title: Computational identification of rare codons of Escherichia coli based on codon pairs preference

text: BACKGROUND: Codon bias is believed to play an important role in the control of gene expression. In Escherichia coli, some rare codons, which can limit the expression level of exogenous protein, have been defined by gene engineering operations. Previous studies have confirmed the existence of codon pair's preference in many genomes, but the underlying cause of this bias has not been well established. Here we focus on the patterns of rarely-used synonymous codons. A novel method was introduced to identify the rare codons merely by codon pair bias in Escherichia coli. RESULTS: In Escherichia coli, we defined the "rare codon pairs" by calculating the frequency of occurrence of all codon pairs in coding sequences. Rare codons which are disliked in genes could make great contributions to forming rare codon pairs. Meanwhile our investigation showed that many of these rare codon pairs contain termination codons and the recognized sites of restriction enzymes. Furthermore, a new index (F(rare)) was developed. Through comparison with the classical indices we found a significant negative correlation between F(rare )and the indices which depend on reference datasets. CONCLUSIONS: Our approach suggests that we can identify rare codons by studying the context in which a codon lies. Also, the frequency of rare codons (F(rare)) could be a useful index of codon bias regardless of the lack of expression abundance information.


title: Origin and Evolution of the Kiwifruit Canker Pandemic

text: Recurring epidemics of kiwifruit (Actinidia spp.) bleeding canker disease are caused by Pseudomonas syringae pv. actinidiae (Psa). In order to strengthen understanding of population structure, phylogeography, and evolutionary dynamics, we isolated Pseudomonas from cultivated and wild kiwifruit across six provinces in China. Based on the analysis of 80 sequenced Psa genomes, we show that China is the origin of the pandemic lineage but that strain diversity in China is confined to just a single clade. In contrast, Korea and Japan harbor strains from multiple clades. Distinct independent transmission events marked introduction of the pandemic lineage into New Zealand, Chile, Europe, Korea, and Japan. Despite high similarity within the core genome and minimal impact of within-clade recombination, we observed extensive variation even within the single clade from which the global pandemic arose.


title: A Focused Ethnographic Study of Alberta Cattle Veterinarians’ Decision Making about Diagnostic Laboratory Submissions and Perceptions of Surveillance Programs

text: The animal and public health communities need to address the challenge posed by zoonotic emerging infectious diseases. To minimize the impacts of future events, animal disease surveillance will need to enable prompt event detection and response. Diagnostic laboratory-based surveillance systems targeting domestic animals depend in large part on private veterinarians to submit samples from cases to a laboratory. In contexts where pre-diagnostic laboratory surveillance systems have been implemented, this group of veterinarians is often asked to input data. This scenario holds true in Alberta where private cattle veterinarians have been asked to participate in the Alberta Veterinary Surveillance Network-Veterinary Practice Surveillance, a platform to which pre-diagnostic disease and non-disease case data are submitted. Consequently, understanding the factors that influence these veterinarians to submit cases to a laboratory and the complex of factors that affect their participation in surveillance programs is foundational to interpreting disease patterns reported by laboratories and engaging veterinarians in surveillance. A focused ethnographic study was conducted with ten cattle veterinarians in Alberta. Individual in-depth interviews with participants were recorded and transcribed to enable thematic analysis. Laboratory submissions were biased toward outbreaks of unknown cause, cases with unusual mortality rates, and issues with potential herd-level implications. Decreasing cattle value and government support for laboratory testing have contributed to fewer submissions over time. Participants were willing participants in surveillance, though government support and collaboration were necessary. Changes in the beef industry and veterinary profession, as well as cattle producers themselves, present both challenges and opportunities in surveillance.


title: 1 Recurring Pitfalls in Hospital Preparedness and Response

text: Publisher Summary This chapter discusses the frequently occurring pitfalls in hospital preparedness and response. Significant systemic constraints make hospitals reluctant partners in preparedness and generate ineffective responses. Such a condition has been highlighted by the antiterrorism training and preparedness programs over the past few years. The results of numerous such exercises and actual responses across the United States indicate a list of pitfalls—such as communications, hospital security, and hospital staff management—which are related to the inherent system limitations that hinder the effective disaster operations in hospitals. Hospitals are required to have and exercise emergency-preparedness plans. An all-hazard approach can allow for preparedness and a measured, flexible response to a variety of potential incidents. Generally, plans may contain annexes for specific hazards, but an all-hazard plan should obviate a separate plan for each hazard—for example, an earthquake plan and a terrorism plan.


title: An Antiviral Mechanism of Nitric Oxide Inhibition of a Viral Protease

text: Abstract Although nitric oxide (NO) kills or inhibits the replication of a variety of intracellular pathogens, the antimicrobial mechanisms of NO are unknown. Here, we identify a viral protease as a target of NO. The life cycle of many viruses depends upon viral proteases that cleave viral polyproteins into individual polypeptides. NO inactivates the Coxsackievirus protease 3C, an enzyme necessary for the replication of Coxsackievirus. NO S-nitrosylates the cysteine residue in the active site of protease 3C, inhibiting protease activity and interrupting the viral life cycle. Substituting a serine residue for the active site cysteine renders protease 3C resistant to NO inhibition. Since cysteine proteases are critical for virulence or replication of many viruses, bacteria, and parasites, S-nitrosylation of pathogen cysteine proteases may be a general mechanism of antimicrobial host defenses.


title: Rennen vliegen rust nemen

text: Hoge werkdruk, personeelstekorten, inspelen op acute - soms dramatische - situaties. Het verpleegkundig beroep gaat vaak gepaard met stress, helemaal in deze crisistijd.(*) Wat kun je daaraan doen? ‘Stress is niet altijd het grootste probleem; veel verpleegkundigen nemen onvoldoende hersteltijd.’


title: Epidemiological aspects of astrovirus and coronavirus in poults in the South Eastern Region of Brazil

text: A survey of Turkey Coronavirus (TCoV) and Astrovirus (TAstV-2) prevalence was carried out from February to December during 2006 year in semiarid region of Brazil, from a turkey producer area, localized in South Eastern of Brazil. To asses the risk factor related to clinical material, climatic condition and type of RT-PCR applied, cloacal swabs (CS), faeces, sera, bursa of Fabricius (BF), thymus (TH) and spleen (SP) and ileum-caeca region were collected from 30-day-old poults suffering of enteritis episode characterized as poult enteritis mortality syndrome (PEMS). The PEMS clinical features were characterized by watery to foamy faeces, light brown-yellow in colour and low mortality rate. Meteorological data (rainfall and relative humidity) observed during along the study presented monthly average temperature ranging from 39.3 and 31.2ºC, precipitation in rainy season from 40 to 270.3 mm/month, and no rain during dry season. Simplex RT-PCR gave odds ratio (OR) values suggesting that ileum-caeca region is at higher chance (OR=1.9; p=0.9741) to have both viral RNA than faeces (OR=1.5; p=0.7319). However, multiplex RT-PCR showed 3.98 (p=0.89982) more chance to give positive results in faeces than CS at dry season. The major risk factors seem to be low rate of humidity and high temperatures at winter, probably responsible for spread, easily, the TCoV and TAstv-2 among the flocks. The positive results of both virus suggested that they can play an important role in enteric disorders, associated to low humidity and high temperatures frequently found in tropical countries.


title: Concept mapping as pre-task planning: A case study of three Japanese ESL writers

text: Abstract The majority of research to date on pre-task planning has investigated the impact of planning time on L2 learners’ oral production, and has generally reported its positive effects on their task performance. However, little research on planning has been conducted in writing contexts, and there is no firm evidence to demonstrate that pre-task planning promotes L2 learners’ written production in the ways that many researchers have reported for L2 speaking contexts. In this paper, I have explored whether and how concept mapping as a form of pre-task planning could benefit the writing performance of three Japanese ESL learners. I analysed four compositions from each of the learners, written with and without concept mapping; using measures of accuracy, complexity, fluency and [Hamp-Lyons, L., 1991. Reconstructing “Academic writing proficiency”. In: Hamp-Lyons, L. (Ed.), Assessing second language writing in academic contexts. Ablex, Norwood, NJ, pp. 127–153.] holistic measures of global quality, communicative quality, organisation, argumentation, linguistic accuracy, and linguistic appropriacy. I also examined through a questionnaire, retrospective interview, and logs, the learners’ applications of the strategy in their writing processes. Pre-task planning was associated positively with the overall measures of the learners’ written production during in-class compositions, with the exception of accuracy. Moreover, each learner made unique applications of the concept mapping strategy in their writing processes, suggesting that concept mapping may help ESL learners improve their composing but in ways unique to individual experience, motivation, and task conditions.


title: In Case You Haven't Heard…

text: China reported a major drop in new coronavirus cases to 2,641 on Feb. 15, a decline after Chinese officials began implementing measures to contain the illness, and a slight increase in new deaths to 143, Fox News reported Feb. 16. The new figures bring the total number of deaths from the virus, now known as COVID‐19, to 1,523 globally, and there are 66,492 confirmed cases in the country, according to China's National Health Commission. The outbreak has taxed health care workers, doctors and nurses throughout China, particularly in Wuhan, where it first originated in December 2019. Robots have been deployed in some hospitals to deliver medicines and disinfect surfaces so workers are free to do other tasks. Survivors of the outbreak in China could face a mental health toll after weeks of being quarantined from the rest of the world, which could create anxiety and fear, according to some mental health professionals.


title: Remote monitoring in clinical trials during the COVID‐19 pandemic

text: The COVID‐19 pandemic has rapidly challenged the pharmaceutical industry to implement remote clinical trials. The industry's lack of extensive experience with remote measurements initiates multiple questions about how to select candidates for remote collection, their validity, and regulatory implications of moving certain assessments to a remote mode. We propose a decision tree for migration of clinic to remote assessments and highlight activities required to ensure that these measurements are valid, safe, and usable.


title: Inhibitory C-type lectin receptors in myeloid cells

text: C-type lectin receptors encoded by the natural killer gene complex play critical roles in enabling NK cell discrimination between self and non-self. In recent years, additional genes at this locus have been identified with patterns of expression that extend to cells of the myeloid lineage where many of the encoded inhibitory receptors have equally important functions as regulators of immune homeostasis. In the present review we highlight the roles of some of these receptors including recent insights gained with regard to the identification of exogenous and endogenous ligands, mechanisms of cellular inhibition and activation, regulated expression within different cellular and immune contexts, as well as functions that include the regulation of bone homeostasis and involvement in autoimmunity.


Diagnosis and treatment strategy of coronavirus disease 2019 with cardiovascular disease in elderly patients


An outbreak of COVID‐19 caused by a new coronavirus: what we know so far


title: Microarray Chip Based Identification of a Mixed Infection of Bovine Herpesvirus 1 and Bovine Viral Diarrhea 2 From Indian Cattle

text: Bovine herpesvirus 1 (BHV1) and bovine viral diarrhea virus 2 (BVD2) are endemic in India although no mixed infection with these viruses has been reported from India. We report first mixed infection of these viruses in cattle during routine screening with a microarray chip. 62 of the 69 probes of BHV1 and 42 of the 57 BVD2 probes in the chip gave positive signals for the virus. The virus infections were subsequently confirmed by RT-PCR. We also discuss the implications of these findings.


title: Synthetic Antibodies with a Human Framework That Protect Mice from Lethal Sudan Ebolavirus Challenge

text: [Image: see text] The ebolaviruses cause severe and rapidly progressing hemorrhagic fever. There are five ebolavirus species; although much is known about Zaire ebolavirus (EBOV) and its neutralization by antibodies, little is known about Sudan ebolavirus (SUDV), which is emerging with increasing frequency. Here we describe monoclonal antibodies containing a human framework that potently inhibit infection by SUDV and protect mice from lethal challenge. The murine antibody 16F6, which binds the SUDV envelope glycoprotein (GP), served as the starting point for design. Sequence and structural alignment revealed similarities between 16F6 and YADS1, a synthetic antibody with a humanized scaffold. A focused phage library was constructed and screened to impart 16F6-like recognition properties onto the YADS1 scaffold. A panel of 17 antibodies were characterized and found to have a range of neutralization potentials against a pseudotype virus infection model. Neutralization correlated with GP binding as determined by ELISA. Two of these clones, E10 and F4, potently inhibited authentic SUDV and conferred protection and memory immunity in mice from lethal SUDV challenge. E10 and F4 were further shown to bind to the same epitope on GP as 16F6 with comparable affinities. These antibodies represent strong immunotherapeutic candidates for treatment of SUDV infection.


title: Influenza A☆

text: Abstract The influenza viruses, which contain single-stranded RNA, are classified into 3 types, A, B, and C and belong to the Orthomyxoviridae family of viruses. Types A and B cause annual epidemics and often pandemics of influenza illness, while type C is a less common disease with fewer symptoms.


title: Methods for air cleaning and protection of building occupants from airborne pathogens

text: Abstract This article aims to draw the attention of the scientific community towards the elevated risks of airborne transmission of diseases and the associated risks of epidemics or pandemics. The complexity of the problem and the need for multidisciplinary research is highlighted. The airborne route of transmission, i.e. the generation of pathogen laden droplets originating in the respiratory tract of an infected individual, the survivability of the pathogens, their dispersal indoors and their transfer to a healthy person are reviewed. The advantages and the drawbacks of air dilution, filtration, ultraviolet germicidal irradiation (UVGI), photocatalytic oxidation (PCO), plasmacluster ions and other technologies for air disinfection and purification from pathogens are analyzed with respect to currently used air distribution principles. The importance of indoor air characteristics, such as temperature, relative humidity and velocity for the efficiency of each method is analyzed, taking into consideration the nature of the pathogens themselves. The applicability of the cleaning methods to the different types of total volume air distribution used at present indoors, i.e. mixing, displacement and underfloor ventilation, as well as advanced air distribution techniques (such as personalized ventilation) is discussed.


title: What factors determine the survival of green innovative enterprises in China? - A method based on fsQCA

text: Increasingly serious environmental problems have generated a large number of small and medium-sized green innovative enterprises. Against the background of rapid technological changes and increasingly fierce market competition, survival is the main problem faced by these enterprises. Exploring the mechanisms and core elements that determine the survival of green innovation enterprises is of great practical significance for improving the survival probability of green innovation enterprises and achieving environmental improvement through green innovation. In this paper, 29 enterprises that have won the title of “Top 10 Green Innovative Enterprises” in China are considered the research objects, and the fuzzy set qualitative comparative analysis (fsQCA) method is used to examine the path combinations that affect the survival of enterprises from the perspectives of resource-based and dynamic capabilities. The findings are as follows. First, government support is key to the survival of green innovative enterprises; second, China's green innovative enterprises have a research and development dilemma, and only matching high R&D capacity with product competitiveness can enhance their survival capabilities; and third, the lack of resource base capacity is the key factor affecting the failure of green enterprises, and dynamic capacity is the key factor for the survival of green innovative enterprises. The main contribution of this paper to the field of management is that enterprises must always pay attention to the coordinated development of internal resource-based capability and external dynamic capability. Conversely, the Chinese government should provide high R&D support to enterprises with competitive products so that these enterprises can rapidly grow into leading enterprises through continuous innovation and drive the sustained and rapid development of China's green innovation industry.


Neurosurgery in Iraq at the Time of Corona


title: Pathogen evolution within host individuals as a primary cause of senescence

text: This paper discusses a novel theory of senescence: the community of pathogens within each host individual evolves during the life-time of the host, and in doing so progressively reduces host vigour. I marshal evidence that asymptomatic host individuals maintain persistent populations of viral pathogens; that these pathogens replicate; that they are often extremely variable; that selection within hosts causes the evolution of pathogens better able to exploit the host; that selection is host-specific; and that such evolving infections cause appreciable and progressive deterioration. Experimental approaches to testing the theory are discussed.


Preserving Operational Capability while Building Capacity during the COVID-19 Pandemic: A Tertiary Urology Centre's Experience


title: Viral evolution

text: Abstract In the last two decades, viruses have been used as model systems to study evolution in short periods of time. Due to their characteristics, virus adapt rapidly to changing conditions, thus allowing the quantification of several evolutionary features under controlled laboratory conditions. Here we review the basic biology of viruses and describe in detail a number of experiments performed with RNA viruses. Particular emphasis is devoted to the interpretation of the experiments and to the involved phenomenology. This analysis sometimes represents the basis to formulate simple evolutionary models that aim at describing the observed dynamics. In other cases, theoretical results have prompted the realization of related experiments, as we discuss. Concepts as fitness loss and fitness recovery, the error threshold, increased mutagenesis, viral sex, or viral competition and interference, are discussed in an empirical framework and from the associated theoretical point of view.


title: NF-κB activation by equine arteritis virus is MyD88 dependent and promotes viral replication

text: NF-κB, a family of transcription factors involved in different cell functions and immune responses is targeted by viruses. The mechanism of NF-κB signalling and its role in replication of EAV have not been investigated. We demonstrate that EAV infection in BHK-21 cells activates NF-κB, and this activation was found to be mediated through the MyD88 pathway. Infection of IKKβ(−/−) murine embryo fibroblasts (MEFs), which are deficient in NF-κB signalling, resulted in lower virus titre, less cytopathic effect, and reduced expression of viral proteins. These findings implicate the MyD88 pathway in EAV-induced NF-κB activation and suggest that NF-κB activation is essential for efficient replication of EAV.


Welcome to Infectious Disease Reports: a message from the Editor


title: Protection by Exclusion: Another Missed Opportunity to Include Pregnant Women in Research During the Coronavirus Disease 2019 (COVID-19) Pandemic

text: Coronavirus disease 2019 (COVID-19) is a novel infectious disease that started in Wuhan, China, and has rapidly spread all across the world. With limited ability to contain the virus and relatively high transmissibility and case fatality rates, governmental institutions and pharmaceutical companies are racing to find therapeutics and vaccines that target this novel coronavirus. However, once again, pregnant and breastfeeding women are excluded from participating in clinical trials during this pandemic. This “protection by exclusion” of pregnant women from drug development and clinical therapeutic trials, even during epidemics and pandemics, is not unprecedented. Moreover, it is both misguided and not justifiable and may have excluded them from potentially beneficial interventions. This is another missed opportunity to obtain pregnancy-specific safety and efficacy data, because therapeutics developed for men and nonpregnant women may not be generalizable to pregnant women. Therefore, we recommend and urge the scientific community and professional societies that, without clear justification for exclusion, pregnant women should be given the opportunity to be included in clinical trials for COVID-19 based on the concepts of justice, equity, autonomy, and informed consent.


title: Efficacy, Safety, and Pharmacokinetics of a New 10 % Liquid Intravenous Immunoglobulin Containing High Titer Neutralizing Antibody to RSV and Other Respiratory Viruses in Subjects with Primary Immunodeficiency Disease

text: PURPOSE: Immune globulins for IgG supplementation have been produced for over 35 years with essentially no differentiating features regarding their specific antibody composition. Furthermore, the compositions of plasma donor pools used for IG manufacturing are not standardized. While all immune globulin products meet the specifications set by the US FDA for antibodies to pathogens like measles and polio, they have variable levels of antibodies to other important viruses and infectious pathogens, particularly respiratory syncytial virus (RSV). METHODS: An IVIG was developed that satisfies the requirements for treating patients with primary immune deficiency disease (PIDD) and also has standardized elevated levels of RSV neutralizing antibodies (RI-002). Plasma donors who have naturally occurring high circulating levels of neutralizing anti-RSV antibody were selected as the source for manufacturing IVIG to treat patients with PIDD to prevent serious bacterial infections. While the introduction of the monoclonal antibody Palivizumab has had a dramatic impact in diminishing the burden of RSV disease in the pediatric population, it does not meet the standards for replacing the deficient immune compartments of patients with PIDD. RESULTS: Fifty-nine patients with PIDD at 9 different sites across the US were enrolled in this study and received regular infusions of RI-002 over the course of 1 year. CONCLUSIONS: There were zero serious bacterial infections, thus meeting the primary endpoint for this trial. The secondary endpoints including days missed from work due to infection, unscheduled visits to the physician, and days of hospitalization due to infection compared favorably to published reports of other IVIG products.


title: Coronavirus 229E-Related Pneumonia in Immunocompromised Patients

text: Coronaviruses strains 229E and OC43 have been associated with various respiratory illnesses ranging from the self-resolving common cold to severe pneumonia. Although chronic underlying conditions are major determinants of severe respiratory virus infections, few data about coronavirus-related pneumonia in immunocompromised patients are available. Here we report 2 well-documented cases of pneumonia related to coronavirus 229E, each with a different clinical presentation. Diagnosis was made on the basis of viral culture and electron microscopy findings that exhibited typical crown-like particles and through amplification of the viral genome by reverse transcriptase—polymerase chain reaction. On the basis of this report, coronaviruses should be considered as potential causative microorganisms of pneumonia in immunocompromised patients.


Letter to the editor in response to the article: “Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis (Kumar et al.)”


COVID‐19 infection in children and adolescents with cancer in Madrid


title: Frailty and COVID-19: A Systematic Scoping Review

text: Older people have paid a huge toll in terms of mortality during the coronavirus disease-19 (COVID-19) pandemic Frailty may have contributed to the vulnerability of older people to more severe clinical presentation We aimed at reviewing available evidence about frailty and COVID-19 We searched PUBMED, Web of Science, and EMBASE from 1 December 2019 to 29 May 2020 Study selection and data extraction were performed by three independent reviewers Qualitative synthesis was conducted and quantitative data extracted when available Forty papers were included: 13 editorials, 15 recommendations/guidelines, 3 reviews, 1 clinical trial, 6 observational studies, 2 case reports Editorials and reviews underlined the potential clinical relevance of assessing frailty among older patients with COVID-19 However, frailty was only investigated in regards to its association with overall mortality, hospital contagion, intensive care unit admission rates, and disease phenotypes in the few observational studies retrieved Specific interventions in relation to frailty or its impact on COVID-19 treatments have not been evaluated yet Even with such limited evidence, clinical recommendations on the use of frailty tools have been proposed to support decision making about escalation plan Ongoing initiatives are expected to improve knowledge of COVID-19 interaction with frailty and to promote patient-centered approaches


title: Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses

text: RNA viruses encode an RNA-dependent RNA polymerase (RdRp) that catalyzes the synthesis of their RNA(s). In the case of positive-stranded RNA viruses belonging to the order Nidovirales, the RdRp resides in a replicase subunit that is unusually large. Bioinformatics analysis of this non-structural protein has now revealed a nidoviral signature domain (genetic marker) that is N-terminally adjacent to the RdRp and has no apparent homologs elsewhere. Based on its conservation profile, this domain is proposed to have nucleotidylation activity. We used recombinant non-structural protein 9 of the arterivirus equine arteritis virus (EAV) and different biochemical assays, including irreversible labeling with a GTP analog followed by a proteomics analysis, to demonstrate the manganese-dependent covalent binding of guanosine and uridine phosphates to a lysine/histidine residue. Most likely this was the invariant lysine of the newly identified domain, named nidovirus RdRp-associated nucleotidyltransferase (NiRAN), whose substitution with alanine severely diminished the described binding. Furthermore, this mutation crippled EAV and prevented the replication of severe acute respiratory syndrome coronavirus (SARS-CoV) in cell culture, indicating that NiRAN is essential for nidoviruses. Potential functions supported by NiRAN may include nucleic acid ligation, mRNA capping and protein-primed RNA synthesis, possibilities that remain to be explored in future studies.


title: Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients

text: Abstract Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥ 140 mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P < 0.01). At admission, hyperglycaemic vs normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P < 0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P < 0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P < 0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.


title: Epidemiology of severe acute respiratory infections from hospital-based surveillance in Madagascar, November 2010 to July 2013

text: BACKGROUND: Few comprehensive data exist regarding the epidemiology of severe acute respiratory infections (SARI) in low income countries. This study aimed at identifying etiologies and describing clinical features of SARI-associated hospitalization in Madagascar. METHODS: It is a prospective surveillance of SARI in 2 hospitals for 3 years. Nasopharyngeal swabs, sputum, and blood were collected from SARI patients enrolled and tested for viruses and bacteria. Epidemiological and clinical information were obtained from case report forms. RESULTS: Overall, 876 patients were enrolled in the study, of which 83.1% (728/876) were tested positive for at least one pathogen. Viral and bacterial infections occurred in 76.1% (667/876) and 35.8% (314/876) of tested samples, respectively. Among all detected viruses, respiratory syncytial virus (RSV) was the most common (37.7%; 348/924) followed by influenza virus A (FLUA, 18.4%; 170/924), rhinovirus (RV, 13.5%; 125/924), and adenovirus (ADV, 8.3%; 77/924). Among bacteria, Streptococcus pneumoniae (S. pneumoniae, 50.3%, 189/370) was the most detected followed by Haemophilus influenzae type b (Hib, 21.4%; 79/370), and Klebsiella (4.6%; 17/370). Other Streptococcus species were found in 8.1% (30/370) of samples. Compared to patients aged less than 5 years, older age groups were significantly less infected with RSV. On the other hand, patients aged more than 64 years (OR = 3.66) were at higher risk to be infected with FLUA, while those aged 15–29 years (OR = 3.22) and 30–64 years (OR = 2.39) were more likely to be infected with FLUB (influenza virus B). CONCLUSION: The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Amongst young children, the demonstrated burden of RSV should guide clinicians for a better case management of children. These findings reveal the need to develop point-of-care tests to avoid overuse of antibiotics and to promote vaccine that could reduce drastically the RSV hospitalizations.


title: Epidemiological characteristics of COVID-19 patients in convalescence period

text: This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = −0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.


title: May COVID-19 outbreaks lead to a worsening of skin chronic inflammatory conditions?

text: The emergence of the novel beta Coronavirus has raised serious concerns due to the virus rapid dissemination worldwide. Many areas throughout the world are now experiencing the COVID 19 outbreaks with government and policy authorities taking many aggressive isolation or restriction measures, drastically reducing also patient’s visits and limiting only to the most urgent ones such as oncological visits or emergencies. Several studies have demonstrated a relationship between increased weight, obesity, diabetes, hypertension and inflammatory skin diseases. Furthermore, weight loss interventions have been shown to improve psoriasis, as well as hidradenitis suppurativa, and increase responsiveness to treatment of this conditions. We suppose that due to aggressive isolation or restriction measures, in the next future dermatologist will face with a common worsening of chronic skin inflammatory conditions due to reduced physical activities, increased intake of calories with the derived increase body weight and always more frequent treatment discontinuation. It is time to start potential preventive strategies which could limit the expected negative impact of COVID-19 related quarantine on skin diseases.


Challenges and Responsibilities in Caring for the Most Vulnerable During the COVID‐19 Pandemic


Curso clínico de la COVID-19 en pacientes con hipertensión arterial pulmonar


title: As ACA marks 10th anniversary, MH care even more critical during COVID‐19

text: March 23, 2020, marked the 10th anniversary of the Affordable Care Act (ACA), which, despite some ups and downs over the past decade, has expanded the scope of coverage for millions of people with mental illnesses and substance use disorders (SUDs).


title: Development of a negative pressure hood for isolation and transportation of individual patient with respiratory infectious disease

text: Abstract The frequent and sudden occurrence of both known and unknown infectious diseases can cause global social panic. If the source of infection can be effectively controlled in the early stages of an outbreak, the spread of infectious diseases can be prevented. In view of this situation, this study developed for infectious or suspected infectious patients a negative pressure isolation hood which effectively achieves direct individual isolation during the early stages of disease outbreak, and facilitates long-distance transport. The hood body is made of flexible transparent polyvinyl chloride (PVC) material, and the combination of the hood material is airtight. The unique inflatable column support structure and the design of the inflatable neck sleeve effectively ensure both stiffness and air tightness of the hood body. The electrical exhaust system maintains a stable negative pressure environment inside the hood, and polluted air inside the hood can be purified by a high efficiency filter. Test results showed that the internal noise of the hood was 68 ± 1 dB (A), the air exhaust volume of the electric exhaust system was not <200 L/min, and the filtration efficiency of the filter to 0.3 μm particles was >99.99%, indicating that the hood achieved effective isolation protection for patients with respiration infectious diseases.


title: Current awareness on yeast

text: In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (4 weeks journals ‐ search completed 10th. Nov. 2004)


title: Mysterious Virus: A Review on Behavior and Treatment Approaches of the Novel Coronavirus, 2019-nCoV

text: Abstract At the end of the year 2019, the novel coronavirus (2019-nCoV) was spreading in Wuhan, China, and the outbreak process has a high speed. It was recognized as a pandemic by the World Health Organization (WHO) on 11 March 2020. Coronaviruses are enveloped and single-stranded RNA that have several families including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The pathogenesis mechanism and disease outcomes of SARS and MERS are now clear to some extent, but little information is available for 2019-nCoV. This newly identified corona virus infection represents flu-like symptoms, but usually the first symptoms are fever and dry cough. There has been no specific treatment against 2019-nCoV up to now, and physicians only apply supportive therapy. In the present article, we made an attempt to review the behavior of the virus around the world, epidemiology, a pathway for influx into the host cells, clinical presentation, as well as the treatments currently in use and future approaches; nitazoxanide may be our dream drug. We hope that this review has a positive impact on public knowledge for helping to deal with the 2019-nCoV and move one step forward toward its treatment in the near future.


title: A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease

text: Live-attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3′-5′ exonuclease activity (ExoN) that likely functions in RNA proofreading. In this study, we demonstrate that engineered inactivation of SARS-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged, and immunocompromised mouse models of human SARS. The ExoN inactivation genotype and mutator phenotype are stable and do not revert to virulence, even after serial passage or long-term persistent infection in vivo. Our approach represents a strategy with potential for broad applications for the stable attenuation of coronaviruses and possibly other RNA viruses.


COVID-19 and Crimean Congo Hemorrhagic Fever: Similarities and Differences


title: Frequency of Common Viruses in Etiology of Acute Respiratory Tract Infections

text: OBJECTIVE: To determine the frequency rate of C. pneumoniae, rhinovirus, respiratory syncytial virus (RSV), influenza virus, metapneumovirus, adenovirus’, parainfluenza virus and coronavirus in acute respiratory tract infections in children. METHODS: One hundred nine pediatric patients having respiratory tract infections were included in this study. Real time PCR, DFA and cell culture method were used for detection of C. pneumoniae, RSV antigen and influenza virus respectively. Multiplex PCR was used for detection of other viruses. RESULTS: No C. pneumoniae DNA was detected in the samples. Virus was detected in 43 cases from larynx swabs (43/109, 39.4 %). The frequency order of the viral agents detected were as follows; rhinoviruses 14.7 %, RSV B 7.3 %, influenza A 6.4 %, metapneumovirus 3.6 %, adenovirus 3.6 %, coronavirus 0.9 %, parainfluenzavirus type 3, 0.9 %, parainfluenzavirus type 4, 0.9 % and RSV A 0.9 %. Sensitivity of the PCR and DFA methods for the diagnosis of RSV infections were detected as 100 % and 100 %, respectively. Specificity of the PCR and DFA methods for RSV infections were detected as 97 % and 100 % respectively. Sensitivity of the PCR and cell culture methods for influenzavirus infections were detected as 100 % and 100 %, respectively. Specificity of the PCR and DFA methods for RSV infections were detected as 96 % and 100 % respectively. CONCLUSIONS: Prevalence of viral agents was detected as 39.4 %. Influenza viruses and RSV were common. Metapneumovirus was also frequent (3.6 %). C. pneumoniae was not found to be a common agent for acute respiratory disease in children.


title: Chapter Eleven Communicating During a Public Health Crisis

text: “Communicating during a Public Health Crisis,” examines how communicating to the public and media during a public health or safety emergency is different. In a serious crisis, all affected people take in information differently, process information differently and act on information differently. This chapter incorporates the Centers for Disease Control and Prevention’s (CDC) best advice for communicating during a public health crisis, including infectious disease outbreaks, bioterrorism, chemical emergencies, natural disasters, nuclear accidents and radiation releases and explosions. This chapter also explores the growing role of social media that is now being used for a variety of traditional and new purposes from distress calls to disease surveillance.


title: Any unique image biomarkers associated with COVID-19?

text: OBJECTIVE: To define the uniqueness of chest CT infiltrative features associated with COVID-19 image characteristics as potential diagnostic biomarkers. METHODS: We retrospectively collected chest CT exams including n = 498 on 151 unique patients RT-PCR positive for COVID-19 and n = 497 unique patients with community-acquired pneumonia (CAP). Both COVID-19 and CAP image sets were partitioned into three groups for training, validation, and testing respectively. In an attempt to discriminate COVID-19 from CAP, we developed several classifiers based on three-dimensional (3D) convolutional neural networks (CNNs). We also asked two experienced radiologists to visually interpret the testing set and discriminate COVID-19 from CAP. The classification performance of the computer algorithms and the radiologists was assessed using the receiver operating characteristic (ROC) analysis, and the nonparametric approaches with multiplicity adjustments when necessary. RESULTS: One of the considered models showed non-trivial, but moderate diagnostic ability overall (AUC of 0.70 with 99% CI 0.56–0.85). This model allowed for the identification of 8–50% of CAP patients with only 2% of COVID-19 patients. CONCLUSIONS: Professional or automated interpretation of CT exams has a moderately low ability to distinguish between COVID-19 and CAP cases. However, the automated image analysis is promising for targeted decision-making due to being able to accurately identify a sizable subsect of non-COVID-19 cases. KEY POINTS: • Both human experts and artificial intelligent models were used to classify the CT scans. • ROC analysis and the nonparametric approaches were used to analyze the performance of the radiologists and computer algorithms. • Unique image features or patterns may not exist for reliably distinguishing all COVID-19 from CAP; however, there may be imaging markers that can identify a sizable subset of non-COVID-19 cases.


Skin manifestations in COVID‐19: A case series of five patients from Elazığ, Turkey


title: A novel CDPK1 inhibitor—a potential treatment for cryptosporidiosis in calves?

text: Cryptosporidium parvum is a zoonotic agent that infects humans and animals occasionally causing severe, watery diarrhoea. In immunocompetent hosts, cryptosporidiosis is self-limiting but can have a fatal outcome in immunocompromised individuals. Cryptosporidium is one of the most common causes of waterborne diseases (recreational water and drinking water) in humans, a leading cause of moderate to severe childhood diarrhoea, and a major agent of diarrhoea in calves leading to high economic losses and up to 10 % lethality. So far, available treatment options are insufficient for both veterinary and human clinical disease cases. Here, we report for the first time that the novel bumped kinase inhibitor (BKI) 1294 targeting the calcium-dependent protein kinase 1 (CDPK1) of Cryptosporidium is able to reduce the oocyst shedding of C. parvum by calves—its natural host—without obvious side effects.


title: Psychological Resilience During the COVID-19 Lockdown

text: Some individuals are more psychologically resilient to adversity than others, an issue of great importance during the emerging mental health issues associated with the COVID-19 pandemic. To identify factors that may contribute to greater psychological resilience during the first weeks of the nation-wide lockdown efforts, we asked 1,004 U.S. adults to complete assessments of resilience, mental health, and daily behaviors and relationships. Average resilience was lower than published norms, but was greater among those who tended to get outside more often, exercise more, perceive more social support from family, friends, and significant others, sleep better, and pray more often. Psychological resilience in the face of the pandemic is related to modifiable factors.


OUTBREAK OF COVID-19 IN A NURSING HOME IN MADRID


title: Vaccines for emerging pathogens: from research to the clinic

text: In this two‐part series of reviews, we have invited experts in their fields to contribute articles on the status of vaccine research and development for emerging pathogens. This topic has been brought into sharp focus in recent years following significant outbreaks of viral diseases such as those causing severe acute respiratory syndrome and Middle East respiratory syndrome, as well as devastating outbreaks of diseases caused by the Ebola, Marburg, Zika and Lassa fever viruses, to name only a few examples. Additionally, bacterial infections leading to bubonic and pneumonic plague, most notably in Madagascar in 2018, as well as malaria in many tropical countries, melioidosis in south east Asia and tularaemia in northern Europe and North America, have incurred significant morbidity and mortality. In this review series, the life cycle of these pathogens and the epidemiology of disease have been reviewed in the context of potential points of intervention for the prevention of human infection. Many of the emerging pathogens are zoonoses and, as such, there is scope for intervention at the animal/insect/environmental reservoir. Other pathogens covered in this review series are considered to be re‐emerging, such as multi‐drug resistant tuberculosis.


title: RETRACTED: Efficacy of novel antibody-based drugs against rhinovirus infection: In vitro and in vivo results

text: This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor in Chief. This article claimed to demonstrate the antiviral activity of ®Anaferon and ®Ergoferon against rhinovirus infection. This report did not reveal that the products tested for antiviral activity were in fact “homeopathically activated form[s] of antibodies,” as described in US patent 8,535,664 B2, submitted by O. I. Epstein and others. Homeopathy is an outmoded form of therapy that is not accepted by modern medical practice and is rejected by modern science. If the manuscript submitted to Antiviral Research had identified the nature of the materials being tested as homeopathic products, it would have been rejected. Now that the Editor in Chief is aware of this information, and has discussed the question extensively with other experts, he has decided to formally retract this article.


title: Therapeutic Immunoglobulin Selected for High Antibody Titer to RSV also Contains High Antibody Titers to Other Respiratory Viruses

text: Specific antibodies against infections most relevant to patients with primary immunodeficiency diseases are not routinely evaluated in commercial polyclonal immunoglobulin preparations. A polyclonal immunoglobulin prepared from plasma of donors having high neutralizing antibody titers to respiratory syncytial virus (RSV) was studied for the presence of antibody titers against seven additional respiratory viruses. While donors were not selected for antibody titers other than against RSV, the immunoglobulin preparation had significantly higher titers to 6 of 7 viruses compared to those present in 10 commercially available therapeutic immunoglobulin products (p ≤ 0.01 to p ≤ 0.001). To consider this as a donor-specific attribute, 20 random donor plasma samples were studied individually and identified a significant correlation between the RSV antibody titer and other respiratory virus titers: donors with high RSV titers were more likely to have higher titers to other respiratory viruses. These findings suggest either some humoral antiviral response bias or more frequent viral exposure of certain individuals.


World Union of Wound Healing Societies Meeting, 2020


title: The efficacy of herbal therapy on quality of life in patients with breast cancer: self-control clinical trial

text: BACKGROUND: Mounting evidence indicates that herbal therapy is effective in alleviating anxiety, lessening cancer treatment-related side-effects, and facilitating rehabilitation. This is the first trial to examine the herbal therapy of combined yunzhi and danshen on quality of life among breast cancer patients. METHODS: A multicenter, longitudinal, and self-control study was used. Eighty-two breast cancer patients were given combined yunzhi and danshen capsules for six months on a daily basis. Data collection including quality of life, vitality status and adverse effects were taken. RESULTS: Results showed a significant improvement in physical function, role-physical, role-emotion and health transition (P < 0.05). Patients also reported less fatigue, better quality of sleep, better appetite, more regular bowel movements and more stable emotions (P < 0.05). As far as side-effects were concerned, only mild discomforts including sore throat (13.4%) and dry mouth (9.8%) were recorded. CONCLUSION: The findings add clinical evidence to support the beneficial effects of herbal therapy on quality of life and vitality status in breast cancer patients. Therefore, herbal therapy has a potentially important role to play in managing psychological distress in cancer patients. This study also suggests that herbal therapy is clinically acceptable and can be used safely with breast cancer patients.


title: Virome Profiling of Bats from Myanmar by Metagenomic Analysis of Tissue Samples Reveals More Novel Mammalian Viruses

text: Bats are reservoir animals harboring many important pathogenic viruses and with the capability of transmitting these to humans and other animals. To establish an effective surveillance to monitor transboundary spread of bat viruses between Myanmar and China, complete organs from the thorax and abdomen from 853 bats of six species from two Myanmar counties close to Yunnan province, China, were collected and tested for their virome through metagenomics by Solexa sequencing and bioinformatic analysis. In total, 3,742,314 reads of 114 bases were generated, and over 86% were assembled into 1,649,512 contigs with an average length of 114 bp, of which 26,698 (2%) contigs were recognizable viral sequences belonging to 24 viral families. Of the viral contigs 45% (12,086/26,698) were related to vertebrate viruses, 28% (7,443/26,698) to insect viruses, 27% (7,074/26,698) to phages and 95 contigs to plant viruses. The metagenomic results were confirmed by PCR of selected viruses in all bat samples followed by phylogenetic analysis, which has led to the discovery of some novel bat viruses of the genera Mamastrovirus, Bocavirus, Circovirus, Iflavirus and Orthohepadnavirus and to their prevalence rates in two bat species. In conclusion, the present study aims to present the bat virome in Myanmar, and the results obtained further expand the spectrum of viruses harbored by bats.


title: Discovery of Hepatitis C Virus NS3 Helicase Inhibitors by a Multiplexed, High‐Throughput Helicase Activity Assay Based on Graphene Oxide

text: A GO‐to solution: A simple graphene oxide (GO)‐based assay to screen for selective inhibitors of a hepatitis C virus (HCV) helicase along with inhibitors of a severe acute respiratory syndrome coronavirus (SARS CoV) helicase was tested (see scheme). A single screen found five inhibitors highly selective for the HCV helicase orthologous to the SARS CoV helicase. Some of these hits were validated using the same GO‐based assay.[Image: see text]


title: Lectins from red algae and their biomedical potential

text: Lectins are unique proteins or glycoproteins of non-immune origin that bind specifically to carbohydrates. They recognise and interact reversibly to either free carbohydrates or glycoconjugates, without modifying their structure. Lectins are highly diverse and widely distributed in nature and have been extensively reported from various red algae species. Numerous red algae species have been reported to possess lectins having carbohydrate specificity towards complex glycoproteins or high-mannose N-glycans. These lectin-glycan interactions further trigger many biochemical responses which lead to their extensive use as valuable tools in biomedical research. Thus, owing to their exceptional glycan recognition property, red algae lectins are potential candidate for inhibition of various viral diseases. Hence, the present report integrates existing information on the red algae lectins, their carbohydrate specificity, and characteristics of purified lectins. Further, the review also reports the current state of research into their anti-viral activity against various enveloped viruses such as HIV, hepatitis, influenza, encephalitis, coronavirus and herpes simplex virus and other biomedical activities such as anti-cancer, anti-microbial, anti-inflammatory, anti-nociceptive and acaricidal activities.


title: "Transition to on‐line is possible: solution for simulation‐based teaching during pandemic"

text: In March 2020, Polish universities had to suspend all on‐site activities due to the SARS‐CoV‐2 pandemic. As a result, we were faced with the problem of how to convert a simulation‐based course in geriatrics into distance‐learning. The main focus of the original course (30 academic hours) is to expose fourth‐year medical students, working in teams of three, to eight simulated cases including acute dyspnea (pneumonia), behavior change (somatic delirium), and cardio‐pulmonary deterioration.


title: Encephalopathy only stroke codes (EoSC) do not result in rt-PA treatments

text: BACKGROUND: Isolated mental status changes as a presenting sign (EoSC+), are not uncommon stroke code triggers. As stroke alerts, they still require the same intensive resources be applied. We previously showed that EoSC+ strokes (EoSC+ Stroke+) account for 0.1–0.2% of all codes. Whether these result in thrombolytic treatment (rt-PA), and the characteristics/ risk factor profiles of EoSC+ Stroke+ patients, have not been reported. METHODS: Retrospective analysis of stroke codes from an IRB approved registry, from 2004 to 2018, was performed. EoSC+ was defined as a NIHSS>0 for Q1a, 1b, or 1c with remaining elements scored 0. Characteristics and risk factors were compared for EoSC+, EoSC−, EoSC+ Stroke+, and rt-PA (EoSC+ Stroke+TPA+) patients. RESULTS: EoSC+ occurred in 55/2982 (1.84%) of all stroke codes. EoSC+ Stroke+ occurred in 8/55 (14.5%) of EoSC+ codes and 8/2982 (0.27%) of all stroke codes. 6/8 (75%) of EoSC+ Stroke+ scored NIHSS=1. When comparing EoSC++versus EoSC−, Hispanic ethnicity (p=0.009), hypertension (p=0.02), and history of stroke/TIA (p=0.002) were less common in EoSC+. No demographic/risk factor differences were noted for EoSC+ Stroke+ vs. EoSC+ Stroke−. No cases of rt-PA eligibility/treatment were noted. In EoSC+ Stroke+ analysis, imaging positive stroke/intracranial hemorrhage was noted on only 3 cases (3/2982=0.10% of all stroke codes) and none were posterior stroke. CONCLUSIONS: EoSC+ rarely results in stroke/TIA (0.27%) or stroke (0.10%), and in our analysis never (0%) resulted in rt-PA. Sub-analysis did not show missed rt-PA or posterior strokes. Understanding characteristics, and knowing that EoSC+ Stroke+ patients are unlikely to receive rt-PA, may help triage stroke resources.


title: Effect of acute respiratory infections in infancy on pulmonary function test at 3 years of age: a prospective birth cohort study

text: INTRODUCTION: Acute respiratory infections (ARIs) in infancy may have a long-term impact on the developing respiratory system. We planned a prospective cohort study to determine the impact of ARI during infancy on the pulmonary function test indices at 3 years of age. METHODS: A cohort of normal, full-term newborns were followed up 6 monthly and during ARI episodes. Infant pulmonary function tests (IPFTs) were performed at baseline and each follow-up visit using tidal breathing flow-volume loop, rapid thoracoabdominal compression (RTC) and raised volume RTC manoeuvres. During each ARI episode, nasopharyngeal aspirates were tested for respiratory pathogens by real-time PCR. RESULTS: We screened 3421 neonates; 310 were enrolled; IPFT was performed in 225 (boys: 125 (55.6%)) at 3 years. During infancy, 470 ARI episodes were documented in 173 infants. At 3 years, children with history of any ARI episode during infancy had lower forced expiratory volume in 1 s (FEV(1.0)), forced expiratory volume in 0.75 s (FEV(0.75)), forced expiratory volume in 0.5 s (FEV(0.5)), forced expiratory flow between 25% and 75% of FVC (FEF(25–75)), and maximal expiratory flow at 25% of FVC (MEF(25)) as compared with those without any ARI episode during infancy. The ratio of tidal expiratory flow (TEF) at 25% or 50% of tidal expiratory volume to peak TEF (TEF(50) or TEF(25)/peak TEF) at 3 years was significantly increased in children who had ARI in infancy. CONCLUSIONS: ARI during infancy is associated with impaired pulmonary function indices such as increased resistance and decreased forced expiratory flow and volume at 3 years of age.


title: Chapter 16 Carbohydrate Microarrays as Essential Tools of Postgenomic Medicine

text: Publisher Summary Carbohydrates are essential biological molecules carrying important biological information. Carbohydrates are prominently displayed on the surface of cell membranes and expressed by virtually all secretory proteins in bodily fluids. This is achieved by the events of posttranslational protein modification called glycosylation. Importantly, expression of cellular glycans, in the form of either glycoproteins or glycolipids, is differentially regulated. Cell display of precise complex carbohydrates is characteristically associated with the stages or steps of embryonic development, cell differentiation, as well as transformation of normal cells to abnormally differentiated tumor or cancer cells. Sugar moieties are also abundantly expressed on the outer surfaces of the majority of viral, bacterial, protozoan, and fungal pathogens. Many sugar structures are pathogen specific, which makes them important molecular targets for pathogen recognition, diagnosis of infectious diseases, and vaccine development. Exploring the biological information content in carbohydrates is one of the current focuses of postgenomic research and technology development. Biophysical, biochemical, and immunological methods have proven very valuable in studying carbohydrate–carbohydrate and carbohydrate–protein interactions. Many well established immunochemical methods have been applied to determine the specificity and cross-reactivity of carbohydrate–antibody and carbohydrate–lectin interactions. A pressing need is, thus, the establishment of high-throughput technologies to enable the large-scale, multiplex analysis of carbohydrates and their cellular receptors. These include especially the characterization of immunological properties of carbohydrates that are important for medical applications of carbohydrate antigens and interactions of carbohydrates with other biomolecules or intact cells that play key roles in establishing comprehensive biological functions of essentially all existing living organisms.


title: The ecology and adaptive evolution of influenza A interspecies transmission

text: Since 2013, there have been several alarming influenza‐related events; the spread of highly pathogenic avian influenza H5 viruses into North America, the detection of H10N8 and H5N6 zoonotic infections, the ongoing H7N9 infections in China and the continued zoonosis of H5N1 viruses in parts of Asia and the Middle East. The risk of a new influenza pandemic increases with the repeated interspecies transmission events that facilitate reassortment between animal influenza strains; thus, it is of utmost importance to understand the factors involved that promote or become a barrier to cross‐species transmission of Influenza A viruses (IAVs). Here, we provide an overview of the ecology and evolutionary adaptations of IAVs, with a focus on a review of the molecular factors that enable interspecies transmission of the various virus gene segments.


title: Signal of Increased Opioid Overdose during COVID-19 from Emergency Medical Services Data

text: BACKGROUND: Individuals with opioid use disorder may be at heightened risk of opioid overdose during the COVID-19 period of social isolation, economic distress, and disrupted treatment services delivery. This study evaluated changes in daily number of Kentucky emergency medical services (EMS) runs for opioid overdose between January 14, 2020 and April 26, 2020. METHODS: We evaluated the statistical significance of the changes in the average daily EMS opioid overdose runs in the 52 days before and after the COVID-19 state of emergency declaration, March 6, 2020. RESULTS: Kentucky EMS opioid overdose daily runs increased after the COVID-19 state emergency declaration. In contrast, EMS daily runs for other conditions leveled or declined. There was a 17% increase in the number of EMS opioid overdose runs with transportation to an emergency department (ED), a 71% increase in runs with refused transportation, and a 50% increase in runs for suspected opioid overdoses with deaths at the scene. The average daily EMS opioid overdose runs with refused transportation increased significantly, doubled to an average of 8 opioid overdose patients refusing transportation every day during the COVID-19-related study period. CONCLUSIONS: This Kentucky-specific study provides empirical evidence for concerns that opioid overdoses are rising during the COVID-19 pandemic and calls for sharing of observations and analyses from different regions and surveillance systems with timely data collection (e.g., EMS data, syndromic surveillance data for ED visits) to improve our understanding of the situation, inform proactive response, and prevent another big wave of opioid overdoses in our communities.


title: Oligomerized transferrin receptors are selectively retained by a lumenal sorting signal in a long-lived endocytic recycling compartment

text: Cross-linking of surface receptors results in altered receptor trafficking in the endocytic system. To better understand the cellular and molecular mechanisms by which receptor cross-linking affects the intracellular trafficking of both ligand and receptor, we studied the intracellular trafficking of the transferrin receptor (TfR) bound to multivalent-transferrin (Tf10) which was prepared by chemical cross- linking of transferrin (Tf). Tf10 was internalized about two times slower than Tf and was retained four times longer than Tf, without being degraded in CHO cells. The intracellular localization of Tf10 was investigated using fluorescence and electron microscopy. Tf10 was not delivered to the lysosomal pathway followed by low density lipoprotein but remained accessible to Tf in the pericentriolar endocytic recycling compartment for at least 60 min. The retained Tf10 was TfR-associated as demonstrated by a reduction in surface TfR number when cells were incubated with Tf10. The presence of Tf10 within the recycling compartment did not affect trafficking of subsequently endocytosed Tf. Retention of Tf10 within the recycling compartment did not require the cytoplasmic domain of the TfR since Tf10 exited cells with the same rate when bound to the wild-type TfR or a mutated receptor with only four amino acids in the cytoplasmic tail. Thus, cross-linking of surface receptors by a multivalent ligand acts as a lumenal retention signal within the recycling compartment. The data presented here show that the recycling compartment labeled by Tf10 is a long-lived organelle along the early endosome recycling pathway that remains fusion accessible to subsequently endocytosed Tf.


title: Studying Coronavirus–Host Protein Interactions

text: To understand the molecular mechanisms of viral replication and pathogenesis, it is necessary to establish the virus–host protein interaction networks. The yeast two-hybrid system is a powerful proteomic approach to study protein–protein interactions. After the identification of specific cellular factors interacting with the target viral protein using the yeast two-hybrid screening system, co-immunoprecipitation and confocal microscopy analyses are often used to verify the virus–host protein interactions in cells. Identification of the cellular factors required for viral survival or eliminating virus infected cells could help scientists develop more effective antiviral drugs. Here we summarize a standard protocol used in our lab to study the coronavirus–host protein interactions, including yeast two-hybrid screening, co-immunoprecipitation, and immunofluorescence microscopy analyses.


title: Détection, quantification et analyse des génomes viraux dans les infections à herpèsvirus humains 6 et 7 (HHV-6, HHV-7)

text: Résumé La détection, la quantification et l’analyse génétique des génomes viraux ont été progressivement introduites dans la pratique quotidienne de la virologie médicale. Dans le cas des infections à herpèsvirus humains 6 et 7 (HHV-6, HHV-7), la détection de l’ADN viral a permis d’impliquer ces infections dans des maladies au-delà de ce qui avait été mis en évidence par les méthodes conventionnelles (culture, sérologie) notamment chez les sujets immunodéprimés. La quantification, en particulier grâce à l’apport récent de la PCR en temps réel, est susceptible d’établir la distinction entre latence et réactivation virales, de prédire la survenue d’évènements cliniques, de suivre les effets d’une thérapeutique spécifique. L’analyse génétique a conduit à l’identification de variants et contribué à caractériser les mutations associées à la résistance aux antiviraux. Comme le montre l’étude des herpèsvirus, ces techniques moléculaires ont aussi des limites qu’il faut connaître mais constituent indiscutablement un progrès décisif en virologie clinique. Abstract The detection, quantification and genetic analysis of viral genomes have become a common practice in clinical virology. This is exemplified by the study of human herpesviruses 6 and 7. The detection of viral DNA has led to implicate theses viruses in human diseases far beyond the evidence obtained by conventional approaches such as virus culture and serology. This is specially the case for immunocompromised subjects. The quantitation of DNA, in particular by means of real-time PCR, is now susceptible to differenciate reactivation from latency, predict the occurrence of clinical events, and monitor the efficacy of antiviral therapy. Genetic analyses have permitted the characterization of variant-specific polymorphisms and mutations responsible for resistance to antivirals. Despite some limitations that users have to be aware of, the study of viral genomes is an outstanding progress in medical virology.


Des propositions pragmatiques pour le suivi respiratoire des patients après une infection à SARS-CoV-2 établies en un temps record à destination de tous les professionnels de santé


title: Trends of participation of post-graduate year training program for dentists in Taiwan dental training institutions from 2010 to 2018

text: BACKGROUND/PURPOSE: The licensed dentists in Taiwan should join the post-graduate year training program for dentists (PGYD) since 2010. This study aimed to analyze the project types and the geographical distribution of the PGYD training institutions in Taiwan from 2010 to 2018. MATERIALS AND METHODS: From 2010 to 2018, 735 hospitals and clinics participated in four types of PGYD project including hospital as the single training institution (project A), clinic as the single training institution (project B), hospital as the main training institution in the joint training group (project C), and clinic as the main training institution in the joint training group (project D). The project types and the geographical distribution of the training institutions were analyzed. RESULTS: The 735 PGYD training projects were proposed by the 735 dental institutions. The project number grew from 119 in 2010 to 195 in 2018. The most common project type was project B (307, 41.8%), followed by the project A (249, 33.9%), the project D (101, 13.7%), and the project C (78, 10.6%). Geographically, these 735 main training institutions were located most commonly in northern region of Taiwan (379, 51.6%), followed by the central region of Taiwan (171, 23.3%), southern region of Taiwan (156, 21.2%), and eastern region of Taiwan (29, 3.9%). CONCLUSION: Hospital or clinic as the single training institution is the two most common PGYD project types in Taiwan from 2010 to 2018. These single or main dental training institutions are mainly located in the northern, central, and southern regions of Taiwan.


title: Chapter 11 Pathology The Clinical Description of Human Disease

text: …Future discoveries will not likely be made by morphologists ignorant of molecular biologic findings, or by biologists unaware or scornful of morphologic data, but by those willing and capable of integrating them through a team approach… Rosai [1].


Chapter 5 Innate Humoral Defense Factors


title: Prevalence and complete genome of bovine norovirus with novel VP1 genotype in calves in China

text: Bovine norovirus (BNoV) is a diarrhea-causing pathogen of calves. In this study, 211 diarrheic fecal samples were collected from 25 farms across six provinces in China, between November 2017 and September 2018. 20.4% of the samples were detected as BNoV-positive by RT-PCR. Phylogenetic analyses based on RdRp, VP1, and VP2 fragments revealed these BNoV strains had unique evolutionary characteristics. The complete genome of strain Bo/BET–17/18/CH was successfully sequenced. It was 7321 nucleotides (nt) in length, shared 79.4–80.9% nt identity with all five BNoV genomes, clustered on a separate branch of the phylogenetic tree, suggesting that strain Bo/BET–17/18/CH could represent a novel BNoV strain. Two interesting characteristics were found in the genome: (i) the VP1 sequence differed greatly from known BNoV VP1 sequences; (ii) a recombination event is predicted within the ORF1–ORF2 overlap. Moreover 16.3% (7/43) of the BNoV were identified as the novel VP1 genotype, which were distributed on four farms across two provinces, indicating that the novel VP1 genotype strain has spread. To our knowledge, this is first description of the molecular and genomic characteristics of BNoV in China. These findings extend our understanding of the genetic evolution and epidemics of BNoV.


title: Maternal choline and respiratory coronavirus effects on fetal brain development

text: Prenatal COVID-19 infection is anticipated by the U.S. Centers for Disease Control to affect fetal development similarly to other common respiratory coronaviruses through effects of the maternal inflammatory response on the fetus and placenta. Plasma choline levels were measured at 16 weeks gestation in 43 mothers who had contracted common respiratory viruses during the first 6–16 weeks of pregnancy and 53 mothers who had not. When their infants reached 3 months of age, mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R), which assesses their infants’ level of activity (Surgency), their fearfulness and sadness (Negativity), and their ability to maintain attention and bond to their parents and caretakers (Regulation). Infants of mothers who had contracted a moderately severe respiratory virus infection and had higher gestational choline serum levels (≥7.5 mM consistent with U.S. Food and Drug Administration dietary recommendations) had significantly increased development of their ability to maintain attention and to bond with their parents (Regulation), compared to infants whose mothers had contracted an infection but had lower choline levels (<7.5 mM). For infants of mothers with choline levels ≥7.5 μM, there was no effect of viral infection on infant IBQ-R Regulation, compared to infants of mothers who were not infected. Higher choline levels obtained through diet or supplements may protect fetal development and support infant early behavioral development even if the mother contracts a viral infection in early gestation when the brain is first being formed.


title: Respiratory Presentation of Pediatric Patients in the 2014 Enterovirus D68 Outbreak

text: Background. In the fall of 2014, a North American outbreak of enterovirus D68 resulted in a significant number of pediatric hospital admissions for respiratory illness throughout North America. This study characterized the clinical presentation and risk factors for a severe clinical course in children admitted to British Columbia Children's Hospital during the 2014 outbreak. Methods. Retrospective chart review of patients with confirmed EV-D68 infection admitted to BCCH with respiratory symptoms in the fall of 2014. Past medical history, clinical presentation, management, and course in hospital was collected and analyzed using descriptive statistics. Comparison was made between those that did and did not require ICU admission to identify risk factors. Results. Thirty-four patients were included (median age 7.5 years). Fifty-three percent of children had a prior history of wheeze, 32% had other preexisting medical comorbidities, and 15% were previously healthy. Ten children (29%) were admitted to the pediatric intensive care unit. The presence of complex medical conditions (excluding wheezing) (P = 0.03) and copathogens was associated with PICU admission (P = 0.02). Conclusions. EV-D68 infection resulted in severe, prolonged presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of wheeze and preexisting medical comorbidities appear to be most severely affected, but the virus can also cause wheezing in previously well children.


Severe Systemic Calciphylaxis in a Young Cat


title: Plagues and adaptation: Lessons from the Felidae models for SARS and AIDS

text: Abstract Research studies of infectious disease outbreaks in wild species of the cat family Felidae have revealed unusual details regarding forces that shape population survival and genetic resistance in these species. A highly virulent feline coronavirus epidemic in African cheetahs, a disease model for human SARS, illustrates the critical role of ancestral population genetic variation. Widespread prevalence of species specific feline immunodeficiency virus (FIV), a relative of HIV–AIDS, occurs with little pathogenesis in felid species, except in domestic cats, suggesting immunological adaptation in species where FIV is endemic. Resolving the interaction of host and pathogen genomes can shed new light on the process of disease outbreak in wildlife and in humankind. The role of disease in endangered populations and species is difficult to access as opportunities to monitor outbreaks in natural populations are limited. Conservation management may benefit greatly from advances in molecular genetic tools developed for human biomedical research to assay the biodiversity of both host species and emerging pathogen. As these examples illustrate, strong parallels exist between disease in human and endangered wildlife and argue for an integration of the research fields of comparative genomics, infectious disease, epidemiology, molecular genetics and population biology for an effective proactive conservation approach.


title: Effect of hydroxychloroquine on prevention of COVID-19 virus infection among healthcare professionals: a structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: Comparison of the effect of hydroxychloroquine with placebo to prevent infection from the COVID -19 virus among healthcare professionals TRIAL DESIGN: Single centre, 2-arm, double-blind randomised (ratio 1:1) placebo-controlled trial PARTICIPANTS: Treatment staff who are in contact with patients and have at least 3 shifts a week in Arash hospital affiliated with Tehran University of Medical Sciences, in Iran and who consent to participate in the study. Exclusion criteria include: History of COVID -19 virus infection, clinical symptoms such as fever, nausea, dyspnea and myalgia in the past two months, history of underlying diseases hypersensitivity to hydroxychloroquine and G6PD enzyme deficiency. INTERVENTION AND COMPARATOR: Intervention group: Hydroxychloroquine 200 mg tablet of Amin Pharmaceutical. Control group: placebo which is completely similar in form and taste to 200 mg hydroxychloroquine tablet and is manufactured by the same factory (Amin Pharmacy). The dosage is two tablets daily, once a week for one to three months (based on the duration of the Coronavirus epidemic in Tehran). MAIN OUTCOMES: Confirmed COVID-19 virus infection using Polymerase chain reaction (PCR) test is the primary outcome. The time period for measuring the primary outcome is any infection within the trial period up to one month after taking the last dose. RANDOMISATION: The randomized block allocation method was developed using Stata version 15 software by an independent researcher, using a block size of six. Allocation to the two treatment groups will be conducted by this researcher using paper labels (random 10-digit codes) in a 1:1 ratio t The labels will be attached to the drug packages in order of randomization. Drug packages will be arranged in a box according to the randomization list. BLINDING (MASKING): Participants and caregivers are blinded to group assignment and the data will be analyzed by an independent statistical expert who is unaware of the treatment allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 282 participants will be randomised with 141 participants the Hydroxychloroquineeach intervention group and 141 participants to the placebo control group TRIAL STATUS: The protocol version number is 99-1-101-47091 and the approval ID is IR.TUMS.VCR.REC.1399.001 and recruitment began April 7, 2020, and is anticipated to be complete by August 7, 2020. TRIAL REGISTRATION: The name of the trial register is Iranian registry of clinical trial (IRCT), registration number is IRCT20120826010664N6, date of trial registration is April 7, 2020, FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Genetic and Molecular Biological Analysis of Protein-Protein Interactions in Coronavirus Assembly


title: Leader Sequence

text: Abstract The region of a messenger RNA (mRNA) molecule that precedes the coding sequence of a gene is called the ‘leader sequence’. This region is also known as the ‘five prime untranslated region’ (Figure 1) of the mRNA. Leader sequences have the propensity for forming secondary structures (stem-loops) by base pairing of complementary sequences. They are involved in the regulation of gene expression in eukaryotes and prokaryotes. In eukaryotes, the leader sequence may vary from few nucleotides to more than 1000 nucleotides. In prokaryotes, the leader sequences are usually short and at times contain an attenuator segment that is translated to a short-leader peptide. The leader peptide functions to terminate transcripts before the RNA polymerase reaches the first structural gene of the operon. The leader sequences in viruses have been shown to play an important role in the regulation of gene expression, replication, and pathogenicity. Mutations in the leader sequences of cellular mRNAs can have implications for disease and tumorigenesis.


title: Outbreak of acute febrile respiratory illness caused by human adenovirus B P14H11F14 in a military training camp in Shandong China

text: This study reports an outbreak of acute febrile respiratory illness caused by human adenovirus B [P14H11F14] in a military training center in China between May and June 2014. In total, 164 military personnel were affected, and two patients were admitted into the intensive care unit of the military regional central hospital. A HAdV-B [P14H11F14] virus was confirmed as the etiological pathogen of this acute outbreak of febrile respiratory illness based on clinical manifestations, epidemiological characteristics, specific molecular detection results, phylogenetic analysis, and serological assays. The virus was isolated by the rhabdomyosarcoma cell culture method, and the complete sequences of the E1A, penton base, hexon, and fiber genes were determined and deposited in the GenBank database. Phylogenetic and sequence homology analyses indicated that the isolated strain is most closely related to some HAdV-55 strains from mainland China. However, this strain appeared to be less virulent than former HAdV-55 strains. According to the chest X-ray results of 31 affected patients, there was no radiological evidence of pneumonia. The most frequent symptoms in these patients were sore throat (95.12 %, 156/164) and tonsillitis (93.29 %, 153/164). During the course of the outbreak, incorrect response measures and some potential risk factors, such as fire training and marching training, may have exacerbated the spread of the infection. This outbreak illustrates the urgent need to improve the epidemiological and etiological surveillance of HAdV infections and to improve the ability of doctors and health officials in basic units of the Chinese army to respond effectively to febrile respiratory illness.


title: Specific coagulation markers may provide more therapeutic targets in COVID‐19 patients receiving prophylactic anticoagulant

text: I read with interest the recent published article from Professor Robert L. Medcalf, entitled “Fibrinolysis and COVID‐19: a plasmin paradox” [1]. As an indirect marker of thrombin and plasmin activation, D‐dimer has been suggested to guide anticoagulant treat in COVID‐19 patients [2, 3]. However, D‐dimer may not be able to reflect accurate fibrinolysis status of COVID‐19 patients, and therefore can’t guide the possible antifibrinolysis or thrombolytic therapy in different stages of COVID‐19, as Professor Robert L. Medcalf discussed. Hence, we speculated that measuring direct markers of thrombin, plasmin and so on, may provide more therapeutic targets in COVID‐19 patients with coagulopathy.


title: A Roadmap to Reopening a Neurosurgical Practice in the age of COVID-19

text: Abstract The Coronavirus Disease 2019 (COVID-19) outbreak has left a lasting mark on medicine globally. Here we outline the steps that the Lenox Hill Hospital/Northwell Health Neurosurgery Department—located within the epicenter of the pandemic in New York City—is currently taking to recover our neurosurgical efforts in the age of COVID-19. We outline measurable milestones to identify the transition to the recovery period and hope these recommendations may serve as a framework for an effective path forward. We believe that recovery following the COVID-19 pandemic offers unique opportunities to disrupt and rebuild the historical patient and office experience as we evolve with modern medicine in a post-COVID-19 world.


title: Detection and characterisation of novel bocavirus (genus Bocaparvovirus) and gastroenteritis viruses from asymptomatic pigs in Ireland

text: BACKGROUND: Livestock animals have been the assumed source of several human epidemics in recent years, for example, influenza H1N1, rotavirus G8/G9, and MERS-CoV. Surveillance of novel viruses in animals is essential to evaluate the risk to human and animal health and to determine any economic impact, for example, failure to thrive. There is a paucity of data regarding detection and characterisation of gastroenteritis viruses, particularly novel viruses, in porcines in Ireland. Recently, a number of small novel porcine DNA viruses have emerged globally, for example, torque teno sus virus, porcine bocavirus, and parvoviruses 2 & 4, and little is known about the biology and potential pathogenicity of these viruses. Bocaparvovirus is a genetically distinct group of viruses which has been recently detected in humans and animals. METHODS: In this study, the presence of gastroenteritis viruses (rotavirus A, porcine circovirus, adenovirus, and porcine bocavirus) was investigated in a selection of archived faecal samples from asymptomatic piglets from a commercial farm in Ireland. A total of 104 specimens were pooled and screened using conventional molecular techniques (PCR and RT-PCR), a subset of specimens (n=44) were then examined individually. Viral diversity was then investigated using statistical and phylogenetic techniques. RESULTS: Initial screening showed a high prevalence of PBoV in this farm, with the formation of three distinct groups in phylogenetic analysis. Other viruses were also investigated in this study with the first report of PCV, PAdV and lineage I G5 RVA in Ireland. Some specimens contained >1 virus, with statistical analysis indicating a strong correlation for mixed infections of PBoV and PAdV on this farm. CONCLUSION: Investigating the diversity of circulating enteric viruses on Irish porcine farms is important to improve the prophylactic tools available and to facilitate the early detection of changes in circulating viruses.


title: Alcohol and isolation: Experts comment on drinking behavior during COVID‐19

text: Are people drinking more now that they are locked in a house with their nearest and dearest, facing job loss or having lost a job, bored and stressed? Probably. Is drinking a healthy way of coping? No.


title: Hemagglutination by calf diarrhea coronavirus

text: Abstract The virus was grown in BEK-1 cells, a stable cell line from bovine embryo kidney, and tested for hemagglutination (HA) with erythrocytes of a variety of species at 4°C, room temperature and 37°C. HA was observed at all temperatures with chicken, mouse, rat, and hamster erythrocytes but not with erthyrocytes of human (O), cattle, horses, sheep, guinea pigs, geese, ducks, pigeons and 1-day-old chicks. Chickens showed an individual variation in agglutinability of their erythrocytes, requiring selection of birds to obtain erythrocytes for HA. HA reaction was inhibited by specific antiserum. Some factors involved in HA and HA inhibition (HI) were investigated and standard HA and HI tests were worked out.


title: Large Arf1 guanine nucleotide exchange factors: evolution, domain structure, and roles in membrane trafficking and human disease

text: The Sec7 domain ADP-ribosylation factor (Arf) guanine nucleotide exchange factors (GEFs) are found in all eukaryotes, and are involved in membrane remodeling processes throughout the cell. This review is focused on members of the GBF/Gea and BIG/Sec7 subfamilies of Arf GEFs, all of which use the class I Arf proteins (Arf1-3) as substrates, and play a fundamental role in trafficking in the endoplasmic reticulum (ER)—Golgi and endosomal membrane systems. Members of the GBF/Gea and BIG/Sec7 subfamilies are large proteins on the order of 200 kDa, and they possess multiple homology domains. Phylogenetic analyses indicate that both of these subfamilies of Arf GEFs have members in at least five out of the six eukaryotic supergroups, and hence were likely present very early in eukaryotic evolution. The homology domains of the large Arf1 GEFs play important functional roles, and are involved in interactions with numerous protein partners. The large Arf1 GEFs have been implicated in several human diseases. They are crucial host factors for the replication of several viral pathogens, including poliovirus, coxsackievirus, mouse hepatitis coronavirus, and hepatitis C virus. Mutations in the BIG2 Arf1 GEF have been linked to autosomal recessive periventricular heterotopia, a disorder of neuronal migration that leads to severe malformation of the cerebral cortex. Understanding the roles of the Arf1 GEFs in membrane dynamics is crucial to a full understanding of trafficking in the secretory and endosomal pathways, which in turn will provide essential insights into human diseases that arise from misregulation of these pathways.


title: Two‐year prospective study of single infections and co‐infections by respiratory syncytial virus and viruses identified recently in infants with acute respiratory disease

text: A prospective 2‐year analysis including 322 infant patients with acute respiratory disease (ARD) hospitalized in a pediatric department in northern Italy was carried out to evaluate the role as respiratory pathogens or co‐pathogens of recently identified viruses. The presence of respiratory syncitial virus (RSV), human Metapneumoviruses (hMPVs), human Bocaviruses (hBoVs), and human Coronaviruses (hCoVs) was assayed by molecular detection and clinical symptoms evaluated. Nasopharyngeal aspirates from 150 of the 322 infants (46.6%) tested positive for at least one pathogen. Ninety samples (28.0%) tested positive for RSV RNA (61.5% genotype A and 38.5% genotype B), 46 (14.3%) for hMPV RNA (71.7% subtype A and 28.3% subtype B), 28 (8.7%) for hCoV RNA (39.3% hCoV‐OC43, 35.7% hCoV‐NL63, 21.4% hCoV‐HKU1, and 3.6% hCoV‐229E), and 7 (2.2%) for hBoV DNA (of the 6 typed, 50% subtype 1 and 50% subtype 2); 21/150 samples revealed the presence of 2 or more viruses. Co‐infection rates were higher for hMPVs, hCoVs, and hBoV (38.3%, 46.4%, and 57.1%,) and lower for RSV (23.3%). RSV was associated with the presence of complications (P < 0.001) and hypoxia (P < 0.015). When the presence of RSV alone and the RSV‐hMPV co‐infections were considered, RSV mono‐infected patients resulted to have longer hospitalization and higher hypoxia (P < 0.001). The data highlight that (i) RSV has a central role as a respiratory pathogen of infants, (ii) the wide circulation of recently identified viruses does not reduce the clinical and epidemiological importance of RSV, and that (iii) recently identified agents (hMPVs, hBoVs, and hCoVs) act as primary pathogens or co‐pathogens. J. Med. Virol. 80:716–723, 2008. © 2008 Wiley‐Liss, Inc.


title: Analysis of clinical features and outcomes of 161 patients with severe and critical COVID‐19: A multicenter descriptive study

text: BACKGROUND: This study aimed to investigate clinical characteristics, laboratory indexes, treatment regimens, and short‐term outcomes of severe and critical coronavirus disease 2019 (COVID‐19) patients. METHODS: One hundred and sixty one consecutive severe and critical COVID‐19 patients admitted in intensive care unit (ICU) were retrospectively reviewed in this multicenter study. Demographic features, medical histories, clinical symptoms, lung computerized tomography (CT) findings, and laboratory indexes on admission were collected. Post‐admission complications, treatment regimens, and clinical outcomes were also documented. RESULTS: The mean age was 59.38 ± 16.54 years, with 104 (64.60%) males and 57 (35.40%) females. Hypertension (44 [27.33%]) and diabetes were the most common medical histories. Fever (127 [78.88%]) and dry cough (111 [68.94%]) were the most common symptoms. Blood routine indexes, hepatic and renal function indexes, and inflammation indexes were commonly abnormal. Acute respiratory distress syndrome (ARDS) was the most common post‐admission complication (69 [42.86%]), followed by electrolyte disorders (48 [29.81%]), multiple organ dysfunction (MODS) (37 [22.98%]), and hypoproteinemia (36 [22.36%]). The most commonly used antiviral drug was lopinavir/ritonavir tablet. 50 (31.06%) patients died, while 78 (48.45%) patients healed and discharged, and the last 33 (20.50%) patients remained in hospital. Besides, the mean hospital stay of deaths was 21.66 ± 11.18 days, while the mean hospital stay of discharged patients was 18.42 ± 12.77 days. Furthermore, ARDS (P < .001) and MODS (P = .008) correlated with increased mortality rate. CONCLUSION: Severe and critical COVID‐19 presents with high mortality rate, and occurrence of ARDS or MODS greatly increases its mortality risk.


title: Identification of a Conserved Non-Protein-Coding Genomic Element that Plays an Essential Role in Alphabaculovirus Pathogenesis

text: Highly homologous sequences 154–157 bp in length grouped under the name of “conserved non-protein-coding element” (CNE) were revealed in all of the sequenced genomes of baculoviruses belonging to the genus Alphabaculovirus. A CNE alignment led to the detection of a set of highly conserved nucleotide clusters that occupy strictly conserved positions in the CNE sequence. The significant length of the CNE and conservation of both its length and cluster architecture were identified as a combination of characteristics that make this CNE different from known viral non-coding functional sequences. The essential role of the CNE in the Alphabaculovirus life cycle was demonstrated through the use of a CNE-knockout Autographa californica multiple nucleopolyhedrovirus (AcMNPV) bacmid. It was shown that the essential function of the CNE was not mediated by the presumed expression activities of the protein- and non-protein-coding genes that overlap the AcMNPV CNE. On the basis of the presented data, the AcMNPV CNE was categorized as a complex-structured, polyfunctional genomic element involved in an essential DNA transaction that is associated with an undefined function of the baculovirus genome.


Management of Leprosy Patients in the Era of COVID19


title: Chapter 3 Features of Host Cells Cellular and Molecular Biology Review

text: Abstract As obligate intracellular parasites, viruses are completely dependent upon a host cell for their replication. They use energy generated by the host cell, and they exploit the host's machinery to manufacture viral proteins. Many of the cell's organelles, as well as the plasma membrane, are involved in viral replication processes. The organelles involved in protein synthesis, processing, and transport—namely the ribosome, rough endoplasmic reticulum, and Golgi complex—are utilized in the manufacture of viral proteins, as well, and viruses use ATP generated by the host cell's mitochondria. The plasma membrane, made of a phospholipid bilayer, is the cell's primary zone of contact with the extracellular world. As such, it is the first obstacle that a virus must overcome for entry into a cell. The Central Dogma of Molecular Biology states that DNA is replicated to create more DNA, DNA is transcribed into mRNA, and mRNA is translated by ribosomes to create proteins. All viruses are dependent upon the host's translation machinery, and many viruses will use other portions of the cell's replication and transcription mechanisms. DNA polymerase is the major enzyme involved in DNA replication, while RNA polymerase creates messenger RNA. Host ribosomes translate the messenger RNA into proteins, composed of amino acids. Viruses also have many unique strategies to ensure the translation of their proteins over host proteins.