title: Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential

text: Rabies is an acute, fatal, neurological disease that affects almost all kinds of mammals. Vaccination (using an inactivated rabies vaccine), combined with administration of rabies immune globulin, is the only approved, effective method for post-exposure prophylaxis against rabies in humans. In the search for novel rabies control and treatment strategies, live-attenuated viruses have recently emerged as a practical and promising approach for immunizing and controlling rabies. Unlike the conventional, inactivated rabies vaccine, live-attenuated viruses are genetically modified viruses that are able to replicate in an inoculated recipient without causing adverse effects, while still eliciting robust and effective immune responses against rabies virus infection. A number of viruses with an intrinsic capacity that could be used as putative candidates for live-attenuated rabies vaccine have been intensively evaluated for therapeutic purposes. Additional novel strategies, such as a monoclonal antibody-based approach, nucleic acid-based vaccines, or small interfering RNAs (siRNAs) interfering with virus replication, could further add to the arena of strategies to combat rabies. In this review, we highlight current advances in rabies therapy and discuss the role that they might have in the future of rabies treatment. Given the pronounced and complex impact of rabies on a patient, a combination of these novel modalities has the potential to achieve maximal anti-rabies efficacy, or may even have promising curative effects in the future. However, several hurdles regarding clinical safety considerations and public awareness should be overcome before these approaches can ultimately become clinically relevant therapies.


title: Delayed Primary and Specialty Care: The Coronavirus Disease–2019 Pandemic Second Wave

text: Time is of the essence to continue the pandemic disaster cycle with a comprehensive post-COVID-19 health care delivery system RECOVERY analysis, plan and operation at the local, regional and state level.The second wave of COVID-19 pandemic response are not the ripples of acute COVID-19 patient clusters that will persist until a vaccine strategy is designed and implemented to effect herd immunity. The COVID-19 second wave are the patients that have had their primary and specialty care delayed. This exponential wave of patients requires prompt health care delivery system planning and response.


title: Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein

text: Influenza A viruses (IAVs) inhibit host gene expression by a process known as host shutoff. Host shutoff limits host innate immune responses and may also redirect the translation apparatus to the production of viral proteins. Multiple IAV proteins regulate host shutoff, including PA-X, a ribonuclease that remains incompletely characterized. We report that PA-X selectively targets host RNA polymerase II (Pol II) transcribed mRNAs, while sparing products of Pol I and Pol III. Interestingly, we show that PA-X can also target Pol II-transcribed RNAs in the nucleus, including non-coding RNAs that are not destined to be translated, and reporter transcripts with RNA hairpin structures that block ribosome loading. Transcript degradation likely occurs in the nucleus, as PA-X is enriched in the nucleus and its nuclear localization correlates with reduction in target RNA levels. Complete degradation of host mRNAs following PA-X-mediated endonucleolytic cleavage is dependent on the host 5’->3’-exonuclease Xrn1. IAV mRNAs are structurally similar to host mRNAs, but are synthesized and modified at the 3’ end by the action of the viral RNA-dependent RNA polymerase complex. Infection of cells with wild-type IAV or a recombinant PA-X-deficient virus revealed that IAV mRNAs resist PA-X-mediated degradation during infection. At the same time, loss of PA-X resulted in changes in the synthesis of select viral mRNAs and a decrease in viral protein accumulation. Collectively, these results significantly advance our understanding of IAV host shutoff, and suggest that the PA-X causes selective degradation of host mRNAs by discriminating some aspect of Pol II-dependent RNA biogenesis in the nucleus.


title: Viral Respiratory Infections in Pre-term Infants During and After Hospitalization

text: OBJECTIVE: To determine the burden of viral respiratory infections in pre-term infants both during and subsequent to Neonatal Intensive Care Unit (NICU) hospitalization and to compare this with term infants living in the community. STUDY DESIGN: From March 2013 through March 2015 we enrolled 189 newborns (96 term and 93 pre-term) into a prospective, longitudinal study obtaining nose/throat swabs within 7 days of birth, weekly while hospitalized and then monthly to four months after hospital discharge. Taqman array cards (TAC) were used to identify 16 viral respiratory pathogens by real time PCR. Demographic, clinical, and laboratory data were gathered from electronic medical records and parent interview while hospitalized with interval histories collected at monthly visits. The hospital course of all pre-term infants who underwent late-onset sepsis evaluations was reviewed. RESULTS: Over 119 weeks, we collected 618 nose/throat swabs from at risk pre-term infants in our Level IV regional NICU. Only four infants had viral respiratory infections, all less than 28 weeks gestation at birth. Two infants were symptomatic with the infections recognized by the clinical team. The daily risk of acquiring a respiratory viral infection in pre-term infants in the NICU was significantly lower than in the full term cohort living in the community. Once discharged from the hospital viral respiratory infections were common in all infants. CONCLUSIONS: Viral respiratory infections are infrequent in a NICU with strict infection prevention strategies, and do not appear to cause unrecognized illness. Both preterm and term infants living in the community quickly acquire respiratory viral infections.


title: JaPaFi: A Novel Program for the Identification of Highly Conserved DNA Sequences

text: We describe the use of Java Pattern Finder (JaPaFi) to identify short (<100 nt) highly conserved sequences in a series of poxvirus genomes. The algorithm utilizes pattern matching to identify approximate matches appearing at least once in each member of a set of genomes; a key feature is that the genomes do not need to be aligned. The user simply specifies the genomes to search, minimum length of sequences to find and the maximum number of mismatches and indels allowed. Many of the most highly conserved segments contain poxvirus promoter elements.


title: Palmitoylation of the Alphacoronavirus TGEV spike protein S is essential for incorporation into virus-like particles but dispensable for S–M interaction

text: Abstract The spike protein S of coronaviruses contains a highly conserved cytoplasmic cysteine-rich motif adjacent to the transmembrane region. This motif is palmitoylated in the Betacoronaviruses MHV and SARS-CoV. Here, we demonstrate by metabolic labeling with [3H]-palmitic acid that the S protein of transmissible gastroenteritis coronavirus (TGEV), an Alphacoronavirus, is palmitoylated as well. This is relevant for TGEV replication as virus growth was compromised by the general palmitoylation inhibitor 2-bromopalmitate. Mutation of individual cysteine clusters in the cysteine-rich motif of S revealed that all cysteines must be replaced to abolish acylation and incorporation of S into virus-like particles (VLP). Conversely, the interaction of S with the M protein, essential for VLP incorporation of S, was not impaired by lack of palmitoylation. Thus, palmitoylation of the S protein of Alphacoronaviruses is dispensable for S–M interaction, but required for the generation of progeny virions.


Systemic steroids and risk of fecal-oral shedding and increased transmission of SARS-Cov-2 in pemphigus cases()()


title: Strengthening timely detection and reporting of unusual respiratory events from health facilities in Yaoundé, Cameroon

text: BACKGROUND: The International Health Regulations state that early detection and immediate reporting of unusual health events is important for early warning and response systems. OBJECTIVE: To describe a pilot surveillance program established in health facilities in Yaoundé, Cameroon in 2017 which aimed to enable detection and reporting of public health events. METHODS: Cameroon’s Ministry of Health, in partnership with the US Centers for Disease Control and Prevention, Cameroon Pasteur Center, and National Public Health Laboratory, implemented event‐based surveillance (EBS) in nine Yaoundé health facilities. Four signals were defined that could indicate possible public health events, and a reporting, triage, and verification system was established among partner organizations. A pre‐defined laboratory algorithm was defined, and a series of workshops trained health facilities, laboratory, and public health staff for surveillance implementation. RESULTS: From May 2017 to January 2018, 30 signals were detected, corresponding to 15 unusual respiratory events. All health facilities reported a signal at least once, and more than three‐quarters of health facilities reported ≥2 times. Among specimens tested, the pathogens detected included Klebsiella pneumoniae, Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenza, Staphylococcus aureus, Pneumocystis jiroveci, influenza A (H1N1) virus, rhinovirus, and adenovirus. CONCLUSIONS: The events detected in this pilot were caused by routine respiratory bacteria and viruses, and no novel influenza viruses or other emerging respiratory threats were identified. The surveillance system, however, strengthened relationships and communication linkages between health facilities and public health authorities. Astute clinicians can play a critical role in early detection and EBS is one approach that may enable reporting of emerging outbreaks and public health events.


title: Treatment of Proximal Femoral Fragility Fractures in Patients with COVID-19 During the SARS-CoV-2 Outbreak in Northern Italy

text: BACKGROUND: From February 20 to April 2020, the coronavirus SARS (severe acute respiratory syndrome)-CoV-2 spread in northern Italy, drastically challenging the care capacities of the national health care system. Unprepared for this emergency, hospitals have quickly reformulated paths of assistance in an effort to guarantee treatment for infected patients. Orthopaedic departments have been focused on elderly traumatology, especially the treatment of femoral neck fractures in patients with coronavirus disease-2019 (COVID-19). The purpose of the present study was to evaluate the orthopaedic management strategy for femoral fragility fractures in COVID-19-positive patients with the hypothesis that operative treatment may contribute to the overall stability of the patient. METHODS: Sixteen patients affected by proximal femoral fracture and a recent history of fever, shortness of breath, and desaturation were admitted to the emergency room. Thoracic computed tomography (CT) and oropharyngeal swabs confirmed that they were positive for COVID-19, requiring hospitalization and prophylaxis with low-molecular-weight heparin. RESULTS: Three patients died before surgery because of severe respiratory insufficiency and multiple-organ-failure syndrome. Ten patients underwent surgery on the day after admission, whereas 3 patients had suspended their use of direct thrombin inhibitors and needed surgery to be delayed until the third day after admission. In all patients except 1, we noted an improvement in terms of O(2) saturation and assisted respiration. In 9 patients, hemodynamic and respiratory stability was observed at an average of 7 days postoperatively. Four patients who underwent surgical treatment died of respiratory failure on the first day after surgery (1 patient), the third day after surgery (2 patients), or the seventh day after surgery (1 patient). CONCLUSIONS: We noted a stabilization of respiratory parameters in 12 COVID-19-positive patients who underwent surgery treatment of proximal femoral fractures. We believe that in elderly patients with COVID-19 who have proximal femoral fractures, surgery may contribute to the overall stability of the patient, seated mobilization, improvement in physiological ventilation, and general patient comfort in bed. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Extracorporeal Support to Treat E-cigarette or Vaping Product Use-associated Lung Injury (EVALI) During a COVID Pandemic


title: Impact of the coronavirus (COVID-19) pandemic on surgical practice - Part 2 (surgical prioritisation)

text: The Coronavirus (COVID-19) Pandemic represents a once in a century challenge to human healthcare with 2.4 million cases and 165,000 deaths thus far. Surgical practice has been significantly impacted with all specialties writing guidelines for how to manage during this crisis. All specialties have had to triage the urgency of their daily surgical procedures and consider non-surgical management options where possible. The Pandemic has had ramifications for ways of working, surgical techniques, open vs minimally invasive, theatre workflow, patient and staff safety, training and education. With guidelines specific to each specialty being implemented and followed, surgeons should be able to continue to provide safe and effective care to their patients during the COVID-19 pandemic. In this comprehensive and up to date review we assess changes to working practices through the lens of each surgical specialty.


title: Spacer-length dependence of programmed −1 or −2 ribosomal frameshifting on a U(6)A heptamer supports a role for messenger RNA (mRNA) tension in frameshifting

text: Programmed −1 ribosomal frameshifting is employed in the expression of a number of viral and cellular genes. In this process, the ribosome slips backwards by a single nucleotide and continues translation of an overlapping reading frame, generating a fusion protein. Frameshifting signals comprise a heptanucleotide slippery sequence, where the ribosome changes frame, and a stimulatory RNA structure, a stem–loop or RNA pseudoknot. Antisense oligonucleotides annealed appropriately 3′ of a slippery sequence have also shown activity in frameshifting, at least in vitro. Here we examined frameshifting at the U(6)A slippery sequence of the HIV gag/pol signal and found high levels of both −1 and −2 frameshifting with stem–loop, pseudoknot or antisense oligonucleotide stimulators. By examining −1 and −2 frameshifting outcomes on mRNAs with varying slippery sequence-stimulatory RNA spacing distances, we found that −2 frameshifting was optimal at a spacer length 1–2 nucleotides shorter than that optimal for −1 frameshifting with all stimulatory RNAs tested. We propose that the shorter spacer increases the tension on the mRNA such that when the tRNA detaches, it more readily enters the −2 frame on the U(6)A heptamer. We propose that mRNA tension is central to frameshifting, whether promoted by stem–loop, pseudoknot or antisense oligonucleotide stimulator.


title: RECOMENDACIONES Y MANEJO PRÁCTICO DE LA GESTANTE CON COVID-19: SCOPING REVIEW

text: Resumen Objetivo: Recopilar recomendaciones y evidencias en el manejo práctico de las gestantes con infección por COVID-19 para clarificar pautas de atención obstétrica ante esta nueva enfermedad. Método: Scope review a partir de búsqueda bibliográfica en bases de datos nacionales e internacionales en ciencias de la salud (Pubmed/Medline, Biblioteca virtual en salud (BVS), Scielo, COCHRANE y CUIDEN) y sitios web y adicionalmente mediante sistema de “bola de nieve”. Se utilizaron los términos MeSH: “COVID-19”, “Pregnancy”, “Delivery, Obstetric”, “Pregnant Women” y “Maternal”. Como límites en la búsqueda se seleccionó como idiomas español e inglés. No se establecieron límites en referencia al año de publicación o tipo de artículo. Resultados: Se detectaron un total de 49 documentos y artículos, de los cuales 27 fueron analizados, utilizándose 18 y desechándose 9 que no contenían recomendaciones prácticas. Las recomendaciones que fueron agrupadas en 9 temáticas: Prevención de la infección en la embarazada, Prevención de la infección en el personal sanitario que atiende a la embarazada, Forma de presentación y severidad en la embarazada, Transmisión materno-fetal (vertical y perinatal), Control materno-fetal de la gestante infectada por COVID-19, Control de la gestante grave por COVID-19, Tratamiento de la gestante con COVID 19, Manejo y vía de finalización del parto, Resultados neonatales en mujeres con COVID-19 y Lactancia Materna. Conclusiones: Falta una evidencia sólida que sustente muchas de las recomendaciones para la mujer gestante respecto al COVID-19, ya que están basadas en la experiencia previa con las infecciones provocadas por los virus SARS-CoV y MERS-CoV. Se necesitan nuevos estudios que confirmen la idoneidad de muchas de las recomendaciones y pautas de actuación en el caso concreto de la mujer gestante y el COVID-19. Abstract Aim: To compile recommendations and evidence on the practical management of pregnant women with COVIC-19 in order to clarify standards of obstetric care in the face of this new disease. Methods: Scoping review based on literaature searches in national and international health science databases (Pubmed/Medline, Biblioteca virtual en salud (BVS), Scielo, COCHRANE and CUIDEN) and websites, and additionally by a "snowball" system. MeSH terms were used: "COVID-19", "Pregnancy", "Delivery, Obstetric" "Pregnant Women" and "Maternal". As limits in the search Spanish and English languages were selected. No limits were established in relation to the year of publication or type of article. Results: A total of 49 documents and articles were detected, of which 27 were analyzed, 18 were used, and 9 were discarded because they did not contain practical recommendations. The recommendations were grouped into 9 subjects: Prevention of infection in pregnant women, Prevention of infection in health care personnel attending pregnant women, Form of presentation and severity in pregnant women, Maternal-fetal transmission (vertical and perinatal), Maternal-fetal control of the pregnant woman infected with COVID-19, Control of the severely pregnant woman with COVID-19, Treatment of the pregnant woman with COVID-19, Management and route of termination of labor, Neonatal outcomes in women with COVID-19 and Breastfeeding. Conclusions: Lack of strong evidence to support many of the recommendations for pregnant women with COVID-19, as they are based on previous experience with SARS-CoV and MERS-CoV infections. Further studies are needed to confirm the appropriateness of many of the recommendations and guidelines for action in the specific case of pregnant women and COVIC-19.


title: Ethics of a partially effective dengue vaccine: Lessons from the Philippines

text: Dengvaxia, a chimeric yellow fever tetravalent dengue vaccine developed by SanofiPasteur is widely licensed in dengue-endemic countries. In a large cohort study Dengvaxia was found to partially protect children who had prior dengue virus (DENV) infections but sensitized seronegative children to breakthrough DENV disease of enhanced severity. In 2019, the European Medicines Agency and the US FDA issued licenses that reconciled safety issues by restricting vaccine to individuals with prior dengue infections. Using revised Dengvaxia efficacy and safety data we sought to estimate hospitalized and severe dengue cases among the more than 800,000 9 year-old children vaccinated in the Philippines. Despite an overall vaccine efficacy of 69% during 4 years post-vaccination we project there will be more than one thousand vaccinated seronegative and seropositive children hospitalized for severe dengue. Assisting these children through a program of enhanced surveillance leading to improved care deserves widespread support. Clinical responses observed during breakthrough dengue infections in vaccinated individuals counsel prudence in design of vaccine policies. Recommendations concerning continued use of this dengue vaccine are: (1) obtain a better definition of vaccine efficacy and safety through enhanced phase 4 surveillance, (2) obtain a valid, accessible, sensitive, specific and affordable serological test that identifies past wild-type dengue virus infection and (3) clarify safety and efficacy of Dengvaxia in flavivirus immunes. In the absence of an acceptable serological screening test these unresolved ethical issues suggest Dengvaxia be given only to those signing informed consent.


title: Primary stratification and identification of suspected Corona virus disease 2019 (COVID-19) from clinical perspective by a simple scoring proposal

text: In this Commentary, we would like to comment on the article titled “A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)” as a featured article in Military Medical Research. In the guideline, except for “confirmed cases”, “suspected cases”, “close contact” and “suspicious exposure” were defined by clinical perspective based on epidemiological risk, clinical symptoms and auxiliary examination. Combined with our experience, we introduced a simple scoring proposal additionally based on not only CT imaging as strongly recommended by the guideline but also blood routine test, especially for primary screening of such patients in the out-patient department.


Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung‐centric coagulopathy may play an important role. Elevated D‐dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3–4‐fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African‐Americans. In this study, we investigated COVID19 coagulopathy in Caucasian patients. Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity. Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC). In rare COVID19 cases where DIC does develop, it tends to be restricted to late‐stage disease. Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary‐specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC. Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.


title: Tools to Detect Influenza Virus

text: In 2009, pandemic influenza A (H1N1) virus (H1N1 09) started to spread quickly in many countries. It causes respiratory infection with signs and symptoms of common infectious agents. Thus, clinicians sometimes may miss the H1N1 patient. Clinical laboratory tests are important for the diagnosis of the H1N1 infection. There are several tests available, however, the rapid test and direct fluorescence antigen test are unable to rule out the influenza virus infection and viral culture test is time consuming. Therefore, nucleic acid amplification techniques based on reverse transcription polymerase chain reaction assays are regarded as a specific diagnosis to confirm the influenza virus infection. Although the nucleic acid-based techniques are highly sensitive and specific, the high mutation rate of the influenza RNA-dependent RNA polymerase could limit the utility of the techniques. In addition, their use depends on the availability, cost and throughput of the diagnostic techniques. To overcome these drawbacks, evaluation and development of the techniques should be continued. This review provides an overview of various techniques for specific diagnosis of influenza infection.


docid: ijodhrwf

title: Severe Fever with Thrombocytopenia Syndrome: Tick-Mediated Viral Disease


title: Diarrheal disease and DRGs

text: Abstract This article has presented a rational protocol for examining stools for enteric pathogens. When modified according to a laboratory's geographical location and patient population, this approach should allow efficient, comprehensive diagnosis of diarrheal disease. Laboratories should be able to examine stools routinely for Campylobacter spp., Salmonella spp., Shigella spp., Y. enterocolitica, intestinal parasites [including Cryptosporidium (14)], rotavirus, and C. difficile toxin. When unusual organisms such as pathogenic E. coli are suspected, or tissue culture facilities for C. difficile toxin assays are unavailable, the use of reference laboratories is strongly encouraged.


title: Expression and partial purification of recombinant tomato ringspot nepovirus 3C-like proteinase: comparison of the activity of the mature proteinase and the VPg-proteinase precursor

text: Abstract The 3C-like proteinase (Pro) from Tomato ringspot virus (genus Nepovirus) is responsible for the processing of the RNA1-encoded (P1) and RNA2-encoded (P2) polyproteins. Cleavage between the VPg and Pro domains is inefficient in vitro and in E. coli, resulting in the accumulation of the VPg-Pro. In this study, we have compared the trans-activity of the Pro and VPg-Pro on various P1- and P2-derived precursors. Recombinant Pro and VPg-Pro were partially purified using an E. coli expression system. A mutation of the VPg-Pro cleavage site was introduced into the VPg-Pro to prevent slow release of the Pro. The Pro was five to ten times more active than the VPg-Pro on two P2 cleavage sites (at the N- and C-termini of the movement protein domain) and was approximately two times more active than the VPg-Pro on the third P2 cleavage site (between the X3 and X4 domains). Neither the Pro nor the VPg-Pro could cleave in trans P1-derived substrates containing the three cleavage sites delineating the X1, X2, putative NTP-binding protein and VPg domains. These results are discussed in light of the possible regulation of the proteinase activity during virus replication.


title: Convalescent Plasma: Therapeutic Hope or Hopeless Strategy in the SARS-CoV-2 Pandemic

text: Abstract As the world faces the current SARS-CoV-2 pandemic, extensive efforts have been applied to identify effective therapeutic agents. Convalescent plasma collected from recovered patients has been a therapeutic modality employed for over a hundred years for various infectious pathogens. Specifically, it has been used in the treatment of many viral infections with varying degrees of clinical efficacy. As we consider the use of convalescent plasma in the battle against this new strain of coronavirus, it is prudent to review what is known from past experiences. Accordingly, the aim of this review is to examine in detail studies of convalescent plasma used during previous viral outbreaks and pandemics with particular focus on hemorrhagic fevers, influenza, and other coronaviruses. The concluding sections of this review address the potential use of convalescent plasma during the present-day SARS-CoV-2 pandemic, not only insofar as its clinical benefit but also the steps required to make convalescent plasma treatments readily available for an exponentially growing patient population. By the end, the authors hope to address the extent to which convalescent plasma represents a realistic therapeutic approach, or a distraction from other potentially useful treatments.


Dexamethasone in community-acquired pneumonia


title: Analysis of Serologic Cross-Reactivity Between Common Human Coronaviruses and SARS-CoV-2 Using Coronavirus Antigen Microarray

text: The current practice for diagnosis of SARS-CoV-2 infection relies on PCR testing of nasopharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk. This testing strategy likely underestimates the true prevalence of infection, creating the need for serologic methods to detect infections missed by the limited testing to date. Here, we describe the development of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A preliminary study of human sera collected prior to the SARS-CoV-2 pandemic demonstrates overall high IgG reactivity to common human coronaviruses and low IgG reactivity to epidemic coronaviruses including SARS-CoV-2, with some cross-reactivity of conserved antigenic domains including S2 domain of spike protein and nucleocapsid protein. This array can be used to answer outstanding questions regarding SARS-CoV-2 infection, including whether baseline serology for other coronaviruses impacts disease course, how the antibody response to infection develops over time, and what antigens would be optimal for vaccine development.


title: Object-oriented biological system integration: a SARS coronavirus example

text: Motivation: The importance of studying biology at the system level has been well recognized, yet there is no well-defined process or consistent methodology to integrate and represent biological information at this level. To overcome this hurdle, a blending of disciplines such as computer science and biology is necessary. Results: By applying an adapted, sequential software engineering process, a complex biological system (severe acquired respiratory syndrome-coronavirus viral infection) has been reverse-engineered and represented as an object-oriented software system. The scalability of this object-oriented software engineering approach indicates that we can apply this technology for the integration of large complex biological systems. Availability: A navigable web-based version of the system is freely available at http://people.musc.edu/~zhengw/SARS/Software-Process.htm Contact: zhengw@musc.edu Supplementary information: Supplemental data: Table 1 and Figures 1–16.


docid: ifwjvvjj

title: Invited review: A systematic review of the effects of early separation on dairy cow and calf health

text: ABSTRACT Concern from the public is growing regarding early cow-calf separation, yet proponents of this practice maintain that artificial rearing is critical for cow and calf health. Early separation is assumed to reduce the risk of transfer of pathogens from dam to neonatal calf, but a wide range of health benefits associated with extended cow-calf contact has also been documented. The aim of this systematic review was to report and synthesize conclusions from the literature on dairy cow and calf health in conventional rearing versus cow-calf contact systems. Peer-reviewed, published manuscripts, written in English, directly comparing dairy cow or calf health in artificial versus suckling systems, were eligible for inclusion. We conducted 7 targeted searches using Web of Science to identify key literature on important health conditions. The resulting manuscripts underwent a 4-step appraisal process, and further manuscripts were sourced from reference lists. This process resulted in a final sample of 70 articles that addressed cow and calf health. Sufficient literature was available to assess mastitis in cows, and scours, cryptosporidiosis, Johne's disease, pneumonia, immunity, and mortality in calves. The results for cryptosporidiosis, pneumonia, immunity, and mortality were mixed, with some differences between studies likely attributable to flawed comparisons between cohorts. Overall, the articles addressing calf scours and mastitis pointed to beneficial or no effects of suckling. The studies addressing Johne's disease did not find cow-calf contact to be a significant risk factor. In conclusion, the scientific peer-reviewed literature on cow and calf health provides no consistent evidence in support of early separation.


title: Bafilomycin A1 and U18666A Efficiently Impair ZIKV Infection

text: Zika virus (ZIKV) is a highly transmissive virus that belongs to the Flaviviridae family, which comprises several other pathogens that threaten human health. This re-emerging virus gained attention during the outbreak in Brazil in 2016, where a considerable number of microcephaly cases in newborns was associated with ZIKV infection during pregnancy. Lacking a preventive vaccine or antiviral drugs, efforts have been made to better understand the viral life cycle. In light of this, the relevance of the endosomal–lysosomal compartment for the ZIKV life cycle was investigated. A549 and SH-SY5Y cells were infected with either the African strain (associated with mild symptoms) or the French Polynesia strain (associated with neurological complications). For both strains, the V-ATPase inhibitor, bafilomycin A1, efficiently inhibited ZIKV entry and prevented the spread of the infection by interfering with viral maturation. Additionally, affecting cholesterol metabolism and transport with the drug U18666A, which inactivates late endosomes and lysosomes, impairs the viral life cycle. The data presented show a clear antiviral effect of two compounds that target the same compartments in different ways. This highlights the relevance of the endosomal–lysosomal compartment for the viral life cycle that should be considered as a target for antivirals.


title: Rhesus macaque θ-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-κB and MAPK pathways

text: θ-Defensins are pleiotropic, macrocyclic peptides that are expressed uniquely in Old World monkeys. The peptides are potent, broad-spectrum microbicides that also modulate inflammatory responses in vitro and in animal models of viral infection and polymicrobial sepsis. θ-Defensins suppress proinflammatory cytokine secretion by leukocytes stimulated with diverse Toll-like receptor (TLR) ligands. Studies were performed to delineate anti-inflammatory mechanisms of rhesus θ-defensin 1 (RTD-1), the most abundant θ-defensin isoform in macaque granulocytes. RTD-1 reduced the secretion of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-8 in lipopolysaccharide (LPS)-stimulated human blood monocytes and THP-1 macrophages, and this was accompanied by inhibition of nuclear factor κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) pathways. Peptide inhibition of NF-κB activation occurred following stimulation of extracellular (TLRs 1/2 and 4) and intracellular (TLR9) receptors. Although RTD-1 did not inhibit MAPK in unstimulated cells, it induced phosphorylation of Akt in otherwise untreated monocytes and THP-1 cells. In the latter, this occurred within 10 min of RTD-1 treatment and produced a sustained elevation of phosphorylated Akt (pAkt) for at least 4 h. pAkt is a negative regulator of MAPK and NF-κB activation. RTD-1 inhibited IκBα degradation and p38 MAPK phosphorylation, and stimulated Akt phosphorylation in LPS-treated human primary monocytes and THP-1 macrophages. Specific inhibition of phosphatidylinositol 3-kinase (PI3K) blocked RTD-1-stimulated Akt phosphorylation and reversed the suppression of NF-κB activation by the peptide. These studies indicate that the anti-inflammatory properties of θ-defensins are mediated by activation of the PI3K/Akt pathway and suppression of proinflammatory signals in immune-stimulated cells.


title: A multiplex PCR for Massachusetts and Arkansas serotypes of infectious bronchitis virus

text: Abstract Infectious bronchitis virus (IBV), the prototype of the coronavirus family, is an enveloped, single-stranded RNA virus with a genome size of approximately 27·6 kilobase. Infectious bronchitis virus causes an acute, highly contagious respiratory and urogenital disease of chickens which results in significant economic losses in commercial broilers, layers and breeders. A rapid, highly sensitive and specific method is needed in the differential diagnosis of infections of different serotypes. A multiplex polymerase chain reaction (PCR) method was developed and optimized to simultaneously detect Massachusetts (Mass) and Arkansas (Ark) serotypes of IBV. One common primer and two serotype specific primers were chosen from the S1 gene sequences of IBV and used in one PCR reaction. Under optimized PCR conditions, two serotype specific PCR products, 1026 bp for Mass and 896 bp for Ark, respectively, were amplified and detected by agarose gel electrophoreses. The specificity of the technique was verified by using 20 different strains and isolates of IBV, and other avian bacterial and viral pathogens. Using a serial 10-fold dilution of the artificial mixture of both Mass and Ark samples, the detection limit was found to be 5 pg RNA after 35 cycles of PCR. The multiplex PCR was able to detect and differentiate both serotypes in embryonated eggs that were co-infected with different EID50virus titers of Mass 41 and Ark 99. The multiplex PCR developed in this study will be valuable for rapid identification, differential diagnosis, and epidemiological studies of these two serotypes of IBV infections.


title: Trajectory of Psychosocial Measures Amongst Informal Caregivers: Case-Controlled Study of 1375 Informal Caregivers from the English Longitudinal Study of Ageing

text: Informal caregivers provide vital support for older adults living in the community with chronic illnesses. The purpose of this study was to assess the psychosocial status of informal caregivers of community-dwelling adults over an eight-year period. Informal caregivers of adult care-recipients were identified from Wave 1 of the English Longitudinal Study of Ageing (ELSA) cohort. Multivariate regression analysis models were constructed to assess the association between participant’s psychosocial characteristics and informal caregiving. Multilevel modelling explored the psychosocial changes between caregivers and non-caregivers over eight years. 1375 informal caregivers and 2750 age-matched non-caregivers were analyzed. Self-reported loneliness (Odd Ratio (OR): 0.26; 95% confidence intervals (CI): 0.01–0.51) and relationship status (OR: 0.36; 95% CI: 0.16–0.46) were independently associated with caregiving. Caregivers were more socially isolated with less holidaying abroad (OR: 0.51; 95% CI: 0.35–0.66), attendance to church (OR: 0.30; 95% CI: 0.11–0.49), or charity groups (OR: 0.35; 95% CI: 0.14–0.55). On multilevel analysis, over time (eight-years), caregivers reported greater loneliness (p < 0.01), change in relationship status (p = 0.01) and reduced control, autonomy, and pleasure (p ≤ 0.01) compared to non-caregivers. Given the deleterious effects caregiving can place on health and wellbeing, further interventions are required to improve these psychosocial factors.


title: Yellow Head Virus

text: Yellow head virus (YHV) infects the black tiger shrimp (Penaeus monodon) – one of the world's major aquaculture species. It is a highly virulent pathogen that can cause 100% mortality within a few days of the first signs of disease in a pond. YHV is a rod-shaped, enveloped (+) single-stranded RNA (ssRNA) virus with a helical nucleocaspsid. In genome organization and transcription strategy, it resembles coronaviruses, toroviruses, and arteriviruses with which it has been classified within the order Nidovirales (genus Okavirus, family Roniviridae). The 26662nt genome comprises four long open reading frames (ORFs). ORF1a and ORF1b encode nonstructural proteins that are expressed as polyproteins (pp1a and pp1ab) and processed to generate elements of a replicase complex. ORF1b is expressed only as an extension of ORF1a via a ribosomal frameshift. ORF2 encodes the nucleocapsid protein (p20). ORF3 encodes envelope glycoproteins (gp64 and gp116) and a small, nonstructural, triple-membrane-spanning protein (p22). YHV is one genotype in a complex of closely related viruses that are endemic in black tiger shrimp in the Indo-Pacific region. These include gill-associated virus which has been associated with less severe forms of disease in Australia and at least four other genotypes that cause low-level chronic infections in healthy shrimp.


title: Infections and Autoimmunity: A Panorama

text: For more than 2,000 years, it was thought that malignant spirits caused diseases. By the end of nineteenth century, these beliefs were displaced by more modern concepts of disease, namely, the formulation of the “germ theory,” which asserted that bacteria or other microorganisms caused disease. With the emergence of chronic degenerative and of autoimmune diseases in the last century, the causative role of microorganisms has been intensely debated; however, no clear explanatory models have been achieved. In this review, we examine the current available literature regarding the relationships between infections and 16 autoimmune diseases. We critically analyzed clinical, serological, and molecular associations, and reviewed experimental models of induction of and, alternatively, protection from autoimmune diseases by infection. After reviewing several studies and reports, a clinical and experimental pattern emerges: Chronic and multiple infections with viruses, such as Epstein–Barr virus and cytomegalovirus, and bacteria, such as H. pylori, may, in susceptible individuals, play a role in the evolvement of autoimmune diseases. As the vast majority of infections pertain to our resident microbiota and endogenous retroviruses and healthy carriage of infections is the rule, we propose to focus on understanding the mechanisms of this healthy carrier state and what changes its configurations to infectious syndromes, to the restoration of health, or to the sustaining of illness into a chronic state and/or autoimmune disease. It seems that in the development of this healthy carriage state, the infection or colonization in early stages of ontogenesis with key microorganisms, also called ‘old friends’ (lactobacilli, bifidobacteria among others), are important for the healthy living and for the protection from infectious and autoimmune syndromes.


title: Prevalence, complete genome sequencing and phylogenetic analysis of porcine deltacoronavirus in South Korea, 2014–2016

text: Porcine deltacoronavirus (PDCoV) is a newly emerged enterotropic swine coronavirus that causes enteritis and diarrhoea in piglets. Here, a nested reverse transcription (RT)‐PCR approach for the detection of PDCoV was developed to identify and characterize aetiologic agent(s) associated with diarrhoeal diseases in piglets in South Korea. A PCR‐based method was applied to investigate the presence of PDCoV in 683 diarrhoeic samples collected from 449 commercial pig farms in South Korea from January 2014 to December 2016. The molecular‐based survey indicated a relatively high prevalence of PDCoV (19.03%) in South Korea. Among those, the monoinfection of PDCoV (9.66%) and co‐infection of PDCoV (6.30%) with porcine epidemic diarrhoea (PEDV) were predominant in diarrhoeal samples. The full‐length genomes or the complete spike genes of the most recent strains identified in 2016 (KNU16‐07, KNU16‐08 and KNU16‐11) were sequenced and analysed to characterize PDCoV currently prevalent in South Korea. We found a single insertion‐deletion signature and dozens of genetic changes in the spike (S) genes of the KNU16 isolates. Phylogenetic analysis based on the entire genome and spike protein sequences of these strains indicated that they are most closely related to other Korean isolates grouped with the US strains. However, Korean PDCoV strains formed different branches within the same cluster, implying continuous evolution in the field. Our data will advance the understanding of the molecular epidemiology and evolutionary characteristics of PDCoV circulating in South Korea.


title: Viral RNA Replication in Association with Cellular Membranes

text: All plus-strand RNA viruses replicate in association with cytoplasmic membranes of infected cells. The RNA replication complex of many virus families is associated with the endoplasmic reticulum membranes, for example, picorna-, flavi-, arteri-, and bromoviruses. However, endosomes and lysosomes (togaviruses), peroxisomes and chloroplasts (tombusviruses), and mitochondria (nodaviruses) are also used as sites for RNA replication. Studies of individual nonstructural proteins, the virus-specific components of the RNA replicase, have revealed that the replication complexes are associated with the membranes and targeted to the respective organelle by the ns proteins rather than RNA. Many ns proteins have hydrophobic sequences and may transverse the membrane like polytopic integral membrane proteins, whereas others interact with membranes monotopically. Hepatitis C virus ns proteins offer examples of polytopic transmembrane proteins (NS2, NS4B), a “tip-anchored” protein attached to the membrane by an amphipathic α-helix (NS5A) and a “tail-anchored” posttranslationally inserted protein (NS5B). Semliki Forest virus nsP1 is attached to the plasma membrane by a specific binding peptide in the middle of the protein, which forms an amphipathic α-helix. Interaction of nsP1 with membrane lipids is essential for its capping enzyme activities. The other soluble replicase proteins are directed to the endo-lysosomal membranes only as part of the initial polyprotein. Poliovirus ns proteins utilize endoplasmic reticulum membranes from which vesicles are released in COPII coats. However, these vesicles are not directed to the normal secretory pathway, but accumulate in the cytoplasm. In many cases the replicase proteins induce membrane invaginations or vesicles, which function as protective environments for RNA replication.


title: Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure

text: Despite the success of renin-angiotensin system (RAS) blockade by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor (AT(1)R) blockers, current therapies for hypertension and related cardiovascular diseases are still inadequate. Identification of additional components of the RAS and associated vasoactive pathways, as well as new structural and functional insights into established targets, have led to novel therapeutic approaches with the potential to provide improved cardiovascular protection and better blood pressure control and/or reduced adverse side effects. The simultaneous modulation of several neurohumoral mediators in key interconnected blood pressure–regulating pathways has been an attractive approach to improve treatment efficacy, and several novel approaches involve combination therapy or dual-acting agents. In addition, increased understanding of the complexity of the RAS has led to novel approaches aimed at upregulating the ACE2/angiotensin-(1-7)/Mas axis to counter-regulate the harmful effects of the ACE/angiotensin II/angiotensin III/AT(1)R axis. These advances have opened new avenues for the development of novel drugs targeting the RAS to better treat hypertension and heart failure. Here we focus on new therapies in preclinical and early clinical stages of development, including novel small molecule inhibitors and receptor agonists/antagonists, less conventional strategies such as gene therapy to suppress angiotensinogen at the RNA level, recombinant ACE2 protein, and novel bispecific designer peptides.


title: A Proposed Plan for Prenatal Care to Minimize Risks of COVID-19 to Patients and Providers: Focus on Hypertensive Disorders of Pregnancy

text: Hypertensive disorders are the most common medical complications of pregnancy and a major cause of maternal and perinatal morbidity and death. The detection of elevated blood pressure during pregnancy is one of the cardinal aspects of optimal antenatal care. With the outbreak of novel coronavirus disease 2019 (COVID-19) and the risk for person-to-person spread of the virus, there is a desire to minimize unnecessary visits to health care facilities. Women should be classified as low risk or high risk for hypertensive disorders of pregnancy and adjustments can be accordingly made in the frequency of maternal and fetal surveillance. During this pandemic, all pregnant women should be encouraged to obtain a sphygmomanometer. Patients monitored for hypertension as an outpatient should receive written instructions on the important signs and symptoms of disease progression and provided contact information to report the development of any concern for change in status. As the clinical management of gestational hypertension and preeclampsia is the same, assessment of urinary protein is unnecessary in the management once a diagnosis of a hypertensive disorder of pregnancy is made. Pregnant women with suspected hypertensive disorders of pregnancy and signs and symptoms associated with the severe end of the disease spectrum (e.g., headaches, visual symptoms, epigastric pain, and pulmonary edema) should have an evaluation including complete blood count, serum creatinine level, and liver transaminases (aspartate aminotransferase and alanine aminotransferase). Further, if there is any evidence of disease progression or if acute severe hypertension develops, prompt hospitalization is suggested. Current guidelines from the American College of Obstetricians and Gynecologists (ACOG) and The Society for Maternal-Fetal Medicine (SMFM) for management of preeclampsia with severe features suggest delivery after 34 (0/7) weeks of gestation. With the outbreak of COVID-19, however, adjustments to this algorithm should be considered including delivery by 30 (0/7) weeks of gestation in the setting of preeclampsia with severe features. Key Points: Outbreak of novel coronavirus disease 2019 (COVID-19) warrants fewer office visits. Women should be classified for hypertension risk in pregnancy. Earlier delivery suggested with COVID-19 and hypertensive disorder.


title: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9), a biomarker for various pathological conditions, is produced in post-blood collection by fibrinolysis and coagulation factors

text: BACKGROUND: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube. However, the mechanism of FIC5.9 releasing from fibrinogen is unclear. METHODS: We formulated a hypothesis that FIC5.9 is released by enzymes that are activated by post-blood collection and may be coagulation and fibrinolysis factors. In this study, we analyzed the mechanisms of FIC5.9 releasing from fibrinogen in healthy blood. RESULTS: Our analysis showed that thrombin acts as an initiator for FIC5.9 releasing, and that mainly plasmin cleaves N-terminal end of FIC5.9 and neutrophil elastase cleave C-terminal end of FIC5.9. CONCLUSION: FIC5.9 reflects minute changes in coagulation and fibrinolysis factors and may be associated with pathological conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12014-016-9129-6) contains supplementary material, which is available to authorized users.


title: Life under lockdown: Notes on Covid‐19 in Silicon Valley

text: This article is a preliminary exploration of the effects of Covid‐19 in Silicon Valley, one of three pandemic ‘hotspots’ on America’s west coast. In particular, it describes how the crisis has deepened and magnified social and economic inequalities in a region where poverty, homelessness and gentrification are rife. Despite the fact that many technology firms are reaping massive profits in the wake of ‘shelter in place’ orders, many Silicon Valley workers have lost their jobs and are struggling to cope with the consequences of Covid‐19. The article also analyzes the different meanings of ‘lockdown’ by comparing examples from China, Brazil, Taiwan and the United States. The authors conclude that anthropologists have a significant role to play in helping to understand how and why communicable diseases emerge, the underlying social and environmental conditions that fuel them and cross‐cultural strategies for the effective mitigation of epidemics and pandemics.


title: Relevancia a corto plazo de la coinfección viral en pacientes menores de 2 años hospitalizados con infecciones de las vías respiratorias inferiores

text: Resumen Introducción Avances en el diagnóstico molecular han hecho posible la detección de agentes virales desconocidos en infecciones de las vías respiratorias inferiores (IVRI). Sin embargo, sigue habiendo dudas relativamente a su frecuencia y relevancia. Objetivo Comparar la clínica y la gravedad entre la infección por virus único y la coinfección en niños admitidos por IVRI. Métodos Se realizó un estudio durante 3 años consecutivos (2012-2015) que incluyó a niños menores de 2 años ingresados por IVRI. La identificación viral se realizó mediante la técnica de PCR para 16 virus. Los datos clínicos y el uso de los recursos hospitalarios se recogieron de forma estándar durante la estancia hospitalaria y se compararon la infección única con coinfecciones virales. Resultados Fueron analizadas 524 muestras (451 pacientes); 448 (85,5%) tuvieron al menos un virus identificado. Coinfecciones virales se encontraron en 159 (35,5%). RSV y HRV fueron los virus más frecuentes; bronquiolitis y neumonía, los diagnósticos principales. Los pacientes con coinfecciones virales eran mayores, iban a la guardería, tenían sibilancias recurrentes con más frecuencia y eran más sintomáticos al ingreso. No fueron sometidos a más exámenes, pero les fueron prescritos medicamentos con más frecuencia. El grupo de la coinfección viral no mostró una mayor duración de la estancia hospitalaria, de la necesidad de oxígeno, de UCI o soporte ventilatorio. Discusión Nuestro estudio mostró una proporción significativa de coinfecciones virales en los niños pequeños ingresados con IVRI y confirma dados previos que muestran que la prescripción es más frecuente en las coinfecciones virales, sin asociación con peor resultado clínico. Abstract Introduction Advances in molecular diagnosis have made it possible to detect previously unknown viral agents as causative agents of lower respiratory tract infections (LRTI). The frequency and relevance of viral coinfections is still debatable. Objective compare clinical presentation and severity between single virus infection and viral coinfection in children admitted for LRTI. Methods A 3-year period observational study (2012-2015) included children younger than two years admitted for LRTI. Viral identification was performed using PCR technique for 16 viruses. Clinical data and use of health resources was gathered during hospital stay using a standard collection form and we compared single virus infection and viral coinfections. Results The study included 524 samples (451 patients); 448 (85,5%) had at least one virus identified. Viral coinfections were found in 159 (35,5%). RSV and HRV were the most commonly identified virus; bronchiolitis and pneumonia the most frequent diagnosis. Patients with viral coinfections were older, attended day-care centers, had previous recurrent wheezing more frequently and were more symptomatic at admission. These patients did not have more complementary exams performed but were prescribed medications more often. Viral coinfection group did not show longer length of hospital stay and oxygen need, more need for ICU nor ventilatory support. Discussion Our study showed a significant proportion of viral coinfections in young infants admitted with LRTI and confirmed previous data showing that prescription was more frequent in inpatients with viral coinfections, without an association with worst clinical outcome.


title: Impact of bacterial and viral coinfection in community-acquired pneumonia in adults

text: Abstract Bacterial and viral coinfected community-acquired pneumonia (CAP) is poorly characterized in adults. The aim of this study was to investigate the influence of bacterial and viral coinfection in patients with CAP. A total of 235 adults who requested molecular tests of pneumonia and were diagnosed with CAP were enrolled in this study. Microbiological tests included blood and sputum cultures, PCR for bacterial and viral pathogens, antigen test for Streptococcus pneumoniae and the influenza virus, and antibody detection of Mycoplasma pneumonia. Of the 235 patients, 32 (13.6%) patients were coinfected with bacteria and virus. Among 64 severe CAP patients, the concurrent infections were confirmed in 14 patients (21.9%). The proportion of severe pneumonia was significantly higher in patients with coinfection, and they showed a significantly higher mortality rate. In conclusion, bacterial and viral coinfection in CAP is not a rare occurrence in adults. Viral and bacterial coinfections have an adverse impact on the severity of the pneumonia, and increase morbidity and mortality in patients with CAP.


title: Foot-and-mouth disease virus 3C protease: Recent structural and functional insights into an antiviral target

text: Abstract The 3C protease from foot-and-mouth disease virus (FMDV 3Cpro) is critical for viral pathogenesis, having vital roles in both the processing of the polyprotein precursor and RNA replication. Although recent structural and functional studies have revealed new insights into the mechanism and function of the enzyme, key questions remain that must be addressed before the potential of FMDV 3Cpro as an antiviral drug target can be realised.


Leveraging Opportunities for Critical Care in Resource-Limited Settings


title: Association between climate variables and global transmission oF SARS-CoV-2

text: Abstract In this study, we aimed at analyzing the associations between transmission of and deaths caused by SARS-CoV-2 and meteorological variables, such as average temperature, minimum temperature, maximum temperature, and precipitation. Two outcome measures were considered, with the first aiming to study SARS-CoV-2 infections and the second aiming to study COVID-19 mortality. Daily data as well as data on SARS-CoV-2 infections and COVID-19 mortality obtained between December 1, 2019 and March 28, 2020 were collected from weather stations around the world. The country's population density and time of exposure to the disease were used as control variables. Finally, a month dummy variable was added. Daily data by country were analyzed using the panel data model. An increase in the average daily temperature by one degree Fahrenheit reduced the number of cases by approximately 6.4 cases/day. There was a negative correlation between the average temperature per country and the number of cases of SARS-CoV-2 infections. This association remained strong even with the incorporation of additional variables and controls (maximum temperature, average temperature, minimum temperature, and precipitation) and fixed country effects. There was a positive correlation between precipitation and SARS-CoV-2 transmission. Countries with higher rainfall measurements showed an increase in disease transmission. For each average inch/day, there was an increase of 56.01 cases/day. COVID-19 mortality showed no significant association with temperature.


title: Combined use of ELISA and Western blot with recombinant N protein is a powerful tool for the immunodiagnosis of avian infectious bronchitis

text: BACKGROUND: The avian infectious bronchitis virus (IBV) remains a significant source of loss in the poultry industry and early diagnosis is required to prevent the disease from spreading. This study examined the combined use of an ELISA and Western blot (WB) to detect antibodies against the nucleocapsid protein (N) of IBV. The coding sequence for N was amplified by RT-PCR and expressed in Escherichia coli. A soluble recombinant N protein (rN) of approximately 50 kDa was obtained. A total of 389 sera were tested against the rN in ELISA and the results were compared with those of the commercial IDEXX IBV Ab test. ELISA-rN achieved a 90.34% sensitivity and 90.16% specificity. WB confirmed all false negative sera in ELISA-rN or IDEXX test as truly positive. The current study indicate that the combined use of rN in ELISA and WB is a powerful tool for the immunodiagnosis of avian infectious bronchitis. METHODS: Constructed recombinant pAE/n expression vectors were used to transform E. coli BL21(DE3) Star competent cells (Invitrogen). The rN of infectious bronchitis virus was purified by affinity chromatography using HisTrap HP 1 mL columns pre-packed with pre-charged Ni Sepharose in the ÄKTAprime Automated Liquid Chromatography system (GE Healthcare). A total of 389 serum samples from chickens were used to develop and evaluate the ELISA-rN test. To standardize the indirect ELISA development, serum dilutions (1:100, 1:200 and 1:400) and different concentrations of purified rN antigen (50, 100 and 200 ng/well) were tested. Positive and negative sera for IBV were used as controls. The results were compared with those obtained from a commercial kit. Serum samples scored as negative with the commercial kit but as positive with the ELISA-rN were further analysed by Western blot analyses using the rN protein as an antigen. The results of the ELISA-rN were compared to the commercial kit results using receiver-operating characteristics curves, area under the curve, and confidence intervals with the software GraphPad Prism version 6.0 for Windows (GraphPad Software, USA). RESULTS: The expected cDNA fragment of approximately 1240 bp was successfully amplified by PCR using primers designed to select for the coding region of the N protein. The rN was expressed as a soluble protein to avoid the refolding steps and, after purification a yield of 10 mg/L of rN was obtained. The SDS-PAGE results demonstrated the presence of two distinct bands that had a molecular mass of approximately 45 and 50 KDa. Out of 244 sera that scored positive in the commercial ELISA IDEXX IBV Ab Test, 220 were also positive in the ELISA-rN, yielding an ELISA-rN test sensitivity of 90.16%. Out of 145 sera that scored negative in the IDEXX IBV Ab Test, 131 also scored negative in the ELISA-rN, indicating a specificity of 90.34%. Sera that tested negative in the ELISA-rN and positive in the commercial test also reacted with the rN protein in Western blot. CONCLUSIONS: The association between the ELISA and Western blot techniques developed in this study with a subunit of IBV (rN) were able to detect antibodies that the commercial ELISA did not detect suggesting that the ELISA-rN has greater sensitivity.


Stay home while going out – possible impacts of earthquake co-occurring with COVID-19 pandemic on mental health and vice versa


title: Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis

text: OBJECTIVES: The safety and efficacy of the 3C-like protease inhibitor GC376 was tested on a cohort of client-owned cats with various forms of feline infectious peritonitis (FIP). METHODS: Twenty cats from 3.3–82 months of age (mean 10.4 months) with various forms of FIP were accepted into a field trial. Fourteen cats presented with wet or dry-to-wet FIP and six cats presented with dry FIP. GC376 was administered subcutaneously every 12 h at a dose of 15 mg/kg. Cats with neurologic signs were excluded from the study. RESULTS: Nineteen of 20 cats treated with GC376 regained outward health within 2 weeks of initial treatment. However, disease signs recurred 1–7 weeks after primary treatment and relapses and new cases were ultimately treated for a minimum of 12 weeks. Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1–7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission. Five kittens aged 3.3–4.4 months with wet FIP were treated for 12 weeks and have been in disease remission after stopping treatment and at the time of writing for 5–14 months (mean 11.2 months). A sixth kitten was in remission for 10 weeks after 12 weeks of treatment, relapsed and is responding to a second round of GC376. The seventh was a 6.8-year-old cat with only mesenteric lymph node involvement that went into remission after three relapses that required progressively longer repeat treatments over a 10 month period. Side effects of treatment included transient stinging upon injection and occasional foci of subcutaneous fibrosis and hair loss. There was retarded development and abnormal eruption of permanent teeth in cats treated before 16–18 weeks of age. CONCLUSIONS AND RELEVANCE: GC376 showed promise in treating cats with certain presentations of FIP and has opened the door to targeted antiviral drug therapy.


The universal system of virus taxonomy of the International Committee on Virus Taxonomy (ICTV), including new proposals ratified since publication of the Sixth ICTV Report in 1995


title: Genetic characterization of 2006–2008 isolates of Chikungunya virus from Kerala, South India, by whole genome sequence analysis

text: Chikungunya virus (CHIKV), a positive-stranded alphavirus, causes epidemic febrile infections characterized by severe and prolonged arthralgia. In the present study, six CHIKV isolates (2006 RGCB03, RGCB05; 2007 RGCB80, RGCB120; 2008 RGCB355, RGCB356) from three consecutive Chikungunya outbreaks in Kerala, South India, were analyzed for genetic variations by sequencing the 11798 bp whole genome of the virus. A total of 37 novel mutations were identified and they were predominant in the 2007 and 2008 isolates among the six isolates studied. The previously identified E1 A226V critical mutation, which enhances mosquito adaptability, was present in the 2007 and 2008 samples. An important observation was the presence of two coding region substitutions, leading to nsP2 L539S and E2 K252Q change. These were identified in three isolates (2007 RGCB80 and RGCB120; 2008 RGCB355) by full-genome analysis, and also in 13 of the 31 additional samples (42%), obtained from various parts of the state, by sequencing the corresponding genomic regions. These mutations showed 100% co-occurrence in all these samples. In phylogenetic analysis, formation of a new genetic clade by these isolates within the East, Central and South African (ECSA) genotypes was observed. Homology modeling followed by mapping revealed that at least 20 of the identified mutations fall into functionally significant domains of the viral proteins and are predicted to affect protein structure. Eighteen of the identified mutations in structural proteins, including the E2 K252Q change, are predicted to disrupt T-cell epitope immunogenicity. Our study reveals that CHIK virus with novel genetic changes were present in the severe Chikungunya outbreaks in 2007 and 2008 in South India. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-009-0411-9) contains supplementary material, which is available to authorized users.


title: Frequently asked questions regarding SARS-CoV-2 in cancer patients—recommendations for clinicians caring for patients with malignant diseases

text: Since early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely as possible, since the most important protection for patients with malignant disease is the best-possible control of the underlying disease.


title: Infecciones previas o coincidentes con la sospecha de enfermedad de Kawasaki ¿debemos cambiar nuestra actitud?

text: Resumen Introducción La enfermedad de Kawasaki (EK) es una vasculitis multisistémica asociada a lesiones en las arterias coronarias. Las infecciones podrían ser un desencadenante de la inflamación. Nuestro objetivo fue describir la presencia de infecciones en los niños con EK y analizar las características clínicas y la presencia de alteraciones coronarias en estos casos. Pacientes y métodos Análisis retrospectivo de los pacientes incluidos en la red KAWA-RACE entre 2011 y 2016. Se estudió tanto a los pacientes que tuvieron una identificación microbiológica confirmada (IMC) en el periodo agudo como a los que presentaron antecedente de infección previa reciente (IPR) las 4 semanas anteriores. Resultados Se incluyó a un total de 621 niños, de los cuales 101 (16,3%) tuvieron una IMC y 107 (17,2%) una IPR. Encontramos una significativa menor afectación ecocardiográfica en el grupo de IPR respecto a los niños sin infección previa (23 vs. 35%; p 0,01), con menor proporción no significativa de las alteraciones coronarias globales (16 vs. 25%; p 0,054). Sin embargo, no se detectaron diferencias en la proporción de aneurismas en ninguno de los 2grupos (IMC o IPR) respecto al resto de los pacientes sin infecciones asociadas. Conclusiones En nuestro estudio no encontramos diferencias en la incidencia de aneurismas coronarios en niños con y sin IMC o IPR, por lo que ante la sospecha de EK debe iniciarse siempre tratamiento, aunque se tenga infección confirmada microbiológicamente. Abstract Introduction Kawasaki disease (KD) is a multisystem vasculitis associated with coronary artery abnormalities. Infections could be a trigger of the inflammation. The main aim of this study was to describe the presence of infections in children with KD, and to analyse the clinical characteristics and the presence of coronary abnormalities in these cases. Patients and methods A retrospective study was performed within the Kawasaki Diseases Network (KAWA-RACE (2011-2016). An analysis was performed that included patients with positive microbiological findings (PMF) during the acute phase, as well as those with a previous recent infection (PRI) during the 4 weeks preceding KD diagnosis. Results The study included total of 621 children with KD, with PMF being found in 101 (16.3%) patients, and a PRI in 107 (17.2%). Significantly less echocardiographic abnormalities were found in the in the group with a PRI, when compared to those without a PRI (23 vs. 35%, P =.01) and also a lower proportion of overall coronary artery lesions (16 vs. 25%, P =.054). No significant differences were found in the proportion of aneurysms in either of these groups (PRI or PMF) when compared to those without infection. Conclusions In the present study, no differences were found in the incidence of coronary aneurysms in either of the groups, with or without PRI or PMF. Therefore, if KD is suspected, appropriate treatment should be started despite having a confirmed infection.


title: The European Virus Archive goes global: A growing resource for research

text: Abstract The European Virus Archive (EVA) was created in 2008 with funding from the FP7-EU Infrastructure Programme, in response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry. Within three years, it developed from a consortium of nine European laboratories to encompass associated partners in Africa, Russia, China, Turkey, Germany and Italy. In 2014, the H2020 Research and Innovation Framework Programme (INFRAS projects) provided support for the transformation of the EVA from a European to a global organization (EVAg). The EVAg now operates as a non-profit consortium, with 26 partners and 20 associated partners from 21 EU and non-EU countries. In this paper, we outline the structure, management and goals of the EVAg, to bring to the attention of researchers the wealth of products it can provide and to illustrate how end-users can gain access to these resources. Organisations or individuals who would like to be considered as contributors are invited to contact the EVAg coordinator, Jean-Louis Romette, at jean-louis.romette@univmed.fr.


title: Novel Poxvirus in Big Brown Bats, Northwestern United States

text: A wildlife hospital and rehabilitation center in northwestern United States received several big brown bats with necrosuppurative osteomyelitis in multiple joints. Wing and joint tissues were positive by PCR for poxvirus. Thin-section electron microscopy showed poxvirus particles within A-type inclusions. Phylogenetic comparison supports establishment of a new genus of Poxviridae.


title: Parameter identification for a stochastic SEIRS epidemic model: case study influenza

text: A recent parameter identification technique, the local lagged adapted generalized method of moments, is used to identify the time-dependent disease transmission rate and time-dependent noise for the stochastic susceptible, exposed, infectious, temporarily immune, susceptible disease model (SEIRS) with vital rates. The stochasticity appears in the model due to fluctuations in the time-dependent transmission rate of the disease. All other parameter values are assumed to be fixed, known constants. The method is demonstrated with US influenza data from the 2004–2005 through 2016–2017 influenza seasons. The transmission rate and noise intensity stochastically work together to generate the yearly peaks in infections. The local lagged adapted generalized method of moments is tested for forecasting ability. Forecasts are made for the 2016–2017 influenza season and for infection data in year 2017. The forecast method qualitatively matches a single influenza season. Confidence intervals are given for possible future infectious levels.


The impact of COVID policies on acute ophthalmology services—experiences from Moorfields Eye Hospital NHS Foundation Trust


title: Newcastle disease virus: Current status and our understanding

text: Abstract Newcastle disease (ND) is one of the highly pathogenic viral diseases of avian species. ND is economically significant because of the huge mortality and morbidity associated with it. The disease is endemic in many third world countries where agriculture serves as the primary source of national income. Newcastle disease virus (NDV) belongs to the family Paramyxoviridae and is well characterized member among the avian paramyxovirus serotypes. In recent years, NDV has lured the virologists not only because of its pathogenic potential, but also for its oncolytic activity and its use as a vaccine vector for both humans and animals. The NDV based recombinant vaccine offers a pertinent choice for the construction of live attenuated vaccine due to its modular nature of transcription, minimum recombination frequency, and lack of DNA phase during replication. Our current understanding about the NDV biology is expanding rapidly because of the availability of modern molecular biology tools and high-throughput complete genome sequencing.


title: Recent advances in the microbiology of respiratory tract infection in cystic fibrosis

text: INTRODUCTION: Infection is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Research on CF infection has highlighted differences from other respiratory infections—both in the range and the nature of the organisms—especially in chronic infection. This is a rapidly advancing field of microbiology and is bringing insights into the complexity and adaptations of bacteria causing chronic infection in the respiratory tract. AREAS OF AGREEMENT AND CONTROVERSY: The epidemiology of some infections in CF has changed, with reduction in spread of Burkholderia cenocepacia following patient segregation. Conversely, epidemic strains of Pseudomonas aeruginosa have emerged, which spread between patients; previously, most P. aeruginosa strains were patient-specific. Studies on hypermutators, quorum sensing, biofilm growth and the development of molecular identification have shed light on pathogenicity, microbial adaptation to the host and complexity of infection in CF. Non-tuberculous mycobacteria are emerging pathogens in CF; however, there is much to learn about pathogenicity and treatment of these infections. Species of aerobic and anaerobic bacteria, more commonly encountered in the upper tract, are found in significant numbers in CF sputum. The significance of this is however under debate. Finally, although the clinical relevance of conventional antibiotic susceptibility testing for chronic CF pathogens has been questioned, there are no clear alternatives. EMERGING AREAS FOR DEVELOPING RESEARCH: Much has been learnt about pathogenicity, evolution of CF pathogens and development of antibiotic resistance. The need is to focus on clinical relevance of these observations to improve diagnosis, prevention and treatment of CF infection.


title: Characterization and evaluation of the pathogenicity of a natural recombinant transmissible gastroenteritis virus in China

text: Abstract Porcine transmissible gastroenteritis virus (TGEV) is one of the major etiological agents of viral enteritis and fetal diarrhea in suckling piglets. In this study, a TGEV JS2012 strain was isolated from the feces of piglets in Jiangsu Province, China. The phylogenetic analysis showed that TGEV JS2012 was placed between the Purdue and the Miller clusters. Analysis of recombination confirmed that TGEV JS2012 is a natural recombinant strain between Miller M6 and Purdue 115. Similar to Miller M6, virulent Purdue and China strain TS, in S gene the JS2012 maintained genetic integrity and the characteristics of the TGEV virulent strains. In vivo, TGEV JS2012 caused 100% mortality in newborn piglets, indicating the strong pathogenicity of this isolate. These results reveal that the JS2012 is a novel natural recombinant TGEV with high virulence. Our findings provide valuable information about genetic diversity and infection mechanism of the coronavirus family.


title: Integrating evolution into medical education for women’s health care practitioners

text: Evolution is a fundamental principle in biology; however, it has been neglected in medical education. We argue that an evolutionary perspective is especially important for women’s health care providers, as selection will act strongly on reproductive parameters, and the biological costs of female reproduction are generally more resource expensive than for men (e.g. due to gestation and lactation) with greater effects on health and wellbeing. An evolutionary perspective is needed to understand antibiotic resistance, disease and health risks associated with mismatches between our evolved adaptations and current conditions, the importance of the microbiome and the maternal role in how infants acquire and develop their early-life microbiome (vaginal birth, lactation), and the importance of breastmilk as a biochemical signal from mothers to their babies. We present data that obstetrician–gynecologists’ views regarding the inclusion of evolution within their training is generally positive, but many barriers are perceived. Requiring coursework in evolutionary biology with an emphasis on evolutionary medicine prior to enrollment in medical school may be a solution.


title: Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation

text: The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.


title: Digital disease detection: A systematic review of event-based internet biosurveillance systems

text: Abstract Background Internet access and usage has changed how people seek and report health information. Meanwhile,infectious diseases continue to threaten humanity. The analysis of Big Data, or vast digital data, presents an opportunity to improve disease surveillance and epidemic intelligence. Epidemic intelligence contains two components: indicator based and event-based. A relatively new surveillance type has emerged called event-based Internet biosurveillance systems. These systems use information on events impacting health from Internet sources, such as social media or news aggregates. These systems circumvent the limitations of traditional reporting systems by being inexpensive, transparent, and flexible. Yet, innovations and the functionality of these systems can change rapidly. Aim To update the current state of knowledge on event-based Internet biosurveillance systems by identifying all systems, including current functionality, with hopes to aid decision makers with whether to incorporate new methods into comprehensive programmes of surveillance. Methods A systematic review was performed through PubMed, Scopus, and Google Scholar databases, while also including grey literature and other publication types. Results 50 event-based Internet systems were identified, including an extraction of 15 attributes for each system, described in 99 articles. Each system uses different innovative technology and data sources to gather data, process, and disseminate data to detect infectious disease outbreaks. Conclusions The review emphasises the importance of using both formal and informal sources for timely and accurate infectious disease outbreak surveillance, cataloguing all event-based Internet biosurveillance systems. By doing so, future researchers will be able to use this review as a library for referencing systems, with hopes of learning, building, and expanding Internet-based surveillance systems. Event-based Internet biosurveillance should act as an extension of traditional systems, to be utilised as an additional, supplemental data source to have a more comprehensive estimate of disease burden.


title: Transplant Infectious Disease: Implications for Critical Care Nurses

text: Infection is an important issue for critical care nurses as they care for patients throughout all phases of the transplant continuum: potential organ donors, transplant candidates, and transplant recipients. This article has reviewed salient issues relative to infections in each of these patient populations, including patients with VADs, and has highlighted key points pertaining to bacterial, viral, and fungal infections.


title: Ibogaine modulates cocaine responses which are altered due to environmental habituation: In vivo microvoltammetric and behavioral studies

text: Abstract Ibogaine, a serotonergic (5-HTergic) indole alkaloid, was studied for cocaine modulatory effects on four parameters of behavior by computerized infrared photocell beam detection. The behavioral parameters were: a) locomotor activity (ambulations), b) rearing, c) stereotypy (fine movements, primarily grooming), and d) agoraphobia [(thigmotaxis) a natural tendency to avoid the center of the behavioral chamber]. With each behavioral data point, dopamine (DA) release, and serotonin (5-HT) release were detected within seconds in nucleus accumbens (NAcc) of the same behaving male Sprague-Dawley rats, using in vivo electrochemistry (voltammetry). Ibogaine was administered (40 mg/kg IP) for 4 consecutive days. Importantly, the DAergic and the 5-HTergic responses to (SC) cocaine and two behavioral responses, ambulations and central ambulations, were reduced in intensity due to extended time spent in the novel behavioral chamber (habituated). Rearing and fine movement patterns were not habituated. The results show that ibogaine downmodulated the (SC) cocaine-induced increase in NAcc DA release (p < 0.0001) and potentiated the (SC) cocaine-induced decrease in NAcc 5-HT release (p < 0.0001). Concurrently, ibogaine downmodulated cocaine-induced ambulation (p < 0.0001) and central ambulation behavior (p < 0.0001). On the other hand, the behavioral parameters that did not exhibit habituation, i.e., rearing behavior and fine movement behavior, were not downmodulated by ibogaine (p < 0.1558) (p < 0.3763), respectively. Furthermore, ibogaine itself did not significantly alter NAcc DA release over the 2-h period studied (p < 0.9113) although individual time points were significantly affected bidirectionally. Concurrently ibogaine significantly increased 5-HT release (p < 0.0155). Behaviorally, ibogaine appears to be a weak psychostimulant. The data show a critical modulatory role for 5-HT in ibogaine-cocaine interactions. Also elucidated as critical is the efficacy of ibogaine when the response to (SC) cocaine is decreased due to the habituation of the animals to their environment.


title: Could urine be useful for the diagnosis of Chlamydia trachomatis pneumonia in infancy?

text: Abstract A 9-week-old infant presented with respiratory distress. The presumptive diagnosis of Chlamydia trachomatis pneumonia was ultimately made in a novel manner by a positive nucleic acid amplification test on a urine sample.


title: Neurosurgical practice during the SARS-CoV-2 pandemic: a worldwide survey

text: Abstract Background and Objective The SARS-CoV-2 pandemic has consistently changed medical practice throughout specialties, regardless of their contribution in facing the disease itself. We surveyed neurosurgeons worldwide to investigate the situation they are experiencing. Design and participants A 17-question, web-based survey was administered to neurosurgeons worldwide through the WFNS and the Neurosurgery Cocktail from March 28 to April 5, 2020 by web link or e-mail invitation. Questions were divided into three subgroups: general information, health system organization, and institutional plans for the SARS-CoV-2 outbreak. Collected data was initially elaborated using Survey Monkey® software. Country specific data were extracted from the WHO website. Statistical analysis was performed using R version 3.6.3. Results Of the 446 respondents, most were from Italy (20%), India (19%), and Pakistan (5%). Surgical activity was significantly reduced in most centers (79%) and dedicated in-hospital routes were created for SARS-CoV-2 patients (58%). Patient screening was performed only when there were symptoms (57%) and not routinely before surgery (18%). The preferred methods included a nasopharyngeal swab and chest x-ray. Health professionals were rarely screened (20%) and sometimes, even if SARS-CoV-2 positive, were asked to work if asymptomatic (26%). Surgical planning was changed in most institutions (92%), while indications were modified for non-urgent procedures (59%) and remained unchanged for subarachnoid hemorrhages (85%). Conclusions Most neurosurgeons worldwide reported work reorganization and practices that respond to current international guidelines. Differences in practice might be related to the perception of the pandemic and significant differences in the health systems. Sharing data and experiences will be of paramount importance to address the present moment and challenges in the near future.


Prospective study of timing and pattern of bacteria and viruses in the nasopharyngeal microbiome in a birth cohort


title: Evaluation of the safety, immunogenicity and pharmacokinetics of equine anti-SARS–CoV F(ab′)2 in macaque

text: Abstract To warrant potential clinical testing, the equine anti-SARS–CoV F(ab′)2 requires evaluation in as many animal models as possible and a safety test in a primate model. In this study, we evaluated the pharmacokinetics, tolerance and immunity of this kind of antibody in macaques and rats. Results showed that the F(ab′)2 fragments had a normal metabolism in injected animals. The general physiological indexes did not differ between animals injected with anti-SARS–CoV F(ab′)2 or saline. However, a mild inflammatory response in local injection site and a moderate immune response against this antibody in the successively injected animals were observed, which however recovered 3 weeks after the last injection. The antibody titring from 1:100 to 400 against the equine anti-SARS–CoV F(ab′)2 in the inoculated hosts could be detected at week 2 during the successive injections of the equine F(ab′)2. The considerable safety of this antibody used in primates and the fact that the immune system of the host can be motivated by post-injection of the F(ab′)2 indicate that this type of anti-SARS–CoV antibody can be used for prevention and treatment of SASR, especially at the early stage of this virus infection. In addition, it can also provide the precious time for the combined use of other anti-SARS–CoV agents such as antiviral drug and vaccine.


title: Canada needs to rapidly escalate public health interventions for its COVID-19 mitigation strategies

text: BACKGROUND: After the declaration of COVID-19 pandemic on March 11th(,) 2020, local transmission chains starting in different countries including Canada are forcing governments to take decisions on public health interventions to mitigate the spread of the epidemic. METHODS: We conduct data-driven and model-free estimations for the growth rates of the COVID-19 epidemics in Italy and Canada, by fitting an exponential curve to the daily reported cases. We use these estimates to predict epidemic trends in Canada under different scenarios of public health interventions. RESULTS: In Italy, the initial growth rate (0.22) has reduced to 0.1 two weeks after the lockdown of the country on March 8th(,) 2020. This corresponds to an increase of the doubling time from about 3.15 to almost 7 days. In comparison, the growth rate in Canada has increased from 0.13 between March 1st and 13th, to 0.25 between March 13th to 22nd. This current growth rate corresponds to a doubling time of 2.7 days, and therefore, unless further public health interventions are escalated in Canada, we project 15,000 cases by March 31st. However, the case number may be reduced to 4000 if escalated public health interventions could instantly reduce the growth rate to 0.1, the same level achieved in Italy. INTERPRETATION: Prompt and farsighted interventions are critical to counteract the very rapid initial growth of the COVID-19 epidemic in Canada. Mitigation plans must take into account the delayed effect of interventions by up to 2-weeks and the short doubling time of 3–4 days.


docid: hfkthquj

title: COVID-19 or Lung Cancer: what should we treat?


title: Introductory College Mathematics for the Life Sciences: Has Anything Changed?

text: This paper focuses on issues concerning the introductory college mathematics sequence with an emphasis on students interested in the life sciences, and concentration on the time after the publication of BIO2010 (BIO2010 in Transforming Undergraduate Education for Future Research Biologists, National Academies of Science, Medicine and Engineering, Washington, 2003). It also explores the potential uses of books targeted at introductory mathematics courses for life science majors today. As relevant background, we look at the evolution of the way that calculus has been taught over the past 50 years, including at the high school level. We also explore the implications of changes in technology and course delivery, such as online education. As we discuss different books and introductory course ideas, we focus on the needs of biology students, the inclusion of real-world problems and models, the role of technology, and the impact of data science. The paper is organized as follows: Sect. 1 provides some personal background with calculus dating back to the 1970s, and changes in calculus prior to BIO2010. Section 2 introduces goals for an introductory mathematics sequence and evaluates the calculus sequence in light of those goals. Sections 3–7 discuss various issues that will help to understand issues and challenges for introductory mathematics for the life sciences: Calculus in high school (Sect. 3), equity issues relative to calculus and other math topics (Sect. 4), the impact of online education (Sect. 5), math as a stumbling block for college students (Sect. 6), and the increasing importance and value of teaching data science (Sect. 7). Section 8 reviews the development of books in light of these issues and challenges. The last section (Sect. 9) summarizes conclusions.


title: Kawasaki disease for dermatologists

text: Kawasaki disease (KD) is a systemic vasculitis that mostly affects children below the age of 5. The vasculitis involves arteries of medium size, especially the coronaries. Various etiologies have been proposed including association with micro-organisms, bacterial superantigens, and genetic factors, however, the exact cause remains unknown. There is no specific laboratory test for KD. Diagnosis is clinical and depends upon the presence of fever for ≥5 days and 4 or more of five principal features, viz. polymorphous exanthem, extremity changes, mucosal changes involving the lips and oral cavity, bilateral bulbar conjunctival injection, and unilateral cervical lymphadenopathy. The term “incomplete KD” refers to the presence of fever and less than four principal clinical features. Recognition of this group of patients is important because it is usually seen in infants and risk of coronary abnormalities is increased probably because of delays in diagnosis. However, what appears to be “incomplete” at a given point of time may not actually be so because some of the features may have already subsided and others may evolve over time. Hence, a detailed dermatological examination is warranted in all cases, especially in incomplete KD, to ensure timely diagnosis. Although KD is a self-limiting disease in most patients, coronary artery abnormalities (CAAs) including coronary dilatations and aneurysms may develop in up to 25% of untreated patients. CAAs are the most common cause of morbidity and mortality in patients with KD. Treatment is aimed at reducing inflammation and consists of intravenous immunoglobulin (IVIG) along with aspirin. Despite treatment, some patients may still develop CAAs, and hence, long-term follow up is of utmost importance.


title: Lausanne medical dispatch centre’s response to COVID-19

text: The COVID-19 crisis is an unprecedented event. It is therefore essential for dispatch centres to share their experiences while the crisis is underway, similar to hospitals, so that we will all benefit from feedback. This letter to the editor describes the Lausanne dispatch centre response to COVID-19 and the lessons learned so far.


title: The Novel Coronavirus – Latest Findings

text: What was initially a lung infection epidemic in the metropolitan area of Wuhan followed by a now contained extension to mainland China has now spread to all continents as a major pandemic with current hotspots in Europe and the USA. This minireview is an update of an earlier report on this novel coronavirus infection (Brüssow, 2020, Microb Biotech 13, 607). I am now summarizing the research literature published between end of February to mid‐April 2020.


title: Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host

text: BACKGROUND: The ability of emerging pathogens to infect new species is likely related to the diversity of pathogen variants present in existing reservoirs and their degree of genomic plasticity, which determines their ability to adapt to new environments. Certain simian immunodeficiency viruses (SIVcpz, SIVsm) have demonstrated tremendous success in infecting new species, including humans, resulting in the HIV-1 and HIV-2 epidemics. Although SIV diversification has been studied on a population level, the essential substrates for cross-species transmission, namely SIV sequence diversity and the types and extent of viral diversification present in individual reservoir animals have not been elucidated. To characterize this intra-host SIV diversity, we performed sequence analyses of clonal viral envelope (env) V1V2 and gag p27 variants present in individual SIVsm-infected sooty mangabeys over time. RESULTS: SIVsm demonstrated extensive intra-animal V1V2 length variation and amino acid diversity (le38%), and continual variation in V1V2 N-linked glycosylation consensus sequence frequency and location. Positive selection was the predominant evolutionary force. Temporal sequence shifts suggested continual selection, likely due to evolving antibody responses. In contrast, gag p27 was predominantly under purifying selection. SIVsm V1V2 sequence diversification is at least as great as that in HIV-1 infected humans, indicating that extensive viral diversification in and of itself does not inevitably lead to AIDS. CONCLUSION: Positive diversifying selection in this natural reservoir host is the engine that has driven the evolution of the uniquely adaptable SIV/HIV envelope protein. These studies emphasize the importance of retroviral diversification within individual host reservoir animals as a critical substrate in facilitating cross-species transmission.