title: Ramipril in High Risk Patients with COVID-19

text: Abstract Background The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2 (ACE-2). This interaction has been proposed as a potential risk factor in patients treated with RAAS-inhibitors. Objectives To analyze if RAAS-inhibitors modify the risk for COVID-19. Methods RASTAVI (NCT03201185) is an ongoing randomized clinical trial randomly allocating Ramipril or control after successful transcatheter aortic valve replacement at 14 centers is Spain. We performed a non-pre-specified interim analysis to evaluate its impact on COVID-19 risk in this vulnerable population. Results As in April 1st 2020, 102 patients (50 Ramipril and 52 controls) were included in the trial. Mean age was 82.3±6.1 years, 56.9% males. Median time of Ramipril treatment was 6 months [IQR:2.9-11.4]. Eleven patients (10.8%) have been diagnosed with COVID-19 (6 in control group and 5 receiving Ramipril, HR=1.150 [95%CI: 0.351-3.768]). The risk of COVID-19 was increased in older patients (p=0.019), those with atrial fibrillation (p=0.066), lower hematocrit (p=0.084), and more comorbidities according to Society of thoracic surgeons score (p=0.065). Admission and oxygen supply was required in 4.9% (2 patients in the Ramipril and 3 in control), and 4 of them died (two in each randomized group). A higher body mass index was the only factor increasing the mortality rate (p=0.039). Conclusions In a high risk population of old patients with cardiovascular disease, randomization to Ramipril had no impact in the incidence or severity of COVID-19. This analysis supports the maintenance of RAAS-inhibitor treatment during COVID-19 crisis.


title: Using iCn3D and the World Wide Web for structure-based collaborative research: Analyzing molecular interactions at the root of COVID-19

text: The COVID-19 pandemic took us ill-prepared and tackling the many challenges it poses in a timely manner requires world-wide collaboration. Our ability to study the SARS-COV-2 virus and its interactions with its human host in molecular terms efficiently and collaboratively becomes indispensable and mission-critical in the race to develop vaccines, drugs, and neutralizing antibodies. There is already a significant corpus of 3D structures related to SARS and MERS coronaviruses, and the rapid generation of new structures demands the use of efficient tools to expedite the sharing of structural analyses and molecular designs and convey them in their native 3D context in sync with sequence data and annotations. We developed iCn3D (pronounced “I see in 3D”) 1 to take full advantage of web technologies and allow scientists of different backgrounds to perform and share sequence-structure analyses over the Internet and engage in collaborations through a simple mechanism of exchanging “lifelong” web links (URLs). This approach solves the very old problem of “sharing of molecular scenes” in a reliable and convenient manner. iCn3D links are sharable over the Internet and make data and entire analyses findable, accessible, and reproducible, with various levels of interoperability. Links and underlying data are FAIR 2 and can be embedded in preprints and papers, bringing a 3D live and interactive dimension to a world of text and static images used in current publications, eliminating at the same time the need for arcane supplemental materials. This paper exemplifies iCn3D capabilities in visualization, analysis, and sharing of COVID-19 related structures, sequence variability, and molecular interactions.


title: Melatonin and viral infections

text: Abstract: The therapeutic effects of melatonin against viral infections, with emphasis on the Venezuelan equine encephalomyelitis (VEE), are reviewed. Melatonin has been shown to prevent paralysis and death in mice infected with the encephalomyocarditis virus and to decrease viremia. Melatonin also postpones the onset of the disease produced by Semliki Forest virus inoculation and reduces the mortality of West Nile virus‐infected mice stressed by either isolation or dexamethasone injection. An increase in the host resistance to the virus via a peripheral immunostimulatory activity is considered responsible for these effects. It has also been demonstrated that melatonin protects some strains of mink against Aleutian disease, and prevents the reduction of B‐ and T‐cells as well as Th1 cytokine secretion in mice infected with leukemia retrovirus. In VEE‐infected mice, melatonin postpones the onset of the disease and death for several days and reduces the mortality rate. This protective effect seems to be due to the increase in the production of interleukin‐1β (IL‐1β), as 100% of the infected mice treated with melatonin die when IL‐1β is blocked with antimurine IL‐1β antibodies. Although melatonin administration raises serum levels of tumor necrosis factor‐alpha (TNF‐α) and interferon‐gamma (IFN‐γ), the mortality observed in neutralization experiments with the corresponding anticytokine antibodies, suggests that neither TNF‐α nor IFN‐γ are essential for the protective effect of melatonin on murine VEE virus infection. Melatonin treatment also enhances the efficiency of immunization against the VEE virus. Reactive oxygen species have been implicated in the dissemination of this virus, and their deleterious effects may be diminished by melatonin. This indole inhibits nitric oxide synthetase activity and it is a potent scavenger of nitric oxide, which also plays an important role in the spread of the VEE virus. In conclusion, the immunomodulatory, antioxidant, and neuroprotective effects of melatonin suggest that this indole must be considered as an additional therapeutic alternative to fight viral diseases.


Virus detectives seek source of SARS in China's wild animals


title: The First Disease X is Caused by a Highly Transmissible Acute Respiratory Syndrome Coronavirus

text: Based on the announcement of the World Health Organization (WHO) in 2018, the Wuhan pneumonia caused by an unknown etiology should be recognized as the first Disease X. Later, the pathogen was identified to be a novel coronavirus denoted 2019-nCoV, which has 79.5% and 96% whole genome sequence identify to SARS-CoV and bat SARS-related coronavirus (SARSr-CoV-RaTG13), respectively, suggesting its potential bat origin. With high human-to-human transmission rate (R0), 2019-nCoV has quickly spread in China and other countries, resulting in 34,953 confirmed cases and 725 deaths as of 8 February 2020, thus calling for urgent development of therapeutics and prophylactics. Here we suggest renaming 2019-nCoV as “transmissible acute respiratory syndrome coronavirus (TARS-CoV)” and briefly review the advancement of research and development of neutralizing antibodies and vaccines targeting the receptor-binding domain (RBD) and viral fusion inhibitors targeting the heptad repeat 1 (HR1) domain in spike protein of 2019-nCoV.


title: Evidence for swine and human papillomavirus in pig slurry in Italy

text: AIMS: The diversity and the geographical distribution of swine papillomaviruses (PVs) are virtually unknown. The occurrence and the diversity of swine PV were therefore investigated in pig slurry collected in Italy, to contribute towards filling this gap in knowledge. METHODS AND RESULTS: Twenty‐two slurry samples underwent analysis by nested PCR and DNA sequencing using published and newly designed specific primer pairs for Sus scrofa papillomavirus (SsPV) type 1 and 2 (SsPV1 and 2), along with degenerate PV‐specific primers targeting the major coat protein L1 and the helicase protein E1. Overall, three samples (13·6%) were positive for SsPV1 by specific primers, and nucleotide (nt) sequences showed 99–100% nt identity with SsPV1 variant a (EF395818), while SsPV2 was not found in any sample. Using generic primers, eight samples (36·4%) were tested positive for human papillomavirus (HPV), and were characterized as follows: β1‐HPV8, β1‐HPV14, β1‐HPV206, β2‐HPV113, β2‐HPV120 and γ1‐HPV173. Moreover, one unclassified γ‐type was detected. CONCLUSIONS: Both swine and human PVs were detected in pig slurry in this study. The unexpected presence of HPV in pig waste could be explained as the result of an improper use of the sewage collection pits and/or with improper procedures of the operators. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports the first detection of SsPV1 in Italy, along with the first detection of HPVs in pig slurry samples in Italy, and expands our knowledge about PV diversity and geographic distribution.


title: #Med StudentCovid – How social media is supporting students during COVID‐19

text: COVID‐19 has disrupted medical education on an international scale with clinical attachments cancelled, assessments and teaching moved online, and numerous universities graduating their final year medical students early to assist pressured health systems. As a result, several innovative educational projects and volunteering opportunities have been established to help care delivery and enhance remote medical education.


title: A new chitin-binding lectin from rhizome of Setcreasea purpurea with antifungal, antiviral and apoptosis-inducing activities

text: Abstract A 48kDa, chitin-binding lectin with antifungal, antiviral and apoptosis-inducing activities was isolated from the rhizomes of Setcreasea purpurea Boom, a member of family Commelinaceae. Setcreasea purpurea lectin (designated as SPL) is a homotetrameric protein consisting of 12031.9Da subunits linked by non-covalent bonds as determined by SDS-PAGE, gel filtration and MS. The N-terminal 25 amino-acid sequence of SPL, NVLGRDAYCGSQNPGATCPGLCCSK was determined and homology analysis suggested that SPL belongs to the family of chitin-binding plant lectins composed of hevein domains. The lectin exhibited strong hemagglutinating activity towards rabbit erythrocytes at 0.95μg/ml and the activity could be reversed exclusively by chitin hydrolysate (oligomers of GlcNAc). Its hemagglutinating activity was stable in pH range of 2.0–9.0 and it showed excellent thermal tolerance. SPL showed antifungal activity against Rhizoctonia solani, Sclerotinia sclerotiorum, Penicillium italicum and Helminthosporiun maydis. It also exhibited inhibitory effect on HIV-1 (IIIB) and HIV-2 (ROD), with an EC50 of 13.8±1.3 and 57.1±15μg/ml, respectively. Subsequently, MTT method, cell morphological analysis and LDH activity-based cytotoxicity assays demonstrated that SPL was highly cytotoxic to CNE-1 cells and induced apoptosis in a dose-dependent manner. Moreover, due to the caspase inhibitors analyses, caspase was also found to play an important role in the potential apoptotic mechanism of SPL.


Is Mycobacterium paratuberculosis or any other infectious agent involved in the pathogenesis of IBD?


title: Clinical Characteristics of Hematological Patients Concomitant with COVID‐19

text: The rapid spread of COVID‐19 represented the most serious issue to public health globally. Hematological patients as immunocompromised hosts are vulnerable to SARS‐CoV‐2 infection. There is rare information available regarding the clinical features of hematological patients concomitant with COVID‐19. In this study, 9 concomitant patients were analyzed for their clinical manifestations, the laboratory data, radiological findings and immunologic features. The median age was 50 years (range, 17‐68) and 6 patients were male. 7 patients were infected via hospital‐associated transmission and other 2 via community‐associated transmission. Onset of COVID‐19 in all patients occurred during routine treatments for their hematological diseases. 8 patients were classified as moderate and 1 patient as critically ill COVID‐19. 4 patients died, 1 from leukemia progression, 2 from life‐threatening secondary infection and the other one from respiratory failure caused by COVID‐19. Abruptly elevated level of cytokines was often correlated with progressive hematological disease or concurrent bacterial infections. 2 patients had the atypical CT imaging findings of COVID‐19. The median interval from the first CT scan imaging to improvement in survivors was 40 days (range 14‐51 days). 4 out of 5 survivors had negative serological tests one month after symptoms onset. Positive viral load in 4 survivors lasted longer than 45 days. Our result indicated concomitant patients formed a distinct subgroup characterized by atypical clinical features, defective viral clearance and lower level of SARS‐CoV‐2‐specific antibodies. Targeted therapies that impair host humoral immunity should be avoided. These findings will be helpful to tailor appropriate management for the concomitant patients.


title: Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action?

text: This review summarizes evidence that commercially available fluoroquinolones used for the treatment of bacterial infections are active against other non-bacterial infectious agents as well. Any of these fluoroquinolones exerts, in parallel to its antibacterial action, antiviral, antifungal, and antiparasitic actions at clinically achievable concentrations. This broad range of anti-infective activities is due to one common mode of action, i.e., the inhibition of type II topoisomerases or inhibition of viral helicases, thus maintaining the selective toxicity of fluoroquinolones inhibiting microbial topoisomerases at low concentrations but mammalian topoisomerases at much higher concentrations. Evidence suggests that standard doses of the fluoroquinolones studied are clinically effective against viral and parasitic infections, whereas higher doses administered topically were active against Candida spp. causing ophthalmological infections. Well-designed clinical studies should be performed to substantiate these findings.


title: National Library of Medicine Disaster Information Management Research Center: Achieving the vision, 2010–2013

text: From 2010 to 2013, the National Library of Medicine (NLM) Disaster Information Management Research Center (DIMRC) continued to build its programs and services on the foundation laid in its starting years, 2008–2010. Prior to 2008, NLM had a long history of providing health information, training, and tools in response to disasters. Aware of this legacy, the NLM long range plan (Charting a Course for the 21st Century: NLM’s Long Range Plan 2006–2016) called for creation of a center to show “a strong commitment to disaster remediation and to provide a platform for demonstrating how libraries and librarians can be part of the solution to this national problem”. NLM is continuing efforts to ensure that medical libraries have plans for the continuity of their operations, librarians are trained to understand their roles in preparedness and response, online disaster health information resources are available for many audiences and in multiple formats, and research is conducted on tools to enhance the exchange of critical information during and following disasters. This paper describes the 2010–2013 goals and activities of DIMRC and its future plans.


title: BOARD-INVITED REVIEW: Recent advances in management of highly stressed, newly received feedlot cattle

text: Morbidity and mortality from bovine respiratory disease (BRD) and associated losses in performance and carcass merit continue to plague the beef cattle industry. Several viral/bacterial agents are responsible for BRD, and interactions occur among the agents. Viral agents often predispose animals to bacterial infections, and Mannheimia haemolytica is the most frequently isolated organism in cattle with BRD. Laboratory tests are available to characterize organisms causing BRD using easily obtained nasal swab samples. Testing for persistent infection with bovine viral diarrhea virus can be done by a 2-stage technique using PCR and immunohistochemistry. Preconditioning programs that include preweaning viral vaccination programs along with castration could have a significant influence on decreasing BRD in the cattle feeding industry. Metaphylactic antibiotic programs continue to be effective; however, antibiotic resistance is a public concern, and additional management options (e.g., direct-fed microbials or other compounds with antimicrobial properties) deserve attention. Diets with an increased energy concentration achieved by decreasing the dietary roughage concentration may slightly increase the rate of BRD morbidity; however, these diets also increase ADG, DMI, and G:F compared with lower-energy, greater-roughage diets. The extent to which performance and BRD morbidity are affected by dietary protein concentration needs further study, but low and high protein concentrations should probably be avoided. Several trace minerals (e.g., Cu, Se, and Zn) affect immune function, but the effects of supplementation on performance and immune function in model challenge systems and in field studies are equivocal. Adding vitamin E to receiving diets at pharmacological levels (e.g., >1,000 IU·animal(−1)·day(−1)) seems beneficial for decreasing BRD morbidity, but it has little effect on performance. Given the limited ability to consistently modify immune function and BRD morbidity through dietary manipulations, we recommend that the diets for newly received cattle be formulated to adjust nutrient concentrations for low feed intake and to provide optimal performance during the receiving period.


title: Diagnosis, Outcome, and Management of Chylous Ascites Following Pediatric Liver Transplantation

text: Data on postoperative chylous ascites (CA) after pediatric liver transplantation (LT) are scarce. This retrospective study was conducted to identify the incidence, risk factors, management, and outcomes of postoperative CA in a large single‐center pediatric LT cohort (2000‐2016). The study cohort comprised 317 LTs (153 living donors and 164 deceased donors) in 310 recipients with a median age of 2.7 years. The incidence of CA was 5.4% (n = 17), diagnosed after a median time of 10 days after LT. Compared with chylomicron detection in peritoneal fluid (the gold standard), a triglyceride cutoff value of 187 mg/dL in peritoneal fluid showed insufficient sensitivity (31%) for CA diagnosis. In univariate logistic regression analyses, ascites before LT, younger age, and lower weight, height, and height‐for‐age z score at LT were associated with CA. Symptomatic management of CA included peritoneal drain (100%) and diuretics (76%). Therapeutic interventions included very low‐fat or medium‐chain triglyceride–rich diets (94%) and intravenous octreotide (6%), leading to CA resolution in all patients. CA was associated with prolonged hospital length of stay (LOS; 40 days in the CA group versus 24 days in the non‐CA group; P = 0.001) but not with reduced patient or graft survival rates after a median follow‐up time of 14 years. In conclusion, CA in the pediatric LT recipient is a relatively uncommon complication associated with increased hospital LOS and morbidity. Measurement of chylomicrons is recommended in patients with ascites that is more severe or persistent than expected. Dietary interventions are effective in most patients.


Supporting the Education of Nurse Practitioners and Physician Assistants in Meeting Shortages in Mental Health Care


title: Constitutional Flavonoids Derived from Epimedium Dose-Dependently Reduce Incidence of Steroid-Associated Osteonecrosis Not via Direct Action by Themselves on Potential Cellular Targets

text: Intravascular-thrombosis and extravascular-lipid-deposit are the two key pathogenic events considered to interrupt intraosseous blood supply during development of steroid-associated osteonecrosis (ON). However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events. The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipid-deposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways. The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis. These findings encourage designing clinical trials to investigate potential of EF in prevention of steroid-associated ON.


title: Pre-existing immunity against Ad vectors: Humoral, cellular, and innate response, what's important?

text: Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to circumvent pre-existing immunity to adenovirus, numerous strategies, such as developing alternative Ad serotypes, varying immunization routes and utilizing prime-boost regimens, are under pre-clinical or clinical phases of development. However, these strategies mainly focus on one arm of pre-existing immunity. Selection of alternative serotypes has been largely driven by the absence in the human population of nAbs against them with little attention paid to cross-reactive Ad specific T cells. Conversely, varying the route of immunization appears to mainly rely on avoiding Ad specific tissue-resident T cells. Finally, prime-boost regimens do not actually circumvent pre-existing immunity but instead generate immune responses of sufficient magnitude to confer protection despite pre-existing immunity. Combining the above strategies and thus taking into account all components regulating pre-existing Ad immunity will help further improve the development of Ad vectors for animal and human use.


title: Influenza Vaccination in Type 2 Diabetes Patients: Coverage Status and Its Determinants in Southwestern Saudi Arabia

text: Despite the significant role of seasonal influenza vaccination in preventing and minimizing the serious complications of influenza infection in type 2 diabetes mellitus (T2DM) patients, unsatisfactory compliance still exists for vaccination. Study objectives were to explore the vaccination status and determinants in T2DM patients in southwestern Saudi Arabia. A cross-sectional study on a representative sample of T2DM patients in Abha city, southwestern Saudi Arabia, was conducted. Data for sociodemographic characteristics, clinical criteria, vaccination status, vaccination motivators and barriers and seasonal influenza knowledge were collected. Out of 353 T2DM patients included in the study, seasonal influenza vaccination coverage was 61% in year 2017. A significant factors associated with non-vaccination were; poor influenza and its vaccine knowledge (OR = 4.31, 95% CI: 2.73–6.80), illiteracy (OR = 1.93, 95% CI: 1.11–3.37), and more than 10 years disease duration (OR = 2.07, 95% CI: 1.11–3.87). Presence of family history of DM and ischemic heart comorbidity minimized the possibility of non-vaccination (OR = 0.54 and 0.28 respectively). Healthcare givers’ advice was the most reported vaccination motivator (84.7%) while; fear of vaccine side effects was the most stated barrier (73%). In conclusion, influenza vaccination rate among T2DM in the present study is less than the recommended level. Continuous primary health care center-based educational programs should be implemented to aware and encourage influenza vaccination among T2DM patients.


title: Adenovirus respiratory infection in hospitalized children in Hong Kong: serotype–clinical syndrome association and risk factors for lower respiratory tract infection

text: Lower respiratory tract infections (LRTI) caused by adenovirus can be severe with resultant chronic pulmonary sequelae. More than 50 serotypes have been recognized; however, the exact association of serotype with clinical phenotype is still unclear. There have been no reports on the adenovirus serotype pattern in Hong Kong, and their relationships with disease manifestations and complications are not known. Clinical and epidemiological data on 287 children (<6 years old) admitted with adenovirus respiratory infections from 2001 to 2004 were reviewed. Common presenting symptoms included fever (97.9 %) and cough and rhinitis (74 %). Extra-pulmonary manifestations were present in 37.3 %. The clinical picture mimicked bacterial infection for its prolonged high fever and neutrophilic blood picture. Forty-two patients (14.6 %) had LRTI, either pneumonia or acute bronchiolitis, but none had severe acute respiratory compromise. Children aged 1 to 2 years old were most at risk for adenovirus LRTI (adjusted p = 0.0165). Serotypes 1 to 7 could be identified in 93.7 % of the nasopharyngeal specimens, with serotypes 2 and 3 being the most prevalent. Different serotypes showed predilection for different age groups and with different respiratory illness association. The majority of acute bronchiolitis (71.4 %) were associated with serotype 2 infection, and this association was statistically significant (p < 0.0001). Serotype 3 infection accounted for over half of the pneumonia cases (57–75 %) in those aged 3–5 years old. Only one patient developed mild bronchiectasis after serotype 7 pneumonia. Children aged 1 to 2 years old were the at-risk group for adenovirus LRTI, but respiratory morbidity was relatively mild in our locality. There was an apparent serotype–respiratory illness association.


title: How COVID-19 Deepens Child Oral Health Inequities

text: ABSTRACT The fallout from COVID-19 will reveal the depth and range of social, economic, and political disparities faced by U.S. families and children. Those same injustices, magnified and worsened by COVID-19, are also responsible for perpetuating child oral health disparities.


docid: qmylxndp

title: COVID-19 pandemic: Ophthalmic practice and precautions in a tertiary eye hospital in Iran

text: The coronavirus disease 2019 (COVID-19) has currently caused a global health threat. Ophthalmic care settings pose a risk of cross-infection. The preventive strategy regarding ophthalmic practice in response to the outbreak is discussed. This is the first report form a tertiary eye hospital in Iran and second of its kind worldwide.


Severe acute respiratory symptoms and severe acute respiratory syndrome


title: Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination

text: Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3′ non-coding region we have further developed a cell-based assay (the 3′CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process.


title: Recent Advances in EPAC-Targeted Therapies: A Biophysical Perspective

text: The universal second messenger cAMP regulates diverse intracellular processes by interacting with ubiquitously expressed proteins, such as Protein Kinase A (PKA) and the Exchange Protein directly Activated by cAMP (EPAC). EPAC is implicated in multiple pathologies, thus several EPAC-specific inhibitors have been identified in recent years. However, the mechanisms and molecular interactions underlying the EPAC inhibition elicited by such compounds are still poorly understood. Additionally, being hydrophobic low molecular weight species, EPAC-specific inhibitors are prone to forming colloidal aggregates, which result in non-specific aggregation-based inhibition (ABI) in aqueous systems. Here, we review from a biophysical perspective the molecular basis of the specific and non-specific interactions of two EPAC antagonists—CE3F4R, a non-competitive inhibitor, and ESI-09, a competitive inhibitor of EPAC. Additionally, we discuss the value of common ABI attenuators (e.g., TX and HSA) to reduce false positives at the expense of introducing false negatives when screening aggregation-prone compounds. We hope this review provides the EPAC community effective criteria to evaluate similar compounds, aiding in the optimization of existing drug leads, and informing the development of the next generation of EPAC-specific inhibitors.


title: Operational efficiency of Asia–Pacific airports

text: Abstract Airports are important drivers of economic development and thus under tremendous pressure from emerging competitors. However, few studies have analysed the operational efficiency of Asia–Pacific airports. This study therefore evaluated the operational efficiency of 21 Asia–Pacific airports between 2002 and 2011. A two-stage method was used: Data Envelopment Analysis (DEA) to assess airport efficiency, followed by the second-stage regression analysis to identify the key determinants of airport efficiency. The first-stage DEA results indicated that Adelaide, Beijing, Brisbane, Hong Kong, Melbourne, and Shenzhen are the efficient airports. The second-stage regression analysis suggested that percentage of international passengers handled by an airport, airport hinterland population size, dominant airline(s) of an airport when entering global airline strategic alliance, and an increase in GDP per capita are significant in explaining variations in airport efficiency.


title: Radiotherapy for pain relief from bone metastases during Coronavirus (COVID‐19) pandemic

text: The worldwide pandemic of coronavirus disease (COVID-19) has drammatically and rapidly spread in Italy the last month. By now, nevertheless Italian government efforts to contain the outbreak with escalating restrictive measures, 205463 cases were confirmed, with 27967 deaths.


title: The potential of the human immune system to develop broadly neutralizing HIV-1 antibodies: implications for vaccine development

text: OBJECTIVES AND DESIGN: Developing an effective HIV-1 vaccine that elicits broadly neutralizing HIV-1 human antibodies (bnAbs) remains a challenging goal. Extensive studies on HIV-1 have revealed various strategies employed by the virus to escape host immune surveillance. Here, we investigated the human antibody gene repertoires of uninfected and HIV-1-infected individuals at genomic DNA (gDNA) and cDNA levels by deep sequencing followed by high-throughput sequence analysis to determine the frequencies of putative germline antibody genes of known HIV-1 monoclonal bnAbs (bnmAbs). METHODS: Combinatorial gDNA and cDNA antibody libraries were constructed using the gDNAs and mRNAs isolated from uninfected and HIV-1-infected human peripheral blood mononuclear cells (PBMCs). All libraries were deep sequenced and sequences analysed using IMGT/HighV-QUEST software (http://imgt.org/HighV-QUEST/index.action). The frequencies of putative germline antibodies of known bnmAbs in the gDNA and cDNA libraries were determined. RESULTS AND CONCLUSION: The human gDNA antibody libraries were more diverse in heavy and light chain V-gene lineage usage than the cDNA libraries, indicating that the human gDNA antibody gene repertoires may have more potential than the cDNA repertoires to develop HIV-1 bnAbs. The frequencies of the heavy and kappa and lambda light chain variable regions with identical V(D)J recombinations to known HIV-1 bnmAbs were extremely low in human antibody gene repertoires. However, we found relatively high frequencies of the heavy and kappa and lambda light chain variable regions that used the same V-genes and had the same CDR3 lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. B-cells bearing B-cell receptors of such heavy and kappa and lambda light chain variable regions may be stimulated to induce HIV-1 bnAbs.


docid: gvdtiitd

title: MHV-JHM infection in immortalized murine oligodendrocytes


title: The landscape of cognitive function in recovered COVID-19 patients

text: This study aims to evaluate the impacts of COVID-19 on cognitive functions in recovered patients and its relationship with inflammatory profiles. Twenty-nine patients recovered from COVID-19 as confirmed by negative nucleic tests for two consecutive times were recruited. A total of 29 age-, gender- and education-matched healthy controls were also recruited. The cognitive functions of all subjects were evaluated by the iPad-based online neuropsychological tests, including the Trail Making Test (TMT), Sign Coding Test (SCT), Continuous Performance Test (CPT), and Digital Span Test (DST). Blood samples from all patients were collected for examining inflammatory profiles, including interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and C-reactive protein (CRP). The relationship between cognitive functions and inflammatory profiles were analyzed by Pearson correlation. In results, although no significant differences were found in TMT, SCT, and DST between the two groups, patients with COVID-19 scored lower in the correct number of the second and third parts of CPT, they also scored higher in the missing number of the third part of CPT (all P < 0.05). In patients with COVID-19, there was a trend of significant difference for lower reaction time in the first and second parts of CPT (P = 0.050, and 0.051, respectively), as well as the lower correct number of the second part of CPT (P = 0.050). Correlation analysis showed that the reaction time for the first and second parts of CPT was positively correlated with the CRP levels (r = 0.557 and 0.410, P < 0.05). In conclusion, our findings indicated that cognitive impairments exist even in patients recovered from COVID-19, and might be possibly linked to the underlying inflammatory processes.


title: Chapter 22 Environmentally Transmitted Pathogens

text: This chapter describes a variety of pathogens found in the environment that are capable of infecting humans and causing disease. Different classes of pathogens are discussed including bacteria, parasites and viruses. For each pathogen, data are provided on the incidence of the organism in a particular environmental matrix such as water, food or municipal waste. In addition, we discuss: the disease caused by the particular microbe; the mode of transmission; the incubation time needed within the host prior to the onset of disease; and the duration of illness. Fate and transport of pathogens in the environment are also described. A variety of bacterial pathogens are discussed including waterborne and waterbased bacteria. Parasites discussed include protozoa, nematodes, cestodes and trematodes. For viruses, both enteric and respiratory viruses are included.


COVID-19: Shades of Grey


title: Ischaemic Stroke in the Time of Coronavirus Disease 2019

text: Each year, between 1.1 and 1.5 million Europeans have a stroke(1). Two to three out of 10 patients die as a consequence of it and about one third remains functionally dependent(2). As we know, the likelihood of a favourable outcome in this disease relies heavily on patients presenting promptly after symptoms onset and on hospitals providing immediate access to optimized stroke care.


title: Homology modeling and virtual screening for antagonists of protease from yellow head virus

text: Yellow head virus (YHV) is one of the causative agents of shrimp viral disease. The prevention of YHV infection in shrimp has been developed by various methods, but it is still insufficient to protect the mass mortality in shrimp. New approaches for the antiviral drug development for viral infection have been focused on the inhibition of several potent viral enzymes, and thus the YHV protease is one of the interesting targets for developing antiviral drugs according to the pivotal roles of the enzyme in an early stage of viral propagation. In this study, a theoretical modeling of the YHV protease was constructed based on the folds of several known crystal structures of other viral proteases, and was subsequently used as a target for virtual screening—molecular docking against approximately 1364 NCI structurally diversity compounds. A complex between the protease and the hit compounds was investigated for intermolecular interactions by molecular dynamics simulations. Five best predicted compounds (NSC122819, NSC345647, NSC319990, NSC50650, and NSC5069) were tested against bacterial expressed YHV. The NSC122819 showed the best inhibitory characteristic among the candidates, while others showed more than 50 % of inhibition in the assay condition. These compounds could potentially be inhibitors for curing YHV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-014-2116-9) contains supplementary material, which is available to authorized users.


L’ennemi invisible


title: Infections and foreign bodies in the ear, nose and throat

text: Infections of the ear, nose and throat are common and may threaten life. Intracranial complications may arise from infections of the ear and paranasal sinuses. Orbital complications (loss of vision) may arise from infection of the paranasal sinus. Respiratory embarrassment may result from infections of the upper aerodiogestive tract. The clinical presentation, implications and management of foreign bodies in the ear, nose and throat depend on the nature of the foreign body and the site at which it becomes lodged.


docid: xswffcqj

title: Erfolglose Eilanträge im Zusammenhang mit der Corona-Pandemie : BVerfGG §§32 Abs. 1 i.V. mit 93d Abs. 2

text: Der Antrag auf Erlass einer einstweiligen Anordnung gegen die bayerische Verordnung über Ausgangsbeschränkungen anlässlich der Corona-Pandemie ist angesichts der überragenden Bedeutung von Leib und Leben abzulehnen – Folgenabwägung


title: Vaccines, emerging viruses, and how to avoid disaster

text: Rino Rappuoli is a graduate of Siena University, where he also earned his PhD before moving to the Sclavo Research Center, the Italian vaccine institute, also in Siena. He then spent two years in the USA, mostly at Harvard with John Murphy and Alwin Pappenheimer working on a new diphtheria vaccine based on a non-toxic mutant of diphtheria toxin which has since become the basis for conjugate vaccines against haemophilus, meningococcus, and pneumococcal infections, before returning to the Sclavo Research Center where he developed an acellular vaccine based on a mutant pertussis toxin. With many achievements in vaccine development to his credit, he is now Global Head of Vaccines Research and Development for Novartis Vaccines in Siena, and has most recently pioneered reverse vaccinology, in which the genome of the pathogen is screened for candidate antigenic and immunogenic vaccine components. We spoke to him about the potential for outbreaks of the kind we are now seeing with Ebolavirus in West Africa, and what can be done to prevent them.


title: COVID-19 and conflict: The devastating impact of withdrawing humanitarian support on universal health coverage in Yemen

text: Abstract The authors warn that, in the context of Yemen, the closure of humanitarian lifesaving programmes and shifting support toward health security, i.e. to support COVID-19 response, at the expense of primary health care support, will undermine existing health system strengthening efforts, worsen the humanitarian crisis and will accentuate the impact of COVID-19. The authors urge the international community and the Government of Yemen to carefully consider a more comprehensive approach to support Yemen’s COVID-19 response while maintaining, and strengthening, essential public health services.


title: COVID‐19 infection in pancreas transplant recipients

text: Coronavirus Disease 2019 (COVID‐19) has become a pandemic since first being described in January 2020. Clinical manifestations in non‐transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID‐19 infection occurring in pancreas transplant recipients.


Mayo Clinic Strategies for COVID-19 Precautions, Utilization of Personal Protective Equipment, and Conservation Strategies During the COVID-19 Pandemic


title: Response to "Dose Rationale for Favipiravir Use in Patients Infected With SARS‐CoV‐2"

text: We appreciate the letter by Eloy P., et al for their comments and complement regarding our review1-2 . Two independent in vitro studies indicated that favipiravir (T-705) inhibited SARS-CoV-2 replication in Vero E6 cells with EC50 values of 61.88 μM (9.4 μg/mL)3 and >100 μM (15.7 μg/mL)4 , respectively. Data from the authors' group suggests an EC50 value in the range 40-80 µg/mL (X. de Lamballerie & F. Touret, unpublished results). I agree with the authors' assumption that favipiravir shows similar EC50 against SARS-CoV-2 and EBOV. As favipiravir is a prodrug that requires metabolic activation through ribosylation and phosphorylation in the host cells to form its triphosphate form (favipiravir-RTP), we think that variation in favipiravir activation by the cultured cells may, at least partially, contribute to the difference in the in vitro EC50 among studies.


title: Recent advances in pharmacological research on Ecklonia species: a review

text: The genus Ecklonia (Lessoniaceae, Phaeophyceae), commonly called kelp (brown algae), is abundant on the coasts of Japan and Korea. During the past few decades, Ecklonia species have received tremendous attention for their wide range of therapeutic properties and multiple health benefits, such as great nutritional value and being rich in vitamins, minerals, dietary fiber, proteins, and polysaccharides. Several novel functional ingredients with diversified biological activities have been isolated and possess antimicrobial, antiviral, hepatoprotective, cardioprotective, anti-inflammatory, neuroprotective, anticarcinogenic, immunomodulatory, hypolipidemic, anti-diabetic, and antioxidant therapeutic properties. The present review discusses the phytochemical, pharmacological, therapeutic, nutritional, and health benefits of different species of genus Ecklonia, as well as their use in the prevention of disease and maintenance of good health.


title: Do checkpoint inhibitors compromise the cancer patients’ immunity and increase the vulnerability to COVID-19 infection?

text: The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has been declared a pandemic by the WHO that claimed the lives of thousands of people within a few months. Cancer patients represent a vulnerable population due to the acquired immunodeficiency associated with anti-cancer therapy. Immune checkpoint inhibitors have largely impacted the prognosis of a multitude of malignancies with significant improvement in survival outcomes and a different, tolerable toxicity profile. In this paper, we assess the safety of ICI administration in cancer patients during the coronavirus pandemic in order to guide the usage of these highly efficacious agents.


title: Complete genome sequence of an astrovirus identified in a domestic rabbit (Oryctolagus cuniculus) with gastroenteritis

text: A colony of domestic rabbits in Tennessee, USA, experienced a high-mortality (~90%) outbreak of enterocolitis. The clinical characteristics were one to six days of lethargy, bloating, and diarrhea, followed by death. Heavy intestinal coccidial load was a consistent finding as was mucoid enteropathy with cecal impaction. Preliminary analysis by electron microscopy revealed the presence of virus-like particles in the stool of one of the affected rabbits. Analysis using the Virochip, a viral detection microarray, suggested the presence of an astrovirus, and follow-up PCR and sequence determination revealed a previously uncharacterized member of that family. Metagenomic sequencing enabled the recovery of the complete viral genome, which contains the characteristic attributes of astrovirus genomes. Attempts to propagate the virus in tissue culture have yet to succeed. Although astroviruses cause gastroenteric disease in other mammals, the pathogenicity of this virus and the relationship to this outbreak remains to be determined. This study therefore defines a viral species and a potential rabbit pathogen.


title: Safe Hospital Preparedness in the Era of COVID-19: The Swiss Cheese Model

text: Abstract Since the first emergence in December 2019, COVID-19 rapidly spread out worldwide. During the pandemic of an emerging infectious disease, it is very important to prevent nosocomial outbreak and operate hospitals safely to maintain their functions. In this article, we presented the strategies for safe hospital operation based on the experiences of the Republic of Korea during early COVID-19 pandemic. Each hospital should keep multiple layered defenses to prevent even small cracks in the hospital’s quarantine system.


title: New causes and treatments for infectious diarrhea in children

text: Infectious diarrhea is a universal and important health problem in the pediatric population. An expanding number of potential viral, bacterial, and parasitic pathogens have been associated with diarrheal disease. However, the epidemiologic association of a microorganism with diarrhea is only one step in the process of identifying new pathogens. Once the virulence mechanisms of these organisms are elucidated, a causal relationship can be more readily defined. This article reviews the etiologic agents of diarrhea in the pediatric population and focuses on the newer treatment and prevention modalities, including probiotics and vaccinations, which are used increasingly to combat these diseases.


title: Risk factors for the evolutionary emergence of pathogens

text: Recent outbreaks of novel infectious diseases (e.g. SARS, influenza H1N1) have highlighted the threat of cross-species pathogen transmission. When first introduced to a population, a pathogen is often poorly adapted to its new host and must evolve in order to escape extinction. Theoretical arguments and empirical studies have suggested various factors to explain why some pathogens emerge and others do not, including host contact structure, pathogen adaptive pathways and mutation rates. Using a multi-type branching process, we model the spread of an introduced pathogen evolving through several strains. Extending previous models, we use a network-based approach to separate host contact patterns from pathogen transmissibility. We also allow for arbitrary adaptive pathways. These generalizations lead to novel predictions regarding the impact of hypothesized risk factors. Pathogen fitness depends on the host population in which it circulates, and the ‘riskiest’ contact distribution and adaptive pathway depend on initial transmissibility. Emergence probability is sensitive to mutation probabilities and number of adaptive steps required, with the possibility of large adaptive steps (e.g. simultaneous point mutations or recombination) having a dramatic effect. In most situations, increasing overall mutation probability increases the risk of emergence; however, notable exceptions arise when deleterious mutations are available.


title: Diseases, Emerging and Infectious

text: Abstract Emerging and infectious diseases have persisted as leading causes of global morbidity and mortality. Caused by pathogens including bacteria, viruses, parasites, or fungi, they are known to pose serious health threats to the world's population dating back to ancient Egypt. In the 14th Century alone, infectious diseases were responsible for decimating 20–45% of the world's population. The discovery of vaccines, coupled with improved sanitation, hygiene, and health care, witnessed the eradication of several infectious diseases, although some have resurfaced or are resurfacing since the latter part of the 20th Century. While geography partly define hotspots for emerging and infectious diseases, low socioeconomic development, poverty, and underfunded health care systems remain driving forces for the reoccurrence of these diseases among vulnerable populations who experience material deprivation. To eradicate infectious diseases, a global response will have to prioritize the allocation of resources by way of expertise and technology to areas that are most affected. Furthermore, an effective surveillance system, and a rigorous vaccine deployment regime targeting vulnerable persons and regions is desirable in mitigating the impacts of these diseases.


title: Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus

text: Summary Nitazoxanide is a broad-spectrum antiviral agent undergoing clinical development for treatment of influenza and other viral respiratory infections. Nitazoxanide exhibits in vitro activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and other coronaviruses, inhibiting expression of the viral N protein. Nitazoxanide also suppresses production of pro-inflammatory cytokines in peripheral blood mononuclear cells and suppresses interleukin 6 production in mice. Having been used extensively in clinical trials and in post-marketing experience, nitazoxanide is an attractive drug candidate for treatment of Middle East respiratory syndrome. Future research should include in vitro mechanism studies, animal models of MERS-CoV infection, clinical trials, including dose-ranging trials, and evaluation of combination therapy with other potential MERS-CoV antivirals.


title: 15 An overview of automated room disinfection systems: When to use them and how to choose them

text: Abstract Conventional disinfection methods are limited by reliance on the operator to ensure appropriate selection, formulation, distribution, and contact time of the agent. Automated room disinfection (ARD) systems remove or reduce reliance on operators and so they have the potential to improve the efficacy of terminal disinfection. The most commonly used systems are hydrogen peroxide vapor (H2O2 vapor), aerosolized hydrogen peroxide (aHP), and ultraviolet (UV) light. These systems have important differences in their active agent, delivery mechanism, efficacy, process time, and ease of use. The choice of ARD system should be influenced by the intended application, the evidence base for effectiveness, practicalities of implementation, and cost considerations.


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title: Quantitative sense-specific determination of murine coronavirus RNA by reverse transcription polymerase chain reaction

text: Abstract In many applications, it is useful to know the sense and amount of viral RNAs present in a sample. In theory, sense-specific measurement of viral RNAs may be achieved by reverse transcription polymerase chain reaction (RT-PCR) assays which utilize primers of defined polarity during the RT step. However, in practice, it has been shown that such assays are prone to artifacts, such as non-specific priming, which drastically diminish their reliability. Using murine coronavirus MHV-4 as a model, we describe and validate several modifications of the RT-PCR procedure which eliminate these artifacts. Key RT-PCR parameters which were optimized include the design of tagged primers, DNase treatment of in vitro transcribed RNA standards, specification of temperature differences between RT and PCR annealing steps, and use of competitive RNA templates for quantitative assays. The assays described may be used to determine the sense and abundance of any viral or host RNA of interest in complex biological specimens.


title: First introduction of pandemic influenza A/H1N1 and detection of respiratory viruses in pediatric patients in Central African Republic

text: BACKGROUND: Acute viral respiratory illnesses in children in sub-Saharan Africa have received relatively little attention, although they are much more frequent causes of morbidity and mortality than in developed countries. Active surveillance is essential to identify the causative agents and to improve clinical management, especially in the context of possible circulation of pandemic viruses. FINDINGS: A prospective study was conducted in the Central African Republic (CAR) between January and December 2010 among infants and children aged 0–15 years attending sentinel sites for influenza-like illness or acute respiratory illness. Nasopharyngeal swabs were collected, and one-step real-time and multiplex reverse transcription-polymerase chain reaction were used to detect respiratory viruses. Respiratory viruses were detected in 49 of the 329 (14.9%) nasopharyngeal samples: 29 (8.8%) contained influenza viruses (5 (1.5%) had pandemic influenza A/H1N1 virus and 24 (7.3%) had influenza B viruses), 11 (3.3%) contained parainfluenza viruses types 1 and 3 and 9 (2.7%) contained human respiratory syncytial virus. Most cases were detected during the rainy season in the CAR. Analysis of the amplicon sequences confirmed the identity of each detected virus. CONCLUSIONS: The influenza surveillance system in the CAR has provided valuable data on the seasonality of influenza and the circulation of other respiratory viruses. Our network could therefore play a valuable role in the prevention and control of influenza epidemics in the CAR.


title: Artificial Intelligence in Modern Medicine – The Evolving Necessity of the Present and Role in Transforming the Future of Medical Care

text: The dexterity of computer systems to resemble and mimic human intelligence is artificial intelligence. Artificial intelligence has reformed the diagnostic and therapeutic precision and competence in various fields of medicine. Artificial intelligence appears to play a bright role in medical diagnosis. Computer systems using artificial intelligence help in the assessment of medical images and enormous data. This research aims to identify how artificial intelligence-based technology is reforming the art of medicine. Artificial intelligence empowers providers in improving efficiency and overall healthcare. Newer machine learning techniques lead the automatic diagnostic systems. Areas of medicine such as medical imaging, automated clinical decision-making support have made significant advances with respect to artificial intelligence technology. With improved diagnosis and prognosis, artificial intelligence possesses the capability to revolutionize various fields of medicine. Artificial intelligence has its own limitations and cannot replace a bedside clinician. In the evolving modern medical digital world, physicians need to support artificial intelligence rather than fear it replacing trained physicians for improved healthcare.


title: Cotranslational Folding Stimulates Programmed Ribosomal Frameshifting in the Alphavirus Structural Polyprotein

text: Viruses maximize their genetic coding capacity through a variety of biochemical mechanisms including programmed ribosomal frameshifting (PRF), which facilitates the production of multiple proteins from a single transcript. PRF is typically stimulated by structural elements within the mRNA that generate mechanical tension between the transcript and ribosome. However, in this work we show that the forces generated by the cotranslational folding of the nascent polypeptide chain can also enhance PRF. Using an array of biochemical, cellular, and computational techniques, we first demonstrate that the Sindbis virus structural polyprotein forms two competing topological isomers during biosynthesis at the ribosome-translocon complex. We then show that the formation of one of these topological isomers is linked to PRF. Coarse-grained molecular dynamic simulations reveal that the translocon-mediated membrane integration of a transmembrane domain upstream from the ribosomal slip-site generates a force on the nascent polypeptide chain that scales with observed frameshifting. Together, our results demonstrate that cotranslational folding of this protein generates a tension that stimulates PRF. To our knowledge, this constitutes the first example in which the conformational state of the nascent chain has been linked to PRF. These findings raise the possibility that, in addition to RNA-mediated translational recoding, a variety of cotranslational folding and/ or binding events may also stimulate PRF.


title: Immunological Response to Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex: An RNA-Sequence Analysis of the Bronchial Lymph Node Transcriptome

text: Susceptibility to bovine respiratory disease (BRD) is multi-factorial and is influenced by stress in conjunction with infection by both bacterial and viral pathogens. While vaccination is broadly used in an effort to prevent BRD, it is far from being fully protective and cases diagnosed from a combination of observed clinical signs without any attempt at identifying the causal pathogens are usually treated with antibiotics. Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence. In this study, we employed RNA sequencing to examine the bronchial lymph node transcriptomes of controls and beef cattle which had individually been experimentally challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimia haemolytica or Mycoplasma bovis to identify the genes that are involved in the bovine immune response to infection. We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD. Mutations affecting the expression or amino acid composition of these genes may affect disease susceptibility and could be incorporated into molecular breeding programs. Genes involved in innate immunity were generally found to be differentially expressed between the control and pathogen-challenged animals suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.


title: Diabetes self-management amid COVID-19 pandemic

text: Abstract Background and aims COVID-19 pandemic has challenged the physician-centered approach of diabetes care in India that is primarily based on routine clinic visits. We aim to review the various aspects of patient-centered care via diabetes self-management education based on available literature. Methods This is a narrative review using Pubmed, EMBASE and Google Scholar search till March 29, 2020. Search terms were “COVID-19”, “diabetes self-care”, “diabetes self-management education”, “DSME”, “diabetes self-management in India”, “diabetes self-care in India” and “DSME in India”. Results We have discussed an educational plan on diabetes self-management that can be adopted for people with diabetes mellitus in our country amid the ongoing pandemic. We have also identified the barriers to diabetes self-management in the current scenario and suggested possible solutions to overcome those. Conclusions We have reemphasized the need for a simultaneous patient-centered approach in routine diabetes care that has to be coordinated by a multidisciplinary team amid the ongoing COVID-19 pandemic.


title: Etiology of respiratory tract infections in the community and clinic in Ilorin, Nigeria

text: OBJECTIVE: Recognizing increasing interest in community disease surveillance globally, the goal of this study was to investigate whether respiratory viruses circulating in the community may be represented through clinical (hospital) surveillance in Nigeria. RESULTS: Children were selected via convenience sampling from communities and a tertiary care center (n = 91) during spring 2017 in Ilorin, Nigeria. Nasal swabs were collected and tested using polymerase chain reaction. The majority (79.1%) of subjects were under 6 years old, of whom 46 were infected (63.9%). A total of 33 of the 91 subjects had one or more respiratory tract virus; there were 10 cases of triple infection and 5 of quadruple. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses in the clinical sample; present in 93.8% (15/16) of clinical subjects, and 6.7% (5/75) of community subjects (significant difference, p < 0.001). Coronavirus OC43 was the most common virus detected in community members (13.3%, 10/75). A different strain, Coronavirus OC 229 E/NL63 was detected among subjects from the clinic (2/16) and not detected in the community. This pilot study provides evidence that data from the community can potentially represent different information than that sourced clinically, suggesting the need for community surveillance to enhance public health efforts and scientific understanding of respiratory infections.


title: Virus Factories and Mini-Organelles Generated for Virus Replication

text: Abstract Many viruses replicate and assemble in subcellular microenvironments called virus factories or ‘viroplasm.’ Virus factories increase the efficiency of replication and at the same time protect viruses from antiviral defenses. We describe how viruses reorganize cellular membrane compartments and cytoskeleton to generate these ‘mini-organelles’ and how these rearrangements parallel cellular responses to stress such as protein aggregation and DNA damage.


title: Viral etiology of severe acute respiratory infections in hospitalized children in Cameroon, 2011–2013

text: BACKGROUND: Severe acute respiratory illness (SARI) is recognized as an important cause of morbidity, mortality, and hospitalization among children in developing countries. Little is known, however, in tropical countries like Cameroon about the cause and seasonality of respiratory infections, especially in hospitalized settings. Objectives: Our study investigates the viral etiology and seasonality of SARI in hospitalized children in Yaounde, Cameroon. METHODS: Prospective clinic surveillance was conducted to identify hospitalized children aged ≤15 years presenting with respiratory symptoms ≤5‐day duration. Demographic and clinical data, and respiratory specimens were collected. Nasopharyngeal samples were tested for 17 respiratory viruses using a multiplex polymerase chain reaction. The viral distribution and demographic data were statistically analyzed. RESULTS: From September 2011 through September 2013, 347 children aged ≤15 years were enrolled. At least one virus was identified in each of 65·4% children, of which 29·5% were coinfections; 27·3% were positive for human adenovirus (hAdV), 13·2% for human respiratory syncytial virus (hRSV), 11·5% for rhinovirus/enterovirus (RV/EV), 10·6% for human bocavirus (hBoV), 9·8% for influenza virus (Inf), 6·6% for human parainfluenza virus (hPIV), 5·7% for human coronavirus (hCoV), and 2·3% for human metapneumovirus (hMPV). While hRSV showed seasonal patterns, hAdV and RV/EV were detected throughout the year and no evident temporal patterns were observed for the remaining viruses. CONCLUSION: Respiratory viruses were associated with a high burden of hospitalizations among children in Cameroon. Nevertheless, additional studies evaluating asymptomatic Cameroonian children will be important in understanding the relationship between viral carriage and disease.


title: Innate sensing of oxidation-specific epitopes in health and disease

text: Ageing, infections and inflammation result in oxidative stress that can irreversibly damage cellular structures. The oxidative damage of lipids in membranes or lipoproteins is one of these deleterious consequences that not only alters lipid function but also leads to the formation of neo-self epitopes — oxidation-specific epitopes (OSEs) — which are present on dying cells and damaged proteins. OSEs represent endogenous damage-associated molecular patterns that are recognized by pattern recognition receptors and the proteins of the innate immune system, and thereby enable the host to sense and remove dangerous biological waste and to maintain homeostasis. If this system is dysfunctional or overwhelmed, the accumulation of OSEs can trigger chronic inflammation and the development of diseases, such as atherosclerosis and age-related macular degeneration. Understanding the molecular components and mechanisms that are involved in this process will help to identify individuals with an increased risk of developing chronic inflammation, and will also help to indicate novel modes of therapeutic intervention. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri.2016.63) contains supplementary material, which is available to authorized users.


title: Chapter 10 Animal Models No Model Is Perfect, but Many Are Useful

text: Abstract Full evaluation of the interactions between a virus and host during infection and clearance requires a living organism. A live animal is also necessary for development of vaccines requiring evaluation of immunogenicity and an immune response that protects from challenge. Study of the natural host for the virus is ideal, but often not possible. Mice have emerged over the last 60 years as the most popular animal model for studying viral pathogenesis due to extensive genetic and immunologic characterization, wide availability of reagents, inbred and transgenic strains, and small size. However, responses in mice are not always predictive of those in the natural host. Other species commonly used include guinea pigs, ferrets, chickens, and nonhuman primates. When choosing an animal model for a study, factors to be considered include host susceptibility to the infection, animal size, cost, availability of housing and reagents, potential confounding coinfections, and ethical restrictions.


title: Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit

text: Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5–9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. [Figure: see text]


title: Unbiased metagenomic sequencing complements specific routine diagnostic methods and increases chances to detect rare viral strains

text: Abstract Multiplex PCR assays for respiratory viruses are widely used in routine diagnostics, as they are highly sensitive, rapid, and cost effective. However, depending on the assay system, cross-reactivity between viruses that share a high sequence homology as well as detection of rare virus isolates with sequence variations can be problematic. Virus sequence-independent metagenomic high-throughput sequencing allows for accurate detection of all virus species in a given sample, as we demonstrate here for human Enterovirus and Rhinovirus in a lung transplant patient. While early in infection a commercial PCR assay recorded Rhinovirus, high-throughput sequencing correctly identified human Enterovirus C104 as the source of infection, highlighting the potential of the technology and the benefit of applying open assay formats in complex diagnostic situations.


Please cite this paper as: Masuet‐Aumatell et al. (2012) Prevention of influenza among travellers attending at a UK travel clinic: beliefs and perceptions. A cross‐sectional study. Influenza and Other Respiratory Viruses 7(4), 574–583. Background Travellers’ compliance with measures to prevent influenza through the use of antivirals and influenza vaccine remains very poor despite influenza being one of the commonest travel and vaccine‐preventable diseases. A study was undertaken to assess travellers’ beliefs, perceptions and intentions to take antivirals for the treatment and prevention of influenza during the H1N1 pandemic. Methods A cross‐sectional survey (n = 96) of travellers who attended the Royal Free Travel Health Centre, London, UK was undertaken in September 2009. A self‐administered questionnaire was completed by a traveller in advance of their pre‐travel health consultation. Logistic regression identified variables independently associated with compliance. Results Influenza vaccination uptake for the 5 years preceding the study was found to be 20·8%. This was statistically significantly higher for older travellers and those with underlying health conditions (P < 0·005). Mean intention to comply with antiviral drugs on a preventive and therapeutic basis was 58% and 72%, respectively, and this varied markedly with age and with dispensed antimalarial chemoprophylaxis. Conclusion This study identifies some beliefs and perceptions travellers consider with regard to the therapeutic and preventive influenza use of antivirals during the H1N1 pandemic; it underscores the importance of travellers receiving hemisphere appropriate influenza vaccination. The external validity of these study findings requires further corroboration involving other travel clinics and different cohorts of travellers during seasonal activity or outbreaks of influenza. These findings could guide the development of future strategies for the prevention of influenza in travellers.


title: Household practices related to disease transmission between animals and humans in rural Cambodia

text: BACKGROUND: Zoonotic diseases are disproportionately affecting poor societies in low-income countries and pose a growing threat to public health and global food security. Rural Cambodian households may face an increased likelihood of exposure to zoonotic diseases as people there live in close association with livestock. The objectives of the study was to identify practices known to influence zoonosis transmission in rural Cambodian households and relate the practices to agro-ecological region, socio-economic position, demographics, livestock management and zoonosis awareness. METHODS: The study was conducted in three different agro-ecological regions of Cambodia; 10 villages each in the central lowlands, north-west wetlands and on the south coast, where information was obtained in questionnaires administered to 300 households, and 30 village heads and animal health workers. RESULTS: Descriptive analysis revealed a gender difference in responsibility for livestock and that the main purpose of raising livestock was for sale. Few respondents (6%) perceived a likelihood of disease transmission in their village between livestock, humans and wildlife, despite household practices related to zoonosis transmission being common. More than one-forth of households practised behaviours such as culling sick animals for consumption, eating animals found dead and allowing animals to enter sleeping and food preparation areas. Associations between household practices and possible explanatory factors were analysed with multivariable models using generalised estimation equations to account for clustering of practices within villages. Factors found to influence household practices were agro-ecological region, socio-economic position, number of people in the household, livestock species reared and awareness of zoonoses. CONCLUSIONS: Cambodia has experienced numerous fatal human cases of zoonotic influenza and extensive influenza information campaigns have been run, yet only a few of the households surveyed here reported the threat of zoonosis to be a concern in their village. Zoonosis awareness was positively related to hand washing behaviour, but other practices associated with an increased or decreased likelihood of exposure to zoonotic pathogens were unaffected by awareness. The findings indicate a knowledge-to-action gap among rural farmers and highlight the necessity for reconstructed interventions in zoonotic disease control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1811-5) contains supplementary material, which is available to authorized users.


title: Development of a SARS Coronavirus Vaccine from Recombinant Spike Protein Plus Delta Inulin Adjuvant

text: Given periodic outbreaks of fatal human infections caused by coronaviruses, development of an optimal coronavirus vaccine platform capable of rapid production is an ongoing priority. This chapter describes the use of an insect cell expression system for rapid production of a recombinant vaccine against severe acute respiratory syndrome coronavirus (SARS). Detailed methods are presented for expression, purification, and release testing of SARS recombinant spike protein antigen, followed by adjuvant formulation and animal testing. The methods herein described for rapid development of a highly protective SARS vaccine are equally suited to rapid development of vaccines against other fatal human coronavirus infections, e.g., the MERS coronavirus.


title: Haemovigilance of reactions associated with red blood cell transfusion: comparison across 17 Countries

text: BACKGROUND AND OBJECTIVES: The recent establishment of the National Healthcare Safety Network Hemovigilance Module in the United States affords an opportunity to compare results with those of other developed nations. MATERIALS AND METHODS: Using data from national haemovigilance systems, reactions associated with red blood cell (RBC) transfusion and residual risks of transfusion‐transmitted infectious diseases were assembled from 17 nations. Country‐specific rates of adverse events were pooled using random‐effects Poisson regression. RESULTS: Febrile non‐haemolytic and delayed serologic transfusion reactions were the most frequent adverse events reported after RBC transfusion, occurring in 26 patients per 100 000 RBC units and 25 patients per 100 000 RBC units administered, respectively. Rates of allergic, febrile non‐haemolytic and delayed haemolytic transfusion reactions in the United States were significantly greater than the pooled rates from other countries. Frequencies of adverse events generated from the national haemovigilance programme in the United States were considerably lower than when obtained through active surveillance. CONCLUSION: Haemovigilance reports of adverse events in the United States are comparable to, or greater than, reports from other developed countries. Rates generated from haemovigilance programmes are lower than those obtained through active surveillance. The lack of universal leucoreduction of RBC units may be a contributing factor to the higher rate of some adverse events in the United States.


title: Emergence of canine parvovirus type 2c in domestic dogs and cats from Thailand

text: Canine parvovirus type 2 (CPV‐2) is an important pathogen causing haemorrhagic enteritis in domestic dogs and wildlife worldwide. In early 2000, canine parvovirus type 2c (CPV‐2c) was first reported and subsequently became a predominant subtype circulating in Europe and the Americas. CPV‐2c has also been reported in Asia, including cases in China, India, Taiwan and Vietnam. However, CPV‐2c has never been reported in Thailand. In this study, we conducted viral enteric disease surveillance in dogs and cats in Thailand during 2016–2018. During 20 months of surveillance, 507 rectal swab samples were collected from dogs (n = 444) and cats (n = 63) with and without clinical signs. The samples were examined for parvovirus by using VP2 gene‐specific PCR for parvovirus. Our results showed that the positivity of canine parvovirus (CPV) was 29.95% and that of feline parvovirus (FPV) was 58.73%. In this study, we characterized 34 parvoviruses by VP2 gene sequencing. Moreover, two Thai‐CPV‐2 (Dog/CU‐24 and Cat/CU‐21) were characterized by whole genome sequencing. The phylogenetic results showed that Thai‐CPV‐2 had the highest nucleotide identities and clustered with Asian‐CPV‐2c but were in separate subclusters from the North American and European CPV‐2c. Similarly, whole genome analyses showed that Thai‐CPVs are closely related to Asian‐CPV‐2c, with unique amino acids at positions 297A, 324I, 370R and 426E. In summary, our results demonstrated the emergence of Asian‐CPV‐2c in dogs and cats in Thailand. Thus, the surveillance of CPV‐2 in domestic dogs and cats should be further conducted on a larger scale to determine the dynamics of predominant variants and their distributions in the country and in the Southeast Asia region.


title: Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk

text: BACKGROUND: The new Middle East respiratory syndrome coronavirus (MERS-CoV) infection shares many clinical, epidemiological, and virological similarities with that of severe acute respiratory syndrome (SARS)-CoV. We aimed to estimate virus transmissibility and the epidemic potential of MERS-CoV, and to compare the results with similar findings obtained for prepandemic SARS. METHODS: We retrieved data for MERS-CoV clusters from the WHO summary and subsequent reports, and published descriptions of cases, and took into account 55 of the 64 laboratory-confirmed cases of MERS-CoV reported as of June 21, 2013, excluding cases notified in the previous 2 weeks. To assess the interhuman transmissibility of MERS-CoV, we used Bayesian analysis to estimate the basic reproduction number (R(0)) and compared it to that of prepandemic SARS. We considered two scenarios, depending on the interpretation of the MERS-CoV cluster-size data. RESULTS: With our most pessimistic scenario (scenario 2), we estimated MERS-CoV R(0) to be 0·69 (95% CI 0·50–0·92); by contrast, the R(0) for prepandemic SARS-CoV was 0·80 (0·54–1·13). Our optimistic scenario (scenario 1) yielded a MERS-CoV R(0) of 0·60 (0·42–0·80). Because of recent implementation of effective contact tracing and isolation procedures, further MERS-CoV transmission data might no longer describe an entire cluster, but only secondary infections directly caused by the index patient. Hence, we calculated that, under scenario 2, eight or more secondary infections caused by the next index patient would translate into a 5% or higher chance that the revised MERS-CoV R(0) would exceed 1—ie, that MERS-CoV might have pandemic potential. INTERPRETATION: Our analysis suggests that MERS-CoV does not yet have pandemic potential. We recommend enhanced surveillance, active contact tracing, and vigorous searches for the MERS-CoV animal hosts and transmission routes to human beings. FUNDING: Agence Nationale de la Recherche (Labex Integrative Biology of Emerging Infectious Diseases), and the European Community's Seventh Framework Programme project PREDEMICS.


title: Method for contamination of filtering facepiece respirators by deposition of MS2 viral aerosols

text: Abstract A droplet/aerosol loading chamber was designed to deliver uniform droplets/aerosols onto substrates. An ultrasonic nebulizer was used to produce virus-containing droplets from artificial saliva to emulate those from coughing and sneezing. The operating conditions were determined by adjusting various parameters to achieve loading density and uniformity requirements. The count median diameter and mass median diameter were 0.5–2 and 3–4μm, respectively, around the loading location when 35% relative humidity was applied. The average loading density was ∼2×103 plaque-forming units/cm2 for 5-min loading time with a virus titer of 107 plaque-forming units/mL. Six different filtering facepiece respirators from commercial sources were loaded to evaluate uniform distribution. For each of the six FFRs, the virus loading uniformity within a sample and across numerous samples was 19.21% and 12.20%, respectively. This system supports a standard method for loading viable bioaerosols onto specimen surfaces when different decontamination techniques are to be compared.


Compassionate use remdesivir for treatment of severe COVID-19 in pregnant women at a United States academic center


title: Cuba y seguridad sanitaria mundial: Cuba’s role in global health security

text: Cuba has been largely absent in academic and policy discourse on global health security, yet Cuba’s history of medical internationalism and its domestic health system have much to offer contemporary global health security debates. In this paper, we examine what we identify as key traits of Cuban health security, as they play out on both international and domestic fronts. We argue that Cuba demonstrates a strong health security capacity, both in terms of its health systems support and crisis response activities internationally, and its domestic disease control activities rooted in an integrated health system with a focus on universal healthcare. Health security in Cuba, however, also faces challenges. These concern Cuba’s visibility and participation in the broader global health security architecture, the social controls exercised by the state in managing disease threats in Cuban territory, and the resource constraints facing the island—in particular, the effects of the US embargo. While Cuba does not frame its disease control activities within the discourse of health security, we argue that the Cuban case demonstrates that it is possible to make strides to improve capacity for health security in resource-constrained settings. The successes and challenges facing health security in Cuba, moreover, provide points of reflection relevant to the pursuit of health security globally and are thus worth further consideration in broader health security discussions.


title: Peptide Bioinformatics- Peptide Classification Using Peptide Machines

text: Peptides scanned from whole protein sequences are the core information for many peptide bioinformatics research subjects, such as functional site prediction, protein structure identification, and protein function recognition. In these applications, we normally need to assign a peptide to one of the given categories using a computer model. They are therefore referred to as peptide classification applications. Among various machine learning approaches, including neural networks, peptide machines have demonstrated excellent performance compared with various conventional machine learning approaches in many applications. This chapter discusses the basic concepts of peptide classification, commonly used feature extraction methods, three peptide machines, and some important issues in peptide classification.


title: Human rights violations in organ procurement practice in China

text: BACKGROUND: Over 90% of the organs transplanted in China before 2010 were procured from prisoners. Although Chinese officials announced in December 2014 that the country would completely cease using organs harvested from prisoners, no regulatory adjustments or changes in China’s organ donation laws followed. As a result, the use of prisoner organs remains legal in China if consent is obtained. DISCUSSION: We have collected and analysed available evidence on human rights violations in the organ procurement practice in China. We demonstrate that the practice not only violates international ethics standards, it is also associated with a large scale neglect of fundamental human rights. This includes organ procurement without consent from prisoners or their families as well as procurement of organs from incompletely executed, still-living prisoners. The human rights critique of these practices will also address the specific situatedness of prisoners, often conditioned and traumatized by a cascade of human rights abuses in judicial structures. CONCLUSION: To end the unethical practice and the abuse associated with it, we suggest to inextricably bind the use of human organs procured in the Chinese transplant system to enacting Chinese legislation prohibiting the use of organs from executed prisoners and making explicit rules for law enforcement. Other than that, the international community must cease to abet the continuation of the present system by demanding an authoritative ban on the use of organs from executed Chinese prisoners. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12910-017-0169-x) contains supplementary material, which is available to authorized users.


title: Assembling an ion channel: ORF 3a from SARS‐CoV

text: Protein 3a is a 274 amino acid polytopic channel protein with three putative transmembrane domains (TMDs) encoded by severe acute respiratory syndrome corona virus (SARS‐CoV). Synthetic peptides corresponding to each of its three individual transmembrane domains (TMDs) are reconstituted into artificial lipid bilayers. Only TMD2 and TMD3 induce channel activity. Reconstitution of the peptides as TMD1 + TMD3 as well as TMD2 + TMD3 in a 1 : 1 mixture induces membrane activity for both mixtures. In a 1 : 1 : 1 mixture, channel like behavior is almost restored. Expression of full length 3a and reconstitution into artificial lipid bilayers reveal a weak cation selective (P (K) ≈ 2 P(Cl)) rectifying channel. In the presence of nonphysiological concentration of Ca‐ions the channel develops channel activity. © 2013 Wiley Periodicals, Inc. Biopolymers 99:628–635, 2013.


title: Epidemiological and clinical study of viral respiratory tract infections in children from Italy

text: Impact of recently discovered viruses on epidemiology of acute respiratory tract infections (ARTI) is still unclear. We studied the impact of recently discovered human metapneumovirus (hMPV), human bocavirus (HBoV), and new coronaviruses (HCoV‐NL63 and HKU1) on the global epidemiology of ARTI. From October 2006 to April 2007, 237 pediatric patients affected by ARTI were enrolled in our study. Specimens were tested for respiratory viruses by polymerase chain reaction. One hundred twenty‐four out of 237 samples (52.3%) were positive for one or more viruses. Picornaviruses were the most prevalent viruses (n = 61, 43.6%), followed by respiratory syncytial virus (n = 34, 24.3%) and Adenovirus (n = 25, 17.9%); hMPV (n = 9, 6.4%) was the fourth most common virus detected. HBoV and HCoV showed a low prevalence (respectively 2.9% and 2.1%). RSV was the prevalent agent of LRTI (38%). Viruses were identified in more than 50% of the studied ARTI, providing useful information on clinical features and epidemiology of specific agents affecting children in cold months. Although routine surveillance of respiratory viruses does not seem cost‐effective, continuous monitoring of ARTI etiology could be a useful tool for planning resources for the development of new vaccines and antiviral agents. J. Med. Virol. 81:750–756, 2009 © 2009 Wiley‐Liss, Inc.


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title: Predictive Value of Sudden Olfactory Loss in the Diagnosis of COVID-19

text: INTRODUCTION: Recent reports suggest that sudden smell loss might be a symptom of SARS-CoV-2 infection. The aim of this study was to investigate the frequency of olfactory loss in an outpatient population who presented to a coronavirus testing center during a 2-week period and to evaluate the diagnostic value of the symptom “sudden smell loss” for screening procedures. METHODS: In this cross-sectional controlled cohort study, 500 patients who presented with symptoms of a common cold to a corona testing center and fulfilled corona testing criteria completed a standardized diagnostic questionnaire which included the patients' main symptoms, time course, and an additional self-assessment of the patients' current smell, taste function, and nasal breathing compared to the level before the onset of symptoms. RESULTS: Out of the 500 patients, 69 presented with olfactory loss. Twenty-two of them subsequently tested positive for SARS-CoV-2. Only 12 out of the patients without olfactory loss tested positive, resulting in a frequency of 64.7% for the symptom “sudden smell loss” in COVID-19 patients. Compared to COVID-19 patients without smell loss, they were significantly younger and less severely affected. Changes in nasal airflow were significantly more pronounced in SARS-CoV-2 negative patients with olfactory complaints compared to the patients with smell loss who tested positive for SARS-CoV-2. By excluding patients with a blocked nose, the symptom “sudden smell loss” can be attested a high specificity (97%) and a sensitivity of 65% with a positive predictive value of 63% and negative predictive value of 97% for COVID-19. CONCLUSION: Considering the high frequency of smell loss in non-hospitalized COVID-19 patients, acute olfactory impairment should be recognized as an early symptom of the disease and should be tested for on a regular basis. In contrast to other acute viral smell impairment, COVID-19-associated smell loss seems to be only rarely accompanied by a severely blocked nose.


title: Surface Plasmon Resonance: A Boon for Viral Diagnostics

text: Abstract Rapidly evolving viral strains leading to epidemics and pandemics necessitates quick diagnostics and treatment to halt the progressive march of the disease. Optical biosensors like surface plasmon resonance (SPR) have emerged in recent times as a most reliable diagnostic device owing to their portability, reproducibility, sensitivity and specificity. SPR analyzes the kinetics of biomolecular interactions in a label-free manner. It has surpassed the conventional virus detection methods in its utility, particularly in medical diagnostics and healthcare. However, the requirement of high-end infrastructure setup and trained manpower are some of the roadblocks in realizing the true potential of SPR. This platform needs further improvisation in terms of simplicity, affordability and portability before it could be utilized in need-based remote areas of under-developed and developing countries with limited infrastructure.


title: Author Correction: China’s response to a novel coronavirus stands in stark contrast to the 2002 SARS outbreak response

text: An amendment to this paper has been published and can be accessed via a link at the top of the paper.


title: Gene silencing by RNAi in mouse Sertoli cells

text: BACKGROUND: RNA interference (RNAi) is a valuable tool in the investigation of gene function. The purpose of this study was to examine the availability, target cell types and efficiency of RNAi in the mouse seminiferous epithelium. METHODS: The experimental model was based on transgenic mice expressing EGFP (enhanced green fluorescent protein). RNAi was induced by in vivo transfection of plasmid vectors encoding for short hairpin RNAs (shRNAs) targeting EGFP. shRNAs were transfected in vivo by microinjection into the seminiferous tubules via the rete testis followed by square wave electroporation. As a transfection reporter, expression of red fluorescent protein (HcRed 1) was used. Cell types, the efficiency of both transfections and RNAi were all evaluated. RESULTS: Sertoli cells were the main transfected cells. A reduction of about 40% in the level of EGFP protein was detected in cells successfully transfected both in vivo and in vitro. However, the efficiency of in vivo transfection was low. CONCLUSION: In adult seminiferous epithelial cells, in vivo post-transcriptional gene silencing mediated by RNAi via shRNA is efficient in Sertoli cells. Similar levels of RNAi were detected both in vivo and in vitro. This also indicates that Sertoli cells have the necessary silencing machinery to repress the expression of endogenous genes via RNAi.


title: Investigations into the presence of nidoviruses in pythons

text: BACKGROUND: Pneumonia and stomatitis represent severe and often fatal diseases in different captive snakes. Apart from bacterial infections, paramyxo-, adeno-, reo- and arenaviruses cause these diseases. In 2014, new viruses emerged as the cause of pneumonia in pythons. In a few publications, nidoviruses have been reported in association with pneumonia in ball pythons and a tiger python. The viruses were found using new sequencing methods from the organ tissue of dead animals. METHODS: Severe pneumonia and stomatitis resulted in a high mortality rate in a captive breeding collection of green tree pythons. Unbiased deep sequencing lead to the detection of nidoviral sequences. A developed RT-qPCR was used to confirm the metagenome results and to determine the importance of this virus. A total of 1554 different boid snakes, including animals suffering from respiratory diseases as well as healthy controls, were screened for nidoviruses. Furthermore, in addition to two full-length sequences, partial sequences were generated from different snake species. RESULTS: The assembled full-length snake nidovirus genomes share only an overall genome sequence identity of less than 66.9% to other published snake nidoviruses and new partial sequences vary between 99.89 and 79.4%. Highest viral loads were detected in lung samples. The snake nidovirus was not only present in diseased animals, but also in snakes showing no typical clinical signs. CONCLUSIONS: Our findings further highlight the possible importance of snake nidoviruses in respiratory diseases and proof multiple circulating strains with varying disease potential. Nidovirus detection in clinical healthy individuals might represent testing during the incubation period or reconvalescence. Our investigations show new aspects of nidovirus infections in pythons. Nidoviruses should be included in routine diagnostic workup of diseased reptiles.


docid: jvrbuiqj

title: Ten Most Important Accomplishments in Risk Analysis, 1980–2010


title: Genesis of an emergency public drug information website by the French Society of Pharmacology and Therapeutics during the COVID‐19 pandemic

text: On March 16, 2020, the French Society of Pharmacology and Therapeutics put online a national Question and Answer (Q&A) website, http://https%20%5Ch://sfpt-fr.org/covid19 on the proper use of drugs during the COVID‐19 pandemic. The working group “Drugs and COVID‐19” was composed of a scientific council, an editorial team and experts in the field. The first questions were posted online during the first evening of home‐confinement in France, March 17, 2020. Six weeks later, 140 Q&As have been posted. Questions on the controversial use of hydroxychloroquine and to a lesser extent concerning azithromycin have been the most consulted Q&As. Q&As has been consulted 226,014 times in 41 days. This large visibility was obtained through an early communication on Twitter, Facebook, traditional print and web media. In addition, an early communication through the French Ministry of Health and the French National Agency for Medicines and Health Products Safety ANSM had a large impact in terms of daily number of views. There is a pressing need to sustain a public drug information service combining the expertise of scholarly pharmacology societies, pharmacovigilance network, and the Ministry of Health to quickly provide understandable, clear, expert answers to the general population’s concerns regarding COVID‐19 and drug use and to counter fake news.


title: Medico-legal assessment of COVID-19 infection in the workplace

text: Abstract Spain is one of the countries most affected by the COVID-19 pandemic. To date, 22% of reported cases are healthcare professionals, and 76% of them are women. Given that many healthcare professionals may have been infected in their workplace, we have reviewed the occupational health challenges posed by COVID-19. The Spanish laws and the recommendations of the International Labor Organization are described. The review covers the classification of SARS-CoV-2 as a biological agent in group 3 and of COVID-19 as an occupational accident or disease, its repercussions in temporary and permanent disabilities, sequelae and death, and the possible claims of those who may have developed the disease due to the lack of preventive measures.