title: Evaluation of a Hospital-Wide Infection Prevention & Control Certification Program: Increasing the Quality Limits for Patient Safety and Staff Satisfaction

text: BACKGROUND/OBJECTIVES: To evaluate the effect of Infection Conrol (IC) certification on confidence and comfort level of the health care workers. METHODS: The Severe Acute Respiratory Syndrome (SARS) Outbreak highlighted the significance of formal training in IC practical aspects as well as the development and publication of standards. Minor errors in the use of personal protective equipment were identified as sources of contamination of Health Care Workers' to SARS CoV. Our hospital's policy mandated that all staff, be certified in IC practices through a competency based educational program. A multi-disciplinary educational module, derived from a SARS specific model used to educate the SARS designated care team; was developed. Essential components included basic IC principles, specimen collection, use of protective clothing, high risk procedures, modified protocols for ventilator management and oxygen/aerosol therapy, transportation and care of equipment and the environment. Competency checklists for each module were developed. Education was customized, depending on the potential risk of exposure. A train the trainer model with direct involvement of the Infection Control Practitioners (ICP)disseminated the program hospital-wide. • A self-directed learning package including a video demonstration of application and removal of the Personal Protective attire was developed for the physicians. RESULTS: Evaluation of staff satisfaction indicated an average staff satisfaction of 98.3% with the pace and content of the sessions and also increased staff confidence while caring for patients in isolation. The result of a survey demonstrated a significant association between the level of confidence and comfort in providing patient care and certification among the two groups of staff (certified versus non- certified, p < 0.001). ∗There was no nosocomial spread of SARS in our hospital, despite the admission of 5 confirmed cases and 27 patients that met the SARS case definitions. CONCLUSIONS: The program was highly successful in preventing the spread of SARS within the institution and easing staff's anxiety. Evaluations of the program participant using a RxC statistical analyses Received Competency based certification Did not receive Competency based certification Very confident 48 (72.7%) 29 (35.8%) Somewhat confident 16 (24.2%) 43 (53.1%) Not Confident 2 (3.0%) 9 (11.1%) Total 66 81 ∗IC Education must be a mandatory and frequent part of the training for medical and paramedical programs with commitment and support from internal and external stakeholders. ∗Directives and policies must have an implementation and a role out plan. ∗There is a need to evaluate the long-term effectiveness and retension level of the competency based program. ∗Ratio/bed of ICPs must be re-evaluated based on the new demands of the field.


Pericarditis aguda secundaria a covid-19 ¿una enfermedad infradiagnosticada?


title: A paradigm shift for the Great Bifurcation

text: This paper is an attempt to achieve an understanding of the situation the evolution of humanity is confronted with in the age of global challenges. Since global challenges are problems of unprecedented complexity, it is argued that a secular paradigm shift is required away from the overemphasis on allegedly neutral standpoints, on a mechanistic picture of the world and on deductive logics towards accounts of emergence, of systemicity, informationality and conviviality, building upon each other and providing together a transdisciplinary edifice of the sciences, in the end, for, and by the inclusion of, citizens. Viewed from such a combined perspective, the current social evolution is punctuated by a Great Bifurcation similar to bifurcations other emergent systems have been facing. On the one hand, humankind is on the brink of extinction. It is the world occurrence of the enclosure of commons that is detrimental to sharing the systemic synergy effects and thus to the cohesion of social systems. On the other hand, humanity is on the threshold of a planetary society. Another leap in integration would be the appropriate response to the complexity confronted with. Humans and their social systems are informational agents and, as such, they are able to generate requisite information and use it to catch up with the complex challenges. They can establish convivial rules of living together in that they disclose the commons world-wide. By doing so, they would accomplish another evolutionary step in anthroposociogenesis. The concept of the Global Sustainable Information Society describes the framework of necessary conditions of conviviality under the new circumstances.


title: The Initial Hospital Response to an Epidemic

text: The last decades have been characterized by the appearance of a substantial number of newly recognized or novel infectious agents and by the re-emergence of infectious diseases with a global impact. The objective of this article is to briefly describe the model of hospital response for early diagnosis and prompt management of patients with highly contagious infectious diseases. We reviewed the main components of hospital preparedness in response to clustering of highly contagious diseases. A model for the initial hospital response to an epidemic in our referral Institute is discussed. Prompt recognition and identification is the initial and indispensable step in facing any communicable diseases, regardless of whether it is a prevalent, a newly emerging one or deliberately released. The importance of developing and implementing nontraditional methods of public health surveillance and a system that allows a wide and immediate dissemination of information and exchange of views on risk assessment and risk management are highlighted. Case identification and laboratory capabilities and isolation procedures are the essential components for an initial hospital response. The recent bioterrorist events and the worldwide outbreaks of highly contagious infectious diseases have evidenced the need for institutional preparedness at each hospital and for identification of referral centers for patient isolation and of laboratories with adequate capabilities. Moreover, hospitals should develop a plan for coordinating all hospital components to respond to critical situations deriving from the admission of patients with highly contagious infectious diseases.


title: Immunisation of pigs with a major envelope protein sub-unit vaccine against porcine reproductive and respiratory syndrome virus (PRRSV) results in enhanced clinical disease following experimental challenge

text: Abstract Disease exacerbation was observed in pigs challenged with virulent porcine reproductive and respiratory syndrome virus (PRRSV) following immunisation with a recombinant GP5 sub-unit PRRSV vaccine (rGP5) produced in E. coli. Eighteen animals were divided into three experimental groups: group A were immunised twice IM with rGP5, 21days apart; group B acted as positive controls (challenged but not immunised); and group C were negative controls. Pigs in groups A and B were challenged 21days after the second immunisation of the group A animals. Following challenge, three pigs given rGP5 exhibited more severe clinical signs than the positive controls, including respiratory distress and progressive weight-loss. Although not statistically significant, the more severe disease exhibited by group A animals may suggest previous immunisation as a contributory factor. The mechanisms of these findings remain unclear and no association could be established between the severity of disease, non-neutralising antibody concentrations and tissue viral loads.


title: Treatment and prevention of necrotizing enterocolitis

text: Abstract Necrotizing enterocolitis (NEC) is the most common serious, acquired gastrointestinal disorder in the newborn infant. Although many variables are associated with development of NEC, only prematurity has been consistently identified in case-controlled studies. Traditionally, the diving seal reflex has been invoked as the mechanism responsible for ischaemic injury and necrosis. Intestinal ischaemia is likely to be the final common pathway in NEC; however, it is due to the release of vasoconstricting substances, such as platelet activating factor, rather than perinatal asphyxia. Bacteria and/or bacterial toxins are likely to have a key role in the pathogenesis of NEC by fostering production of inflammatory mediators. The role of feeding practices in the pathogenesis of NEC remains controversial. Treatment of infants with NEC generally includes a regimen of bowel rest, gastric decompression, systemic antibiotics and parenteral nutrition. Infants with perforation are generally operated upon; however, there has been recent interest in primary peritoneal drainage as an alternative. Prevention of NEC still remains elusive. Avoidance of preterm birth, use of antenatal steroids and breast-milk feeding are practices that offer the greatest potential benefits. Use of any other strategy should await further trials.


title: Chapter 14 Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) Infection

text: MERS-CoV infection is an emerging infectious disease with a high mortality rate. The exact incidence and prevalence of the disease is not known as we do not have yet reliable serologic tests. The diagnosis of MERS-CoV infection relies on detection of the virus using real-time RT-PCR. Currently, the origin of the virus and the source is not known and future studies are needed to elucidate possible sources and the best therapeutic options.


title: A comprehensive immunoinformatics and target site study revealed the corner-stone toward Chikungunya virus treatment

text: Abstract Recent concerning facts of Chikungunya virus (CHIKV); a Togaviridae family alphavirus has proved this as a worldwide emerging threat which causes Chikungunya fever and devitalizing arthritis. Despite severe outbreaks and lack of antiviral drug, a mere progress has been made regarding to an epitope-based vaccine designed for CHIKV. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites by using various immunoinformatics and docking simulation tools. Initially, whole proteome of CHIKV was retrieved from database and perused to identify the most immunogenic protein. Structural properties of the selected protein were analyzed. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell were checked for the selected protein. The peptide region spanning 9 amino acids from 397 to 405 and the sequence YYYELYPTM were found as the most potential B cell and T cell epitopes respectively. This peptide could interact with as many as 19 HLAs and showed high population coverage ranging from 69.50% to 84.94%. By using in silico docking techniques the epitope was further assessed for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post therapeutic strategy, three dimensional structure was predicted along with validation and verification that resulted in molecular docking study to identify the potential drug binding sites and suitable therapeutic inhibitor against targeted protein. Finally, pharmacophore study was also performed in quest of seeing potent drug activity. However, this computational epitope-based peptide vaccine designing and target site prediction against CHIKV opens up a new horizon which may be the prospective way in Chikungunya virus research; the results require validation by in vitro and in vivo experiments.


Surgical systems redesign in response to COVID-19 Invited Commentary on “Optimizing response in surgical systems during and after COVID-19 pandemic: Lessons from China and the UK- perspective”


title: The Curious Case of the Nidovirus Exoribonuclease: Its Role in RNA Synthesis and Replication Fidelity

text: Among RNA viruses, the order Nidovirales stands out for including viruses with the largest RNA genomes currently known. Nidoviruses employ a complex RNA-synthesizing machinery comprising a variety of non-structural proteins (nsps). One of the postulated drivers of the expansion of nidovirus genomes is the presence of a proofreading 3′-to-5′ exoribonuclease (ExoN) belonging to the DEDDh family. ExoN may enhance the fidelity of RNA synthesis by correcting nucleotide incorporation errors made by the RNA-dependent RNA polymerase. Here, we review our current understanding of ExoN evolution, structure, and function. Most experimental data are derived from studies of the ExoN domain of coronaviruses (CoVs), which were triggered by the bioinformatics-based identification of ExoN in the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) and its relatives in 2003. Although convincing data supporting the proofreading hypothesis have been obtained, from biochemical assays and studies with CoV mutants lacking ExoN functionality, the features of ExoN from most other nidovirus families remain to be characterized. Remarkably, viable ExoN knockout mutants were obtained only for two CoVs, mouse hepatitis virus (MHV) and SARS-CoV, whose RNA synthesis and replication kinetics were mildly affected by the lack of ExoN function. In several other CoV species, ExoN inactivation was not tolerated, and knockout mutants could not be rescued when launched using a reverse genetics system. This suggests that ExoN is also critical for primary viral RNA synthesis, a property that poorly matches the profile of an enzyme that would merely boost long-term replication fidelity. In CoVs, ExoN resides in a bifunctional replicase subunit (nsp14) whose C-terminal part has (N7-guanine)-methyltransferase activity. The crystal structure of SARS-CoV nsp14 has shed light on the interplay between these two domains, and on nsp14’s interactions with nsp10, a co-factor that strongly enhances ExoN activity in vitro assays. Further elucidation of the structure-function relationships of ExoN and its interactions with other (viral and/or host) members of the CoV replication machinery will be key to understanding the enzyme’s role in viral RNA synthesis and pathogenesis, and may contribute to the design of new approaches to combat emerging nidoviruses.


docid: mwtifswp

title: Towards good practice for health statistics: lessons from the Millennium Development Goal health indicators

text: Summary Health statistics are at the centre of an increasing number of worldwide health controversies. Several factors are sharpening the tension between the supply and demand for high quality health information, and the health-related Millennium Development Goals (MDGs) provide a high-profile example. With thousands of indicators recommended but few measured well, the worldwide health community needs to focus its efforts on improving measurement of a small set of priority areas. Priority indicators should be selected on the basis of public-health significance and several dimensions of measurability. Health statistics can be divided into three types: crude, corrected, and predicted. Health statistics are necessary inputs to planning and strategic decision making, programme implementation, monitoring progress towards targets, and assessment of what works and what does not. Crude statistics that are biased have no role in any of these steps; corrected statistics are preferred. For strategic decision making, when corrected statistics are unavailable, predicted statistics can play an important part. For monitoring progress towards agreed targets and assessment of what works and what does not, however, predicted statistics should not be used. Perhaps the most effective method to decrease controversy over health statistics and to encourage better primary data collection and the development of better analytical methods is a strong commitment to provision of an explicit data audit trail. This initiative would make available the primary data, all post-data collection adjustments, models including covariates used for farcasting and forecasting, and necessary documentation to the public.


title: The influence of interferon-lambda on restricting Middle East Respiratory Syndrome Coronavirus replication in the respiratory epithelium

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe respiratory in human with high mortality and it has been a challenge to determine optimum treatment for MERS-CoV-induced respiratory infection. Here, we observed the distribution of MERS-CoV receptors using human respiratory mucosa and also evaluated the contribution of interferon-lambdas (IFN-λs) in response to MERS-CoV infection using in vitro normal human nasal epithelial (NHNE) and bronchial epithelial (NHBE) cells. We found that the gene and protein expression of DPPIV, MERS-CoV receptor, were more dominantly located in nasal and bronchial epithelium although human nasal mucosa exhibited relatively lower DPPIV expression than lung parenchymal tissues. The quantitative mRNA level of the MERS-CoV envelope (upE) gene was significantly induced in MERS-CoV-infected cultured NHNE and NHBE cells until 3 days after infection. The induction of IFNs was identified in in NHNE and NHBE cells after MERS-CoV infection and IFN-λs were predominantly increased in MERS-CoV-infected respiratory epithelial cells. Inoculation of IFN-λs to NHNE and NHBE cells suppressed MERS-CoV replication and in particular, IFN-λ(4) showed a strong therapeutic effect in reducing MERS-CoV infection with higher induction of IFN-stimulated genes. Thus, IFN-λ has a decisive function in the respiratory epithelium that greatly limits MERS-CoV replication, and may be a key cytokine for better therapeutic outcomes against MERS-CoV infection in respiratory tract.


title: Contribution of common and recently described respiratory viruses to annual hospitalizations in children in South Africa

text: The contribution of viruses to lower respiratory tract disease in sub‐Saharan Africa where human immunodeficiency virus may exacerbate respiratory infections is not well defined. No data exist on some of these viruses for Southern Africa. Comprehensive molecular screening may define the role of these viruses as single and co‐infections in a population with a high HIV‐AIDS burden. To address this, children less than 5 years of age with respiratory infections from 3 public sector hospitals, Pretoria South Africa were screened for 14 respiratory viruses, by PCR over 2 years. Healthy control children from the same region were included. Rhinovirus was identified in 33% of patients, RSV (30.1%), PIV‐3 (7.8%), hBoV (6.1%), adenovirus (5.7%), hMPV (4.8%), influenza A (3.4%), coronavirus NL63 (2.1%), and OC43 (1.8%). PIV‐1, PIV‐2, CoV‐229E, ‐HKU1, and influenza B occurred in <1.5% of patients. Most cases with adenovirus, influenza A, hMPV, hBoV, coronaviruses, and WU virus occurred as co‐infections while RSV, PIV‐3, and rhinovirus were identified most frequently as the only respiratory pathogen. Rhinovirus but not RSV or PIV‐3 was also frequently identified in healthy controls. A higher HIV sero‐prevalence was noticed in patients with co‐infections although co‐infections were not associated with more severe disease. RSV, hPMV, PIV‐3, and influenza viruses had defined seasons while rhinovirus, adenovirus, and coronavirus infections occurred year round in this temporal region of sub‐Saharan Africa. J. Med. Virol. 83:1458–1468, 2011. © 2011 Wiley‐Liss, Inc.


Laboratory response to Middle East Respiratory Syndrome outbreak in Korea, 2015


Clinical and conceptual comments on “Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis”


docid: jdyouzqg

title: The «moonlighting protein» able to explain the T(h)1 immune lockdown in severe COVID-19()

text: COVID-19 is a major public health issue around the world and new data about its etiological agent, SARS-CoV-2, are urgently necessary, also translating the scientific knowledge acquired on its more similar predecessors, SARS-CoV-1 and MERS-CoV, the coronaviruses responsible for SARS and MERS, respectively. Like SARS-CoV-1, SARS-CoV-2 exploits the ACE2 receptors to enter the host cells; nevertheless, recent bioinformatics insights suggest a potential interaction of SARS-CoV-2 with the «moonlighting protein» CD26/DPP4, exactly how MERS-CoV works. CD26/DPP4 is overexpressed on T-helper type 1 (T(h)1) cells and its expression increases with aging, all factors which could well explain the T(h)1 immune lockdown, especially in the elderly, during fatal SARS-CoV-2 infections. Facing with this scenario, it is possible that T(h)1 and T-cytotoxic lymphocytes are the immune cells most affected by SARS-CoV-2, and that the immune system is forced to mount a T-helper type 2 (T(h)2) response, the only one still mountable, in the attempt to counteract the viral load. However, in this way, the symptomatic patient experiences all the negative effects of the T(h)2 response, which can seriously aggravate the clinical picture.


title: Saliva and viral infections

text: Over the last 10 years there have been only a handful of publications dealing with the oral virome, which is in contrast to the oral microbiome, an area that has seen considerable interest. Here, we survey viral infections in general and then focus on those viruses that are found in and/or are transmitted via the oral cavity; norovirus, rabies, human papillomavirus, Epstein‐Barr virus, herpes simplex viruses, hepatitis C virus, and HIV. Increasingly, viral infections have been diagnosed using an oral sample (e.g. saliva mucosal transudate or an oral swab) instead of blood or urine. The results of two studies using a rapid and semi‐quantitative lateral flow assay format demonstrating the correlation of HIV anti‐IgG/sIgA detection with saliva and serum samples are presented. When immediate detection of infection is important, point‐of‐care devices that obtain a non‐invasive sample from the oral cavity can be used to provide a first line diagnosis to assist in determining appropriate counselling and therapeutic path for an increasing number of diseases.


title: In vitro and in vivo antimicrobial activity of two α-helical cathelicidin peptides and of their synthetic analogs

text: Two α-helical antimicrobial peptides (BMAP-27 and -28) and four synthetic analogs were compared for in vitro and in vivo antimicrobial efficacy. All peptides proved active in vitro at micromolar concentrations against a range of clinical isolates, including antibiotic-resistant strains. BMAP-27 and two analogs were more effective towards Gram-negative, and BMAP-28 towards Gram-positive organisms. In addition, BMAP-28 provided some protection in vitro against human herpes simplex virus type 1 (HSV-1). The parent peptides and mBMAP-28 analog protected mice from lethal i.p. infections in an acute peritonitis model at peptide doses significantly lower than those toxic to the animals, suggesting a satisfactory therapeutic index.


A development strategy to fast establish the Taqman qPCR based method to detect SNP mutations


title: Human Virus Transcriptional Regulators

text: Viral genomes encode transcriptional regulators that alter the expression of viral and host genes. Despite an emerging role in human diseases, a thorough annotation of human viral transcriptional regulators (vTRs) is currently lacking, limiting our understanding of their molecular features and functions. Here, we provide a comprehensive catalog of 419 vTRs belonging to 20 different virus families. Using this catalog, we characterize shared and unique cellular genes, proteins, and pathways targeted by particular vTRs and discuss the role of vTRs in human disease pathogenesis. Our study provides a unique and valuable resource for the fields of virology, genomics, and human disease genetics.


title: Safety issues and harmful pharmacological interactions of nutritional supplements in Duchenne muscular dystrophy: considerations for Standard of Care and emerging virus outbreaks

text: At the moment, little treatment options are available for Duchenne muscular dystrophy (DMD). The absence of the dystrophin protein leads to a complex cascade of pathogenic events in myofibres, including chronic inflammation and oxidative stress as well as altered metabolism. The attention towards dietary supplements in DMD is rapidly increasing, with the aim to counteract pathology-related alteration in nutrient intake, the consequences of catabolic distress or to enhance the immunological response of patients as nowadays for the COVID-19 pandemic emergency. By definition, supplements do not exert therapeutic actions, although a great confusion may arise in daily life by the improper distinction between supplements and therapeutic compounds. For most supplements, little research has been done and little evidence is available concerning their effects in DMD as well as their preventing actions against infections. Often these are not prescribed by clinicians and patients/caregivers do not discuss the use with their clinical team. Then, little is known about the real extent of supplement use in DMD patients. It is mistakenly assumed that, since compounds are of natural origin, if a supplement is not effective, it will also do no harm. However, supplements can have serious side effects and also have harmful interactions, in terms of reducing efficacy or leading to toxicity, with other therapies. It is therefore pivotal to shed light on this unclear scenario for the sake of patients. This review discusses the supplements mostly used by DMD patients, focusing on their potential toxicity, due to a variety of mechanisms including pharmacodynamic or pharmacokinetic interactions and contaminations, as well as on reports of adverse events. This overview underlines the need for caution in uncontrolled use of dietary supplements in fragile populations such as DMD patients. A culture of appropriate use has to be implemented between clinicians and patients’ groups.


Testing contamination and cleaning effectiveness in theatre during the COVID‐19 pandemic using UV fluorescent powder


title: Co‐circulation of genetically distinct human metapneumovirus and human bocavirus strains in young children with respiratory tract infections in Italy

text: The discovery of human Metapneumovirus (hMPV) and human Bocavirus (hBoV) identified the etiological causes of several cases of acute respiratory tract infections in children. This report describes the molecular epidemiology of hMPV and hBoV infections observed following viral surveillance of children hospitalized for acute respiratory tract infections in Milan, Italy. Pharyngeal swabs were collected from 240 children ≤3 years of age (130 males, 110 females; median age, 5.0 months; IQR, 2.0–12.5 months) and tested for respiratory viruses, including hMPV and hBoV, by molecular methods. hMPV‐RNA and hBoV‐DNA positive samples were characterized molecularly and a phylogenetical analysis was performed. PCR analysis identified 131/240 (54.6%) samples positive for at least one virus. The frequency of hMPV and hBoV infections was similar (8.3% and 12.1%, respectively). Both infections were associated with lower respiratory tract infections: hMPV was present as a single infectious agent in 7.2% of children with bronchiolitis, hBoV was associated with 18.5% of pediatric pneumonias and identified frequently as a single etiological agent. Genetically distinct hMPV and hBoV strains were identified in children examined with respiratory tract infections. Phylogenetic analysis showed an increased prevalence of hMPV genotype A (A2b sublineage) compared to genotype B (80% vs. 20%, respectively) and of the hBoV genotype St2 compared to genotype St1 (71.4% vs. 28.6%, respectively). Interestingly, a shift in hMPV infections resulting from A2 strains has been observed in recent years. In addition, the occurrence of recombination events between two hBoV strains with a breakpoint located in the VP1/VP2 region was identified. J. Med. Virol. 83:156–164, 2011. © 2010 Wiley‐Liss, Inc.


title: Patient blood management – a new paradigm for transfusion medicine?

text: The saving of many lives in history has been duly credited to blood transfusions. What is frequently overlooked is the fact that, in light of a wealth of evidence as well as other management options, a therapy deemed suitable yesterday may no longer be the first choice today. Use of blood has not been based upon scientific evaluation of benefits, but mostly on anecdotal experience and a variety of factors are challenging current practice. Blood is a precious resource with an ever limiting supply due to the aging population. Costs have also continually increased due to advances (and complexities) in collection, testing, processing and administration of transfusion, which could make up 5% of the total health service budget. Risks of transfusions remain a major concern, with advances in blood screening and processing shifting the profile from infectious to non‐infectious risks. Most worrying though, is the accumulating literature demonstrating a strong (often dose‐dependent) association between transfusion and adverse outcomes. These include increased length of stay, postoperative infection, morbidity and mortality. To this end, a recent international consensus conference on transfusion outcomes (ICCTO) concluded that there was little evidence to corroborate that blood would improve patients’ outcomes in the vast majority of clinical scenarios in which transfusions are currently routinely considered; more appropriate clinical management options should be adopted and transfusion avoided wherever possible. On the other hand, there are patients for whom the perceived benefits of transfusion are likely to outweigh the potential risks. Consensus guidelines for blood component therapy have been developed to assist clinicians in identifying these patients and most of these guidelines have long advocated more conservative ‘triggers’ for transfusion. However, significant variation in practice and inappropriate transfusions are still prevalent. The ‘blood must always be good philosophy’ continues to permeate clinical practice. An alternative approach, however, is being adopted in an increasing number of centres. Experience in managing Jehovah’s Witness patients has shown that complex care without transfusion is possible and results are comparable with, if not better than those of transfused patients. These experiences and rising awareness of downsides of transfusion helped create what has become known as ‘patient blood management’. Principles of this approach include optimizing erythropoiesis, reducing surgical blood loss and harnessing the patient’s physiological tolerance of anaemia. Treatment is tailored to the individual patient, using a multidisciplinary team approach and employing a combination of modalities. Results have demonstrated reduction of transfusion, improved patient outcomes and patient satisfaction. Significant healthcare cost savings have also followed. Despite the success of patient blood management programmes and calls for practice change, the potential and actual harm to patients caused through inappropriate transfusion is still not sufficiently tangible for the public and many clinicians. This has to change. The medical, ethical, legal and economic evidence cannot be ignored. Patient blood management needs to be implemented as the standard of care for all patients.


title: The inevitable Hajj cough: Surveillance data in French pilgrims, 2012–2014

text: Summary Background Respiratory tract infections are the most common infection affecting Hajj pilgrims, and the ‘‘Hajj cough’’ is considered by pilgrims almost de rigueur. Methods French pilgrims were recruited between January 2012–December 2014 and information on demographics, medical history, compliance with preventive measures and health problems during travel were collected. Results A total of 382 pilgrims were included with 39.3% aged ≥65 years and 55.1% suffering from a chronic disease, most frequently hypertension and diabetes. The prevalence of cough was 80.9% and a high proportion presented with associated sore throat (91.0%), rhinitis (78.7%) and hoarseness (63.0%). Myalgia was reported in 48.3% of cases and subjective fever in 47.3%. The incubation time of respiratory symptoms was 7.7 days (range 0–25 days) and 51.9% of pilgrims presenting with a cough during their stay were still symptomatic on return. Among pilgrims with a cough, 69.4% took antibiotics. The prevalence of cough was significantly higher among females than men, but age, chronic conditions and preventive measures had no significant effect. Conclusions The Hajj cough is highly common, likely a result of crowded conditions at religious places. Pilgrims should be advised to carry symptomatic relief for the Hajj cough such as cough suppressant, soothing throat lozenges and paracetamol. Use of antibiotics should be discouraged.


title: SARS‐CoV‐2 oral associated lesions: discussion of elicited response

text: This pandemic phenomenon has generated a large number of publications (19 May in Pubmed 2267), all of them aimed a better knowledge of its microbiological and serological characteristics, clinical expressions, and complications, trying to find those situations that could be more serious indicators. The search for these characteristics does not escape the oral sphere. Our group had the opportunity to find the cases presented and the only thing we tried to do was to shed some light on the fact that oral lesions may be part of the syndromic complex that causes COVID-19. We were extremely carefully with our words when we reported lesions associated with COVID-19 disease, and not due to it. (Al-Khatib, 2020; Lombardo & Pagnoncellia, 2020; Ponce & Tjioe, 2020; Rocha, Figueiredo & Resende, 2020).


title: Antiviral activities of niclosamide and nitazoxanide against chikungunya virus entry and transmission

text: Abstract Chikungunya disease results from an infection with the arbovirus, chikungunya virus (CHIKV). Symptoms of CHIKV include fever and persistent, severe arthritis. In recent years, several antiviral drugs have been evaluated in clinical trials; however, no registered antivirals have been approved for clinical therapy. In this study, we established a high-throughput screening (HTS) system based on CHIKV 26S mediated insect cell fusion inhibition assay. Our screening system was able to search potential anti-CHIKV drugs in vitro. Using this system, four compounds (niclosamide, nitazoxanide, niflumic acid, tolfenamic acid) were identified. These compounds were then further analyzed using a microneutralization assay. We determined that niclosamide and nitazoxanide exhibit ability to against CHIKV-induced CPE. The anti-CHIKV abilities of these compounds were further confirmed by RT-qPCR and IFA. Moreover, niclosamide and nitazoxanide were found to (1) limit virus entry, (2) inhibit both viral release and cell-to-cell transmission, and (3) possess broad anti-alphavius activities, including against two clinical CHIKV isolates and two alphaviruses: Sindbis virus (SINV) and Semliki forest virus (SFV). In conclusion, our findings suggested that niclosamide and nitazoxanide were able to inhibit CHIKV entry and transmission, which might provide a basis for the development of novel human drug therapies against CHIKV and other alphavirus infections.


title: Rapid changes in shape and number of MHC class II expressing cells in rat airways after Mycoplasma pulmonis infection

text: Abstract Mycoplasma pulmonis infection in rodents causes a chronic inflammatory airway disease with a strong immunological component, leading to mucosal remodeling and angiogenesis. We sought to determine the effect of this infection on the shape and number of dendritic cells and other major histocompatibility complex (MHC) class II expressing cells in the airway mucosa of Wistar rats. Changes in the shape of subepithelial OX6 (anti-MHC class II)-immunoreactive cells were evident in the tracheal mucosa 2 days after intranasal inoculation with M. pulmonis. By 1 week, the shape of the cells had changed from stellate to rounded (mean shape index increased from 0.42 to 0.77). The number of OX6-positive cells was increased 6-fold at 1 week and 16-fold at 4 weeks. Coincident with these changes, many columnar epithelial cells developed OX6 immunoreactivity, which was still present at 4 weeks. We conclude that M. pulmonis infection creates a potent immunologic stimulus that augments and transforms the OX6-immunoreactive cell population in the airways by changing the functional state of airway dendritic cells, initiating an influx of MHC class II expressing cells, and activating expression of MHC class II molecules by airway epithelial cells.


title: Compensation de la dose totale en cas d’interruption temporaire de radiothérapie externe dans le contexte de la pandémie de COVID-19: mise au point pratique

text: Abstract Overall treatment time is an important factor of local recurrence and indirectly of distant evolution, namely in case of protracted treatments. The current pandemic impacts on the duration of radiotherapy if patients under treatments and synchronously suffering from COVID-19. The models used to compensate the total dose in case of temporary treatment interruption are well known but it is of importance in that pandemic context to update and homogenize clinical practice in order to improve local control without increasing normal tissue complications.


title: Immunohistochemistry for detection of avian infectious bronchitis virus strain M41 in the proventriculus and nervous system of experimentally infected chicken embryos

text: BACKGROUND: Infectious bronchitis virus primarily induces a disease of the respiratory system, different IBV strains may show variable tissue tropisms and also affect the oviduct and the kidneys. Proventriculitis was also associated with some new IBV strains. Aim of this study was to investigate by immunohistochemistry (IHC) the tissue tropism of avian infectious bronchitis virus (IBV) strain M41 in experimentally infected chicken embryos. RESULTS: To this end chicken embryos were inoculated in the allantoic sac with 10(3 )EID(50 )of IBV M41 at 10 days of age. At 48, 72, and 120 h postinoculation (PI), embryos and chorioallantoic membranes (CAM) were sampled, fixed, and paraffin-wax embedded. Allantoic fluid was also collected and titrated in chicken embryo kidney cells (CEK). The sensitivity of IHC in detecting IBV antigens in the CAM of inoculated eggs matched the virus reisolation and detection in CEK. Using IHC, antigens of IBV were detected in nasal epithelium, trachea, lung, spleen, myocardial vasculature, liver, gastrointestinal tract, kidney, skin, sclera of the eye, spinal cord, as well as in brain neurons of the inoculated embryos. These results were consistent with virus isolation and denote the wide tissue tropism of IBV M41 in the chicken embryo. Most importantly, we found infection of vasculature and smooth muscle of the proventriculus which has not seen before with IBV strain M41. CONCLUSION: IHC can be an additional useful tool for diagnosis of IBV infection in chickens and allows further studies to foster a deeper understanding of the pathogenesis of infections with IBV strains of different virulence. Moreover, these results underline that embryonic tissues in addition to CAM could be also used as possible source to generate IBV antigens for diagnostic purposes.


title: Enterovirus 71‐induced autophagy detected in vitro and in vivo promotes viral replication

text: Enterovirus 71 (EV71) is an important pathogen causing death in children under 5 years old worldwide. However, the underlying pathogenesis remains unclear. This study reveals that EV71 infection in rhabdomyosarcoma (RD) and neuroblastoma (SK‐N‐SH) cells stimulated the autophagic process, which was demonstrated by an increase of punctate GFP‐microtubule‐associated protein 1 light chain 3 (GFP‐LC3), the level of autophagosome‐bound LC3‐II protein and double‐membrane autophagosome formation. EV71‐induced autophagy benefited EV71 replication, which was confirmed by the autophagic inducer rapamycin and the inhibitor 3‐methyladenine. Signaling pathway investigation revealed that the decreased expression of phosphorylated mTOR and phosphorylated p70S6K is involved in EV71‐induced autophagy in a cell‐specific manner. The expression of phosphorylated extracellular signal‐regulated kinase (Erk) was suppressed consistently in EV71‐infected cells. However it did not participate in the autophagic response of the cell. Other signaling pathway molecules, such as Erk, PI3K/Akt, Bcl‐2, BNIP3, and Beclin‐1 were not affected by infection with EV71. Electron microscopy showed co‐localization of autophagosome‐like vesicles with either EV71‐VP1 or LC3 protein in neurons of the cervical spinal cord in ICR mice infected with EV71. In conclusion, EV71 infection triggered autophagic flux and induced autophagosome formation both in vitro and in vivo. Autophagy induced by EV71 is beneficial for viral replication. Understanding the role of autophagy induced by EV71 in vitro and the formation of autophagosome‐like vesicle in vivo provide new insights into the pathogenesis of EV71 infection. J. Med. Virol. 81:1241–1252, 2009. © 2009 Wiley‐Liss, Inc.


title: Exploring sodium glucose co-transporter-2 (SGLT2) inhibitors for organ protection in COVID-19

text: Hospital admissions and mortality from the Coronavirus disease 2019 (COVID-19) pandemic are spreading throughout the world, and second and third waves are thought to be likely. Risk factors for severe COVID-19 include diabetes, chronic kidney disease and cardiovascular disease. Currently, there is no vaccine and no approved therapy. Therapeutic approaches are aimed at preventing viral replication and spread, limiting the impact of the inflammatory overdrive (cytokine storm), preventing thromboembolic complications and replacing or supporting organ function. However, despite organ support, mortality is currently 65% for those receiving advanced respiratory support and 78% for those requiring renal replacement therapies. Thus, efforts should be made to provide adjuvant organ protection therapy. This may imply novel therapies in clinical development (e.g., the Fas ligand trap asunercept), but uptake of repurposed drugs already in clinical use may be faster. In this regard, sodium glucose co-transporter-2 (SGLT2) inhibitors were recently shown to protect the heart and kidney both within and outside of a diabetic milieu context. Further, preclinical data support a beneficial effect for the lung. We now discuss the potential benefits and risks of SGLT2 inhibitors in COVID-19 and an ongoing clinical trial testing the impact of dapagliflozin on outcomes in COVID-19 patients with respiratory failure.


title: Porcine amino peptidase N domain VII has critical role in binding and entry of porcine epidemic diarrhea virus

text: Abstract Porcine epidemic diarrhea virus (PEDV) infects swine intestinal cells causing enteric disease. Research has shown that the entry into these cells is through porcine aminopeptidase N (pAPN) receptor. To gain insights into mechanisms of PEDV-pAPN interactions, the present study aimed at identifying the domain that is critical for PEDV binding. To this end, NIH3T3 cell lines constitutively expressing pAPN or pAPN mutants were generated. The mutants were; domain VII deletion mutant and domains IV–VI deletion mutant. In the latter, domain VII was linked to the transmembrane segment through domain III. Results showed PEDV infection was restricted to pAPN and pAPN domain VII expressing NIH3T3 cells. Further, reducing PEDV titre 10 fold resulted in 37.8% decrease in foci indicating positive correlation. A time course test at 12, 24, 36, 48 and 60h showed that foci increased 6 fold in the overall time range. Also, PEDV harvested from pAPN or domain VII expressing NIH3T3 cells was induced indirect plaques in Vero cells confirming successful entry and replication. Collectively, our results demonstrate that PEDV recognizes pAPN and that the main interactive point is lodged within domain VII of the pAPN. These findings are important for therapeutic development as well as creating a platform for future studies on PEDV.


docid: pfklwion

title: Early administered antibiotics do not impact mortality in critically ill patients with COVID-19.


title: Household transmissions of SARS-CoV-2 in the time of unprecedented travel lockdown in China

text: IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, China, in December 2019 and then spread globally. Limited information is available for characterizing epidemiological features and transmission patterns in the regions outside of Hubei Province. Detailed data on transmission at the individual level could be an asset to understand the transmission mechanisms and respective patterns in different settings. OBJECTIVE: To reconstruct infection events and transmission clusters of SARS-CoV-2 for estimating epidemiological characteristics at household and non-household settings, including super-spreading events, serial intervals, age- and gender-stratified risks of infection in China outside of Hubei Province. DESIGN, SETTING, AND PARTICIPANTS: 9,120 confirmed cases reported online by 264 Chinese urban Health Commissions in 27 provinces from January 20 to February 19, 2020. A line-list database is established with detailed information on demographic, social and epidemiological characteristics. The infection events are categorized into the household and non-household settings. EXPOSURES: Confirmed cases of SARS-CoV-2 infections. MAIN OUTCOMES AND MEASURES: Information about demographic characteristics, social relationships, travel history, timelines of potential exposure, symptom onset, confirmation, and hospitalization were extracted from online public reports. 1,407 infection events formed 643 transmission clusters were reconstructed. RESULTS: In total 34 primary cases were identified as super spreaders, and 5 household super-spreading events were observed. The mean serial interval is estimated to be 4.95 days (standard deviation: 5.24 days) and 5.19 days (standard deviation: 5.28 days) for households and non-household transmissions, respectively. The risk of being infected outside of households is higher for age groups between 18 and 64 years, whereas the hazard of being infected within households is higher for age groups of young (<18) and elderly (>65) people. CONCLUSIONS AND RELEVANCE: The identification of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of age between 18 and 64 indicate a significant barrier to the case identification and management, which calls for intensive non-pharmaceutical interventions (e.g. cancellation of public gathering, limited access of public services) as the potential mitigation strategies.


docid: apohpbrb

title: Mass Gatherings and Public Health: Case Studies from the Hajj to Mecca

text: Abstract Background Many new and challenging risks can be introduced during mass gatherings. The Hajj, as one of the largest mass gatherings, provides an excellent annual opportunity to reflect on the public health risk posed by international and multicultural crowds and the value of mitigation strategies. Objectives To identify the gap between preparation and training taken before being exposed to the mass gathering and postexposure experiences, and the breach between the expectations and reality of the holy place. Methods This was a qualitative study with in-depth interviews using semistructured questionnaires among Hajjis from 4 different countries (Bangladesh, Pakistan, Myanmar, and New Zealand). Purposive sampling was done. The present study was also supported by literature review. Findings Findings pointed to weaknesses in implementation and enforcement of law, for both the custodian country and countries of origin of Hajjis. Disparities among developed and developing countries were also noticeable. Conclusions From a global health and human security perspective, strengthening of core capacities in managing mass gatherings as well as researching risks posed by such gatherings are paramount to safeguard the public’s health. Attention of health professionals worldwide and adoption of strategic planning at custodian country and sending countries are obligatory.


title: Recommendations for eye care during the alarm state by the coronavirus disease pandemic COVID-19

text: Abstract Objective Minimize exposure to the SARS-CoV-2, reduce the chances of cross-transmission between patients and healthcare personnel, and prevent the development of postoperative complications from the management of patients with eye diseases during the 2019 coronavirus disease pandemic (COVID-19). Methods COVID-19 literature review and consensus establishment between different Spanish ophthalmology societies in order to provide guidelines and recommendations of maximum resources primarily conditioned by the state of alert, confinement and social distancing that occurs in Spain since March 16, 2020. Results The recommendations will promote the adoption of action and protection measures for eye care in outpatient clinics, surgical areas and hospitalization, for unconfirmed (asymptomatic and symptomatic) and confirmed COVID-19 patients. Measures must be adapted to the circumstances and availability of personal protective equipment in each of the centers and Autonomous Communities, which will be updated according to the pandemic phases and the measures adopted by the Spanish Government. Conclusions During the COVID-19 pandemic, attention to the potential health risks to the population caused by coronavirus should prevail over the possible progression of the common eye diseases. Ophthalmologists and other eye care professionals must assume a possible progression of these diseases due to the impossibility of adequate patient follow-up.


title: The role of accessory proteins in the replication of feline infectious peritonitis virus in peripheral blood monocytes

text: Abstract The ability to productively infect monocytes/macrophages is the most important difference between the low virulent feline enteric coronavirus (FECV) and the lethal feline infectious peritonitis virus (FIPV). In vitro, the replication of FECV in peripheral blood monocytes always drops after 12h post inoculation, while FIPV sustains its replication in the monocytes from 45% of the cats. The accessory proteins of feline coronaviruses have been speculated to play a prominent role in virulence as deletions were found to be associated with attenuated viruses. Still, no functions have been ascribed to them. In order to investigate if the accessory proteins of FIPV are important for sustaining its replication in monocytes, replication kinetics were determined for FIPV 79-1146 and its deletion mutants, lacking either accessory protein open reading frame 3abc (FIPV-Δ3), 7ab (FIPV-Δ7) or both (FIPV-Δ3Δ7). Results showed that the deletion mutants FIPV-Δ7 and FIPV-Δ3Δ7 could not maintain their replication, which was in sharp contrast to wt-FIPV. FIPV-Δ3 could still sustain its replication, but the percentage of infected monocytes was always lower compared to wt-FIPV. In conclusion, this study showed that ORF7 is crucial for FIPV replication in monocytes/macrophages, giving an explanation for its importance in vivo, its role in the development of FIP and its conservation in field strains. The effect of an ORF3 deletion was less pronounced, indicating only a supportive role of ORF3 encoded proteins during the infection of the in vivo target cell by FIPVs.


title: Complicated Alcohol Withdrawal—An Unintended Consequence of COVID-19 Lockdown

text: AIM: To assess the impact of COVID-19-related lockdown in India on alcohol-dependent persons. METHOD: We examined the change in the incidence of severe alcohol withdrawal syndrome presenting to hospitals in the city of Bangalore. RESULTS: A changepoint analysis of the time series data (between 01.01.20 to 11.04.20) showed an increase in the average number of cases from 4 to 8 per day (likelihood ratio test: χ(2) = 72, df = 2, P < 0.001). CONCLUSION: An unintended consequence of the lockdown was serious illness in some patients with alcohol use disorders.


title: Pandemic Stories: Rhetorical Motifs in Journalists’ Coverage of Biomedical Risk

text: This paper argues that journalists’ discursive actions in an outbreak context manifest in identifiable rhetorical motifs, which in turn influence the delivery of biomedical information by the media in such a context. Via a critical approach grounded in rhetorical theory, I identified three distinct rhetorical motifs influencing the reportage of health information in the early days of the H1N1 outbreak. A public-health motif was exhibited in texts featuring a particular health official and offering the statements of such an official as a mechanism of reassurance. A concealment-of-information motif was exhibited in texts emphasizing the importance of the transparency of health officials, and in texts demonstrating ambivalence about information provided by socially-sanctioned sources. Finally, in texts mythologizing the outbreak to the exclusion of other functions of the text (e.g., conveying who is at risk, protective behaviours, symptoms), I identified a pandemic motif. Each motif differs in the conclusions it offers to audiences seeking to gauge relative levels of risk, and to receive information about protective behaviours. I suggest that one means of interpreting the manifestation of distinct rhetorical motifs in the context of a high-risk health threat is the certainty that this context alters moral responsibilities, consequently influencing the manifestation of narrative role.


Síndrome coronario agudo y shock en contexto de infección aguda por COVID-19


title: Coronavirus disease 2019 (COVID‐19) and decrease in blood donation: experience of Iranian Blood Transfusion Organization (IBTO)

text: According to the World Health Organization (00:00CET 19 March 2020), coronavirus disease 2019 (COVID-19), has invaded up to 150 countries/territories. With 17,361 confirmed cases and 1135 deaths, after China and Italy, Iran is the 3rd most affected country in the world and the first one in the Eastern Mediterranean Region [1].


title: COVID‐19 Pandemic: Consensus Guidelines for Preferred Practices in an Aesthetic Clinic

text: BACKGROUND: Strict infection control measures in response to the current COVID‐19 pandemic are expected to remain for an extended period. In aesthetic clinics, most procedures are provided on one to one basis by the physician or therapist. In such a scenario, guidelines detailing the infection control measures for aesthetic clinics are of particular importance. METHODS: An online meeting of an international group of experts in the field of aesthetic medicine, with experience in administration of an aesthetic clinic, was convened. The meeting aimed to provide a set of consensus guidelines to protect clinic staff and patients from SARS‐CoV‐2 infection. RESULTS: Consensus guidelines for ‘preferred practices' were provided for scheduling of patients, patient evaluation and triaging, and for safety precautions about the different procedures. Procedures were categorized into low‐risk, moderate risk, and high‐risk based on the likelihood of transmission of SARS‐CoV‐2 virus from the patient to the treating physician or therapist. CONCLUSIONS: While not intended to be complete or exhaustive, these guidelines provide sound infection control measures for aesthetic practices. Since guidelines regarding safety measures and use of PPEs may vary from country to country, the local guidelines should also be followed to prevent COVID‐19 infection in aesthetic clinics. This article is protected by copyright. All rights reserved.


docid: qrnsmhws

title: Respiratory Hygiene in the Emergency Department

text: The emergency department (ED) is an essential component of the public health response plan for control of acute respiratory infectious threats. Effective respiratory hygiene in the ED is imperative to limit the spread of dangerous respiratory pathogens, including influenza, severe acute respiratory syndrome, avian influenza, and bioterrorism agents, particularly given that these agents may not be immediately identifiable. Sustaining effective respiratory control measures is especially challenging in the ED because of patient crowding, inadequate staffing and resources, and ever-increasing numbers of immunocompromised patients. Threat of contagion exists not only for ED patients but also for visitors, health care workers, and inpatient populations. Potential physical sites for respiratory disease transmission extend from out-of-hospital care, to triage, waiting room, ED treatment area, and the hospital at large. This article presents a summary of the most current information available in the literature about respiratory hygiene in the ED, including administrative, patient, and legal issues. Wherever possible, specific recommendations and references to practical information from the Centers for Disease Control and Prevention are provided. The “Administrative Issues” section describes coordination with public health departments, procedures for effective facility planning, and measures for health care worker protection (education, staffing optimization, and vaccination). The patient care section addresses the potentially infected ED patient, including emergency medical services concerns, triage planning, and patient transport. “Legal Issues” discusses the interplay between public safety and patient privacy. Emergency physicians play a critical role in early identification, treatment, and containment of potentially lethal respiratory pathogens. This brief synopsis should help clinicians and administrators understand, develop, and implement appropriate policies and procedures to address respiratory hygiene in the ED.


title: Chimeric calicivirus-like particles elicit specific immune responses in pigs

text: Abstract Virus-like particles (VLPs) have received considerable attention due to their potential application in veterinary vaccines and, in particular, VLPs from rabbit haemorrhagic disease virus (RHDV) have successfully shown to be good platforms for inducing immune responses against an inserted foreign epitope in mice. The aim of this study was to assess the immunogenicity of chimeric RHDV-VLPs as vaccine vectors in pigs. For this purpose, we have generated chimeric VLPs containing a well-known T epitope of 3A protein of foot-and-mouth disease virus (FMDV). Firstly, RHDV-VLPs were able to activate immature porcine bone marrow-derived dendritic cells (poBMDCs) in vitro. Secondly, pigs were inoculated twice in a two-week interval with chimeric RHDV-VLPs at different doses intranasally or intramuscularly. One intramuscularly treated group was also inoculated with adjuvant Montanide™ ISA 206 at the same time. Specific IgG and IgA antibodies against RHDV-VLPs were induced and such levels were higher in the adjuvanted group compared with other groups. Interestingly, anti-RHDV-VLP IgA responses were higher in groups inoculated intramuscularly than those that received the VLPs intranasally. Two weeks after the last immunisation, specific IFN-γ-secreting cells against 3A epitope and against RHDV-VLPs were detected in PBMCs by ELISPOT. The adjuvanted group exhibited the highest IFN-γ-secreting cell numbers and lymphoproliferative specific T cell responses against 3A epitope and RHDV-VLP. This is the first immunological report on the potential use of chimeric RHDV-VLPs as antigen carriers in pigs.


title: Characterization of nuclear factors modulating the apolipoprotein D promoter during growth arrest: Implication of PARP-1, APEX-1 and ERK1/2 catalytic activities

text: Abstract Human Apolipoprotein D (apoD) is upregulated under several stress conditions and pathological situations such as neurodegenerative diseases and cancers. We previously showed that apoD mRNA expression is induced in growth-arrested cells and demonstrated the specific binding of nuclear proteins to the region −514 to −475 of the promoter. Such region contains a pair of Serum Responsive Elements (SRE), an Ets-Binding Site (EBS) and a Glucocorticoid Responsive Element (GRE). In this study, we show that Parp-1, HnRNP-U, CBF-A, BUB-3, Kif4, APEX-1 and Ifi204 bind these regulatory elements of the apoD promoter. Specific binding of HnRNP-U and Parp-1 was confirmed by Electrophoretic Mobility Shift Assay (EMSA). In a biotin pull-down assay, Kif4 and BUB-3 bind preferentially the SRE1 and the EBS-GRE sites, respectively, while APEX-1 seems recruited indirectly to these elements. We found that the mRNA expression of some of these binding factors is upregulated in growth-arrested cells and that these proteins also transactivate the apoD promoter. In agreement with these results, mutants of APEX-1 and of Parp-1 defective for their DNA-binding and catalytic activities could not transactivate the promoter. The knockdown of Parp-1 and HnRNP-U and the use of specific inhibitors of MEK1/2 and of Parp-1 also inhibited the induction of apoD gene expression. Moreover, ERK1/2 was found activated in a biphasic manner post serum-starvation and the inhibition of Parp-1 causes a sustained activation of ERK2 but not ERK1 for up to 2h. Altogether, these findings demonstrate the importance of Parp-1, APEX-1 and ERK1/2 catalytic activities in the growth arrest-induced apoD gene expression.


title: Isatis tinctoria L. (Woad): A Review of Its Botany, Ethnobotanical Uses, Phytochemistry, Biological Activities, and Biotechnological Studies

text: Isatis tinctoria L. (Brassicaceae), which is commonly known as woad, is a species with an ancient and well-documented history as an indigo dye and medicinal plant. Currently, I. tinctoria is utilized more often as medicinal remedy and also as a cosmetic ingredient. In 2011, I. tinctoria root was accepted in the official European phytotherapy by introducing its monograph in the European Pharmacopoeia. The biological properties of raw material have been known from Traditional Chinese Medicine (TCM). Over recent decades, I. tinctoria has been investigated both from a phytochemical and a biological point of view. The modern in vitro and in vivo scientific studies proved anti-inflammatory, anti-tumour, antimicrobial, antiviral, analgesic, and antioxidant activities. The phytochemical composition of I. tinctoria has been thoroughly investigated and the plant was proven to contain many valuable biologically active compounds, including several alkaloids, among which tryptanthrin, indirubin, indolinone, phenolic compounds, and polysaccharides as well as glucosinolates, carotenoids, volatile constituents, and fatty acids. This article provides a general botanical and ethnobotanical overview that summarizes the up-to-date knowledge on the phytochemistry and biological properties of this valuable plant in order to support its therapeutic potential. Moreover, the biotechnological studies on I. tinctoria, which mainly focused on hairy root cultures for the enhanced production of flavonoids and alkaloids as well as on the establishment of shoot cultures and micropropagation protocols, were reviewed. They provide input for future research prospects.


title: Clinical characteristics of 34 COVID-19 patients admitted to intensive care unit in Hangzhou, China

text: OBJECTIVE: This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit (ICU) for complications from coronavirus disease 2019 (COVID-19) at the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China from Jan. 22 to Mar. 5, 2020. METHODS: A total of 34 patients were divided into two groups, including those who required noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) with additional extracorporeal membrane oxygenation (ECMO) in 11 patients. Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared. RESULTS: The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases. Most patients had lymphocytopenia on admission, with lymphocyte levels dropping progressively on the following days, and the more severe lymphopenia developed in the IMV group. In both groups, T lymphocyte counts were below typical lower limit norms compared to B lymphocytes. On admission, both groups had higher than expected amounts of plasma interleukin-6 (IL-6), which over time declined more in NIV patients. The prothrombin time was increased and the levels of platelet, hemoglobin, blood urea nitrogen (BUN), D-dimer, lactate dehydrogenase (LDH), and IL-6 were higher in IMV cases compared with NIV cases during hospitalization CONCLUSIONS: Data showed that the rates of complications, dynamics of lymphocytopenia, and changes in levels of platelet, hemoglobin, BUN, D-dimer, LDH and IL-6, and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.


title: STRUGGLING FOR FOOD IN A TIME OF CRISIS: A comment on Caplan (see pp 8–10 in this issue)

text: This commentary sets Caplan’s arguments about food banks and food poverty in the broader context of changes to the welfare state, the ‘charitization’ of state welfare and the need to address food poverty within a framework of dignity rather than charity.


title: Nonsense-Mediated Decay Serves as a General Viral Restriction Mechanism in Plants

text: (+)strand RNA viruses have to overcome various points of restriction in the host to establish successful infection. In plants, this includes RNA silencing. To uncover additional bottlenecks to RNA virus infection, we genetically attenuated the impact of RNA silencing on transgenically expressed Potato virus X (PVX), a (+)strand RNA virus that replicates in Arabidopsis. A genetic screen in this sensitized background uncovered how nonsense-mediated decay (NMD), a host RNA quality control mechanism, recognizes and eliminates PVX RNAs with internal termination codons and long 3′ UTRs. NMD also operates in natural infection contexts, and while some viruses have evolved genome expression strategies to overcome this process altogether, the virulence of NMD-activating viruses entails their ability to directly suppress NMD or to promote an NMD-unfavorable cellular state. These principles of induction, evasion, and suppression define NMD as a general viral restriction mechanism in plants that also likely operates in animals.


title: Acyclic nucleoside phosphonates containing the amide bond: hydroxy derivatives

text: ABSTRACT: To study the influence of a linker rigidity and changes in donor–acceptor properties, three series of nucleotide analogs containing a P–X–HN–C(O)– residue (X=CH(OH)CH(2), CH(OH)CH(2)CH(2), CH(2)CH(OH)CH(2)) as a replacement for the P–CH(2)–O–CHR– fragment in acyclic nucleoside phosphonates, e.g., adefovir, cidofovir, were synthesized. EDC proved to provide good yields of the analogs from the respective ω-amino-1- or -2-hydroxyalkylphosphonates and nucleobase-derived acetic acids. New phosphorus–nucleobase linkers are characterized by two fragments of the restricted rotation within amide bonds and in four-atom units (P–CH(OH)–CH(2)–N, P–CH(OH)–CH(2)–C and P–CH(2)–CH(OH)–C) in which antiperiplanar disposition of P and N/C atoms was deduced from (1)H and (13)C NMR spectral data. The synthesized analogs P–X–HNC(O)–CH(2)B [X=CH(OH)CH(2), CH(OH)CH(2)CH(2), CH(2)CH(OH)CH(2)] appeared inactive in antiviral assays on a wide variety of DNA and RNA viruses at concentrations up to 100 μM, while two phosphonates showed cytostatic activity towards myeloid leukemia (K-562) and multiple myeloma cells (MM.1S) with IC(50) of 28.8 and 40.7 μM, respectively. GRAPHICAL ABSTRACT: [Image: see text]


title: Equipment-free recombinase polymerase amplification assay using body heat for visual and rapid point-of-need detection of canine parvovirus 2

text: Abstract A visible and equipment-free recombinase polymerase amplification assay combined with a lateral flow strip (LFS RPA) was developed to detect canine parvovirus type 2 (CPV-2), which is the etiological agent of canine parvovirus disease. The CPV-2 LFS RPA assay was developed based on the VP2 gene and is performed in a closed fist using body heat for 15 min; the products are visible to the naked eye on the LFS within 5 min. The assay could detect CPV-2a, CPV-2b and CPV-2c, and there was no cross-reaction with the other viruses tested. Using the standard CPV-2 DNA as a template, the analytical sensitivity was 1.0 × 102 copies per reaction, which was the same result as that of a real-time PCR. The assay performance was further evaluated by testing 60 canine fecal samples, and CPV-2 DNA was detected in 46 samples (76.7%, 46/60) by LFS RPA, which was the same result as that of the real-time PCR assay and higher than that of the SNAP method (48.3%, 29/60). The novel CPV-2 LFS RPA assay is an attractive and promising tool for rapid and convenient diagnosis of CPV disease, especially cage side and in underequipped laboratories.


title: Unexpected receptor functional mimicry elucidates activation of coronavirus fusion

text: Recent outbreaks of severe acute respiratory syndrome and Middle-East respiratory syndrome along with the threat of a future coronavirus-mediated pandemic underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.


title: Conserved B and T cell epitopes prediction of ebola virus glycoprotein for vaccine development: An immuno-informatics approach

text: Ebola virus (EBOV), a non-segmented single-stranded RNA virus, is often-most transmitted through body fluids like sweat, tears, saliva, and nasal secretions. Till date, there is no licensed vaccine of EBOV is available in the market; however, the world is increasingly vulnerable to this emerging threat. Hence, it is the need of time to develop a vaccine for EBOV to hinder its dissemination. The current study has been designed for identification and characterization of the potential B and T-cell epitopes using the Immuno-informatics tools, and it helped in finding the potent vaccine candidates against EBOV. Prediction, antigenicity and allergenicity testing of predicted B and T cells' epitopes was done as well to identify their potential as a vaccine candidate and to measure their safety level respectively. Among B-cell epitopes “WIPAGIGVTGVIIA” showed a high antigenicity score and it would play an important role in evoking the immune response. In T-cell epitopes, peptides “AIGLAWIPY” and “IRGFPRCRY” presented high antigenicity score, which binds to MHC class-I and MHC class-II alleles respectively. All predicted epitopes were analyzed and compared with already reported peptides carefully. Comparatively, Peptides predicted in the present study showed more immunogenicity score than already reported peptides, used as positive control, and are more immunogenic as compared to them. Peptides reported in the present study do not target only Zaire EBOV (ZEBOV), as in previous studies, but also other species, i.e. Tai Forest EBOV (TAFV), Sudan EBOV (SUDV), Bundibugyo EBOV (BDBV), and Reston EBOV (RESTV) and would bring the promising results as potent vaccine candidates.


title: CORONAVIRUS E PROTEIN FORMS ION CHANNELS WITH FUNCTIONALLY AND STRUCTURALLY-INVOLVED MEMBRANE LIPIDS

text: Coronavirus (CoV) envelope (E) protein ion channel activity was determined in channels formed in planar lipid bilayers by peptides representing either the transmembrane domain of severe acute respiratory syndrome CoV (SARS-CoV) E protein, or the full-length E protein. Both of them formed a voltage independent ion conductive pore with symmetric ion transport properties. Mutations N15A and V25F located in the transmembrane domain, prevented the ion conductivity. E protein derived channels showed no cation preference in non-charged lipid membranes, whereas they behaved as pores with mild cation selectivity in negatively-charged lipid membranes. The ion conductance was also controlled by the lipid composition of the membrane. Lipid charge also regulated the selectivity of a HCoV-229E E protein derived peptide. These results suggested that the lipids are functionally involved in E protein ion channel activity, forming a protein-lipid pore, a novel concept for CoV E protein ion channel entity.


title: Lack of nasal carriage of novel corona virus (HCoV-EMC) in French Hajj pilgrims returning from the Hajj 2012, despite a high rate of respiratory symptoms

text: A cohort of 154 French Hajj pilgrims participating in the 2012 Hajj were systematically sampled with nasal swabs prior to returning to France, and screened for the novel HCoV-EMC coronavirus by two real-time RT-PCR assays. Despite a high rate of respiratory symptoms (83.4%), including 41.0% influenza-like illness, no case of HCoV-EMC infection was detected. Despite the fact that zoonotic transmission was suspected in the first few cases, a recent family cluster in the Kingdom of Saudi Arabia suggests that the virus might show at least limited spread from person to person, which justifies continuing epidemiological surveillance.


title: Vitamin E and immune response in the aged: molecular mechanisms and clinical implications

text: Summary: Nutritional status has been indicated as a contributing factor to age‐related dysregulation of the immune response. Vitamin E, a lipid‐soluble antioxidant vitamin, is important for normal function of the immune cells. The elderly are at a greater risk for vitamin E intake that is lower than recommended levels. Vitamin E supplementation above currently recommended levels has been shown to improve immune functions in the aged including delayed‐type hypersensitivity skin response and antibody production in response to vaccination, which was shown to be mediated through increased production of interleukin (IL)‐2, leading to enhanced proliferation of T cells, and through reduced production of prostaglandin E(2), a T‐cell suppressive factor, as a result of a decreased peroxynitrite formation. Vitamin E increased both cell‐dividing and IL‐producing capacities of naïve T cells, but not memory T cells. The vitamin E‐induced enhancement of immune functions in the aged was associated with significant improvement in resistance to influenza infection in aged mice and a reduced risk of acquiring upper respiratory infections in nursing home residents. Further studies are needed to determine the signaling mechanisms involved in the upregulation of naïve T‐cell function by vitamin E as well as the specific mechanisms involved in reduction of risk for upper respiratory infections.


docid: bbnhmruf

title: Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease

text: Abstract We recently established a mouse model (288–330+/+) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 106 PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 103 and 105 PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10–1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease.


title: Field‐Deployable Reverse Transcription‐Insulated Isothermal PCR (RT‐iiPCR) Assay for Rapid and Sensitive Detection of Foot‐and‐Mouth Disease Virus

text: Foot‐and‐mouth disease (FMD) is a highly contagious viral disease of cloven‐hoofed animals, which can decimate the livestock industry and economy of countries previously free of this disease. Rapid detection of foot‐and‐mouth disease virus (FMDV) is critical to containing an FMD outbreak. Availability of a rapid, highly sensitive and specific, yet simple and field‐deployable assay would support local decision‐making during an FMDV outbreak. Here we report validation of a novel reverse transcription‐insulated isothermal PCR (RT‐iiPCR) assay that can be performed on a commercially available, compact and portable POCKIT (™) analyser that automatically analyses data and displays ‘+’ or ‘−’ results. The FMDV RT‐iiPCR assay targets the 3D region of the FMDV genome and was capable of detecting 9 copies of in vitro‐transcribed RNA standard with 95% confidence. It accurately identified 63 FMDV strains belonging to all seven serotypes and showed no cross‐reactivity with viruses causing similar clinical diseases in cloven‐hoofed animals. The assay was able to identify FMDV RNA in multiple sample types including oral, nasal and lesion swabs, epithelial tissue suspensions, vesicular and oral fluid samples, even before the appearance of clinical signs. Clinical sensitivity of the assay was comparable or slightly higher than the laboratory‐based real‐time RT‐PCR assay in use. The assay was able to detect FMDV RNA in vesicular fluid samples without nucleic acid extraction. For RNA extraction from more complex sample types, a commercially available taco(™) mini transportable magnetic bead‐based, automated extraction system was used. This assay provides a potentially useful field‐deployable diagnostic tool for rapid detection of FMDV in an outbreak in FMD‐free countries or for routine diagnostics in endemic countries with less structured laboratory systems.


Emerging phenotype of SARS-CoV2 associated pancreatitis.


title: Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis

text: BACKGROUND: Since December 2019, 2019 novel coronavirus pneumonia emerged in Wuhan city and rapidly spread throughout China and even the world. We sought to analyse the clinical characteristics and laboratory findings of some cases with 2019 novel coronavirus pneumonia . METHODS: In this retrospective study, we extracted the data on 95 patients with laboratory-confirmed 2019 novel coronavirus pneumonia in Wuhan Xinzhou District People’s Hospital from January 16th to February 25th, 2020. Cases were confirmed by real-time RT-PCR and abnormal radiologic findings. Outcomes were followed up until March 2th, 2020. RESULTS: Higher temperature, blood leukocyte count, neutrophil count, neutrophil percentage, C-reactive protein level, D-dimer level, alanine aminotransferase activity, aspartate aminotransferase activity, α - hydroxybutyrate dehydrogenase activity, lactate dehydrogenase activity and creatine kinase activity were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and so were lower lymphocyte count, lymphocyte percentage and total protein level. Age below 40 or above 60 years old, male, higher Creatinine level, and lower platelet count also seemed related to severe 2019 novel coronavirus pneumonia and composite endpoint, however the P values were greater than 0.05, which mean under the same condition studies of larger samples are needed in the future. CONCLUSION: Multiple factors were related to severe 2019 novel coronavirus pneumonia and composite endpoint, and more related studies are needed in the future.


title: Utilizing Nontraditional Data Sources for Near Real-Time Estimation of Transmission Dynamics During the 2015-2016 Colombian Zika Virus Disease Outbreak

text: BACKGROUND: Approximately 40 countries in Central and South America have experienced local vector-born transmission of Zika virus, resulting in nearly 300,000 total reported cases of Zika virus disease to date. Of the cases that have sought care thus far in the region, more than 70,000 have been reported out of Colombia. OBJECTIVE: In this paper, we use nontraditional digital disease surveillance data via HealthMap and Google Trends to develop near real-time estimates for the basic (R(0)) and observed (R(obs)) reproductive numbers associated with Zika virus disease in Colombia. We then validate our results against traditional health care-based disease surveillance data. METHODS: Cumulative reported case counts of Zika virus disease in Colombia were acquired via the HealthMap digital disease surveillance system. Linear smoothing was conducted to adjust the shape of the HealthMap cumulative case curve using Google search data. Traditional surveillance data on Zika virus disease were obtained from weekly Instituto Nacional de Salud (INS) epidemiological bulletin publications. The Incidence Decay and Exponential Adjustment (IDEA) model was used to estimate R(0) and R(obs) for both data sources. RESULTS: Using the digital (smoothed HealthMap) data, we estimated a mean R(0) of 2.56 (range 1.42-3.83) and a mean R(obs) of 1.80 (range 1.42-2.30). The traditional (INS) data yielded a mean R(0) of 4.82 (range 2.34-8.32) and a mean R(obs) of 2.34 (range 1.60-3.31). CONCLUSIONS: Although modeling using the traditional (INS) data yielded higher R(0) estimates than the digital (smoothed HealthMap) data, modeled ranges for R(obs) were comparable across both data sources. As a result, the narrow range of possible case projections generated by the traditional (INS) data was largely encompassed by the wider range produced by the digital (smoothed HealthMap) data. Thus, in the absence of traditional surveillance data, digital surveillance data can yield similar estimates for key transmission parameters and should be utilized in other Zika virus-affected countries to assess outbreak dynamics in near real time.


title: Health promotion practices as perceived by primary healthcare professionals at the Ministry of National Guard Health Affairs, Saudi Arabia

text: Introduction: In recent years, several research studies have investigated health promotion practices in Saudi healthcare organizations, yet no published literature exists on health promotion practices of primary healthcare professionals working for the Ministry of National Guard Health Affairs (MNG-HA). Methods: A cross-sectional study was conducted in a convenience sample of 206 primary healthcare professionals at the MNG-HA. A self-reporting questionnaire was used to investigate the attitudes, awareness, satisfaction, and methods regarding health promotion practices of primary healthcare professionals. Results: Of the 206 primary healthcare professionals surveyed, 58.1% reported awareness of health promotion programs conducted in the hospitals and 64.6% reported that the health promotion system in the hospitals needs to be improved. Language barriers and cultural beliefs were viewed as obstacles to carrying out effective health promotion by 65% and 64.6% of primary healthcare professionals, respectively. The majority (79.9%) of the primary healthcare professionals perceived themselves as having the necessary skills to promote health and 80.6% believed that printed educational materials are the most prevalent method of health promotion/education, whereas 55.8% reported that counseling was the most preferred method of health promotion. Conclusion: The awareness level of health promotion policies, strategies, and programs conducted in the hospitals was not found to be satisfactory. Therefore, widespread training programs are recommended to improve the health promotion system in the hospitals. These programs include facilitating behavioral change, introducing health promotion policies and strategies in hospitals, mandatory workshops, and systematic reminders.


title: Long-term sequelae of SARS in children

text: Summary Severe acute respiratory syndrome (SARS) runs a more benign course in children during the acute phase. Unlike adult patients, no fatalities were reported among the paediatric SARS patients. Published data on long-term sequelae of SARS are very limited. In our follow-up study, although patients have clinically recovered from their initial illness, exercise impairment and residual radiological abnormalities were demonstrated at 6 months after diagnosis. It is important to assess these patients on a regular basis to detect and provide appropriate management for persistent or emerging long-term sequelae in the physical, psychological and social domains.


title: Evolution of ORF5 of Spanish porcine reproductive and respiratory syndrome virus strains from 1991 to 2005

text: Abstract ORF5 sequences of porcine reproductive and respiratory syndrome virus (PRRSV) were analysed to determine genetic diversity, codon usage, positive and negative selection sites and potential changes in the predicted glycoprotein 5 (GP5). A hypothetical GP5 containing all selected sites was constructed to determine its characteristics. These sequences corresponded to isolates obtained 10 years apart (1991–1995, 18 strains) and a second set (n =46) from 2000 to 2005. Similarity to Lelystad virus (LV) decreased from 95.5% in 1991–1995 to 89.5% in 2000–2005. Three highly variable regions were found in ORF5. Codon usage was different in both sets for leucine, glutamine, serine and proline. Thus, 2000–2005 sequences used codons more similar to those present in highly expressed pig genes compared to the 1991–1995 set. Twenty four sites of positive selection and 20 sites of negative selection were found in GP5, most of them in transmembrane regions. Additional glycosylation in N37 of GP5 was common in 2000–2005 but some sequences lack a glycosylation site in N46. The hypothetical GP5 was only 88.1% similar to LV and was less hydrophobic. Taking together these results suggest that PRRSV is still adapting to pig cells.


The anthropologist amidst and beyond: notes on temporalities of COVID‐19


title: Performance of Facepiece Respirators and Surgical Masks Against Surgical Smoke: Simulated Workplace Protection Factor Study

text: OBJECTIVE: Surgical smoke generated during electrocautery contains toxins which may cause adverse health effects to operating room (OR) personnel. The objective of this study was to investigate the performance of surgical masks (SMs), which are routinely used in ORs, more efficient N95 surgical mask respirator (SMRs) and N100 filtering facepiece respirator (FFRs), against surgical smoke. METHODS: Ten subjects were recruited to perform surgical dissections on animal tissue in a simulated OR chamber, using a standard electrocautery device, generating surgical smoke. Six respiratory protective devices (RPDs) were tested: two SMs, two SMRs, and two N100 FFRs [including a newly developed faceseal (FS) prototype]. Fit testing was conducted before the experiment. Each subject was then exposed to the surgical smoke while wearing an RPD under the tests. Concentrations inside (C(in)) and outside (C(out)) of the RPD were measured by a particle size spectrometer. The simulated workplace protection factor (SWPF) was determined by the ratio of C(out) and C(in) for each RPD-wearing subject. RESULTS: For the SMs, the geometric means of SWPF(total) (based on the total aerosol concentration) were 1.49 and 1.76, indicating minimal protection. The SWPF(total) values of the SMRs and N100 FFRs were significantly higher than those of the SMs: for the two SMRs, the SWPF(total) were 208 and 263; for the two N100s, the SWPF(total) values were 1,089 and 2,199. No significant difference was observed between either the two SMs or the two SMRs. The SWPF(total) for the novel FS prototype N100 FFR was significantly higher than the conventional N100 FFR. The correlation between SWPF(total) and fit factor (FF) determined for two N95 SMRs was not significant. CONCLUSIONS: SMs do not provide measurable protection against surgical smoke. SMRs offer considerably improved protection versus SMs, while the N100 FFRs showed significant improvement over the SMRs. The FS prototype offered a higher level of protection than the standard N100 FFR, due to a tighter seal. While we acknowledge that conventional N100 FFRs (equipped with exhalation valves) are not practical for human OR use, the results obtained with the FS prototype demonstrate the potential of the new FS technology for implementation on various types of respirators.


title: Review of Literature for Air Medical Evacuation High-Level Containment Transport

text: Abstract Introduction Aeromedical evacuation (AE) is a challenging process, further complicated when a patient has a highly hazardous communicable disease (HHCD). We conducted a review of the literature to evaluate the processes and procedures utilized for safe AE high-level containment transport (AE-HLCT) of patients with HHCDs. Methods A literature search was performed in PubMed/MEDLINE (from 1966 through January 2019). Authors screened abstracts for inclusion criteria and full articles were reviewed if the abstract was deemed to contain information related to the aim. Results Our search criteria yielded 14 publications and were separated based upon publication dates, with the natural break point being the beginning of the 2013-2016 Ebola virus disease epidemic. Best practices and recommendations from identified articles are subdivided into pre-flight preparations, inflight operations, and post-flight procedures. Conclusions Limited peer-reviewed literature exists on AE-HLCT, including important aspects related to healthcare worker fatigue, alertness, shift scheduling, and clinical care performance. This hinders the sharing of best practices to inform evacuations and equip teams for future outbreaks. Despite the successful use of different aircraft and technologies, the unique nature of the mission opens the opportunity for greater coordination and development of consensus standards for AE-HLCT operations.


title: Zoonotic disease risk perceptions in the British veterinary profession

text: Abstract In human and veterinary medicine, reducing the risk of occupationally-acquired infections relies on effective infection prevention and control practices (IPCs). In veterinary medicine, zoonoses present a risk to practitioners, yet little is known about how these risks are understood and how this translates into health protective behaviour. This study aimed to explore risk perceptions within the British veterinary profession and identify motivators and barriers to compliance with IPCs. A cross-sectional study was conducted using veterinary practices registered with the Royal College of Veterinary Surgeons. Here we demonstrate that compliance with IPCs is influenced by more than just knowledge and experience, and understanding of risk is complex and multifactorial. Out of 252 respondents, the majority were not concerned about the risk of zoonoses (57.5%); however, a considerable proportion (34.9%) was. Overall, 44.0% of respondents reported contracting a confirmed or suspected zoonoses, most frequently dermatophytosis (58.6%). In veterinary professionals who had previous experience of managing zoonotic cases, time or financial constraints and a concern for adverse animal reactions were not perceived as barriers to use of personal protective equipment (PPE). For those working in large animal practice, the most significant motivator for using PPE was concerns over liability. When assessing responses to a range of different “infection control attitudes”, veterinary nurses tended to have a more positive perspective, compared with veterinary surgeons. Our results demonstrate that IPCs are not always adhered to, and factors influencing motivators and barriers to compliance are not simply based on knowledge and experience. Educating veterinary professionals may help improve compliance to a certain extent, however increased knowledge does not necessarily equate to an increase in risk-mitigating behaviour. This highlights that the construction of risk is complex and circumstance-specific and to get a real grasp on compliance with IPCs, this construction needs to be explored in more depth.


docid: fhonfnxq

title: CXCR4 antagonist AMD3100 reverses the resistance to tamoxifen in breast cancer via inhibiting AKT phosphorylation

text: Abstract Endocrine therapy is a systemic therapy and has become the main treatment strategy for patients with estrogen receptor (ER) positive breast cancer. However, tamoxifen resistance has become an insurmountable clinical challenge and the underlying mechanisms are still poorly understood. In this study, we explored the roles of CXCR4 in tamoxifen-treated breast cancer and tamoxifen resistance. Based on Gene Expression Omnibus (GEO) database, high expression of CXCR4 was found to be associated with worse overall survival (HR = 4.646, p < 0.001) and cancer-specific survival (HR = 4.480, p < 0.001) in tamoxifen-treated breast cancer. CXCR4 was also positively correlated with the level of AKT phosphorylation and the resistance to tamoxifen in breast cancer. AMD3100 is a CXCR4 antagonist and was found to decrease p-AKT levels of tamoxifen-resistant cells. The reversal effect of AMD3100 on tamoxifen resistance was also confirmed in vitro and in vivo. Taken together, our study demonstrated that CXCR4 could be a potential prognostic biomarker for tamoxifen-treated breast cancer and the combination of AMD3100 with tamoxifen could be a more efficacious therapeutic strategy for the treatment of tamoxifen resistance.


Psychosocial Impact of SARS


title: Porcine parvovirus replication is suppressed by activation of the PERK signaling pathway and endoplasmic reticulum stress-mediated apoptosis

text: Abstract Endoplasmic reticulum (ER) stress is associated with numerous mammalian diseases, especially viral diseases. Porcine parvovirus (PPV) is the causative agent of reproductive failure in swine. Here, we observed that the PPV infection of porcine kidney 15 and porcine testis cells resulted in the activation of ER stress sensors mediated by protein kinase R-like ER kinase (PERK), but not inositol-requiring enzyme 1 and activating transcription factor 6 (ATF6). ER stress activation obviously blocked PPV replication. Depletion of proteins, such as PERK, eukaryotic initiation factor 2, and ATF4, by small interfering RNA significantly enhanced PPV replication. Moreover, the pro-apoptotic factor C/EBP homologous protein was identified a key factor in the inhibition of PPV replication. These data demonstrate that PPV infection activates ER stress through the PERK signaling pathway and that ER stress inhibits further PPV replication by promoting apoptosis.


title: How inclusive are we, really?

text: Abstract Research has revealed that nurses and nursing students with disabilities experience discrimination. There are relatively few nurses with obvious physical disabilities working in clinical settings. Misconceptions abound regarding what a nurse with a disability can do. The focus tends to be on disability rather than ability. Similarly, prospective nursing students with disabilities are viewed with apprehension and caution. The overriding concern regarding nurses and nursing students with disabilities is that they will jeopardize patient safety. Nurse educators worry that students will not be able to complete the required skills and often confuse essential functions of nursing work with the academic standards required to graduate successfully. This article proposes that based on the research, we are not truly inclusive of nurses or nursing students with disabilities.


title: Optimal control of a fractional order model for granular SEIR epidemic with uncertainty

text: In this study, we present a general formulation for the optimal control problem to a class of fuzzy fractional differential systems relating to SIR and SEIR epidemic models. In particular, we investigate these epidemic models in the uncertain environment of fuzzy numbers with the rate of change expressed by granular Caputo fuzzy fractional derivatives of order β ∈ (0, 1]. Firstly, the existence and uniqueness of solution to the abstract fractional differential systems with fuzzy parameters and initial data are proved. Next, the optimal control problem for this fractional system is proposed and a necessary condition for the optimality is obtained. Finally, some examples of the fractional SIR and SEIR models are presented and tested with real data extracted from COVID-19 pandemic in Italy and South Korea.


title: Influenza is now a preventable disease

text: Abstract The world is waiting with apprehension for the predicted pandemic of H5N1 (avian) influenza as an increasing number of countries in Asia, Europe and Africa report cases of influenza in migrating birds. All is not ‘despondency’, however. Targeted and controlled administration of antiviral drugs, alone or in combination, to contacts and cases, together with well tried public health measures, should slow down the spread of the infection and allow time for vaccines to be developed, thus preventing a worldwide pandemic of the type that occurred in 1918.