title: Streptococcus zooepidemicus: An emerging canine pathogen

text: Abstract Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) has caused several outbreaks of haemorrhagic pneumonia in dogs in recent years. This highly contagious and often fatal disease is characterised by sudden onset of clinical signs including pyrexia, dyspnoea and haemorrhagic nasal discharge. Post mortem examination typically reveals pulmonary haemorrhage and pleural effusion. Histopathology demonstrates fibrino-suppurative, necrotising and haemorrhagic pneumonia in most cases. The pathogenesis of S. zooepidemicus infection in dogs is incompletely understood. Bacterial virulence factors as well as host factors may contribute to the severe outcome. S. zooepidemicus occasionally causes zoonotic infections with potentially serious consequences. Canine vaccines for S. zooepidemicus are currently not available and prevention of the disease therefore relies on limiting bacterial spread by implementing stringent control measures in kennels. Further research, particularly sequence analysis of canine strains, is required to gain insights into epidemiology and pathogenesis of this emerging disease.


title: Effects of curcumin in treatment of experimental pulmonary fibrosis: A comparison with hydrocortisone

text: Abstract To compare curcumin with hydrocortisone for treating bleomycin-induced pulmonary fibrosis (BLMPF), four groups of rats were injected with 1.5mg/kg bleomycin intratracheally. Then the Group HC rats were treated with three injections of 2mg/kg hydrocortisone i.p.; Group CH and CL rats, respectively, were orally given 500 or 250mg/kg curcumin daily; and Group PC rats were given deionized water alone. After 28 days of treatment, lung samples were examined by H-E staining, Masson's staining and immunohistochemical analyses and pulmonary type I collagen (Col-I), inducible nitric oxide synthetase (iNOS) and transforming growth factor-β1 (TGF-β1) were determined by Western blotting and real-time RT PCR analyses. The results showed that (1) Group PC rats had histopathological characteristics of BLMPF with significant increase in their protein/mRNA expressions of Col-I (+114%/+173%), iNOS (+146%/+523%) and TGF-β1 (+476%/+527%) (P <0.01); (2) in Group HC, CH and CL rats, protein/mRNA expressions of Col-I (−39%/−52%, −31%/−57%, −33%/−58%), iNOS (−31%/−51%, −31%/−79%, −31%/−47%) and TGF-β1 (−64%/−78%, −75%/−74%, −81%/−79%) were significantly lower than Group PC (P <0.05); (3) except for levels of TGF-β1 protein, there was no significant difference among Group CH, CL and HC rats (P >0.05). It suggests that curcumin may play a similar role as hydrocortisone in preventing BLMPF.


title: Towards appropriate mainstreaming of “Theory of Change” approaches into agricultural research for development: Challenges and opportunities

text: Abstract Food insecurity persists in many parts of Africa and Asia, despite ongoing agricultural research for development (AR4D) interventions. This is resulting in a growing demand for alternative approaches to designing and evaluating interventions in complex systems. Theory of Change (ToC) is an approach which may be useful because it enables stakeholders to present and test their theories and assumptions about why and how impact may occur, ideally within an environment conducive to iterative reflection and learning. However, ToC is yet to be appropriately mainstreamed into development by donors, researchers and practitioners. We carried out a literature review, triangulated by interviews with 26 experts in African and Asian food security, consisting of researchers, advisors to programs, and donors. Although 17 (65%) of the experts had adopted ToC, their responses and the literature revealed four challenges to mainstreaming: (i) different interpretations of ToC; (ii) incoherence in relationships among the constituent concepts of ToC; (iii) confused relationships between ToC and project “logframes”; and (iv) limitations in necessary skills and commitment for enacting ToC. A case study of the evolution of a ToC in a West African AR4D project over 4 years which exemplified these challenges is presented. Five recommendations arise to assist the mainstreaming of ToC: (i) select a type of ToC suited to the relative complexity of the problem and focal system of interest; (ii) state a theory or hypotheses to be tested as the intervention progresses; (iii) articulate the relationship between the ToC and parallel approaches (e.g. logframe); (iv) accept that a ToC is a process, and (v) allow time and resources for implementers and researchers to develop ToC thinking within projects. Finally, we suggest that communities of practice should be established among AR4D and donor organisations to test, evaluate and improve the contribution that ToCs can make to sustainable food security and agricultural development.


Emerging infections and sensationalism: in Aesop's fable, the boy who cried wolf had a dreadful fate


COVID-19 in a lung transplant Recipient


In Reference to Anosmia and Ageusia: Common Findings in COVID‐19 Patients


Prevalence of Anxiety and Depression among the Healthcare Workers in Nepal during the COVID-19 Pandemic


Public responses to the novel 2019 coronavirus (2019‐nCoV) in Japan: Mental health consequences and target populations


title: Rare Presentation of Pulmonary Embolism Amidst Coronavirus Disease 2019 Era: Utility of Multiorgan Ultrasonography

text: Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is the underlying cause of a global crisis that the entire world is facing. It is a highly contagious viral infection, which is why social distancing seems to be effective. Its ability to survive on various surfaces and aerosolize necessitates very meticulous precautions, including airborne isolation for severely ill patients requiring mechanical ventilation. However, these patients may need routine diagnostic investigations including chest computed tomography and chest tomography angiogram scans (CT and CTA) to rule out other potential differential diagnoses and guide management. In this case, we focus on the utility of multiorgan ultrasonography (MOU) at the bedside to diagnose and manage pulmonary embolism (PE) in COVID-19 patients.


title: High-cell-density cultivations to increase MVA virus production

text: Abstract Increasing the yield and the productivity in cell culture-based vaccine manufacturing using high-cell-density (HCD) cultivations faces a number of challenges. For example, medium consumption should be low to obtain a very high concentration of viable host cells in an economical way but must be balanced against the requirement that accumulation of toxic metabolites and limitation of nutrients have to be avoided. HCD cultivations should also be optimized to avoid unwanted induction of apoptosis or autophagy during the early phase of virus infection. To realize the full potential of HCD cultivations, a rational analysis of the cultivation conditions of the appropriate host cell line together with the optimal infection conditions for the chosen viral vaccine strain needs to be performed for each particular manufacturing process. We here illustrate our strategy for production of the modified vaccinia Ankara (MVA) virus isolate MVA-CR19 in the avian suspension cell line AGE1.CR.pIX at HCD. As a first step we demonstrate that the adjustment of the perfusion rate strictly based on the measured cell concentration and the glucose consumption rate of cells enables optimal growth in a 0.8 L bioreactor equipped with an ATF2 system. Concentrations up to 57 × 106 cells/mL (before infection) were obtained with a viability exceeding 95%, and a maximum specific cell growth rate of 0.019 h−1 (doubling time = 36.5 h). However, not only the cell-specific MVA-CR19 virus yield but also the volumetric productivity was reduced compared to infections at conventional-cell-density (CCD). To facilitate optimization of the virus propagation phase at HCD, a larger set of feeding strategies was analyzed in small-scale cultivations using shake flasks. Densities up to 63 × 106 cells/mL were obtained at the end of the cell growth phase applying a discontinuous perfusion mode (semi-perfusion) with the same cell-specific perfusion rate as in the bioreactor (0.060 nL/(cell d)). At this cell concentration, a medium exchange at time of infection was required to obtain expected virus yields during the first 24 h after infection. Applying an additional fed-batch feeding strategy during the whole virus replication phase resulted in a faster virus titer increase during the first 36 h after infection. In contrast, a semi-continuous virus harvest scheme improved virus accumulation and recovery at a rather later stage of infection. Overall, a combination of both fed-batch and medium exchange strategies resulted in similar cell-specific virus yields as those obtained for CCD processes but 10-fold higher MVA-CR19 titers, and four times higher volumetric productivity.


title: Geographical structure of bat SARS-related coronaviruses

text: Abstract Bats are the natural reservoirs of severe acute respiratory syndrome coronavirus (SARS-CoV) which caused the outbreak of human SARS in 2002–2003. We introduce the genetic diversity of SARS-related coronaviruses (SARSr-CoVs) discovered in bats and provide insights on the bat origin of human SARS. We also analyze the viral geographical structure that may improve our understanding of the evolution of bat SARSr-CoVs.


title: AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

text: Abstract Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1β, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.


title: Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus

text: Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2)) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.


title: Coding-Complete Genome Sequences of Two SARS-CoV-2 Isolates from Egypt

text: This report announces the complete genome sequences of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolates detected in Egypt. The isolates were obtained from oropharyngeal swab specimens from two Egyptians in Upper and Lower Egypt. Sequence analysis showed mutations that differentiate Egyptian strains from the reference strain 2019-nCoV WHU01.


title: Test, test, test for COVID-19 antibodies: the importance of sensitivity, specificity and predictive powers

text: Abstract SARS-CoV-2 antibody tests of varying specificity and sensitivity are now available. For informing individuals whether they have had COVID-19, they need to be very accurate. For measuring population prevalence of past infection, the numbers of false positives and negatives need to be roughly equal. With a series of worked examples for a notional population of 100,000 people, we show that even test systems with a high specificity can yield a large number of false positive results, especially where the population prevalence is low. For example, at a true population prevalence of 5%, using a test with 99% sensitivity and specificity, 16% of positive results will be false and thus 950 people will be incorrectly informed they have had the infection. Further confirmatory testing may be needed. Giving false reassurance upon which personal or societal decisions might be based could be harmful for individuals, undermine public confidence and foster further outbreaks.


title: Case series of coronavirus (SARS-CoV-2) in a military recruit school: clinical, sanitary and logistical implications

text: INTRODUCTION: A new coronavirus, called Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2), has emerged from China in late 2019 and has now caused a worldwide pandemic. The impact of COVID-19 has not been described so far in a military setting. We therefore report a case series of infected patients in a recruit school in Switzerland and the herein associated challenges. METHODS: Retrospective review of COVID-19 cases among Swiss Armed Forces recruits in the early weeks of SARS-CoV-2 pandemic in the canton of Ticino, the southernmost canton of Switzerland. Positive cases were defined with two positive PCR testing for SARS-CoV-2 from nasopharyngeal swabs. Serological testing was performed with a commercially available kit according to manufacturers’ instructions. RESULTS: The first case was likely contaminated while skiing during weekend permission. He became symptomatic 4 days later, tested positive for SARS-CoV-2 and was put into isolation. He showed complete symptom resolution after 48 hours. Quarantine was ordered for all recruits with close contact in the past 2 days, a total of 55 persons out of 140 in the company. Seven out of nine recruits in one particular quarantine room became mildly symptomatic. SARS-CoV-2 PCR was positive in one of them. Seven days after initial diagnosis, the index patient and the other one from the quarantine retested positive for SARS-CoV-2, although they had been completely asymptomatic for over 96 hours. Serological testing revealed positive for both patients. All others showed negative IgM and IgG. CONCLUSIONS: Young healthy recruits often showed a mild course of COVID-19 with rapid symptom decline but were persistent SARS-CoV-2 carriers. This illustrates how asymptomatic patients may be responsible for covert viral transmission. An early and prolonged establishment of isolation and quarantine for patients and close contacts is essential to slow down the spread of SARS-CoV-2, especially in the confined space of a military environment.


title: From Anonymous to Public Enemy: How Does a Mosquito Become a Feared Arbovirus Vector?

text: The past few decades have seen the emergence of several worldwide arbovirus epidemics (chikungunya, Zika), the expansion or recrudescence of historical arboviruses (dengue, yellow fever), and the modification of the distribution area of major vector mosquitoes such as Aedes aegypti and Ae. albopictus, raising questions about the risk of appearance of new vectors and new epidemics. In this opinion piece, we review the factors that led to the emergence of yellow fever in the Americas, define the conditions for a mosquito to become a vector, analyse the recent example of the new status of Aedes albopictus from neglected mosquito to major vector, and propose some scenarios for the future.


title: Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study

text: BACKGROUND: High serum levels of certain aromatic microbial metabolites (AMM) are associated with severity and mortality in critically ill patients. Omics-based studies suggest gut dysbiosis and reduced microbiome diversity in critical conditions. However, the landscape of gut microbial metabolites is still to be outlined, not to mention the interplay correlation between the metabolome and gut microbiome in critically ill patients. The aim of this study was to analyze the association between serum and fecal levels of AMM and compare them with the composition of gut microbiota in critically ill patients in the acute and chronic stages. METHODS: In this prospective observational pilot study, we analyzed the temporal dynamics of the gut microbiome and the AMM spectrum across two distinct subgroups—acute critical ill (ACI) patients with nosocomial pneumonia and chronically critically ill (CCI) patients (9 subjects each group)—as well as performed comparison with 23 healthy volunteers. The AMM levels for each patient were measured using GC-MS in simultaneously taken serum and fecal samples (SFS). These parameters were compared with 16S rRNA fecal microbiome profiles. RESULTS: The observed proportions of bacterial taxa suggest a significant gut dysbiosis in the ACI and the CCI patients. Stronger imbalance in microbiome composition and dynamics observed in the ACI patients compared to the CCI ones resonates with a higher severity in the former group. The total levels of AMM in serum samples were higher for the ACI patients than for the CCI patients (3.7 (1.4–6.3) and 1.1 (1.0–1.6) μM, respectively; p = 0.0003). The qualitative composition of the SFS was also altered. We discovered significant associations between gut microbial taxa levels and metabolite concentrations in blood serum as well as in feces in each of the ACI and the CCI patients. CONCLUSIONS: Aromatic microbial metabolite profiles in the gut and the serum are interlinked and reflect a disruption of the gut microbial community in critically ill patients.


title: Could Ergothioneine Aid in the Treatment of Coronavirus Patients?

text: Infection with SARS-CoV-2 causes the coronavirus infectious disease 2019 (COVID-19), a pandemic that has, at present, infected more than 11 million people globally Some COVID-19 patients develop a severe and critical illness, spurred on by excessive inflammation that can lead to respiratory or multiorgan failure Numerous studies have established the unique array of cytoprotective properties of the dietary amino acid ergothioneine Based on studies in a range of in vitro and in vivo models, ergothioneine has exhibited the ability to modulate inflammation, scavenge free radicals, protect against acute respiratory distress syndrome, prevent endothelial dysfunction, protect against ischemia and reperfusion injury, protect against neuronal damage, counteract iron dysregulation, hinder lung and liver fibrosis, and mitigate damage to the lungs, kidneys, liver, gastrointestinal tract, and testis, amongst many others When compiled, this evidence suggests that ergothioneine has a potential application in the treatment of the underlying pathology of COVID-19 We propose that ergothioneine could be used as a therapeutic to reduce the severity and mortality of COVID-19, especially in the elderly and those with underlying health conditions This review presents evidence to support that proposal


title: Virus Hunters: Catching Bugs in the Field

text: Densely populated areas in rural China require constant vigilance and state-of-the-art technology to stop new pandemics in their tracks. Hurdles are not only scientific in some parts of the developing world.


docid: olyzmson

title: Lack of Middle East Respiratory Syndrome Coronavirus Transmission from Infected Camels

text: To determine risk for Middle East respiratory syndrome coronavirus transmission from camels to humans, we tested serum from 191 persons with various levels of exposure to an infected dromedary herd. We found no serologic evidence of human infection, suggesting that zoonotic transmission of this virus from dromedaries is rare.


title: COVID19 inhibitors: A prospective therapeutics

text: Abstract The inhibition of viral targets might provide new therapies for coronavirus disease abbreviated as COVID-19. The rational drug design identified as much of the recent discoveries of potent drugs molecule against any targets. This results in an improvement in bindings for better potency and selectivity. The drugs containing ethanolamine/propylamine fragments along with heterocycles have shown potential antiviral results. Similarly, there is the possibility of controlling the COVID-19 infection by nucleotide analogues. Here we also highlight drugs ACEIs/ARBs inhibitory discussing both their advantages and disadvantages. The class of compounds/antibodies inhibiting interleukin-6 works in antirheumatoid drugs are found useful in alleviating overactive inflammatory responses in the lungs of the patient. These inclusion based approaches counter some of the side-effects associated with the heterocycles and also potentiate the efficacy of the molecules. In this review article, design strategies for some of the drugs effective against SARS-CoV-2 are represented. The review also focuses on the listing of drugs that are currently testing under clinical trials for the COVID-19 virus with their mechanism of action. This conversation undertakes the opportunity to do a bit for the newer researchers working in this arena.


title: COVID-19 occurring during Natalizumab treatment: a case report in a patient with extended interval dosing approach

text: Abstract Background The novel Coronavirus SARS-CoV-2, which was identified after a recent outbreak in Wuhan, China, in December 2019, has generated a global pandemic impacting over 200 countries around the world. Recent reports suggest that ACE2, which is the target protein to invade the host, has a ubiquitous presence in human organs, including lung parenchyma, gastrointestinal tract, nasal mucosa, renal and urinary tract, airway epithelia, lymphoid tissues, reproductive organs, vascular endothelium and neurons. In this scenario, neurologists are particularly involved into considering even more specific therapeutic strategies according to the available data during the pandemic. In particular, MS patients are usually receiving disease-modifying therapies (DMTs) with immunosuppressant or immunomodulatory effects, which increase the risk of infections and morbidity, compared with the general population. Development of PML or other serious opportunistic infections during treatment with natalizumab forces to consider whether de-risking strategies are needed in this particular context and how to manage a high-efficacy treatment. Methods In this paper we report on a patient treated with natalizumab for relapsing MS who developed COVID-19 and recovered in a few days without complications. Results After recovery natalizumab has been administered in the window of the extended interval dosing (EID), without reporting any worsening or new symptoms. Discussion This case supports the opportunity to avoid discontinuing or delaying the retreatment over 8 weeks in patients recovered from a recent COVID-19.


title: Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore

text: Abstract Severe acute respiratory syndrome (SARS) is an infectious condition caused by the SARS-associated coronavirus (SARS-CoV), a new member in the family Coronaviridae. To evaluate the lung pathology in this life-threatening respiratory illness, we studied postmortem lung sections from 8 patients who died from SARS during the spring 2003 Singapore outbreak. The predominant pattern of lung injury in all 8 cases was diffuse alveolar damage. The histology varied according to the duration of illness. Cases of 10 or fewer days’ duration demonstrated acute-phase diffuse alveolar damage (DAD), airspace edema, and bronchiolar fibrin. Cases of more than 10 days’ duration exhibited organizing-phase DAD, type II pneumocyte hyperplasia, squamous metaplasia, multinucleated giant cells, and acute bronchopneumonia. In acute-phase DAD, pancytokeratin staining was positive in hyaline membranes along alveolar walls and highlighted the absence of pneumocytes. Multinucleated cells were shown to be both type II pneumocytes and macrophages by pancytokeratin, thyroid transcription factor-1, and CD68 staining. SARS-CoV RNA was identified by reverse transcriptase-polymerase chain reaction in 7 of 8 cases in fresh autopsy tissue and in 8 of 8 cases in formalin-fixed, paraffin-embedded lung tissue, including the 1 negative case in fresh tissue. Understanding the pathology of DAD in SARS patients may provide the basis for therapeutic strategies. Further studies of the pathogenesis of SARS may reveal new insight into the mechanisms of DAD.


title: Workforce Considerations, Training, and Diseases in the Middle East

text: Evaluating and providing global health assistance, humanitarian aid, and medical missions to Middle Eastern countries can be rewarding and challenging. A broad spectrum of financial capabilities supports effective health care delivery and infrastructure. Middle East tension can make obtaining a visa difficult. Personal safety considerations may hinder efforts to develop and carry out clinical and educational programs. Several Middle East countries have sophisticated and modern health care systems. Medical education and specialty training compares with that of Western medicine. The Middle East has a proud heritage as the foundation of many fundamental and modern medical and surgical principles.


title: Ebola: werknemers in de frontlijn: Infectieziekten en Arbeid

text: Ebola is de zoveelste zoönose die de Nederlandse samenleving treft binnen een paar jaar tijd. Denk maar aan de Mexicaanse griep, het Schmallenbergvirus, H5N8 aviaire influenza, MERS-CoV(16), Q-koorts en de ziekte van Lyme. De schaal waarop Nederlandse UMC’s en andere ketenpartners zich voorbereiden op een mogelijke introductie van ebola is ongeëvenaard. Sinds augustus 2014 houden vele duizenden professionals, beleidsmakers, et cetera, zich intensief bezig met de voorbereidingen. Uniek bij deze ebola-uitbraak is de grote aandacht voor de bedrijfsgeneeskunde. Was er bij eerdere zoönosen minimaal aandacht voor bedrijfsgeneeskundige aspecten, bij ebola zijn veilige arbeidsomstandigheden een centraal thema – terecht, want werknemers staan hier in de frontlijn. Never waste a good crisis. Wellicht is dit een uitgelezen kans om het thema veilige arbeidsomstandigheden en biologische agentia weer eens bij klanten op de agenda te zetten, ook in andere sectoren.


title: Incremental Validity of Coronaphobia: Coronavirus Anxiety explains Depression, Generalized Anxiety, and Death Anxiety

text: The adverse psychological effects of COVID-19 have increased globally. Moreover, the psychological toll may be worsening for this health crisis due to the growing numbers of mass deaths and unemployment levels. Coronaphobia, a relatively new pandemic-related construct, has been shown to be strongly related to functional impairment and psychological distress. However, the extent to which coronaphobia is uniquely accountable for the psychological distress experienced during the COVID-19 crisis has not been systematically investigated. The current study examined this question of incremental validity using online data from 453 adult MTurk workers in the U.S. The results of a series of hierarchical multiple regression analyses demonstrated that coronaphobia explained additional variance in depression, generalized anxiety, and death anxiety, above sociodemographics, COVID-19 factors, and the vulnerability factors of neuroticism, health anxiety, and reassurance-seeking behaviors. These findings suggest that health professionals should be aware of coronaphobia as this expression of pandemic-related stress has reliably demonstrated incremental validity in accounting for major indicators of psychological distress.


title: 100% peer review in radiation oncology: is it feasible?

text: PURPOSE: Peer review has been proposed as a strategy to ensure patient safety and plan quality in radiation oncology. Despite its potential benefits, barriers commonly exist to its optimal implementation in daily clinical routine. Our purpose is to analyze peer-review process at our institution. METHODS AND MATERIALS: Based on our group peer-review process, we quantified the rate of plan changes, time and resources needed for this process. Prospectively, data on cases presented at our institutional peer-review conference attended by physicians, resident physicians and physicists were collected. Items such as time to present per case, type of patient (adult or pediatric), treatment intent, dose, aimed technique, disease location and receipt of previous radiation were gathered. Cases were then analyzed to determine the rate of major change, minor change and plan rejection after presentation as well as the median time per session. RESULTS: Over a period of 4 weeks, 148 cases were reviewed. Median of attendants was six physicians, three in-training-physicians and one physicist. Median time per session was 38 (4–72) minutes. 59.5% of cases presented in 1–4 min, 32.4% in 5–9 min and 8.1% in ≥ 10 min. 79.1% of cases were accepted without changes, 11.5% with minor changes, 6% with major changes and 3.4% were rejected with indication of new presentation. Most frequent reason of change was contouring corrections (53.8%) followed by dose or fractionation (26.9%). CONCLUSION: Everyday group consensus peer review is an efficient manner to recollect clinical and technical data of cases presented to ensure quality radiation care before initiation of treatment as well as ensuring department quality in a feedback team environment. This model is feasible within the normal operation of every radiation oncology Department.


title: Differential innate immune responses induced by classical and variant infectious bronchitis viruses in specific pathogen free chicks

text: Abstract Avian infectious bronchitis virus (IBV) continues to cause serious economic losses in global chicken production. Concurrent circulation of both classic and variant IBVs have been identified in most parts of the world, raising major challenges to global prevention and control efforts. Therefore, immunopathogenesis, particularly early host responses, needs to be better understood for effective control of diseases caused by different strains of IBVs. We investigated differing immunopathogenesis in chickens following infection with IS/885/00-like (885), QX-like (QX) and M41 IBV strains. We confirmed that the histopathological changes, proinflammatory and innate immune gene responses were induced to different magnitudes, depending on the IBV strain. Results indicated that upregulation of proinflammatory cytokines (such as IL-6 and IL-1β) and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF) expression is induced by IBV M41 in the trachea and by IBV 885 and QX in the kidney, which mainly coincides with tracheal and renal histopathological lesions respectively caused by these strains. In addition, elevated levels of TLR3, MDA5 and IFN-β expression occurred concurrently with greater lesion severity in IBV infected trachea and kidney tissues. Overall, this study reports marked differences in the activation of early host responses by pathogenic IBV strains.


title: Establishment of a recombinase polymerase amplification (RPA) assay for the detection of Brucella spp. Infection

text: Abstract Brucellosis is a worldwide re-emerging zoonosis. It has an economic impact due to abortion and loss of fertility in livestock. In this study, Real-time recombinase polymerase amplification (RT-RPA-BP26) targeting Brucella spp. bp26 gene and Lateral flow dipstick (LFD-RPA-IS711) combined with SYBR- Green recombinase polymerase amplification (RPA) targeting insertion sequence IS711 region of Brucella spp. bp26 gene, was developed to detect Brucella spp. from different sample types in domestic animals. The sensitivity and specificity of the two developed RPAs were compared with real-time PCR, PCR, and Rose Bengal Plate Test (RBPT). The analytical sensitivity and detection limit of Real-time RPA and LFD RPA were four and six copies per reaction respectively. The detection of six colony forming units (CFU) of the bacteria-bearing construct with the target sequence was within 20 min at 40 °C for Real-time RPA and 37 °C for LFD RPA. The LFD RPA could work at temperatures between 30 and 35 °C and could be completed within 10–30 min. No significant differences were observed when comparing the results from Real-time RPA and LFD RPA to Real-time PCR and PCR. Both methods showed no cross reactivity with Chlamydia abortus, Toxoplasma gondii, Salmonella typhimurium, and Escherichia coli. In conclusion, RPA is a useful and convenient field and point of care test for brucellosis.


title: Phage display technique identifies the interaction of severe acute respiratory syndrome coronavirus open reading frame 6 protein with nuclear pore complex interacting protein NPIPB3 in modulating Type I interferon antagonism

text: Abstract Background/Purpose Severe acute respiratory syndrome coronavirus (SARS-CoV) proteins including ORF6 inhibit Type I interferon (IFN) signaling. Methods This study identified SARS-CoV ORF6-interacting proteins using the phage displayed human lung cDNA libraries, and examined the association of ORF6–host factor interaction with Type I IFN antagonism. After the fifth round of biopanning with Escherichia coli-synthesized ORF6-His tagged protein, the relative binding affinity of phage clones to ORF6 was determined using direct enzyme-linked immunosorbent assay. Results The highest affinity clone to ORF6 displayed the C-terminal domain of NPIPB3 (nuclear pore complex interacting protein family, member B3; also named as phosphatidylinositol-3-kinase-related kinase SMG-1 isoform 1 homolog). The coimmunoprecipitation assay demonstrated the direct binding of ORF6 to the C-terminal domain of NPIPB3 in vitro. Confocal imaging revealed a close colocalization of SARS-CoV ORF6 protein with NPIPB3 in human promonocytes. The dual luciferase reporter assay showed that the C-terminal domain of NPIPB3 attenuated the antagonistic activity of SARS-CoV ORF6 on IFN-β-induced ISRE (IFN stimulated response element)-responsive firefly luciferase activity. In addition, confocal imaging and Western blotting assays revealed that the increases in STAT-1 nuclear translocation and phosphorylation occurred in the transfected cells expressing both genes of ORF6 and NPIPB3, but not in the ORF6-expressing cells in response to IFN-β. Conclusion The overexpression of NPIPB3 restored the IFN-β responses in SARS-CoV ORF6 expressing cells, indicating that the interaction of SARS CoV ORF6 and NPIPB3 reduced Type I IFN antagonism by SARS-CoV ORF6.


title: Expression, crystallization and preliminary crystallographic study of the functional mutant (N60K) of nonstructural protein 9 from Human coronavirus HKU1

text: Human coronavirus HKU1 (HCoV-HKU1), which mainly causes acute self-limited respiratory-tract infections, belongs to group A of the Betacoronavirus genus. Coronavirus genomes encode 16 nonstructural proteins (nsp1–16), which assemble into a large replication–transcription complex mediating virus propagation. Nonstructural protein 9, which binds to the single-stranded DNA/RNA, has been shown to be indispensible for viral replication. Interestingly, a functional mutant (N60K) of nsp9 was identified to compensate for a 6 nt insertion mutation of the 3′-untranslated region (UTR), which is critical for viral RNA synthesis. It has been proposed that the N60K mutation may cause certain conformational changes of nsp9 to rescue the defective insertion mutant. To further investigate the underlying structural mechanism, the N60K mutant of nsp9 from HCoV-HKU1 was successfully crystallized in this study. The crystals diffracted to 2.6 Å resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 31.9, b = 85.0, c = 95.0 Å. Two molecules were identified per asymmetric unit.


title: Nafamostat Mesylate Blocks Activation of SARS-CoV-2: New Treatment Option for COVID-19

text: The currently unfolding coronavirus pandemic threatens health systems and economies worldwide.….


title: Epidemiology of COVID-19 in older persons, Wuhan, China

text: BACKGROUND: The epidemiological characteristics of older patients with COVID-19 was far from clear. OBJECTIVE: To explore the epidemiology of older patients with COVID-19 in Wuhan, China. DESIGN: A retrospective cross-sectional study. SETTING: A population-based study. SUBJECTS: The resident older patients (older than 65 years old) diagnosed with COVID-19. METHODS: Citywide case series reported to Wuhan Center for Disease Control and Prevention from 12 December 2019 to 17 March 2020 were included. The epidemic curves were constructed by dates of disease onset. RESULTS: 14238 confirmed COVID-19 cases were older persons. The number of male cases were slightly less than female cases (1:1.01). The attack rate of COVID-19 in the older persons was 11.49‰ in Wuhan. There was a rapid increase of disease at the early stage of the epidemic and then a gradual and steady decrease was performed. 3,723 (26.15%) and 734 (5.16%) patients were diagnosed as severe and critical cases, respectively. The attributable crude fatality ratio of COVID-19 in the older population was 222.57/100,000, and the crude fatality ratio of COVID was 19.37%. The proportion of severe and critical cases, and fatality ratio were both higher in downtown area and increased with age. CONCLUSIONS: The older persons are sensitive to COVID-19. The proportion of severe and critical cases and fatality ratio are higher than that in children and younger adults. Strengthen the protection and control strategies for the older adults is of priorities. More detailed epidemiological and clinical information should be measured in further studies.


title: Assembling evidence for identifying reservoirs of infection

text: Many pathogens persist in multihost systems, making the identification of infection reservoirs crucial for devising effective interventions. Here, we present a conceptual framework for classifying patterns of incidence and prevalence, and review recent scientific advances that allow us to study and manage reservoirs simultaneously. We argue that interventions can have a crucial role in enriching our mechanistic understanding of how reservoirs function and should be embedded as quasi-experimental studies in adaptive management frameworks. Single approaches to the study of reservoirs are unlikely to generate conclusive insights whereas the formal integration of data and methodologies, involving interventions, pathogen genetics, and contemporary surveillance techniques, promises to open up new opportunities to advance understanding of complex multihost systems.


title: Contingency Plan for the Intensive Care Services for the COVID-19 pandemic

text: Abstract In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC, have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.


title: An uncommon cold

text: The covid-19 virus isn't the first coronavirus to jump from animals to humans. What can we learn from previous encounters, asks Anthony King


title: Essential Long‐Term Care Workers Commonly Hold Second Jobs and Double‐ or Triple‐Duty Caregiving Roles

text: OBJECTIVES: Long‐term care (LTC) facilities are particularly dangerous places for the spread of COVID‐19 given that they house vulnerable high‐risk populations. Transmission‐based precautions to protect residents, employees, and families alike must account for potential risks posed by LTC workersʼ second jobs and unpaid care work. This observational study describes the prevalence of their (1) second jobs, and (2) unpaid care work for dependent children and/or adult relatives (double‐ and triple‐duty caregiving) overall and by occupational group (registered nurses [RNs], licensed practical nurses [LPNs], or certified nursing assistants [CNAs]). DESIGN: A descriptive secondary analysis of data collected as part of the final wave of the Work, Family and Health Study. SETTING: Thirty nursing home facilities located throughout the northeastern United States. PARTICIPANTS: A subset of 958 essential facility‐based LTC workers involved in direct patient care. MEASUREMENTS: We present information on LTC workersʼ demographic characteristics, health, features of their LTC occupation, additional paid work, wages, and double‐ or triple‐duty caregiving roles. RESULTS: Most LTC workers were CNAs, followed by LPNs and RNs. Overall, more than 70% of these workers agreed or strongly agreed with this statement: “When you are sick, you still feel obligated to come into work.” One‐sixth had a second job, where they worked an average of 20 hours per week, and more than 60% held double‐ or triple‐duty caregiving roles. Additional paid work and unpaid care work characteristics did not significantly differ by occupational group, although the prevalence of second jobs was highest and accompanying work hours were longest among CNAs. CONCLUSION: LTC workers commonly hold second jobs along with double‐ and triple‐duty caregiving roles. To slow the spread of COVID‐19, both the paid and unpaid activities of these employees warrant consideration in the identification of appropriate clinical, policy, and informal supports.


title: Advax Delta Inulin Adjuvant Overcomes Immune Immaturity In Neonatal Mice Thereby Allowing Single–Dose Influenza Vaccine Protection

text: Neonates are at high risk for influenza morbidity and mortality due to immune immaturity and lack of priming by prior exposure. Inactivated influenza vaccines are ineffective in infants under six months and to provide protection in older children generally require two doses given a month apart. This leaves few options for rapid protection of infants, e.g. during an influenza pandemic. We investigated whether Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles could help overcome neonatal immune hypo-responsiveness and also whether it was possible to obtain single-dose influenza vaccine protection of babies against lethal infection. Inactivated influenza A/H1N1 vaccine (iH1N1) combined with Advax™ adjuvant administered as a single immunization to 7-day-old mouse pups significantly enhanced serum influenza-specific IgM, IgG1, IgG2a and IgG2b levels in association with a 3–4 fold increase in the frequency of splenic influenza-specific IgM and IgG antibody secreting cells versus pups immunized with iH1N1 alone. Pups immunized with Advax-adjuvanted iH1N1 had significantly higher influenza-stimulated splenocyte production of IFN-γ, IL-2, IL-4, and IL-10 and a 3–10 fold higher frequency of T cells IFN-γ secreting IL-2, IL-4 or IL-17 by ELISPOT. Immunisation with iH1N1+Advax adjuvant induced robust protection against influenza virus challenge 3 weeks post-immunization, whereas pups immunized with iH1N1 alone had no protection. Protection by Advax-adjuvanted iH1N1 was mediated by serum antibody and memory B cells rather than memory T cells as protection was lost in neonatal µMT mice that are B-cell deficient. Hence, Advax adjuvant overcame neonatal immune hypo-responsiveness and enabled single-dose protection of pups against otherwise lethal influenza infection, thereby supporting development of Advax™ as a neonatal vaccine adjuvant.


title: Thin-section CT assessment of spontaneous pneumomediastinum in interstitial lung disease: Correlation with serial changes in lung parenchymal abnormalities

text: Summary Purpose The purpose of this study was to analyze thin-section computed tomography (CT) appearances of interstitial lung diseases before and at the time of detection of pneumomediastinum, and to evaluate the relationship between pneumomediastinum and parenchymal changes on thin-section CT. Materials & methods We reviewed CT images before and at the time of detection of pneumomediastinum in 13 patients with idiopathic pulmonary fibrosis (8 patients) and collagen vascular diseases (5 patient). The extent of the total area of reticular opacity, increased opacity (ground-glass opacity and consolidation), and honeycombing were scored, and these scores were compared before and at the time of detection of pneumomediastinum. We also divided patients into two groups according to therapy received. Patients in group 1 experienced pneumomediastinum after or during treatment with corticosteroids or immunosuppressive agents for acute or subacute exacerbation of interstitial lung disease. Patients in group 2 experienced pneumomediastinum without therapy. Results The mean score of all patients for honeycombing significantly increased at the time of detection of pneumomediastinum ( P = 0.003 ). In group 1, the extent of increasing opacity had been decreased significantly at the time of detection of pneumomediastinum ( P = 0.028 ). In group 2, the mean CT score of reticular opacity, increasing opacity, and honeycombing significantly increased at the time of detection of pneumomediastinum ( P = 0.028 , 0.018, and 0.018, respectively). Conclusions Spontaneous pneumomediastinum associated with interstitial lung disease appears to have a tendency to occur under conditions of altered of parenchymal interstitial lesions.


title: RNA chaperone activity of the tombusviral p33 replication protein facilitates initiation of RNA synthesis by the viral RdRp in vitro

text: Small plus-stranded RNA viruses do not code for RNA helicases that would facilitate the proper folding of viral RNAs during replication. Instead, these viruses might use RNA chaperones as shown here for the essential p33 replication protein of Tomato bushy stunt virus (TBSV). In vitro experiments demonstrate that the purified recombinant p33 promotes strand separation of a DNA/RNA duplex. In addition, p33 renders dsRNA templates sensitive to single-strand specific S1 nuclease, suggesting that p33 can destabilize highly structured RNAs. We also demonstrate that the RNA chaperone activity of p33 facilitates self-cleavage by a ribozyme in vitro. In addition, purified p33 facilitates in vitro RNA synthesis on double-stranded (ds)RNA templates up to 5-fold by a viral RNA-dependent RNA polymerase. We propose that the RNA chaperone activity of p33 facilitates the initiation of plus-strand synthesis as well as affects RNA recombination. Altogether, the TBSV RNA chaperone might perform similar biological functions to the helicases of other RNA viruses with much larger coding capacity.


title: Research Note: Lyophilization of hyperimmune egg yolk: effect on antibody titer and protection of broilers against Campylobacter colonization

text: Abstract Oral administration of antibodies is a promising strategy against various infectious diseases. Previously, it was demonstrated that passive immunization by providing hyperimmune egg yolk through the feed reduces Campylobacter jejuni colonization in broilers. Campylobacteriosis is the most commonly reported bacterial foodborne zoonosis worldwide, and poultry products are the number one origin of these bacteria for human infection. To date, no effective control measures exist to limit Campylobacter colonization in the chicken's intestinal tract. Here, the effect of lyophilization of hyperimmune egg yolk on protection of broilers against C. jejuni was investigated. During an in vivo trial, broiler chickens were prophylactically given feed with lyophilized hyperimmune or non-immunized egg yolk powder starting from day 1 after hatch. At day 11, broilers were inoculated with C. jejuni according to a seeder model. Five days later, all broilers were euthanized and cecal content was examined for C. jejuni colonization. No decrease in C. jejuni colonization was found. The freeze-drying resulted in a 16-fold decrease of the antibody titer in the yolk powder compared to the fresh yolks, presumably caused by structural changes in the antibodies. In conclusion, applying freeze-dried hyperimmune egg yolk failed to protect broilers against C. jejuni colonization, possibly because lyophilization affected the antibodies' functionality.


title: Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety

text: Abstract We describe here the design, synthesis and biological evaluation of a series of molecules toward the development of novel peptidomimetic inhibitors of SARS-CoV 3CLpro. A docking study involving binding between the initial lead compound 1 and the SARS-CoV 3CLpro motivated the replacement of a thiazole with a benzothiazole unit as a warhead moiety at the P1′ site. This modification led to the identification of more potent derivatives, including 2i, 2k, 2m, 2o, and 2p, with IC50 or K i values in the submicromolar to nanomolar range. In particular, compounds 2i and 2p exhibited the most potent inhibitory activities, with K i values of 4.1 and 3.1nM, respectively. The peptidomimetic compounds identified through this process are attractive leads for the development of potential therapeutic agents against SARS. The structural requirements of the peptidomimetics with potent inhibitory activities against SARS-CoV 3CLpro may be summarized as follows: (i) the presence of a benzothiazole warhead at the S1′-position; (ii) hydrogen bonding capabilities at the cyclic lactam of the S1-site; (iii) appropriate stereochemistry and hydrophobic moiety size at the S2-site and (iv) a unique folding conformation assumed by the phenoxyacetyl moiety at the S4-site.


title: Evidence-based guidelines for managing patients with primary ER+ HER2− breast cancer deferred from surgery due to the COVID-19 pandemic

text: Many patients with ER+ HER2− primary breast cancer are being deferred from surgery to neoadjuvant endocrine therapy (NeoET) during the COVID-19 pandemic. We have collated data from multiple international trials of presurgical endocrine therapy in order to provide guidance on the identification of patients who may have insufficiently endocrine-sensitive tumors and should be prioritised for early surgery or neoadjuvant chemotherapy rather than NeoET during or in the aftermath of the COVID-19 pandemic for safety or when surgical activity needs to be prioritized. For postmenopausal patients, our data provide strong support for the use of ER and PgR status at diagnosis for triaging of patients into three groups in which (taking into account clinical factors): (i) NeoET is likely to be inappropriate (Allred ER <6 or ER 6 and PgR <6) (ii) a biopsy for Ki67 analysis (on-treatment Ki67) could be considered after 2–4 weeks of NeoET (a: ER 7 or 8 and PgR <6 or b: ER 6 or 7 and PgR ≥6) or (iii) NeoET is an acceptable course of action (ER 8 and PgR ≥6). Cut-offs for percentage of cells positive are also given. For group (ii), a high early on-treatment level of Ki67 (>10%) indicates a higher priority for early surgery. Too few data were available for premenopausal patients to provide a similar treatment algorithm. These guidelines should be helpful for managing patients with early ER+ HER2− breast cancer during and in the aftermath of the COVID-19 crisis.


Covid-19 Pandemic Experience: Can It Serve as a Clarion Call to Establish or Revamp a Specialty Known as ‘Infectious Diseases Physiotherapy’?


title: Role of regulatory T cells in coronavirus-induced acute encephalitis

text: Abstract C57BL/6 mice infected with mouse hepatitis virus, strain JHM (JHMV) develop a rapidly fatal acute encephalitis. Previously, we showed that this disease is partially CD4 T cell-mediated since infection with a recombinant JHMV (rJ) mutated in only a single immunodominant CD4 T cell epitope (epitope M133, rJ.MY135Q) results in a nonlethal disease. Increased mortality correlated with a greater number of JHMV-specific CD4 T cells in the brains of rJ compared to rJ.MY135Q-infected mice. Here, we extend these results to show that the diminished number of virus-specific T cells correlates with a reduced cytokine/chemokine response in the infected brain. We also show that regulatory CD4 T cells (Tregs) are critical for mild disease in rJ.MY135Q-infected mice because their depletion results in increased mortality. Further, a relative paucity of Tregs characterizes lethal infection because adoptive transfer of Tregs into rJ-infected mice increases survival from 0% to 50%. These results support the notion that clinical disease in coronavirus-induced acute encephalitis results from a balance between factors critical for virus clearance, such as virus-specific effector T cells and anti-inflammatory elements, such as Tregs. These findings also show that unlike chronic infections, in which an excessive number of Tregs contributes to pathogen persistence, Tregs in the setting of acute encephalitis may help to limit immunopathological disease without delaying virus clearance.


title: The time is now: moving toward virus-specific T cells after allogeneic hematopoietic stem cell transplantation as the standard of care

text: Abstract Adoptive immunotherapy—in particular, T-cell therapy—has recently emerged as a useful strategy with the potential to overcome many of the limitations of antiviral drugs for the treatment of viral complications after hematopietic stem cell transplantation. In this review, we briefly summarize the current methods for virus-specific T-cell isolation or selection and we report results from clinical trials that have used these techniques, focusing specifically on the strategies aimed to broaden the application of this technology.


title: Rapid detection of Acinetobacter baumannii and molecular epidemiology of carbapenem-resistant A. baumannii in two comprehensive hospitals of Beijing, China

text: Acinetobacter baumannii is an important opportunistic pathogen associated with a variety of nosocomial infections. A rapid and sensitive molecular detection in clinical isolates is quite needed for the appropriate therapy and outbreak control of A. baumannii. Group 2 carbapenems have been considered the agents of choice for the treatment of multiple drug-resistant A. baumannii. But the prevalence of carbapenem-resistant A. baumannii (CRAB) has been steadily increasing in recent years. Here, we developed a loop-mediated isothermal amplification (LAMP) assay for the rapid detection of A. baumannii in clinical samples by using high-specificity primers of the bla(OXA-51) gene. Then we investigated the OXA-carbapenemases molecular epidemiology of A. baumannii isolates in two comprehensive hospitals in Beijing. The results showed that the LAMP assay could detect target DNA within 60 min at 65°C. The detection limit was 50 pg/μl, which was about 10-fold greater than that of PCR. Furthermore, this method could distinguish A. baumannii from the homologous A. nosocomialis and A. pittii. A total of 228 positive isolates were identified by this LAMP-based method for A. baumannii from 335 intensive care unit patients with clinically suspected multi-resistant infections in two hospitals in Beijing. The rates of CRAB are on the rise and are slowly becoming a routine phenotype for A. baumannii. Among the CRABs, 92.3% harbored both the bla(OXA-23) and bla(OXA-51) genes. Thirty-three pulsotypes were identified by pulsed-field gel electrophoresis, and the majority belonged to clone C. In conclusion, the LAMP method developed for detecting A. baumannii was faster and simpler than conventional PCR and has great potential for both point-of-care testing and basic research. We further demonstrated a high distribution of class D carbapenemase-encoding genes, mainly OXA-23, which presents an emerging threat in hospitals in China.


title: The peptide specificities of the autoantibodies elicited by mouse hepatitis virus A59

text: Abstract Synthetic decapeptides (N =206) covering the entire sequence of mouse liver fumarylacetoacetate hydrolase (FAH) were used to analyze the specificities of the autoantibodies (autoAb) elicited towards this enzyme in mice infected with mouse hepatitis virus (MHV). These autoAb bound mainly to N- and C-terminal FAH peptides, the most reactive sequences being 1–50 and 390–420, respectively. Surprisingly, although FAH sequence 1–50 shares a high degree of homology with various MHV proteins, the C-terminal portion does not. Moreover, whereas the autoAb reacted with homologous peptides surrounding residues 70, 160 and 360, non-similar sequences around residues 130, 210, 240, 250, and 300 were also recognized, indicating that autoAb were not restricted to epitopes with sequence homologies. There was also a lack of correlation between the amount of anti-MHV or anti-FAH antibodies produced and the reactivity towards the peptides. Moreover, the spectrum of peptides recognized by the autoAb of a given mouse did not change significantly with time, which suggests that the MHV-elicited autoimmune response does not induce an epitope recognition spreading. Finally, anti-FAH Ab produced after immunization with rat liver FAH recognized essentially the same mouse FAH regions than autoAb from MHV-infected mice. Results indicated that the induction of the autoAb is not only related to molecular or structural mimicry, but rather supports the Danger model, in which any aggression, in this case the MHV infection, is susceptible to trigger the production of autoAb.


title: Diagnostics of Dairy and Beef Cattle Diarrhea

text: Calf diarrhea is a multifactorial disease related to a combination of host and pathogen factors. The most common pathogens found in diarrheic calves are cryptosporidium, rotavirus, coronavirus, Salmonella, attaching and effacing E coli and F5 (K99) Escherichia coli. Increased mortality and morbidity are often due to the presence of more than one pathogen. This article includes a discussion of key information to obtain a clinical history, the pathogens, pathology findings, and diagnostic methods.


title: Vaccinology at the beginning of the 21st century

text: Today, the main challenges for vaccinologists include improving vaccines against as yet undefeated pathogens, rapid identification and response to emerging diseases and successful intervention in chronic diseases in which ongoing immune responses are insufficient. Reverse genetics and reverse vaccinology are now used to generate rapidly new vaccine strains and to mine whole genomes in the search for promising antigens. The rational design of adjuvants has become possible as a result of the discovery of the receptors that recognize microbial patterns and lead to dendritic cell activation. Antigen-loaded dendritic cells, DNA in naked, formulated or viral form, and other delivery systems are used to maximize immune responses. Although work on the ‘easy’ vaccines has already been completed, it is hoped that a combination of conceptual and technical innovation will enable the development of more complex and sophisticated vaccines in the future.


title: Who’s afraid of the big bad wolf? The experience of an Oral Medicine Unit in the time of Corona‐Virus.

text: To cope with the emergency from COVID‐19 (2019‐nCoV) and to increase the supply of intensive care beds, all over the world it was necessary to remodel or suspend the deferred and non‐urgent inpatient and outpatient activities, including those provided by the dental clinics.


title: Importance of homo-dimerization of Fanconi-associated nuclease 1 in DNA flap cleavage

text: Abstract Fanconi-associated nuclease 1 (FAN1) removes interstrand DNA crosslinks (ICLs) through its DNA flap endonuclease and exonuclease activities. Crystal structures of human and bacterial FAN1 bound to a DNA flap have been solved. The Pseudomonas aeruginosa bacterial FAN1 and human FAN1 (hFAN1) missing a flexible loop are monomeric, while intact hFAN1 is homo-dimeric in structure. Importantly, the monomeric and dimeric forms of FAN1 exhibit very different DNA binding modes. Here, we interrogate the functional differences between monomeric and dimeric forms of FAN1 and provide an explanation for the discrepancy in oligomeric state between the two hFAN1 structures. Specifically, we show that the flexible loop in question is needed for hFAN1 dimerization. While monomeric and dimeric bacterial or human FAN1 proteins cleave a short 5′ flap strand with similar efficiency, optimal cleavage of a long 5′ flap strand is contingent upon protein dimerization. Our study therefore furnishes biochemical evidence for a role of hFAN1 homodimerization in biological processes that involve 5′ DNA Flap cleavage.


Reumataxi: Una experiencia solidaria en tiempos de COVID-19


title: Light as a potential treatment for pandemic coronavirus infections: A perspective

text: Abstract The recent outbreak of COVID-19, which continues to ravage communities with high death tolls and untold psychosocial and catastrophic economic consequences, is a vivid reminder of nature's capacity to defy contemporary healthcare. The pandemic calls for rapid mobilization of every potential clinical tool, including phototherapy—one of the most effective treatments used to reduce the impact of the 1918 “Spanish influenza” pandemic. This paper cites several studies showing that phototherapy has immense potential to reduce the impact of coronavirus diseases, and offers suggested ways that the healthcare industry can integrate modern light technologies in the fight against COVID-19 and other infections. The evidence shows that violet/blue (400–470 nm) light is antimicrobial against numerous bacteria, and that it accounts for Niels Ryberg Finsen's Nobel-winning treatment of tuberculosis. Further evidence shows that blue light inactivates several viruses, including the common flu coronavirus, and that in experimental animals, red and near infrared light reduce respiratory disorders, similar to those complications associated with coronavirus infection. Moreover, in patients, red light has been shown to alleviate chronic obstructive lung disease and bronchial asthma. These findings call for urgent efforts to further explore the clinical value of light, and not wait for another pandemic to serve as a reminder. The ubiquity of inexpensive light emitting lasers and light emitting diodes (LEDs), makes it relatively easy to develop safe low-cost light-based devices with the potential to reduce infections, sanitize equipment, hospital facilities, emergency care vehicles, homes, and the general environment as pilot studies have shown.


docid: ybbwqgxg

title: Strengthening what we already have: collaborations to prevent medication shortages amid COVID‐19


title: Skin fragility syndrome in a cat with cholangiohepatitis and hepatic lipidosis

text: A case of acquired skin fragility syndrome associated with hepatic disease in a 9-year-old, spayed female, domestic shorthair cat is described. The cat was admitted to the veterinary hospital of the University of São Paulo (Brazil) with a 6-week history of vomiting, inappetence and weight loss. Remarkable signs were weakness, lethargy and profound jaundice that had been present for 10 days according to the owner. On completion of the physical examination, when the cat was gently manipulated for blood collection the thoracic limb and interscapular skin tore. Liver enzymes and bilirubin levels were all above the normal range. On histological examination of skin and liver, Masson's trichrome stain showed collagen fibre alteration and major hepatocyte abnormalities. Findings were consistent with feline skin fragility syndrome associated with cholangiohepatitis and hepatic lipidosis.


title: Prevención y tratamiento del Covid-19 en la población pediátrica desde una perspectiva familiar y comunitaria

text: Resumen Partiendo del informe sobre la situación de COVID-19 en España, del 3 de abril de 2020, los casos confirmados ascienden a 117.710, de los que 343 tienen una edad inferior a 14 años (< del 1%). Es fundamental conocer la especificidad de este proceso en la población infantil, así como las recomendaciones específicas para una adecuada prevención y cuidado de los niños durante la Pandemia por el COVID-19. Este artículo tiene como objetivo es analizar la evidencia científica sobre las recomendaciones específicas para la atención pediátrica en casos de COVID-19 desde el ámbito familiar y comunitario. Se han seleccionado y analizado las principales recomendaciones y medidas preventivas en los entornos de atención primaria de salud y el domicilio desde un enfoque integrador dónde se incluyen los aspectos biopsicosociales del niño durante el confinamiento. La importancia de los cuidados de la infancia frente a la enfermedad, radican sobre todo en asegurar las correctas medidas de prevención del contagio por la condición de actuar como posibles portadores durante un período de incubación de hasta 21 días. La recomendación es que los niños participen activamente en las acciones preventivas habituales para la contención de la expansión de la enfermedad. A nivel domiciliario, el aislamiento supone un importante reto para las familias dónde se presentan manifestaciones de incertidumbre, miedo e indefensión ante los cambios y entre las recomendaciones se encuentran establecer rutinas orden mediante horarios de actividades y ocio unido a las medidas de higiene. Dada la rapidez con la que se ha producido la pandemia por COVID-19, existen pocas evidencias del impacto en niños en España por el momento. Es necesario desarrollar estudios específicos sobre prevención y tratamiento en la edad pediátrica para mejorar las recomendaciones disponibles. Abstract Based on the report on the situation of COVID-19 in Spain, dated April 3, 2020, the confirmed cases amount to 117,710, of which 343 are under 14 years of age (<1%). It is essential to know the specificity of this process in the child population, as well the specific recommendations for proper prevention and care of children during the COVID-19 Pandemic. Our objective is to analyze the scientific evidence on the specific recommendations for pediatric care in cases of COVID-19 from the family and community settings. The main recommendations and preventive measures in primary health care settings and at home have been selected and analyzed from an integrative approach that includes the biopsychosocial aspects of the child during confinement. The importance of caring for children in the face of the disease lies above all in ensuring the correct measures for the prevention of contagion due to the condition of acting as possible carriers during an incubation period of up to 21 days. The recommendation is that children actively participate in routine preventive actions to contain the spread of the disease. At the household level, isolation is an important challenge for families where there are manifestations of uncertainty, fear and helplessness in the face of changes and among the recommendations are establishing routines and order through schedules of activities and leisure together with hygiene measures. Given the rapidity with which the COVID-19 pandemic has occurred, there is little evidence at the moment. Research on prevention and treatment in the pediatric age needs to be developed to improve the available recommendations.


title: Characteristics and serological patterns of COVID‐19 convalescent plasma donors: optimal donors and timing of donation

text: BACKGROUND: The lack of effective treatments against the 2019 coronavirus disease (COVID‐19) has led to the exploratory use of convalescent plasma for treating COVID‐19. Case reports and case series have shown encouraging results. This study investigated SARS‐CoV‐2 antibodies and epidemiological characteristics in convalescent plasma donors, to identify criteria for donor selection. METHODS: Recovered COVID‐19 patients, aged 18‐55 years, who had experienced no symptoms for more than 2 weeks, were recruited. Donor characteristics such as disease presentations were collected and SARS‐CoV‐2 N‐specific IgM, IgG, and S‐RBD‐specific IgG levels were measured by enzyme‐linked immunosorbent assay (ELISA). RESULTS: Whereas levels of N‐specific IgM antibody declined after recovery, S‐RBD‐specific and N‐specific IgG antibodies increased after 4 weeks from the onset of symptoms, with no significant correlation to age, sex, or ABO blood type. Donors with the disease presentation of fever exceeding 38.5°C or lasting longer than 3 days exhibited higher levels of S‐RBD‐specific IgG antibodies at the time of donation. Of the 49 convalescent plasma donors, 90% had an S‐RBD‐specific IgG titer of ≥1:160 and 78% had a titer of ≥1:640 at the time of plasma donation. Of the 30 convalescent plasma donors, who had donated plasma later than 28 days after the onset of symptoms and had a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C, 100% had an S‐RBD‐specific IgG titer of ≥1:160 and 93% had a titer of ≥1:640. CONCLUSION: This study indicates that the S‐RBD‐specific IgG antibody reaches higher levels after 4 weeks from the onset of COVID‐19 symptoms. We recommend the following selection criteria for optimal donation of COVID‐19 convalescent plasma: 28 days after the onset of symptoms and with a disease presentation of fever lasting longer than 3 days or a body temperature exceeding 38.5°C. Selection based on these criteria can ensure a high likelihood of achieving sufficiently high S‐RBD‐specific IgG titers.


title: Gastritis, Enteritis, and Colitis in Horses

text: The gastrointestinal system of horses is affected by a large variety of inflammatory infectious and noninfectious conditions. The most prevalent form of gastritis is associated with ulceration of the pars esophagea. Although the diagnostic techniques for alimentary diseases of horses have improved significantly over the past few years, difficulties still exist in establishing the causes of a significant number of enteric diseases in this species. This problem is compounded by several agents of enteric disease also being found in the intestine of clinically normal horses, which questions the validity of the mere detection of these agents in the intestine.


docid: ebjwkvvj

title: Organization and Finance of China’s Health Sector: Historical Antecedents for Macroeconomic Structural Adjustment

text: China has exploded onto the world economy over the past few decades and is undergoing rapid transformation toward relatively more services. The health sector is an important part of this transition. This article provides a historical account of the development of health care in China since 1949. It also focuses on health insurance and macroeconomic structural adjustment to less saving and more consumption. In particular, the question of how health insurance impacts precautionary savings is considered. Multivariate analysis using data from 1990 to 2012 is employed. The household savings rate is the dependent variable in 3 models segmented for rural and urban populations. Independent variables include out-of-pocket health expenditures, health insurance payouts, housing expenditure, education expenditure, and consumption as a share of gross domestic product (GDP). Out-of-pocket health expenditures were positively correlated with household savings rates. But health insurance remains weak, and increased payouts by health insurers have not been associated with lower levels of household savings so far. Housing was positively correlated, whereas education had a negative association with savings rates. This latter finding was unexpected. Perhaps education is perceived as investment and a substitute for savings. China’s shift toward a more service-oriented economy includes growing dependence on the health sector. Better health insurance is an important part of this evolution. The organization and finance of health care is integrally linked with macroeconomic policy in an environment constrained by prevailing institutional convention. Problems of agency relationships, professional hegemony, and special interest politics feature prominently, as they do elsewhere. China also has a dual approach to medicine relying heavily on providers of traditional Chinese medicine. Both of these segments will take part in China’s evolution, adding another layer of complexity to policy.


title: COVID‐19 in recent heart transplant recipients: Clinicopathologic features and early outcomes

text: BACKGROUND: The impact of COVID‐19 on heart transplant (HTx) recipients remains unclear, particularly in the early post‐transplant period. METHODS: We share novel insights from our experience in five HTx patients with COVID‐19 (three within 2 months post‐transplant) from our institution at the epicenter of the pandemic. Results: All five exhibited moderate (requiring hospitalization, n = 3) or severe (requiring ICU and/or mechanical ventilation, n = 2) illness. Both cases with severe illness were transplanted approximately 6 weeks before presentation and acquired COVID‐19 through community spread. All five patients were on immunosuppressive therapy with mycophenolate mofetil (MMF) and tacrolimus, and three that were transplanted within the prior 2 months were additionally on prednisone. The two cases with severe illness had profound lymphopenia with markedly elevated C‐reactive protein, procalcitonin, and ferritin. All had bilateral ground‐glass opacities on chest imaging. MMF was discontinued in all five, and both severe cases received convalescent plasma. All three recent transplants underwent routine endomyocardial biopsies, revealing mild (n = 1) or no acute cellular rejection (n = 2), and no visible viral particles on electron microscopy. Within 30 days of admission, the two cases with severe illness remain hospitalized but have clinically improved, while the other three have been discharged. CONCLUSIONS: COVID‐19 appears to negatively impact outcomes early after heart transplantation.


title: Early Intervention Can Improve Clinical Outcome of Acute Interstitial Pneumonia

text: Study objectives: To report on our experience with acute interstitial pneumonia (AIP) in which patients underwent early diagnostic procedures and received mechanical ventilation with a “lung-protective” strategy and early institution of immunosuppressive therapy. Design: A retrospective chart review. Setting: A tertiary referral hospital. Participants: Ten patients with AIP who presented with idiopathic ARDS and showed diffuse alveolar damage on surgical lung biopsy specimens from July 1995 to March 2004. Measurements and results: The median age of patients was 65.5 years (age range, 38 to 73 years). Patients presented with a median duration of severe dyspnea of 9.5 days (range, 2 to 34 days) at the hospital visit. All patients required mechanical ventilation beginning at median time of hospital day 1 (range, hospital day 0 to 5), which continued for a median duration of 9.5 days (range, 4 to 98 days). Patients received ventilation in the pressure assist-control mode with a median tidal volume of 6.97 mL/kg (range, 6.05 to 8.86 mL/kg) and median positive end-expiratory pressure of 11 cm H2O (range, 8 to 16 cm H2O). An aggressive diagnostic workup for respiratory infection, including BAL at a median time of hospital day 2 (range, hospital day 1 to 5) was performed. High-dose steroid pulse therapy was initiated on median hospital day 3.5 (range, hospital day 1 to 8), while surgical lung biopsy was performed on median hospital day 4 (range, hospital day 2 to 7). Eight patients (80%) survived to hospital discharge. Conclusion: Earlier intervention, such as an aggressive diagnostic approach, mechanical ventilation with lung-protective strategy, and the early institution of immunosuppressive may improve clinical outcome in patients with AIP.


title: Use of Dipstick Assay and Rapid PCR-DNA Analysis of Nasal Secretions for Diagnosis of Bacterial Sinusitis in Children With Chronic Cough

text: BACKGROUND: Chronic cough in children is a diagnostic challenge. OBJECTIVE: To discover the utility of nasal dipsticks and polymerase chain reaction (PCR)-DNA analysis in differentiating bacterial sinusitis from other causes of chronic cough and identifying pathogens from the nasal cavity. METHOD: We recruited 22 patients under 15 years of age with cough lasting longer than 4 weeks (group 1), 7 controls with allergic rhinitis (group 2), and 10 controls without respiratory symptoms (group 3). Based on symptoms, the results of nasal secretion assays, and nasal endoscopy, a diagnosis of clinical bacterial sinusitis was made. We identified potential pathogens by quantitative PCR of nasal secretions. RESULTS: Group 1A (cough with clinical bacterial sinusitis n = 10): Eight (80%) patients had bacterial sinusitis associated with dominant potential pathogenic bacteria (PPB): Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Group 1B (cough without clinical bacterial sinusitis n = 12): None had dominant PPB. Group 2 (allergic rhinitis n = 7): None had dominant PPB. Group 3 (asymptomatic n = 10): None had dominant PPB. Twenty to 57% of all groups were colonized with Staphylococcus aureus. Fifty to 70% were colonized with Staphylococcus epidermidis, Corynebacterium pseudodiphtheriticum, and Dolosigranulum pigrum. CONCLUSION: In children with chronic cough, clinicians can utilize a simple and inexpensive nasal secretion dipstick assay for rapid diagnosis of sinusitis and identify PPB by DNA-PCR test for specific antibiotic treatment.


title: Beyond Disaster Preparedness: Building a Resilience-Oriented Workforce for the Future

text: Enhancing citizens’ and communities’ resilience is critical to adapt successfully to ongoing challenges faced by communities, as well as acute shocks resulting from disasters. While significant progress has been made in this area, several research and practice gaps remain. A crucial next step to advance resilience is the development of a resilience-oriented workforce. This narrative review examines existing literature to determine key components of a resilience-oriented workforce, with a focus on organizational structures, training and education, and leadership models. Reviewed articles spanned a variety of study types, including needs assessments of existing workforce, program evaluations, and reviews/commentaries. A resilience-oriented workforce spans many disciplines and training programs will need to reflect that. It requires a collaborative organizational model that promotes information sharing structures. Leadership models should foster a balance between workforce autonomy and operation as a collective entity. Optimal strategies to develop a resilience-oriented workforce have yet to be realized and future research will need to collect and synthesize data to promote and evaluate the growth of this field.


title: Mesenchymal stem cells and management of COVID-19 pneumonia

text: Abstract Human coronavirus, hCoV-19, is highly pathogenic with severe pneumonia associated with rapid virus replication. Arising in Wuhan China December 2019, the current COVID-19 epidemic has rapidly grown with person-to-person infection expanding to become a global health emergency now on pandemic scale. Governments will not be able to minimise both deaths from COVID-19 and the economic impact of viral spread in mitigation of this current COVID-19 pandemic, according to Anderson et al. 2020 [1], Keeping mortality as low as possible will be the highest priority for individuals; hence governments must put in place measures to ameliorate the inevitable economic downturn. The current global picture shows small chains of transmission in many countries and large chains resulting in extensive spread in a few countries, such as Italy, Iran, South Korea, and Japan. Most countries are likely to have spread of COVID-19, at least in the early stages, before any mitigation measures have an impact. The scale of the problem is massive. Here I consider new approaches to improve patient's biological resistance to COVID-19 using stem cells, and how benefit might be scaled and simplified using synthetic stem cells to meet logistical needs within a short time frame.


Address COVID‐19 Issues With Volunteers


title: SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus

text: A vaccine for severe acute respiratory syndrome (SARS) is being intensively pursued against its re-emergence. We generated a SARS coronavirus (SARS-CoV) spike protein-expressing recombinant vaccinia virus (RVV-S) using highly attenuated strain LC16m8. Intradermal administration of RVV-S into rabbits induced neutralizing (NT) antibodies against SARS-CoV 1 week after administration and the NT titer reached 1:1000 after boost immunization with RVV-S. Significantly, NT antibodies against SARS-CoV were induced by administration of RVV-S to rabbits that had been pre-immunized with LC16m8. RVV-S can induce NT antibodies against SARS-CoV despite the presence of NT antibodies against VV. These results suggest that RVV-S may be a powerful SARS vaccine, including in patients previously immunized with the smallpox vaccine.


title: Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications

text: Summary Background Since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea was reported on 20th May 2015, there have been 186 confirmed cases, 38 deaths and 16,752 suspected cases. Previously published research on South Korea's MERS outbreak was limited to the early stages, when few data were available. Now that the outbreak has ended, albeit unofficially, a more comprehensive review is appropriate. Methods Data were obtained through the MERS portal by the Ministry for Health and Welfare (MOHW) and Korea Centres for Disease Control and Prevention, press releases by MOHW, and reports by the MERS Policy Committee of the Korean Medical Association. Cases were analysed for general characteristics, exposure source, timeline and infection generation. Sex, age and underlying diseases were analysed for the 38 deaths. Findings Beginning with the index case that infected 28 others, an in-depth analysis was conducted. The average age was 55 years, which was a little higher than the global average of 50 years. As in most other countries, more men than women were affected. The case fatality rate was 19.9%, which was lower than the global rate of 38.7% and the rate in Saudi Arabia (36.5%). In total, 184 patients were infected nosocomially and there were no community-acquired infections. The main underlying diseases were respiratory diseases, cancer and hypertension. The main contributors to the outbreak were late diagnosis, quarantine failure of ‘super spreaders’, familial care-giving and visiting, non-disclosure by patients, poor communication by the South Korean Government, inadequate hospital infection management, and ‘doctor shopping’. The outbreak was entirely nosocomial, and was largely attributable to infection management and policy failures, rather than biomedical factors.


docid: zilqyfjl

title: Histidine-rich Modification of a Scorpion-derived Peptide Improves Bioavailability and Inhibitory Activity against HSV-1

text: Rationale: HSV is one of the most widespread human viral pathogens. HSV-1 infects a large portion of the human population and causes severe diseases. The current clinical treatment for HSV-1 is based on nucleoside analogues, the use of which is limited due to drug resistance, side effects and poor bioavailability. AMPs have been identified as potential antiviral agents that may overcome these limitations. Therefore, we screened anti-HSV-1 peptides from a scorpion-derived AMP library and engineered one candidate into a histidine-rich peptide with significantly improved antiviral activity and development potential. Methods: A venomous gland cDNA library was constructed from the scorpion Euscorpiops validus in the Yunnan Province of China. Six putative AMPs were characterized from this cDNA library, and the synthesized peptides were screened via plaque-forming assays to determine their virucidal potential. Time of addition experiments according to the infection progress of HSV-1 were used to identify the modes of action for peptides of interest. The histidine-rich modification was designed based on structural analysis of peptides by a helical wheel model and CD spectroscopy. Peptide cellular uptake and distribution were measured by flow cytometry and confocal microscopy, respectively. Results: The peptide Eval418 was found to have high clearance activity in an HSV-1 plaque reduction assay. Eval418 exhibited dose-dependent and time-dependent inactivation of HSV-1 and dose-dependent inhibition of HSV-1 attachment to host cells. However, Eval418 scarcely suppressed an established HSV-1 infection due to poor cellular uptake. We further designed and modified Eval418 into four histidine-rich derivative peptides with enhanced antiviral activities and lower cytotoxicities. All of the derivative peptides suppressed established HSV-1 infections. One of these peptides, Eval418-FH5, not only had strong viral inactivation activity and enhanced attachment inhibitory activity but also had high inhibitory activity against intracellular HSV-1, which was consistent with its improved intracellular uptake and distribution as confirmed by confocal microscopy and flow cytometry. Conclusion: We successfully identified an anti-HSV-1 peptide, Eval418, from a scorpion venom peptide library and designed a histidine-rich Eval418 derivative with significantly improved potential for further development as an anti-HSV-1 drug. This successful modification can provide a design strategy to improve the bioavailability, cellular distribution and antiviral activity of peptide agents.


title: Interaction of the innate immune system with positive-strand RNA virus replication organelles

text: Abstract The potential health risks associated with (re-)emerging positive-strand RNA (+RNA) viruses emphasizes the need for understanding host-pathogen interactions for these viruses. The innate immune system forms the first line of defense against pathogenic organisms like these and is responsible for detecting pathogen-associated molecular patterns (PAMPs). Viral RNA is a potent inducer of antiviral innate immune signaling, provoking an antiviral state by directing expression of interferons (IFNs) and pro-inflammatory cytokines. However, +RNA viruses developed various methods to avoid detection and downstream signaling, including isolation of viral RNA replication in membranous viral replication organelles (ROs). These structures therefore play a central role in infection, and consequently, loss of RO integrity might simultaneously result in impaired viral replication and enhanced antiviral signaling. This review summarizes the first indications that the innate immune system indeed has tools to disrupt viral ROs and other non- or aberrant-self membrane structures, and may do this by marking these membranes with proteins such as microtubule-associated protein 1A/1B-light chain 3 (LC3) and ubiquitin, resulting in the recruitment of IFN-inducible GTPases. Further studies should evaluate whether this process forms a general effector mechanism in +RNA virus infection, thereby creating the opportunity for development of novel antiviral therapies.


docid: rlltakvn

title: Carbon dioxide gas leaks during transanal minimally invasive surgery


title: Socioeconomic marginalization and opioid-related overdose: A systematic review

text: BACKGROUND: Socioeconomic marginalization (SEM) is an important but under-explored determinant of opioid overdose with important implications for health equity and associated public policy initiatives. This systematic review synthesizes evidence on the role of SEM in both fatal and non-fatal overdose among people who use opioids. METHODS: Studies published between January 1, 2000 and March 31, 2018 were identified through searching electronic databases, citations, and by contacting experts. The titles, abstracts, citation information, and descriptor terms of citations were screened by two team members. Data were synthesized using the lumping technique. RESULTS: A total of 37 studies met inclusion criteria and were included in the review, with 34 of 37 finding a significant association between at least one socioeconomic factor and overdose. The included studies contained variables related to eight socioeconomic factors: criminal justice system involvement, income, employment, social support, health insurance, housing/homelessness, education, and composite measures of socio-economic status. Most studies found associations in the hypothesized direction, whereby increased SEM was associated with a higher rate or increased likelihood of the overdose outcome measured. The review revealed an underdeveloped evidence base. CONCLUSIONS: Nearly all reviewed studies found a connection between a socioeconomic variable and overdose, but more research is needed with an explicit focus on SEM, using robust and nuanced measures that capture multiple dimensions of disadvantage, and collect data over time to better inform decision making around opioid overdose.


title: Colchicina: una herramienta terapéutica potencial frente a COVID-19. Experiencia en 5 pacientes

text: Resumen COVID-19 es una enfermedad de aparición reciente, que se ha convertido en un reto global de salud pública. Debido a la falta de conocimiento acerca del virus, se ha propuesto un número significativo de objetivos potenciales para utilizar un fármaco en particular. Presentamos aquí cinco casos con historia clínica de biopolímeros en la región glútea, que desarrollaron alogenosis iatrogénica (AI). A los 5 casos se les administró tratamiento de colchicina debido a crisis de AI, no teniendo síntomas específicos (cefalea, tos sin disnea, y artralgias), con resultado positivo en el test de SARS-CoV-2. Sus contactos cercanos tenían síntomas de leves a graves, y tres de ellos fallecieron. En la infección por SARS-CoV-2 se alteran diferentes rutas inflamatorias, en las que la colchicina reduce los niveles de citocinas y la activación de macrófagos, neutrófilos e inflamasoma. Revisamos también en este artículo los posibles mecanismos que puede utilizar colchicina para prevenir el síndrome de distrés respiratorio agudo (SDRA) en pacientes con COVID-19. Abstract COVID-19 is a newly emerged disease that has become a global public health challenge. Due to a lack of knowledge about the virus, a significant number of potential targets for using a particular drug have been proposed. Five cases with a clinical history of biopolymers in the gluteal region that developed iatrogenic allogenosis (IA) are presented here. The 5 cases were put under colchicine treatment for IA crisis and had non-specific symptoms (headache, cough without dyspnoea, and arthralgias) with a positive SARS-CoV-2 test. Their close contacts had mild to severe symptoms and three of them died. In the SARS-CoV-2 infection different inflammatory pathways are altered where colchicine reduces cytokine levels as well as the activation of macrophages, neutrophils, and the inflammasome. The possible mechanisms that colchicine may use to prevent acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection are also reviewed in this article.


title: Chapter 16 Passive Monoclonal and Polyclonal Antibody Therapies

text: Abstract Passive antibody therapies have a long history of use. In the 19th century, antibodies from xenographic sources of polyclonal antibodies were used to treat infections (diphtheria). They were used often as protection from infectious agents and toxins. Complications related to their use involved development of immune complexes and severe allergic reactions. As a result, human source plasma for polyclonal antibodies became the preferential source for antibodies. They are used to treat infection, remove toxins, prevent hemolytic disease of the newborn, modify inflammatory reactions, and control autoimmune diseases. Continued improvements in processing decreased the transfusion/infusion transmission of infections. In the late 20th century (∼1986), monoclonal antibodies were developed. The first monoclonal antibodies were of xenographic source and were wrought with problems of immunogenicity. These forms of antibodies did not gain favor until chimerization took pace in the mid-1990s and in 1998 two monoclonal antibodies were approved one to treat respiratory syncytial virus and the other for breast cancers. Further development of humanized and then fully human monoclonal antibodies has led to an evolution of therapies with these agents. Monoclonal antibodies are being researched or approved to treat a multitude of diseases to include oncologic, inflammatory, autoimmune, cardiovascular, respiratory, neurologic, allergic, benign hematologic, infections, orthopedic, coagulopathy, metabolic and to decrease morbidity of disease (diminution of pain), modify disease progression, and potentially anatomic development. In this chapter, we will review the history of use of these passive antibody therapies, their mechanism of action, pharmacologic-therapeutic classification, particular medical indication, adverse reactions, and potential future use of these medications.


title: The Promise of Proteomics for the Study of ADP-Ribosylation

text: ADP-ribosylation is a post-translational modification where single units (mono-ADP-ribosylation) or polymeric chains (poly-ADP-ribosylation) of ADP-ribose are conjugated to proteins by ADP-ribosyltransferases. This post-translational modification and the ADP-ribosyltransferases (also known as PARPs) responsible for its synthesis have been found to play a role in nearly all major cellular processes, including DNA repair, transcription, translation, cell signaling, and cell death. Furthermore, dysregulation of ADP-ribosylation has been linked to diseases including cancers, diabetes, neurodegenerative disorders, and heart failure, leading to the development of therapeutic PARP inhibitors, many of which are currently in clinical trials. The study of this therapeutically important modification has recently been bolstered by the application of mass spectrometry-based proteomics, arguably the most powerful tool for the unbiased analysis of protein modifications. Unfortunately, progress has been hampered by the inherent challenges that stem from the physicochemical properties of ADP-ribose, which as a post-translational modification is highly charged, heterogeneous (linear or branched polymers, as well as monomers), labile, and found on a wide range of amino acid acceptors. In this Perspective, we discuss the progress that has been made in addressing these challenges, including the recent breakthroughs in proteomics techniques to identify ADP-ribosylation sites, and future developments to provide a proteome-wide view of the many cellular processes regulated by ADP-ribosylation.