title: High-Efficiency Same-Day Approach to Breast Reconstruction During the COVID-19 Crisis

text: PURPOSE: As our hospitals conserve and re-allocate resources during the COVID-19 crisis, there is urgent need to determine how best to continue caring for breast cancer patients. During the time window before the COVID-19 critical peak and particularly thereafter, as hospitals are able to resume cancer operations, we anticipate that there will be great need to maximize efficiency to treat breast cancer. The goal of this study is to present a same-day protocol that minimizes resource utilization to enable hospitals to increase inpatient capacity, while providing care for breast cancer patients undergoing mastectomy and immediate breast reconstruction during the COVID-19 crisis. METHODS: IRB exempt patient quality improvement initiative was conducted to detail the operationalization of a novel same-day breast reconstruction protocol. Consecutive patients having undergone immediate breast reconstruction were prospectively enrolled between February and March of 2020 at Massachusetts General Hospital during the COVID-19 crisis. Peri-operative results and postoperative complications were summarized. RESULTS: Time interval from surgical closure to patient discharge was 5.02 ± 1.29 h. All patients were discharged home, with no re-admissions or emergency department visits. No postoperative complications were observed. CONCLUSION: This report provides an instruction manual to operationalize a same-day breast reconstruction protocol, to meet demands of providing appropriate cancer treatment during times of unprecedented resource limitations. Pre-pectoral implant-based breast reconstruction can be the definitive procedure or be used as a bridge to autologous reconstruction. Importantly, we hope this work will be helpful to our patients and community as we emerge from the COVID-19 pandemic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-020-05739-7) contains supplementary material, which is available to authorized users.


title: Epidemic Investigation

text: One of the key roles of public health is to manage outbreaks that endanger the public's health. The nature of an outbreak can be due to a wide range of causes, and a variety of approaches to detection of epidemics is possible, but the main points are very similar for all outbreaks and are described in this article. The first challenge is to notice an increase in cases and to confirm an outbreak. Based on descriptive epidemiology, a case definition and hypothesis are developed, which is preferably confirmed by at least an epidemiologic study. Other aspects of investigation described in this article are the organization of the outbreak investigation and the importance of communication.


title: Astroglial IFITM3 mediates neuronal impairments following neonatal immune challenge in mice

text: Interferon‐induced transmembrane protein 3 (IFITM3) ıplays a crucial role in the antiviral responses of Type I interferons (IFNs). The role of IFITM3 in the central nervous system (CNS) is, however, largely unknown, despite the fact that its expression is increased in the brains of patients with neurologic and neuropsychiatric diseases. Here, we show the role of IFITM3 in long‐lasting neuronal impairments in mice following polyriboinosinic‐polyribocytidylic acid (polyI:C, a synthetic double‐stranded RNA)‐induced immune challenge during the early stages of development. We found that the induction of IFITM3 expression in the brain of mice treated with polyI:C was observed only in astrocytes. Cultured astrocytes were activated by polyI:C treatment, leading to an increase in the mRNA levels of inflammatory cytokines as well as Ifitm3. When cultured neurons were treated with the conditioned medium of polyI:C‐treated astrocytes (polyI:C‐ACM), neurite development was impaired. These polyI:C‐ACM‐induced neurodevelopmental abnormalities were alleviated by ifitm3(−/−) astrocyte‐conditioned medium. Furthermore, decreases of MAP2 expression, spine density, and dendrite complexity in the frontal cortex as well as memory impairment were evident in polyI:C‐treated wild‐type mice, but such neuronal impairments were not observed in ifitm3(−)(/)(−) mice. We also found that IFITM3 proteins were localized to the early endosomes of astrocytes following polyI:C treatment and reduced endocytic activity. These findings suggest that the induction of IFITM3 expression in astrocytes by the activation of the innate immune system during the early stages of development has non‐cell autonomous effects that affect subsequent neurodevelopment, leading to neuropathological impairments and brain dysfunction, by impairing endocytosis in astrocytes. GLIA 2013


docid: grofnanh

title: Inhibition of hepatitis E virus replication by proteasome inhibitor is nonspecific

text: The ubiquitin proteasome system plays important role in virus infection. A previous study showed that the proteasome inhibitor MG132 could potentially affect hepatitis E virus (HEV) replication. In this study, we found that MG132 could inhibit HEV and hepatitis C virus (HCV) replication-related luciferase activity in subgenomic models. Furthermore, treatment with MG132 in a HEV infectious model resulted in a dramatic reduction in the intracellular level of HEV RNA. Surprisingly, MG132 concurrently inhibited the expression of a luciferase gene used as a control as well as a wide range of host genes. Consistently, the total cellular RNA and protein content was concurrently reduced by MG132 treatment, suggesting a nonspecific antiviral effect.


title: Can an etiologic agent be identified in adults who are hospitalized for community-acquired pneumonia: Results of a one-year study

text: Summary Introduction Determining the cause of community-acquired pneumonia (CAP) remains problematic. In this observational study, we systematically applied currently approved diagnostic techniques in patients hospitalized for CAP in order to determine the proportion in which an etiological agent could be identified. Methods All patients admitted with findings consistent with CAP were included. Sputum and blood cultures, urine tests for pneumococcal and Legionella antigens, nasopharyngeal swab for viral PCR, and serum procalcitonin were obtained in nearly every case. Admission-related electronic medical records were reviewed in entirety. Results By final clinical diagnosis, 44 patients (17.0%) were uninfected. A causative bacterium was identified in only 60 (23.2%) cases. PCR identified a respiratory virus in 42 (16.2%), 12 with documented bacterial coinfection. In 119 (45.9%), no cause for CAP was found; 69 (26.6%) of these had a syndrome indistinguishable from bacterial pneumonia. Procalcitonin was elevated in patients with bacterial infection and low in uninfected patients or those with viral infection, but with substantial overlap. Conclusions Only 23.2% of 259 patients admitted with a CAP syndrome had documented bacterial infection; another 26.6% had no identified bacterial etiology, but findings closely resembled those of bacterial infection. Nevertheless, all 259 received antibacterial therapy. Careful attention to the clinical picture may identify uninfected patients or those with viral infection, perhaps with reassurance by a non-elevated procalcitonin. Determining an etiologic diagnosis remains elusive. Better discriminators of bacterial infection are sorely needed.


Key Considerations for Radiologists When Diagnosing the Novel Coronavirus Disease (COVID-19)


title: Upsurge of Enterovirus D68, the Netherlands, 2016

text: In June and July 2016, we identified 8 adults and 17 children with respiratory enterovirus D68 infections. Thirteen children required intensive care unit admission because of respiratory insufficiency, and 1 had concomitant acute flaccid myelitis. Phylogenetic analysis showed that all of 20 sequences obtained belong to the recently described clade B3.


title: Factors affecting cross-hospital exchange of Electronic Medical Records

text: Abstract Adopting Electronic Medical Record (EMR) exchange may save patients’ lives and also improve their health. Most Electronic Data Interchange studies have considered commercial enterprises and necessary funding to support business activities, EMR exchange focuses on saving patients’ lives. Our study combined transaction cost and sociological perspectives to identify factors that affect a hospitals’ willingness to implement EMR exchange. A survey was conducted with regional hospitals and medical centers in Taiwan to justify the validity of a resulting model. Our findings indicated that the model was valuable and determined which factors influenced the decision to implement EMR exchange at these hospitals (perceived benefits, uncertainty, influence, and reciprocal investments). Based on these findings, healthcare policy makers can promote EMR exchange and hospitals can identify desirable partners that will form a strategic alliance to meet the dynamic challenges in the healthcare industry.


docid: ppsvfyjl

title: Rinofaringitis

text: La rinofaringitis es la infección más banal de la primera infancia. Se trata de una enfermedad de adaptación y se ve favorecida por diversos factores que conviene conocer en detalle para disminuir la frecuencia en la población y las recidivas en una misma persona. Esta infección vírica carece de gravedad siempre que no se presente en su forma complicada o crónica. Su tratamiento consiste sobre todo en el lavado de las fosas nasales con suero fisiológico, la evitación (cuando sea posible) de los factores de riesgo) y la adenoidectomía, cuyas indicaciones están bien definidas.


title: Effects of surgical and FFP2/N95 face masks on cardiopulmonary exercise capacity

text: BACKGROUND: Due to the SARS-CoV2 pandemic, medical face masks are widely recommended for a large number of individuals and long durations. The effect of wearing a surgical and a FFP2/N95 face mask on cardiopulmonary exercise capacity has not been systematically reported. METHODS: This prospective cross-over study quantitated the effects of wearing no mask (nm), a surgical mask (sm) and a FFP2/N95 mask (ffpm) in 12 healthy males (age 38.1 ± 6.2 years, BMI 24.5 ± 2.0 kg/m(2)). The 36 tests were performed in randomized order. The cardiopulmonary and metabolic responses were monitored by ergo-spirometry and impedance cardiography. Ten domains of comfort/discomfort of wearing a mask were assessed by questionnaire. RESULTS: The pulmonary function parameters were significantly lower with mask (forced expiratory volume: 5.6 ± 1.0 vs 5.3 ± 0.8 vs 6.1 ± 1.0 l/s with sm, ffpm and nm, respectively; p = 0.001; peak expiratory flow: 8.7 ± 1.4 vs 7.5 ± 1.1 vs 9.7 ± 1.6 l/s; p < 0.001). The maximum power was 269 ± 45, 263 ± 42 and 277 ± 46 W with sm, ffpm and nm, respectively; p = 0.002; the ventilation was significantly reduced with both face masks (131 ± 28 vs 114 ± 23 vs 99 ± 19 l/m; p < 0.001). Peak blood lactate response was reduced with mask. Cardiac output was similar with and without mask. Participants reported consistent and marked discomfort wearing the masks, especially ffpm. CONCLUSION: Ventilation, cardiopulmonary exercise capacity and comfort are reduced by surgical masks and highly impaired by FFP2/N95 face masks in healthy individuals. These data are important for recommendations on wearing face masks at work or during physical exercise.


title: Coronavirus IBV glycopolypeptides: locational studies using proteases and saponin, a membrane permeabilizer

text: Abstract [35S]methionine-labelled avian infectious bronchitis virus (IBV) (strain 41) and its purified protein components and virions of IBV-Beaudette were incubated with 10 proteases. Several proteases hydrolysed all or some of the membrane glycopoly-peptide (M; M r 30K) and removed about 1.3K of peptide from the amino-(N-)-terminus plus both glycans, as determined by SDS-polyacrylamide gel electrophoresis. N-terminal analysis of [3H]isoleucine-labelled M after hydrolysis by bromelain revealed that the first nine residues had been removed. After the virions had been permeabilised with saponin, a further 2.5K decrease in molecular weight was produced and this was shown to be from the carboxy-(C-)terminus. When considered with the hydropathicity plot analysis of the amino acid sequence of M (Boursnell, M.E.G. et al., 1984, Virus Res. 1, 303–313) these results suggest that as few as 9–20 N-terminal amino acid residues may protrude at the outer membrane surface and that there is a highly protease sensitive sequence of an estimated 20–25 residues at the C-terminus of M exposed in the lumen of the virion. S2 but not SI was cleaved to a major glycopolypeptide of approximately 71K by several proteases, and to 76K by trypsin. N-terminal sequencing of the 71K glycopolypeptide revealed that it had the same N-terminus as intact S2. After hydrolysis in the presence and absence of saponin it was concluded that S2 is very sensitive to hydrolysis near its carboxy terminus at residues close to the outer membrane surface.


Impact of COVID-19 on People with Mental Disabilities in Japan


title: Public health investments: neglect or wilful omission? Historical trends in Quebec and implications for Canada

text: This commentary explores public health (PH) investments in Quebec and underlines the challenge of tracking PH resources across Canada. We analyzed governmental data to compare investments across all health and social programs in Quebec from 2004–2005 to 2017–2018. The province’s PH budgets suffered from disproportionately low investments and abrupt cuts. These cuts were the largest among all health programs in 2015–2016 (− 7.1%). PH budgets did not keep up with inflation and, in constant dollars, have declined over the last decade. Furthermore, their evolution over the span of 14 years significantly differed from other health programs. On average, programs providing direct services experienced overall budget increases of 81%, whereas PH budgets had the lowest increase of all such programs at only 46%. PH suffers from serious erosion of its capacity. Unfortunately, there is a dire lack of comparable data for provincial, national, and international PH budgets, which further complicates the monitoring of PH erosion. We contend that systematic tracking of PH budgets remains profoundly inadequate across Canada. We recommend (1) regular, comprehensive, and publicly reported analyses of PH budgets; (2) in-depth comparisons of PH investments across Canadian jurisdictions; and (3) a strong PH systems and services research agenda for Canada.


title: Apical barriers to airway epithelial cell gene transfer with amphotropic retroviral vectors

text: Gene transfer to airway epithelia with amphotropic pseudotyped retroviral vectors is inefficient following apical vector application. To better understand this inefficiency, we localized the expression of Pit2, the amphotropic receptor, in polarized human airway epithelia. Pit2 was expressed on both the apical and basolateral surfaces of the cells, suggesting that factors other than receptor abundance may limit apical gene transfer efficiency. Binding studies performed with radiolabeled amphotropic MuLV suggested that the apically applied virus binds to Pit2. Hypothetical barriers to retroviral gene transfer include the apical glycocalyx and other secreted products of epithelia. In this study, we demonstrated that sialic acid, keratan sulfate and collagen type V are present on the apical surface of well-differentiated human airway epithelia. While enzyme treatment reduced the abundance of these components, the treatment also decreased the transepithelial resistance to ~35% of the controls, suggesting that the epithelial integrity was impaired. To attain an airway epithelial culture with a modified apical surface and intact epithelial integrity, we utilized 100 mM 2-deoxy-D-glucose, a glycosylation inhibitor, to prevent the glycocalyx from reforming following enzyme treatment. This approach allowed the resistance, but not the apical glycocalyx to recover. Despite this physical modification of the cell surface, the amphotropic retroviral vector failed to transduce airway epithelia following apical application. These results suggest that factors other than apical receptor abundance and the glycocalyx inhibit amphotropic retroviral gene transfer in human airway epithelia.


title: Impact of COVID-19 on transportation in Lagos, Nigeria

text: Abstract The growing number of studies on the impact of COVID-19 is often discussed in the context of developed countries, highlighting a gap in the understanding of how the pandemic is impacting developing countries. This theoretical commentary focuses on the present and long-term impact of COVID-19 on transportation in Lagos State, Nigeria. The paper recognises the effect on transportation in emerging economies, where lockdowns and restrictions on movement may be ineffective, a state with high population density, poor transportation infrastructure and a large informal economy. Adopting the ‘avoid-shift-improve’ framework, this paper presents practical implications for public and private sector policymakers, as they navigate this precarious time and chart a new path for individuals and Nigeria.


title: Prevalence, codetection and seasonal distribution of upper airway viruses and bacteria in children with acute respiratory illnesses with cough as a symptom

text: Abstract Most studies exploring the role of upper airway viruses and bacteria in paediatric acute respiratory infections (ARI) focus on specific clinical diagnoses and/or do not account for virus–bacteria interactions. We aimed to describe the frequency and predictors of virus and bacteria codetection in children with ARI and cough, irrespective of clinical diagnosis. Bilateral nasal swabs, demographic, clinical and risk factor data were collected at enrollment in children aged <15 years presenting to an emergency department with an ARI and where cough was a symptom. Swabs were tested by polymerase chain reaction for 17 respiratory viruses and seven respiratory bacteria. Logistic regression was used to investigate associations between child characteristics and codetection of the organisms of interest. Between December 2011 and August 2014, swabs were collected from 817 (93.3%) of 876 enrolled children, median age 27.7 months (interquartile range 13.9–60.3 months). Overall, 740 (90.6%) of 817 specimens were positive for any organism. Both viruses and bacteria were detected in 423 specimens (51.8%). Factors associated with codetection were age (adjusted odds ratio (aOR) for age <12 months = 4.9, 95% confidence interval (CI) 3.0, 7.9; age 12 to <24 months = 6.0, 95% CI 3.7, 9.8; age 24 to <60 months = 2.4, 95% CI 1.5, 3.9), male gender (aOR 1.46; 95% CI 1.1, 2.0), child care attendance (aOR 2.0; 95% CI 1.4, 2.8) and winter enrollment (aOR 2.0; 95% CI 1.3, 3.0). Haemophilus influenzae dominated the virus–bacteria pairs. Virus–H. influenzae interactions in ARI should be investigated further, especially as the contribution of nontypeable H. influenzae to acute and chronic respiratory diseases is being increasingly recognized.


title: SARS‐CoV‐2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells

text: The SARS‐CoV‐2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID‐19 pathogenesis, especially host factors facilitating virus infection and replication. SARS‐CoV‐2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS‐CoV‐2 infection. Our data provide a rich resource for future investigations of COVID‐19 infection and pathogenesis.


docid: gortqvwa

title: Congenital nasal masses: CT and MR imaging features in 16 cases Barkovich A.J.; Vandermarck P.; Edwards M.S.B.; Cogen P.H. Am. J. Neuroradiol. (1991) 12/1 (105–116)


title: Pediatric laryngoscopy and bronchoscopy during the COVID-19 pandemic: A four-center collaborative protocol to improve safety with perioperative management strategies and creation of a surgical tent with disposable drapes

text: Abstract Aerosolization procedures during the COVID-19 pandemic place all operating room personnel at risk for exposure. We offer detailed perioperative management strategies and present a specific protocol designed to improve safety during pediatric laryngoscopy and bronchoscopy. Several methods of using disposable drapes for various procedures are described, with the goal of constructing a tent around the patient to decrease widespread contamination of dispersed droplets and generated aerosol. The concepts presented herein are translatable to future situations where aerosol generating procedures increase risk for any pathogenic exposure. This protocol is a collaborative effort based on knowledge gleaned from clinical and simulation experience from Children’s Hospital Colorado, Children’s Hospital of Philadelphia, The Hospital for Sick Children in Toronto, and Boston Children’s Hospital.


title: EpiBasket: how e-commerce tools can improve epidemiological preparedness

text: BACKGROUND: Should an emerging infectious disease outbreak or an environmental disaster occur, the collection of epidemiological data must start as soon as possible after the event's onset. Questionnaires are usually built de novo for each event, resulting in substantially delayed epidemiological responses that are detrimental to the understanding and control of the event considered. Moreover, the public health and/or academic institution databases constructed with responses to different questionnaires are usually difficult to merge, impairing necessary collaborations. We aimed to show that e-commerce concepts and software tools can be readily adapted to enable rapid collection of data after an infectious disease outbreak or environmental disaster. Here, the ‘customers’ are the epidemiologists, who fill their shopping ‘baskets’ with standardised questions. METHODS: For each epidemiological field, a catalogue of questions is constituted by identifying the relevant variables based on a review of the published literature on similar circumstances. Each question is tagged with information on its source papers. Epidemiologists can then tailor their own questionnaires by choosing appropriate questions from this catalogue. The software immediately provides them with ready-to-use forms and online questionnaires. All databases constituted by the different EpiBasket users are interoperable, because the corresponding questionnaires are derived from the same corpus of questions. RESULTS: A proof-of-concept prototype was developed for Knowledge, Attitudes and Practice (KAP) surveys, which is one of the fields of the epidemiological investigation frequently explored during, or after, an outbreak or environmental disaster. The catalogue of questions was initiated from a review of the KAP studies conducted during or after the 2003 severe acute respiratory syndrome epidemic. CONCLUSION: Rapid collection of standardised data after an outbreak or environmental disaster can be facilitated by transposing the e-commerce paradigm to epidemiology, taking advantage of the powerful software tools already available.


title: Discovery of G-quadruplex-forming sequences in SARS-CoV-2

text: The outbreak caused by the novel coronavirus SARS-CoV-2 has been declared a global health emergency. G-quadruplex structures in genomes have long been considered essential for regulating a number of biological processes in a plethora of organisms. We have analyzed and identified 25 four contiguous GG runs (G(2)N(x)G(2)N(y)G(2)N(z)G(2)) in the SARS-CoV-2 RNA genome, suggesting putative G-quadruplex-forming sequences (PQSs). Detailed analysis of SARS-CoV-2 PQSs revealed their locations in the open reading frames of ORF1 ab, spike (S), ORF3a, membrane (M) and nucleocapsid (N) genes. Identical PQSs were also found in the other members of the Coronaviridae family. The top-ranked PQSs at positions 13385 and 24268 were confirmed to form RNA G-quadruplex structures in vitro by multiple spectroscopic assays. Furthermore, their direct interactions with viral helicase (nsp13) were determined by microscale thermophoresis. Molecular docking model suggests that nsp13 distorts the G-quadruplex structure by allowing the guanine bases to be flipped away from the guanine quartet planes. Targeting viral helicase and G-quadruplex structure represents an attractive approach for potentially inhibiting the SARS-CoV-2 virus.


docid: fambtykj

title: Racial and Ethnic Digital Divides in Posting COVID-19 Content on Social Media Among US Adults: Secondary Survey Analysis

text: BACKGROUND: Public health surveillance experts are leveraging user-generated content on social media to track the spread and effects of COVID-19. However, racial and ethnic digital divides, which are disparities among people who have internet access and post on social media, can bias inferences. This bias is particularly problematic in the context of the COVID-19 pandemic because due to structural inequalities, members of racial and ethnic minority groups are disproportionately vulnerable to contracting the virus and to the deleterious economic and social effects from mitigation efforts. Further, important demographic intersections with race and ethnicity, such as gender and age, are rarely investigated in work characterizing social media users; however, they reflect additional axes of inequality shaping differential exposure to COVID-19 and its effects. OBJECTIVE: The aim of this study was to characterize how the race and ethnicity of US adults are associated with their odds of posting COVID-19 content on social media and how gender and age modify these odds. METHODS: We performed a secondary analysis of a survey conducted by the Pew Research Center from March 19 to 24, 2020, using a national probability sample (N=10,510). Respondents were recruited from an online panel, where panelists without an internet-enabled device were given one to keep at no cost. The binary dependent variable was responses to an item asking whether respondents “used social media to share or post information about the coronavirus.” We used survey-weighted logistic regressions to estimate the odds of responding in the affirmative based on the race and ethnicity of respondents (white, black, Latino, other race/ethnicity), adjusted for covariates measuring sociodemographic background and COVID-19 experiences. We examined how gender (female, male) and age (18 to 30 years, 31 to 50 years, 51 to 64 years, and 65 years and older) intersected with race and ethnicity by estimating interactions. RESULTS: Respondents who identified as black (odds ratio [OR] 1.29, 95% CI 1.02-1.64; P=.03), Latino (OR 1.66, 95% CI 1.36-2.04; P<.001), or other races/ethnicities (OR 1.33, 95% CI 1.02-1.72; P=.03) had higher odds than respondents who identified as white of reporting that they posted COVID-19 content on social media. Women had higher odds of posting than men regardless of race and ethnicity (OR 1.58, 95% CI 1.39-1.80; P<.001). Among men, respondents who identified as black, Latino, or members of other races/ethnicities were significantly more likely to post than respondents who identified as white. Older adults (65 years or older) had significantly lower odds (OR 0.73, 95% CI 0.57-0.94; P=.01) of posting compared to younger adults (18-29 years), particularly among those identifying as other races/ethnicities. Latino respondents were the most likely to report posting across all age groups. CONCLUSIONS: In the United States, members of racial and ethnic minority groups are most likely to contribute to COVID-19 content on social media, particularly among groups traditionally less likely to use social media (older adults and men). The next step is to ensure that data collection procedures capture this diversity by encompassing a breadth of search criteria and social media platforms.


title: The study of parasite sharing for surveillance of zoonotic diseases

text: Determining the factors that influence the transmission of parasites among hosts is important for directing surveillance of animal parasites before they successfully emerge in humans, and increasing the efficacy of programs for the control and management of zoonotic diseases. Here we present a review of recent advances in the study of parasite sharing, wildlife ecology, and epidemiology that could be extended and incorporated into proactive surveillance frameworks for multi-host infectious diseases. These methods reflect emerging interdisciplinary techniques with significant promise for the identification of future zoonotic parasites and unknown reservoirs of current zoonoses, strategies for the reduction of parasite prevalence and transmission among hosts, and decreasing the burden of infectious diseases.


title: The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus

text: Chick embryo tracheal organ cultures showed increased resistance to infection by a coronavirus after exposure to ascorbate, while chick respiratory epithelium and allantois-on-shell preparations showed no increase in resistance to infection by an influenza virus or a paramyxovirus.


title: Genomics and Public Health Research: Can the State Allow Access to Genomic Databases?

text: Because many diseases are multifactorial disorders, the scientific progress in genomics and genetics should be taken into consideration in public health research. In this context, genomic databases will constitute an important source of information. Consequently, it is important to identify and characterize the State’s role and authority on matters related to public health, in order to verify whether it has access to such databases while engaging in public health genomic research. We first consider the evolution of the concept of public health, as well as its core functions, using a comparative approach (e.g. WHO, PAHO, CDC and the Canadian province of Quebec). Following an analysis of relevant Quebec legislation, the precautionary principle is examined as a possible avenue to justify State access to and use of genomic databases for research purposes. Finally, we consider the Influenza pandemic plans developed by WHO, Canada, and Quebec, as examples of key tools framing public health decision-making process. We observed that State powers in public health, are not, in Quebec, well adapted to the expansion of genomics research. We propose that the scope of the concept of research in public health should be clear and include the following characteristics: a commitment to the health and well-being of the population and to their determinants; the inclusion of both applied research and basic research; and, an appropriate model of governance (authorization, follow-up, consent, etc.). We also suggest that the strategic approach version of the precautionary principle could guide collective choices in these matters.


title: First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany over 140,000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital of Münster (UHM). METHODS: Single-step real-time RT-PCR from nasopharyngeal swaps was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and chart reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Threshold cycle (C(t)) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory confirmed COVID-19 infections. Two SARS-CoV-2 positive cases remained clinically asymptomatic. Eleven cases reported flu-like symptoms without positive results. C(t) values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (p =0.007). CONCLUSION: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at the UHM. Semi quantitative real-time RT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2 infected HCWs in order to prevent COVID-19 outbreaks in the hospital setting.


docid: jmaqkovs

title: Spray drying of siRNA-containing PLGA nanoparticles intended for inhalation

text: Abstract Local delivery of small interfering RNA (siRNA) to the lungs constitutes a promising new area in drug delivery. The present study evaluated parameters of importance for spray drying of siRNA-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) into nanocomposite microparticles intended for inhalation. The spray drying process was optimised using a statistical design of experiment and by evaluating powder characteristics upon systematic variation of the formulation parameters. Concentration, carbohydrate excipient (trehalose, lactose and mannitol) and the ratio of NP to excipient were varied to monitor the effects on moisture content, particle morphology, particle size and powder yield. The identified optimum conditions were applied for spray drying of siRNA-loaded nanocomposite microparticles, resulting in a product with a low water content (0.78% w/w) and an aerodynamic particle diameter considered suitable for inhalation. The use of mannitol in the formulation allowed a significantly lower moisture content than trehalose and lactose. The inclusion of 50% (w/w) or higher amounts of NPs resulted in a marked change in the surface morphology of the spray-dried particles. Importantly, the integrity and biological activity of the siRNA were preserved during the spray drying process. In conclusion, the present results show that spray drying is a suitable technique for producing nanocomposite microparticles comprising siRNA-containing PLGA NPs for potential use in inhalation therapy.


title: Epidemiology of COVID-19 in Mexico: From the 27th of February to the 30th of April 2020()

text: BACKGROUND: The first case of COVID-19 detected in Mexico was on the 27th of February 2020. On the 30th of April, 64 days after this first diagnosis, the number of patients had increased exponentially, reaching 19,224 confirmed cases and 1859 (9.67%) deaths. In response to this global outbreak, we summarize the current state of our understanding regarding COVID-19 in Mexico. METHODS: We obtained the data from the official website of the Ministry of Health in Mexico. The study period covered the 27th of February to the 30th of April 2020. The cases were confirmed using real-time reverse transcription-polymerase chain reaction assays, and we analyzed the epidemiological, demographic and clinical data. RESULTS: In Mexico, most cases of COVID-19 were located in Mexico City. The mean age of the patients was 46 years. Of the 12,656 confirmed cases, most infected individuals were between the ages of 30 and 59 years (65.85%), and there was a higher incidence rate for men (58.18%) than for women (41.82%). The patients who died had one or more comorbidities, mainly hypertension (45.53%), diabetes (39.39%) and obesity (30.4%). In the first 64 days of the epidemic, China had reported 80,304 cases, with a mortality rate of 3.66%. CONCLUSIONS: Our results indicate the early transmission of COVID-19 in Mexico. The descriptive epidemiology shows similarities between the cases of COVID-19 in Mexico and those in China. In the same period of the epidemic curve, we observed a reduction in the number of confirmed cases of COVID-19 in Mexico and a higher mortality rate compared with that of China.


title: Sequence analysis of the leader RNA of two porcine coronaviruses: Transmissible gastroenteritis virus and porcine respiratory coronavirus

text: The leader RNA sequence was determined for two pig coronaviruses, tranmissible gastroenteritis virus (TGEV), and porcine respiratory coronavirus (PRCV). Primer extension, of a synthetic oligonucleotide complementary to the 5′ end of the nucleoprotein gene of TGEV was used to produce a single-stranded DNA copy of the leader RNA from the nucleoprotein mRNA species from TGEV and PRCV, the sequences of which were determined by Maxam and Gilbert cleavage. Northern blot analysis, using a synthetic oligonucleotide complementary to the leader RNA, showed that the leader RNA sequence was present on all of the subgenomic mRNA species. The porcine coronavirus leader RNA sequences were compared to each other and to published coronavirus leader RNA sequences. Sequence homologies and secondary structure similarities were identified that may play a role in the biological function of these RNA sequences.


title: Emerging and Neglected Infectious Diseases: Insights, Advances, and Challenges

text: Infectious diseases are a significant burden on public health and economic stability of societies all over the world. They have for centuries been among the leading causes of death and disability and presented growing challenges to health security and human progress. The threat posed by infectious diseases is further deepened by the continued emergence of new, unrecognized, and old infectious disease epidemics of global impact. Over the past three and half decades at least 30 new infectious agents affecting humans have emerged, most of which are zoonotic and their origins have been shown to correlate significantly with socioeconomic, environmental, and ecological factors. As these factors continue to increase, putting people in increased contact with the disease causing pathogens, there is concern that infectious diseases may continue to present a formidable challenge. Constant awareness and pursuance of effective strategies for controlling infectious diseases and disease emergence thus remain crucial. This review presents current updates on emerging and neglected infectious diseases and highlights the scope, dynamics, and advances in infectious disease management with particular focus on WHO top priority emerging infectious diseases (EIDs) and neglected tropical infectious diseases.


Sars Cov Replication and Pathogenesis in Human Airway Airway Epithelial Cultures


title: The in vitro effect of pH on osteoclasts and bone resorption in the cat: Implications for the pathogenesis of FORL

text: Dental disease due to osteoclast over‐activity reaches epidemic proportions in older domestic cats and has also been reported in wild cats. Feline osteoclastic resorptive lesions (FORL) involve extensive resorption of the tooth leaving it liable to root fracture and subsequent tooth loss. The aetio‐pathogenesis of FORL is not known. Recent work has shown that systemic acidosis causes increased osteoclast activation and that loci of infection or inflammation in cat mouth are likely to be acidotic. To investigate this, we generated osteoclasts from cat blood and found that they formed in large numbers (∼400) in cultures on bovine cortical bone slices. Acidosis caused an increase in the size of cells—in cultures maintained up to 14 days at basal pH 7.25, mean osteoclast area was 0.01 ± 0.003 mm(2), whereas an 8.6‐fold increase was observed in cells cultured between 11 and 14 days at pH 7.15 (0.086 ± 0.004 mm(2)). Acidosis caused a modest increase in the number of osteoclasts. Exposure to pH 6.92 exhibited a 5‐fold increase in the area of bone slices covered by resorption lacunae (∼70% bone slice resorbed). In line with this finding, significant increases were observed in the expression of cathepsin K and proton pump enzymes (both approximately 3‐fold) that are key enzymes reflective of resorptive activity in osteoclasts. These results demonstrate that acidosis is a major regulator of osteoclast formation and functional activation in the cat, and suggest that local pH changes may play a significant role in the pathogenesis of FORL. J. Cell. Physiol. 213: 144–150, 2007. © 2007 Wiley‐Liss, Inc.


title: COVID‐19: a brief history and treatments in development

text: Coronavirus disease (COVID‐19) is now dominating the lives of everyone, and its history is constantly being rewritten. This article gives a brief account of the story so far: where SARS‐CoV‐2 might have originated, how it compares with other viruses that cause major respiratory disease, and some of the treatments and vaccines currently being investigated to combat it.


A Message from the Editor-in-Chief


title: Evaluation of Health Policy Governance in the Introduction of the New DRG-Based Hospital Payment System from Interviews with Policy Elites in South Korea

text: The study provides evidence of the governance and its context according to the introduction of the New Diagnosis-Related Groups (DRGs)-based payment system in Korea. In-depth interviews with 14 core policy elites from four health areas were conducted. As governance is a multidimensional concept, interviewees were asked to evaluate different dimensions based on the World Bank’s five elements (Coherent decision-making structures, Consistency and Stability, Stakeholder participation, Supervision and Regulation, and Transparency and Information). Overall, the new payment system was perceived as poorly governed. Since its introduction, it has not offered a new governance perspective because it used a conventional top-down approach, while political windows for cooperation were not wide open. Of the five governance dimensions, the scores were lowest in Stakeholder participation. There was a large perception gap between physicians and government officers here. Participants from academia perceived Consistency and Stability as ineffectively governed. In the meantime, the government has mainly created health policy in Korea. As a result, stakeholder participation, especially the participation of medical personnel, has been insufficient in the process of health policy formulation. The study suggests that the decision-making process in health policy needs to be more participatory and reliable, with governance regarded as a high priority.


Neumonía por SARS-CoV-2 (COVID-19): Hallazgo casual en estudio PET/TC con 18F-FDG para el diagnóstico de vasculitis


The “mind” behind the “mask”: Assessing mental states and creating therapeutic alliance amidst COVID-19


title: Middle East Respiratory Syndrome Coronavirus (MERS-CoV): State of the Science

text: Coronaviruses belong to a large family of viruses that can cause disease outbreaks ranging from the common cold to acute respiratory syndrome Since 2003, three zoonotic members of this family evolved to cross species barriers infecting humans and resulting in relatively high case fatality rates (CFR) Compared to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV, CFR = 10%) and pandemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, CFR = 6%), the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has scored the highest CFR (approximately 35%) In this review, we systematically summarize the current state of scientific knowledge about MERS-CoV, including virology and origin, epidemiology, zoonotic mode of transmission, and potential therapeutic or prophylactic intervention modalities


title: Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase

text: The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. Here we show that Favipiravir exerts an antiviral effect as a nucleotide analogue through a combination of chain termination, slowed RNA synthesis and lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.


title: Reaching Up, Down, In, and Around: Couple and Family Coping During the Corona Virus Pandemic

text: The worldwide corona virus (COVID‐19) has had profound effects on all aspects of life: physical health, the ability to travel locally or to more distant destinations, material and financial resources, and psychosocial wellbeing. Couples, families, and communities and individual persons in those relationships have struggled to cope with emerging depression, anxiety, and trauma, and the rise of relational conflict. In this article, we suggest that the existential nature of the pandemic’s challenges require more than just the usual psychosocial interventions. We propose a taxonomy of responses to foster coping and resilience – “Reaching Up, Down, In, and Around”. “Reaching Up” includes accessing spiritual, religious, and ethical values. “Reaching Down” includes ideas and practices that foster a revised relationship with the Earth and its resources, and that engage families to participate in activities that aid the Earth’s recovery from decades of human‐caused damage. “Reaching In” represents a turn towards experiences available in the mind and in shared minds in relationships that provide pleasure, excitement, joy, and peace, given that external sources of these emotions are of limited availability due to quarantine. “Reaching Around” involves reframing the mandate for “social distancing” as fostering social connection and support while maintaining physical distancing. The challenges for family therapists, whose practices are confined largely to online therapy, and who are struggling with the same fears and constraints as those persons they are attempting to help, are also discussed.


title: Antiphospholipid antibodies are not elevated in patients with severe COVID-19 pneumonia and venous thromboembolism

text: • COVID-19 pneumonia could be associated with an increased risk of venous thrombosis. • Antiphospholipid antibodies might be involved in thrombosis in COVID-19 patients. • Prevalence of antiphospholipid antibodies in COVID-19 and venous thrombosis was low.


title: Recombination in RNA

text: Abstract The aphthovirus genome consists of a single molecule of single-stranded RNA that encodes all the virus-induced proteins. We isolated recombinant aphthoviruses from cells simultaneously infected with temperature-sensitive mutants of two different subtype strains. Analysis of the proteins induced by 16 independently generated recombinants revealed two types of protein pattern, which were consistent with single genetic crossovers on the 5′ side and 3′ side, respectively, of the central P34-coding region. Recombinants invariably inherited all four coat proteins from the same parent, and novel recombinant proteins were not observed. RNAase T1 fingerprints of virus RNA, prepared from representatives of each recombinant type, confirmed the approximate crossover sites that had been deduced from the inheritance of proteins. These fingerprints provide molecular evidence of recombination at the level of RNA and demonstrate the potential of RNA recombination for producing genetic diversity among picornaviruses.


title: Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells

text: Abstract Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors.


title: Class II Fusion Proteins

text: Enveloped viruses rely on fusion proteins in their envelope to fuse the viral membrane to the host-cell membrane. This key step in viral entry delivers the viral genome into the cytoplasm for replication. Although class II fusion proteins are genetically and structurally unrelated to class I fusion proteins, they use the same physical principles and topology as other fusion proteins to drive membrane fusion. Exposure of a fusion loop first allows it to insert into the host-cell membrane. Conserved hydrophobic residues in the fusion loop act as an anchor, which penetrates only partway into the outer bilayer leaflet of the host-cell membrane. Subsequent folding back of the fusion protein on itself directs the C-terminal viral transmembrane anchor towards the fusion loop. This fold-back forces the host-cell membrane (held by the fusion loop) and the viral membrane (held by the C-terminal transmembrane anchor) against each other, resulting in membrane fusion. In class II fusion proteins, the fold-back is triggered by the reduced pH of an endosome, and is accompanied by the assembly of fusion protein monomers into trimers. The fold-back occurs by domain rearrangement rather than by an extensive refolding of secondary structure, but this domain rearrangement and the assembly of monomers into trimers together bury a large surface area. The energy that is thus released exerts a bending force on the apposed viral and cellular membranes, causing them to bend towards each other and, eventually, to fuse.


title: Complete Genome Sequences of the SARS-CoV: the BJ Group (Isolates BJ01-BJ04)

text: Beijing has been one of the epicenters attacked most severely by the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) since the first patient was diagnosed in one of the city’s hospitals. We now report complete genome sequences of the BJ Group, including four isolates (Isolates BJ01, BJ02, BJ03, and BJ04) of the SARS-CoV. It is remarkable that all members of the BJ Group share a common haplotype, consisting of seven loci that differentiate the group from other isolates published to date. Among 42 substitutions uniquely identified from the BJ group, 32 are non-synonymous changes at the amino acid level. Rooted phylogenetic trees, proposed on the basis of haplotypes and other sequence variations of SARS-CoV isolates from Canada, USA, Singapore, and China, gave rise to different paradigms but positioned the BJ Group, together with the newly discovered GD01 (GD-Ins29) in the same clade, followed by the H-U Group (from Hong Kong to USA) and the H-T Group (from Hong Kong to Toronto), leaving the SP Group (Singapore) more distant. This result appears to suggest a possible transmission path from Guangdong to Beijing/Hong Kong, then to other countries and regions.


docid: szhmhsdr

title: The Efficacy of Social Distance and Ventilation Effectiveness in Preventing COVID-19 Transmission

text: Social distancing and ventilation were emphasized broadly to control the ongoing pandemic COVID-19 in confined spaces. Rationales behind these two strategies, however, were debated, especially regarding quantitative recommendations. The answers to “what is the safe distance” and “what is sufficient ventilation” are crucial to the upcoming reopening of businesses and schools, but rely on many medical, biological, and engineering factors. This study introduced two new indices into the popular while perfect-mixing-based Wells-Riley model for predicting airborne virus related infection probability – the underlying reasons for keeping adequate social distance and space ventilation. The distance index P(d) can be obtained by theoretical analysis on droplet distribution and transmission from human respiration activities, and the ventilation index E(z) represents the system-dependent air distribution efficiency in a space. The study indicated that 1.6-3.0 m (5.2-9.8 ft) is the safe social distance when considering aerosol transmission of exhaled large droplets from talking, while the distance can be up to 8.2 m (26 ft) if taking into account of all droplets under calm air environment. Because of unknown dose response to COVID-19, the model used one actual pandemic case to calibrate the infectious dose (quantum of infection), which was then verified by a number of other existing cases with short exposure time (hours). Projections using the validated model for a variety of scenarios including transportation vehicles and building spaces illustrated that (1) increasing social distance (e.g., halving occupancy density) can significantly reduce the infection rate (20-40%) during the first 30 minutes even under current ventilation practices; (2) minimum ventilation or fresh air requirement should vary with distancing condition, exposure time, and effectiveness of air distribution systems.


title: In vivo imaging in NHP models of malaria: Challenges, progress and outlooks

text: Abstract Animal models of malaria, mainly mice, have made a large contribution to our knowledge of host–pathogen interactions and immune responses, and to drug and vaccine design. Non-human primate (NHP) models for malaria are admittedly under-used, although they are probably closer models than mice for human malaria; in particular, NHP models allow the use of human pathogens (Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium knowlesi). NHPs, whether natural hosts or experimentally challenged with a simian Plasmodium, can also serve as robust pre-clinical models. Some simian parasites are closely related to a human counterpart, with which they may share a common ancestor, and display similar major features with the human infection and pathology. NHP models allow longitudinal studies, from the early events following sporozoite inoculation to the later events, including analysis of organs and tissues, particularly liver, spleen, brain and bone marrow. NHP models have one other significant advantage over mouse models: NHPs are our closest relatives and thus their biology is very similar to ours. Recently developed in vivo imaging tools have provided insight into malaria parasite infection and disease in mouse models. One advantage of these tools is that they limit the need for invasive procedures, such as tissue biopsies. Many such technologies are now available for NHP studies and provide new opportunities for elucidating host/parasite interactions. The aim of this review is to bring the malaria community up to date on what is currently possible and what soon will be, in terms of in vivo imaging in NHP models of malaria, to consider the pros and the cons of the various techniques, and to identify challenges.


title: The combined therapy of a traditional Chinese medicine formula and Western medicine for a critically ill case infected with COVID-19

text: OBJECTIVE: Presentation of a case illustrating the benefits of traditional Chinese medicine (TCM) for treatment of Coronavirus disease 2019 (COVID-19) in critically ill patients. CLINICAL FEATURES AND OUTCOME: A 58-year-old woman presented with cough, fever, dizziness, chest tightness, polypnea and poor appetite. She was admitted to Guizhou Provincial People’s hospital, and diagnosed with critically ill type of COVID-19 in February, 2020. According to the patient's symptoms and signs, the TCM syndrome differentiation was qi deficiency, dampness-stasis and toxin accumulation. Then she received the combined therapy of a modified Chinese herbal formula and Western medicine. During a twelve-day period of treatment, her respiratory distress and appetite quickly improved. Abnormal laboratory indicators were resumed in time and lung lesions in CT scan largely absorbed. no side effects associated with this Chinese herbal formula were found. Before discharge, two consecutive nasopharyngeal swabs were shown to be negative for severe acute respiratory coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Our case report suggests that collaborative treatments with traditional Chinese medicine prove beneficial in the management of COVID-19 in critically ill patients. In order to give optimal care for this COVID-19 crisis for the whole world, Chinese medicine practitioners and Western medical doctors should work together in frontline.


title: Genetic Characterization of Middle East Respiratory Syndrome Coronavirus, South Korea, 2018

text: We evaluated genetic variation in Middle East respiratory syndrome coronavirus (MERS-CoV) imported to South Korea in 2018 using specimens from a patient and isolates from infected Caco-2 cells. The MERS-CoV strain in this study was genetically similar to a strain isolated in Riyadh, Saudi Arabia, in 2017.


title: Colonization of Severe Acute Respiratory Syndrome-Associated Coronavirus Among Health-Care Workers Screened by Nasopharyngeal Swab

text: Study objectives To report the efficacy and findings of a large-scale preventive screening program for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) using amplification of the virus from a nasopharyngeal swab (NPS) obtained from the health-care workers (HCWs). Design A prospective observational study. Setting A medical center in Taiwan. Participants Two hundred thirty HCWs. Intervention NPS examination for the presence of SARS-CoV by two nested reverse transcription-polymerase chain reaction (RT-PCR) assays. Measurements and results During the outbreak of severe acute respiratory syndrome (SARS), NPS polymerase chain reaction screening of HCWs for SARS-CoV was performed. SARS-CoV was examined by two nested RT-PCRs and a quantitative RT-PCR. Serum-specific antibodies were assessed by enzyme immunoassay and indirect immunofluorescence. We monitored 230 HCWs, including 217 first-line HCWs and 13 non–first-line HCWs. One hundred ninety first-line HCWs and 13 non–first-line HCWs had negative results in both nested RT-PCR assays. Two first-line HCWs who were positive on both nested RT-PCR assays had SARS. They had 16,900 ± 7,920 copies (mean ± SD) of RNA per milliliter in the NPS and had detectable anti-SARS antibodies. The remaining 25 first-line HCWs were negative for the first nested RT-PCR but positive for the second nested RT-PCR. Their corresponding titers were 338 ± 227 copies of RNA per milliliter; antibodies developed in none of these 25 HCWs. The expression and function of angiotensin-converting enzyme-2 were not different among these HCWs. This study shows that colonization of SARS-CoV occurred in 25 of 217 well-protected first-line HCWs on a SARS-associated service, but they remained seronegative. Conclusion With the second RT-PCR assay more sensitive than the first RT-PCR assay, we are able to show that approximately 11.5% of well-protected HCWs exposed to SARS patients or specimens may have colonization without seroconversion. Only those with significant clinical symptoms or disease would have active immunity. Thus, regular NPS screening for nested RT-PCR assays in conjunction with a daily recording of body temperature in all first-line HCWs may provide an effective way of early detection.


title: A review of the animal disease outbreaks and biosecure animal mortality composting systems

text: Abstract Despite the development of new vaccines and the application of rigorous biosecurity measures, animal diseases pose a continuing threat to animal health, food safety, national economy, and the environment. Intense livestock production, increased travel, and changing climate have increased the risk of catastrophic animal losses due to infectious diseases. In the event of an outbreak, it is essential to properly manage the infected animals to prevent the spread of diseases. The most common disposal methods used during a disease outbreak include burial, landfilling, incineration and composting. Biosecurity, transportation logistics, public perception, and environmental concerns limit the use of some of these methods. During a disease outbreak, the large number of mortalities often exceeds the capacity of local rendering plants and landfills. Transporting mortalities to disposal and incineration facilities outside the production operation introduces biosecurity risks. Burying mortalities is limited by the size and availability of suitable sites and it has the risk of pathogen survival and contamination of groundwater and soil. Portable incinerators are expensive and have the potential to aerosolize infectious particles. Composting, on the other hand, has been recognized as a biosecure disposal method. Research showed that it eliminates bacterial pathogens such as Escherichia coli O157: H7, Salmonella spp., as well as viruses including highly pathogenic avian influenza, foot-and-mouth disease, Newcastle disease, and porcine epidemic diarrhea. This paper summarizes the lessons learned during the major animal disease outbreaks including the 2010 foot-and-mouth disease, 2016 highly pathogenic avian influenza, and recent African swine fever outbreaks. The purpose of this review is to critically discuss the biosecurity of composting as a mortality disposal method during the outbreaks of infectious animal diseases.


title: A Precision Medicine Approach to SARS-CoV-2 Pandemic Management

text: PURPOSE OF REVIEW: Precision medicine (PM) represents a new paradigm in disease diagnosis, prevention, and treatment. To apply PM premises in an emerging coronavirus pandemic acquires potentially greater relevance in order to allow the selection of specific preventive measures as well as biomarkers that will be useful in disease management. RECENT FINDINGS: The identification of the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the responsible for the coronavirus disease 2019 (COVID-19) pandemic had led to a plethora of strategies to contain viral dissemination, affecting life styles and personal behaviors. Viral genomic sequencing has shown that SARS-CoV-2 spike protein utilizes angiotensin-converting enzyme 2 (ACE2) found on ciliated epithelial cells of the human lungs as its specific receptor. Neutralizing antibodies to the receptor-binding domain of the spike protein were detected in patients recovered from COVID-19; however, both T cells and NK cells were reduced in severe cases. Excessive and uncontrolled releases of pro-inflammatory cytokines such as IL-1B, IL-1RA, IL-7, IL-8, IL-9, IL-10, fibroblast growth factor (FGF), granulocyte–macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNFα) were increased in severe patients. These cytokines might be useful biomarkers of disease worsening and potential targets for new biological therapies currently under investigation. SUMMARY: Present knowledge and recent developments in PM approach to COVID-19 disease prevention, evaluation, and management are pointed out. Better understanding of pathogenic pathways together with an accurate phenotype classification of patients presented with SARS-CoV-2 infection and symptoms might contribute to a more accurate definition of biomarkers and other diagnostic tools, which may lead to more precise mitigation strategies, personalized pharmacologic options, as well as new biological therapy developments.


title: Defining Lyfe in the Universe: From Three Privileged Functions to Four Pillars

text: Motivated by the need to paint a more general picture of what life is—and could be—with respect to the rest of the phenomena of the universe, we propose a new vocabulary for astrobiological research. Lyfe is defined as any system that fulfills all four processes of the living state, namely: dissipation, autocatalysis, homeostasis, and learning. Life is defined as the instance of lyfe that we are familiar with on Earth, one that uses a specific organometallic molecular toolbox to record information about its environment and achieve dynamical order by dissipating certain planetary disequilibria. This new classification system allows the astrobiological community to more clearly define the questions that propel their research—e.g., whether they are developing a historical narrative to explain the origin of life (on Earth), or a universal narrative for the emergence of lyfe, or whether they are seeking signs of life specifically, or lyfe at large across the universe. While the concept of “life as we don’t know it” is not new, the four pillars of lyfe offer a novel perspective on the living state that is indifferent to the particular components that might produce it.


An Appropriate Lower Respiratory Tract Specimen Is Essential for Diagnosis of Middle East Respiratory Syndrome (MERS)


docid: jgyvigkl

title: Correction to Lancet Infect Dis 2020; 20: 533–34


title: Characterisation of Structural Proteins from Chronic Bee Paralysis Virus (CBPV) Using Mass Spectrometry

text: Chronic bee paralysis virus (CBPV) is the etiological agent of chronic paralysis, an infectious and contagious disease in adult honeybees. CBPV is a positive single-stranded RNA virus which contains two major viral RNA fragments. RNA 1 (3674 nt) and RNA 2 (2305 nt) encode three and four putative open reading frames (ORFs), respectively. RNA 1 is thought to encode the viral RNA-dependent RNA polymerase (RdRp) since the amino acid sequence derived from ORF 3 shares similarities with the RdRP of families Nodaviridae and Tombusviridae. The genomic organization of CBPV and in silico analyses have suggested that RNA 1 encodes non-structural proteins, while RNA 2 encodes structural proteins, which are probably encoded by ORFs 2 and 3. In this study, purified CBPV particles were used to characterize virion proteins by mass spectrometry. Several polypeptides corresponding to proteins encoded by ORF 2 and 3 on RNA 2 were detected. Their role in the formation of the viral capsid is discussed.


title: New glimpses of caveolin-1 functions in embryonic development and human diseases

text: Caveolin-1 (Cav-1) isoforms, including Cav-1α and Cav-1β, were identified as integral membrane proteins and the major components of caveolae. Cav-1 proteins are highly conserved during evolution from {itCaenorhabditis elegans} to human and are capable of interacting with many signaling molecules through their caveolin scaffolding domains to regulate the activities of multiple signaling pathways. Thus, Cav-1 plays crucial roles in the regulation of cellular proliferation, differentiation and apoptosis in a cell-specific and contextual manner. In addition, Cav-1 is essential for embryonic development of vertebrates owing to its regulation of BMP, Wnt, TGF-β and other key signaling molecules. Moreover, Cav-1 is mainly expressed in terminally differentiated cells and its abnormal expression is often associated with human diseases, such as tumor progression, cardiovascular diseases, fibrosis, lung regeneration, and diseases related to virus. In this review, we will further discuss the potential of Cav-1 as a target for disease therapy and multiple drug resistance.


title: High serum levels of neopterin in patients with Crimean–Congo hemorrhagic fever and its relation with mortality

text: Summary Objective Neopterin is generated and released in increased amounts by macrophages upon activation by interferon-gamma during cellular immune response. In this study, we aimed to investigate serum neopterin levels in patients with Crimean–Congo hemorrhagic fever (CCHF) and its clinical significance as a predictor factor of mortality. Methods Neopterin concentrations on the first day of hospitalization were measured in serum samples from 51 CCHF patients. Serum neopterin levels and other clinical–laboratory parameters for fatal and nonfatal CCHF patients were compared. Results Serum neopterin levels (73.22±54.30nmol/L) were highly elevated in all CCHF patients (p <0.0001) with higher levels in fatal group (153.66±81.34nmol/L, p =0.0001) compared to nonfatal disease (55.99±24.09nmol/L). In univariate analysis, the level of neopterin on the first day of hospitalization, bleeding, platelet count, aspartate transferase and lactate dehydrogenase were associated with mortality. In multivariate analysis, only the serum level of neopterin was associated with mortality. As a mortality risk factor, area under the curve was 0.939 (p =0.0001, 95% confidence interval: 0.85–1.00). Conclusions In this first study of serum neopterin levels for CCHF, elevated serum neopterin level showing strong activation of monocytes/macrophages was a risk factor for CCHF.


title: Evaluation of Endotoxaemia in the Prognosis and Treatment of Scouring Merino Lambs

text: This study looked at measurement of endotoxaemia as a tool in determining prognosis and probable response to treatment in scouring lambs. One hundred eighty‐three lambs in the first 15–20 days of life, from eight Merino sheep farms located in the region of La Serena, south‐west Spain, were used in this experiment. Scouring and normal/control lambs were selected following a clinical examination, the scouring group was further divided into subgroups, specifically those that did or did not survive 72 h following treatment. At the time of the clinical examination, faecal and blood samples were taken. Faecal culture and commercial faecal antigen tests for detection of enteropathogens in faeces and serum endotoxin measurement using chromogenic lymulus amoebocyte lysate (LAL) were carried out. Scouring lambs received 0.07 mg/kg liveweight halofuginone once a day for 3 days, a single oral dose of 0.20 mg/kg liveweight of spectinomycin and oral rehydration fluid. The pathogens isolated were Cryptosporidium spp. and Escherichia coli. The case fatality rate was 51% in the scouring lambs. Postmortem findings were consistent with enterotoxigenic E. coli infection. The concentration of endotoxin was 0.18 ± 0.12 ng/ml in the control group, 0.35 ± 0.17 ng/ml in the surviving lambs and 0.46 ± 0.14 ng/ml in the non‐surviving lambs. Significant differences between groups were found. Case fatality rate of the scouring lambs with endotoxaemia below 0.30 ng/ml was 0%, while it was 100% above 0.50 ng/ml. These results may be utilized as a prognostic indicator in lambs affected by E. coli and Cryptosporidium that will help aid in decision‐making as to whether to treat a lamb or not based on its chances of survival.


title: Cluster Detection Mechanisms for Syndromic Surveillance Systems: Systematic Review and Framework Development

text: BACKGROUND: The time lag in detecting disease outbreaks remains a threat to global health security. The advancement of technology has made health-related data and other indicator activities easily accessible for syndromic surveillance of various datasets. At the heart of disease surveillance lies the clustering algorithm, which groups data with similar characteristics (spatial, temporal, or both) to uncover significant disease outbreak. Despite these developments, there is a lack of updated reviews of trends and modelling options in cluster detection algorithms. OBJECTIVE: Our purpose was to systematically review practically implemented disease surveillance clustering algorithms relating to temporal, spatial, and spatiotemporal clustering mechanisms for their usage and performance efficacies, and to develop an efficient cluster detection mechanism framework. METHODS: We conducted a systematic review exploring Google Scholar, ScienceDirect, PubMed, IEEE Xplore, ACM Digital Library, and Scopus. Between January and March 2018, we conducted the literature search for articles published to date in English in peer-reviewed journals. The main eligibility criteria were studies that (1) examined a practically implemented syndromic surveillance system with cluster detection mechanisms, including over-the-counter medication, school and work absenteeism, and disease surveillance relating to the presymptomatic stage; and (2) focused on surveillance of infectious diseases. We identified relevant articles using the title, keywords, and abstracts as a preliminary filter with the inclusion criteria, and then conducted a full-text review of the relevant articles. We then developed a framework for cluster detection mechanisms for various syndromic surveillance systems based on the review. RESULTS: The search identified a total of 5936 articles. Removal of duplicates resulted in 5839 articles. After an initial review of the titles, we excluded 4165 articles, with 1674 remaining. Reading of abstracts and keywords eliminated 1549 further records. An in-depth assessment of the remaining 125 articles resulted in a total of 27 articles for inclusion in the review. The result indicated that various clustering and aberration detection algorithms have been empirically implemented or assessed with real data and tested. Based on the findings of the review, we subsequently developed a framework to include data processing, clustering and aberration detection, visualization, and alerts and alarms. CONCLUSIONS: The review identified various algorithms that have been practically implemented and tested. These results might foster the development of effective and efficient cluster detection mechanisms in empirical syndromic surveillance systems relating to a broad spectrum of space, time, or space-time.


title: The COVID-19 epidemic, its mortality, and the role of non-pharmaceutical interventions

text: COVID-19 has developed into a pandemic, hitting hard on our communities. As the pandemic continues to bring health and economic hardship, keeping mortality as low as possible will be the highest priority for individuals; hence governments must put in place measures to ameliorate the inevitable economic downturn. The course of an epidemic may be defined by a series of key factors. In the early stages of a new infectious disease outbreak, it is crucial to understand the transmission dynamics of the infection. The basic reproduction number (R(0)), which defines the mean number of secondary cases generated by one primary case when the population is largely susceptible to infection (‘totally naïve’), determines the overall number of people who are likely to be infected, or, more precisely, the area under the epidemic curve. Estimation of changes in transmission over time can provide insights into the epidemiological situation and identify whether outbreak control measures are having a measurable effect. For R(0) > 1, the number infected tends to increase, and for R(0) < 1, transmission dies out. Non-pharmaceutical strategies to handle the epidemic are sketched and based on current knowledge, the current situation is sketched and scenarios for the near future discussed.


title: Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression

text: Pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses an unprecedented challenge to healthcare systems due to the lack of a vaccine and specific treatment options. Accordingly, there is an urgent need to understand precisely the pathogenic mechanisms underlying this multifaceted disease. There is increasing evidence that the immune system reacts insufficiently to SARS-CoV-2 and thus contributes to organ damage and to lethality. In this review, we suggest that the overwhelming production of reactive oxygen species (ROS) resulting in oxidative stress is a major cause of local or systemic tissue damage that leads to severe COVID-19. It increases the formation of neutrophil extracellular traps (NETs) and suppresses the adaptive arm of the immune system, i.e. T cells that are necessary to kill virus-infected cells. This creates a vicious cycle that prevents a specific immune response against SARS-CoV-2. The key role of oxidative stress in the pathogenesis of severe COVID-19 implies that therapeutic counterbalancing of ROS by antioxidants such as vitamin C or NAC and/or by antagonizing ROS production by cells of the MPS and neutrophil granulocytes and/or by blocking of TNF-α can prevent COVID-19 from becoming severe. Controlled clinical trials and preclinical models of COVID-19 are needed to evaluate this hypothesis.


title: Porcine epidemic diarrhea virus infection: Etiology, epidemiology, pathogenesis and immunoprophylaxis

text: Abstract Porcine epidemic diarrhea virus (PEDV), a member of the genera Alphacoronavirus in the family Coronaviridae, causes acute diarrhea/vomiting, dehydration and high mortality in seronegative neonatal piglets. For the last three decades, PEDV infection has resulted in significant economic losses in the European and Asian pig industries, but in 2013–2014 the disease was also reported in the US, Canada and Mexico. The PED epidemic in the US, from April 2013 to the present, has led to the loss of more than 10% of the US pig population. The disappearance and re-emergence of epidemic PED indicates that the virus is able to escape from current vaccination protocols, biosecurity and control systems. Endemic PED is a significant problem, which is exacerbated by the emergence (or potential importation) of multiple PEDV variants. Epidemic PEDV strains spread rapidly and cause a high number of pig deaths. These strains are highly enteropathogenic and acutely infect villous epithelial cells of the entire small and large intestines although the jejunum and ileum are the primary sites. PEDV infections cause acute, severe atrophic enteritis accompanied by viremia that leads to profound diarrhea and vomiting, followed by extensive dehydration, which is the major cause of death in nursing piglets. A comprehensive understanding of the pathogenic characteristics of epidemic or endemic PEDV strains is needed to prevent and control the disease in affected regions and to develop an effective vaccine. This review focuses on the etiology, epidemiology, disease mechanisms and pathogenesis as well as immunoprophylaxis against PEDV infection.


title: Eight-Month Prospective Study of 14 Patients With Hospital-Acquired Severe Acute Respiratory Syndrome

text: OBJECTIVE To define the clinical characteristics and clinical course of hospital-acquired severe acute respiratory syndrome (SARS). PATIENTS AND METHODS This 8-month prospective study of 14 patients with hospital-acquired SARS in Taipei, Taiwan, was conducted from April through December 2003. RESULTS The most common presenting symptoms in our 14 patients with hospital-acquired SARS were fever, dyspnea, dizziness, malaise, diarrhea, dry cough, muscle pain, and chills. Lymphopenia and elevated serum levels of lactate dehydrogenase (LDH) and C-reactive protein (CRP) were the most common initial laboratory findings. Initial chest radiographs revealed various pattern abnormalities and normal results. Five of the 14 patients required mechanical ventilation. The need for mechanical ventilation was associated with bilateral lung involvement on the initial chest radiograph and higher peak levels of LDH and CRP. Clinical severity of disease varied from mild to severe. At 8 months after disease onset, patients with mild or moderate SARS had normal findings or only focal fibrosis on chest high-resolution computed tomography. However, bilateral fibrotic changes remained in the 4 patients who had recovered from severe SARS, 1 of whom had mild restrictive ventilatory impairment. One patient with severe SARS died; she was elderly and had other comorbidities. Five additional patients had reduced diffusing capacity. CONCLUSION The clinical picture of our patients presenting with hospital-acquired SARS revealed atypical pneumonia associated with lymphopenia, elevated serum levels of LDH, rapid clinical deterioration, and lack of response to empirical antibiotic therapy. Substantially elevated levels of LDH and CRP correlated with severe illness requiring mechanical ventilatory support. In those receiving mechanical ventilation, pulmonary function was only mildly reduced at 6 to 8 months after acute illness, consistent with the natural history of acute respiratory distress syndrome due to other causes.


SARS Revisited: The Challenge of Controlling Emerging Infectious Diseases at the Local, Regional, Federal, and Global Levels


title: New 3D graphical representation of DNA sequence based on dual nucleotides

text: We introduce a 3D graphical representation of DNA sequences based on the pairs of dual nucleotides (DNs). Based on this representation, we consider some mathematical invariants and construct two 16-component vectors associated with these invariants. The vectors are used to characterize and compare the complete coding sequence part of beta globin gene of nine different species. The examination of similarities/dissimilarities illustrates the utility of the approach.


docid: vxrwrzlj

title: Declining Emergency Department Visits and Costs During the Severe Acute Respiratory Syndrome (SARS) Outbreak

text: Background The immediate and long-term impact of severe acute respiratory syndrome (SARS) outbreak on emergency department (ED) visits and hospital expenditures for these visits has not been thoroughly investigated. The objectives of this retrospective observational study investigated the impact of SARS outbreak on ED visits and the cost of these visits in a designated SARS medical center. Methods Data related to the total number of ED visits and their costs were collected for the SARS epidemic period in 2003 and the same period in the preceding year in 2002. Data collected included total number of ED visits, services provided, triage categories, and total expenditures for all patients. Data for before and during the outbreak were retrieved and compared. Results At the peak of the SARS epidemic, the reduction in daily ED visits reached 51.6% of pre-epidemic numbers (p < 0.01). In pediatric, trauma and non-trauma patients, the maximum mean decreases in number of visits were 80.0% (p < 0.01), 57.6% (p < 0.01) and 40.8% (p < 0.01), respectively. In triage 1, 2 and 3 patients, the maximum mean decreases were 18.1% (p < 0.01), 55.9% (p < 0.01) and 53.7% (p < 0.01), respectively. The maximum decrease in total costs was 37.7% (p < 0.01). The maximum mean costs per patient increased 35.9% (p < 0.01). The proportions of increases in mean costs for each patient were attributed to laboratory investigations (31.4%), radiography (21.9%) and medications (29.5%). Conclusion The SARS outbreak resulted in a marked reduction in the number of ED visits which persisted for 3 months after the end of the epidemic. Total cost of treating individual patients showed a simultaneous marked increase, while overall operational costs in the ED showed a marked decrease. The increased total cost for each patient was attributed to the increased number of diagnostic procedures to screen for possible SARS in the ED.


title: Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020

text: A novel coronavirus (2019-nCoV) is causing an outbreak of viral pneumonia that started in Wuhan, China. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan in the early outbreak phase, we estimate the mean incubation period to be 6.4 days (95% credible interval: 5.6–7.7), ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values should help inform 2019-nCoV case definitions and appropriate quarantine durations.


title: In vivo functional characterization of the SARS-Coronavirus 3a protein in Drosophila

text: Abstract The Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3a locus encodes a 274 a.a. novel protein, and its expression has been confirmed in SARS patients. To study functional roles of 3a, we established a transgenic fly model for the SARS-CoV 3a gene. Misexpression of 3a in Drosophila caused a dominant rough eye phenotype. Using a specific monoclonal antibody, we demonstrated that the 3a protein displayed a punctate cytoplasmic localization in Drosophila as in SARS-CoV-infected cells. We provide genetic evidence to support that 3a is functionally related to clathrin-mediated endocytosis. We further found that 3a misexpression induces apoptosis, which could be modulated by cellular cytochrome c levels and caspase activity. From a forward genetic screen, 78 dominant 3a modifying loci were recovered and the identity of these modifiers revealed that the severity of the 3a-induced rough eye phenotype depends on multiple cellular processes including gene transcriptional regulation.


title: Chapter Four Arthropod-Borne Flaviviruses and RNA Interference Seeking New Approaches for Antiviral Therapy

text: Abstract Flaviviruses are the most prevalent arthropod-borne viruses worldwide, and nearly half of the 70 Flavivirus members identified are human pathogens. Despite the huge clinical impact of flaviviruses, there is no specific human antiviral therapy available to treat infection with any of the flaviviruses. Therefore, there is a continued search for novel therapies, and this review describes the current knowledge on the usage of RNA interference (RNAi) in combating flavivirus infections. RNAi is a process of sequence-specific gene silencing triggered by double-stranded RNA. Antiviral RNAi strategies against arthropod-borne flaviviruses have been reported and although several hurdles must be overcome to employ this technology in clinical applications, they potentially represent a new therapeutic tool.


title: Discovery of Small-Molecule HIV-1 Fusion and Integrase Inhibitors Oleuropein and Hydroxytyrosol: I. Fusion Inhibition

text: We have identified oleuropein (Ole) and hydroxytyrosol (HT) as a unique class of HIV-1 inhibitors from olive leaf extracts effective against viral fusion and integration. We used molecular docking simulation to study the interactions of Ole and HT with viral targets. We find that Ole and HT bind to the conserved hydrophobic pocket on the surface of the HIV-gp41 fusion domain by hydrogen bonds with Q577 and hydrophobic interactions with I573, G572, and L568 on the gp41 N-terminal heptad repeat peptide N36, interfering with formation of the gp41 fusion-active core. To test and confirm modeling predications, we examined the effect of Ole and HT on HIV-1 fusion complex formation using native polyacrylamide gel electrophoresis and circular dichroism spectroscopy. Ole and HT exhibit dose dependent inhibition on HIV-1 fusion core formation with EC(50)s of 66–58 nM, with no detectable toxicity. Our findings on effects on HIV-1 integrase are reported separately.


Influenza A and B Viruses but Not MERS-CoV in Hajj Pilgrims, Austria, 2014


title: Current Precautions and Future Directions in Lung Transplantation during the COVID‐19 Pandemic

text: The unprecedented public health emergency caused by the acute viral respiratory coronavirus disease (COVID‐19) has drastically changed current practices in solid organ transplantation, markedly so for transplantation of the lungs, the major target of the virus. Although national and state authorities do not recommend postponing transplant procedures, most specialists are reluctant to proceed due to substantial uncertainty and increased risks in the midst of the pandemic. There is an urgent need for evidence‐based directions to move forward. Here, we offer our insights as specialists at a high‐volume center located in a geographical area with high infection rates.


title: Zinc Iodide in combination with Dimethyl Sulfoxide for treatment of SARS-CoV-2 and other viral infections

text: Zinc Iodide and Dimethyl Sulfoxide composition is proposed as therapeutic agents to treat and prevent chronic and acute viral infections including SARS-CoV-2 infected patients. The therapeutic combinations have a wide range of virucidal effect on DNA and RNA containing viruses. The combination also exhibits anti-inflammatory, immunomodulating, antifibrotic, antibacterial, antifungal and antioxidative effects. Given the fact that Zinc Iodide has been used as an oral antiseptic agent and DMSO have already proven as a safe pharmaceutical solvent and therapeutic agent, we hypothesize that the combination of these two agents can be applied as an effective, safe and inexpensive treatment for SARS-CoV-2 and other viral infection. The therapeutic compound can be applied as both etiological and pathogenesis therapy and used as an effective and safe antiseptic (disinfectant) for human and animals as well.


Living in pandemic times


title: Metagenomic analysis of viral genetic diversity in respiratory samples from children with severe acute respiratory infection in China

text: Abstract Severe acute respiratory infection (SARI) in children is thought to be mainly caused by infection with various viruses, some of which have been well characterized; however, analyses of respiratory tract viromes among children with SARI versus those without are limited. In this study, nasopharyngeal swabs from children with and without SARI (135 versus 15) were collected in China between 2008 and 2010 and subjected to multiplex metagenomic analyses using a next-generation sequencing platform. The results show that members of the Paramyxoviridae, Coronaviridae, Parvoviridae, Orthomyxoviridae, Picornaviridae, Anelloviridae and Adenoviridae families represented the most abundant species identified (>50% genome coverage) in the respiratory tracts of children with SARI. The viral population found in the respiratory tracts of children without SARI was less diverse and mainly dominated by the Anelloviridae family with only a small proportion of common epidemic respiratory viruses. Several almost complete viral genomes were assembled, and the genetic diversity was determined among several samples based on next-generation sequencing. This research provides comprehensive mapping of the viromes of children with SARI and indicates high heterogeneity of known viruses present in the childhood respiratory tract, which may benefit the detection and prevention of respiratory disease.


title: Digitally aided telemedicine during the SARS‐CoV‐2 pandemic to screen oral medicine emergencies

text: A new human coronavirus, known as severe acute respiratory coronavirus 2 syndrome (SARS‐CoV‐2), emerged at the end of 2019 in Wuhan, China, and we are now facing a pandemic (WHO 2020). The virus has been found in saliva (Meng et al 2020, Sabino et al 2020). In vitro experimental findings suggest that SARS‐CoV‐2 remained viable in aerosols for 3 hours (van Doremalen et al 2020).


title: “Monoclonal-Type” Plastic Antibodies for COVID-19 Treatment: What Is the Idea?

text: In late December 2019, an outbreak due to a novel coronavirus, initially called 2019-nCoV, was reported in Wuhan, China [...].


title: Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV)

text: Abstract In three successive experiments, the immune functions of pigs persistently infected with the porcine reproductive and respiratory syndrome virus (PRRSV) have been evaluated. Non-specific immune responses were analyzed over a period of 12 weeks post-infection (PI). In addition, the capacity of PRRSV-infected pigs to develop an efficient immune response against pseudorabies virus (PRV) glycoproteins and to resist to a subsequent virulent challenge was investigated. Our results demonstrate that PRRSV produced minor effects on the immune system of pigs. The skin delayed type hypersensitivity (DTH) in response to phytohemagglutinine injection was slightly diminished one week after challenge, but was restored thereafter. However, three weeks after the infection, the total white blood cell count, and the number of CD2+, CD8+ and IgM+ cells were enhanced. The increase in numbers of CD8+ cells persisted for three consecutive weeks. Serum immunoglobulins in infected pigs also increased by week 3 PI and up to 8 weeks PI. These results show that PRRSV may have stimulating effects on the pig immune system during the phase of long-lasting infection. After immunization with PRV glycoproteins, the production of anti-PRV antibodies and skin DTH response against PRV glycoproteins were not affected. On the contrary, following a virulent PRV challenge, PRRSV-infected pigs developed a better secondary antibody response and their resistance to the infection was as effective as in control pigs. Taken together, our data do not support a systemic immunosuppressive effect of PRRSV, during the persistent phase of infection. Other mechanisms may therefore apply to explain the emergence of secondary infections in endemically infected herds.


title: Analyzing the impact of the coronavirus crisis on business models

text: Abstract In the light of the current coronavirus crisis, business-to-business firms face a variety of challenges in a complex and fast-changing environment. In order to provide structured analysis and to guide strategic decision-making, we present a novel, five-step approach for analyzing the impact of a crisis on a firm's business model. We applied the approach with eight business-to-business firms and find support for its usefulness. The evidence suggests very different impacts of the coronavirus crisis on business-to-business firms, and that understanding these differences is important for strategizing during the crisis but also to navigating successfully into the future. We also describe six different types of crisis impacts on business models. We conclude by developing managerial implications and questions for future research.


title: Baculovirus Surface Display of Zika Virus Envelope Protein Protects against Virus Challenge in Mouse Model

text: Zika virus (ZIKV) is emerging as a significant pathogen worldwide and may cause severe neurological disorders such as fetal microcephaly and Guillain-Barre syndrome. No drug or listed vaccines are currently available for preventing ZIKV infection. As a major target of neutralizing, ZIKV envelop (E) protein usually used for vaccine development. Nevertheless, the immunogenicity of ZIKV envelop (E) protein expressed by baculovirus display system has never been assessed. In this study, we reported a new strategy for surface display of ZIKV E protein by a recombinant baculovirus vector derived from Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) and assessed its immunogenicity in mice. We produced recombinant fusion ZIKV E protein linked with signal peptide (SP) and transmembrane domain (TM) of AcMNPV GP64. The results showed that the recombinant protein was easy to produce by baculovirus display system. BALB/c mice immunized with this recombinant E protein developed ZIKV specific serum antibodies. The anti-E protein sera from the mice were able to effectively neutralize ZIKV in vitro. More importantly, AG6 (IFN-α/β and IFN-γ receptor deficient) mice immunized with recombinant E protein were protected against lethal ZIKV challenge. Together, these findings demonstrated that the recombinant E protein displayed by baculovirus can be conveniently prepared and displayed good immunogenicity in immunized mice. It is a promising practical approach for prompting the development of vaccine and related immunology research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00238-x) contains supplementary material, which is available to authorized users.


title: Lactic acid bacteria: reviewing the potential of a promising delivery live vector for biomedical purposes

text: Lactic acid bacteria (LAB) have a long history of safe exploitation by humans, being used for centuries in food production and preservation and as probiotic agents to promote human health. Interestingly, some species of these Gram-positive bacteria, which are generally recognized as safe organisms by the US Food and Drug Administration (FDA), are able to survive through the gastrointestinal tract (GIT), being capable to reach and colonize the intestine, where they play an important role. Besides, during the last decades, an important effort has been done for the development of tools to use LAB as microbial cell factories for the production of proteins of interest. Given the need to develop effective strategies for the delivery of prophylactic and therapeutic molecules, LAB have appeared as an appealing option for the oral, intranasal and vaginal delivery of such molecules. So far, these genetically modified organisms have been successfully used as vehicles for delivering functional proteins to mucosal tissues in the treatment of many different pathologies including GIT related pathologies, diabetes, cancer and viral infections, among others. Interestingly, the administration of such microorganisms would suppose a significant decrease in the production cost of the treatments agents since being live organisms, such vectors would be able to autonomously amplify and produce and deliver the protein of interest. In this context, this review aims to provide an overview of the use of LAB engineered as a promising alternative as well as a safety delivery platform of recombinant proteins for the treatment of a wide range of diseases.