title: Is the ultrasonic scalpel recommended in head and neck surgery during the COVID‐19 pandemic? State‐of‐the‐art review

text: BACKGROUND: Guidelines for ultrasonic devices use are imperative because infectious aerosols arising from airway procedures were a key etiologic factor in prior coronavirus outbreaks. This manuscript aims to summarize the available recommendations and the most relevant concepts about the use of ultrasonic scalpel during the SARS‐CoV‐2 pandemic. METHODS: Literature review of manuscripts with patients, animal models, or in vitro studies where the ultrasonic scalpel was used and the plume produced was analyzed in a quantitative and/ or qualitative way. DISCUSSION: Activated devices with tissue produce a biphasic bioaerosol composed (size 68.3‐994 nm) of tissue particles, blood, intact and no viable cells, and carcinogenic or irritant hydrocarbons (benzene, ethylbenzene, styrene, toluene, heptene, and methylpropene). CONCLUSION: It is imperative to use an active smoke evacuator, to avoid ultrasonic scalpel use in COVID‐19 positive patients and in upper airway surgery, as well as to follow the protection recommendations of the guidelines for management this type of patients.


title: Type 2 Inflammation Modulates ACE2 and TMPRSS2 in Airway Epithelial Cells

text: Abstract Background SARS-CoV-2 has dramatically changed our world, country, communities and families. There is controversy regarding risk factors for severe COVID-19 disease. It has been suggested that asthma and allergy are not highly represented as co-morbid conditions associated with COVID-19. Objective To extend our work in interleukin (IL)-13 biology to determine if airway epithelial cell expression of two key mediators critical for SARS-CoV-2 infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) are modulated by IL-13. Methods We determined effects of IL-13 treatment on ACE2 and TMPRSS2 expression ex vivo in primary airway epithelial cells from participants with and without type 2 asthma obtained by bronchoscopy. We also examined expression of ACE2 and TMPRSS2 in two datasets containing gene expression data from nasal and airway epithelial cells from children and adults with asthma and allergic rhinitis. Results IL-13 significantly reduced ACE2 and increased TMPRSS2 expression ex vivo in airway epithelial cells. In two independent datasets, ACE2 expression was significantly reduced and TMPRSS2 was significantly increased in the nasal and airway epithelial cells in type 2 asthma and allergic rhinitis. ACE2 expression was significantly negatively associated with type 2 cytokines while TMPRSS2 expression was significantly positively associated with type 2 cytokines. Conclusion IL-13 modulates ACE2 and TMPRSS2 expression in airway epithelial cells in asthma. This deserves further study with regard to any effects asthma and atopy may render in the setting of COVID-19 infection.


title: Epidemiological characteristics of confirmed COVID-19 in Guizhou province, China

text: OBJECTIVE: To explore the epidemiological characteristics of COVID-19 associated with SARS-Cov-2 in Guizhou province, and to compare the differences in epidemiology with other provinces. METHODS: The data were extracted from National Health Commission of the People’s Republic of China, Health Commission of Guizhou province, and Health Commission of Hubei province from January 20 to February 12, 2020. Information included such as general demographic indicators, population data and clinical outcome. RESULTS: A total of 135 cases were analyzed in the study. The average age was 39.46±18.95 years. The ratio of males to females was 0.985:1. Most of COVID-19 patients were 18-45 years old (52.27%). Close contact history was the most common (37.88%), followed by residence history in Hubei (34.85%). There was no difference between males and females in age (P=0.953) and exposure condition (P=0.186). Correlation analysis showed that there was a significant positive correlation between the migration index and the number of confirmed cases (r=0.816, P=0.007). CONCLUSION: Among the cases, most patients were young adults. Most epidemiological characteristics were no difference between males and females. Family-based transmission should not be ignored, as a close contact history was the top reason of exposure. Moreover, population movements also had significant impact on outbreaks.


title: Recomendaciones de “hacer” y “no hacer” en el tratamiento de los pacientes críticos ante la pandemia por coronavirus causante de COVID-19 de los Grupos de Trabajo de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC)◊

text: Abstract On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic.


title: Neighborhood Disadvantage and Children’s Cognitive Skill Trajectories

text: This study examined how neighborhood poverty is associated with children’s trajectories of growth in math and reading skills in early elementary school, and how these associations vary by student characteristics, using multilevel growth models with nationally representative data from the 2011 Early Childhood Longitudinal Study-Kindergarten Cohort. About one-quarter (25.6%) of children lived in communities of concentrated poverty. Findings suggest that achievement gaps by neighborhood disadvantage are large and present before Kindergarten, shrink during the Kindergarten year, but then widen the year following, and remain relatively consistent in the first years of elementary school. Growth in math skills appeared to vary more with neighborhood poverty than growth in reading skills. There was limited evidence that the relationship between neighborhood poverty and test score trajectories varied by child race, ethnicity, early education and Kindergarten experience, and parents’ immigration status, but growth differences across student characteristics were small. Policy and research implications are discussed.


Immunity, the God-given weapon against infection


title: Localization of Neurovirulence Determinant for Rats on the S1 Subunit of Murine Coronavirus JHMV

text: Abstract A cloned virus of murine coronavirus JHMV, cl-2, was shown to be highly neurovirulent for rats in comparison with other JHMV variants. We have isolated cl-2-derived variant viruses resistant to neutralization by monoclonal antibodies (MAbs) specific for the spike (S) protein of cl-2. The variants MM6 and MM13, selected by the MAbs specific for the JHMV S protein, were revealed to have a point mutation located within the N-terminal 100 amino acids (aa) of the S1 protein. The variants MM56, MM85, and MM78, selected by MAbs specific for the larger S protein of JHMV, were shown to have a deletion composed of about 150 aa located in the middle of the S1 subunit (MM56 and MM85) or one amino acid deletion, aspattic acid at number 543 from the N-terminus of the S1 (MM78). These five MAb-resistant variants were not different from cl-2 in growth pattern on cultured DBT cells. MM6 and MM13 were shown to be highly neurovirulent for 4-week-old Lewis rats, growing to high titers in the brain and causing as high an incidence of neurological disease and death as the parental cl-2. In contrast, MM56 and MM85 were nonneurovirulent for rats. They did not cause any central nervous system disorders nor did they multiply in the rat brains. MM78 showed intermediate neurovirulence as well as intermediate growth potential in the rat brain. However, there was no apparent difference in neurovirulence between the parental and the MAb-resistant variants for mice; all of these viruses showed high neurovirulence for mice. These results suggest that the domain composed of about 150 aa in the middle of the S1 is critical for high neurovirulence of JHMV for rats. Furthermore, it is suggested that the neurovirulence of cl-2 for mice is controlled by a different viral factor.


title: The significance of rhinovirus detection in hospitalized children: clinical, epidemiological and virological features

text: Recent developments in molecular diagnostic tools have led to the easy and rapid detection of a large number of rhinovirus (HRV) strains. However, the lack of clinical and epidemiological data hampers the interpretation of these diagnostic findings. From October 2009 to January 2011, we conducted a prospective study in hospitalized children from whom samples were taken for the detection of respiratory viruses. Clinical, epidemiological and microbiological data from 644 patients with 904 disease episodes were collected. When HRV tested positive, strains were further characterized by sequencing the VP4/VP2 region of the HRV genome. HRV was the single respiratory virus detected in 254 disease episodes (28%). Overall, 99 different serotypes were detected (47% HRV-A, 12% HRV-B, 39% HRV-C). Patients with HRV had more underlying pulmonary illness compared with patients with no virus (p 0.01), or patients with another respiratory virus besides HRV (p 0.007). Furthermore, cough, shortness of breath and a need for oxygen were significantly more present in patients with HRV infection. Particularly, patients with HRV-B required extra oxygen. No respiratory symptom, except for oxygen need, was predictive of the presence of HRV. In 22% of HRV-positive disease episodes, HRV infection was hospital acquired. Phylogenetic analysis revealed several clusters of HRV; in more than 25% of these clusters epidemiological information was suggestive of transmission within specific wards. In conclusion, the detection of HRV may help in explaining respiratory illness, particular in patients with pulmonary co-morbidities. Identifying HRV provides opportunities for timely implementation of infection control measures to prevent intra-hospital transmission.


title: 10 Select agent program impact on the IBC

text: Abstract Stringent, exacting and local oversight for the control and use of Select Agents and Toxins is crucial to ensuring biosecurity. However, review of research involving Select Agents and Toxins can present particular challenges to the Institutional Biosafety Committee (IBC). Institutional review for biosecurity programs focuses on security assessments and access control, whereas most IBCs primarily focus on occupational exposure assessment, biohazard control, and biosafety practices. Determining how and where to interweave biosecurity program requirements into programs based on occupational health priorities is the key to integrated and effective compliance management. Recent new or pending regulations on dual use or gain of function research suggests or mandates additional duties for the IBC. This chapter explores challenges and strategies for institutional oversight and support of Select Agent program compliance.


title: The infectious march: the complex interaction between microbes and the immune system in asthma

text: There has been significant progress in our knowledge about the relationship between infectious disease and the immune system in relation to asthma, but many unanswered questions still remain. Respiratory tract infections such as those caused by respiratory syncytial virus and rhinovirus during the first two years of life are still clearly associated with later wheezing and asthma, but the mechanism has not been completely worked out. Is there an ‘infectious march’ triggered by infection in infancy that progresses to disease pathology or are infants who contract respiratory infections predisposed to developing asthma? This review focuses on the common themes in the interaction between microbes and the immune system and presents a critical appraisal of the evidence to date. The various mechanisms whereby microbes alter the immune response and how this might influence asthma are discussed along with new and promising clinical practices for prevention and therapy. Recent advances in utilizing sensitive PCR detection methods have allowed more rigorous testing of the causality hypothesis of virus infection leading to asthma, but the evidence is still equivocal. Various exceptions and inconsistencies in the clinical trials are discussed in light of new guidelines for subject inclusion/exclusion in hopes of providing some standardization. In spite of past failures in vaccination and disappointing results of some clinical trials, the new strategies for prophylaxis including RNA interference and targeted delivery of microbicides offer a large dose of hope to a world suffering from an increasing incidence of asthma and a huge burden of healthcare cost and loss of quality of life.


Building a global atlas of zoonotic viruses


title: The Identification of a Calmodulin-Binding Domain within the Cytoplasmic Tail of Angiotensin-Converting Enzyme-2

text: Angiotensin-converting enzyme (ACE)-2 is a homolog of the well-characterized plasma membrane-bound angiotensin-converting enzyme. ACE2 is thought to play a critical role in regulating heart function, and in 2003, ACE2 was identified as a functional receptor for severe acute respiratory syndrome coronavirus. We have recently shown that like ACE, ACE2 undergoes ectodomain shedding and that this shedding event is up-regulated by phorbol esters. In the present study, we used gel shift assays to demonstrate that calmodulin, an intracellular calcium-binding protein implicated in the regulation of other ectodomain shedding events, binds a 16-amino acid synthetic peptide corresponding to residues 762–777 within the cytoplasmic domain of human ACE2, forming a calcium-dependent calmodulin-peptide complex. Furthermore, we have demonstrated that ACE2 expressed in Chinese hamster ovary cells specifically binds to glutathione-S-transferase-calmodulin, but not glutathione-S-transferase alone, in pull-down assays using cell lysates. Finally, to investigate whether calmodulin has any effect on ACE2 ectodomain shedding in cells that endogenously express the enzyme, cells from a human liver cell line (Huh-7) expressing ACE2 were incubated with calmodulin-specific inhibitors, trifluoperazine and calmidazolium. Both trifluoperazine (25 μmol/liter) and calmidazolium, (25 μmol/liter) significantly increased the release of ACE2 into the medium (44.1 ± 10.8%, P < 0.05, Student’s t test; unpaired, two-tailed, and 51.1 ± 7.4% P < 0.05, one-way ANOVA, respectively;), as analyzed by an ACE2-specific quenched fluorescence substrate assay. We also show that the calmodulin-specific inhibitor-stimulated shedding of ACE2 is independent from phorbol ester-induced shedding. In summary, we have demonstrated that calmodulin is able to bind ACE2 and suggest that the ACE2 ectodomain shedding and/or sheddase(s) activation regulated by calmodulin is independent from the phorbol ester-induced shedding.


title: Histidine Triad-Like Motif of the Rotavirus NSP2 Octamer Mediates Both RTPase and NTPase Activities

text: Rotavirus NSP2 is an abundant nonstructural RNA-binding protein essential for forming the viral factories that support replication of the double-stranded RNA genome. NSP2 exists as stable doughnut-shaped octamers within the infected cell, representing the tail-to-tail interaction of two tetramers. Extending diagonally across the surface of each octamer are four highly basic grooves that function as binding sites for single-stranded RNA. Between the N and C-terminal domains of each monomer is a deep electropositive cleft containing a catalytic site that hydrolyzes the γ-β phosphoanhydride bond of any NTP. The catalytic site has similarity to those of the histidine triad (HIT) family of nucleotide-binding proteins. Due to the close proximity of the grooves and clefts, we investigated the possibility that the RNA-binding activity of the groove promoted the insertion of the 5′-triphosphate moiety of the RNA into the cleft, and the subsequent hydrolysis of its γ-β phosphoanhydride bond. Our results show that NSP2 hydrolyzes the γP from RNAs and NTPs through Mg(2+)-dependent activities that proceed with similar reaction velocities, that require the catalytic His(225) residue, and that produce a phosphorylated intermediate. Competition assays indicate that although both substrates enter the active site, RNA is the preferred substrate due to its higher affinity for the octamer. The RTPase activity of NSP2 may account for the absence of 5′-terminal γP on the (−) strands of the dsRNA genome segments. This is the first report of a HIT-like protein with a multifunctional catalytic site, capable of accommodating both NTPs and RNAs during γP hydrolysis.


title: SARS-CoV and IFN: Too Little, Too Late

text: Dysregulated type I interferon (IFN-I) expression can lead to severe pathology and disease. In this issue of Cell Host & Microbe, Channappanavar et al. (2016) use a SARS-coronavirus animal model to describe how rapid and robust virus replication with delayed IFN-I can lead to lung immunopathology, with fatal outcomes.


title: Will healthcare workers improve infection prevention and control behaviors as COVID-19 risk emerges and increases, in China?

text: BACKGROUND: COVID-19 arise global attention since their first public reporting. Infection prevention and control (IPC) is critical to combat COVID-19, especially at the early stage of pandemic outbreak. This study aimed to measure level of healthcare workers’ (HCW’) self-reported IPC behaviors with the risk of COVID-19 emerges and increases. METHODS: A cross-sectional study was conducted in two tertiary hospitals. A structured self-administered questionnaire was delivered to HCWs in selected hospitals. The dependent variables were self-reported IPC behavior compliance; and independent variables were outbreak risk and three intent of infection risk (risk of contact with suspected patients, high-risk department, risk of affected area). Chi-square tests and multivariable negative binomial regression models were employed. RESULTS: A total of 1386 participants were surveyed. The risk of outbreak increased self-reported IPC behavior on each item (coefficient varied from 0.029 to 0.151). Considering different extent of risk, HCWs from high-risk department had better self-reported practice in most IPC behavior (coefficient ranged from 0.027 to 0.149). HCWs in risk-affected area had higher self-reported compliance in several IPC behavior (coefficient ranged from 0.028 to 0.113). However, HCWs contacting with suspected patients had lower self-reported compliance in several IPC behavior (coefficient varied from − 0.159 to − 0.087). CONCLUSIONS: With the risk of COVID-19 emerges, HCWs improve IPC behaviors comprehensively, which benefits for better combat COVID-19. With the risk (high-risk department and affected area) further increases, majority of IPC behaviors achieved improvement. Nevertheless, under the risk of contact with suspected patients, HCWs show worse IPC behaviors. Which may result from higher work load and insufficient supplies and resources among these HCWs. The preparedness system should be improved and medical assistance is urgently needed.


title: InTRONs in Biotech

text: Eukaryotic gene expression relies on several complex molecular machineries that act in a highly coordinated fashion. These machineries govern all the different steps of mRNA maturation, from gene transcription and pre-mRNA processing in the nucleus to the export of the mRNA to the cytoplasm and its translation. In particular, the pre-mRNA splicing process consists in the joining together of sequences (known as “exons”) that have to be differentiated from their intervening sequences commonly referred to as “introns.” The complex required to perform this process is a very dynamic macromolecular ribonucleoprotein assembly that functions as an enzyme, and is called the “spliceosome.” Because of its flexibility, the splicing process represents one of the main mechanisms of qualitative and quantitative regulation of gene expression in eukaryotic genomes. This flexibility is mainly due to the possibility of alternatively recognizing the various exons that are present in a pre-mRNA molecule and therefore enabling the possibility of obtaining multiple transcripts from the same gene. However, regulation of gene expression by the spliceosome is also achieved through its ability to influence many other gene expression steps that include transcription, mRNA export, mRNA stability, and even protein translation. Therefore, from a biotechnological point of view the splicing process can be exploited to improve production strategies and processes of molecules of interest. In this work, we have aimed to provide an overview on how biotechnology applications may benefit from the introduction of introns within a sequence of interest.


title: Responding to natural disasters vs. disease outbreaks: Do emergency medical service providers have different views?

text: Abstract Introduction Our planet has been experiencing a huge burden of natural disasters and public health emergencies in the last three decades. Emergency medical service providers are expected to be in the frontlines during such emergencies. Yet, this system is badly understudied when it comes to its roles and performance during disasters and public health emergencies. This study is designed to enhance understanding by assessing a sample U.S EMS providers’ views about working during natural disasters and disease outbreaks and explores whether they are coming to work during such conditions. Methods This study utilized a qualitative approach using face-to-face interviews with EMS workers from the State of Delaware, USA. Participants were asked about their views, insights, and potential behavior of working during natural disasters and disease outbreaks. Data collected were transcribed and coded using ATLAS.ti software to develop themes of the study using an inductive approach. Results Three themes were emerged from interviews regarding working during natural disasters; respondents expressed excitement, concern, or no real differences. For disease outbreaks, however, the two themes were concerned and no additional risk. While participants expressed varying concerns about working during disasters and pandemic conditions, everyone felt willing and obligated to come to work despite the perceived high risk for some of them to work in some conditions. Conclusion This study helps to provide the base upon which EMS, public health, and emergency management agencies can formulate actions that emerged from the views of EMS providers concerning work during disasters and public health emergencies.


title: The geography of institutional psychiatric care in France 1800–2000: Historical analysis of the spatial diffusion of specialised facilities for institutional care of mental illness

text: As in other European countries, specialised psychiatric hospitals were established throughout France during the 19th Century. The construction of these hospitals can be considered as the concrete expression of a therapeutic innovation which recognized insanity as an illness that could be treated in such specialised institutions. The spatial diffusion of these innovative institutions through 19th and 20th century France is analysed and we explore how far this can be understood through theories of diffusion of innovations including geographical models of hierarchical and expansion diffusion (or whether other conceptual models are more appropriate). The research reported here particularly focuses on the period 1800–1961. It involved the construction of an original historical database of both psychiatric hospitals and information on the cities where these institutions were located. This was used to examine and interpret the different phases of development of psychiatric institutions and the parts of the country and types of geographical setting where they were concentrated. A multiple correspondence analysis was then performed to examine the connections between different aspects of the diffusion process. The study shows the limitations of classical models of spatial diffusion, which are found to be consistent with some, but not all aspects of the development of psychiatric institutions in France. An alternative political ecology approach seems more appropriate to conceptualise the various processes involved; national policies, social representations, medicalisation of care of mental illness, and urban and economic growth all seem to be associated with the emergence of a variable and complex pattern. This paper also opens a large field of research. Compared with other western countries, the geography of French psychiatric care is relatively under-researched, although there has been a strong spatial dimension to mental health policy in the country. This analysis provides a context for studies of more contemporary processes of French deinstitutionalisation, which is strongly structured by the past heritage of these large asylum facilities.


docid: rtfoqcwg

title: A mobile terminal application program was used for endotracheal tube cuff pressure measurement

text: We studied the application of a mobile terminal application program in endotracheal tube (ETT) cuff pressure measurement to improve the implementation rate of scientific ETT cuff pressure measurement and to ensure that the pressure falls within the recommended range. A pre-post controlled study lasting for 18 months was undertaken in a 40-bed general intensive care unit (GICU). This included a 6-month baseline period (baseline group) and a 6-month intervention period (intervention group). The mobile terminal application program was applied to monitor the cuff pressure of endotracheal intubation as an intervention measure during the intervention period. ETT pressure was the main outcome measure, while gender, age, causes for ICU admission, sedation score, duration of prior intubation, size of ETT, and number of VAP patients were secondary outcomes. ETT cuff pressure was monitored 742 times in both the baseline group and the intervention group. A total of 56.9% of the cuff pressure measurements in the baseline group were within the recommended range, while 78.4% of measurements in the intervention group were within the recommended range, reflecting a statistically significant difference (P < 0.05). The application of the mobile terminal application program used for ETT cuff pressure measurement could improve the percentage of ETT cuff pressure measurements falling within the recommended range.


title: Cloning of IRAK1 and its upregulation in symptomatic mandarin fish infected with ISKNV

text: Abstract Interleukin-1 receptor activated kinases (IRAKs) play crucial roles in the Toll-like receptor (TLR) mediated signal transduction pathways that control host innate immune responses. Here we report the cloning of an IRAK1 cDNA (named ScIRAK1) from the mandarin fish. The predicted ScIRAK1 peptide contains a death domain and a serine/threonine-specific kinase domain. Quantitative RT-PCR showed that ScIRAK1 mRNA was primarily expressed in blood cells and posterior kidney. Seven days following infection with infectious spleen and kidney necrosis virus (ISKNV), the ScIRAK1 mRNA level was significantly higher in the blood cells of clinically symptomatic fish than in the blood cells of asymptomatic fish or control fish injected with phosphate-buffered saline. Additional experiments showed that overexpression of ScIRAK1 in the 293T cells could induce NF-κB activation. These results suggest that ScIRAK1 may play a role in the pathology of ISKNV infection in the mandarin fish.


docid: mettlmhz

title: Clinical, molecular and epidemiological characterization of the SARS-CoV2 virus and the Coronavirus disease 2019 (COVID-19), a comprehensive literature review

text: Abstract Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms. Those that infect animals can evolve and become infectious to humans. Three recent examples of these viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19). COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 20th May 2020 show more than 5 million people had been infected with the virus, causing more than 330,000 deaths in over 210 countries worldwide. The large amount of information received daily relating to COVID-19 is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).


title: Inhibition of avian leukosis virus subgroup J replication by miRNA targeted against env

text: No effective vaccine has been developed against the subgroup J avian leukosis virus (ALV-J). The genetic diversity of ALV-J might be related to the env gene, therefore, we selected conserved sequences of the env gene and designed interference sequence. In this study, microRNAs (miRNAs) were designed and synthesized, corresponding to conserved regions of the env gene. These miRNAs were cloned into the linearized eukaryotic expression vector. The recombinant plasmids were transfected into DF-1 cells. After transfection, the cells were inoculated with ALV-J. In reporter assays, the transfection efficiency is 80 % by indirect immunofluorescence (IFA). Expression of the virus envelope glycoprotein was measured by IFA and western blotting assays. The relative expression of env gene was determined using quantitative PCR. Our results show that the mi-env 231 and mi-env 1384 could effectively suppress the replication of ALV-J with an efficiency of 68.7–75.2 %. These data suggest that the miRNAs targeting the env can inhibit replication of ALV-J efficiently. This finding provides evidence that miRNAs could be used as a potential tool against ALV infection.


title: Identfication of viral and bacterial etiologic agents of the pertussis-like syndrome in children under 5 years old hospitalized

text: BACKGROUND: Acute respiratory infections (ARIs) represent an important cause of morbidity and mortality in children, remaining a major public health concern, especially affecting children under 5 years old from low-income countries. Unfortunately, information regarding their epidemiology is still limited in Peru. METHODS: A secondary data analysis was performed from a previous cross-sectional study conducted in children with a probable diagnosis of Pertussis from January 2010 to July 2012. All samples were analyzed via Polymerase Chain Reaction (PCR) for the following etiologies: Influenza-A, Influenza-B, RSV-A, RSV-B, Adenovirus, Parainfluenza 1 virus, Parainfluenza 2 virus, Parainfluenza 3 virus, Mycoplasma pneumoniae and Chlamydia pneumoniae. RESULTS: A total of 288 patients were included. The most common pathogen isolated was Adenovirus (49%), followed by Bordetella pertussis (41%) from our previous investigation, the most prevelant microorganisms were Mycoplasma pneumonia (26%) and Influenza-B (19.8%). Coinfections were reported in 58% of samples and the most common association was found between B. pertussis and Adenovirus (12.2%). CONCLUSIONS: There was a high prevalence of Adenovirus, Mycoplasma pneumoniae and other etiologies in patients with a probable diagnosis of pertussis. Despite the presence of persistent cough lasting at least two weeks and other clinical characteristics highly suspicious of pertussis, secondary etiologies should be considered in children under 5 years-old in order to give a proper treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-019-3671-6) contains supplementary material, which is available to authorized users.


title: Genetic and molecular aspects of demyelination

text: Abstract Three groups of investigators came together to learn from each other in a workshop: neurologists and neuropathologists interested in the pathogenesis of multiple sclerosis (MS) and other demyelinative diseases of man and similar autoimmune and virus-induced model diseases in animals; immunologists and virologists concerned with the genetic controls found to play a role in these diseases; and geneticists and molecular biologists investigating specific gene products and their role in recognition function and cell interactions in model immunological systems.


title: Appréhender le COVID-19 au fil de l’eau en tant que psychiatre d’enfant et d’adolescent

text: Résumé Le COVID-19 est une maladie multi-organes liée à une infection par le virus SARS-CoV2 qui est devenue une pandémie au début de l’année 2020. Difficile de décrire autrement qu’en témoignant à chaud ce que cette pandémie implique pour un psychiatre d’enfants. Je propose de parcourir les principales questions éthiques qui se sont posées; de décrire comment mon équipe hospitalière s’est réorganisée pour faire face aux nouvelles demandes et questionnements, en particulier en ouvrant une unité dédiée aux personnes avec autisme et comportements défis atteints par le COVID-19; et d’aborder, dans un contexte de discussion nationale, comment la discipline a cherché à comprendre les conditions d’un certain bien-être pendant le confinement. Enfin, j’essaierai de terminer par des réflexions plus spéculatives concernant le déconfinement. Abstract COVID-19 is a multi-organ disease due to an infection with the SARS-CoV2 virus. It has become a pandemic in early 2020. The disease appears less devastating in children and adolescents. However, stress, quarantine and eventually mourning have major impacts on development. It is difficult to describe what this pandemic implies for a child psychiatrist, other than by giving a first-hand account. I propose to go through the main ethical questions that have arisen; to describe how my hospital team has reorganized itself to meet the new demands and questions, in particular by opening a unit dedicated to people with autism and challenging behaviors affected by COVID-19; and to address, in a context of national discussion, how the discipline has sought to understand the conditions of a certain well-being during quarantine. Finally, I will try to conclude with more speculative reflections on re-opening.


title: Hepatitis E Virus Drug Development

text: Hepatitis E virus (HEV) is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. The current therapy options are limited to the unspecific antivirals Ribavirin (RBV) and pegylated Interferon-α (pegIFN-α). RBV leads to viral clearance in only 80% of patients treated, and is, similar to pegIFN-α, contraindicated in the major risk group of pregnant women, emphasizing the importance of new therapy options. In this review, we focus on the urgent need and current efforts in HEV drug development. We provide an overview of the current status of HEV antiviral research. Furthermore, we discuss strategies for drug development and the limitations of the approaches with respect to HEV.


docid: srfrzqwc

title: Strategies for Targeting Tetraspanin Proteins: Potential Therapeutic Applications in Microbial Infections

text: The identification of novel targets and strategies for therapy of microbial infections is an area of intensive research due to the failure of conventional vaccines or antibiotics to combat both newly emerging diseases (e.g. viruses such as severe acute respiratory syndrome (SARS) and new influenza strains, and antibiotic-resistant bacteria) and entrenched, pandemic diseases exemplified by HIV. One clear approach to this problem is to target processes of the host organism rather than the microbe. Recent data have indicated that members of the tetraspanin superfamily, proteins with a widespread distribution in eukaryotic organisms and 33 members in humans, may provide such an approach. Tetraspanins traverse the membrane four times, but are distinguished from other four-pass membrane proteins by the presence of conserved charged residues in the transmembrane domains and a defining ‘signature’ motif in the larger of the two extracellular domains (the EC2). They characteristically form promiscuous associations with one another and with other membrane proteins and lipids to generate a specialized type of microdomain: the tetraspanin-enriched microdomain (TEM). TEMs are integral to the main role of tetraspanins as ‘molecular organizers’ involved in functions such as membrane trafficking, cell-cell fusion, motility, and signaling. Increasing evidence demonstrates that tetraspanins are used by intracellular pathogens as a means of entering and replicating within human cells. Although previous investigations focused mainly on viruses such as hepatitis C and HIV, it is now becoming clear that other microbes associate with tetraspanins, using TEMs as a ‘gateway’ to infection. In this article we review the properties and functions of tetraspanins/TEMs that are relevant to infective processes and discuss the accumulating evidence that shows how different pathogens exploit these properties in infection and in the pathogenesis of disease. We then investigate the novel and exciting possibilities of targeting tetraspanins for the treatment of infectious disease, using specific antibodies, recombinant EC2 domains, small-molecule mimetics, and small interfering RNA. Such therapies, directed at host-cell molecules, may provide alternative options for combating fast-mutating or newly emerging pathogens, where conventional approaches face difficulties.


title: Clinical features of COVID‐19 convalescent patients with re‐positive nucleic acid detection

text: BACKGROUND: Coronavirus disease 2019 (COVID‐19) is a pandemic that has rapidly spread worldwide. Increasingly, confirmed patients being discharged according to the current diagnosis and treatment protocols, follow‐up of convalescent patients is important to knowing about the outcome. METHODS: A retrospective study was performed among 98 convalescent patients with COVID‐19 in a single medical center. The clinical features of patients during their hospitalization and 2‐week postdischarge quarantine were collected. RESULTS: Among the 98 COVID‐19 convalescent patients, 17 (17.3%) were detected positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleic acid during 2‐week postdischarge quarantine. The median time from discharge to SARS‐CoV‐2 nucleic acid re‐positive was 4 days (IQR, 3‐8.5).The median time from symptoms onset to final respiratory SARS‐CoV‐2 detection of negative result was significantly longer in re‐positive group (34 days [IQR, 29.5‐42.5]) than in non‐re‐positive group (19 days [IQR, 16‐26]). On the other hand, the levels of CD3‐CD56 + NK cells during hospitalization and 2‐week postdischarge were higher in re‐positive group than in non‐re‐positive group (repeated measures ANOVA, P = .018). However, only one case in re‐positive group showed exudative lesion recurrence in pulmonary computed tomography (CT) with recurred symptoms. CONCLUSION: It is still possible for convalescent patients to show positive for SARS‐CoV‐2 nucleic acid detection, but most of the re‐positive patients showed no deterioration in pulmonary CT findings. Continuous quarantine and close follow‐up for convalescent patients are necessary to prevent possible relapse and spread of the disease to some extent.


The SARS-Cov-2 threat in Cracolândia, an open-air drug use scene in Brazil


title: Viral respiratory infections at the Hajj: comparison between UK and Saudi pilgrims

text: A high incidence of respiratory infection, including influenza, has been reported at the Hajj in Mecca, Saudi Arabia. Reported rates of influenza have been higher among UK than among domestic pilgrims, but this could be explained by methodological differences among studies. Accordingly, the present study compared the frequencies of respiratory viruses among UK and Saudi pilgrims using the same study design. Pilgrims with upper respiratory tract symptoms were recruited from Mecca and the neighbouring valley Mina during the Hajj 2006. Nasal swabs were used for point-of-care influenza testing and real-time RT-PCR (rtRT-PCR) tests for influenza virus, rhinovirus, parainfluenza virus, adenovirus, human metapneumovirus and respiratory syncytial virus. Of 260 pilgrims investigated, 150 were from the UK and 110 were Saudi; of these, 38 (25%) UK pilgrims and 14 (13%) Saudi pilgrims had respiratory infections detectable by rtRT-PCR (p 0.01). In the UK group, there were 19 (13%) cases of rhinovirus infection, 15 (10%) cases of influenza virus infection, two (1%) cases of dual infections with influenza virus and rhinovirus, one (3%) case of parainfluenza virus infection, and one (1%) case of respiratory syncytial virus infection. Fifty-six (37%) UK pilgrims had been vaccinated against influenza virus, with the rates of influenza in the vaccinated and unvaccinated group being 7% and 14%, respectively (p 0.19). In the Saudi group, there were three (3%) cases of rhinovirus infection and 11 (10%) cases of influenza. Only four (4%) Saudi pilgrims had been vaccinated against influenza virus, and none of these was infected with influenza virus. Overall, a significantly higher proportion of the UK pilgrims had detectable respiratory infections (25% vs. 13%, p 0.01). Influenza rates were similar in both groups, but the reported rates of influenza vaccination differed.


title: Infection of cats with atypical feline coronaviruses harbouring a truncated form of the canine type I non-structural ORF3 gene

text: Abstract Feline and canine coronaviruses (FCoV and CCoV, respectively) are common pathogens of cats and dogs sometimes leading to lethal infections named feline infectious peritonitis (FIP) and canine pantropic coronavirus infection. FCoV and CCoV are each subdivided into two serotypes, FCoV-I/II and CCoV-I/II. A phylogenetic relationship is evident between, on one hand, CCoV-I/FCoV-I, and on the other hand, CCoV-II/FCoV-II, suggesting that interspecies transmission can occur. The aim of the present study was to evaluate the prevalence of coronavirus (CoV)-infected cats according to their contact with dogs and to genetically analyse the CoV strains infecting cats. From 2003 to 2009, we collected 88 faecal samples from healthy cats and 11 ascitic fluids from FIP cats. We investigated the possible contact with dog in the household and collected dogs samples if appropriate. Out of 99 cat samples, 26 were coronavirus positive, with six cats living with at least one dog, thus showing that contact with dogs does not appear as a predisposing factor for cats CoV infections. Molecular and phylogenetic analyses of FCoV strains were conducted using partial N and S sequences. Six divergent strains were identified with the N gene clustering with CCoV-I whereas the 3′ end of S was related to FCoV-I. Further analysis on those six samples was attempted by researching the presence of the ORF3 gene, the latter being peculiar to CCoV-I to date. We succeeded to amplify the ORF3 gene in five samples out of six. Thus, our data strongly suggest the circulation of atypical FCoV strains harbouring the CCoV-I ORF3 gene among cats. Moreover, the ORF3 genes recovered from the feline strains exhibited shared deletions, never described before, suggesting that these deletions could be critical in the adaptation of these strains to the feline host.


title: Certain enteropathogens in calves of Finnish dairy herds with recurrent outbreaks of diarrhea

text: Abstract The occurrence and distribution of certain enteropathogenic organisms and the manifestation of diarrhea, especially in relation to colostral management, were studied in neonatal calves of eight southern Finnish dairy herds with recurrent outbreaks of enteric disturbances. The fecal samples were obtained from the calves and were provided by the farmers. Potentially pathogenic agents were demonstrated in 52 of the 68 calves studied. Cryptosporidium was found in 36 of them while rotavirus was found in 29 and Escherichia coli in 15 of them, either singly or in combination. Salmonella, coronavirus or parvovirus were not detected in any of the calves. Twenty-six of the 36 calves contracted their Cryptosporidium infection and 18 of the 29 calves their rotavirus infection within the first week of life. Eighteen of the 52 infected calves developed diarrhea of microbial origin within 20 days of age; the most frequent finding was mixed infection with Cryptosporidium and rotavirus. In addition there were six diarrheic calves where no infection could be demonstrated. Only 10 of the 68 calves had neither infections nor diarrhea. There was a highly significant difference between the mean times of the first colostral feeding of the uninfected non-diarrheic and diarrheic calves and a significant difference between the mean times of the first colostral feeding of the subclinically infected and diarrheic calves. The importance of sucking of colostrum at the first feeding was observed. The smallest amount protecting the calves from infections was 0.75 1 given within 1 h of delivery.


title: Viral Suppressors of Gene Silencing

text: Virus-induced gene silencing and viral suppression of gene silencing was first described in plants using plant poty- and potexviruses. This research began by a few laboratories has burgeoned into a larger field of study surrounding the role of small 21–25nt RNAs in modulating disease and development. Gene silencing is often referred to as an antiviral defense mechanism producing siRNAs which target viral genomes for degradation. Many viruses encode silencing suppressor proteins which function to block production of siRNAs or the ability of siRNAs to reach their targets. miRNAs are small RNAs which regulate development and nuclear gene expression. Recent studies have shown that viruses manipulate the miRNA pathway in a manner that alters host gene expression, sometimes causes developmental defects, and modulates disease symptoms.


Möglichkeiten und Grenzen von Ethikberatung im Rahmen der COVID-19-Pandemie (Stand: 31.03.2020): Ein Diskussionspapier der Akademie für Ethik in der Medizin


title: Transgenic Organs and Xenotransplants

text: A dvances in immunosuppressive treatments reached in the last decades of the 20th century have made solid organ transplantation the treatment of choice for cases of irreversible organ failure. However, the availability of human cadaver organs is limited and the demand for transplants is still on the rise. Also, there is a recognised lack of cells and human tissues for generalised use in transplantation for the treatment of diseases that are characterised by failure of specialised cells (such as pancreatic cells to cure diabetes). Xenotransplantation, which is the transplant of cells, tissues or organs from other species, became the focus of attention in the nineteen-nineties as a solution to the lack of organs and tissues for transplantation. Previous clinical studies using nonhuman primates produced poor outcomes (survival from days to a few months) and confirmed the difficulty of obtaining organs from these species. Since then, progress in xenotransplantation has been slow and still now various immunological and non-immunological barriers need to be overcome. These barriers are reviewed in this chapter and the various approaches explored to date to overcome them, in particular those based on the genetic modification of pigs. Also, cell transplant studies such as those of pancreatic islets in monkeys have led to even more hopeful results. The range of possibilities offered by this technology will be unlimited, making it possible for xenotransplantation to be a clinical reality in a not very distant future.


title: Limiting operations for acute appendicitis in children: lessons learned from the U.S. epicenter of the COVID-19 pandemic()

text: INTRODUCTION: The COVID-19 pandemic resulted in the suspension of non-emergent surgeries throughout New York. Our tertiary care children's hospital pivoted towards a trial of non-operative management (NOM) for all patients presenting with acute appendicitis to limit operating room use. We describe our pandemic-based NOM strategy for appendicitis, with expanded inclusion criteria and limited intravenous antibiotics. METHODS: We performed a retrospective study of children treated for acute appendicitis at our center from 3/31/2020–5/3/2020 during the peak of the New York pandemic. We compared appendicitis volume to similar months in prior years. We evaluated failure of NOM, length of stay, and compared characteristics of children we successfully treated with our expanded NOM protocol to previously published inclusion criteria for NOM. RESULTS: 45.5% of children (25/55) with acute appendicitis underwent NOM. Of the 30 who underwent surgery, 13 had complicated appendicitis while 17 had simple appendicitis. Three patients were COVID-positive, although none had respiratory symptoms. The majority of patients presenting with acute appendicitis (78.2%) did not meet previously published criteria for NOM. CONCLUSIONS: We treated a similar volume of children with acute appendicitis during the pandemic compared to prior years. We applied NOM to nearly half of patients, even as we expanded published inclusion criteria to minimize operative resources. TYPE OF STUDY: Retrospective study, level of evidence: IV.


title: Chapter 68 Mucosal Veterinary Vaccines Comparative Vaccinology

text: Abstract Infections of mucosal surfaces are major causes of morbidity, mortality, and economic loss in species of veterinary interest, and a concern for animal welfare. Vaccines are used extensively in veterinary medicine, and innovative vaccine technologies such as recombinant DNA-vectored and distinguishing infected from vaccinated animals (DIVA) vaccines and automated in ovo vaccination (of embryonated chicken eggs) have been rapidly adopted commercially. Immunological research using outbred, nonrodent animal models has contributed to a broader understanding of mucosal defenses, and has provided the initial impetus for investigation of the common mucosal immune system. Studies of the potential of novel adjuvants to improve vaccine efficacy against genetically unstable, immune-subverting RNA viruses, such as porcine reproductive and respiratory syndrome virus in pigs, should assist in the control of pathogens with similar characteristics in other species. Successful development of vaccines to prevent and treat ascending infections of the reproductive tract of cattle set a precedent for applications in other species including humans. Studies of mucosal adjuvants and delivery systems continue at the interface between passive and active immunity, with the goal of inducing the earliest possible protection against enteric and respiratory pathogens of neonates.


title: Bat mammalian orthoreoviruses cause severe pneumonia in mice

text: Mammalian orthoreovirus (MRV) infections are ubiquitous in mammals. Increasing evidence suggests that some MRVs can cause severe respiratory disease and encephalitis in humans and other animals. Previously, we isolated six bat MRV strains. However, the pathogenicity of these bat viruses remains unclear. In this study, we investigated the host range and pathogenicity of 3 bat MRV strains (WIV2, 3 and 7) which represent three serotypes. Our results showed that all of them can infect cell lines from different mammalian species and displayed different replication efficiency. The BALB/c mice infected by bat MRVs showed clinical symptoms with systematic infection especially in lung and intestines. Obvious tissue damage were found in all infected lungs. One of the strains, WIV7, showed higher replication efficiency in vitro and vivo and more severe pathogenesis in mice. Our results provide new evidence showing potential pathogenicity of bat MRVs in animals and probable risk in humans.


title: Co-infection with two strains of Brome mosaic bromovirus reveals common RNA recombination sites in different hosts

text: We have previously reported intra-segmental crossovers in Brome mosaic virus (BMV) RNAs. In this work, we studied the homologous recombination of BMV RNA in three different hosts: barley (Hordeum vulgare), Chenopodium quinoa, and Nicotiana benthamiana that were co-infected with two strains of BMV: Russian (R) and Fescue (F). Our work aimed at (1) establishing the frequency of recombination, (2) mapping the recombination hot spots, and (3) addressing host effects. The F and R nucleotide sequences differ from each other at many translationally silent nucleotide substitutions. We exploited this natural variability to track the crossover sites. Sequencing of a large number of cDNA clones revealed multiple homologous crossovers in each BMV RNA segment, in both the whole plants and protoplasts. Some recombination hot spots mapped at similar locations in different hosts, suggesting a role for viral factors, but other sites depended on the host. Our results demonstrate the chimeric (‘mosaic’) nature of the BMV RNA genome.


docid: syyjsdip

title: Comparative survey of canine parvovirus, canine distemper virus and canine enteric coronavirus infection in free-ranging wolves of central Italy and south-eastern France

text: Diseases likely affect large carnivore demography and can hinder conservation efforts. We considered three highly contagious viruses that infect a wide range of domestic and wild mammals: canine parvovirus type 2 (CPV-2), canine distemper virus (CDV) and canine enteric coronaviruses (CECoV). Infection by either one of these viruses can affect populations through increased mortality and/or decreased general health. We investigated infection in the wolf populations of Abruzzo, Lazio e Molise National Park (PNALM), Italy, and of Mercantour National Park (PNM), France. Faecal samples were collected during one winter, from October to March, from four packs in PNALM (n = 79) and from four packs in PNM (n = 66). We screened samples for specific sequences of viral nucleic acids. To our knowledge, our study is the first documented report of CECoV infection in wolves outside Alaska, and of the large-scale occurrence of CPV-2 in European wolf populations. The results suggest that CPV-2 is enzootic in the population of PNALM, but not in PNM and that CECoV is episodic in both areas. We did not detect CDV. Our findings suggest that density and spatial distribution of susceptible hosts, in particular free-ranging dogs, can be important factors influencing infections in wolves. This comparative study is an important step in evaluating the nature of possible disease threats in the studied wolf populations. Recent emergence of new viral strains in Europe additionally strengthens the need for proactive monitoring of wolves and other susceptible sympatric species for viral threats and other impairing infections.


title: Market-crash forecasting based on the dynamics of the alpha-stable distribution

text: This paper investigates on the alpha-stable distribution capacity to capture the probability of market crashes by means of the dynamic forecasting of its alpha and beta parameters. On the basis of the GARCH-stable model, we design a market crash forecasting methodology that involves three-stepwise procedure: (i) Recursively estimation the GARCH-stable parameters through a rolling window; (ii) alpha-stable parameters forecasting according to a VAR model; and (iii) Crash probabilities forecasting and analysis. The model performance for alternative crash definitions is assessed in terms of different accuracy criteria, and compared with a random walk model as benchmark. Our applications to a wide variety of stock indexes for developed and emerging markets reveals a high degree of accuracy and replicability of the results. Hence the model represents an interesting tool for risk management and the design of early warning systems for future crashes.


title: Chapter 12 Biosecurity Programs and Assets

text: Abstract Chapter 12 explores the programs and assets that have been assembled internationally, nationally, and regionally to safeguard populations from the threat of biological agents. The programs and assets can be viewed with the framework of comprehensive emergency management, which is made up of mitigation, preparedness, response, and recovery. Nations have come together and taken a stance individually to mitigate the threat. For the most part, these programs produce policy and procedures that support the Biological and Toxin Weapons Convention of 1972. Responding to a biological disaster will be frustrating, confusing, and dangerous for first responders, first receivers, and public health officials. Developed countries are far better trained and equipped to deal with the release of a formulated biological agent than they were 15years ago. Specific examples of programs and assets that match up with mitigation, preparedness, response, and recovery are discussed herein.


title: Conserved strategies for pathogen evasion of cGAS-STING immunity

text: Abstract The cGAS-STING pathway of cytosolic DNA sensing allows mammalian cells to detect and respond to infection with diverse pathogens. Pathogens in turn encode numerous factors that inhibit nearly all steps of cGAS-STING signal transduction. From masking of cytosolic DNA ligands, to post-translational modification of cGAS and STING, and degradation of the nucleotide second messenger 2′3′-cGAMP, pathogens have evolved convergent mechanisms to evade cGAS-STING sensing. Here we examine pathogen inhibitors of innate immunity in the context of newly discovered regulatory features controlling cellular cGAS-STING activation. Comparative analysis of these strategies provides insight into mechanisms of action and suggests aspects of cGAS-STING regulation and immune evasion that remain to be discovered.


title: MicroRNA Regulation of RNA Virus Replication and Pathogenesis

text: microRNAs (miRNAs) are non-coding RNAs that regulate many processes within a cell by manipulating protein levels through direct binding to mRNA and influencing translation efficiency, or mRNA abundance. Recent evidence demonstrates that miRNAs can also affect RNA virus replication and pathogenesis through direct binding to the RNA virus genome or through virus-mediated changes in the host transcriptome. Here, we review the current knowledge on the interaction between RNA viruses and cellular miRNAs. We also discuss how cell and tissue-specific expression of miRNAs can directly affect viral pathogenesis. Understanding the role of cellular miRNAs during viral infection may lead to the identification of novel mechanisms to block RNA virus replication or cell-specific regulation of viral vector targeting.


title: The Singaporean response to the SARS outbreak: knowledge sufficiency versus public trust

text: During the outbreak of severe acute respiratory syndrome (SARS) in Singapore from 1 March to 11 May 2003, various national prevention and control measures were undertaken to control and eliminate the transmission of the infection. During the initial period of the epidemic, public communication was effected through press releases and media coverage of the epidemic. About a month into the epidemic, a public education campaign was mounted to educate Singaporeans on SARS and adoption of appropriate behaviours to prevent the spread of the disease. A survey was conducted in late April 2003 to assess Singaporeans' knowledge about SARS and infection control measures, and their concerns and anxiety in relation to the outbreak. The survey also sought to assess their confidence in the ability of various institutions to deal with SARS and their opinion on the seemingly tough measures enforced. The study involved 853 adults selected from a telephone-sampling frame. Stratified sampling was used to ensure adequate representation from major ethnic groups and age groups. The study showed that the overall knowledge about SARS and control measures undertaken was low (mean per cent score of 24.5 ± 8.9%). While 82% of respondents expressed confidence in measures undertaken by Tan Tock Seng Hospital (the hospital designated to manage SARS), only 36% had confidence in nursing homes. However, >80% of the public agreed that the preventive and control measures instituted were appropriate. Despite the low knowledge score, the overall mean satisfaction score of the government's response to SARS was 4.47 (out of possible highest score of 5.00), with >93% of adult Singaporeans indicating that they were satisfied or very satisfied with the government's response to SARS. Generally, Singaporeans had a high level of public trust (satisfaction with government, confidence in institutions, deeming government measures appropriate), scoring 11.4 out of possible maximum of 14. The disparity between low knowledge on the one hand and high confidence and trust in the actions of the government on the other suggests that Singaporeans do not require high knowledge sufficiency to be confident in measures undertaken by the government to control the SARS crisis.


docid: bkpbzbaw

title: A micro cell culture method utilizing modified microscope slides for use in fluorescent antibody and enzyme immunoassays

text: A technique for culturing small quantities of mammalian cells on modified microscope slides is described. The modified microscope slides were Bellco Glass, Inc., toxoplasmosis slides and the cell cultures used were early passage bovine embryonic lung cells and continuous cell lines of porcine and canine origins. The slide cell cultures were either uninfected or infected with selected viruses or the obligate intracellular protozoanEncephalitozoon caniculi for utilization in direct and indirect fluorescent antibody testing or in peroxidase antiperoxidase immunosorbant assays.


title: Acidose lactique chez un nourrisson au cours d’une crise d’asthme grave

text: Résumé La survenue d’une acidose lactique dans l’asthme aigu grave (AAG) est classique chez l’adulte mais peu décrite chez l’enfant. Sa reconnaissance peut avoir des conséquences sur la prise en charge thérapeutique de la crise d’asthme. Une petite fille de 2 ans a été hospitalisée en réanimation pédiatrique pour un AAG, traité par oxygénothérapie à haut débit, méthylprednisolone et salbutamol par voie intraveineuse. Elle a présenté une acidose métabolique (pH=7,29) avec hypocapnie (26 mmHg), chute des bicarbonates (12 mmol/L), trou anionique (20 mmol/L) et augmentation des lactates (8 mmol/L). La recherche d’une maladie métabolique sous-jacente a été négative. L’évolution a été favorable avec amélioration spontanée de l’acidose lactique permettant la sortie de l’unité de réanimation après 72 heures. L’origine d’une acidose lactique au cours de l’AAG est multifactorielle. Bien que sa résolution soit spontanée, il est essentiel de la reconnaître car elle peut modifier la symptomatologie respiratoire et conduire à une escalade thérapeutique inappropriée. Summary Lactic acidosis is a recognized event in adult patients with acute severe asthma (ASA). Only a few cases have been reported in children. Hereinafter is reported the case of a 2-year-old girl hospitalized in the pediatric intensive care unit for ASA, which was treated with high-flow oxygen therapy and intravenous methylprednisolone and salbutamol. During hospitalization, she had metabolic acidosis with a 7.29 pH, a 26mmHg hypocapnia, and a decrease in bicarbonates to 12 mmol/L. The anion gap was increased to 20 mmol/L and lactates to 8 mmol/L. The work-up for a congenital metabolic disease was normal. Progression was propitious with spontaneous improvement of lactic acidosis, and the child was discharged from the intensive care unit after 72 h. The origin of lactic acidosis during ASA seems to be multifactorial. Although its recovery can be spontaneous, it is important to know how to identify it because it can worsen respiratory symptoms and can lead to incongruous therapeutic escalation.


title: Clinical Impact of Human Coronaviruses 229E and OC43 Infection in Diverse Adult Populations

text: Background. The incidence and clinical impact of coronavirus (CoV) infection in elderly persons and those with underlying cardiopulmonary disease over a long duration is not well described. We determined the incidence and clinical impact of 229E and OC43 CoV in this population during 4 consecutive winters, and compared illnesses to influenza A, respiratory syncytial virus, and human metapneumovirus. Methods. CoV 229E and OC43 were detected by reverse transcription polymerase chain reaction and serology in 4 adult populations under surveillance for acute respiratory illness during the winters of 1999–2003. Cohorts included healthy young adults, healthy elderly adults, high-risk adults with underlying cardiopulmonary disease, and a hospitalized group. Results. Three hundred ninety-eight CoV infections were identified, with annual infection rates ranging from 2.8% to 26% in prospective cohorts, and prevalence ranging from 3.3% to 11.1% in the hospitalized cohort. The incidence of infections with each strain was similar, although asymptomatic infection and viral coinfection was significantly more common with 229E than OC43 infection. Although the incidence and clinical manifestations were similar for each strain, OC43-infected subjects tended to seek more medical care, as OC43 was twice as common as 229E among the hospitalized cohort. Conclusions. CoV infections in the elderly are frequent, likely causing substantial medical disease burden.


title: Quantitative Delineation of Herpesviruses in Bats for use in Ecological Studies

text: Public health concerns about recent viral epidemics have motivated researchers to seek transdisciplinary understanding of infection in wildlife hosts. With its deep history devoted to explaining the abundance and distribution of organisms, ecology can augment current methods for studying viral dynamics. However, datasets allowing ecological explorations of viral communities are lacking, and common methods for delineating viral operational taxonomic units (OTUs), or “species”, are subjective. Here, we comprehensively sampled 1,086 bats from two Puerto Rican caves and tested them for infection with herpesviruses. Using percent identity of nucleotides and a machine learning algorithm, we categorized herpesviruses into 41 OTUs, representing approximately 80% of all herpesviruses in the host community. Although 13 OTUs were detected in multiple host species, OTUs generally exhibited host specificity by infecting a core host species at a significantly higher prevalence than in all other species combined. Only two OTUs showed significantly different prevalence between host sexes. This work is the first exploration of viral community ecology in a community of wildlife hosts.


title: Multidimensional scaling analysis of virus diseases

text: Abstract Background and Objective Viruses are infectious agents that replicate inside organisms and reveal a plethora of distinct characteristics. Viral infections spread in many ways, but often have devastating consequences and represent a huge danger for public health. It is important to design statistical and computational techniques capable of handling the available data and highlighting the most important features. Methods This paper reviews the quantitative and qualitative behaviour of 22 infectious diseases caused by viruses. The information is compared and visualized by means of the multidimensional scaling technique. Results The results are robust to uncertainties in the data and revealed to be consistent with clinical practice. Conclusions The paper shows that the proposed methodology may represent a solid mathematical tool to tackle a larger number of virus and additional information about these infectious agents.


title: Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks

text: The transmission potential of a novel infection depends on both the inherent transmissibility of a pathogen, and the level of susceptibility in the host population. However, distinguishing between these pathogen- and population-specific properties typically requires detailed serological studies, which are rarely available in the early stages of an outbreak. Using a simple transmission model that incorporates age-stratified social mixing patterns, we present a novel method for characterizing the transmission potential of subcritical infections, which have effective reproduction number R<1, from readily available data on the size of outbreaks. We show that the model can identify the extent to which outbreaks are driven by inherent pathogen transmissibility and pre-existing population immunity, and can generate unbiased estimates of the effective reproduction number. Applying the method to real-life infections, we obtained accurate estimates for the degree of age-specific immunity against monkeypox, influenza A(H5N1) and A(H7N9), and refined existing estimates of the reproduction number. Our results also suggest minimal pre-existing immunity to MERS-CoV in humans. The approach we describe can therefore provide crucial information about novel infections before serological surveys and other detailed analyses are available. The methods would also be applicable to data stratified by factors such as profession or location, which would make it possible to measure the transmission potential of emerging infections in a wide range of settings.


title: Advances in Diagnosis of Respiratory Virus Infections

text: The diagnosis of respiratory virus infections has evolved substantially in recent years, with the emergence of new pathogens and the development of novel detection methods. While recent advances have improved the sensitivity and turn-around time of diagnostic tests for respiratory viruses, they have also raised important issues such as cost, and the clinical significance of detecting multiple viruses in a single specimen by molecular methods. This article reviews recent advances in specimen collection and detection methods for diagnosis of respiratory virus infections, and discusses the performance characteristics and limitations of these methods.


Impact of COVID-19 on the future of Pediatric Urology practice. Do guidelines apply to medical practice worldwide?


title: Use of gerontechnology to assist older adults to cope with the COVID-19 pandemic

text: Brief summary The public health measures associated COVID-19 have induced many challenges for older adults, caregivers, and healthcare providers. Gerontechnology–such as information and communication technologies, robots, telehealth, wearable technologies, remote sensors, and Internet of Things–can assist older people and caregivers to cope with the pandemic.


Commentary: Lung surgery in the time of COVID-19.


Changes in Gastroenterology and Endoscopy Practices in Response to the COVID-19 Pandemic: Results from a North American Survey


title: Further Requirements for Cleavage by the Murine Coronavirus 3C-like Proteinase: Identification of a Cleavage Site within ORF1b

text: Abstract The coronavirus mouse hepatitis virus strain A59 (MHV-A59) encodes a 3C-like proteinase (3CLpro) that is proposed to be responsible for the majority of the processing events that take place within the replicase polyproteins pp1a and pp1ab. In this study we demonstrate that the Q939↓S940 peptide bond, located between the polymerase and Zn-finger regions of pp1ab (the POL↓Zn site), is processed by the 3CLpro, albeit inefficiently. Mutagenesis of the POL↓Zn site, as well as the previously identified HD1↓3C site in the 1a region of pp1a and pp1ab, demonstrated that the amino acid residues at the P2 and P1 positions of the cleavage site, occupied by L and Q, respectively, were important determinants of 3CLpro substrate specificity. Finally, a direct comparison of the 3CLpro-mediated cleavages at the HD1↓3C and POL↓Zn sites was made by determining the rate constants using synthetic peptides. The results show that while a larger polypeptide substrate carrying the HD1↓3C site was processed more efficiently than a polypeptide substrate carrying the POL↓Zn site, cleavage of the synthetic peptide substrates containing these two cleavage sites occurred at similar efficiencies. This indicates that the overall conformation of a large polyprotein substrate is important in the accessibility of the cleavage site to the proteinase.


title: “The impact of socio-cultural influences on the COVID-19 measures – reflections from Singapore.”

text: Abstract The coronavirus disease 2019 (COVID-19) pandemic presents unique challenges to Asian countries like Singapore with a predominantly Confucian culture. Palliative care providers play an important role in supporting their patients and family members in these difficult times.


title: Coronavirus Disease 2019: Coronaviruses and Blood Safety

text: Abstract With the outbreak of unknown pneumonia in Wuhan, China, in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19). The World Health Organization declared COVID-19 in China as a Public Health Emergency of International Concern. Two other coronavirus infections—SARS in 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2012—both caused severe respiratory syndrome in humans. All 3 of these emerging infectious diseases leading to a global spread are caused by β-coronaviruses. Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS–CoV, and SARS-CoV-2 through blood products as of February 10, 2020, and also discuss pathogen inactivation methods on coronaviruses.


title: Impact of Covid‐19 epidemics in Pediatric Morbidity and utilization of Hospital Pediatric Services in Italy

text: we read with great interest the article by Pata et al. published online on June 2(nd) in the Journal (1). Indeed, the current Covid‐19 epidemic in Italy and the associated, two months (March‐April) strict lockdown have impacted on the overall epidemiology and use of adult and pediatric medical resources –also due to dramatic changes in lifestyle.


title: Real-time assessment of COVID-19 impact on global surgical case volumes

text: IMPORTANCE: The COVID-19 pandemic has disrupted global surgical capacity. The impact of the pandemic in low and middle income countries has the potential to worsen already strained access to surgical care. Timely assessment of surgical volumes in these countries remains challenging. OBJECTIVE: To determine whether usage data from a globally used anesthesiology calculator mobile application can serve as a proxy for global surgical case volume and contribute to monitoring of the impact of the COVID-19 pandemic, particularly in World Bank low income countries where official data collection is not currently practical. DESIGN: Subset of data from an ongoing observational cohort study of users of the application collected from October 1, 2018 to April 18, 2020. SETTING: The mobile application is available from public sources; users download and use the application per their own clinical needs on personal mobile devices. PARTICIPANTS: No user data was excluded from the study. EXPOSURE(S): Events with impacts on surgical case volumes, including weekends, holidays, and the COVID-19 pandemic. MAIN OUTCOME(S) AND MEASURE(S): It was previously noted that application usage was decreased on weekends and during winter holidays. We subsequently hypothesized that more detailed analysis would reveal impacts of country-specific or region-specific holidays on the volume of app use. RESULTS: 4,300,975 data points from 92,878 unique users were analyzed. Physicians and other anesthesia providers comprised 85.8% of the study population. Application use was reduced on holidays and weekends and correlated with fluctuations in surgical volume. The COVID-19 pandemic was associated with substantial reductions in app use globally and regionally. There was strong cross correlation between COVID-19 case count and reductions in app use. By country, there was a median global reduction in app use to 58% of baseline (interquartile range, 46%−75%). Application use in low-income continues to decline but in high-income countries has stabilized. CONCLUSIONS AND RELEVANCE: Application usage metadata provides a real-time indicator of surgical volume. This data may be used to identify impacted regions where disruptions to surgical care are disproportionate or prolonged. A dashboard for continuous visualization of these data has been deployed.


title: Virus discovery by sequence‐independent genome amplification

text: Genome sequences from several blood borne and respiratory viruses have recently been recovered directly from clinical specimens by variants of a technique known as sequence‐independent single primer amplification. This and related methods are increasingly being used to search for the causes of diseases of presumed infectious aetiology, but for which no agent has yet been found. Other methods that do not require prior knowledge of the genome sequence of any virus that may be present in the patient specimen include whole genome amplification, random PCR and subtractive hybridisation and differential display. This review considers the development and application of these techniques. Copyright © 2006 John Wiley & Sons, Ltd.


Tele-ophthalmology amid COVID-19 pandemic—Hong Kong experience


title: Expression of coronavirus E1 and rotavirus VP10 membrane proteins from synthetic RNA

text: Some viruses acquire their envelopes by budding through internal membranes of their host cell. We have expressed the cloned cDNA for glycoproteins from two such viruses, the E1 protein of coronavirus, which buds in the Golgi region, and VP10 protein of rotavirus, which assembles in the endoplasmic reticulum. Messenger RNA was prepared from both cDNAs by using SP6 polymerase and either translated in vitro or injected into cultured CV1 cells or Xenopus oocytes. In CV1 cells, the El protein was localised to the Golgi region and VP10 protein to the endoplasmic reticulum. In Xenopus oocytes, the E1 protein acquired post‐translational modifications indistinguishable from the sialylated, O‐linked sugars found on viral protein, while the VP10 protein acquired endoglycosidase‐H‐sensitive N‐linked sugars, consistent with their localisation to the Golgi complex and endoplasmic reticulum, respectively. Thus the two proteins provide models with which to study targeting to each of these intracellular compartments. When the RNAs were expressed in matured, meiotic oocytes, the VP10 protein was modified as before, but the E1 protein was processed to a much lesser extent than in interphase oocytes, consistent with a cessation of vesicular transport during cell division.


title: Dose‐dependent Inhibition of Gynecophoral Canal Protein Gene Expression in Vitro in the Schistosome (Schistosoma japonicum) by RNA Interference

text: Abstract The gynecophoral canal protein gene SjGCP of Schistosoma japonicum that is necessary for the pairing between the male and female worms is specifically expressed in the adult male worm. This protein is widely distributed in the adult female worm after pairing. Reverse transcription‐polymerase chain reaction (RT‐PCR) and immunofluorescence were employed to analyze the relationship between the RNAi effect and dsRNA dosage in the parasites. The results revealed that the inhibition of SjGCP expression by siRNA is dose‐dependent. RT‐PCR analysis showed that the SjGCP transcript level was reduced by 75% when 100 nM dsRNA was applied. Edited by: Wang‐Yi LIU


title: Identification of highly conserved regions in L-segment of Crimean–Congo hemorrhagic fever virus and immunoinformatic prediction about potential novel vaccine

text: Crimean–Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic viral disease with a disease fatality rate between 15% and 70%. Despite the wide range of distribution, the virus (CCHFV) is basically endemic in Africa, Asia, eastern Europe, and the Middle East. Acute febrile illness associated with petechiae, disseminated intravascular coagulation, and multiple-organ failure are the main symptoms of the disease. With all these fatal effects, CCHFV is considered a huge threat as no successful therapeutic approach is currently available for the treatment of this disease. In the present study, we have used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of CCHFV. Both the T-cell and B-cell epitopes were assessed, and the epitope “DCSSTPPDR” was found to be the most potential one, with 100% conservancy among all the strains of CCHFV. The epitope was also found to interact with both type I and II major histocompatibility complex molecules and is considered nonallergenic as well. In vivo study of our proposed peptide is advised for novel universal vaccine production, which might be an effective path to prevent CCHF disease.


title: Provision of community pharmacy services during COVID-19 pandemic: a cross sectional study of community pharmacists’ experiences with preventative measures and sources of information

text: Background An infectious disease caused by a novel coronavirus (later called COVID-19) reached pandemic levels in 2020 and community pharmacists were involved in responding to this pandemic, also in Kosovo. Objectives To explore the experiences of community pharmacists in relation to provision of community pharmacy services during COVID-19 pandemic. Setting Community pharmacists in Kosovo. Methods This was a cross-sectional study where data was collected via a self-administered online questionnaire, from 264 pharmacists actively practicing in Kosovo during the pandemic. The questionnaire consisted of a combination of closed and open-ended questions, optional statements and statements on a five-point Likert scale, derived at least in part from the Transtheoretical Model. One-way analysis of variance was used to analyze differences in responses to Likert-type items whereas categorical variables were analyzed using Chi square testing. Main outcome measures Community pharmacists’ perceptions on COVID-19 related preventative measures. Results A response rate of 40.6% was achieved. Sufficient and adequate COVID-19-related preventative measures were being implemented by a majority of pharmacies (n = 232; 87.9%), and over two-thirds of respondents agreed/strongly agreed that their pharmacies were sufficiently prepared with protective equipment for their personnel. Implementation of preventative measures was associated with respondents’ perception that pharmacists and the pharmacy profession were valued more by patients during the pandemic and to a lesser degree, by other health professionals. Most commonly stated pros dealt with employee and patient safety, while key cons dealt with increased costs and running out of the necessary protective equipment. Key barriers to pharmacy activities were price increases by wholesalers, and patients’ panic and excessive buying, whereas drivers dealt with professional obligation to assist and opportunity to prove inseparable to other health professionals. The most popular means of accessing COVID-19 related information by pharmacists was via mobile devices and information from professional organizations was considered most useful by pharmacists. Conclusions Community pharmacies actively implemented various measures as precautions to mitigate the spread of COVID-19. Our findings highlight the value of continuous provision of information by professional organizations and use of mobile devices as key means to access information by pharmacists.


title: SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done?

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has infected over 3.5 million people all over the world since the first case was reported from Wuhan, China 5 months ago. As more epidemiological data regarding COVID-19 patients is acquired, factors that increase the severity of the infection are being identified and reported. One of the most consistent co-morbidities associated with worse outcome in COVID-19 patients is diabetes, along with age and cardiovascular disease. Studies on the association of diabetes with other acute respiratory infections, namely SARS, MERS, and Influenza, outline what seems to be an underlying factor in diabetic patients that makes them more susceptible to complications. In this review we summarize what we think may be the factors driving this pattern between diabetes, aging and poor outcomes in respiratory infections. We also review therapeutic considerations and strategies for treatment of COVID-19 in diabetic patients, and how the additional challenge of this co-morbidity requires attention to glucose homeostasis so as to achieve the best outcomes possible for patients.


title: Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza

text: Summary The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC-MAN has the potential to become an important pan-coronavirus inhibition strategy.


title: Clinicopathological Features of Globoid Cell Leucodystrophy in Cats

text: Summary Clinical and pathological findings consistent with globoid cell leucodystrophy (GLD) were evaluated in two domestic shorthaired cats, aged 3 and 4 months. Both showed neurological signs mainly characterized by progressive pelvic limb ataxia, paraplegia with loss of deep pain perception in the pelvic limb, and intentional tremors of the thoracic limbs. Pathological changes affecting the central and peripheral nervous systems were characterised by diffuse, bilateral and symmetrical myelin loss, and marked astrogliosis. In the leucodystrophic areas there was perivascular accumulation of large PAS-positive, non-metachromatic macrophages (globoid cells), with intracytoplasmic accumulation of crystalloid tubular aggregates. Peripheral nerves showed demyelinating features with thin myelin sheaths, myelin splitting, and ballooning; the nerve fibres had bizarre shapes due to the presence of pale inclusions in the Schwann cells. GLD in cats shares clinical and pathological features with the disease described in other animals and human beings. The neurological signs differed from those of other feline inborn neurometabolic diseases and cerebellar hypoplasia.


title: Diversity in cell surface sialic acid presentations: implications for biology and disease

text: Sialic acids (Sias) are typically found as terminal monosaccharides attached to cell surface glycoconjugates. They play many important roles in many physiological and pathological processes, including microbe binding that leads to infections, regulation of the immune response, the progression and spread of human malignancies and in certain aspects of human evolution. This review will provide some examples of these diverse roles of Sias and briefly address immunohistochemical approaches to their detection.


title: Analysis of the intricate effects of polyunsaturated fatty acids and polyphenols on inflammatory pathways in health and disease

text: Prevention and treatment of non-communicable diseases (NCDs), including cardiovascular disease, diabetes, obesity, cancer, Alzheimer’s and Parkinson’s disease, arthritis, non-alcoholic fatty liver disease and various infectious diseases; lately most notably COVID-19 have been in the front line of research worldwide. Although targeting different organs, these pathologies have common biochemical impairments – redox disparity and, prominently, dysregulation of the inflammatory pathways. Research data have shown that diet components like polyphenols, poly-unsaturated fatty acids (PUFAs), fibres as well as lifestyle (fasting, physical exercise) are important factors influencing signalling pathways with a significant potential to improve metabolic homeostasis and immune cells’ functions. In the present manuscript we have reviewed scientific data from recent publications regarding the beneficial cellular and molecular effects induced by dietary plant products, mainly polyphenolic compounds and PUFAs, and summarize the clinical outcomes expected from these types of interventions, in a search for effective long-term approaches to improve the immune system response.


title: Effect of experimental infection of cattle with bovine herpesvirus-1 (BHV-1) on the ex vivo interaction of bovine leukocytes with Mannheimia (Pasteurella) haemolytica leukotoxin

text: Abstract Mannheimia (Pasteurella) haemolytica A1 produces an extracellular leukotoxin (LKT) that is reported to bind the β2-integrin CD11a/CD18 (LEA-1) on ruminant leukocytes. LKT binding induces activation, and subsequent cytolysis, of these cells. It is well known that active viral infection greatly increases the susceptibility of cattle to pasteurellosis. To better understand the mechanism by which this occurs, we investigated the effects of experimental in vivo infection of cattle with bovine herpes virus-1 (BHV-1) on the ex vivo interaction of bovine leukocytes with the M. haemolytica LKT. In this study, we demonstrated that active BHV-1 infection increased the expression of the β2-integrin CD11a/CD18 (as defined by the mAb BAT75) on bovine peripheral blood neutrophils, enhanced the binding of LKT to bronchoalveolar lavage (BAL) leukocytes and peripheral blood neutrophils, and increased the killing of BAL leukocytes and peripheral blood leukocytes by LKT. In addition, BHV-1 greatly increased the number of BAL, resulting in many more LKT-responsive cells being present in the lungs. These findings might explain in part the increased susceptibility of BHV-1 infected cattle to pneumonic pasteurellosis.


title: Inflammation-associated genes: risks and benefits to Foxp3(+) regulatory T-cell function

text: Foxp3(+) regulatory T (Treg) cells prevent the development of autoimmunity and immunopathology, as well as maintaining homeostasis and tolerance to commensal microorganisms. The suppressive activity of Treg cells is their defining characteristic, generating great interest in their therapeutic potential. However, suppressive and effector functions are not entirely exclusive. Considerable evidence points to the ability of supposedly anti-inflammatory Foxp3-expressing Treg cells to also express transcription factors that have been characterized as cardinal drivers of T effector cell function. We will consider the mounting evidence that Treg cells can function in non-suppressive capacities and review the impetus for this functional change, its relevance to developing immune and autoimmune responses and its significance to the development of Treg-based therapies.


title: Chapter 40 Integration of Specialized Research Services into Clinical Laboratory Operations

text: The clinical laboratory can play a useful role in a clinical research program at multiple levels including assistance in developing a laboratory test menu during protocol design, often focused on identifying testing approaches that address specific research questions. Laboratory staff also can provide important input in test performance and test result interpretation in the setting of the specific research questions. In addition, the laboratory can collaborate with investigators in identifying available test methods or developing new testing that will be useful answering specific questions raised in the protocol. Finally, the clinical laboratory can provide important support in translating research questions into new laboratory methods that may not only be useful for the protocol but that may mature into alternative diagnostic or therapeutic applications for patient care. As a model, we outline the approach taken in our laboratory in support of clinical research performed at the National Institutes of Health (NIH) Clinical Center.


title: Five common skin manifestations of COVID‐19 identified

text: COVID‐19, also called coronavirus, is an infectious disease caused by SARS‐CoV‐2. First identified in December 2019, in March 2020 it was announced by the World Health Organisation that COVID‐19 had become a global pandemic. The disease can affect different organ systems, and early reports have suggested skin symptoms. The researchers, working with dermatologists across Spain, reviewed 375 patients with suspected, or confirmed, COVID‐19, with the aim of developing a detailed classification of the different types of skin symptoms associated with COVID‐19 with corresponding images. An initial 120 images were reviewed by four dermatologists, without knowing any other clinical information, and they identified patterns of symptoms associated with COVID‐19. These patterns were then applied to the rest of the images and further refined. Five common skin symptoms were identified this way. These symptoms are chilblain‐like lesions, outbreaks of small blisters, wheals, rashes comprised of small flat and raised red bumps, and livedo and necrosis. Livedo is a skin condition where circulation is impaired within the blood vessels of the skin, necrosis refers to the premature death of skin tissue. These symptoms are associated with different severity of COVID‐19 infection, from less severe disease in the chilblain‐like lesions, to most severe in patients with livedo. The researchers noted that some of the skin symptoms associated with COVID‐19 are common and can have many causes, particularly wheals and rashes. As such, they may not be particularly helpful as an aide to diagnosis.


title: How Has COVID-19 Affected Our Orthopedic Implant Industry Partners? Implications for the Surgeon-Industry Relationship in 2020 and Beyond

text: BACKGROUND: The COVID-19 pandemic has had far-reaching societal and financial consequences. The purpose of this study was to evaluate how COVID-19 has affected AAHKS industry partners and the surgeon-industry relationship, emphasizing education, resource allocation, and strategic direction for the 2nd half of 2020. METHODS: AAHKS industry partners were contacted to participate in a blinded survey and optional interview with the AAHKS Industry Relations Committee. Based on the results, a group of AAHKS member surgeons with disparate practice types were asked to postulate on how the COVID-19 pandemic has and will affect their practice and relationship with Industry. RESULTS: AAHKS industry partner responses indicated decreased resource allocation for regional, “other national,” and AAHKS annual meetings (67%, 55%, and 30%, respectively). Web-based educational content was expected to increase in 2020 and will likely remain a point of emphasis in 2021 (100% and 70% of responders). For Q3/Q4 2020, a significant emphasis was placed on site of service/outpatient TJA and COVID-19-related safety measures (70% and 90% of responders), as well as increased availability of instrumentation and implants (40% and 60%, respectively). CONCLUSION: The COVID-19 pandemic has altered the orthopedic landscape for the foreseeable future. Survey responses by AAHKS industry partners demonstrate a continued commitment to surgeon education with and increasing shift to a web-based platform. Increased resource allocation for outpatient TJA and COVID-19-related safety measures were significant. Articulating optimal mechanisms to aid industry in supporting surgeons with different practice models to meet demand during the second half of fiscal year 2020 will be critical.