niryuu/sni-each-converted huggingface dataset:
A young ferret was presented for a posterior paresis, urinary and fecal incontinence, weight loss, anorexia and lethargy. Biochemichemistry and hematology revealed hyperproteinemia with hyperglobulinemia and anemia. Abdominal ultrasonography showed splenomegaly, adenomegaly and nephromegaly with abdnomal echogenicity of the abdominal organs, compatible with a diagnosis of systemic coronavirosis. The ferret was humanely euthanized. On histopathology, a severe pyogranulomatous inflammation with neutrophilic vasculitis was seen in several organs (kidney, liver, lung, spleen and lymph node). Immunochemistry with FIPV3-70 antibody revealed the presence of coronaviral antigen within the lesions, confirming the diagnosis of Feline Infectious Peritonitis-like disease. A slight mononuclear radiculoneuritis was also present in the sciatic nerve, possibly explaining the peripheral neuropathy observed in this ferret. Whereas posterior paresis is common and non-specific in ferrets, fecal and urinary incontinence are rarely described. Radiculoneuritis caused by systemic coronavirus should be considered in young patients presenting these symptoms. Un jeune furet est présenté pour une parésie postérieure, une incontinence fécale et urinaire ainsi qu'une perte de poids, une anorexie et de la léthargie. Des examens biochimiques et hématologiques révèlent une hyperprotéinémie, hyperglobulinémie, et une anémie. Après la réalisation d'une échographie abdominale et de cytoponctions, le diagnostic de ଝ Crédits de formation continue. -La lecture de cet article ouvre droit à 0,05 CFC. La déclaration de lecture, individuelle et volontaire, est à effectuer auprès du CNVFCC (cf.sommaire).
Output: Unusual presentation of systemic coronavirosis in a ferret ଝ Présentation atypique d'une coronavirose systémique chez un furet MOTS CLÉS
Previously, recombinant vesicular stomatitis virus (rVSV) pseudotypes expressing Ebolavirus glycoproteins (GPs) in place of the VSV G protein demonstrated protection of nonhuman primates from lethal homologous Ebolavirus challenge. Those pseudotype vectors contained no additional attenuating mutations in the rVSV genome. Here we describe rVSV vectors containing a full complement of VSV genes and expressing the Ebola virus (EBOV) GP from an additional transcription unit. These rVSV vectors contain the same combination of attenuating mutations used previously in the clinical development pathway of an rVSV/human immunodeficiency virus type 1 vaccine. One of these rVSV vectors (N4CT1-EBOVGP1), which expresses membrane-anchored EBOV GP from the first position in the genome (GP1), elicited a balanced cellular and humoral GP-specific immune response in mice. Guinea pigs immunized with a single dose of this vector were protected from any signs of disease following lethal EBOV challenge, while control animals died in 7-9 days. Subsequently, N4CT1-EBOVGP1 demonstrated complete, single-dose protection of 2 macaques following lethal EBOV challenge. A single sham-vaccinated macaque died from disease due to EBOV infection. These results demonstrate that highly attenuated rVSV vectors expressing EBOV GP may provide safer alternatives to current EBOV vaccines.
Output: Vaccination With a Highly Attenuated Recombinant Vesicular Stomatitis Virus Vector Protects Against Challenge With a Lethal Dose of Ebola Virus
Rotaviruses (RVs), a leading cause of severe diarrhea in young children and many mammalian species, have evolved multiple strategies to counteract the host innate immunity, specifically interferon (IFN) signaling through RV non-structural protein 1 (NSP1). However, whether RV structural components also subvert antiviral response remains under-studied. Here, we found that MAVS, critical for the host RNA sensing pathway upstream of IFN induction, is degraded by the RV RNA methyl-and guanylyl-transferase (VP3) in a host-range-restricted manner. Mechanistically, VP3 localizes to the mitochondria and mediates the phosphorylation of a previously unidentified SPLTSS motif within the MAVS proline-rich region, leading to its proteasomal degradation and blockade of IFN-l production in RV-infected intestinal epithelial cells. Importantly, VP3 inhibition of MAVS activity contributes to enhanced RV replication and to viral pathogenesis in vivo. Collectively, our findings establish RV VP3 as a viral antagonist of MAVS function in mammals and uncover a novel pathogen-mediated inhibitory mechanism of MAVS signaling.
Output: Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells
We aimed to assess the profile of respiratory viruses in young children hospitalized for acute lower respiratory tract infection (ALRI) and its association with disease severity, defined as need for pediatric intensive care unit (PICU) admission. Prospective observational cohort study. A tertiary-care university hospital in Brazil. Children younger than three years attending the pediatric emergency room with ALRI who were admitted to the hospital. None. Nasopharyngeal aspirates were collected from patients from June 1 st , 2008 to May 31 st , 2009within the first 48 hours of hospitalization. Nasopharyngeal aspirates were tested for 17humanrespiratory viruses by molecular and immunofluorescence based assays. Simple and multiple log-binomial regression models were constructed to assess associations of virus type with a need for PICU admission. Age, prematurity, the presence of an underlying disease and congenital heart disease were covariates. Nasopharyngeal aspirates were positive for at least one virus in 236 patients. Rhinoviruses were detected in 85.6% of samples, with a preponderance of rhinovirus C (RV-C) (61.9%). Respiratory syncytial virus was detected in 59.8% and human coronavirus (HCoV) in 11% of the samples. Co-detections of two to five viruses were found in 78% of the patients. The detection of HCoV alone (adjusted relative risk (RR) 2.18; 95% CI 1. 15-4.15) or in co-infection with RV-C (adjusted RR 2.37; 95% CI 1.23-4.58) was independently associated with PICU admission. The detection of HCoV alone or in co-infection with RV-C was independently associated with PICU admission in young children hospitalized for ALRI. Human coronavirus alone or in coinfection with rhinovirus C is a risk factor for severe respiratory disease PLOS ONE | https://doi.
Output: Human coronavirus alone or in co-infection with rhinovirus C is a risk factor for severe respiratory disease and admission to the pediatric intensive care unit: A one-year study in Southeast Brazil
Background: Local malaria transmission has decreased rapidly since the National Malaria Elimination Action Plan was launched in China in 2010. However, imported malaria cases from Africa and Southeast Asia still occur in China due to overseas laborers. Diagnosis by microscopy is the gold standard for malaria and is used in most hospitals in China. However, the current capacity of microscopists to manage malaria cases in hospitals and public health facilities to meet the surveillance needs to eliminate and prevent the reintroduction of malaria is unknown. Methods: Malaria diagnoses were assessed by comparing the percentage of first visit and confirmed malaria diagnoses at Centers for Disease Control and Prevention (CDCs) and hospitals. The basic personnel information for public health departments and hospitals at different levels was investigated. The skills of microscopists for blood smear preparation and slide interpretation were also examined at the county and township levels. Results: Inaccurate rate with 13.49% and 7.32%, respectively, in 2013 and 2014, from 341 and 355 reported cases from sub-provincial levels in Jiangsu province. Most of the 523 malaria cases reported in Nantong Prefecture from 2000 to 2014 involved patients who first visited county CDCs seeking treatment, however, none of these cases received confirmed diagnosis of malaria in townships or villages.The staff at county CDCs and hospitals with a higher education background performed better at making and interpreting blood smears than staff from townships. Conclusions: The network for malaria elimination in an entire province has been well established. However, an insufficient capacity for malaria diagnosis was observed, especially the preparing and reading the blood smears at the township and village levels, which is a challenge to achieving and maintaining malaria elimination.
Output: The challenge of maintaining microscopist capacity at basic levels for malaria elimination in Jiangsu Province, China
Rosa SGV and Santos WC. Clinical trials on drug repositioning for COVID-19 treatment. Rev Panam Salud Publica. 2020;44:e40. ABSTRACT The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants' clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.
Output: Clinical trials on drug repositioning for COVID-19 treatment
Healthcare management is currently undergoing substantial changes, and reshaping our perception of the medical field. One spectrum is that of the considerable changes that we see in surgical machines and equipment, and the way the procedures are performed. Computing power, Internet and associated technologies are transforming surgical operations into model based procedures. The other spectrum is the management side of healthcare, which is equally critical to the medical profession. In particular, recent advances in the field of Information Technology (IT) is assisting in better management of health appointments and record management. With the proliferation of IT and management, data is now playing a vital role in diagnostics, drug administration and management of healthcare services. With the advancement in data processing, large amounts of medical data collected by medical centres and providers, can now be mined and analysed to assist in planning and making appropriate decisions. In this article, we shall provide an overview of the role of IT that have been reshaping the healthcare management, hospital, health profession and industry.
Output: IT applications in healthcare management: a survey
The Middle East Respiratory Syndrome (MERS-CoV) emerged in the Kingdom of Saudi Arabia in 2012 causing a critical challenge to public health. The epidemiology of MERS-CoV remain enigmatic as human-to-human transmission is not fully understood. One possible scenario that might play a role in the virus transmission is the cultural waterpipe smoking. Cafés providing waterpipe smoking in cities within Saudi Arabia have been moved to areas outside city limits that frequently place them close to camels markets. We report results of a surveillance study wherein waterpipe hoses throughout several regions in Saudi Arabia were tested for the presence of MERS-CoV. A total of 2489 waterpipe samples were collected from cities where MERS-CoV cases were continuously recorded. MERS-CoV RNA wasn't detected in collected samples. Irrespective of the negative results of our survey, the public health risk of waterpipe smoking should not be underestimated. To avoid a possible transmission within country where MERS-CoV is prevalent, we recommend the replacement of resusable hoses with ''one-timeuse" hoses in addition to a close inspection of waterpipe components to assure the appropriate cleaning and sanitization.
Output: Waterpipe smoking as a public health risk: Potential risk for transmission of MERS-CoV-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Interferon-induced transmembrane proteins (IFITMs) have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Rhesus macaques (Macaca mulatta) are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV) is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh) IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals.
Output: Rhesus macaque IFITM3 gene polymorphisms and SIV infection
Background: On-farm biosecurity is an important part of disease prevention and control, this applies to live animal contacts as well as indirect contacts e.g. via professionals visiting farms in their work. The objectives of this study were to investigate how professionals visiting animal farms in Sweden in their daily work perceive the on-farm conditions for biosecurity, the factors that influence their own biosecurity routines and what they describe as obstacles for biosecurity. Suggestions for improvements were also asked for. Questionnaires were distributed to professionals visiting farms in their daily work; veterinarians, livestock hauliers, artificial insemination technicians, animal welfare inspectors and cattle hoof trimmers. The sample was a convenience sample, based on accessibility to registers or collaboration with organisations distributing the questionnaire. Respondents were asked about the availability of certain biosecurity conditions related to farm visits, e.g. if facilities for hand washing were available, how important different factors were for their own routines and, through open ended questions, to describe obstacles and suggestions for improvement. Results: After data cleaning, there were responses from 368 persons. There was a difference in the proportion of visited farms reported to have certain biosecurity measures in place related to animal species present on the farm. In general, visited pig farms had a higher proportion of biosecurity measures in place, whereas the conditions were poorer on sheep and goat farms and horse farms. There were also differences between the visitor categories; the perceived conditions for biosecurity varied between the groups, e.g. livestock hauliers did not have access to hand washing facilities as often as veterinarians did. In all groups, a majority of the respondents perceived obstacles for on-farm biosecurity, among veterinarians 66% perceived that there were obstacles. Many of the reported obstacles related to the very basics of biosecurity, such as access to soap and water. Responsibility was identified to be a key issue; while some farmers expect visitors to take responsibility for keeping up biosecurity they do not provide the adequate on-farm conditions. Conclusions: Many of the respondents reported obstacles for keeping good biosecurity related to on-farm conditions. There was a gap when it came to responsibility which needs to be clarified. Visitors need to take responsibility for avoiding spread of disease, while farmers need to assume responsibility for providing adequate conditions for on-farm biosecurity.
Output: On-farm biosecurity as perceived by professionals visiting Swedish farms
Data are limited regarding 2 new human polyomaviruses, KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV), in immunocompromised patients. We used realtime PCR to test for these and 12 respiratory viruses in 2,732 nasal wash samples collected during the fi rst year after allogeneic hematopoietic cell transplantation from 222 patients. Specimens were collected weekly until day 100; then at least every 3 months. One year after hematopoietic cell transplantation, the cumulative incidence estimate was 26% for KIPyV and 8% for WUPyV. Age <20 years predicted detection of KIPyV (hazard ratio [HR] 4.6) and WUPyV (HR 4.4), and detection of a respiratory virus in the previous 2 weeks predicted KIPyV detection (HR 3.4). Sputum production and wheezing were associated with detection of KIPyV in the past week and WUPyV in the past month. There were no associations with polyomavirus detection and acute graft versus host disease, cytomegalovirus reactivation, neutropenia, lymphopenia, hospitalization, or death.
Output: WU and KI Polyomaviruses in Respiratory Samples from Allogeneic Hematopoietic Cell Transplant Recipients
Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections.
Output: Characterization of the Lipidomic Profile of Human Coronavirus-Infected Cells: Implications for Lipid Metabolism Remodeling upon Coronavirus Replication
Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV-and HeV-infected individuals.
Output: An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections Author contributions
Background The Binational Border Infectious Disease Surveillance program began surveillance for severe acute respiratory infections (SARI) on the US-Mexico border in 2009. Here, we describe patients in Southern Arizona. Methods Patients admitted to five acute care hospitals that met the SARI case definition (temperature ≥37Á8°C or reported fever or chills with history of cough, sore throat, or shortness of breath in a hospitalized person) were enrolled. Staff completed a standard form and collected a nasopharyngeal swab which was tested for selected respiratory viruses by reverse transcription polymerase chain reaction. Results From October 2010-September 2014, we enrolled 332 SARI patients. Fifty-two percent were male and 48% were white non-Hispanic. The median age was 63 years (47% ≥65 years and 5Á2% <5 years). During hospitalization, 51 of 230 (22%) patients required intubation, 120 of 297 (40%) were admitted to intensive care unit, and 28 of 278 (10%) died. Influenza vaccination was 56%. Of 309 cases tested, 49 (16%) were positive for influenza viruses, 25 (8Á1%) for human metapneumovirus, 20 (6Á5%) for parainfluenza viruses, 16 (5Á2%) for coronavirus, 11 (3Á6%) for respiratory syncytial virus, 10 (3Á2%) for rhinovirus, 4 (1Á3%) for rhinovirus/ enterovirus, 3 (1Á0%) for enteroviruses, and 3 (1Á0%) for adenovirus. Among the 49 influenza-positive specimens, 76% were influenza A (19 H3N2, 17 H1N1pdm09, and 1 not subtyped), and 24% were influenza B. Conclusion Influenza viruses were a frequent cause of SARI in hospitalized patients in Southern Arizona. Monitoring respiratory illness in border populations will help better understand the etiologies. Improving influenza vaccination coverage may help prevent some SARI cases.
Output: Surveillance for severe acute respiratory infections in Southern Arizona
Risk communication guidelines widely used in public health are based on the psychometric paradigm of risk, which focuses on risk perception at the level of individuals. However, infectious disease outbreaks and other public health emergencies are more than public health events and occur in a highly charged political, social and economic environment. This study examines other sociological and cultural approaches from scholars such as Ulrich Beck and Mary Douglas for insights on how to communicate in such environments. It recommends developing supplemental tools for outbreak communication to deal with issues such as questions of blame and fairness in risk distribution and audiences who do not accept biomedical explanations of disease. Une traduction en français de ce résumé figure à la fin de l'article. Al final del artículo se facilita una traducción al español. ‫املقالة.‬ ‫لهذه‬ ‫الكامل‬ ‫النص‬ ‫نهاية‬ ‫يف‬ ‫الخالصة‬ ‫لهذه‬ ‫العربية‬ ‫الرتجمة‬
Output: Policy & practice Risk and outbreak communication: lessons from alternative paradigms
Here we report the rescue of a recombinant porcine reproductive and respiratory syndrome virus (PRRSV) carrying an enhanced green fluorescent protein (EGFP) reporter gene as a separate transcription unit. A copy of the transcription regulatory sequence for ORF6 (TRS6) was inserted between the N protein and 3′-UTR to drive the transcription of the EGFP gene and yield a general purpose expression vector. Successful recovery of PRRSV was obtained using an RNA polymerase II promoter to drive transcription of the full-length virus genome, which was assembled in a bacterial artificial chromosome (BAC). The recombinant virus showed growth replication characteristics similar to those of the wild-type virus in the infected cells. In addition, the recombinant virus stably expressed EGFP for at least 10 passages. EGFP expression was detected at approximately 10 h post infection by live-cell imaging to follow the virus spread in real time and the infection of neighbouring cells occurred predominantly through cell-to-cell-contact. Finally, the recombinant virus generated was found to be an excellent tool for neutralising antibodies and antiviral compound screening. The newly established reverse genetics system for PRRSV could be a useful tool not only to monitor virus spread and screen for neutralising antibodies and antiviral compounds, but also for fundamental research on the biology of the virus.
Output: A novel porcine reproductive and respiratory syndrome virus vector system that stably expresses enhanced green fluorescent protein as a separate transcription unit
Objective-To determine whether there are racial differences in social support among patients with knee osteoarthritis (OA) and whether the impact of social support on patient preferences for total knee replacement (TKR) varies by race and gender. white & 285 African-American (AA) patients with knee OA were surveyed. Logistic regression models were performed to determine if the relationship between willingness to undergo TKR and the interaction of patient race and sex were mediated by social support. Results-Compared to whites with knee OA, AA patients were less likely to be married (p<0.001), reported less close friends/relatives (p<0.001) and had lower Medical Outcomes Study-Social Support Scale (MOS-SSS) scores (p<0.001). AA patients were also less willing to undergo TKR (62% vs. 80%, p<0.001) than whites. The odds of willingness to undergo TKR was less in white females compared to white males when adjusted for recruitment site, age, income and WOMAC (OR 0.57, 95% CI 0.34-0.96). This difference was no longer significant when further adjusted for marital status, number of close friends/relatives and MOS-SSS score, but the effect size remained unchanged (OR 0.60, 95% CI 0.35-1.02). The odds of willingness to undergo TKR remained much less in AA females (OR 0.35, 95% CI 0.19-0.64) and AA males (OR 0.28, 95% CI 0.14-0.54) compared to white males when controlled for sociodemographic, clinical and social support measures.
Output: RACE, GENDER AND TOTAL KNEE REPLACEMENT CONSIDERATION: THE ROLE OF SOCIAL SUPPORT
We propose a compartmental disease transmission model with an asymptomatic (or subclinical) infective class to study the role of asymptomatic infection in the transmission dynamics of infectious diseases with asymptomatic infectives, e.g., influenza. Analytical results are obtained using the respective ratios of susceptible, exposed (incubating), and asymptomatic classes to the clinical symptomatic infective class. Conditions are given for bistability of equilibria to occur, where trajectories with distinct initial values could result in either a major outbreak where the disease spreads to the whole population or a lesser outbreak where some members of the population remain uninfected. This dynamic behavior did not arise in a SARS model without asymptomatic infective class studied by Hsu and Hsieh (SIAM J. Appl. Math. 66(2), 2006). Hence, this illustrates that depending on the initial states, control of a disease outbreak with asymptomatic infections may involve more than simply reducing the reproduction number. Moreover, the presence of asymptomatic infections could result in either a positive or negative impact on the outbreak, depending on different sets of conditions on the parameters, as illustrated with numerical simulations. Biological interpretations of the analytical and numerical results are also given.
Output: On the Role of Asymptomatic Infection in Transmission Dynamics of Infectious Diseases
CAP = community-acquired pneumonia; CMV = conventional mechanical ventilation; HAP = hospital-acquired pneumonia; HCAP = health-careassociated pneumonia; NIV = non-invasive ventilation; PTC = protected telescoping aspiration; VAP = ventilator-associated pneumonia. Respiratory failure is one of the leading admission diagnoses on the critical care unit, and the journals have reflected this over the past few months. An understanding of the aetiology of pulmonary sepsis is important but your choice of ventilator gas humidification system is not. There are prophecies of more pandemics, but panic is futile because survival is all down to your genes.
Output: Recently published papers: pulmonary care, pandemics, and eugenics in surviving sepsis?
This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS. The 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the Republic of Korea developed from a traveler returning from the Middle East, 1 which is the largest outbreak outside of the Arabian Peninsula to date. This unprecedented nationwide outbreak resulted in 186 laboratory-confirmed cases with 38 fatalities and > 16,000 individuals being quarantined. 2-4 During the outbreak, a comprehensive screening test including MERS-CoV real-time reverse transcription polymerase chain reaction (rRT-PCR) was performed in all possible contactors to prevent further spread of the disease. Positive MERS-CoV rRT-PCR findings were observed in patients with no or mild symptoms, who were also subjected to epidemiological investigation and follow-up. 1 There have been many reports of long-term sequelae of severe acute respiratory syndrome (SARS), 5-10 but to the best of our knowledge no report has addressed long-term sequelae in
Output: Brief Communication Correlation between Pneumonia Severity and Pulmonary Complications in Middle East Respiratory Syndrome
We replaced the HIV-1 nucleocapsid (NC) domain with different N-coding sequences to test SARS-CoV nucleocapsid (N) self-interaction capacity, and determined the capabilities of each chimera to direct viruslike particle (VLP) assembly. Analysis results indicate that the replacement of NC with the carboxyl-terminal half of the SARS-CoV N resulted in the production of wild type (wt)-level virus-like particles (VLPs) with the density of a wt HIV-1 particle. When co-expressed with SARS-CoV N, chimeras containing the N carboxyl-terminal half sequence efficiently packaged N. However, the same was not true for the chimera bearing the N amino-terminal half sequence, despite its production of substantial amounts of VLPs. According to further analysis, HIV-1 NC replacement with N residues 2-213, 215-421, or 234-421 resulted in efficient VLP production at levels comparable to that of wt HIV-1, but replacement with residues 215-359, 302-421, 2-168, or 2-86 failed to restore VLP production to wildtype levels. The results suggest that the domain conferring the ability to direct VLP assembly and release in SARS-CoV N is largely contained between residues 168 and 421.
Output: Severe acute respiratory syndrome coronavirus nucleocapsid protein confers ability to efficiently produce virus-like particles when substituted for the human immunodeficiency virus nucleocapsid domain
The discovery of angiotensin-(1-7) [Ang-(1-7)] in 1988 represented the first deviation from the traditional biochemical cascade of forming bioactive angiotensin peptides. Prior to that time, the biological actions of angiotensin II (Ang II) were being investigated as it relates to cardiovascular function, including hypertension, cardiac hypertrophy and failure, as well as biological actions in the brain and kidney. We now know that Ang II elicits a whole host of actions both within and outside of the cardiovascular system. Furthermore, the discovery of Ang-(1-7) by our laboratory was also the first indication of a biologically active angiotensin peptide that further studies revealed served to counter-balance the actions of Ang II. This chapter reviews the data demonstrating the role of the vasodepressor axis of the renin angiotensin system in the regulation of cardiovascular function and the new data that shows the existence of angiotensin-(1-12) as a novel alternate substrate for the production of angiotensin peptides. The ultimate role of this discovery, as well as the continuing elucidation of mechanisms pertaining to RAS physiology, will likely be clarified in the coming years, in hopes of improving the treatment of cardiovascular disease.
Output: Angiotensin-(1-7), Angiotensin-Converting Enzyme 2, and New Components of the Renin Angiotensin System
Unbiased metagenomic sequencing holds significant potential as a diagnostic tool for the simultaneous detection of any previously genetically described viral nucleic acids in clinical samples. Viral genome sequences can also inform on likely phenotypes including drug susceptibility or neutralization serotypes. In this study, different variables of the laboratory methods often used to generate viral metagenomics libraries were compared for their abilities to detect multiple viruses and generate full genome coverage. A biological reagent consisting of 25 different human RNA and DNA viral pathogens was used to estimate the effect of filtration and nuclease digestion, DNA/RNA extraction methods, pre-amplification and the use of different library preparation kits on the detection of viral nucleic acids. Filtration and nuclease treatment led to slight decreases in the percentage of viral sequence reads and number of viruses detected. For nucleic acid extractions silica spin columns improved viral sequence recovery relative to magnetic beads and Trizol extraction. Pre-amplification using random RT-PCR while generating more viral sequence reads resulted in detection of fewer viruses, more overlapping sequences, and lower genome coverage. The ScriptSeq library preparation method retrieved more viruses and a greater fraction of their genomes than the TruSeq and Nextera methods. Viral metagenomics sequencing was able to simultaneously detect up to 22 different viruses in the biological reagent analyzed including all those detected by qPCR. Further optimization will be required for the detection of viruses in biologically more complex samples such as tissues, blood, or feces.
Output: Comparing viral metagenomics methods using a highly multiplexed human viral pathogens reagent
The coronavirus E protein is a small membrane protein with a single predicted hydrophobic domain (HD), and has a poorly defined role in infection. The E protein is thought to promote virion assembly, which occurs in the Golgi region of infected cells. It has also been implicated in the release of infectious particles after budding. The E protein has ion channel activity in vitro, although a role for channel activity in infection has not been established. Furthermore, the membrane topology of the E protein is of considerable debate, and the protein may adopt more than one topology during infection. We previously showed that the HD of the infectious bronchitis virus (IBV) E protein is required for the efficient release of infectious virus, an activity that correlated with disruption of the secretory pathway. Here we report that a single residue within the hydrophobic domain, Thr16, is required for secretory pathway disruption. Substitutions of other residues for Thr16 were not tolerated. Mutations of Thr16 did not impact virus assembly as judged by virus-like particle production, suggesting that alteration of secretory pathway and assembly are independent activities. We also examined how the membrane topology of IBV E affected its function by generating mutant versions that adopted either a transmembrane or membrane hairpin topology. We found that a transmembrane topology was required for disrupting the secretory pathway, but was less efficient for virus-like particle production. The hairpin version of E was unable to disrupt the secretory pathway or produce particles. The findings reported here identify properties of the E protein that are important for its function, and provide insight into how the E protein may perform multiple roles during infection.
Output: A Single Polar Residue and Distinct Membrane Topologies Impact the Function of the Infectious Bronchitis Coronavirus E Protein
were denied by insurance. Of 41 patients initially screened, 10% lacked an available haploidentical donor, 29% had elevated donor-specific antibodies (DSAs), and 34% declined to proceed to HSCT. All 10 patients who were transplanted received peripheral blood stem cells. The initial 2 were conditioned with alemtuzumab/total body irradiation (TBI) 3 Gy followed by post-transplant cyclophosphamide and failed to engraft. The next 8 patients received the regimen developed at Johns Hopkins University with TBI 3 Gy. Granulocyte colony-stimulating factor was administered from day +12 in those with HbS < 30%. All 8 patients engrafted with a median time to neutrophil >.5 × 10 9 /L of 22 days (range, 18 to 23). One patient subsequently lost the graft, and 7 (87.5%) maintained >95% donor cell chimerism at 1-year post-HSCT. Two patients developed acute graft-versus-host disease (GVHD) of at least grade II. One had chronic GVHD and died >1 year after HSCT of unknown causes. With a median follow-up of 16 months (range, 11 to 29), 7 patients (87.5%) are alive. Our findings suggest that limited insurance coverage, high rate of DSAs, and patient declining HSCT may limit the availability of haploidentical HSCT in adult SCD patients. The modified Hopkins regimen used here demonstrates high engraftment and low morbidity rates and should be tested in larger, multicenter, prospective clinical trials.
Output: Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease We report on the screening and development of haploidentical hematopoietic stem cell transplantation (HSCT) for adult patients with clinically aggressive sickle cell disease (SCD) at our institution. Of 50 adult SCD pa- tients
The purpose of disease mapping is to find spatial clustering and identify risk areas and potential epidemic initiators. Rather than relying on plotting either the case number or incidence rate, this chapter proposes three temporal risk indices: the probability of case occurrence (how often did uneven cases occur), the duration of an epidemic (how long did cases persist), and the intensity of a transmission (were the case of chronological significance). By integrating the three indicators using the local indicator of spatial autocorrelation (LISA) statistic, this chapter intends to develop a novel approach for evaluating spatial-temporal relationships with different risk patterns in the 2002 dengue epidemic, the worst outbreak in the past sixty years. With this approach, not only are hypotheses generated through the mapping processes in furthering investigation, but also procedures provided to identify spatial health risk levels with temporal characteristics.
Output: A Spatial-Temporal Approach to Differentiate Epidemic Risk Patterns A Spatial-Temporal Approach to Differentiate Epidemic Risk Patterns
Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the swine industry. p53 protein exists in a wide variety of animal cells, which is involved in cell cycle regulation, apoptosis, cell differentiation and other biological functions. In this study, we investigated the effects of PEDV infection on the cell cycle of Vero cells and p53 activation. The results demonstrated that PEDV infection induces cell cycle arrest at G0/G1 phase in Vero cells, while UV-inactivated PEDV does not cause cell cycle arrest. PEDV infection up-regulates the levels of p21, cdc2, cdk2, cdk4, Cyclin A protein and down-regulates Cyclin E protein. Further research results showed that inhibition of p53 signaling pathway can reverse the cell cycle arrest in G0/G1 phase induced by PEDV infection and cancel out the up-regulation of p21 and corresponding Cyclin/cdk mentioned above. In addition, PEDV infection of the cells synchronized in various stages of cell cycle showed that viral subgenomic RNA and virus titer were higher in the cells released from G0/G1 phase synchronized cells than that in the cells released from the G1/S phase and G2/M phase synchronized or asynchronous cells after 18 h p.i.. This is the first report to demonstrate that the p53-dependent pathway plays an important role in PEDV induced cell cycle arrest and beneficially contributes to viral infection.
Output: Porcine epidemic diarrhea virus through p53-dependent pathway causes cell cycle arrest in the G0/G1 phase
Balanced transmembrane signals maintain a competent peripheral B cell pool limited in selfreactive B cells that may produce pathogenic autoantibodies. To identify molecules regulating peripheral B cell survival and tolerance to self-antigens (Ags), a gene modifier screen was performed with B cells from CD22-deficient C57BL/6 (CD22 /[B6] ) mice that undergo activation-induced cell death (AICD) and fail to up-regulate c-Myc expression after B cell Ag receptor ligation. Likewise, lysozyme auto-Ag-specific B cells in Ig Tg hen egg lysozyme (HEL) transgenic mice inhabit the spleen but undergo AICD after auto-Ag encounter. This gene modifier screen identified EndoU, a single-stranded RNA-binding protein of ancient origin, as a major regulator of B cell survival in both models. EndoU gene disruption prevents AICD and normalizes c-Myc expression. These findings reveal that EndoU is a critical regulator of an unexpected and novel RNA-dependent pathway controlling peripheral B cell survival and Ag responsiveness that may contribute to peripheral B cell tolerance.
Output: Article EndoU is a novel regulator of AICD during peripheral B cell selection
Objective: Salmonella enterica remains a major cause of food-borne disease in humans, and Salmonella Typhimurium (ST) contamination of poultry products is a worldwide problem. Since macrophages play an essential role in controlling Salmonella infection, the aim of this study was to evaluate the effect of glycyrrhizic acid (GA) on immune function of chicken HD11 macrophages. Methods: Chicken HD11 macrophages were treated with GA (0, 12.5, 25, 50, 100, 200, 400, or 800 μg/ml) and lipopolysaccharide (LPS, 500 ng/ml) for 3, 6, 12, 24, or 48 h. Evaluated responses included phagocytosis, bacteria-killing, gene expression of cell surface molecules (cluster of differentiation 40 (CD40), CD80, CD83, and CD197) and antimicrobial effectors (inducible nitric oxide synthase (iNOS), NADPH oxidase-1 (NOX-1), interferon-γ (IFN-γ), LPS-induced tumor necrosis factor (TNF)-α factor (LITAF), interleukin-6 (IL-6), and IL-10), and production of nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ). Results: GA increased the internalization of both fluorescein isothiocyanate (FITC)-dextran and ST by HD11 cells and markedly decreased the intracellular survival of ST. We found that the messenger RNA (mRNA) expression of cell surface molecules (CD40, CD80, CD83, and CD197) and cytokines (IFN-γ, IL-6, and IL-10) of HD11 cells was up-regulated following GA exposure. The expression of iNOS and NOX-1 was induced by GA and thereby the productions of NO and H 2 O 2 in HD11 cells were enhanced. Notably, it was verified that nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways were responsible for GA-induced synthesis of NO and IFN-γ gene expression. Conclusions: Taken together, these results suggested that GA exhibits a potent immune regulatory effect to activate chicken macrophages and enhances Salmonella-killing capacity.
Output: Glycyrrhizic acid activates chicken macrophages and enhances their Salmonella-killing capacity in vitro *#
In 2019, a novel coronavirus (SARS-CoV-2) was first discovered in Wuhan, Hubei, China, causing severe respiratory disease in humans, and has been identified as a public health emergency of international concern. With the spread of the virus, there are more and more false negative cases of RT-PCR nucleic acid detection in the early stage of potential infection. In this paper, we collected the epidemiological history, clinical manifestations, outcomes, laboratory results and images of a SARS-CoV-2 carrier with no significant past medical history. The patient was quarantined because of her colleague had been diagnosed. After the onset of clinical symptoms, chest CT results showed patchy ground-glass opacity (GGO) in her lungs, but it took a total of nine nucleic acid tests to confirm the diagnosis, among which the first eight RT-PCR results were negative or single-target positive. In addition to coughing up phlegm during her stay in the hospital, she did not develop chills, fever, abdominal pain, diarrhea and other clinical symptoms. Since initial antiviral treatment, the lung lesions were absorbed. But the sputum nucleic acid test was still positive. In combination with antiviral and immune therapy, the patient tested negative for the virus. Notably, SARS-CoV-2 was detected only in the lower respiratory tract samples (sputum) throughout the diagnosis and treatment period. This is a confirmed case of SARS-CoV-2 infection with common symptoms, and her diagnosis has undergone multiple false negatives ,suggesting that it is difficult to identify certain carriers of the virus and that such patients may also increase the spread of the SARS-CoV-2.
Output: A case of SARS-CoV-2 carrier for 32 days with several times false negative nucleic acid tests