title: Discovery of novel Cyclophilin D inhibitors starting from three dimensional fragments with millimolar potencies

text: Abstract Fragment-based screening by SPR enabled the discovery of chemical diverse fragment hits with millimolar binding affinities to the peptidyl-prolyl isomerase Cyclophilin D (CypD). The CypD protein crystal structures of 6 fragment hits provided the basis for subsequent medicinal chemistry optimization by fragment merging and linking yielding three different chemical series with either urea, oxalyl or amide linkers connecting millimolar fragments in the S1′ and S2 pockets. We successfully improved the in vitro CypD potencies in the biochemical FP and PPIase assays and in the biophysical SPR binding assay from millimolar towards the low micromolar and submicromolar range by >1000-fold for some fragment derivatives. The initial SAR together with the protein crystal structures of our novel CypD inhibitors provide a suitable basis for further hit-to-lead optimization.


title: Wildlife trade shifts from brick-and-mortar markets to virtual marketplaces: A case study of birds of prey trade in Thailand

text: Abstract The shift of wildlife trade from brick-and-mortar markets to virtual online marketplaces is reported using the trade of birds of prey (raptors) in Thailand from 1968 to 2019 as a case study. We analyzed data obtained from physical market survey data for 2,782 individuals from 27 species, with 2,420 individuals reported in early surveys (1968-1988) and 362 individuals reported in later surveys (2003-2015) and online surveys (February 2017 to January 2019). We compared information on asking prices and what species were traded using two comparative approaches to analyze how species composition may have changed over time (physical markets and online platforms; pre-Internet and Internet era). In comparison with the five previous market surveys, we did not find a statistically significant difference between species and availability of species offered for sale when comparing physical bird markets and online markets. In all data sets, biological factors such as wingspan were significant factors in explaining price variation. We conclude that sustained monitoring is needed to make direct comparisons between the trade platforms. With a continued increase of wildlife trade on online platforms, we recommend increased regulation and enforcement of wildlife trade laws.


title: Association of Interleukin-8 and Neutrophils with Nasal Symptom Severity During Acute Respiratory Infection

text: Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (r(s) = 0.082, P = 0.022; r(s) = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = <0.00001; r = 0.18, P = <0.003), plugged nose (r = 0.045, P = 0.003; r = 0.14, P = 0.058), and sneezing (r = −0.02, P = <0.0001; r = −0.0055, P = 0.31). Neutrophils correlate with some quality of life measures such as sleeping well (r = 0.15, P = 0.026). Thus, the study demonstrates that IL-8 and neutrophils are correlated with severity of nasal symptoms during acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness.


Figuring out the New Normal: Completing my fellowship at home, with my children, while the Coronavirus rages


title: RNAi therapeutics: a potential new class of pharmaceutical drugs

text: The rapid identification of highly specific and potent drug candidates continues to be a substantial challenge with traditional pharmaceutical approaches. Moreover, many targets have proven to be intractable to traditional small-molecule and protein approaches. Therapeutics based on RNA interference (RNAi) offer a powerful method for rapidly identifying specific and potent inhibitors of disease targets from all molecular classes. Numerous proof-of-concept studies in animal models of human disease demonstrate the broad potential application of RNAi therapeutics. The major challenge for successful drug development is identifying delivery strategies that can be translated to the clinic. With advances in this area and the commencement of multiple clinical trials with RNAi therapeutic candidates, a transformation in modern medicine may soon be realized.


title: Global Hidradenitis Suppurativa COVID‐19 Registry: A Registry to Inform Data‐Driven Management Practices

text: The management of hidradenitis suppurativa (HS), a chronic inflammatory skin disease, deserves special consideration in the context of the Coronavirus 2019 (COVID‐19) pandemic. A new Global Hidradenitis Suppurativa COVID‐19 Registry has been developed to capture data on risks, clinical course, and outcomes of COVID‐19 in HS patients. Caused by the virus SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus‐2), COVID‐19 is an easily transmissible disease which, in its most severe form, is characterized by respiratory failure and multiple organ dysfunction triggered by a cytokine storm response that predominates in older adults and those with significant comorbidities.


Do pregnant women have protective immunity against COVID‐19?


title: Sequence and analysis of BECV F15 matrix protein

text: Abstract Clones from the bovine enteric coronavirus (F15) cDNA library were cloned in pBR322 and sequenced by the method of Sanger and Coulson. This led to the identification of a sequence of 1,300 bases which contained a single open reading frame of 690 bases yielding a protein having properties of the matrix protein (M). It was comprised of 230 amino acids with a molecular weight of 26,376 Da. It was hydrophobic and had a net charge of +8 at neutral pH. Analysis of its secondary structure could not establish a simple transmembrane arrangement of the amino acids. Comparison of its nucleotide sequence with that of BECV Mebus strain showed only a two-base change resulting in a 100% homology between the two amino acid sequences. Furthermore, a very conserved structure of M appeared on comparison with the Dayoff optimal alignment of MHV-A59, MHV-JHM, TGEV, IBV Beaudette and IBV 6/82M amino acid sequences. As the two strains of BECV, F15 and Mebus present some antigenic differences, this led us to reconsider the role of M in viral antigen specificity. A hypothesis is that, as it seems to possess the necessary information on its transmembrane region, it is an ideal candidate for the viral budding process.


title: Adapting palliative radiation therapy for bone metastases during the Covid-19 pandemic: GEMO position paper

text: Abstract The current health crisis caused by COVID-19 is a challenge for oncology treatment, especially when it comes to radiotherapy. Cancer patients are already known to be very fragile and COVID-19 brings about the risk of severe respiratory complications. In order to treat patients safely while protecting medical teams, the entire health care system must optimize the way it approaches prevention and treatment at a time when social distancing is key to stemming this pandemic. All indications and treatment modalities must be re-discussed. This is particularly the case for radiotherapy of bone metastases for which it is possible to reduce the number of sessions, the frequency of transport and the complexity of treatments. These changes will have to be discussed according to the organization of each radiotherapy department and the health situation, while medical teams must remain vigilant about the risks of complications of bone metastases, particularly spinal metastases. In this short piece, the members of the GEMO (the European Study Group of Bone Metastases) offer a number of recommendations to achieve the above objectives, both in general and in relation to five of the most common situations on radiation therapy for bone metastases.


title: Prevention of healthcare-associated infections in neonates: room for improvement

text: Summary Infants in neonatal intensive care units (NICUs) are highly susceptible to infection due to the immaturity of their immune systems. Healthcare-associated infections (HCAIs) are associated with prolonged hospital stay, and represent a significant risk factor for neurological development problems and death. Improving HCAI control is a priority for NICUs. Many factors contribute to the occurrence of HCAIs in neonates such as poor hand hygiene, low nurse–infant ratios, environmental contamination and unnecessary use of antibiotics. Prevention is based on improving neonatal management, avoiding unnecessary use of central venous catheters, restricting use of antibiotics and H2 blockers, and introducing antifungal prophylaxis if necessary. Quality improvement interventions to reduce HCAIs in neonates seem to be the cornerstone of infection control.


title: Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2

text: Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen A [HLA-A], -B, and -C genes) may affect susceptibility to and severity of the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We performed a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA-A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explored the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome was successfully sampled and was represented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting that individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (M. Lin, H.-T. Tseng, J. A. Trejaut, H.-L. Lee, et al., BMC Med Genet 4:9, 2003, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting that it could enable cross-protective T-cell-based immunity. Finally, we reported global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic. IMPORTANCE Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.


title: Caution Warranted: Using the Institute for Health Metrics and Evaluation Model for Predicting the Course of the COVID-19 Pandemic

text: The Institute for Health Metrics and Evaluation model for predicting the course of the coronavirus disease 2019 pandemic has attracted considerable attention, including from the U.S. government. The appearance of certainty of model estimates is seductive when the world is desperate to know what lies ahead, but caution is warranted regarding the validity and usefulness of the model projections for policymakers.


title: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes

text: Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells.


title: Children at risk: multisystem inflammatory syndrome and COVID-19

text: [Figure: see text]


title: Quantitative analysis of an anti-viral immune escape compound ML-7 in feline plasma using ultra performance liquid chromatography/electrospray ionization mass spectrometry

text: Abstract An analytical method for the quantitative measurement of ML-7, a product with possible anti-immune escape activity for feline infectious peritonitis virus (FIPV), in feline plasma was developed and validated. The sample preparation consists of a solid-phase extraction step on an MCX cartridge. ML-7 and ML-9, used as the internal standard for the analysis, were separated on an ACQUITY UPLC™ BEH C18 reversed-phase column (1.7μm, 50mm×2.1mm I.D.), using isocratic elution with acetonitrile and 0.1% formic acid in water as the mobile phase. Both compounds were subsequently quantified in MRM mode on a Micromass® Quattro Premier™ XE triple quadrupole mass spectrometer. The use of a Thermo Scientific® Exactive™ orbitrap mass spectrometer made it possible to confirm the proposed fragmentation pattern of both ML-7 and ML-9. A validation study according to EC requirements was carried out, in which the method showed good performance. Linear behaviour was observed in the 1–2500ngml−1 range, which is relevant for real sample analysis. Accuracy and precision were within the criteria requested by the EC requirements throughout this concentration range. Extraction recovery of ML-7 was 72%. Matrix effect for ML-7 was not higher than 8%. The method was successfully used for the monitoring of ML-7 in feline plasma after intravenous, subcutaneous or oral administration of an ML-7 formulation, for the determination of pharmacokinetic parameters, with a limit of quantification of 1ngml−1 and a limit of detection of 0.4ngml−1. The proposed method also shows good characteristics for the analysis of ML-7 in plasma of other animal species and human plasma.


title: The human gut microbiota and virome: Potential therapeutic implications

text: Abstract Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut “virome” composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut “virome” in the larger microbial ecosystem.


docid: nzgsunqr

title: Evaluation of acute and sublethal effects of chloroquine (C(18)H(26)CIN(3)) on certain enzymological and histopathological biomarker responses of a freshwater fish Cyprinus carpio

text: In this study the toxicity of antimalarial drug chloroquine (CQ) on certain enzymological (GOT, GPT and LDH) and histopathological alterations (Gill, liver and kidney) of a freshwater fish Cyprinus carpio was studied after acute (96 h) and sublethal (35 days) exposure. The median lethal concentration (96 h) of CQ was 31.62 mg/ml. During acute treatment (CQ at 31.62 mg/ml) the treated fish groups showed a significant increase in GOT and GPT activities in blood plasma; whereas LDH activity was decreased when compare to control groups. To analyse the effects of drug at the lowest concentration, the fish were exposed to 3.16 mg/ml (1/10th of 96 h LC50 value) for 96 h. In sublethal treatment (3.16 mg/ml) GOT activity increased up to 14th day and decreased during the rest of the exposure period (21, 28 and 35th day). A biphasic response in GPT activity was observed. LDH activity was found to be increased throughout the study period (35 days) compare to control groups. The alterations in enzyme activities in blood plasma were found to be significant at p < 0.05 (DMRT). Many histopathological changes in vital organs such as gill, liver and kidney of fish were observed in CQ treated group (acute and sub-lethal) compare to normal group. The alterations in the enzymological and histopathological study in the present investigation indicate that the drug CQ has toxic effects on non-target organisms. We conclude that the alterations in enzymological parameters and histopathological changes can be used as biomarker to assess the health of the aquatic organism/environment. Further data on molecular studies are needed to define the mode of action and toxicity of these emerging pollutants.


title: Relatedness of the incidence decay with exponential adjustment (IDEA) model, “Farr's law” and SIR compartmental difference equation models

text: Mathematical models are often regarded as recent innovations in the description and analysis of infectious disease outbreaks and epidemics, but simple mathematical expressions have been in use for projection of epidemic trajectories for more than a century. We recently introduced a single equation model (the incidence decay with exponential adjustment, or IDEA model) that can be used for short-term epidemiological forecasting. In the mid-19th century, Dr. William Farr made the observation that epidemic events rise and fall in a roughly symmetrical pattern that can be approximated by a bell-shaped curve. He noticed that this time-evolution behavior could be captured by a single mathematical formula (“Farr's law”) that could be used for epidemic forecasting. We show here that the IDEA model follows Farr's law, and show that for intuitive assumptions, Farr's Law can be derived from the IDEA model. Moreover, we show that both mathematical approaches, Farr's Law and the IDEA model, resemble solutions of a susceptible-infectious-removed (SIR) compartmental differential-equation model in an asymptotic limit, where the changes of disease transmission respond to control measures, and not only to the depletion of susceptible individuals. This suggests that the concept of the reproduction number [Formula: see text] was implicitly captured in Farr's (pre-microbial era) work, and also suggests that control of epidemics, whether via behavior change or intervention, is as integral to the natural history of epidemics as is the dynamics of disease transmission.


title: Does atopy affect the course of viral pneumonia?

text: Abstract Background The presence of atopy is considered as a risk factor for severe respiratory symptoms in children. The objective of this study was to examine the effect of atopy on the course of disease in children hospitalised with viral pneumonia. Methods Children between the ages of 1 and 6 years hospitalised due to viral pneumonia between the years of 2013 and 2016 were included to this multicentre study. Patients were classified into two groups as mild–moderate and severe according to the course of pneumonia. Presence of atopy was evaluated with skin prick tests. Groups were compared to evaluate the risk factors associated with severe viral pneumonia. Results A total of 280 patients from nine centres were included in the study. Of these patients, 163 (58.2%) were male. Respiratory syncytial virus (29.7%), Influenza A (20.5%), rhinovirus (18.9%), adenovirus (10%), human metapneumovirus (8%), parainfluenza (5.2%), coronavirus (6%), and bocavirus (1.6%) were isolated from respiratory samples. Eighty-five (30.4%) children had severe pneumonia. Atopic sensitisation was found in 21.4% of the patients. Ever wheezing (RR: 1.6, 95% CI: 1.1–2.4), parental asthma (RR: 1.5, 95% CI: 1.1–2.2), other allergic diseases in the family (RR: 1.8, 95% CI: 1.2–2.9) and environmental tobacco smoke (RR: 1.6, 95% CI: 1.1–3.5) were more common in the severe pneumonia group. Conclusions When patients with mild–moderate pneumonia were compared to patients with severe pneumonia, frequency of atopy was not different between the two groups. However, parental asthma, ever wheezing and environmental tobacco smoke exposure are risk factors for severe viral pneumonia in children.


docid: eekytsst

title: A Proposed COVID-19 Testing Algorithm

text: The 2019 coronavirus disease (COVID-19) pandemic has led to physical distancing measures in numerous countries in an attempt to control the spread. However, these measures are not without cost to the health and economies of the nations in which they are enacted. Nations are now looking for methods to remove physical distancing measures and return to full functioning. To prevent a massive second wave of infections, this must be done with a data-driven methodology. The purpose of this article is to propose an algorithm for COVID-19 testing that would allow for physical distancing to be scaled back in a stepwise manner, which limits ensuing infections and protects the capacity of the health care system.


title: Household preparedness for emergency events: a cross-sectional survey on residents in four regions of China

text: OBJECTIVE: This study aimed to assess household preparedness for emergency events and its determinants in China. DESIGN: A cross-sectional questionnaire survey was conducted on 3541 households in China in 2015. PARTICIPANTS: Households were selected using a stratified cluster sampling strategy, representing central, eastern, western and southern regions of China. The designed questionnaires were administered through face-to-face interviews. OUTCOME MEASURES: Household emergency preparedness was measured with 14 indicators, tapping into the supply of nine emergency necessities (food and water, extra batteries, battery-powered radio, battery-operated torch, first-aid kit, gas mask, fire extinguisher, escape ropes, whistle), coverage of accident insurance, knowledge of local emergency response systems (emergency numbers, exit routes and shelters) and availability of a household evacuation plan. If an individual acted on 9 of the 14 indicators, they were deemed well prepared. Logistic regression models were established to identify predictors of well preparedness based on 3541 returned questionnaires containing no missing values. RESULTS: Only 9.9% of households were well prepared for emergencies: 53.6% did not know what to do and 31.6% did not want to think about it. A higher level of preparedness was found in the respondents who have attained higher education (adjusted OR=0.826 compared with the higher level), participated in emergency training activities (adjusted OR=2.299), had better emergency knowledge (adjusted OR=2.043), reported less fate-submissiveness (adjusted OR=1.385) and more self-reliance (adjusted OR=1.349), prior exposure to emergency events (adjusted OR=1.280) and held more positive attitudes towards preparedness (adjusted OR=1.286). CONCLUSION: Household preparedness for emergency events is poor in China. Lack of motivation, negative attitude to preparedness and knowledge shortfall are major but remediable barriers for household preparedness.


Untangling the complexity of diseases such as calf diarrhoea is crucial to future productivity


There may be virus in conjunctival secretion of patients with COVID‐19


title: Lessons learned from the 2019-nCoV epidemic on prevention of future infectious diseases

text: Abstract Only a month after the outbreak of pneumonia caused by 2019-nCoV, more than forty-thousand people were infected. This put enormous pressure on the Chinese government, medical healthcare provider, and the general public, but also made the international community deeply nervous. On the 25th day after the outbreak, the Chinese government implemented strict traffic restrictions on the area where the 2019-nCoV had originated—Hubei province, whose capital city is Wuhan. Ten days later, the rate of increase of cases in Hubei showed a significant difference (p = 0.0001) compared with the total rate of increase in other provinces of China. These preliminary data suggest the effectiveness of a traffic restriction policy for this pandemic thus far. At the same time, solid financial support and improved research ability, along with network communication technology, also greatly facilitated the application of epidemic prevention measures. These measures were motivated by the need to provide effective treatment of patients, and involved consultation with three major groups in policy formulation—public health experts, the government, and the general public. It was also aided by media and information technology, as well as international cooperation. This experience will provide China and other countries with valuable lessons for quickly coordinating and coping with future public health emergencies.


title: Resultados de un modelo de organización asistencial para Covid-19 en hemodiálisis en un hospital terciario y sus centros concertados

text: RESUMEN Se describe la experiencia de un hospital terciario y cuatro centros concertados de hemodiálisis adscritos al mismo durante la epidemia de COVID-19. Se resume la organización asistencial que se ha llevado a cabo y el curso clínico de los 16 casos de COVID-19 en pacientes en hemodiálisis. La aplicación conjunta de medidas que incluyen el cribado de pacientes, la investigación precoz de casos posibles, el aislamiento de los casos confirmados, en investigación o en contactos, así como la utilización de medidas de protección individuales, ha permitido controlar la epidemia. Se compara el curso clínico de estos 16 pacientes con la serie publicada por el Hospital Universitario de Wuhan y con los datos del registro de infecciones Covid-19 de la Sociedad Española de Nefrología. En nuestra experiencia y, a diferencia de lo comunicado por el centro de Wuhan, la enfermedad COVID-19 en los pacientes en hemodiálisis es grave en un porcentaje importante de los casos y la letalidad, elevada, es mayormente causada por la propia infección. Las medidas de contención de la epidemia son eficaces. ABSTRACT The experience of a tertiary hospital and four hemodialysis centers attached to it during the COVID-19 epidemic is described. The organization of care that has been carried out and the clinical course of the 16 cases of COVID-19 in hemodialysis patients are summarized. The joint application of measures, including patient screening, the early investigation of possible cases, the isolation of confirmed, investigational or contact cases, as well as the use of individual protection measures, has enabled the epidemic to be controlled. The clinical course of these 16 patients is compared with the series published by the Wuhan University Hospital and with the data from the Covid-19 infection registry of the Spanish Society of Nephrology. In our experience, and unlike what was reported by the Wuhan Center, COVID-19 disease in hemodialysis patients is severe in a significant percentage of cases, and high lethality is mostly caused by the infection itself. Measures to contain the epidemic are effective.


title: Building a Social Mandate for Climate Action: Lessons from COVID-19

text: The COVID-19 imposed lockdown has led to a number of temporary environmental side effects (reduced global emissions, cleaner air, less noise), that the climate community has aspired to achieve over a number of decades. However, these benefits have been achieved at a massive cost to welfare and the economy. This commentary draws lessons from the COVID-19 crisis for climate change. It discusses whether there are more sustainable ways of achieving these benefits, as part of a more desirable, low carbon resilient future, in a more planned, inclusive and less disruptive way. In order to achieve this, we argue for a clearer social contract between citizens and the state. We discuss how COVID-19 has demonstrated that behaviours can change abruptly, that these changes come at a cost, that we need a ‘social mandate’ to ensure these changes remain in the long-term, and that science plays an important role in informing this process. We suggest that deliberative engagement mechanisms, such as citizens’ assemblies and juries, could be a powerful way to build a social mandate for climate action post-COVID-19. This would enable behaviour changes to become more accepted, embedded and bearable in the long-term and provide the basis for future climate action.


title: Multi-sectorial research is paramount for preventing and controlling emerging infectious diseases

text: Abstract The social, economic and political consequences of emerging infectious disease (EID) may escape the sphere in which they first arise. In recent years, many EIDs have revealed the close links between human, animal and plant health, highlighting the need for multi-scale, multisectorial EID management. Human beings play a dual role in EID because they can promote their development through numerous human-environment interfaces and expanding international trade. On the other hand, their ability to analyze, interpret and act on the determinants of EID allows them to access the expertise necessary to control these EIDs. This expertise must be constantly adapted to remain relevant as the EID evolves, particularly in its virulence or transmission channels. Flexibility should become an inherent part of the expertise-based decision-making process even if it means going backwards. A certain degree of transparency and feedback to citizens is necessary for the acceptability of political decisions basing on expertise. A key step in the management of EID is the appropriate management of the early signal of infectious emergence. This step combines multidisciplinary skills allowing access to the best pathway for containing EID by implementing early countermeasures adapted to the situation. New digital technologies could significantly improve this early detection phase. Finally, experts have a fundamental role to play because they are located at the interface between operational actors and decision-makers, which allows multidirectional feedback, ideally in real time, between professional actors and decision makers. To combat current and future EIDs, expertise should be based on a multi-sectorial approach, promotion of collegiality and continuously adaptation to the evolving nature of EIDs.


title: Bordetella pertussis in infants hospitalized for acute respiratory symptoms remains a concern

text: BACKGROUND: Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak. METHODS: In order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR. RESULTS: Infants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p <0.06). Clinically, significantly fewer infants with pertussis than controls had more episodes of whooping cough (63.2% vs 0.0%; p < 0.001) and also less frequently fever at admission (15.8% vs 68.4%; p <0.01), apnea (52.6% vs 10.5%; p <0.006), and cyanosis (52.6% vs 10.5%; p < 0.006). Infants with pertussis had more often no abnormal chest sounds on auscultation than infants with RSV bronchiolitis (0% vs 42,1%; p < 0.005). The absolute blood lymphocyte and eosinophil counts were higher in infants with B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm(3), p < 0.0001 and 13.653 ± 10.430 vs 4.730 ± 2.400 cells/mm(3), p < 0.001). The molecular analysis of 2 B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants. CONCLUSIONS: When infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment.


title: Clinical characteristics of COVID‐19 in children: Are they similar to those of SARS?

text: Although the number of SARS‐CoV‐2 infections has been rising amid the current pandemic of COVID‐19, the low infection rate of SARS‐CoV‐2 in children has been low. By examining the clinical data available in the public domain, the present work clarifies the clinical presentations in children with COVID‐19 in China. Statistical significance tests and adjusted odds ratios estimation were performed on the children (age below 18) and adults (age 18 or above) cohorts in China. SARS‐CoV and SARS‐CoV‐2 shared similar clinical features. Lower respiratory tract infection was less prominent in children as evidenced by the relatively low prevalence in chest pain/discomfort and dyspnea. Similar to SARS, younger children had a less aggressive clinical course, compared with adolescents. While fewer symptoms were observed in children compared to adults, there is not yet sufficient evidence to conclude shorter hospital stay in children.


title: Chapter 2 Molecular Basis of Genetic Variation of Viruses Error-Prone Replication

text: Abstract Genetic variation is a necessity of all biological systems. Viruses use all known mechanisms of variation: mutation, several forms of recombination, and segment reassortment in the case of viruses with a segmented genome. These processes are intimately connected with the replicative machineries of viruses, as well as with fundamental physico-chemical properties of nucleotides when acting as template or substrate residues. Recombination has been viewed as a means to rescue viable genomes from unfit parents, or to produce large modifications for the exploration of phenotypic novelty. All types of genetic variation can act conjointly as blind processes to provide the raw materials for adaptation to the changing environments in which viruses must replicate.


title: Synthetic double-stranded RNA oligonucleotides are immunostimulatory for chicken spleen cells

text: Abstract Toll-like receptors (TLRs) are an integral part of the innate immune system that recognize microbe-derived molecular patterns and initiate innate and adaptive defenses against invading pathogens. TLR3 and TLR7 are involved in sensing virus-associated single-stranded and double-stranded RNA (dsRNA) molecules in cellular endosomes to activate the type I interferon pathway in mammals. Although certain synthetic dsRNA molecules have been identified to show immunostimulation in mammalian cells, very little is known about the ability of these sequences to stimulate avian cells. The current study investigated immunostimulatory properties of four synthetic oligonucleotide sequences using chicken splenocytes. Expression of TLR3 and 7, type I interferons and several other cytokines as well as TLR signaling pathway-related genes at different time points post-stimulation was quantified by real-time PCR. A dose-dependent increase in expression of TLR3 was observed in splenocytes treated with poly-UGUGU (poly-UG) and β-galactosidase dsRNA molecules. TLR3 and TLR7 gene expression was significantly up-regulated upon stimulation with all four dsRNA molecules. Furthermore, in a time course study, a significant increase was noted in the expression of TLR3, TLR7, interferon (IFN)-α, IFN-β, interleukin (IL)-1β, IL-6 as well as 2′,5′-OAS in splenocytes treated with poly-UG. In conclusion, the present study demonstrated the immunostimulatory properties of dsRNA oligonucleotides, especially those that contain a poly-UG motif, in chickens.


title: The China-UK Global Health Support Programme: looking for new roles and partnerships in changing times

text: China’s engagement in global affairs has changed substantially in the 2010s. One aspect of the country’s global reorientation has been its increased interest in, and willingness to play a role in, global health. In the early 2010s, the UK Department for International Development (DFID) initiated a collaboration with the Chinese government on a programme to support the country to play a greater and more effective global role in health and explore how the UK and China could work together on issues of key concern and contribute to improved global development outcomes. The programme worked with key Chinese agencies to carry out capacity building, support analysis of China’s approaches to engagement in global health governance and assistance, and provide support to government decision making. It also trialled several small-scale interventions in third countries through which Chinese agencies gained experience of working on health programmes overseas. The article reports on the main findings of an evaluation commissioned by DFID to learn from the programme. The programme provided support at a key time in China’s global reorientation; however, there is a need for continued development of capacity and systems for China to play the role envisaged by the country’s leadership. There is also a need for continued exploration on the part of China and partners of how to effectively collaborate to support improved global outcomes.


9. Coronaviruses: Development of Novel Oncolytic Vectors


title: Pneumonia Awareness Year, 2004: Scientific Impact Through Publications in Archivos de Bronconeumología

text: Pneumonia is a common and potentially serious infectious disease. Morbidity and mortality rates continue to be high in spite of major advances and steady progress in diagnosis and treatment. The economic impact of the disease is also great. It is therefore necessary to enlist the public, primary care and emergency physicians, and public policy administrators to join forces to treat and prevent pneumonia for the common good. The annual incidence of pneumonia in the population over the age of 14 years is 1.6 to 2.6 episodes/1000 inhabitants. The mortality rate is 14.1 per 100000 inhabitants, and the associated costs are €115 million annually. The RESPIRA Foundation and the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) declared 2004 to be pneumonia awareness year with the aim of coordinating efforts to raise awareness, distribute information, and foster debate.


title: Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia

text: BACKGROUND: Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV) is a poorly understood disease with no known treatments. We describe the clinical features and treatment outcomes of patients with laboratory confirmed MERS-CoV at a regional referral center in the Kingdom of Saudi Arabia. METHODS: In 2014, a retrospective chart review was performed on patients with a laboratory confirmed diagnosis of MERS-CoV to determine clinical and treatment characteristics associated with death. Confounding was evaluated and a multivariate logistic regression was performed to assess the independent effect of treatments administered. RESULTS: Fifty-one patients had an overall mortality of 37 %. Most patients were male (78 %) with a mean age of 54 years. Almost a quarter of the patients were healthcare workers (23.5 %) and 41 % had a known exposure to another person with MERS-CoV. Survival was associated with male gender, working as a healthcare worker, history of hypertension, vomiting on admission, elevated respiratory rate, abnormal lung exam, elevated alanine transaminase (ALT), clearance of MERS-CoV on repeat PCR polymerase chain reaction (PCR) testing, and mycophenolate mofetil treatment. Survival was reduced in the presence of coronary artery disease, hypotension, hypoxemia, CXR (chest X-ray) abnormalities, leukocytosis, creatinine >1 · 5 mg/dL, thrombocytopenia, anemia, and renal failure. In a multivariate analysis of treatments administered, severity of illness was the greatest predictor of reduced survival. CONCLUSIONS: Care for patients with MERS-CoV remains a challenge. In this retrospective cohort, interferon beta and mycophenolate mofetil treatment were predictors of increased survival in the univariate analysis. Severity of illness was the greatest predictor of reduced survival in the multivariate analysis. Larger randomized trials are needed to better evaluate the efficacy of these treatment regimens for MERS-CoV.


title: To sense or not to sense viral RNA—essentials of coronavirus innate immune evasion

text: An essential function of innate immunity is to distinguish self from non-self and receptors have evolved to specifically recognize viral components and initiate the expression of antiviral proteins to restrict viral replication. Coronaviruses are RNA viruses that replicate in the host cytoplasm and evade innate immune sensing in most cell types, either passively by hiding their viral signatures and limiting exposure to sensors or actively, by encoding viral antagonists to counteract the effects of interferons. Since many cytoplasmic viruses exploit similar mechanisms of innate immune evasion, mechanistic insight into the direct interplay between viral RNA, viral RNA-processing enzymes, cellular sensors and antiviral proteins will be highly relevant to develop novel antiviral targets and to restrict important animal and human infections.


title: Characteristics and Therapeutic Options of the Coronavirus Disease 2019

text: Abstract The Coronavirus Disease 2019 (COVID-19) is a new type of pneumonia caused by SARS-CoV-2 infection. COVID-19 is affecting millions of patients and the infected number keeps increasing. SARS-CoV-2 is highly infectious, has a long incubation period, and causes a relatively high death rate, resulting in severe health problem all over the world. Currently there is no effective proven drugs for the treatment of COVID-19, therefore, development of effective therapeutic drugs to suppress SARS-CoV-2 infection is urgently needed. In this review, we first summarize the structure and genome features of SARS-CoV-2, and introduce its infection and replication process. Then we review the clinical symptoms, diagnosis and treatment options of COVID-19 patients. We further discuss the potential molecular targets and drug development strategies for treatment of the emerging COVID-19. Finally, we summarize clinical trials of some potential therapeutic drugs and the results of vaccine development. This review provides some insights for the treatment of COVID-19.


title: Branched-chain C-cyano pyranonucleosides: Synthesis of 3′-C-cyano & 3′-C-cyano-3′-deoxy pyrimidine pyranonucleosides as novel cytotoxic agents

text: This report describes the total and facile synthesis of 3′-C-cyano & 3′-C-cyano-3′-deoxy pyrimidine pyranonucleosides. Reaction of 3-keto glucoside 1 with sodium cyanide gave the desired precursor 3-C-cyano-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (2). Hydrolysis followed by acetylation led to the 1,2,3,4,6-penta-O-acetyl-3-C-cyano-D-glucopyranose (4). Compound 4 was condensed with silylated 5-fluorouracil, uracil, thymine and N(4)-benzoylcytosine, respectively and deacetylated to afford the target 1-(3′-C-cyano-β-D-glucopyranosyl)nucleosides 6a–d. Routine deoxygenation at position 3′ of cyanohydrin 2, followed by hydrolysis and acetylation led to the 3-C-cyano-3-deoxy-1,2,4,6-tetra-O-acetyl-D-allopyranose (10). Coupling of sugar 10 with silylated pyrimidines and subsequent deacetylation yielded the target 1-(3′-C-cyano-3′-deoxy-β-D-allopyranosyl)nucleosides 12a–d. The new analogues were evaluated for their antiviral and cytostatic activities. It was found that 6a was endowed with a pronounced anti-proliferative activity that was only 2- to 8-fold less potent than that shown for the parental base 5-fluorouracil. None of the compounds showed activity against a broad panel of DNA and RNA viruses.


title: COVID-19: unanswered questions on immune response and pathogenesis

text: Abstract The novel coronavirus disease 2019 (COVID-19) has rapidly increased in pandemic scale since it first appeared in Wuhan, China, in December 2019. In these troubled days the scientific community is asking rapid replies to prevent and combat the emergency. It is generally accepted that only achieving a better understanding of the interactions between the virus and host immune response and of the pathogenesis of infection is crucial to identify valid therapeutic tools to control virus entry, replication and spread as well as to impair its lethal effects. Based on the recent research progress of SARS-CoV-2 and the results on previous coronaviruses, in this contribution we underscore some of the main unsolved problems, mostly focusing on pathogenetic aspects and host immunity to the virus. On this basis, we also touch important aspects regarding the immune response in asymptomatic subjects, the immune-evasion of SARS-CoV-2 in severe patients and differences in disease severity by age and gender.


title: Genetic diversity of MERS-CoV spike protein gene in Saudi Arabia

text: Abstract Background Middle East respiratory syndrome coronavirus (MERS-CoV) was primarily detected in 2012 and still causing disease in human and camel. Camel and bats have been identified as a potential source of virus for disease spread to human. Although, significant information related to MERS-CoV disease, spread, infection, epidemiology, clinical features have been published, A little information is available on the sequence diversity of Spike protein gene. The Spike protein gene plays a significant role in virus attachment to host cells. Recently, the information about recombinant MERS-CoV has been published. So, this work was designed to identify the emergence of any another recombinant virus in Jeddah, Saudi Arabia. Methods In this study samples were collected from both human and camels and the Spike protein gene was amplified and sequenced. The nucleotide and amino acid sequences of MERS-CoV Spike protein gene were used to analyze the recombination, genetic diversity and phylogenetic relationship with selected sequences from Saudi Arabia. Results The nucleotide sequence identity ranged from 65.7% to 99.8% among all the samples collected from human and camels from various locations in the Kingdom. The lowest similarity (65.7%) was observed in samples from Madinah and Dammam. The phylogenetic relationship formed different clusters with multiple isolates from various locations. The sample collected from human in Jeddah hospital formed a closed cluster with human samples collected from Buraydah, while camel sample formed a closed cluster with Hufuf isolates. The phylogenetic tree by using Aminoacid sequences formed closed cluster with Dammam, Makkah and Duba isolates. The amino acid sequences variations were observed in 28/35 samples and two unique amino acid sequences variations were observed in all samples analyzed while total 19 nucleotides sequences variations were observed in the Spike protein gene. The minor recombination events were identified in eight different sequences at various hotspots in both human and camel samples using recombination detection programme. Conclusion The generated information from this study is very valuable and it will be used to design and develop therapeutic compounds and vaccine to control the MERS-CoV disease spread in not only in the Kingdom but also globally.


title: APE-Type Non-LTR Retrotransposons of Multicellular Organisms Encode Virus-Like 2A Oligopeptide Sequences, Which Mediate Translational Recoding during Protein Synthesis

text: 2A oligopeptide sequences (“2As”) mediate a cotranslational recoding event termed “ribosome skipping.” Previously we demonstrated the activity of 2As (and “2A-like sequences”) within a wide range of animal RNA virus genomes and non-long terminal repeat retrotransposons (non-LTRs) in the genomes of the unicellular organisms Trypanosoma brucei (Ingi) and T. cruzi (L1Tc). Here, we report the presence of 2A-like sequences in the genomes of a wide range of multicellular organisms and, as in the trypanosome genomes, within non-LTR retrotransposons (non-LTRs)—clustering in the Rex1, Crack, L2, L2A, and CR1 clades, in addition to Ingi. These 2A-like sequences were tested for translational recoding activity, and highly active sequences were found within the Rex1, L2, CR1, and Ingi clades. The presence of 2A-like sequences within non-LTRs may not only represent a method of controlling protein biogenesis but also shows some correlation with such apurinic/apyrimidinic DNA endonuclease-type non-LTRs encoding one, rather than two, open reading frames (ORFs). Interestingly, such non-LTRs cluster with closely related elements lacking 2A-like recoding elements but retaining ORF1. Taken together, these observations suggest that acquisition of 2A-like translational recoding sequences may have played a role in the evolution of these elements.


title: Obesity, adipokines and COVID‐19

text: The SARS‐CoV‐2 pandemic has led to worldwide research aiming to identify the risk factors for developing critical illness and mortality caused by COVID‐19. It quickly became apparent that besides older age, obesity is one of the most important risk factors for a more severe course of COVID‐19, although the mechanisms remain largely unknown [1‐3]. Notably, with respect to acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), evidence is mounting that obesity is a risk factor for ARDS/ALI, but among people with ARDS/ALI, obesity is associated with better outcome, a phenomenon which has been called the “obesity paradox” [4,5].


title: The Influence of the COVID-19 Pandemic on Technology Adoption in Healthcare

text: ABSTRACT SARS-CoV-2 (COVID-19) has impacted nearly every aspect of our lives. It has certainly changed how we deliver health care. In part, it has accelerated the development/use of technology solutions in health care. These technology tools were originally identified as mechanisms that would make future care “easier or better”, however, these tech solutions amidst COVID-19 are now viewed as “essential”. The use of technology discussed in this article has been accelerated during the current crisis because they provide distance, safety for healthcare professionals and patients, faster results reporting, virtual visits, and more. As we move forward, technology will continue to be positioned to best address public health needs, improve care efficiencies as well as develop treatments and vaccines. Specifically, this article explores the adoption and growth of technology tools including; telehealth, artificial intelligence, and robotics over the first 90 days of the COVID-19 pandemic in the United States.


title: Bayesian analysis of robust Poisson geometric process model using heavy-tailed distributions

text: Abstract We propose a robust Poisson geometric process model with heavy-tailed distributions to cope with the problem of outliers as it may lead to an overestimation of mean and variance resulting in inaccurate interpretations of the situations. Two heavy-tailed distributions namely Student’s t and exponential power distributions with different tailednesses and kurtoses are used and they are represented in scale mixture of normal and scale mixture of uniform respectively. The proposed model is capable of describing the trend and meanwhile the mixing parameters in the scale mixture representations can detect the outlying observations. Simulations and real data analysis are performed to investigate the properties of the models.


title: Application of network analysis parameters in risk-based surveillance – Examples based on cattle trade data and bovine infections in Sweden

text: Abstract Financial resources may limit the number of samples that can be collected and analysed in disease surveillance programmes. When the aim of surveillance is disease detection and identification of case herds, a risk-based approach can increase the sensitivity of the surveillance system. In this paper, the association between two network analysis measures, i.e. ‘in-degree’ and ‘ingoing infection chain’, and signs of infection is investigated. It is shown that based on regression analysis of combined data from a recent cross-sectional study for endemic viral infections and network analysis of animal movements, a positive serological result for bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) is significantly associated with the purchase of animals. For BCV, this association was significant also when accounting for herd size and regional cattle density, but not for BRSV. Examples are given for different approaches to include cattle movement data in risk-based surveillance by selecting herds based on network analysis measures. Results show that compared to completely random sampling these approaches increase the number of detected positives, both for BCV and BRSV in our study population. It is concluded that network measures for the relevant time period based on updated databases of animal movements can provide a simple and straight forward tool for risk-based sampling.


title: To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic

text: Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17–45% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34–58%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24–65% (and peak deaths 15–69%), compared to 2–9% mortality reduction in New York (peak death reduction 9–18%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.


title: The death and life of Twitter

text: The social media site was once a fun place, full of cat memes and a culture of sharing. Now, it could be on the brink of self-destruction, writes Annalee Newitz


title: Are virus infections triggers for autoimmune disease?

text: Abstract Viruses have been implicated in the initiation, progression, and exacerbation of several human autoimmune diseases, including multiple sclerosis. However, no single virus has been demonstrated as the etiologic agent. Multiple different infections may be involved, first in priming the immune system for autoimmunity and then in triggering the actual disease. A model based on experimental allergic encephalomyelitis, an animal model of multiple sclerosis, has been developed, which shows that an initial early infection with a virus having molecular mimicry to self-epitopes can prime for disease that occurs after a subsequent non-specific immunologic stimulus, such as a different infection. The role of multiple infections in the development of autoimmune disease may explain why no one virus has been implicated.


title: COVID-19: Presumed Infection Routes and Psychological Impact on Staff in Administrative and Logistics Departments in a Designated Hospital in Wuhan, China

text: Objective: Our aim was to explore the presumed infection routes and psychological impact of COVID-19 on staff in administrative and logistics departments (ALDs). Methods: We gathered data from all 18 staff members with COVID-19 in ALDs in Zhongnan Hospital of Wuhan University, China. The baseline, job before diagnosis, presumed infection environment, use of protective equipment, and psychological status before and after diagnosis were collected and analyzed. A total of 18 uninfected staff members working alongside them in the same environment and 18 random matched infected doctors and nurses formed two control groups; the psychological impact of these three groups was then compared. Results: Of the 18 members of staff, 88.89% were infected due to the working environment (hospital), and nine had face-to-face conversations with doctors and nurses in their daily work. Many staff members did not take any protective measures in their routine work. Before they were diagnosed, 12 staff members were aware of the seriousness of the epidemic, and most of the staff maintained a neutral attitude to the COVID-19 outbreak. A total of 77.78% of the staff experienced psychological stress or emotional changes after diagnosis, which were mainly caused by family health and disease related issues. Most of them managed their emotions by self-control and video calls with their families. There was no significant difference in psychological impact among the three groups, but uninfected staff members were fully aware of the seriousness of the epidemic. Conclusions: Effective protective measures should be taken for staff members in ALDs. Psychological interventions are very important to help infected staff members in ALDs cope with psychological distress.


title: Effect of pressure on refolding of recombinant pentameric cholera toxin B

text: Abstract The production of recombinant proteins is an essential tool for the expansion of modern biological research and biotechnology. The expression of heterologous proteins in Escherichia coli often results in an incomplete folding process that leads to the accumulation of inclusion bodies (IB), aggregates that hold a certain degree of native-like secondary structure. High hydrostatic pressure (HHP) impairs intermolecular hydrophobic and electrostatic interactions, leading to dissociation of aggregates under non-denaturing conditions and is therefore a useful tool to solubilize proteins for posterior refolding. Cholera toxin (CT) is composed of a non-toxic pentamer of B subunits (CTB), a useful adjuvant in vaccines, and a toxic subunit A (CTA). We studied the process of refolding of CTB using HHP. HHP was shown to be effective for dissociation of CTB monomers from IB. Posterior incubation at atmospheric pressure of concentrated CTB (1mg/ml) is necessary for the association of the monomers. Pentameric CTB was obtained when suspensions of CTB IB were compressed at 2.4kbar for 16h in the presence of Tween 20 and incubated at 1bar for 120h. Soluble and biologically active pentameric CTB was obtained, with a yield of 213mg CTB/liter of culture. The experience gained in this study can be important to improve the refolding of proteins with quaternary structure.


title: cGAS and CD-NTase enzymes: structure, mechanism, and evolution

text: Cyclic GMP–AMP synthase (cGAS) is a signaling enzyme in human cells that controls immune-sensing of cytosolic DNA. The recent discoveries of diverse structural homologs of cGAS in animals and bacteria reveal that cGAS-like signaling is surprisingly ancient and widespread in biology. Together with the Vibrio cholerae protein dinucleotide cyclase in Vibrio (DncV), cGAS and DncV homologs comprise a family of cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes that synthesize noncanonical RNA signals including cyclic dinucleotides, cyclic trinucleotides, and linear oligonucleotides. Structural and biochemical breakthroughs provide a framework to understand how CD-NTase signaling allows cells to respond to changing environmental conditions. The CD-NTase family also includes uncharacterized human genes like MB21D2 and Mab21L1, highlighting emerging functions of cGAS-like signaling beyond innate immunity.


title: Genomic analysis of HAdV-B14 isolate from the outbreak of febrile respiratory infection in China

text: Abstract Human adenovirus type 14 (HAdV-B14) was first reported in 1955 from the Netherlands and since then had been associated with outbreaks of febrile respiratory illness (FRI). In China, sporadic HAdV-B14 infections were first identified in 2010, in Guangzhou and Beijing. In 2012, an outbreak of FRI occurred in Beijing and the etiological agent was determined to be HAdV-B14. We present a complete HAdV-B14 genome sequence isolated from this recent FRI outbreak. Virus in 30 throat swab samples was detected using polymerase chain reaction assays, and confirmed by sequencing of the fiber, hexon and penton genes. Comparative genomics and phylogenetic analysis showed that the newly isolated HAdV-B14 (HAdV-B14 CHN) shared highest sequence homology with a 2006 isolate from the United States and clustered closely with other HAdV-B14 strains. It is expected that data from the present study will help in devising better protocols for virus surveillance, and in developing preventative measures.


title: Establishing Telemedicine in an Academic Total Joint Arthroplasty Practice: Needs and Opportunities Highlighted by the COVID-19 Pandemic

text: Abstract The COVID-19 pandemic has prompted rapid restructuring of the healthcare system in an effort to stop the spread of the virus and to treat patients who are acutely ill with COVID-19, while continuing to provide outpatient care for the remainder of patients. To help control spread of this pandemic, many centers have boosted telemedicine capability to care for patients who would typically be seen in person in outpatient settings, including total joint arthroplasty clinics. We review key components relevant to the establishment and effective use of telemedicine, focused on patient education, practice logistics, technological considerations, and sensitive patient health information–associated compliance factors, which are necessary to provide care remotely for total joint arthroplasty patients.


title: Quantifying the risk of respiratory infection in healthcare workers performing high-risk procedures

text: This study determined the risk of respiratory infection associated with high-risk procedures (HRPs) performed by healthcare workers (HCWs) in high-risk settings. We prospectively studied 481 hospital HCWs in China, documented risk factors for infection, including performing HRPs, measured new infections, and analysed whether HRPs predicted infection. Infection outcomes were clinical respiratory infection (CRI), laboratory-confirmed viral or bacterial infection, and an influenza infection. About 12% (56/481) of the study participants performed at least one HRP, the most common being airway suctioning (7·7%, 37/481). HCWs who performed a HRP were at significantly higher risk of developing CRI and laboratory-confirmed infection [adjusted relative risk 2·9, 95% confidence interval (CI) 1·42–5·87 and 2·9, 95% CI 1·37–6·22, respectively]. Performing a HRP resulted in a threefold increase in the risk of respiratory infections. This is the first time the risk has been prospectively quantified in HCWs, providing data to inform occupational health and safety policies.


title: Le bocavirus humain (HBoV)

text: Résumé Le bocavirus humain (HBoV) a été récemment identifié dans les sécrétions respiratoires de sujets présentant une atteinte respiratoire aiguë grâce à l’utilisation de techniques de criblage moléculaire. Ce virus qui appartient à la famille des Parvoviridae a été retrouvé dans toutes les régions du monde avec une prévalence de l’ordre de 5 à 10 % chez les enfants présentant des atteintes respiratoires hautes ou basses, essentiellement en période hivernale. Une étude séroépidémiologique a montré que pratiquement tous les enfants étaient porteurs d’anticorps à l’âge de cinq ans et l’infection paraît rare chez l’adulte. Ce virus est souvent retrouvé en association avec d’autres virus respiratoires. Le virus a été retrouvé également dans les selles, mais son rôle dans les gastroentérites n’a pas été établi. Le diagnostic virologique repose sur la détection d’ADN viral par PCR. La charge virale, déterminée dans les sécrétions respiratoires par quantification de l’ADN viral, pourrait permettre de différencier une infection symptomatique d’un simple portage du virus. Abstract The human bocavirus (HBoV) has been recently identified by means of molecular screening techniques in respiratory tract secretions from children with acute respiratory tract disease. This virus, which belongs to the Parvoviridae family, has been detected worldwide with a 5 to 10% prevalence among children with upper or lower respiratory tract infections, essentially during the winter period. A seroepidemiological study has shown that almost all the children have antibodies to HBoV by the age of five years, and HBoV infection seems to be rare in adults. HBoV is often detected in association with other respiratory viruses. This virus has also been detected in stools, but its role in gastroenteritis has not been yet established. Virological diagnostic of HBoV infection is based on the detection of viral DNA by PCR. Viral load determination by viral DNA quantitation in respiratory tract secretions could be a tool to differentiate between symptomatic HBoV infection and virus carriage.


title: Successful natural interferon-β plus ribavirin therapy in a chronic hepatitis C patient after discontinuation of interferon-α treatment due to arrhythmia and interstitial pneumonia

text: A 71-year-old female patient with hepatitis C virus genotype 1 had previously discontinued interferon (IFN)-α plus ribavirin therapy, pegylated IFN-α (pegIFN-α) monotherapy, and natural IFN-α monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. She subsequently completed 72 weeks of natural IFN-β plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of IFN-α and IFN-β. Thus, natural IFN-β plus ribavirin therapy may be a treatment option for patients with poor tolerance to IFN-α or pegIFN-α treatments.


title: Pleconaril, a Novel Antipicornaviral Agent

text: Despite the availability of therapy for selected symptoms, no specific antiviral agents are available to treat or prevent infections due to the viruses of the Picornaviridae family—rhinoviruses and enteroviruses. Characterization of the three‐dimensional structure of picornaviruses in the 1980s allowed development of compounds targeted at the virus itself. Pleconaril is a novel, orally available, systemically acting molecule whose pharmacokinetics are characterized by a two‐compartment open model with first‐order absorption and with a safety profile similar to that of placebo. It shows promising results in treatment of picornaviral respiratory tract infections, meningitis, and other life‐threatening infections.


title: Genetics, antigenicity and virulence properties of three infectious bronchitis viruses isolated from a single tracheal sample in a chicken with respiratory problems

text: Abstract Three different IBV genotypes/serotypes, designated ck/CH/LDL/150434–I (LDL/150434–I), ck/CH/LDL/150434–II (LDL/150434–II) and ck/CH/LDL/150434–III (LDL/150434–III), were detected in a single tracheal sample from a chicken showing signs of respiratory disease. The viruses were isolated using a cross-neutralization test and limiting dilution in embryonated specific-pathogen-free (SPF) eggs. Isolate LDL/150434–I was a re-isolation of H120 vaccine strain that was introduced into the chicken flock by vaccination, transmitted between chickens, and later accumulated several genomic mutations. Isolate LDL/150434–II was a novel variant that originated from recombination events between H120 and ck/CH/LDT3/03-like viruses. The widespread use of H120 vaccine, which offered incomplete protection against heterotypic IBVs in the fields, may play important roles in the emergence of such a novel genetic variant. Based on the analysis of S1 and complete genomic sequence, isolate LDL/150434–III was related genetically but distinct from the established strains of nrTW I type viruses of GI-7 lineage circulating in Mainland China since 2009. The three IBV isolates were avirulent when they infected SPF chickens. Furthermore, synergistic effects on pathogenicity were not observed when the different types co-infected the SPF chickens. However, the isolates persisted in the respiratory tracts longer in combined infected birds than those in individual infected birds. The results provide insights into the evolution of the viruses and co-infection of chickens with different virus serotypes.


title: Detection and molecular characterization of feline hemoplasmas in wild felid species in Iran in the Middle East

text: Abstract Three feline hemoplasma species exist in felids: Mycoplasma haemofelis, ‘Candidatus Mycoplasma haemominutum’, and ‘Candidatus Mycoplasma turicensis’. The aims of the study were to determine the presence of, and molecularly characterize, any hemoplasmas in wild felids, including the endangered Persian leopard in Iran, the Middle East. Blood samples were collected from 19 wild felids, including three Persian leopards. Using species-specific hemoplasma PCRs and ELISA serological testing for feline leukaemia virus and feline immunodeficiency virus (FIV), two Persian leopards were found to be infected with ‘Ca. M. haemominutum’ and were seropositive for FIV. Partial 16S rRNA gene sequences were generated for these ‘Ca. M. haemominutum’ species and subsequent phylogenetic analysis revealed 97.70% to 99.45% sequence identity with those found in domestic cats from Iran and other countries. This study confirms the presence of ‘Ca. M. haemominutum’ and concurrent FIV antibody in wild felids in Iran. This represents the first report of hemoplasma in wild felids in the Middle East as well as the first report of infection in Persian leopards.


title: Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans

text: A novel human coronavirus (HCoV-EMC/2012) was isolated from a man with acute pneumonia and renal failure in June 2012. This report describes the complete genome sequence, genome organization, and expression strategy of HCoV-EMC/2012 and its relation with known coronaviruses. The genome contains 30,119 nucleotides and contains at least 10 predicted open reading frames, 9 of which are predicted to be expressed from a nested set of seven subgenomic mRNAs. Phylogenetic analysis of the replicase gene of coronaviruses with completely sequenced genomes showed that HCoV-EMC/2012 is most closely related to Tylonycteris bat coronavirus HKU4 (BtCoV-HKU4) and Pipistrellus bat coronavirus HKU5 (BtCoV-HKU5), which prototype two species in lineage C of the genus Betacoronavirus. In accordance with the guidelines of the International Committee on Taxonomy of Viruses, and in view of the 75% and 77% amino acid sequence identity in 7 conserved replicase domains with BtCoV-HKU4 and BtCoV-HKU5, respectively, we propose that HCoV-EMC/2012 prototypes a novel species in the genus Betacoronavirus. HCoV-EMC/2012 may be most closely related to a coronavirus detected in Pipistrellus pipistrellus in The Netherlands, but because only a short sequence from the most conserved part of the RNA-dependent RNA polymerase-encoding region of the genome was reported for this bat virus, its genetic distance from HCoV-EMC remains uncertain. HCoV-EMC/2012 is the sixth coronavirus known to infect humans and the first human virus within betacoronavirus lineage C.


docid: fctcwpyc

title: Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel enzootic betacoronavirus that was first described in September 2012. The clinical spectrum of MERS-CoV infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi-organ failure; overall mortality is around 35.7%. Bats harbour several betacoronaviruses that are closely related to MERS-CoV but more research is needed to establish the relationship between bats and MERS-CoV. The seroprevalence of MERS-CoV antibodies is very high in dromedary camels in Eastern Africa and the Arabian Peninsula. MERS-CoV RNA and viable virus have been isolated from dromedary camels, including some with respiratory symptoms. Furthermore, near-identical strains of MERS-CoV have been isolated from epidemiologically linked humans and camels, confirming inter-transmission, most probably from camels to humans. Though inter-human spread within health care settings is responsible for the majority of reported MERS-CoV cases, the virus is incapable at present of causing sustained human-to-human transmission. Clusters can be readily controlled with implementation of appropriate infection control procedures. Phylogenetic and sequencing data strongly suggest that MERS-CoV originated from bat ancestors after undergoing a recombination event in the spike protein, possibly in dromedary camels in Africa, before its exportation to the Arabian Peninsula along the camel trading routes. MERS-CoV serosurveys are needed to investigate possible unrecognized human infections in Africa. Amongst the important measures to control MERS-CoV spread are strict regulation of camel movement, regular herd screening and isolation of infected camels, use of personal protective equipment by camel handlers and enforcing rules banning all consumption of unpasteurized camel milk and urine.


title: Resumption of laser/IPL skin services post COVID-19 lockdown—British Medical Laser Association (BMLA) guidance document

text: The COVID-19 pandemic has had a significant negative impact on the global health economies. As health care resources have been prioritised to cater for patients affected by COVID-19, routine health care services have remained suspended. In an effort to slow the spread of SARS-CoV-2 virus, the UK introduced a country-wide lockdown which came into effect on the 23rd March 2020. Since then, clinics offering laser and intense pulsed light services have remained closed for business. As the rate of COVID-19 infection slows, the UK government has issued guidance for lifting of the lockdown in a cautious and phased manner. With this in view and to facilitate safe resumption of laser and intense pulsed light services, the British Medical Laser Services has issued this guidance document, based on best available and current scientific evidence.


title: Discovery and validation of serum biomarkers expressed over the first twelve weeks of Fasciola hepatica infection in sheep

text: Abstract Serum biomarkers associated with Fasciola hepatica infection of Corriedale sheep were analysed during the first 12 weeks of infection using surface-enhanced laser desorption ionisation time of flight mass spectrometry (SELDI-TOF MS). In the discovery phase of analysis, pooled sera collected at week 0 and at each week p.i. to week 12 were fractionated by anion-exchange chromatography and the protein mass fingerprints obtained in individual fractions were in the M/z range 1.5–150kDa. A total of 2302 protein clusters (peaks) were identified that varied between time-points following infection with peaks increasing or decreasing in intensity, or showing transient variation in intensity, during the 12 weeks of parasite challenge. In the validation phase, candidate biomarkers in sera of individual sheep at weeks 3 and 9 p.i. were analysed, identifying 100 protein peaks, many of which are small peptides <10kDa in size: 54% of these peaks were up-regulated in intensity at week 3 or 9 p.i. Twenty-six biomarkers were chosen for further study, ranging in size from 1832 to 89,823Da: six biomarkers were up-regulated at weeks 3 and 9 p.i., 16 biomarkers were up-regulated only at week 9 p.i. and four biomarkers were down-regulated at week 9 p.i. Two biomarkers up-regulated at week 9 were identified as transferrin (77.2kDa) and Apolipoprotein A-IV (44.3kDa), respectively. The results show that the interaction between the host and F. hepatica is complex, with changes in biomarker patterns beginning within 3 weeks of infection and either persisting to weeks 9–12 or showing transient changes during infection. Identification of biomarkers expressed during ovine fasciolosis may provide insights into mechanisms of pathogenesis and immunity to Fasciola and may assist in the rational development and delivery of vaccines.


title: Guidelines for TMS/tES Clinical Services and Research through the COVID-19 Pandemic

text: BACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain relevant expertise spanning NIBS technology, clinical services, and basic and clinical research – with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.


A data driven time-dependent transmission rate for tracking an epidemic: a case study of 2019-nCoV


Staying ahead of the curve: Early lessons from a New York City Otolaryngology Department's organizational response to the coronavirus pandemic


title: Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein

text: COVID-19, caused by SARS-CoV-2 has recently emerged as a global pandemic. Intense efforts are ongoing to find a vaccine or a drug to control the disease across the globe. Meanwhile, alternative therapies are also being explored to manage the disease. Phytochemicals present in essential oils are promising candidates which have been known to possess wide range of therapeutic activities. In this study, major components of several essential oils which are known for their antimicrobial properties have been docked against the S1 receptor binding domain of the spike (S) glycoprotein, which is the key target for novel antiviral drugs, to ascertain their inhibitory effects based on their binding affinities. It has been found that some monoterpenes, terpenoid phenols and phenyl propanoids such as anethole, cinnamaldehyde, carvacrol, geraniol, cinnamyl acetate, L-4-terpineol, thymol and pulegone from essential oils extracted from plants belonging to families such as Lamiaceae, Lauraceae, Myrtaceae, Apiaceae, Geraniaceae and Fabaceae are effective antiviral agents that have potential to inhibit the viral spikeprotein.


A crucial time for public health preparedness: Zika virus and the 2016 Olympics, Umrah, and Hajj


title: XDR-TB in South Africa: No Time for Denial or Complacency

text: Singh and colleagues discuss the threat to regional and global public health posed by XDR-TB in KwaZulu-Natal, and propose new measures to control the outbreak.


title: Prophylactic antibody treatment and intramuscular immunization reduce infectious human rhinovirus 16 load in the lower respiratory tract of challenged cotton rats

text: Abstract Human rhinoviruses (HRV) represent the single most important etiological agents of the common cold and are the most frequent cause of acute respiratory infections in humans. Currently the performance of available animal models for immunization studies using HRV challenge is very limited. The cotton rat (Sigmodon hispidus) is a well-recognized model for the study of human respiratory viral infections. In this work we show that, without requiring any genetic modification of either the host or the virus, intranasal infection of cotton rats with HRV16 resulted in measurable isolation of infective virus, lower respiratory tract pathology, mucus production, and expression of interferon-activated genes. Intramuscular immunization with live HRV16 generated robust protective immunity that correlated with high serum levels of neutralizing antibodies. In addition, cotton rats treated prophylactically with hyperimmune anti-HRV16 serum were protected against HRV16 intranasal challenge. Finally, protection by immunization was efficiently transferred from mothers to newborn animals resulting in a substantial reduction of infectious virus loads in the lung following intranasal challenge. Overall, our results demonstrate that the cotton rat provides valuable additional model development options for testing vaccines and prophylactic therapies against rhinovirus infection.


docid: cuhqkcyl

title: Febrile Illness in the Athlete

text: CONTEXT: Acute febrile illnesses are common in athletes over the course of training and competition seasons. Complete recovery and rapid yet safe return to participation are critical for competitive athletes. Alterations in thermoregulation, metabolism, fluid homeostasis, muscle strength, and endurance, as well as potential complications for the athlete and others, must be considered. EVIDENCE ACQUISITION: The PubMed database was searched (1970-2013) for all English-language articles related to febrile illness in sport, using the keywords fever, febrile, body temperature, thermoregulation, infection, illness, disease, exercise, athlete, sport, performance, return to play, metabolism, hydration, and dehydration. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Limited data confirm that febrile illness is correlated with alterations in the body’s thermoregulatory system, with increases in metabolic rate, and with effects in fluid homeostasis. Human and animal studies demonstrate a decrease in muscle strength and endurance secondary to muscle catabolism in febrile illness. However, indirect evidence suggests that regular exercise enhances the immune response. No strong clinical research has been published on return to play during or following acute febrile illness, excluding mononucleosis and myocarditis. CONCLUSION: Fever is correlated with an increase in insensible fluid losses, dehydration, metabolic demands, and dysregulation of body temperature. Fever can have detrimental effects on the musculoskeletal system, including decreasing strength and endurance, generalized muscle catabolism, and increase in perceived fatigue. Participating in strenuous exercise during febrile illness can worsen the illness and has demonstrated increased lethality in animal models. No consensus recommendations support return to activity before resolution of fever, and training should be resumed gradually once fever and dehydration have resolved.


title: Recombination between North American strains of porcine reproductive and respiratory syndrome virus

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV), a recently discovered arterivirus swine pathogen, was shown to undergo homologous recombination. Co-infection of MA-104 cells with two culture-adapted North American PRRSV strains resulted in recombinant viral particles containing chimeric ORF 3 and ORF 4 proteins. Nucleotide sequence analysis of cloned recombinant PCR products, encompassing 1182 bases of the 15.4 kb viral genome, revealed six independent recombination events. Recombinant products persisted in culture for at least three passages, indicating continuous formation of recombinant viruses, growth of recombinant viruses in competition with parental viruses, or both. The frequency of recombination was estimated from <2% up to 10% in the 1182 b fragment analyzed, which is similar to recombination frequencies observed in coronaviruses. An apparent example of natural ORF 5 recombination between naturally occurring wild type viruses was also found, indicating that recombination is likely an important genetic mechanism contributing to PRRSV evolution.


title: Colostrum supplementation with n-3 fatty acids and α-tocopherol alters plasma polyunsaturated fatty acid profile and decreases an indicator of oxidative stress in newborn calves

text: ABSTRACT Our objective was to characterize the effects of supplementing newborn calves with n-3 fatty acids (FA) and α-tocopherol on blood lipid profiles and oxidant status in early life. Sixteen calves received 0 or 60 mL of 1:1 fish and flaxseed oil with 200 mg of α-tocopherol in 2.8 L of colostrum within 6 h after birth. Colostrum was >22% on the Brix scale. Blood was sampled on d 1, 2, 4, 7, 14, and 21 after birth for assessment of plasma polyunsaturated FA, α-tocopherol, total serum protein, and oxidant status index, an indirect indicator of oxidative stress that examines the balance between the concentration of reactive oxygen and nitrogen species and antioxidant capacity in serum. Health was observed daily. Weight and hip height were recorded at birth, 3 wk, and 8 wk. Data were analyzed with a Mixed procedure of SAS 9.4 (SAS Institute Inc., Cary, NC). Treatment did not alter concentration of total protein in blood serum, prevalence of diarrhea or other signs of disease, or rate of growth. Feeding n-3 FA and α-tocopherol increased plasma concentrations of the n-3 FA, including α-linolenic, eicosapentaenoic, and docosahexaenoic acids, with a concomitant decrease in oxidant status index during the first week of life. Concentrations of α-tocopherol decreased with supplementation, but all calves maintained adequate concentrations. Oxidant status index of treated calves returned to the level of control calves by d 14. We conclude that a colostrum supplement of n-3 FA and α-tocopherol is safe to administer to newborn calves, reduces oxidant status in the first week of life, and may improve health and performance.


title: Evaluation of the PrimerDesign™ genesig real-time reverse transcription–polymerase chain reaction assay and the INFINITI® Respiratory Viral Panel Plus assay for the detection of human metapneumovirus in Kuwait

text: Abstract Human metapneumovirus (hMPV) is a respiratory pathogen that was discovered in 2001 and is considered a major cause of both upper and lower respiratory tract infections. A sensitive, fast, and high-throughput diagnostic test is needed for the detection of hMPV that may assist in the clinical management as well as in the reduction of inappropriate therapy. Therefore, a comparison assessment was performed in this study between the PrimerDesign™ genesig real-time reverse transcription–polymerase chain reaction (RT-PCR) Assay and the INFINITI® Respiratory Viral Panel Plus Assay (RVP-Plus) for the detection of hMPV infection in patients with respiratory tract infections. A total of 200 respiratory samples were collected from 185 hospitalized patients, during the winter season in Kuwait. Of 185 patients, 10 (5.4%) were positive for hMPV RNA by the in-house RT-PCR assay, while 7 (4%) were positive for hMPV RNA by the real-time RT-PCR assay and 9 (5%) were positive for hMPV RNA by the INFINITI® RVP-Plus assay. The high incidence rate (60%) of hMPV infection was in January 2011. The sensitivity of the real-time RT-PCR and INFINITI® RVP-Plus assays was 70% and 90%, respectively, with specificity of 100% for both assays. hMPV types A and B could be identified in this study; however, discordant genotyping results were found between the direct sequencing method and the INFINITI® RVP-Plus assay in 33% of hMPV-positive patients.


title: COVID-19: risk for cytokine targeting in chronic inflammatory diseases?

text: COVID-19, caused by the SARS-CoV-2 virus, has become pandemic. With sharply rising infection rates, patient groups characterized by an enhanced infection risk will be challenged by the virus. In this context, patients with chronic immune-mediated inflammatory diseases are of particular interest, as these diseases are characterized by an intrinsic immune dysfunction leading to inflammation that may enhance risk for severe infection.


title: American Corrections System Response to COVID-19: an Examination of the Procedures and Policies Used in Spring 2020

text: This article will explore the federal and state correction system responses to COVID-19 as of early May 2020. Current statistics of infection rates and policy responses will be discussed. In addition, adjustments to inmate activities and staff will be reviewed, as well as responses by community corrections agencies.


title: Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity

text: Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease. The potential recurrence of the disease from animal reservoirs highlights the significance of development of safe and efficient vaccines to prevent a future SARS epidemic. In this study, we expressed the recombinant receptor-binding domain (rRBD) in mammalian (293T) cells, insect (Sf9) cells, and E. coli, respectively, and compared their immunogenicity and protection against SARS-CoV infection in an established mouse model. Our results show that all rRBD proteins expressed in the above systems maintained intact conformation, being able to induce highly potent neutralizing antibody responses and complete protective immunity against SARS-CoV challenge in mice, albeit the rRBD expressed in 293T cells elicited stronger humoral immune responses with significantly higher neutralizing activity (P < 0.05) than those expressed in Sf9 and E. coli cells. These results suggest that all three rRBDs are effective in eliciting immune responses and protection against SARS-CoV and any of the above expression systems can be used for production of rRBD-based SARS subunit vaccines. Preference will be given to rRBD expressed in mammalian cells for future evaluation of the vaccine efficacy in a non-human primate model of SARS because of its ability to refold into a native conformation more readily and to induce higher level of neutralizing antibody responses than those expressed in E. coli and insect cells.


docid: fkqohnyz

title: The aetiology, origins, and diagnosis of severe acute respiratory syndrome

text: Summary Severe acute respiratory syndrome (SARS) is a new infectious disease that first emerged in Guangdong province, China, in November, 2002. A novel coronavirus was later identified in patients with SARS. The detection of the virus in these patients, its absence in healthy controls or other patients with atypical pneumonia, and the reproduction of a similar disease in a relevant animal model fulfilled Koch's postulates for implicating this coronavirus as the causal agent of SARS. The full genome sequence was determined within weeks of the virus's identification. The rapid progress in the aetiology, the development of laboratory diagnostic tests, and the defining of routes of viral transmission were facilitated through a unique WHO-coordinated virtual network of laboratories, which shared information on a real-time basis through daily teleconferences. Subsequent studies have indicated that the SARS coronavirus is of animal origin, that its precursor is still present in animal populations within the region, and that live-animal markets in southern China may have provided the animal-human interphase that allowed this precursor virus to adapt to human-human transmission. These findings underscore the potential for the re-emergence of SARS and the need for laboratory tests for early diagnosis. However, the low viral load in the respiratory tract makes early diagnosis of SARS a diagnostic challenge, although improvements in the sensitivity of molecular diagnostic methods continue to be made.


title: Covid-19 cases in a no-Covid-19 geriatric acute care setting. A sporadic occurrence?

text: • Covid-19 cases are frequent in elderly patients admitted to acute no-Covid-19 units; • Healthcare personnel is at high risk to present coronavirus infection; • Hospital transmission of Covid-19 can be frequent in older individuals; • Maximum efforts should be given to screen patients and staff even if asymptomatic; • Prevention is very important for Covid-19 severe prognosis in older patients.