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

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


Emerging phenotype of SARS-CoV2 associated pancreatitis.


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

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


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

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


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

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


title: Long-term sequelae of SARS in children

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


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

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


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


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

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


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

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


title: Zoonotic disease risk perceptions in the British veterinary profession

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


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

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


Psychosocial Impact of SARS


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

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


title: How inclusive are we, really?

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


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

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


title: Influenza is now a preventable disease

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


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

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


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

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


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

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


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

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


title: Neighborhood Disadvantage and Children’s Cognitive Skill Trajectories

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


Immunity, the God-given weapon against infection


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

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


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

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


title: 10 Select agent program impact on the IBC

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


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

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


Building a global atlas of zoonotic viruses


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

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


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

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


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

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


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

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


title: InTRONs in Biotech

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


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

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


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

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


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

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


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

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


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

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


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

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


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

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


title: Genetic and molecular aspects of demyelination

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


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

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


title: Hepatitis E Virus Drug Development

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


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

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


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

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


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


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

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


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

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


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

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


title: Viral Suppressors of Gene Silencing

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


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


title: Transgenic Organs and Xenotransplants

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


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

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


title: Chapter 68 Mucosal Veterinary Vaccines Comparative Vaccinology

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


title: Bat mammalian orthoreoviruses cause severe pneumonia in mice

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


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

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


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

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


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

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


title: Chapter 12 Biosecurity Programs and Assets

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


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

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


title: MicroRNA Regulation of RNA Virus Replication and Pathogenesis

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


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

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


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

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


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

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


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

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


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

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


title: Multidimensional scaling analysis of virus diseases

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


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

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


title: Advances in Diagnosis of Respiratory Virus Infections

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


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


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

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


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


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


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

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


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

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


title: Coronavirus Disease 2019: Coronaviruses and Blood Safety

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


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

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