title: The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD

text: COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe–COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe–host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD.


Nutritional Considerations in Frail Older Patients with COVID-19


title: Identification of encoding proteins related to SARS-CoV

text: By sampling 100 encoding proteins from SARS-coronavirus (SARS-CoV, NC 004718) and other six coronaviruses and selecting 23 variables through stepwise multiple regression (SMR) from 172 variables, the multiple linear regression (MLR) model was established with good results of the quantitative modelling correlation coefficient R (2) = 0.645 and the cross-validation correlation coefficient R (CV)(2) = 0.375. After removing 4 outliers, the quantitative modelling and cross-validation correlation coefficients were R (2)= 0.743 and R (CV)(2) = 0.543, respectively.


Cytokine Storm: is it the only major death factor in COVID-19 patients? Coagulation role


title: Evaluation of an Immunochromatographic Assay for the Rapid and Simultaneous Detection of Rotavirus and Adenovirus in Stool Samples

text: BACKGROUND: We evaluated the analytical and clinical performances of the SD BIOLINE Rota/Adeno Rapid kit (SD Rota/Adeno Rapid; Standard Diagnostics, Inc., Korea), an immunochromatographic assay (ICA), for the simultaneous detection of rotaviruses and adenoviruses in human stool samples. METHODS: We tested 400 clinical stool samples from patients with acute gastroenteritis and compared the ICA results with the results obtained by using ELISA, enzyme-linked fluorescent assays (ELFA), PCR, and multiplex reverse transcription-PCR (mRT-PCR). To assess the analytical performance of the SD BIOLINE Rota/Adeno Rapid kit, we determined its detection limit, reproducibility, cross-reactivity, and analytical reactivity for adenovirus subtypes, and performed interference studies. RESULTS: The overall agreement rates among the tested methods were 91.5% for rotavirus and 85.5% for adenovirus. On the basis of mRT-PCR, the overall agreement, positive agreement, and negative agreement rates of the ICA were 95.6%, 100%, and 94.9% for rotavirus, and 94.0%, 71.4%, and 94.8% for adenovirus, respectively. Using the ICA, we detected all the subtypes of adenovirus tested, but the analytical reactivities for adenovirus subtypes were different between the 4 adenovirus detection methods. The high reproducibility was confirmed, and no cross-reactivity or interference was detected. CONCLUSIONS: The SD BIOLINE Rota/Adeno Rapid kit showed acceptable analytical and clinical performances. However, interpretation of adenovirus positive/negative result should be cautious because of different detectability for adenovirus subtypes among adenovirus detection methods.


title: Origin and dispersal of Hepatitis E virus

text: Hepatitis E virus (HEV, genus Orthohepevirus) is a common cause of hepatitis worldwide. Human-infecting HEV strains (Orthohepevirus A) include human-restricted and enzootic genotypes. Viruses in the Orthohepevirus A species also infect rabbits (HEV-3ra), camels, and swine. Using a selection-informed method, we dated the origin of the Orthohepevirus genus at least 21 million years ago, whereas the Orthohepevirus A species originated in Asia, most likely from a human-infecting ancestor that existed ~4500 to 6800 years ago. In this period, the appearance of large human settlements probably facilitated HEV emergence and spread. The earliest events in Orthohepevirus A evolutionary history involved the separation of the enzootic and human-restricted genotypes, as well as the split of the camel-infecting genotypes, which occurred during the time-frame of camel domestication. The place and timing of HEV-3ra divergence also correspond to the circumstances of rabbit domestication. This study clarifies the origin and historical events underlying HEV dispersal.


title: Convergence of carbon intensity in the Yangtze River Delta, China

text: As China's industrialization and urbanization have grown rapidly in recent years, China's CO(2) emissions rose from 3405.1799 Mt to 10,249.4630 Mt from 2000 to 2013, and it has reached the highest levels in the word since 2006. Chinese government has emphasized the importance of reducing carbon emissions and set the target of reducing carbon intensity to 60–65% of 2005 levels by 2030. Investigating the convergence of carbon intensity can identify the convergence rate, which is helpful in guiding allocations of carbon intensity reduction. The Yangtze River Delta is one of the key carbon emission regions in China, with higher urbanization levels and larger carbon emissions; thus, we employed prefecture-level panel data derived from grid data between 2000 and 2010 to examine whether the convergence of carbon intensity exists across prefecture-level cities in the Yangtze River Delta. Spatial panel data models were utilized to investigate β-convergence of carbon intensity. The results indicated that carbon intensity showed divergence during 2002–2004 and σ-convergence over other periods (2000–2002 and 2004–2010). Carbon intensity exhibited stochastic convergence, indicating that the shocks to carbon intensity relative to the average level of carbon intensity are only transitory. There was a spatial spillover effect and β-convergence of carbon intensity, suggesting that prefecture-level cities with higher carbon intensity would decrease rapidly in the Yangtze River Delta. Our results highlight the importance of considering the present state of carbon intensity, spatial factors, and socioeconomic factors such as industrial structure and economic levels during allocation planning for reducing carbon intensity.


title: BVDV Npro protein mediates the BVDV induced immunosuppression through interaction with cellular S100A9 protein

text: Abstract The innate immune response is a vital part of the body's antiviral defense system. The innate immune response is initiated by various receptor interactions, including danger associated molecular patterns (DAMPs). The S100A9 is a member of the DAMPs protein family and, is released by activated phagocytic cells such as neutrophils, monocytes, macrophages or endothelial cells, and S100A9 induces its effect through TLR4/MyD88 pathway. Bovine viral diarrhea virus (BVDV) is one of the major devastating disease in the cattle industry worldwide. It shows its effect through immunosuppression and develops persistent infection in calves born from infected cows. The current study revealed that BVDV potentially induced immunosuppression by the interaction of BVDV Npro protein with cellular S100A9 protein. The Inhibition of S100A9 protein expression by small interfering RNA (siRNA) enhanced the virus replication in infected cells. Overexpression of bovine S100A9 enhanced the ncpBVDV2a 1373 mediated Type-I interferon production. A co-immunoprecipitation experiment demonstrated a strong interaction between ncp BVDV2a 1373 Npro protein and cellular S100A9 protein. This suggested that BVDV Npro reduced the S100A9 protein availability/activity in infected cells, resulting in reduced Type-I interferon production. A further study of S100A9-BVDV interaction will be need for better understanding of BVDV pathophysiology.


title: Use of recombinant interferon omega in feline retrovirosis: From theory to practice

text: Abstract Type-I interferons (IFNs) are cytokines that have non-specific antiviral activity, participating mostly in innate defense mechanisms. Their administration has been proposed to treat several viral and immunomediated diseases as an immunomodulatory therapy. Due to its availability, recombinant human interferon-alpha (rHuIFN-α) has been studied in relation to feline retrovirosis, both in vitro and in vivo. However, IFNs are species-specific and antibodies have been shown to develop in response to the high rHuIFN-α doses necessary for an effective therapy. A recombinant feline IFN has been developed, which has been characterized as interferon-omega (rFeIFN-ω), designed to overcome these problems. Nonetheless, very few studies have been undertaken to evaluate its efficacy in cats naturally infected with FIV or FeLV. In an initial study, we here demonstrated that rFeIFN-ω can dramatically improve the clinical condition of infected cats, and induce improvement of hematologic parameters. Minor changes or no change was observed for hypergammaglobulinemia, CD4/CD8 ratio, proviral load, viremia and RT activity, suggesting that the overall effect of IFN was on innate immunity. More studies are needed in order to better understand its in vivo mechanisms.


title: Health in times of uncertainty in the eastern Mediterranean region, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

text: BACKGROUND: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. METHODS: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. FINDINGS: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. INTERPRETATION: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region’s health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. FUNDING: Bill & Melinda Gates Foundation.


title: 5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines: synthesis and inhibitory effects on immune-activated nitric oxide production

text: A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier–Haack–Arnold reagent, followed by immediate deprotection of the (dimethylamino)methylene protecting groups, has been developed to convert the 2-amino-4,6-dihydroxypyrimidine analogs to novel 5-substituted 2-amino-4,6-dichloropyrimidines in high yields. Pilot screening for biological properties of the prepared compounds was done in mouse peritoneal cells using the in vitro nitric oxide (NO) assay. Irrespective of the substituent at the 5 position, 2-amino-4,6-dichloropyrimidines inhibited immune-activated NO production. The most effective was 5-fluoro-2-amino-4,6-dichloropyrimidine with an IC (50) of 2 µM (higher activity than the most potent reference compound) while the IC (50)s of other derivatives were within the range of 9–36 µM. The 2-amino-4,6-dihydroxypyrimidine counterparts were devoid of any NO-inhibitory activity. The compounds had no suppressive effects on the viability of cells. The Mechanism of action remains to be elucidated.


title: Guidance for Remote Reporting of Digital Pathology Slides During Periods of Exceptional Service Pressure: An Emergency Response from the UK Royal College of Pathologists

text: Pathology departments must rise to new staffing challenges caused by the coronavirus disease-19 pandemic and may need to work more flexibly for the foreseeable future. In light of this, many pathologists and departments are considering the merits of remote or home reporting of digital cases. While some individuals have experience of this, little work has been done to determine optimum conditions for home reporting, including technical and training considerations. In this publication produced in response to the pandemic, we provide information regarding risk assessment of home reporting of digital slides, summarize available information on specifications for home reporting computing equipment, and share access to a novel point-of-use quality assurance tool for assessing the suitability of home reporting screens for digital slide diagnosis. We hope this study provides a useful starting point and some practical guidance in a difficult time. This study forms the basis of the guidance issued by the Royal College of Pathologists, available at: https://www.rcpath.org/uploads/assets/626ead77-d7dd-42e1-949988e43dc84c97/RCPath-guidance-for-remote-digital-pathology.pdf.


title: Recommandations CCAFU sur la prise en charge des cancers de l’appareil urogénital en période d’épidémie au Coronavirus COVID-19

text: Résumé Objectif La population française est confrontée à la pandémie de COVID-19 et le système de santé a été réorienté en urgence pour la prise en charge des patients atteints du coronavirus. La prise en charge des cancers de l’appareil urinaire et génital masculin doit être adaptée à ce contexte. Matériel et méthode Un avis d’experts documenté par une revue de la littérature a été formulé par le Comité de Cancérologie de l’Association Française d’Urologie (CCAFU). Résultats La prise en charge médicale et chirurgicale des patients atteints de cancers de l’appareil urinaire et génital masculin doit être adaptée en modifiant les modalités de consultation, en priorisant les interventions en fonction du pronostic intrinsèque des cancers en tenant compte des comorbidités du patient. La protection des urologues vis-à-vis du COVID-19 doit être prise en considération. Conclusion Le CCAFU émet un avis d’experts quant aux mesures à prendre pour adapter la prise en charge des cancers de l’appareil urinaire et génital masculin au contexte de pandémie par COVID-19. Summary Aim The French population is facing the COVID-19 pandemic and the health system have been reoriented in emergency for the care of patients with coronavirus. The management of cancers of the urinary and male genital tracts must be adapted to this context. Material and method An expert opinion documented by a literature review was formulated by the Cancerology Committee of the French Association of Urology (CCAFU). Results The medical and surgical management of patients with any cancers of the urinary and male genital tracts must be adapted by modifying the consultation methods, by prioritizing interventions according to the intrinsic prognosis of cancers, taking into account the patient's comorbidities. The protection of urologists from COVID-19 must be considered. Conclusion The CCAFU issues an expert opinion on the measure to be taken to adapt the management of cancers of the male urinary and genital tract to the context of pandemic by COVID-19.


title: Insights From Deep Sequencing of the HBV Genome—Unique, Tiny, and Misunderstood

text: Hepatitis B virus (HBV) is a unique, tiny, partially double-stranded, reverse-transcribing DNA virus with proteins encoded by multiple overlapping reading frames. The substitution rate is surprisingly high for a DNA virus, but lower than that of other reverse transcribing organisms. More than 260 million people worldwide have chronic HBV infection, which causes 0.8 million deaths a year. Because of the high burden of disease, international health agencies have set the goal of eliminating HBV infection by 2030. Nonetheless, the intriguing HBV genome has not been well characterized. We summarize data on the HBV genome structure and replication cycle, explain and quantify diversity within and among infected individuals, and discuss advances that can be offered by application of next-generation sequencing technology. In-depth HBV genome analyses could increase our understanding of disease pathogenesis and allow us to better predict patient outcomes, optimize treatment, and develop new therapeutics.


title: Incidence of acute disseminated encephalomyelitis in the Jiangsu province of China, 2008–2011

text: BACKGROUND: It is important to have an estimate of the incidence of acute disseminated encephalomyelitis (ADEM) because the incidence of ADEM is unknown and the outcomes undefined in China. OBJECTIVES: This study attempts to describe ADEM incidence in large Chinese populations located in four geographically different and moderately distant areas of the same province. METHODS: A retrospective investigation was conducted with ADEM patients in Nanjing, Nantong, Yancheng and Xuzhou. The survey was carried out in regions that might have received patients meeting the case definition of ADEM provided by the International Pediatric MS Study Group from 2008 to 2011. A total of 125 hospitals were included and 412 patients were identified through the hospital information systems (HIS). RESULTS: The incidence of ADEM was 0.32/100,000/year. There are two peaks on the age-specific ADEM rates curve. One is 0.77/100,000/year among 0- to 9-year-olds, the other is 0.45/100,000/year in those aged 50–59 years. The incidence rate found for ADEM in males was 0.34/100,000/year, and in females was 0.29/100,000/year. The highest incidence rate was in Nanjing (0.40/100,000/year). CONCLUSIONS: The average annual incidence of ADEM was 0.32/100,000/year. The peak age of onset was 50–59 years old and 0–9 years old. The incidence among males was insignificantly higher than that among females. There was no significant difference in incidence by seasonal variation.


title: Chapter 16 RNA Viruses in Parasitoid Wasps

text: Publisher Summary This chapter describes the different RNA viruses that have been detected at least once in parasitoid wasps. It could be wondered whether the other families of parasitoids are really absent, or if this is due to the fact that inadequate techniques were used to detect viruses. In fact, several different methods have been used: TEM of the venom glands of females, extraction of nucleic acids, followed by DNAse digestion to eliminate the polydnavirus or ascovirus genome, RT-PCR with primers specific of RdRp or data mining in an EST library. To resolve this problem of detecting RNA viruses, a systematic search for viruses in parasitoids should be carried out using a combination of these different methods. Only a few hymenopteran species are known to be infected by RNA viruses, although thousands of species are known to carry polydnaviruses or VLPs. This could suggest that the presence of polydnaviruses or VLPs may block infections with other viruses.


title: Protocolo terapéutico empírico de las infecciones bucales y faríngeas

text: Resumen Introducción La mayoría de las infecciones de la cavidad bucal son odontogénicas, aunque también pueden afectar a las estructuras extradentales (infecciones no odontogénicas). La faringitis es la inflamación y/o la infección de la faringe y/o área periamigdalar. Tratamiento Ambas infecciones tienen una prevalencia muy alta en la población, siendo uno de los motivos más frecuentes de consulta y prescripción de antibióticos en las consultas de Atención Primaria. El tratamiento de ambas infecciones suele ser empírico, basado en el diagnóstico clínico y la prevalencia y sensibilidad antibiótica de los microorganismos implicados con más frecuencia. Abstract Introduction Most oral cavity infections are odontogenic, although they can also affect extradental structures (non-odontogenic infections). Pharyngitis is inflammation and/or infection of the pharynx and /or the peri-tonsillar area. Treatment Both infections are highly prevalent in the population, and one of the most common reasons for consultation and the prescription of antibiotics in primary care clinics. Both infections are usually treated empirically, based on clinical diagnosis and the prevalence and antibiotic sensitivity of the most commonly implicated microorganisms.


title: Sexual and reproductive health (SRH): a key issue in the emergency response to the coronavirus disease (COVID- 19) outbreak

text: The novel coronavirus disease (COVID-19) outbreak was first declared in China in December 2019, and WHO declared the pandemic on 11 March 2020. A fast-rising number of confirmed cases has been observed in all continents, with Europe at the epicentre of the outbreak at this moment. Sexual and reproductive health (SRH) and rights is a significant public health issue during the epidemics. The novel coronavirus (SARS-CoV-2) is new to humans, and only limited scientific evidence is available to identify the impact of the disease COVID-19 on SRH, including clinical presentation and outcomes of the infection during pregnancy, or for persons with STI/HIV-related immunosuppression. Beyond the clinical scope of SRH, we should not neglect the impacts at the health system level and disruptions or interruptions in regular provision of SRH services, such as pre- and postnatal checks, safe abortion, contraception, HIV/AIDS and sexually transmitted infections. Furthermore, other aspects merit attention such as the potential increase of gender-based violence and domestic abuse, and effects of stigma and discrimination associated with COVID-19 and their effects on SRH clients and health care providers. Therefore, there is an urgent need for the scientific community to generate sound clinical, epidemiological, and psycho-social behavioral links between COVID-19 and SRH and rights outcomes.


Rapid prototype feasibility testing with simulation: Improvements and updates to the Taiwanese “aerosol box”


title: Enfermedades infecciosas importadas en España

text: Con el crecimiento de los viajes internacionales y la inmigración, en España ha aumentado el número de pacientes con enfermedades infecciosas importadas, muchas de ellas desde zonas tropicales o subtropicales. Paralelamente también se ha multiplicado el número de publicaciones científicas de autores españoles sobre infecciones importadas causadas por parásitos, hongos, micobacterias, bacterias o virus. El riesgo que representan para la salud pública es bajo, aunque para su correcta prevención y su control es importante facilitar el acceso universal a la asistencia sanitaria y a unas condiciones socioeconómicas dignas, así como mantener una formación clínica y epidemiológica actualizada del personal sanitario. Estas medidas a escala nacional deben compaginarse con las iniciativas internacionales de control global de estas infecciones. In Spain, owing to the rise of international travels and immigration, the number of patients with imported infectious diseases has increased, many of them from tropical or subtropical areas. In parallel, there has been a multiplication in the number of scientific papers with Spanish authors about imported infections due to parasites, fungus, mycobacteriae, bacteriae or viruses. The risk for public health is low, althought for their correct prevention and control it is important to ease an universal access to healthcare and fair socioeconomic conditions, along with maintaining an updated clinical and epidemiological training of the health personnel. These nationwide measures must be supplemented with worldwide initiatives of global control of these infections.


title: 21 Adenoviral Vector Vaccines Antigen Transgene

text: Abstract In the past decade adenovirus-based vaccines have progressed from preclinical studies, which universally showed the vectors’ high immunogenicity, to testing in humans. Clinical trials showed that adenovirus vectors are well tolerated by humans. They induce robust immune responses that can be expanded by booster immunization. The effect of preexisting neutralizing antibodies on vectors’ immunogenicity appears to be less severe than was observed in experimental animals and can readily be circumvented by using vectors to which most humans lack neutralizing antibodies. Additional clinical studies are needed to firmly establish the efficacy of adenoviral vector vaccines.


title: Adherence to precautions for preventing the transmission of microorganisms in primary health care: a qualitative study

text: BACKGROUND: Health care associated infections (HAIs) are a source of concern worldwide. No health service in any country can be considered HAI risk-free. However, there is scarcity of data on the risks to which both patients and health workers are subject in non-hospital settings. The aim of this study was to identify issues that determine the adherence of professionals to precautions for preventing transmission of microorganisms in primary health care. METHOD: This was a qualitative study, using focus groups of primary health care staff, in two Brazilian municipalities. The data were analysed using content analysis. RESULTS: Four focus groups were conducted with 20 professionals (11 community health workers, 5 nursing assistants and 4 nurses), and the analysed content was organized into four thematic categories. These categories are: low risk perception, weaknesses in knowledge, insufficient in-service training and infrastructure limitations. Participants expressed their weaknesses in knowledge of standard and transmission based precautions, mainly for hand hygiene and tuberculosis. A lack of appropriate resources and standardization in sharps disposal management was also highlighted by the participants. CONCLUSION: The study points out the need to provide in-service training for professionals on the transmission of microorganisms in primary health care to ensure adequate level of risk perception and knowledge. Further recommendations include investment to improve infrastructure to facilitate adherence to precautions and to minimize the risk of disease transmission for both patients and health care workers.


title: The effects of the COVID-19 pandemic on oncological surgery

text: The COVID-19 global pandemic is changing the practice of oncologic surgery. Accustomed to fighting cancer with all available means, surgeons are now being asked to delay treatment or make use of alternate strategies to conserve resources. Telemedicine is being widely employed. We present our thoughts on this topic and where we might be in the next several months.


title: Cryptosporidium Infection: Epidemiology, Pathogenesis, and Differential Diagnosis

text: Cryptosporidium is a protozoan that infects a wide variety of vertebrates, including humans, causing acute gastroenteritis. The disease manifests with abdominal pain and diarrhea similar to that of choleric infection. In the immunocompromised hosts, the parasite causes prolonged infections that can also be fatal. For this reason, cryptosporidiosis is considered one of riskiest opportunistic infections for patients with acquired immunodeficiency syndrome. The best way to control the infection in these patients is setting up sensitive and specific diagnostic tests for epidemiological surveillance and morbidity reduction. Here, we summarized the general aspects of Cryptosporidium infection focusing on available diagnostic tools used for the diagnosis of cryptosporidiosis. Molecular methods currently available for its detection and progress in the development of new diagnostics for cryptosporidiosis are also discussed.


title: Chapter 46 Harnessing γδ T Cells as Natural Immune Modulators

text: Abstract There has been renewed interest in harnessing the power of the immune system as a countermeasure against infectious pathogens and cancers. One immune cell target in the development of these approaches is the γδ T cell. These cells are involved in innate and adaptive immune responses against infectious agents and cancers, and they migrate to, and reside in, mucosal tissues. γδ T cells exhibit a broad array of natural (or constitutive) and induced effector functions, including antigen presentation, that can be fine-tuned depending on their stimulation. They express unique antigen receptors as well as nonantigen, innate immune type surface receptors that can be targeted. In this chapter, we will review the biology and the basis for use of γδ T cells as a therapeutic target. We will then summarize novel plant- and microbe-derived materials that enhance γδ T cell activity in animal models and humans that can be used as a new strategy for mucosal vaccine development.


title: Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion

text: Abstract The SARS-coronavirus (SARS-CoV) is the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. To delineate functional domains of the SARS-CoV S glycoprotein, single point mutations, cluster-to-lysine and cluster-to-alanine mutations, as well as carboxyl-terminal truncations were investigated in transient expression experiments. Mutagenesis of either the coiled-coil domain of the S glycoprotein amino terminal heptad repeat, the predicted fusion peptide, or an adjacent but distinct region, severely compromised S-mediated cell-to-cell fusion, while intracellular transport and cell-surface expression were not adversely affected. Surprisingly, a carboxyl-terminal truncation of 17 amino acids substantially increased S glycoprotein-mediated cell-to-cell fusion suggesting that the terminal 17 amino acids regulated the S fusogenic properties. In contrast, truncation of 26 or 39 amino acids eliminating either one or both of the two endodomain cysteine-rich motifs, respectively, inhibited cell fusion in comparison to the wild-type S. The 17 and 26 amino-acid deletions did not adversely affect S cell-surface expression, while the 39 amino-acid truncation inhibited S cell-surface expression suggesting that the membrane proximal cysteine-rich motif plays an essential role in S cell-surface expression. Mutagenesis of the acidic amino-acid cluster in the carboxyl terminus of the S glycoprotein as well as modification of a predicted phosphorylation site within the acidic cluster revealed that this amino-acid motif may play a functional role in the retention of S at cell surfaces. This genetic analysis reveals that the SARS-CoV S glycoprotein contains extracellular domains that regulate cell fusion as well as distinct endodomains that function in intracellular transport, cell-surface expression, and cell fusion.


title: Endogenous Lipid Pneumonia in a Ferret (Mustela putorius furo)

text: Abstract A 1-year-old female ferret was presented with an acute history of severe respiratory distress. Abnormal clinical signs noted during the initial physical examination were hypothermia, dehydration, pale mucous membranes, tachypnea, and severe dyspnea. Thoracic radiographs revealed pleural effusion, an enlarged cardiac silhouette, and areas of lung consolidation. Both blood and thoracic fluid were hyperproteinemic and hypergammaglobulinemic. Antibiotic, corticosteroid, and diuretic supportive treatment provided temporary improvement. After the initial positive response to treatment, the ferret's condition progressively deteriorated until the owners decided to euthanize the patient 15 days after initial presentation. Gross necropsy results revealed 5 mL of serosanguinous fluid within the thoracic cavity, cardiomegaly, and consolidated lungs that had a patchy, pale golden tissue pattern. The histologic diagnosis was endogenous lipid pneumonia. Findings suggest that endogenous lipid pneumonia can be associated with severe respiratory disease in ferrets.


title: Chapter 40 Waterborne Transmission of Enteric Viruses and Their Impact on Public Health

text: Abstract Viruses of human or animal origin can spread in the environment and infect people via water and food. These viruses are released into the environment by various routes including water runoffs and aerosols. Furthermore, zoonotic viruses may infect humans exposed to contaminated surface waters. Viruses are emerging pathogens and are able to adapt by mutation, recombination, and reassortment and can thus become able to infect new hosts and to adjust to new environments. Enteric viruses are among the commonest and most hazardous waterborne pathogens, causing both sporadic and outbreak-related illness. While considerable research has documented the risk of enteric viruses to human health from contact with contaminated water, the current bacterial indicator-based methods for the evaluation of water quality are often ineffectual proxies for pathogenic viruses, but no correlation was established between the enteric bacteria and viruses studied. The present chapter will focus on viral pathogens shown to be transmitted through water. It will also provide an overview of viruses that had not been a concern for waterborne transmission in the past, but that may represent potentially emerging waterborne pathogens due to their occurrence and persistence in water environments. Monitoring effluents from wastewater treatment plants is important to preventing both environmental contamination and the spread of disease.


title: Gastrointestinal endoscopy in the era of the acute pandemic of coronavirus disease 2019: Recommendations by Japan Gastroenterological Endoscopy Society (Issued on April 9th, 2020)

text: All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID‐19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID‐19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID‐19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID‐19; (ii) practical protective equipment for medical personnel depending on the risk for COVID‐19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow‐up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID‐19.


title: Nucleosides for the treatment of respiratory RNA virus infections

text: Influenza virus, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, coronaviruses, and rhinoviruses are among the most common viruses causing mild seasonal colds. These RNA viruses can also cause lower respiratory tract infections leading to bronchiolitis and pneumonia. Young children, the elderly, and patients with compromised cardiac, pulmonary, or immune systems are at greatest risk for serious disease associated with these RNA virus respiratory infections. In addition, swine and avian influenza viruses, together with severe acute respiratory syndrome-associated and Middle Eastern respiratory syndrome coronaviruses, represent significant pandemic threats to the general population. In this review, we describe the current medical need resulting from respiratory infections caused by RNA viruses, which justifies drug discovery efforts to identify new therapeutic agents. The RNA polymerase of respiratory viruses represents an attractive target for nucleoside and nucleotide analogs acting as inhibitors of RNA chain synthesis. Here, we present the molecular, biochemical, and structural fundamentals of the polymerase of the four major families of RNA respiratory viruses: Orthomyxoviridae, Pneumoviridae/Paramyxoviridae, Coronaviridae, and Picornaviridae. We summarize past and current efforts to develop nucleoside and nucleotide analogs as antiviral agents against respiratory virus infections. This includes molecules with very broad antiviral spectrum such as ribavirin and T-705 (favipiravir), and others targeting more specifically one or a few virus families. Recent advances in our understanding of the structure(s) and function(s) of respiratory virus polymerases will likely support the discovery and development of novel nucleoside analogs.


title: Analysis of concentration fluctuations in gas dispersion around high-rise building for different incident wind directions

text: Abstract This article presents experimental results that illustrate the unsteady characteristics of gas dispersion around a complex-shaped high-rise building for different incident wind directions. A series of wind tunnel experiments were conducted using a 1:30 scale model that represented the real structures under study. The objective of this paper is to study the behaviour of concentration fluctuations through transient analysis. Tracer gas was continuously released from a point source located at different positions, and a time series of fluctuating concentrations were recorded at a large number of points using fast flame ionization detectors. The experimental data were analysed to provide a comprehensive data set including variances and associated statistical quantities. Both the unsteady characteristics of the system and their potential practical impact are presented and discussed. Under crowd living conditions, the air pollutant exhausted from one household could probably re-enter into the neighbouring households, traveling with ambient airflow. Such pollutant dispersion process is defined as air cross-contamination in this study. The results indicate that the wind-induced cross-contamination around the studied type of high-rise building should not be overlooked, and the fluctuating concentrations should be paid attention to particularly during the evaluation of a potential contamination risk. This study can help deepen our understanding of the mechanisms of air cross-contamination, and will be useful for implementing optimization strategies to improve the built environments in metropolitan cities such as Hong Kong.


title: The trafficking of natural killer cells

text: Summary: Natural killer (NK) cells are large granular lymphocytes of the innate immune system that participate in the early control of microbial infections and cancer. NK cells can induce the death of autologous cells undergoing various forms of stress, recognizing and providing non‐microbial ‘danger’ signals to the immune system. NK cells are widely distributed in lymphoid and non‐lymphoid organs. NK cell precursors originate from the bone marrow and go through a complex maturation process that leads to the acquisition of their effector functions, to changes in their expression of integrins and chemotactic receptors, and to their redistribution from the bone marrow and lymph nodes to blood, spleen, liver, and lung. Here, we describe the tissue localization of NK cells, using NKp46 as an NK cell marker, and review the current knowledge on the mechanisms that govern their trafficking in humans and in mice.


title: Synthesis of adenine dinucleosides SAM analogs as specific inhibitors of SARS-CoV nsp14 RNA cap guanine-N7-methyltransferase

text: The spreading of new viruses is known to provoke global human health threat. The current COVID-19 pandemic caused by the recently emerged coronavirus SARS-CoV-2 is one significant and unfortunate example of what the world will have to face in the future with emerging viruses in absence of appropriate treatment. The discovery of potent and specific antiviral inhibitors and/or vaccines to fight these massive outbreaks is an urgent research priority. Enzymes involved in the capping pathway of viruses and more specifically RNA N7- or 2’O-methyltransferases (MTases) are now admitted as potential targets for antiviral chemotherapy. We designed bisubstrate inhibitors by mimicking the transition state of the 2’-O-methylation of the cap RNA in order to block viral 2’-O MTases. This work resulted in the synthesis of 16 adenine dinucleosides with both adenosines connected by various nitrogen-containing linkers. Unexpectedly, all the bisubstrate compounds were barely active against 2’-O MTases of several flaviviruses or SARS-CoV but surprisingly, seven of them showed efficient and specific inhibition against SARS-CoV N7-MTase (nsp14) in the micromolar to submicromolar range. The most active nsp14 inhibitor identified is as potent as but particularly more specific than the broad-spectrum MTase inhibitor, sinefungin. Molecular docking suggests that the inhibitor binds to a pocket formed by the S-adenosyl methionine (SAM) and cap RNA binding sites, conserved among SARS-CoV nsp14. These dinucleoside SAM analogs will serve as starting points for the development of next inhibitors for SARS-CoV-2 nsp14 N7-MTase.


title: In silico target fishing and pharmacological profiling for the isoquinoline alkaloids of Macleayacordata (Bo Luo Hui)

text: BACKGROUND: Some isoquinoline alkaloids from Macleaya cordata (Willd). R. Br. (Bo Luo Hui) exhibited antibacterial, antiparasitic, antitumor, and analgesic effects. The targets of these isoquinoline alkaloids are undefined. This study aims to investigate the compound–target interaction network and potential pharmacological actions of isoquinoline alkaloids of M. cordata by reverse pharmacophore database screening. METHODS: The targets of 26 isoquinoline alkaloids identified from M. cordata were predicted by a pharmacophore-based target fishing approach. Discovery Studio 3.5 and two pharmacophore databases (PharmaDB and HypoDB) were employed for the target profiling. A compound–target interaction network of M. cordata was constructed and analyzed by Cytoscape 3.0. RESULTS: Thirteen of the 65 predicted targets identified by PharmaDB were confirmed as targets by HypoDB screening. The targets in the interaction network of M. cordata were involved in cancer (31 targets), microorganisms (12 targets), neurodegeneration (10 targets), inflammation and autoimmunity (8 targets), parasitosis (5 targets), injury (4 targets), and pain (3 targets). Dihydrochelerythrine (C6) was found to hit 23 fitting targets. Macrophage migration inhibitory factor (MIF) hits 15 alkaloids (C1–2, C11–16, C19–25) was the most promising target related to cancer. CONCLUSION: Through in silico target fishing, the anticancer, anti-inflammatory, and analgesic effects of M. cordata were the most significant among many possible activities. The possible anticancer effects were mainly contributed by the isoquinoline alkaloids as active components.


title: Automatically quantifying the scientific quality and sensationalism of news records mentioning pandemics: validating a maximum entropy machine-learning model

text: Abstract Objective To develop and validate a method for automatically quantifying the scientific quality and sensationalism of individual news records. Study design After retrieving 163,433 news records mentioning the Severe Acute Respiratory Syndrome (SARS) and H1N1 pandemics, a maximum entropy model for inductive machine learning was used to identify relationships among 500 randomly sampled news records that correlated with systematic human assessments of their scientific quality and sensationalism. These relationships were then computationally applied to automatically classify 10,000 additional randomly sampled news records. The model was validated by randomly sampling 200 records and comparing human assessments of them to the computer assessments. Results The computer model correctly assessed the relevance of 86% of news records, the quality of 65% of records, and the sensationalism of 73% of records, as compared to human assessments. Overall, the scientific quality of SARS and H1N1 news media coverage had potentially important shortcomings, but coverage was not too sensationalizing. Coverage slightly improved between the two pandemics. Conclusion Automated methods can evaluate news records faster, cheaper, and possibly better than humans. The specific procedure implemented in this study can at the very least identify subsets of news records that are far more likely to have particular scientific and discursive qualities.


The Postdigital in Pandemic Times: a Comment on the Covid-19 Crisis and its Political Epistemologies


title: Purification of cell culture‐derived human influenza A virus by size‐exclusion and anion‐exchange chromatography

text: A process comprising of size‐exclusion chromatography (SEC) and anion‐exchange chromatography (AEC) was investigated for downstream processing of cell culture‐derived influenza A virus. Human influenza virus A/PR/8/34 (H1N1) was propagated in serum‐free medium using MDCK cells as a host. Concentrates of the virus were prepared from clarified and inactivated cell culture supernatants by cross‐flow ultrafiltration as described before. SEC on Sepharose 4 FF resulted in average product yields of 85% based on hemagglutination (HA) activity. Productivity was maximized to 0.15 column volumes (cv) of concentrate per hour yielding a reduction in total protein and host cell DNA (hcDNA) to 35 and 34%, respectively. AEC on Sepharose Q XL was used to separate hcDNA from virus at a salt concentration of 0.65 M sodium chloride. Product yields >80% were achieved for loads >160 kHAU/mL of resin. The reduction in hcDNA was 67‐fold. Split peak elution and bimodal particle volume distributions suggested aggregation of virions. Co‐elution with hcDNA and constant amounts of hcDNA per dose indiciated association of virions to hcDNA. An overall product yield of 52% was achieved. Total protein was reduced more than 19‐fold; hcDNA more than 500‐fold by the process. Estimation of the dose volume from HA activity predicted a protein content at the limit for human vaccines. Reduction of hcDNA was found insufficient (about 500 ng per dose) requiring further optimization of AEC or additional purification steps. All operations were selected to be scalable and independent of the virus strain rendering the process suitable for vaccine production. Biotechnol. Bioeng. 2007;96:932–944. © 2006 Wiley Periodicals, Inc.


title: Huile essentielle de Laurier noble

text: L’huile essentielle (HE) de Laurier noble est sans doute moins célèbre que d’autres. Toutefois, tout le monde connaît cet arbre méditerranéen dont les feuilles, aujourd’hui utilisées dans la cuisine, étaient tressées sous forme de couronne scindant la tête des vainqueurs et des empereurs dans l’Antiquité. Cette HE est d’une grande utilité en infectiologie mais aussi d’un point de vue psychologique. Elle a aussi un effet anesthésiant très apprécié lors des soins, notamment en milieu hospitalier.


title: Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019

text: IMPORTANCE: Health care workers exposed to coronavirus disease 2019 (COVID-19) could be psychologically stressed. OBJECTIVE: To assess the magnitude of mental health outcomes and associated factors among health care workers treating patients exposed to COVID-19 in China. DESIGN, SETTINGS, AND PARTICIPANTS: This cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements from 1257 health care workers in 34 hospitals from January 29, 2020, to February 3, 2020, in China. Health care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 were eligible. MAIN OUTCOMES AND MEASURES: The degree of symptoms of depression, anxiety, insomnia, and distress was assessed by the Chinese versions of the 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder scale, the 7-item Insomnia Severity Index, and the 22-item Impact of Event Scale–Revised, respectively. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes. RESULTS: A total of 1257 of 1830 contacted individuals completed the survey, with a participation rate of 68.7%. A total of 813 (64.7%) were aged 26 to 40 years, and 964 (76.7%) were women. Of all participants, 764 (60.8%) were nurses, and 493 (39.2%) were physicians; 760 (60.5%) worked in hospitals in Wuhan, and 522 (41.5%) were frontline health care workers. A considerable proportion of participants reported symptoms of depression (634 [50.4%]), anxiety (560 [44.6%]), insomnia (427 [34.0%]), and distress (899 [71.5%]). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers (eg, median [IQR] Patient Health Questionnaire scores among physicians vs nurses: 4.0 [1.0-7.0] vs 5.0 [2.0-8.0]; P = .007; median [interquartile range {IQR}] Generalized Anxiety Disorder scale scores among men vs women: 2.0 [0-6.0] vs 4.0 [1.0-7.0]; P < .001; median [IQR] Insomnia Severity Index scores among frontline vs second-line workers: 6.0 [2.0-11.0] vs 4.0 [1.0-8.0]; P < .001; median [IQR] Impact of Event Scale–Revised scores among those in Wuhan vs those in Hubei outside Wuhan and those outside Hubei: 21.0 [8.5-34.5] vs 18.0 [6.0-28.0] in Hubei outside Wuhan and 15.0 [4.0-26.0] outside Hubei; P < .001). Multivariable logistic regression analysis showed participants from outside Hubei province were associated with lower risk of experiencing symptoms of distress compared with those in Wuhan (odds ratio [OR], 0.62; 95% CI, 0.43-0.88; P = .008). Frontline health care workers engaged in direct diagnosis, treatment, and care of patients with COVID-19 were associated with a higher risk of symptoms of depression (OR, 1.52; 95% CI, 1.11-2.09; P = .01), anxiety (OR, 1.57; 95% CI, 1.22-2.02; P < .001), insomnia (OR, 2.97; 95% CI, 1.92-4.60; P < .001), and distress (OR, 1.60; 95% CI, 1.25-2.04; P < .001). CONCLUSIONS AND RELEVANCE: In this survey of heath care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 in Wuhan and other regions in China, participants reported experiencing psychological burden, especially nurses, women, those in Wuhan, and frontline health care workers directly engaged in the diagnosis, treatment, and care for patients with COVID-19.


title: Leadzyme formed in vivo interferes with tobacco mosaic virus infection in Nicotiana tabacum

text: We developed a new method for inhibiting tobacco mosaic virus infection in tobacco plants based on specific RNA hydrolysis induced by a leadzyme. We identified a leadzyme substrate target sequence in genomic tobacco mosaic virus RNA and designed a 16‐mer oligoribonucleotide capable of forming a specific leadzyme motif with a five‐nucleotide catalytic loop. The synthetic 16‐mer RNA was applied with nontoxic, catalytic amount of lead to infected tobacco leaves. We observed inhibition of tobacco mosaic virus infection in tobacco leaves in vivo due to specific tobacco mosaic virus RNA cleavage effected by leadzyme. A significant reduction in tobacco mosaic virus accumulation was observed even when the leadzyme was applied up to 2 h after inoculation of leaves with tobacco mosaic virus. This process, called leadzyme interference, is determined by specific recognition and cleavage of the target site by the RNA catalytic strand in the presence of Pb(2+).


title: Posttraumatic stress disorder and depression of survivors 12 months after the outbreak of Middle East respiratory syndrome in South Korea

text: BACKGROUND: The 2015 outbreak of Middle East Respiratory Syndrome (MERS) in the Republic of Korea is a recent and representative occurrence of nationwide outbreaks of Emerging Infectious Diseases (EIDs). In addition to physical symptoms, posttraumatic stress disorder (PTSD) and depression are common following outbreaks of EID. METHODS: The present study investigated the long-term mental health outcomes and related risk factors in survivors of MERS. A prospective nationwide cohort study was conducted 12 months after the MERS outbreak at multi-centers throughout Korea. PTSD and depression as the main mental health outcomes were assessed with the Impact of Event Scale-Revised Korean version (IES-R-K) and the Patient Health Questionnaire-9 (PHQ-9) respectively. RESULTS: 42.9% of survivors reported PTSD (IES-R-K ≥ 25) and 27.0% reported depression (PHQ-9 ≥ 10) at 12 months post-MERS. A multivariate analysis revealed that anxiety (adjusted odds ratio [aOR], 5.76; 95%CI, 1.29–25.58; P = 0.021), and a greater recognition of stigma (aOR, 11.09, 95%CI, 2.28–53.90; P = 0.003) during the MERS-affected period were independent predictors of PTSD at 12 months after the MERS outbreak. Having a family member who died from MERS predicted the development of depression (aOR, 12.08, 95%CI, 1.47–99.19; P = 0.020). CONCLUSION: This finding implies that psychosocial factors, particularly during the outbreak phase, influenced the mental health of patients over a long-term period. Mental health support among the infected subjects and efforts to reduce stigma may improve recovery from psychological distress in an EID outbreak.


title: Using research to prepare for outbreaks of severe acute respiratory infection

text: Severe acute respiratory infections (SARI) remain one of the leading causes of mortality around the world in all age groups. There is large global variation in epidemiology, clinical management and outcomes, including mortality. We performed a short period observational data collection in critical care units distributed globally during regional peak SARI seasons from 1 January 2016 until 31 August 2017, using standardised data collection tools. Data were collected for 1 week on all admitted patients who met the inclusion criteria for SARI, with follow-up to hospital discharge. Proportions of patients across regions were compared for microbiology, management strategies and outcomes. Regions were divided geographically and economically according to World Bank definitions. Data were collected for 682 patients from 95 hospitals and 23 countries. The overall mortality was 9.5%. Of the patients, 21.7% were children, with case fatality proportions of 1% for those less than 5 years. The highest mortality was in those above 60 years, at 18.6%. Case fatality varied by region: East Asia and Pacific 10.2% (21 of 206), Sub-Saharan Africa 4.3% (8 of 188), South Asia 0% (0 of 35), North America 13.6% (25 of 184), and Europe and Central Asia 14.3% (9 of 63). Mortality in low-income and low-middle-income countries combined was 4% as compared with 14% in high-income countries. Organ dysfunction scores calculated on presentation in 560 patients where full data were available revealed Sequential Organ Failure Assessment (SOFA) scores on presentation were significantly associated with mortality and hospital length of stay. Patients in East Asia and Pacific (48%) and North America (24%) had the highest SOFA scores of >12. Multivariable analysis demonstrated that initial SOFA score and age were independent predictors of hospital survival. There was variability across regions and income groupings for the critical care management and outcomes of SARI. Intensive care unit-specific factors, geography and management features were less reliable than baseline severity for predicting ultimate outcome. These findings may help in planning future outbreak severity assessments, but more globally representative data are required.


title: Why Do Exceptionally Dangerous Gain-of-Function Experiments in Influenza?

text: This chapter makes the case against performing exceptionally dangerous gain-of-function experiments that are designed to create potentially pandemic and novel strains of influenza, for example, by enhancing the airborne transmissibility in mammals of highly virulent avian influenza strains. This is a question of intense debate over the last 5 years, though the history of such experiments goes back at least to the synthesis of viable influenza A H1N1 (1918) based on material preserved from the 1918 pandemic. This chapter makes the case that experiments to create potential pandemic pathogens (PPPs) are nearly unique in that they present biosafety risks that extend well beyond the experimenter or laboratory performing them; an accidental release could, as the name suggests, lead to global spread of a virulent virus, a biosafety incident on a scale never before seen. In such cases, biosafety considerations should be uppermost in the consideration of alternative approaches to experimental objectives and design, rather than being settled after the fact, as is appropriately done for most research involving pathogens. The extensive recent discussion of the magnitude of risks from such experiments is briefly reviewed. The chapter argues that, while there are indisputably certain questions that can be answered only by gain-of-function experiments in highly pathogenic strains, these questions are narrow and unlikely to meaningfully advance public health goals such as vaccine production and pandemic prediction. Alternative approaches to experimental influenza virology and characterization of existing strains are in general completely safe, higher throughput, more generalizable, and less costly than creation of PPP in the laboratory and can thereby better inform public health. Indeed, virtually every finding of recent PPP experiments that has been cited for its public health value was predated by similar findings using safe methodologies. The chapter concludes that the unique scientific and public health value of PPP experiments is inadequate to justify the unique risks they entail and that researchers would be well-advised to turn their talents to other methodologies that will be safe and more rewarding scientifically.


title: COVID‐19 IN THE LONG‐TERM CARE SETTING: THE CMS PERSPECTIVE

text: ABSTRACT Safeguarding the health and promoting the wellbeing and quality of life of the most vulnerable and fragile citizens is a top priority for the Centers for Medicare & Medicaid Services (CMS). In response to the COVID‐19 pandemic, numerous regulatory policies and 1135 waivers of federal requirements have been implemented by CMS to give long‐term care providers and professionals flexibilities to meet to the demands of resident and patient care needs during this public health emergency. Goals for these policies and waivers include to increase capacity, enhance workforce and capability, improve oversight and transparency, prevent COVID‐19 transmission and reduce provider burden. This article is protected by copyright. All rights reserved.


title: Distribution of ACE2, CD147, CD26 and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors

text: BACKGROUND: Morbidity and mortality from COVID‐19 caused by novel coronavirus SARS‐CoV‐2 is accelerating worldwide and novel clinical presentations of COVID‐19 are often reported. The range of human cells and tissues targeted by SARS‐CoV‐2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS‐CoV‐2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID‐19. METHODS: We performed RNA sequencing and explored available RNA‐Seq databases to study gene expression and co‐expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4(+) and CD8(+) T cells, B cells and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID‐19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells. We also observed a distinct age‐related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2‐ and CD147‐related genes in the bronchial biopsy, BAL or blood. Additionally, CD147‐related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of ACE2‐ and CD147‐related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS‐CoV‐2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related with age, gender, obesity and smoking, as well as with the disease status might contribute to COVID‐19 morbidity and severity patterns.


title: 10 Realism and the Art of Simulation

text: Publisher Summary Patient simulation offers clinical educators a new type of “canvas” where they can apply the principles of realism. While having the latest high-tech robotic patient simulators emplaced within fully functional clinical spaces is great, that alone does not provide enough realism. Naïve people are generally impressed by the mannequin and its capabilities, but the “patient” is the most artificial thing about simulation. It's more important to use the technology as a lens to focus on the human aspect of interactions. In the quest for realism, clinical educators create context by placing the mannequin in a simulated or real environment, breathe life into it with human interaction, and take advantage of the learner's imagination. To facilitate learners being more receptive to the educators, the Patient Simulation Center located at St. Michael's Hospital in downtown Toronto, Canada, always presents a supportive and nonthreatening atmosphere. It aims to provide experiential acquisition of skills and judgment, allowing lessons to be learned from errors made. Before starting, learners are familiarized to the environment and the mannequin, and provided with a set of ground rules. This is done on a need-to-know basis, being careful not to cognitively overload the learners with too many rules. There is no need to share all the capabilities and limitations of simulation or to explain how the props work. Keep it simple and user friendly. The rules will vary with the different levels of learners and with how they utilize simulation.


title: Detection and phylogenetic analyses of spike genes in porcine epidemic diarrhea virus strains circulating in China in 2016–2017

text: BACKGROUND: Large-scale outbreaks of porcine epidemic diarrhea (PED) have re-emerged in China in recent years. However, little is known about the genetic diversity and molecular epidemiology of field strains of PED virus (PEDV) in China in 2016–2017. To address this issue, in this study, 116 diarrhea samples were collected from pig farms in 6 Chinese provinces in 2016–2017 and were detected using PCR for main porcine enteric pathogens, including PEDV, porcine deltacoronavirus (PDCoV), porcine transmissible gastroenteritis virus (TGEV) and porcine kobuvirus (PKV). In addition, the complete S genes from 11 representative PEDV strains were sequenced and analyzed. RESULTS: PCR detection showed that 52.6% (61/116) of these samples were positive for PEDV. Furthermore, sequencing results for the spike (S) genes from 11 of the epidemic PEDV strains showed 93–94% nucleotide identity and 92–93% amino acid identity with the classical CV777 strain. Compared with the CV777 vaccine strain, these strains had an insertion (A(133)), a deletion (G(155)), and a continuous 4-amino-acid insertion ((56)NNTN(59)) in the S1 region. Phylogenetic analysis based on the S gene indicated that the 11 assessed PEDV strains were genetically diverse and clustered into the G2 group. These results demonstrate that the epidemic strains of PEDV in China in 2016–2017 are mainly virulent strains that belong to the G2 group and genetically differ from the vaccine strain. Importantly, this is the first report that the samples collected in Hainan Province were positive for PEDV (59.2%, 25/42). CONCLUSIONS: To our knowledge, this article presents the first report of a virulent PEDV strain isolated from Hainan Island, China. The results of this study will contribute to the understanding of the epidemiology and genetic characteristics of PEDV in China.


title: A clinical approach to respiratory disease in patients with hematological malignancy, with a focus on respiratory infection

text: Respiratory complications, in particular infections, are common in the setting of hematological malignancy and after hematopoetic stem cell transplant. The symptoms can be nonspecific; therefore, it can be difficult to identify and treat the cause. However, an understanding of the specific immune defect, clinical parameters such as speed of onset, and radiological findings, allows the logical diagnostic and treatment plan to be made. Radiological findings can include consolidation, nodules, and diffuse changes such as ground glass and tree-in-bud changes. Common infections that induce these symptoms include bacterial pneumonia, invasive fungal disease, Pneumocystis jirovecii and respiratory viruses. These infections must be differentiated from inflammatory complications that often require immune suppressive treatment. The diagnosis can be refined with the aid of investigations such as bronchoscopy, computed tomography (CT) guided lung biopsy, culture, and serological tests. This article gives a schema to approach patients with respiratory symptoms in this patient group; however, in the common scenario of a rapidly deteriorating patient, treatment often has to begin empirically, with the aim to de-escalate treatment subsequently after targeted investigations.


title: 11 Proteomics and Host–Pathogen Interactions A Bright Future?

text: Abstract The host–vector–pathogen interactions are governed since their origin by a subtle balance between attack and transmission strategies and defense mechanisms. Molecular dialogues are established between a pathogen and its host, these ones will generate a mutual selection pressure that will result in profound changes in expression of host and pathogen genes. In the post-genomic era, proteomics is in its infancy, but represents a promising tool to fill the blanks that still exist in biology despite the sequencing of the genomes of many organisms. This chapter presents the interest in proteomics toward a better understanding of host–vector–pathogen cross talks through a synthetic review of the available data generated by proteomics studies, discussing the pitfalls of current approaches, and presenting new approaches to decipher from molecular interactions with population proteomics leading to biomarkers discovery for diagnosis, therapy, and vaccine purposes.


title: National Institute for the Infectious Diseases “L. Spallanzani”, IRCCS. Recommendations for COVID-19 clinical management

text: On January 9 2020, the World Health Organization (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a disease (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The “L. Spallanzani” National Institute for the Infectious Diseases, IRCCS, Rome, Italy, has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; they should be considered as expert opinions, which may be modified according to newly produced literature data.


title: Neutrophil extracellular traps (NETs) as markers of disease severity in COVID-19

text: In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have potential to propagate inflammation and microvascular thrombosis, including in the lungs of patients with acute respiratory distress syndrome. While elevated levels of blood neutrophils predict worse outcomes in COVID-19, the role of NETs has not been investigated. We now report that sera from patients with COVID-19 (n=50 patients, n=84 samples) have elevated levels of cell-free DNA, myeloperoxidase(MPO)-DNA, and citrullinated histone H3 (Cit-H3); the latter two are highly specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute phase reactants including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. In summary, these data reveal high levels of NETs in many patients with COVID-19, where they may contribute to cytokine release and respiratory failure. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts, and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19.


title: COVID‐19 and access to labour epidural analgesia in UK hospitals

text: Even before COVID-19 had a significant impact on public health in the UK, there were media reports that access to epidural analgesia for women during labour was being restricted in some NHS hospitals [1]. To determine whether the crisis management of COVID-19 in NHS hospitals was having an adverse effect on the availability of labour epidural analgesia, the Obstetric Anaesthetists' Association (OAA) surveyed consultant anaesthetists who are service leads for obstetric anaesthesia in their hospital. The link to an online survey was posted on a WhatsApp group, created for consultant service leads for obstetric anaesthesia to share information about COVID-19 disease, and was also emailed to all 209 consultants who the OAA believed to be service leads.


title: Regulation of TGF-β Signal Transduction

text: Transforming growth factor-β (TGF-β) signaling regulates diverse cellular processes, including cell proliferation, differentiation, apoptosis, cell plasticity, and migration. TGF-β signaling can be mediated by Smad proteins or other signaling proteins such as MAP kinases and Akt. TGF-β signaling is tightly regulated at different levels along the pathways to ensure its proper physiological functions in different cells and tissues. Deregulation of TGF-β signaling has been associated with various kinds of diseases, such as cancer and tissue fibrosis. This paper focuses on our recent work on regulation of TGF-β signaling.


title: The effect of gramicidin inclusions on the local order of membrane components

text: ABSTRACT. We study the local effect of the antimicrobial peptide Gramicidin A on bilayers composed of lipids or surfactants using nuclear magnetic resonance spectroscopy and wide-angle X-ray scattering, techniques that probe the orientational and positional order of the alkyl chains, respectively. The two types of order vary with temperature and peptide concentration in complex ways which depend on the membrane composition, highlighting the subtlety of the interaction between inclusions and the host bilayer. The amplitude of the variation is relatively low, indicating that the macroscopic constants used to describe the elasticity of the bilayer are unlikely to change with the addition of peptide. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material in the form of a .pdf file available from the Journal web page at 10.1140/epje/i2018-11644-5 and accessible for authorised users.


title: 1.22 Bioethical Issues in Medicinal Chemistry and Drug Treatment

text: The use of drugs to treat human disease is a pursuit that extends back into our evolutionary ancestors. Drugs are powerful substances with a great capacity to cause harm if misused or overused. Even when used correctly, pharmaceuticals can elicit disputes about their relative harms and benefits in specific situations. The establishment of modern intermediaries – physicians or pharmacists – in the allocation of the most powerful drugs increases the potential for conflict between those who control the resource and those who desire access to it. The size and influence of the pharmaceutical–industrial complex places disproportionate power in those whose interests lie in promoting and expanding pharmaceutical use in society. The expense of certain drugs complicates equitable allocation, and the concentration of pharmaceutical power in Western, industrialized countries promotes research and drug discovery disproportionately for diseases that are prevalent in the wealthier nations. The increasing sophistication of drug action challenges the traditional model of using drugs as a means to treat pathological conditions and processes, and raises the specter of lifestyle and enhancement uses of pharmaceuticals. New means of drug discovery – such as the use of stem cells – have elicited debate about the relative values placed on the status of the embryo and the potential treatment for intractable conditions that could result from stem cell research. Finally, the overall emphasis on drugs as the first line defense against what ails us has provoked some societal soul-searching. In this chapter, we review some of the ethical issues attendant to drug production and distribution, including issues of safety, justice, economic inequality, and the changing demands for drugs that exceed therapeutic uses. Suggestions are made to make pharmaceutical companies more responsive to these issues and to make oversight bodies more responsible for their roles.


Enteric Coronavirus in Ferrets, the Netherlands


Brief recommendations on the management of adult patients with familial hypercholesterolemia during the COVID-19 pandemic


title: Current Status of Porcine Epidemic Diarrhoea (PED) in European Pigs

text: Porcine epidemic diarrhoea (PED) is a highly contagious and devastating enteric disease of pigs caused by porcine epidemic diarrhoea virus (PEDV), an enveloped, single-stranded RNA virus belonging to the Alphacoronavirus genus of the Coronaviridae family. The disease is clinically similar to other forms of porcine gastroenteritis. Pigs are the only known host of the disease, and the occurrence of PED in wild boars is unknown. The virus causes acute diarrhoea, vomiting, dehydration, and high mortality in suckling piglets reaching 100%. Heavy economic losses in the pig-farming industry were sustained in the USA between 2013 and 2015 when PEDV spread very quickly and resulted in epidemics. The loss in the US pig industry has been estimated at almost seven million pigs. The purpose of this review is a description of the current status of porcine epidemic diarrhoea in European pigs and the risk presented by the introduction of PEDV to Poland in comparison to the epidemics in the USA.


title: Bat cells from Pteropus alecto are susceptible to influenza A virus infection and reassortment

text: Waterfowl are primary hosts for influenza A viruses (IAVs); however, there is sporadic infection of swine and other species that pose a risk of zoonotic spread. Yellow‐shouldered bats were shown to be hosts of an IAV, thereby constituting a potential novel reservoir. We show that Pteropus alecto kidney cells (PaKi) are susceptible to infection and sustain replication of A/WSN/33 (H1N1) and A/Vietnam/1203/04 (H5N1). Importantly, we show that co‐infection of PaKi cells results in novel reassortants.


title: Chapter Two Coronavirus Spike Protein and Tropism Changes

text: Abstract Coronaviruses (CoVs) have a remarkable potential to change tropism. This is particularly illustrated over the last 15 years by the emergence of two zoonotic CoVs, the severe acute respiratory syndrome (SARS)- and Middle East respiratory syndrome (MERS)-CoV. Due to their inherent genetic variability, it is inevitable that new cross-species transmission events of these enveloped, positive-stranded RNA viruses will occur. Research into these medical and veterinary important pathogens—sparked by the SARS and MERS outbreaks—revealed important principles of inter- and intraspecies tropism changes. The primary determinant of CoV tropism is the viral spike (S) entry protein. Trimers of the S glycoproteins on the virion surface accommodate binding to a cell surface receptor and fusion of the viral and cellular membrane. Recently, high-resolution structures of two CoV S proteins have been elucidated by single-particle cryo-electron microscopy. Using this new structural insight, we review the changes in the S protein that relate to changes in virus tropism. Different concepts underlie these tropism changes at the cellular, tissue, and host species level, including the promiscuity or adaptability of S proteins to orthologous receptors, alterations in the proteolytic cleavage activation as well as changes in the S protein metastability. A thorough understanding of the key role of the S protein in CoV entry is critical to further our understanding of virus cross-species transmission and pathogenesis and for development of intervention strategies.


title: Process Control Charts in Falls Prevention: The Experience of the Local Healthcare Authority of Romagna, Italy

text: Patient safety is a great concern of healthcare institutions and the correct reporting and management of adverse events is a key element for supporting safety improvement efforts. Patient falls are the most frequent adverse event in hospitals and often cause serious patient outcomes. In this work, we describe the experience of the Local Healthcare Authority of Romagna, Italy that, within the framework of a quality and safety improvement programme, designed, developed and implemented a desktop application for monitoring inpatient falls. A multidisciplinary team created a software tool based on R, an open source software for statistical computing that, appropriately combined with the existing hospital information system, is used to obtain Shewhart u-control charts for monitoring the monthly fall rates. The tool had been implemented in twenty nine hospital units. The results indicate that the proposed application gave a valuable contribution in the safety improvement activities. Its usefulness extended beyond the “safety problem” as it also enabled hospital managers to identify a number of critical issues in data collection. As a result, where necessary, improvement actions had been implemented. Furthermore, the use of open source software led to a considerable cost reduction and facilitated customization of the software tool.


title: A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs

text: Abstract With the recent emergence of Middle East Respiratory Syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. However, anti-coronavirus drugs currently are not available. In an effort to assist rapid development of anti-coronavirus drugs, here we screened the NIH Clinical Collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. Of the 727 compounds screened, 84 were found to have a significant anti-coronavirus effect. Further experiments revealed that 51 compounds blocked virus entry while 19 others inhibited viral replication. Additional validation studies with the top 3 inhibitors (hexachlorophene, nitazoxanide and homoharringtonine) demonstrated robust anti-coronavirus activities (a reduction of 6 to 8log10 in virus titer) with an IC50 ranging from 11nM to 1.2μM. Furthermore, homoharringtonine and hexachlorophene exhibited broad antiviral activity against diverse species of human and animal coronaviruses. Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs.


title: Lessons from the field on COVID-19: a public health point of view

text: The COVID-19 pandemic in world affected all strata of population. It started on 28 January 2020 in Wuhan province of China and since then it has been spreading all over the globe rapidly. Today there are nearly 6 million cases of COVID-19 all over the globe. India with its second largest population in the world, with approximately 1.2 billion, has 22% of its population below poverty line and illiteracy at large. Kashmir, a Union Territory of India with a population of 7 million, has been equally hit by the Severe Acute Respiratory Syndrome-Corona Virus-(SARS-CoV) pandemic. In such a limited-resource setting, working under constraints leads to generation of innovations which are the support system of community medicine/public health management.


title: Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020

text: As of April 2, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in >890,000 cases and >45,000 deaths worldwide, including 239,279 cases and 5,443 deaths in the United States (1,2). In the United States, 22% of the population is made up of infants, children, and adolescents aged <18 years (children) (3). Data from China suggest that pediatric COVID-19 cases might be less severe than cases in adults and that children might experience different symptoms than do adults (4,5); however, disease characteristics among pediatric patients in the United States have not been described. Data from 149,760 laboratory-confirmed COVID-19 cases in the United States occurring during February 12-April 2, 2020 were analyzed. Among 149,082 (99.6%) reported cases for which age was known, 2,572 (1.7%) were among children aged <18 years. Data were available for a small proportion of patients on many important variables, including symptoms (9.4%), underlying conditions (13%), and hospitalization status (33%). Among those with available information, 73% of pediatric patients had symptoms of fever, cough, or shortness of breath compared with 93% of adults aged 18-64 years during the same period; 5.7% of all pediatric patients, or 20% of those for whom hospitalization status was known, were hospitalized, lower than the percentages hospitalized among all adults aged 18-64 years (10%) or those with known hospitalization status (33%). Three deaths were reported among the pediatric cases included in this analysis. These data support previous findings that children with COVID-19 might not have reported fever or cough as often as do adults (4). Whereas most COVID-19 cases in children are not severe, serious COVID-19 illness resulting in hospitalization still occurs in this age group. Social distancing and everyday preventive behaviors remain important for all age groups as patients with less serious illness and those without symptoms likely play an important role in disease transmission (6,7).


title: SARS Coronavirus Redux

text: As an atypical pneumonia began to appear in December 2019, Zhou et al . worked with remarkable speed to identify the associated virus, determine its relationship to animal viruses, and evaluate factors conferring infection susceptibility and resistance. These foundational results are being advanced to control the current worldwide human coronavirus epidemic.


title: Psychosocial determinants of influenza vaccination intention: A cross-sectional study on inpatient nurses in Singapore

text: Nurses have the closest interaction with inpatients and could transmit influenza to patients. From a self-administered questionnaire survey among inpatient nurses at a tertiary hospital, we observed that the strongest factors associated with intention for future vaccination were perceived benefits of and motivations for vaccination (adjusted odds ratio [aOR], 3.30; 95% confidence interval [CI], 2.55-4.27), and perceived nonsusceptibility to influenza and preference for vaccination alternatives (aOR, 0.26; 95% CI, 0.20-0.34). These factors need to be addressed to increase vaccination uptake and prevent nosocomial transmission.


title: Snowbirds and infection--new phenomena in pneumonia and influenza hospitalizations from winter migration of older adults: A spatiotemporal analysis

text: BACKGROUND: Despite advances in surveillance and prevention, pneumonia and influenza (P&I) remain among the leading causes of mortality in the United States. Elderly adults experience the most severe morbidity from influenza-associated diseases, and have the highest rates of seasonal migration within the U.S. compared to other subpopulations. The objective of this study is to assess spatiotemporal patterns in influenza-associated hospitalizations in the elderly, by time, geography, and intensity of P&I. Given the high seasonal migration of individuals to Florida, this state was examined more closely using harmonic regression to assess spatial and temporal patterns of P&I hospitalizations by state of residence. METHODS: Data containing all Medicare-eligible hospitalizations in the United States for 1991-2006 with P&I (ICD-9-CM codes 480-487) were abstracted for the 65+ population. Hospitalizations were classified by state of residence, provider state, and date of admissions, specifically comparing those admitted between October and March to those admitted between April and September. We then compared the hospitalization profile data of Florida residents with that of out-of-state residents by state of primary residence and time of year (in-season or out-of-season). RESULTS: We observed distinct seasonal patterns of nonresident P&I hospitalizations, especially comparing typical winter destination states, such as California, Arizona, Texas, and Florida, to other states. Although most other states generally experienced a higher proportion of non-resident P&I during the summer months (April-September), these states had higher nonresident P&I during the traditional peak influenza season (October-March). CONCLUSIONS: This study is among the first to quantify spatiotemporal P&I hospitalization patterns in the elderly, focusing on the change of patterns that are possibly due to seasonal population migration. Understanding migration and influenza-associated disease patterns in this vulnerable population is critical to prepare for and potentially prevent influenza outbreaks in this vulnerable population.


title: Asthma and COVID‐19: is asthma a risk factor for severe outcomes?

text: When I first read the manuscript that accompanies this editorial, upon its online publication on February 19(th) 2020(1), COVID‐19 had already killed 2118 people in China, but only one person in Europe – an 80‐year‐old tourist from China, who died in France on the 15(th) February. I read the manuscript with grim fascination, as it was clear that SARS‐CoV‐2 had spread very rapidly in China which already had 74,576 cases and in South Korea which already had 58 cases, and that it was then invading Europe also, as France already had 12 cases, Germany 16, the UK 9, Italy 3, Spain 2 and other countries too.


title: APOB‐associated cholesterol deficiency in Holstein cattle is not a simple recessive disease

text: In 2015, cholesterol deficiency (CD) was reported for the first time as a new recessive defect in Holstein cattle. After GWAS mapping and identification of a disease‐associated haplotype, a causative loss‐of‐function variant in APOB was identified. CD‐clinically affected APOB homozygotes showed poor development, intermittent diarrhea and hypocholesterolemia and, consequently, a limited life expectation. Herein, we present a collection of 18 cases clinically diagnosed as CD‐affected APOB heterozygotes. CD‐clinically affected heterozygotes show reduced cholesterol and triglyceride blood concentrations. The differences in total blood cholesterol and triglycerides between nine CD‐clinically affected and 36 non‐affected heterozygotes were significant. As only some APOB heterozygotes show the clinical CD phenotype, we assume that the penetrance is reduced in heterozygotes compared to the fully penetrant effect observed in homozygotes. We conclude that APOB‐associated CD represents most likely an incomplete dominant inherited metabolic disease with incomplete penetrance in heterozygotes.


Mental health assessment of frontline COVID‐19 dermatologists: A Pan‐Indian multicentric cross‐sectional study


title: Fingerprint characteristics and health risks of trace metals in market fish species from a large aquaculture producer in a typical arid province in Northwestern China

text: Concentrations of nine metals were measured in eight common cultured fish species obtained from forty-three aquatic product markets across three cities in Xinjiang province, to establish fingerprint characteristics and assess potential human health risks due to the consumption of fish. Metal levels ([Formula: see text] g/kg, wet weight) in fish muscles were: 1204.88–5113.19 Al, 2.09–12.44 V, 6.10–31.86 Cr, 2368.80–8949.52 Fe, 2.01–10.26 Co, 4082.72–12785.68 Zn, 174.89–763.83 Cu, 0.33–2.24 Cd, and 5.74–9.90 Pb. Fingerprint analysis revealed that the studied fish species from the three cities exhibited a similar pattern of distribution. From the viewpoint of human health, the assessment of non-carcinogenic risk indicated no significant adverse health effects due to consumption of the assessed fish species.


title: A Double-Edged Sword—Cardiovascular Concerns of Potential Anti-COVID-19 Drugs

text: Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). COVID-19 significantly affects multiple systems including the cardiovascular system. Most importantly, in addition to the direct injury from the virus per se, the subsequent cytokine storm, an overproduction of immune cells and their activating compounds, causes devastating damage. To date, emerging anti-SARS-CoV-2 treatments are warranted to control epidemics. Several candidate drugs have been screened and are currently under investigation. These primarily include antiviral regimens and immunomodulatory regimens. However, beyond the anti-SARS-CoV-2 effects, these drugs may also have risks to the cardiovascular system, especially altering cardiac conduction. Herein, we review the cardiovascular risks of potential anti-COVID-19 drugs.


title: The infectious aetiology of disease: the search for new agents

text: Abstract There are many diseases for which a microbial aetiology is suspected. The hypothesis that a disease has an infectious cause is supported by: clinical features (similar to those of known infectious diseases, e.g. fever, leucocytosis), epidemiology (case clustering in time or location), histology (inflammation of affected tissues, e.g. granulomata) or characteristic microbial structures, treatment (clinical response to antimicrobial treatment), and prevention of disease by vaccines targeting microbial antigens. Proof that a microbe causes a disease requires more rigorous evidence. Future attempts to identify novel microbes associated with human disease may use sequence-based approaches. High-throughput sequencing may allow identification of unique microbial nucleic acid sequences in a background of host DNA. The complete sequencing of the human genome and multiple microbial genomes make this approach more feasible. DNA microarrays are also likely to be used in the search for novel pathogens.


title: Genotyping of human rhinovirus in adult patients with acute respiratory infections identified predominant infections of genotype A21

text: Human rhinovirus (HRV) is an important causative agent of acute respiratory tract infections (ARTIs). The roles of specific HRV genotypes in patients suffering from ARTIs have not been well established. We recruited 147 adult inpatients with community-acquired pneumonia (CAP) and 291 adult outpatients with upper ARTIs (URTIs). Respiratory pathogens were screened via PCR assays. HRV was detected in 42 patients, with 35 species A, five B and two C. Seventeen genotypes were identified, and HRV-A21 ranked the highest (9/42, 21.4%). The HRV-A21-positive infections were detected in four patients with CAP and in five with URTIs, all without co-infections. The HRV-A21 genome sequenced in this study contained 12 novel coding polymorphisms in viral protein (VP) 1, VP2 EF loop, VP3 knob and 3D regions. The infections of HRV-A21 virus obtained in this study could not be neutralized by antiserum of HRV-A21 prototype strain (VR-1131), indicating remarkable antigenic variation. Metagenomic analysis showed the HRV-A21 reads were dominant in bronchoalveolar lavage fluid of the three HRV-A21-positive patients with severe CAP, in which two dead. Our results highlight an unexpected infection of genotype HRV-A21 in the clinic, indicating the necessity of precise genotyping and surveillance of HRVs to improve the clinical management of ARTIs.


title: COVID-19 virus outbreak forecasting of registered and recovered cases after sixty day lockdown in Italy: A data driven model approach

text: Abstract Background Till 31 March 2020, 105,792 COVID-19 cases were confirmed in Italy including 15,726 deaths which explains how worst the epidemic has affected the country. After the announcement of lockdown in Italy on 9 March 2020, situation was becoming stable since last days of March. In view of this, it is important to forecast the COVID-19 evaluation of Italy condition and the possible effects, if this lock down could continue for another 60 days. Methods COVID-19 infected patient data has extracted from the Italian Health Ministry website includes registered and recovered cases from mid February to end March. Adoption of seasonal ARIMA forecasting package with R statistical model was done. Results Predictions were done with 93.75% of accuracy for registered case models and 84.4% of accuracy for recovered case models. The forecasting of infected patients could be reach the value of 182,757, and recovered cases could be registered value of 81,635 at end of May. Conclusions This study highlights the importance of country lockdown and self isolation in control the disease transmissibility among Italian population through data driven model analysis. Our findings suggest that nearly 35% decrement of registered cases and 66% growth of recovered cases will be possible.