title: Expression of Helicobacter pylori cag12 gene in Lactococcus lactis MG1363 and its oral administration to induce systemic anti-Cag12 immune response in mice

text: To develop an oral vaccine against Helicobacter pylori infection, we have expressed the H. pyloricag12 (HP0532) gene, encoding the outer membrane protein Cag12 (31 kDa), in a live delivery vehicle Lactococcus lactis. The cag12 gene was amplified by polymerase chain reaction (PCR) using the genomic DNA of H. pylori K51 isolated from Korean patients. DNA sequence analysis revealed that the cag12 gene of H. pylori K51 has 98.1 and 97.4% identity with individual cag12 genes of the H. pylori 26695 and J99, respectively. The GST–Cag12 fusion protein, produced using the Escherichia coli expression system, was used to raise a rat polyclonal anti-Cag12 antibody. The PCR-amplified cag12 gene of H. pylori K51 was cloned in the E. coli–L. lactis shuttle vector (pMG36e) and transformed into L. lactis. Western blot analysis demonstrated that the Cag12 protein was expressed in the L. lactis transformant, with a maximum level at the log phase without extracelluar secretion. The oral administration of the transformant into mice resulted in the generation of the anti-Cag12 antibody in serum in two out of five cases. These results suggest that the recombinant L. lactis, which expresses Cag12, may be applicable as an oral vaccine to induce protective immunity against H. pylori.


title: The Damage–Response Framework as a Tool for the Physician-Scientist to Understand the Pathogenesis of Infectious Diseases

text: The Damage–Response Framework (DRF) is a powerful tool to inform research in infectious diseases. It can integrate clinical observation with microbiology and immunology to incorporate the role of the host response into the outcome of microbial pathogenesis. Although the role that microbial factors may play in the pathogenesis of infectious diseases is well recognized, the DRF brings the indispensable role of the host response to the fore. For example, inflammation may induce microbial control, but it can also produce host damage. On the other hand, insufficient inflammation may fail to induce sufficient microbial control. Each scenario may lead to the diagnosis of an infectious disease. Given the central role that the host response plays in the pathogenesis of infectious diseases, new strategies for treatment need to consider the nature of the host response as well as microbial factors.


title: Mobile Health in Urology: The Good, the Bad and the Ugly

text: Our aim is to present the current position of mobile health (mHealth) and the delivery of healthcare services via mobile communication devices in urology. We conducted a literature review of urology mHealth papers on PubMed. Results indicate that mHealth is becoming ubiquitous in contemporary healthcare systems. Although its potential has been shown, urology lags behind other areas, representing just 0.1% of the 300,000 available medical apps in the Apple App Store and Google Play Store. Furthermore, there is a lack of expert healthcare professional involvement in app development. To avoid harm, it is critical that the scientific accuracy, patient privacy, and user safety of urology mHealth applications are assured. This is because there is no globally enforced medical app regulation, compulsory scientific guidelines, nor mandatory industry standards. Urologists, either individually or via scientific organizations, should have a pivotal position in the design, development, review, certification, and recommendation of apps. mHealth holds great potential in urology, as it can aid multiple stakeholders: citizens, patients, healthcare professionals, health organizations, and public authorities (e.g., Ministry of Health). Even though it is mostly used to improve existing medical activities at present, the future will include revolutionary and ground-breaking technology solutions. This innovative field should be seen by urologists as an opportunity to provide greater care to our patients and better tools and knowledge to our peers.


title: Demyelinating encephalomyelitis induced by a long-term corona virus infection in rats: A preliminary report

text: About 30% of weanling rats inoculated with JHM virus developed a subacute demyelinating encephalomyelitis (SDE) 3 weeks after inoculation (a.i.). From the remaining animals, 5% displayed overt neurological signs 3,6, and 8 months a.i. Animals with and without clinical signs 6–8 months a.i. were morphologically examined. Fresh demyelinating lesions could be demonstrated in paralyzed animals. Viral antigen was demonstrated and infectious JHM virus could be recovered from one animal which developed clinical signs at 3 months a.i. In one animal with clinical onset of 8 months a.i., completely remyelinated areas as well as recent demyelinating lesions were observed, suggesting a recurrence of the disease process. Remyelinated areas were also found in 40% of clinically silent animals. The morphology of the late onset of the demyelination was similar to that occurring in SDE. Remyelination consisted of both CNS and PNS-type. This animal model offers the possibility to investigate the virus-host relationship which is responsible for the induction of a demyelinating process after a long incubation period.


docid: dmkhmebk

title: The effect of herd formation among healthcare investors on health sector growth in China

text: BACKGROUND: China has become the world‘s second largest healthcare market based on a recent report by the World Health Organization. Eventhough China achieved universal health insurance coverage in 2011, representing the largest expansion of insurance coverage in human history achieved; health inequality remains endemic in China. Lessons from the effect of market crisis on health equity in Europe and other places has reignited interest in exploring the potential healthcare market aberrations that can trigger distributive injustice in healthcare resource allocation among China’s provinces. Recently, many healthcare investors in China have become more concerned about capital preservation, and are responding by abandoning long term investments strategies in healthcare. This investment withdrawal en mass is perceived to be influenced by herding tendencies and can trigger or consolidate endemic health inequality. METHODS: Our study simultaneously employs four testing models (two state spaced models and two return dispersion models) to establish the existence of procyclical (herding) behavior among the stocks and its health equity implications. These are applied to a large set of data to compare and contrast results of herd formation among investors in fourteen healthcare sectors in China. RESULTS: The study reveals that apart from the cross sectional standard deviation (CSSD) model, the remaining two models and our augmented state space model yields significant evidence of herding in all subsectors of the healthcare market. We also find that the herding effect is more prominent during down movements of the market. CONCLUSION: Herding behavior may lead to contemporaneous loss of investor confidence and capital withdrawal and thereby deprive the healthcare sector of the much needed capital for expansion. Thus there may be obvious delay in efforts to bridge the gap in access to healthcare facilities, medical support services, medical supplies, pharmaceuticals, biotechnology, diagnostic substances, medical laboratory and advanced medical equipment across China. Moreover, a potential crash in the healthcare market is possible in the healthcare sector as a result of persistent herding tendencies among investors and that may have more damaging consequences for health inequality in China.


title: Longitudinal changes of pneumonia complicating novel influenza A (H1N1) by high-resolution computed tomography

text: Abstract Purpose To assess lung lesions in patients with pneumonia complicating novel influenza A (H1N1) by serial high-resolution computed tomography (HRCT) during the early, progressive and convalescent stages. Samples and methods Serial HRCT scans in 39 patients with pneumonia complicating novel influenza A (H1N1) were reviewed for predominant patterns of lung abnormalities as well as distribution and extent of involvement. Longitudinal changes were assessed at different time points. Results In the early stage, the most common HRCT finding was patchy ground-glass opacity (GGO) (n = 4, 54.7%). In the progressive stage, bilaterally distributed GGO mixed with consolidation was the most commonly observed feature (n = 28, 71.8%). The diffuse pattern deteriorated to a peak (n = 17, 43.6%) at this stage. In the convalescent stage, the most common finding was fibrosis (n = 25, 64.1%). Averagely, fibrosis was observed at d 18.5 ± 6.4 after the onset of symptoms. Three patterns of longitudinal changes of the lesions were observed, including: type 1, improvement after deterioration; type 2, concurrent improvement and deterioration followed by improvement; and type 3, gradual improvement. Type 1 was the more common pattern (n = 27, 69.2%). Complete serial HRCT scans from initial and final scan were obtained in 24 patients, and the mean CT score peaked at d 8–14 of the illness. Conclusion HRCT may play a role in detecting and characterizing pulmonary lesions for the cases of pneumonia complicating influenza A. In addition, it may contribute to monitoring longitudinal changes of pneumonia and assessing therapeutic response.


title: Obesity aggravates COVID‐19: a systematic review and meta‐analysis

text: OBJECTIVE: Obesity and COVID‐19 are both world epidemics now. There may be some potential relationships between them, but we knew little. This work was to explore the relationship through literature searching, systematic review, and meta‐analysis. METHODS: Pubmed, Embase, WOS, Cochrane, CNKI, Wanfang, and Sinomed databases were searched to collect the literature concerning obesity and COVID‐19. Systematic review and meta‐analysis were conducted after literature screening, quality assessment, and data extraction. RESULTS: 180 articles were initially searched after duplicate removal and 9 were finally included in our analysis. Results show that severe COVID‐19 patients have higher BMI than non‐severe ones(WMD =2.67, 95%CI[1.52‐3.82]); COVID‐19 patients with obesity were more severe and have a worse outcome than those without(OR=2.31, 95%CI[1.3‐4.12]). CONCLUSION: Obesity may aggravate COVID‐19. This article is protected by copyright. All rights reserved.


title: Pathogenicity of 2 Porcine Deltacoronavirus Strains in Gnotobiotic Pigs

text: To verify whether porcine deltacoronavirus infection induces disease, we inoculated gnotobiotic pigs with 2 virus strains (OH-FD22 and OH-FD100) identified by 2 specific reverse transcription PCRs. At 21–120 h postinoculation, pigs exhibited severe diarrhea, vomiting, fecal shedding of virus, and severe atrophic enteritis. These findings confirm that these 2 strains are enteropathogenic in pigs.


title: Mental health in chronic disease patients during the COVID-19 quarantine in Greece

text: OBJECTIVE: To investigate the effect of the time spent on quarantine on distress, anxiety, depression, and somatization of chronic disease patients during the COVID-19 quarantine in Greece and the differences in these parameters between healthy individuals and chronic disease patients. METHOD: The sample consisted of 943 healthy individuals and 163 patients (respiratory, autoimmune, cardiovascular, endocrine, patients with other diseases, and patients with more than one disease) completing sociodemographic assessments as well as the 4-Dimensional Symptom Questionnaire (4DSQ) during March 30, 2020 to May 3, 2020. Pearson's correlation was used to search for the association between time spent on quarantine and the 4DSQ subscales (distress, anxiety, depression, and somatization). Independent sample T-test and Glass's Δ were used for differences between healthy individuals and chronic disease patients in these subscales, an analysis also carried out between healthy individuals and all patient subgroups. RESULTS: No statistically significant correlations were noted between the 4DSQ subscales and the quarantine duration, both for the patient and the healthy individuals’ group. Chronic disease patients had significantly higher levels of distress (p = 0.001, Δ = 0.28) and somatization (p = 0.000, Δ = 0.47), but not there were no significant differences in anxiety (p = 0.098, Δ = 0.14) and depression (p = 0.052, Δ = 0.19). Concerning head-to-head comparisons between the healthy individuals’ group and each patient group, significantly higher scores in distress were found only for patients with respiratory diseases (p = 0.028, Δ = 0.42). Regarding somatization, significantly higher scores were noted for the healthy individuals’ group compared with patients with autoimmune diseases (p = 0.010, Δ = 0.62), respiratory diseases (p = 0.027, Δ = 0.42), other diseases (p = 0.003, Δ = 0.55), and more than one disease (p = 0.012, Δ = 0.60). No statistically significant differences were found in anxiety and depression. SIGNIFICANCE OF RESULTS: The results of this study indicate that interventional programs for chronic disease patients during quarantine should focus on distress and somatization, not on anxiety and depression. Respiratory patients might have more supportive care needs compared with patients with other diseases.


title: Oncocardiology: new challenges, new opportunities

text: Patients with cancer are at a higher risk of cardiovascular disease, which contributes to significant morbidity and mortality. The rapid progress in the field of oncological treatments has led to a steady increase in long-term cancer survivors. Care for cardiovascular complications is therefore becoming increasingly important. In addition, the establishment of new oncological therapies has resulted in the identification of previously unknown cardiovascular side effects. Oncocardiology aims to detect and treat cardiovascular diseases associated with cancer and cancer therapy. Continuous scientific, clinical, and structural developments are necessary as the basis for the best care of the growing number of affected patients. This review summarizes current developments in the field of oncocardiology with regard to advances in cancer therapy and challenges in clinical oncocardiology work. Cardiovascular side effects by targeted cancer therapies are characterized and recent advances in the field of cardiovascular diagnostics are outlined. Developments to better integrate oncocardiology into the medical care system and perspectives for modern, patient-oriented care are shown. In light of the coronavirus disease 2019 (COVID-19) pandemic, current challenges and opportunities are highlighted. The relevance of profitable further advances in oncocardiology including standardized guidelines and educational programs is delineated as a mandatory requirement for the successful development of oncocardiology.


title: Scientific Collaboration During the COVID-19 Pandemic: N95DECON.org

text: Many academics and researchers have responded to the COVID-19 pandemic by forming on-line national and international collaborative groups to rapidly investigate issues of prevention and treatment. This commentary describes the spontaneous formation of an international team of 115 researchers who summarized the literature on safe methods for decontaminating N95 filtering facepiece respirators in response to the supply crisis. The summary reports and fact sheets on the (www.n95decon.org) website have had more than 200 000 unique visits and the organization’s webinars have reached health care professionals from more than 50 countries. The team is extending its mission to cover other personal protective equipment. The success of these collaborations may alter how scientific questions are tackled in the future.


title: How HIV patients construct liveable identities in a shame based culture: the case of Singapore

text: This article interrogates the mainstream healthcare narrative that frames human immunodeficiency virus (HIV) as a chronic disease, and triangulates it with the lived experiences of people with HIV in Singapore. It also examines how HIV patients reconstruct their identities after the diagnosis of HIV. Four HIV patients (two males and two females) were interviewed in depth by an experienced medical social worker. Findings revealed that even as the illness trajectory of HIV has shifted from a terminal condition to a chronic one, living with HIV continues to be fraught with difficulty as society, especially in the Asian context, perceives HIV with much fear and disapproval. The participants had an overwhelming sense of shame when they were initially diagnosed with HIV and they had to reconstruct a liveable identity by containing the shroud of shame, reinforcing their normative identities and constructing new ones. These strategies help them to keep their shame at bay. This paper also unpacks nuanced insights of shame experienced by Chinese HIV patients in an Asian city dominated by Confucian values.


title: Knowledge and understanding among medical imaging professionals in India during the rapid rise of the covid-19 pandemic

text: During the first week of March,2020 the surge of coronavirus disease (COVID-19) cases reached all over the globe with more than 100,000 cases. Healthcare national and international authorities have already initiated awareness and lockdown activities. A poor understanding of the disease among medical imaging professionals (MIPs) may result in rapid spread of infection. This study aimed to investigate the knowledge and understanding of MIPs about COVID-19. A cross-sectional, web-based study was conducted among MIPs about COVID- 19 during the fourth week of March 2020. An online sample of MIPs was successfully recruited via the authors’ networks in India using data collection tool – write google forms. A self-developed online KAP questionnaire was completed by the participants. The knowledge and understanding questionnaire consisted questions regarding the clinical characteristics and transmission routes of COVID-19. Assessment on practices towards COVID-19 included questions on techniques while imaging against COVID-19 suspected patients. Of 700 participants, a total of 550 MIPs completed the survey (response rate: 78.57%); 56.7% were males, 85.4.1% were aged 17–26 years, and most were undergraduates (77.6%) and postgraduates (17.1%). Regarding COVID-19, most of the participants answered correctly (95.5%) on symptoms, (84.4%) time interval for visible symptoms, (98.0%) transmission and (44%) airborne transmission respectively. A significant proportion of MIPs (36.4%) had poor knowledge about wearing multiple masks as an effective measure against coronavirus infection. Most of the respondents (48.5%) incorrectly considered X-ray as the reliable method of diagnosis for suspected COVID-19 patients. 44.6% of the respondents lacked knowledge about the steps involved in hand washing technique which is one of the most important safety practice methods in medical imaging to prevent spread of infection. Factors such as age and occupation were associated with inadequate knowledge and poor perception of COVID-19. As the current global threat of COVID-19 continues to emerge, it is crucial and critical to improve the knowledge and understanding of MIPs. Educational videos and live webinars are urgently needed to reach MIPs and further detailed studies are the need of the hour. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12553-020-00437-2) contains supplementary material, which is available to authorized users.


title: Democracy and the Politics of Coronavirus: Trust, Blame and Understanding

text: This article explores the relationship between crises and democracy through a focus on the unfolding coronavirus pandemic. Its central argument is that to interpret the current pandemic purely in terms of its epidemiology and public health implications risks overlooking its potentially more significant socio-political consequences. This is because the challenges posed by the coronavirus crisis have themselves become overlaid or layered-upon a pre-existing set of concerns regarding the performance, efficiency and capacity of democratic political structures. The aim of this article is to try and understand and warn against what might be termed a rather odd form of cross-contamination whereby the cynicism, negativity and frustration concerning politicians, political processes and political institutions that existed before the coronavirus outbreak is allowed to direct, define and automatically devalue how democratic structures are subsequently judged in terms of how they responded to the challenge. As such, this article focuses on the link between the Coronavirus crisis and the democratic crisis; or, more precisely, the risk that the Coronavirus crisis may mutate into and fuel a broader crisis of democracy.


title: SARS-CoV related Betacoronavirus and diverse Alphacoronavirus members found in western old-world

text: Abstract The emergence of SARS-CoV and MERS-CoV, triggered the discovery of a high diversity of coronaviruses in bats. Studies from Europe have shown that coronaviruses circulate in bats in France but this reflects only a fraction of the whole diversity. In the current study the diversity of coronaviruses circulating in western Europe was extensively explored. Ten alphacoronaviruses in eleven bat species belonging to the Miniopteridae, Vespertilionidae and Rhinolophidae families and, a SARS-CoV-related Betacoronavirus in Rhinolophus ferrumequinum were identified. The diversity and prevalence of bat coronaviruses presently reported from western Europe is much higher than previously described and includes a SARS-CoV sister group. This diversity demonstrates the dynamic evolution and circulation of coronaviruses in this species. That said, the identified coronaviruses were consistently associated with a particular bat species or genus, and these relationships were maintained no matter the geographic location. The observed phylogenetic grouping of coronaviruses from the same species in Europe and Asia, emphasizes the role of host/pathogen coevolution in this group.


title: Mental Health Services in Lombardy during COVID-19 outbreak

text: Abstract Lombardy is the Region in Italy the most heavily affected by coronavirus disease (COVID-19) contagion. The Regional Health Authority mandates that mental health services should be guaranteed, identifying mental health as a priority for their citizens. Recommendations for occupational and health safety have been provided to patients and hospital staff, including support for telemedicine activities and remote psychosocial interventions. Services of the Mental Health Departments of Milano “Niguarda” and Brescia “Spedali Civili” Hospitals are providing continued care at a community, residential and hospital level, and to positive COVID-19 psychiatric patients in need of hospitalization.


title: Cathepsins: Proteases that are vital for survival but can also be fatal

text: Abstract The state of enzymes in the human body determines the normal physiology or pathology, so all the six classes of enzymes are crucial. Proteases, the hydrolases, can be of several types based on the nucleophilic amino acid or the metal cofactor needed for their activity. Cathepsins are proteases with serine, cysteine, or aspartic acid residues as the nucleophiles, which are vital for digestion, coagulation, immune response, adipogenesis, hormone liberation, peptide synthesis, among a litany of other functions. But inflammatory state radically affects their normal roles. Released from the lysosomes, they degrade extracellular matrix proteins such as collagen and elastin, mediating parasite infection, autoimmune diseases, tumor metastasis, cardiovascular issues, and neural degeneration, among other health hazards. Over the years, the different types and isoforms of cathepsin, their optimal pH and functions have been studied, yet much information is still elusive. By taming and harnessing cathepsins, by inhibitors and judicious lifestyle, a gamut of malignancies can be resolved. This review discusses these aspects, which can be of clinical relevance.


title: Tissue distribution of a feline AGP related protein (fAGPrP) in cats with feline infectious peritonitis (FIP)

text: Abstract Feline α 1-acid glycoprotein (fAGP) increases during feline infectious peritonitis (FIP). We have recently identified a 29 kDa protein that we named feline AGP-related protein (fAGPrP) due to its cross-reactivity with an anti-human AGP monoclonal antibody. In this work we describe the tissue distribution of fAGPrP during FIP, and its relationship with feline coronavirus (FCoV) and myeloid cells. Tissues from five control cats and from 15 cats with FIP were examined by immunohistochemistry using monoclonal antibodies against human AGP, FCoV and myeloid antigens. Diffuse fAGPrP positivity within the lesions, likely due to vascular plasma leakage, endothelial and epithelial lining were detectable. Compared to controls, fAGPrP-expressing cells often increased in number and were diffusely distributed in lymph nodes, as usually occurs for IgM-producing plasma cells during early immune responses. These findings did not depend on the presence of FCoVs or of myeloid cells, suggesting that fAGPrP is not directly involved in the pathogenesis of FIP.


title: Antibiofilm coatings through atmospheric pressure plasma for 3D printed surgical instruments

text: Recently, medical applications for 3D printing are expanding rapidly and are expected to revolutionize health care, specifically, manufacturing surgical guides and protective face mask against coronavirus (COVID-19). These instruments come in contact with the human tissues, being necessary 3D printed materials free of pathogenic microbes or other contaminants. Therefore, they must be sterilized to avoid that bacteria can attach to the surface and produce biofilm. With the aim of avoiding bacterial biofilm formation and minimize the health risks, acrylic acid (AcAc) coatings applied by plasma-polymerization have been deposited on 3D printed polylactic acid (PLA) Petri dishes. Six antimicrobial-resistant clinical and two susceptible control strains of Pseudomonas aeruginosa and Staphylococcus aureus species were analyzed. AcAc coatings provide the surface with greater hydrophilicity and, consequently, the formation of a hydration layer, whose thickness is related to the surface roughness. This hydration layer could explain the reduction of bacterial attachment and, consequently, the biofilm formation. Antibiofilm coatings are more successful against P. aeruginosa strains than against S. aureus ones; due to some coatings presents a smaller topography scale than the P. aeruginosa length, reducting the contact area between the bacteria and the coating, and causing a potential rupture of the cellular membrane. AcAc coatings with less number of plasma passes were more effective, and showed up to a 50% relative biofilm reduction (in six of the eight strains studied) compared with the untreated plates.


Absence of MERS-CoV in domestic camels, Republic of Korea, 2015


title: Recommendations for Risk Stratified Use of Cardiac Computed Tomography for Congenital Heart Disease During the COVID-19 Pandemic

text: The impact of the coronavirus disease (COVID-19) pandemic in the United States and around the world has required significant changes to medical practice. Amidst the rapidly evolving public health emergency, hospital centers have been required to postpone elective procedures, preserve personal protective equipment (PPE), practice social distancing and limit staff exposures. Patients with congenital heart disease (CHD) often need urgent evaluation, most commonly for preprocedural evaluation. We have stratified the most common indications for cardiac computed tomography (CCT) imaging in patients with CHD to help guide care for these patients during the COVID-19 pandemic including considerations for reopening.


title: Peptide inhibitors of tembusu virus infection derived from the envelope protein

text: Abstract The outbreak and spread of Tembusu virus (TMUV) has caused very large losses in the waterfowl-breeding industry since 2010. The viral envelope (E) protein, the principal surface protein of viral particles, plays a vital role in viral entry and fusion. In this study, two peptides derived from domain II (DII) and the stem of the TMUV envelope protein, TP1 and TP2, respectively, were tested for their antiviral activity. TP1 and TP2 inhibited TMUV infection in BHK-21 cells, and their 50% inhibitory concentrations (IC50) were 14.19 mg/L and 7.64 mg/L, respectively. Viral inhibition assays in different cell lines of avian origin showed that the inhibitory effects of TP1 and TP2 are not cell type dependent. Moreover, TP2 also exhibited inhibitory activity against Japanese encephalitis virus (JEV) infection. The two peptides inhibited antibody-mediated TMUV infection of duck peripheral blood lymphocytes. Co-immunoprecipitation assays and indirect enzyme-linked immunosorbent assays (ELISAs) indicated that both peptides interact with the surface of the TMUV virion. RNase digestion assays confirmed the release of viral RNA following incubation with TP1, while incubation with TP1 or TP2 interfered with the binding between TMUV and cells. Taken together, these results show that TP1 and TP2 may be developed into antiviral treatments against TMUV infection.


Mild COVID-19 infection in an NMO patient treated with tocilizumab: a confirmation of anti-IL-6 protective role?


title: The virus whose family expanded

text: The discovery of many new species of hepaciviruses and pegiviruses, which exhibit enormous genetic diversity, in wild rodent and bat populations might help us to understand the origins of the hepatitis C virus.


title: Clinical performance of the Sofia™ Influenza A+B FIA in adult patients with influenza-like illness

text: Abstract The Sofia™ Influenza A+B FIA demonstrated 74.0% sensitivity and 95.4% specificity for influenza A in patients with influenza-like illness in 2012–2013 season. It yielded higher sensitivity than SD Bioline Influenza Ag A/B/A(H1N1/2009) (54.1%) for influenza A (P <0.01). The Sofia™ Influenza A+B FIA might be useful for rapid diagnosis of influenza.


docid: kxbhlcce

title: Global Warming and Its Health Impact

text: Since the mid-19(th) century, human activities have increased greenhouse gases such as carbon dioxide, methane, and nitrous oxide in the Earth's atmosphere that resulted in increased average temperature. The effects of rising temperature include soil degradation, loss of productivity of agricultural land, desertification, loss of biodiversity, degradation of ecosystems, reduced fresh-water resources, acidification of the oceans, and the disruption and depletion of stratospheric ozone. All these have an impact on human health, causing non-communicable diseases such as injuries during natural disasters, malnutrition during famine, and increased mortality during heat waves due to complications in chronically ill patients. Direct exposure to natural disasters has also an impact on mental health and, although too complex to be quantified, a link has even been established between climate and civil violence. Over time, climate change can reduce agricultural resources through reduced availability of water, alterations and shrinking arable land, increased pollution, accumulation of toxic substances in the food chain, and creation of habitats suitable to the transmission of human and animal pathogens. People living in low-income countries are particularly vulnerable. Climate change scenarios include a change in distribution of infectious diseases with warming and changes in outbreaks associated with weather extreme events. After floods, increased cases of leptospirosis, campylobacter infections and cryptosporidiosis are reported. Global warming affects water heating, rising the transmission of water-borne pathogens. Pathogens transmitted by vectors are particularly sensitive to climate change because they spend a good part of their life cycle in a cold-blooded host invertebrate whose temperature is similar to the environment. A warmer climate presents more favorable conditions for the survival and the completion of the life cycle of the vector, going as far as to speed it up as in the case of mosquitoes. Diseases transmitted by mosquitoes include some of the most widespread worldwide illnesses such as malaria and viral diseases. Tick-borne diseases have increased in the past years in cold regions, because rising temperatures accelerate the cycle of development, the production of eggs, and the density and distribution of the tick population. The areas of presence of ticks and diseases that they can transmit have increased, both in terms of geographical extension than in altitude. In the next years the engagement of the health sector would be working to develop prevention and adaptation programs in order to reduce the costs and burden of climate change.


title: Cycloartenol triterpenoid saponins from Cimicifuga simplex (Ranunculaceae) and their biological effects

text: Abstract The constituents of Cimicifuga plants have been extensively investigated, and the principal metabolites are 9,19-cyclolanostane triterpenoid glycosides, which are distributed widely in Cimicifuga plants, but not in other members of the Ranunculaceae family, and are considered to be characteristics of the Cimicifuga genus. This type of triterpenoid glycoside possesses several important biological activities. More than 120 cycloartane triterpene glycosides have been isolated from Cimicifuga simplex Wormsk. The aim of this review article is to summarize all the major findings based on the available scientific literatures on C. simplex, with a focus on the identified 9,19-cyclolanostane triterpenoid glycosides. Biological studies of cycloartane triterpene glycosides from Cimicifuga spp. are also discussed.


title: Are urologists in trouble by SARS‐CoV‐2? Reflexions and recommendations for specific interventions

text: OBJECTIVE: We aim to assess the risk of infection during urologic surgeries. Therefore possible hazards in tissue, blood, urine and aerosolized particles generated during surgery, are evaluated. Understanding the risk, recommendations for clinical practice are provided. MATERIALS AND METHODS: Review of available literature on urological and other surgical procedures in patients with virus infections such as HPV, HIV and hepatitis B and current publications on COVID‐19. RESULTS: Several possible pathways for viral transmission appear in the literature. Recent groups detected SARS‐CoV‐2 in the urine and faeces, even after negative pharyngeal swabs. In addition, viral RNA can be detected in the blood and several tissues. During surgery, viral particles are released, aerosole‐borne and present a certain risk for transmission and infection. However, there is currently no evidence on the exact risk for infection by the substances mentioned above. It remains unclear whether or not viral particles in the urine, blood or faeces are infectious. CONCLUSIONS: Whether SARS‐CoV‐2 can be transmitted by aerosols remains controversial. In any case, standard surgical masks offer inadequate protection from SARS‐CoV‐2. Full PPE including at least FFP‐2 masks and safety goggles should be used. Aerosolized particles might remain for a longer time in the operation theatre and contaminate other surfaces, like floors or computer input devices. Therefore scrupulous hygiene and disinfection of surfaces must be carried out. To prevent aerosolization during laparoscopic interventions, the pneumoperitoneum should be evacuated with suction devices. The use of virus proof HEPA filters is recommended. Local separation of anesthesia/intubation and operation theatre can reduce the danger of viral transmission. Lumbar anaesthesia should be considered especially in endourology. Based on current knowledge, COVID‐19 is no contraindication for acute urological surgery. If possible however, as european guideline committees recommend, non‐emergency urological interventions should be postponed until negative SARS‐CoV‐2 tests become available.


title: Comparison of the Allplex(TM) Respiratory Panel Assays and the automated Fast Track Diagnostics Respiratory pathogens 21 assay for the diagnosis of pediatric respiratory viral infections

text: Acute respiratory tract infections frequently occur in children and represent one of the leading causes of morbidity and mortality worldwide. Quick and accurate pathogen detection can lead to a more appropriate use of antimicrobial treatment as well as timely implementation of isolation precautions. In the last decade, several commercial assays have been developed for the simultaneous diagnosis of respiratory pathogens, which substantially vary in formulation and performance characteristics. The aim of this study was to compare the performance of the “Allplex(TM) Respiratory Panel Assays” (Seegene) with that of the automated “Fast Track Diagnostics Respiratory pathogens 21” assay (Siemens) for the diagnosis of pediatric respiratory viral infections. One hundred forty-five nasopharyngeal wash samples, collected at the Bambino Gesù Pediatric Hospital in Rome during the fall-winter 2017-2018 season, were processed and analyzed with both workflows. Our results suggest a high concordance between the two methods for positive and negative samples. Sensitivity and specificity were calculated with both tests as a reference method. For the Allplex(TM) Respiratory Panel Assays, they were 98% and 100%, respectively, and for the Fast Track Diagnostics Respiratory pathogens 21 assay, they were both 100%. This comparative study allowed us to highlight the characteristics of the two assays to evaluate the best solution, on the basis of diagnostic routine and laboratory workflows, keeping in mind local epidemiology.


title: DNA recombination defects in Kuwait: Clinical, immunologic and genetic profile

text: Abstract Defects in DNA Recombination due to mutations in RAG1/2 or DCLRE1C result in combined immunodeficiency (CID) with a range of disease severity. We present the clinical, immunologic and molecular characteristics of 21 patients with defects in RAG1, RAG2 or DCLRE1C, who accounted for 24% of combined immune deficiency cases in the Kuwait National Primary Immunodeficiency Disorders Registry. The distribution of the patients was as follow: 8 with RAG1 deficiency, 6 with RAG2 deficiency and 7 with DCLRE1C deficiency. Nine patients presented with SCID, 6 with OS, 2 with leaky SCID and 4 with CID and granuloma and/or autoimmunity (CID-G/AI). Eight patients [(7 SCID and 1 OS) (38%)] received hematopoietic stem cell transplant (HSCT). The median age of HSCT was 11.5months and the median time from diagnosis to HSCT was 6months. Fifty percent of the transplanted patients are alive while only 23% of the untransplanted ones are alive.


title: Ibuprofen use and clinical outcomes in COVID-19 patients

text: OBJECTIVE: It was recently suggested that Ibuprofen might increase the risk for severe and fatal COVID-19 disease and should therefore be avoided in this patient population. We aimed to evaluate whether ibuprofen use in patients with COVID-19 was associated with more severe disease, compared to patients using paracetamol or no antipyretics. METHODS: In a retrospective cohort study of patients with COVID-19 from Shamir Medical Center, Israel, we monitored any use of ibuprofen from a week prior to diagnosis of COVID-19 throughout the disease. Primary outcomes were mortality and the need for respiratory support, including oxygen administration and mechanical ventilation. RESULTS: The study included 403 confirmed cases of COVID-19, with a median age of 45 years. Of the entire cohort, 44 patients (11%) needed respiratory support and 12 (3%) patients died. One hundred and seventy-nine (44%) patients had fever, with 32% using paracetamol and 22% using ibuprofen, for symptom-relief. In the Ibuprofen group, 3 (3.4%) patients died, while in the non-Ibuprofen group 9 (2.8%) patients died (P=0.95). Nine (10.3%) patients from the Ibuprofen group needed respiratory support, as compared with 35 (11%) from the non-Ibuprofen group (P=1). When compared to exclusive paracetamol users, no differences were observed in mortality rates or the need for respiratory support among patients using ibuprofen. CONCLUSIONS: In this cohort of COVID-19 patients, Ibuprofen use was not associated with worse clinical outcomes, compared to paracetamol or no antipyretic.


title: Impacto de una modificación de la guía de práctica clínica de la Academia Americana de Pediatría en el manejo de la bronquiolitis aguda grave en una unidad de cuidados intensivos pediátricos

text: OBJECTIVE: To describe the characteristics and evolution of patients with bronchiolitis admitted to a pediatric intensive care unit, and compare treatment pre- and post-publication of the American Academy of Pediatrics clinical practice guide. DESIGN: A descriptive and observational study was carried out between September 2010 and September 2017. SETTING: Pediatric intensive care unit. PATIENTS: Infants under one year of age with severe bronchiolitis. INTERVENTIONS: Two periods were compared (2010-14 and 2015-17), corresponding to before and after modification of the American Academy of Pediatrics guidelines for the management of bronchiolitis in hospital. MAIN VARIABLES: Patient sex, age, comorbidities, severity, etiology, administered treatment, bacterial infections, respiratory and inotropic support, length of stay and mortality. RESULTS: A total of 706 patients were enrolled, of which 414 (58.6%) males, with a median age of 47 days (IQR 25-100.25). Median bronchiolitis severity score (BROSJOD) upon admission: 9 points (IQR 7-11). Respiratory syncytial virus appeared in 460 (65.16%) patients. The first period (2010-14) included 340 patients and the second period (2015-17) 366 patients. More adrenalin and hypertonic saline nebulizations and more corticosteroid treatment were administered in the second period. More noninvasive ventilation and less conventional mechanical ventilation were used, and less inotropic support was needed, with no significant differences. The antibiotherapy rate decreased significantly (P = .003). CONCLUSIONS: Despite the decrease in antibiotherapy, the use of nebulizations and glucocorticoids in these patients should be limited, as recommended by the guide.


title: AGILE-ACCORD: A Randomized, Multicentre, Seamless, Adaptive Phase I/II Platform Study to Determine the Optimal Dose, Safety and Efficacy of Multiple Candidate Agents for the Treatment of COVID-19: A structured summary of a study protocol for a randomised platform trial

text: OBJECTIVES: Phase I - To determine the optimal dose of each candidate (or combination of candidates) entered into the platform. Phase II - To determine the efficacy and safety of each candidate entered into the platform, compared to the current Standard of Care (SoC), and recommend whether it should be evaluated further in a later phase II & III platforms. TRIAL DESIGN: AGILE-ACCORD is a Bayesian multicentre, multi-arm, multi-dose, multi-stage open-label, adaptive, seamless phase I/II randomised platform trial to determine the optimal dose, activity and safety of multiple candidate agents for the treatment of COVID-19. Designed as a master protocol with each candidate being evaluated within its own sub-protocol (Candidate Specific Trial (CST) protocol), randomising between candidate and SoC with 2:1 allocation in favour of the candidate (N.B the first candidate has gone through regulatory approval and is expected to open to recruitment early summer 2020). Each dose will be assessed for safety sequentially in cohorts of 6 patients. Once a phase II dose has been identified we will assess efficacy by seamlessly expanding into a larger cohort. PARTICIPANTS: Patient populations can vary between CSTs, but the main eligibility criteria include adult patients (≥18 years) who have laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We will include both severe and mild-moderate patients defined as follows: Group A (severe disease) - patients with WHO Working Group on the Clinical Characteristics of COVID-19 infection 9-point ordinal scale of Grades 4 (hospitalised, oxygen by mask or nasal prongs), 5 (hospitalised, non-invasive ventilation or high flow oxygen), 6 (hospitalised, intubation and mechanical ventilation) or 7 (hospitalised, ventilation and additional organ support); Group B (mild-moderate disease) - ambulant or hospitalised patients with peripheral capillary oxygen saturation (SpO(2)) >94% RA. If any CSTs are included in the community setting, the CST protocol will clarify whether patients with suspected SARS-CoV-2 infection are also eligible. Participants will be recruited from England, North Ireland, Wales and Scotland. INTERVENTION AND COMPARATOR: Comparator is the current standard of care (SoC), in some CSTs plus placebo. Candidates that prevent uncontrolled cytokine release, prevention of viral replication, and other anti-viral treatment strategies are at various stages of development for inclusion into AGILE-ACCORD. Other CSTs will be added over time. There is not a set limit on the number of CSTs we can include within the AGILE-ACCORD Master protocol and we will upload each CST into this publication as each opens to recruitment. MAIN OUTCOMES: Phase I: Dose limiting toxicities using Common Terminology Criteria for Adverse Events v5 Grade ≥3 adverse events. Phase II: Agreed on a CST basis depending on mechanism of action of the candidate and patient population. But may include; time to clinical improvement of at least 2 points on the WHO 9-point category ordinal scale [measured up to 29 days from randomisation], progression of disease (oxygen saturation (SaO(2)) <92%) or hospitalization or death, or change in time-weighted viral load [measured up to 29 days from randomisation]. RANDOMISATION: Varies with CST, but default is 2:1 allocation in favour of the candidate to maximise early safety data. BLINDING (MASKING): For the safety phase open-label although for some CSTs may include placebo or SoC for the efficacy phase. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Varies between CSTs. However simulations have shown that around 16 participants are necessary to determine futility or promise of a candidate at a given dose (in efficacy evaluation alone) and between 32 and 40 participants are required across the dose-finding and efficacy evaluation when capping the maximum number of participants contributing to the evaluation of a treatment at 40. TRIAL STATUS: Master protocol version number v5 07 May 2020, trial is in setup with full regulatory approval and utilises several digital technology solutions, including Medidata’s Rave EDC [electronic data capture], RTSM for randomisation and patient eConsent on iPads via Rave Patient Cloud. The recruitment dates will vary between CSTs but at the time of writing no CSTs are yet open for recruitment. TRIAL REGISTRATION: EudraCT 2020-001860-27 14(th) March 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


docid: rcljauve

title: COVID-19 in the Cancer Patient

text: The novel Coronavirus Disease 2019 (COVID-19) was first reported in China in December 2019. Since then, it has spread across the world to become one of the most serious life-threatening pandemics since the influenza pandemic of 1918. This review article will focus on the specific risks and nuanced considerations of COVID-19 in the cancer patient. Important perioperative management recommendations during this outbreak are emphasized, in addition to discussion of current treatment techniques and strategies available in the battle against COVID-19.


title: Peer-to-Peer Contact Tracing: Development of a Privacy-Preserving Smartphone App

text: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic is an urgent public health crisis, with epidemiologic models predicting severe consequences, including high death rates, if the virus is permitted to run its course without any intervention or response. Contact tracing using smartphone technology is a powerful tool that may be employed to limit disease transmission during an epidemic or pandemic; yet, contact tracing apps present significant privacy concerns regarding the collection of personal data such as location. OBJECTIVE: The aim of this study is to develop an effective contact tracing smartphone app that respects user privacy by not collecting location information or other personal data. METHODS: We propose the use of an anonymized graph of interpersonal interactions to conduct a novel form of contact tracing and have developed a proof-of-concept smartphone app that implements this approach. Additionally, we developed a computer simulation model that demonstrates the impact of our proposal on epidemic or pandemic outbreak trajectories across multiple rates of adoption. RESULTS: Our proof-of-concept smartphone app allows users to create “checkpoints” for contact tracing, check their risk level based on their past interactions, and anonymously self-report a positive status to their peer network. Our simulation results suggest that higher adoption rates of such an app may result in a better controlled epidemic or pandemic outbreak. CONCLUSIONS: Our proposed smartphone-based contact tracing method presents a novel solution that preserves privacy while demonstrating the potential to suppress an epidemic or pandemic outbreak. This app could potentially be applied to the current COVID-19 pandemic as well as other epidemics or pandemics in the future to achieve a middle ground between drastic isolation measures and unmitigated disease spread.


title: A multi-region discrete time mathematical modeling of the dynamics of Covid-19 virus propagation using optimal control

text: We study in this work a discrete mathematical model that describes the dynamics of transmission of the Corona virus between humans on the one hand and animals on the other hand in a region or in different regions. Also, we propose an optimal strategy to implement the optimal campaigns through the use of awareness campaigns in region j that aims at protecting individuals from being infected by the virus, security campaigns and health measures to prevent the movement of individuals from one region to another, encouraging the individuals to join quarantine centers and the disposal of infected animals. The aim is to maximize the number of individuals subjected to quarantine and trying to reduce the number of the infected individuals and the infected animals. Pontryagin’s maximum principle in discrete time is used to characterize the optimal controls and the optimality system is solved by an iterative method. The numerical simulation is carried out using Matlab. The Incremental Cost-Effectiveness Ratio was calculated to investigate the cost-effectiveness of all possible combinations of the four control measures. Using cost-effectiveness analysis, we show that control of protecting susceptible individuals, preventing their contact with the infected individuals and encouraging the exposed individuals to join quarantine centers provides the most cost-effective strategy to control the disease.


title: Surface Treatments to Enhance the Functionality of PPEs

text: The outbreak of unknown viral pneumonia in Wuhan China in December 2019 led to a new coronavirus (SARS-CoV-2), which attracted worldwide attention, with the related COVID-19 disease quickly becoming a global pandemic. In about 5 months, this disease has led to ~ 4 million cases and claimed more than 200 k deaths as a result of its highly contagious nature. The present understanding is that SARS-CoV-2 is a type of influenza virus that can be transmitted through respiratory droplets and aerosols; Lewis (Nature 580:175, 2020). The primary methodology to prevent the spreading of this disease has been “social distancing” and usage of personal protective equipment (PPE) at the front lines of healthcare and other critical operations. The scale of the disease has led to unprecedented demand for PPEs and increased functionality of the same. This paper focuses on improving PPE functionality in a scalable manner by surface treatment and coating with appropriate materials and other functional enhancements, such as exposure to UV rays or other sterilizing agents (e.g., hydrogen peroxide).


title: Acute diarrhea: a practical review

text: Abstract This review provides a practical, simple, and logical approach to the diagnosis and management of patients with acute infectious diarrhea, one of the most common diagnoses in clinical practice. Diarrhea in the immunocompromised host, traveler’s diarrhea, and diarrhea in the hospitalized patient are also discussed. Most episodes of acute diarrhea are self-limited, and investigations should be performed only if the results will influence management and outcome. After an adequate history and physical examination, the clinician should be able to classify the acute diarrheal illness, assess the severity, and determine whether investigations are needed. Most patients do not require specific therapy. Therapy should mainly be directed at preventing dehydration. Various home remedies frequently suffice in mild, self-limited diarrhea. However, in large-volume, dehydrating diarrhea, oral rehydration solutions should be used, as they are formulated to stimulate sodium and water absorption. Antidiarrheal agents can be useful in reducing the number of bowel movements and diminishing the magnitude of fluid loss. The most useful agents are opiate derivatives and bismuth subsalicylate. Antibiotic therapy is not required in most patients with acute diarrheal disorders. Guidelines for their use are presented.


title: Reproductive Biology of the Coyote (Canis latrans): Integration of Mating Behavior, Reproductive Hormones, and Vaginal Cytology

text: The reproductive biology of wild Canis species is often described as unique among mammals because an unusual combination of behavioral and physiological characteristics including a seasonally monestrous cycle, copulatory lock or tie, obligatory pseudopregnancy, social monogamy, and biparental care of the young. We investigated social behavior, endocrine profiles, and vaginal cytology of female coyotes (Canis latrans) during 4 breeding seasons, 2000–2003. Blood levels of estradiol, progesterone, prolactin, and relaxin were measured, and mating behavior and changes in vaginal epithelium were documented. After aligning the data from each individual to her estimated day of ovulation, we compared pregnant coyotes with nonpregnant females and evaluated temporal relationships among hormone levels, behavior, and vaginal cytology. We found that patterns of proceptive and receptive behaviors correlated with the secretion of steroid hormones, as did vaginal epithelial cytomorphosis. In addition, although progesterone levels of pregnant and pseudopregnant coyotes were indistinguishable, prolactin demonstrated a discernible intergroup difference and relaxin was only detectable in pregnant females. Although this study included characteristics not previously published for this species, it also showed how key aspects of reproduction were correlated temporally, and emphasized the importance of an integrated perspective when addressing the reproductive biology of coyotes, or other wild species of canids.


title: IMMUNITY AND IMMUNOPATHOLOGY TO VIRUSES: what decides the outcome?

text: Many viruses infect humans and most are controlled satisfactorily by the immune system with limited damage to host tissues. Some viruses, however, do cause overt damage to the host, either in isolated cases or as a reaction that commonly occurs after infection. The outcome is influenced by properties of the infecting virus, the circumstances of infection and multiple factors controlled by the host. In this Review, we focus on host factors that influence the outcome of viral infection, including genetic susceptibility, the age of the host when infected, the dose and route of infection, the induction of anti-inflammatory cells and proteins as well as the presence of concurrent infections and past exposure to cross-reactive agents.


title: Virus Factories

text: Viral factories are intracellular compartments of the host cell that contain viral replication organelles and necessary elements for assembly and maturation of new infectious viral particles. In this article we revise the methods used to study viral factories and the current knowledge on the structure, functions and biogenesis of these structures. We also describe some of the most emblematic examples of viral factories characterized so far. Finally, we describe how the identification of mechanisms involved in the biogenesis and functional architecture of viral factories will provide new means for antiviral intervention.


title: Adaptive modeling of viral diseases in bats with a focus on rabies

text: Abstract Many emerging and reemerging viruses, such as rabies, SARS, Marburg, and Ebola have bat populations as disease reservoirs. Understanding the spillover from bats to humans and other animals, and the associated health risks requires an analysis of the disease dynamics in bat populations. Traditional compartmental epizootic models, which are relatively easy to implement and analyze, usually impose unrealistic aggregation assumptions about disease-related structure and depend on parameters that frequently are not measurable in field conditions. We propose a novel combination of computational and adaptive modeling approaches that address the maintenance of emerging diseases in bat colonies through individual (intra-host) models of the response of the host to a viral challenge. The dynamics of the individual models are used to define survival, susceptibility and transmission conditions relevant to epizootics as well as to develop and parametrize models of the disease evolution into uniform and diverse populations. Applications of the proposed approach to modeling the effects of immunological heterogeneity on the dynamics of bat rabies are presented.


title: Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths

text: Abstract Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.


title: A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques

text: Abstract Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100–1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages had a high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques.


title: Misdiagnosis in the COVID era: When Zebras are Everywhere, Don’t Forget the Horses

text: Abstract We report a patient who presented with respiratory failure, chest pain, and fever. In the COVID-19 pandemic era, the focus was diverted to the coronavirus infection, and STEMI was missed. Even though we need to be vigilant in the diagnosis of COVID-19, we should not forget about the common pathologies.


COVID-19 R0: Magic number or conundrum?


title: Update on Streptococcus suis Research and Prevention in the Era of Antimicrobial Restriction: 4th International Workshop on S. suis †

text: Streptococcus suis is a swine pathogen and a zoonotic agent afflicting people in close contact with infected pigs or pork meat. Sporadic cases of human infections have been reported worldwide. In addition, S. suis outbreaks emerged in Asia, making this bacterium a primary health concern in this part of the globe. In pigs, S. suis disease results in decreased performance and increased mortality, which have a significant economic impact on swine production worldwide. Facing the new regulations in preventive use of antimicrobials in livestock and lack of effective vaccines, control of S. suis infections is worrisome. Increasing and sharing of knowledge on this pathogen is of utmost importance. As such, the pathogenesis and epidemiology of the infection, antimicrobial resistance, progress on diagnosis, prevention, and control were among the topics discussed during the 4th International Workshop on Streptococcus suis (held in Montreal, Canada, June 2019). This review gathers together recent findings on this important pathogen from lectures performed by lead researchers from several countries including Australia, Canada, France, Germany, Japan, Spain, Thailand, The Netherlands, UK, and USA. Finally, policies and recommendations for the manufacture, quality control, and use of inactivated autogenous vaccines are addressed to advance this important field in veterinary medicine.


title: Global Capacity for Emerging Infectious Disease Detection, 1996–2014

text: The speed with which disease outbreaks are recognized is critical for establishing effective control efforts. We evaluate global improvements in the timeliness of outbreak discovery and communication during 2010–2014 as a follow-up to a 2010 report. For all outbreaks reported by the World Health Organization’s Disease Outbreak News, we estimate the number of days from first symptoms until outbreak discovery and until first public communication. We report median discovery and communication delays overall, by region, and by Human Development Index (HDI) quartile. We use Cox proportional hazards regression to assess changes in these 2 outcomes over time, along with Loess curves for visualization. Improvement since 1996 was greatest in the Eastern Mediterranean and Western Pacific regions and in countries in the middle HDI quartiles. However, little progress has occurred since 2010. Further improvements in surveillance will likely require additional international collaboration with a focus on regions of low or unstable HDI.


docid: cgzqwbzs

title: Policy Recommendations regarding Skilled Nursing Facility Management of COVID-19: Lessons From New York State

text: ABSTRACT To provide policy recommendations for managing COVID-19 in Skilled Nursing Facilities (SNFs), a group of certified medical directors from several facilities in New York state with experience managing the disease used email, phone, and video conferencing to develop consensus recommendations. The resulting document provides recommendations on screening, and protection of staff, screening of residents, management of COVID-19 positive and presumed positive cases, communication during an outbreak, management of admissions and readmissions, and providing emotional support for staff. These consensus guidelines have been endorsed by the Executive Board of the New York Medical Directors Association and the Board of the Metropolitan Area Geriatrics Society.


title: Towards individualized and optimalized positioning of non-ventilated COVID-19 patients: Putting the affected parts of the lung(s) on top?

text: Abstract The outbreak of COVID-19 led to an unprecedented inflow of hospitalized patients with severe acute respiratory syndrome (SARS) requiring high-flow non-invasive oxygenation, if not invasive mechanical ventilation. While the best option in terms of non-invasive systems of oxygen delivery is still a matter of debate, it also remains unclear as to whether or not the optimal in-bed positioning of patients might also help to improve their oxygen saturation levels. On the basis of three representative cases, it is possible to propose the following hypotheses: (i) how patients are positioned has a strong influence on their oxygen saturation levels; (ii) saturation-optimalized positions are patient-specific; (iii) prone positions require ergonomic devices; and (iv) saturation-optimalized positions should aim to place the most affected part(s) of the lung(s) on top. Considered together, these hypotheses have led us to recommend that COVID-19 patients should undergo a specific assessment at admission to determine their saturation-optimalized in-bed position. However, further studies are still needed to assess the benefits of such a strategy on clinical outcomes.


title: Assessing the role of live poultry trade in community-structured transmission of avian influenza in China

text: The live poultry trade is thought to play an important role in the spread and maintenance of highly pathogenic avian influenza A viruses (HP AIVs) in Asia. Despite an abundance of small-scale observational studies, the role of the poultry trade in disseminating AIV over large geographic areas is still unclear, especially for developing countries with complex poultry production systems. Here we combine virus genomes and reconstructed poultry transportation data to measure and compare the spatial spread in China of three key subtypes of AIV: H5N1, H7N9, and H5N6. Although it is difficult to disentangle the contribution of confounding factors, such as bird migration and spatial distance, we find evidence that the dissemination of these subtypes among domestic poultry is geographically continuous and likely associated with the intensity of the live poultry trade in China. Using two independent data sources and network analysis methods, we report a regional-scale community structure in China that might explain the spread of AIV subtypes in the country. The identification of this structure has the potential to inform more targeted strategies for the prevention and control of AIV in China.


title: Porcine reproductive and respiratory syndrome virus: An update on an emerging and re-emerging viral disease of swine

text: Abstract Recognized in the late 1980s in North America and Europe the syndrome that caused reproductive and respiratory problems in swine was initially called “mystery swine disease” and is now termed “porcine reproductive and respiratory syndrome (PRRS)”. In the early 1990s an arterivirus, referred to as PRRS virus (PRRSV), was determined to be the etiologic agent of this disease. Since then research has progressed substantially. Most recently “porcine high fever disease” was reported in China starting in 2006 with PRRSV being a critical virus associated with high morbidity and mortality (20%) associated with this syndrome which in 2010 is still causing severe pathology in pigs in China, with spread to Vietnam and Cambodia. This volume contains a series of reviews that highlight the virus, its pathogenesis, epidemiology, immunology, vaccinology and host genetic control. This paper provides a brief historical review of PRRS and the associated PRRSV. It presents areas of research gaps that inhibit current progress towards PRRS elimination through production of effective vaccines and current plans for PRRS elimination or eradication programs. It is hoped that this discussion will stimulate further collaboration between researchers and swine veterinarians throughout the world to provide answers that enhance our understanding of PRRS and PRRSV in an effort to eliminate this economically important disease.


title: One country, two systems: Public health in China

text: Summary This paper, presented in Lisbon in May 2007, uses the framework of the three domains of public health practice—namely, health protection, health improvement and health services—as a reference to outline some of the main current public health challenges in Hong Kong and Mainland China [Griffiths S, Jewell T, Donnelly P. Public health in practice: the three domains of public health. Public Health 2005;119:907–13. 1 ].


title: A Genome Sequence of Novel SARS-CoV Isolates: the Genotype, GD-Ins29, Leads to a Hypothesis of Viral Transmission in South China

text: We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral genome replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.


title: NK Cells in Mucosal Defense against Infection

text: Conventional natural killer cells (NK cells) provide continual surveillance for cancer and rapid responses to infection. They develop in the bone marrow, emerge as either NK precursor cells, immature, or mature cells, and disperse throughout the body. In the periphery NK cells provide critical defense against pathogens and cancer and are noted to develop features of adaptive immune responses. In the tightly regulated and dynamic mucosal tissues, they set up residency via unknown mechanisms and from sources that are yet to be defined. Once resident, they appear to have the ability to functionally mature dependent on the mucosal tissue microenvironment. Mucosal NK cells play a pivotal role in early protection through their cytolytic function and IFNγ production against bacteria, fungi, viruses, and parasitic infections. This review presents what is known about NK cell development and phenotypes of mucosal tissue resident conventional NK cells. The question of how they come to reside in their tissues and published data on their function against pathogens during mucosal infection are discussed. Dissecting major questions highlighted in this review will be important to the further understanding of NK cell homing and functional diversity and improve rational design of NK cell based therapies against mucosal infection.


docid: iicbaevw

title: Incubation periods of acute respiratory viral infections: a systematic review

text: Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications.


title: Clinical Features of 33 Cases in Children Infected With SARS-CoV-2 in Anhui Province, China–A Multi-Center Retrospective Cohort Study

text: Background: As of 23rd February 2020, China had 77,048 patients with confirmed SARS-CoV-2 infections, and only 2. 1% of patients were under the age of 19 years. Morbidity among children was much lower, with milder or absent signs and symptoms; chest CT scans showed milder symptoms, if at all, compared to adults. Objective: Report the epidemiological, clinical features, laboratory, radiological characteristics, and treatment of SARS-CoV-2 infections. Compare additional signs and symptoms, investigate familial clustering, compare laboratory results, and find out relevance between age and typical chest CT scans in patients. Methods: We studied 33 young patients with laboratory-confirmed SARS-CoV-2 infection in Anhui Province of China by 16th February 2020. Their signs, symptoms, and familial clustering were analyzed. We compared the laboratory test results, age, and gender among three parts based on their chest CT scans. Results: Familial clustering was seen in 30 (30/33; 90.91%) patients; three families had seven confirmed members infected with the disease. Eight (8/33; 24.24%) patients had no symptoms, 12 (12/33; 36.36%) patients had only fever, nine (9/33; 27.27%) patients had fever and additional symptoms, and 12 (12/33; 36.36%) patients had no fever. Dry cough was the most common additional symptom. In 25 (25/33; 75.76%) patients, the percent of lymphocytes decreased; 26 (26/33; 78.79%) patients were older than 7 years. More male than female patients and patients older than 8 years showed typical abnormalities in the chest CT scans (P = 0.038). Only two 18 years old patients had hepatic injury. Conclusion: Children's infection is mild and familial clustering was the most common channel. The older patients had more typical ground glass opacity (GGO) or consolidation in chest CT scans. Cases without fever strongly suggested that non-symptomatic children should not be assumed to be free of infection when their family members have confirmed infection. Most children showed clinical features distinguishable from adults and with increased susceptibility within family members.


Wars versus SARS: Are epidemiological studies biased?


title: Asymptomatic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: Extent and implications for infection control: A systematic review

text: Abstract Background The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in 2012 and attracted an international attention as the virus caused multiple healthcare associated outbreaks. There are reports of the role of asymptomatic individuals in the transmission of MERS-CoV, however, the exact role is not known. Method The MEDLINE/PubMed and Scopus databases were searched for relevant papers published till August 2018 describing asymptomatic MERS-CoV infection. Results A total of 10 papers were retrieved and included in the final analysis and review. The extent of asymptomatic MERS infection had increased with change in the policy of testing asymptomatic contacts. In early cases in April 2012–October 2013, 12.5% were asymptomatic among 144 PCR laboratory-confirmed MERS-CoV cases while in 2014 the proportion rose to 25.1% among 255 confirmed cases. The proportion of asymptomatic cases reported among pediatric confirmed MERS-CoV cases were higher (41.9%–81.8%). Overall, the detection rate of MERS infection among asymptomatic contacts was 1-3.9% in studies included in this review. Asymptomatic individuals were less likely to have underlying condition compared to fatal cases. Of particular interest is that most of the identified pediatric cases were asymptomatic with no clear explanation. Conclusions The proportion of asymptomatic MERS cases were detected with increasing frequency as the disease progressed overtime. Those patients were less likely to have comorbid disease and may contribute to the transmission of the virus.


title: Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin

text: The identification of a novel β coronavirus, nCoV, as the causative agent of severe respiratory illness in humans originating in Saudi Arabia, Qatar and Jordan has raised concerns about the possibility of a coronavirus pandemic similar to that of SARS-CoV. As a definitive treatment regimen has never been thoroughly evaluated for coronavirus infections, there is an urgent need to rapidly identify potential therapeutics to address future cases of nCoV. To determine an intervention strategy, the effect of interferon-α2b and ribavirin on nCoV isolate hCoV-EMC/2012 replication in Vero and LLC-MK2 cells was evaluated. hCoV-EMC/2012 was sensitive to both interferon-α2b and ribavirin alone in Vero and LLC-MK2 cells, but only at relatively high concentrations; however, when combined, lower concentrations of interferon-α2b and ribavirin achieved comparable endpoints. Thus, a combination of interferon-α2b and ribavirin, which are already commonly used in the clinic, may be useful for patient management in the event of future nCoV infections.


title: Epidemiology of Imported Infectious Diseases, China, 2005–2016

text: Imported infectious diseases are becoming a serious public health threat in China. However, limited information concerning the epidemiologic characteristics of imported infectious diseases is available. In this study, we collected data related to imported infectious diseases in mainland China from the National Information Reporting System of Infectious Diseases and analyzed demographic, temporal, and spatial distributions. The number of types of imported infectious diseases reported increased from 2 in 2005 to 11 in 2016. A total of 31,740 cases of infectious disease were imported to mainland China during 2005–2016; most of them were found in Yunnan Province. The cases were imported mainly from Africa and Asia. As a key and effective measure, pretravel education should be strengthened for all migrant workers and tourists in China, and border screening, cross-border international cooperation, and early warning should be further improved.


title: Evaluation of MERS-CoV Neutralizing Antibodies in Sera Using Live Virus Microneutralization Assay

text: The microneutralization (MN) assay is a standard and important technique in virology, immunology, and epidemiology. It is a highly specific and sensitive assay for evaluating virus-specific neutralizing antibodies (nAbs) in human and animal sera. It provides the most precise answer to whether or not an individual or animal has antibodies that can neutralize or inhibit the infectivity of a specific virus strain. However, using live virus-based MN assay might require working under high containment facilities especially when dealing with high-risk pathogens such as the Middle East respiratory syndrome-coronavirus (MERS-CoV). In this chapter, we describe the isolation, amplification, and titration of MERS-CoV, as well as detailed MN assay to measure nAb levels in sera from different mammalian species.


title: A core competence-based objective structured clinical examination (OSCE) in evaluation of clinical performance of postgraduate year-1 (PGY1) residents

text: Abstract Background Clinical competency certifications are important parts of internal medicine residency training. This study aims to evaluate a composite objective structured clinical examination (OSCE) that assesses postgraduate year-1 (PGY1) residents’ acquisition of the six core competencies defined by the Accreditation council for Graduate Medical Education (ACGME). Methods Six-core-competency-based OSCE was used as examination of the clinical performance of 192 PGY1 residents during their 3-month internal medicine training between 2007 January and 2009 December. For each year, the reliability of the entire examination was calculated with Cronbach’s alpha. Results The reliability of six-core-competency-based OSCE was acceptable, ranging from 0.69 to 0.87 between 2007 and 2009. In comparison with baseline scores, the summary scores and core-competency subscores all showed significant increase after PGY1 residents finished their 3-month internal medicine training program. Conclusion By using a structured development process, the authors were able to create reliable evaluation items for determining PGY1 residents’ acquisition of the ACGME core competencies.


title: Case report: A kidney transplant patient with mild COVID‐19

text: Coronavirus Disease 2019 (COVID‐19) is currently a pandemic with a mortality rate of 1%‐6% in the general population. However, the mortality rate seems to be significantly higher in elderly patients, especially those hospitalized with comorbidities, such as hypertension, diabetes, or coronary artery diseases. Because viral diseases may have atypical presentations in immunosuppressed patients, the course of the disease in the transplant patient population is unknown. Hence, the management of these patients with COVID‐19 is an area of interest, and a unique approach is warranted. Here, we report the clinical features and our treatment approach for a kidney transplant patient with a diagnosis of COVID‐19. We believe that screening protocols for SARS‐Cov‐2 should be re‐evaluated in patients with solid‐organ transplants.


title: Advances in ligase chain reaction and ligation-based amplifications for genotyping assays: Detection and applications

text: Abstract Genetic variants have been reported to cause several genetic diseases. Various genotyping assays have been developed for diagnostic and screening purposes but with certain limitations in sensitivity, specificity, cost effectiveness and/or time savings. Since the discovery of ligase chain reaction (LCR) in the late nineties, it became one of the most favored platforms for detecting these variants and also for genotyping low abundant contaminants. Recent and powerful modifications with the integration of various detection strategies such as electrochemical and magnetic biosensors, nanoparticles (NPs), quantum dots, quartz crystal and leaky surface acoustic surface biosensors, DNAzyme, rolling circle amplification (RCA), strand displacement amplification (SDA), surface enhanced raman scattering (SERS), chemiluminescence and fluorescence resonance energy transfer have been introduced to both LCR and ligation based amplifications to enable high-throughput and inexpensive multiplex genotyping with improved robustness, simplicity, sensitivity and specificity. In this article, classical and up to date modifications in LCR and ligation based amplifications are critically evaluated and compared with emphasis on points of strength and weakness, sensitivity, cost, running time, equipment needed, applications and multiplexing potential. Versatile genotyping applications such as genetic diseases detection, bacterial and viral pathogens detection are also detailed. Ligation based gold NPs biosensor, ligation based RCA and ligation mediated SDA assays enhanced detection limit tremendously with a discrimination power approaching 1.5aM, 2aM and 0.1fM respectively. MLPA (multiplexed ligation dependent probe amplification) and SNPlex assays have been commercialized for multiplex detection of at least 48 SNPs at a time. MOL-PCR (multiplex oligonucleotide ligation) has high-throughput capability with multiplex detection of 50 SNPs/well in a 96 well plate. Ligase detection reaction (LDR) is one of the most widely used LCR versions that have been successfully integrated with several detection strategies with improved sensitivity down to 0.4fM.


title: Biosecurity and biocontainment in alpaca operations

text: Abstract Biosecurity on South American camelid operations involves both external and internal measures to prevent the introduction and spread of disease. External biosecurity involves practices and techniques directed at the prevention of entry of new diseases into a group of animals. Internal biosecurity or biocontainment, involves practices and techniques that are directed at the prevention or spread of disease within an existing group of animals. External biosecurity is particularly important in North America camelid operations due to the extensive movement of animals for breeding or show purposes. Internal biosecurity typically involves this the prevention and treatment of failure of passive transfer, maintenance of proper nutrition and housing, and the implementation of an appropriate vaccination program for endemic or relevant diseases. Attention to appropriate cleaning and disinfection procedures related to housing, feeding, and treatment equipment is important for the maintenance of both internal and external biosecurity practices. This paper discusses various risk factors associated with the control of infectious disease in the context of external and internal biosecurity measures in camelids operations.


title: Cleaning the River Ganga: Impact of lockdown on water quality and future implications on river rejuvenation strategies

text: Abstract Clean rivers and healthy aquatic life symbolize that the ecosystem is functioning well. The Ganga River has shown signs of rejuvenation and a significant improvement on many parameters, following the eight-week nationwide lockdown due to coronavirus pandemic. Since industrial units and commercial establishments were closed, water was not being lifted by them with a negligible discharge of industrial wastewater. It was observed that during the lockdown period most of the districts falling under the Ganga basin observed 60% excess rainfall than the normal, which led to increased discharge in the river, further contributing towards the dilution of pollutants. Further, data analysis of live storages in the Ganga Basin revealed that the storage during the beginning of the third phase of lockdown was almost double than the storage during the same period the previous year. Analysis of the storage data of the last ten years revealed that the storage till May 6, 2020 was 82.83% more than the average of the previous ten years, which meant that more water was available for the river during the lockdown period. The impact could be seen in terms of increased dissolved oxygen (DO) and reduced biological oxygen demand (BOD) and nitrate (NO3-) concentration. A declining trend in nitrate concentration was observed in most of the locations due to limited industrial activities and reduction in agricultural run-off due to harvesting season. The gradual transformation in the quality of the water has given a sign of optimism from the point of restoration. Yet, it is believed that this improvement in water quality is ‘short-lived’ and quality would deteriorate once the normal industrial activities are resumed, indicating a strong influence of untreated commercial–industrial wastewater. The paper concludes that the river can be rejuvenated if issues of wastewater and adequate flow releases are addressed.


title: Effects of inhalation exposure to a high-boiling (288 to 454°C) coal liquid

text: Abstract Coal liquids have been evaluated in a variety of short-term toxicological assays; however, few studies have been conducted to determine the systemic effects after inhalation exposure to these materials. To extend the data base on potential health effects from coal liquefaction materials, we performed a study with solvent refined coal (SRC)-II heavy distillate (HD). Fischer-344 rats were exposed for 6 hr/day, 5 days/week for 5 or 13 weeks to an aerosol of HD (boiling range, 288 to 454°C) at concentrations of 0.69, 0.14, 0.03, or 0.0 mg/liter of air for the high, middle, low, and control groups, respectively. Survival through 13 weeks of exposure was greater than 90% for all groups; body weights for exposed animals were decreased in a dose-dependent manner. significant increases in liver weights and decreases in thymus and ovary weights were observed for treated animals compared with controls. There were also significant treatment-related decreases in erythrocytes, hemoglobin, volume of packed red blood cells, lymphocytes, eosinophils, and total white blood cells. After 5 weeks of exposure serum cholesterol concentrations increased in a dose-dependent manner for both sexes and serum triglyceride amounts decreased for males but not for females. After 13 weeks of exposure, high-dose animals had significant increases in cholesterol (males only), triglycerides, blood urea nitrogen, and serum glutamic pyruvic transaminase (SGPT; males) and significant decreases in albumin, SGPT (females), and lactate dehydrogenase (LDH). Examination of bone-marrow preparations from exposed animals demonstrated consistent decreases in the degree of cellularity, suggesting that this organ is a target for HD. Microscopic evaluation of organ sections indicated exposure-related changes for nasal mucosa, pulmonary macrophages, thymus, liver, kidney, bone marrow, ovaries, and cecum. Results from this study indicated dose-dependent increases in the severity of the lesions observed, with few effects in the low-exposure group that were attributable to the exposure.


title: Quantifying the effect of lactogenic antibody on porcine epidemic diarrhea virus infection in neonatal piglets

text: Abstract The contribution of lactogenic antibody to the protection of piglets against porcine epidemic diarrhea virus (PEDV) was evaluated. Pregnant multiparous sows and their litters were allocated to one of 3 treatment groups: Group 1–6 serum antibody-negative sows and a subset (n=11) of their piglets. Group 2–8 serum antibody-positive sows and their 91 piglets. Piglets were orally inoculated with PEDV at 4 (Group 1) or 2 (Group 2) days of age. Group 3–2 PEDV serum antibody-negative sows and 22 piglets, provided a baseline for piglet survivability and growth rate. Piglets were monitored daily for clinical signs, body weight, and body temperature through day post-inoculation (DPI) 12 (Groups 2 and 3) or 14 (Group 1). Serum and mammary secretions were tested for PEDV IgG, IgA, and virus-neutralizing antibody. Feces were tested by PEDV real-time, reverse transcriptase PCR (rRT-PCR). Piglets on sows without (Group 1) or with (Group 2) anti-PEDV antibody showed significantly different responses to PEDV infection in virus shedding (p < 0.05), thermoregulation (p < 0.05), growth rate (p < 0.05), and survivability (p <0.0001). Specifically, Group 1 piglets shed more virus on DPIs 1 to 5, were hypothermic at all sampling points except DPIs 9, 11, and 12, gained weight more slowly, and exhibited lower survivability than Group 2 piglets. Within Group 2 litters, significant differences were found in virus shedding (p < 0.05), and body temperature (p < 0.05), but not in piglet survival rate. The number of sows and litters in Group 2 was insufficient to derive the relationship between specific levels of lactogenic antibody (FFN, IgA, and IgG) and the amelioration of clinical effects. However, when combined with previous PEDV literature, it can be concluded that the optimal protection to piglets will be provided by dams able to deliver sufficient lactogenic immunity, both humoral and cellular, to their offspring.


title: Potential Role of Paramyxoviruses in Multiple Sclerosis

text: At the present time, the cause of multiple sclerosis (MS) remains unknown, although it seems likely that one or more infectious agents triggers the disease, perhaps through an autoimmune mechanism. In this article, evidence linking the paramyxoviruses, canine distemper, and measles to MS is reviewed.


title: Design, Synthesis and Antiviral Efficacy of a Series of Potent Chloropyridyl Ester-derived SARS-CoV 3CLpro Inhibitors

text: Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS 3Clpro IC(50) value of 30 nM and antiviral EC(50) value of 6.9 μM. Molecular Docking studies have provided possible binding modes of these inhibitors. [Image: see text]


title: A human SARS-CoV neutralizing antibody against epitope on S2 protein

text: Abstract An immune antibody phage-display library was constructed from B cells of SARS convalescent patients. More than 80 clones were selected from the library by using the whole inactivated SARS-CoV virions as target. One human scFv, B1, was characterized extensively. The B1 recognized SARS pseudovirus in vivo and competed with SARS sera for binding to SARS-CoV with high affinity (equilibrium dissociation constant, K d =105nM). The B1 also has potent neutralizing activities against infection by pseudovirus expressing SARS-CoV S protein in vitro. Finally, we found that the B1 recognized an epitope on S2 protein, especially within amino acids 1023–1189 of S2 protein. This study not only first made a human neutralizing antibody, which recognized an epitope on S2 protein like natural antibody in sera, but also may help us to better understand the immunological characteristics of SARS protein and SARS vaccine design.


title: A Novel Bocavirus Associated with Acute Gastroenteritis in Australian Children

text: Acute gastroenteritis (AGE) is a common illness affecting all age groups worldwide, causing an estimated three million deaths annually. Viruses such as rotavirus, adenovirus, and caliciviruses are a major cause of AGE, but in many patients a causal agent cannot be found despite extensive diagnostic testing. Proposing that novel viruses are the reason for this diagnostic gap, we used molecular screening to investigate a cluster of undiagnosed cases that were part of a larger case control study into the etiology of pediatric AGE. Degenerate oligonucleotide primed (DOP) PCR was used to non-specifically amplify viral DNA from fecal specimens. The amplified DNA was then cloned and sequenced for analysis. A novel virus was detected. Elucidation and analysis of the genome indicates it is a member of the Bocavirus genus of the Parvovirinae, 23% variant at the nucleotide level from its closest formally recognized relative, the Human Bocavirus (HBoV), and similar to the very recently proposed second species of Bocavirus (HBoV2). Fecal samples collected from case control pairs during 2001 for the AGE study were tested with a bocavirus-specific PCR, and HBoV2 (sequence confirmed) was detected in 32 of 186 cases with AGE (prevalence 17.2%) compared with only 15 controls (8.1%). In this same group of children, HBoV2 prevalence was exceeded only by rotavirus (39.2%) and astrovirus (21.5%) and was more prevalent than norovirus genogroup 2 (13.4%) and adenovirus (4.8%). In a univariate analysis of the matched pairs (McNemar's Test), the odds ratio for the association of AGE with HBoV2 infection was 2.6 (95% confidence interval 1.2–5.7); P = 0.007. During the course of this screening, a second novel bocavirus was detected which we have designated HBoV species 3 (HBoV3). The prevalence of HBoV3 was low (2.7%), and it was not associated with AGE. HBoV2 and HBoV3 are newly discovered bocaviruses, of which HBoV2 is the thirdmost-prevalent virus, after rotavirus and astrovirus, associated with pediatric AGE in this study.


title: Hematology and Biochemistry of Small Mammals

text: The first part of this chapter describes the normal and abnormal hematology findings of small mammals including rats and mice, hamsters and gerbils, guinea pigs, chinchillas, rabbits, ferrets, and hedgehogs, along with images of peripheral blood of these species. It also reviews the expected hematologic changes in a variety of species-specific disease processes as well as the correlation with other clinicopathologic parameters. The second part of this chapter pertains to the interpretation of serum biochemical data with respect to reference intervals and preanalytical, analytical, and biologic variables. Similarities and differences between species are elucidated. Brief discussions regarding methods of analysis for some analytes are included where methodology may impact test interpretation.