characteristics and outcome in this group of patients.


title: Taking forward the World TB Day 2016 theme ‘Unite to End Tuberculosis’ for the WHO Africa Region

text: Summary Tuberculosis (TB) remains a global emergency, with an estimated 9.6 million new TB cases worldwide reported in 2014. Twenty-eight percent of these cases were in the World Health Organization (WHO) Africa Region, where the annual case detection rate was 281 per 100000 population—more than double the global average of 133 per 100000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive, and the Africa Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480000 had multidrug-resistant TB (MDR-TB). Whilst of the African countries, only South Africa has reported a high prevalence of MDR-TB, it is likely that all of Sub-Saharan Africa has an unreported high load of drug-resistant TB. Tragically, in 2014, only 48% of individuals diagnosed with MDR-TB had successful treatment and an estimated 190000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the Africa Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life-expectancy and demographic profile of many countries in Sub-Saharan Africa. The theme designated for this year's World TB Day, March 24, 2016, is ‘Unite to End TB’. From the Africa Region, there is an urgent need to seriously address the political, economic, and social factors that influence host–Mycobacterium tuberculosis interactions and result in disease. Recent political and funder initiatives that provide renewed hope for the alleviation of Africa's TB and TB/HIV problems are discussed.


title: Factors associated with nosocomial SARS-CoV transmission among healthcare workers in Hanoi, Vietnam, 2003

text: BACKGROUND: In March of 2003, an outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi, initiating a serious and substantial transmission event within the hospital, and subsequent limited spread within the community. METHODS: We surveyed Hospital A personnel for exposure to the index patient and for symptoms of disease during the outbreak. Additionally, serum specimens were collected and assayed for antibody to SARS-associated coronavirus (SARS-CoV) antibody and job-specific attack rates were calculated. A nested case-control analysis was performed to assess risk factors for acquiring SARS-CoV infection. RESULTS: One hundred and fifty-three of 193 (79.3%) clinical and non-clinical staff consented to participate. Excluding job categories with <3 workers, the highest SARS attack rates occurred among nurses who worked in the outpatient and inpatient general wards (57.1, 47.4%, respectively). Nurses assigned to the operating room/intensive care unit, experienced the lowest attack rates (7.1%) among all clinical staff. Serologic evidence of SARS-CoV infection was detected in 4 individuals, including 2 non-clinical workers, who had not previously been identified as SARS cases; none reported having had fever or cough. Entering the index patient's room and having seen (viewed) the patient were the behaviors associated with highest risk for infection by univariate analysis (odds ratios 20.0, 14.0; 95% confidence intervals 4.1–97.1, 3.6–55.3, respectively). CONCLUSION: This study highlights job categories and activities associated with increased risk for SARS-CoV infection and demonstrates that a broad diversity of hospital workers may be vulnerable during an outbreak. These findings may help guide recommendations for the protection of vulnerable occupational groups and may have implications for other respiratory infections such as influenza.


title: DNA single-base mismatch study with an electrochemical enzymatic genosensor

text: A thorough selectivity study of DNA hybridization employing an electrochemical enzymatic genosensor is discussed here. After immobilizing on a gold film a 30-mer 3′-thiolated DNA strand, hybridization with a biotinylated complementary one takes place. Then, alkaline phosphatase is incorporated to the duplex through the interaction streptavidin–biotin. Enzymatic generation of indigo blue from 3-indoxyl phosphate and subsequent electrochemical detection was made. The influence of hybridization conditions was studied in order to better discern between fully complementary and mismatched strands. Detection of 3, 2 and 1 mismatch was possible. The type and location of the single-base mismatch, as well as the influence of the length of the strands was studied too. Mutations that suppose displacement of the reading frame were also considered. The effect of the concentration on the selectivity was tested, resulting a highly selective genosensor with an adequate sensitivity and stability.


title: Influence of Oyster Mushroom Waste on Growth Performance, Immunity and Intestinal Morphology Compared With Antibiotics in Broiler Chickens

text: Oyster mushroom waste (OMW) is a by-product of the agriculture industry with valuable antimicrobial, antioxidant, antifungal, and prebiotic properties. This by-product might be a useful alternative to antibiotic growth stimulators in poultry nutrition. The purpose of this research was to test the impact of OMW on the immune responses and on the morphology of intestine of broiler chickens. Four dietary therapies with five replicas of 15 birds in each, totalling 300 day- Ross 308 broiler chickens, were utilized in this study. Control chickens were fed a mixed diet that included a maize-soybean meal complemented by 1 and 2% OMW in addition to the basal diet. Furthermore, Enramycin (125 g/kg) was added to the control diet as an antibiotic. Throughout this experiment, performance was studied as well as the immune response to the Newcastle Disease Virus (NDV) and intestinal morphological traits. A substantial surge was noted in body weight gain (BWG) and feed intake (FI) of chickens after the addition of 1% OMW (p ≤ 0.05). In contrast, feed supplementation with 2% OMW, compared with the control diet, produced no noteworthy increase in BWG or the feed conversion rate (FCR). Antibiotic addition, on the other hand, increased serum cholesterol (p ≤ 0.05). After 42 days, neither OMW nor antibiotic addition affected organ mass. In contrast, antibiotic addition reduced the small intestine percentage, crypt depth and villus height (p ≤ 0.05). The Newcastle disease vaccine (NDV) antibody titer improved after feed supplementation with 1% OMW comparing with the control and antibiotic diet group. Furthermore, OMW supplementation decreased the heterophil-to-lymphocyte H/L ratio (p ≤ 0.05). The use of OMW led to a reduction in the malondialdehyde (MDA) content of the breast and liver and an increase in glutathione peroxidase. It helped to reduce glutathione, glutathione reductase, and glutathione S-transferase. In conclusion, the impact of OMW were dose-dependent, and the use of 1% OMW in broiler diets enhanced their growth and immunity. Nonetheless, supplementation with 2% OMW produced conflicting results.


title: COVID-19-Related Economic Anxiety Is As High as Health Anxiety: Findings from the USA, the UK, and Israel

text: As the COVID-19 outbreak peaks, millions of individuals are losing their income, and economic anxiety is felt worldwide. In three different countries (the USA, the UK, and Israel: N = 1200), the present study addresses four different sources of anxiety: health-related anxiety, economic-related anxiety, daily routine-change anxiety, and anxiety generated by social isolation. We hypothesized that, economic anxiety would have a similar or greater effect, compared to health anxiety. Results show that in all three countries, the levels of economic and health anxiety were essentially equal, and both surpassed routine-change and isolation anxiety. Although the COVID-19 crisis originated in the health field, this study emphasizes the need to move from a generalized concept of anxiety to specific types of distress, most notably economic anxiety. Economic anxiety results in serious mental and physical health problems and should be attended to by clinical professionals and by policy makers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s41811-020-00078-3) contains supplementary material, which is available to authorized users.


title: Nasopharyngeal microbiota in infants and changes during viral upper respiratory tract infection and acute otitis media

text: BACKGROUND: Interferences between pathogenic bacteria and specific commensals are known. We determined the interactions between nasopharyngeal microbial pathogens and commensals during viral upper respiratory tract infection (URI) and acute otitis media (AOM) in infants. METHODS: We analyzed 971 specimens collected monthly and during URI and AOM episodes from 139 infants. The 16S rRNA V4 gene regions were sequenced on the Illumina MiSeq platform. RESULTS: Among the high abundant genus-level nasopharyngeal microbiota were Moraxella, Haemophilus, and Streptococcus (3 otopathogen genera), Corynebacterium, Dolosigranulum, Staphylococcus, Acinetobacter, Pseudomonas, and Bifidobacterium. Bacterial diversity was lower in culture-positive samples for Streptococcus pneumoniae, and Haemophilus influenzae, compared to cultured-negative samples. URI frequencies were positively associated with increasing trend in otopathogen colonization. AOM frequencies were associated with decreasing trend in Micrococcus colonization. During URI and AOM, there were increases in abundance of otopathogen genera and decreases in Pseudomonas, Myroides, Yersinia, and Sphingomonas. Otopathogen abundance was increased during symptomatic viral infection, but not during asymptomatic infection. The risk for AOM complicating URI was reduced by increased abundance of Staphylococcus and Sphingobium. CONCLUSION: Otopathogen genera played the key roles in URI and AOM occurrences. Staphylococcus counteracts otopathogens thus Staphylococcal colonization may be beneficial, rather than harmful. While Sphingobium may play a role in preventing AOM complicating URI, the commonly used probiotic Bifidobacterium did not play a significant role during URI or AOM. The role of less common commensals in counteracting the deleterious effects of otopathogens requires further studies.


title: Identification of Protein Interaction Partners in Mammalian Cells Using SILAC-immunoprecipitation Quantitative Proteomics

text: Quantitative proteomics combined with immuno-affinity purification, SILAC immunoprecipitation, represent a powerful means for the discovery of novel protein:protein interactions. By allowing the accurate relative quantification of protein abundance in both control and test samples, true interactions may be easily distinguished from experimental contaminants. Low affinity interactions can be preserved through the use of less-stringent buffer conditions and remain readily identifiable. This protocol discusses the labeling of tissue culture cells with stable isotope labeled amino acids, transfection and immunoprecipitation of an affinity tagged protein of interest, followed by the preparation for submission to a mass spectrometry facility. This protocol then discusses how to analyze and interpret the data returned from the mass spectrometer in order to identify cellular partners interacting with a protein of interest. As an example this technique is applied to identify proteins binding to the eukaryotic translation initiation factors: eIF4AI and eIF4AII.


title: Cyclooxygenase activity is important for efficient replication of mouse hepatitis virus at an early stage of infection

text: Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy.


title: A Specialized Few Among Many: Identification of a Novel Lung Epithelial Stem Cell Population

text: Summary The landscape of lung epithelial stem cells is getting more nuanced. In this issue of Cell Stem Cell, Kathiriya et al. (2020) describe a novel distal airway epithelial cell population with high regenerative potential.


title: Ensuring adequate health financing to prevent and control the COVID-19 in Iran

text: On February 19(th) 2020, the Iranian Ministry of Health and Medical Education (MoHME) has announced the first 2 cases of SARS-CoV-2, a novel emerging coronavirus which causes an infection termed as COVID-19, in Qom city. As such, the Iranian government, through the establishment of the “National Headquarters for the management and control of the novel Coronavirus”, has started implementing policies and programs for the prevention and control of the virus. These measures include schools and universities closure, reduced working hours, and increased production and delivery of equipment such as masks, gloves and hygienic materials for sterile environments. The government has also made efforts to divulge high-quality information concerning the COVID-19 and to provide laboratories and hospitals with diagnostic kits and adequate resources to treat patients. However, despite such efforts, the number of cases and deaths has progressively increased with rising trends in total confirmed cases and deaths, as well as in new daily cases and deaths associated with the COVID-19. Iran is a developing country and its economic infrastructure has been hit hardly by embargo and sanctions. While developed countries have allocated appropriate funding and are responding adequately to the COVID-19 pandemics, Iran has experienced a serious surge of cases and deaths and should strive to provide additional resources to the health system to make healthcare services more accessible and to increase the fairness of that access. All relevant actors and stakeholders should work together to fight this disease.


title: A Snapshot of the Global Race for Vaccines Targeting SARS-CoV-2 and the COVID-19 Pandemic

text: A novel coronavirus SARS-CoV-2 causing Coronavirus disease 2019 (COVID-19) has entered the human population and has spread rapidly around the world in the first half of 2020 causing a global pandemic. The virus uses its spike glycoprotein receptor-binding domain to interact with host cell angiotensin-converting enzyme 2 (ACE2) sites to initiate a cascade of events that culminate in severe acute respiratory syndrome in some individuals. In efforts to curtail viral spread, authorities initiated far-reaching lockdowns that have disrupted global economies. The scientific and medical communities are mounting serious efforts to limit this pandemic and subsequent waves of viral spread by developing preventative vaccines and repurposing existing drugs as potential therapies. In this review, we focus on the latest developments in COVID-19 vaccine development, including results of the first Phase I clinical trials and describe a number of the early candidates that are emerging in the field. We seek to provide a balanced coverage of the seven main platforms used in vaccine development that will lead to a desired target product profile for the “ideal” vaccine. Using tales of past vaccine discovery efforts that have taken many years or that have failed, we temper over exuberant enthusiasm with cautious optimism that the global medical community will reach the elusive target to treat COVID-19 and end the pandemic.


title: Drugs to cure avian influenza infection – multiple ways to prevent cell death

text: New treatments and new drugs for avian influenza virus (AIV) infection are developed continually, but there are still high mortality rates. The main reason may be that not all cell death pathways induced by AIV were blocked by the current therapies. In this review, drugs for AIV and associated acute respiratory distress syndrome (ARDS) are summarized. The roles of antioxidant (vitamin C) and multiple immunomodulators (such as Celecoxib, Mesalazine and Eritoran) are discussed. The clinical care of ARDS may result in ischemia reperfusion injury to poorly ventilated alveolar cells. Cyclosporin A should effectively inhibit this kind of damages and, therefore, may be the key drug for the survival of patients with virus-induced ARDS. Treatment with protease inhibitor Ulinastatin could also protect lysosome integrity after the infection. Through these analyses, a large drug combination is proposed, which may hypothetically greatly reduce the mortality rate.


title: A real option analysis for stochastic disease control and vaccine stockpile policy: An application to H1N1 in Korea

text: Abstract Vaccination is mostly used for controlling the diffusion of an infectious disease. This paper attempts to bridge a gap between economic model and epidemiological model to analyze the optimal vaccination strategy when the diffusion of pandemic disease follows a stochastic process. Impulsive vaccination is considered as an effective option to control an infectious disease. A real option model under stochastic Susceptible-Infected-Susceptible (SIS) environment is developed to examine the optimal vaccination threshold when the social costs and benefits of vaccination efforts are considered. A numerical illustration is provided for the case of H1N1 in Korea to show the herd immunity level as a policy rule to suppress epidemic. Policy implications are discussed regarding the vaccine stockpile as a countermeasure to epidemic diffusion.


title: Characterization of the Virus of Sialodacryoadenitis of Rats: A Member of the Coronavirus Group

text: The virus that causes sialodacryoadenitis in rats has been isolated in mice and in primary cultures of rat-kidney cells and has been characterized as a heat-labile RNA virus that is sensitive to lipid solvents and is relatively stable at pH 3.0. This virus is antigenically related to the virus of hepatitis in mice and to coronavirus of rats. The range of hosts of this agent appears to be narrow. On the basis of available biologic characteristics, it has been placed in the coronavirus group.


title: Comparative analysis of viral RNA signatures on different RIG-I-like receptors

text: The RIG-I-like receptors (RLRs) play a major role in sensing RNA virus infection to initiate and modulate antiviral immunity. They interact with particular viral RNAs, most of them being still unknown. To decipher the viral RNA signature on RLRs during viral infection, we tagged RLRs (RIG-I, MDA5, LGP2) and applied tagged protein affinity purification followed by next-generation sequencing (NGS) of associated RNA molecules. Two viruses with negative- and positive-sense RNA genome were used: measles (MV) and chikungunya (CHIKV). NGS analysis revealed that distinct regions of MV genome were specifically recognized by distinct RLRs: RIG-I recognized defective interfering genomes, whereas MDA5 and LGP2 specifically bound MV nucleoprotein-coding region. During CHIKV infection, RIG-I associated specifically to the 3’ untranslated region of viral genome. This study provides the first comparative view of the viral RNA ligands for RIG-I, MDA5 and LGP2 in the presence of infection. DOI: http://dx.doi.org/10.7554/eLife.11275.001


title: Covid-19 pandemic impact on colonoscopy service and suggestions for managing recovery

text: Background and aim As the post-peak phase of the epidemic is approaching, there is an urgent need of an action plan to help resume endoscopy activity. To manage the Covid-19 pandemic-imposed backlog of postponed colonoscopy examinations, an efficient approach is needed. The practice of on-demand sedation with benzodiazepines and/or opiates will allow most patients to complete a water-aided examination with minimal or no sedation. Other methods reported to minimize patient discomfort during colonoscopy can be used, in addition to water-aided techniques. Unsedated or minimally sedated patients who do not require recovery or require a shorter one allow rapid turnaround. The practice obviates the need for assistance with deep sedation from anesthesiologists, who may be in short supply. Trainee education in water-aided colonoscopy has been demonstrated to confer benefits. This review provides some insights into the impact of Covid-19 on endoscopy services, challenges ahead, and possible solutions to help recovery of colonoscopy work and training.


title: Pos Covid-19 And The Portuguese National Eye Care System Challenge

text: Abstract The pandemic of the severe acute respiratory syndrome disease caused by the new coronavirus SARS-CoV-2 (COVID-19), had profound impact in many countries and their health care systems. Regarding Portugal, a suppression strategy with social distancing was adopted, attempting to break the transmission chains, bending the epidemy curve and reducing mortality. These measures seek to prevent an eventual National Health Service over-running, enforcing the suspension of all elective and non-urgent health care. Despite the success in so far, there is a consensus on the need to recover the previous level of health care provision and further enhance it. The Portuguese National Health Service, as a public, universal access, health care system funded by the State proved, in this context, its importance and relevance to the Portuguese population. However, long standing issues, such as the pre pandemic over long waiting lists for hospital ophthalmology attendance, whose determinants are fully identified but still unmet, emerge amplified from this pandemic. The lack of primary eye care in the National Health Service is a significant bottleneck, placing a huge stress on hospital-based care. An exclusive ophthalmologist’s centre care was over-runned before pandemic and will be even more so. The optometrist’s exclusion from differentiated, multisectoral and multidisciplinary eye care teams remains the main hurdle to overcome and insure universal eye care in Portugal. National Health Service highlights the consequences of an overcome model. Universal eye care more than ever demands an evidence-based, integrated approach with primary eye care, in the community, on time and of proximity.


title: BILL E. KUNKLE INTERDISCIPLINARY BEEF SYMPOSIUM: Impact of mineral and vitamin status on beef cattle immune function and health(,)

text: The importance of optimal mineral and vitamin nutrition on improving immune function and health has been recognized in the preceding decades. In the southeast, beef cattle are raised predominantly on forages that may be limiting in nutrients for optimal health, especially trace minerals such as Cu, Zn, and Se. Clinical deficiencies of these nutrients produce classic symptoms that are common to several nutrient deficiencies (e.g., slow growth and unthrifty appearance); however, subclinical deficiencies are more widespread and more difficult to detect, yet may result in broader economic losses. Dietary mineral concentrations often considered adequate for maximum growth, reproductive performance, or optimal immune function have been found to be insufficient at times of physiological stress (weaning, transport, comingling, etc.), when feed intake is reduced. The impacts of these deficiencies on beef cattle health are not apparent until calves have been subjected to these stressors. Health problems that are exacerbated by mineral or vitamin deficiencies include bovine respiratory disease, footrot, retained placenta, metritis, and mastitis. Many micronutrients have antioxidant properties through being components of enzymes and proteins that benefit animal health. In dairy cattle, high levels of supplemental Zn are generally associated with reduced somatic cell counts and improved foot health, possibly reflecting the importance of Zn in maintaining effective epithelial barriers. Neutrophils isolated from ruminants deficient in Cu or Se have reduced ability to kill ingested bacteria in vitro. Supplemental vitamin E, in its role as an intracellular antioxidant has been shown to decrease morbidity in stressed calves. There is more understanding of the important biological role that these nutrients play in the functioning of the complex and multifaceted immune system. However, there is still much to be learned about determining the micronutrient status of herds (and hence when supplementation will be beneficial), requirements for different genetic and environmental conditions, understanding the bioavailability of these nutrients from feedstuffs and forages, quantifying the bioavailability of different supplemental sources of these nutrients, and identifying the impact of dietary antagonists on these nutrients.


title: Astroviruses

text: Astroviruses are positive-sense, single-stranded RNA viruses. Their genomes contain three open reading frames, but the exact number of encoded proteins remains unknown. Astroviruses were originally identified in association with childhood diarrhea; subsequently, they have been identified as a common enteric virus infecting children under the age of 2. Infection is not restricted to humans, however, and host-specific astroviruses have been found in association with a variety of mammalian and avian species. Generally, infection causes a mild, self-limiting gastroenteritis, although infection in chickens and ducklings can result in nephritis or severe hepatitis, respectively. The immune response to astrovirus infection is only poorly characterized and may differ between mammalian and avian species. In this article, the current knowledge of astroviruses is reviewed, including their molecular virology, viral evolution, pathogenesis, and immune response.


title: Animal toxins — Nature’s evolutionary-refined toolkit for basic research and drug discovery

text: Venomous animals have evolved toxins that interfere with specific components of their victim’s core physiological systems, thereby causing biological dysfunction that aids in prey capture, defense against predators, or other roles such as intraspecific competition. Many animal lineages evolved venom systems independently, highlighting the success of this strategy. Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. We provide examples of each of these areas of venom research, highlighting the potential that venom molecules hold for basic research and drug development.


Isolating children is not the answer to COVID‐19


title: Chapter 32 Nidoviruses of Fish and Crustaceans

text: Abstract Viruses with diverse virion architectures demarcated into four families in the order Nidovirales have been discovered in vertebrate mammalian and fish species, as well as in invertebrate crustacean and mosquito species. The order is unified by nidoviruses sharing intermediate (12.7kb) to very long (31.7kb) (+) ssRNA genomes, each possessing a long 5′-terminal gene encoding overlapping ORF1a and ORF1b reading frames that contain a diversity of functionally related enzymes and that are translated in toto using a −1 ribosomal frameshift mechanism, as well as by semiconserved strategies for transcribing a nested set of 3′-coterminal subgenomic mRNAs that translate the viral proteins. The nidovirus that is most important to an aquaculture species is yellow head virus (YHV), which causes disease in shrimp farmed throughout the Eastern Hemisphere and is classified in the genus Okavirus, family Roniviridae. Fathead minnow nidovirus, genus Bafinivirus, subfamily Torovirinae, family Coronaviridae, also causes disease in minnows grown for the baitfish industry in the United States. Virions similar in morphology to okaviruses and bafiniviruses have also been detected in several crab species. Of these, however, only Eriocheir sinensis ronivirus, which causes disease in the Chinese mitten crab, an important freshwater aquaculture species in China, has been shown to possess a ~22kb ssRNA genome that supports its being a nidovirus, but its taxonomic classification awaits genome sequence analysis. This chapter provides an overview of the structure, replication and biology of these viruses with a particular focus on YHV disease characteristics, diagnostic methods and disease prevention strategies.


Les réanimations françaises se mobilisent : un exemple d’organisation régionale contre l’épidémie de COVID-19


title: ESTs analyses of Lampetra japonica liver and comparation transcriptome with the jawed vertebrates

text: A cDNA library was constructed from the liver of Lampetra japonica. 10077 ESTs were obtained by random selecting clones for sequencing. The results demonstrated that 8515 ESTs were assembled into 648 consensus sequences, represented 2210 unique transcripts, 47.06% of which were predicted as full length cDNAs. In addition, 1562 ESTs were singlets. Using the BLAST to align the assembled ESTs, we found that 93.9% (2053) transcripts shared similarity to sequences published in GenBank databases. The functional annotations to assembled ESTs showed that the genes, involved in immunology, blood coagulation and metabolism of jawed vertebrates, were highly expressed in the liver of L. japonica. Furthermore, 8 potential novel genes were identified. Further comparing liver transcriptome of L. japonica with Fundulus heteroclitus, Mus musculus, Bos Taurus, and Homo sapiens revealed that the genes of Chitinase and Polysaccharides metabolism were more highly expressed in L. japonica than the others, which implied that they may play an important role in immunity of L. japonica. In addition, using the TargetScan, we marked microRNA target within 3′ UTR of L. japonica liver transcriptome. The data indicated that some microRNA targets were homology with the targets embeded in human cancer genes. The result seems to provide a useful clue to the treatment of human cancer. Therefore, the present work will be an important resource for investigating the functional genomics and proteomics of L. japonica as well as evolution of vertebrates.


title: Bacterial Artificial Chromosome-Based Lambda Red Recombination with the I-SceI Homing Endonuclease for Genetic Alteration of MERS-CoV

text: Over the past two decades, several coronavirus (CoV) infectious clones have been engineered, allowing for the manipulation of their large viral genomes (~30 kb) using unique reverse genetic systems. These reverse genetic systems include targeted recombination, in vitro ligation, vaccinia virus vectors, and bacterial artificial chromosomes (BACs). Quickly after the identification of Middle East respiratory syndrome-CoV (MERS-CoV), both in vitro ligation and BAC-based reverse genetic technologies were engineered for MERS-CoV to study its basic biological properties, develop live-attenuated vaccines, and test antiviral drugs. Here, I will describe how lambda red recombination can be used with the MERS-CoV BAC to quickly and efficiently introduce virtually any type of genetic modification (point mutations, insertions, deletions) into the MERS-CoV genome and recover recombinant virus.


The association between severe or death COVID-19 and autoimmune disease: a systematic review and meta-analysis


META-ANALYSES ON DOUBLE-BLIND RCTS ADDING DRUGS WITH ANTI-INFLAMMATORY PROPERTIES TO ANTIPSYCHOTIC MEDICATION