title: A rate equation approach to model the denaturation or replication behavior of the SARS coronavirus

text: As a newly emerging virus, little is known about the SARS coronavirus, whose outbreak has brought away several hundred people’s lives over the world in the year of 2003 and is seriously imperiling the human health. Revealing the denaturation and replication mechanisms of SARS coronavirus has great importance for successfully fighting SARS. However, experiments related to SARS coronavirus are extremely dangerous and therefore restricted only to certain specific labs with high safety standard. Clearly, predicting the behaviors of SARS coronavirus in a wide variety of environmental conditions, which are not easily accessible, are thus critically necessary. In this study, we proposed to quantify the survival time of SARS coronavirus either in vitro or in vivo, through introducing thermal rate process models established from the well-known Arrhenius law. The complex physical and chemical behaviors of the SARS coronavirus can then be attributed to its activation energy, frequency factor, damage function as well as the surrounding environmental conditions. Based on the first data on stability and resistance of SARS coronavirus measured by members of WHO laboratory network, the rate coefficients involved in the above equations were estimated for the first time. Predictions on the survival time of SARS coronavirus in different temperature scale were then performed. It was found theoretically that, such survival time falls in an extremely wide range, say from several seconds in high temperature to an almost infinitely long time in a low temperature environment, which has already or is being supported by the currently available tests data. Applications of the present theory to interpret several existing phenomena were presented and their implementations in developing new technical ways for SARS prevention and clinical therapy were discussed. Uncertainties involved in the theoretical models were also analyzed and predicted. Parametric studies were performed to test the effects of the rate coefficients to the survival time of SARS coronavirus. Some important factors, which can significantly vary the denaturation or replication process of SARS coronavirus were pointed out. Through regulating the parameters involved in the equation, certain potential therapies either through drug delivery or engineering approach to treat the SARS disease can possibly be established. Extension of the present model for further studies was also suggested. This study opens a new theoretical way for probing into the complex behaviors of SARS coronavirus. Modellierung der Denaturierung oder Repliziryng von SARS-Korona-Viren Zusammenfassung Der Kenntnisstand über die Eigenschaften des in 2003 neu aufgetretenen SARS Korona Virus, der einige Hundert Menschenleben gekostet hat, ist relativ gering. Die Ermittlung des Denaturierungs- und Replizierungsmechanismuses des SARS Virus ist für seine Bekämpfung von hoher Bedeutung. Experimentelle Untersuchungen an diesem extrem gefährlichen Virus dürfen nur durch Laboratorien mit einem hohen Sicherheitsstandard erfolgen. Die Vorhersage des Verhaltens des SARS Virus in unterschiedlichen Umgebungsbedingungen ist dabei erforderlich. In der vorliegenden Studie wird die überlebensdauer des Virus unter Labor- und realen Bedingungen durch Anwendung der bekannten Arrhenius-Beziehung für temperaturabhängige Vorgänge ermittelt. Das physikalische und chemische Verhalten des SARS Virus wird anhand der zugrundeliegenden Modell- Parameter beschrieben. Basierend auf den ersten Messungen von Mitgliedern des WHO-laboratory-network über die Stabilität und Widerstandsfähigkeit des Virus wurden erstmalig die Geschwindigkeitskoeffizienten des Berechnungsmodells bestimmt. Vorhersagen der Überlebensdauer des SARS-Virus unter unterschiedlichen Temperaturbedingungen wurden ausgeführt. Das sich hieraus ergebende, sehr unterschiedliche Ausmaß der Überlebensfähigkeit in Abhängigkeit der Umgebungstemperatur ist durch den Vergleich mit verfügbaren experimentellen Ergebnissen bestätigt worden. Die Anwendung der vorgestellten Modellierung zur Interpretation realer Phänomene und zur Entwicklung technischer Maßnahmen zur Vorbeugung und klinischen Therapierung von SARS wird diskutiert. Der Einfluß von Unsicherheiten des Modells wird analysiert und abgeschätzt. Parametrische Studien sind durchgeführt worden, um den Einfluß der Geschwindigkeitskoeffizienten auf die Überlebensdauer des SARS Virus darzustellen. Einige wichtige Einflußgrößen auf die Denaturierung und Replikationsfähigkeit des SARS Virus werden aufgezeigt. Durch eine Variation der Modellparameter kann die potentielle Wirksamkeit medikamentöser oder physikalischer Therapien abgeschätzt werden. Erweiterungsmöglichkeiten des vorgestellten Modells werden vorgeschlagen. Die vorliegende Studie ermöglicht neue, theoretische Vorgehensweisen zur Untersuchung des komplexen Verhaltensmusters des SARS Virus.


title: Two cellular proteins that interact with a stem loop in the simian hemorrhagic fever virus 3′(+)NCR RNA

text: Abstract Both full-length and subgenomic negative-strand RNAs are initiated at the 3′ terminus of the positive-strand genomic RNA of the arterivirus, simian hemorrhagic fever virus (SHFV). The SHFV 3′(+) non-coding region (NCR) is 76 nts in length and forms a stem loop (SL) structure that was confirmed by ribonuclease structure probing. Two cell proteins, p56 and p42, bound specifically to a probe consisting of the SHFV 3′(+)NCR RNA. The 3′(+)NCR RNAs of two additional members of the arterivirus genus specifically interacted with two cell proteins of the same size. p56 was identified as polypyrimidine tract-binding protein (PTB) and p42 was identified as fructose bisphosphate aldolase A. PTB binding sites were mapped to a terminal loop and to a bulged region of the SHFV 3′SL structure. Deletion of either of the PTB binding sites in the viral RNA significantly reduced PTB binding activity, suggesting that both sites are required for efficient binding of this protein. Changes in the top portion of the SHFV 3′SL structure eliminated aldolase binding, suggesting that the binding site for this protein is located near the top of the SL. These cell proteins may play roles in regulating the functions of the genomic 3′ NCR.


title: A structural view of coronavirus–receptor interactions

text: Abstract In the coronavirus (CoV), the envelope spike (S) glycoprotein is responsible for CoV cell entry and host-to-host transmission. The S is a multifunctional glycoprotein that mediates both attachment of CoV particles to cell surface receptor molecules as well as membrane penetration by fusion. Receptor-binding domains (RBD) have been identified in the S of diverse CoV; they usually contain antigenic determinants targeted by antibodies that neutralize CoV infections. To penetrate host cells, the CoV can use various cell surface molecules, although they preferentially bind to ectoenzymes. Several crystal structures have determined the folding of CoV RBD and the mode by which they recognize cell entry receptors. Here we review the CoV–receptor complex structures reported to date, and highlight the distinct receptor recognition modes, common features, and key determinants of the binding specificity. Structural studies have established the basis for understanding receptor recognition diversity in CoV, its evolution and the adaptation of this virus family to different hosts. CoV responsible for recent outbreaks have extraordinary potential for cross-species transmission; their RBD bear large platforms specialized in recognition of receptors from different species, which facilitates host-to-host circulation and adaptation to man.


title: Enzima conversiva de la angiotensina 2 y su papel emergente en la regulación del sistema renina-angiotensina

text: El sistema renina-angiotensina-aldosterona (SRAA) es un importante regulador de la función cardiovascular y renal. Su bloqueo mediante los inhibidores de la enzima conversiva de la angiotensina (ECA) y/o los antagonistas del receptor de la angiotensina II se acompaña de una reducción de los valores de presión arterial, reducción del riesgo cardiovascular y enlentecimiento de la progresión de la insuficiencia renal. El descubrimiento de la ECA2, una enzima homóloga de la ECA encargada de la degradación de la angiotensina II a angiotensina 1-7, ofrece una nueva línea de estudio en el SRAA. La presente revision expone la importancia de la ECA2 en diferentes órganos: el corazón, el pulmón y el riñón. A su vez, se detalla la importancia de dicha enzima mediante los diversos estudios realizados en modelos genéticamente manipulados con deleción del gen de la ECA2 y mediante la administración de un inhibidor de la ECA2. Los resultados de dichos estudios apuntan a un papel emergente de la ECA2 como una nueva diana terapéutica del SRAA. The renin-angiotensin system (RAS) plays a key role in the regulation of cardiovascular and renal function. Thus, RAS blockade with an angiotensin- converting enzyme (ACE) and/or angiotensin receptor blocker decreases blood pressure, cardiovascular events, and delays the progression of kidney disease. The discovery of ACE2, a homologue of ACE, capable of degrading angiotensin II to angiotensin 1-7, may offer new insights into the RAS. In this review we discuss the possible protective role of ACE2 in different organs, namely heart, lungs and kidneys. The role of this enzyme is inferred from recent studies performed using genetically manipulated mice that lack the ACE2 gene and also mice treated with pharmacological ACE2 inhibitors. These results suggest that ACE2 might be a new therapeutic target within the RAS.


title: Potential effects of “social” distancing measures and school lockdown on child and adolescent mental health

text: Age-related metabolic and renal changes predispose older people to an increased risk of diabetes mellitus and diabetic kidney disease, respectively. As the prevalence of the ageing population is increasing, because of increased life expectancy, the prevalence of older people with diabetic kidney disease is likely to increase. Diabetic kidney disease is associated with an increased risk of adverse outcomes and increased costs to healthcare systems. The management includes promotion of a healthy lifestyle and control of cardiovascular risk factors such as hyperglycaemia, hypertension and dyslipidaemia. Older people are a heterogeneous group of people from a community-living fit and independent person to a fully dependent individual residing in a care home. Therefore, management in this age group should be based on a patient’s functional level adopting tight metabolic control in the fit individual and relaxed targets in the frail person. However, despite the maximum available therapy, a significant number of patients with diabetic kidney disease still progress to renal failure and experience adverse cardiac outcomes. Therefore, future research is required to explore methods of early detection of diabetic kidney disease and to investigate novel therapeutic interventions to further improve the outcomes.Age-related metabolic and renal changes predispose older people to an increased risk of diabetes mellitus and diabetic kidney disease, respectively. As the prevalence of the ageing population is increasing, because of increased life expectancy, the prevalence of older people with diabetic kidney disease is likely to increase. Diabetic kidney disease is associated with an increased risk of adverse outcomes and increased costs to healthcare systems. The management includes promotion of a healthy lifestyle and control of cardiovascular risk factors such as hyperglycaemia, hypertension and dyslipidaemia. Older people are a heterogeneous group of people from a community-living fit and independent person to a fully dependent individual residing in a care home. Therefore, management in this age group should be based on a patient’s functional level adopting tight metabolic control in the fit individual and relaxed targets in the frail person. However, despite the maximum available therapy, a significant number of patients with diabetic kidney disease still progress to renal failure and experience adverse cardiac outcomes. Therefore, future research is required to explore methods of early detection of diabetic kidney disease and to investigate novel therapeutic interventions to further improve the outcomes.Age-related metabolic and renal changes predispose older people to an increased risk of diabetes mellitus and diabetic kidney disease, respectively. As the prevalence of the ageing population is increasing, because of increased life expectancy, the prevalence of older people with diabetic kidney disease is likely to increase. Diabetic kidney disease is associated with an increased risk of adverse outcomes and increased costs to healthcare systems. The management includes promotion of a healthy lifestyle and control of cardiovascular risk factors such as hyperglycaemia, hypertension and dyslipidaemia. Older people are a heterogeneous group of people from a community-living fit and independent person to a fully dependent individual residing in a care home. Therefore, management in this age group should be based on a patient’s functional level adopting tight metabolic control in the fit individual and relaxed targets in the frail person. However, despite the maximum available therapy, a significant number of patients with diabetic kidney disease still progress to renal failure and experience adverse cardiac outcomes. Therefore, future research is required to explore methods of early detection of diabetic kidney disease and to investigate novel therapeutic interventions to further improve the outcomes.


title: Human Saliva: Non-Invasive Fluid for Detecting Novel Coronavirus (2019-nCoV)

text: The breakthrough of novel coronavirus (2019-nCoV) in Wuhan, a city of China, has damaged the status of health and quality of life. In the sequel of this epidemic or contagious disease, the patient experiences fever, chest paint, chills, a rapid heartbeat, breathing difficulties, pneumonia, and kidney failure. It has been suggested that this disease can spread through human-to-human transmission or by super spreading. By the help of the non-invasive fluid “saliva”, it is easy to detect the virus. This can help with the comfort of the patient as well as healthcare personnel. Under this perspective, we discuss the epidemic situation of 2019-nCOV and its relationship with human saliva.


title: Emerging Viruses: Coming in on a Wrinkled Wing and a Prayer

text: The role that bats have played in the emergence of several new infectious diseases has been under review. Bats have been identified as the reservoir hosts of newly emergent viruses such as Nipah virus, Hendra virus, and severe acute respiratory syndrome–like coronaviruses. This article expands on recent findings about bats and viruses and their relevance to human infections. It briefly reviews the history of chiropteran viruses and discusses their emergence in the context of geography, phylogeny, and ecology. The public health and trade impacts of several outbreaks are also discussed. Finally, we attempt to predict where, when, and why we may see the emergence of new chiropteran viruses.


title: Mathematical Modeling of Viral Zoonoses in Wildlife

text: Zoonoses are a worldwide public health concern, accounting for approximately 75% of human infectious diseases. In addition, zoonoses adversely affect agricultural production and wildlife. We review some mathematical models developed for the study of viral zoonoses in wildlife and identify areas where further modeling efforts are needed.


title: Optimizing Hydroxychloroquine Dosing for Patients With COVID‐19: An Integrative Modeling Approach for Effective Drug Repurposing

text: Hydroxychloroquine (HCQ) is a promising candidate for Coronavirus disease of 2019 (COVID‐19) treatment. The optimal dosing of HCQ is unknown. Our goal was to integrate historic and emerging pharmacological and toxicity data to understand safe and efficacious HCQ dosing strategies for COVID‐19 treatment. The data sources included were (i) longitudinal clinical, pharmacokinetic (PK), and virologic data from patients with severe acute respiratory syndrome‐2 (SARS‐CoV‐2) infection who received HCQ with or without azithromycin (n = 116), (ii) in vitro viral replication data and SARS‐CoV‐2 viral load inhibition by HCQ, (iii) a population PK model of HCQ, and (iv) a model relating chloroquine PKs to corrected QT (QTc) prolongation. A mechanistic PK/virologic/QTc model for HCQ was developed and externally validated to predict SARS‐CoV‐2 rate of viral decline and QTc prolongation. SARS‐CoV‐2 viral decline was associated with HCQ PKs (P < 0.001). The extrapolated patient half‐maximal effective concentration (EC(50)) was 4.7 µM, comparable to the reported in vitro EC(50s). HCQ doses > 400 mg b.i.d. for ≥5 days were predicted to rapidly decrease viral loads, reduce the proportion of patients with detectable SARS‐CoV‐2 infection, and shorten treatment courses, compared with lower dose (≤ 400 mg daily) regimens. However, HCQ doses > 600 mg b.i.d. were also predicted to prolong QTc intervals. This prolongation may have clinical implications warranting further safety assessment. Due to COVID‐19's variable natural history, lower dose HCQ regimens may be indistinguishable from controls. Evaluation of higher HCQ doses is needed to ensure adequate safety and efficacy.


title: 9th Annual Report on the International Status of Engineering Geology—Year 2003–2004. Encompassing hydrogeology, environmental geology and the applied geosciences

text: Abstract The year began with additional evidence that global warming effects were bringing about unusual increases in free precipitation, as rain in greater amounts, but not as snow, in the mid latitudes of Europe and North America, setting new records for flooding. These effects surely will continue to magnify as practical concerns for Engineering Geologists, not the least of which will be slope instability. Worldwide, the profession appeared to be in a truly advanced state, as marked by a new high in indigenous practice, a broad base of authors in this journal, and of cooperation between practitioners of the various nations.


Quelle conduite à tenir pour le suivi des patients glaucomateux en cette période d’épidémie de Covid-19 à virus SARS-CoV-2 ?()()


COVID-19 and Type 1 Diabetes: Challenges and actions


title: Does lockdown reduce air pollution? Evidence from 44 cities in northern China

text: Abstract Responding to the ongoing novel coronavirus (agent of COVID-19) outbreak, China implemented “the largest quarantine in human history” in an attempt to prevent the spread of the virus on 23 January 2020. Human mobility and relevant production and consumption activities have since decreased significantly. As a likely side effect of this decrease, many regions have recorded significant reductions in air pollution. We employed daily air pollution data and Intracity Migration Index (IMI) data form Baidu between 1 January and 21 March 2020 for 44 cities in northern China to examine whether, how, and to what extent travel restrictions affected air quality. On the basis of this quantitative analysis, we reached the following conclusions: (1) The reduction of air pollution was strongly associated with travel restrictions during this pandemic—on average, the air quality index (AQI) decreased by 7.80%, and five air pollutants (i.e., SO2, PM2.5, PM10, NO2, and CO) decreased by 6.76%, 5.93%, 13.66%, 24.67%, and 4.58%, respectively. (2) Mechanism analysis illustrated that the lockdowns of 44 cities reduced human movements by 69.85%, and a reduction in the AQI, PM2.5, and CO was partially mediated by human mobility, and SO2, PM10, and NO2 were completely mediated. (3) Our findings highlight the importance of understanding the role of green production and consumption.


title: Update on childhood and adult infectious tracheitis

text: Abstract The trachea is a pivotal organ of the respiratory tract. Rather than a genuine anatomic border, it acts as a crossroad in all respiratory infectious processes. Even though not strictly limited to the trachea, infections such as laryngotracheitis and tracheobronchitis are frequently diagnosed in children, in particular during the winter season. Infectious tracheitis etiologies are diverse and the distinction between viral and bacterial origins, albeit difficult, remains relevant considering the substantial differences in terms of gravity and therapeutic management. This literature review summarizes the microbiological and clinical aspects of community-acquired and nosocomial tracheitis in adults and children, as well as the adequate diagnostic and therapeutic approaches. It also highlights the emergence of fungal tracheitis in immunocompromised patients, of ventilator-associated tracheitis in intensive care medicine, and beyond all that the potential short and long-term consequences of tracheitis.


title: Packed Red Blood Cell Transfusion as a Potential Treatment Option in COVID-19 Patients With Hypoxemic Respiratory Failure: A Case Report

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), an ongoing pandemic that started as an outbreak in China. The clinical picture varies from asymptomatic or mild cases to critically ill patients. Most of the critically ill patients present with hypoxia due to acute respiratory distress syndrome. These patients have a poor prognosis, especially in people with underlying co-morbidities. We present a case report of a 78-year-old male with multiple co-morbidities initially presenting with cardiac arrest and COVID-19 who showed drastic clinical improvement after he was administered a packed red blood cell transfusion. The patient was initially intubated for acute respiratory failure but was extubated on the second day as the patient’s respiratory status improved. Although this patient had multiple comorbidities, he did extremely well after he received a packed red blood cell transfusion. Recently, there is some evidence showing the effect of the novel coronavirus on hemoglobin levels. Poor clinical outcomes of critically ill patients are most likely due to the impaired gaseous exchange in the lungs in addition to the decreased oxygen-carrying capacity caused by the destruction of red blood cells. Currently, there is limited evidence available in this area and further research may help in developing effective treatment strategies.


title: Generalized reproduction numbers, sensitivity analysis and critical immunity levels of an SEQIJR disease model with immunization and varying total population size

text: Abstract An SEQIJR model of epidemic disease transmission which includes immunization and a varying population size is studied. The model includes immunization of susceptible people (S), quarantine (Q) of exposed people (E), isolation (J) of infectious people (I), a recovered population (R), and variation in population size due to natural births and deaths and deaths of infected people. It is shown analytically that the model has a disease-free equilibrium state which always exists and an endemic equilibrium state which exists if and only if the disease-free state is unstable. A simple formula is obtained for a generalized reproduction number R g where, for any given initial population, R g < 1 means that the initial population is locally asymptotically stable and R g > 1 means that the initial population is unstable. As special cases, simple formulas are given for the basic reproduction number R 0 , a disease-free reproduction number R d f , and an endemic reproduction number R e n . Formulas are derived for the sensitivity indices for variations in model parameters of the disease-free reproduction number R d f and for the infected populations in the endemic equilibrium state. A simple formula in terms of the basic reproduction number R 0 is derived for the critical immunization level required to prevent the spread of disease in an initially disease-free population. Numerical simulations are carried out using the Matlab program for parameters corresponding to the outbreaks of severe acute respiratory syndrome (SARS) in Beijing, Hong Kong, Canada and Singapore in 2002 and 2003. From the sensitivity analyses for these four regions, the parameters are identified that are the most important for preventing the spread of disease in a disease-free population or for reducing infection in an infected population. The results support the importance of isolating infectious individuals in an epidemic and in maintaining a critical level of immunity in a population to prevent a disease from occurring.


title: Pandemically challenged: developing a ward‐based cross‐skilling programme

text: Due to the COVID‐19 pandemic, North Bristol NHS Trust (NBT) doctors were redeployed to unfamiliar clinical teams, where they would work at the level of a fully‐registered Foundation doctor. As undergraduate clinical teaching fellows, we were re‐purposed to rapidly produce a training programme to refresh the medical knowledge of doctors who were from a wide variety of non‐medical specialities and grades. Building on our experience of facilitating medical students, wedevised medical ward‐based scenarios in an informal Objective Structure Clinical Examination (OSCE) style to promote focused active learning and prompt further independent study.


title: Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003

text: BACKGROUND: The SARS coronavirus is the etiologic agent for the epidemic of the Severe Acute Respiratory Syndrome. The recent emergence of this new pathogen, the careful tracing of its transmission patterns, and the ability to propagate in culture allows the exploration of the mutational dynamics of the SARS-CoV in human populations. METHODS: We sequenced complete SARS-CoV genomes taken from primary human tissues (SIN3408, SIN3725V, SIN3765V), cultured isolates (SIN848, SIN846, SIN842, SIN845, SIN847, SIN849, SIN850, SIN852, SIN3408L), and five consecutive Vero cell passages (SIN2774_P1, SIN2774_P2, SIN2774_P3, SIN2774_P4, SIN2774_P5) arising from SIN2774 isolate. These represented individual patient samples, serial in vitro passages in cell culture, and paired human and cell culture isolates. Employing a refined mutation filtering scheme and constant mutation rate model, the mutation rates were estimated and the possible date of emergence was calculated. Phylogenetic analysis was used to uncover molecular relationships between the isolates. RESULTS: Close examination of whole genome sequence of 54 SARS-CoV isolates identified before 14(th )October 2003, including 22 from patients in Singapore, revealed the mutations engendered during human-to-Vero and Vero-to-human transmission as well as in multiple Vero cell passages in order to refine our analysis of human-to-human transmission. Though co-infection by different quasipecies in individual tissue samples is observed, the in vitro mutation rate of the SARS-CoV in Vero cell passage is negligible. The in vivo mutation rate, however, is consistent with estimates of other RNA viruses at approximately 5.7 × 10(-6 )nucleotide substitutions per site per day (0.17 mutations per genome per day), or two mutations per human passage (adjusted R-square = 0.4014). Using the immediate Hotel M contact isolates as roots, we observed that the SARS epidemic has generated four major genetic groups that are geographically associated: two Singapore isolates, one Taiwan isolate, and one North China isolate which appears most closely related to the putative SARS-CoV isolated from a palm civet. Non-synonymous mutations are centered in non-essential ORFs especially in structural and antigenic genes such as the S and M proteins, but these mutations did not distinguish the geographical groupings. However, no non-synonymous mutations were found in the 3CLpro and the polymerase genes. CONCLUSIONS: Our results show that the SARS-CoV is well adapted to growth in culture and did not appear to undergo specific selection in human populations. We further assessed that the putative origin of the SARS epidemic was in late October 2002 which is consistent with a recent estimate using cases from China. The greater sequence divergence in the structural and antigenic proteins and consistent deletions in the 3' – most portion of the viral genome suggest that certain selection pressures are interacting with the functional nature of these validated and putative ORFs.


title: Alpha, Beta, gamma human PapillomaViruses (HPV) detection with a different sets of primers in oropharyngeal swabs, anal and cervical samples

text: BACKGROUND: Recent studies have shown a 13-fold increase of oropharyngeal cancer in the presence of HPV, while α-HPV detection seems to be rare in oral cavity in comparison to anal or cervical district, many novel β and γ types have been isolated in this anatomical site suggesting a wide tropism range. Currently, there are no guidelines recommending HPV oral cavity screening as a mandatory test, and it remains unknown which HPV types should be included in HPV screening programs. Our goal was to assess HPV prevalence in oropharyngeal, anal, and cervical swabs using different sets of primers,which are able to amplify α, β, γ HPV types. METHODS: We analysed the presence of HPV DNA in oropharyngeal (n = 124), anal (n = 186), cervical specimens (n = 43) from HIV positive and negative patients using FAP59/64 and MY09/11 primers. All untyped strains were genetically characterized through PCR amplification and direct sequencing of partial L1 region, and the resulting sequences were classified through phylogenetic analysis. RESULTS: HPV prevalence was 20.9% in 124 oropharyngeal swab samples, including infections with multiple HPV types (5.6%). HPV prevalence in this anatomical site was significantly associated with serostatus: 63.3%in HIV positive and 36.3% in HIV negative patients (p < 0.05). Unclassified types were detected in 6 specimens. In our analysis, we did not observe any difference in HPV (α, β, γ) prevalence between men and women. Overall, β species were the most frequently detected 69.7%. When using anal swabs, for HIV positive patients, β genus prevalence was 1% and γ genus was 3.7% including 6 unclassified types. In cervical samples from 43 HIV positive women (18 HPV negative and 25 positive by MY09/11 PCR), only one sample was positivite for β(1) species (2.4%) using FAP primers. Six of the untyped strains clustered with sequences from species 7, 9, 10, 8,12 of γ genus. Four sequences remained unclassified. Finally, β and γ HPV prevalence was significantly lower than their respective HPV prevalence as identified by the Luminex system in all anatomical sites that were analyzed in previous studies. CONCLUSION: This study provides new information about viral isolates present in oropharyngeal site and it will contribute to improve the monitoring of HPV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1132-x) contains supplementary material, which is available to authorized users.


title: COVID-19: How prepared are front line healthcare workers in England?

text: Summary National efforts are underway to prepare our health service for the pandemic of COVID-19; however, the efficacy of these interventions is unknown. In view of this, we carried out a cross-sectional survey of front line healthcare workers (HCW) at two large acute NHS hospital Trusts in England, to assess their confidence and perceived level of preparedness for the virus. We demonstrate that there has been moderate success in readying HCW to manage COVID-19, but that more still needs to be done, particularly in relation to educating HCW about the laboratory diagnostics.


title: Inhibition of Viruses by RNA Interference

text: RNA-mediated interference (RNAi) is a recently discovered process by which dsRNA is able to silence specific gene functions. Although initially described in plants, nematodes and Drosophila, the process is currently considered to be an evolutionarily conserved process that is present in the entire eukaryotic kingdom in which its original function was as a defense mechanism against viruses and foreign nucleic acids. Similarly to the silencing of genes by RNAi, viral functions can be also silenced by the same mechanism, through the introduction of specific dsRNA molecules into cells, where they are targeted to essential genes or directly to the viral genome in case RNA viruses, thus arresting viral replication. Since the pioneering work of Elbashir and coworkers, who identified RNAi activity in mammalian cells, many publications have described the inhibition of viruses belonging to most if not all viral families, by targeting and silencing diverse viral genes as well as cell genes that are essential for virus replication. Moreover, virus expression vectors were developed and used as vehicles with which to deliver siRNAs into cells. This review will describe the use of RNAi to inhibit virus replication directly, as well as through the silencing of the appropriate cell functions.


title: Isolation of influenza viruses in MDCK 33016PF cells and clearance of contaminating respiratory viruses

text: This paper summarizes results obtained by multiplex PCR screening of human clinical samples for respiratory viruses and corresponding data obtained after passaging of virus-positive samples in MDCK 33016PF cells. Using the ResPlexII v2.0 (Qiagen) multiplex PCR, 393 positive results were obtained in 468 clinical samples collected during an influenza season in Germany. The overall distribution of positive results was influenza A 42.0%, influenza B 38.7%, adenovirus 1.5%, bocavirus 0.5%, coronavirus 3.3%, enterovirus 5.6%, metapneumovirus 1.0%, parainfluenza virus 0.8%, rhinovirus 4.1%, and respiratory syncytial virus (RSV) 2.5%. Double infections of influenza virus together with another virus were found for adenovirus B and E, bocavirus, coronavirus, enterovirus and for rhinovirus. These other viruses were rapidly lost upon passages in MDCK 33016PF cells and under conditions as applied to influenza virus passaging. Clinical samples, in which no influenza virus but other viruses were found, were also subject to passages in MDCK 33016PF cells. Using lower inoculum dilutions than those normally applied for preparations containing influenza virus (total dilution of the original sample of ∼10(4)), the positive results for the different viruses turned negative already after 2 or 3 passages in MDCK 33016PF cells. These results demonstrate that, under practical conditions as applied to grow influenza viruses, contaminating viruses can be effectively removed by passages in MDCK cells. In combination with their superior isolation efficiency, MDCK cells appear highly suitable to be used as an alternative to embryonated eggs to isolate and propagate influenza vaccine candidate viruses.


title: Artificial intelligence and the future of global health

text: Concurrent advances in information technology infrastructure and mobile computing power in many low and middle-income countries (LMICs) have raised hopes that artificial intelligence (AI) might help to address challenges unique to the field of global health and accelerate achievement of the health-related sustainable development goals. A series of fundamental questions have been raised about AI-driven health interventions, and whether the tools, methods, and protections traditionally used to make ethical and evidence-based decisions about new technologies can be applied to AI. Deployment of AI has already begun for a broad range of health issues common to LMICs, with interventions focused primarily on communicable diseases, including tuberculosis and malaria. Types of AI vary, but most use some form of machine learning or signal processing. Several types of machine learning methods are frequently used together, as is machine learning with other approaches, most often signal processing. AI-driven health interventions fit into four categories relevant to global health researchers: (1) diagnosis, (2) patient morbidity or mortality risk assessment, (3) disease outbreak prediction and surveillance, and (4) health policy and planning. However, much of the AI-driven intervention research in global health does not describe ethical, regulatory, or practical considerations required for widespread use or deployment at scale. Despite the field remaining nascent, AI-driven health interventions could lead to improved health outcomes in LMICs. Although some challenges of developing and deploying these interventions might not be unique to these settings, the global health community will need to work quickly to establish guidelines for development, testing, and use, and develop a user-driven research agenda to facilitate equitable and ethical use.


title: Rapid systematic review of neonatal COVID-19 including a case of presumed vertical transmission

text: OBJECTIVE: To carry out a systematic review of the available studies on COVID-19 (coronavirus disease 2019) in neonates seen globally since the onset of the COVID-19 global pandemic in 2020. The paper also describes a premature baby with reverse transcription (RT)-PCR-positive COVID-19 seen at the Blackpool Teaching Hospitals NHS Foundation Trust, UK. DESIGN: We conducted a multifaceted search of the Cumulative Index to Nursing and Allied Health Literature, Embase, Medline and PubMed from 1 December 2019 to 12 May 2020 to harvest articles from medical journals and publications reporting cases of COVID-19 in neonates from anywhere in the world. Additional searches were also done so as not to miss any important publications. Write-up was in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the protocol for the review was registered with International Prospective Register of Systematic Reviews (PROSPERO), and risk of bias was analysed with the Newcastle-Ottawa tool. Additionally, the preterm neonate with COVID-19 from our hospital is also reported. RESULTS: The systematic review has revealed eight studies where neonates have been described to have confirmed COVID-19, with low risk of bias. Of the 10 reported cases elsewhere, only three are likely to be vertically transmitted, while seven occurred in the postperinatal period and are likely to have been postnatally acquired. All neonates had a mild course, recovered fully and were negative on retesting. Our case of COVID-19 in a 32-week premature baby from the UK was delivered by emergency caesarean section, with the mother wearing a face mask and the family having no contact with the neonate, suggesting vertical transmission. On day 33, the neonate was asymptomatic but was still RT-PCR-positive on nasopharyngeal airway swab. CONCLUSIONS: Neonatal infection is uncommon, with only two previously reported cases likely to be of vertical transmission. The case we report is still RT-PCR-positive on day 28 and is asymptomatic. Ongoing research is needed to ascertain the epidemiology of COVID-19 in neonates.


title: Population Behavior Patterns in Response to the Risk of Influenza A(H7N9) in Hong Kong, December 2013–February 2014

text: BACKGROUND: A novel avian influenza A(H7N9) virus, first identified in Mainland China in February and March 2013, caused an outbreak in humans in April and May, 2013. Closure of live poultry markets in some affected cities dramatically reduced numbers of cases during summer of 2013, but the epidemic resurged during the winter 2013–14, increasing reported cases to 393 in Mainland China as of 30 March 2014. PURPOSE: The study aimed to explore population behavior patterns responding to an epidemic of influenza A(H7N9) virus. METHOD: Three cross-sectional surveys were conducted among 1000, 680, and 1011 respondents in December 2013, January 2014, and February 2014, with response rates of 68.0, 64.4, and 66.6 %, respectively, in Hong Kong. Adults were recruited and interviewed using random digit-dialing telephone survey. Latent class analysis was employed to explore heterogeneity in protective behavior patterns across the three surveys. Multinomial regression models were developed to determine factors associated with latent class membership. RESULTS: Three comparable latent classes were identified across the three surveys: Moderate hygiene compliance (Class 1), High hygiene compliance (Class 2), and Vigilance (Class 3). The prevalence of Class 1 was 48–52 % across the three surveys while Class 3 prevalence increased significantly from 13 % in the Dec-2013 survey to 20 % in the Feb-2014 survey. Compared with Class 1, Class 3 were more likely to be female, older, better educated, married, perceive higher susceptibility to H7N9, attribute greater severity to H7N9, report higher current worry, and anticipated worry about H7N9 infection. CONCLUSION: The three classes reflect different levels of adoption of protection and thereby may have different levels of vulnerability toward contracting H7N9 infection. It appears that as the epidemic intensifies, Class 2 (Good hygiene compliance) members are likely to transfer to Class 3 (Vigilance) while Class 1 (Moderate hygiene compliance) could be unchanged. The young, mostly single males and those with lower educational achievement represent a group for whom public health messages need to be targeted.


title: Developing Universal Influenza Vaccines: Hitting the Nail, Not Just on the Head

text: Influenza viruses have a huge impact on public health. Current influenza vaccines need to be updated annually and protect poorly against antigenic drift variants or novel emerging subtypes. Vaccination against influenza can be improved in two important ways, either by inducing more broadly protective immune responses or by decreasing the time of vaccine production, which is relevant especially during a pandemic outbreak. In this review, we outline the current efforts to develop so-called “universal influenza vaccines”, describing antigens that may induce broadly protective immunity and novel vaccine production platforms that facilitate timely availability of vaccines.


Rapid Antibody Testing for SARS-CoV-2 in Asymptomatic and Paucisymptomatic Healthcare Professionals in Hematology and Oncology Units Identifies Undiagnosed Infections


Abordaje terapéutico del SARS-CoV-2 (COVID-19) mediante células mesenquimales de médula ósea alogénica expandidas. Conceptos a propósito de un primer caso


title: Projected Increases in Suicide in Canada as a Consequence of COVID-19

text: Macroeconomic indicators, notably unemployment, are significant moderators of suicide. We projected the number of excess suicides in Canada as a consequence of the impact of COVID-19 on unemployment. Annual suicide mortality (2000-2018) and unemployment (2000-2019) data were derived from Statistics Canada. Time-trend regression models were used to evaluate and predict the number of excess suicides in 2020 and 2021 for two possible projection scenarios following the COVID-19 pandemic: 1) an increase in unemployment of 1.6% in 2020, 1.2% in 2021, or 2) an increase in unemployment of 10.7% in 2020, 8.9% in 2021. A percentage point increase in unemployment was associated with a 1.0% increase in suicide between 2000-2018. In the first scenario, the rise in unemployment rates resulted in a projected total of 418 excess suicides in 2020-2021 (suicide rate per 100,000: 11.6 in 2020). In the second scenario, the projected suicide rates per 100,000 increased to 14.0 in 2020 and 13.6 in 2021, resulting in 2,114 excess suicides in 2020-2021. These results indicate that suicide prevention in the context of COVID-19-related unemployment is a critical priority. Furthermore, timely access to mental healthcare, financial provisions and social/labour support programs, as well as optimal treatment for mental disorders is urgently needed.


title: Demonstration of the presence of a specific interferon-γ receptor on murine astrocyte cell surface

text: Abstract Interferon gamma (IFN-γ) is a pleiotropic lymphokine produced by T-lymphocytes which acts as a soluble mediator in immunological reactions. In addition to several immune target cells, such as monocytes and macrophages, it acts on the principal glial population, the astrocytes, inducing Ia antigen expression. We have developed a binding assay for 125I-labeled recombinant murine IFN-γ, and show that, using this assay, IFN-γ interacts with a single specific receptor on the murine astrocyte cell membrane. The binding is specific and saturable and it takes place with a K d = 1.64 × 10−9 M, with 11,100 receptor molecules per astrocytic cell. The binding shows, as for macrophages, species specificity. Using an immune assay including rabbit antibodies to IFN-γ and 125I-labeled protein A, we have demonstrated an internalization of the ligand. This is an energy-dependent process, as around 50% of the bound IFN-γ is endocytosed after 4 h at 37°C when cultures are maintained in complete culture medium.


title: Preprocessing alternatives for compositional data related to water, sanitation and hygiene

text: Abstract The Sustainable Development Goals (SDGs) 6.1 and 6.2 measure the progress of urban and rural populations in their access to different levels of water, sanitation and hygiene (WASH) services, based on multiple sources of information. Service levels add up to 100%; therefore, they are compositional data (CoDa). Despite evidence of zero value, missing data and outliers in the sources of information, the treatment of these irregularities with different statistical techniques has not yet been analyzed for CoDa in the WASH sector. Thus, the results may present biased estimates, and the decisions based on these results will not necessarily be appropriate. In this article, we therefore: i) evaluate methodological imputation alternatives that address the problem of having either zero values or missing values, or both simultaneously; and ii) propose the need to complement the point-to-point identification of the WHO/UNICEF Joint Monitoring Program (JMP) with other robust alternatives, to deal with outliers depending on the number of data points. These suggestions have been considered here using statistics for CoDa with isometric log-ratio (ilr) transformation. A selection of illustrative cases is presented to compare performance of different alternatives.


title: Absolute and Relative Quantification of Multiplex DNA Assays Based on an Elemental Labeling Strategy

text: Elemente und Quantifizierung: Ein Nucleinsäure‐Assay, der auf einer Elementmarkierungsstrategie mit magnetischen Mikropartikeln (MMPs) beruht, ermöglicht die Quantifizierung mehrfacher DNA‐Ziele. Seltenerdelemente, Indium und stabile Isotope konnten mit Oligonucleotiden, die als DNA‐Sonden dienen, markiert werden. Die quantitative Analyse wurde dann mit den entworfenen Systemen (siehe Bild) und Massenspektrometrie durchgeführt.[Image: see text]


Prevención e identificación temprana de casos sospechosos COVID-19 en el primer nivel de atención en Centro América


title: Lupus anticoagulant is frequent in patients with Covid‐19: Response to Reply

text: We have recently published in the Journal of Thrombosis and Haemostasis the presence of lupus anticoagulant (LAC) at high frequency in Covid‐19 patients (1). Different authors had confirmed these results (2). Connell and colleagues had discussed, in the Journal, technical points concerning LAC as well as anti‐phospholipids (aPL) auto‐antibodies detection (3).


title: The Future of Antisense Oligonucleotides in the Treatment of Respiratory Diseases

text: Antisense oligonucleotides (ASO) are short synthetic DNA molecules designed to inhibit translation of a targeted gene to protein via interaction with messenger RNA. More recently, small interfering (si)RNA have been developed as potent tools to specifically inhibit gene expression. ASO directed against signaling molecules, cytokine receptors, and transcription factors involved in allergic immune and inflammatory responses, have been applied in experimental models of asthma and demonstrate potential as therapeutics. Several ASO-based drugs directed against oncogenes have been developed for therapy of lung cancer, and some have recently reached clinical trials. ASO and siRNA to respiratory syncytial virus infection have demonstrated good potential to treat this condition, particularly in combination with an antiviral drug. Although ASO-based therapeutics are promising for lung diseases, issues of specificity, identification of correct molecular targets, delivery and carrier systems, as well as potential adverse effects must be carefully evaluated before clinical application.


title: Novel insights into the aetiology and pathophysiology of increased airway inflammation during COPD exacerbations

text: Airway inflammation increases during acute exacerbations of COPD. Extrinsic factors, such as airway infections, increased air pollution, and intrinsic factors, such as increased oxidative stress and altered immunity may contribute to this increase. The evidence for this and the potential mechanisms by which various aetiological agents increase inflammation during COPD exacerbations is reviewed. The pathophysiologic consequences of increased airway inflammation during COPD exacerbations are also discussed. This review aims to establish a cause and effect relationship between etiological factors of increased airway inflammation and COPD exacerbations based on recently published data. Although it can be speculated that reducing inflammation may prevent and/or treat COPD exacerbations, the existing anti-inflammatory treatments are modestly effective.


title: Identification and Characterization of a New Orthoreovirus from Patients with Acute Respiratory Infections

text: First discovered in the early 1950s, reoviruses (respiratory enteric orphan viruses) were not associated with any known disease, and hence named orphan viruses. Recently, our group reported the isolation of the Melaka virus from a patient with acute respiratory disease and provided data suggesting that this new orthoreovirus is capable of human-to-human transmission and is probably of bat origin. Here we report yet another Melaka-like reovirus (named Kampar virus) isolated from the throat swab of a 54 year old male patient in Kampar, Perak, Malaysia who was suffering from high fever, acute respiratory disease and vomiting at the time of virus isolation. Serological studies indicated that Kampar virus was transmitted from the index case to at least one other individual and caused respiratory disease in the contact case. Sequence analysis of the four small class genome segments indicated that Kampar and Melaka viruses are closely related. This was confirmed by virus neutralization assay, showing an effective two-way cross neutralization, i.e., the serum against one virus was able to neutralize the other. Although the exact origin of Kampar virus is unknown, epidemiological tracing revealed that the house of the index case is surrounded by fruit trees frequently visited by fruit bats. There is a high probability that Kampar virus originated from bats and was transmitted to humans via bat droppings or contaminated fruits. The discovery of Kampar virus highlights the increasing trend of emergence of bat zoonotic viruses and the need to expand our understanding of bats as a source of many unknown viruses.


title: Developing a vaccine for human rhinoviruses

text: Rhinoviruses (RV’s) are common human pathogens of the respiratory tract being the most frequent cause of mild diseases of the upper respiratory tract (common cold) but more importantly they are a major initiator of acute exacerbations of chronic airway diseases. Infections can be life threatening in the latter context however RV -induced common colds have an associated economic cost from loss of productivity due to absence from work or school. There are no appropriate antiviral therapies available and vaccine strategies have failed because of the large number of viral serotypes and the lack of cross-serotype protection generated. Here, approaches past and present for development of a vaccine to these widespread human pathogens are highlighted.


title: Molecular characterization of a novel cryptic virus infecting pigeonpea plants

text: A new member of the genus Deltapartitivirus was identified containing three dsRNAs with an estimated size of 1.71, 1.49 and 1.43 kb. The dsRNAs were extracted from symptomless pigeonpea [Cajanus cajan (L.) Millspaugh] plants cv. Erra Kandulu. This new virus with 4.64 kb genome was tentatively named Arhar cryptic virus-1 (ArCV-1). The genomic RNAs were amplified and characterized by sequence independent single primer amplification. The dsRNAs shared a highly conserved 16 nt 5’ non-coding region (5’-GATAATGATCCAAGGA-3’). The largest dsRNA (dsRNA-1) was identified as the viral RNA dependent RNA polymerase (replicase), predicted to encode a putative 55.34 kDa protein (P1). The two other smaller dsRNAs (dsRNA-2 and dsRNA-3) predicted to encode for putative capsid proteins of 38.50kDa (P2) and 38.51kDa (P3), respectively. Phylogenetic analysis indicated that ArCV-1 formed a clade together with Fragaria chiloensis cryptic virus, Rosa multiflora cryptic virus and Rose cryptic virus-1, indicating that ArCV-1 could be a new member of the genus Deltapartitivirus. ArCV-1 3D(pol) structure revealed several interesting features. The 3D(pol) in its full-length shares structural similarities with members of the family Caliciviridaeand family Picornaviridae. In addition, fourth dsRNA molecule (dsRNA-2A), not related to ArCV-1 genome, was found in the same plant tissue. The dsRNA-2A (1.6 kb) encodes a protein (P4), with a predicted size of 44.5 kDa. P4 shares similarity with coat protein genes of several cryptic viruses, in particular the bipartite cryptic viruses including Raphanus sativus cryptic virus-3. This is the first report of occurrence of a cryptic virus in pigeonpea plants.


title: Fear of the coronavirus (COVID-19): Predictors in an online study conducted in March 2020

text: Fear is an adaptive response in the presence of danger. However, when threat is uncertain and continuous, as in the current coronavirus disease (COVID-19) pandemic, fear can become chronic and burdensome. To identify predictors of fear of the coronavirus, we conducted an online survey (N = 439) three days after the World Health Organization declared the coronavirus outbreak a pandemic (i.e., between March 14 and 17, 2020). Fear of the coronavirus was assessed with the newly developed Fear of the Coronavirus Questionnaire (FCQ) consisting of eight questions pertaining to different dimensions of fear (e.g., subjective worry, safety behaviors, preferential attention), and an open-ended question. The predictors included psychological vulnerability factors (i.e., intolerance of uncertainty, worry, and health anxiety), media exposure, and personal relevance (i.e., personal health, risk for loved ones, and risk control). We found four predictors for the FCQ in a simultaneous regression analysis: health anxiety, regular media use, social media use, and risks for loved ones (R(2) = .37). Furthermore, 16 different topics of concern were identified based participants’ open-ended responses, including the health of loved ones, health care systems overload, and economic consequences. We discuss the relevance of our findings for managing people’s fear of the coronavirus.


title: Spread of Canine Influenza A(H3N2) Virus, United States

text: A canine influenza A(H3N2) virus emerged in the United States in February–March 2015, causing respiratory disease in dogs. The virus had previously been circulating among dogs in Asia, where it originated through the transfer of an avian-origin influenza virus around 2005 and continues to circulate. Sequence analysis suggests the US outbreak was initiated by a single introduction, in Chicago, of an H3N2 canine influenza virus circulating among dogs in South Korea in 2015. Despite local control measures, the virus has continued circulating among dogs in and around Chicago and has spread to several other areas of the country, particularly Georgia and North Carolina, although these secondary outbreaks appear to have ended within a few months. Some genetic variation has accumulated among the US viruses, with the appearance of regional-temporal lineages. The potential for interspecies transmission and zoonotic events involving this newly emerged influenza A virus is currently unknown.


title: Stochastic dynamics of an epidemics with recurrent spillovers from an endemic reservoir

text: Most emerging human infectious diseases have an animal origin. Yet, while zoonotic diseases originate from a primary reservoir, most theoretical studies have principally focused on single-host processes, either exclusively humans or exclusively animals, without considering the importance of animal to human transmission for understanding the dynamics of emerging infectious diseases. Here we aim to investigate the importance of spillover transmission for explaining the number and the size of outbreaks. We propose a simple stochastic Susceptible-Infected-Recovered model with a recurrent infection of an incidental host from a reservoir (e.g. humans by a zoonotic species), considering two modes of transmission, (1) animal-to-human and (2) human-to-human. The model assumes that (i) epidemiological processes are faster than other processes such as demographics or pathogen evolution and (ii) that an epidemic occurs until there are no susceptible individuals left. The results show that during an epidemic, even when the pathogens are barely contagious, multiple outbreaks are observed due to spillover transmission. Overall, the findings demonstrate that the only consideration of direct transmission between individuals is not sufficient to explain the dynamics of zoonotic pathogens in an incidental host.


title: Climate factors and incidence of Middle East respiratory syndrome coronavirus

text: Abstract Background Our understanding of climate factors and their links to the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreaks is incomplete. This study aimed to estimate the monthly incidence of MERS-CoV cases and to investigate their correlation to climate factors. Methods The study used aggregated monthly MERS-CoV cases that reported to the Saudi Center for Disease Prevention and Control from the Riyadh Region between November 1, 2012 and December 31, 2018. Data on the meteorological situation throughout the study period was calculated based on Google reports on the Riyadh Region (24.7136°N, 46.6753°E). The Poisson regression was used to estimate the incidence rate ratio (IRR) and its 95% confidence intervals (CI) for each climate factor. Results A total of 712 MERS-CoV cases were included in the analysis (mean age 54.2±9.9 years), and more than half (404) (56.1%) MERS-CoV cases were diagnosed during a five-month period from April to August. The highest peak timing positioned in August 2015, followed by April 2014, June 2017, March 2015, and June 2016. High temperatures (IRR=1.054, 95% CI: 1.043–1.065) and a high ultraviolet index (IRR=1.401, 95% CI: 1.331–1.475) were correlated with a higher incidence of MERS-CoV cases. However, low relative humidity (IRR=0.956, 95% CI: 0.948–0.964) and low wind speed (IRR=0.945, 95% CI: 0.912–0.979) were correlated with a lower incidence of MERS-CoV cases. Conclusion The novel coronavirus, MERS-CoV, is influenced by climate conditions with increasing incidence between April and August. High temperature, high ultraviolet index, low wind speed, and low relative humidity are contributors to increased MERS-CoV cases. The climate factors must be evaluated in hospitals and community settings and integrated into guidelines to serve as source of control measures to prevent and eliminate the risk of infection.


title: Emergence of porcine epidemic diarrhea virus in southern Germany

text: BACKGROUND: Over the last years, porcine epidemic diarrhea virus (PEDV) has caused devastating enteric diseases in the US and several countries in Asia, while outbreaks in Europe have only been reported sporadically since the 1980s. At present, only insufficient information is available on currently circulating PEDV strains in Europe and their impact on the European swine industry. In this case report, we present epidemic outbreaks of porcine epidemic diarrhea in three farms in South-Western Germany. CASE PRESENTATION: Epidemic outbreaks of diarrhea affecting pigs of all age groups were reported in three farms, one fattening farm and two piglet producing farms, in South-Western Germany between May and November 2014. In the fattening farm yellowish, watery diarrhea without evidence of mucus or blood was associated with a massive reduction of feed consumption. Severity of clinical signs and mortality in young suckling pigs varied significantly between the two affected sow farms. While mortality in suckling piglets reached almost 70 % in one sow herd, no increase in suckling piglet mortality was observed in the second sow farm. In all three cases, PEDV was confirmed in feces and small intestines by RT-qPCR. Phylogenetic analyses based on full-length PEDV genomes revealed high identity among strains from all three herds. Moreover, the German strains showed very high nucleotide identity (99.4 %) with a variant of PEDV (OH851) that was isolated in the United States in January 2014. This strain with insertions and deletions in the S-gene (so called INDEL strains) was reported to show lower virulence. Slightly lower identities were found with other strains from the US and Asia. CONCLUSION: Phylogenetic information on the distribution of PEDV strains in Europe is severely lacking. In this case report we demonstrate that acute outbreaks of PEDV occurred in southern Germany in 2014. Current strains were clearly different from isolates found in the 1980s and were closely related to a PEDV variant found in the US in 2014. Moreover, the present case report indicates that variant strains of PEDV, containing insertions and deletions in the S gene, which were reported to be of lower virulence, might be able to cause high mortality in suckling piglets.


docid: cxjnczwv

title: Molluscum contagiosum effectively treated with a topical acidified nitrite, nitric oxide liberating cream

text: A double‐blind, group‐sequential clinical trial of acidified nitrite was performed to demonstrate the efficacy of this nitric oxide donor in treating molluscum contagiosum. Subjects received either 5% sodium nitrite co‐applied with 5% salicylic acid under occlusion, or identical cream with 5% salicylic acid, omitting sodium nitrite. Active and control treatment groups were well matched for the number and duration of lesions and made a similar number of applications. We found a 75% cure rate in the active treatment group and 21% cure with control treatment (P = 0·01). The mean time to cure was 1·83 months. Staining of the skin and irritation were frequent side‐effects but did not prevent successful treatment.


title: Characterization of the budding compartment of mouse hepatitis virus: evidence that transport from the RER to the Golgi complex requires only one vesicular transport step

text: Mouse hepatitis coronavirus (MHV) buds into pleomorphic membrane structures with features expected of the intermediate compartment between the ER and the Golgi complex. Here, we characterize the MHV budding compartment in more detail in mouse L cells using streptolysin O (SLO) permeabilization which allowed us to better visualize the membrane structures at the ER-Golgi boundary. The MHV budding compartment shares membrane continuities with the rough ER as well as with cisternal elements on one side of the Golgi stack. It also labeled with p58 and rab2, two markers of the intermediate compartment, and with PDI, usually considered to be a marker of the rough ER. The membranes of the budding compartment, as well as the budding virions themselves, but not the rough ER, labeled with the N-acetyl- galactosamine (GalNAc)-specific lectin Helix pomatia. When the SLO- permeabilized cells were treated with guanosine 5'-(3-O- thio)triphosphate (GTP gamma S), the budding compartment accumulated a large number of beta-cop-containing buds and vesicular profiles. Complementary biochemical experiments were carried out to determine whether vesicular transport was required for the newly synthesized M protein, that contains only O-linked oligosaccharides, to acquire first, GalNAc and second, the Golgi modifications galactose and sialic acid. The results from both in vivo studies and from the use of SLO- permeabilized cells showed that, while GalNAc addition occurred under conditions which block vesicular transport, both cytosol and ATP were prerequisites for the M protein oligosaccharides to acquire Golgi modifications. Collectively, our data argue that transport from the rough ER to the Golgi complex requires only one vesicular transport step and that the intermediate compartment is a specialized domain of the endoplasmatic reticulum that extends to the first cisterna on the cis side of the Golgi stack.


Is there a role for lung perfusion [(99m)Tc]-MAA SPECT/CT to rule out pulmonary embolism in COVID-19 patients with contraindications for iodine contrast?


title: Epidemiological and clinical features of 200 hospitalized patients with Corona Virus Disease 2019 outside Wuhan, China: A descriptive study

text: BACKGROUND: The recent outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide, with especially severe epidemics occurring in cities across China. OBJECTIVES: To report the epidemiological and clinical futures of the 200 patients infected with COVID-19 in Yichang, Hubei Province, China. STUDY DESIGN: 200 patients confirmed with COVID-19 in a designated hospital in Yichang from Jan 30 to Feb 8, 2020 were investigated retrospectively. The epidemiological data and clinical characteristics were collected. The data between the ICU patients and non-ICU patients were compared. The patients were followed up till Feb 26, 2020. RESULTS: Of the 200 hospitalized patients with COVID-19, 98 (49.0%) were male, and the mean age was 55 years. Eighty-seven (43.5%) had no linkage to Wuhan or contact history. Familial clustering was found in 34 patients. Sixtyfive (32.5%) suffered from chronic diseases. The common symptoms included fever (171[85.5%]), cough (116[58.0%]), and fatigue (64[32%]). Most patients had lymphopenia. One hundred and seventy-two (86%) patients showed typical imaging findings of viral pneumonia. Most patients received antiviral, antibiotic, and corticosteroid treatment. Compared with the non-ICU patients, 29 (14.5%) patients in the ICU were older and more likely to show dyspnea and complications including ARDS. As of Feb 26, 15 (51.7%) patients in the ICU had died. CONCLUSIONS: The COVID-19 infection was of clustering onset and can cause severe respiratory disease and even death. The mortality of ICU patients with COVID-19 was considerably high.


docid: pztrwvib

title: Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea

text: BACKGROUND: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. MATERIALS AND METHODS: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. RESULTS: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.


title: Evaluation of the effects of COVID‐19 pandemic on hair diseases through a web‐based questionnaire

text: AIM: Current quarantine conditions are a difficult process for individuals and can worsen the psychological state. Increased psychosocial stress can affect the course of many common “stress‐sensitive” skin conditions. This study examined the possible effects of COVID‐19 on hair and scalp diseases such as telogen effluvium (TE), alopecia areata (AA), and seborrheic dermatitis (SD) in individuals who had to stay at home for a long time and the patients’ methods of dealing with these diseases. METHODS: The study was conducted using an online questionnaire. All the individuals were asked questions about pre and post‐pandemic TE, AA, and SD. Participants with complaints were asked what they did for treatment. RESULTS: During the pandemic, TE was seen in 27.9% of the participants, AA on the scalp was seen in 2.8%, AA on the face was seen in 2.5% and SD was seen in 19.9%. Applying to a dermatologist for complaints during the pandemic was lower than before pandemic. TE was higher in women before and during the pandemic CONCLUSION: It was found that the rates of referring to a dermatologist for the complaints before the pandemic varied between 15 and 28% and that these rates decreased significantly during the pandemic (2.5‐12.5%). This article is protected by copyright. All rights reserved.


Coronavirus motif


title: Kawasaki Disease: Laboratory Findings and an Immunopathogenesis on the Premise of a "Protein Homeostasis System"

text: Kawasaki disease (KD) is a self-limited systemic inflammatory illness, and coronary artery lesions (CALs) are a major complication determining the prognosis of the disease. Epidemiologic studies in Asian children suggest that the etiologic agent(s) of KD may be associated with environmental changes. Laboratory findings are useful for the diagnosis of incomplete KD, and they can guide the next-step in treatment of initial intravenous immunoglobulin non-responders. CALs seem to develop in the early stages of the disease before a peak in inflammation. Therefore early treatment, before the peak in inflammation, is mandatory to reduce the risk of CAL progression and severity of CALs. The immunopathogenesis of KD is more likely that of acute rheumatic fever than scarlet fever. A hypothetical pathogenesis of KD is proposed under the premise of a "protein homeostasis system"; where innate and adaptive immune cells control pathogenic proteins that are toxic to host cells at a molecular level. After an infection of unknown KD pathogen(s), the pathogenic proteins produced from an unknown focus, spread and bind to endothelial cells of coronary arteries as main target cells. To control the action of pathogenic proteins and/or substances from the injured cells, immune cells are activated. Initially, non-specific T cells and non-specific antibodies are involved in this reaction, while hyperactivated immune cells produce various cytokines, leading to a cytokine imbalance associated with further endothelial cell injury. After the emergence of specific T cells and specific antibodies against the pathogenic proteins, tissue injury ceases and a repair reaction begins with the immune cells.


title: 26 Community-Acquired Pneumonia, Bacterial

text: Abstract Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma in a patient who has acquired the infection in the community and has not had recent hospitalization or association with other healthcare facilities such as nursing homes, dialysis centers, and outpatient clinics. CAP is a common and potentially serious illness, particularly in elderly patients and those with significant comorbidities. CAP may be caused by myriad pathogens, but bacteria are the most common causes. Bacteria have traditionally been divided into two groups: typical and atypical agents. Typical organisms include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, group A streptococci, Moraxella catarrhalis, anaerobes, and aerobic gram-negative bacteria. Atypical organisms include Legionella species, Mycoplasma pneumoniae, Chlamydophila (also known as Chlamydia) pneumoniae, and Chlamydophila psittaci. This chapter will focus on the general approach to CAP in adults, with a concentration primarily on typical bacterial causes. Other chapters focus specifically on pneumonia caused by aspiration, viruses, or atypical organisms.


title: Biology of portal hypertension

text: Portal hypertension develops as a result of increased intrahepatic vascular resistance often caused by chronic liver disease that leads to structural distortion by fibrosis, microvascular thrombosis, dysfunction of liver sinusoidal endothelial cells (LSECs), and hepatic stellate cell (HSC) activation. While the basic mechanisms of LSEC and HSC dysregulation have been extensively studied, the role of microvascular thrombosis and platelet function in the pathogenesis of portal hypertension remains to be clearly characterized. As a secondary event, portal hypertension results in splanchnic and systemic arterial vasodilation, leading to the development of a hyperdynamic circulatory syndrome and subsequently to clinically devastating complications including gastroesophageal varices and variceal hemorrhage, hepatic encephalopathy from the formation of portosystemic shunts, ascites, and renal failure due to the hepatorenal syndrome. This review article discusses: (1) mechanisms of sinusoidal portal hypertension, focusing on HSC and LSEC biology, pathological angiogenesis, and the role of microvascular thrombosis and platelets, (2) the mesenteric vasculature in portal hypertension, and (3) future directions for vascular biology research in portal hypertension.


title: Smart monitoring and controlling of Pandemic Influenza A (H1N1) using Social Network Analysis and cloud computing

text: Abstract H1N1 is an infectious virus which, when spread affects a large volume of the population. It is an airborne disease that spreads easily and has a high death rate. Development of healthcare support systems using cloud computing is emerging as an effective solution with the benefits of better quality of service, reduced costs and flexibility. In this paper, an effective cloud computing architecture is proposed which predicts H1N1 infected patients and provides preventions to control infection rate. It consists of four processing components along with secure cloud storage medical database. The random decision tree is used to initially assess the infection in any patient depending on his/her symptoms. Social Network Analysis (SNA) is used to present the state of the outbreak. The proposed architecture is tested on synthetic data generated for two million users. The system provided 94% accuracy for the classification and around 81% of the resource utilization on Amazon EC2 cloud. The key point of the paper is the use of SNA graphs to calculate role of an infected user in spreading the outbreak known as Outbreak Role Index (ORI). It will help government agencies and healthcare departments to present, analyze and prevent outbreak effectively.


docid: bosursqx

title: Surveillance for respiratory and diarrheal pathogens at the human-pig interface in Sarawak, Malaysia

text: BACKGROUND: The large livestock operations and dense human population of Southeast Asia are considered a hot-spot for emerging viruses. OBJECTIVES: To determine if the pathogens adenovirus (ADV), coronavirus (CoV), encephalomyocarditis virus (EMCV), enterovirus (EV), influenza A-D (IAV, IBV, ICV, and IDV), porcine circovirus 2 (PCV2), and porcine rotaviruses A and C (RVA and RVC), are aerosolized at the animal-interface, and if humans working in these environments are carrying these viruses in their nasal airways. STUDY: This cross-sectional study took place in Sarawak, Malaysia among 11 pig farms, 2 abattoirs, and 3 animal markets in June and July of 2017. Pig feces, pig oral secretions, bioaerosols, and worker nasal wash samples were collected and analyzed via rPCR and rRT-PCR for respiratory and diarrheal viruses. RESULTS: In all, 55 pig fecal, 49 pig oral or water, 45 bioaerosol, and 78 worker nasal wash samples were collected across 16 sites. PCV2 was detected in 21 pig fecal, 43 pig oral or water, 3 bioaerosol, and 4 worker nasal wash samples. In addition, one or more bioaerosol or pig samples were positive for EV, IAV, and RVC, and one or more worker samples were positive for ADV, CoV, IBV, and IDV. CONCLUSIONS: This study demonstrates that nucleic acids from a number of targeted viruses were present in pig oral secretions and pig fecal samples, and that several viruses were detected in bioaerosol samples or in the nasal passages of humans with occupational exposure to pigs. These results demonstrate the need for future research in strengthening viral surveillance at the human-animal interface, specifically through expanded bioaerosol sampling efforts and a seroepidemiological study of individuals with exposure to pigs in this region for PCV2 infection.


title: Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine

text: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), kills 5,000 people per day globally. Rapid development and spread of various multi drug-resistant strains of Mtb emphasize that an effective vaccine is still the most cost-effectives and efficient way of controlling and eradicating TB. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, still remains the most widely administered human vaccine, but is inefficient in protecting from pulmonary TB in adults. The protective immunity afforded by BCG is thought to wane with time and considered to last only through adolescent years. Heterologous boosting of BCG-primed immune responses using a subunit vaccine represents a promising vaccination approach to promote strong cellular responses against Mtb. In our earlier studies, we discovered lipopeptides of ESAT-6 antigen with strong potential as a subunit vaccine candidate. Here, we have investigated that potential as a booster to BCG vaccine in both a pre-exposure preventive vaccine and a post-exposure therapeutic vaccine setting. Surprisingly, our results demonstrated that boosting BCG with subunit vaccine shortly before Mtb challenge did not improve the BCG-primed immunity, whereas the subunit vaccine boost after Mtb challenge markedly improved the quantity and quality of effector T cell responses and significantly reduced Mtb load in lungs, liver and spleen in mice. These studies suggest that ESAT-6 lipopeptide-based subunit vaccine was ineffective in overcoming the apparent immunomodulation induced by BCG vaccine in Mtb uninfected mice, but upon infection, the subunit vaccine is effective in re-educating the protective immunity against Mtb infection. These important results have significant implications in the design and investigation of effective vaccine strategies and immunotherapeutic approaches for individuals who have been pre-immunized with BCG vaccine but still get infected with Mtb.


title: Haemagglutinin-esterase protein (HE) of murine corona virus: DVIMD (diarrhea virus of infant mice)

text: The acetylesterase (AE) activity of DVIM (diarrhea virus of infant mice) was assigned to the haemagglutinin-esterase (HE) protein. The substrate specificity was examined using the natural substrate bovine submaxillary mucin (BSM) and/or synthetic substrates p-nitrophenylacetate (p-NiA) and α-naphthylacetate (α-NA) and compared with several strains of MHV and influenza viruses. The AE of DVIM hydrolyzed the O-acetylester bond of BSM, and the two synthetic substrates p-NiA and α-NA in vitro. MHV-S reacted efficiently with both p-NiA and α-NA but less with BSM. Influenza virus (C/Miyagi/77) reacted with BSM efficiently, however reacted with p-NiA weakly, but not with α-NA at all. Thus, the AE-reactivity of DVIM was distinctly different from that of MHV-S and influenza C virus, suggesting that the AE of HE may have a modified function. Isolation of HE by the treatment with non ionic detergent NP40, resulted in globules approximately 5 nm in diameter. DVIM-binding proteins were demonstrated in the plasma membrane of mouse intestinal brush-border cells and hepatocytes. The same protein was recognized by MHV-S and MHV-4. The cell membranes obtained from these target tissues were substrates for the AE of DVIM. The biological importance of the HE protein for DVIM is discussed.


title: Receptor-binding domain-based subunit vaccines against MERS-CoV

text: Development of effective vaccines, in particular, subunit-based vaccines, against emerging Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) will provide the safest means of preventing the continuous spread of MERS in humans and camels. This review briefly describes the structure of the MERS-CoV spike (S) protein and its receptor-binding domain (RBD), discusses the current status of MERS vaccine development, and illustrates the strategies used to develop RBD-based subunit vaccines against MERS. It also summarizes currently available animal models for MERS-CoV and proposes a future direction for MERS vaccines. Taken together, this review will assist researchers working to develop effective and safe subunit vaccines against MERS-CoV and any other emerging coronaviruses that might cause future pandemics.


title: Corona virus induced subacute demyelinating encephalomyelitis in rats: A morphological analysis

text: Thirty percent of weanling rats infected with JHM murine corona virus developed a subacute demyelinating encephalomyelitis approximately 3 weeks after intracerebral inoculation. Small demyelinating foci were located in the deep cerebral white matter and large, sharply demarcated demyelinating lesions were detectable in optic chiasma, pons and spinal cord. Axons as well as neurons were well preserved in the demyelinating plaques in areas where the lesions extended to the gray matter. Perivascular cuffings, consisting of plasma cells and mononuclear cells, were frequently found. Viral antigen was found mostly in the white matter and in glial cells, leaving neurons unstained. Electron microscopic studies of the early lesions of white matter disclosed two different kinds of cell degeneration which developed prior to the myelin disruption and mononuclear cell infiltration. One was a small pyknotic cell, which is thought to be an oligodendrocyte and the other is a ballooned cell containing abundant microtubules. Virus particles could be demonstrated only in the latter cell type. Discussion about astrocytes as well as oligodendrocytes was made in relation to the initial stage of demyelination caused by virus infection. This animal model may be useful in the analysis of the mechanisms leading to demyelination in subacute or chronic infections.


title: Dermatology residents and COVID‐19: life behind the frontlines

text: the CoronaVirus Disease 2019 (COVID‐19) pandemic outbreak in Italy completely changed patients’ access to healthcare systems and therefore the doctor‐patient relationship, in particular during the national lockdown (from March 11th to May 18th).


title: A novel bocavirus in canine liver

text: BACKGROUND: Bocaviruses are classified as a genus within the Parvoviridae family of single-stranded DNA viruses and are pathogenic in some mammalian species. Two species have been previously reported in dogs, minute virus of canines (MVC), associated with neonatal diseases and fertility disorders; and Canine bocavirus (CBoV), associated with respiratory disease. FINDINGS: In this study using deep sequencing of enriched viral particles from the liver of a dog with severe hemorrhagic gastroenteritis, necrotizing vasculitis, granulomatous lymphadenitis and anuric renal failure, we identified and characterized a novel bocavirus we named Canine bocavirus 3 (CnBoV3). The three major ORFs of CnBoV3 (NS1, NP1 and VP1) shared less than 60% aa identity with those of other bocaviruses qualifying it as a novel species based on ICTV criteria. Inverse PCR showed the presence of concatemerized or circular forms of the genome in liver. CONCLUSIONS: We genetically characterized a bocavirus in a dog liver that is highly distinct from prior canine bocaviruses found in respiratory and fecal samples. Its role in this animal’s complex disease remains to be determined.


title: The Anxiety Status of Chinese Medical Workers During the Epidemic of COVID-19: A Meta-Analysis

text: OBJECTIVE: To analysis the anxiety status of Chinese medical workers during the epidemic of COVID-19 by meta-analysis method. METHODS: CNKI, VIP, WanFang Data, SinoMed, PubMed, Cochrane, EMBASE, MEDLINE, Scopus, Google Scholar and other databases were searched to collect literature on the anxiety status of Chinese medical workers during the epidemic of COVID-19. The retrieval time is from the database construction to 11/03/2020. Meta-analysis was performed on the included articles by using Stata 16.0 software. RESULTS: A total of 7 articles were included, with a total sample size of 7,741 people. Meta-analysis using the random effects model showed that the anxiety score of Chinese medical during the epidemic of COVID-19 was significantly higher than that of the national norm in each study, the difference was statistically significant [SMD (95% CI)=1.145 (0.705–1.584), p<0.001]. CONCLUSION: The anxiety level of Chinese medical workers has increased significantly during the epidemic of COVID-19.


title: DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial

text: BACKGROUND: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood. The objectives of this study are: 1) to compare the effect of ‘high dose’ (2000 IU/day) vs. ‘standard dose’ (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of ‘high dose’ vitamin D supplementation on vitamin D serum levels and specific viruses that cause URTI. METHODS/DESIGN: This study is a pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1–5 years of age. Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be randomized to the ‘standard dose’ or ‘high dose’ oral supplemental vitamin D for a minimum of 4 months (200 children per group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma exacerbations and the frequency of specific viral agents between groups. DISCUSSION: Identifying whether vitamin D supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may reduce population wide morbidity and associated health care and societal costs. This information will assist in determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian preschoolers.


title: LABORATORIO DE VIROLOGÍA EN LA PRÁCTICA CLÍNICA

text: Resumen Las infecciones virales continúan siendo frecuentes en la práctica clínica. Los avances en el manejo de pacientes críticos, de inmunosuprimidos y la posibilidad de ofrecer un tratamiento antiviral oportuno han exigido que el diagnóstico virológico sea hoy un servicio central dentro de los laboratorios clínicos. Un correcto y completo diagnóstico virológico permite además monitorizar pacientes con infecciones crónicas, detectar seroconversión o susceptibilidad de la población vacunada y caracterizar eventuales epidemias causadas por estos agentes. En el siguiente artículo se revisan los conceptos en los que se basan las técnicas utilizadas para el diagnóstico virológico y se entrega un resumen de los exámenes de laboratorio a solicitar ante las infecciones más frecuentes. SUMMARY Viral infections remain a frequent cause of medical consultation. Advances in support and treatment of critically ill and immunocompromised patients, and the introduction of antiviral drugs have resulted that viral diagnosis is now an important function in clinical laboratories. A complete and precise viral diagnostic also allows monitoring chronic infections, to detect serologic response or susceptibility on vaccinated population and to characterize the course of viral outbreaks. In this article, we review the basic concepts behind the most frequently used virology techniques and summarized the laboratory tests that can be performed according to the most frequent infections.


title: Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China

text: Background Crucial roles of hematologic and immunologic responses in progression of COVID-19 remains largely unclear. Objective We sought to address the dynamic changes of hematologic and immunologic biomarkers and their associations with severity and outcomes of the disease. Methods A retrospective study including 548 COVID-19 patients with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. Results On admission, the counts of lymphocytes, T cell subsets, eosinophils and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or non-survivors. During hospitalization, eosinophils, lymphocytes and platelets were shown an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in non-survivors. Non-survivors kept high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein and C-reactive protein, which were kept stable or shown downward trend in survivors. Positive correlation between CD8+ T cell and lymphocytes count was found in survivors but not in non-survivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils and platelets could serve as the predictors for the recovery, while progressive increases in neutrophils, basophils and IL-6 were associated with fatal outcome. Conclusions Hematologic and immunologic impairment showed a significantly different profile between survivors and non-survivors in COVID-19 patients with different severity. The longitudinal variations of these biomarkers could serve to predict recovery or fatal outcome.


title: Estudio retrospectivo de 10 años de la infección por rotavirus en la provincia de Castellón

text: Objetivo El objetivo de este trabajo es conocer el porcentaje de la infección por rotavirus en niños menores de 14 años y su epidemiología en el área 02 de la provincia de Castellón. Material y métodos Se realizó un estudio retrospectivo desde enero de 1995 hasta diciembre de 2004 en el que se analizaron 14.068 muestras de heces de pacientes pediátricos con gastroenteritis aguda. Las variables analizadas fueron: sexo, edad, procedencia, diagnóstico de rotavirus y fecha de diagnóstico. Se consideraron valores significativos p<0,05. Resultados El rotavirus fue detectado en el 11,9 % (1.687 casos) en los 10 años del estudio; el 12,14 % en varones y el 11,81 % en mujeres (p=0,5459). La edad media de la población del estudio fue de 2,63 años. El grupo que presentó el mayor porcentaje de casos fue el de 1 a 4 años con el 14,1 % (p<0,001) y pacientes ambulatorios con el 12,76 % (p<0,05). En nuestra área, el rotavirus predomina significativamente (p<0,001) en los meses de invierno. Conclusión El rotavirus es una de las causas más importantes de morbilidad en la edad pediátrica en el hospital y en el ambulatorio. Afecta más frecuentemente a los niños menores de 4 años, y principalmente a los de 1 año. La infección se presentó de forma predominante en el invierno. Objective To determine the percentage of rotavirus infection in children aged less than 14 years old and the epidemiology in area 02 of the province of Castellón (Spain). Material and methods We performed a retrospective study from January 1995 to December 2004 in which 14,068 stool samples from pediatric patients with acute gastroenteritis were analyzed. The variables analyzed were sex, age, origin, diagnosis of rotavirus, and date of diagnosis. Differences were considered statistically significant if p<0.05. Results Rotavirus was detected in 11.9 % of the samples (1687 cases) in the 10 years of the study, 12.14 % corresponded to boys and 11.81 % to girls (p=0.5459). The mean age of the population was 2.63 years. The highest percentage of cases occurred in the group aged 1- 4 years old (14.1 %; p<0.001) and in outpatients (12.76 %; p<0.05). In this geographical region, there was a significant tendency (p<0.001) for rotavirus to occur in the winter months. Conclusion Rotavirus is one of the main causes of morbidity in children both in the hospital and the outpatient setting. Children aged less than 4 years old are most frequently affected, especially those aged 1 year. The infection appears mainly in winter.


title: Mood, anxiety and olfactory dysfunction in COVID‐19: evidence of central nervous system involvement?

text: INTRODUCTION: The objective of this study was to determine the burden of depressed mood and anxiety in COVID‐19, and associated disease characteristics. MATERIALS AND METHODS: This is a prospective, cross‐sectional study of 114 COVID‐19 positive patients diagnosed using RT‐PCR‐based testing over a 6‐week period. The 2‐item Patient Health Questionnaire (PHQ‐2) and the 2‐item Generalized Anxiety Disorder questionnaire (GAD‐2) were used to measure depressed mood and anxiety level, respectively, at enrollment and for participants’ baseline, pre‐COVID‐19 state. Severity of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough and shortness of breath (SOB) during COVID‐19 were assessed. RESULTS: PHQ‐2 and GAD‐2 significantly (p<0.001) increased from baseline to enrollment. PHQ‐2 was associated with smell loss (adjusted incidence rate ratio [aIRR]=1.40, 95%CI: 1.10‐1.78, p=0.006), age (aIRR=1.02, 95%CI: 1.01‐1.04, p=0.006), and baseline PHQ‐2 score (aIRR=1.39, 95%CI: 1.09‐1.76, p=0.007). GAD‐2 score was associated with smell loss (aIRR=1.29, 95%CI: 1.02‐1.62, p=0.035), age (aIRR=1.02, 95%CI: 1.01‐1.04, p=0.025) and baseline GAD‐2 score (aIRR=1.55, 95%CI: 1.24‐1.93, p<0.001). Loss of taste also exhibited similar associations with PHQ‐2 and GAD‐2. PHQ‐2 and GAD‐2 scores were not associated with severities of any other symptoms during the COVID‐19 course. CONCLUSIONS: Despite the occurrence of symptoms—such as SOB—associated with severe manifestations of COVID‐19, only the severities of smell and taste loss were associated with depressed mood and anxiety. These results may raise the novel possibility of emotional disturbance as a CNS manifestation of COVID‐19 given trans‐olfactory tract penetration of the central nervous system (CNS) by coronaviruses.


title: Neutrophils in respiratory syncytial virus infection: A target for asthma prevention

text: Lower respiratory tract infections by respiratory syncytial virus (RSV) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. Neutrophils infiltrate the airways of pediatric patients with RSV-induced bronchiolitis in vast numbers: approximately 80% of infiltrated cells are neutrophils. However, why neutrophils are recruited to the site of viral respiratory tract infection is not clear. In this review we discuss the beneficial and pathologic contributions of neutrophils to the immune response against RSV infection. Neutrophils can limit viral replication and spread, as well as stimulate an effective antiviral adaptive immune response. However, low specificity of neutrophil antimicrobial armaments allows for collateral tissue damage. Neutrophil-induced injury to the airways during the delicate period of infant lung development has lasting adverse consequences for pulmonary architecture and might promote the onset of asthma in susceptible subjects. We suggest that pharmacologic modulation of neutrophils should be explored as a viable future therapy for severe RSV-induced bronchiolitis and thereby prevent the inception of subsequent asthma. The antiviral functions of neutrophils suggest that targeting of neutrophils in patients with RSV-induced bronchiolitis is best performed under the umbrella of antiviral treatment.


title: Unpacking the puzzle of China's innovation S. Dai M. Taube

text: Unknown