title: The “Intubox”: Enhancing Frontline Healthcare Worker Safety During Coronavirus Disease 2019 (COVID-19)

text: There has been a substantial burden of healthcare worker infection during the current coronavirus (COVID-19) pandemic, likely due to a lack of adequate preparedness, suboptimal institutional infection control measures, atypical patient presentation, poor compliance with personal protective equipment (PPE) and exposure to high-risk aerosol generating procedures, such as endotracheal intubation. There is significant concern that developing countries will face heightened levels of staff exposure during the COVID-19 pandemic. To mitigate this exposure risk during procedures, such as endotracheal intubation, various “aerosol boxes” have been designed by frontline healthcare workers. However, in practice these boxes were found to hamper endotracheal intubation and other procedures due to the limited space and manoeuvrability they allow. To further reduce particle dispersion and to improve on the practicality and ergonomic design of the prototype “aerosol box”, the Intubox was developed by staff at the Charlotte Maxeke Johannesburg Academic Hospital after instituting several changes to the prototype design.


title: Reluctance to seek pediatric care during the COVID-19 pandemic and the risks of delayed diagnosis

text: Since the outbreak of COVID-19 pandemic, the number of cases registered worldwide has risen to over 3 million. While COVID-19 per se does not seem to represent a significant threat to the pediatric population, which generally presents a benign course and a low lethality, the current emergency might negatively affect the care of pediatric patients and overall children welfare. In particular, the fear of contracting COVID-19 may determine a delayed access to pediatric emergency facilities. Present report focuses on the experience of The Children Hospital in Alessandria (northern Italy). The authors document a drop in the number of admissions to the emergency department (A&E) during the lock-down. They will also focus on four emblematic cases of pediatric patients who were seen to our A&E in severe conditions. All these cases share a significant diagnostic delay caused by the parents’ reluctance to seek medical attention, seen as a potential risk factor for COVID-19 contagion. None was found positive to all COVID-19 swab or immunologic testing. All in all, our data strongly support the importance of promoting a direct and timely interaction between patients and medical staff, to prevent the fear of COVID-19 from causing more harm than the virus itself.


title: Infección nosocomial en el paciente receptor de un trasplante de órgano sólido o de precursores hematopoyéticos()

text: Bacterial infections are the most common infections in solid organ transplant recipients. These infections occur mainly in the first month after transplantation and are hospital-acquired. Nosocomial infections cause significant morbidity and are the most common cause of mortality in this early period of transplantation. These infections are caused by multi-drug resistant (MDR) microorganisms, mainly Gram-negative enterobacteria, non-fermentative Gram-negative bacilli, enterococci, and staphylococci. The patients at risk of developing nosocomial bacterial infections are those previously colonized with MDR bacteria while on the transplant waiting list. Intravascular catheters, the urinary tract, the lungs, and surgical wounds are the most frequent sources of infection. Preventive measures are the same as those applied in non-immunocompromised, hospitalized patients except in patients at high risk for developing fungal infection. These patients need antifungal therapy during their hospitalization, and for preventing some bacterial infections in the early transplant period, patients need vaccinations on the waiting list according to the current recommendations. Although morbidity and mortality related to infectious diseases have decreased during the last few years in haematopoietic stem cell transplant recipients, they are still one of the most important complications in this population. Furthermore, as occurs in the general population, the incidence of nosocomial infections has increased during the different phases of transplantation. It is difficult to establish general preventive measures in these patients, as there are many risk factors conditioning these infections. Firstly, they undergo multiple antibiotic treatments and interventions; secondly, there is a wide variability in the degree of neutropenia and immunosuppression among patients, and finally they combine hospital and home stay during the transplant process. However, some simple measures could be implemented to improve the current situation.


title: Epidemics on networks: Reducing disease transmission using health emergency declarations and peer communication

text: Understanding individual decisions in a world where communications and information move instantly via cell phones and the internet, contributes to the development and implementation of policies aimed at stopping or ameliorating the spread of diseases. In this manuscript, the role of official social network perturbations generated by public health officials to slow down or stop a disease outbreak are studied over distinct classes of static social networks. The dynamics are stochastic in nature with individuals (nodes) being assigned fixed levels of education or wealth. Nodes may change their epidemiological status from susceptible, to infected and to recovered. Most importantly, it is assumed that when the prevalence reaches a pre-determined threshold level, [Formula: see text] , information, called awareness in our framework, starts to spread, a process triggered by public health authorities. Information is assumed to spread over the same static network and whether or not one becomes a temporary informer, is a function of his/her level of education or wealth and epidemiological status. Stochastic simulations show that threshold selection [Formula: see text] and the value of the average basic reproduction number impact the final epidemic size differentially. For the Erdős-Rényi and Small-world networks, an optimal choice for [Formula: see text] that minimize the final epidemic size can be identified under some conditions while for Scale-free networks this is not case.


title: Changing pattern of premature mortality burden over 6 years of rapid growth of the economy in suburban south-west China: 1998–2003

text: Summary Background This study was conducted in Kunming, the capital of Yunnan, a poor province in south-west China experiencing rapid economic growth. The study examined the short-term trend in premature mortality burden from common causes of death in a suburban region between 1998 and 2003. Methods Years of life lost (YLL) per 1000 population and mortality rate per 100,000 population were calculated from medical death certificates, and broken down by cause of death, sex and year without age weighting but with a discounting rate of 3%. Results Non-communicable diseases contributed over 80% of all causes of YLL, with a slightly increasing trend. The combined rate for communicable, maternal, prenatal and nutritional deficiencies declined from 4.7 to 2.4 per 1000 population. Remarkably, declining trends in YLL were also seen for chronic obstructive pulmonary disease, drug use and road traffic accidents, whereas increasing trends were seen for ischaemic heart disease (IHD) and liver cancer (males). The YLL rate for stroke, self-inflicted injuries, lung cancer and stomach cancer fluctuated over time. Conclusions The region should focus on further control of IHD and liver cancer.


title: Characterization of antiviral T cell responses during primary and secondary challenge of laboratory cats with feline infectious peritonitis virus (FIPV)

text: BACKGROUND: Feline infectious peritonitis (FIP) is considered highly fatal in its naturally occurring form, although up to 36% of cats resist disease after experimental infection, suggesting that cats in nature may also resist development of FIP in the face of infection with FIP virus (FIPV). Previous experimental FIPV infection studies suggested a role for cell-mediated immunity in resistance to development of FIP. This experimental FIPV infection study in specific pathogen free (SPF) kittens describes longitudinal antiviral T cell responses and clinical outcomes ranging from rapid progression, slow progression, and resistance to disease. RESULTS: Differences in disease outcome provided an opportunity to investigate the role of T cell immunity to FIP determined by T cell subset proliferation after stimulation with different viral antigens. Reduced total white blood cell (WBC), lymphocyte and T cell counts in blood were observed during primary acute infection for all experimental groups including cats that survived without clinical FIP. Antiviral T cell responses during early primary infection were also similar between cats that developed FIP and cats remaining healthy. Recovery of antiviral T cell responses during the later phase of acute infection was observed in a subset of cats that survived longer or resisted disease compared to cats showing rapid disease progression. More robust T cell responses at terminal time points were observed in lymph nodes compared to blood in cats that developed FIP. Cats that survived primary infection were challenged a second time to pathogenic FIPV and tested for antiviral T cell responses over a four week period. Nine of ten rechallenged cats did not develop FIP or T cell depletion and all cats demonstrated antiviral T cell responses at multiple time points after rechallenge. CONCLUSIONS: In summary, definitive adaptive T cell responses predictive of disease outcome were not detected during the early phase of primary FIPV infection. However emergence of antiviral T cell responses after a second exposure to FIPV, implicated cellular immunity in the control of FIPV infection and disease progression. Virus host interactions during very early stages of FIPV infection warrant further investigation to elucidate host resistance to FIP.


title: Review of economic evaluations of mask and respirator use for protection against respiratory infection transmission

text: BACKGROUND: There has been increasing debate surrounding mask and respirator interventions to control respiratory infection transmission in both healthcare and community settings. As decision makers are considering the recommendations they should evaluate how to provide the most efficient protection strategies with minimum costs. The aim of this review is to identify and evaluate the existing economic evaluation literature in this area and to offer advice on how future evaluations on this topic should be conducted. METHODS: We searched the Scopus database for all literature on economic evaluation of mask or respirator use to control respiratory infection transmission. Reference lists from the identified studies were also manually searched. Seven studies met our inclusion criteria from the initial 806 studies identified by the search strategy and our manual search. RESULTS: Five studies considered interventions for seasonal and/or pandemic influenza, with one also considering SARS (Severe Acute Respiratory Syndrome). The other two studies focussed on tuberculosis transmission control interventions. The settings and methodologies of the studies varied greatly. No low-middle income settings were identified. Only one of the reviewed studies cited clinical evidence to inform their mask/respirator intervention effectiveness parameters. Mask and respirator interventions were generally reported by the study authors to be cost saving or cost-effective when compared to no intervention or other control measures, however the evaluations had important limitations. CONCLUSIONS: Given the large cost differential between masks and respirators, there is a need for more comprehensive economic evaluations to compare the relative costs and benefits of these interventions in situations and settings where alternative options are potentially applicable. There are at present insufficient well conducted cost-effectiveness studies to inform decision-makers on the value for money of alternative mask/respirator options.


Elective colorectal cancer surgery at the oncologic hub of Lombardy inside a pandemic COVID‐19 area


title: COVID‐19 Presenting with Atypical Sweet’s Syndrome

text: On March 11, 2020, the first case of the novel coronavirus 2019 disease (COVID‐19) was officially confirmed in Turkey. The disease continues to spread, and the number of patients has risen to 120,000 by the end of April. In this observation, we report an atypical presentation of COVID‐19 in a patient with indurated painful nodules. A‐61‐years‐old woman with a one‐week history of fever (axillary 38°C) and nodules on the cheek was admitted to the hospital with fatigue, arthralgia and myalgia.


title: A Jia-shaped Artistic Patch Antenna for Dual-band Circular Polarization

text: Abstract This article presents a novel single-feed circularly polarized patch antenna for dual-band (2.6 and 3.4 GHz) applications. Details of the design procedure and design considerations of the proposed antenna are described. The novelties of the proposed antenna are counted by (i) a meaningful Jia-shaped patch used as the primary radiator; (ii) a 3D L-shaped feeding probe used to excite the stacked patches so that the near degenerate-modes are excited at the desired dual band; (iii) down-tilt beams achieved that are particularly suitable for wall-mount base-stations. The measured 3-dB axial-ratio bandwidths are 2.41-2.61 GHz and 3.25-3.42 GHz, where the maximum gains are recorded as 7.3 and 6.3 dBic, respectively. Methods for the adjustment of band ratio down to 1.18 are discussed. The overall antenna size is 100×100×12.8 mm3.


title: Type I interferon signaling facilitates the development of IL-10-producing effector CD8(+) T cells during influenza virus infection

text: Recent evidence has suggested that IL-10-producing effector CD8(+) T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL-10-producing effector CD8(+) T cells are not completely defined. Here we show that type I interferons (IFNs) are required for the development of IL-10-producing effector CD8(+) T cells during influenza virus infection. We find that type I IFNs can enhance IL-27 production by lung antigen presenting cells, thereby facilitating IL-10-producing CD8(+) T cell development through a CD8(+) T cell non-autonomous way. Surprisingly, we also demonstrate that direct type I IFN signaling in CD8(+) T cells is required for the maximal generation of IL-10-producing CD8(+) T cells. Type I IFN signaling in CD8(+) T cells, in cooperation with IL-27 and IL-2 signaling, promotes and sustains the expression of IRF4 and Blimp-1, two transcription factors required for the production of IL-10 by effector CD8(+) T cells. Our data have revealed a critical role of the innate antiviral effector cytokines in regulating the production of a regulatory cytokine by effector CD8(+) T cells during respiratory virus infection. The potential implications of these findings for influenza virus infection are also discussed.


docid: ppzvrojz

title: Prevalence and Characteristics of Gastrointestinal Symptoms in Patients with SARS-CoV-2 Infection in the United States: A Multicenter Cohort Study


docid: opltcnyi

title: Collection and disinfection of forensic biological specimens in five cases concerning COVID-19 in Guangzhou, China

text: There have been many cases of pneumonia caused by novel coronavirus infections in China and around the world. This will inevitably lead to a rise in the number of patients. At the present time, clinical and forensic autopsies have given guidance and explanations in relation to the problem of COVID-19 transmission and defense. However, less attention is paid to the handling of COVID-19 biological samples in forensic practice. Particularly, COVID-19 can survive on some surfaces for days. Since there were many cases involving COVID-19 during the epidemic, this article shares the methods and strategies for handling such inspection materials and the biological samples related specifically to COVID-19 cases.


title: A compendium of reviews in biochemistry and molecular biology published in the first half of 1991

text: Abstract 1. 1. A compendium of reviews and minireviews in Biochemistry and Molecular Biology published in the first half of 1991 is presented. In all there are 380 titles from 81 different publications. 2. 2. The compendium includes the main keywords associated with each review; over 2500 different keywords are used.


Impacto Psicológico Del Confinamiento En Población Infantil Y Como Mitigar Sus Efectos: Revisión Rápida De La Evidencia


docid: vxywolgo

title: 2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation

text: Abstract Introduction Several recent case reports have described common early chest imaging findings of lung pathology caused by 2019 novel Coronavirus (SARS-COV2) which appear to be similar to those seen previously in SARS-CoV and MERS-CoV infected patients. Objective We present some remarkable imaging findings of the first two patients identified in Italy with COVID-19 infection travelling from Wuhan, China. The follow-up with chest X-Rays and CT scans was also included, showing a progressive adult respiratory distress syndrome (ARDS). Results Moderate to severe progression of the lung infiltrates, with increasing percentage of high-density infiltrates sustained by a bilateral and multi-segmental extension of lung opacities, were seen. During the follow-up, apart from pleural effusions, a tubular and enlarged appearance of pulmonary vessels with a sudden caliber reduction was seen, mainly found in the dichotomic tracts, where the center of a new insurgent pulmonary lesion was seen. It could be an early alert radiological sign to predict initial lung deterioration. Another uncommon element was the presence of mediastinal lymphadenopathy with short-axis oval nodes. Conclusions Although only two patients have been studied, these findings are consistent with the radiological pattern described in literature. Finally, the pulmonary vessels enlargement in areas where new lung infiltrates develop in the follow-up CT scan, could describe an early predictor radiological sign of lung impairment.


title: Addition of Casein or Whey Protein to Colostrum or a Colostrum Supplement Product on Absorption of IgG in Neonatal Calves

text: Abstract The effects of the addition of nonimmunoglobulin protein on absorption of immunoglobulin G (IgG) from colostrum or colostrum supplement products were determined in two experiments. In experiment 1, 48 Holstein calves were fed 4L of pooled maternal colostrum or 4L of reconstituted colostrum supplement with 0, 200, or 400g of added whey protein concentrate or casein. In experiment 2, 38 Jersey calves were fed 2L of pooled maternal colostrum with 100 or 200g of whey protein concentrate or casein added immediately before feeding. Blood was collected at 24h of age and plasma IgG concentration, total protein, hematocrit (experiment 1 only), and plasma urea N were determined. In experiment 1, blood samples were also collected at 4, 8, 12, 16, and 20h to evaluate absorption of IgG and protein and urea N concentrations. The addition of 400g of casein to colostrum supplement in experiment 1 reduced plasma IgG from 5.66g/L (0g of casein addition) to 3.88g/L, increased plasma urea N at 24h, and reduced the change in plasma total protein from 0 to 24h. Hourly plasma IgG concentrations increased with the consumption of colostrum or supplements but increased more rapidly in calves fed whey protein concentrate and more slowly in calves fed casein. The addition of 200g of casein or whey protein concentrate to colostrum supplements had no effect on plasma IgG concentration at 24h of age. The addition of 100 or 200g of casein or whey protein concentrate to maternal colostrum had no effect on plasma urea N, total protein, or plasma IgG in experiment 2. The addition of nonimmunoglobulin protein to colostrum supplements or maternal colostrum did not affect IgG absorption from the intestine of newborn calves unless the amount of total protein exceeded 500g of protein.


title: Severe and fatal forms of COVID-19 in children

text: ABSTRACT OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n = 19, 70 %) were mainly neurological (n = 7), respiratory, (n = 4), or sickle cell disease (n = 4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n = 9), catecholamine (n = 4), erythropheresis (n = 4), renal replacement therapy (n = 1), and extracorporeal membrane oxygenation (n = 1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children


title: Which preventive measures might protect health care workers from SARS?

text: BACKGROUND: Despite the use of a series of preventive measures, a high incidence of severe acute respiratory syndrome (SARS) was observed among health care workers (HCWs) during the SARS epidemic. This study aimed to determine which preventive measures may have been effective in protecting HCWs from infection, and which were not effective. METHODS: A retrospective study was performed among 758 'frontline' health care workers who cared for SARS patients at the Second Affiliated Hospital and the Third Affiliated Hospital of Sun Yat-sen University. The HCWs with IgG against SARS and those without IgG against SARS were respectively defined as the "case group" and the "control group", and logistic regression was conducted to explore the risk factors for SARS infection in HCWs. RESULTS: After adjusting for age, gender, marital status, educational level, professional title, and the department in which an individual worked, the results of a multivariate logistic regression analysis indicated that incidence of SARS among HCWs was significantly and positively associated with: performing tracheal intubations for SARS patients, methods used for air ventilation in wards, avoiding face-to-face interaction with SARS patients, the number of pairs of gloves worn by HCWs, and caring for serious SARS cases. CONCLUSION: Some measures, particularly good air ventilation in SARS wards, may be effective in minimizing or preventing SARS transmission among HCWs in hospitals.


title: Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro)

text: The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle. Communicated by Ramaswamy H. Sarma.


title: Changes in temperature alter susceptibility to a virus following a host shift

text: Host shifts - where a pathogen jumps between different host species - are an important source of emerging infectious disease. With ongoing climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species’ susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, whilst the mean viral load did not, such that as temperature increased the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species’ susceptibility across temperatures and proxies for thermal optima; critical thermal maximum and minimum or basal metabolic rate. These results suggest that whilst the rank order of species susceptibilities can remain the same with changes in temperature, the likelihood of host shifts into a given species may increase or decrease. Author Summary Emerging infectious diseases are often the result of a host shift, where a pathogen jumps from one host species into another. Understanding the factors underlying host shifts is a major goal for infectious disease researchers. This effort has been further complicated by the fact that host-parasite interactions are now taking place in a period of unprecedented global climatic warming. Here, we ask how host shifts are affected by temperature by carrying out experimental infections using an RNA virus across a wide range of related species, at three different temperatures. We find that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. This has important consequences for our understanding of host shift events in a changing climate, and suggests that temperature changes may affect the likelihood of a host shift into certain species.


title: Analysis of heart injury laboratory parameters in 273 COVID‐19 patients in one hospital in Wuhan, China

text: An outbreak of severe acute respiratory syndrome novel coronavirus (SARS‐CoV‐2) epidemic spreads rapidly worldwide. SARS‐CoV‐2 infection caused mildly to seriously and fatally respiratory, enteric, cardiovascular, and neurological diseases. In this study, we detected and analyzed the main laboratory indicators related to heart injury, creatine kinase isoenzyme‐MB (CK‐MB), myohemoglobin (MYO), cardiac troponin I (ultra‐TnI), and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), in 273 patients with COVID‐19 and investigated the correlation between heart injury and severity of the disease. It was found that higher concentration in venous blood of CK‐MB, MYO, ultra‐TnI, and NT‐proBNP were associated with the severity and case fatality rate of COVID‐19. Careful monitoring of the myocardiac enzyme profiles is of great importance in reducing the complications and mortality in patients with COVID‐19.


title: Unterricht an der Berufsfachschule für Notfallsanitäter der Landeshauptstadt München im Angesicht der COVID-19-Pandemie

text: The ongoing Coronavirus crisis forced both the Berufsfachschule für Notfallsanitäter (emergency paramedic vocational school) of the Munich fire department and all other German schools to quit classroom teaching within just a few days. Similarly, all practical trainings at clinics and on ambulances had to be put on hold. As the apprentices’ training objective was acutely endangered by the expected lengthy teaching downtimes, it was of crucial importance to successfully establish homeschooling. While members of our teaching staff were additionally bound by support for the Munich crisis unit, the switch to virtual classroom teaching for all ongoing courses significantly increased the overall workload of the staff. In a first step, we established a fast video and communication platform via Microsoft Skype. All other issues had to be solved on the fly due to the lack of preparation time. Soon it became obvious that using only classic upfront teaching methods was not an option due to the resulting monotony of a full-time 35 h training week. Additionally, we had to ensure that exams would also be possible during homeschooling to avoid the accumulation of missing performance assessments. Within a few days, it became clear that almost all forms of social interactions and teaching methods could be integrated into the virtual classroom with minor limitations. A survey among students showed that while homeschooling cannot fully replace classroom teaching, it is considered a good alternative in emergency situations. Furthermore, many trainees think that homeschooling could be a valuable addition to normal classroom teaching. Maybe this crisis could turn out to be the beginning of a new complementary teaching strategy.


title: Quercetin inhibits rhinovirus replication in vitro and in vivo

text: Rhinovirus (RV), which is responsible for the majority of common colds, also causes exacerbations in patients with asthma and chronic obstructive pulmonary disease. So far, there are no drugs available for treatment of rhinovirus infection. We examined the effect of quercetin, a plant flavanol on RV infection in vitro and in vivo. Pretreatment of airway epithelial cells with quercetin decreased Akt phosphosphorylation, viral endocytosis and IL-8 responses. Addition of quercetin 6 h after RV infection (after viral endocytosis) reduced viral load, IL-8 and IFN responses in airway epithelial cells. This was associated with decreased levels of negative and positive strand viral RNA, and RV capsid protein, abrogation of RV-induced eIF4GI cleavage and increased phosphorylation of eIF2α. In mice infected with RV, quercetin treatment decreased viral replication as well as expression of chemokines and cytokines. Quercetin treatment also attenuated RV-induced airway cholinergic hyperresponsiveness. Together, our results suggest that quercetin inhibits RV endocytosis and replication in airway epithelial cells at multiple stages of the RV life cycle. Quercetin also decreases expression of pro-inflammatory cytokines and improves lung function in RV-infected mice. Based on these observations, further studies examining the potential benefits of quercetin in the prevention and treatment of RV infection are warranted.


title: (+) RNA virus replication compartments: a safe home for (most) viral replication

text: This review describes recent advances in our understanding of the mechanisms by which (+) RNA viruses establish their replication niche.


title: Reye Syndrome

text: Reye syndrome has emerged as the quintessential example of an acute metabolic encephalopathy with an annual incidence ranging from 0.3 to 6.0 cases per 100,000 children. The general management has become standardized, and the mortality has declined to approximately 10 per cent. The role of aspirin in the etiopathogenesis remains controversial.


title: WU Polyomavirus (WUPyV): A Recently Detected Virus Causing Respiratory Disease?

text: The WU polyomavirus (WUPyV) is a novel member of the family Polyomaviridae recently detected in respiratory tract specimens by shotgun sequencing. Intriguingly, viral genome has been detected in 0.4% to 11.5% of respiratory tract specimens from children with respiratory disease. The levels of co-infection with established respiratory viruses were in the range between 30.8% and 91.7%. Moreover, some studies report detection of WUPyV in stool or serum. So far, WUPyV infections can not be distinguished from other viral infections by means of clinical symptoms. Respiratory tract disease like pneumonia or bronchitis is frequently observed in patients harbouring WUPyV. Detection of viremia suggests systemic infections. However, the available data do not prove WUPyV to be a human pathogen. Further investigations are necessary.


COVID‐19 and biodiversity: The paradox of cleaner rivers and elevated extinction risk to iconic fish species


title: IbMADS1 (Ipomoea batatas MADS-box 1 gene) is Involved in Tuberous Root Initiation in Sweet Potato (Ipomoea batatas)

text: BACKGROUND AND AIMS: The tuberization mechanism of sweet potato (Ipomoea batatas) has long been studied using various approaches. Morphological data have revealed that the tuberizing events result from the activation of the cambium, followed by cell proliferation. However, uncertainties still remain regarding the regulators participating in this signal-transduction pathway. An attempt was made to characterize the role of one MADS-box transcription factor, which was preferentially expressed in sweet potato roots at the early tuberization stage. METHODS: A differential expression level of IbMADS1 (Ipomoea batatas MADS-box 1) was detected temporally and spatially in sweet potato tissues. IbMADS1 responses to tuberization-related hormones were assessed. In order to identify the evolutionary significance, the expression pattern of IbMADS1 was surveyed in two tuber-deficient Ipomoea relatives, I. leucantha and I. trifida, and compared with sweet potato. In functional analyses, potato (Solanum tuberosum) was employed as a heterologous model. The resulting tuber morphogenesis was examined anatomically in order to address the physiological function of IbMADS1, which should act similarly in sweet potato. KEY RESULTS: IbMADS1 was preferentially expressed as tuberous root development proceeded. Its expression was inducible by tuberization-related hormones, such as jasmonic acid and cytokinins. In situ hybridization data showed that IbMADS1 transcripts were specifically distributed around immature meristematic cells within the stele and lateral root primordia. Inter-species examination indicated that IbMADS1 expression was relatively active in sweet potato roots, but undetectable in tuber-deficient Ipomoea species. IbMADS1-transformed potatoes exhibited tuber morphogenesis in the fibrous roots. The partial swellings along fibrous roots were mainly due to anomalous proliferation and differentiation in the xylem. CONCLUSIONS: Based on this study, it is proposed that IbMADS1 is an important integrator at the initiation of tuberization. As a result, the initiation and development of tuberous roots seems to be well regulated by a network involving a MADS-box gene in which such hormones as jasmonic acid and cytokinins may act as trigger factors.


title: Discovery of Variants Underlying Host Susceptibility to Virus Infection Using Whole-Exome Sequencing

text: The clinical course of any viral infection greatly differs in individuals. This variation results from various viral, host, and environmental factors. The identification of host genetic factors influencing inter-individual variation in susceptibility to several pathogenic viruses has tremendously increased our understanding of the mechanisms and pathways required for immunity. Next-generation sequencing of whole exomes represents a powerful tool in biomedical research. In this chapter, we briefly introduce whole-exome sequencing in the context of genetic approaches to identify host susceptibility genes to viral infections. We then describe general aspects of the workflow for whole-exome sequence analysis together with the tools and online resources that can be used to identify and annotate variant calls, and then prioritize them for their potential association to phenotypes of interest.


title: A novel nucleic acid amplification system based on nano-gap embedded active disk resonators

text: Recent advances in nucleic acid based testing using bio-optical sensor approaches have been introduced but most are based on hybridization between the optical sensor and the bio-molecule and not on an amplification mechanism. Direct nucleic acid amplification on an optical sensor has several technical limitations, such as the sensitivity of the temperature sensor, instrument complexity, and high background signal. We here describe a novel nucleic acid amplification method based on a whispering gallery mode active resonator and discuss its potential molecular diagnostic application. By implanting nanoclusters as active compounds, this active resonator operates without tapered fiber coupling and emits a strong photoluminescence signal with low background in the wavelength of low absorption in an aqueous environment that is typical of biosensors. Our method also offers an extremely low detection threshold down to a single copy within 10 min due to the strong light-matter interaction in a nano-gap structure. We envision that this active resonator provides a high refractive index contrast for tight mode confinement with simple alignment as well as the possibility of reducing the device size so that a point-of-care system with low-cost, high-sensitivity and simplicity.


Effects of COVID‐19 lockdown on epidemic diseases of childhood


title: Detection of Pathogenic Viruses in the Ambient Air in Seoul, Korea

text: The possible transport of pathogenic microorganisms during Asian dust events could be an important concern for health workers; however, this is still uncertain owing to a lack of supporting evidence. The present study aimed to investigate the presence of pathogenic microorganisms in air samples collected during the Asian and non-Asian dust periods. Between March and September 2016, air samples were collected at three weather observation stations in Seoul using a high-volume air sampler. Multiplex PCR was performed using the Allplex™ respiratory and gastrointestinal panel assay kits to detect 46 microorganisms. RT-PCR was performed for klassevirus, Aichivirus, and human parechovirus (HPeV) detection. In total, 71 air samples were collected during the Asian (8 samples) and non-Asian (63 samples) dust events. During an Asian dust event, only one human rhinovirus (HRV)-positive air sample was collected on April 23. During the non-Asian dust period, HRV, HPeV, norovirus (NoV), enteroaggregative Escherichia coli (EAEC), enterotoxigenic E. coli (ETEC), and Blastocystis hominis were detected in four, two, one, one, one, and one air samples, respectively. Pathogenic viruses were mostly detected in ambient air samples during the non-Asian dust period, which suggests a possible air-borne transmission of viral pathogens; however, the role of Asian dust in epidemics caused by pathogenic viruses is unclear.


title: Speed and strength of an epidemic intervention

text: An epidemic can be characterized by its speed (i.e., the exponential growth rate r) and strength (i.e., the reproductive number ℛ). Disease modelers have historically placed much more emphasis on strength, in part because the effectiveness of an intervention strategy is typically evaluated on this scale. Here, we develop a mathematical framework for this classic, strength-based paradigm and show that there is a corresponding speed-based paradigm which can provide complementary insights. In particular, we note that r = 0 is a threshold for disease spread, just like ℛ = 1, and show that we can measure the speed and strength of an intervention on the same scale as the speed and strength of an epidemic, respectively. We argue that, just as the strength-based paradigm provides the clearest insight into certain questions, the speed-based paradigm provides the clearest view in other cases. As an example, we show that evaluating the prospects of “test-and-treat” interventions against the human immunodeficiency virus (HIV) can be done more clearly on the speed than strength scale, given uncertainty in the proportion of HIV spread that happens early in the course of infection. We suggest that disease modelers should avoid over-emphasizing the reproductive number at the expense of the exponential growth rate, but instead look at these as complementary measures.


Absence of 2019 Novel Coronavirus in Semen and Testes of COVID-19 Patients


title: Experimental reproduction of poult enteritis syndrome: Clinical findings, growth response, and microbiology

text: Poult enteritis syndrome (PES) is an infectious disease of turkey poults characterized by diarrhea, dullness, and depression. Five experiments were conducted to reproduce the disease in turkey poults using intestinal contents of PES-affected birds. In all experiments, poults at 14 d of age were divided into 4 groups and were orally given 2 mL of unfiltered supernatant, filtered supernatant, sediment dissolved in PBS, or PBS alone. Inocula in experiments 1, 3, and 5 consisted of intestinal contents from PES-affected birds of less than 2 wk of age, whereas those in experiments 2 and 4 consisted of intestinal contents from PES-affected birds of 4 to 6 wk of age. Poults in all groups were observed daily for clinical signs. The BW and microbiological criteria in experiments 1, 3, and 5 were evaluated at 5, 10, and 15 d postinoculation, whereas in experiments 2 and 4, these observations were made at 10 and 20 d postinoculation. Rotavirus, astrovirus, and Salmonella were present in all 5 inocula. Diarrhea and depression were the major signs in poults given PES material. Significant retardation of growth was observed in poults given any of the 3 PES materials, but this effect was more pronounced in poults given the sediment inoculum. Rotavirus, astrovirus, and Salmonella were detected in poults given PES material. In some cases, enterovirus was also detected. No major difference was noticed in experimental reproduction of PES when intestinal contents from different age birds were used as the inoculum.


MP85-05 LONG-TERM FOLLOW-UP REVEALS DIFFERENTIAL PHENOTYPES OF NEUROLOGIC IMPAIRMENT AND BLADDER FUNCTION IN A MURINE MODEL OF NEURODEGENERATION


title: Utility of massive open online courses (MOOCs) concerning outbreaks of emerging and reemerging diseases

text: The emergence and re-emergence of infectious diseases such as Ebola, chikungunya, and Zika increase the necessity of knowledgeable and skilled health professionals. Massive open online courses (MOOCs) arise as opportunities that allow people around the world to participate in higher education courses. A search was conducted on specialized MOOC platforms to find courses related to outbreaks, using terms included in the list of the WHO disease outbreaks from January 1st to December 31 (st), 2016. We found seven courses about Ebola, two about Zika, three about the dynamics of epidemics and pandemics, and only one course about dengue, chikungunya, and malaria. Most of the courses were conducted in English. The courses on Ebola, Zika and chikungunya were released after their last outbreak. MOOCs could be used to learn about health issues of global relevance, and with the necessity of fast divulgation of knowledge and skills. Translating the courses into more languages could give these courses more traction, and allow participation of professionals in regions affected by these outbreaks.


title: Optimizing safety surveillance for COVID-19 vaccines

text: Evolution of the current infrastructure for surveillance of vaccine safety will be essential to meet our commitments to the public in the deployment of a vaccine (or vaccines) to COVID-19. The incorporation of concepts and tools within the fields of data science and systems immunology can be used to propel vaccine safety monitoring into the twenty-first century.


Please cite this paper as: Ahn et al. (2011) Role of procalcitonin and C‐reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia. Influenza and Other Respiratory Viruses 5(6), 398–403. Background Mixed bacterial infection is an important contributor to morbidity and mortality during influenza pandemics. We evaluated procalcitonin (PCT) and C‐reactive protein (CRP) in differentiating pneumonia caused by mixed bacterial and 2009 H1N1 influenza infection from 2009 H1N1 influenza infection alone. Methods Data were collected retrospectively over a 7‐month period during the 2009 H1N1 influenza pandemic. Patients visiting emergency department and diagnosed as community‐acquired pneumonia caused by 2009 H1N1 infection were included (n = 60). Results Mixed bacterial and viral infection pneumonia (n = 16) had significantly higher PCT and CRP levels than pneumonia caused by 2009 H1N1 influenza alone (n = 44, P = 0·019, 0·022 respectively). The sensitivity and specificity for detection of mixed bacterial infection pneumonia was 56% and 84% for PCT > 1·5 ng/ml, and 69% and 63% for CRP > 10 mg/dl. Using PCT and CRP in combination, the sensitivity and specificity were 50% and 93%, respectively. Conclusion Procalcitonin and CRP alone and their combination had a moderate ability to detect pneumonia of mixed bacterial infection during the 2009 H1N1 pandemic. Considering high specificity, combination of low CRP and PCT result may suggest that pneumonia is unlikely to be caused by mixed bacterial infection.


title: Genomic Profiling of Collaborative Cross Founder Mice Infected with Respiratory Viruses Reveals Novel Transcripts and Infection-Related Strain-Specific Gene and Isoform Expression

text: Genetic variation between diverse mouse species is well-characterized, yet existing knowledge of the mouse transcriptome comes largely from one mouse strain (C57BL/6J). As such, it is unlikely to reflect the transcriptional complexity of the mouse species. Gene transcription is dynamic and condition-specific; therefore, to better understand the mouse transcriptional response to respiratory virus infection, we infected the eight founder strains of the Collaborative Cross with either influenza A virus or severe acute respiratory syndrome coronavirus and sequenced lung RNA samples at 2 and 4 days after infection. We found numerous instances of transcripts that were not present in the C57BL/6J reference annotation, indicating that a nontrivial proportion of the mouse genome is transcribed but poorly annotated. Of these novel transcripts, 2150 could be aligned to human or rat genomes, but not to existing mouse genomes, suggesting functionally conserved sequences not yet recorded in mouse genomes. We also found that respiratory virus infection induced differential expression of 4287 splicing junctions, resulting in strain-specific isoform expression. Of these, 59 were influenced by strain-specific mutations within 2 base pairs of key intron–exon boundaries, suggesting cis-regulated expression. Our results reveal the complexity of the transcriptional response to viral infection, previously undocumented genomic elements, and extensive diversity in the response across mouse strains. These findings identify hitherto unexplored transcriptional patterns and undocumented transcripts in genetically diverse mice. Host genetic variation drives the complexity and diversity of the host response by eliciting starkly different transcriptional profiles in response to a viral infection.


title: Viral aetiology of acute respiratory infections among children and associated meteorological factors in southern China

text: BACKGROUND: Acute respiratory infections (ARIs) are common in children and mostly caused by viruses, but the significance of the detection of multiple viruses in ARIs is unclear. This study investigated 14 respiratory viruses in ARIs among children and associated meteorological factors in Shantou, southern China. METHODS: Paired nasal/throat-flocked swabs collected from 1,074 children with ARIs, who visited outpatient walk-in clinics in a tertiary hospital between December 2010 and November 2011, were examined for fourteen respiratory viruses - influenza viruses (FluA, FluB), respiratory syncytial viruses (RSV A and B), human coronaviruses (hCoV: 229E, OC43, HKU1, NL63), human metapneumoviruses (hMPV A and B), parainfluenza viruses (PIV1-4), human rhinoviruses (HRV A, B, C), enteroviruses (EV), adenoviruses (ADV), human bocavirus (hBoV), and human parechoviruses (hPeV) - by multiplex real-time PCR. RESULTS: We identified at least one virus in 82.3% (884/1,074) and multiple viruses in 38.6% (415/1,074) of patients. EV and HRV were the most frequently detected single viruses (42.3%, 374/884 and 39.9%, 353/884 respectively) and co-detected pair (23.1%, 96/415). Overlapping seasonal trends of viruses were recorded over the year, with dual peaks for EV and single peaks for the others. By logistic regression analysis, EV was positively associated with the average temperature and humidity, hCoV, and PIV4, but negatively with HRV, PIV3, and hBoV. HRV was inversely associated with EV and PIV3. CONCLUSIONS: This study reports high viral detection and co-detection rates in pediatric ARI cases mainly due to EV and HRV. Many viruses circulated throughout the year with similar seasonal trends in association with temperature, humidity, and wind velocity. Statistically significant associations were present among the viruses. Understanding the polyviral etiology and viral interactions in the cases with multiple viruses warrants further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0863-6) contains supplementary material, which is available to authorized users.


title: Functional long-range RNA–RNA interactions in positive-strand RNA viruses

text: Positive-strand RNA viruses are important human, animal and plant pathogens that are defined by their single-stranded positive-sense RNA genomes. In recent years, it has become increasingly evident that interactions that occur between distantly positioned RNA sequences within these genomes can mediate important viral activities. These long-range intragenomic RNA–RNA interactions involve direct nucleotide base pairing and can span distances of thousands of nucleotides. In this Review, we discuss recent insights into the structure and function of these intriguing genomic features and highlight their diverse roles in the gene expression and genome replication of positive-strand RNA viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro3288) contains supplementary material, which is available to authorized users.


title: Baricitinib: A chance to treat COVID‐19?

text: Currently, there are no approved therapies for the treatment of COVID-19. With most of the world on lockdown and the looming threat of millions of deaths, there is immense pressure to find a therapy for this disease. This article is protected by copyright. All rights reserved.


title: Host Resistance and Immune Responses in Advanced Age

text: Immunosenescence results in populating immune tissues with less functional T cells, and perhaps B cells dendritic cells, that do not function well and produce more type 2 cytokines and fewer type 1 cytokines. Impaired immunity, distinct from immunosenescence, correlates more with disease burden than chronologic age. Older adults who have chronic diseases or chronic infections are more susceptible to common infections and have poor vaccine responses. Understanding specific mechanisms and targeting interventions are dependent on research to resolve the relationship between frailty-associated impaired immunity and the role of chronic infection versus immunosenescence in developing impaired immunity.


title: Health Café Series: a Potential Platform to Reduce Health Disparities

text: To help bridge the increasing gap between health scientists/physicians and the community, we have developed a new seminar program—Health Café series. Health Café takes place in causal settings, is open to everyone, and features a keynote speaker regarding prevalent healthcare-related topics. Health Café topics are usually generated via community feedback and are coordinated in partnership with local nonprofit community organizations. The Health Café series is completely free, and no prior knowledge is required to attend seminars. We have been collaborating with a web of community organizations in the Hartford areas of Connecticut, especially among populations with health disparities. We believe our new Health Café series program would serve as a forum to reduce health disparities in the region.


Mayo Clinic Strategies for COVID-19 Clinical Guidance and the Delivery of Care for Patients With Coronavirus Disease 2019


title: Is hydroxychloroquine beneficial for COVID-19 patients?

text: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world(1–3), the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 2020(4). The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir(5), to control the disease and halt the pandemic.


title: Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: A review

text: Abstract Ethnopharmacological relevance Polygonum multiflorum Thunb., which is known as Heshouwu (何首乌 in Chinese) in China. It is traditionally valued and reported for hair-blacking, liver and kidney-tonifying and anti-aging effects as well as low toxicity. The aim of this review is to provide comprehensive information on the botany, traditional uses, phytochemistry, pharmacological research and toxicology of Polygonum multiflorum, based on the scientific literature. Moreover, trends and perspectives for future investigation of this plant are discussed. It will build up a new foundation for further study on Polygonum multiflorum. Materials and methods A systematic review of the literature on Polygonum multiflorum was performed using several resources, including classic books on Chinese herbal medicine and various scientific databases, such as PubMed, SciFinder, the Web of Science, Science Direct, China Knowledge Resource Integrated (CNKI). Results Polygonum multiflorum is widely distributed throughout the world and has been used as a traditional medicine for centuries in China. The ethnomedical uses of Polygonum multiflorum have been recorded in many provinces of China and Japan for nine species of adulterants in six families. More than 100 chemical compounds have been isolated from this plant, and the major components have been determined to be stilbenes, quinones, flavonoids and others. Crude extracts and pure compounds of this plant are used as effective agents in pre-clinical and clinical practice due to their anti-aging, anti-hyperlipidaemia, anti-cancer and anti-inflammatory effects and to promote immunomodulation, neuroprotection, and the curing of other diseases. However, these extracts can also lead to hepatotoxicity, nephrotoxicity and embryonic toxicity. Pharmacokinetic studies have demonstrated that the main components of Polygonum multiflorum, such as 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucopyranoside and emodin are distributed among many organs and tissues. Conclusion Therapeutic potential of Polygonum multiflorum has been demonstrated in the conditions like Alzheimer׳s disease, Parkinson׳s disease, hyperlipidaemia, inflammation and cancer, which is attributed to the presence of various stilbenes, quinones, flavonoids, phospholipids and other compounds in the drug. On the other hand, the adverse effects (hepatotoxicity, nephrotoxicity, and embryonic toxicity) of this plant were caused by the quinones, such as emodin and rhein. Thus more pharmacological and toxicological mechanisms on main active compounds are necessary to be explored, especially the combined anthraquinones (Emodin-8-O-β-d-glucopyranoside, Physcion-8-O-β-d-glucopyranoside, etc.) and the variety of stilbenes.


title: Pathogenesis of virus-induced immune-mediated demyelination

text: Theiler's murine encephalomyelitis virus-induced demyelinating disease has been extensively studied as an attractive infectiousmodel for human multiple sclerosis. Virus-specific inflammatory Th1 cell responses followed by autoimmune responses to myelin antigens play a crucial role in the pathogenic processes leading to demyelination. Antibody and cytotoxic T cells (CTL) responses to virus appears to be primarily protective from demyelinating disease. Although the role of Th1 and CTL responses in the induction of demyelinating disease is controversial, assessment of cytokine sproduced locally in the central nervous system (CNS) during the course of disease and the effects of altered inflammatory cytokine levels strongly support the importance of Th1 responses in this virus-induced demyelinating disease. Induction of various chemokines and cytokines in different glial and antigen presenting cells upon viral infection appears to be an important initiation mechanism for inflammatory Th1 responses in the CNS. Coupled with the initial inflammatory responses, viral persistence in the CNS may be acritical factor for sustaining inflammatory responses and consequent immune-mediated demyelinating disease.


docid: qatoduvc

title: Obstetric and intensive-care strategies in a high-risk pregnancy with critical respiratory failure due to COVID-19: A case report

text: BACKGROUND: With the disease burden increasing daily, there is a lack of evidence regarding the impact of COVID-19 in pregnancy. Healthy pregnant women are still not regarded as a susceptible group despite physiological changes that make pregnant women more vulnerable to severe infection. However, high-risk pregnancies may be associated with severe COVID-19 disease with respiratory failure, as outlined in this report. We discuss the importance of timely delivery and antenatal steroid administration in a critically ill patient. CASE: A 27-year-old pregnant woman (gravida 2, para 1) with type I diabetes, morbid obesity, hypothyroidism and a previous Caesarean section presented with critical respiratory failure secondary to COVID-19 at 32 weeks of gestation. A preterm emergency Caesarean section was performed, after steroid treatment for foetal lung maturation. The patient benefited from prone positioning; however, transient acute renal injury, rhabdomyolysis and sepsis led to prolonged intensive care and mechanical ventilation for 30 days. The baby had an uncomplicated recovery. CONCLUSION: COVID-19 infection in high-risk pregnancies may result in severe maternal and neonatal outcomes such as critical respiratory failure requiring mechanical ventilation and premature termination of the pregnancy. Antenatal steroids may be of benefit for foetal lung maturation but should not delay delivery in severe cases.


title: Operating costs and capacity in the airline industry

text: Abstract This study illustrates how to calculate accurate costs, including the operating costs for individual airplanes and flights, as well as the costs per available seat kilometers, and per available ton kilometers using activity based costing. It also identifies the main activity items and drivers of each airplane and flight. Additionally, it uses a case study to illustrate the calculation of production variance, marketing variance and expected idle passenger capacity in the airline industry. This is useful information when the purchase or lease an airplane under the conditions of idle capacity.


title: Chapter 9 Infectious diseases of the ear, nose, throat, and bronchus

text: Abstract Infectious diseases occur based on the interrelationship of the capabilities of the host and the virulence of the microorganism. Each person has a terrain that determines the susceptibility to infection and response to an infection. According to the theory of endobiogeny, the majority of symptoms related to an infectious disease are related to the patient’s response to the infector and not the intrinsic agent itself. This chapter discusses common infectious maladies: rhinopharyngitis, sinusitis, otitis media, tonsillitis, and bronchitis. For each of these disorders, the neuroendocrine and emunctory elements in the precritical and critical terrain are discussed. Treatment options are discussed based on treating the patient rather than the microorganism.


docid: gceffbfp

title: Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein

text: Abstract Heptad repeat regions (HR1 and HR2) are highly conserved sequences located in the glycoproteins of enveloped viruses. They form a six-helix bundle structure and are important in the process of virus fusion. Peptides derived from the HR regions of some viruses have been shown to inhibit the entry of these viruses. SARS-CoV was also predicted to have HR1 and HR2 regions in the S2 protein. Based on this prediction, we designed 25 peptides and screened them using a HIV-luc/SARS pseudotyped virus assay. Two peptides, HR1-1 and HR2-18, were identified as potential inhibitors, with EC50 values of 0.14 and 1.19μM, respectively. The inhibitory effects of these peptides were validated by the wild-type SARS-CoV assay. HR1-1 and HR2-18 can serve as functional probes for dissecting the fusion mechanism of SARS-CoV and also provide the potential of further identifying potent inhibitors for SARS-CoV entry.


title: Nod2 is required for antigen-specific humoral responses against antigens orally delivered using a recombinant Lactobacillus vaccine platform

text: Safe and efficacious orally-delivered mucosal vaccine platforms are desperately needed to combat the plethora of mucosally transmitted pathogens. Lactobacillus spp. have emerged as attractive candidates to meet this need and are known to activate the host innate immune response in a species- and strain-specific manner. For selected bacterial isolates and mutants, we investigated the role of key innate immune pathways required for induction of innate and subsequent adaptive immune responses. Co-culture of murine macrophages with L. gasseri (strain NCK1785), L. acidophilus (strain NCFM), or NCFM-derived mutants—NCK2025 and NCK2031—elicited an M2b-like phenotype associated with TH2 skewing and immune regulatory function. For NCFM, this M2b phenotype was dependent on expression of lipoteichoic acid and S layer proteins. Through the use of macrophage genetic knockouts, we identified Toll-like receptor 2 (TLR2), the cytosolic nucleotide-binding oligomerization domain containing 2 (NOD2) receptor, and the inflammasome-associated caspase-1 as contributors to macrophage activation, with NOD2 cooperating with caspase-1 to induce inflammasome derived interleukin (IL)-1β in a pyroptosis-independent fashion. Finally, utilizing an NCFM-based mucosal vaccine platform with surface expression of human immunodeficiency virus type 1 (HIV-1) Gag or membrane proximal external region (MPER), we demonstrated that NOD2 signaling is required for antigen-specific mucosal and systemic humoral responses. We show that lactobacilli differentially utilize innate immune pathways and highlight NOD2 as a key mediator of macrophage function and antigen-specific humoral responses to a Lactobacillus acidophilus mucosal vaccine platform.


COVID -19 outbreak – Diabetes aspect and perspective


title: Privacy and Confidentiality in Emergency Medicine: Obligations and Challenges

text: Respect for privacy and confidentiality have been professional responsibilities of physicians throughout recorded history. This article reviews the moral, religious, and legal foundations of privacy and confidentiality and discusses the distinction between these two closely related concepts. Current federal and state laws are reviewed, including HIPAA regulations and their implications for research and care in the emergency department. In the emergency department, privacy and confidentiality often are challenged by physical design, crowding, visitors, film crews, communication, and other factors. These problems are reviewed, and advice and guidelines are offered for helping preserve patients' dignity and rights to privacy and confidentiality.


docid: xzpkpdee

title: Society of gynecologic oncology surgery considerations during when to operate, hesitate and reintegrate the COVID-19 pandemic

text: The COVID-19 pandemic has challenged our ability to provide timely surgical care for our patients. In response, the American College of Surgeons, U.S. Surgeon General, and other surgical professional specialties have recommended postponing elective surgical procedures and proceeding cautiously with cancer procedures that may require significant hospital resources and expose vulnerable patients to the virus. These challenges are particularly distressing for women with a gynecologic cancer diagnosis and their providers. Currently, circumstances vary greatly by region and by hospital, depending on COVID-19 prevalence, case mix, hospital type, and available resources. Therefore, COVID-19-related modifications to surgical practice guidelines must be individualized. Special consideration is necessary to evaluate the appropriateness of procedural interventions, recognizing the significant resources and personnel they require. Additionally, the pandemic may occur in waves, with patient demand for surgery ebbing and flowing accordingly. Hospitals, cancer centers and providers must prepare themselves to meet this demand. The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to pause, and re-integrate surgery. Triage and prioritization of surgical cases, preoperative COVID-19 testing, peri-operative safety principles, surgical training, and preparations for the post-COVID-19 peak and surgical re-integration are reviewed.


title: Chapter Five Pleiotropic Roles of Type 1 Interferons in Antiviral Immune Responses

text: Abstract Since Isaac's and Lindenmann's seminal experiments over 50 years ago demonstrating a soluble factor generated from heat killed virus-stimulated chicken embryos could inhibit live influenza virus replication, the term interferon has been synonymous with inhibition of virus replication. While the antiviral properties of type 1 interferon (IFN-I) are undeniable, recent studies have reported expanding and somewhat unexpected roles of IFN-I signaling during both acute and persistent viral infections. IFN-I signaling can promote morbidity and mortality through induction of aberrant inflammatory responses and recruitment of inflammatory innate immune cell populations during acute respiratory viral infections. During persistent viral infection, IFN-I signaling promotes containment of early viral replication/dissemination, however, also initiates and maintains immune suppression, lymphoid tissue disorganization, and CD4 T cell dysfunction through modulation of multiple immune cell populations. Finally, new data are emerging illuminating how specific IFN-I species regulate immune pathology and suppression during acute and persistent viral infections, respectively. Systematic characterization of the cellular populations that produce IFN-I, how the timing of IFN-I induction and intricacies of subtype specific IFN-I signaling promote pathology or immune suppression during acute and persistent viral infections should inform the development of treatments and modalities to control viral associated pathologies.


title: Flex-nucleoside analogues – Novel therapeutics against filoviruses

text: Abstract Fleximers, a novel type of flexible nucleoside that have garnered attention due to their unprecedented activity against human coronaviruses, have now exhibited highly promising levels of activity against filoviruses. The Flex-nucleoside was the most potent against recombinant Ebola virus in Huh7 cells with an EC50 =2μM, while the McGuigan prodrug was most active against Sudan virus-infected HeLa cells with an EC50 of 7μM.


title: Can Routine Laboratory Tests Discriminate between Severe Acute Respiratory Syndrome and Other Causes of Community-Acquired Pneumonia?

text: Background. The clinical presentation of severe acute respiratory syndrome (SARS) resembles that of other etiologies of community-acquired pneumonia, making diagnosis difficult. Hematological and biochemical abnormalities, particularly lymphopenia, are common in patients with SARS. Methods. With the use of 2 databases, we compared the ability of the absolute lymphocyte count, absolute neutrophil count, lactate dehydrogenase level, creatine kinase level, alanine aminotransferase level, and serum calcium level at hospital admission to discriminate between cases of SARS and cases of community-acquired pneumonia. The SARS database contained data for 144 patients with SARS from the 2003 Toronto SARS outbreak. The community-acquired pneumonia database contained data for 8044 patients with community-acquired pneumonia from Edmonton, Canada. Patients from the SARS database were matched to patients from the community-acquired pneumonia database according to age, and receiver operating characteristic curves were constructed for each laboratory variable. Results. The areas under the receiver operating characteristic curves (AUCs) demonstrated fair to poor discriminatory ability for all laboratory variables tested except absolute neutrophil count, which had an AUC of 0.80, indicating good discriminatory ability (although there was no cutoff value of the absolute neutrophil count at which reasonable sensitivity or specificity could be obtained). Combinations of any 2 tests did not perform significantly better than did the absolute neutrophil count alone. Conclusions. Routine laboratory tests, including determination of absolute lymphocyte count, should not be used in the diagnosis of SARS or incorporated into current case definitions of SARS. The role of the absolute neutrophil count in SARS diagnosis is likely limited, but it should be assessed further.


Essential medicines for universal health coverage


docid: ipbhsoxs

title: Canine coronavirus induces apoptosis in cultured cells

text: Abstract Canine coronavirus (CCoV) is widespread in dogs in several countries and causes mild enteric illness evolving to severe enteritis in young pups. In in vitro cultures canine coronaviruses generally induce extensive cell death, however nature of the events leading to cell death remains largely unknown. We analysed the induction of cytopathic effect by CCoV in a canine fibrosarcoma cell line (A-72) in order to characterize the apoptotic effect in homologous cell system. Following CCoV infection A-72 cell line, which is permissive to CCoV, showed reduced growth rate, as detected by MTT assay, a standard colorimetric assay for measuring cellular proliferation, and underwent to apoptotic death. Starting from 24h after CCoV infection, cells morphology appeared dramatically changed, with cells rounding and detachment from culture surface. Morphologic and biochemical features of apoptosis, such as blebbing of the plasma membrane, translocation of phosphatidilserine to cell surface and annexin V positive staining, nuclear fragmentation, apoptotic bodies formation and DNA laddering, were detected in CCoV-infected cells. Propidium iodide staining of infected culture indicated the appearance of hypodiploid DNA peak corresponding to apoptotic cell population. Commonly to other animal coronavirus infection caspase-3 is likely to contribute to the execution phase of apoptosis induced by CCoV in A-72 cells since we found activation of enzymatic activity as well as procaspase-3 activating cleavage. Apoptotic death of infected cells is detrimental as it causes cell and tissue destruction as well as inflammatory responses. Therefore in the case of CCoV associated gastroenteritis, apoptosis of epithelial mucosa cells may be responsible for pathology induced by CCoV infection.


title: Dengue Virus Type 2 (DENV2)-Induced Oxidative Responses in Monocytes from Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient and G6PD Normal Subjects

text: BACKGROUND: Dengue virus is endemic in peninsular Malaysia. The clinical manifestations vary depending on the incubation period of the virus as well as the immunity of the patients. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is prevalent in Malaysia where the incidence is 3.2%. It has been noted that some G6PD-deficient individuals suffer from more severe clinical presentation of dengue infection. In this study, we aim to investigate the oxidative responses of DENV2-infected monocytes from G6PD-deficient individuals. METHODOLOGY: Monocytes from G6PD-deficient individuals were infected with DENV2 and infection rate, levels of oxidative species, nitric oxide (NO), superoxide anions (O(2) (−)), and oxidative stress were determined and compared with normal controls. PRINCIPAL FINDINGS: Monocytes from G6PD-deficient individuals exhibited significantly higher infection rates compared to normal controls. In an effort to explain the reason for this enhanced susceptibility, we investigated the production of NO and O(2) (−) in the monocytes of individuals with G6PD deficiency compared with normal controls. We found that levels of NO and O(2) (−) were significantly lower in the DENV-infected monocytes from G6PD-deficient individuals compared with normal controls. Furthermore, the overall oxidative stress in DENV-infected monocytes from G6PD-deficient individuals was significantly higher when compared to normal controls. Correlation studies between DENV-infected cells and oxidative state of monocytes further confirmed these findings. CONCLUSIONS/SIGNIFICANCE: Altered redox state of DENV-infected monocytes from G6PD-deficient individuals appears to augment viral replication in these cells. DENV-infected G6PD-deficient individuals may contain higher viral titers, which may be significant in enhanced virus transmission. Furthermore, granulocyte dysfunction and higher viral loads in G6PD-deificient individuals may result in severe form of dengue infection.


title: Identification of acute myeloid leukemia patients with diminished expression of CD13 myeloid transcripts by competitive reverse transcription polymerase chain reaction (RT-PCR)

text: Abstract Normal myeloid cells of monocytic and granulocytic origin express the metallopeptidase cluster of differentiation 13 (CD13) on the surface just as leukemic blasts in most acute myeloid leukemias (AML). A minor percentage of AML patients, however, lack the surface expression of CD13 antigen. To study this difference in CD13 surface expression, specific CD13 mRNA from 44 individuals were quantified by competitive reverse transcription polymerase chain reaction (RT-PCR). Absolute values for CD13 transcripts were normalised against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcript levels to control for variations in sample preparation and mRNA degradation. By correlating normalised CD13 transcript levels and CD13 surface expression, a subgroup of AML patients was identified, having simultaneous diminished levels of myeloid CD13 transcripts and surface expression of the corresponding antigen. For this subgroup we suggest CD13/aminopeptidase N (APN) gene expression to be restricted primarily by limited amounts of transcripts. For the majority of AML patients determinants in addition to transcript levels must be involved in regulating CD13/APN gene expression.


title: Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection

text: Abstract Objective To evaluate the in vitro activities of the ethyl acetate (EA) fraction of Houttuynia cordata (H. cordata) Thunb. (Saururaceae) and three of its constituent flavonoids (quercetin, quercitrin and rutin) against murine coronavirus and dengue virus (DENV). Methods The antiviral activities of various concentrations of the EA fraction of H. cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus (MHV) and DENV type 2 (DENV-2). Cinanserin hydrochloride was also tested against MHV. The EA fraction of H. cordata was tested for acute oral toxicity in C57BL/6 mice. Results The EA fraction of H. cordata inhibited viral infectivity up to 6 d. Cinanserin hydrochloride was able to inhibit MHV for only 2 d. The 50% inhibitory concentrations (IC50) of the EA fraction of H. cordata added before the viral adsorption stage were 0.98 μg/mL for MHV and 7.50 μg/mL for DENV-2 with absence of cytotoxicity. The mice fed with the EA fraction up to 2000 mg/kg did not induce any signs of acute toxicity, with normal histological features of major organs. Certain flavonoids exhibited comparatively weaker antiviral activity, notably quercetin which could inhibit both MHV and DENV-2. This was followed by quercitrin which could inhibit DENV-2 but not MHV, whereas rutin did not exert any inhibitory effect on either virus. When quercetin was combined with quercitrin, enhancement of anti-DENV-2 activity and reduced cytotoxicity were observed. However, the synergistic efficacy of the flavonoid combination was still less than that of the EA fraction. Conclusions The compounds in H. cordata contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in vivo. H. cordata has much potential for the development of antiviral agents against coronavirus and dengue infections.


title: A solution to renewable hydrogen economy for fuel cell buses – A case study for Zhangjiakou in North China

text: Abstract Fuel cell vehicles fueled with renewable hydrogen is recognized as a life-cycle carbon-free option for the transport sector, however, the profitability of the H2 pathway becomes a key issue for the FCV commercialization. By analyzing the actual data from the Zhangjiakou fuel cell transit bus project, this research reveals it is economically feasible to commercialize FCV in areas with abundant renewable resources. Low electricity for water electrolysis, localization of H2 supply, and curtailed end price of H2 refueling effectively reduce the hydrogen production, delivery and refueling cost, and render a chance for the profitability of refueling stations. After the fulfillment of the intense deployment of both vehicles and hydrogen stations for the 2022 Winter Olympics, the H2 pathway starts to make a profit thereafter. The practices in the Zhangjiakou FCB project offer a solution to the hydrogen economy, which helps to break the chicken-egg dilemma of vehicles and hydrogen infrastructure.


title: Dynamical transmission model of MERS-CoV in two areas

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a disease first reported in Saudi Arabia in 2012 and it can be transmitted from human to human. This disease has spread to several other countries, most confirmed cases have displayed symptoms of severe acute respiratory illness and many of these patients have died. This research is aimed to construct a mathematical model for the transmission of MERS-CoV in two areas by separating the human population into two groups; susceptible and infectious groups. The dynamics of the disease is studied by a compartmental model involving ordinary differrential equations. The basic reproductive number of this disease is discussed to control the outbreak of this disease. Sensitivity analysis of this model is performed to determine the relative importance of the model parameters to the MERS-CoV transmission.


title: Potential Drugs Targeting Early Innate Immune Evasion of SARS-Coronavirus 2 via 2’-O-Methylation of Viral RNA

text: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing the COVID-19 respiratory disease pandemic utilizes unique 2′-O-methyltransferase (2′-O-MTase) capping machinery to camouflage its RNA from innate immune recognition. The nsp16 catalytic subunit of the 2′-O-MTase is unusual in its requirement for a stimulatory subunit (nsp10) to catalyze the ribose 2′-O-methylation of the viral RNA cap. Here we provide a computational basis for drug repositioning or de novo drug development based on three differential traits of the intermolecular interactions of the SARS-CoV-2-specific nsp16/nsp10 heterodimer, namely: (1) the S-adenosyl-l-methionine-binding pocket of nsp16, (2) the unique “activating surface” between nsp16 and nsp10, and (3) the RNA-binding groove of nsp16. We employed ≈9000 U.S. Food and Drug Administration (FDA)-approved investigational and experimental drugs from the DrugBank repository for docking virtual screening. After molecular dynamics calculations of the stability of the binding modes of high-scoring nsp16/nsp10–drug complexes, we considered their pharmacological overlapping with functional modules of the virus–host interactome that is relevant to the viral lifecycle, and to the clinical features of COVID-19. Some of the predicted drugs (e.g., tegobuvir, sonidegib, siramesine, antrafenine, bemcentinib, itacitinib, or phthalocyanine) might be suitable for repurposing to pharmacologically reactivate innate immune restriction and antagonism of SARS-CoV-2 RNAs lacking 2′-O-methylation.


title: Vulnerability of nurse and physicians with COVID‐19: Monitoring and surveillance needed

text: SARS‐CoV‐2, the virus that causes COVID‐19, is wreaking havoc around the world. This unprecedented pandemic has led to illness, death, and economic destruction. The pandemic has challenged health care systems globally for a range of reasons. In developed economies the focus on non‐communicable diseases rather than infectious diseases have caught us short. A period of complacency and a lack of focus on potential pandemics has meant that documented shortages of personnel, workforce and equipment has limited healthcare delivery.


title: The detection and phylogenetic analysis of porcine deltacoronavirus from Guangdong Province in Southern China

text: Porcine deltacoronavirus (PDCoV) is a newly discovered coronavirus that causes diarrhoea, vomiting and dehydration in sucking and nursing piglets. It was first reported in Hong Kong in 2012 and has since been discovered in the United States, Canada, South Korea, mainland China, Thailand and Laos. PDCoV has been experimentally proved to lead to diarrhoea in swine and it was detected positive in pigs in Guangdong, southern China. In our study, 252 faecal and intestinal samples from sucking piglets and sows with diarrhoea were surveyed for common enteric viruses. We found a prevalence of PDCoV (21.8%), porcine epidemic diarrhoea virus (65.5%), transmissible gastroenteritis virus (0%), rotavirus group A (25.0%) and porcine kobuvirus (68.7%). We isolated 13 PDCoV strains and discovered that PDCoV infections were often co‐infections with kobuvirus rather than the commonly linked porcine epidemic diarrhoea virus. Phylogenetic analysis of S gene and N gene revealed that 11 of 13 PDCoV strains belonged to Chinese lineage. As for the left two strains, one single strain (CHN‐GD16‐05) belonged to American and Korean lineages while another strain (CHN‐GD16‐03) was similar to a Thai strain, but only in the S gene. This suggested a possible recombination event between the Thai and the newly described Chinese strain.


title: Are Saudi medical students aware of middle east respiratory syndrome coronavirus during an outbreak?

text: Summary Recently, an outbreak of MERS-CoV occurred in King Abdulaziz Medical City (KAMC), Riyadh. This outbreak contributed to the students at the King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) becoming more involved in promoting health awareness in their communities. This was a cross-sectional study that evaluated students in the clinical phase of medical school. The data were collected by an online questionnaire. The measurements were obtained using a researcher-administered and a self-reported questionnaire that had been previously validated. A p-value of less than 0.05 was considered statistically significant. One hundred and thirty-six students participated and showed good awareness regarding the clinical aspects of MERS, such as etiology, diagnosis, management, and prevention. However, 76% of the students were not aware of the mortality rate. Conversely, this study uncovered a low level of awareness in the basic sciences. Interestingly, fifth year medical students were more familiar with the incubation period than final year students (p-value <0.05). Regarding gender differences, more female students were knowledgeable about the incubation period and the possible asymptomatic presentation of the disease than male students (p-value <0.05). However, male students were more aware of the diagnostic tests for MERS than their female counterparts. Medical students were knowledgeable about the clinical aspects of MERS but were lacking background awareness in the basic sciences.


title: Impact of infectious disease epidemics on tuberculosis diagnostic, management, and prevention services: experiences and lessons from the 2014–2015 Ebola virus disease outbreak in West Africa

text: Summary The World Health Organization (WHO) Global Tuberculosis Report 2015 states that 28% of the world's 9.6 million new tuberculosis (TB) cases are in the WHO Africa Region. The Mano River Union (MRU) countries of West Africa–Guinea, Sierra Leone, and Liberia–have made incremental sustained investments into TB control programmes over the past two decades. The devastating Ebola virus disease (EVD) outbreak of 2014–2015 in West Africa impacted significantly on all sectors of the healthcare systems in the MRU countries, including the TB prevention and control programmes. The EVD outbreak also had an adverse impact on the healthcare workforce and healthcare service delivery. At the height of the EVD outbreak, numerous staff members in all MRU countries contracted EBV at the Ebola treatment units and died. Many healthcare workers were also infected in healthcare facilities that were not Ebola treatment units but were national hospitals and peripheral health units that were unprepared for receiving patients with EVD. In all three MRU countries, the disruption to TB services due to the EVD epidemic will no doubt have increased Mycobacterium tuberculosis transmission, TB morbidity and mortality, and decreased patient adherence to TB treatment, and the likely impact will not be known for several years to come. In this viewpoint, the impact that the EVD outbreak had on TB diagnostic, management, and prevention services is described. Vaccination against TB with BCG in children under 5 years of age was affected adversely by the EVD epidemic. The EVD outbreak was a result of global failure and represents yet another ‘wake-up call’ to the international community, and particularly to African governments, to reach a consensus on new ways of thinking at the national, regional, and global levels for building healthcare systems that can sustain their function during outbreaks. This is necessary so that other disease control programmes (like those for TB, malaria, and HIV) are not compromised during the emergency measures of a severe epidemic.


title: Assay development and high throughput antiviral drug screening against Bluetongue virus

text: Bluetongue virus (BTV) infection is one of the most important diseases of domestic livestock. There are no antivirals available against BTV disease. In this paper, we present the development, optimization and validation of an in vitro cell-based high-throughput screening (HTS) assay using the luminescent-based CellTiter-Glo reagent to identify novel antivirals against BTV. Conditions of the cytopathic effect (CPE)-based assay were optimized at cell density of 5 000 cells/well in medium containing 1% FBS and a multiplicity of infection at 0.01 in 384-well plate, with Z'-values ≥ 0.70, Coefficient of Variations ≥ 5.68 and signal-to-background ratio ≥ 7.10. This assay was further validated using a 9 532 compound library. The fully validated assay was then used to screen the 194 950 compound collection, which identified 693 compounds with > 30% CPE inhibition. The ten-concentration dose response assay identified 185 structures with IC(50) ≤ 100 μM, out of which 42 compounds were grouped into six analog series corresponding to six scaffolds enriched within the active set compared to their distribution in the library. The CPE-based assay development demonstrated its robustness and reliability, and its application in the HTS campaign will make significant contribution to the antiviral drug discovery against BTV disease.


title: In Vitro and In Vivo Activity of a Novel Antifungal Small Molecule against Candida Infections

text: Candida is the most common fungal pathogen of humans worldwide and has become a major clinical problem because of the growing number of immunocompromised patients, who are susceptible to infection. Moreover, the number of available antifungals is limited, and antifungal-resistant Candida strains are emerging. New and effective antifungals are therefore urgently needed. Here, we discovered a small molecule with activity against Candida spp. both in vitro and in vivo. We screened a library of 50,240 small molecules for inhibitors of yeast-to-hypha transition, a major virulence attribute of Candida albicans. This screening identified 20 active compounds. Further examination of the in vitro antifungal and anti-biofilm properties of these compounds, using a range of Candida spp., led to the discovery of SM21, a highly potent antifungal molecule (minimum inhibitory concentration (MIC) 0.2 – 1.6 µg/ml). In vitro, SM21 was toxic to fungi but not to various human cell lines or bacterial species and was active against Candida isolates that are resistant to existing antifungal agents. Moreover, SM21 was relatively more effective against biofilms of Candida spp. than the current antifungal agents. In vivo, SM21 prevented the death of mice in a systemic candidiasis model and was also more effective than the common antifungal nystatin at reducing the extent of tongue lesions in a mouse model of oral candidiasis. Propidium iodide uptake assay showed that SM21 affected the integrity of the cell membrane. Taken together, our results indicate that SM21 has the potential to be developed as a novel antifungal agent for clinical use.


title: Pathogenesis of neurotropic murine coronavirus is multifactorial

text: Although coronavirus tropism is most often ascribed to receptor availability, mounting evidence suggests that, for the neurotropic strains of the murine coronavirus mouse hepatitis virus (MHV), spike-receptor interactions cannot fully explain neurovirulence. The canonical MHV receptor CEACAM1a and its spike-binding site have been extensively characterized. However, CEACAM1a is poorly expressed in neurons, and the extremely neurotropic MHV strain JHM.SD infects ceacam1a−/− mice and spreads among ceacam1a−/− neurons. Two proposed alternative MHV receptors, CEACAM2 and PSG16, also fail to account for neuronal spread of JHM.SD in the absence of CEACAM1a. JHM.SD has been reported to have an unusually labile spike protein, enabling it to perform receptor-independent spread (RIS), but it is not clear that the ability to perform RIS is fully responsible for the extremely neurovirulent phenotype. We propose that the extreme neurovirulence of JHM.SD is multifactorial and might include as-yet unidentified neuron-specific mechanisms of spread.


title: Adjuvant oils induce arthritis in the DA rat. I. Characterization of the disease and evidence for an immunological involvement

text: Abstract An intradermal injection of Freund's incomplete adjuvant oil (FIA) without further additives was shown to induce erosive polyarthritis in dark Agouti (DA) rats, but not in Lewis rats. Histological examination revealed joint inflammation, first with polymorphonuclear cells and synovial hyperplasia, and subsequently, with multinucleated giant cells. Both constituents of FIA, mineral oil and Arlacel® A, as well as Pristane oil were arthritogenic, whereas vegetable oils were not. Re-administration of adjuvant oil after recovery failed to induce arthritis, thus making possible a role of specific immunity in this new form of arthritis in rats.


title: Respiratory Infection in Institutions during Early Stages of Pandemic (H1N1) 2009, Canada

text: Outbreaks of respiratory infection in institutions in Ontario, Canada were studied from April 20 to June 12, 2009, during the early stages of the emergence of influenza A pandemic (H1N1) 2009. Despite widespread presence of influenza in the general population, only 2 of 83 outbreaks evaluated by molecular methods were associated with pandemic (H1N1) 2009.


title: G-Quadruplexes: More Than Just a Kink in Microbial Genomes

text: G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich DNA and RNA sequences. In this review we aim to provide an overview of the biological roles of G4s in microbial genomes with emphasis on recent discoveries. G4s are enriched and conserved in the regulatory regions of microbes, including bacteria, fungi, and viruses. Importantly, G4s in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomes modulate genes crucial for virus replication. Recent studies on Epstein–Barr virus (EBV) shed light on the role of G4s within the microbial transcripts as cis-acting regulatory signals that modulate translation and facilitate immune evasion. Furthermore, G4s in microbial genomes have been linked to radioresistance, antigenic variation, recombination, and latency. G4s in microbial genomes represent novel therapeutic targets for antimicrobial therapy.


title: Equine arteritis virus: An overview

text: Abstract The causative agent of the respiratory disease equine viral arteritis is a small, single-stranded RNA virus with a genome organization and replication strategy related to that of coronaviruses and toroviruses. Clinical signs of infection in horses vary widely and severe infection can lead to pregnant mares aborting. Infected horses generally make good recoveries but stallions may become semen shedders of equine arteritis virus (EAV). These carrier stallions play an important role in the dissemination and perpetuation of EAV. Laboratory tests exist to detect virus and the equine immune response to infection. However, vaccines are not currently licensed in the UK to combat viral arteritis, the incidence of which may increase due to changes in European legislation.


title: Identification of N-linked glycosylation sites in the spike protein and their functional impact on the replication and infectivity of coronavirus infectious bronchitis virus in cell culture

text: Abstract Spike (S) glycoprotein on the viral envelope is the main determinant of infectivity. The S protein of coronavirus infectious bronchitis virus (IBV) contains 29 putative asparagine(N)-linked glycosylation sites. These post-translational modifications may assist in protein folding and play important roles in the functionality of S protein. In this study, we used bioinformatics tools to predict N-linked glycosylation sites and to analyze their distribution in IBV strains and variants. Among these sites, 8 sites were confirmed in the S protein extracted from partially purified virus particles by proteomics approaches. N-D and N-Q substitutions at 13 predicted sites were introduced into an infectious clone system. The impact on S protein-mediated cell-cell fusion, viral recovery and infectivity was assessed, leading to the identification of sites essential for the functions of IBV S protein. Further characterization of these and other uncharacterized sites may reveal novel aspects of N-linked glycosylation in coronavirus replication and pathogenesis.